LECTURE #1: INTRODUCTION

 How do organisms work? Why does the human body look and function the way it does?
These are themes of INTEGRATIVE FUNCTION and EVOLUTION, with COMPARATIVE
BIOLOGY, EVOLUTIONARY HISTORY and ADAPTATION. SYSTEMS are sets of organs,
comprised of tissues, comprised of cells, which perform particular functions. They are
SKELETAL, RESPIRATORY, ENDOCRINE, DIGESTIVE, MUSCLUAR, NERVOUS,
CIRCULATORY, etc. HOMEOSTASIS is the regulation of stable internal body functions.
 DARWIN’S BIG IDEAS: (1) In all populations there is variation. (2) Some variation is
heritable. (3) Organisms compete for limited resources with DIFFERENTIAL
SURVIVORSHIP. These all contribute to the property of NATURAL SELECTION, whereby
organisms with heritable variations that help them to survive and reproduce will be
more likely to pass on those variations, which gradually leads to change.
 (1) We are all modified versions of each other, sharing many similarities. (2) More
closely related organisms tend to share the same novel features (demonstrated through
PHYLOGENY, a tree of TAXONOMIC RELATIONSHIPS). (3) Gradually, evolution
generates increasingly complex organisms made up of many parts that are beautifully
integrated.

LECTURE #2: EMBRYOLOGY

 EMBRYOLOGY is the study of developmental processes, helping to explain why and how
the body gets its shape. EVO-DEVO helps us to understand mechanisms by which
evolution generates new forms.
 The body is a set of folding tubes and sheets, each deriving from the three initial layers
of cells. The body’s parts fit and work together because of how they grow, through a
branching process with many interactions between units. All vertebrates share basic
CHORDATE PLAN and novelties are modifications of this basic plan. The earlier you
alter development, the bigger the phenotypic consequences.
 A ZYGOTE is a single cell, derive from two GAMETE CELLS, the SPERM and the EGG. The
human body with millions of cells has about 350 different kinds of cells, each with
membrane, cytoplasm and nucleus. All cells have four basic functions, multiplication,
movement, differentiation, and signaling.
 FERTILIZATION occurs 12 to 24 hours after OVULATION. The one-cell stage is when
two PRONUCLEI from the sperm and the egg fuse to form the zygote. The two-cell stage
is the first CLEAVAGE, about 30 hours after ovulation, and cleavage continues as the
cells become smaller and form into a ball. At the four-cell stage, all cells are identical
(the Armadillo makes four identical babies from this stage). Cleavage requires stored
energy from the egg. The MORULA has 12 to 32 cells, the BLASTULA has 128 around a
central cavity, and the BLASTOCYST has 700-800, where they have already begun to
differentiate (the number of cells determine the names). The inner cell mass is the
EMRYOBLAST, the future organism, and the outer cell mass is the TROPHOBLAST, the
supporting structure (which becomes the PLACENTA in mammals). After the blastocyst
implants into the uterine wall via the trophoblast, the embryoblast divides into the
EPIBLAST (nearest to the wall), the future embryo, and the HYPOBLAST, the yolk sac.
 GASTRULATION is the formation of the three GERM LAYERS or cell lineages common
to all animals through a process of MIGRATION (moving to different layers) and
DIFFERENTIATION (changing). In mammals the presence of the PRIMITIVE STREAK
will establish bilateral symmetry, determine the site of gastrulation, and initiates germ
layer formation. It grows from the CAUDAL (tail end) toward the middle in the
CEPHALIC (head) direction, when viewed from the top. During gastrulation, cells in the
midline of the epiblast go downwards and spread, as they migrate, they form two new
layers, the MESODERM and the ENDODERM. The epiblast layer is now called the
ECTODERM. In all chordates, the NOTOCORD is also formed from a stiffened rod of
mesoderm, the future core of the axial skeleton. The GUT TUBE is also created. ? The
germ layer derivatives for the ectoderm are the epidermis, nervous system, eyes, ears,
nose and most of the head, the endoderm is the digestive, respiratory, and most of the
endocrine, the mesoderm is skeletal tissue, muscle, circulatory, lymph and
reproductive.
 To create an organism, it needs (1) a nervous system, (2) segments, and (3) a gut and
body cavity. The nervous system forms through NEURALATION, when the central
plate of ectoderm folds into a NEURAL TUBE, adjacent to the notochord. Incomplete
fusion of the neural tube results in SPINA BIFIDA. Lateral border stem cells differentiate
and migrate into mesoderm, becoming NEURAL CREST.
 SEGMENTS are the key basis for complexity in the body plan. The HOMEOBOX or HOX
GENES are an array of 39 genes on 4 chromosomes, the order and pattern of expression
determining position and identity of SOMITES, paired masses of mesoderm distributed
along the left and right sides of the neutral tube and notochord that will be eventually
become dermis, skeletal muscle and vertebrae. The somites set up the central axis of the
body and play a key role in segmentation of other parts of the body, the number of
which differs among species (humans have 42). The mesoderm lateral to the somites
also differentiates, from inner to outer, being the PARAXIAL (vertebrate and muscles),
INTERMEDIATE (urogenital system), and the LATERAL PLATE (i.e. circulatory system,
limbs). The LATERAL PLATE mesoderm splits into the SOMATIC (body wall) layer on
the inner and the SPLANCHNIC (gut wall) layer on the outer, which fold around the
VENTRAL side of the embryo, meeting in the midline and forming a central body cavity
for organs called the COELOM, as well as a GUT TUBE. ? So far, this has produced a
central nervous system, a central axis, a segmented body and a gut.
 The processes by which development occurs permit and promote complexity and
evolution change. The body has many MODULES (i.e. cells) that develop via a
HIERARCHIAL process with many interactions (i.e. growth) between modules, causing
INTEGRATION, when the parts become combined into whole. Because the modules
share basic components they can be recombined in new ways to create variations that
selection can act on, and since development is hierarchical there is a lot of opportunity
for change. For example, heads and limbs are evolutional novelties, generated by using
old cells and organs in a new way, with many distance modules that become highly
integrated with lots of opportunities for variation.
 The neural tube also forms segments, the FOREBRAIN (PROSENCEPHALON), MID
BRAIN (MESENCEPHALON) and HINDRAIN (RHOMBENCEPHAON), above the SPINAL
CORD. Other parts differentiate into PRIMORDIAL SENSORY ORGANS (i.e. olfactory
 cells, eyes, etc.). Neural crest cells from the upper lateral border that migrate into the
mesoderm are PLURIPOTENT (or differentiate into many types), and form much of the
head, going from the back of the head towards the front, over the top and around the
sides. The cells that go around the sides become the rest of the face and neck (around
the mouth and gut tube), called BRANCHIALARCHES. Each branchial arch has
everything it needs (nerve, blood vessel, ectoderm, mesoderm and endoderm), number
I goes from inner ear to lower jaw, II goes from inner ear to HYOID (top of voice box),
and pouch between the two remains as EUSTACHIAN TUBE. The cells that go over the
top become the CRANIAL VAULT and the upper face (around eyes, nose). These cells
interact with cells from the future eyes (OCCULAR PLACODE) and olfactory bulbs
(OLFACTORY PLACODES) to form structures of upper face above the mouth (opening of
gut tube). All these structures grow toward the midline and fuse. Incorrect fusion
results in CLEFT PALATE.

