OB - Transes

PHYSIOLOGY OB
2nd Year NOTES By Ge Cas Year 2011-2012
Physiologic OB
TABLE OF CONTENTS
CHAPTER 2: Anatomy of the Female Pelvis CHAPTER 2: Maternal Anatomy CHAPTER 3: Ovarian & Endometrial Cycle CHAPTER 3: Placenta & Fetal Membranes CHAPTER 3: Placental Hormones CHAPTER 4 Fetal Growth & Development I CHAPTER 4 Fetal Growth & Development I TABLE CHAPTER 4 Fetal Growth & Development II CHAPTER 4 Fetal Growth & Development II TABLE CHAPTER 5 Maternal Physiology I CHAPTER 5 Maternal Physiology II CHAPTER 6 Phases of Parturition CHAPTER 6 Physiological & Biochemical Processes Regulating Parturition CHAPTER 8 Prenatal Care I CHAPTER 8 Prenatal Care II CHAPTER 13 Prenatal Diagnosis & Fetal Therapy CHAPTER 14 Teratology CHAPTER 15 Antepartum Assessment CHAPTER 16 Fetal Imaging CHAPTER 17 Management of Normal Labor CHAPTER 17 Mechanism & Characteristics of Labor CHAPTER 18 Intrapartum Assessment CHAPTER 19 Obstetric Anesthesia CHAPTER 30 Peurperium
2 5 8 12 16 21
25
33 37 43 47 51 54 58 63 69 73 81 85 88 98 105
Reference: PHYSIOLOGIC OBSTETRICS by Williams
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CHAPTER 2
MATERNAL ANATOMY Anatomy of Female Pelvis

Dr. Garcia
Increase success of bearing down reflex d/t roomier pelvic architecture Increase pelvic outlet diameter by 1.5-2.0 cm Useful for McRoberts Maneuver: maneuver used in shoulder dystocia where there is difficulty delivering shoulder of big babies, maternal legs are raised w/ feet towards maternal head Flex legs over abdomen Dislodge shoulders and deliver baby
4 imaginary planes of pelvis Pelvic inlet Pelvic Outlet Midpelvis Plane of greatest dimension
4 bones of the pelvis Sacrum Coccyx 2 innominate bones Ilium Ischium Pubis House product of conception Pelvic Anatomy Divided into false & true pelvis by LINEA TERMINALIS False pelvis above the linea terminalis Were baby is found before onset of labor Bounded laterally iliac fossa Anteriorly rectus abdominis (lower portion of anterior abdominal wall) Post linea terminalis True Pelvis Where fetus is found after engagement Fetus descends into the pelvis before it goes to the vaginal canal Below linea terminalis Important in childbearing Boundaries Above Promontory Alae of sacrum Linea terminalis Upper margin of pubic bones Below pelvic outlet Posteriorly anterior surface of sacrum Laterally ischial bones Anteriorly pubic bones Relaxation of pelvic joints in pregnancy From hormonal changes: rd 3 trimester: pelvic bone goes into relaxation d/t RELAXIN, hCG, Estrogen & Progesterone Increased during the last 3 months Mid-trimester: relaxation of pelvic jts would start occurring Regression completed in 3-5 months after birth Increased width of symphysis pubis Accommodates passage of fetal head Greatest displacement of sacroiliac joint in dorsal lithotomy position
4 planes of pelvis PELVIC Inlet Dystocia common during the inlet observation & midpelvic plane Boundaries Posterior promontory and ala of sacrum Lateral linea terminalis Anterior symphysis pubis 4 diameters Anteroposterior diameter Transverse 2 Obliques Transverse 5 cm from sacral promontory Normally measure 13.5 cm Interspinous 10 cm Narrowest
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Boundaries Anterior pubic arch Lateral ischial tuberosities (approximated by a fisted hand) Posterior tip of coccyx Transverse diameter 11 cm Antero-posterior diameter 9.5 11 cm
4 diameters Anteroposterior (AP) Diameter of Pelvic Inlet Most important diameter True conjugate upper rim of symphysis pubis to sacral promontory Diagonal conjugate 1.2 cm = 10.8 cm Bigger than obstetric conjugate Diagonal conjugate: When doing internal pelvic pelvimetry Know expanse of the tip of your middle finger & arch Internal Examination (IE): see figure below arch b/w your thumb & index finger would be hugging symphysis pubis If finger can reach sacral promontory: sacral promontory reached at ~ 12 cm DIAGNONAL CONJUGATE Lies under the subpubic arch Lower portion of symphysis pubis & sacral promontory Only one that can be directly measured: 12cm Can be CLINICALLY MEASURED Obstetric conjugate to sacral promontory Narrowest Shortest distance b/w sacral promontory & symphysis pubis MOST IMPORTANT Not measure directly (Diagonal conjugate 1.5 to 2 cm) = 9.5 o 10 cm Hence if fetal biparietal diameter is > 10cm, difficult labor Dystocia Anterior Posterior Diameter of Midpelvis Measured from lower border of symphysis pubis to any point of the sacrum Known by the expanse of middle & index finger Interspinous diameter N: 10 cm Hence, if biparietal diameter is > 10cm, difficult labor Dystocia ANTEROPOSTERIOR DIAMETER POSTERIOR SAGITTAL DIAMETER Pelvic Outlet
Midpelvis least pelvic dimensions A contraction of midpelvis will have concomitant contraction of pelvic outlet At the level of ischial spines Interspinous diameter 10 cm AP diameter 11.5 Posterior sagittal diameter 4.5 cm Plane of greatest pelvic dimensions
PELVIC Shape: CLASSIFIED BY CALDWELL-MALOY P type of pelvis N inclination, anterior tendency
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Gynecoid Circular and equal Mc in females Oval shape more AP AP segment equal Sacrum well curved Anthropoid Longer PA, Shorter transverse Shorter posterior-sagittal Oval AP Android Heart shaped Wider posterior than anterior Male pelvis Platypelloid Longer transverse, Shorter PA Transversely oval
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CHAPTER 2
Maternal, Pelvic Anatomy

Dr. San Jose
EXTERNAL GENERATIVE ORGANS
Pudenda Aka: vulva all structures visible externally from the pubis to perineum Mons Pubis Aka: Mons Veneris Fat-filled cushion that lies over the symphysis pubis Covered by pubic hair: Escutcheon Women triangular shape Men no defined shape Clitoris Principal female erogenous organ Homologous to penis Covered by stratified squamous keratinized epithelium Contents of the VULVA Urethral Meatus Skenes Ducts Hymen Bartholins Glands Labia Majora Homologous with male scrotum Round ligament terminates at its upper border Continuous with mons pubis Merge posterior & medially: Posterior Commissure Less prominent in multiparous women More prominent in nulliparous women Composition: Sebaceous glands Dense connective tissues (elastic fibers) Adipose tissues Epithelial appendages Rich plexus of veins straddle injury rupture vulvar hematoma Labia Minora May not be seen in nulliparous More prominent in multiparous No hair follicles Many sebaceous follicles Few sweat glands 2 lamellae (superiorly) Upper pair prepuce Lower pair frenulum of clitoris Fuse posterior & inferiorly: Fourchette Vestibule Bounded by Laterally: labia minora
Superiorly: clitoris Inferiorly: fourchette Openings Urethra Immediately above the anterior vaginal wall in the midline of the vestibule Skene ducts open on either side Vagina Covered by stratified squamous nonkeratinized epithelium Tissue rich in glycogen especially in pregnancy From vulva to uterus Boundaries Anteriorly: Urinary bladder divided by the vesicovaginal septum Posteriorly: Rectum Rectouterine pouch (cul-de-sac of Douglas) Site for culdocentesis of Blood Pus Any other fluid Divided from the vagina by the Rectovaginal septum Origin Upper Mullerian ducts Lower urogenital sinus Upper Vagina Subdivided into: 2 lateral fornices Anterior Fornix Posterior: access to cul-de-sac Vaginal Wall Nullipara (+) Rugae Multipara smooth; appear again rd after 3 week post-partum Blood Supply Upper 1/3 cervicovaginal branch of uterine Middle inferiorly vesical artery Lower middle rectal and internal pudendal arteries (same with perineum) Lymphatic Supply Lower 1/3 inguinal lymph nodes Middle internal iliac nodes Upper iliac nodes (not palpable) Perineum Major support structures must not be damaged Pelvic diaphragm Levator ani muscles (L4) Origin Superior pubic rami Ischial spines Obturator fascia Insertion vagina and rectum Coccygeus muscles (C4) Urogenital diaphragm External to the pelvic diaphragm Triangular area between ischial tuberosity Made up of Deep transverse perineal muscles Constrictor Clinical Significance Rectal incontinence produced by damage to sphincters following vaginal delivery
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Blood Supply Internal pudendal arteries: Inferior rectal arteries Posterior labial arteries Innervation Pudendal nerve (S2, S3, S4) passes just behind the ischial spine can block bilaterally with local (lidocaine), below and beneath ischial spine Perineal Body Central Tendon of the Perineum Reinforced by: medial raphe of the levator ani Bulbocavernosus Superficial transverse perineal External anal sphincter muscles Episiotomy Right mediolateral to avoid the area perineal body w/c can lead to rectal incontinence if injured INTERNAL GENERATIVE ORGANS Uterus Boundaries Anterior: Urinary bladder Posterior: Rectum Entire posterior wall and only the upper portion of the anterior wall is covered by tunica serosa or parietal peritoneum Pouch of Douglas Fold of peritoneum between the lower portion of the posterior wall of the uterus and the rectum Parts of uterus (view on slide is posterior of broad ligament) Body or corpus pear shaped 3 layers Serosa Muscular Mucosa endometrium Mucosal lining of the uterus in non-pregnant women Columnar ciliated cells Thickness: 0.5 5 mm Thinnest during early proliferative stage of endometrial cycle Thickest during secretory phase of endometrial cycle Perforated by tubular uterine glands From endometrium to myometrium Secrete thin alkaline fluid Vascular in pregnancy Uterine and ovarian arteries Arcuate arteries Radial arteries basal arteries nonresponsive remain straight throughout cycle myometrium Coiled arteries responsive to hormonal action Unique to endometrium Constricted during menstrual cycle Myometrium Bundles of smooth muscle that makes up the major portion of the uterus Undergoes marked hypertrophy during pregnancy Supporting Ligaments of the uterus Broad ligament Divide pelvic cavity into anterior and posterior cavity 2 wing-like structures Mesosalpinx Part of broad ligament Supports fallopian tube Parametrium lower part Infundibulopelvic/suspensory ligament Contains ovarian vessels Contains neurovascular structures Cardinal ligament Found at base of uterus Attach laterally/anteriorly to cervix Transverse cervical ligament Mackenrod Ligament Medially united firmly to the supravaginal portion of the cervix Strong lig of the uterus during hysterectomy, this is where vaginal stump is supported post-surgically Round ligament Terminates at labia majora From the lateral portion of the uterus, anterior to the oviducts, terminating at the labia majora Homologue of gubernaculum testis Uterosacral ligament Attached to posterior lower portion of uterus, sac root
Hymen No glandular/muscular elements st Torn at several sites during 1 coitus Not used to determine virginity Childbirth cicatricized nodules Types Annular circular with small hole Septate two openings Cribriform multiple small openings Parous introitus - viable birth th liporus introitus - non viable after 20 week Imperforate Hymen: Hematocolpus a vaginal opening completely occluded retention of menstrual blood painful for girl at menarche dx should have been made at birth; procedure should be done early Ducts of bartholin (2) Aka: Major vestibular glands Secrete mucoid material at arousal May harbor N. gonorrhea or other bacteria infection bartholin gland abscess Obstruction can cause accumulation of secretions Skene Ducts (2) Fossa Navicularis posterior portion of the vestibule between the fourchette and vaginal opening Not seen in multiparous Vestibular Bulbs Anlage of corpus spongiosum of the penis Partially covered by Ischiocavernosus muscles Constrictor vaginae muscle Rupture vulvar hematoma Labia Minora, Labia Majora & Clitoris (+) network of free nerve endings tactile discs Genital corpuscles Free nerve endings
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From supravaginal portion of the cervix, and inserts into the fascia over the sacrum Strong lig of the uterus NOTE: RTO front to back Round Tube (fallopian tube) Ovaries Blood Supply Uterine artery Supravaginal portion cannot be assessed Portio vaginalis measures 2 cm what is seen during speculum felt during pelvic exam th Ultrasound of length of cervix 24 28 week of gestation 25 cm or less = preterm labor Ciliated columnar epithelium (+) cervical glands Nabothian Cyst: retention cysts formed when the ducts of the cervical glands are occluded External Cervical OS Non-parous (< 20 weeks gestation) round Parous not round Isthmus Between the internal cervical os and endometrial cavity Forms lower uterine segment during pregnancy Measures .5-1 cm in non-pregnant Transformed into the lower uterine segment during pregnancy 5 cm
Branch of internally iliac artery (from common iliac and aorta) Cervicovaginal branch Ovarian branch Tubal branch Fundal branch Ovarian artery Branches to ovarian branch Venous Drainage Arcuate uterine internal iliac common iliac Right ovarian IVC Lymphatic Drainage Myometrium lymphatic plexus Cervix hypogastric plexus Body internal iliac nodes, periaortic nodes Innervation Uterus, bladder, upper vagina Sympathetic uterovaginal plexus of frankenhauser blocked by continuous lumbar epidural anesthesia this doesnt block motor pathways can still contract Sensory T11- 12 Cervix, upper birth canal Sensory S2-S4 Lower Birth Canal Pudendal nerves can be blocked by OB/GYN
Uterus size of the corpus relative to the cervix Premenarchal Nullipara Multipara Corpus long as Corpus = cervix Cervix 1/3 as long cervix as corpus
Pregnancy-induced uterine changes o Uterine growth secondary to muscle hypertrophy o Volume ~ 5 L o Fundus becomes more domeshaped o Round ligaments appear to insert between middle and upper 1/3 of uterus o Fallopian tube elongate o Ovaries unchanged Fallopian Tubes Aka oviducts Divided into Interstitial Isthmus (narrowest Ampulla widest Most common site of ectopic pregnancy infundibulum Ovaries Ovarian fossa of waldeyer Slight depression between the external and internal iliac vessels w Utero-ovarian ligament ___ Infundibulopelvic suspensory ligaments ___ Parts only 10% needed for ovulation Cortex Location of the ova and graafian follicles Tunica albuginea outermost portion Medulla Continuous with the mesovarium and suspensory ligament Consists of large arteries and veins
Parts of the Uterus Cornua Fundus Cervix
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CHAPTER 3 IMPLANTATION, EMBRYOGENESIS & PLACENTAL DEVELOPMENT
Ovarian & Endometrial Cycle

3 LEVELS OF HORMONES Hypothalamus Pituitary Ovaries
Downregulation and dec in GnRH Rc
2 CYCLES Ovarian Cycle Endometrial Cycle
NEUROENDOCRINOLOGY Anatomy Reproductive Hormones Feedback Mechanisms
ANATOMY Hypothalamus Neural structure at the base of the brain rd Below the 3 ventricle and above the optic chiasm 3 Zones Periventricular Medial Lateral Connections to: Pituitary Amygdala Hippocampus Thalamus Pons Feedback Mechanism Long- from circulating Hormones Short- from pituitary hormones Ultra short- from hypothalamic secretion Secretions GnRH CRH GHRH TRH Posterior Pituitary is a direct extension of the hypothalamus connected by the infundibulum Pituitary 3 Lobes Anterior- Adenohypophysis Intermediate Posterior- Neurohypophysis Direct physical extension of the hypothalamus Anterior Lobe Major blood supply- portal vessels, which carry the hypothalamic secretions to the anterior lobe Posterior Lobe Supplied by the superior, middle and inferior hypophyseal arteries
Early follicular phase Frequent small amplitude pulses Late follicular phase frequency, amplitude Luteal phase frequency GnRH Agonist Leads to persistent activation of GnRH Initial release of gonadotrophins stored in pituitary Later, suppression of gonadotrophin secretion, and eventually sex steroids GnRH Antagonist Has no intrinsic activity but competes with GnRH for the same Rc Competitive blockage of Rc Endogenous GnRH cannot bind Immediately fall in gonadotropin secretion, and eventually sex steroids **Recent evidence : down regulation of the Rc Endorphins and GnRH Endogenous opioids produced in the hypothalamus regulation of temperature, appetite, mood, behavior Inhibits GnRH release Ovarian hormones can stimulate production of endorphins inhibition of GnRH Peak levels in luteal phase and lowest during menses may explain dysphoria in premenstrual phase
HORMONES Hypothalamus GnRH Decepeptide produced by the cell bodies in Arcuate nucleus Axons terminate on the portal vessels secretions delivered to the anterior pituitary Unique because: Simultaneously regulates secretion of two hormones FSH and LH MUST BE secreted in pulsatile manner to be effective Phases
Anterior Pituitary Secretions FSH LH
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TSH ACTH GH Prolactin Gonadotrophins FSH and LH are glycoproteins produced by the gonadotrophs in the anterior pituitary Same subunits with TSH and HCG Different subunits Rc specificity Rate-regulating step in biosynthesis FSH Granulosa cells- exclusive site of FSH Rc Effects of FSH FSH Rc Induces aromatase enzyme androstenedione to estradiol Expansion of antrum of growing follicles Initiate the expression of LH Rc on the theca cells LH Effects of LH Follicular phase: stimulates theca cells to produce androgen Mid-cycle estrogen has a positive feedback on the hypothalamus LH surge Initiates ovulation Conversion of follicle into corpus luteum Luteal Phase secretion of estrogen and progesterone by the corpus luteum Prolactin Polypeptide responsible for production of milk Under tonic inhibition by dopamine Increased levels: amenorrhea, galactorrhea Stimulates release: Breast Manipulation Drugs Stress Exercise Posterior Pituitary Neurohypophysis- composed of neural tissue and is a direct extension of the hypothalamus Axons in posterior pituitary have cell bodies in supraoptic paraventricular nuclei in the hypothalamus Oxytocin Nanopeptide produced by paraventricular nucleus Actions: Uterine muscle contraction Myoepithelial contractions of the breast lactiferous duct milk down reflex Stimulus to release : Suckling Nipple stimulation Olfactory, auditory, visual clues reflex in nursing animals
MENSTRUAL CYCLE Definition: st st Starts on the 1 day of menses up to the 1 day of the next menstruation Average Duration: 28 days Range: 21-35 days Menstruation Duration: 2-6 days of flow Average Blood loss: 20-60 ml
OVARIAN FOLLICULAR DEVELOPMENT Oocytes and Follicles Fetal Life: Primordial follicles- single primary oocyte lined by a few squamous cells Seen in the ovarian cortex At 20 weeks AOG # of oocytes peaks at 6-7 million At birth: 2 million oocytes At puberty: 400,000 oocytes Ovulation opportunity: 400 The remaining oocytes undergo atresia 1000/month until age 35 >35 y/o atresia accelerates OVARIAN CYCLE - FOLLICULAR PHASE Definition: orderly development of a single dominant follicle Average length: 10-14 days
FEMALE REPRODUCTIVE ORGANS INTRODUCTION The female reproductive system is geared towards two goals- to achieve a pregnancy and to maintain it Very narrow window for Fertilization: day of ovulation and two days before it Implantation: approx. cycle days 20-24
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Follicular development stages: Gonadotrophin- independent recruitment of primordial follicles growth to antral phase Transforming growth factors 9 and 10 produced by the oocytes Proliferation and differentiation of granulose cells FSH- dependent growth Recruitment of surrounding stromal cells theca cells Cohort of antral follicles continue to grow AKA selection window of the ovarian cycle OVARIAN CYCLE RECRUITEMENT OF THE GRAFFIAN FOLLICLE Granulosa cells produce inhibin More estradiol produced by granulose cells (-) feedback on pituitary Decrease FSH release Follicle with the most amount of estradiol produced mature to become the Graafian follicle Other follicles become atretic Rupture Unlike their sisters in the animal kingdom, human females dont openly advertise their ovulation. But even without a human version of the baboons bright pink behind, signs of fertility sneak out Subconsciously, women dress more provocatively and men find them prettier when its primetime for conception. Changes in body odor, waist to hip ratio and facial features, subtle shifts in their behavior- how they talk and move. OVARIAN CYCLE - LUTEAL PHASE Definition: time from ovulation to the onset of menses Average: 14 days More constant length After the ovulation, the remnants of the Graafian follicle undergo luteinization Corpus Luteum Basement membrane between the granulose cells and theca cells break down Neovascularization in granulose cells Hypertrophy of cells and increased capacity to produce hormones Hormone secretion is different from follicular phase progesterone secretion by the granulose cells Access to LDL and HDL cholesterol from circulation precursors of progesterone 25-50 mg/day in midluteal phase Estrogen decrease right after ovulation, followed by a secondary rise in midluteal phase, and a decrease toward the end of the luteal phase
OVARIAN CYCLE FOLLICULAR PHASE After the appearance of LH Rc, granulose cells start producing progesterone (+) feedback on pituitary Release more LH 34-36 hrs LH surge 10-24 hrs
ENDOMETRIAL CYCLE Cyclic histologic changes in the endometrium which proceed in an orderly manner in response to ovarian steroids Phases: Proliferative Phase Secretory Phase Layers of the endometrium Stratum functionalis Stratum compactum Stratum spongiosum Stratum Basalis Endomentrial CycleProliferative Phase st 1 day of menstrual bleeding = day 1 of the cycle 2/3 of the functional endometrium is shed off after menstruation After menstruation, production of estradiol is the MOST IMPORTANT factor in the recovery of the endometrium (EM) th By the 5 day, the epithelial surface has been restored, and revascularization has begun Early Proliferative Phase- EM is thin (2mm) Glands are narrow tubular and straight Mitotic figures are seen in glandular epithelium persist until day 16-17 Stroma is dense and compact Later proliferative phase- EM thickens Glandular hyperplasia stromal edema and proteinaceous material Glands are widely separated near the surface, denser near the basement membrane Glandular epithelium becomes tall and pseudostratified Loose stroma Estrogen Action 17- estradiol -- most potent naturally occurring estrogen Secreted by the granulose cells of dominant follicle and granulose cells of the corpus luteum 2 receptors- ER and ER Product of separate genes
Ovulation OVULATION Estrogen 34-36 hrs LH surge 10-13 hrs Resumption of meiosis Release of 1 polar body Stigma develops Follicular rupture LH Progesterone and prostaglandins Activation of proteases Weakening of follicular basement membrane
st
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Exhibit distinct tissue differences Initiate synthesis of specific proteins, including estrogen Rc and progesterone Rc Stimulate nitric oxide production in endothelial cells Causes replication of the endometrium during the proliferative phase Endometrial Cycle- Secretory Phase Phase is very stable 14 days EM response to rising levels of progesterone Highly predictable Precise dating possible Glands are very numerous, elongates to stretch the length of the endometrium and have the characteristic spiral or corkscrew appearance Day 14- ovulation occurs Day 16-17- glycogen accumulates in the basal portion of the glandular epithelium subnuclear vacuoles and pseudostratification First sign of progesterone action indirect sign of ovulation Day 18- vacuoles move to the apical portion Day 19-20- secretion of glycoprotein and mucopolysaccharides starts Mitosis stops because progesterone antagonizes the mitotic effects of estrogen Day 21-24 stroma becomes edematous Day 22-25 stromal cells surrounding spiral arterioles enlarge, stromal mitosis Extensive coiling of glands Secretion found in lumen Day 23-28 predecidual cells surround spiral arterioles Postovulatory days 6-7 secretory activity is maximal and edometrium isoptimally prepared for implantation Days 20-24 window of implantation microvilli and cilia on cell surfaces Pinopods preparation for blastocyst implantation Continuing growth and development of spiral arterioles Dating of the Endometrium Precise nature of the histologic changes that occur in the secretory endometrium in relation to the LH surge allows the assessment of the :normalcy of the endometrial development Endometrial biopsy Any discrepancy by more that 2 days is called luteal phase defect Linked to failure of implantation and early pregnancy Menstruation In the absence of implantation, glandular secretion cease and irregular breakdown of deciduas functionalis occurs Corpus luteum dies drop in progesterone Inflammatory response Premenstrual Phase endometrium Infiltration of neutrophils 1-2 days prior to menstruation Stromal and epithelial cells produce IL-8 chemotactic for neutrophils Monocyte chemotactic protein-1 (MCP-1) chemoattractant to monocytes Infiltration of leukocytes KEY to the initiation of extracellular matrix breakdown of the functional layer Leukocytes secretes metalloproteinase Vessel coiling becomes severe increased resistance hypoxia of the endometrium endometrial ischemia and tissue degeneration Period of vasoconstriction precedes menstruation most constant event Also limits blood loss during menstruation Prostaglandins and Menstruation Produced throughout the menstrual cycle, but is highest during menses PGF2 vasoconstrictor produced by endometrium Abundant menstrual blood Endothelin-1 vasoconstrictor produced by vascular endothelial cells Menstrual Blood Bothe arterial and venous in origin, arterial > venous Bleeding starts with rupture of a coiled artery or leakage through a spinal artery hematoma forms endometrium distends and ruptures fissures develop in the functionalis layer blood and fragment of tissue detach Hemorrhage stops Arterioles are constricted Under the influence of estrogen, glands form flanges or collars which spread fusion of these edges Interval Between Menses Interval: 28 +/- 7 days Range: 21-35 days Duration: 2-6 days of flow Average Blood loss: 20-60 ml Decidua Specialized, highly modified endometrium of pregnancy Decidualization- transformation of the secretory endometrium to decidua, is dependent on estrogen and progesterone action Cells enlarge and become pale staining and filled with glycogen. This provides nourishment for the embryo until the placenta is vascularized 3 Part Based on anatomical location Decidua Basalis- directly under blastocyst implantation Decidua Capsularis- overlying the blastocyst Decidua Parietalis- remainder of the uterus Decidua vera- when capsularis and parietalis are joined together Early pregnancy- space between capsularis and parietalis By 14-16 weeks- expanding sacs has enlarged enough to fill the uterine cavity Early pregnancy- decidua thickens to 5-10mm As the fetus grows, deciduas thins because of the pressure of the expanding uterine contents 3 Layers Zona compacta Zona spongiosa
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Implantation & Formation of Fetal membrane
ENDOMETRIUM-DECIDUA: Anatomical site of blastocyst apposition, implantation, & placental development MENSTRUAL CYCLE days 20-24 Narrow window of endometrial receptivity to blastocyst implantation Menstrual Cycle: ave 28 days (25-32) Follicular or Preovulatory Ovarian Phase 2 million oocytes at birth 400,000 follicles present at onset of puberty 1000 follicles depleted per month until age 35 then rate accelerates Only 400 follicles ovulates 99.9% of follicles undergo atresia via APOPTOSIS Follicular development Gonadotropin-independent recruitment of primordial follicle to antral stage Controlled by growth factors from TGF family produced by the oocytes Growth differentiation factor 9 (GDF9) Bone morphogenic protein 15 (BMP15) FUNCTION: Regulate proliferation & differentiation of granulosa cells as primary follicles grow together w/ in progesterone & prostaglandin after LH surge: Stabilize & expand the hyaluronan-rich ECM of cumulus oocyte complex EXPANSION FSH Not required at early stages of follicular development during EARLY luteal phase Required during late luteal phasefor further development of large antral follicles known as a COHORT FSH rise lead to follicle development called SELECTION WINDOW where only the follicles that progress through this stage has the capacity to produce ESTROGEN (95%) Induces cytochrome P450 aromatase Induces expansion of the antrum of growing follicles Granulosa Cells: exclusive site for FSH receptor expression LH Primary luteotrophic factor Granulosa Lutein Cells Increased capacity to produce progesterone d/t Increased access to considerably more steroidogenic precursors through bloodborne LDL-derived cholesterol Increase in steriodogenic acute regulatory proteins 17-estradiol Most biologically potent, naturally occurring estrogen Secreted by granulosa cells of dominant follicle & corpus luteum Upregulates estrogen & progesterone receptors Stimulate NO production Follicular Phase production of Estradiol is the most important factor in endometrial recovery following menstruation Epithelial Cell Growth during endometrial bleeding is regulated by: EGF
TGF Stromal Cell Proliferation is regulated by: Paracrine & autocrine action of estrogen local levels of FGF9 Glandular Lining Epithelium Early Proliferative phase: Simple Columnar Late Proliferative Phase: Pseudostratified Columnar w/ microvilli & cilia
ENDOMETRIAL DATING Early Secretory phase: based on GLANDULAR epithelium histology Mid to Late Secretory Phase: based on changes of the endometrial STROMA EARLY SECRETORY PHASE Day 17 of endometrial cycle: Glycogen accumulates in the basal portion of glandular epithelium, creating subnuclear vacoules & pseudostratification st 1 sign of ovulation HISTOLOGICALLY Result of direct progesterone action Day 18 of Endometrial Cycle Vacoules move to the apical portion of the secretory nonciliated cells Day 19 of Endometrial Cycle Cells begin to secrete glycoprotein & mucopolysaccharide contents into lumen Glandular cell mitosis ceases w/ secretory activity d/t rising progesterone levels Estradiol is converted to estrone by 17HSD type2 MID to LATE SECRETORY PHASE Day 21 to 24 of endometrial cycle: Stroma becomes edematous Mark the so called WINDOW OF IMPLANTATION (day 20-24) Epithelial cell surface PINOPODES are important in preparation for blastocyst implantation Changes in surface glycocalyx to allow acceptance of blastocyst Day 22 to 25 of Endometrial Cycle Stromal cells around spiral arteries enlarges Stromal mitosis apparent IMPORTANT FEATURE OF SECRETORY PHASE: striking changes associated w/ predecidual transformation of the upper 2/3rds of the functionalis layer Glands exhibit extensive coiling & luminal secretion become visible Day 23 to 28 of Endometrial Cycle Pre-decidual cells surround spiral arteries LATE LUTEAL or PREMENSTRUAL PHASE HISTOLOGICAL CHARACTERISTIC Stromal infiltration of NEUTROPHILS giving a proinflammatory appearance Appear 1-2 days prior to onset of menses Chemotactic activator: IL-8 MENSTRUATION LEUKOCYTE INFILTRATION KEY to ECM breakdown of the functionalis layer Secrete Matrix metalloproteinase (MMP) STASIS is the primary cause of emndometrial ischmia & tissue degeneration PERIOD OF VASOCONTRICTION Precedes menstruation & is the MOST STRIKING & CONSTANT event observed Dysmennorhea: Mediated by PGF2
Reference: WILLIAMS OBSTETRICS 23rd Edition
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DECIDUA Specialized Highly modified A function of hemochorial placentation Decidualization Dependent on: Estrogen Progesterone Factors secreted by Blastocyst Implantation Decidua of Pregnancy Structure based on anatomical location: Decidua Basalis Where blastocyst implants Has blood vessels Decidua Capsularis Facing the uterine cavity Devoid of blood vessels Decidua Parietalis Area not implanted by blastocyst Decidua Vera Fusion of decidua parietalis & capsularis Uterine cavity obliterated 14 16 weeks AOG Layers of the Decidua Parietalis & Basalis Zona Compacta Zona Spongiosa Large distended glands with hyperplasia minimal stroma Becoming cuboidal to flat in later pregnancy Zona Basalis Spongy zone is mainly arteries & veins Invaded by interstitial trophoblast & giant cells Decidua Reaction Commences mid-luteal phase Completed with Blastocyst Implantation Endometrial Stromal Cells Enlarge, polygonal Round & vesicular nuclei Clear & basophilic cytoplasm Pericellular membrane Pericellular Membrane provides Attachment for the Trophoblast Protection against proteases Blood Supply: Decidua Parietalis Spiral arteries w/c is responsive to vasoactive agents Decidua Capsularis lost as the fetus grows Decidua Basalis Spiral arteries invaded by cytothrophoblast Decidual Histology True Decidual Cells is differentiated from: Endometrial Stroma Maternal Bone Marrow Derived Cells Endometrial large granular lymphocytes (decidual NK cells) Nitabuchs Layer/ Fibrinoid Degeneration Cases of Placenta Accreta when layer is absent Rohr Stria found at the bottom of the intervillous space & surrounding the anchoring villi FERTILIZATION & IMPLANTATION Blastocyst Stage of release from the zona pellucida Due to proteases from the secretory endometrium Blastocyst directly influence the receptivity of the endometrium Receptivity of the Endometrium Cytokines from the Blastocyst Estrogen Progesterone Endometrial Response Leukemia Inhibiting Factor Colony Stimulating Factor Effect: increase Protease secretion by Trophoblast to degrade the extracellular matrix
IMPLANTATION Occurs within 6 7 days post fertilization Must be on Days 20 24 of the endometrial ovarian cycle If it does not occur within this period: FAILURE of IMPLANTATION Placenta Previa or Ectopic Pregnancy in the Cervical Wall st Apposition is the 1 step of implantation
BIOLOGY OF THE TROPHOBLAST Trophoblast Differentiation th 8 day Post Fertilization Trophoblast differentiates into: Primitive Syncytiotrophoblast Multi-nucleated No individual cells Lacks the ability for DNA synthesis Primitive mononuclear Cytotrophoblast Germinal cells of the syncytium Well-demarcated cell border Can undergo DNA synthesis Villous Trophoblast Gives rise to the chorionic villi Function: Transport of oxygen & nutrients Extravillous Trophoblast Migrates to the decidua & myometrium Gives rise to the primary villous stalk Penetrates the maternal vasculature Interstitial trophoblast
PROLACTIN PRODUCTION Produced by the same gene in the pituitary Identical amino acid sequence Different promoter to initiate transcription Role of Prolactin Maintenance of Amniotic Fluid volume Regulate immune function in the decidua Regulate angiogenesis
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Penetrates the maternal decidua & myometrium Surrounds the maternal spiral arteries Acts in an autocrine manner Promotes invasion into the endometrium Decidual Cells Insulin like growth factor binding protein type 4 Blocks the autocrine loop HENCE: controlled invasiveness Secured by Fetal Fibronectin Oncofetal Fibronectin or Fetal-Specific Fibronectin A Trophoblastic Glue
Endovascular trophoblast Penetrates the lumen of the spiral arteries Trophoblast Invasion th 10 day the blastocyst is totally encased within the decidua Similar invasion characteristic of metastatic cancer cells CHORION Trophoblast with an underlying mesenchyme VILLI Primary Villi Secondary Villi Tertiary Villi PLACENTAL ORGANIZATION
DECIDUAL SPIRAL ARTERY INVASION Carried out by two populations of Extravillous Trophoblast: Interstitial Trophoblast Aggregates around the maternal spiral arteries Prepares the arteries to facilitate invasion Endovascular Trophoblast Enters the lumen of the spiral arteries Initially forming cellular plugs Destroys the endothelium Fibrinoid material replaces muscle and connective tissue Does not involve the Decidua Parietalis Decidual Veins are not invaded Stages of Uteroplacental Vessel Development st 1 Stage Before 12 weeks AOG Invasion & Modification of Spiral Arteries nd 2 Stage Between 12 16 weeks Invasion of intramyometrial parts of the spiral arteries Producing low-resistance vessels
HEMOCHORIAL PLACENTATION Hemo: maternal Blood bathing the Syncytiotrophoblast Chorio: Chorion Placenta
LANGHAN CELLS Inner layer of cytotrophoblast in a chorionic villi ANCHORING VILLI Proliferation of trophoblast at the tip that is anchored to the decidua
CHORIONIC PLATE Formed by 8 10 weeks When amnion & mesenchyme of chorion fuse together Hemodichorial Hemomonochorial
ESTABLISHMENT OF MATERNAL BLOOD FLOW Occurs approximately 4 weeks post fertilization
VILLUS BRANCHING Some become anchoring villi Majority would arborize and end freely in the intervillous space Each truncal villi and ramification is one lobule/ cotyledon Each lobule has one artery and vein
PLACENTAL DEVELOPMENT DEVELOPMENT OF THE CHORION & DECIDUA Blastocyst Outer pole expands towards the endometrial cavity Forms the chorion leave Due to the degeneration of the villi in contact with the decidua capsularis More translucent than the amnion Composed of cytotrophoblast and mesenchyme Inner pole forms the placenta Composed of the villous trophoblast & anchoring cytotrophoblast Chorionic villi proliferate to form the chorionic frondosum Amniochorion Formed by the union of the amnion and chorion Site of molecular transfer & metabolic activity Paracrine Arm of the Fetal-Maternal Communication System
PLACENTAL GROWTH & MATURATION PLACENTAL GROWTH 17 week AOG placenta & fetal weights are approximately equal At Term, placenta is 1/6 of the fetal weight
th
PLACENTAL DIMENSIONS Diamter: 185 mm Thickness: 23 mm Volume: 497 mL Weight: 508 g
TROPHOBLAST INVASION Due to its ability to secrete proteolytic enzymes to digest the extracellular matrix And activate proteinases already present in the endometrium st Ability to invade in the 1 trimester and limited Invasiveness in the last trimester is controlled by Autocrine & Paracrine Trophoblastic Endometrial Factors Trophoblast Insulin like growth Factor
PLACENTAL MATURATION Stroma of the Villi Abundant and loose intracellular matrix early in gestation Later becomes dense and cells more spindly and closely packed Infiltration of Hofbauer cells Fetal Macrophages
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Increase in number and maturation as pregnancy progress Capable of paracrine regulation of Trophoblast Function Histological Changes that provides an increased efficiency of transport & exchange Decrease in thickness of the syncytium Decrease Stroma Increase Vascularity Fibroblast-like mesenchymal cells Acellular zona spongiosa Development Amniogenic cells precursor of amnionic epithelium Growth of the amnion eventually engulfs the embryo and prolapses into the cavity st End of the 1 trimester apposition of the mesoblast of the chorion and amnion Epithelial Cells Major site of transfer between AF and amnion Metabolically Active Inhibits metalloprotinase-1 synthesis Produce PGE2 & Fetal Fibronectin Site of Prostaglandin production Synthesis of vasoactive peptides
FETAL & MATERNAL BLOOD CIRCULATION IN MATURE PLACENTA FETAL CIRCULATION Deoxygenated Blood flows through two umbilical arteries Umbilical vessels branch repeatedly beneath the amnion and diving villi Blood with a higher O2 content passes thru the umbilical vein Placental Surface / Chorionic vessels Umbilical vessels along the fetal surface of the chorionic plate Responsive to vasoactive substances Arteries always cross over the veins Truncal Arteries Perforating branches of the surface arteries Each supply one cotyledon Decrease amount of smooth muscle but has increase in caliber
MATERNAL CIRCULATION Physiological Maternal-Placental Circulation Maternal blood thru the basal plate and driven high up to the chorionic plate Blood flows back down as it baths the microvillous surface Maternal blood drains back to the venous orifices
MATERNAL=PLACENTAL CIRCULATION Factors Regulating Blood Flow Arterial Blood Pressure Intrauterine Pressure Pattern of Uterine Contractions Factors acting on the arterial wall
IMMUNOLOGICAL CONSIDERATIONS The acceptance and survival of the conceptus in the maternal uterus must be attributed to: Immunological peculiarity of the Trophoblast
IMMUNOGENICITY OF THE TROPHOBLAST Major Histocompatibility complex (MHC) class I and II antigens are absent from villous trophoblast Making it appear immunologically Inert But invasive cytotrophoblast express MHC class I molecules Trophoblast HLA (MHC) Class I Expression normal implantation is dependent on controlled trophoblastic invasion of maternal endometriumdecidua and spiral arteries Human Leukocyte Antigens Express by the Trophoblasts Classical HLA C Non Classical HLA E Non Classical HLA G
AMNION Provides almost all of the tensile strength of the fetal membranes Structure Single layer of epithelial cells-ectoderm derived Basement membrane Acellular Compact Layer composed of interstitial collagen
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Placental Hormones
HORMONES PRODUCED STEROID HORMONES Estrogen Progesterone Aldosterone Deoxycorticosterone Cortisol PROTEIN HORMONES hPL hCG ACTH hGH-V parathyroid hormone-related peptide calcitonin relaxin inhibins activins atrial natriuretic peptide HYPOTHALAMIC-LIKE RELEASING AND INHIBITING HORMONES TRH CRH Somatostatin GHRH GnRH HUMAN CHORIONIC GONADOTROPIN (HCG) Pregnancy hormone Biological activity similar to luteinizing hormone Act via the plasma membrane LH-hCG receptor Produced by the syncytiotrophoblasts B-hCG is also produced in the fetal kidney Also secreted by trophoblastic neoplasm: hCG also use as a tumor marker Found in very small amounts in tissues of men and nonpregnant women Detection in blood and urine is almost always indicative of pregnancy < 8 wks AOG: cytotrophoblast and syncytiotrophoblasts release hCG > 8 wks AOG: only syncytiotrophoblast secretes hCG Chemical characteristics Is a glycoprotein Highest carbohydrate content of any human hormone (30%) Plasma half-life of 36 hours Composed of alpha (92 amino acids) and beta (145 amino acids) subunits Alpha subunit is structurally identical with LH, FSH, and TSH Beta subunit is structurally related to LH Biosynthesis Single gene located at chromosome 6 encodes the alpha subunit of hCG, LH, FSH and TSH Of the 7 genes, 6 genes code for beta-hCG and one for beta-LH Both subunits are synthesized and cleaved by endopeptidases hCG is assembled and rapidly released by exocytosis of secretory granules. Site of hCG synthesis Before 5 wk AOG (early part of pregnancy), hCG is expressed in both syncytiotrophoblast and cytotrophoblast When maternal serum levels peak: 8 wk AOG ( latter part of pregnancy), hCG is almost exclusively produced solely by syncytiotrophoblasts hCG mRNAs for both alpha and beta subunits are greater than at term pregnancy can be use as a screening procedure to identify abnormal foetuses some fetuses have chromosomal abnormalities such as trisomies 13,18, and 21 hCG is secreted by cytotrophoblast and syncytiotrophoblast regardless of age of gestation Molecular forms of hCG in plasma and urine Result from enzymatic degradation, modifications during molecular synthesis and processing Circulating free beta subunit levels are low to undetectable throughout pregnancy Free alpha subunits increase gradually and steadily until they plateau at 36 weeks Complete beta hCG molecule is maximal at 8 to 10 weeks. Concentrations of hCG in serum and urine Intact hCG is detectable in plasma of pregnant women 7 to 9 days after the midcycle surge of LH that preceded ovulation hCG enters maternal blood at the time of blastocyst implantation Evidence of hCG: level doubles within 48 to 72 hours peak maternal plasma levels reach about 100 000 th th mIU/ml between 60 to 80 days of menses (2 to 3 months of LMP) begins to decline at 10 to 12 weeks and undetectable in the serum by 16 wks AOG hCG appearance in fetal blood is similar to its mother (about 3% of maternal plasma) principal urinary form is the terminal degradation hCG product: beta-core fragment The beta-subunit antibody used in most pregnancy test reacts with both intact hCG (major form in the plasma) and with fragments of hCG (major form found in urine.) Significance of abnormally high or low hCG levels higher maternal plasma hCG levels Multifetal pregnancy: bigger placenta compared to normal pregnancy Erythroblastosis fetalis Fetal haemolytic anemia Gestational trophoblastic disease: Hydatidiform mole Choriocarcinoma Midtrimester in women carrying a fetus with Down Syndrome (trisomy 21) 3 biochemical markers for Down Syndrome: PAPP protein estradiol/estrogen concentration serum beta-HCG nd There are soft makers in UTZ in 2 trimester that can detect Down Syndrome. OTHER causes: SYPHILLIS Big placenta d/t diabetes mellitus Lower hCG plasma levels Early pregnancy wastage (spontaneous abortion) Ectopic pregnancy Metabolic clearance of hCG Renal clearance of hCG accounts for 30 percent of its metabolic clearance. The remainder is likely cleared by metabolism in the liver. Clearances of beta- and alpha-subunit are about 10fold and 30-fold, respectively, greater than that of intact hCG. By contrast, renal clearance of these subunits is considerably lower than that of dimeric hCG Biological functions of hCG Both hCG subunits are required for binding to the LHhCG receptor in the corpus luteum (located in the ovary) and the fetal testis
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Most important function is the rescue and maintenance of function of the corpus luteum (progesterone production) to maintain the early pregnancy then placenta will take place to maintain pregnancy at the most part Acts as an LH surrogate to stimulate replication of Leydig cells and testosterone synthesis to promote male sexual differentiation. Also stimulates maternal thyroid gland: in the case of H-mole: maternal is associated with hyperthyroidism there is a concomitant increase of T3 and T4 Women who have GTD sometimes develop hyperthyroidism Promotes relaxin secretion by the corpus luteum: to promote uterine vascular vasodilatation and myometrial muscle relaxation Two of relaxin genes (h2 and H3) are transcribed in the corpus luteum Other tissues, decidua, placenta and membranes express H1 and H2 Along with progesterone, acts on myometrium to promote relaxation and quiescence in early pregnancy, so you will not have an abortion Relaxin expression has been demonstrated in human corpus luteum, decidua, and placenta. This peptide is synthesized as a single 105 amino-acid preprorelaxin molecule that is cleaved to A and B molecules. Relaxin is structurally similar to insulin and insulin-like growth factor. Two of the three relaxin genesH2 and H3are transcribed in the corpus luteum, others such as decidua, placenta, and membranes, express H1 and H2.
HUMAN PLACENTAL LACTOGEN (HPL) Prolactin-like activity (secreted by the anterior pituitary) A potent lactogen and growth hormone like bioactivity Immunochemical resemblance to human growth hormone Concentrated in syncytiotrophoblasts nd rd Detected as early as 2 or 3 week of fertilization Demonstrated in cytotrophoblast before 6 weeks Chemical characteristics Single nonglycosylated polypeptide chain 191 amino acid residues Structurally similar to human Prolactin (hPRL) Gene structure and expression hPL gene located at chromosome 17 hPL2 and hPL3 encode hPL Prolactin gene is located at chromosome 6 The production rate of hPL near term approximately 1 g/day greatest of any known hormone in humans Asses after 6 wks postpartum for gestational diabetes: concentration during pregnancy and post-partum Serum concentration Detected in placenta within 5 to 10 days after conception Detected in maternal serum as early as 3 wks Maternal plasma concentration are linked to placental mass and rises steadily until 34 to 36 wks Concentration levels reach 5 to 15 ug/ml Half life is between 10 and 30 minutes Regulation of hPL biosynthesis Secretion is proportional to placental mass Prolonged maternal starvation in the first half of pregnancy leads to an increase in hPL plasma concentration hPL synthesis is stimulated by insulin and insulin like growth factor I and inhibited by PGE2 and PGE2 alpha Metabolic actions Maternal lipolysis with increased levels of circulating free fatty acids hPL inhibits leptin secretion by term trophoblast anti-insulin or diabetogenic action that leads to increased maternal insulin levels potent angiogenic hormone that may play an important role in the formation of fetal vasculature
PARATHYROID HORMONE-RELATED PROTEIN (PTH-rP) Significantly elevated within maternal but no fetal circulation Found in myometrium, endometrium, corpus luteum and lactating mammary tissue Not produced in the thyroid gland of normal adults May activate trophoblast receptors to promote calcium transport for fetal bone growth and ossification GROWTH HORMONE VARIANT (hGH-V) Gene encoding hGH-V is located in the hGH-hPL gene cluster on chromosome 17 Also called placental growth hormone Synthesized in the syncytium. Present in maternal plasma by 21 to 26 weeks increase in concentration until approximately 36 weeks Secretion by trophoblast is inhibited by glucose in dose dependent manner Is a likely candidate to mediate insulin resistance of pregnancy Placenta expresses a growth hormone variant that is not expressed in the pituitary. The gene encoding hGH-V is located in the hGHhPL gene cluster on chromosome 17. Sometimes referred to as placental growth hormone 191 amino-acid protein that differs in 15 amino-acid positions from the sequence for hGH. Placental hGH-V presumably is synthesized in the syncytium, but its pattern of synthesis and secretion during gestation is not precisely known because antibodies against hGH-V cross-react with hGH. Present in maternal plasma by 21 to 26 weeks, increases in concentration until approximately 36 weeks, and remains relatively constant thereafter Correlation between the levels of hGH-V in maternal plasma and those of insulin-like growth factor-1. Secretion of hGH-V by trophoblasts in vitro is inhibited by glucose in a dose-dependent manner. Overexpression of hGH-V in mice causes severe insulin resistance, and thus it is a likely candidate to mediate insulin resistance of pregnancy CHORIONIC THYROTROPIN Produced by placenta No biological significance
OTHER PLACENTAL PROTEIN HORMONES CHORIONIC ADRENOCORTICOTROPIN physiologic role unclear secreted in both maternal and foetal circulation maternal ACTH is not transported to the fetus placental ACTH is not under feedback regulation by glucocorticoids placental CRH stimulates synthesis and release of chorionic ACTH CRH production is positively regulated by cortisol RELAXIN Demonstrated in human corpus luteum, decidua and placenta Structurally similar to insulin and IGF
OTHER PEPTIDE HORMONES LEPTIN Normally secreted by adipocytes Synthesised by both cytotrophoblast and syncytiotrophoblast. Fetal leptin levels are correlated positively with birth weight and likely play an important role in fetal development and growth. inhibits apoptosis and promotes trophoblastic proliferation normally secreted by adipocytes.
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Functions: anti-obesity hormone that decreases food intake through its hypothalamic receptor Regulates bone growth and immune function Leptin Synthesized by both cytotrophoblast and syncytiotrophoblast. Maternal serum levels are significantly higher than those in nonpregnant women. Fetal leptin levels are correlated positively with birthweight and likely play an important role in fetal development and growth. STEROID HORMONES PROGESTERONE < 8 wks AOG: produced by Corpus Luteum > 8 wks AOG: placenta assume progesterone secretion Normal production rate in pregnancy women in about 250 mg In Multifetal pregnancies it may exceed 600 mg/day Placental progesterone production Cholesterol is converted to pregnenolone within the mitochondria in a reaction catalyzed by cytochrome P450 cholesterol side chain cleavage enzyme It is then converted to progesterone in the endoplasmic reticulum by 3beta-hydroxysteroid dehydrogenase Released through the process of diffusion There is limited capacity for trophoblast cholesterol biosynthesis Placenta relies on exogenous cholesterol for progesterone formation As much as 90% of maternal cholesterol was found to be the principal precursor of progesterone biosynthesis Trophoblast uses LDL cholesterol for progesterone biosynthesis Estrogens relies principally on fetal adrenal precursor Precursor of progesterone is CHOLESTEROL Progesterone metabolism during pregnancy During pregnancy, there is an increase in plasma concentration of 5 alpha dihydroprogesterone Progesterone is also converted to potent mineralocorticoid deoxycorticosterone in pregnant women and in the fetus ESTROGEN Primary hormone during proliferative phase Placental estrogen production: Produce from the maternal and fetal glands Near term, normal pregnancy is in hyperestrogenic state that terminates abruptly after delivery First 2 to 4 weeks of pregnancy, rising hCG levels maintain production of estradiol in the maternal corpus luteum (hyperestrogenic state) th Decreases significantly at 7 week: Luteal-phase transition ESTRADIOL is the most potent estrogen in the system Placental estrogen biosynthesis Estradiol production within the corpus luteum of nonpregnant women as well as in early pregnancy continues to require interaction between the luteinized theca and granulosa cells Steroid 17 alpha-hydroxylase/17, 20 lyase (CYP17) is not expressed in human placenta conversion of C21 to C19 steroid is impossible C19 steroid is the obligatory precursor of estrogen Placenta has a high capacity to convert C19 to estrone and estradiol. Placenta expresses high levels of steroid sulfatase (STS, which converts the conjugated DHEA-S to DHEA DHEA is then acted upon by 3beta-hydroxysteroid dehydrogenase type 1 to produce androstenedione Cytochrome P450 aromatase then converts androstenedione to estrone which is then converted to 17 beta-hydroxysteroid dehydrogenase type 1 (17beta HSD1). Plasma C19-steroids as estrogen precursor It is found that women who had anencephalic fetuses has a very low estrogens level of about 10% Adrenal glands of anencephalic foetuses were found to be atrophic because of absent hypothalamicpituitary functions (this is occur in anencephalic fetus need folic acid and Vit B12) Fetal adrenal glands might provide substances used for placental estrogens formation DHEA-S is the principal precursor for placental estradiol synthesis Fetal adrenal glands are the most important source of placental estrogen
NEUROPEPTIDE Y Widely disturbed in the brain Also found in sympathetic neurons innervating the cardiovascular respiratory, GIT, and GUT systems Localized in the cytotrophoblast Causes CRH release INHIBIN Acts to inhibit pituitary FSH release Produced by human testis and by ovarian granulosa cells including corpus luteum and trophoblast Maternal serum levels peak at term Act in concert with the large amounts of sex steroids hormones to inhibit FSH secretion and thereby inhibit ovulation during pregnancy Act via GnRH to regulate placental hCG synthesis. ACTIVIN Expressed in the placental and amnion No detectable in fetal blood before labor but is present in umbilical cord blood after labor beings Levels declines rapidly after delivery
HYPOTHALAMIC-LIKE RELEASING HORMONES GONADOTROPIN-RELEASING HORMONE (GnRH) Secreted solely by cytotrophoblast Functions to regulate trophoblast and hCG production Placental derived GnRH is also the likely cause of elevated maternal GnRH level in pregnancy CORTICOTROPHIN RELEASING HORMONE (CRH) Has relatively low serum levels of 5 to 10 pmol/L rd Increase to about 100 pmol/L in the early 3 trimester and to almost 500 pmol/L abruptly during the last 5 to 6 weeks After labor begins, levels increase 2 to 3 fold Receptor present in placenta, adrenal gland, sympathetic ganglia, lymphocytes, GIT, pancreas, gonads and myometrium Increases trophoblast ACTH secretion supporting an autocrine-paracrine role Roles include induction of smooth muscle relaxation in vascular and myometrial tissue and immunosuppression (same function as relaxin hormone) Maybe involved with parturition initiation Glucocorticoids act in the hypothalamus to inhibit CRH release In the trophoblast, glucocorticoids stimulate CRH gene expression. Positive feedback loop in the placenta by which placental CRH stimulates placental ACTH to stimulate fetal and maternal adrenal glucocorticoid production with subsequent stimulation of placental CRH expression. GROWTH HORMONE RELEASING HORMONE (GHRH) Role is not clear Ghrelin is another regulator of hGH secretion Trophoblast ghrelin expression peaks at midpregnancy and is a potential regulator of hGH-V production or a paracrine regulator of differentiation
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Dose is 400 mg of folic acid to prevent neural tube defect. It is found that women who had anencephalic fetuses has a very low estrogen level of about 10% Adrenal glands of anencephalic fetuses were found to be atrophic because of absent hypothalamic-pituitary functions Fetal adrenal glands might provide substances used for placental estrogens formation DHEA-S is the principal precursor for placental estradiol synthesis HEMOCHORIOENDOTHELIAL PLACENTATION More than 90% of estradiol and estriol formed enters maternal plasma 85% or more of placental progesterone enters maternal plasma Steroids secreted from syncytiotrophoblast can enter maternal blood directly unlike when hormones enter blood Principal secretory products of fetal adrenal glands: Pregnenolone DHEA-S Steroidogenesis MINOR FRACTION: Progesterone & Pregnenolone produced by the placenta Cholesterol from de novo synthesis of acetate by the fetal adrenals MAJOR FRACTION Hydrolysis of circulating lipoproteins (LDL) from the fetal circulation Regulation of cholesterol levels in fetus Fetal plasma cholesterol Principal precursor for steroidogenesis Sources of fetal cholesterol Maternal transfer: 20% De novo synthesis by fetal liver: 80% Fetal plasma LDL is low because of rapid use by fetal adrenals for steroidogenesis
FETAL ADRENAL GLAND HORMONES Composed primarily of fetal zone which has a great capacity for steroid biosynthesis Daily steroid production at near term is 100 to 200 mg/day Fetal zone is lost in the first year of life
PLACENTAL ESTRIOL SYNTHESIS Estradiol is the primary placental estrogen secretory product at term Fetal hepatic 16 alpha-hydroxylated C19-steroids were converted to estriol by placental tissues Near term, the fetus is the source of 90% of placental estriol and estradiol precursor in human pregnancy Steroid levels indicate fetal well being FETAL ADRENAL STEROID PRECURSOR The precursor for fetal adrenal steroidogenesis is cholesterol. Plasma cholesterol is present in the form of VLDL, LDL and HDL. LDL was more effective Most fetal plasma cholesterol arises by novo synthesis in the fetal liver low levels of LDL in fetal plasma is explained by the rapid use for steroid synthesis Anencephalic fetuses have high levels of LDL in their umbilical cord plasma FETAL ADRENAL GLANDS Function Steroidogenic tissue Largest organ of the fetus Fetal Daily production: 100-200 mg/day Adults: 30-40 mg/day Morphology Fetal Zone: source of steroid precursors used by the placenta to produce estrogens Involutes immediately after birth Neocortex or Definitive Zone: outer zone that gives rise to the adult adrenal glomerulosa Transitional Zone: gives rise to the cortisol producing zona fasciculate Growth Last 5-6 wks AOG: very rapid increase in adrenal size Fetal adrenal glands at term are 25x larger than adults Early development: under trophic influence by fetal ACTH, pituitary PRL & growth factor from placenta Development Enzymatic Consideration Severe deficiency in microsomal enzyme 3hydroxy steroid dehydrogenase, 3HSD in adrenal fetal zone There is a very active steroid sulfotransferase activity in fetal adrenal glands
FETAL CONDITIONS THAT AFFECT ESTROGENS PRODUCTION Fetal Demise or Ligation of the Umbilical Cord Reduction in levels of urinary estrogens Fetal anencephaly: Dx by UTZ Production of estrogens can be increased by maternal administration of ACTH to stimulate the rate of secretion of DHEA-S by the maternal adrenal gland C-19 steroid precursor because of absence of adrenal cortex Fetal adrenal hypoplasia Miniature adult form (abnormal pituitary function) Cytomegalic form (nodular formation of eosinophilic cells in the fetal zone) Fetal-placental sulfatase deficiency a/w very low estrogens levels in otherwise normal pregnancies an X-linked disorder and all affected fetuses are males a/w delayed onset of labor and with development of ichthyosis in affected males later in life fetal-placental aromatase deficiency androgen metabolites of DHEA including androstenedione and some testosterone are secreted into the maternal or fetal circulation causing virilization of the mother and fetus delayed epiphyseal closure during puberty Trisomy 21-Down Syndrome nd 2 trimester maternal serum screening for abnormal levels of hCG and alpha-feto protein Low serum unconjugated estriol levels Inadequate formation of C19 steroids Reduced DHEA-S levels in both amnionic fluid and maternal serum Deficiency in fetal LDL cholesterol biosynthesis Restricted progesterone formation in corpus luteum & placenta Levels of estriol lower than normal Depressed Adrenal use of LDL d/t maternal hypertension & severe DM Fetal Erythroblastosis In some cases of severe fetal D-antigen isoimmunisation, estrogen levels in maternal plasma are elevated above normal due to increase placental mass Accumulation of fluid, hydramnios: ascites, pericardial effusion MATERNAL CONDITIONS THAT AFFECT PLACENTAL ESTROGEN PRODUCTION Glucocorticoid treatment Glucocorticoid inhibits ACTH: reduction in placental estrogens formation Maternal adrenal dysfunction
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Mothers with Addisons disease have decrease urinary estrogens levels Principally affects estrone and estradiol particularly in the latter part of pregnancy. Maternal ovarian androgen producing tumors Fetus is not virilised because androgen passing through the placenta is efficiently converted to estradiol Maternal renal disease Lower estriol levels in urine of pregnant women because of decreased renal clearance Hypertensive disorder & DM estrogen formation d/r uteroplacental blood flow Gestational trophoblastic disease Low estrogen d/t no fetal adrenal source of C-19 steroids
ESTRIOL ASSESS FETAL STATUS Measurement of urinary or plasma estriol has no clinical use in high-risk pregnancy management Part of triple screening of Downs Syndrome together w/ AFP and hCG
PLACENTAL PROGESTERONE > 6-7 wks AOG: produced by Placenta, very little from ovary < 6wks AOG: produced by Corpus Luteum (Ovary) th 7-10 wk AOG: will not reduce urinary levels of pregnanediole or estrogen even if corpus luteum is surgically removed or w/ bilateral oophorectomy > 8 wks AOG: produced entirely by Placenta Production Rates Biosynthesis by Syncytiotrophoblasts Production in: late, SINGLE, normal pregnancy: 250 mg/day Multiple fetus: >600 mg/day Maternal plasma LDL cholesterol: 90% precursor Synthesis & Fetal well being No relationship b/w fetal well-being & progesterone Biosynthesis may persist long after fetal death, same w/ hCG 85% placental progesterone enters maternal plasma Metabolic clearance the same w/ non-pregnant states
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CHAPTER 4
FETAL GROWTH & DEVELOPMENT PART 1