LECTURE #3: ENDOCRINOLOGY

 The ENDOCRINE SYSTEM deals with HORMONES (not DUCTS, can be permanently
altered), chemical mediators that are released from ENDOCRINE TISSUE that travel to
TARGET TISSUES and generate a response. They regulate various human functions
including, metabolism, growth and development, tissue function, and mood. The
endocrine system’s effects are slow to initiate and prolonged in their response, from a
few hours up to weeks. The field of study dealing with the endocrine system and its
disorders is ENDOCRINOLOGY, in internal medicine. The endocrine broadcasts from a
fixed source to dispersed targets, deals with coordination of physiology, integration of
physiology and behavior, and regulation of gene expression. There are ENDOCRINE
HORMONES and PARACRINE HORMONES, which are localized cell-to-cell interactions.
 Hormones can be PEPTIDES (short amino acid chains, neurosecretion), or PROTEINS
(long amino acid chains, glandular secretion). Both are coded in genome, and utilize
membrane receptors. Because they are coded in the genome, peptide and protein
hormones evolve (i.e. varying binding affinity between human and pig insulin).
STEROIDS (i.e. adrenals, testes, ovaries) are small, lipid soluble, derived from dietary
precursors cholesterol, glandular secretion and utilize cytoplasmic receptors.
THYRONINES (i.e. thyroid) are small, lipid soluble, derived from dietary precursors,
glandular secretions, and cytoplasmic receptors. ? CATECHOLAMINES (i.e. brain) are
small, water-soluble, derived from dietary precursors, glandular neurosecretions, and
utilize membrane receptors. Although steroid molecules themselves don’t differ
between species, different species can use them differently. CORTICOSTERONE is the
rodent analog to human CORTISOL. CYTOPLASMIC RECEPTORS are intracellular,
directly regulate gene expressions, with steroids and thyronines, and are slower, than
MEMBRANE RECEPTORS, which regulate enzymes, with proteins, peptides and
catecholamines, and are faster. MEMBRANE RECEPTORS trigger actions that usually
involve cascading pathways of enzyme activation or inactivation, through which the
signal becomes amplified, altering the cell’s biochemical activity.
 Hormonal signals are often passed along AXES of interacting organs or tissues,
upstream organs sending signals to downstream targets, which in turn send signals to
 other targets, integrating diverse responses. There are multiple types of receptors of
hormones, and various hormones with various levels of affinity. Downstream hormones
usually FEEDBACK on the activity of upstream parts of the axis. If the feedback is
NEGATIVE or SUPPRESSIVE, the result is thermostat-like control, as in
THERMOREGULATION. If the feedback is POSITIVE or STIMULATORY, the result can be
runaway escalation. Negative feedback is generally more common, whereby the
circulating levels of the levels of hormones throughout the axis are maintained in a
target range unless some outside influence changes the thermostat setting. There are
few positive feedback systems because homeostasis is desired.
 The POSTERIOR PITUITARY comes down from the brain during embryology; the
ANTERIOR PITUITARY comes up from the mouth. The posterior pituitary is wired to
the HYPOTHALAMUS. Peptide hormones (i.e. oxytocin) are secreted into the blood
stream directly from neurons projecting from nuclei of the hypothalamus. The anterior
pituitary has no direct connection, but receives peptide signals secreted by the
hypothalamus into a tiny vascular bed know as the HYPOPHYSEAL or PITUITARY
PORTAL SYSTEM. The anterior pituitary secretes protein hormones that target a host of
downstream organs and tissues, many of which respond by secreting hormones of their
own (i.e. luteinizing, follicle-stimulating, thyroid-stimulating, adrenocorticopic, human
growth). The coupling of the hypothalamus and the pituitary allows information
flowing into the central nervous system to be transduced into hormonal information to
pass along to the rest of the body.
 In the HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL (HPA) AXIS, the cycle is
CORTICOTROPIN RELEASING HORMONE (CRH) to ADRENOCORTICOTROPIC
HORMONE (ACTH) to CORTISOL. ? CRH is a peptide hormone, from the hypothalamus,
targeted to the anterior pituitary, for the function of releasing ACTH. ACTH is a protein
hormone, from the anterior pituitary, targeted to the adrenal cortex, for the function of
releasing cortisol. CORTISOL is a steroid hormone, from the adrenal cortex, to multiple
targets, for the function of inhibiting energy storage, reproduction, immunity and
releasing stored energy.
 COTISOL doesn’t cause the emotional state, it carries information about the emotional
state to the body so that the body can react accordingly. It deals with the body’s
challenges by storing and regulating how energy is utilized, interactions with immune
system (inflammatory) and behavior, which can be acute or chronic. The HPA axis is
very damaging to the body and becomes hypo responsive (levels aren’t as high, is
slower, cortisol is deleterious). ? Cortisol levels fluctuate throughout the day, higher
with less fluctuation but always come back to the same level. Certain people in high
stress situations response to challenges when closely spaces different. Emotions cause
physiological response through endocrine chronic stress (i.e. bereaved, who have
higher levels of stress and anxiety, as well as higher levels of cortisol and ACTH). HPA
axis is differentially responsive to outside treatment depending on length of time (i.e.
bereaved, who have higher levels of cortisol and ACTH and lower lymphocyte mitosis
immediately following traumatic events). DEXAMENTHASONE is a synthetic
GLUCOCORTICOID that provides exogenous negative feedback to the hypothalamus.
The responsivity and regulation of hormonal axis must be evaluated (i.e. adult subject
 with history of abuse trauma had increased anticipatory cortisol response before
cognitive challenge).