Dr. Lourdes R. Abella
DETERMINATION OF GESTATIONAL AGE Gestational Age or Menstrual Age st Time elapsed since the 1 day of the last menstrual period Time that actually precedes conception Starts: 2 weeks before ovulation & fertilization 3 weeks before implantation of the blastocyst th 37 to 42 weeks: TERM 3 wks before & 2 wks after CASE 1: Jelena 27 y.o. G1P0 consulted an OB-GYN for amenorrhea. Her LNMP was May 18, 2006. She claimed to have regular cycle with 25 days interval, 4 days duration, Her PNMP was April 20, 2006. A pregnancy test was positive. What is her gestational age? AOG: 7wks & 4 days st 1 trimester of pregnancy When is her EDC? February 25, 2007 Ovulation Age or Postconceptional Age Embryofetal development used by the embryologist Time in days or weeks from ovulation Reference used in discussing the earliest human development Estimated Date of Confinement (EDC) Naegeles Rule 280 days or 40 wks 9 & 1/3 calendar mos (+) 7days, (-) 3 mos, (+) 1 yr Example: LMP May 18,2011 05 18 2011 -3 +7 +1 02 25 2012 (EDC) Trimesters Traditional division of the gestational period into 3 calendar months Phases of Development 2 Weeks after Ovulation Ovulation Fertilization Formation of Free Blastocyst Implantation of Blastocyst Fetal Morphological Growth Normal fetal development is divided into 21 stages Based on specific external features & on somite development during early stages on embryonic (CRL) crown-rump length during later stage CRL or sitting height More accurate than standing height Length is more accurate criterion of gestational age than weight Stages of Earliest Human Development: Stage 1: 0-2 days Zygote Blastomere 2 cell stage 4 cell stage 8 cell stage Stage 2: 2-4 days Morula Solid ball 12-16 cells Blastocyst Fluid filled cavity w/ inner & outer cell layer Stage 3 & 4: 4-6 days Zona pellucida disappears Blastocyst attaches to endometrial epithelium Apposition Adhesion Invasion
Embryonic Period Starts at 3rd weeks & lasts till 8th wk When organogenesis takes place Baby termed as EMBRYO rd 3 wk after ovulation & fertilization Pregnancy tests (+): but most are (+) at day 35 or 5 wks Embryonic disc well defined Body stalk is differentiated Chorionic sac is ~ 1 cm diameter fetal blood vessels appear in chorionic villi 4th wk after ovulation & fertilization CVS formed true circulation established (B) w/in the embryo & the chorionic villi chorionic sac is 2-3 cm in diameter partitioning of the primitive heart arm & leg buds present amnion is beginning to form 6th wk after ovulation & fertilization embryo is 22-24 mm length head large compared to trunk heart is completely formed finger & toes are present w/ arms bend at elbows upper lip complete external ears form definitive elevations Fetal Period Starts 8 wks after fertilization & ovulation 10 wks AOG or after LMP Embryofetus is nearly 4 cm long Baby already termed as FETUS Where growth & maturation of structures already formed during embryonic period 12 wks AOG Uterus is just palpable above symphysis pubis CRL 6-7 cm Centers of ossification in most fetal bones Fingers & toes differentiated Skin & nails developed External genitalia starts to show definitive signs of male or female gender fetus begins to make spontaneous movement scattered rudiments of hair 16 wks AOG CRL 12 cm Weight: 110g Phenotypic sex identified by 14 wks 20 wks AOG MIDPOINT of pregnancy Weight: >300g Fetus moves about every minute & is active 10-30% of the time fetal skin less transparent w/ downy lanugo scalp hair has developed 24 wks AOG Weight: 630g skin wrinkled fat deposition begins head comparatively large eyebrows & eyelashes recognizable canalicular period of lung development if born: will attempt to breathe but most will die 28 wks AOG CRL 25 cm
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Weight 1100g Thin skin is red & covered w/ vernix caseosa (more vernix caseosa at birth likely preterm) pupillary membrane just disappeared from eye moves limbs & cries weakly with expert care, often will survive 32 wks AOG CRL ~28cm Weight ~ 1800g Skin red & wrinkled Usually survive intact 36 wks AOG CRL 32 cm Weight 2.5 Kg Deposition of subcutaneous fat Excellent chance of survival w/ proper care 40 wks AOG full term CRL 36 cm Weight: 3400 g fetus now fully developed characteristic feature of a newborn infant Basis of AOG: head diameter length of femur biparietal diameter WEIGHT of NEWBORN USA average: 3000-3600 g FACTORS: Race Parental economic status Size of parents Parity Altitude SGA: <2500g LGA: > 4000 g Rate of Fetal weight gain rd 3 Trimester: 30 gms/ day greatest transverse diameter of the fetus that has to pass through the pelvis (smallest diameter of pelvis is 10cm: biaxial diameter) 9.5 cm Bitemporal (BTD) 8 cm Suboccipitobregmatic (SOB) smallest plane of head circumference: 32 cm large fontanel to under occiput 9.5 cm Temporobregmatic (TBD) Molding: allows considerable shifting or sliding or each bone
FETAL HEAD Important because an essential feature of labor adaptation b/w the head & the maternal bony pelvis 2 frontal 2 parietal 2 temporal Upper portion of the occipital Wings of sphenoid Separated by sutures Frontal: b/w 2 frontal bones Sagittal: b/w 2 parietal bones Coronal: b/w the frontal & parietal bones Lamdoidal sutures Temporal sutures Fontanels Membranous spaces produced by 3 or more sutures Anterior or Greater Fontanel: BREGMA Posterior or Lesser Fontanel: LAMBDA Temporal Fontanel: CASSERIAN You Can tell if head is flexed or extended hence when you do your IE by palpating the fontanels Babys head is flexed if you feel the posterior fontanels Critical Diameters & circumferences of the newborn head Occipitofrontal (OFD): greatest plane of head circumference: 34.5 cm 11.5 cm Root of nose to occiput Occipitomental (OMD) 12.5 cm Chin to occiput Biparietal (BPD): important to take note
FETAL BRAIN Steady gestational age-related change in the appearance of the fetal brain possible to identify fetal age from its external appearance Neuronal proliferation & migration proceed along w/ gyral growth & maturation Myelination of the ventral roots of the cerebrospinal nerves & BS begins at 6 mos but major portion of the myelination occurs after birth FETAL MATERNAL COMMUNICATION SYSTEM PLACENTAL ARM Organ of transfer b/w mother & fetus Maternal-fetal interface where transfer of O2 & nutrients from the mother to fetus takes place No direct communication b/w fetal & maternal blood Bidirectional transfer Occasional breaks in the chorionic villi permit escape Chimerism: occurs in multifetal pregnancy
INTERVILLOUS SPACE (Maternal Blood)
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Maternal blood in the extravascular compartment is the primary biologic unit of maternal-fetal transfer Blood from the maternal spiral arteries Substances transported from the mother are transferred from the intervillous space to the syncytiotrophoblasts Chorionic villi & intervillous space function as the fetal lung, GIT, & kidney Intervillous & uteroplacental blood flow increases throughout the placenta as AOG Maternal blood directly bathes trophoblasts IgG: transferred by trophoblast receptor mediated mechanism Transfer by O2 & CO2 Transfer of CO2 in placenta: diffusion limited Traverse placenta more rapidly than O2 Fetal blood has less affinity for CO2 than the blood of mother favoring transfer from fetus to mother Transfer of O2 in placenta: blood flow limited Despite low pO2, fetus does not suffer lack of O2 d/t: High Cardiac Output O2 carrying capacity of the fetal blood Higher Hgb concentration Babies Hgb (16-18) Mother Hgb (11-12) Hyperventilation fall in pCO2 favors transfer of CO2 from fetus to mother Placenta serves as a fetal lung Selective Transfer & Facilitated Diffusion Ascorbic Acid: 2-4x higher in fetal plasma than in maternal plasma Iron: Unidirectional transfer across the placenta, maternal plasma iron concentration is much lower than that in her fetus. Transferred actively from maternal plasma to fetal plasma Virus, bacteria, protozoa may cross placenta & cause infection Rarely, malignant cells are transferred to the placenta
GESTATIONAL AGE 2 weeks before ovulation & fertilization 3 weeks before implantation Aka: Menstrual Age
OVULATION AGE Age of embyofetal development Time in days/ weeks from ovulation Aka: Postconceptional age
ESTIMATED DATE OF BIRTH About 280 days or 40 wks b/w the 1 day of the LMP & the birth of the fetus Corresponds to 9 1/3 calendar months Naegeles Rule: st Add 7 days to the 1 day of LMP, subtract 3 mos & add 1 yr. Example: st = 1 day of LMP: July 5 2010 = due date: April 12, 2011 = Term: 3 wks before & 2 wks after MORPHOLOGICAL GROWTH 1st 2 wks after OVULATION: Fertilization Blastocyst formation Blastocyst Implantation EMBRYO: term used to product of conception when the chorionic villi is already developed
st
st
FETAL NUTRITION 1 few days after implantation: nutrition of the blastocyst comes from the interstitial fluid of the endometrium & the surrounding maternal tissue st 1 2 months: growth of the embryo fetus is dependent on maternal nutrients Maternal diet is transferred into storage forms to meet her demands for energy, tissue repair, & new growth including maternal needs for pregnancy 3 major maternal storage depots: Liver Muscle Adipose tissue Insulin: sustained by increased serum levels of glucose & amino acid involved in the metabolism of nutrients in the GUT NET EFFECT: glucose is stored as glycogen primarily in liver & muscle STORAGE: amino acid as protein, excess CHO & CHON as fat nd Storage of excess as fat: peaks in the 2 trimester & then declines as fetal demands increase in late pregnancy Lipolysis is activated by: Glucagon Norepinephrine Placental Lactogen Glucocorticoids Thyroxine Placenta appears to act as a nutrient sensor, altering transport based on the maternal supply & environmental stimuli Times of Fasting glucose is released from glycogen But maternal glycogen stores cannot provide an adequate amount of glucose to meet requirements for maternal energy & fetal growth
PLACENTA & FETAL GROWTH Structures Traversed Syncytiotrophoblasts Stroma of intervillous space Fetal capillary wall Regulation of Placental Transfer Concentration of substance in the fetal blood Rate of maternal blood flow Area available for exchange Physical properties of tissue barrier in diffusion Capacity of the biochemical machinery in active transport Amount of the substance metabolized by placenta Area of exchange across the fetal capillaries Specific binding or carrier proteins Mechanism of Transfer Simple Diffusion Substances w/ molecular mass < 500d diffuse readily The smaller the molecule the more rapid the transfer rate Transfers at a fast rate: Oxygen Carbon dioxide Water Most electrolytes Anesthetic gases Transfers at a slower rate: Insulin Steroid hormones Thyroid hormones
GLUCOSE & FETAL GROWTH Midpregnancy: fetal glucose concentration is independent of& may exceed maternal levels
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Glucose: major nutrient for fetal growth & energy Human Placental Lactogen Found in abundance in mother but not in fetus Block peripheral uptake & use of glucose Mobilize & use free fatty acid by maternal tissue Vitamin C: Ascorbic Acid Transported by energy dependent carrier-mediated process Vitamin D: Cholecalciferol Metabolites are greater in maternal than in fetal plasma
GLUCOSE TRANSPORT LEPTIN Carrier mediated Stereospecific Nonconcentrating process Uses 6 glucose transport proteins (GLUT) Important for big babies Hormone that has a role in normal menstruation Product of adipocytes & a regulator of energy homeostasis
GLUCOSE, INSULIN, & FETAL MACROSOMIA Hyperinsulinemia GF expression of GLUT proteins in syncytiotrophoblasts excessive fetal growth
LACTATE Transported across the placenta by FACILITATED DIFFUSION as Lactic Acid
FREE FATTY ACIDS & TRIGLYCERIDES Neutral fat (TG) does not cross placenta Most fatty Acids cross by SIMPLE DIFFUSION Fatty acid transferred to the fetus can be converted to triacylglycerols in the fetal liver Apoprotein & cholesterol of LDL are hydrolyzed by enzymes to give: Cholesterol for progesterone Free amino acids Essential fatty acids
AMINO ACIDS Concentrated in the syncytiotrophoblasts & transferred to fetal side by DIFFUSION
PROTEINS & OTHER LARGE MOLECULES Limited by transfer of larger proteins except for IgG & retinol-binding proteins in placenta IgM is found in fetus only after the fetal immune system has been provoked by infection IgA in milk
HEAVY METALS Cigarette smoking: most common cause of cadmium Low levels of cadmium in the fetus are attributable to the sequestration of cadmium in trophoblast by metallothionine I Premature rupture of fetal membranes is in smokers mainly because cadmium provokes metallothionine synthesis in amnion causing sequestration of Cu2+ & thereby affecting amnion synthesis
IONS & TRACE METALS Transferred by CARRIER-MEDIATED TRANSPORT Energy requiring active transport
CALCIUM & PHOSPHORUS ACTIVE TRANSPORT PTH-rP produced in the fetal parathyroid placenta & other fetal tissues is important for calcium transfer to the fetus & in calcium homeostasis in the fetal compartment
VITAMINS Vitamin A: Retinol Greater amount in fetal than in maternal plasma Bound to retinol-binding protein & albumin
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Physiologic OB FETAL GROWTH & DEVELOPMENT II Fetal Physiology

Dr. Daisy F. Estimo CHAPTER 4
MECONIUM Fetal bowel contents consist of various products of secretion: glycerophospholipids from the lung desquamated fetal cells lanugo
scalp hair AMNIONIC FLUID Changes in Amniotic Fluid < 12 WEEKS: amnionic fluid is an ultrafiltrate of maternal plasma. > 12 WEEKS: consists of ECF that diffuses through the fetal skin and thus reflects fetal plasma > 20 WEEKS: cornification of fetal skin prevents diffusion, & amniotic fluid is composed largely of fetal urine. FETAL URINE 12 WEEKS: fetal kidneys starts producing urine 18 WEEKS: 7-14 ml/day Contains more of the following than fetal plasma:: Urea Creatinine Uric acid Other components Desquamated fetal cells Vernix caseosa Lanugo Various secretions OSMOLARITY The above components makes the amniotic fluid HYPOTONIC; hence, the net effect is that amnionic fluid osmolality decreases with advancing gestation. AMNIOTIC VOLUME: Origin: Small Proportion: Pulmonary fluid Major Proportion: Fluid filtering through the placenta Volume is quite variable 8th WEEK: increases by 10 mL per week 21st WEEK: increases up to 60 mL per week 33rd WEEK: declines gradually back to a steady state FUNCTION Serves to cushion the fetus, allowing musculoskeletal development and protecting it from trauma. Amniotic membrane can touch the fetus when there is decreased amniotic fluid, w/c can prevent fetal growth. Maintains temperature and has a minimal nutritive function. Ingestion of Fluid into gastrointestinal tract & inhalation into the lung may promote growth & differentiation of these tissues Epidermal growth factor (EGF) and EGF-like growth factors, such as transforming growth factor-beta, are present in amnionic fluid. If baby is not swallowing enough, will result to POLYHYDRAMNIOS Decreased fluids in lungs can lead to pulmonary hypoplasia. can be d/t: draining off amnionic fluid chronically draining pulmonary fluid through the trachea physically preventing the prenatal chest excursions that mimic breathing Thus, the formation of intrapulmonary fluid and, at least as important, the alternating egress and retention of fluid in the lungs by breathing movements are essential to normal pulmonary development.
FETAL CIRCULATION Most blood goes from the right atrium to the left atrium Different from that of the adult and functions until the moment of birth, when it is required to change dramatically. Fetal blood does not need to enter the pulmonary vasculature to be oxygenated, most of the right ventricular output bypasses the lungs. Fetal heart chambers work in parallel, not in series, which effectively supplies the brain and heart with more highly oxygenated blood than the rest of the body. Oxygen and nutrient materials required for fetal growth and maturation are delivered from the placenta by the single umbilical vein. Umbilical vein divides into the ductus venosus and the portal sinus. Ductus venosus major branch traverses the liver to enter the inferior vena cava directly. does not supply oxygen to the intervening tissues; hence, carries well-oxygenated blood directly to the heart. Portal sinus carries blood to the hepatic veins primarily on the left side of the liver where oxygen is extracted. The relatively deoxygenated blood from the liver then flows back into the inferior vena cava, which also receives less oxygenated blood returning from the lower body.
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Blood flowing to the fetal heart from the inferior vena cava, therefore, consists of an admixture of arterial-like blood that passes directly through the ductus venosus and less welloxygenated blood that returns from most of the veins below the level of the diaphragm. The oxygen content of blood delivered to the heart from the inferior vena cava is thus lower than that leaving the placenta. Remaining right ventricular output returns to the placenta through the 2 hypogastric arteries, which distally become the umbilical arteries. In the placenta, this blood picks up oxygen from the uterine arteries of mother in the villous space. PARALLEL vs SERIES Circulation: PRENATAL life: ventricles of the fetal heart work in parallel POSTNATAL life: ventricles work in series. Well-oxygenated blood enters the left ventricle, which supplies the heart and brain, and less oxygenated blood enters the right ventricle, which supplies the rest of the body. The two separate circulations are maintained by the structure of the right atrium, which effectively directs entering blood to either the left atrium or the right ventricle, depending on its oxygen content. This separation of blood according to its oxygen content is aided by the pattern of blood flow in the inferior vena cava. WELL-oxygenated blood: course along the medial aspect of the inferior vena cava LESS oxygenated blood: stays along the lateral vessel wall. This aids their shunting into opposite sides of the heart. CRISTA DIVIDENS Once blood enters the right atrium, the configuration of the upper interatrial septumthe crista dividensis such that it preferentially shunts the well-oxygenated blood from the medial side of the inferior vena cava and the ductus venosus through the foramen ovale into the left heart and then to the heart and brain. After head, neck & upper body have extracted needed oxygen, the resulting less oxygenated blood returns to the right heart through the superior vena cava. The less oxygenated blood coursing along the lateral wall of the inferior vena cava enters the right atrium and is deflected through the tricuspid valve to the right ventricle. The superior vena cava courses inferiorly and anteriorly as it enters the right atrium, ensuring that less-oxygenated blood returning from the brain and upper body also will be shunted directly to the right ventricle. Similarly, the ostium of the coronary sinus lies just superior to the tricuspid valve so that less oxygenated blood from the heart also returns to the right ventricle. As a result of this blood flow in the right ventricle is 15 to 20 percent less saturated than blood in the left ventricle. Almost 90 % of blood exiting the right ventricle is shunted through the ductus arteriosus to the descending aorta d/t high pulmonary vascular resistance & comparatively lower resistance in the ductus arteriosus. 1/3rd of the blood passing though the ductus arteriosus is delivered to the body. High pulmonary vascular resistance and comparatively lower resistance in the ductus arteriosus and the umbilicalplacental vasculature ensure that only about 15 % of right ventricular output (8 % of the combined ventricular output) goes to the lungs. 1/3rd of the blood passing through the ductus arteriosus is delivered to the body via descending aorta. Remaining 2/3rd right ventricular output returns to the placenta through the two hypogastric arteries, which distally become the umbilical arteries. In the placenta, this blood picks up oxygen and other nutrients and is recirculated through the umbilical vein. Intra-abdominal remnants of the umbilical vein form the ligamentum teres hepatis. ductus arteriosus functional closure of the ductus arteriosus with the expansion of the lungs, allows blood leaving from the right ventricle to preferentially enter the pulmonary vasculature to become oxygenated before it returns to the left heart. Becomes ligametum arteriosus foramen ovale closes w/ (L) atrial pressure becomes the fovea ovale ductus venosus Constricts by 10 to 96 hours after birth and is anatomically closed by 2 to 3 weeks becomes the ligamentum venosum Virtually instantaneously, the ventricles, which had worked in parallel in fetal life, now effectively work in series.
FETAL BLOOD Hemopoiesis 1st: yolk sac: very early embryo, 17 wks AOG 2nd: liver: 23 wks AOG 3rd: bone marrow: 10.5 wks old till adulthood The first erythrocytes released into the fetal circulation are nucleated and macrocytic. Mean cell volumes are expressed in femtoliters (fL), and one femtoliter equals one cubic micrometer. The mean cell volume is at least 180 fL in the embryo and decreases to 105 to 115 fL at term. The erythrocytes of aneuploid fetuses generally do not undergo this maturation and maintain high mean cell volumes130 fL on average. As fetal development progresses, more and more of the circulating erythrocytes are smaller and nonnucleated. As the fetus grows, both the volume of blood in the common fetoplacental circulation and hemoglobin concentration increase. Hgb of fetal blood increases from 12 g/dL at midpregnancy and to 18 g/dL at term. Because of their large size, fetal erythrocytes have a short life span, which progressively lengthens to approximately 90 days at term. As a consequence, RBC production is . Reticulocytes are initially at high levels, but to 4 to 5% at term. The fetal erythrocytes differ structurally and metabolically from those of the adult. more deformable, which serves to offset their higher viscosity contain several enzymes with appreciably different activities During pregnancy, the mother is anemic if Hgb is <10 mg/dL
CIRCULATORY CHANGES AT BIRTH The following vessels constrict or collapse after birth: umbilical vessels UMBILICAL ARTERIES Distal portions of the hypogastric arteries course from the level of the bladder along the abdominal wall to the umbilical ring and into the cord undergo atrophy & obliteration within 3 to 4 days after birth. become the umbilical ligaments UMBILICAL VEIN
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ERYTHROPOIESIS controlled by fetal erythropoietin because maternal erythropoietin does not cross the placenta. Fetal erythropoietin production is influenced by Testosterone Estrogen Prostaglandins Thyroid hormone Lipoproteins Serum levels of erythropoietin with fetal maturity, as do the numbers of responsive erythrocytes. Site of erythropoietin production: fetal liver appears to be an important source until renal production begins. Close correlation b/w the concentration of erythropoietin in amnionic fluid and that in umbilical venous blood obtained by cordocentesis. After birth, erythropoietin may not be detectable for up to 3 months. First 6 to 12 months of life: proportion of Hgb F continues to and eventually reaches the low levels found in adult erythrocytes. Glucocorticosteroids mediate the switch from fetal to adult hemoglobin, and the effect is irreversible. Hgb A binds 2,3-diphosphoglycerate (2,3-DPG) more avidly than does hemoglobin F, thus lowering the affinity of hemoglobin A for oxygen. During pregnancy, maternal 2,3-DPG levels are , and because fetal erythrocytes have lower concentrations of 2,3-DPG, the latter has increased oxygen affinity.
FETAL COAGULATION FACTORS There are no embryonic forms of the various hemostatic proteins except fibrinogen, the fetus starts producing normal, adult-type procoagulant, fibrinolytic, and anticoagulant proteins by 12 weeks. DO NOT cross the placenta, their concentrations at birth are markedly below the levels that develop within a few weeks of life. In normal neonates, the levels of factors II, VII, IX, X, XI, prekallikrein, Protein S, Protein C, antithrombin, and plasminogen are all ~50% of adult levels. factors V, VIII, XIII, and fibrinogen are closer to adult values Without prophylactic treatment, the vitamin K-dependent coagulation factors usually decrease even further during the first few days after birth PREVENTIVE MEASURE: vitamin K injection at birth BREAST FEEDING amplifies the decrease of vitamin Kdependent coagulation factors may lead to hemorrhage in newborn Fetal fibrinogen appears as early as 5 weeks same amino acid composition as adult fibrinogen but has different properties forms a less compressible clot, and the fibrin monomer has a lower degree of aggregation Plasma fibrinogen levels at birth are less than those in nonpregnant adults.
FETAL BLOOD VOLUME Term normal newborns average 78 mL/kg when immediate cordclamping was conducted. Volume of fetal blood contained in the placenta after prompt cord clamping to average 45 mL/kg of fetal weight. Fetoplacental blood volume at term is ~ 125 mL/kg of fetal weight.
FETAL HEMOGLOBIN Tetrameric protein two copies of two different peptide chains, which determine the type of hemoglobin produced. Normal adult hemoglobin A: ALPHA and BETA chains. During embryonic and fetal life, a variety of ALPHA and BETA chain precursors are produced. BETA -type chains: chromosome 11 ALPHA -type chains: chromosome 16. Each of these genes is turned on and then off during fetal life, until the ALPHA and BETA genes, which direct the production of hemoglobin A, are permanently activated. Fetal blood is first produced in the yolk sac, where hemoglobins Gower 1, Gower 2, and Portland are made. Erythropoiesis then moves to the liver, where fetal hemoglobin F is produced. Hemopoiesis finally moves to the bone marrow, adult-type hemoglobin A appears in fetal red blood cells and is present in progressively greater amounts as the fetus matures Final adult version of the alpha chain is produced exclusively by 6 weeks. If an gene mutation or deletion occurs, there is no alternate type chain that could substitute to form functional hemoglobin. In contrast, theres at least two versions of the chain and In the case of a -gene mutation or deletion, these two other versions of the chain often continue to be produced, resulting in hemoglobin A2 or hemoglobin F, which substitute for the abnormal or missing hemoglobin. Genes are turned off by methylation of the control region: Fragile X Syndrome. In some situations, methylation does not occur, and in newborns of diabetic women, there may be persistence of hemoglobin F from hypomethylation of the gene. With sickle cell anemia, the gene remains unmethylated, and large quantities of fetal hemoglobin continue to be produced. hemoglobin F levels are associated with fewer sickle-cell disease symptoms Pharmacological modification of these levels by hemoglobin F-inducing drugs is one approach to disease treatment. Functional difference between hemoglobins A and F Hgb F: At any given oxygen tension and at identical pH, fetal erythrocytes bind more oxygen than do those that contain nearly all hemoglobin A Amount in fetal erythrocytes begins to in the last weeks of pregnancy so that at term, about 3/4ths of total hemoglobin is hemoglobin F.
Levels of functional fetal factor XIII fibrin-stabilizing factor are significantly reduced compared with those in adults. Severe deficiencies of factors VIII, IX, XI, or XIII are usually suspected after observing a continuous ooze from the umbilical stump. low levels of plasminogen and increased fibrinolytic activity in cord plasma compared with that of maternal plasma. Platelet counts in cord blood are in the normal range for nonpregnant adults. Despite this relative reduction in procoagulants, fetal Hge is a rare event & does not usually occur even after invasive fetal procedures like cordocentesis. amnionic fluid thromboplastins and clotting factor in Wharton jelly combine to aid coagulation at the umbilical cord puncture site. A variety of thrombophilias, such as protein C, S, antithrombin III deficiency, or the factor V Leiden mutation, may cause thromboses and pregnancy complications in adults.
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If the fetus inherits one of these mutations, thrombosis and infarction can develop. usually seen with homozygous inheritance some were heterozygous for factor V Leiden mutation who suffered with ischemic infarction or hemorrhagic stroke MONOCYTES In the newborn, can process and present antigen when tested with maternal antigen-specific T cells. NERVOUS SYSTEM AND SENSORY ORGANS SC Termination 24th week: S1 at birth: L3 adult: L1 Myelination of the spinal cord begins at midgestation till 1 y.o 7th week: rudimentary taste buds 8th week: Synaptic function for flexion of the neck and trunk 10th week: local stimuli may evoke squinting, opening of the mouth, incomplete finger closure, and flexion of the toes, swallowing. 12th week: mature taste receptors 14 -16 weeks: respiration. 20th week (Mid pregnancy): internal, middle & external ear well developed 24th week: ability to suck 24-26 weeks: hears sounds 28 weeks: eye is sensitive to light but perception of form & color is not complete until long after birth third trimester: integration of nervous and muscular function proceeds rapidly. GASTROINTESTINAL SYSTEM 10 to 12 weeks Swallowing begins Small intestine can undergo peristalsis Transport glucose actively Much of the water in swallowed fluid is absorbed, and unabsorbed matter is propelled to the lower colon. Potential FACTORS that initiate SWALLOWING: fetal neural analogue of thirst, gastric emptying, and change in the amnionic fluid composition The fetal taste buds may play a role because saccharin injected into amnionic fluid increases swallowing njection of a noxious chemical inhibits it Fetal swallowing EARLY PREGNANCY: appears to have little effect on amnionic fluid volume because the volume swallowed is small compared with the total. LATE PREGNANCY: volume regulated substantially by fetal swallowing if inhibited: hydramnios Term fetuses swallow between 200 and 760 mL per dayan amount comparable to that of the neonate. Hydrochloric acid and some digestive enzymes are present in the stomach and small intestine in very small amounts in the early fetus. 11 weeks: Intrinsic factor is detectable 16 weeks: pepsinogen detectable The preterm neonate, may have transient deficiencies of these enzymes Stomach emptying appears to be stimulated primarily by volume. Movement of amnionic fluid through the gastrointestinal system may enhance growth and development of the alimentary canal; hence, maintain the patency of GIT. Other regulatory factors are involved because anencephalic fetuses, in whom swallowing is limited, often have normal amnionic fluid volumes and normal-appearing gastrointestinal tracts. LATE PREGNANCY: 800 mg of soluble protein is ingested daily by the fetus. Several anomalies can affect normal fetal gastrointestinal function. Hirschsprung disease aka congenital aganglionic megacolon prevents the bowel from undergoing parasympatheticmediated relaxation and thus from emptying normally recognized prenatally by grossly enlarged bowel during sonography. Obstructions such as duodenal atresia, megacysticmicrocolon syndrome, or imperforate anus also prevent the bowel from emptying normally. Meconium ileus commonly found with fetal cystic fibrosis bowel obstruction caused by thick, viscid meconium that blocks the distal ileum
FETAL PLASMA PROTEINS Liver enzymes and other plasma proteins are produced by the fetus, and these levels do not correlate with maternal levels Concentrations of plasma protein, albumin, lactic dehydrogenase, aspartate aminotransferase, -glutamyl transpeptidase, and alanine transferase levels of prealbumin with gestational age At birth, mean total plasma protein and albumin are similar to maternal levels ONTOGENY OF THE FETAL IMMUNE RESPONSE Immunological Competence: 13 weeks. Late 1st Trimester: Fetal synthesis of complement Cord blood or Near Term: ~ 1/2 adult values.
FETAL IMMUNOCOMPETENCE NO Infection: mostly transferred maternal immunoglobulin G (IgG). Antibodies in the newborn are reflective of maternal immunological experiences: Fetal IgM production indicates that the mother had an infection during pregnancy.
IMMUNOGLOBULIN G Maternal IgG transport to fetus: 16 weeks and thereafter. Bulk of IgG is acquired: last 4 weeks of pregnancy Preterm neonates have poor protective maternal antibodies. Newborns IgG adult values attained by 3 y.o. Transfer of IgG antibodies from mother to fetus can be harmful rather than protective to the fetus: Hemolytic disease of the fetus and newborn resulting from D-antigen isoimmunization causing Erythroblastosis Fetalis
IMMUNOGLOBULIN M ADULTS: IgM production in response to an antigenic stimulus is superseded in a week or so predominantly by IgG production. FETUS:, very little IgM is produced may include antibody to maternal T lymphocytes With infection, the IgM response is dominant in the fetus and remains so for weeks to months in the newborn. And because IgM is not transported from the mother, any IgM in the fetus or newborn is that which it produced. levels of IgM are found in newborns with congenital infection such as rubella, cytomegalovirus infection, or toxoplasmosis. Serum IgM levels in umbilical cord blood and identification of specific antibodies may be useful in the diagnosis of intrauterine infection. Adult levels: 9 months
IMMUNOGLOBULIN A Newborn does not acquire significant passive immunity from the absorption of humoral antibodies ingested in colostrum. IgA ingested in colostrum provides mucosal protection against enteric infections. This may also explain the small amount of fetal secretory IgA found in amnionic fluid.
LYMPHOCYTES B lymphocytes appear in fetal liver by 9 weeks, and in blood and spleen by 12 weeks. T lymphocytes begin to leave the thymus at about 14 weeks Newborn responds poorly to immunization especially to bacterial capsular polysaccharides d/t: deficient response of B cells to polyclonal activators lack of T cells that proliferate in response to specific stimuli.
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vernix undigested debris from swallowed amnionic fluid dark greenish-black appearance is caused by pigments: biliverdin. can pass from normal bowel peristalsis in the mature fetus or from vagal stimulation. also pass when hypoxia stimulates arginine vasopressin (AVP) release from the fetal pituitary gland. AVP stimulates the smooth muscle of the colon to contract, resulting in intra-amnionic defecation Small bowel obstruction may lead to vomiting in utero Fetuses who suffer from congenital chloride diarrhea may have diarrhea in utero, which leads to hydramnios and preterm delivery EXTRA NOTES: Amniotic Fluid is usually clear colored. Normal Fetal HR: 110-160 bpm Biliary atresia = babies without gallbladder, stool is whitish Jaundice: may occur a few days or few hours after delivery URINARY SYSTEM Two primitive urinary systems that precede the development of the metanephros Pronephros mesonephros 2 weeks: pronephros involutes 5 weeks: mesonephros produces urine 9 to 12 weeks: ureteric bud & nephrogenic blastema interact to produce the metanephros 11 to 12 weeks: mesonephros degenerates 14 weeks: loop of Henle is functional & reabsorption occurs Failure of these two structures either to form or to regress may result in anomalous development of the definitive urinary system. ANLAGE & FATE ANLAGE FATE Intermediate Mesoderm Kidney Ureter Urogenital Sinus Urinary Bladder Urethra External Genitalia Lower 3rd of Vagina Allantois Urinary Bladder Greater maternal anthropometrics and fetal biometrics are associated with larger fetal kidneys, whereas preferential fetal blood flow to the brain is associated with smaller kidneys New nephrons continue to be formed until 36 weeks. preterm neonates: formation continues after birth Although the fetal kidneys produce urine, their ability to concentrate and modify the pH is limited even in the mature fetus. Fetal urine is hypotonic with respect to fetal plasma and has low concentrations of electrolytes. Renal vascular resistance is high, and the filtration fraction is low compared with values in later life Fetal renal blood flow and thus urine production are controlled or influenced by: renin-angiotensin system sympathetic nervous system prostaglandins kallikrein atrial natriuretic peptide. GFR increases with gestational age: 12 weeks: < 0.1 mL/min 20 weeks: 0.3 mL/min Later gestation: rate remains constant when corrected for fetal weight Hemorrhage or hypoxia generally results in a decrease in renal blood flow, glomerular filtration rate, and urine output. Urine usually is found in the bladder even in small fetuses. 12 weeks: start producing urine 18 weeks: produce 7 to 14 mL/day At term: increases to 27 mL/hr or 650 mL/day FACTORS AFFECTING URINE PRODUCTION: Maternally administered furosemide increases fetal urine formation, Uteroplacental insufficiency and other types of fetal stress decrease it. FACTORS AFFECTING FETAL GFR & TUBULAR WATER REABSORPTION: in 1/3rd of growth-restricted newborns & 1/6th w/ diabetic mothers. normal in anencephalic neonates and in those with hydramnios. Kidneys not essential for survival in utero, but are important in the control of amniotic fluid volume & composition. at birth, important for elimination of metabolic waste products; hence is essential for survival Obstruction of the urethra, bladder, ureters, or renal pelves can damage renal parenchyma and distort fetal anatomy. URETHRAL OBSTRUCTION bladder may become sufficiently distended that it ruptures or dystocia results. chronic anuria is usually accompanied by oligohydramnios and pulmonary hypoplasia.
LIVER Serum liver enzyme levels increase with gestational age but in reduced amounts. Fetal liver has a gestational-age related diminished capacity for converting free unconjugated bilirubin to conjugated bilirubin life span of normal fetal macrocytic erythrocytes is brief, relatively more unconjugated bilirubin is produced. fetal liver conjugates only a small fraction, which is excreted into the intestine and ultimately oxidized to biliverdin. Most of the unconjugated bilirubin is excreted into the amnionic fluid after 12 weeks and is then transferred across the placenta placental transfer is bidirectional. pregnant woman with severe hemolysis has excess unconjugated bilirubin that readily passes to the fetus and then into the amnionic fluid. conjugated bilirubin is NOT exchanged to any significant degree between mother and fetus. Most fetal cholesterol is from hepatic synthesis, which satisfies the large demand for LDL cholesterol by the fetal adrenal glands. Hepatic glycogen 2nd Trimester: present in low concentration Near Term: rapid and marked increase to levels two to three times those in the adult liver. After birth: falls precipitously.
PANCREAS 8 weeks: Glucagon 9 to 10 weeks: Insulin-containing granules 12 weeks: insulin detected in fetal plasma 16 weeks: most enzymes are present responds to hyperglycemia by secreting insulin Serum insulin levels are unusually high in newborns of diabetic mothers and other large-for-gestational age neonates, insulin levels are low in those small-for-gestational age In the adult rhesus monkey, hypoglycemia and infused alanine cause an increase in maternal glucagon levels. In the human, similar stimuli do not evoke a fetal response, by 12 hours after birth, the newborn is capable of responding fetal pancreatic cells do respond to L-dopa infusions Therefore, nonresponsiveness to hypoglycemia is likely the consequence of failure of glucagon release rather than inadequate production. This is consistent with findings of the developmental expression of pancreatic genes in the fetus 14 weeks: low levels of Trypsin, chymotrypsin, phospholipase A, and lipase Amylase has been identified in amnionic fluid at 14 weeks exocrine function of the fetal pancreas is limited Physiologically important secretion occurs only after stimulation by a secretagogue such as acetylcholine, which is released locally after vagal stimulation Cholecystokinin normally is released only after protein ingestion and thus ordinarily would not be found in the fetus.
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Physiologic OB
LUNGS Morphological or functional immaturity at birth leads to the development of the respiratory distress syndrome ANATOMICAL MATURATION 3 essential stages of lung development: Pseudoglandular Stage growth of the intrasegmental bronchial tree between the 5th and 17th weeks. lung looks microscopically like a gland. Canalicular Stage 16 to 25 weeks bronchial cartilage plates extend peripherally Each terminal bronchiole gives rise to several respiratory bronchioles, and each of these in turn divides into multiple saccular ducts. Terminal Sac Stage after 25 weeks alveoli give rise to the primitive pulmonary alveolithe terminal sacs. extracellular matrix develops from proximal to distal lung segments until term. extensive capillary network is built, the lymph system forms, and type II pneumonocytes begin to produce surfactant. At birth, only about 15 percent of the adult number of alveoli are present, and thus the lung continues to grow, adding more alveoli for up to 8 years. Various insults can upset this process, and their timing determines the sequela. Fetal Renal Agenesis there is no amnionic fluid at the beginning of lung growth major defects occur in all three stages Membrane Rupture Before 20 Weeks subsequent oligohydramnios d/t rupture usually exhibits nearly normal bronchial branching and cartilage development but has immature alveoli. Membrane Rupture After 24 Weeks may have little long-term effect on pulmonary structure. SURFACTANT presence of a sufficient amount of this surface-active materials in the amnionic fluid is evidence of fetal lung maturity After the first breath, the terminal sacs must remain expanded despite the pressure imparted by the tissue-to-air interface, and surfactant keeps them from collapsing. formed specifically in type II pneumonocytes that line the alveoli. characterized by multivesicular bodies that produce the lamellar bodies in which surfactant is assembled. LATE FETAL LIFE: at a time when the alveolus is characterized by a water-to-tissue interface, the intact lamellar bodies are secreted from the lung and swept into the amnionic fluid during respiratory-like movements that are termed fetal breathing. AT BIRTH: with the first breath, an air-to-tissue interface is produced in the lung alveolus. Surfactant uncoils from the lamellar bodies, and it then spreads to line the alveolus to prevent alveolar collapse during expiration. Thus, it is the capacity for fetal lungs to produce surfactant, and not the actual laying down of this material in the lungs in utero, that establishes lung maturity. Surfactant Composition 90 % of surfactant dry-weight is lipid. 10% Proteins Glycerophospholipids ~80% are phosphatidylcholines (lecithins). principal active component of surfactant is a specific lecithin dipalmitoylphosphatidylcholine (DPPC or PC) nearly 50 % 8-15% Phosphatidylglycerol (PG) precise role is unclear other major constituent phosphatidylinositol (PI). is
Surfactant Synthesis Biosynthesis takes place in the type II pneumocytes. Apoproteins produced in the endoplasmic reticulum aid the forming and reforming of a surface film Glycerophospholipids synthesized by cooperative interactions of several cellular organelles. primary surface tension-lowering component of surfactant surface properties of the surfactant phospholipids are determined principally by the composition and degree of saturation of their long-chain fatty acids. APOPROTEINS Surfactant A (SP-A) major apoprotein a glycoprotein with a molecular weight of 28,000 to 35,000 Da synthesized in the type II cells Synthesis is by treatment of fetal lung tissue with: cyclic adenosine monophosphate (AMP) analogues epidermal growth factors triiodothyronine
apoprotein synthesis precedes surfactant glycerophospholipid synthesis. content in amnionic fluid increases with gestational age and fetal lung maturity. FUNCTION: play a role in the onset of parturition GENE EXPRESSION demonstrable by 29 weeks 2 separate genes on chromosome 10 SP-A1 SP-A2 regulation is distinctive and different cyclic AMP is more important in SPA2 expression dexamethasone decreases SP-A2 expression. SP-B and SP-C Smaller apoproteins important in optimizing the action of surfactant deletions in SP-B gene are incompatible with survival despite production of large amounts of surfactant. CORTICOSTEROIDS AND FETAL LUNG MATURATION fetal cortisol stimulates lung maturation and surfactant synthesis. It is unlikely that corticosteroids are the only stimulus for augmented surfactant formation, as clearly, respiratory distress syndrome is not universal in neonates with limited cortisol production. These include those with anencephaly, adrenal hypoplasia, or congenital adrenal hyperplasia.
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Physiologic OB
Glucocorticosteroids administered at certain critical times during gestation effect an increase in the rate of fetal lung maturation. betamethasone and dexamethasone as well as neonatal replacement surfactant therapy accelerate fetal lung maturity Usually give steroid treatment if AOG during parturition is <34 weeks. fetal thyroid concentrates iodide more avidly than does the maternal thyroid. maternal administration of either radioiodide or appreciable amounts of ordinary iodide is hazardous after this time. Normal fetal levels of free thyroxine (T4), free triiodothyronine (T3), and thyroxin-binding globulin increase steadily throughout gestation Compared with adult levels, by 36 weeks, fetal serum concentrations of TSH are higher, total and free T3 concentrations are lower, and T4 is similar. Hence, fetal pituitary may not become sensitive to feedback until late in pregnancy Fetal thyroid hormone plays a role in the normal development of virtually all fetal tissues, but especially the brain. congenital hyperthyroidism occurs when maternal thyroid-stimulating antibody crosses the placenta to stimulate the fetal thyroid. fetuses develop tachycardia, hepatosplenomegaly, hematological abnormalities, craniosynostosis, and growth restriction. As children, they have perceptual motor difficulties, hyperactivity, and reduced growth placenta prevents substantial passage of maternal thyroid hormones to the fetus by rapidly deiodinating maternal T4 and T 3 to form reverse T3, a relatively inactive thyroid hormone. A number of antithyroid antibodiesimmunoglobulin Gcross the placenta when present in high concentrations. Antibodies like long-acting thyroid stimulators (LATS) LATS-protector (LATS-P) thyroid-stimulating immunoglobulin (TSI) normal fetal growth and development, which occurs despite fetal hypothyroidism, provided evidence that T4 was not essential for fetal growth. growth proceeds normally because small quantities of maternal T4 prevent antenatal cretinism in fetuses with thyroid agenesis fetus with congenital hypothyroidism typically does not develop stigmata of cretinism until after birth. Because administration of thyroid hormone will prevent this, all newborns are tested for high serum levels of TSH Immediately after birth, there are major changes in thyroid function and metabolism. Cooling to room temperature evokes sudden and marked increase in TSH secretion, which in turn causes a progressive increase in serum T4 levels that are maximal 24 to 36 hours after birth. There are nearly simultaneous elevations of serum T3 levels.
RESPIRATION FEW MINUTES AFTER BIRTH: respiratory system must provide oxygen as well as eliminate carbon dioxide. 11 weeks: Respiratory muscles develop and fetal chest wall movements are detected by sonographic techniques 4th month: fetus is capable of respiratory movement sufficiently intense to move amnionic fluid in and out of the respiratory tract.
ENDOCRINE GLANDS Pituitary Gland Fetal endocrine system is functional for some time before the central nervous system reaches maturity Adenohypophysis develops from oral ectodermRathke pouch Neurohypophysis derives from neuroectoderm. Anterior Pituitary Aka adenohypophysis differentiates into five cell types that secrete six protein hormones: lactotropes produce prolactinPRL somatotropes produce growth hormoneGH corticotropes produce corticotrophinACTH thyrotropes produce thyrotropin or thyroid-stimulating hormoneTSH gonadotropes produce: luteinizing hormoneLH follicle-stimulating hormoneFSH. ACTH 7th week: first detected in the fetal pituitary gland GH & LH identified by 13 weeks Levels of immunoreactive GH are high in cord blood, although its role in fetal growth and development is not clear. 17th week: fetal pituitary gland is able to synthesize and store all pituitary hormones fetal pituitary is responsive to hormones and is capable of secreting these early in gestation. The fetal pituitary secretes BETA -endorphin, and cord blood levels of BETAendorphin and BETA-lipotropin increase with fetal PCO2 Neurohypophysis Aka posterior pituitary gland 10-12 weeks: well developed, and oxytocin and arginine vasopressin (AVP) are demonstrable. Both hormones probably function in the fetus to conserve water by actions largely at the lung and placenta rather than kidney. AVP Levels in umbilical cord plasma are increased strikingly compared with maternal levels Elevated fetal blood AVP appears to be associated with fetal stress Intermediate Pituitary Gland well-developed intermediate lobe in the fetal pituitary gland. cells of this structure begin to disappear before term and are absent from the adult pituitary. principal secretory products of the intermediate lobe cells are ALPHA-melanocytestimulating hormone (ALPHA-MSH) and BETA-endorphin.
Thyroid Gland 1st trimester: pituitarythyroid system is functional 10-12 weeks: able to synthesize hormones TSH, thyroxine, and thyroid-binding globulin (TBG) have been detected in fetal serum as early as 11 weeks placenta actively concentrates iodide on the fetal side, and by 12 weeks and throughout pregnancy
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Physiologic OB
Coronary Sinus 1 Umbilical Vein Portal Sinus Hepatic Vein SVC
Ductus venosus
IVC
Right Atrium
Lower Body
Foramen Ovale
Chorionic Villi
Left Atrium
Right Ventricle
Left Ventricle
Pulmonary Trunk Lungs
Brain
Heart
Ductuc Arteriosus
Asscendin g Aorta
Intervillous Space: Maternal Blood from UTERINE arteries Chorionic Villi 2 Umbilical A. 2 Hypogastric A. Descending Aorta
Body
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Physiologic OB Maternal Physiology I

Dr. Rebecca Brillantes Chapter 5
ADAPTATIONS TO PREGNANCY: Physiological perceived as abnormal in the nonpregnant woman CVS changes during pregnancy normally include in blood volume & CO, w/c may mimic thyrotoxicosis Can lead to ventricular failure if there is underlying heart disease Anatomical Biochemical Remarkable changes begin soon after fertilization & continue throughout gestation & most occur in response to physiological stimuli provided by the fetus & placenta Can unmask or worsen pre-existing dse Hypervolemnia of pregnancy can unmask heart disease Changes can alter appreciably criteria for diagnosis & treatment of disease REPRODUCTIVE TRACT
UTERUS Non-pregnant: almost solid structure weighing 70 g w/ a cavity of 10 ml Pregnant: thin-walled muscular organ w/ capacity to accommodate fetus, placenta, & amniotic fluid End of pregnancy: uterus capacity has reached 500 1000x greater than non-pregnant state Total volume at term: ave ~5 L (can be 20L or more) Organ wt: ~ 1100 g Uterine enlargement involves the following w/c ensures that the uterine wall is strengthened, stimulated by estrogen & progesterone stretching and hypertrophy of muscle cells Limited production of new myocytes Uterine Hypertrophy: < 12 WEEKS pf PREGNANCY: not entirely in response to mechanical distension by the products of conception because similar changes occur in ectopic pregnancy > 12 WEEKS of PREGNANCY: in uterine size is R/T pressure exerted by the expanding products of conception. 20 WEEKS AOG: level of umbilicus Stimulating HORMONES: chiefly ESTROGEN perhaps progesterone accompanied by accumulation of fibrous tissue particularly in the external mm layer most marked in the FUNDUS elastic tissue Uterine Corpus: walls are considerably thicker during the first few months of pregnancy but thin gradually as gestation advances By term: 1-2 cm thick Changed into muscular sac w/ thin, soft, readily indentable walls through w/c the fetus can be palpated Attachment of Fallopian Tubes & the Ovarian & Round Ligaments EARLY PREGANCY: slightly below apex of fundus LATE PREGNANCY: slightly above middle of the uterus Position of Placenta Influences the extent of uterine hypertrophy in that the portion of the uterus surrounding the placental site enlarges more than the rest placenta implants at the fundus; hence, fundus has the most enlargement Arrangement of Muscle Cells Uterine muscles arranged in 3 layers: OUTER HOOLIKE LAYER: arches over fundus & extends into the various ligaments MIDDLE LAYER:
Composed of a dense network of mm fibers perforated in all directions by blood vessels Main portion of the uterine wall consists of a network of vessels & mm cells Each cell has a double curve so that the interlacing of 2 muscles forms a figure of eight; when muscle cells contract they constrict the penetrating blood vessels INTERNAL LAYER: w/ sphincter-like fibers around the fallopian tube orifices & internal os of the cervix Uterine Size, Shape & Position < 12 WEEKS: PEAR shaped Pelvic organ > 12 WEEKS: Corpus & Fundus: GLOBULAR form to SPHERICAL Organ more rapidly in length than width & assumes an OVOID shape Abdominal organ Displaces intestines laterally and superiorly, & rises almost to the liver As uterus ascends from the pelvis, it rotates to the RIGHT Rectosigmoid is at the left of pelvic cavity; hence, when the uterus enlarges, it tends to rotate to the right: DEXTROROTATION Tension is exerted on the broad & round ligaments Contractility BRAXTON HICKS CONTRACTIONS: sporadic, nonrhythmic uterine contractions, may account for false labor 2nd Trimester: detected by bimanual examination Varies from 5 25 mmHg Initially infrequent but during the last 1-2 weeks of pregnancy May occur every 10-20 minutes & become rhythmic , intense & synchronized at term Uteroplacental Blood Flow MOTHER IN SUPINE: enlarged uterus can compress the great vessels, esp. Inferior vena cava & aorta Uterine arteries are branches of the aorta w/c can be compressed when mother is in supine; hence, uteroplacental blood flow is affected with maternal position Delivery of substances for fetal growth & metabolism and removal of metabolic wastes depend on adequate uteroplacental perfusion, which is dependent on total uterine blood flow from the uterine and ovarian arteries Uterine veins has reduced elastin content & adrenergic nerve density resulting to increased venous caliber and distensibility thereby increasing uteroplacental blood flow AT TERM: 450-650 mL Regulation of Uteroplacental Blood Flow MATERNAL-PLACENTAL BLOOD FLOW thru vasodilatation FETAL-PLACENTAL BLOOD FLOW by growth of placental vessels. Uterine artery diameter doubles by 20 wks w/ mead Doppler velocimetry 8-fold d/t estradiol & progesterone stimulation Uteroplacental perfusion, other than maternal position, is also affected by relationship of blood vessels to your mms, when uterus is in contraction, it decreases blood flow to the baby. Uterine contraction can obliterate blood flow to the baby; hence depriving fetus from blood flow: TACHYSYSTOLE if sustained Contaction should be no longer than 40-60 secs otherwise will lead to fetal compromise INCREASED UTEROPLACENTAL PERFUSIONIS BROUGHT ABOUT BY: Increased distensibility: Vasodilatation is mediated principally by estrogen and progesterone
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Vascular refractoriness to pressor effects of angiotensin II serves to increase uteroplacental blood flow Endothelial cells secrete Nitric oxide: or endothelium derived relaxing factor; vasodilator released by endothelial cells; abnormal synthesis linked to development of preeclampsia. large placenta i.e. DM, D-issoimmunization, multiple fetusus; chronic renal failure and in hyperthyroidism,; usually asymptomatic but may cause abdominal pain and maternal virilization; spontaneously resolves after delivery In uncomplicated pregnancy change from exaggerated ovarian response to Normal hCG
CERVIX Undergoes softening and cyanosis due to increased vascularity & edema, hypertrophy & hyperplasia of cervical glands Soft d/t edema Cyanosis during speculum examination Endocervical glands are hypertrophied & hyperplastic w/c produces tenacious mucus Endocervical mucosal cells produce copius tenacious mucus rich in immunoglobulins & cytokines that act as an immunological barrier to protect the uterine contents against infection coming from the vagina into the intrauterine environment. During cervical dilation, blood may get admixed w/ mucous creating bloody show. Bloody show: expulsion of mucus plug before or at onset of labor. Can occur 2 or 3 weeks before onset of labor especially for primiparas. Beading: crystallization of cervical mucus, result from presence of progesterone. Ferning: arborization of the crystals, result of amniotic fluid leakage. On assessment is cervical mucus is admixed w/ amniotic fluid PAPS SMEAR: screening tool for cervical cancer for every sexually active woman annually. Result in pregnancy is less than optimal; hence, difficult to identify CA cells during pregnancy. Arias Stella Reaction: endocervical gland hyperplasia & hypersecretory Estrogen induces basal cells near the squamocolumnar junction to undergo changes in size, shape and staining qualities hence pap smear in pregnant woman is less-than-optimal OVARIES: Ovulation ceases; maturation of new follicles suspended Only a single corpus luteum can be found in pregnant women Corpus luteum functions maximally during first 6 to 7 weeks (4 to 5 weeks postovulation) thereafter contributes little to progesterone production Progesterone is important for maintenance of pregnancy on 1st 7 wks If corpus Luteum is removed before 6-7 wks: ABORTION After 6-7 wks, placenta takes over the production of progesterone Decidual reaction on & beneath surface may be observed Decidual reaction also occurs in ovaries & fallopian tubes Ovarian vascular pedicle increases in diameter Generalized vasodilatation Clinical significance: wait postpartum when doing any surgery because if you do surgery on a pregnant woman, there is increased blood loss w/ dilated blood vessels Relaxin: Secreted by heart, brain & kidney secreted by corpus luteum, decidua, placenta protein hormone similar to insulin & insulin-like GF I & II major biological action: remodelling of CT of reproductive tract especially the cervix; implicated in pre-term birth due to effect on myometrial contractility. 2 OVARIAN CYSTS ASSOCIATED W/ PREGNANCY: benign, can cause maternal virilisation Luteoma of pregnancy: solid ovarian tumor exaggerated luteinisation reaction of the ovary regress after delivery but may recur androgen secreting; hence, may result in maternal virilisation (mother looks like a male d/t high androgen content) but not the fetus because of the protective role of the placenta w/c converts androgens to estrogen. Theca-Lutein Cyst: cystic, benign ovarian lesion due to exaggerated physiological follicle stimulation (hyperreactio luteinalis) usually bilateral. Associated with markedly elevated serum HCG found in GTD
FALLOPIAN TUBES: Musculature undergoes little hypertrophy flattening of tubal mucosa epithelium stromal decidual cells may develop. VAGINA & PERINEUM Chadwick Sign: increased vascularity w/ resultant violet color Hyperemia Softening of the underlying abundant Vaginal walls increase in mucosal thickness, assume hobnail appearance; with hypertrophy of smooth muscle cells, loosening of CT in preparation for distension during labor Hyperaemia in skin and muscles of perineum and vulva with softening of connective tissue Acidic pH due to increased lactic acid production from glycogen in the vaginal epithelium Histopath of vaginal epithelial cells same as Luteal phase Navicular cells: small intermediate cells seen in pap smear; ovoid cells with vesicular elongated nucleus Naked nuclei: vesicular nuclei without cytoplasm seen with an abundance of lactobacillus. Areolar and genital pigmentation may be accentuated but disappear or regress after delivery Oral Contraceptives produce similar pigmentation MSH elevated: Estrogen & Progesterone are reported to have melanocytes stimulating effects Changes in preparation from distention during labor & delivery Increase mucosal thickness Loosening of the CT Hypertrophy SKIN: increased cutaneous blood flow in pregnancy serves to dissipate heat d/t increased BMR Abdominal wall: Striae gravidarum: stretch marks, reddish, slightly depressed streaks in the skin of the abdomen, breasts and thighs; previous striae appear glistening or silvery Diastasis recti: rectus muscle separate in the midline because the abdominal walls cannot withstand the tension to which they are subjected HYPERPIGMENTATION Linea nigra: linea alba becomes markedly pigmented Chloasma/melasma gravidarum: mask of pregnancy irregular brownish patches on the face and neck. Lightens or disappears following delivery Areolar & genital pigmentation maybe accentuated but disappear or regress after delivery d/t melanocyte stimulating effects of estrogen & progesterone & melanin stimulating hormone is increased during pregnancy Oral Contraceptives pro hyperpigmentation Vascular spiders: minute, red elevations on arms, the skin of face, neck, upper chest; with radicles branching out from a central lesion, designate as nevus, angioma, telangiectasis Palmar erythema: of no clinical significance disappear after pregnancy most likely due to hyperestrogenemia. BREASTS: Breast tenderness and tingling Increase in size, veins become prominent Areola becomes broader, more pigmented Nipple enlarges, more deeply pigmented and erectile Colostrum: a thick yellowish fluid expressed from the nipples Glands of Montgomery: hypertrophic sebaceous glands seen scattered through the areola Gigantomastia: extensive pathologic breast enlargement that may be life threatening & require surgical intervention Pregnancy breast size and volume of milk production do not correlate.
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METABOLIC CHANGES: By 3rd trimester, maternal BMR increases by 10-20% weight gain in pregnancy is attributable to the uterus & its contents, the breast, increased blood volume, increased extravascular extracellular fluid and increased cellular water & deposition of new fat & protein (maternal reserves); average of 12.5 kg (27.5 lbs) Water metabolism: Increased water retention due to a fall in plasma osmolality demonstrated as pitting edema of ankles & legs Resetting of osmotic threshold for thirst & vasopressin secretion fall in plasma osmolality edema ankles & legs Decrease in interstitial colloid osmotic pressure favors edema Edema also attributed to compressing effect of heavy uterus on blood vessels thereby obstructing venous return on vena cava, hence edema most prominent at the end of the day Pitting edema of the ankles Minimum amount of extra water accrued during pregnancy = 6.5 L (water contents of the fetus, placenta, amniotic fluid, increase in the maternal blood volume & in the size of the uterus & breast) Maternal body water rather than fat contributes more to infant birthweight. Protein Metabolism: products of conception, uterus, maternal blood are rich in protein At term: Fetus + placenta = 500 g Uterus (contractile Protein) Breast (glands) = 500 g Maternal blood (hgb & plasma) -------------total 1000 gram nitrogen balance increased with gestation suggesting a more efficient use of dietary protein amino acid concentrations higher in the fetal than in the maternal compartment Pregnancy is associated with nitrogen conservation, because we need protein to supply the demands of fetal growth Breakdown of maternal muscle is not required to meet demands of growing maternal & fetal tissue, unlike in calcium Carbohydrate metabolism: Normal pregnancy is characterized by mild fasting hypoglycemia, post prandial hyperglycemia and hyperinsulinemia Pregnancy induces a state of peripheral resistance to insulin to ensure sustained supply of glucose to the fetus; mediated by E & P (estrogen and progesterone) Increased plasma levels of: placental lactogen: aid in insulin resistance, a protein hormone with growth hormone-like action that increases lipolysis with liberation of free fatty acids thereby increasing tissue resistance to insulin Accelerated starvation: pregnancy induced switch in fuels form glucose to lipids during fasting, as evidence by higher plasma concentrations of FFA, triglycerides and cholesterol Can occur in early labor where patient is NPO Prevented by administering D5W fluids When fasting is prolonged in the pregnant woman, ketonemia rapidly appears Fat metabolism: Plasma lipids, lipoproteins, and apolipoproteins increase Storage of fat occurs at midpregnancy; fat is deposited in central rather than peripheral sites It becomes available for placental transfer during 3rd trimester Progesterone hypothalamic lipostat energy storage (protects mother & fetus) Maternal Hyperlipidemia As fetal nutritional demands increase, maternal fat storage decrease Lactation increases fat loss LDL-C & HDL-C increase believed to be mediated by estrogens & progesterone Lactation speeds the rate of fat decrease Leptin & Ghrelin: a peptide hormone secreted by adipose tissue and placenta; role in body fat regulation and energy expenditure; increased during pregnancy, help regulate fetal growth Electrolyte and mineral metabolism: Na & K: excretion near nonpregnant range 1000 mEq Na & 300 mEq K retained Conc in serum is still less d/t expanded plasma hence conc appears like nonpregnant state Serum Ca decrease; 200 mg deposited in fetal skeleton/day in 3rd trimester (fetus imposes a significant deman on maternal calcium homeostasis. This demand is largely met doubling of maternal intestinal Ca absorption mediated by 1, 25 dihydroxyvitamin D3) Ionized Ca the same Mg: decreases PO2: within nonpregnant range Fe: increased requirements: Normal: 2-2.5 g adult, 300 mg young 300 mg: actively transferred to fetus & placenta : obligatory 200 mg: lost thru excretion in the GIT: obligatory 500 mg: used in creased circulating erythrocytes of 450 ml (1ml RBC contains 1.1 mg Fe) 1000 mg total pregnancy requirement Obligatory losses occur even when mother is Fe deficient Amount of Fe from diet together with that mobilized from stores is insufficient to meet pregnancy demands hence supplementation. Fe requirement at midpregnancy is 6-7 mg/ day
HAEMATOLOGICAL CHANGES: Blood volume Physiologic hypervolemia d/t increase in plasma & erythrocytes but more plasm leading to hemodilution Increases beginning 1st trimester, expands most rapidly in 2nd trimester, slower rate in the 3rd; expansion results from increase in both plasma & erythrocytes; plasma increase greater than erythrocyte increase Moderate bone marrow erythroid hyperplasia Reticulocyte count slightly elevated (related to increased plasma erythropoietin) Functions of pregnancy; induced hypervolemia: To meet demands of enlarged uterus with its greatly hypertrophied vascular system To protect mother and in turn the fetus vs. The deleterious effects of impaired venous return in the supine & erect positions To safeguard the mother vs. Adverse effects of blood loss /w parturition. Hemoglobin: decrease slightly together with hematocrit d/t increase in plasma thus whole blood viscosity decreases; average: 12.5 g/dL at term Hgb concentration below 11g/dL especially late in pregnancy should be considered abnormal & usually due to iron deficiency rather than hypervolemia: ANEMIA Blood loss: Bleeding form implantation site, episiotomy/lacerations, lochia; Must supply iron Average: 500 mL for singleton NSD (normal spontaneous delivery): 1000 mL for twins/CS (caesarean section) IMMUNOLOGICAL & LEUKOCYTE FUNCTION: suppressed humoral & cell mediated immunological functions to accommodate the foreign semiallogenic fetal graft Suppressed T-helper and T-cytotoxic cells decreases secretion of interleukin-2, interferon-Y, tumor necrosis factor Beta May explain pregnancy-related remission of some autoimmune disorders (RA, MS, & autoimmune thyroiditis) Interferon-alpha is absent Depressed PMN leukocyte chemotaxis & adherence functions account for increased susceptibility to infections Leukocyte count = 5000 to 12 000 / uL, may rise even more during labor & early puerperium (cause unknown) If levels are in a non-pregnant woman: severe infection or sepsis Normal in pregnancy especially w/vigorous labor; hence, physiologic Inflammatory markers are unreliable d/t intrinsically elevated Leukocyte alkaline phosphatase CRP ESR Complement factors C3 & C4
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Leukocyte alkaline phosphatise which is seen in a wide variety of conditions i.e. inflammatory state, is increased. C-reactive protein, ESR elevated thus cannot be used reliably to diagnose inflammation during pregnancy Complement factors C3 & C4 also significantly elevated. Cervical mucus increase:
COAGULATION (contraceptive pill create the same effect; hence, risk for thromboembolism during surgery) In activated state Increased concentrations of all clotting factors, except XI & XIII Percentage of high molecular weight fibrinogen is unchanged resulting to increase ESR Clotting time same Platelet count decreases slightly due to hemodilution but may also be due to increased platelet consumption hence greater proportion of younger, larger platelets Thromboxane A2 which induces platelet aggregation progressively increases Fibrinolytic activity reduced due to increased plasminogenactivator inhibitors Antithrombin levels are constant. REGULATORY PROTEINS Inhibitors of coagulation decreased during pregnancy SPLEEN Enlarge by 50 %
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Physiologic OB Maternal Physiology II

Dr. Rebecca Brillantes CHAPTER 5
CARDIOVASCULAR SYSTEM Most important changes in cardiovascular function occur in 1st 8 weeks of pregnancy CO as early as 5th week HR & systemic vascular resistance Ventricular performance influenced by systemic vascular resistance & changes in pulsatile arterial flow Vascular Capacity: d/t vascular compliance d/t restructuring of bv walls Systemic Vascular resistance + increased HR = increased CO preload due to plasma volume at 10 to 20 weeks Resting pulse rate by 10 beats/min Unchanged
CVS Cardiac Output HR Systemic Vascular Resistance Vascular Capacity Vascular Compliance Preload Plasma Volume Arterial BP RAAS PGE2 PGI2 ANP
HEART Diaphragm progressively elevated Displaced to the left & upwards & rotated on its long axis CXR: Increase in size of cardiac silhouette in radiographs Heart apex is moved somewhat laterally from its usual position d/t elevated of diaphragm displaces heart to the left & upwards on its axis With some degree of BENIGN PERICARDIAL EFFUSION adding to increase silhouette (difficult to identify moderate cardiomegaly) ECG: slight L axis deviations Why do you think this is a physiologic phenomenon in a pregnant patient? Its not pathologic d/t alteration and rotation of the heart On ECG, you can pick it up b/c there is a slight left axis deviation Altered cardiac sounds: Murmurs: NORMAL or does not necessarily point out as cardiac pathology especially when auscultating by the chest or breast, you might end up auscultating the vein and mistake it as murmurs. Exaggerated splitting of S1 w/ loudness of both components No definite changes in the aortic & pulmonary elements of the S2 Loud, easily heard S3 90% Systolic murmur heard thats intensified during inspiration or expiration & disappears shortly after delivery 20% Soft Diastolic Murmur 10% Continuous Murmurs arising from breast vasculature Little change in inotropic state of the myocardium Greater CO in Multifetal pregnancies because of greater stroke volume & HR Sustained cardiac changes similar to acute changes in moderate to strenuous exercise Normal pregnancy: arterial blood pressure & vascular resistance while basal metabolic rate
CO in late pregnancy higher in lateral recumbent position than supine, increase is lost soon after delivery IMPORTANT: Blood flow in the legs is retarded with tendency toward stagnation of blood in the lower extremity leading to: dependent edema varicose veins haemorrhoids. Supine hypotensive syndrome: large pregnant uterus compresses venous system that returns blood from the lower half of the body causing arterial hypotension. All components of the renin-angiotensin-aldosterone system important in blood pressure maintenance are angiotensinogen production in fetal & maternal liver are a result of estrogen level during pregnancy Normal nulliparas who remained normotensive were refractory to the pressor effects of Angiotensin II, those destined to be hypertensive lose this refractoriness CARDIAC NATRIURETIC PEPTIDES ANP: non preganant range despite plasma volume; ANP-induced physiological adaptations participate in the expansion of plasma volume BNP CNP PROSTAGLANDINS Increased PG serves to control vascular tone, blood pressure & Na balance PG E2: elevated, presumed natriuretic PGI2: increased Prostacyclin (PGI2), the principal prostaglandin of endothelium, also is increased during late pregnancy and regulates blood pressure and platelet function. Implicated in the angiotensin resistance characteristic of normal pregnancy. Ratio of PGI2 to thromboxane in maternal urine and blood has been considered important in the pathogenesis of preeclampsia ENDOTHELINS Endothelin-1: potent vasoconstrictor produced in endothelial & vascular smooth mm cells & regulates local vasomotor tone Production is influenced by: angiotensin II AVP Thrombin Influence secretion of: ANP Aldosterone catecholamine Endothelin receptors present in pregnant & nonpregnant myometrium Vascular sensitivity to endothelin-1 is not altered during normal pregnancy Identified in: Amnion amniotic fluid decidua placental tissue NITRIC OXIDE Potent vasodilator released by endothelial cells Important for modifying vascular resistance during pregnancy Abnormal NO synthesis has been linked to the development of PREECLAMPSIA PREGNANCY INDUCED HYPERTENSION: usually comes in during 2nd trimester Circulation & BP BP is lower in lateral recumbent than supine In supine position: femoral venous pressure rises steadily, venous flow in the legs is retarded
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Tendency toward stagnation of blood in the LE d/t occlusion of pelvic veins & IVC thus: Dependent edema Varicose veins in legs & vulva Haemorrhoids DVT SUPINE HYPOTENSIVE SYNDROME Large pregnant uterus compress venous system that returns blood from the lower half of the body causing arterial hypotension Uterine arterial pressure decreased > blood flow decreased > fetal HR pattern Also occurs in Hge & spinal anesthesia RAAS Intimately involved High level of estrogen: angiotensinogen production by maternal & fetal liver RESPIRATORY TRACT Diaphragm rises 4 cm Subcostal angle widens as transverse diameter of thoracic cage increases ~ 2 cm Thoracic circumference about 6 cm but not significantly to prevent a reduction in the residual lung volume created by elevated diaphragm Increased in RMV is caused by: Enhanced respiratory drive d/t stimulatory effect of progesterone Low expiratory reserve volume Compensatory respiratory alkalosis ACID-BASE EQUILIBRIUM Acid-Base Equilibrium Desire to breathe PCO2 Plasma HCO3 Blood pH 2,3 DPG (compensatory)
Unchanged
PULMONARY FUNCTION Pulmonary FUNCTION Respiratory rate Tidal Volume Resting Minute ventilation FRC Residual Volume Peak expiratory flow rate Lung Compliance Airway Conductance Total Pulmonary Resitance Maximum Breathing Capacity Forced or Timed Vital Capacity Oxygen Requirements Critical Closing Volume
Unchanged
Increased awareness of a desire to breath interpreted as dyspnea, w.c may suggest pulmonary or cardiac abnormalities when none exist: PHYSIOLOGIC DYSPNEA d/t tidal volume that lowers PCO2 slightly, w/c paradoxically causes dyspnea induced largely by progesterone & to a lesser degree by estrogen PROGESTERONE Act centrally, lowers the threshold & the sensitivity of the chemoreflex response to CO2 Progesterone (estrogen) centrally threshold & sensitivity of chemoreflex response to CO2 (resetting of sensitivity to CO2) TV (d/t greater diaphragmatic excurtion) physiologic dyspnea (paradoxic: want to breathe some more) blood PCO2 (respiratory alkalosis) HCO3 BOHR effect but is counter acted by 2,3 DPG w/c cause release of O2 Aids CO2 transfer from fetus to mother & O2 release to fetus Bohr effect: shift to the left d/t increased affinity of maternal Hgb for O2 thereby decreasing the O2 releasing capacity of maternal blood Increased 2,3 DPG in maternal erythrocytes counteracts the Bohr effect, facilitating O2 release of the fetus. Respiratory Disease become more serious during Gestation GASTROINTESTINAL TRACT & ACCESSORY ORGANS
GIT Gastric Emptying Time (pregnancy) Gastric Emptying Time (labor) Lower Esophageal Sphincter Tone Intraesophageal Pressure Intragastric Pressure Esophageal Peristalsis wave speed & amplitude
Unchanged
Functional residual capacity & residual volume decreased as a consequence of the elevated diaphragm Peak expiratory flow rates decline progressively w/ increased AOG Total pulmonary resistance d/t progesterone
OXYGEN DELIVERY Unchanged
Oxygen delivery Amount of Oxygen Delivered into the Lungs Total Hgb Mass Total O2-carrying capacity CO Maternal Arteriovenous O2 Difference
Appendix displaced upward & laterally & can reach the right flank Gastric emptying time unchanged except after analgesia at labor MAJOR DANGER: regurgitation & aspiration of either food-laden or highly acidic gastric contents Pyrosis (heartburn) d/t reflux of acid secretions into the lower esophagus Contributing Factors: altered position of the stomach lower esophageal sphincter tone intraesophageal pressure intragastric pressure esophageal peristaltic wave speed & amplitude Epulis: focal highly vascular swelling of gums rendering them hyperaemic, softened & bleed when mildly traumatized,; spontaneously regress after pregnancy Hemorrhoids: caused by constipation & elevated pressure in veins below the uterus.
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LIVER Total serum alkaline phosphate activity almost doubles mostly d/t heat stable placental alkaline phosphatase isoenzymes Decrease in serum albumin to 3.0 (N: 4.3g/dL) Decrease albumin-globulin ratio similar to that seen in hepatic diseases Leucine Aminopeptidase is usually increased in liver disease but is normally increased in pregnancy Unchanged RENAL FUNCTION Renal Function Serum Creatinine Creatine Clearance Bile cholesterol saturation
Unchanged
LIVER Liver Size Hepatic Blood Flow Portal Vein Diam Alkaline Phosphatase AST ALT GGT Bilirubin Serum Albumin Total Albumin Serum Globulin Leucine Aminopeptidase GALLBLADDER GALLBLADDER Contractility Residual Volume Bile cholesterol saturation
Unchanged
reduced contractility leads to stasis hence increased prevalence of gallstones especially in multigravids Progesterone GB contraction by inhibiting cholecystokinin-mediated smooth muscle stimulation w/c is the primary regulator of GB contraction Propensity to retained bile salts causing pruritus gravidarum Intrahepatic Cholestasis linked to circulating estrogen w/c inhibit intraductal transport of bile acids
URINARY SYSTEM KIDNEY KIDNEY Size GFR Renal Plasma Flow
early
Unchanged
late
Slight increase in kidney size: 1.5 cm longer GFR 25% by 2nd week after conception & 50% by 2nd trimester ~ 60% of women report urinary frequency Along w/ renal plasma flow, it is mediated by relaxin & neuronal NO synthase Kallikrein tissue protease synthesized in cells of the distal renal tubule increased in several conditions associated with increased glomerular perfusion in nonpregnant individuals increased urinary kallikrein excretion rates in women at 18 and 34 weeks, but excretion returned to nonpregnant levels by term. Late in pregnancy, urinary flow and sodium excretion average >1/2 the excretion rate in the supine position compared with that in the lateral recumbent position. The impact of posture on glomerular filtration and renal plasma flow is much more variable LOSS OF NUTRIENTS Amino acids & water-soluble vitamins are lost in the urine in much greater amounts
SERUM CREATININE: 0.7 to 0.5mg/dL If 0.9 mg/dL, it suggests underlying renal disease Creatinine Clearance 30% than the 100-115 mL/min in nonpregnants Estimate renal function During the DAY: accumulate water as DEPENDENT edema During the NIGHT: mobilization of fluid: nocturia Urine is more dilute than nonpregnant Failure to excrete concentrated urine after 18 hrs of withholding fluids does not signify renal damage URINALYSIS GLUCOSURIA: Not necessarilty abnormal but should not be ignored d/t GFR & Impaired tubular reabsorptive capacity for filtered glucose PROTENURIA: slight amounts during or soon after vigorous labor albumin excretion from 5 to 30 mg/day, can also increase w/ preeclampsia HEMATURIA: Often Suggest UTI Common after difficult labor & delivery URETERS Ureteral dilatation greater on the right side in 86% d/t cushioning of sigmoid on (L) ureter greater compression on right ureter as the consequence of dextrorotation of the uterus dilated R ovarian vein complex lying obliquely over R ureter dilatation likely d/t Progesterone Elongation accompanies dilatation & is often thrown into curves: KINKS BLADDER Bladder trigone elevated & thickening of the posterior or intrauterine margin d/t uterine size Hyperaemia that affects all pelvic organs Hyperplasia of the bladders mm & CT Urinary Bladder Unchanged Mucosa Blood vessels Bladder Bladder Capacity Urethral length Intraurethral Pressure Bladder pressure (8 cm H2O to 20 cm H2O) w/c is assessed via URETHROCYSTOMETRY Urethral length to compensate for reduced bladder capacity Maximal intraurethral pressure increased from 70 to 93 cm H2O, and thus continence is maintained. Half of women experience some degree of urinary incontinence by the third trimester w/c is always considered in the differential diagnosis of ruptured membranes. Toward the end of pregnancy in nulliparas, entire base of the bladder is pushed forward and upward, converting the normal convex surface into a concavity. The pressure of the presenting part impairs the drainage of blood and lymph from the bladder base, often rendering the area edematous, easily
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traumatized, and probably more susceptible to infection. total triiodothyronine (T3) is more pronounced up to 18 weeks, and thereafter, it plateaus. Thyroid-releasing hormone (TRH) levels are unchanged during normal pregnancy, but this neurotransmitter does cross the placenta and may serve to stimulate the fetal pituitary to secrete thyrotropin Approximately a third of women experience relative hypothyroxinemia, preferential T3 secretion, and higher, albeit normal, serum thyrotropin levels. Thus, there may be considerable variability in thyroidal adjustments during normal pregnancy. Human Chorionic Gonadotropin (hCG) alpha-subunits of the two glycoproteins are identical beta-subunits, although similar, differ in their amino acid sequence. d/t structural similarity, hCG has intrinsic thyrotropic activity, and thus, high serum levels cause thyroid stimulation. thyrotropin levels in more than 80 % of pregnant women, whereas they remain in the normal range for nonpregnant women Normal suppression of TSH during pregnancy may lead to a misdiagnosis of subclinical hyperthyroidism. Of greater concern is the potential failure to identify women with early hypothyroidism because of suppressed TSH concentrations. basal metabolic rate progressively during normal pregnancy by as much as 25 %, most of this in oxygen consumption can be attributed to fetal metabolic activity. If fetal body surface area is considered along with that of the mother, the predicted and observed basal metabolic rates are similar to those in nonpregnant women. PARATHYROID GLAND The regulation of calcium concentration is closely interrelated to magnesium, phosphate, parathyroid hormone, vitamin D, and calcitonin physiology. All markers of bone turnover increased during normal pregnancy and failed to reach baseline level by 12 months postpartum. calcium needed for fetal growth and lactation may be drawn at least in part from the maternal skeleton. Parathyroid Hormone and Calcium Acute or chronic in plasma calcium or magnesium stimulate the release of parathyroid hormone in calcium and magnesium suppress parathyroid hormone levels. The action of this hormone on bone resorption, intestinal absorption, and kidney reabsorption is to extracellular fluid calcium and phosphate. Parathyroid hormone plasma concentrations st during the 1 trimester and progressively throughout the remainder of pregnancy. levels likely result from the lower calcium concentration in the pregnant woman w/c is the result of: plasma volume glomerular filtration rate maternal-fetal transfer of calcium Ionized calcium is only slightly, suggest that during pregnancy a new "set point" is established for ionized calcium and parathyroid hormone. Estrogens also appear to block the action of parathyroid hormone on bone resorption, resulting in another mechanism to increase parathyroid hormone during pregnancy physiological hyperparathyroidism of pregnancy, likely to supply the fetus with adequate calcium. Calcitonin and Calcium
ENDOCRINE SYSTEM PITUITARY GLAND Enlarges to 135% Can compress the optic chiasma & reduce visual fields Decreased calcium & magnesium stimulates increase in parathyroid Maternal pituitary gland is not essential for maintenance of pregnancy GROWTH HORMONE produced by maternal pituitary as well as by the placenta, GH in fetal circulation is not a major regulator of fetal growth: placental GH correlates more to fetal growth rate PROLACTIN markedly increased; 150 ng/mL at term decrease after delivery even in breastfeeding women pulsatile bursts occur in response to suckling estrogen stimulation increases the number of anterior pituitary lactotrophs and may stimulate their release of prolactin Thyroid-releasing hormone also acts to cause an increased prolactin level in pregnant compared with nonpregnant women, but the response decreases as pregnancy advances Serotonin also is believed to increase prolactin Dopaminepreviously known as prolactininhibiting factorinhibits its secretion. Principal function: ensure lactation. Early in pregnancy, prolactin acts to initiate DNA synthesis and mitosis of glandular epithelial cells and presecretory alveolar cells of the breast. Prolactin also increases the number of estrogen and prolactin receptors in these cells. Prolactin promotes mammary alveolar cell RNA synthesis, galactopoiesis, and production of casein, lactalbumin, lactose, and lipids Prolactin is present in amnionic fluid in high concentrations Levels of up to 10,000 ng/mL are found at 20 to 26 weeks. Decrease and reach a nadir after 34 weeks. Uterine decidua is the site of prolactin synthesis found in amnionic fluid Prolactin impairs water transfer from the fetus into the maternal compartment, thus preventing fetal dehydration. THYROID GLAND Thyroidal stimulatory factors of placental origin produced in excess production of thyroid hormones by 40 to 100 % to meet maternal and fetal needs Undergoes moderate enlargement during pregnancy caused by glandular hyperplasia and vascularity. Mean thyroid volume from 12 mL in the 1st trimester to 15 mL at delivery. 1st trimester: principal carrier proteinthyroxine-binding globulin: & reaches its zenith at about 20 weeks stabilizes at approximately double baseline values for the remainder of pregnancy. d/t estrogen Total serum thyroxine (T4) sharply beginning 6 and 9 weeks and reaches a plateau at 18 weeks. Free serum T4 levels slightly and peak along with hCG levels, and then they return to normal.
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The calcitonin-secreting C cells are derived embryologically from the neural crest and are located predominantly in the perifollicular areas of the thyroid gland. Calcium and magnesium increase the biosynthesis and secretion of calcitonin. Various gastric hormonesgastrin, pentagastrin, glucagon, and pancreozyminand food ingestion also increase calcitonin plasma levels. actions oppose those of parathyroid hormone and vitamin D to protect skeletal calcification during times of calcium stress. Pregnancy and lactation cause profound calcium stress, and during these times, calcitonin levels are appreciably higher than those in nonpregnant women Vitamin D and Calcium After its ingestion or synthesis in the skin, vitamin D is converted by the liver into 25hydroxyvitamin D3. This form then is converted in the kidney, decidua, and placenta to 1,25-dihydroxyvitamin D3, serum levels of which are increased during normal pregnancy. Although its control is unclear, the conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 is facilitated by parathyroid hormone and by low calcium and phosphate plasma levels and is opposed by calcitonin. ADRENAL GLANDS In normal pregnancy, the maternal adrenal glands undergo little, if any, morphological change. Cortisol The serum concentration of circulating cortisol is increased, but much of it is bound by transcortin, the cortisol-binding globulin. The rate of adrenal cortisol secretion is not increased, and probably it is compared with that of the nonpregnant state. The metabolic clearance rate of cortisol, however, is lower during pregnancy because its half-life is nearly doubled over that for nonpregnant women Administration of estrogen, including most oral contraceptives, causes changes in serum cortisol levels and transcortin similar to those of pregnancy During early pregnancy, the levels of circulating corticotropin (ACTH) are reduced strikingly. As pregnancy progresses, the levels of ACTH and free cortisol rise. Higher free cortisol levels observed in pregnancy are the result of a "resetting" of the maternal feedback mechanism to higher levels.In response to elevated progesterone levels during pregnancy, an elevated free cortisol is needed to maintain homeostasis. Aldosterone As early as 15 weeks, the maternal adrenal glands secrete considerably increased amounts of aldosterone. third trimester, about 1 mg/day is secreted. If sodium intake is restricted, aldosterone secretion is elevated even further renin and angiotensin II substrate normally are increased, especially during the latter half of pregnancy. This scenario gives rise to increased plasma levels of angiotensin II, which by acting on the zona glomerulosa of the maternal adrenal glands, accounts for the markedly elevated aldosterone secretion. increased aldosterone secretion during normal pregnancy affords protection against the natriuretic effect of progesterone and atrial natriuretic peptide. Deoxycorticosterone Maternal plasma levels of this potent mineralocorticosteroid progressively increase during pregnancy. plasma levels of deoxycorticosterone rise to near 1500 pg/mL by term, a more than 15-fold increase marked elevation is not derived from adrenal secretion but instead represents increased kidney production resulting from estrogen stimulation. The levels of deoxycorticosterone and its sulfate in fetal blood are appreciably higher than those in maternal blood, which suggests transfer of fetal deoxycorticosterone into the maternal compartment. Dehydroepiandrosterone Sulfate Maternal serum and urine levels of dehydroepiandrosterone sulfate are decreased during normal pregnancy. consequence of increased metabolic clearance through extensive maternal hepatic 16 alphahydroxylation and placental conversion to estrogen. Androstenedione and Testosterone Maternal plasma levels of both of these androgens are increased during pregnancy. Maternal plasma androstenedione and testosterone are converted to estradiol in the placenta, which increases their clearance rates. plasma sex hormone-binding globulin in pregnant women retards testosterone clearance. production rates of maternal testosterone and androstenedione during human pregnancy are increased. source of this increased C19-steroid production is unknown, but it likely originates in the ovary. little or no testosterone in maternal plasma enters the fetal circulation as testosterone. Even when massive testosterone levels are found in the circulation of pregnant women, as with androgen-secreting tumors, testosterone levels in umbilical cord blood are likely to be undetectable and are the result of the near complete trophoblastic conversion of testosterone to 17 beta-estradiol
MUSCULOSKELETAL SYSTEM compensatory lordosis shifts the center of gravity back over the lower extremities Sacroiliac, sacrococcygeal & pubic joints have increased mobility contributing to alteration in posture, in turn to lower back discomfort Aching, numbness & weakness in the upper extremities result from marked lordosis with anterior neck flexion & slumping of the shoulder girdle causing traction on ulnar & median nerve Relaxation of pelvic bones & ligaments particularly the Symphysis pubis. EYES Intraocular pressure decreases due to increased vitreous outflow Corneal sensitivity decreases greatest changes are late in gestation. Most pregnant women demonstrate a measurable but slight increase in corneal thickness, thought to be due to edema. may have difficulty with previously comfortable contact lenses. Brownish-red opacities on the posterior surface of the corneaKrukenberg spindles Hormonal effects similar to those observed for skin lesions are postulated to cause this increased pigmentation. transient loss of accommodation reported with both pregnancy and lactation, visual function is unaffected by pregnancy.
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CNS Transient pregnancy related memory decline seen in the 3 rd trimester Difficulty going to sleep, frequent awakenings, fewer hours of sleep, reduced sleep efficiency Greatest sleep disruption occurs post-partum and may contribute to pospartum blues.
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CHAPTER 6
PARTURITION Phases of Parturition