LECTURE #4: PREGNANCY & BIRTH

 PREGNANCY is about women taking food and turning it into a baby. The body requires
fuel, which can be burned through CATABOLIC PROCESSES or used in building as in
ANABOLIC PROCESSES or stored for later, which also requires energy to maintain.
CORTISOL sends signals to tell the body what to do with fuel, and during pregnancy,
cortisol controls catabolic processes and retrieving fuel from storage and thus is a
METABOLIC HORMONE.
 The PLACENTA is the FETAL MATERAL INTERPHASE, constantly moving resources such
as glucose, amino acids and oxygen from mother to fetus, from a CATABOLIC STATE in
the mother to an ANABOLIC STATE in the fetus, and moving waste such as urea and
carbon dioxide from fetus to mother. Mothers allocate energy taken in early in
pregnancy to storage on body as fat to be mobilized later in pregnancy to be given to
fetus. Fetus has accelerated growth sustained by maternal fat reserves. With the
INCOME STRATEGY of breeding (i.e. rodents, smaller mammals), mothers must take in
food during pregnancy and lactation in order to sustain pregnancy and infant once
born. If food is interrupted or decreased, reproductive effort will fail. In the CAPITAL
STRATEGEY of breeding, the mother eats a lot of food in advance of reproductive effort,
storing energy on the body as fat, and turning fat into babies. Humans are an
intermediate, relying on both stored energy and energy taken in.
 IMPLANTATION occurs during a metabolic crisis that the conceptus is running out of
food, diffusion from the egg is inadequate and the uterine lining is about to be shed. The
OVARY releases the egg, in the FALLOPIAN TUBE the OVUM is FERTILIZED by
SPERMATOZUM, then CLEAVAGE occurs to MORULA and BLASTOCYST with
TROPHOBLAST, which will implant deeply in the ENDOMETRIUM of the UTERUS.
Hormones are preparing the ENDOMETRIUM to be able to support an implanted
conceptus should it arrive. Thickening of the endometrial lining is initially stimulated by
ESTROGEN from endocrine system in FOLLICULAR PHASE before the egg is released.
The FOLLICLE then releases ESTROGEN and PROGESTERONE during LUTEAL PHASE
for thickening and maintains the ENDOMETRIUM that will provide energy for the
conceptus. The abortion pill RU486 blocks PROGESTERONE receptors, causing the
endometrial lining to be unmaintained and therefore sheds, and also promotes
PROSTAGLANDINS that stimulates smooth muscle contractions and soften cervix that
makes it a hostile environment to conceptus. HUMAN CHORIONIC GONADOTROPIN
(HCG) makes the body aware that conception and implantation has occurs, therefore
used in pregnancy tests, also keeping the corpus luteum alive and pumping out
progesterone until the placenta can take over.
 Drugs consumed during pregnancy can cross the placenta and affect the embryo in its
development (i.e. Thalidomide for anti-nausea medication stunts arm and leg growth).
If RH- woman and an PH+ man conceive a child, which results in a RH- woman with an
RH+ fetus, cells from the RH+ fetus enter the mother’s bloodstream and the mother
becomes sensitive with antibodies to fight RH+ blood cells, such that in the next RH+
 pregnancy the maternal antibodies attack fetal RBCs, resulting in ERYTHROBLASTOSIS
FETALIS. High prevalence of RH+ may be maintained through evolution in gene pool
because could possibly protect against TOXOPLASMOSIS with heterozygotes, which also
causes spontaneous abortion as well as other issues. Risk of pregnancy failure
decreases as pregnancy continues, early development is sensitive to toxins and also has
the essential steps of development. IN VITRO is complex in attempting to recreate
maternal environment.
 MARSUPIALS (mammals) do not have a placenta, so no pathway between mother and
child after conceptus runs out of food, so born early in embryonic development with
arms to climb to mother’s nipple where it will continue to develop while being
sustained with milk. There are placental and marsupial analogues, with the exception of
hoofed animals because of the intense selective pressure on hands that grip.
 PLACENTAS are the most morphological variable organs among mammalian taxa (i.e.
discs in primates and rodents, bands of tissue in carnivores, round patches in sheep,
diffusely covering the uterine wall in horses, pigs and cetaceans). The UMBILICAL CORD
delivers well-oxygenated blood to embryo with UMBILICAL VEIN and return embryonic
blood to placenta with UMBILICAL ARTERIES. CHORIONIC VILLI contain embryonic
blood vessels that the maternal blood bathes directly, and the blood in the intervillous
space is exchanged 2 to 3 times per minute. PLACENTA is part of the endocrine system
and generates own hormones to communicate and receptors to receive signals for both
mother and fetus. In mammals, the EPITHELIOCHORIAL placenta is the least invasive. It
adheres to the epithelial lining of the uterine wall without penetrating and having no
contact with underlying material vasculature. ENDOTHELIOCHORIAL is the next most
invasive, as the chorion penetrates the endometrial surface and is in contact with the
endothelium of maternal vessels but is not immediately adjunct to maternal blood. The
HEMOCHORIAL is the most invasive, when the chorion penetrates the endometrial
epithelium and the deeper endometrial stoma to arrive in contact with maternal
vessels, penetrates the vessel walls, and placental tissue is in direct contact with
maternal blood. Within hemochorial, INTERSITIAL IMPLANATION is deeper, but even
deeper in humans. TROPHOBLASTS invade and remodel maternal vasculature, in
primates but especially in humans. Human fetuses require more PLACENTAL SURFACE
AREA, and are thus more invasive and require more surface area, suggesting that
relative to other primates fetal nutrient requirements are higher in human. Human
fetuses also have more GLUCOSE FLUX, requiring more energy and transferring more
energy. The problem with this system being so deep is there is no forced blood flow in
pool and no pipes, thus there is no COUNTER CURRENT EFFICIENCY. So to counter this
problem, one can raise MATERNAL BLOOD GLUCOSE LEVELS and UTERINE
PERFUSION PRESSURE. This then leads GESTATIONAL DIABETES, GESTATIONAL
HYPERTENSION and ECLAMPSIA. POSTPARTUM HEMORRAGE is leading cause of
maternal mortality worldwide, another possible side affect of deep implantations with
disruption of musculature. These risks are undertaken for the BRAIN, which is
metabolically expensive.
 PARTURITION is triggered by another metabolic crisis, the fetus needs more energy
than the mother can provide across the placenta when the glucose transport costs
become too high. The fetus will begin to draw on its own fat supply to sustain brain,
 with the baby’s own HPA axis. Positive feedback system initiates with CRH, ACTH and
cortisol, which also stimulates production of SURFACTANT in lungs for breathing. Other
hormones include RELAXIN, which soften the ligaments of the pelvis, and OXYTOCIN,
which synchronizes smooth muscle contraction.

LECTURE #5: LACTATION

 LACATION is the defining characteristic of mammals. Little is know about lactation but
research comes from dairy science, cancer research and breast-feeding vs. formula
feeding. MAMMARY TISSUE begins to develop before sexual differentiation, and is
further promoted by female hormones in puberty. The ability to secrete fluids from
abdomen developed 250-300 millions of years ago as sweat glands, which may have
transferred hydration or immunofactors to porous eggs. MILK is the most variable fluid
that mammals produce. Lactation is about duration until weaning, frequency of nursing
bouts, size of litter and volume and composition of milk synthesis. Milk is composed of
milk fat globules with nutrients, essential vitamins (i.e. vitamin A), minerals, hormones
(i.e. cortisol), immunofactors (secretory immunoglobulin) and water. The composition
of milk depends on environment (i.e. high water content in desert, high fat as fuel in the
Artic for thermoregulation), diet, ontogeny or developmental priorities (i.e. protein for
growth, fat for blubber, sugar for slow growth as in brain growth for learning), and
phylogeny or evolutionary relationships with related species (i.e. humans and other
primates). Milk can also change in composition, from high in sugar for development as a
fetus to high in fat and proteins for energy (i.e. Kangaroos, which can also make both
kinds at the same time). Humans have a relatively slow developmental trajectory,
weaning our infants at younger ages than apes thus transfer more fat in a shorter
period of time in percentage energy from fat, and small proportion of our energy from
protein. Human attributes take a long time to develop. The bigger the species, the
slower it grows, the more dilute the milk is.
 Until puberty, the mammary FAT PAD grows normally, then ESTROGEN and
PROGESTERONE stimulate the branching growth of the DUCT and TEB. During
pregnancy, PROLACTIN, PROGESTERONE and PLACENTAL LACTEGEN promote further
growth of ALVEOLAR at implantation, to develop during 39 weeks until ALVEOLI are
mature, which are condensed into LOBULES. Milk is secreted by LUMINAL CELLS when
MYOEPITHELIAL CELLS contract, stimulated by OXYTOCIN. The secretory pathways
through which materials enter the milk are exocytosis (i.e. proteins and sugars), lipids,
apical transport (i.e. Na, K, Cl, sugars, H2O), transcytosis (i.e. immunoglobulins) and
paracellular. The PLACENTRA produces a lot of progesterone, so once the placenta
leaves, milk synthesis is stimulated. The stages of lactation are LACTOGENESIS 1,
SECRETORY ACTIVATION and INVOLUTION. LACTOGENESSIS 1 produces COLOSTRUM
or the initial milk produced with very little energetic content for nutrition. It contains
sugars and immunofactors, with high concentrations of the protective protein
LACTOFERRIN and IMMUNOGLOBULINS sIgA, because when baby is born, the digestive
tract is sterile so milk is to feed and promote establish of beneficial gut bacteria,
allowing HUMORAL IMMUNITY in the early post-partum period which is important in
protection of mucosal surfaces from intestinal tract. SECRETORY ACTIVATION occurs 1-
 3 days after birth with copious milk production, when volume, fat and protein increases
and becomes comprehensive for diet. INVOLUTION is the regression of mammary tissue
to a non-secreting state with the disappearance of much of the epithelial tissue, and a
complex interaction between physiology and behavior. The more frequently and
completely the mammary gland is evacuated, lactose synthesis is stimulated, and water
is pulled into mammary glad, increasing the volume of milk; as WEANING occurs, and
nursing becomes less frequent, milk production is down regulated. During FEEDING, the
amount of protein and carbs stay stable, but fat increases.
 POST-NATAL CHALLENGES include behavioral activity and temperament. For infants
during early development, the more calories that are received from milk, the more
behaviorally active you are and the better at coping with new situations, and also are
more confident, playful, exploratory, active and curious. Milk must shape the brain,
because behavior is mediated through the brain. CORTISOL in milk reflects peripheral
bloodstream circulation in mother, stimulates protein synthesis in mammary glands.
Infants have glucocorticoid receptors in the stomach, which decreases during weaning,
thus must be there to bind ingested cortisol. In rats, higher density of glucocorticoid
receptors in hippocampus helps in negative feedback of HPA axis, thus helps in dealing
with stressful situation, as well as monkeys with playful behavior in stressful situations,
but only with males. However, research did not integrate cortisol with available milk
energy, though cortisol regulates digestion, energy use and metabolic processes. What
are the effects that are hormonally driven as opposed to nutritionally driven? Another
is immunological challenges. Milk also affects the INTESTINAL MICROBIOME or
COMMENSAL BACTERIA in intestine, which fights pathogens and helps to absorb
minerals. Microbial communities established in infancy, such as the BIFIDOBACTERIUM
INFANTIS, which helps infants digest HUMAN MILK OLIGOSACCHARIDES. Humans
produce more oligosaccharides, although substantial individual variation in
oligosaccharide profiles within species remains unexplained. Commensal bacteria are
present and probably translocated in milk but through an unknown pathway. Microbes
that prevent ROTOVIRUS are present in milk. Breast milk is personalized from mother
to infant based on diet, pathogens and antibodies, hormonal state, and bacteria. Its
composition is personalized with various amounts of energy, minerals, hormones,
vitamins, immunofactors and water. Breast milk is effective at promoting health.

LECTURE #6: MUSCULOSKELETAL DEVELOPMENT

 The SKELETON provides (1) stiffness, or resistance to deformation, by opposing

gravity, permitting muscles to generate movement via set of levers and protecting soft-
tissue organs (i.e. brain with cranial vault, thorax with ribs). STIFFNESS is a measure of
how much deformation a given force produces on a linearly elastic material, which is
force over deformation or slope (high slope means high stiffness, low slope means
compliancy) on a linear graph where area is work or energy done to extend structure
absorption, how hard it is to break, or TOUGHNESS. Bones must have intermediate
stiffness to absorb energy without breaking (like glass). A skeleton must also have (2)
strength, or resistance to FRACTURE, and must be able to withstand weight or load.
Bone has evolved to feature material properties to be able to withstand normal
 properties in a lifetime of use. A skeleton must also be able to (3) store calcium, which is
important ion for cell signaling and other cell processes. 99% of the body’s calcium is
stored in bone. The PARATHYROID GLANDS sense plasma calcium levels in blood and
can stimulate calcium reabsorption from blood when insufficient amount, and
absorption of calcium from blood when excessive. VITAMIN D increases absorption of
calcium from gut. Calcium is important in mother’s milk for growth of baby’s skeleton.
Skeleton must also (4) make blood cells through haematopoesis of stem cells in bone
marrow, which is a store of stem cells for various cells (i.e. RBCs, WBCs, platelets). A
skeleton also permits muscles to (5) generate movement at JOINTS through flexion,
extension and rotation. Joint motion is where FLEXIBILITY occurs, also based on shape
of the joint and articulation of bone. Bone is a strong, stiff, dynamic tissue that is
modifiable for growth and as such, can change in size and shape, which has been
evolutionarily selected.
 Macroscopically, there are two types of bone: COMPACT CORTICAL BONE, in the walls
of the shaft of the bone, and TRABECULAR CANCELLOUS BONE at the head of the bone,
which is sponge-like with spaces to decrease weight and increase ability to support
cartilage such that it isn’t damaged and overloaded as it acts as a shock absorber.
Allows expanded surface area for high amount of calcium and range of motion, as well
as transmission of force. Bone is COMPOSITE MATERIAL, or a two-phase substance
with multiple mechanical properties, which is made up of TYPE 1 COLLAGEN (organic)
and CALCIUM PHOSPHATE (mineral), with water for hydrating collagen and a few other
proteins. Collagen provides reinforcement of stiff mineral to increase toughness by
absorbing more energy before facture (i.e. reinforced concrete). Collagen is the most
obiquitious material in mammals. Collagen FIBRILS provide mineralization sites for
crystallization of HYDROXYAPATITE (calcium phosphate material) to embed in mineral
matrix and are bundled into rope-like FIBERS, which increase toughness. Fibers are
arranged in perpendicular cross sections, to reduce areas of weakness in a certain
direction or plane, so bone has both stiffness and strength in multiple directions. BONE
LAMELLAE is oriented in various ways: CIRCUMFERENTIAL (layers around surface of
bone), TRABECULAR (layers in small struts), and OSTEONAL (tube-like layers around a
vascular channel), thus it has uniform properties in various directions and is well
vascularized or supplied by blood vessels.
 Because bone is a mineralized rigid tissue, changes in shape and repair of damaged
tissue can only occur by means of APPOSITIONAL MODELING (surface bone mineral
deposition or resorption). SECONDARY OSTEONS (HARVERSIAN SYSTEM) within
PRIMARY OSTEONS are the major way bone can replace old damaged tissues or
MICROCRACKS before they can propagate through many years of accumulated use with
new undamaged tissue, along with vascular support (if unfixed, cracks could grow and
become catastrophic, i.e. fatigue damage). Thus, as one ages, bone is increasing filled
with osteons.
 Other CONNECTIVE TISSUES associated with skeleton are: CARTILAGE, which overlays
bone, LIGAMENTS, which is collagen from one bone to another bone, TENDONS that is
collagen from bones to muscle. Muscle fibers form from differentiation of MYOBLASTS
that grow via growth factors to MYOCYTES, through migration and adhesion, that fuse to
create MYOTUBES, which though further fusion, form contractile MULTINUCLEATED
 MUSCLE FIBERS, which help to grow bigger and change shape. Muscles develop as
skeleton is growing, growing attachments directly or through tendons.
 The skeleton is dynamic with several major types of cells that respond to physical and
biochemical stimuli. Bone is formed by OSTEOBLASTS (produce cartilage and mineral)
on outside, OSTEOCYTES are interior cells that are matured osteoblasts inside tissue
sense damage and signal repair, OSTEOCLASTS perform repair by resorption.
CHONDROBLASTS and CHONDROCYTES form cartilage, CHONDROCLASTS and
OSTEOCLASTS perform resorption by secreting digestive enzymes to locally produce
acidic environment. RESORPTIVE CELLS remove old, damaged materials. Ligaments and
tendons are formed by FIBROBLASTS. OSTEOBLASTS synthesize bone in a two-step
process by (1) laying down a collagen matrix of OSTEOIDS and then (2) mineralizing it
by producing locally a SUPERSATURATED SOLUTION into collagen matrix where
calcification CRYSTALLITES precipitate and reinforce until the material is 2/3 minerals,
1/3 collagen. The two pathways of bone growth both come from undifferentiated
MESENCHYME, which also forms myoblasts. INTRAMEMBRANOUS BONE FORMATION
is direct transformation, forms PERIOSTEAL MEMBRANE, which forms OSTEOBLASTS,
which produces COLLAGEN MATRIX (osteoid) and then undergoes
BIOMINERALIZATION (i.e. cranial vault). INTRAMEMBRANOUS BONES form around
organs and spaces (i.e. brain, eye). Bone is added in active growth SUTURES which
allows for growth around organs, and bones grow and change shape through DRIFT,
which is bone resorption on one surface with a faster rate of bone deposition on
opposite surface to increase thickness. ENDOCHONDRAL OSSIFICATION starts with
PERICHONDRIAL MEMBRANE, which forms CHONDROCYTES, which produces a
CARTILAGE MODEL and undergoes REPLACEMNT of cartilage as calcified with bone
into osteoblasts. Masses of MESENCHYME become filled with CARTILAGE MATRIX,
which becomes the CARTILAGE MODELS of bone elements. CARTILAGE is a flexible
tissue that allows for both internal and surface growth, so that early embryonic skeletal
growth can be more rapid, that can then develop into bone later. After formation of
CHONDROCYTES for cartilage model grows bigger, nutrient vessels stimulate elevation
of blood oxygen levels, which triggers transformation of cartilage into bone through
ENDOCHONDRAL OSSIFICATION. Chondroblasts calcify in local matrix and as
osteoclasts perform resorption, osteoblast formation is triggered by VASCULAR
INVASION.
 Grow in width by appositional remodeling. Increase in length or height occurs via the
GROWTH PLATE, which remains CARTILAGENOUS until adulthood, so that cartilage
cells divide going down and mature, and become transformed to form spongy bone.
This displaces EPIPHYSIS away from the shaft. When growth plates FUSE, growing is
finished. As bone is growing with age, functional integration of the body is permitted.
Skeleton also allows adaptability, or ability to change during life in response to stimuli
with ADAPTIVE BONE REMODELING, force that stimulates added bone mass, especially
in youth. When active, thicker walled bone, when inactive resorption of bone.
OSTEOPOROSIS occurs when bone resorption is faster than bone deposition, which
most severely affects trabecular bone with increased space and less bone density. 21%
of postmenopausal US women suffer from this affliction, because (1) women stop
growing earlier than men and thus attain a lower peak bone mass, as well as (2) effects
 of lower estrogen levels, which inhibits bone resorption, following menopause. Most
severely affects trabecular bone as TRABECULAR ELEMENTS are lost over time. Major
factors affecting bone health include exercise (which lowers rate of resorption), calcium
(the threshold effect), smoking, genetics and pregnancy.