PARTURITION Bringing forth of the young Divided into 4 overlapping phases that correspond to the major physiological transitions of the myometrium & cervix PHASE 1: Uterine Quiescence PHASE 2: Uterine Activation PHASE 3: Uterine Stimulation PHASE 4: Uterine Involution NOTE: PHASES of Labor should not be confused with CLINICAL STAGES of labor which is PHASE 3 of parturition. Enhance extracellular matrix changes that allow progressive in tissue compliance to allow preparation for birth What else is in the endocervical canal? Mucous Plug functions for protection Cervical softening: Characterized by in tissue compliance yet cervix remains firm & unyielding HEGAR Sign: palpable softening of the lower uterine segment at 4-6 weeks gestation used to diagnose pregnancy Structural changes vascularity, stromal hypertrophy, glandular hypertrophy and hyperplasia and structural changes in the extracellular matrix Slow progressive turnover of matrix components i.e. Hyaluronic acid Physiological softening is preceded by an in collagen solubility cross-linking of newly synthesized collagen may aid cervical softening because transcripts & activity of the cross-linking enzyme, lysyl oxidase Cervical shortening b/w 14-24 weeks associated w/ risk of preterm Cervix remains firm and unyielding: Essential for a successful parturition CONSISTENCY: Nonpregnant: cervix is firm & closed w/ consistency similar to the nasal cartilage Pregnant: cervix is easily distensible w/ consistency similar to the lips of the oral cavity Preterm delivery if with: Cervical dilatation Structural incompetence
PHASE 1 OF PARTURITION: UTERINE QUIESCENCE & CERVICAL SOFTENING prelude to labor Beginning even before implantation Period of myometrial quiescence is imposed. 95 % of pregnancy Characterized by uterine smooth muscle tranquility with maintenance of cervical structural integrity. Uterine muscle is rendered unresponsive to natural stimuli Concurrently, the uterus must initiate extensive changes in its size and vascularity to accommodate the pregnancy and prepare for uterine contractions in phase 3 of parturition. Myometrial unresponsiveness of phase 1 continues until near the end of pregnancy. During ovulation the uterus will have to contract to propel the sperm up the fallopian tubes During the menstrual phase, the uterus has to contract to bring out all of those menstrual debris, but during pregnancy it cannot contract Clinical term of expelling fetus? Miscarriage, abortion. Uterine changes: Uterine muscle unresponsive to natural stimuli Changes in size and vascularity to accommodate the pregnancy Some contractions may occur but do not cause cervical dilatation What do you call those contractions: Braxton Hicks contractions irregular contractions you feel during pregnancy but do not cause cervical dilatation CHARACTERISTICS: Irregular Unpredictable Low intensity Brief duration Discomfort is usually confined to lower abdomen or groin Near term, contractions becomes more common & is referred to as Braxton Hicks or False Labor Cervical changes: Myometrium must be able to stretch BUT remain quiescent Is the size of watermelon Cervix during pregnancy has multiple functions: Barrier: protect reproductive tract from infection Maintenance of cervical competence despite increasing gravitation forces imposed by the expanding uterus (the weight of the fetus)
PHASE 2 OF PARTURITION: UTERINE ACTIVATION & CERVICAL RIPENING preparation for labor uterine awakening or activation progression of uterine changes during the last 6-8 weeks of pregnancy Cervical changes: Changes in the connective tissue: collagen breakdown & rearrangement of collagen bundles due to an increase in dermatan sulphate hyaluronic acid in the cervix cytokines Cervical ripening: Cervical thinning Cervical softening Cervical relaxation Allow cervical yielding & dilatation upon initiation of forceful uterine contractions in the 3rd phase of parturition Transition from softening to ripening begins weeks or days before onset of contractions What initiates cervical changes: Prostaglandins PGE2 PGF2alpha progesterone Endocervical Epithelia Cells proliferate in such a way that endocervical glands occupy a significant percentage of cervical mass by the end of pregnancy Endocervical canal is lined w/ mucus-secreting columnar & stratified squamous epithelia w/c protect against microbial invasion
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Mucosal epithelia function as antigens, respond in ways that lead to bacterial & viral killing & signal to underlying immune cells when pathogenic challenge exceeds their protective capacity Aid in cervical remodeling by regulating tissue hydration & maintenance of barrier function Hydration may be regulated by expression of aquaporins w/c are water channel proteins Paracellular transport of ions & solutes & maintenance of barrier function is regulated by tight junction proteins: CLAUDINS 1 & 2 Cervical Connective Tissue Cervix is made of: Smooth muscle: 10-15% Extracellular CT: Type I, III, & IV collagen Glycosaminoglycans Proteoglycans Elastin Collagen Major component of the cervix: Type I, III, IV Responsible for its structural disposition of the cervix Most abundant mammalian protein Multiple collagen triple-helical molecules are cross-linked to one another by the actions of lysyl oxidase to form long fibrils Collagen fibrils interact w/ small proteoglycans suc as decorin or biglycan, as well as matricellular proteins like thrombospondin 2 Interactions determine fibril size, packing, & organization so collagen fibrils are uniform diameter & are packed together in a regular & highly organized pattern During cervical ripening, collagen fibrils are disorganized, & there is increased spacing b/w fibrils Matrix Metalloproteinases (MMPs) proteases capable of degrading ECM proteins Collagenase Member of MMP family that degrade collagen Collagen Solubility: a marker of less mature collagen collagen solubility early in the cervical softening phase & continues for the remainder of the pregnancy Glycosaminoglycans High molecular weight polysaccharide Contain amino sugars & can form complexes w/ proteins to form proteoglycans Hyaluronan (HA) Carbohydrate polymer whose synthesis is carried out by hyaluronan synthase isoenzymes Expression is in the cervix during ripening Function is dependent on size & the breakdown of LMW HA to SMW products is carried out by hyaluronidases LMW HA: creates & fills space to viscoelastic & matrix disorganization proinflammatory properties connexin 43 uterine irritability & responsiveness to uterotonins w/c are agents that stimulate contractions Formation of the lower uterine segment from the isthmus (becomes thin and stretches) Leading to lightening Fetal head often descends to or even through the pelvic inlet as the lower uterine segment forms Abdomen changes in the shape the baby dropped Inflammatory changes Marked changes w/in the ECM during cervical ripening are accompanied by stromal invasion w/ inflammatory cells Cervical chemoattractants attract inflammatory cells, w/c in turn release proteases that aid in degradation of collagen & other matrix components Phase 3 & 4 of parturition, there is cervical expression of chemokines & collagenase/ protease activity Activation of neutrophils, proinflammatory M1 macrophages, & alternatively, activated M2 macrophages is w/in 2 hours after birth, suggesting a role for inflammatory cell in postpartum cervical remodeling Induction & Prevention of Cervical Ripening Therapies to promote cervical ripening for labor induction include direct application of PGE2 & PGF2a These modify collagen & alter relative glycosaminoglycan concentrations This property is useful clinically to aid labor induction Administration of progesterone antagonists causes cervical ripening
PHASE 3 OF PARTURITION: CERVICAL DILATATION & EFFACEMENT Process of labor or active labor Has 3 stages STAGE 1: Uterine Contraction & Cervical Dilatation
Proteoglycans Glycoproteins found in abundance in the cervix Changes in proteoglycan composition w/in cervical matrix accompanies cervical ripening Myometrial changes: From occasional painless contractions to frequent forceful contractions Contraction associated proteins Oxytocin Receptors PGF receptors Connexin 43: number & surface areas of myometrial cell gap junction Myometrial oxytocin receptors remarkably along w/ in numbers & surface area of gap junction proteins
STAGE 2: Fetal Descent & Delivery STAGE 3: Delivery of Placenta STAGE 1: STAGE OF CERVICAL EFFACEMENT & DILATATION Uterine contractions that bring about progressive cervical dilatation and delivery Characteristics of the first stage of labor: Bloody show Extrusion of mucus plug that heralds the initiation of labor mucus plug that previously fills the cervical canal during pregnancy passage indicates that labor is in progress or will ensue in hours or days not all women will experience this timing is VARIABLE and NOT FIXED. Characteristic uterine contractions Pregnant women will feel pain Rupture of bag of water Formation of distinct lower & upper uterine segments
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2 FUNDAMENTAL CERVICAL changes during 1st Stage of Labor CERVICAL Effacement: Obliteration or taking up of the cervix Mm fiber at the level of internal cervical os are pulled upward, or taken up, into the lower uterine segment cervical thinning brought about by widely spaced uterine contractions of sufficient frequency, intensity & duration Shortening of the cervical canal from 2 cm to paper thin Causes expulsion of the mucus plug as the cervical canal is shortened CERVICAL Dilatation: Stage ends when cervix is fully dilated: 10 cm Due to the centrifugal pull during uterine contraction As uterine contractions cause pressure on the membranes, the hydrostatic action of the amniotic sac in turn dilates the cervical canal into a wedge From undilated, uneffaced cervix partly dilated, partly effaced (start to see babies head) fully dilated, fully effaced The process of cervical dilatation & effacement causes the formation of the FOREBAG of amniotic fluid Leading portion of the amniotic sac & fluid located in front of the presenting part CHARACTERISTIC UTERINE CONTRACTIONS Causes of pain: Hypoxia of the contracted myometrium Compression of the nerve ganglia of the cervix and lower uterus Stretching of the cervix: FERGUSON REFLEX (remember this) Stretching of the peritoneum: this will also cause pain Contractions: Starts at about 10 minutes interval to 1 minute or less Periods of rest are essential for fetal welfare. Unremitting contractions compromise uteroplacental blood flow sufficiently to cause fetal hypoxemia Mechanical stretching of the cervix enhances uterine activity: Ferguson reflex Manipulation of the cervix & stripping the fetal membranes is associated w/an in blood levels of PGF2a metabolite w/c stimulates uterine contraction Formation of the lower & upper uterine segment: Actively contracting part: UPPER segment Firm & hard on palpation For baby to pass birth canal it has to be pushed downward: b/c it has to go through the pelvis: so if you have the entire uterus contracting at the same time: will you have a net force of baby coming out? No, baby will stay inside the uterus. Hence, need a net force to push baby downward. Lower segment will have to accept the baby as it comes down. Contracts & Retracts to Expel the fetus Does not relax to original length; Hence, becomes THICKER Contractions causes the lower segment to thin out & the cervix to dilate thereby form a greatly expanded, thinned-out tube through w/c fetus can pass Contracts down on its diminishing contents but myometrial tension remains constant w/ net effect to take up slack, thus maintaining the advantage gained in the expulsion of the fetus d/t the successive shortening of mm fibers, the upper segment becomes progressively thickened throughout the 1st & 2nd stage of labor. Inactive lower part: LOWER segment Softer, distended & more passive Result of the thickening and thinning of the uterine segments: Physiologic retraction ring A marked ridge or boundary formed as a result of the lower segment thinning & concomitant upper segment thickening. Pathologic retraction ring: BANDL Ring Occurs when the thinning of the lower segment is extreme Occurs in OBSTRUCTED LABOR Changes in uterine shape during labor: Causes elongation of the uterus with decrease in horizontal diameter Straightening of the vertebral column causes better pressure on the baby: fetal axis pressure As baby lengthens the baby goes down and vertebral column becomes longer Longitudinal fibers are drawn taut causing the lower segment to be pulled over the lower pole of the fetus cervical dilatation The lower segment & the cervix are the only parts that are flexible & are pulled upwards & around the lower pole of the fetus 2 PHASES of Stage 1 Stage of Labor Latent phase: 0-8 hours Variable duration Sensitive to extraneous factors Little bearing on course of labor This phase is almost flat in the curve: from zero to 2 cm. Sensitive to extraneous factors: so if you give anesthesia, contractions can go away. No matter how long the latent phase is, there is no bearing on how fast the labor will be. Active phase: 8-14 hours Duration: 30 to 90 seconds Average: 1 minute Amniotic fluid pressure average: 40 mm Hg (Range: 20-60 mmHg) Interval shortens and duration lengthens and duration of contractions becomes longer and intensity increases: characteristic pain will start Women starting labor will have a characteristic pain in hypogastric area and transfer to lumbar sacral area Starts in the acceleration phase + phase of maximum slope + deceleration phase Predictive of labor outcome: So anything that is different from this curve is abnormal and this is called dystocia: and instead of vaginal delivery, you will do a cesarian section. Dilatation is accomplished by cervical retraction 3 DIVISIONS of Stage 1 Stage of Labor: PREPARATORY DIVISION: is 0 to 10 hour (will have both latent and acceleration phase) Latent Phase: 0-8th hour Acceleration Phase: 8-10th hour This will be used to monitor progress of labor by using friedmans labor curve PHASE OF MAXIMUM SLOPE: 10-12th hour aka dilatational division PELVIC DIVISION: 12-16th hour from deceleration phase till 2nd stage of labor STAGE 2: STAGE OF FETAL EXPULSION After full cervical dilatation: 10 cm Begins with full cervical dilatation and ends with expulsion of the fetus Ancillary FORCES in labor
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MATERNAL INTRA-ABDOMINAL PRESSURE After full cervical dilatation, it is the most important force in fetal expulsion PUSHING Contraction of abdominal muscles simultaneous w/ respiratory efforts w/ closed glottis Nature of the force is similar to defecation but w/ much higher intensity Accomplishes little during the 1st stage of labor & will just exhaust the mother & the intrauterine pressures may be harmful to the fetus Useful during 2nd stage of labor Fetal descent: Typically follows a hyperbolic curve when plotted Onset usually occurs it the maximum slope Speed of descent increase to maximum It starts to have a rapid change at maximum slope: so onset will usually occur in the maximum slope HYPERBOLIC CURVE descent pattern of normal labor formed when the station of the fetal head is plotted as a function of labor duration STATION Describes descent of the fetal biparietal diameter in relation to a line drawn b/w maternal ischial spines NULLIPARA rate of descent are observed ordinarily during cervical dilatation phase of maximum slope full cervical dilatation STATION: (+) 4 plot onto friedmans curve: for cervical dilatation: put a small circle and for fetal head descent use an X Compare the graph of the patient to the friedmans curve. If it looks similar: labor is normal progression deliver vaginally. CASE 2: dystocia IE findings AFTER 13th hour: Still 7 cm dilated station zero IE findings AFTER 14th hour: station 1 Failed fetal descent d/t incomplete cervical dilatation dystocia deliver by CS Changes in the pelvic floor: Stretching of the levator ani muscles Thinning of the central portion of the perineum STAGE 3: STAGE OF PLACENTAL SEPARATION & EXPULSION Delivery of placenta & membranes directly after birth Placenta being born Placental separation is due to a disproportion between the uterine cavity and placental size Ordinarily occurs within a few minutes After fetal delivery, The fundus is normally lies below the level of the umbilicus Separation of the amniochorion: Occurs until the separation of the placenta is complete Peeled off by: Further uterine contraction Traction from the separating placenta Placental extrusion: Separated after uterine contraction Occupies lower uterine segment or upper vagina Expelled by intraabdominal pressure Completion of 3rd stage is accomplished by alternately compressing & elevating the fundus with minimal traction on the umbilical cord Duncan mechanism: Blood from the placental site is able to escape on the periphery of the placenta: Dirty Duncan Starts w/ peripheral separation causing blood to com out. As you pull the placenta further, the placenta inverts and shows you the maternal surface. what is maternal and what is fetal? The fetal surface is covered by two membranes: amnion and chorion: And maternal surface attaches to uterus Schultze mechanism: Blood from the placental site does not escape externally until after expulsion separation starts in the middle where you have central separation so blood stays there and you dont expect a lot of blood to come out until the placenta comes out; hence, you will still see the fetal surface: Shiny Schultze
CASE 1: We admitted a 24 yo primegravid: into the ER and she said that she has been having regular contractions for the past 8 hours. IE findings on admission: normal vital signs, low risk and no problems: CERVIX: 4 cm dilated & 1 cm long STATION: (-) 1 intact bag of waters IE findings AFTER 2 hours of regular intrauterine contractions: CERVIX: 7 cm dilated & 0.5 cm long Cephalic STATION: zero Spontaneous rupture of membranes IE findings AFTER another 2 hours full cervical dilatation STATION: (+) 1 IE findings AFTER another 1 hour
PHASE 4 OF PARTURITION: PEURPERIUM Characteristics of phase 4: Myometrium must be held in a state of rigid and persistent contraction Important to prevent bleeding: the uterus has become vascular, so this keeps blood vessels constricted and prevent postpartum hemorrhage Maternal: infant bonding begins: Start breastfeeding and moving them in your arms for the first time Onset of lactogenesis & milk let down: a/w Prolactin and oxytocin Involution of the uterus within 4 to 6 weeks from a watermelon size back to bell pepper type of uterus
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CHAPTER 6 PARTURITION
Physiological & Biochemical Process Regulating Parturition