LECTURE #7: NERVOUS SYSTEM I

 The NERVOUS SYSTEM is a network of billions of NERVE CELLS linked together in a

highly organized fashion to form the rapid control center of the body. In the brain there
are 100 billion NEURONS and 100 trillion SYNAPSES. These enable the computations
that the nervous system and the brain do. The functions include integration for
information coming into the body from the periphery or internally by sensation,
generation of movement, regulation of many body functions, and consciousness. The
two major divisions are (1) the CENTRAL NERVOUS SYSTEM (CNS), which is composed
the BRAIN and SPINAL CORD and centrally located, and (2) the PERIPHERAL NERVOUS
SYSTEM (PNS), which is outside of the brain and spinal cord (i.e. skin) and carries
information to and from the CNS.
 The PNS is (i) SOMATIC, which is voluntary (i.e. skeletal muscle), afferent and efferent,
with 12 pairs of CRANIAL NERVES and 31 pairs of SPINAL NERVES, and (ii)
AUTONOMIC, which is involuntary (i.e. smooth or cardiac muscles, glands, GI neurons,
breathing, heart rate), visceral and efferent, consisting of a SYMPATHETIC
COMPONENT (“fight or flight”) (i.e. accelerator, speeding up heart rate) in the thoraco-
lumbar region and a PARASYMPATHETIC COMPONENT (“rest/digest”) (i.e. brake,
slowing down heart rate) in the cranio-sacral region.
 AFFERENT or sensory PNS nerve cells conduct impulses from receptors to the CNS,
informing the CNS of the state of the interior and exterior body. SENSORY NERVE
FIBERS can be SOMATIC, from the skin, skeletal muscles or joints; or VISCERAL from
organs within the ventral body cavity. EFFERENT or motor PNS nerve cells conduct
impulses from CNS to effectors (muscles). MOTOR NERVE FIBERS can be both
autonomic and somatic.
 NERVE CELLS have a cell body with DENDRITES and a nucleus, that narrows down into
the AXON HILLOCK or INITIAL SEGMENT (where electrical signals originate) and then
the AXON, which can branch thousands of times into COLLATERALS, eventually ending
in the AXON TERMINALS. Electrical signals travel from left to right, from cell body to
axon terminals. NEURONS come in various types and shapes, but MYELINATED
NEURONS conduct action potentials most rapidly, without traveling along the
membrane. SCHWANN CELLS form myelin or fatty, insulating coating, wrapped around
peripheral neuronal axons; OLIGODENDROCYTES form myelin on central (in the brain)
neuronal axons. The DENDRITIC SPINES are projections from dendrites, which change
shape and strength of connection with other nerve cells in response to learning. AXON
POTENTIALS travel from the axon terminal of the PRESYNAPTIC NERVE CELL, to the
SYNAPSE, to the DENRITIC SPINE of the POSTSYNAPTIC NEURON, thereby
communicating with downstream neurons.
 Of the CRANIAL NERVES, NERVE II or the OPTIC NERVE is an sensory afferent nerve,
NERVE III or the OCCULAR MOTOR NERVE is a motor efferent nerve, NERVE V is the
 TRIGEMINAL NERVE and is mixed nerve with both afferent and efferent axons (i.e.
chewing and tasting), and NERVE X is the VEGAS NERVE and is also a mixed nerve with
both. The pairs of spinal nerves correspond to the segmented spine. Skeletal muscles
have efferent motor axons; Skin has afferent sensory axon terminals buried in skin that
sense various things (i.e. touch) and goes back to spinal cord along spinal nerve with a
cell body outside the spinal cord. The SPINAL NERVE contains both afferent and efferent
axons. In a cross section of the spinal cord, the GRAY MATTER of the spinal cord is
efferent motor nerve cell bodies and the WHITE MATTER (myelinated sheaths) of the
spinal cord is nerve cell axons. Impulses travel from the receptor (i.e. skin), through the
DORSAL ROOT GANGLION on the DORSAL ROOT of the sensory neuron, up the spinal
cord towards the brain or to the INTERNEURON or the association neuron in the
INTEGRATING CENTER (all parts of interneurons are in the CNS) and out through the
VENTRAL ROOT of the motor neuron to the effector for reflexes. Between the two roots,
the space in between separates sensory and motor axons in most vertebrates, which
may have to do with segregation for central processing or preserving one. A ganglion is
a collection of cell bodies in the PNS.
 The PARASYMPATHETIC nerves come out with some of the cranial nerves (i.e. III and X)
and sacral region, and connects to a second nerve cell before stimulation of smooth
muscle, cardiac muscle or glands (i.e. heart, intestine). For parasympathetic nerves, the
first preganglionic cell is long with acetylcholine and the second postganglionic is short
with acetylcholine. The SYMPATHETIC nerves come out through the thoracic and
lumbar region of the spinal cord. For sympathetic nerves, the first preganglionic cell is
short with a line of ganglions on either side of the spinal cord and with ache choline and
the second postganglionic is long with norepinephrine.
 Only the autonomic nervous system has GANGLIONS with preganglionic and
postganglionic fibers and only the ANS has neurotransmitters.

LECTURE #8: NERVOUS SYSTEM II

 The evolution of the SPINAL NERVE PATTERN starts with lampreys, which does not
have a single combined SPINAL NERVE (separate ventral and dorsal roots).
 The intracellular RESTING MEMBRANE POTENTIAL is recorded at -70mV in reference to
the extracellular fluid. Only a very thin shell of charge difference is needed to establish a
membrane potential. The interior is negatively charged compared to the exterior due to
differences in ion concentrations. There are selective ion channels in the membrane,
including voltage-gated Na+ and K+ channels. Sodium channels can be open, inactive
(with INACTIVATION REGION when channel is open but nothing can pass) and closed,
while potassium can only be open or closed. Ion channels that utilize diffusion down a
concentration gradient also need pumps to maintain relative concentration gradients.
Ion concentrations and diffusivity through the nerve cell membrane can be used to
predict the resting membrane potential using the NERNST AND GOLDMAN EQUATIONS.
In a typical nerve cell, NA+ is at 150 mmol/L and CL- is at 110 mmol/L in the
extracellular; K+ is at 150 mmol/L in the intracellular.
 Some MEMBRANE CHANNELS change conformation in response to voltage change in
the surrounding membrane, which are called VOLTAGE-GATED; others change
 conformation in response to binding by an ion or other compound, called LIGAND-
GATED. They are selective in which ions pass through the pore in the center and amino
acid charges around the pore can attract specific ions. They may have deactivated,
inactivated, and activated states. In the SODIUM-POTASSION PUMP model, 3 NA+ ions
move out and 2 K+ ions move in, using the splitting of ATP (into ADP and Pi) to power
the protein conformational change.
 GRADED POTENTIALS can be EXCITATORY when an action potential is more likely to
occur, as with DEPOLARIZATION after a stimulus of positive ions, or INHIBITORY when
an action potential is less likely to occur, as with HYPERPOLARIZATION after injecting of
negative ions or removal of positive ions. Potentials can be graphed on a voltage versus
time graph. The size of a graded potential is proportional to the size and strength of the
STIMULUS and amount of depolarization. Graded potentials are small, local changes in
membrane potential and decay as they move over a distance, and are usually about 0.5
mV. They are also additive with multiple injects of ions, called SUMMATION.
 ACTION POTENTIALS are rapid, high-altitude, large magnitude changes in membrane
potential, usually 100 mV in 3 ms. They do not summate and are usually identical to
each other, thus all-or-none sequence of changes in membrane potential, as well as an
example of positive feedback. ? -55 mV is considered a THRESHOLD VALUE, which is a
15mV change needed to open sodium channels and once open, there is a rapid influx of
sodium ions to depolarize the cell (without a way to stop it). After a certain period of
time, the sodium channels are inactivating, while the potassium channels open (slower
to open because of amino acid structure and stay open for longer) and allow potassium
to flow out, thus hyperpolarizing past resting potential. Sub threshold will never
stimulate but once done they go to the same height and doesn’t matter how far over
threshold it can go. Then pumps work to restore the original balance. They result from a
sequence of changes in ion permeability due to the operation of voltage-gated Na+ and
K+ channels. The rapid or initial opening of the voltage-gated Na+ channels allows
rapid entry of Na+, and the slower or secondary opening of voltage-gated K+ channels
allows K+ to exit. All action potentials with THRESHOLD STIMULI, or stimuli strong
enough to cause depolarization, all reach the same membrane potential.
 As ions flow from one region to another, it will stimulate and depolarization the next
region further down. The propagation of the action potential from the dendrites to the
axon-terminal end is typically one-way because the ABSOLUTE REFRACTORY PERIOD
follows along in the wake of the moving action potential and the action potential starts
at the neuron’s INITIAL SEGMENT. The region behind the action potential, the sodium
channels are inactivated and impossible to stimulate. RELATIVE REFARACTORY
PERIOD enables you to generate another action potential with a strong enough
stimulus, relative to the absolute refractory period. SALTATORY CONDUCTION is when
the action potentials jump from one NODE OF RANVIER to the next as they propagate
along a myelinated axon (no channels under sheath).
 The SYNAPSE is the point of communication between two neurons. CHMEICAL
SYNAPES have a SYNAPTIC CLEFT, which separates the two cells, and the
neurotransmitter, from synaptic vesicles, diffuses across the cleft to bind to receptors,
often ligand-gated ion channels, on the postsynaptic neuron membrane, which has a
POSTSYNAPTIC DENSITY, which is a region of many channels. The presynaptic axon
 terminal has calcium voltage gated channels which open and allow calcium to flow in
and interact with proteins that causes vesicles containing transmit to fuse with
membrane, released into the cleft, travelling across, and bind to ligand-gated receptors
on post-synaptic cell. These are one-directional, after the enzymatic breakdown of
neurotransmitters to be reused prevents restimulation. An action potential in a
presynaptic neuron results in a graded potential in the postsynaptic neuron, thus
multiple action potentials are needed from the presynaptic cell to bring the
postsynaptic cell to threshold in order to fire an action potential. The influence the
transmitter has on the postsynaptic cell is dependent on identity and structure of
postsynaptic channel.
 At an EXCITITAORY POSTSYNAPTIC POTENTIAL (EPSP), for which GLUTAMATE is the
main neurotransmitter, non-selective ion channels open and mostly Na+ ions move
down the gradient, stimulating depolarization. At an INHIBITORY POSTYNAPTIC
POTENIAL (IPSP), for which GABA and GLYCINE are the main neurotransmitters, Cl-
and K+ channels open, creating hyperpolarization. For neural integration, the
membrane potential of a real neuron typically undergoes many EPSPs and IPSPs, since
it constantly receives excitatory and inhibitory input from the many axon terminals that
reach it, from as many as 200,000 synapses each. Ion flows from all inputs SUMMATE or
average at the initial segment. TEMPORAL SUMMATION is firing the same EPSP multiple
times and summing them in time. SPACIAL SUMMATION is summing presynaptic action
potentials that differ in special arrangement. An action potential in the postsynaptic
neuron occurs if the membrane potential at the voltage-gated initial segment reaches
threshold.

LECTURE #9: MUSCLES I

 SPINAL NERVES connect to the middle of muscle fibers, often multiple going to the same
muscle from the gray matter or cell bodies of spinal cord through voluntary somatic
motor neuron axons, stimulating every muscle fibers its attached to to contract.
 MUSCLE TISSUE represents about 40% of body weight. MOTOR NERVE CELLS make
contact with muscle cells at the NEUROMUSCULAR JUNCTION. FASCICLES are bundles
of smaller subunit MUSCLE FIBERS in muscle cells, which also have nuclei and
mitochondria, confined in PERIMYSIUM (collagen connective tissue) sheaths. The fibers
are muscle cells, usually 10-60 micrometers in diameter, 2 to 10 (and up to 30) cm long,
which can be overlapped. The MYOFIBRILS (80% of muscle volume) are about 1
micrometer in diameter and made up of contractile MYOFILAMENTS with functional
units of striated, skeletal SACROMERE segments stacked end-to-end, which are 2.5
micrometers in length. ACTIN is 5 nm in diameter and MYOSIN is 12 nm in diameter
and TITIN is 26,926 amino acids and 5 micrometers in diameter.
 When a muscle contracts, sarcomeres shorten and the Z-DISCS or Z-LINES (which
delimit sarcomeres with proteins) come towards center or the M-LINE, which connect
the middle of the thick filaments with proteins at the middle of the sarcomere. High
resolution ELECTRON MICROGRAPH reveals that each MYOFIBRIL is made up of
parallel filaments. These are MYOSIN or THICK FILAMENTS, and ACTIN or THIN
FILAMENTS, both also proteins. Actin is a polymer of globular actin molecules in a
 double helix structure, which make up thin filaments. 200 to 300 myosin molecules are
stacked in a circular pattern with tail, neck and head. Each myosin itself is a helical
structure with two heads. Thick filaments are between thin filaments, which are
attached to the Z-lines. These two filaments are linked at intervals called CROSS
BRIDGES, which project up and down from the thick filaments at the MYOSIN HEADS or
ratchets. Thick filaments also have TITIN molecules, which extend into myosin and
attach to Z-line (and possibly to M-line) in spring-like fashion, which is an important.
TITIN is a very big protein responsible for the elastic properties of muscle, also for the
patterning and development of muscle. During contraction the myosin heads bind to
actin and the cross bridges flex to slide actin. Each head exerts a force of 1 pN and
moves actin about 10 nm. Small efforts but many. Thick filaments have a 3D structure
with myosin molecules arrayed around the circumference of the thick filament. The
thick filament is actually a polymer of myosin molecules, each of which has a flexible
cross bridge that binds both actin and ATP. Muscle myosin is a dimer of two identical
motor heads, with catalytic cores. One head binds actin, the other binds ATP to power
movement.
 The SLIDING FILAMENT MECHANISM OF MUCLE CONTRACTION happens with
conformational changes in the structure of the heads of myosin. The CROSS-BRIDGE
CYCLE generates force in a muscle (1) when the myosin binding site on the actin
becomes available so the energized cross-bridge binds (2) the full hydrolysis and
departure of Pi and then ADP causes the flex of the bound cross-bridge with energy
from split causing sliding (3) the binding of a new ATP to the myosin head at the cross
bridge releases the myosin from the actin (i.e. at death muscles are stiff because myosin
is still attached to actin without production of ATP, or rigor mortis) and (4) partial
hydrolysis of the bound ATP into ADP and Pi energizes and resets the cross bridge. One
ATP molecule is split by each cross bridge in each cycle, which takes only a few
milliseconds. During a muscle contraction, thousands of cross bridges in each sarcomere
go through this cycle, although the cross bridges are out of sync so there are always
many cross bridges attached at any one time to maintain force and make contraction
smooth.
 In the absence of calcium or in a relaxed skeletal muscle, TROPOMYOSIN blocks the
myosin-binding site on the actin, preventing cross bridge attachment. Contraction is
allowed in an activated muscle when calcium ions bind to the TROPNIN COMPLEX with
3 binding sites or sub complexes (for actin, tropomyosin, and calcium ions) that then
changes conformation and removes tropomysoin from the actin cross-bridge binding
site. Calcium is crucial for regulation, which is controlled by the nerve.
 MOTOR NERVE CELLS make contact with muscle cells at the NEUROMUSCULAR
JUNCTION. An action potential in the motor nerve axon causes all the innervated muscle
fibers to contract.