FRIEDMANS LABOR CURVE CERVICAL CHANGES: Effacement: Shortening of the cervical canal From 2 cm to paper thin Dilatation: Due to the centrifugal pull during a contraction From close to full dilation (10 cm) Closed cervix open cervix Undilated, uneffaced partly dilated, partly effaced (start to see babies head) fully dilated, fully effaced Dilatation is accomplished by cervical retraction 3 phases: Acceleration phase: predicts the outcome of labor if FLAT: indicates longer labor if STEEP: labor is shorter, cervical dilates slowly Predictive of labor outcome If curve is abnormal: DYTOCIA instead of vaginal delivery, you will do a cesarian section Phase of maximal slope: reflects how powerful the uterine contractions are, steep curve indicates power of the uterus, that is, the uterus is contracting well & cervical dilatation is good, cervix dilates rapidly. End of this slope at 7-8 cm Deceleration of Phase: starts at 7-8 cm cervical dilatation is slowing down however fetal head descent is occurring really quickly where fetal head is going down into the pelvis which starts sometime before the end of maximum slope & occur rapidly at deceleration phase, cervix dilates slowly; fetal head descend 1 cm/ hr in deceleration phase 2nd STAGE OF LABOR: Fetal Decent & Delivery Starts after deceleration phase Sigmoidal Curve: Cervical dilatation From bottom left to top right Parabolic Curve: Fetal Head descent to the pelvis From top left to bottom right 2nd Stage of Labor Typically follows a hyperbolic curve when plotted Onset usually occurs it the maximum slope Speed of descent increase to point of maximum slope where fetal descent starts to have a rapid change CASE #1: 24 y.o. primegravid having regular contractions for the past 8 hours w/ following examination findings 8th hour: normal vital signs no medical problems cervix is 4 cm dilated & 1 cm long STATION -1 intact bag of waters after 2 hours of regular intrauterine contractions: 10th hour cervix 7 cm dilated & 0.5 cm long Cephalic STATION zero spontaneous rupture of membranes/ bag of water after 2 hours: 12th hour full cervical dilatation: 10 cm Station +1 after 1 hour: 13th hour full cervical dilatation: 10 cm station +4 plot onto friedmans curve: LEGEND: cervical dilatation: put a small circle and fetal head descent use an X
Used for active labor X axis: cervical dilatation: 0 to10 cm 10 cm indicates full dilatation Y axis: hours in time, time elapsed from start to end of labor Represents the stages of labor 1st STAGE: Contractions & Cervical Dilation Latent Phase Active Phase Acceleration Phase of Maximum Slope Deceleration Phase 2nd Stage: Fetal Descent & Delivery 3rd Stage: Delivery of Placeta PHASE 3 PARTURITION: 3 Divisions Of Labor
PREPARATORY DIVISION: is 0 to 10 hour (will have both latent and acceleration phase) LATENT PHASE: 0 to 8th hour ACTIVE PHASE (Acceleration Phase): from 8th to 10th hour used to monitor progress of labor and when you monitor progess of labor: you use friedmans labor to see if pt has normal labor or abnormal labor (distortion) DILATION DIVISION: Aka: ACTIVE PHASE (Phase of maximum slope) 10th to 12th hour PELVIC DIVISION: from deceleration phase up until the second stage of labor 12th to 16th hour PHASE 3 PARTURITION: 3 Stages Of Labor 1st STAGE OF LABOR: Contractions & Cervical Dilation & Effacement 0-8 hours: LATENT PHASE take note of cervical dilatation (relatively flat): hence not a lot of cervical dilatation Not always 8 hours, can be shorter or longer Variable duration Sensitive to extraneous factors Sedatives will cause patient to sleep and contractions can go away Anesthesia can cause contractions can go away. No matter how long the latent phase is, there is no bearing on how fast the labor will be. This phase is almost flat in the friedmans curve: from zero to 2 cm 8-14 hours: ACTIVE PHASE Cervical dilation will rise Predictive labor outcome From a closed cervix to a dilated cervix
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start plotting at the 8th hour and for the station you put an X. STATION: babies head is still high at -1at 8th hour then goes down at zero on the 10th hour to +1 at 12th hour & full descent at +4 at 13th hour. On friedmans curve: Curve looks similar; hence, labor is in normal progression: VAGINAL DELIVERY CASE #2: DYSTOCIA. 13th hour: Cervical Dilation: still 7 cm Station zero after 1 hour: 14th hour station 1 Cervical Dilation 7 cm Dystocia: fetal head unable to descend d/t insufficient cervical dilation After full cervical dilatation Begins with full cervical dilatation and ends with expulsion of the fetus Follows hyperbolic curve Speed of descent increases at point of end of maximum slope in active phase Ancillary forces in labor Most important force in the expulsion of the fetus is that produced by MATERNAL INTRAABDOMINAL PRESSURE after the cervix is fully dilated, have the patient push Full cervical dilatation: 10 cm. Dont have mother push unless fully dilated Changes in the pelvic floor: Stretching of the levator ani muscles Thinning of the central portion of the perineum 1st prerequisite to birth is FETAL HEAD DESCENT Begins w/ full cervical dilatation (10cm) & ends w/ expulsion of the fetus Cardinal movement of labor: POSITIONS Assumed INTERNAL ROTATION: Baby internally rotates after fetal head descent such that baby is looking downwards & prone EXTENSION: as baby comes out, when the vagina opens, the babys head extends Suctioning no longer encouraged EXPULSION: Once, babys head is out, be ready coz babys body will follow very quickly; hence, CATCH the baby! DELIVERY of Baby 3rd STAGE OF LABOR: Placental Delivery Uterus shrinks after baby is delivered, placenta follows directly after birth: PLACENTA BEING BORN Fundus shrinks from xiphoid process level to umbilicus which leads to separation of the placenta Placental separation is due to a disproportion between the uterine cavity and placental size Ordinarily occurs within a few minutes Uterine space shrunk, placenta is separated by formation of hematoma at the back Uterus parts: Placenta is attached to the endometrium: Decidua Placenta separates d/t Nitabuchs Layer allowing placenta to separate Placental parts: Maternal surface: has cotyledons attaches towards the uterus Fetal surface: 2 membranes: Amnionic sac lined by: Amnion Chorion Smooth surface that faces towards the fetus Separation of the amniochorion: Occurs until the separation of the placenta is complete: Peeled off by: Further uterine contraction Traction from the separating placenta Placental extrusion: Uterine contraction Increase intraabdominal pressure Compress & elevate the fundus with minimal traction of the umbilical cord 2 ways to deliver Placenta: comes out in ~ 5 minutes after baby is born. If not, its delayed Schultz: Shinny Schultz Hematoma formation in the center No blood will be visualized as it comes out of the vagina Central separation, fetal surface of placenta would be visualized Blood from the placental site does not escape externally until after extrusion Separation starts in the middle; hence, central separation, blood stays there and you dont expect a lot of blood coming out and as you pull the placenta going out, so you will still see the fetal surface. Duncan: Dirty Duncan Separation starts from the side Will see a lot of blood & escapes the vagina Maternal surface is visualized Blood from the placental site is able to escape on the periphery of the placenta you pull the placenta further, the placenta inverts and shows you the maternal surface PHASE 4 PARTURITION: Peurperium Myometrium must be held in a state of rigid & persistent contraction to prevent bleeding uterus has become vascular, so this keeps blood vessels constricted and prevent postpartum hemorrhage Maternal-infant bonding begins via breast feeding Start breastfeeding and holding infant for the first time Onset of lactogenesis & milk letdown Prolactin & Oxytocin respectively Involution of uterus w/in 4 to 6 wks So from a watermelon size to bell pepper sized uterus
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PHYSIOLOGICAL & BIOCHEMICAL PROCESSES REGULATING PARTURITION ANATOMICAL & PHYSIOLOGICAL CONSIDERATIONS OF THE MYOMETRIUM Advantages of uterine smooth mm from striated mms Degree of shortening is greater Force is exerted in any direction Organization is different Multidirectional force is generated allows uterine mm to contract as a whole actin & myosin are arranged randomly; hence force generated is multidirectional & degree of shortening is much greater. Regulation of myometrial contraction & relaxation: What is a CORNU? At the opening of the fallopian tube into the uterus, INTRAMURAL REGION, like the heart having an SA node where the impulse starts, this is where the uterus starts contraction and transmits electrical impulses. It the spreads throughout the uterus and entire uterus will act as one and contract where UPPER SEGMENT contracts forcefully and lower segment relaxes. Remember: Increase in cytoplasmic calcium will cause contraction and decrease calcium will cause relaxation. ACUTE MECHANISM Increased intracellular Ca concentration promote contraction e.g Rho kinase receptor dependent activation Ca promote contraction Ca comes from extracellular or intracellular (Sarcolasmic reticulum) Decreased intracellular Ca concentration cause mm relaxation E.g. increase cAMP & cGMP Myosin will have to stretch, the actin will have to form and they have to interact with each other. Remember your skeletal muscle where you have actin myosin, when muscle contracts: it shortens and direction is linear. But in SMOOTH MUSCLE: its not linear, direction of force is in all directions. So the muscle can contract as a whole & the degree of shortening is greater CHRONIC MECHANISM Thru chronic action of hormones By mediating the transcription of key genes that repress or enhance contraction More Contraction Associated Proteins (CAPS) more contraction Myometrial Gap Junctions Establish electrical synchrony in myometrium More gap junction = more contractions Less gap junctions = means more relaxation Uterotonic stimulatory/inhibitory receptors. Facilitate the passage of electrical/ionic coupling currents Made up of a two protein channel known as CONNEXIN 43 Coordinated contraction = greater force during labor Myometrium is regulated by cell surface receptors 2 FAIL-SAFE SYSTEM IN DIFFERENT PHASES OF PARTURITION KEY HORMONES: Estrogen Progesterone Oxytocin Prostaglandins CRH PHASE I of parturition (Myometrial Quiescence) is likely a result of: Estrogen & progesterone action on intracellular receptors Progesterone: promotes quiescence Inhibit expression of gap junction protein Negates stimulatory effect of estrogen on development of gap junctions Blocks effects of estrogen Has direct/ indirect effects Estrogen: early during pregnancy promote progesterone responsiveness by inducing progesterone receptors synthesis increasing the organs sensitivity to progesterone; hence, more relaxation. Estrogen promotes gap junction proteins. Estrogen normally produces contractions but in phase 1 it promotes progesterone receptor synthesis. So the more receptors you have, the more sensitive a tissue is to progesterone Receptors that promote myometrial relaxation: Beta-adrenoreceptors: Increases cAMP
PHASE II contributions In lower animals withdrawal of progesterone directly precede the progression from phase 1 to phase 2 For labor to start, progesterone level has to drop to bring about onset of labor In humans, progesterone is presumed to establish & maintain Phase I Functional withdrawal of progesterone progesterone will not have an effect anymore d/t: Change or inactivation of progesterone receptors; hence, progesterone is not sensitive to the receptor Posttranslational modifications of the progesterone receptors Changes in the expression of the progesterone receptor Alteration of co-activators/repressors that influence receptor function Local inactivation by steroid metabolizing enzymes/synthesis of a natural antagonist Progesterone receptor antagonists and human parturition RU 486/mifepristone may cause premature menstruation or abortion early in pregnancy If you give RU 486 in the first 3 months will it induce abortion If you only give oxytocin before first 3 months or pregnancy, will it cause abortion? Minimal effect. b/c you only have minimal amount of oxytocin receptors; hence, wont have any effect in Phase I of parturition But less effective in inducing abortion nor labor late in pregnancy. Estrogen promotes progesterone responsiveness Estrogen effects: increase CAPs Oxytocin Receptors Estradiol increases the oxytocin receptors on the cell surface Increased levels will lead to development of uterotonin sensitivity Progesterone increases oxytocin receptor degradation within the cell and inhibits receptor activation on the surface. What is hormone important in Phase 2? Progesterone 38 weeks, Phase 2, oxytocin & estrogen receptors are abundant hence will affect myometrial activity More Gap junction Improved intercellular communicability Alteration in the concentration of cytoplasmic Ca; hence, uterus is now contracting Morphological & functional changes in phase 2 of parturition: Development of uterotonin sensitivity Improved intercellular communicability: secondary to gap junctions Alteration in the concentration of cytoplasmic calcium: increase Ca++ leads to increased myometrial activitity STRETCH & PARTURITION: Fetal contribution to initiation of parturition: Role of uterine stretch in parturition Twin pregnancies are at a higher risk to preterm labor than singleton Preterm labor is increased in hydramnios or big babies
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The bigger stretch of the uterus, earlier contractions will start, i.e. multifetal pregnancy, polyhydramnios. Fetal anomalies & delayed parturition: Hypoestrogenic pregnancy sometimes are associated with prolonged pregnancy: e.g. anencephaly & adrenal hypoplasia Brain & pituitary gland is abnormal leading to adrenal hypoplasia & no production of DHEAs: HYPOESTROGENIC STATE baby has prolonged pregnancy and it proceeds to up to 42 weeks. If you find this in ultrasound early on, 4 to 5 months: do you tell the mom? Yes. So she can be emotionally prepared. Delayed Labor: FETAL ANOMALIES: Anencephaly No skull bones Does not develop fully; hence, no pituitary No ACTH no stimulation of fetal adrenal gland no conversion of DHEAS to estrogen hence no uterine contraction Low levels of estrogen: HYPOESTROGENIC state , delayed labor Fetal endocrine cascades leading to parturition Unique ability of the placenta to produce large amounts of CRH. Early in pregnancy CRH will promote relaxation and Later in pregnancy it promotes contraction Placental-fetal adrenal endocrine cascade: Placental CRH stimulates fetal adrenal to produce: Cortisol & DHEA-S Cortisol stimulates production of placental CRH: (+) feedback Fetal DHEA-S used by placenta to produce placental estrogens. Fetal adrenals and effect on estrogen placental CRH stimulates the fetal pituitary to produce ACTH which stimulate fetal adrenal to produce fetal cortisol and fetal DHEA-S. DHEA-S is a precursor for estrogen during pregnancy. It promotes contraction. So more DHEA-S, means more estrogen produced by placenta, therefore promoting contraction. Fetal cortisol stimulate Trophoblasts to produce more CRH and creates a cycle. PHASE 3 Oxytocin & Parturition REMEMBER: oxytocin & prostaglandins OXYTOCIN 50 fold increase in # of oxytocin receptors increase uterine responsiveness Prolonged gestation associated w/ a delay in the increase of oxytocin receptors Stimulate oxytocin release by stimulating nipples Effective in inducing labor at term Very potent uterotonin Promotes prostaglandin release from decidual tissues. PROSTAGLANDINS Came from decidual tissues & membranes Anything that injures the decidua & bag of waters will promote the release of prostaglandins causing uterine contractions Forebag: bag of water in front of the head that is exposed to the out side (ph changes, trauma) Promote release of prostaglandins Increase levels of cytokines AMNIOTOME: used to rupture bag of water to facilitate release of prostaglandin Increase levels during labor Causes abortion/labor in all stages of pregnancy Inhibitors will delay onset of labor/arrest preterm labor Causes myometrial contraction in vitro. DRUGS: Mesopristol Pg E2 Aka star tablet. High levels of E2 promotes contraction Low levels of E2 promotes relaxation. Dinoprostone Pg and is a gel and softens cervix to promote phase 2 of parturition. Indomethacin an NSAID w/c prevent preterm labor and will block Pg and prevent preterm baby. Uterine events regulating prostaglandin production: Trauma to decidual tissues Devascularisation of decidual fragments Action of vaginal fluid on forebag Vaginal fluid is rich in inflammatory materials i.e. cytokines w/c stimulates the forebag to release prostaglandins & stimulate entire decidua to release Pg causing uterine contractions. PHASE IV- Recovery 2 hormones to remember: Oxytocin: milk let down Prevents postpartum Hge Helps in uterine involution to normal size w/c take 4 -6 wks Maintains the uterus in rigid, persistent contraction -> prevent postpartum Hge Prolactin: lactogenesis Natural family planning Causing a negative feedback of reducing the production of GnRH Natural family planning: lactation amenorrhea method Mechanism: high levels of Prolactin when breastfeeding inibhits GnRH release; hence, FSH and LH will not be released leading to no ovulation: CANT GET PREGNANT
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CHAPTER 8
Prenatal Care I
Dr. Crisostomo Ordono. Jr. MD Probable sign that patient is pregnant During the 1st trimester: growth of uterus is not r/t to progress of pregnancy Doughy/ elastic 20 wks: uterus is found at the level of the umbilicus 6 - 8 wks: Hegar Sign Hegar Sign: when lower part of uterus softens up Uterus size measured by bimanual examination where one hand is pressing on the abdomen while the other is pressing on the cervix During pregnancy, the lower part of the body of the uterus is softer Uterine souffl Rush of blood passing through the dilated uterine arteries because it has to supply the placenta w/ blood Can be heard How do you differentiate b/w fetal heart tone and uterine souffl? Use stethoscope with bell side and feel for the pulse of the mother as well, while you listen to fetal heart tone. Uterine Souffle coincides w/ maternal HR soft, blowing sound that is synchronous with the maternal pulse. produced by the passage of blood through the dilated uterine vessels heard most distinctly near the lower portion of the uterus coincides w/ maternal pulse Funic Souffle Movement of blood flowing through the umbilical arteries & veins but mostly the veins sharp, whistling sound that is synchronous with the fetal pulse. caused by the rush of blood through the umbilical arteries and may not be heard consistently coincides w/ fetal pulse Cervical changes Normally pink but becomes violet: CHADWICKs Sign Vaginal Mucosa, during pregnancy, appears dark bluish- or purplish-red and congested Changes d/t: Hypervascularity some eversion of endocervical epithelium Perception of Fetal Movement: QUICKENING Felt on the 16th 20th wk AOG Perceived earlier in multigravids: 16th to 18th wk AOG Primi gravid: felt 18th to 20th wk Examiner: 20 wks (+) sign that patient is pregnant ANCILLARY PROCEDURES Pregnancy Test Test beta subunit hCG Normally not present in blood Beta subunit is checked because alpha subunits is shared by 3 other hormones like FSH, LH, TSH Hence, beta subunits more specific for hCG hCG beta subunit is similar to LH FSH similar to TSH One line: control line 2nd line present: pregnant Should read w/in 2 minutes, if longer than that might have slight coloration on 2nd line which leads to false positive results
DIAGNOSIS OF PREGNANCY GOAL: decrease morbidity & Mortality rate SIGNS & SYMPTOMS Cessation of menses Highly suggestive but not an absolute or positive sign of pregnancy Female athletes are known to have amenorrhea Know LMP to get AOG LMP: know flow, # of pads/day, volume of bleeding, If LMP is erroneous, wrong AOG LMP is one of the most inaccurate data At least 10 days Implantation bleeding Blastocyst has burrowed in decidual layer Mistaken as LMP Changes in the cervical mucus Ferning pattern: d/t very high NaCl content r/t high estrogen levels No ferning pattern if pregnant If pregnant or not fertile anymore (menopausal), BEADING or CELLULAR pattern occurs Estrogen dependent (+) 7th-18th day Breast Changes Late Pregnancy: grows in size, darkening of areola & nipple, enlarging glands of Montgomery Need full term pregnancy for the final development of breast Vaginal Mucosa Ave diameter of fetal head: 11 cm Increase mucosal thickness Loosening of CT Hypertrophy of smooth mm Increase volume of cervical secretions pH: 3.5 to 6 becomes neutral in pregnancy making it prone to infection Skin Changes Increase cutaneous blood flow Stretch marks: ruptures in the underlying collagen fiber in the skin, skin only has a certain number of tensile strength before it rips apart. Lightens in color eventually unless there is hypertrophic scar formation. D/t the following factors: Wt gain in pregnancy Young maternal age Family history Diastasis recti Rectus mm separate in the midline Atrophy of rectus abdominis mm Hyperpigmantation Linea nigra: common among fair complexioned female, more distinct among women w/ male babies (along w/ darkish discoloration in neck) Melasma gravidarum or chloasma or mask of pregnancy: common on fair complexioned females Angiomas: minute red elevations w/ radicles branching from the central lesion in the face, neck & upper chest Palmar erythema: no clinical significance Changes in the Uterus 12 wks: average 8 cm diameter Will start to reach abdominal cavity, hence now palpable through the abdomen at hypogastric area
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Ultrasound (+) sign of pregnancy 3 signs of pregnancy (REMEMBER THIS) Perception of fetal movement by examiner at 20 weeks Ultrasound result of a presence of baby inside or gestational sac Fetal heart tone heard upon auscultation ILLICIT DRUG USE Cause Fetal distress Low birth weight w/c can cause delayed mental development Drug withdrawal after birth Preterm birth
INITIAL PRENATAL EVALUATION Define the health status of the mother & fetus Estimate gestational age Initiate a plan for continuing obstetrical care COMPONENTS OF PRENATAL CARE HISTORY Get complete history Update Previous hospitalization is important, i.e. know hx of heart disease, asthma, diabetes. OB history How many pregnancies? How many alive? Any abortions? Deaths? Should include what happened to each individual pregnancy Year of pregnancy Full term? Preterm? Mode of delivery? Normal, CS CS d/t? forceps why? Abortion? Raspa, D&C (Dilation & Curettage) weeks of abortion complete? With D&C Gender of baby Birth weight Complications w/ delivery? Infections? Bleeding? Blood transfusions? Gynecologic Hx Surgeries Menstrual Hx Menarche? Regular menses may not immediately follow menarche Regular menses usually follows 6 months to 1 yr after menarche Duration & amount of blood flow Interval b/w menses Contraceptive hx Methods? Withdrawal, IUD, cortal PSYCHOCOSIAL SCREENING Nonbiomedical factors affecting mental & physical well being Lack of transportation, child care or family support Unstable housing Unintended pregnancies Communication barriers Nutritional problems Smoking Substance abuse Depression Domestic violence Poverty CIGARETTE SMOKING Adverse outcomes of smoking: Placenta pravia Placenta abruption PROM (premature rupture of membrane) Prematurity Small for Gestational Age (SGA) Abortions Fetal death Fetal digital anomalies ALCOHOL USE Fetal alcohol Syndrome Growth restrictions Facial abnormalities CNS dysfunction
COMPONENTS OF ROUTINE PRENATAL CARE Physical Examination Complete PE Check h/o of heart dse: RHD usually baby is normal but complications occur during 2nd pregnancy maybe done once during initial visit BP Maternal wt Pelvic/ Cervical Examination Do this during 1st prenantal visit unless theres problem in subsequent visits Fundic Ht Done in every prenatal visit Fetal HR/ Position Done in every prenatal visit PHYSICAL EXAMINATION Speculum Exam: difficult to do d/t apprehension Bluish-red hyperemic cervix: CHADWICKs sign Ectocervical mucosa Nabothian cyst Paps smear: done during 1st prenatal visit Bimanual Exam Cervix Consistency Feel for cervix and is firm when nonpregnant. When pregnant, cervix becomes soft: Cervical Softening & Ripening Length cervical length will shorten, especially when near delivery will become paper thin near term Dilation: Full dilation at 10 cm Uterus UTERINE SIZE: 2 hands: middle finger push cervix upwards toward abdomen, other hand on abdomen pressing down on fundus First few weeks of pregnancy, the increase in uterine size is limited principally to the anteroposterior diameter. By 12 weeks, the body of the uterus is almost globular with an average diameter of 8 cm At 6 to 8 weeks' menstrual age, a firm cervix is felt which contrasts with the now softer fundus and compressible interposed softened isthmus the Hegar sign. The softening at the isthmus may be so marked that the cervix and the body of the uterus seem to be separate organs Fetal presentation Bony structure Pelvimetry: assess pelvic bony structures so you can estimate if it has an adequate passage way for the baby Any anomalies of vagina & perineum COMPONENTS OF ROUTINE PRENATAL CARE Lab test: done on 1st visit Hemoglobin & Hct Blood type & Rh factor Antibody screen Pap smear Urine Protein Assessment Normally you dont see protein and glucose in urine, but in pregnancy you may see some glucose, which is normal. Urine culture: unless pt has recurrent UTI Rubella serology: dont usually request this, unless high risk patients like sex workers Syphilis serology: dont usually request this, unless high risk patients like sex workers
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Chlamydial culture: dont usually request this, unless high risk patients like sex workers Hepatitis serology: usually require this, as its common in phil. Other tests Glucose challenge test Screen for gestational DM 24 to 28 wks AOG Confirmatory GTT If (+) glucose challenge test Fetal aneuploidy screening = *1st visit Neural tube defect screening = *15 to 20 weeks Cystic fibrosis screening = 1st visit Gonococcal culture = high risk women HIV serology = *1st visit. NOTE: (*) not required, unless pt is at risk.
DEFINITION OF TERMS Nulligravid: never pregnanct Gravida: women who had become pregnant but not necessarily delivered a baby G1PO, pregnant, but not delivered Nullipara: female has not delivered Primipara: female has delivered first time Multipara: female has delivered several times OB SCORING GaPb(c,d,e,f) Where: A = # of pregnancies B = # of pregnancies reaching > 20wks C = # of term deliveries D = # of preterm deliveries E = # of abortions F = # of children alive EXAMPLES: 25 yo female who delivered G1 @ 2005 fullterm, NSVD (normal spontaneous vaginal delivery), birthweight 7 lbs, male. next pregnancy is 2007, abortion, D & C. G3 2009, PT, NS ( IUFD:intrauterine fetal death). G3P2 (1,1,1,1) NORMAL PREGNANCY DURATION 280 days or 40 wks LMP AOG About 40 and 3 over 7 days. Expected date of Confinement/ Delivery about 280 days from time of LMP, so you can estimate if the pregnancy is preterm or postterm, based on EDC alone. Naegeles Rule: add 7 days to the date of the 1st day of LMP then subtract 3 months LMP: May 1, 2011 Compute for EDC May (5th month) 5 1 2011 -3 +7 2 8 EDC: Feb 8, 2012 Since today is feb 11 and you expected her to deliver feb 8th, and she hasnt delivered yet, so AOG is 40 weeks, so age is 40 weeks over 3 over 7 days.
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CHAPTER 8
Prenatal Care II
Dr. Crisostomo Ordono. Jr. MD
TRIMESTERS: 1st trimester Up to 14 weeks 2nd trimester 15 to 28 weeks 3rd trimester 29 to 42 weeks PRENATAL CARE Goal: Morbidity & Mortality rate
Develop into preterm labor at least 3-fold Abnormal dilation of cervix & bag of waters Prior fetal/chromosomal abnormalities
CHANGES IN CERVIX DURING CERVIX: Hegars Sign: Cervical Softening Chadwicks Sign: Bluish discoloration ULTRASOUND AOG Most accurate AOG if US is taken during 1st trimester Measure gestational sac & CRL If after 1st trimester, genetic factors come in like size of baby; hence, AOG error Cross reference AOG based on LMP & based on US result Example: Aug 1 US results AOG 10 wks If pt comes to you on Aug 20 what is AOG? 13 wks AOG by US Get LMP & compute AOG based on LMP if 11wks WRITE: 13 wks by US & 11 wks by LMP 1 PRENATAL CARE 1st establish that pt is pregnant If pt is c/o abdominal pain: always r/o pregnancy especially if pain is coming from epigastric area KNOW LMP LMP is one of the most inaccurate data HIGH-RISK PREGNANCIES: What are high risk pregnancies? Where you expect pts to have higher morbidity with respect to the pt and baby. Main goal of prenatal checkup is to decrease mortality to pregnant women Medical history and conditions: any medical problems during pregnancy puts patient at high risk Asthma Cardiac disease Diabetes mellitus Screening Procedure: Glucose Challenge Test done on 24th wk to assess Gestational DM Come to laboratory dissolve 50g sugar & drink in front of tech & test done after 1 hr If (+): Gestational DM, marked as high risk especially w/ h/o DM in family Confirmatory Test: OGTT Pt have to undergo fasting for 10 hrs, drink100g of sugar, extract blood every 1 hr 4x to confirm DM Drug and alcohol use Epilepsy Family history of genetic problems Hemoglobinopathy HTN History of pulmonary/DVT Psychiatric illness Pulmonary disease Renal disease Obstetrical history and conditions: > 35 y/o at delivery Usually delivered by CS Mc fetal abnormality: Trisomy 21 Prior caesarean section Dont have to do CS on the next delivery Can still do vaginal birth especially if the prior condition that caused CS is not present during the next baby but are still labelled as HIGH risk Incompetent cervix
ST
h/o recurrent abortion 35 y.o at G4 with 3 abortions on previous pregnancies Primary Infertility: if no pregnancy after regular sexual contact w/o contraception for 1 yr If gets pregnant eventually: high risk for chromosomal abnormalities Prior neonatal death Prior fetal death Prior preterm birth /PPROM (Preterm Premature Rupture of Membranes) Prior Large BW (LBW) baby If baby weight is 4.8 kg & small mother Mothers w/ Gestational GM 2nd trimester pregnancy loss
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Uterine myomas/malformation Any abN in the anatomy of the uterus puts pt at high-risk LeioMyoma, whorl-like pattern of myometrial cell, if found very near the cervix; may interfere w/ Normal Vaginal delivery CS delivery (+) HIV test Blood group isoimmunisation Diagnosed condylomata. Condyloma accuminata: genital warts Dont recommend vaginal delivery d/t risk of infecting the baby Vaginal exam late in pregnancy Dont have to do pelvic exam every prenatal care, can do it when close to term Confirmation of presenting part and station Most common: cephalic Next mc: Breech By doing Leopolds maneuver, can assess presentation of baby Clinical pelvimetry Measurement of birth canal Assess if baby can pass through by estimation If birth canal is small, first do trial of labor before deciding for CS Usually done during labor or term Consistency, effacement and dilatation of the cervix IE done when pt is at 42 weeks AOG to induce labor
SUBSEQUENT PRENATAL VISIT: Traditional schedule for prenatal care: Every 4 weeks up to 28 weeks Every 2 weeks up to 36 weeks Weekly up to delivery 110/70 mmHg: already hypotensive for pregnant women If high risk, frequency of visits Drawback for traditional schedule: You will be flooded w/ a lot of patient everyday WHO trial: 1st trimester if no risk factors subsequent visits Undergo prenatal check-up only 4 times 26, 32 and 38 weeks. Ask for subjective complaints PE focused on the abdomen unless there is lung or cardiac complaints Leopolds Maneuver Maneuver to examine the uterus PRENATAL SURVEILLANCE: Fetal evaluation: Fetal heart rate: Normal: 110-160 bpm (120-160) Uterine Size: current and rate of change 1st Trimester: growth of uterus not dependent on size of product of conception Uterus can increase in size even if fetus is dead inside during 1st trimester Uterus grows d/t hypertrophy of uterine mm d/t estrogen 2nd trimester onwards: growth of uterus is reflective of size of baby inside Measure fundic height by putting tape measure at fundic hump to the pubic symphisis, straight line Full term: 35 cm Amount of amniotic fluid Measured by US Done near term if you suspect watery discharge from amniotic fluid from the vagina If suspicion of polyhydramnios 3rd Trimester Presenting part and station (late in pregnancy) Only way to establish station of the baby is through examination Leopolds maneuver: preferably performed after 24 weeks gestation when fetal outline can be already palpated. Consists of four distinct actions, each helping to determine the position of the fetus. important because they help determine the position and presentation of the fetus, which in conjunction with correct assessment of the shape of the maternal pelvis can indicate whether the delivery is going to be complicated, or whether a Cesarean section is necessary. Fetal Activity Maternal evaluation: Blood pressure Weight Symptoms Fundic height in centimetres
ASSESSMENT OF GESTATIONAL AGE Fundal height 20 to 34 cm height = AOG in weeks Symphysis pubis to top of the fundus: is about 12 week size: You measure fundal height in cm from Symphysis pubic to top of fundus. Fetal heart sounds: Detectable by 16 to 29 weeks especially when Doppler US is used Hard to hear fetal heart tones before 20th wk if using stethoscope 80% audible at 20 weeks depending on stethoscope used 110 to 160 bpm Sonography NUTRITION: Recommendations for weight gain Mid 1900s = < 20 lbs or 9.1 kg 1970s = at least 25 lbs or 11.4 kg 1990 = 25 to 35 lbs or 11.5 to 16 kg if normal prepregnancy BMI Over nutrition = birthweight Average wt gain: 1 lb/wk Table 8-7. Recommended Ranges of Weight Gain during Singleton Gestations Stratified by Prepregnancy Body Mass a Index Weight-for-Height Recommended Total Weight Category Gain Category Low Normal High Obese BMI < 19.8 19.826 2629 > 29 Kg 12.518 11.516 711.5 <7 Lb 2840 2535 1525 < 15
The range for twin pregnancy is 35 to 45 lb (16 to 20 kg). Young adolescents (< 2 years after menarche) and African-American women should strive for gains at the upper end of the range. Shorter women (< 62 in. or < 157 cm) should strive for gains at the lower end of the range. Effects of nutrition: Weight retention after pregnancy: Not related to pregnancy, we tend to accumulate wt as we grow older Average weight of 3 lbs or 1.4 kg is retained Prepregnancy BMI or weight gain (not equal) weight retention Therefore: accruing weight with age = weight gain over time. Recommended dietary allowances: Vitamins and minerals with potential toxic effects Fe Zn Se Vit A, B6, C & D Calories: need to memorize 100 to 300 kcal/day
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If low BMI: Proteins: 5 to 6 grams/day Most protein go down during pregnancy except: Glutamic acid and alanine concentration Minerals Iron Needed during the 2nd trimester 27 mg per day Singleton 60 to 100 mg per day for: Large women Twin pregnancies Anemia Calcium: RDA 1000 to 1300 mg/day For replenishment of bone calcium Zinc: RDA 12 mg Deficiency may lead to: Poor appetite Suboptimal growth Impaired wound healing Iodine: RDA 200 ug Deficiency: Maternal subclinical hypothyroidism Cretinism & neuro-development defects in the fetus Seen in pts who live in high altitudes, b/c you get iodine from sea food, until they iodize the salt. Magnesium: Deficiency due to pregnancy has not been recognized. Copper Selenium Chromium Manganese Potassium Fluoride NOTE: most are provided by balanced diet Vitamins: Vitamin C = RDA 80 to 85 mg Thiamine = RDA 1.4 mg Riboflavin = RDA 1.4 mg Niacin = RDA 18 mg Vitamin B6 = RDA 1.9 mg Combined with doxylamine: reduce vomitting. Combined w/ doxylamine for hyperemesis gravidarum Doxylamine is an anti-histamine Avoid triggering factors like odor Small frequent meals if gets nauseous easy Vitamin B12 RDA 2.6 ug Present in foods of animal origin only Deficiency may lead to neural tube defects. a/w folic acid also Vitamin B2: Folic acid 4 mg before and during the 1st trimester 70% reduction of neural tube defects Drink folic acid even before they become pregnant & continue till term but most important before pregnancy & during 1 st trimester Vitamin A RDA 750 to 770 ug Potentially teratogenic Can be found in acne or dematologic meds Isotretinoin Retinoic acid But topical prep only reach the blood stream at minute amts Some preps tend to get stored in adipose tissue for as long as 5 years Deficiencies: Anemia: Spontaneous preterm birth
PRAGMATIC NUTRITIONAL SURVEILLANCE: Eat what she wants in amounts she desires and salted to taste Ensure the availability of food Monitor weight gain Periodically explore food intake Supplements: iron at least 27 mg, folate Recheck Hgb and Hct at 28 to 32 weeks.
COMMON CONCERNS: Employment Avoid severe physical strain Minimize physical work if with hx of preterm labor Exercise: Generally has no limit provided its in moderation Regular moderate intensity work put for 30 mins Exercise with a high risk of falling/abdominal trauma must be avoided Scuba diving is not recommended. Low impact aerobics, exercises, walking Fish consumption: Avoid fish with potentially high methylmercury levels: Mercury found in skin & fat of fish Ex: sharks, swordfish, king mackerel, tile fish Avoid bottom dweller fish because mercury gravitates towards the sea floor Attacks nerves tremors Mercury in fluorescent lamps LEDs now used & CFCs Travel: Automobile: Lap belt portion: under the abdomen and across the upper thighs Shoulder belt between the breast Air travel: safe to travel up to 36 weeks airline policy: no travelling if 7 months AOG Coitus: generally safe oral vaginal intercourse occasionally harmful: i.e. suffering from air embolism from partner blowing air inside vagina. Dental care Dental treatment not contraindicated in pregnancy Immunization: TT1 as early as possible during pregnancy TT2 at least 4 wks later 80% TT3 at least 6 mos later Caffeine: Caffeine intake < 300 mg daily Nausea & vomiting Small frequent feedings Mild: vit B6 and doxylamine May also give phenothiazine or H1 receptor blocker Hyperemesis gravidarum Backache: Reduced w/ squatting than bending Provide back support Avoid high-heeled shoes Varicosities Congenital predisposition Can be present in the legs & perineum Exaggerated with: Prolonged standing Weight increase Length of time standing Tx: periodic rest w/ legs elevated and use elastic stockings Lay down in lateral decubitus Haemorrhoids: Rx. Topical anesthetics, warm soaks, stool softeners but better to ask patient to have high fiber diet Iron intake can cause constipation Heartburn: Small frequent feedings
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Avoid bending or lying flat Antacids ex. AlMgOH High back rest when you lay down to decrease chances of reflux Eat small meals Pica: May be related to severe Fe deficiency anemia cravings of pregnant women for strange foods can be non-food items such as icepagophagia, starchamylophagia, or claygeophagia may predominate. Although the craving usually is ameliorated after correction of iron deficiency, not all pregnant women with pica are necessarily iron deficient. Indeed, if strange "foods" dominate the diet, iron deficiency will be aggravated or will develop eventually. Ptyalism: Usually unexplained: craving for unusual food Women during pregnancy are occasionally distressed by profuse salivation. Although usually unexplained, the cause of such ptyalism sometimes appears to be stimulation of the salivary glands by the ingestion of starch. Sleeping and fatigue: Likely due to effect of progesterone Rx: daytime naps & mild sedatives Leukorrhea: May be normal in pregnancy thick, whitish or yellowish vaginal discharge Due to hyperestrogenemia But may predispose to bacterial vaginosis, candidiasis, trichomoniasis. d/t pH form 3.5 to 6
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CHAPTER 13 Prenatal Diagnosis and Fetal Therapy Dr. Aida J. Bautista: MD Aneuploidy (Trisomy 13, 18, triploidy) Exposure to environmental agents Diabetes: hyperglycemias Hyperthermia: hot tubs, sauna, fever Medications: Valproic acid Coumadin/ Warfarin Carbamazepine Aminopterin Thalidomide Efavirenz Geographical regions United kingdom India China Egypt Mexico Southern Appalachian US
Incidence of major abnormalities at birth: 2 to 3 % Cause of neonatal death Prenatal diagnosis: Science of identifying structural or functional abnormalities or birth defects in the fetus Fetal therapy can be used to improve intrauterine environment Fetal therapy: Blood product transfusion Administration of medication transplacentally or via fetal circulation Laser or radiofrequency ablation of vascular anastomosis Amnioreduction Shunt placement Extensive fetal surgery Etiology of Birth defects: Malformation Deformation Disruption Malformation: Most common abnormality Intrinsic abnormality programmed during development Ex. Spina bifida Deformation: Genetically normal fetus develops abnormally because of mechanical forces in the uterine environment Ex. Contractures of a normal limb from prolonged oligohydramnios Disruption: More severe change in form or function Modified genetically normal tissue resulting from an insult Ex. Cephalocoele or limb reduction abnormality from an amnionic band Syndrome: A cluster of several anomalies or defects All the anomalies have the same case Ex. Trisomy 18 or Edwads Syndrome Sequence: Sequential development resulting from one initial insult Ex. Oligohydramnios pulmonary hypoplasia, limb contracture, facial deformity. Association: Anomalies occurring together but not linked etiologically Ex. VATER: Vertebral defects, Anal atresia, Trachea-esophageal fistula w/ Esophageal atresia, Radial dysplasia
ALPHA FETOPROTEIN Glycoprotein synthesized early in gestation by the fetal yolk sac Synthesized later by the fetal GIT & liver A major serum protein in the embryo analogous to albumin Concentration increases in fetal serum & amniotic fluid until 13 weeks then decreases in level AFP increases in maternal serum after 12 weeks Normal concentration gradient between fetal plasma & maternal serum is 50 000:1 Increased maternal serum levels if with fetal body wall defect (NTD) due to AFP leakage into the amniotic fluid Maternal serum AFP ACOG recommends 2nd trimester screening at 15 to 20 weeks Reported as multiples of the median (MoM) of the unaffected population 2 to 2.5 MoM 90% of anencephaly 80% of spina bifida Factors influencing maternal serum AFP Maternal weight Gestational age Race or ethnicity: African Americans IDDM: lower AFP Multifetal gestation Elevated AFP > 2.5 MoM Do counselling Ultrasound Amniocentesis ALGORITHM: With an elevated value, if not already performed, evaluation begins with a standard sonographic examination, which can reliably exclude three common causes of AFP elevation: underestimation of gestational age multifetal gestation fetal demise. Most cases of NTD may be detected or suspected during this initial examination Once the screening test is confirmed to be abnormal, the patient is offered diagnostic evaluation as subsequently discussed. Example of an algorithm: Evaluating maternal serum alpha-fetoprotein screening values (MSAFP). Conditions associated with HIGH AFP NTD Underestimated AOG Multifetal gestation Fetal death Gastroschisis Omphalocoele Low maternal weight
NEURAL TUBE DEFECTS Prenatal diagnosis of neural tube defects: Open neural tube defects: Anencephaly Spina bifida Cephalocoele Spinal fusion Neural tube defects: 1.4 to 2 per 1000 pregnancies 2nd most common class of birth defects Maternal serum AFP concentration at 16 to 18 weeks is > 2.5 multiples of the median (MoM) 88%: anencephaly 79%: spina bifida Risk factors for neural tube defects: Genetic cause Family history (Multifactorial inheritance) Methylene Tetrahydrofolate reducase (MTHFR) mutation Syndromes with autosomal recessive inheritance
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Pilonidal cysts Skin defects Esophageal/intestinal obstruction Liver necrosis Cystic hygroma Sacrococcygeal teratoma Urinary obstruction Renal anomalies Osteogenesis imperfecta Placental abruption Conditions associated with LOW AFP Obesity Diabetes Chromosomal trisomies: Downs Syndrome Gestational trophoblastic disease Fetal death Overestimated gestational age PICTURE 1: Axial image of the fetal head at the level of the lateral ventricles w/ ventriculomegaly & inward bowing or scalloping of the frontal bones (arrows) in the setting of spina bifida produces the "lemon sign." Banana sign: bowing of the cerebellum w/ effacement of the cistern magna absent cisterna magna d/t disappearance of cerebellar vermis PICTURE 2: Fetal head at the level of the posterior fossa, downward herniation of the cerebellum (white arrows), with effacement of the cisterna magna, produces the "banana sign." AMNIOCENTESIS Once considered gold standard for diagnosis of NTDs Now replaced by specialized sonography Fetal karyotyping maybe offered maternal serum AFP w/ normal AF, AFP & no UTZ detected anomaly: no risk for abnormal karyotype maternal serum and amniotic fluid AFP and no visible anomaly on ultrasound: 5X chromosomal anomaly. Unexplained maternal AFP elevation: Elevated maternal serum AFP when no fetal/placental anomaly detected after an ultrasound with or without amniocentesis Increased risk for adverse pregnancy outcomes MANAGEMENT of FETUS w/ NTD CS vs NVD CS may risk of mechanical trauma & fetal spinal infection Scheduled delivery to allow precise timing so that appropriate management team can be assembled
PRENATAL DIAGNOSIS OF DOWNS SYNDROME Aneuploidy screening protocols Fetal Trisomy: risk increases with increasing maternal age 35 year & above considered advanced maternal age
SPECIALIZED ULTRASOUND GOLD STANDARD for NTD diagnosis Specialized sonography for NTD in 2nd trimester: ArnoldChiari Malformation Lemon sign: frontal bone scalloping
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Before 1980s, prenatal diagnostic testing offered only to 35 yo pregnant patients Downs syndrome: low MSAFP at 15 to 20 weeks American College of Ob-Gyn Offer screening to all pregnant patients < 20 weeks AOG with option for invasive diagnostic testing Second trimester screening: Performed at 15 to 20 weeks Diagnose Trisomy 18 & 21 Downs syndrome: Triple test to diagnose 65 to 70% AFP: 0.7 MoM HCG: 2 MoM Unconjugated estriol: 0.8 MoM Trisomy 18: all serum markers decreased Quad test add dimeric inhibin alpha with value of 1.8 MoM will diagnose 80% of Downs syndrome 5% false positive rate If positive screen offer: Amniocentesis Fetal blood sampling First trimester screening Performed at 11 to 14 weeks, ideally 11 weeks for Downs syndrome Downs Syndrome HCG or free hCG: 2 MoM Pregnancy associated plasma Protein (PAPPA): 0.4 MoM Nuchal translucency: > 3.5 mm Combined 1st and 2nd trimester screening: Integrated screening Detects highest downs syndrome at 90 to 96% Incorporates serum marker of 1st trimester with second trimester quadruple marker testing Offered if unavailable Results available 2nd trimester Sequential screening Discloses results of 1st trimester screening then if abnormal, invasive testing is done Second trimester markers of soft signs in Downs Syndrome: Nuchal fold thickening/ translucency Nasal bone absence/ hypoplasia Shortened frontal lobe: Brachycephaly Short ear length Echogenic intracardiac focus Echogenic bowel: Double bubble sign Mild renal pelvis dilation Widened iliac angle Sandal gap: widened gap b/w 1st & 2nd toes Clinodactyly Single transverse palmar crease: Simian Crease Short femur Short humerus First trimester Nuchal translucency (NT) Increased sonoluscent area at the back of the fetal neck Associated with Downs syndrome & other aneuploidies, genetic syndromes & birth defects Can identify 64 to 70% of Downs when used alone Can detect 79 to 87% of Downs when combined with other markers Absent Nasal bone: First trimester marker Found in 73% of high risk patients with Downs syndrome 5 to 7% of all stillbirths & neonatal deaths i.e. if pt comes to her for first baby and had an abortion: may be something was wrong with the baby if she had a miscarriage and it was a genetical problem
FETUSES AT INCREASED RISK FOR GENETIC DISORDERS Fetus at risk: Fetal aneuploidy Familial genetic Disease Ethnic Groups Cystic Fibrosis Autosomal recessive Disease in Jews Fetal aneuploidy 8% of all conceptus 50% of all 1st trimester abortions
Diagnostic techniques: 2nd TRIMESTER Amniocentesis performed at 15 to 20 weeks under ultrasound guidance (g 20 to 22 spinal needle passed into amniotic sac, avoiding the placenta) discard 1st 1 to 2 ml of aspirate as it contains maternal cells get 20 ml for karyotyping Amniocentesis complications: transient vaginal bleeding amniotic fluid leakage 1st TRIMESTER Amniocentesis done at 11 to 14 weeks more difficult due to lack of membrane fusion to uterine wall less fluid withdrawn higher complication rate: clubfoot Chorionic villus sampling: done at 10 to 13 weeks samples obtained transcervically or transabdominally depending on which route allows easiest access to placenta relative contraindications vaginal bleeding
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active genital tract infection extreme uterine ante- or retroflexion Same indications as amniocentesis Advantage: get results earlier If normal, anxiety relieved If abnormal, earlier pregnancy termination Complications: same as amniocentesis (limb reduction defects) Fetal blood sampling: Percutaneous umbilical blood sampling or cordocentesis Purpose: To assess & confirm red cell or platelet alloimmunization To evaluate non-immune hydrops To obtain cells for genetic testing Fetal blood sampling technique: under UTZ guidance, a g 22 spinal needle punctures umbilical vein at or near placental origin & blood is withdrawn avoid umbilical artery puncture to avoid vasospasm fetal bradycardia Access to the umbilical vein varies depending on placental location and cord position. With an anterior placenta, the needle may traverse the placenta. Inset: With posterior placentation, the needle passes through amnionic fluid before penetrating the umbilical vein. Alternately, a free loop of cord may be accessed. Cordocentesis: complications: cord vessel bleeding: 50% fetal-maternal hemorrhage: 66% fetal bradycardia: 3 to 17% fetal death: 1 to 4% Graves thyrotoxicosis s/p RAI Produce IgG thyroid stimulating antibodies that cross placenta to cause fetal thyrotoxicosis Cordocentesis needed to check thyroid hormones If with hyperthyroidism, give propylthiouracil (PTU) to mother Congenital adrenal hyperplasia: 21-OH deficiency Impaired cortisol synthesis from cholesterol by the adrenal cortex Excessive fetal adrenal androgen production Cause female virilization & salt-wasting adrenal crisis TREATMENT: dexamethasone at < 9 weeks AOG to mother CVS or amniocentesis done later KARYOTYPING: If male, stop dexamethasone; if female, continue till term Arrhythmia: Tachyarrhythmias lead to cardiac decompensation & hydrops fetalis Give antiarrhythmic drugs that cross placenta to mother If fetus becomes hydropic, may give drug via umbilical vein. Congenital infection: Maternal syphilis Other STDs Metabolic disorders: Methylmalonic acidemia: given maternal vitamin B12 oral or IM Smith-Lemli-Opitz syndrome: given Fresh Frozen Plasma (FFP) transfusion 3 phophoglycerate dehydrogenase Deficiency: maternal oral L-serine Fetal stem cell transplantation: In 1st & 2nd trimester, fetus has an adaptive immune response to foreign antigen preimmune Treats hematological, metabolic & immunological diseases Fetal gene therapy: Experimental Therapeutic gene transfer Normal gene inserted into target cells Fetal surgery Performed only when fetal outcome is improved & withholding this would be catastrophic Types: Open fetal surgery Fetoscopic surgery Percutaneous procedure ex-utero-intrapartum treatment procedure Open fetal surgery: done under General Anesthesia (GA) UTZ guidance to avoid placenta during hysterotomy Stapling device for hemostasis Partial exteriorization of the fetus Venous access Surgery for selected life threatening anomalies Tocolysis: give medication to mother to prevent contraction of the uterus. Its to relax the uterus. Abnormalities amenable to open fetal surgery: cystic adenomatoid malformation extralobar pulmonary sequestration sacrococcygeal teratoma spina bifida PICTURE: open fetal surgery for resection of a sacrococcygeal teratoma. Hysterotomy has been completed, and the caudal portion of the fetus has been delivered onto the surgical field. The tumor is held by the surgeon's hand. Morbidities of open fetal surgery: maternal pulmonary edema; 28% maternal blood transfusion: 13% preterm labor & delivery: 33% Premature Rupture of Membranes (PROM): 52% Chorion-amnion separation: 20% Chorioamnionitis: 9%
FETAL TISSUE Biopsy Muscle: muscular dystrophy or mitochondrial myopathy Skin: epidermolysis bullosa Preimplantation genetic diagnosis: identify severe genetic disorders in zygotes prior to implantation in In vitro fertilization (IVF) to find a match for human leukocyte antigen for potential stem cell transplant Fetal cells in maternal circulation: 2 to 6 fetal cells seen per mL of maternal blood Might obviate need for invasive procedures FETAL THERAPY Fetal therapy Most fetal abnormalities cannot be corrected by fetal therapy Prenatal diagnosis allow maternal psychological preparation & may alter delivery plans A lethal anomaly may allow termination of pregnancy or not perform a CS Therapy options Fetal transfusion Fetal medical therapy Fetal stem cell therapy Fetal gene therapy Fetal transfusion INDICATIONS: fetal anemia & thrombocytopenia Causes of anemia Alloimmunization: most common Infection Genetic disease: Thalassemia Feto to maternal hemorrhage Fetal medical therapy:
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Placental abruption: 9% Fetoscopic surgery: use of Fiberoptic endoscopes (1 to 2mm) and lasers minimally invasive procedure lower risks performed in highly specialized centers investigational Abnormalities amenable to fetoscopic surgery twin to twin transfusion: laser of placental anastomosis Diaphragmatic hernia: fetal endoscopic tracheal occlusion (FETO) Posterior urethral valves: cytoscopic laser Congenital high airway obstruction: vocal cord laser Amniotic band release Laser therapy: INDICATIONS: Twin to twin transfusions, posterior urethral valves Fetoscopic surgery: complications maternal pulmonary edema: 25% preterm delivery 27% PROM: 44% Chorion-amnion separation: 65% Placental abruption: 6% Percutaneous procedures: done under sonographic guidance uses radiofrequency needles or angioplasty catheters may drain fluid in fetal bladder obstruction or thoracic pleural effusion Abnormalities amenable to Percutaneous procedures: Shunt therapy Posterior urethral valve/bladder outlet obstruction Pleural effusion: chylothorax Radiofrequency ablation Twin-reversed arterial perfusion (TRAP) sequence Monochorionic twin with severe anomalies Chorangioma Fetal intracardiac catheter procedures: Aortic or pulmonic valvuloplasty for stenosis Atrial septostomy for hypoplastic left heart with restrictive atrial septum Ex-utero intrapartum (EXIT) procedure: Designed to allow fetus to remain perfused by placental circulation after partial delivery so a life saving treatment can be performed. treat airway obstruction caused by neck masses and laryngeal or tracheal atresia/stenosis Abnormalities amenable to ex-utero-intrapartum treatment (EXIT) Congenital diaphragmatic hernia Congenital high airway obstruction sequence Severe micrognathia EXIT for resection: resection of fetal thoracic or mediastinal mass or tumors of airway or neck EXIT to Extracorporeal Membrane Oxygenation (ECMO) for severe congenital diaphragmatic hernia Cystic hygroma Ex-utero intrapartum treatment EXITprocedure. This fetus was diagnosed prenatally with large lymphatic abnormality of the neck, lower face, and mediastinum. The EXIT procedure was planned because of concern for tracheal compression and possibly deviation. Upon delivery of the head, with the placental circulation maintained, the surgeon evaluates the airway and prepares to attempt intubation. B. Infant following a controlled intubation, oxygenating well, and supported by the neonatal intensive care unit team
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CHAPTER 14 Teratology and Medications That Affects The Fetus Dr. Crisostomo Ordono
Birth defect is a major deviation from normal physiology/function 3% of all birth in the US 7% detectable by 1 y/o 12 to 14% detectable when they enter school 17% detectable by 18 years old Only 10% of malformation at birth are caused by teratogens
TERATOLOGY Definitions Teratogen any agent that acts during embryonic/fetal development to produce a permanent alteration of form or function Teratology study of environmental contributions to abnormal development Hadegen agent that interferes with normal maturation & function of an organ generally affect processes occurring after organogenesis or even after birth Trophogen agent that alters growth generally affect processes occurring after organogenesis or even after birth Currently recognized teratogens Chemicals Viruses Environmental agents Physical factors Drugs EVALUATION OF POTENTIAL TERATOGENS: Defect must be completely characterized The agent must cross the placenta Exposure must occur during a critical developmental period Cause and effect must be biologically plausible Epidemiological studies must be consistent The suspected teratogen causes a defect in animals Defect must be completely characterized A wide variety of genetic & environmental factors can produce the same defects EXAMPLE: cleft lip & palate associated with antenatal hydantoin exposure and with 300 other known genetic causes: Fetal Hydantoin Syndrome Phenocopies identical defects with different etiologies The agent must cross the placenta Must cross the placenta in sufficient doses to directly influence fetal development or alter maternal/placental metabolism to exert an indirect fetal effect Depends on: Maternal metabolism livers ability to metabolize teratogen for elimination Protein binding & storage Molecular size Electrical charge Lipid solubility Exposure must occur during a critical developmental period st 1 8 weeks: Embryopathy After 8 weeks: Fetopathy
Gestation is divided into the following 3 periods Preimplantation period 2 weeks from fertilization to implantation This is the all or none period where either the embryo can cope and survive or just die. An insult damaging a lot of cells would cause the death of the embryo abortion Few cells damaged may cause no effect on the gestation normal gestation Embryonic period nd th 2 to the 8 week AOG Most crucial period with regards to structural malformations: organonesis neural tube defect or baby w/o kidneys Fetal period 9th week to term AOG Maturation is important for functional development hypoplastic left heart aortic coarctation from reduce cardiac blood flow hypoplastic lung d/t amniotic fluid going in the lungs when fetus doesnt produce enough urine Cause & effect must be plausible Points to consider before considering that the agent causes teratogenic effects drug pharmacology: nefidipine Calcium channel blocker if you give it to the mother and if it enters the baby, what can happen? All the functional cells associated /w calcium entry into the cell maybe compromised b/c of the action of nefidipine. So there should be a cause and effect. Theoretically it is possible. maternal metabolism fetal metabolism Epidemiological studies must be consistent recurrent findings of abnormalities associated with environmental exposure e.g. recurrent pregnancy loss, IUGR initial evaluation is retrospective recall bias chances are that the women will not be able to recall everything that happened to her inadequate reporting mom working to carton factory exposed to paint and fumes of paint could have caused abnormality incomplete assessment of the population 2 or more high quality epidemiological studies must give a similar finding teratogenic studies are usually case reports no mother wants to be a test subject to see if a substance is going to be safe for a pregnancy. Its unethical. So there are no such studies. But what we have are CASE STUDIES and are the RESULTS AFTER THE FACT. Suspected teratogen causes a defect in animal studies if teratogenic in animals, IT MAY BE HARMFUL TO HUMANS the more the drug is teratogenic to other animal species the more teratogenic it is to humans BUT not always true as in the case of THALIDOMIDE
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Did not show teratogenic effects on mice, but it showed effects in humans. HISTORY: was given in the 1950s and 60s to help maintain pregnancy associated /w hyperemesis gravidarum. caused babies w/o limbs: Amelia or Phocomelia Some substances could be teratogenic to animals but not to humans. FDA Categories For Drugs & Medications Category A Controlled studies show no fetal risk Very safe Example: Most Vitamins Levothyroxine Potassium supplementation Category B Most safe Animal studies no fetal risk NO human studies No animal adverse effects/no controlled human studies Examples: Penicillins Macrolides Most cephalosporins Category C NO adequate animal nor human studies NO animal adverse effects NO human studies Category D No evidence of fetal risk Benefits outweigh the risk carbamazepine and phenytoin antiepileptic medication given at a lower dose to manage pregnant pt who is epileptic and is suffering from a seizure Category X Proven fetal risk for Teratogenicity Risk outweigh the benefits This is most severe!!! So you dont give it!!! Example: MOST anticonvulsive medication Rubella vaccine Genetic & Physiologic Mechanisms Of Teratogenicity Acts by disturbing a pathogenetic pathway causing: Cell death Altered tissue growth Abnormal cellular differentiation Disruption of normal development Mechanism for most teratogens: UNKNOWN TWO known causes of teratogenesis: Disruption of folic acid metabolism: Leads to Neural tube defects Cardiac anomalies Cleft lip and palate Drugs that causes impaired folate absorption or acts as antagonist Hydantoin Carbamazepine Valproic acid Metronidazole folic acid antagonist Contrainidicated during pregnancy d/t risk of defect OTHER CAUSES OF TERATOGENESIS Oxidative intermediates: Antiseizure drug metabolites produce oxidative intermediates Hydantoin Carbamazepine Epoxides Phenobarbital Epoxide hydroxylase
Detoxified epoxides EPOXIDES are oxidative intermediates which are harmful free radicals normally reduced to detoxified epoxides by EPOXIDE HYDROXYLASE Some women have a genetic predisposition to have a epoxide hydroxylase cannot detoxify the epoxides epoxides MENTAL RETARDATION. Maternal Exposure: Maternal disease Heredity and socioeconomic factors Maternal malnutrition Lead to babies w/ low birthweight w/c correlates w/: Babies that they tend not to do well in school have learning disabilities underachievers Alcohol abuse Drug abuse Combined w/ alcohol abuse, risk of teratogenic effect than with alcohol alone Fetal genetic composition Multifactorial anomalies are caused by interaction of environment & genes Hydantoin exposure risk of genetic anomaly with a homozygous gene Paternal Exposure: Exposure to drugs & environmental influence increase risk of sperm abnormalities: Induction of gene mutation/chromosome abnormality Drug in the seminal fluid may gain access to the fetus during intercourse
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Male germ cell exposure to drugs/environmental factors may alter genomic imprinting or other changes in gene expression Teratogens: Category X Most common effects LUNGS & KIDNEYS: Late onset growth restrictions Oligohydramnios: kidney will not produce urine (anuria), so you have low amounts of amniotic fluid and will have effects of lungs Prolonged and profound neonatal hypotension Anuria Most severe consequence: RENAL TUBULAR AGENESIS Isotretinoin: vitamin A, used for acne One of the most potent and commonly used drugs Teratogenic especially when taken orally st 1 trimester = high rate of fetal loss and malformation Malformation involves: Cranium Microtia and anotia Craniofacial malformation most strongly associated w/ isotretinoin Frequently associated with agenesis or stenosis of the external ear canal Heart : conotruncal or outflow tract defect CNS: hydrocephalus Thymus: aplasia, hypoplasia There is a derivative in oral form of vitamin A that is given to treat psoriasis. If taken, Vitamin A will help psoriasis but drug can get deposited into adipose tissue of mother and stays w/in the system (as long as three years). If patient becomes pregnant within 3 years, the fetus still develops abnormalities. Hormones Exogenous androgen exposure at 7 to 12 weeks AOG can result in: Full masculinization occurs in females If you give exogenous, it usually effects just the genitalia: st 1 Trimester: Labioscrotal fusion nd rd 2 & 3 Trimester: hypertrophy of clitoris or phallic enlargement. Areas of brain with receptors may be influenced in areas such as: Gender identity: tend to be more masculine, tomboy, play with guns, are rough, etc. Sexual behavior Levels of aggression Gender-specific play behaviours are affected Expected sex of baby unless told so is? Female! DHT more potent than Testosterone Diethylstilbestrol (DES) Used for pregnancy maintenance (before!) has carcinogenic effects to baby w/ onset during adolescent period: CLEAR CELL ADENOCARCINOMA of the cervix and vagina When baby becomes older (teenagers, 18 years old) they develop cancers i.e clear cell adenoCA in cervix, vulva or vagina. Teratogenic effects if ingested before 18 weeks Interruption of normal vaginal development Hypoplastic T shaped uterine cavity Cervical collars withered fallopian tubes DES is an incomplete carcinogen b/c it has many effects. Antineoplastic drugs Because of their mechanism of action, most are teratogenic Cyclophosphamide: Missing and hypoplastic digits on hands and feet Methotrexate/aminopterin Growth restrictions Failure of calvarial ossification
Alcohol Ethyl alcohol is one of the most potent teratogens Common cause of mental retardation Exposure dose: Safe threshold has never been established Greatest risk in those who chronically ingest large quantities and engage in binge drinking. Anticonvulsant medications: Most frequent defects are: Orofacial deformities: 10X incidence Congenital heart disease Example Phenytoin Carbamazepine Trimethadione & paramethadione Valproic acid
Anticoagulant/ Warfarin compounds: Low molecular wt; hence, can cross the placenta Distinct defects with two different etiologies resulting from exposure at two different periods th th 6 to 9 week AOG Warfarin embryopathy Nasal hypoplasia & stippled vertebral & femoral epiphyses No Vit-K dependent clotting factors d/t inhibition of posttranslational carboxylation of coagulation proteins (embryonic control of calcification) th after 9 week AOG hemorrhage leading to disharmonic growth and deformation from scarring Dorsal midline CNS dysplasia What is the safest anticoagulant to give during pregnancy? Heparin big molecular weight; hence, wont cross placenta. Angiotensin-converting enzyme inhibitor & AngiotensinReceptor Blockers an antihypertensive meds st No structural malformation from 1 trimester exposure nd PRIMARILY affects fetus during the 2 TRIMESTER
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Craniosyntosis Hypoplastic supraorbital ridges Micrognathia neural tube defects: b/c methotrexate is an antifolic acid medication. Antineoplastic drugs target the cell cycle and they target cells in mitosis. Developing baby has a high rate of mitosis. Antimicrobials Tetracycline: yellow brown discoloration of the teeth/long bones in children when exposed to this drug in utero acute fatty liver change in pts with renal insufficiency one acceptable use: maternal syphilis if penicillin allergic Aminoglycosides: Streptomycin cause CN 8 damage (vestibulocochlear nerve) Sulfonamides: Commonly used for UTI nd Okay to use up to 2 trimester rd During 3 TRIMESTER: will compete with protein binding with bilirubin, so you end up with a lot of active bilirubin Hyperbilirubinemia KERNICTERUS DO NOT GIVE NEAR TERM!!! Griseofulvin; USED AS AN ANTIFUNGAL increased anomalies of the CNS & skeleton: Ribavirin: IS AN ANTIVIRAL MEDICATION given by aerosol inhalation to treat Respiratory Syncitial Virus hydrocephalus & limb abnormalities in rodents: but in humans has NO current reported CASES. Tobacco Potential teratogens: Nicotine Cotinine Cyanide Thiocyanate carbon monoxide cadmium lead hydrocarbons has vasoactive & fetotoxic effects Most documented adverse outcome Fetal growth restriction IUGR, so you end up with smaller babies. Others adverse outcomes Spontaneous abortion Placenta previa & abruption Preterm delivery Thalidomide Is a Anxiolytic and sedative drug th Produces malformation on 20% of exposed b/w 34 th to 50 day o Defects 1 limited to mesoderm derived structures e.g. limbs, bowel musculature, ears, CVS Demonstrated relationship between time of exposure and type of defect. Days 27 to 30 AOG = upper limb phocomelia Days 30 to 33 AOG = lower limb phocomelia. Phocomelia = baby who looks like a frog (with no limbs) Days 42 to 43 AOG = GB aplasia Herbal Drugs Blue and black cohosh directly stimulate uterine musculature maternal deaths Pennyroyal work by irritating the bladder and uterus and causing strong uterine contractions. Recreational Drugs Amphetamines Methamphetamines symmetrical fetal-growth restriction Cocaine vasoconstrictive and hypertensive effects risk of vascular disruption within the embryo, fetus, or placenta is highest after the first trimester accounts for the increased incidence of stillbirth with this drug skull defects, cutis aplasia, porencephaly, subependymal and periventricular cysts, ileal atresia, cardiac anomalies, and visceral infarcts Opiates/ Narcotics Heroin Fetalgrowth restriction, perinatal death, and several perinatal complications Methadone higher rate of preterm labor, rapid labor, placental abruption, and meconium staining
DRUGS COMMONLY USED IN PREGNANCY Conditions during Pregnancy requiring medication Infections CVD Seizure disorders Psych conditions Analgesics Local analgesia & anesthesia Antiemetics Immunosuppressive drugs Hormones Natural (herbal) remedies Illicit drugs Infections: Antibacterial agents Majority are within Category B & C Except for aminoglycosides & tetracyclines: Category D Drugs that cross the placenta Cephalosporins Clindamycin Chloramphenicol Vancomycin may be associated with nephrotoxicity & ototoxicity Recommendation is to lower the dose if you need these medications during pregnancy Antifungal agents: Majority are in Category C Commonly used drugs for vaginal candidiasis Clotrimazole Miconazole Nystatin No increase in congenital malformations If only given in vaginal canal, chances for systemic contraction is not that high, therefore no increase risk for congenital malformation Antiviral agents: Limited experience in pregnancy Most of the drugs appear to be safe but further studies still have to be made st Amantadine use in the 1 trimester resulted in cardiac defects Antiparasitic agents Metronidazole category B: safe Intravaginal suppository for bacterial vaginosis w/c is common d/t alkaline pH of vagina Antimalarial drugs relatively safe except for Quinine & Quinidine Associated with CNS defects, hearing impairment, limb & urogenital anomalies
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But not reported if given in therapeutic doses Withheld unless patient is severely ill with malaria Mebendazole: is an antihelmintic: i.e. worms No reported teratogenic effects Cardiovascular disease: Heart failure & arrhythmias Digoxin rapidly crosses the placenta No convincing evidence it causes adverse fetal outcome Beta-adrenergic blocking drugs (propranolol) Associated w/ decreased blood flow to baby IUGR Baby will also have hypotension but for as long as there is adequate perfusion of blood from mother to baby then it is okay but if mother becomes hypotensive as well then blood flow to baby becomes compromised Common seizure cause: Eclampsia Antiarrhythmic drugs all cross the placenta but with no adverse fetal outcome. What happens to heart if you give lidocaine to arrhythmic heart? You end up with a normal heart. But what happens if you give lidocaine to normal beating heart? Arrhythmia. Antihypertensive drugs: Most are safe for use: Methyldopa: used in chronic hypertension Hydralazine Clonidine DONT use ACE inhibitors: Category X Na Nitroprusside Readily cross the placenta Can theoretically cause accumulation of cyanide in fetal liver only given w/ severely pathologic Htn uncontrolled by any other anti-Htn meds ++ Ca channel blockers (Nifedipine) Use with caution, as it can cause decrease in uterine blood flow: you will end up with a smaller baby and there is a sudden drop in blood pressure, so you can have sudden decrease in blood flow Diuretics: For chronic hypertension and pulmonary edema Dont give in eclamptic pt w/ edema unless w/ pulmonary congestion Thiazides associated w/ thrombocytopenia, bleeding and electrolyte disturbance when given near delivery Spironolactone causes feminization in rats: its a potassium sparing diuretic Furosemide stimulates prostaglandin E2 synthesis which increases incidence of PDA in preterm infants Anticoagulants Heparin is the drug of choice: i.e. pts prone to DVT Coumarin derivatives cause embryo-fetal defects hence not used in pregnancy: Thrombolytic agents use in pregnancy show no increase in teratogenic effect Asthma Most medications for asthma are safe Includes: Epinephrine Terbutaline: this is usually given also a uterine muscle relaxant; hence, used to prevent premature labor Aminophylline Ephedrine Inhaled corticosteroids Only used for a short period Seizure disorders: Most commonly used are teratogenic: Category X Drugs with no increased frequency of teratogenic effects: Category B Phenobarbital Ethosuximide Methosuximide Psychiatric conditions Benzodiazepines Associated with cleft palate & limb malformations in rodents Lithium salts Cardiovascular abnormalities May be taken during pregnancy but discontinued at least until 6 to 8 weeks AOG when cardiac function has finished Analgesics: Aspirin: a low dose of aspirin for heart problem is 80 mg. (60 mg in textbook will not have adverse effect) Prostaglandin inhibitor Premature closure of the ductus arteriosus Paracetamol: safe for pregnancy Other NSAIDs Not teratogenic but may have reversible fetal effects when used in the third trimester Associated with constriction of the ductus arteriosus & subsequent persistent fetal circulation Decreased urine output & decrease AF volume Hence use to treat hydramnios If child has PDA, Rx: is a NSAID: indomethacin. Local analgesia & anesthesia None of the currently used anesthetic agents are teratogenic Exposure during pregnancy is brief and not at toxic levels But data supporting this is imperfect Antiemetics No evidence that any antiemetics are associated with increased risk of congenital anomalies Metoclopramide No adverse effect in humans reported st Whats MC antiemetic used in 1 trimester? Metoclopramide and these are safe. Remember with prenatal check up: what was the advise? You give for hyperemesis? You give Vitamin B12 + doxylamine (a sedative, which is an antiallergy1) Immunosuppressive drugs Azathioprine Teratogenic to animals but safe for human pregnancy Cyclosporine Significant maternal nephrotoxicity appears to be safe for the fetus Cyclophosphamide A suspected teratogen Hormones: Oral contraceptive pills High dose OCP = cardiovascular & limb reduction defects Gonadotrophin releasing hormones Little information regarding use in pregnancy Natural (herbal) remedies
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Difficult to estimate due to: Unknown ingredients No human or animal studies Knowledge of complication limited to acute toxicity Due to this better to avoid this remedies Illicit drugs
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CHAPTER 15
Antepartum Assessment
ANTEPARTUM ASSESSMENT Test done antenatally to determine fetal well being Focus on testing procedures that depend on fetal physical activities, including movement, breathing, amniotic fluid production, & heart rate GOALS of antepartum fetal surveillance Prevention of fetal death Avoidance of unnecessary interventions
AFV estimated using US Decreased fetal activity w/ decreased amniotic vol w/c lead to restricted intrauterine space w/c might physically limit fetal movements Oligohydramnios can put fetus in jeopardy & lead to termination of pregnancy
SIGNIFICANCE OF FETAL MOVEMENTS IN DETERMINING FETAL WELL BEING Methods to quantify fetal movement: Tocodynamometer Sonography Maternal subjective perceptions Reported excellent correlation b/w maternally perceived fetal motions/ documented by instrumentation Rayburn 80% of movements on US were perceived by the mother Hohnson et al only 16% beyond 36 wks AOG were perceived by mother Several fetal movement counting protocols have been used No definition of the optimal number of movements nor the ideal duration for counting For example: perception of 10 fetal movements in up to 2 hours is considered normal Or women are instructed to count fetal movements for 1 hr a day & is accepted as reassuring if it equals or exceeds a previously established baseline count For history of failed pregnancy, record 8 movements for every 4 hours is normal Other tests: Non-stress test Contraction stress tests Pregnancy outcome for women who complained of decreased fetal movt were not significantly different than those women without this complaint. Nonetheless, it is recommended that evaluation be done to reassure the mother A diminishing number of fetal movements taken daily seem to indicate poor status that has to be critically looked into Test may be repeated weekly or more frequently depending on AOG
FETAL MOVEMENTS 7 wks: Passive unstimulated fetal activity commences where fetus starts to show rest activity cycles > 8 wks: Fetal body movements are never absent for time periods exceeding 13 minutes 20 to 30 wks: organized General body movements restactivity cycle 36 wks or 3rd trimester: Fetal movement maturation when 4 behavioral states are established in 80% of normal fetuses US picture measure crown rump length to determine AOG based on CRL (crown rump length) notice the yolk sac, that supplies nutrients to growing embryo (the round image in the US) there is somatic activity as early as 8 to 9 weeks of AOG. If there is no movement or cardiac activity you can assess embryo and embryo could have some problems and early embryonic demise
4 STAGES OF FETAL BEHAVIORAL STATES State 1F: quiescent state quiet sleep with a narrow oscillatory bandwidth of the fetal heart rate State 2F: Active Sleep includes frequent gross body movements continuous eye movements wider oscillation of the fetal heart rate. analogous to rapid eye movement (REM) or active sleep in the neonate Diminished bladder volume State 3F continuous eye movements in the absence of body movements and no heart rate accelerations. existence of this state is disputed. State 4F: Awake State vigorous body movement with continuous eye movements and heart rate accelerations. This state corresponds to the awake state in infants. NOTE: Most fetuses are in state 1F &2F 38 weeks, 75% of time is spent in these two states 1F and 2F, correspond to Quiet sleep and active sleep Urine production bladder volumes increased during state 1F quiet sleep. During state 2F, the fetal heart rate baseline bandwidth increased appreciably, and bladder volume was significantly diminished. The latter was due to fetal voiding as well as decreased urine production. These phenomena were interpreted to represent reduced renal blood flow during active sleep.
SIGNIFICANCE OF FETAL BREATHING IN DETERMINING FETAL WELL BEING Interesting feature of fetal respiration was paradoxical chest wall movement During inspiration the chest wall paradoxically collapses & the abdomen protrude (the opposite in newborn or adult): PARADOXICAL CHEST WALL MOVEMENT Might be coughing to clear amniotic fluid debris Exchange of amnionic fluid appears to be essential for normal lung development 2 types of respiratory movements were identified: Gasps or sighs w/c occurs at frequency of 1-4 pre minute Irregular bursts of breathing: 240 cpm like REM in infant Color flow & spectral Doppler analysis of nasal fluid flow as an index of lung function tests to determine maturation of fetal breathing Fetal respiratory rate decreased w/ increased respiratory volume at 33 36 wks & coincidental w/ lung maturation FACTORS affecting fetal respiratory movements: Hypoxia Labor: normal for respiration to cease Hypoglycemia Sound Stimuli Cigarette Smoking Amniocentesis Impending Preterm Labor Gestational Age
SLEEP CYCLICITY Important determinant of fetal activity Independent of maternal sleep-awake state Varies: 20 to 75 mins Mean length of the quite or inactive state for term fetuses was 23 minutes
AMNIOTIC FLUID VOLUME Important determinant of fetal activity
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Fetal Heart Rate Diurnal variation wherein breathing at night Breathing following maternal meals Fetal breathing is a component of BIOPHYSICAL PROFILE Assessed by: Ultrasound Color Flow Spectral Doppler consumed. contraction So evidence of deceleration occurs after
PRINCIPLE OF CONTRACTION STRESS TEST aka oxytocin challenge test test Uteroplacental Function as amniotic fluid pressure increases w/ uterine contractions, myometrial pressure exceeds collapsing pressure for vessels in uterine mms, ultimately decreasing blood flow to the intervillous space brief periods of impaired oxygen exchanges, if uteroplacental pathology is present leads to late fetal HR decelerations contractions also lead to a pattern of variable decelerations (cord compression), suggesting oligohydramnios (concominant of placental insufficiency) deceleration not related to peak or end of contraction late decelerations is usually noted at the peak & end of contraction: drop of basal HR WAYS TO PERFORM TEST 10 units of oxytocin into 1 L of IV fluid Contractions were induced using IV oxytocin, & the FHR response was recorded using standard monitoring Criterion for a positive (abnormal) test was uniform repetitive fetal heart rate decelerations w/c could be due to uteroplacental insufficiency Negative (normal) contraction stress test forecast fetal health No repetitive deceleration even at the peak or end of contraction Fetal HR & uterine contractions are recorded simultaneously w/ an external monitor If at least 3 spontaneous contractions of 40 secs or longer are present in 10 mins, no uterine stimulation is necessary Contractions are induced w/ either oxytocin or nipple stimulation if there are fewer than 3 in 10 mins If oxytocin is preferred, a dilute IV infusion is initiated at a rate of 0.5 mU/min (10 drops) & doubled every 20 mins until a satisfactory contraction pattern is established NIPPLE STIMULATION Involves the women rubbing 1 nipple through her clothing for 2 mins or until a contraction begins Instructed to restart after 5 mins if the 1st nipple stimulation did not induce 3 contractions in 10mins CRITERIA FOR INTERPRETATION Negative/ NORMAL: no late or significant variable decelerations, baby is in good health Positive: late decelerations following 50% or more of contractions even if the contraction frequency is fewer than 3 in 10 mins Equivocal-suspicious: intermittent late decelerations or significant variable decelerations need to repeat test: ask the patient to rest and repeat the contraction stress test Equivocal-hyperstimulatory: FHR decelerations that occur in the presence of contractions more frequent than every 2 mins or lasting longer than 90 sec. about 5 contractions every 10 mins or longer duration contractions Unsatisfactory: fewer than 3 contractions in 10 mins or an uninterpretable tracing Done after NON-STRESS TEST When there is initial contraction, and blood is coming from reserve of placenta and after the reserve is used, the contraction is at the peak and reserve of blood from placenta is being used from the baby so as the contraction subsides there is no more blood supply and there is decrease in blood supply and tendency will decelerate. Reserve of blood being used during contraction is being
NON-STRESS TEST Test of FETAL well being Aka NST Describe fetal heart rate acceleration in response to fetal movement as a sign of fetal health NST is primarily a test of fetal condition, whereas, the CST, is a test of uteroplacental function Currently, NST is the most widely used primary testing method for assessment of fetal well-being; and now also a part of the BPS (Biophysical Profile Scoring) testing system. FETAL HEART RATE ACCELERATION Normally increase or decrease by autonomic influences mediated by SNS or PNS impulses from the BS centers Beat-to-beat variability is also under the control of ANS Pathological loss of acceleration seen with significantly decreased beat-to-beat variability of FHR Central depression 2ndary to meds also result in loss of reactivity & associated with sleep cycles NST is based on the hypothesis that the HR of a fetus who is not acidotic as a result of hypoxia or neurological depression will temporarily accelerate in response to fetal movement Fetal movt during testing are identified by the maternal perception & recorded
In a woman w/ diabetic ketoacidosis: TRACING A: obtained during maternal & fetal acidemia: Shows absence of accelerations, diminished variability, & late decelerations w/ weak spontaneous contractions
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TRACING B: return of normal accelerations & variability of the fetal HR following correction of maternal academia Percentage of body movements accompanied by acceleration & the amplitude of these accelerations increased w/ gestational age The NICHHD definition of NORMAL ACCELERATION: (KNOW THIS by HEART!) > 32 weeks AOG: The acme of acceleration is 15 bpm or more above the baseline rate, & the acceleration lasts 15 seconds or longer but less than 2 minutes. < 32 weeks AOG: accelerations are defined as having an acme 10 bpm or more above baseline for 10 seconds or longer. WAYS TO PERFORM NST Involved the use of Doppler-detected fetal HR acceleration coincident w/ fetal movt perceived by mother NORMAL NST 2 or more accelerations that poeak 15 bpm or more above baseline, each lasting 15 sec or more & all occurring w/in 10 min of the beginning the test Fetal movements indicated by vertical marks on the lower part of the recording It was also recommended that accelerations w/ or w/out fetal movt be accepted, & that a 40 min or longer tracing to account for fetal sleep cycles should be performed before concluding that there was insufficient fetal reactivity Vibroacoustic stimulator can produce a high sound like the take off of a jet w/c can stimulate the baby to wake up Average sleep cyclicity of baby is 23 mins, max at 25 mins Abnormal NST Silent oscillatory pattern: consisted of a FHR baseline that oscillated less than 5 bpm & presumably indicated absent acceleration & beat-to-beat variability Bad tracing Terminal Cardiotocogram: baby is about to expire Baseline oscillation of less than 5 bpm Absent accelerations Late decelerations w/ spontaneous uterine contraction NOTE: Oxytocin challenge test can also be done to show decelerations The lack of FHR acceleration, when not d/t maternal sedation, is an ominous finding. Can be d/t: Fetal-growth restriction Oligohydramnios Fetal acidosis Meconium Placental Infarction NST that were nonreactive for 90 mins were almost invariably (94%) associated w/ significant perinatal pathology INTERVAL B/W TESTING Reactive NST: Good The interval b/w test, originally 7 days, has been shortened as experience evolved w/ NST More frequent testing for the following conditions: postterm pregnancy multifetal gestation Type 1 DM Fetal growth restriction Gestational Htn 2x wkly tests are advised w/ additional testing performed for maternal or fetal deterioration Others perform NST daily or even more frequently in women w/ severe preeclampsia remote from term Decelerations during NST Fetal movts commonly produce HR decelerations Variable decelerations, if nonrepetitive & brief less than 30 secs do not indicate fetal compromise or the need for obstetrical intervention In contrast, repetitive variable decelerations at least 3 in 20 mins even if mild, have been associated w/ an increased risk of cesarean delivery for fetal distress Decelerations lasting 1 min or longer have an even worse prognosis INTERPRETATION OF NST False-normal NST Causes fetal death w/in 1 wk of normal NST: Postterm pregnancy Most common autopsy finding was meconium aspiration Intrauterine infection Abnormal cord position Malformations Placental abruption NST was inadequate to preclude such an acute asphyxia event; other biophysical characteristics might be beneficial adjuncts like: BPS testing Counting & recording of fetal movements
ACOUSTIC STIMULATION NONSTRESS TESTS Loud external sounds are used to startle the fetus, provoking acceleration of the HR an acoustic stimulation NST Applied to maternal abdomen Sound intensity 100 & 105 dB was maintained until the stimulator was moved more than 20 cm from the maternal abdomen Acoustic stimulator is positioned on the maternal abdomen & a stimulus of 1 to 2 secs is applied; may be repeated up to 3x for up to 3 secs Positive response rapid FHR acceleration following stimulation
BIOPHYSICAL PROFILE
Combined use of 5 fetal biophysical variable is a more accurate means of assessing fetal health than a single element Performed by OBGYN sinologist EQUIPMENTS to record HR: Sonography machine Doppler US
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TEST DURATION: 30-60 mins SCORING: 0-10 Normal: 2 Abnormal: 0 5 components FHR acceleration: NST: score of 2: accelerations of 15 beats/min for 15 sec in 20-40 min Fetal breathing: score of 2: 1 episode of rhythmic breathing lasting 30 sec w/In 30 mins Fetal movements: score of 2: 3 discrete body or limb movt w/in 30 mins: score of 2: 1 episode of extension of a fetal extremity w/ return to flexion or opening or closing of hand w/in 3 min Fetal tone: score of 2: single vertical pocket >2 cm Amniotic Fluid Volume If score is 8/10, NST is no longer tested Normal variable: score of 2 each Abnormal score = zero score Highest normal score= 10 BPS score of zero significant fetal academia, Normal scores of 8 to 10 normal pH Score of 6 an equivocal test result a poor predictor of abnormal outcome Score of 2-4-0 more accurate predictor of abnormal outcome Causes of fetal death after normal BPS d/t fetomaternal hemorrhage umbilical cord accidents placental abruption MODIFIED BIOPHYSICAL PROFILE Consists of the vibroacoustic NST + determination of amniotic fluid index Done 2x/wk DURATION: 10 mins Acceptable means of antepartum fetal surveillance according to ACOG CURRENT ANTENATAL TESTING RECOMMENDATION There is no best test to evaluate fetal well being 3 testing systems: have different end points that are considered Contraction stress test NST BPS Severity of maternal dse is another important consideration especially w/ severe/ uncontrolled preeclampsia In general, w/ the majority of high-risk pregnancies, most authorities recommend that testing begin by 32 wks to 34 wks, 26 wks to 28 wks if w/ severe complications
SIGNIFICANCE OF FETAL TESTING Fetal death rate significantly less in the tested high-risk pregnancies Antenatal forecasts of fetal health focus of intense interest for more than 2 decades Fetal biophysical performance is characterized by wide range of normal variation Abnormal results are seldom reliable, prompting antenatal testing to forecast fetal wellness rather than illness
AMNIOTIC FLUID VOLUME Indicator of fetal health Mechanism of amniotic fluid formation in relation fetal status Decreased utero placental perfusion fetal renal blood flow urine production oligohydramnios Amniotic Fluid Index, the deepest vertical pocket, & the 2x2 pocket used in the biophysical profile ultrasonic techniques used to estimate amniotic fluid volume Index of 5.o cm or less significantly increased the risk of either casarean delivery for fetal distress or a low 5-min Apgar Score An AFI of 5 cm or less has increased perinatal morbidity & mortality rates
UMBILICAL ARTERY DOPPLER VELOCIMETRY Doppler US noninvasive technique to assess blood flow by characterizing downstream impedance The umbilical artery systolic diastolic (S/D) ratio, the most commonly used index abnormal if above the 95th percentile for gestational or diastolic flow is either absent or reversed ABSENT or REVERSED DIASTOLIC FLOW: Signifies impedance to umbilical artery blood flow d/t poor vascularized placental villi seen in extreme cases of fetal growth restriction Utility of umbilical artery Doppler velocimetry NO BENEFIT has been demonstrated other than in pregnancies w/ suspected fetal growth restriction No benefit demonstrated for velocimetry for other conditions, such as postterm pregnancy, DM, SLE, or antiphospholipid antibody syndrome Similarly, velocimetry has not proved of value as screening test for detecting fetal compromise in the general obstetrical population Test is quite expensive
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CHAPTER 16
SONOGRAPHY IN OBSTETRICS 2 probes Transabdominal: probe is placed on the abdomen of the pt to assess different pevic organs Transvaginal: probe is inserted inside the vagina so there is close proximity in assessing the uterus, ovaries, fallopian tube used during 1st trimester of pregnancy Types 2D US: Most commonly used if abnormal findings, request for 3D & 4D 3D US 4D US: can record movement of fetus inside womb TECHNOLOGY Produced by sound waves reflected back from organs, fluids & tissues interfaces of the fetus within the uterus Transducers Made of piezoelectric crystals convert electrical energy into sound waves that are emitted in synchronized pulses, then listen for the returning echoes Types: High Frequency Transducers Yield better image resolution Low Frequency Transducers Penetrate tissue more effectively Wide Bandwidth Transducers Perform over a range of frequecies Soluble gel is applied to the skin to act as a coupling agent Dense tissue such as bone produces high velocity reflected waves, which are displayed bright on the screen Fluid generates few reflected waves & appears dark or anechoic on the screen 1st trimester 0 to 15 wks AOG 4 to 9 mHz-bandwith transvaginal transducers provide excellent resolution because the small embryo is close to the transducer 2nd trimester 16 to 24 wks AOG 4 to 6 mHz-bandwith transducer is often in close enough proximity to the fetus to provide precise images 3rd trimester 25 to 40 wks AOG 2 to 5 mHz-bandwith transducer may be needed for penetration, but can lead to compromised resolution Resolution also compromised in obese patients SAFETY ALARA principle: As Low As Reasonably Achievable US should be performed only w/ valid medical indication & w/ the lowest possible exposure to gain necessary information Prolonged exposure to US affects the migration of brain cells in fetal mice Duplex Doppler coupled w/ real-time imaging requires monitoring of the thermal index Microbubble US contrast agents are not used in pregnancy because they might raise the mechanical index American Institute of US in Medicine recommends that fetal sonography be performed only by trained professionals who can recognize medically important conditions such as: Fetal Anomalies Artifacts that may mimic pathology
Techniques to avoid US exposure beyond what is considered safe for the fetus CLINICAL APPLICATIONS MAJOR BENEFITS of US: Assessment of AOG Assessment of Fetal growth Detection of fetal & placental abnormalities FACTORS affecting sensitivity of US in detecting fetal anomalies: Gestational age Maternal Habitus Position of the fetus Features of the equipment Skill of the sonographer Specific abnormality in question INDICATIONS for 1st Trimester US Examination Confirm an intrauterine pregnancy: gestational sac is the first evidence of intrauterine pregnancy Evaluate a suspected ectopic pregnancy Define the cause of vaginal bleeding: any form of bleeding during pregnancy is abnormal can be a form of Abortion during 1st trimester Evaluate pelvic pain Estimate gestational age: assess sac diameter Most sensitive: measurement of CRL Diagnose or evaluate multifetal gestations Confirm cardiac activity: confirm viability Assist chorionic villus sampling, embryo transfer, & localization & removal of an intrauterine device: for karyotyping purposes, embryo transfer for the transfer or for fertility work-up, etc Assess for certain fetal anomalies, such as anencephaly, in high-risk patients Evaluate maternal pelvic masses & or uterine abnormalities: Most common lesions: myoma Intramural Subserous Subendothelial Assess adnexa primarily right & left fallopian tube Measure nuchal translucency when a part of a screening program for fetal aneuploidy Very sensitive, if there is abnormal thickness of nuchal translucency: Aneuploidy Mc: Trisomy 21 (Downs Syndrome) Others: Trisomy 13 (Pataus) Evaluate suspected gestational trophoblastic disease Aka: Hydatidiform mole COMPONENTS of standard US exam by Trimester 1st TRIMESTER EVALUATION Anembryonic gestation, embryonic demise, & molar & ectopic pregnancies can be reliably diagnosed Multifetal gestation can be identified early Optimal time to determine chorionicity Ideal time to evaluate certain maternal pelvic structures: Uterus Adnexa Cul-de-sac Early pregnancy can be evaluated using Transabdominal or Transvaginal US or both. Transvaginal US Gestational sac is reliably seen in the uterus by 5 weeks
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Fetal echoes & cardiac activity by 6 weeks Cardiac motion typically observed when the embryo is 5 mm in length Crown-rump Length Most accurate biometric predictor of gestational age Obtained in a sagittal plane & does NOT include yolk sac nor a limb bud Variation of only 3 to 5 days COMPONENTS OF US EXAM ON 1st TRIMESTTER
Assess Presentation Cephalic Breech Transverse Assess placental location & its relationship to the internal cervical os Placenta Praevia Marginalis Placenta Praevia Totalis During 2nd trimester, most common cause of bleeding is placenta praevia INDICATIONS for 2nd & 3rd Trimester US:
FETAL ABNORMALITIES Anencephaly Acceptable indication for 1st Trimester US examination 17 of 24 fetal defects can be discovered by Transvaginal US during the 1st semester w/c include malformations in: CNS Neck Neural Tube Heart Nuchal Translucency Maximum thickness of the subcutaneous translucent area b/w the skin & soft tissue overlying the fetal spine at the back of the neck Measured in the sagittal plane b/w 1114 wks AOG When , indicates higher risk for: Fetal Aneuploidy 1st Trimester Aneuploidy Screening includes: Nuchal Translucency Measurement Maternal Serum Chorionic Gonadotropin BIOCHEMICAL MARKERS: serum HCG, PAPP A, NT Pregnancy-associated Plasma Protein A BIOCHEMICAL MARKERS: alpha feto protein Other structural anomalies Cardiac dysfunction Venous congestion of the head & neck Altered composition of the ECM Failure of the lymphatic drainage Fetal infection Fetal hypoprotenemia 2nd & 3rd TRIMESTER EVALUATION Cervical length is best evaluated during 2nd trimester COMPONENTS OF US EXAM ON 2nd & 3 rd TRIMESTTER
3 types of US evaluation Standard Specialized Limited Standard US Evaluation Aka: Basic US Evaluation Survey of fetal anatomy With Multifetal gestation, documentation includes: Number of chorions & amnions Comparison of fetal sizes Estimation of amniotic fluid volume in each sac Description of fetal genitalia Fetal anatomy may be adequately assessed after ~ 18 weeks May not be adequately obtained d/t: Oligohydramnios Fetal Position Maternal Obesity
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COMPONENTS Examination of Standard US Most accurate in the 1st trimester Biparietal Diameter (BPD) Most accurate from 14-26 wks, w/ a variation of 7-10 days Measured from the outer edge of the proximal skull to the inner edge of the distal skull, at the level of the thalami & cavum septum pellucidum Head Circumference (HC) Head shape: Flattened: dolichocephaly Rounded: brachycephaly more reliable than the BPD Femur Length (FL) Correlates well w/ (B) BPD & gestational age Measured w/ the beam perpendicular to the long axis of the shaft, excluding the epiphysis Has variation of 7 to 11 days in the 2nd trimester Abdominal Circumference (AC) Widest variation of up to 2 to 3 weeks because it involves soft tissue like LIVER Shrinkage of liver small abdominal circumference Circumference is mostly affected by fetal growth Fetal macrosomia greater AC Measured at the skin line in a transverse view of the fetus at the level of the fetal stomach & the confluence of the umbilical vein w/ the portal sinus Variability of gestational age estimation w/ advancing pregnancy Least accurate in the 3rd Trimester Estimates are improved by averaging the 4 parameters US to evaluate fetal growth should typically be performed at least 2-4 weeks apart AMNIOTIC FLUID Oligohydramnios Obvious crowding of the fetus Absence of significant fluid pockets Hydramnios Apparent fluid excess o US Amniotic fluid index Most widely used tool to measure amniotic fluid volume calculated by adding the depth in centimeters of the largest vertical pocket in each of four equal uterine quadrants Umbilicus as landmark Measure widest vertical diameter & the summation of the 4 quadrants is the amniotic fluid index Reference range established from 16 weeks onwards N: 8-24 cm Largest Vertical Pocket Another way to measure amniotic fluid volume N values: 2-8 cm AbN values: < 2 cm: oligohydramnios > 8 cm: Hydramnios Commonly used for TWIN pregnancies
Specialized US Examination Targeted examination: is a detailed anatomical survey performed when an anomaly is suspected on the basis of: History Maternal serum screening test abnormalities Abnormal findings on standard examination Other Specialized examinations include: Fetal Echocardiography Doppler Evaluation Biophysical Profile Additional Biometric Studies Specialized studies are performed & interpreted by an experiences operator who determines the examination components on a case-by-case basis Limited US Examination Done when a specific question requires investigation such as: Amniotic fluid assessment For water vaginal discharge during pregnancy Placental location Evaluation of fetal presentation or viability Appropriate only when a prior complete examination is on record FETAL BIOMETRY CRL Estimates AOG Assess thickness of subQ: nuchal translucency Biparietal Diameter, Head & Abdominal Circuference, & Femur Length Estimates AOG & fetal weight Nomograms for individual structures are used to address specific questions about organ system abnormalities or syndromes like: Fetal Cerebellum Ears Interocular & Binocular orbital distances Thoracic circumference Kidneys Long bones Feet VIEWS: Transthalamic View Transverse axial image obtained at the level of the thalami & cavum septum pellucidum BPD & HC are measure in this view Transcerebellar: assess posterior fossa Transventricular Nuchal fold Gestational Age Determination Parameters of AOG Crown-rump Length (CRL)
NORMAL & ABNORMAL FETAL ANATOMY IMPORTANT GOAL OF US: Categorize fetal components as anatomically normal or abnormal CNS Brain anomalies are the most common findings such as: NTD Ventriculomegaly
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Holoprosencephaly Hydranencephaly Dandy-Walker malformation Agenesis of the Corpus Callosum Porencephaly Intracranial Tumor 3 transverse axial views: Transthalamic view Used to measure BPD & HC includes the thalami & cavum septum pellucidum Transventricular view Includes the atria of the lateral ventricles contain the echogenic choroid plexus Transcerebellar view Obtained by angling the view back through the posterior fossa Measures the cerebellum & cisterna magna 15-22 weeks: cerebellar diameters = AOG in weeks Neural Tube Defects (NTD) 2nd most common class of CONGENITAL abnormalities CARDIAC anomalies are the MC 1.6/1000 live nirths in US Incomplete closure of the neural tube by embryonic age of 26 to 28 days Prenantal Tools to diagnose for NTD: Maternal serum alpha-fetoprotein screening Sonography Anencephaly Lethal defect characterized by the absence of the brain & cranium above the base of the skull & orbits Can be diagnosed in the late 1st trimester by inability to view the biparietal diameter Hydramnios from impaired swallowing is common in the 3rd Trimester Incompatible w/ life Theories Failure of the anterior neuropore or neural grove to close correctly Excess CSF causing disruption Decreased blood levels of some vitamins most notably folic acid give folic acid 3 months prior to pregnancy Cephalocele Aka: Encephalocele Herniation of meninges & brain tissue through a cranial defect, typically an occipital midline defect Commonly associated w/ Hydorcephalus & Microcephaly High incidence of MENTAL RETARDATION Meckel-Gruber Syndrome: Autosomal recessive Cephalocele that is NOT in the occipital midline CAUSE: Amniotic Band Sequence lethal monogenic disorder at chromosome 17 Spina Bifida Opening of the vertebrau through w/c a menigeal sac may protrude Subtypes: Meningomyelocele Aka: Spina Bifida Cystica 90% of cases sac contains neural elements Meningocele Aka: Spina Bifida Occulta Sac alone protrudes through the defect Transverse images provide the best visualization of the extent of the defect & overlying soft tissue Arnold Chiari Malformation Associated w/ spina bifida Downward displacement of the SC pulls a portion of the cerebellum through the foramen magnum into the upper cervical canal Sonographic findings: LEMON SIGN: Scalloping of the frontal bones BANANA SIGN: Bowing of the cerebellum w/ effacement of the cisterna magna absent cisterna magna d/t disappearance of cerebellar vermis Small Biparietal Diameter Ventriculomegaly protrusion of fetal bone d/t ventriculomegaly Ventriculomegaly Enlargement of the cerebral ventricles Non-specific marker of abnormal brain development Lateral ventricles commonly measured at its Atrium Atrium confluence of the temporal & occipital horns N: 5-10 mm at > 15 weeks AbN values: Atria appear unusually prominent on US 10-15 mm: MILD VENTRICULOMEGALY > 15 mm: SEVERE
VENTRICULOMEGALY
CHARACTERISTIC FEATURE: Dangling Choroid Plexus d/t genetic & environmental insults other EVALUTATION TOOLS done: Examination of fetal Anatomy Fetal Karyotyping Testing for congenital infections Cytomegalovirus Toxoplasmosis Prognosis is variable Holoprocencephaly Procencephalon fails to divide completely into 2 separate cerebral hemispheres & underlying diencephalic structures Alobar Holoprocencephaly Most severe form Single monoventricle w/ or w/o a covering mantle of cortex fused central thalami differentiation into 2 cerebral hemispheres is induced by prechordal mesenchyme responsible for differentiation of the midline face; hence, HOLOPROCENCEPHALY is associated w/: Hypotelorism Aka: Cyclopia Anomaly of the eye or orbits Proboscis Aka: Arthinia Anomaly of the nose Median Cleft Anomaly of the lips Associated w/ chromosomal anomalies like Trisomy 13 (Pataus Syndrome) Do fetal karyotyping Cystic Hygroma Dandy-Walker Malformation Abnormality of the posterior fossa characterized by: Agenesis of the cerebellar vermis
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Enlargement of the posterior fossa Elevation of the tentorium US findings: Fluid in the enlarged cisterna magna visibly communicates w/ the 4th ventricle through the defect in the cerebellar vermis d/t vermian agenesis Absence of cerebellar vermis Visible separation of the cerebellar hemisphere Ventriculomegaly Associated w/ large number of genetic & sporadic syndromes: Aneuploidy Congenital viral infections Teratogens Poor prognosis LYMPHATIC SYSTEM CYSTIC HYGROMA Malformation of the lymphatic system Fluid sacs extend in the posterior neck Often large & multiseptated Typically develop as part of a lymphatic obstruction sequence where the lymph from the head fails to drain into the jugular vein & accumulates instead in the jugular lymphatic sacs Enlarged thoracic duct can impinge on the developing heart; hence, risk for cardiac malformations like flow related abnormalities: Hypoplastic left heart Coarctation of the aorta Associated problems: Aneuploidy 60-70% Turners Syndrome 75% of aneuploid cases 45, XO Mc diagnosed during the 2nd trimester Trisomy 21 Aka: Downs Syndrome Mc aneuploid diagnosed during the 1st Trimester 1st trimester fetuses w/ cystic hygroma were 5x more likely to be aneuploid than the fetuses w/ an nuchal translucency Genetic Syndromes Noonan Syndrome autosomal dominant congenital disorder a type of dwarfism Hydrops Fetalis Usually find large cystic hygromas that rarely resolve & carry poor prognosis abnormal amounts of fluid build up in two or more body areas of a fetus or newborn Prognosis maybe good if: Small hygromas May undergo spontaneous resolution Normal fetal karyotype Normal echocardiography THORAX LUNGS best visualized after 20-25 weeks appear as homogeneous structures surrounding the heart comprise 2/3rd of the chest Thoracic Malformations seen on US as cystic or solid space-occupying lesions Cystic Adenomatoid Malformation Extralobar Pulmonary Sequestration Bronchogenic Cysts Diaphragmatic Hernia Bochdaleks Hernia Left sided hernia w/c is 90% of all diaphragmatic hernias SONOGRAPHIC FINDINGS: Repositioning of the heart to the middle or right side of the thorax by the stomach & the bowel Associated findings: Absence of the stomach bubble within the abdomen: Magenblaze Sign Small abdominal circumference Bowel peristalsis seen in the fetal chest of cases associated w/ aneuploidy; hence, fetal karyotyping is done
HEART Cardiac malformations most common congenital anomalies incidence of 8/1000 live births multifactorial or polygenic 1-2% d/t exposure of teratogens: Isotretinoin Hydantoin Diabetic Hyperglycemia 30-40% d/t chromosomal abnormalities or aneuploidies such as: Downs Syndrome Trisomy 13 Trisomy 18 Turners Syndrome: 45,X Components of Examination STANDARD cardiac assessment includes: 4-chamber view Evaluation of rate & rhythm Evaluation of cardiac outflow tracts FOUR CHAMBER VIEW Transverse plane view through the fetal thorax at the level immediately above the diaphragm Evaluates: heart size position in the chest cardiac axis N: apex of the heart at 45 degree angle w/ the left anterior chest wall AbN: Apex angle > 75 degrees 75% of fetuses w/ congenital heart anomalies Left axis deviation: 45% atria & ventricles N: (B) should be similar in size foramen ovale atrial septum primum interventricular septum atrioventricular valves CARDIAC OUTFLOW TRACTS Aid detection of abnormalities not initially appreciated in the 4-chamber view such as: Transposition of the Great Vessels Tetralogy of Fallot Truncus Arteriosus FETAL ECHOCARDIOGRAPHY Specialized examination done when there are abnormalities noted in the 4-chamber view or outflow tracts Arrhythmia Extracardiac anomalie that confers risk Known genetic syndrome that may include cardiac defect nuchla translucency in the 1st trimester in a fetus w/ normal karyotype Insulin-treated diabetes p/t pregnancy Family Hx of congenital heart defect Exposure to a medication associated w/ risk for cardiac malformation ABDOMINAL WALL Ventral wall Defects 2 common anomalies Gastrochisis Omphalocele
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Often detected d/t maternal serum alphafetoprotein screening Gastrochisis Full thickness abdominal wall defect typically located to the right of the umbilical cord insertion Bowel hernitaes through defect into the amniotic cavity Anomaly more common in infants of younger mothers (20 y.o) Associated problems: Jejunal Atresia Bowel anomalies d/t vascular damage or mechanical trauma risk of growth restriction Longer hospitalization if born before 36 wks NOT associated w/ an risk of aneuploidy Survival rate is ~90% Omphalocele Lateral ectomesodermal folds fail to meet in the midline leaving abdominal contents covered only by a 2-layered sac of amnio & peritoneum Umbilical cord inserts at the apex of the sac Associated problems: Aneuploidy The smaller the defect, the greater the risk for aneuploidy Syndromes: Beckwith-Weidmann Cloacal exstrophy Pentalogy of Cantrell Mandates a complete fetal evaluation & karyotyping GASTROINTESTINAL TRACT 14 weeks: stomach visible in nearly all fetuses 2nd & 3rd trimester: liver, spleen, GB, & bowel can be identified Nonvisualization of the stomach w/ in the abdomen can be d/t: Esophageal atresia Diaphragmatic hernia Abdominal wall defects Neurological abnormalities that inhibit fetal swallowing ECHOGENIC Bowels appear bright on US exam w/ higher frequency transducer most commonly a normal variant or indicative of swallowed intra-amniotic blood if it appears as bright as fetal bone risk for underlying: GI malformation Congenital infection like Cytomegalovirus Cystic fibrosis Trisomy 21 GASTROINTESTINAL ATRESIA Most are characterized by obstruction w/ proximal bowel dilatation The more proximal the obstruction, the more likely it is associated w/ HYDRAMNIOS Esophagial Atresia Suspected when the stomach can not be visualized & HYDRAMNIOS is present In 90% of cases, a concomitant tracheoesophagial fistula allows fluid to enter the stomach makes prenatal detaction is problematic Associated anomalies: Aneuploidy: 20% Growth restriction: 40% Cardiac malformation Duodenal Atresia US exam: Bubble Sign Represents distension of the stomach & the 1st part of duodenum Not usually present prior to 24 wks Associated anomalies Trisomy 21 Distal bowel obstructions Result in multiple dilated loops that may have peristaltic activity Large bowel obstruction & Anal atresia Less readily diagnosed on US d/t hydramnios is not a typical feature Bowel may not be significantly dilated Transverse view through the pelvis may reveal enlarged rectum as a fluid-filled structure b/w the bladder & the sacrum
KIDNEYS & URINARY TRACT 14- 18 wks: Fetal kidneys visible adjacent to the fetal spine < 18 weeks: Placenta & membranes are the major source of amniotic fluid > 18 weeks: most of the fluid is produced by the kidneys Fetal urine Production from 5 ml/hr at 20 weeks to 50 ml/hr at term Unexplained oligohydramnios Suggests a urinary tract abnormality Normal amniotic fluid volume in the 2nd half of pregnancy Urinary tract patency Must have at least 1 functioning kidney Renal Agenesis 1 or both kidneys are congenitally absent Kidneys not visible on US & the adrenal glands typically enlarges to fill the renal fossa: lying down adrenal sign Bilateral Renal Agenesis No urine production ANHYDRAMNIOS Anhydramnios leads to Potter Syndrome Pulmonary Hypoplasia Limb Contracture Compressed Face Death from cord compression or pulmonary hypoplasia NOTE: if above abnormalities result from scant amniotic fluid of some other etiology it is called Potter Sequence Polycystic Kidneys Disease Infantile Autosomal Recessive Polycystic Kidney Disease Only form that can be reliably diagnosed antenatally Characteristics: Abnormally large kidneys that fill the fetal abdomen & appear to have a solid, ground-glass texture Enlarged abdominal circumference Severe oligohydramnios Cystic changes can only be identified microscopically Autosomal dominant conditions usually dont manifest until adulthood Multicystic Dysplastic Kidney Disease Renal changes arise from complete obstruction or atresia at the level of the renal pelvis or proximal ureter prior to 10 weeks Diagnosis can be made antenatally by identifying abnormally dense renal parenchyma w/ multiple peripheral cysts of varying size that do not communicate w/ each other or w/ the renal pelvis Distinguished from Obstructive Pyelectasis where the fluid-filled areas can be seen to connect Prognosis is GOOD if: Unilateral Normal amniotic fluid volume Prognosis is POOR if BILATERAL Uteropelvic Junction Obstruction
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Most common cause of neonatal hydronephrosis Affects males 2x as often as females Actual obstruction is generally functional rather than anatomical Bilater in 1/3rd of cases Characterized by dilatation of the renal pelvis: Pyelectasis NORMAL renal pelvis diameter: 4mm before 20 weeks Collecting System Duplication Most common genitourinary anomaly Characteristic obstruction of the upper pole is evident as PYELECTASIS Associated w/: dilated ureter that may be mistaken for a loop of bowel ectopic ureterocele w/in the bladder reflux of lower pole moiety is common VOIDING CYSTOURETHOGRAPHY done during the neonatal period to determine whether antimicrobial treatment is needed to urinary infections assist w/ planning f/u appointments or surgical interventions Bladder Outlet Obstruction Distal Obstruction More common in male fetuses MOST COMMON ETIOLOGY: Posterior Urethral Valves Urethra resembles a keyhole & the bladder wall is thickened OLIGOHYDRAMNIOS portends a POOR prognosis d/t pulmonary hypoplasia Overcrowding of structures obscures the captured image Lengthens time of completion of the study Limitations on image resolution, data storage, & manipulation RECOMMENDATIONS from AIUM & ACOG 3D US should only be used as an adjunct to conventional sonography
DOPPLER Used primarily in: duplex velocimetry color mapping Doppler shift phenomenon that occurs when a source of light or sound waves is moving relative to an observer and is detected by the observer as a shift in the wave frequency When sound waves strike a moving target, the frequency of the sound waves reflected back is shifted proportionate to the velocity and direction of the moving target. magnitude and direction of the frequency shift depend on the relative motion of the moving target, the velocity and direction of the target can be determined. Indications: used to determine the volume and rate of blood flow through maternal and fetal vessels. Two types of Doppler: Continuous wave Doppler equipment has two separate types of crystals: one transmits high-frequency sound waves other continuously receives signals It cannot be used for imaging of the blood vessel(s). M-mode echocardiography Continuous wave Doppler used to evaluate motion through time. Pulse wave Doppler uses only one crystal, which transmits the signal and then waits until the returning signal is received before transmitting another one allows precise targeting and visualization of the vessel of interest. can be configured to allow color-flow mapping with software that displays blood flowing away from the transducer as blue & blood flowing toward the transducer as red Various combinations of pulse wave Doppler, color-flow Doppler,and real-time sonography are commercially available and are loosely referred to as duplex Doppler. Clinical Applications systolic-diastolic ratio (S/D ratio) compares maximum (peak) systolic flow with end-diastolic flow, thereby evaluating downstream impedance to flow. Flow in numerous maternal and fetal vessels have been studied to better understand antenatal pathophysiology. Umbilical Artery Doppler normally has forward flow throughout the cardiac cycle, and the amount of flow during diastole increases as gestation advances considered to be a useful adjunct in the management of pregnancies complicated by fetal-growth restriction not recommended for screening of low-risk pregnancies or for complications other than growth restriction. Normal S/D ratio decreases, from about 4.0 at 20 weeks to 2.0 at term. generally less than 3.0 after 30 weeks Abnormal S/D ratio If above the 95th percentile for gestational age In extreme growth restriction: end-diastolic flow may become absent or even reversed
3 AND 4 DIMENSIONAL SONOGRAPHY GOAL of 3D imaging: obtain a volume & then to render that volume to enhance real-time 2D findings Special transducers are used to obtain volumes as still images 3D - & as a function of time 4D 3D imaging For 3-D portrait of the fetal face: surface rendering is the most popular technique provide additional useful information on face & skeleton anomalies ADVANTAGE over 2D imaging: Ability to reformat images in any plane Volume acquisition can allow the image to be reformatted in sagittal, coronal, or even oblique planes Sequential slices can be generated, similar to CTscan or MRI APPLICATIONS: Evaluation of intracranial anatomy in sagittal plane Corpus callosum Evaluation of palate & skeletal system 4D imaging Used to improve visualization of cardiac anatomy Spatiotemporal Image Correlation Postprocessing algorithms & techniques that has taken advantage of real-time image volumes w/ or w/o color Doppler mapping Used to evaluate the complex cardiac anatomy & function Inversion Mode Algorithm Aid imaging of blood flow w/in the heart & great vessels Allow measurement of ventricular volume LIMITATIONS 3D sonography To adequately image fetal surface structure, it must be surrounded by AMNIOTIC FLUID
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almost 50% associated with fetal aneuploidy or a major anomaly In the absence of a reversible maternal complication or a fetal anomaly: reversed end-diastolic flow suggests severe fetal circulatory compromise and usually prompts immediate delivery. fetuses of preeclamptic women who had absent or reversed end-diastolic flow were more likely to have hypoglycemia and polycythemia. Ductus Arteriosus Doppler used primarily to monitor fetuses exposed to indomethacin and other nonsteroidal antiinflammatory agentsNSAIDs. Indomethacin used for tocolysis cause ductal constriction or closure cause increased pulmonary flow w/c may cause reactive hypertrophy of the pulmonary arterioles and eventual development of pulmonary hypertension NSAIDS increased the odds of ductal constriction by 15-fold Uterine Artery Doppler Uterine blood flow is estimated to increase from 50 mL/mim early in gestation to 500 to 750 mL/min by term characterized by high diastolic flow velocities similar to those in systole Increased resistance to flow and development of a diastolic notch have been associated with pregnancyinduced hypertension increased impedance of uterine artery velocimetry at 16 to 20 weeks was predictive of superimposed preeclampsia developing in women with chronic hypertension. Middle Cerebral Artery (MCA) Doppler for detection of fetal anemia and in the assessment of growth restriction. measurement of velocity in other vessels may be limited by Fetal anemia peak systolic velocity is increased due to increased cardiac output decreased blood viscosity adjunct to the evaluation of fetal-growth restriction increased impedance of flow in the umbilical artery may be detected first followed by redistribution of flow to the brain, with decreasing resistance that has been termed brain sparing, and eventually by abnormalities in venous flow Ductus Venosus Doppler In the setting of severe fetal-growth restriction, cardiac dysfunction may lead to venous flow abnormalities, including pulsatile flow in the umbilical vein and abnormal ductus venosus waveforms Ductus venosus abnormalities may identify preterm growth-restricted fetuses that are at greatest risk for adverse outcomes use of venous Doppler for the management of fetalgrowth restriction requires demonstration of perinatal benefit before adoption. Abnormal venous flow indicates breakdown of hemodynamic compensatory mechanism Newer applications of color mapping onto the M-mode tracing permit exquisite evaluation of wall motion and blood velocity and categorization of complex arrhythmias such as: Supraventricular tachycardias Premature atrial contractions
M-MODE ECHOCARDIOGRAPHY Motion-mode, or M-mode sonography is a linear display of the events of the cardiac cycle, with time on the x-axis and motion on the y-axis. Used commonly to measure the fetal heart rate, and deviations from the normal rate and rhythm If there is an abnormality, an evaluation of cardiac anatomy is performed. allow precise characterization of an arrhythmia, including separate evaluation of atrial and ventricular waveforms. Used to assess ventricular function and atrial and ventricular outputs, as well as the timing of these events.
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CHAPTER 17 NORMAL LABOR & DELIVERY Management of Normal Labor
IDENTIFICATION OF LABOR Patient recommendation In the absence of rupture membranes or bleeding: Uterine Contraction every 5 mins in 1 hour or >= 12 Uterine Contractions per hour: ONSET OF LABOR Active labor: cervical dilatation >= 4 cm + UC
NORMAL LABOR & DELIVERY Management: Admission procedure Management of 1st stage of labor Management of second stage of labor Spontaneous delivery Management of 3rd stage of labor Lacerations of the birth canal Episiotomy & repair Labor management protocol active management of labor Two opposing viewpoints: Birthing be recognized as a normal physiological process that most women experience without complications The intrapartum complications often arising quickly and unexpectedly, should be anticipate ADMISSION PROCEDURE Identification of labor One of the most critical diagnoses is the accurate diagnosis of labor Differentiate true labor vs false labor Ascertain general condition of mother & fetus Determine status of fetal membranes True versus False labor True labor Regular Regular Shorter Increases Back abdomen - Relieve False labor Irregular Irregular Long Unchanged Chiefly lower abdomen + Relief
Contractions Interval Intensity Discomfort Cervical dilatation Sedation
Preadmission & admission electronic FHR monitoring fetal admission test monitoring women with lowrisk pregnancies upon admission as test for fetal wellbeing performed for at least 1 hour before discharging women in false labor vital signs & review of pregnancy records identify complications identify problems during antepartum period Vaginal examination performed unless there is bleeding in excess of bloody show number of vaginal examinations during labor correlated with infectious morbidity Detection of ruptured membranes speculum examination in dorsal lithotomy position significance: possibility of cord prolapse/compression greatly increased labor likely to begin soon intrauterine infection is more likely if delivery is delayed > 24 hours conclusive diagnosis: + pooling of amniotic fluid on speculum examination Other diagnostic method: Nitrazine test (pH > 6.5 is consistent with ruptured membranes) Normal pH of vagina 4.5 to 5.5 Amniotic fluid pH 7.0 to 7.5
False positive: occur w/ coexistent blood, semen or untreated bacterial vaginosis False negative: scanty fluid for analysis + Ferning of vaginal fluid due to relative concentration of NaCl, CHON & CHO in amniotic fluid + identification of AFP in vaginal vault (expensive) Transabdominal dye injection : indigo carmine dye injected transabdominally into the amniotic sac Least favoured d/t invasive CERVICAL EXAMINATION Internal examination: insert index & middle finger & reach for the cervix Observe for Cervical Effacement: uneffaced for filipinos is ave 2-2.5 cm Uneffaced: 0% Cervical dilatation position of the cervix consistency of the cervix Something to do w/ Bishops scoring Cervical effacement: Expressed in terms of the length of the cervical canal compared with that of an uneffaced cervix 50% effaced cervix is reduced by one half 100% effaced cervix becomes as thin as the adjacent lower uterine segment, like the feel of web of hand Cervical dilatation: Determine by estimating the average diameter of the cervical opening by sweeping the examining finger from the margin of the cervical opening on one side to that of the opposite side I finger = 1 cm 10 cm fully dilated Position of the cervix: Relationship of cervical os to fetal head Posterior Midposition Anterior: indicates that baby is ready to deliver Consistency of the Cervix Firm or soft Station: Level of the presenting part in relation to the ischial spines w/c is used as a landmark because the ischial spine is midway b/w th inlet & outlet Relationship of the lowermost portion of the fetal presenting part to the ischial spine Station -5 Station -4 Station -3 Station -2 Station -1 Station 0 Lowermost portion of fetal presenting part is at the level of ischial spine Engaged leading part of fetal head is at station 0 or below Engaged: biparietal plane pelvic diameter has cross the pevic inlet Faulty forceps delivery molding or caput succedaneum Station +1 Station +2 Station +3 Station +4 Station +5 Fetal head visible at the introitus BISHOPS SCORING five characteristics: cervical dilatation
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cervical effacement cervical consistency cervical position fetal station Pelvic Exam External genitalia: I.E.: cervix is soft, position, cm dilated % effaced, cephalic Intact/ ruptured BOW, Station +/ Speculum Exam Laboratory studies: Hgb & Hct should be rechecked Unrinalysis: Urine protein analysis in hypertensive women Blood Type In PX w/ no prenatal care: Syphilis HIV Antibody screening Hep B Blood typing MANAGEMENT OF 1ST STAGE OF LABOR Uterine contraction to full cervical dilatation Longest duration Monitor fetal well-being Low risk pregnancy: immediately after UC, FHT q 30mins (1st stage) then q 15 mins (2nd stage) High risk pregnancy: FHT q 15 mins (1st stage) the q 5 mins (2nd stage) For continuous EFM, evaluate tracing q interval stated N: 110-160 bpm, heard best LQ Duration: Nulliparous 7 hours Multiparous 4 hours Fetal heart rate Monitored after a uterine contraction Normal pregnancies every 30 minutes High risk every 15 minutes Cephalic presentation: FHR assessed at lower abdominal quadrant Why check FHR right after uterine contraction? Smooth mm contraction can cause decrease uteroplacental blood flow If fetus is compromised, the fetus may not tolerate uterine contraction bradycardia Uterine contractions: Put hands on fundus to monitor uterine contractions, because contraction happen first at the fundus Gradient of contraction starts from the fundus going down to propel the fetus downward Time of onset of contractions until contraction disappears Intensity (mild, moderate, strong) Frequency: Measured from acme to acme Measured in mins Good uterine contractions: q 2-3 mins Freq q <1min: not good Uterine relaxation is insufficient fetal compromise duration (time during acme/peak up to the time it will disappear) Normal duration of uterine cx: 40-60 sec (90 sec acceptable) >90 sec: tachysystole or tetanic contraction, notify physician especially when oxytocin is given fetal compromise Manual vs electronic fetal monitoring; acme of effective contraction (firm) to the time the contraction disappears Maternal VS T, PR,BP q 4 hrs Tq1hr for membrane rupture: only reliable indicator of chorioamonitis is fever Subsequent vaginal examinations Performed at 2 to 3 hours intervals to evaluate progress of labor To detect dystocia Immediate reexam in case of rupture prior to engagement Maternal vital signs Evaluate at least every 4 hours In prolonged membrane rupture: Membrane rupture of > 18 hours Evaluate temperature q hourly Antimicrobial prophylaxis for group B streptococcal infection Oral intake: Food withheld during active labor & delivery: NPO In anticipation of analgesia d/t risk of aspiration & vomiting Gastric emptying time prolonged once labor is established consequence: vomiting/aspiration May be permitted: sips of liquid, ice chips & lip moisturizers Intravenous fluids There is seldom any real need for such in the normal pregnant woman at least until analgesia is administered Advantageous during the immediate puerperium or prolonged labor for prevention of dehydration & acidosis from prolonged fasting ketonemia administer oxytocin Administration of glucose, sodium & water to a fasting parturient at 60 to 120 ml/hr prevents dehydration & acidosis Maternal position during labor According to comfort Should be allowed to assume most comfortable position (usually lateral recumbency Walking neither enhance nor impair active labor & is not harmful Analgesia: Pain relief should depend on the needs & desires of the woman Amniotomy: Fetal head must be well applied to the cervix to avert cord prolapse Artificial rupture of membrane Head should be engaged before amniotomy is done Use amniotome, insert finger then use amniotome to rupture forebag Presumed benefits: More rapid labor Early detection of meconium-stained amniotic fluid AF fetal jeopardy Apply electrode to the fetus or a pressure catheter to the uterine cavity Monitor w/ hands on fundus Bladder distention should be avoided cause it will present as a soft tissue obstruction on UZ Accelerates labor by 1 to 2 hours Assisted with significantly shorter labor by 4 hours Complications: Chorioamnionitis Cord compression patterns Cord prolapse: when fetal head is not yet engaged but cord came out w/c gets obliterated FHR bradycardia NOTE: general anesthesia not favourable because anesthesia can reach the baby, epidural better urinary bladder function avoid bladder distension may hinder descent of presenting part may lead to bladder hypotonia & infection risk factors for urinary retention in vaginal deliveries
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operational vaginal delivery regional analgesia MANAGEMENT OF 2ND STAGE OF LABOR Full cervical dilatation to delivery of neonate Mean duration: 50 mins (nullipara), 20 mins (multipara) Fetal heart monitoring Low risk every 15 min High risk every 5 min Maternal expulsive efforts Reflexive vs coached Open glottis pushing superior to closed glottis valsalva type Bearing down reflexive & spontaneous FHR immediately after contraction is likely to be slow but should recover to normal before next expulsive effort Crowning: encirclement of the largest head diameter by the vulvar ring Preparation for delivery Duration Primipara 50 min Multipara 20 min Dorsal Lithotomy position Anatomic basis: upward gliding movement of sacroiliac joint giving an additional 1.5 2 cm room for passage of the baby For better exposure, leg holders or stirrups are used Legs may cramp during the 2nd stage, in part because of pressure by the fetal head on nerves in the pelvis relieved by changing the position of the leg & brief massage Vulvar & perineal cleansing Sterile drapes SPONTANEOUS DELIVERY Delivery of the head Crowning encirclement of the largest head diameter by the vulvar ring RITGEN maneuver Allows controlled delivery of fetal head Favors neck extension toward maternal symphisys so the smallest diameter passes through the introitus Often assoc with 3rd degree laceration & episiotomy When the head distends the vulva and perineum enough to open the vaginal introitus to a diameter of 5 cm or more, a towel-draped, gloved hand may be used to exert forward pressure on the chin of the fetus through the perineum just in front of the coccyx. Concurrently, the other hand exerts pressure superiorly against the occiput Hand-poised Method attendant did not touch the perineum during delivery of the head. method had similar associated laceration rates as the modified Ritgen maneuver, but with a lower incidence of third-degree tears Delivery of shoulders: Avoid hooking fingers in the axilla to prevent injury to nerves of the UE that may cause transient/permanent paralysis Traction exerted only in the direction of the long axis After delivery of the head the occiput turns toward one of the maternal thighs & the head assumes the transverse position External rotation Position of restitution the bisacromial diameter, transverse diameter of the thorax, has rotated into the AP diameter of the pelvis Gentle downward traction is applied until the anterior shoulder appears under the pubic arch next upward movement, the posterior shoulder is delivered Clearing of the nasopharynx minimizes fetal aspiration of amnionic fluid, particulate matter, and blood. Compression of the thorax while in the abdominal cavity will help in the extrusion of the secretions To minimize aspiration of amniotic fluid, particulate matter, & blood once the thorax is delivered & the newborn can inspire Nuchal cord Slipped over head if loose cut between 2 clumps if tight Cord clamping Cut between 2 clamps placed 4 to 5 cm from fetal abdomen And later an umbilical cord clamp is applied 2 to 3 cm from the fetal abdomen MANAGEMENT OF THE 3RD STAGE OF LABOR Delivery of neonate to delivery of placenta Signs of placental separation 1 to 5 min after delivery of newborn Uterus becomes firm & globular Sudden gush of blood: not in all cases Duncan: sudden gush of blood because placental detachment occurs at the periphery Schultz: no blood comes out d/t placental separation occurs first at the center Uterus rises in the abdomen Umbilical cord protrudes farther out of the vagina Uterine inversion: complication associated w/ premature placental delivery especially when traction Placental separation: physiological management After ensuring that the uterus is contracted firmly, pressure is exerted with the hand on the fundus to propel the detached placenta into the vagina Done if spontaneous expulsion of the placenta is not possible Delivery of the placenta Push fundus towards maternal head Traction on the umbilical cord MUST NOT be used to pull the placenta out of the uterus Inversion of the uterus grave complication Placental separation: Modified Credes maneuver Brandt Andrews maneuver Manual removal of the placenta If there is brisk bleeding and the placenta cannot be delivered: Give adequate analgesia/anesthesia. The hand covered with antiseptic cream is introduced into the vagina, following the cord Locate margin of placenta and insinuate ulnar border of the hand between it and uterine wall peel off placenta like separating book pages after complete separation, entire placenta is grasped and hand is slowly withdrawn. Never gasp the placenta until it is separated Note that the abdominal hand presses the uterus into the placenta and prevents tearing of the lower segment The placenta is inspected at once to see that it is complete and if there is any doubt, the uterus is re-explored Active management of the third stage 5 units of oxytocin with 0.5 mg of ergometrine & controlled cord traction Reduction in the length of the 3rd stage, but no reduction in blood loss compared with that of physiological management Side effects of ergotamine: nausea, vomiting and blood pressure elevations MANAGEMENT OF THE 4th STAGE OF LABOR The hour immediately following delivery, uterine atony more likely; maternal BP & PR q 15 mins
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Critical stage Maternal vital signs every 15 minutes Evaluate uterus, bleeding per vagina Postpartum hemorrhage more likely at this time Use of oxytocic agent After uterine has been emptied the primary mechanism by which hemostasis is achieved at the placental site is vasoconstriction Other ways to induce uterine contraction Uterine massage Oxytocic agents Oxytocic agents Stimulate myometrial contraction resulting to vasoconstriction and hemostasis at placental site Cardiac effects: Fall in arterial BP followed by abrupt increase in cardiac output Water intoxification due to antidiuretic action Convulsion in mother & neonate d/t too much dilute oxytocin in a large volume of electrolyte-free aqueous dextrose solution If high dose requirement in hypotensive pts>> increase concentration rather than increase flow rate of a dilute solution or use NSS or LR Half life: 3 minutes Ergonovine/methylergonovine: (ergometrine/ergostetrine) Produces sustained myometrial contraction Effective for postpartum hemorrhage but dangerous to delivery May initiate transient but severe hypertension Alkaloids Powerful stimulant of uterine contractions that persist for hours Dont give if baby is in utero d/t tetanic contractions Prostaglandin Not used routinely Less effective Reserved for treatment of haemorrhage Villar and colleagues (2002): prophylactic use of misoprostol to prevent postpartum hemorrhage and concluded that oxytocin-ergot preparation are more effective LACERATIONS OF BIRTH CANAL First degree Involve fourchette, perineal skin, vaginal mucus membrane not underlying fascia and muscle Includes periurethral lacerations Second degree Fascia and muscles but not anal sphincter Third degree Skin, mucus membrane, perineal body and anal sphincter Fourth degree Extends through the rectal mucosa to expose the lumen of the rectum Urethral damage RISK FACTORS for 3rd & 4th lacerations Midline episiotomy Nulliparity 2nd stage arrest of labor: wrong position or big baby POPP: persistent occiput posterior Mid/low forceps Use of anesthesia Asian race EPISIOTOMY & REPAIR Perionotomy or incision of perineum Median/midline can cause 3rd or 4th degree laceration, more superior than mediolat episiotomy Mediolateral Hockey stick episiotomy Only done w/ shoulder dystocia, breech delivery, forceps/vacuum extraction, occiput posterior Substration of a straight surgical incision, which is easier to repair than the ragged laceration Prevented pelvic relaxation: Cystocele, rectocele, and urinary incompetence Should not be performed routinely NO SUBSTITUTE FOR SURGICAL JUDGEMENT AND COMMON SENSE. Timing of episiotomy: Performed when the head is visible during a contraction to a diameter of 3 to 4 cm Performed after application of blades during forceps delivery Midline vs mediolateral episiotomy character istic Surgical repair faulty healing Post-OP pain Anatomical results Blood loss Dyspareunia Extension Type of Episiotomy: midline Easy Rare Minimal Excellent Less Rare Common Type of Episiotomy: mediolateral Difficult More common Common Occasionally faulty More Occasional Uncommon
Timing of repair of episiotomy After delivery of placenta Episiotomy repair is not interrupted or disrupted by the obvious necessity of delivering the placenta, especially if manual removal must be performed Technique: Hemostasis & anatomical restoration without excessive suturing are essential Continuous method was assisted with less perineal pain PAIN after episiotomy Tx: Application of ice packs Analgesics Examine for hematoma/ cellulitis if persistent pain Fourth degree laceration Emphasis on the prevention Postrepair stool softeners & antimicrobials Avoid enemas Pain after episiotomy Ice packs reduces swelling & allay discomfort Topical lidocaine not effective Analgesics Pain may be a signal of hematoma formation if severe or persistent LABOR MANAGEMENT PROTOCOL
Active management of labor Labor is diagnosed when painful contractions are accompanied by complete cervical effacement, bloody show, or ruptured membranes Women with such findings are committed to delivery within 12 hours.
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CHAPTER 17
NORMAL LABOR & DELIVERY
MECHANISM OF LABOR
Fetal Lie, Presentation, Attitude & Position