LECTURE #10: MUSCLES II

 A single MOTOR UNIT consists of a motor neuron, motor nerve axon and all of the muscle
fibers it innervates. The NEUROMUSCULAR JUNCTION is the point of synaptic contact
between voluntary somatic nerve cells and muscle, with the axon terminal of a motor
neuron and the muscle fiber it controls. Action potentials flow down the axon, which is
 often myelinated, to the axon terminal with voltage-gated calcium channels and vesicles
of acetylcholine. At the junction, which is approximately in the middle, the muscle fiber
membrane is a series of curves, which increase its surface area, which contain a series of
ligand-gated sodium channels. Activation of presynaptic calcium channels cause vesicles
to fuse with presynaptic membrane, exit through exocytosis and for the
neurotransmitters to bind to sodium channels, causing sodium to come flowing in.
Action potentials in the motor neuron cause ACETYLCHOLINE to be released into the
neuromuscular junction. Neuromuscular junctions are always EXCITATORY in skeletal
muscle (unlike neural, which could be both, no relaxation) and always excite the muscle
to threshold (no sub threshold stimulus). The END PLATE POTENTIAL is which is about
60 to 70 mV of depolarization at the MOTOR END PLATE in the junction. The outside of
the muscle cells is the muscle membrane SACROLEMMA, within which is many packed
myofibrils. The depolarization at the center spread to the left and right from the motor
end plate, travelling down the sarcolemma, which has T-TUBULUES or transverse
tubules, involutions which are consistent with the membrane. The end plate potential at
threshold depolarizes as a result of a single action potential throughout the T-tubules
into its interior. The SACROPLASMIC RETICULUM is full of calcium ions, connected to
the T-tubules via DHP RECEPTORS which transmits the depolarization by sensing
voltage change and causes calcium release (through change in its conformation) from
the sarcoplasmic reticulum via specialized voltage gated calcium channels called
RYANODINE RECEPTORS. These calcium ions are release into the cytosolic interior of
the muscle cell, around the myofibrils, which binds to the troponin, removes
tropomyosin and contracts the sarcomeres. The sarcoplasmic reticulum has CALCIUM
PUMPS that require ATP to pump cytosolic calcium released back into the cell, which
would otherwise constantly stimulate muscles and cross bridge cycling if not returned
to sarcoplasmic reticulum, eventually removing all calcium so that muscle may relax.
This process goes against a large concentration gradient, requiring many pumps and
much ATP.
 The eyes of fast-moving predatory fishes (i.e. tuna) have modified muscle tissue next to
several of the eye muscles that acts as a heating system under neutral control to warm
the retina, which improves vision (FLICKER FUSION FREQUENCY) when fish dive to
cold water. The HEATER ORGAN is a modified eye muscle that has lost all muscle fibers
(no sarcomeres or myofibrils), are mitochondria and sacks of sarcoplasmic reticulum,
The cycling of calcium ion alone via calcium pump generates heat through cleavage,
breaking bonds of ATP (made by mitochondria), which can be maintained near the eye
with a countercurrent exchanger. They are innervated by the OCCULAR MOTOR NERVE.
This is the cellular basis of FUTILE CYCLING to produce heat.
 WHOLE MUSCLE MECHANICS features a detached muscle attached to an apparatus. One
is a muscle attached to a weight, stimulated by a motor nerve that then shortens and,
with appropriate weight, the weight moves up. Downward force of mass and gravity
will be balanced by upwards force of muscle. ISOTONIC is the same tension or force
(with same mass). Muscle at the same length stimulated to contract generates force.
This is an ISOMETRIC or same length condition. Force/tension versus time graphs in
isometric conditions, produces a curve after a 2 ms delay between stimulation and
conduction. Muscles varies in peak contraction time, a function of how fast calcium can
 be released, and relaxation time is a measure of how fast and how many calcium pumps
can remove free calcium to stop cross-bridge cycling. Fast contraction depends on fast
relaxation. Multiple stimulations from nerve create summations that are a result of
more calcium release and increments where pumps cannot keep up. Fast stimulations
result in greater force, eventually resulting in a maximum force or MAXIMUM
TETANTIC TENSION at TETANUS at 70 to 100 ppsec, while a single stimulus produces
TWITCH (3 to 5 times less than tetanus). To increase force, in addition to frequency, one
may also recruit more motor units by stimulating more neurons to stimulate more
muscles. If one varies the length in an isometric apparatus, one can measure the force at
various lengths. In a force/tension versus length plot is 100% is a muscle in a resting,
relaxed state. At a higher percentage when muscle is stretched, the maximum tetanic
force decreases, because fewer cross bridges can attach when actin and myosin is
pulled apart. At a lower percentage when muscle is squeezed, the maximum tetanic
force also decreases, because actin and myosin structure is deformed. This is an ACTIVE
TENSION CURVE in sarcomeres. PASSIVE TENSION CURVE of muscle (i.e. rubber band)
due to elastic properties of muscle, that increases exponentially from 0 at 100%. The
TOTAL TENSION is a summation of passive and active tension. The latent period
between excitation and development of tension in a skeletal muscle includes the time
needed to release calcium from sarcoplasmic reticulum, move tropomyosin and cycle
the cross bridges.