Childbirth LABOR Period from the onset of regular uterine contractions until expulsion of the placenta CHARCATERISTICS: Toil, trouble, suffering, bodily exertion, painful Attendants supportive of the labouring womans needs effective pain relief 53%: spontaneous labor & delivery Some would have ineffective labor requiring augmentation give oxytocin Other medical or obstetric complication requiring induction of labor When bag of membrane is ruptured, need to deliver baby w/in 24 hours Breech presentation or malrepresentation Epidural anesthesia: PAINLESS labor TWILIGHT: amnestic effect after given medications to relieve pain like Medazolam/ Dormicum LABOR Baby should fit the pelvis Size of the baby should be proportionate to size of pelvis for normal vaginal delivery Factors: Size of baby Size of pelvis Presentation Onset of labor: position of the fetus w/ respect to the birth canal is critical to the route of delivery FETAL LIE, PRESENTATION, ATTITUDE & POSITION Fetal Lie Relation of the fetal long axis to that of the mother Longitudinal: vertex presentation or breech presentation 99% of labor at term Transverse: shoulder presentation Oblique: Fetal & maternal axes cross at 45 degrees angle Unstable & can be changed to transverse or longitudinal lie as labor progress Predisposing factors for TRANSVERSE LIE Multiparity: uterus could be so lax Placenta previa: placenta is located inferiorly Normal: Posterior fundus Hydramnios: baby can move freely inside uterus Uterine anomalies: myoma at lower uterine segment Fetal presentation Presenting part portion of the fetal body that is either foremost w/in the birth canal or in closest proximity to it Can be felt through the cervix on vaginal examination In LONGITUDINAL LIE, the presenting part can be cephalic or breech presentation In TRANSVERSE LIE, the presenting part is the shoulder Cephalic presentation Head is very important Fontanel & sagittal suture Determine ant & post fontanel Classification according to the relationship b/w the head & body of the fetus Vertex or Occiput Presentation: Usual presentation Head is flexed sharply so that the chin is in contact w/ the thorax Occipital/ Posterior fontanel is presenting part on IE Face presentation: Uncommon fetal neck may be sharply extended so that the occiput & back come in contact face is foremost in the birth canal Fully extended Look for 2 malar eminences w/ the opening w/c will create a triangle Palpate for the ischial tuberosity w/c will create a straight line Sinciput presentation: partially flexed head the anterior/large fontanel, or bregma, presenting transient can lead to dystocia if does not change to vertex or face presentation Brow presentation: partially extended transient can lead to dystocia is does not change to vertex or face presentation Uterus is piriform/ pear shaped Fetal head or Cephalic Pole: at term is slightly larger than the breech (podalic pole) composed of fetal head Breech or Podalic Pole Breech & its flexed extremities is bulkier & more mobile than cephalic pole BREECH PRESENTATION Incidence w/ gestational age 25% at 28 wks AOG 3% at term HIGH INCIDENCE in: Hydrocephalus Placenta previa Frank breech presentation: thighs flexed, legs extended over anterior surfaces of the body Only one among the breech presentations that has room for vaginal delivery unless preterm FETAL ATTITUDE: extended vertebral column Complete breech: thighs are flexed, legs flexed upon thighs CS delivery unless preterm or small baby Problem: cord prolapse Incomplete breech: one or both feet, or one or both knees may be lowermost CS delivery unless preterm or small baby Problem: cord prolapse TRANSVERSE PRESENTATION Aka: Shoulder presentation, Transverse Lie, Back up or Back down
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Fetal Attitude or Posture Attitude or Habitus: characteristic posture assumed by the fetus RULE: Fetus forms an ovoid mass that corresponds roughly to the shape of the uterine cavity fetus becomes folded or bent upon itself CHARACTERISTIC POSTURE resulting from mode of growth & its accommodation to the uterine cavity 1. back becomes markedly convexed 2. head is sharply flexed so that the chin is almost in contact w/ the chest 3. thighs are flexed over the abdomen 4. legs are bent at the knees 5. arches of the feet rest upon the anterior surface of the leg 6. arms are usually crossed over the thorax or become parallel to the sides 7. umbilical cord lies in the space b/w them & the lower extremities FACE PRESENTATION Fetal head becomes progressively more extended from the vertex to the face presentation FETAL ATTITUDE: Concave (extended) contour of the vertebral column FETAL POSITION Refers to the relationship of an arbitrarily chosen portion of the fetal presentating part to the right or left side of the birth canal Occipital fontanel: triangular shape Anterior fontanel: diamond shaped Normal position: LOP At delivery: LOA DETERMINING POINTS Vertex Presentation: Fetal Occiput Face Presentation: Chin (mentum) Breech Presentation: Sacrum Shoulder Presentation: Acromion TYPES/ KINDS Right/ Left Occipital Presentation: RO/LO Right/ Left Mental Presentation: RM/ LM Right/Left Sacral Presentation: RS/ LS Cephalic presentation: Palpate if presenting part is: Occiput mentum chin MA: vaginal MP: CS Breech presentation Varieties of Presentations & Positions 6 varieties of each of the 3 presentation OCCIPUT/ VERTEX PRESENTATION
DIAGNOSIS OF FETAL PRESENTATION & POSITION Methods: Abdominal Palpation Vaginal Examination Auscultaion Sonography Plain Radiographs CT MRI ABDOMINAL Palpation: LEOPOLDS MANEUVER POSITION: supine w/ abdomen bare DIFFICULT if: Obese Hydramnios Placenta anteriorly planted 4 maneuvers 1st three facing mothers face Last, facing mothers feet 1st maneuver/ FUNDAL GRIP Identification of which fetal pole - cephalic or podalic - occupies the uterine fundus BREECH: large, nodular mass CEPHALIC: hard, round, mobile & ballottable 2nd maneuver/ UMBILICAL GRIP Palms are placed on either side of the maternal abdomen Gentle but deep pressure is exerted BACK: hard, convex & resistant Orientation of the fetus can be determined if back is directed anteriorly, transversely, or posteriorly FETAL EXTREMITIES: numerous small, irregular, mobile parts 3rd maneuver/ PAWLIKs GRIP Grasping w/ the thumb & fingers of one hand the lower portion of the maternal abdomen just above the symphysis pubis PRESENTING PART NOT ENGAGED: movable mass will be felt, usually the head PRESENTING PART ENGAGED: Indicative that the lower fetal pole is in the pelvis If cephalic presentation, the shoulder is felt as a relatively fixed, knob like part 4th maneuver/ PELVIC GRIP Examiner faces the mothers feet Tips of 3 fingers of each hand exerts deep pressure in the direction of the axis of the pelvic inlet One hand descends further than the other In cephalic presentation, the part of the fetus that prevents the deep descent of the hand is the CEPHALIC PROMINENCE FLEXION ATTITUDE: if cephalic prominence is felt on the same side of the fetal extremities
2/3rd are LO 1/3rd are RO
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EXTENSION ATTITUDE: if cephalic promence is felt on the same side of the fetal back When the head has descended into the pelvis,the anterior shoulder may be differentiaited readily by the 3rd maneuver Confirms findings of the 3rd maneuver Latent phase & acceleration phase Prolonged Latent phase Can be d/t: excessive sedation or apidural analgesia, unfavourable cervical condition, false labor Amniotomy discouraged Sensitive to sedation & conduction anesthesia Dilatational division Best time to give epidural anesthesia Dilatation occurs at most rapid rate Unaffected by sedation & conduction anesthesia Pelvic Division Deceleration phase & 2nd stage of labor Mechanism of labor occurs 2nd stage Full cervical dilatation to expulsion 3rd stage of labor Expulsion to delivery of placenta
BASIS FOR STATION: Ischial spine CARDINAL MOVEMENTS OF LABOR Asynclitism Sagittal suture frequently is deflected either posteriorly toward the promontory or anteriorly toward the symphisis Baby will have a harder time to navigate across pelvis ANTERIOR asynclitism POSTERIOR asynclitism Descent 1st requisite for birth Nulliparas: engagement may take place before the onset of labor, & further descent may not follow until the onset of the 2nd stage Multiparas: descent usually begins w/ engagement Brought about by: Pressure of amniotic fluid Pressure of fundus on the breech Bearing down efforts of mother Extension & straightening of fetal body Flexion When the descending head meets resistance, whether from the cervix, walls of the pelvis, or pelvic floor The chin is brought into more intimate contact w/ the fetal thorax Internal rotaion The movement consists of a turning of the head in such a manner that the baby is looking downwards & prone Extension 2 forces: uterus & pelvic floor External rotation The delivered head next undergoes restitution goes back to original position Restitution of the head to the oblique position completion of external rotation to the transverse position Expulsion
PARTOGRAPH:pt should dilate 1 cm/ hr FRIEDMANS CURVE: Nullipara 1.2cm/hr, Multipara 1.5cm/hr
FRIEDMANS LABOR CURVE
MECHANISM OF LABOR W/ OCCIPIT POSTERIOR PRESENTATION OP: 20% Assoc w/ narrow forepelvis, anterior placentation Rotate promptly Effective contraction Adequate flexion of the head Average size fetus Pt w/ epidural anesthesia may cause failure of rotation in OP babies
CHANGES IN SHAPE OF THE FETAL HEAD Caput Succedaneum Prolonged labor before complete cervical dilatation, the portion Molding Overlapping of sutures Not common
CHARCATERISTIC of NORMAL LABOR Uterine contractions that bring about demonstrable effacement Admission for labor: Painful contractions Cervical dilatation of 3 4 cm 1st stage of labor Preparatory Division
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CHAPTER 18
Intrapartum assessment
Dr. Richard Jordias
Continuous Electronic Fetal Monitoring (EFM) The most prevalent obstetrical procedure in the United States Continuous graph-paper portrayal of the fetal HR Potentially diagnostic in assessing pathophysiological events affecting Expectations: Electrical fetal heart rate monitoring provided accurate information Information was of value in diagnosing fetal distress It would make it possible to intervene to prevent fetal death or morbidity Continuous electronic fetal HR monitoring was superior to intermittent methods ELECTRONIC FETAL MONITORING
Types: Internal Electronic Monitoring External Electronic Monitoring Fetal HR Patterns Internal Electronic Monitoring Fetal HR measured by attaching a bipolar spiral or coiled electrode directly to the fetus Wire electrode penetrates fetal scalp Requires ruptured amniotic membranes Vaginal body fluids create a saline electrical bridge that completes the circuit & permits measurement of the voltage differences b/w 2 poles 2 wires of the bipolar electrode attached to a reference electrode on the maternal thigh to eliminate electrical interference Electrical fetal cardiac signal (P wave, QRS complex, T wave) is amplified & fed into a cardiotachometer for fetal heart rate calculation Peak R-wave voltage Portion of the fetal electrocardiogram most reliably detected BEAT-to-BEAT Variability Phenomenon of continuous R-to-R wave FHR computation Maternal ECG Signal is ~5x stronger than the fetal ECG Maternal heart and corresponding electrical complex (M) that is detected. Amplitude is diminished when it is recorded through the fetal scalp electrode LIVE FETUS Low maternal ECG signal is detected but masked by the fetal ECG DEAD FETUS Weaker maternal signal will be amplified & displayed as the fetal HR Hence, when the fetus is dead, the maternal R waves are still detected by the scalp electrode as the next best signal and are counted by the cardiotachometer External (Indirect) Electronic Monitoring ADVANTAGE: Membrane rupture & uterine invasion is avoided DISADVANTAGE: Does NOT provide the precision of fetal HR measurement or the quantification of uterine pressure Fetal HR detected through maternal abdominal wall using Ultrasound Doppler principle US waves undergo a shift in frequency as they are reflected from moving fetal heart valves & from pulsatile blood ejected during systole Transducer applied on maternal abdomen at site where fetal heart action is best detected
PREMISE: FHR has regularity whereas noise is random & without regularity Fetal Heart Rate Patterns FLAG SIGN: fetal heart tone at upper right quadrant BREECH PRESENTATION NORMAL: fetal heart tone @ lower abdomen CEPHALIC PRESENTATION 2 probes: Doppler: monitors fetal activity Toco: monitors uterine activity PURPOSE: To look at the cardiac activity of the fetus as it responds to uterine contraction or any pathologic problems while mother is in labor BASELINE FETAL HEART ACTIVITY Modal characteristics that prevail apart from periodic accelerations or decelerations associated w/ uterine contractions Descriptive Characteristics: Rate Beat-to-Beat variability Fetal arrhythmia Distinct Patterns of FHR Sinusoidal Saltatory RATE AOG: FHR NORMAL POSTNATAL: 90 bpm 24 bpm b/w 16 weeks & term or ~1 bpm/wk Normal gradual slowing of the FHR corresponds to maturation of PARASYMPATHETIC (vagal) heart control Definition of BASELINE FHR According to National Institute of Child Health and Human Development Research Planning Workshop: NORMAL: 110-160 bpm Is the approximate mean rate rounded to increments of 5 beats/min during a 10-minute tracing segment. Minimum interpretable baseline duration must be at least 2 minutes in any 10 minute segment DO NOT SAY 123 bpm or 127 bpm but round it to 5 bpm increments; hence should be 125 or 130 bpm Its universally acceptable to report as: 125, 130, 135, 140 bpm EXCLUDES: Periodic or episodic changes Accelerations and decelerations NOTE: These are peaks, BASELINE FHR only looks at average FHR. These are periods of marked FHR variability Segments of FHR that differ >25bpm BRADYCARDIA: <110 bpm TACHYCARDIA: >160 bpm AVERAGE FHR The result of tonic balance b/w accelerator & decelerator influences on pacemaker cells SYMPATHETIC SYSTEM Accelerator influence PARASYMPATHETIC SYSTEM Decelerator factor
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Mediated via vagal slowing of heart rate OTHER CONTROL: Arterial Chemoreceptors Both hypoxia & hypercapnia can modulate rate More severe & prolonged hypoxia, w/ a rising blood lactate level & severe metabolic acIdemia induces a prolonged fall in HR BRADYCARDIA < 110 beats/min Rate between 100 and 119 beats/min, in the absence of other changes, usually is not considered to represent fetal compromise. Such low but potentially normal baseline heart rates also have been attributed to head compression from occiput posterior or transverse positions, particularly during second-stage labor. Bradycardia range: 80 to 120 beats/min with good variability: REASSURING < 80 bpm: NONREASSURING Classification OF Bradycardia: Mild: 100-119 bpm Moderate: 80 100 bpm 3 minutes Severe: < 80 bpm CAUSES of fetal bradycardia: Congenital heart block Serious fetal compromise Maternal hypothermia under general anesthesia d/t repair of a cerebral aneurysm or during maternal cardiopulmonary bypass for open-heart surgery Severe pyelonephritis TACHYCARDIA Category: Mild: 161-180 bpm Severe > 180 bpm Causes: Maternal Infection not associated with fetal compromise unless there are associated periodic heart rate changes or fetal sepsis. Maternal fever 36.5C 37.5C: NORMAL >37.5: 10 bpm in FHR per 1 C . Amnionitis MOST COMMON cause of fetal tachycardia is maternal fever from chorioamnionitis Can induce fetal tachycardia before onset of maternal fever. Fetal compromise KEY FEATURE to distinguish fetal compromise in association with tachycardia seems to be concomitant heart rate decelerations. Prompt relief of the compromising event, such as correction of maternal hypotension caused by epidural analgesia, can result in fetal recovery. Cardiac arrhythmias Drugs: Parasympathetic drugs : Atropine Sympathomimetic drug : Terbutaline Used in asthma Crosses placenta & cause fetal tachycardia WANDERING BASELINE Unsteady and wanders b/w 120 and 160 bpm Suggestive of neurologically abnormal fetus May occur as a preterminal event BEAT TO BEAT VARIABILITY REFLECTS the function of ANS MOST Important parameters of the fetal HR Important INDEX of cardiovascular function regulated by ANS GOOD baseline variation: 110-150 bpm BASELINE VARIABILITY SNS & PNS push & pull mediated via sinoatrial node produces momentto-moment or beat-to-beat oscillation of baseline heart rate Baseline must be for a minimum of 2 minutes in any 10 minute segment Fluctuations in the FHR of 2 cycles per minute or greater Variability is visually quantitated as the amplitude of peak-to-trough in bpm GRADE of Beat to Beat Variability: GRADE 1: Absent Amplitude: UNDETECTABLE straight line of cardiac rate where there is no acceleration or deceleration Management: Deliver baby ASAP via CS as this is a dying fetus GRADE 2: Minimal Amplitude: < 5 bpm Management: dissociate and put the mother in the left lateral position to decompress the abdominal aorta give oxygen as well. If after resuscitation, there is no change: DELIVER THE BABY ASAP GRADE 3: Moderate Amplitude: 6 25 bpm NORMAL GRADE 4: Marked Amplitude: > 25 bpm 2 divisions: SHORT TERM VARIABILITY instantaneous change in FHR from one beat (R wave) to the next Measure the time interval b/w cardiac systoles Not seen by the naked eye Normally present only when electrocardiac cycles are measured directly w/ scalp electrode Microscopic portion of variability LONG TERM VARIABILITY oscillatory changes that occur in one minute and results in the waviness of the baseline NORMAL frequency: 3-5 cpm The more wave the better w/c reflects that the fetus is not compromised
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NORMAL beat to beat variability: 6-25 bpm INCREASED VARIABILITY > 25 bpm Increased during: fetal breathing in infants, short-term variability is attributable to respiratory sinus arrhythmia fetal body movement it is normal w/ every fetal movement, there is an in fetal heart tone 1st parameter that develop in the biophysical scoring FETAL TONE 2nd parameter in biophysical scoring Last one diminished during fetal compromise FHR Last to develop advancing gestation < 30 wks: baseline characteristics were similar during both fetal rest & activity > 30 wks: variability w/ fetal activity Fetal gender does NOT affect FHR variability FHR: BASELINE FHR becomes physiologically fixed or less variable Less cardiovascular physiological wandering as beat-to-beat intervals shorten FHR: more instability or variability of the baseline DIMINISHED VARIABILITY < 5 bpm Ominous sign indicating serious fetal compromise SINGLE MOST reliable sign of fetal compromise variability for 1 hour: DIAGNOSTIC of developing acidemia & imminent fetal death Should NOT be used as the only indicator for fetal well being & good variability should not be interpreted as reassuring Causes of decreased variability: fetal acidemia Decreased variability + decelerations Less waviness w/ decreased variability FETAL Scalp Sampling Fetal scalp pH 1119x in these pregnancies pH is ~7.10 w/ severe decelerations combined w/ < 5 bpm variability compared to 7.20 w/ > 5bpm variability. MATERNAL acidemia beat-to-beat variability seen in diabetic ketoacidos METABOLIC Acidemia r/t hypoxia Leads to depression of fetal brainstem or the heart itself Analgesic drugs during labor CNS depressants can cause transient beat-to-beat variability Includes: Narcotics Meperidine: variability w/in 510 mins of administration & effects may last for 60 mins or longer Butorphanol: FHR reactivity Barbiturates Phenothiazines Tranquilizers General anesthetics MgSO4 Used as tocolytic agent & to manage Htn in women variability during the 3rd hour of administration Blunts the frequency of accelerations drug for preeclampsia to prevent convulsions Anticonvulsion drug for pregnant patients variability in the absence of decelerations is unlikely to be d/t fetal hypoxia FLAT FHR BASELINE Absent variability Reflect previous insult to the fetus that has resulted to neurologic damage CARDIAC ARRYTHMIA Findings include: Baseline bradycardia Intermittent baseline bradycardia is frequently d/t congenital heart block Tachycardia Abrupt baseline spiking Conduction defects Mc complete AV block Found in association w/ maternal CT diseases Detecting arrhythmia can only be accomplished when using FETAL SCALP ELECTRODES Supraventricular arrhythmias little significance during labor unless there is a coexistent heart failure as evidenced by FETAL HYDROPS many disappear in the immediate neonatal period some are associated w/ structural cardiac defects Forms of arrhythmias: Atrial Extrasystoles: Mc (68%) Low mortality rate 97% live Atrial tachycardia: 12% Atrioventricular block: 12% High mortality rate Sinus bradycardia: 5% Ventricular extrasystole: 2.5% Can impair interpretation of intrapartum heart rate tracings Intrapartum fetal cardiac arrhythmias, especially w/ clear amniotic fluid, are managed conservatively SINUSOIDAL HEART RATE r/t waves of arterial blood pressure Reflects oscillations in the baroreceptorchemoreceptor feedback mechanism for control of the circulation TRUE SINUSOIDAL PATTERN observed w/: Severe Fetal Anemia from Rh Isoimmunization Feto-maternal Hge Twin-twin transfusion Syndrome multiple pregnancies where two or more fetuses share a chorion and hence a single placenta Vasa Previa w/ bleeding
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fetal vessels crossing or running in close proximity to the inner cervical os Fetal Intracranial Hge Severe Fetal Asphyxia INSIGNIFICANT SINUSOIDAL PATTERN can be seen after administration of: Meperidine Characteristic pattern: sine frequency of 6 cpm Morphine Alphaprodine Butorphanol Other causes of sinusoidal pattern: Chorioamnionitis Fetal Distress Umbilical Cord occlusion STRICT DEFINITION: Stable baseline FHR: 120 to 160 bpm w/ regular oscillations Amplitude: 5 to 15 bpm Long-term variability frequency: 2 to 5 cpm Fixed or flat short-term variability Oscillation of the sinusoidal waveform above or below a baseline Absence of accelerations CLASSIFICATION: MILD: amplitude of 5 to 15 bpm INTERMEDIATE: 16 to 24 bpm MAJOR: > 25 bpm PSEUDOSINUSOIDAL Intrapartum sine wave-like baseline variation w/ periods of acceleration MILD PSEUDOSINUSOIDAL Assoc. w/ use of meperidine & epidural analgesia INTERMEDIATE PSEUDOSINUSOIDAL Linked to fetal sucking or transient episodes of fetal hypoxia caused by umbilical cord compression PATHOPHYSIOLOGY: Unclear Antepartum sine wave baseline undulation portends to severe fetal anemia PERIODIC FETAL HEART RATE CHANGES deviations from baseline r/t uterine contractions ACCELERATIONS in fetal HR above baseline abrupt rise (peak <30 sec) in FHR baseline waviness is secondary to variability concomintant to uterine contractions especially decelerations w/c is appreciated by TOCO probe most commonly occur: antepartum early labor common in labor associated w/ fetal movement confirms that fetus is not acidemic at that time FHR accelerations during the 1st or last 30 minutes, or both, is a favorable sign of fetal well being in association with variable decelerations MECHANISM OF INTRAPARTUM ACCELERATIONS Fetal movement uterine contractions umbilical cord occlusion pelvic examination fetal scalp blood sampling acoustic stimulation no apparent stimulus absence is not unfavorable unless there are other nonreassuring changes like beat-to-beat variability, it represents the intact neurohormonal cardiovascular control mechanisms linked to fetal behavioral states DECELERATIONS below baseline rate Nomenclature based on timing of decelerations in relation to contraction Early Late Variable EARLY DECELERATION Type I dips WAVEFORM: slope of FHR change is gradual, resulting in curvilinear & uniform or symmetrical waveform PATHOPHYSIOLOGICAL EVENT: head compression Causes vagal nerve activation as a result of dural stimulation w/c mediates the FHR deceleration Is a likely cause not only to early decelerations but also occur during 2nd stage of labor A likely cause of many variable decelerations classically attributed to cord compression Gradual physiologic decrease and return to baseline in FHR associated with a uterine contraction drop in HR w/ uterine contractions r/t cervical dilation Physiologic findings
seen in active labor b/w 4-7 cm cervical dilatation proportional to the strength of contraction rarely falls below 100 to 110 bpm or 20 to 30 bpm below baseline mirror image of the uterine contraction Gradual FHR w/ both onset and recovery coincident with the onset and recovery of the uterine contraction Nadir of the deceleration is 30 seconds or more after the onset of the deceleration. Commonly seen in: Active labor & are not associated w/ tachycardia Loss of variability Fetal HR changes NOT ASSOCIATED W/ Fetal hypoxia Acidemia Low Apgar scores Associated with: Fetal movement Stimulation Uterine contraction LATE DECELERATION Type II dips PATHOPHYSIOLOGICAL EVENT: uteroplacental insufficiency Uteroplacental insufficiency fetal hypoxia Interval or lag from the contraction onset until the late deceleration onset was directly related to basal fetal oxygenation length of the lag phase was predictive of the fetal PO2 but not fetal pH. The lower the fetal PO2 prior to contractions, the shorter
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the lag phase to onset of late decelerations lag period reflected the time necessary for the fetal PO2 to fall below a critical level necessary to stimulate arterial chemoreceptors, which mediated decelerations 1st FHR consequence of uteroplacentalinduced hypoxia Occurs 1st before acidemia Once acidemia is developed variability of baseline HR deliver baby b/c the fetus is not having enough oxygenation. MAGNITUDE: rarely more than 30 to 40 beats/min below baseline and typically not more than 10 to 20 beats/min smooth, gradual, symmetrical decrease in fetal heart rate beginning at or after the peak of the contraction and returning to baseline only AFTER the contraction has ended onset, nadir, and recovery of the deceleration occur AFTER the beginning, peak, and ending of the contraction, respectively Gradual decrease in the heart rate with the nadir and recovery occurring after the end of the contraction NADIR of the deceleration occurs 30 seconds or more AFTER the onset of the deceleration fetal heart rate response to uterine contractions can be an index of either uterine perfusion or placental function usually are NOT accompanied by accelerations. Causes: maternal hypotension mc d/t epidural analgesia excessive uterine activity d/t oxytocin stimulation placental dysfunction maternal diseases hypertension, diabetes, collagenvascular disorders chronic placental dysfunction placental abruption cause acute late decelerations need immediate C/S delivery VARIABLE DECELERATION Type III dips WAVEFORM: Slope of FHR change is abrupt & erratic w/ Jagged appearance Visually apparent abrupt decrease in FHR PATHOPHYSIOLOGICAL EVENT: cord compression Variable deceleration occur when there is 50% in umbilical blood flow EFFECTS OF TOTAL UMBILICAL CORD OCCLUSION fetal aortic pressure in umbilical vein pressure in umbilical artery pressure Onset varies with successive contractions Variable in duration, intensity, and timing most commonly encountered during labor d/t umbilical cord compression OTHER FHR PATTERNS ASSOCIATED w/ UMBILICAL CORD COMPRESSION Saltatory baseline heart rate Linked to umbilical cord complications during labor rapidly recurring couplets of acceleration and deceleration causing relatively large oscillations of the baseline FHR Acceleration-deceleration is due to compression and decompression of the umbilical cord relationship w/ cord occlusion in the absence of other FHR findings, it does NOT signal fetal compromise Lambda Acceleration followed by a variable deceleration w/ no acceleration at the end of deceleration Seen early in labor & is NOT ominous Result from mild cord compression or stretch Overshoot Variable deceleration followed by acceleration
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Controversial clinical significance Periodic Fetal Heart Rate Changes Variable Deceleration Deceleration onset can be on, during or after uterine contraction. So its variable. DURATION: < 2 minutes measure 15 beats/min for 15 seconds or longer ONSET-TO-NADIR PHASE: < 30 seconds Two types of variable decelerations (Figure 18-21) Deceleration A Seen w/ complete umbilical cord occlusion Results in fetal systemic hypertension d/t obstruction of umbilical artery flow w/c stimulates baroreceptormediated DECELERATION. Deceleration B: exhibits "shoulders" of acceleration compared with Deceleration A d/t differing degrees of partial cord occlusion occlusion of only the vein reduces fetal blood return, thereby triggering a baroreceptormediated ACCELERATION Variable decelerations are mediated vagally d/t chemoreceptor or baroreceptor activity or both. Partial or complete cord occlusion produces an afterload (baroreceptor) & fetal arterial O2 content (chemoreceptor). These both result in vagal activity leading to deceleration. baroreceptor reflexes operate during the first 15 to 20 seconds of umbilical cord occlusion followed by decline in PO2 at ~30 seconds, which then serves as a chemoreceptor stimulus THEREFORE, variable decelerations represent fetal heart rate reflexes that reflect: BP changes d/t interruption of umbilical flow changes in oxygenation. SIGNIFICANT VARIABLE DECELERATIONS < 70 bpm w/ a duration of > 60 seconds Fetal heart rate effects with partial and complete umbilical cord occlusion Uterine pressures generated early in a contraction cause cord compression predominantly of the thin-walled umbilical vein in fetal CO initial compensatory in FHR As cord compression intensifies, umbilical arteries are then also compressed in fetal sBP vagal-mediated FHR deceleration. As the contraction abates and compression is relieved first on the umbilical arteries elevated fetal systolic blood pressures drop & deceleration resolves. A final increase in fetal heart rate is seen as a result of persistent umbilical vein occlusion. With completion of the uterine contraction and cord compression, the fetal heart rate returns to baseline. PROLONGED DECELERATION isolated deceleration > 2 minutes or longer but < 10 minutes from onset to return to baseline difficult to interpret but common causes include: cervical examination uterine hyperactivity cord entanglement maternal supine hypotension Epidural, spinal, or paracervical analgesia maternal hypoperfusion or hypoxia from any cause placental abruption umbilical cord knots or prolapsed maternal seizures including eclampsia and epilepsy application of a fetal scalp electrode impending birth maternal Valsalva maneuver Placenta: very effective in resuscitating the fetus if the original insult does not recur immediately. Occasionally followed by: loss of beat-to-beat variability baseline tachycardia period of late decelerations fetus may die during prolonged decelerations RECURRENT DECELERATION Occurs >50% in any 20 minute period FHR during 2nd Stage of Labor Decelerations are virtually ubiquitous during the second stage. Both cord compression and fetal head compression have been implicated as causes of decelerations and baseline bradycardia during second-stage labor. profound, prolonged fetal heart rate deceleration in 10 minutes preceding vaginal delivery of 18 healthy infants. Asscoiated w/ low APGAR scores: variable decelerations at 5 minutes. persistent or progressive baseline bradycardia baseline tachycardia Predictive w/ acidemia: Loss of beat-to-beat variability baseline FHR < 90 bpm abrupt FHR deceleration to < 100 bpm inevitable fetal compromise can occur during 2nd stage of labor when the following occurs: abnormal baseline heart rateeither bradycardia or tachycardia absent beat-to-beat variability second-stage labor decelerations
ADMISSION FETAL MONITORING IN LOW-RISK PREGNANCIES women with low-risk pregnancies are monitored for a short time on admission for labor continuous monitoring is used only if abnormalities of the fetal heart rate are identified. Complications of Internal Electronic Fetal Monitoring Injury to the fetal scalp or breech by the electrode is rarely a major problem Severe cord compression from entanglement with the catheter Penetration of the placenta, causing hemorrhage and possibly uterine perforation during catheter insertion increased risk of infection as the consequence of internal monitoring. Scalp wounds from the electrode may become infected, and subsequent cranial osteomyelitis Puerperal infection
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Relative Contraindications to Internal FHR human immunodeficiency virus (HIV) herpes simplex virus hepatitis B virus hepatitis C virus, OTHER INTRAPARTUM ASSESSMENT TECHNIQUES Fetal Scalp Blood Sampling measurements of the pH in capillary scalp blood help identify fetal distress but is now used uncommonly Technique endoscope is inserted through the dilated cervix after membrane rupture An incision is made through the skin, a drop of blood is immediately collected & the pH of the blood is measured Interpretation The pH of fetal capillary scalp blood is usually LOWER than that of umbilical VENOUS blood and approaches that of umbilical ARTERIAL blood. pH > 7.25: labor is observed pH 7.20 - 7.25: measurement is repeated within 30 minutes pH < 7.20: another scalp blood sample is collected immediately, and the mother is taken to an operating room and prepared for surgery. Delivery is performed promptly if the low pH is confirmed. The only benefits reported for scalp pH testing are fewer cesarean deliveries for fetal distress use of fetal scalp blood lactate concentration as an adjunct to pH. equivalent in predicting fetal acidemia. ADVANTAGE: smaller amount of blood was needed lower procedure failure rate compared with scalp sampling for pH. Scalp Stimulation acceleration of FHR in response to pinching of the scalp with an Allis clamp just prior to obtaining blood was invariably associated with a normal pH. FHR accelerated > 10 bpm after 15 seconds of gentle digital stroking of the scalp: 100 % had a scalp pH of > 7.20 Vibroacoustic Stimulation Electronic artificial larynx placed approximately 1 centimeter from or directly onto the maternal abdomen Normal Response: FHR acceleration of at least 15 bpm for at least 15 seconds occurs within 15 seconds after the stimulation and with prolonged fetal movements effective predictor of fetal acidosis in the setting of variable decelerations. intrapartum stimulation tests were useful to exclude fetal acidemia. Fetal Pulse Oximetry Assessment of fetal oxyhemoglobin saturation once membranes are ruptured. brief, transient fetal oxygen saturations < 30 %: NORMAL during labor persistent, > 2 minutes fetal oxygen saturation < 30%: risk of fetal compromise CS done when pulse oximetry values remained < 30 % for the entire interval b/w 2 contractions or when FHR patterns met predefined guidelines. Fetal Electrocardiography internal monitoring of the fetal heart rate mature fetus w/ hypoxemia: elevated ST segment w/ a progressive rise in T-wave height that can be expressed as a T:QRS ratio increasing T:QRS ratios reflect fetal cardiac ability to adapt to hypoxia and appears before neurological damage. Progression of hypoxia increasingly negative ST-segment deflection where it appears as a biphasic waveform useful in preventing fetal acidosis and neonatal encephalopathy when standard fetal heart rate (FHR) monitoring suggested abnormal patterns. Intrapartum Doppler Velocimetry Doppler analysis of the umbilical artery abnormal Doppler waveforms: pathological umbilical-placental vessel resistance. Assess blood flow of the fetus from the placenta to the fetal circulations, so we can see how it changes as labor progresses The fetal heart rate response to uterine contractions: INDEX of either uterine perfusion or placental function
FETAL DISTRESS Pathophysiology based on heart rate patterns Physiological control of heart rate depend on blood flow & oxygenation. influenced by the preexisting state of fetal oxygenation normal labor is a process of increasing acIdemia asphyxia: defined as hypoxia leading to acidemia, normal parturition is an asphyxiating event for the fetus. Diagnosis INCREASED incidence of ADVERSE fetal outcome: Prolonged bradycardia or tachycardia or fetal heart rate patterns absence of accelerations severe variable or late decelerations TRUE FETAL DISTRESS PATTERNS: beat-tobeat variability is zero in conjunction with severe decelerations or persistent baseline rate changes, or both. Meconium in the Amnionic Fluid From a.a. ARGININE meconium passage is a potential warning of fetal asphyxia meconium passage d/t relaxation of the sphincter ani muscle induced by faulty aeration of the (fetal) blood. Three theories: fetuses pass meconium in response to hypoxia and that meconium therefore signals fetal compromise in utero passage of meconium may represent normal gastrointestinal tract maturation under neural control meconium passage could follow vagal stimulation from common but transient umbilical cord entrapment and resultant increased peristalsis Meconium aspiration syndrome associated with fetal acidemia at birth Other significant correlates of aspiration: cesarean delivery forceps to expedite delivery intrapartum heart rate abnormalities depressed Apgar scores need for assisted ventilation at delivery. acute event, because most acidemic fetuses had abnormally PCO2 values rather than a pure metabolic acidemia. Hypercarbia induces gasping and resultant increased amnionic fluid inhalation. PATHOPHYSIOLOGY: fetal hypercarbia: stimulates fetal respiration leading to aspiration of meconium into the alveoli Lung parenchymal injury is secondary to acidemia-induced alveolar cell damage MARKERS of chronic hypoxia: fetal erythropoietin levels newborn nucleated RBC counts management:
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if the infant is DEPRESSED: trachea is intubated, and meconium suctioned from beneath the glottis. If the newborn is VIGOROUS: having strong respiratory efforts, good muscle tone, and FHR 100 bpm tracheal suction is NOT necessary and may injure the vocal cords. Prophylactic Amnioinfusion for Variable Decelerations. useful in reducing the occurrence of variable decelerations, improving neonatal outcome, and reducing cesarean delivery rates for fetal distress. Prophylactic Amnioinfusion for Oligohydramnios. Used prophylactically in an effort to avoid intrapartum fetal heart rate patterns from cord occlusion. Significantly decreased frequency and severity of variable decelerations in labor. no improvement in the cesarean delivery rate or condition of term infants. In postterm pregnancies complicated by both thick meconium and oligohydramnios. Amnioinfusion significantly reduced cesarean delivery rates for fetal distress as well as meconium aspiration syndrome. Amnioinfusion for Meconium-Stained Amnionic Fluid. CS rate lower but did not improve perinatal outcome American College of Obstetricians and Gynecologists does not recommend amnioinfusion to dilute meconium-stained amnionic fluid.
Management Options principal management options for significantly variable fetal heart rate patterns consist of correcting any fetal insult, if possible. Moving the mother to the lateral position correcting maternal hypotension caused by regional analgesia discontinuing oxytocin serve to improve uteroplacental perfusion Tocolysis single intravenous or subcutaneous injection of 0.25 mg of terbutaline sulfate or small intravenous doses of nitroglycerin given to relax the uterus maneuver in the management of nonreassuring fetal heart rate patterns during labor. RATONALE: inhibition of uterine contractions might improve fetal oxygenation, thus achieving in utero resuscitation resuscitation improved fetal scalp blood pH values Amnioinfusion Removal of amnionic fluid produced variable decelerations and that replenishment of fluid with saline relieved the decelerations. three clinical areas: Treatment of variable or prolonged decelerations Prophylaxis for women with oligohydramnios, as with prolonged ruptured membranes Attempts to dilute or wash out thick meconium
Fetal Heart Rate Pattern and Brain Damage identified as a result of medicolegal actions. most cerebral palsy is unrelated to labor events. perinatal brain damage found following an asphyxial event into three categories based on microscopic findings: 18 to 48 hoursneuronal necrosis with pyknosis or lysis of the nucleus in shriveled eosinophilic cells 48 to 72 hoursmore intense neuronal necrosis with macrophage response > 3 daysall the preceding plus astrocytic response with gliosis and in some, early cavitation. 1 hour of fetal hypoxia associated with profound metabolic acidemiapH less than 7.0was required before neurological abnormalities could be diagnosed at age 6 to 12 months. hypoxic-ischemic encephalopathy will show other signs of damage to include: metabolic acidosis in umbilical cord artery bloodpH < 7 and base deficit > 12 mmol/L Apgar scores 03 beyond 5 minutes Neurological sequelae seizures, coma, hypotonia, and one or more of cardiovascular, gastrointestinal, hematological, pulmonary, hepatic, or renal system dysfunction. spastic quadriplegia and, less commonly, dyskinetic cerebral palsy are the only types of cerebral palsy associated with acute hypoxic intrapartum events.
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Montevideo units define uterine activity uterine performance is the product of the intensityincreased uterine pressure above baseline toneof a contraction in mm Hg multiplied by contraction frequency per 10 minutes. Example 3 cx in 10 mins w/ 50mmHg = 150 Montevideo units. 1st 30 weeks: Uterine activity is comparatively quiescent. Contractions not >20 mm Hg After 30 wks: Uterine activity increases gradually Braxton Hicks contractions Further increases in uterine activity are typical of the last weeks of pregnancy: prelabor cervix ripens labor usually commences when uterine activity reaches values between 80 and 120 Montevideo units. 3 contractions of 40 mm Hg every 10 minutes. first-stage labor uterine contractions increase progressively in intensity from approximately 25 mm Hg at commencement of labor to 50 mm Hg at the end. frequency increases from three to five contractions per 10 minutes uterine baseline tone from 8 to 12 mm Hg. 2nd- stage labor Uterine activity further increases aided by maternal pushing. contractions of 80 to 100 mm Hg are typical and occur as frequently as five to six per 10 minutes. duration of uterine contractions 60 to 80 seconds does not increase appreciably from early active labor through the second stage constancy serves fetal respiratory gas exchange. During a uterine contraction, the intervillous space, where respiratory gas exchange occurs, becomes isolated. leads to functional fetal breath holding, which has a 60- to 80-second limit that remains relatively constant uterine contractions: > 10 mmHg: clinically palpable 40 mm Hg: uterine wall can readily be depressed by the finger > 40 mmHg: uterine wall becomes so hard that it resists easy depression. >15 mmHg: Uterine contractions associated w/ pain Minimum pressure required for distending the lower uterine segment and cervix. follows that Braxton Hicks contractions perceived as uncomfortable because distension of the uterus, cervix, and birth canal is generally thought to elicit discomfort. uterus that performs poorly before delivery is also prone to atony and puerperal hemorrhage. Origin and Propagation of Contractions Normal contractile wave of labor originates near the uterine end of one of the fallopian tubes: pacemakers right pacemaker usually predominates over the left and starts most contractile waves. Contractions spread from the pacemaker area throughout the uterus at 2 cm/sec, depolarizing the whole organ within 15 seconds. Depolarization wave propagates downward toward the cervix. Intensity is greatest in the fundus, and it diminishes in the lower uterus w/c reflect reductions in myometrial thickness from the fundus to the cervix. descending gradient of pressure serves to: direct fetal descent toward the cervixas efface the cervix
CRITERIA to define an ACUTE INTRAPARTUMHYPOXIC event to cause CP: ESSENTIAL, must have, CRITERIA metabolic acidosis in umbilical cord artery bloodpH < 7 and base deficit > 12 mmol/L early onset of severe or moderate neonatal encephalopathy in infants born at > 34 wks AOG spastic quadriplegia and, less commonly, dyskinetic cerebral palsy exclusion of trauma, coagulation disorders, infectious conditions, or genetic disorders INTRAPARTUM TIMING: NON-specific asphyxia insults w/in 0-48 hours of delivery Sentinel hypoxial signal immediately before or during labor Sudden & sustained fetal bradycardia or absence of FHR variability in presence of persistent, late or variable decelerations, usually afeter hypoxic sentinel event when pattern was previously normal Apgar scores 03 beyond 5 minutes Multisystemic involvement w/in 72 hrs of birth Imaging study showing evidence of acute nonfocal cerebral abnormality Current Recommendations methods most commonly used for intrapartum FHR: auscultation with a fetal stethoscope or a Doppler ultrasound device continuous electronic monitoring of the heart rate and uterine contractions. Intermittent auscultation or continuous electronic monitoringis considered an acceptable method of intrapartum surveillance in both low- and high-risk pregnancies. The recommended interval w/ auscultation: performed after a contraction and for 60 seconds. 1-to-1 nursepatient ratio
INTRAPARTUM SURVEILLANCE OF UTERINE ACTIVITY Analysis of electronically measured uterine activity permits some generalities concerning the relationship of certain contraction patterns to labor outcome. Internal Uterine Pressure Monitoring Amnionic fluid pressure measured b/w & during contractions by a fluidfilled plastic catheter w/ its distal tip located above the presenting part External Monitoring Uterine contractions measured by a displacement transducer in w/c the transducer button, or plunger, is held against the abdominal wall. As the uterus contracts, the button moves in proportion to the strength of the contraction w/c is converted into a measurable electrical signal that indicates the relative intensity of the contraction BUT does not give an accurate measure of intensity. give a good indication of the onset, peak, and end of the contraction. Patterns of Uterine Activity Contractile waves of uterine activity were usually measured using intra-amnionic pressure catheter
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all parts of the uterus are synchronized and reach their peak pressure almost simultaneously, giving rise to the curvilinear waveform each contraction is triggered by a tissue-level bioelectric event. Pacemaker theory also serves to explain the varying intensity of adjacent coupled contractions: incoordination contractile wave begins in one cornual-region pacemaker, but does not synchronously depolarize the entire uterus. As a result, another contraction begins in the contralateral pacemaker and produces the second contractile wave of the couplet. These small contractions alternating with larger ones appear to be typical of early labor. labor would progress slowly if regular contractions were hypotonicthat is, contractions with intensity less than 25 mm Hg or frequency less than 2 per 10 minutes. Normal labor: Minimum of 3 contractions of >25 mmHg & <4minute intervals between contractions. A lesser amount of uterine activity was associated with arrest of active labor CS
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Chapter 19
Obstetrical Anesthesia
Dr Aida San Jose, MD, FPOGS
INTRODUCTION Vomiting w/ Aspiration of Gastric Contents Constant threat during labor
Physiologic Adaptations of Pregnancy that requires Special Consideration Preeclampsia Htn & proteinuria in pregnancy Placental Abruption Sepsis Syndrome
Types of Anesthesia Regional Anesthesia Pudendal Paracervical Spinal Epidural Combined Spinal-Epidural Anesthesia Local Infiltration General Anesthesia
NON-PHARMACOLOGICAL METHODS OF PAIN CONTROL Fear of the unknown potentiate pain READ: Intensity of pain during labor is related largely to EMOTIONAL TENSION LAMAZE: Psychoprophylactic method Pain can be lessened by relaxed breathing & psychological support of labor partners Emphasized childbirth as a natural physiologic process Mother is not taking any pharmacologic drugs
Anesthesia Complications 1.6% of pregnancy-related maternal deaths in US
Factors that Contributed to Improved Safety of Obstetrical Anesthesia use of Regional Anesthesia Most significant factor availability of in-house anesthesia coverage
GENERAL PRINCIPLES Obstetrical Anesthesia Services Indications: Womans request for pain relief ACADEMY of PEDIATRICS & the AMERICAN COLLEGE of OBSTETRICIANS & GYNECOLOGISTS: It is the responsibility of the OB or nurse midwife & the anesthesiologist to develop the most suitable response to accomplish the request for pain relief
ANALGESIA & SEDATION DURING LABOR Analgesia & Sedation during Labor Given when uterine contractions & cervical dilatation that cause discomfort Subsequent cervical dilatation & effacement d/t uterine contractions causes pain Mother should rest quietly b/w contractions Discomfort usually felt at acme of contraction but should be bearable
Identification of risk factors should prompt consult w/ anesthesia Marked Obesity More soft tissue along the airway can go down as the patient is anesthetized & can compress the airway Role of Obstetrician Should be proficient in local & pudendal anesthesia General anesthesia should be administered only by those w/ special training i.e. Endotracheal intubation anesthesia Principles of Pain Relief Labor pain is interpreted differently by individual parturient Stimuli are modified by emotional, motivational, cognitive, social & cultural circumstances Limited ability of woman & her caregivers to anticipate her pain experience prior to labor. Thus, choice among methods of pain relief is desirable.
Parenteral Agents Meperidine & Promethazine Meperidine 50-100 mg + Promethazine 25 mg IM q 2-4 hrs IV: (For more rapid/ IMMEDIATE effect) Meperidine 25-50 mg IV q 1-2 hrs IM: maximal analgesia after 30-45 mins Neonatal depressant effect closely follows after maximal analgesic effect baby is depressed If baby is delivered 2-3 hours after, baby will likely not be depressed Readily cross the PLACENTA Half-life in newborn: > 13 hours Butorphanol (Stadol) Synthetic narcotic Dose: 1-2 mg Antagonize narcotic effect of meperidine Associated w/ sinusoidal FHR pattern Side Effects:
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Somnolence Dizziness Dysphoria Less neonatal depression than miperidine Fentanyl Dose: 50-100 mcg IV q1 Disadvantage: Short duration of action Requires frequent dosing Butorphanol provide better initial analgesia than Fentanyl EFFICACY & SAFETY Meperidine is the most common opiod worldwide No convincing evidence that alternative opiods are better No evidence that parenteral opiods influence length of labor & need for obstetrical intervention Patient who is well sedated, has less anxiety, will have shorter labor Epidural anesthesia provides superior pain relief Continuous lumbar epidural anesthesia RISKS OF IV & IM SEDATION Aspiration Inadequate ventilation OD Newborn respiratory depression Narcotic Antagonists Naloxone Reverses respiratory depression Acts by displacing narcotic from specific receptors in CNS Can precipitate withdrawal symptoms in narcotic dependents Contraindicated in a newborn of a narcotic-addicted mother Nitrous Oxide Mixture: 50% N2O & 50% O2 (50:50) Gas anesthetic Administered by the use of mask: intermittent inhalation Patient controlled analgesia Pain not eliminated but should provide some relief Can provoke fits of laughter Passes beneath the POSTERIOR surface of sacrospinous ligament at its attachment to ISCHIAL SPINE (landmark) SENSORY fibers: from VENTRAL branches of S2-S4 nerve
REGIONAL ANESTHESIA Techniques Pudendal Block Paracervical Block Spinal Block Epidural Uterine innervation Pain during 1st stage of labor is generated largely from the uterus Visceral sensory Fibers from uterus, cervix, upper vagina Frankenhauser ganglion Pelvic plexus Middle & superior internal iliac plexus lumbar & lower thoracic sympathetic chains enter SC via white rami communicantes at T10 T12 and L1 nerves. Early in labor, the pain of uterine contractions is transmitted predominantly through the T11 and T12 nerves. MOTOR pathway: T7 - T8 Not blocked w/ epidural block; hence, will still have uterine contractions Lower Genital Tract Innervation Pain from vaginal delivery transmitted through pudendal nerve Provide sensory innervation to Perineum Anus Vulva: medial & inferior parts Clitoris
LOCAL ANESTHETIC AGENTS USED IN OBSTETRICS Amino-esters Metabolized by plasma choline esterase 2-Chloroprocaine ONSET: Rapid TYPE OF ANESTHESIA: Local/ Pudendal Block Epidural Anesthesia: CS Tetracaine ONSET: Slow TYPE OF ANESTHESIA: Low spinal block Spinal block: CS Amino-amides Metabolized in liver Lidocaine ONSET: Rapid TYPE OF ANESTHESIA: Local/ Pudendal Block Epidural/ Spinal Anesthesia: CS Bupivicaine ONSET: Slow TYPE OF ANESTHESIA: Epidural Anesthesia: NVD/ CS Spinal Anesthesia: CS Ropivacaine ONSET: Slow TYPE OF ANESTHESIA: Epidural Anesthesia: NVD/ CS ANESTHETIC AGENTS Onset, duration & quality of analgesia enhanced by increasing dose Dilute epinephrine is used to prolong action of the anesthetic Most often, serious toxicity follows inadvertent intravenous injection. when epidural analgesia is initiated, dilute epinephrine is sometimes added and given as a test dose. A sudden significant rise in the maternal heart rate or blood pressure immediately
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after administration suggests intravenous catheter placement. Systemic toxicity from local anesthetics typically manifests in the central nervous and cardiovascular systems. CNS TOXICITY Early symptom: STIMULATION Late Symptom: DEPRESSION Symptoms Light-headedness Dizziness Tinnitus Metallic taste Numbness of tongue & mouth Bizarre behavior Slurred speech Mm fasciculation Excitation Generalized convulsion LOC AGENTS to manage CNS toxicity: Succinylcholine Abolishes peripheral manifestations of convulsions & allow tracheal intubation Thiopental & Diazepam Act centrally to inhibit convulsions Magnesium Sulfate Controls convulsions Used for pregnancy Htn Anticonvulsant of choice for eclampsia CONVULSION maternal hypoxia & lactic acidosis abnormal FHR pattern: late deceleration & fetal bradycardia Administer O2 fetus usually recovers more quickly inutero than following immediate CS CARDIOVASCULAR TOXICITY Develop later than CNS toxicity at high serum drug levels except: Bupivacaine: associated with the development of neurotoxicity and cardiotoxicity Early symptom: STIMULATION Late Symptom: DEPRESSION EARLY Symptoms Htn Tachycardia LATE Symptoms Hypotention Cardiac arrhythmia d/t impaired uteroplacental perfusion & fetal distress Uteroplacental hypoperfusion HYPOTENSION Mx: Turn woman to either side to avoid aortocaval compression Hydration IV administration of EPHEDRINE (DOC for hypotension) w/ crystalloid solution Emergency CS if maternal VS is not restored in 5 mins of cardiac arrest fetus is likely to recover more quickly in utero once maternal cardiac output is reestablished PUDENDAL BLOCK For spontaneous vaginal delivery 15-cm, 22-gauge needle is used Needle pushed unto the mucosa beneath the tip of the ischial spine Infusion of 1 mL of 1% LIDOCAINE Needle then advance to the sacrospinous ligament & infiltrated w/ 3mL LIDOCAINE Needle is advanced further beyond the sacrospinous ligament, & through the mucosa & the rest of the 10 mL Lidocaine is infiltrated Approach Transvaginal Transperineal : more practical PARACERVICAL BLOCK satisfactory pain relief during the first stage of labor. not used routinely because the pudendal nerves are not blocked, hence, additional analgesia is required for delivery. use lidocaine or chloroprocaine, 5 to 10 mL of a 1-percent solution, injected into the cervix laterally at 3 and 9 oclock. Bupivacaine is contraindicated because of an increased risk of cardiotoxicity DISADVANTAGE: Anesthetics used are relatively short acting Paracervical block may have to be repeated during labor COMPLICATION: fetal bradycardia Develop w/in 10 mins Transient ~ 30 mins d/t transplacental transfer of agent or its metabolites can result to placental perfusion following drug-induced vasospasm & myometrial hypertonus
SPINAL (SUBARACHNOID) BLOCK Needle inserted at subarachnoid space POSITION: lateral decubitus, fetal position Advantages Short procedure time Rapid onset of block High success rate Compared to epidural technique Vaginal delivery Low spinal block w/c can be used for forceps or vacuum deliery of analgesia should extend to T10 DERMATOME (umbilicus) Excellent pain relief from uterine contraction Lidocaine/bupivacaine w/ glucose (hyperbaric solution) Administered only w/ fully dilated cervix Preanalgesic IV hydration w/ 1L crystalloid will prevent or minimize hypotension CS Sensory block to T4 DERMATOME Lidocaine/bupivacaine w/ glucose (hyperbaric solution) + Fentanyl Bupivacaine (0 to 12 mg) in a hyperbaric solution or Lidocaine (50
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to 75 mg) hyperbaric solution are administered. Fentanyl (20 to 25 mg) increases the rapidity of blockade onset and reduces shivering. Morphine (0.2 mg) improves pain control during delivery and postoperatively. Mx: tx seizusres & blood patch Bladder Dysfunction Frequent postpartum complication Bladder sensation obtunded & bladder emptying impaired w/in 1st few hours after delivery Oxytocics & Hypertension Paradoxical hypertension d/t ergonovine or methylergonovine injection occurs postpartum more common in women who have received a spinal or epidural block Arachnoiditis & Meningitis
COMPLICATIONS OF REGIONAL ANESTHESIA obese women have significantly impaired ventilation and thus close clinical monitoring is imperative Hypotension Consequence of vasodilation from sympathetic block + obstructed venous return from uterine compression of vena cava Tx Uterine displacement by positioning pt in left lateral decubitus IV hydration IV bolus of EPHEDRINE or PHENYLEPHRINE Ephedrine: Sympathomimetic BP by HR, CO & PVR Preferred vasopressor for obstetric use Phenylephrine BP through vasoconstriction High Spinal Block Consequence of administration of excessive dose of local anesthetic agent Hypotension & apnea develops & must be immediately treated to prevent CARDIAC ARREST Mx: Undelivered woman: uterus is immediately displaced laterally to minimize aortocaval compression Ventilation is established, preferably with tracheal intubation IV fluids and ephedrine are given to correct hypotension Spinal (postdural puncture) HA Aka: Postdural Puncture Cephalgia CSF leak from puncture site of the meninges CSF volume Traction of pain sensitive CNS structures when sitting or standing Spinal Headache Mx: Use small gauge needle Avoid multiple puncture Hydration Caffeine: cerebral vasoconstrictor Epidural blood patch: for severe HA Bedrest Analgesics Convulsions d/t CSF hypotention
ABSOLUTE CONTRAINIDICATIONS OF REGIONAL ANALGESICS Refractory maternal hypotension CASE 1: Severe Hge d/t ruptured ectopic pregnancy w/ 2-3L hemoperitoneum who is hypotensive & tachycardic, what would be the anesthesia of choice? General endotracheal intubation Regional block is CONTRAINDICATED CASE 2: Patient w/ abruption placenta or placenta previa w/ profuse bleeding, what would be the anesthesia of choice? General endotracheal intubation anesthesia Regional block is CONTRAINDICATED Maternal coagulopathy: ITP Untreated bacteremia: use of regional block can spread infection to CNS Skin infection (Cellulitis) over needle site can lead to spread of infection ICP: should not be an absolute contraindication but if she later on develops paralysis, can lead to litigation Neurological Disorders RELATIVE Contraindication of REGIONAL ANESTHESIA Aortic Stenosis Pulmonary Htn PREECLAMPSIA Associated w/ markedly decreased BP when SPINAL analgesia is used Anesthesia of Choice: EPIDURAL ANESTHESIA General anesthesia has inherent risk of: Difficult intubation d/t airway edema CVA d/t BP
EPIDURAL ANESTHESIA Introduction of local anesthetic into a catheter into the epidural space or peridural space through a Touhy needle Entry through lumbar IVS, sacral hiatus or sacral canal
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Can use of indwelling catheter for repeat or continuous infusion of local anesthetic Can give in single dose CONTINUOUS LUMBAR EPIDURAL BLOCK indications Vaginal delivery Necessitates block from T10-S5 dermatome CS Necessitates block from T4 to S1 dermatome spread of the anesthetic depends upon the location of the catheter tip; the dose, concentration, and volume of anesthetic agent used and whether the mother is headdown, horizontal, or head-up Complications of Epidural Block Total Spinal Blockade c/o DOB caused by dural puncture w/ inadvertent subarachnoid injection Ineffective analgesia Risk factors: Nulliparity Heavier fetal wt Epidural catheter placement at early cervical dilatation BMI Mx pudendal block or systemic analgesia or rarely general anesthesia may be added Hypotension & CO Lesser in degree compared to spinal anesthesia Mx: Prevented by rapid infusion of 5001000 mL crystalloids fast drip 3060min before spinal tap Lateral decubitus Mc side effect CNS stimulation Convulsions: uncommon Acute onset intrapartum HA d/t postdural pneumocephalus Maternal Fever Precise etiology: UNKNOWN THEORIES: maternal-fetal infection dysregulation of body temperature Other proposed mechanism: Alteration in hypothalamic thermoregulatory set point Impairment of peripheral thermoregulatory setpoint Impairment of peripheral thermoreceptor INPUT Imbalance b/w heat production & heat loss Back pain Common complication Transient No evidence w/ chronic back pain EFFECT ON LABOR Prolongs active phase of labor by 1 hr Increase need for oxytocin stimulation Increase need for vaginal instrumental delivery d/t prolonged 2nd stage of labor No adverse neonatal effects EFFECT ON FHR beat to beat variability & fewer accelerations are more common in MEPERIDINE use associated with improved neonatal acid-base status compared with meperidine CS delivery RATE No increase in CS rate No increase in prevalence of fetal malpresentation Increased duration of 2nd stage labor by 25 mins Nullipara: 50 mins to 2 hrs + 1 hr if w/ epidural Multipara: 30 mins to 1 hr + 1 hr if w/ epidural TIMING OF EPIDURAL Timing of epidural has no effect on the risk of CS, forceps delivery, or fetal malposition Women in labor should not be required to reach 4-5 cm cervical dilation before receiving epidural anesthesia SAFETY: few anesthesia-related deaths associated with epidural use potentially life-threatening complications followed either inadvertent intravenous or intrathecal injection of lidocaine, bupivacaine, or both calculated risks: 1:145,000 for deep epidural infection 1:168,000 for epidural hematoma 1:240,000 for persistent neurological injury. CONTRAINDICATIONS: Same as SPINAL Anesthesia actual or anticipated serious maternal hemorrhage Infection at or near the sites for puncture suspicion of neurological disease RISKS Factors THROMBOCYTOPENIA Anticoagulation risk for SPINAL hematoma & compression ACOG Recommendation Unfractionated Heparin Therapy: may receive regional anesthesia provided aPTT is NORMAL Prophylactic unfractionated Heparin or low dose Aspirin: can be offered regional anesthesia Once daily low dose LMW Heparin: regional anesthesia should not be placed until 12 hours after last injection LMW heparin should be withheld at least 2 hours after removal of epidural catheter Severe Preeclampsia-Eclampsia Complications of Epidural anesthesia Hypotention Hypertension Pulmonary Edema Cerebral Edema ICH epidural analgesia can be safely used when specially trained anesthesiologists and obstetricians are responsible for the woman and her fetus Standardized protocol for prehydration, incremental epidural administration, and ephedrine EPIDURAL OPIATE ANALGESIA MOA: Interaction w/ specific receptors in dorsal horn & dorsal roots ADVANTAGE of Combination: Rapid onset of pain relief shivering Opiates alone will not provide adequate analgesia Less dense motor blockade S/E: Pruritus Mx: Droperidol 5 mg epidurally Urinary Retention COMBINED SPINAL-EPIDURAL TECHNIQUES Aka: Needle-through-needle Technique Both spinal & epidural anesthesia if operation duration is for prolonged period Spinal for early onset analgesia Single bolus of OPIOD cause RAPID ONSET of profound pain relief without motor blockade Epidural for long duration analgesia No difference in side-effects
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LOCAL INFILTRATION FOR CS Local block that is used to augment an inadequate or patchy regional block Used to perform emergency CS to save the life of a fetus in the absence of any anesthesia support TECHNIQUE: 1st technique skin is infiltrated in the line of the proposed incision, and the subcutaneous, muscle, and rectus sheath layers are injected as the abdomen is opened dilute solution of lidocaine30 mL of 2percent with 1:200,000 epinephrine diluted with 60 mL of normal saline 100 to 120 mL is infiltrated. Injection of large volumes into the fatty layers is avoided to limit the total dose of local anesthetic needed. 2nd technique field block of the major branches supplying the abdominal wall: 10th, 11th, and 12th intercostal nerves: midway between the costal margin and iliac crest in the midaxillary line needle is directed medially and injection is carried down to the transversalis fascia, avoiding injection of the subcutaneous fat 5 to 8 mL of 0.5-percent lidocaine is injected. procedure is repeated at a 45degree angle cephalad and caudad to this line Only one skin puncture is made at each of the four sites (right and left sides) ilioinguinal and genitofemoral nerves external inguinal ring injection is started at a site 2 to 3 cm lateral from the pubic tubercle at a 45-degree angle. 3rd Technique skin overlying the planned incision is injected. Taken from the market by human rights activists d/t being used for lethal injection Induce sleep ADVANTAGES: easy and rapid induction prompt recovery minimal risk of vomiting DISADVANTAGES poor analgesic agents administration of sufficient drug given alone to maintain anesthesia may cause appreciable newborn depression
GENERAL ANESTHESIA Main cause of maternal mortality common cause of death cited for general anesthesia is failed intubation Pt is put to sleep Patient PREPARATION Step to minimize complication: Antacids H2-receptor antagonist, or metoclopramide lateral uterine displacement avoid aortocaval compression preoxygenation administered to minimize hypoxia d/t functional reserve lung capacity is reduced; hence, pregnant women become hypoxemic more rapidly during periods of apnea than do nonpregnant patients w/c is exacerbated w/ Obesity minimize hypoxia between the time of muscle relaxant injection and intubation, it is important first to replace nitrogen in the lungs with oxygen. administering 100% oxygen via face mask for 2 to 3 minutes prior to anesthesia induction. INDUCTION OF ANESTHESIA THIOPENTAL Favorite IV anesthesia for normal delivery or forceps When done episiorrhapy, pt normally dont have side effects
KETAMINE Truth serum Render pt unconscious 1 mg/kg induce general anesthesia low doses of 0.2 to 0.3 mg/kg produce analgesia and sedation just prior to vaginal delivery useful in women with acute hemorrhage because, unlike thiopental, it is not associated with hypotension causes a rise in blood pressure thus avoided in women who are hypertensive. Induce Unpleasant delirium and hallucinations INTUBATION Immediately after a patient is rendered unconscious, a muscle relaxant is given to aid intubation. Succinylcholine rapid-onset and short-acting agent Cricoid pressurethe Sellick maneuver Occlude the esophagus from the onset of induction until intubation is completed. Before the operation begins, proper placement of the endotracheal tube must be confirmed FAILED INTUBATION Alternative for difficult intubation: LMA (laryngeal mask airways) Uncommon major cause of anesthesia-related maternal mortality careful assessment of anatomical features of the neck and of maxillofacial, pharyngeal, and laryngeal structures may help predict a difficult intubation. RISK FACTORS h/o previous intubation edema may develop intrapartum and present considerable difficulties Morbid obesity is also a major risk factor for failed or difficult intubation. appropriate preoperative preparation to include: the immediate availability of specialized equipment:
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laryngoscopes laryngeal mask airways fiber-optic bronchoscope transtracheal ventilation set liberal use of awake oral intubation techniques MANAGEMENT Start procedure only after it has been ascertained that intubation has been successful & adequate ventilation is accomplished Awake intubation Open cricothyrotomy GAS ANESTHETICS Once the endotracheal tube is secured, a 50:50 mixture of nitrous oxide and oxygen is administered to provide analgesia. Usually, a volatile halogenated agent is added to provide amnesia and additional analgesia VOLATILE ANESTHETICS Mc used: Isoflurane Desflurane Sevoflurane Potent, nonexplosive agents that produce remarkable uterine contraction Used when uterine relaxation is requisite Internal podalic version of 2nd twin Breech decomposition Replacement of acutely inverted uterus S/E: Cardiodepressant Hypotension Anesthesia Gas Exposure & Pregnancy Outcome All anesthetic agents that depress maternal CNS cross placenta & depress fetal CNS Induction-to-delivery time should be minimized Fetal exposure of more than 8 mins was associated w/ increased neonatal depression EXTUBATION The tracheal tube may be safely removed only if the woman is conscious to a degree that enables her to follow commands and is capable of maintaining oxygen saturation with spontaneous respiration Consideration should be given to emptying the stomach via a nasogastric tube prior to extubation. COMPLICATION: hypoventilation or airway obstruction during emergence, extubation, or recovery ASPIRATION Massive gastric acidic inhalation causing pulmonary insufficiency from aspiration pneumonitis: MENDELSONS Syndrome Mc cause of anesthetic death in OB PROPHYLAXIS Antacids Skillful intubation NGT use to empty stomach Use regional anesthesia as much as possible Fasting of > 8 hrs is preferred for uncomplicated parturients undergoing elective CS delivery or puerperal tubal ligation PATHOPHYSIOLOGY Severe chemical pneumonitis develop Usually via right mainstem bronchus Right lobe is often involved Woman develops respiratory distress Mx: mechanical ventilation with positive end-expiratory pressure Large amount of solid matter aspirated AIRWAY OBSTRUCTION Mx: Bronchoscopy Smaller particles w/o acidic liquid aspirated patchy atelectasis bronchoPNA
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CHAPTER 30
Puerperium
Dr. Daisy F Estimo DEFINITION Period of confinement during and just after giving birth Includes subsequent six (6) weeks during which normal pregnancy involution occurs Duration: between 4 and 6 weeks Physiological changes: large vessels return to small ones Changes in the cervix: lacerated laterally w/ canal narrowed Lower Uterine Segment: contract and become the isthmus Tummy size still 5 months size Pregnancy Risk Assessment Monitoring SystemPRAMS Population based surveillance system was initiated in 1987 by the Centers for Disease Control and Prevention (2007a) to better understand why infant mortality rates had plateaued. ANATOMICAL, PHYSIOLOGICAL, AND CLINICAL ASPECTS Vagina and Vaginal Outlet Early in the puerperium, what forms a capacious, smoothwalled passage that gradually diminishes in size but rarely returns to nulliparous dimensions? the vagina and its outlet What begin to reappear by the third week but are not as prominent as before? Rugae The hymen is represented by several small tags of tissue, which scar to form the? myrtiform caruncles. Vaginal epithelium begins to proliferate by? 4 to 6 weeks, usually coincidental with resumed ovarian estrogen production Vaginal outlet relaxation & uterine prolapse: Extensive laceration Overstretching, changes in pelvic support during parturition Some damage to the pelvic floor may be inevitable, and parturition predisposes to uterine prolapse as well as urinary and anal incontinence. Uterus Vessels Pregnancy blood vessels enlarge remarkably growth of new vessels The massively increased uterine blood flow necessary to maintain pregnancy is made possible by significant hypertrophy and remodeling of all pelvic vessels After delivery, their caliber diminishes to the size of the prepregnant state. Within the puerperal uterus, larger blood vessels become obliterated by hyaline changes, gradually resorbed, and replaced by smaller ones Minor vestiges of the larger vessels, however, may persist for years Cervix and Lower Uterine Segment During labor, the outer cervical margin (external os) is lacerated laterally Cervical opening contracts slowly and for a few days immediately after labor readily admits two fingers End of the first week, this opening narrows, the cervix thickens, and the endocervical canal reforms External os does not completely resume its pregravid appearance remains somewhat wider, and typically, bilateral depressions at the site of lacerations become permanent Changes are characteristic of a parous cervix Lower Uterine Segment (LUS): contracts and retracts but not as forcefully as the body of the uterus Uterine Involution: Involution of the uterine corpus Immediately after placental expulsion, the fundus of the contracted uterus lies slightly below the umbilicus It consists mostly of myometrium covered by serosa and lined by basal deciduas The anterior and posterior walls, in close apposition, each measure? 4 to 5 cm thick Immediately postpartum, the uterus weighs approximately? 1000 g Two days after delivery, the uterus begins to involute One week later, it weighs about? 500 g 2 weeks, it weighs about? 300 g and has descended into the true pelvis 4 weeks after delivery, it regains its previous nonpregnant size of? 100 g or less Because separation of the placenta and membranes involves the spongy layer, what still remains in the uterus and is not sloughed? decidua basalis The decidua that remains has striking variations in thickness, has an irregular jagged appearance, and is infiltrated with blood, especially at the placental site Afterpains Primiparas, the uterus tends to remain tonically contracted following delivery Multiparas, it often contracts vigorously at intervals and gives rise to afterpains, which are similar to but milder than the pain of labor contractions More pronounced as parity increases and worsen when the infant suckles, likely because of oxytocin release Usually, afterpains decrease in intensity and become mild by the third day Can stimulate the nipple by squeezing it in between and oxytocin will be release Lochia Sloughing of decidual residue remnants in vaginal discharge in variable quantity, that consists of erythrocytes, shredded decidua, epithelial cells, and bacteria Types: IDENTIFY lochia rubra: For the first few days after delivery, there is blood sufficient to color red lochia serosa: After 3 or 4 days, lochia becomes progressively pale in color (white) lochia alba: After about the 10th day, because of an admixture of leukocytes and reduced fluid content, lochia assumes a white or yellowish-white color Lochia will persists for up to? 4 to 8 weeks after delivery Endometrial Regeneration Within 2 or 3 days after delivery, the remaining decidua becomes differentiated into two layers Superficial layer and basal layer rapid Superficial layer becomes necrotic and is sloughed in the lochia The basal layer adjacent to the myometrium remains intact and is the source of new endometrium Endometrium arises from proliferation of the endometrial glandular remnants and the stroma of the interglandular connective tissue. rd 3 week: entire endometrium is restored
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Endometritis during puerperium Fallopian tubes: between 5 to 15 days demo microscopic inflammatory changes character of acute salpingitis NOTE: Histological endometritis is part of the normal reparative process. Moreover, microscopic inflammatory changes characteristic of acute salpingitis are seen in almost half of postpartum women between 5 and 15 days. However, these do not reflect infection Subinvolution Arrest or a retardation of involution Prolongation of lochial discharge and irregular or excessive uterine bleeding, which sometimes may be profuse On bimanual examination, the uterus is larger and softer than would be expected If mother does not breast feed can cause subinvolution in contrast if there is breast feeding the involution is faster Causes: What causes subinvolution? Placental fragment retention & pelvic infection Ergonovine or methylergonovine (Methergine), 0.2 mg every 3 to 4 hours for 24 to 48 hours, is recommended by some for subinvolution, but its efficacy is questionable. On the other hand, bacterial metritis responds to oral antimicrobial therapy What is the treatment for subinvolution? Ergonovine & methylegornovine Almost a third of cases of late postpartum uterine infection are caused by Chlamydia trachomatis. Thus, azithromycin or doxycycline therapy is appropriate empirical therapy rd In 1/3 of cases what causes late postpartum uterine infection? Chlamydia trachomatis Treatment for chlamydia trachomatis? Azithromycin & doxycycline Placental Site Involution Complete extrusion of the placental site takes up to 6 weeks Process if defective, late-onset puerperal hemorrhage may ensue Process of exfoliation: necrotic slough of infracted superficial tissues reparative process Immediately after delivery, the placental site is approximately the size of the palm, but it rapidly decreases thereafter Within hours of delivery, the placental site normally consists of many thrombosed vessels that ultimately undergo organization By the end of the second week, it is 3 to 4 cm in diameter Exfoliation consists of both extension and "downgrowth" of endometrium from the margins of the placental site, as well as development of endometrial tissue from the glands and stroma left deep in the decidua basalis after placental separation Concluded that placental site exfoliation results from sloughing of infarcted and necrotic superficial tissues followed by a remodeling process. Late Postpartum Hemorrhage bleeding 24 hours to 12 weeks after delivery o secondary postpartum hemorrhage Develops within 1 to 2 weeks in perhaps 1 percent of women Such bleeding most often is the result of abnormal involution of the placental site Caused by retention of a placental fragment The retained piece undergoes necrosis with deposition of fibrin and may eventually form a socalled placental polyp The retained placental fragment that undergoes necrosis with fibrin deposition will form? Placental polyp As the eschar of the polyp detaches from the myometrium, hemorrhage may be brisk Treatment is? IV oxytocin, ergonovine, prostaglandin methylergometrine It will persist or recur curettage
Urinary tract Normal pregnancy; increase in extracellular water nd th Diuresis occurs postpartum between 2 to 5 day: increase urination In preeclampsia: retention of fluid antepartum & diuresis postpartum may be greatly increased. Puerperal bladder: increase capacity and relative insensitivity to intravesical fluid pressure Common: over distension, incomplete emptying, excessive residual urine Incontinence Bladder trauma is associated most closely with the length of labor and thus to some degree is a normal accompaniment of vaginal delivery Immediately postpartum and described varying degrees of submucosal hemorrhage and edema. Pathophysiology: underlying puerperal incontinence impaired muscle function in or around the urethra during vaginal delivery 3 months postpartum: most women return to normal micturition Ureter and kidney The dilated ureters and renal pelvis return to their prepregnant state over the course of 2 to 8 weeks after delivery No evidence for bladder hypotonia when: Prolonged labors are avoided Catheterization done promptly Associated with development of stress incontinence: nd Length of 2 stage of labor Infant head circumference Birth weight episiotomy Predisposing factors to urinary tract infection Urinary tract infection is of concern because: residual urine and bacteriuria in a traumatized bladder, coupled with a dilated collecting system, are conducive to infection. PREVENTION: Prompt catheterization
Peritoneum and Abdominal Wall The broad and round ligaments require considerable time to recover from the stretching and loosening that occur during pregnancy As a result of ruptured elastic fibers in the skin and prolonged distension caused by the pregnant uterus The abdominal wall remains soft and flaccid Recovery is aided by exercise, except for silvery striae, the abdominal wall usually resumes its prepregnancy appearance When muscles remain atonic, however, the abdominal wall also remains lax Silvery striae: Striae result of ruptured elastic fibers in the skin. Marked separation of the rectus musclesdiastasis recti may result. What is marked separation of rectus muscles? Diastasis recti
Blood and Fluid Changes
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Marked leukocytosis and thrombocytosis may occur during and after labor The white blood cell count sometimes reaches 30,000/L, with the increase predominantly due to granulocytes There is a relative lymphopenia and an absolute eosinopenia. Normally, during the first few postpartum days, hemoglobin concentration and hematocrit fluctuate moderately If they fall much below the levels present just prior to labor, a considerable amount of blood has been lost st 1 week after delivery: blood volume has returned nearly to its nonpregnant level By 2 week: changes return to its nonpregnant value Cardiac output usually remains elevated for 24 to 48 hours postpartum and declines to nonpregnant values by 10 days Heart rate changes follow this pattern. Systemic vascular resistance follows inversely. It remains in the lower range characteristic of pregnancy for 2 days postpartum and then begins to steadily increase to normal nonpregnant values Pregnancy-induced changes in blood coagulation factors persist for variable periods during the puerperium Elevation of plasma fibrinogen is maintained at least through the first week, and hence, so is the sedimentation rate. NOTE: Normal pregnancy is associated with an appreciable increase in extracellular water, and postpartum diuresis is a physiological reversal of this process. This regularly occurs between the second and fifth days and corresponds with loss of residual pregnancy hypervolemia. In preeclampsia, both retention of fluid antepartum and diuresis postpartum may be greatly increased Secretion persists for approximately 5 days, with gradual conversion to mature milk during the ensuing 4 weeks Colostrum contains antibodies, and its content of immunoglobulin A (IgA) offers the newborn protection against enteric pathogens Other host resistance factors found in colostrum and milk include complement, macrophages, lymphocytes, lactoferrin, lactoperoxidase, and lysozymes.
Milk Human milk is a suspension of fat and protein in a carbohydrate-mineral solution Nursing mother produces 600 mL of milk daily, and maternal gestational weight gain has little impact on its quantity or quality Milk is isotonic with plasma, and lactose accounts for half of the osmotic pressure Most milk proteins are unique and include alphalactalbumin, beta-lactoglobulin, and casein Fatty acids are synthesized in the alveoli from glucose and are secreted by an apocrine-like process All vitamins except K are found in human milk, but in variable amounts Vitamin D content is low22 IU/mL, and newborn supplementation is recommended by the American Academy of Pediatrics Whey is milk serum and has been shown to contain large amounts of interleukin-6 It is associated closely with local IgA production by the breast Prolactin appears to be actively secreted into breast milk Epidermal growth factor (EGF) has been identified in human milk, and because it is not destroyed by gastric proteolytic enzymes, it may be absorbed to promote growth and maturation of newborn intestinal mucosa. Low iron concentration
Weight Loss In addition to the loss of 5 to 6 kg due to uterine evacuation and normal blood loss, there is usually a further decrease of 2 to 3 kg through diuresis Women approach their self-reported prepregnancy weight 6 months after delivery but still retain an average surplus of 1.4 kg (3 lb) Indigent women are more likely to retain weight gained during pregnancy Factors that increase the puerperal weight loss weight gain during pregnancy primiparity early return to work smoking
Endocrinology of Lactation Progesterone, estrogen, and placental lactogen, as well as prolactin, cortisol, and insulin, appear to act in concert to stimulate the growth and development of the milksecreting apparatus With delivery, there is an abrupt and profound decrease in the levels of progesterone and estrogen. Progesterone withdrawal also allows prolactin to act unopposed in its stimulation of alpha-lactalbumin production. The intensity and duration of subsequent lactation are controlled, in large part, by the repetitive stimulus of nursing Prolactin is essential for lactation, and women with extensive pituitary necrosisSheehan syndromedo not lactate Although plasma prolactin levels fall after delivery to levels lower than during pregnancy, each act of suckling triggers a rise in levels Presumably a stimulus from the breast curtails the release of dopamine (prolactin-inhibiting factor) from the hypothalamus, and this in turn transiently induces increased prolactin secretion. Breast stimulation stops release of Prolactin inhibiting factor from the hypothalamus thus increase Prolactin secretion The neurohypophysis secretes oxytocin in pulsatile fashion This stimulates milk expression from a lactating breast by causing contraction of myoepithelial cells in the alveoli and small milk ducts Milk ejection, or letting down, is a reflex initiated especially by suckling, which stimulates the neurohypophysis to liberate oxytocin The reflex may even be provoked by an infant cry and can be inhibited by maternal fright or stress.
Breasts and Lactation Anatomically , Each mature mammary gland or breast is composed of 15 to 25 lobes Arranged radially and are separated from one another by varying amounts of fat. Each lobe consists of several lobules, which in turn are composed of large numbers of alveoli Each alveolus is provided with a small duct that joins others to form a single larger duct for each lobe These lactiferous ducts open separately on the nipple, where they may be distinguished as minute but distinct orifices
Colostrum After delivery, the breasts begin to secrete colostrum, which is a deep lemon-yellow liquid Can be expressed from the nipples by the second postpartum day Compared with mature milk, colostrum contains more minerals and amino acids It also has more protein, much of which is globulin, but less sugar and fat
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Immunological Consequences of Breast Feeding Antibodies in human colostrum and milk are poorly absorbed by infants This does not lessen their importance because the predominant immunoglobulin is secretory IgA This macromolecule is secreted across mucous membranes and has important antimicrobial functions Milk contains secretory IgA antibodies against Escherichia coli, and breast-fed infants are less prone to enteric infections than bottle-fed infants Human milk also provides protection against rotavirus infections, which cause up to half of cases of infant gastroenteritis in this country Breast feeding also likely reduces the risk of atopic dermatitis and wheezing illnesses in early childhood Milk contains both T and B lymphocytes Ovulation may resume as early as 3 weeks after delivery, even in lactating women Its timing depends on individual biological variation as well as the intensity of breast feeding Progestin-only contraceptives"mini-pills," depot medroxyprogesterone, or progestin implantsdo not affect the quality or quantity of milk OCP: Started 2 to 3 weeks postpartum DMPA: started at 6 weeks postpartum Hormonal implants inserted at 6 weeks postpartum Estrogen-progestin contraceptives likely reduce the quantity of breast milk, but under the proper circumstances, they too can be used by breast-feeding women
Contraindications to Breast Feeding Nursing Human milk is ideal food for neonates. It provides agespecific nutrients as well as immunological factors and antibacterial substances Milk also contains factors that act as biological signals for promoting cellular growth and differentiation Women who breast feed have a lower risk of breast cancer, and their children have increased adult intelligence independent of a wide range of possible confounding factors Breast feeding is associated with decreased postpartum weight retention Breast feeding for at least two cumulative years had a 23percent lower risk of coronary heart disease Suckling is continued- for adequate supply of milk Accelerates uterine involution release of oxytocin Women taking street drugs or do not control their alcohol use Infant with galactosemia HIV infection Breast feeding has been recognized for some time as a mode of HIV transmission Active, untreated tuberculosis; take certain medications Undergoing treatment for breast cancer NOTE: Some viral infections do NOT contraindicate breast feeding: Maternal cytomegalovirus CMV infection: both virus and antibodies are present in breast milk. Hepatitis B virus: excreted in milk but breast feeding is not contraindicated if hepatitis B immune globulin is given to these infants. Maternal hepatitis C: not a contraindication because the 4-percent risk of infant transmission is the same for breast- and bottle-fed infants. Active herpes simplex virus: may suckle their infants if there are no breast lesions and if particular care is directed to hand washing before nursing.
Breast Engorgement Women who do not breast feed may experience engorgement, milk leakage, and breast pain, which peaks at 3 to 5 days after delivery As many as half require analgesia for breast-pain relief. Up to 10 percent of women report severe pain up to 14 days. Breasts should be supported with a well-fitting brassiere Well-fitting brassiere, ice packs and oral analgesics Pharmacological or hormonal agents are not recommended to suppress lactation. Instead, ice packs and oral analgesics for 12 to 24 hours can be used to relieve discomfort Breast binder is used at Parkland Hospital for these women, and a "sports bra" is used at the University of Alabama Hospital Bromocriptine not advisable to be used anymore, use well fitting bra. Associated w/ strokes, MI, seizures & psych disturbances Give analgesics, antipyretics.
Care of the breasts and nipples: Clean the areola with water and mild soap Irritated nipples: use nipple shield Inverted or retracted nipples: tease it out Woman who does not desire to breastfeed During stage of engorgement well fitting brassiere, ice packs, oral analgesics Breast binders Medicine
Contraception for Breast-Feeding Women
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Other commonly isolated organisms: coagulase-negative staphylococci viridans streptococci Immediate source of organisms that cause mastitis is almost always the infant's nose and throat Bacteria enter the breast through the nipple at the site of a fissure or small abrasion Infecting organism can usually be cultured from milk Treatment Most recommend: Milk be expressed from the affected breast onto a swab and cultured before beginning therapy Bacterial identification and antimicrobial sensitivities provide information mandatory for a successful surveillance program of nosocomial infections Dicloxacillin, 500 mg orally four times daily Erythromycin is given to women who are penicillin sensitive If the infection is caused by resistant, penicillinaseproducing staphylococci, or if resistant organisms are suspected while awaiting the results of culture, then vancomycin or another anti-MRSA antimicrobial should be given Even though clinical response may be prompt, treatment should be continued for 10 to 14 days. When nursing bilaterally, it is best to begin suckling on the uninvolved breast. This allows let-down to commence before moving to the tender breast
Drugs secreted in milk: Factors influencing secretion: Concentration of the drug Degree of protein binding Plasma and milk pH Degree of ionization Lipid solubility Molecular weight Cytotoxic drugs: may interfere with cellular metabolism of the infant & causes immune suppression of neutropenia, effect growth or increase risk of cancer Acebutolol 5-aminosalicylic acid Aspirin Atenolol Clemastine Ergotamine Lithium Phenindione Phenobarbital Primidone Sulfasalazine
Breast Abscess An abscess should be suspected when defervescence does not follow within 48 to 72 hours of mastitis treatment, or when a mass is palpable Traditional therapy: surgical drainage, which usually requires general anesthesia Incision should be made corresponding to Langer skin lines for a cosmetic result Single incision over the most dependent portion of fluctuation is usually sufficient, but multiple abscesses require several incisions and disruption of loculations The resulting cavity is loosely packed with gauze, which should be replaced at the end of 24 hours by a smaller pack Less invasive alternative is sonographic-guided needle aspiration using local anesthesia, which has success rates of 80 to 90 percent
Breast fever: Commencement of lactation: first 24 hours Breast is distended, firm & nodular transient elevation of temperature (seldom persist for longer than 4 to 16 hours) Treatment: Breast binders or brassiere Ice bag Analgesic Expression of milk-pump or manual
Galactocele result of the clogging of a duct by inspissated secretion milk accumulate
Mastitis Parenchymatous infection of the mammary glands is a rare complication antepartum but is estimated to develop in up to a third of breast-feeding women Unilateral Marked engorgement usually precedes inflammation S/SX: suppurative mastitis seldom appear before the end of the first week postpartum and as a rule, not until the third or fourth week chills or actual rigor, which are soon followed by fever and tachycardia Breast becomes hard and reddened, and there is severe pain About 10 percent of women with mastitis develop an abscess. Detection of fluctuation may be difficult, and sonography may be helpful to detect an abscess. Etiology Staphylococcus aureus: most commonly isolated organism Toxic shock syndrome from mastitis has been reported
Abnormalities of the nipple: depression Inverted nipples Fissures Supernumerary breasts: extra nipple at the axilla or other part of the chest. Some are functional also secretes milk
Abnormalities of secretion Agalactia complete lack of mammary secretion Polygalactia excessive mammary secretion
CARE OF THE MOTHER DURING THE PUERPERIUM Attention immediately after labor 1 hour of delivery: vital signs every 15 minutes Monitor amount of vaginal bleeding, palpate fundus
st
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Early Ambulation Be out of bed within a few hours after delivery Attendant should be present for at least the first time, in case the woman becomes syncopal Advantages of early ambulation: bladder complications frequent constipation frequency of puerperal venous thrombosis frequency of pulmonary embolism This prevents recurrence and allows recovery of normal bladder tone and sensation. When the catheter is removed, it is necessary subsequently to demonstrate ability to void appropriately If a woman cannot void after 4 hours, she should be catheterized and the urine volume measured > 200 mL: bladder is not functioning appropriately, and the catheter is left for another day < 200 mL: catheter can be removed and the bladder rechecked subsequently If women developed bacteriuria: a single-dose or short course of antimicrobial therapy is reasonable after the catheter is removed.
Perineal Care Cleanse the vulva from anterior to posteriorthe vulva toward the anus Ice bag: on the perineum may help edema and discomfort during the first several hours if there is a laceration or an episiotomy Local Anesthetic Spray: relief may be obtained from the periodic application of a local anesthetic spray Severe discomfort usually indicates a problem: Hematoma within the first day or so Infection after the third or fourth day Severe perineal, vaginal, or rectal pain always warrants careful inspection and palpation Beginning approximately 24 hours after delivery, moist heat as provided with warm sitz baths can be used to reduce local discomfort Tub bathing after uncomplicated delivery is allowed The episiotomy incision normally is firmly healed and nearly asymptomatic by the third week.
Depression It is fairly common for a mother to exhibit some degree of depressed mood a few days after delivery Termed postpartum blues Consequence of a number of factors: emotional let down that follows the excitement & fears experienced during pregnancy and delivery Discomforts of the early puerperium fatigue from sleep deprivation anxiety over the ability to provide appropriate infant care body image concerns Anxiety over her capabilities Fear that she will become less attractive. effective treatment includes: anticipation recognition reassurance Disorder is usually mild and self-limited to 2 to 3 days, although it sometimes lasts for up to 10 days
Bladder Function Oxytocin, in doses that have an antidiuretic effect, is commonly infused postpartum, and rapid bladder filling is common Rapid bladder filling: due to: Infused fluid Sudden withdrawal of antidiuretic effect of oxytocin Both bladder sensation and capability to empty spontaneously may be diminished by: local or conduction analgesia episiotomy or lacerations instrumented delivery Urinary retention with bladder overdistension is common in the early puerperium Risk factors that increased likelihood of retention: Primiparity oxytocin-induced or augmented labor perineal lacerations instrumented delivery catheterization during labor labor with duration over 10 hours. Bladder becomes overdistended indwelling catheter for at least 24 hours NOTE: Prevention of bladder overdistension demands observation after delivery to ensure that the bladder does not overfill and that with each voiding, it empties adequately. The enlarged bladder can be palpated suprapubically, or it is evident abdominally indirectly as it elevates the fundus above the umbilicus. Management If NO voiding within 4 hours after delivery, it is likely that shes having urinary retention If she has trouble voiding initially, she also is likely to have further trouble An examination for perineal and genital-tract hematomas is made. Overdistended bladder: indwelling catheter should be left in place until the factors causing retention have abated Even without a demonstrable cause, it usually is best to leave the catheter in place for at least 24 hours.
Abdominal wall relaxation Diet NO dietary restrictions: calories and protein Continue iron supplementation Abdominal binders unnecessary Exercise to restore abdominal wall tone
Obstetrical neuropathies Branches of lumbosacral nerve plexus pressure intense neuralgia or cramplike pain, variable degrees of sensory loss or muscle paralysis Lateral femoral Cutaneous neuropathies Femoral neuropathies External popliteal nerves weakened ankles dorsiflexion and footdrop
Pelvic joint separation Symphysis pubis or sacroiliac synchondroses marked interference with locomotion
Immunization: 300 ug unit of anti-D immune globulin in D-negative woman who is not isoimmunized and whose baby is Dpositive Diphtheria tetanus toxoid Measles (rubeola) immunization
Time of Discharge
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Following uncomplicated vaginal delivery, hospitalization is seldom warranted for more than 48 hours Woman should receive instructions concerning anticipated normal physiological changes of the puerperium, including lochia patterns, weight loss from diuresis, and milk letdown She also should receive instructions concerning fever, excessive vaginal bleeding, or leg pain, swelling, or tenderness. Shortness of breath or chest pain warrants immediate concern rd th 3 to 4 day: CS
Contraception If a woman is not breast feeding, menses usually return within 6 to 8 weeks Ovulation may resume in 3 weeks A minority of women bleed small to moderate amounts intermittently, starting soon after delivery Ovulation occurs at a mean of 7 weeks, but ranges from 5 to 11 weeks, ovulation before 28 days has been described Conception is possible during the artificially defined 6week puerperium Women who become sexually active during the puerperium, and who do not desire to conceive should initiate contraception Identified ovulation as early as 36 to 42 days
Breast Feeding and Ovulation Women who breast feed ovulate much less frequently compared with those who do not, and there are great variations Lactating women may first menstruate as early as the second or as late as the 18th month after delivery Other findings in their study included the following: Resumption of ovulation was frequently marked by return of normal menstrual bleeding Breast-feeding episodes lasting 15 minutes seven times each day delayed resumption of ovulation Ovulation can occur without bleeding Bleeding can be anovulatory The risk of pregnancy in breast-feeding women was approximately 4 percent per year
Coitus There are no evidence-based rules concerning resumption of coitus after delivery It seems best to use common sense. After 2 weeks, coitus may be resumed based on desire and comfort Intercourse too soon may be unpleasant, if not frankly painful, due to incomplete healing of the episiotomy or lacerations Vaginal epithelium is thin and very little lubrication follows sexual stimulation Due to the hypoestrogenic state following delivery and lasting until ovulation resumes Treatment: small amounts of topical estrogen cream can be applied daily for several weeks to vaginal and vulvar tissues Vaginal lubricants may be used with coitus. Breastfeeding prolonged period of hypoestrogenemia
Infant follow up Must receive appropriate follow-up care
Follow-up care Time of discharge: can resume most activities including bathing, driving and household function
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PHYSIOLOGY OB

2nd Year NOTES By Ge Cas Year 2011-2012

Reference: PHYSIOLOGIC OBSTETRICS by Williams

MATERNAL ANATOMY Anatomy of Female Pelvis

Reference: PHYSIOLOGIC OBSTETRICS by Williams

PELVIC Shape: CLASSIFIED BY CALDWELL-MALOY P type of pelvis N inclination, anterior tendency

Reference: PHYSIOLOGIC OBSTETRICS by Williams

Reference: PHYSIOLOGIC OBSTETRICS by Williams

Maternal, Pelvic Anatomy

EXTERNAL GENERATIVE ORGANS

Reference: PHYSIOLOGIC OBSTETRICS by Williams

Reference: PHYSIOLOGIC OBSTETRICS by Williams

Parts of the Uterus Cornua Fundus Cervix

Reference: PHYSIOLOGIC OBSTETRICS by Williams

Ovarian & Endometrial Cycle

2 CYCLES Ovarian Cycle Endometrial Cycle

NEUROENDOCRINOLOGY Anatomy Reproductive Hormones Feedback Mechanisms

Anterior Pituitary Secretions FSH LH

Reference: PHYSIOLOGIC OBSTETRICS by Williams

Reference: PHYSIOLOGIC OBSTETRICS by Williams

Reference: PHYSIOLOGIC OBSTETRICS by Williams

Reference: PHYSIOLOGIC OBSTETRICS by Williams

Implantation & Formation of Fetal membrane

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

ESTABLISHMENT OF MATERNAL BLOOD FLOW Occurs approximately 4 weeks post fertilization

PLACENTAL DIMENSIONS Diamter: 185 mm Thickness: 23 mm Volume: 497 mL Weight: 508 g

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

FETAL GROWTH & DEVELOPMENT PART 1

Reference: WILLIAMS OBSTETRICS 23rd Edition

INTERVILLOUS SPACE (Maternal Blood)

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

LACTATE Transported across the placenta by FACILITATED DIFFUSION as Lactic Acid

Reference: WILLIAMS OBSTETRICS 23rd Edition

Physiologic OB FETAL GROWTH & DEVELOPMENT II Fetal Physiology

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

Coronary Sinus 1 Umbilical Vein Portal Sinus Hepatic Vein SVC

Pulmonary Trunk Lungs

Reference: WILLIAMS OBSTETRICS 23rd Edition

Physiologic OB Maternal Physiology I

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition

Physiologic OB Maternal Physiology II

Reference: WILLIAMS OBSTETRICS 23rd Edition

OXYGEN DELIVERY Unchanged

Reference: WILLIAMS OBSTETRICS 23rd Edition

URINARY SYSTEM KIDNEY KIDNEY Size GFR Renal Plasma Flow

Reference: WILLIAMS OBSTETRICS 23rd Edition

Reference: WILLIAMS OBSTETRICS 23rd Edition