LECTURE #11: MUSCLES III

 Under ISOTONIC conditions, with a fixed muscle stimulated with tetanic (high
frequency, 100 pulses per sec) to contact with various weights, one can measure
distance that the weight moves, which can be plotted on a distance versus time graph.
The maximum slope is the maximum VELOCITY or speed the muscle can contract. On a
graph of shortening velocity of the muscle versus weight. At a weight that is too heavy
for the muscle, the shortening velocity will be zero (ISOMETIC condition), and velocity
will increase as weight decreases in a hyperbola for a FORCE VELOCITY CURVE (i.e.
maximizing force of foot while running with low frequency).
 The types of muscle are SKELETAL, CARDIAC and SMOOTH. Skeletal muscle is
STRIATED. SMOOTH MUSCLE is spindle shaped cells stacked into sheath, no troponin
and no striation (although actin and myosin). SMOOTH MUSCLE is innervated by
efferent, autonomic nerves (sympathetic and parasympathetic), which have
VARICOSITIES with neurotransmitters in SYNAPTIC VESICLES. Neurotransmitters
cover the surface of smooth muscle cells, no neuromuscular junction. No Smooth
muscle, similar to skeletal muscle fibers., is made up of THICK FILAMENTS (which are
myosin-based) and THIN FILAMENTS (which are actin-based), which interact to cause
smooth muscle contraction. No Z-DICS but DENSE BODIES. Smooth muscle can also
RELAX with different neurotransmitters, as well as contract to a “blob”. CARDIC
MUSCLE cells are connected electrically at junctions called INTERCALATED DISCS with
GAP JUNCTIONS (trans membrane proteins that can depolarize next downstream cell).
Cardiac muscle has distinct striations, so more like skeletal muscle than smooth muscle.
STRIATED SKELETAL MUSCLES have four types of design, STRAP, FUSIFORM,
UNIPENNATE, and BIPENNATE. Strap-like muscles tend to be compartmentalized to
 work in parts, pull origin and insertion together. Fusiform collapse down to tendon.
Unipennate has tendons on each with fibers connecting across in an angular fashion,
with different like. FLEXORS and EXTENSORS work in antagonistic sets to refine
movement and to allow force generation in two opposite directions. They are often co-
activated to stabilize joints.
 MOTOR RECUITMENT or action of vertebrate muscles is based on neural recruitment
(activation) of MOTOR UNITS, which are MOTORNEURONS plus the population of
muscle fibers (10 to 100) that the motor nerve innervates. Small muscles or muscles
with many motor units allow for finely graded increases in muscle, which allows for
greater control and increased precision of manipulation and grip. Individual motor units
consist of a similar muscle fiber type. Motor neuron axons come from the motor neuron
cell body within the spinal cord and go to muscle fibers.
 Factors determining MUSCLE TENSION include (1) tension developed by each fiber in
action potential frequency (frequency-tension relation), fiber length (length-tension
relation), fiber diameter (generates more force) and fatigue, (2) number of active fibers
in number of fibers per motor unit and number of active motor units, and (3) muscle
fiber type (not all muscle fiber types are the same, but all the same in a motor unit).
MUSCLE FIBER TYPES include SLOW OXIDATIVE FIBER (RED-SO) (smaller), FAST
OXIDATIVE GLYCOLYTIC FIBER (FOG) and FAST GLYCOLYTIC FIBER (FG) (larger),
stained for activity of ATP on myosin head. Red fibers are slow contracting, well
supplied with oxygen, aerobic, resistance to fatigue, a lot of capillaries and
mitochondria (for slow running). White fibers are fast contracting, anaerobic and
generate more force. FOG are intermediate. FISH MUSCLE has been a model system for
studying muscle recruitment patterns due to the spatial segregation of muscle fiber
types, unlike human muscle, which is mixed (i.e. RED SO for slow, steady swimming and
WHITE FG for burst, fast swimming). When moving slow, red motor units will be
recruiting first, then moving faster using FOG, then fast using mostly white. The SIZE
PRINCIPLE of motor unit recruitment within a muscle is that the recruitment threshold
increases from low to intermediate to high in SO to FOG to FG from small, slow to large,
fast. Different muscles have different proportions of different types. Different fiber
types between muscles also affect their recruitment pattern (i.e. SO for posture vs.
FOG/FG running and jumping). All three types of muscle fibers are represented in a
typical skeletal muscle and a schematic cross section through a muscle can demonstrate
this. Under tetanic stimulation, these three types make different contributions to the
development of muscle tension, FG contributes most.
 SIR CHARLES SCOTT SHERRINGTON contributed the concept of a REFLEX ARC, coined
the term SYNAPSE, was the first to isolate and analyze a single motor unit and
categorized the types of sensory receptors in the body. These SENSORY RECEPTORS are
INTEROCEPTORS (i.e. taste receptors), EXTEROCEPTORS (i.e. detect sound, light, touch)
and PROPRIOCEPTORS, which are any reports that are sensitive to movement, pressure,
or stretching within the body. Proprioceptors that occur in muscles, tendons and
ligaments are important for the coordination of muscular activity and the maintenance
of balance and posture (i.e. Golgi tendon organs and muscle spindles).
 An example of reflexes is the neural components of the PAIN-WITHDRAWL REFLEX.
Pain sensory afferents detect pain in the foot (i.e. via pressure, temperature), causes
 depolarization and send action potentials via afferent neurons to the CNS, where IPSPs
inhibit extensor muscle. Interneurons in the cord activate muscles to lift the leg and also
muscles on the opposite side of the body to support body weight, as well as signals to
brain. Muscles move the foot away from the painful stimulus. Acting on local reflex
circuits by relaying impulses to the brain, MUSCLE SPINDLES (length, inside muscle,
long and parallel to muscle) and GOLGI TENDON ORGANS (force, around tendon)
provide information about muscle length and force in order to regulate the speed and
intensity of muscle contraction, as well special recognition. Stretched muscle spindles
generate a burst of action potentials as the muscle is lengthened. Shortened muscle
spindles produce fewer action potentials. Frequency as relative. The Golgi tendon organ
sense muscle force as stretch in collagen fibers stretches the nerve cell membrane,
cause deploraztion by mechanical stretch-induced opening of ion channels and thus
causes an action potential that travels back to the CNS. Compared to when a muscle is
contracting, passive stretching of the relaxed muscle produces less stretch of the tendon
and fewer action potentials from the Golgi tendon organ.
 ELECTROMYOGRAPHY is one way of studying muscle function in vivo, by needle or
surface electrodes (less accurate because have to read through skin which produces
average instead of specific numbers), which record membrane depolarization. Electrical
activity is multiphasic patterned and spike height (represent depolarization in mV) is
relative to the baseline, information about electrical activity and generation of force, not
specific to contraction or expanding. EMGs can assess the relative degree of activity and
in some cases, with statistical analysis of activity patterns, can be used to roughly assess
the amount of force generated by muscles. The muscle VASTUS LATERALLS, a knee
extensor in dogs, is acts like a strut (active stiffening element) during a walk and hardly
changes in length although much muscle electrical activity (isometric), which activated
when the foot is on the ground. During a gallop, the muscle functions both like a brake
and a motor. Muscles length when foot goes down and then shorten, while electrically
activity (so isotonic).

LECTURE #12: ENERGY METABOLISM

 How is ENERGY METABOLISM regulated? CELLULAR METABOLISM serves the

functions of (1) Growth and Reproduction, (2) Feeding, (3) Activities of Daily Living, (4)
Exercise and Sport. Things to Know: ANABOLIC vs. CATABOLIC metabolism, ANEROBIC
vs. AEROBIC metabolism, and understanding the distinction in cellular metabolism;
where and how ATP is produced anaerobically and aerobically within cells; how is
metabolism regulated with respect to cellular activity and other body functions that
require energy; how and why metabolism is linked to respiratory and cardiovascular
function; how metabolic rate or rate of energy use is measured and the meaning of
steady state metabolism; how is fuel stored within the body for energy use; how does
the endocrine system regulate glucose and energy metabolism more generally; and
what does a respiratory quotient tell you about the source of fuel for cellular
metabolism.
 The two basic ENERGY STATES are CATABOLISM which is breaking down food fuels to
produce ATP energy associated with post-absorptive metabolism, and ANABOLISM
 which is building up energy stores and synthesizing new tissue growth associated with
absorptive metabolism (after a meal with nutrients). Heat production as a by-product of
catabolic reactions help maintains temperature homeostasis. In the ABSORPTIVE
STATE (after a meal with absorption of nutrients in intestines) amino acids are made
into proteins (building body structures), glycerol and fatty acids (storage) into
triglyceride (adipose tissue), glucose into glycogen, and glucose goes to CO2/H2O/ATP
energy in most cells, while glucose goes to glycogen in the liver and muscle cells or (in
high carb/glucose diet) shift to fat in adipose tissue. In the POSTABSORPTIVE STATE
(fasting state, without food in digestive state) proteins are broken down into amino
acids, triglycerides into glycerol and fatty acids, glycogen to glucose, and fatty
acids/ketones go to CO2/H2O/energy in most cells while pyruvate lactate, glycerol and
amino acids go to glucose in the liver.
 Cellular metabolism or RESPIRIATION occurs in two cell compartments: GLYCOLYSIS
occurs in the CYTOSOL (glucose  pyruvate) and OXIDATIVE PHOSPHORYLATION and
the KREBS CYCLE (where fats and proteins enter) occur in the MITOCHONDRIA
(pyruvate KC  coenzymes (NADH) KC  electron/protein flow OP  energy for
synthesizing ATP OP). SEE DRAWING CARBOHYDRATE (SUGAR AND STARCH)
METABOLISM makes 38 ATP from GLYCOGEN or glucose stored as carbohydrates in
cells (1 C6H12O6 + 6O2  6CO2 + 6H2O + ATP). 2 ATP are made via ANAEROBIC
GLYCOLYSIS (without oxygen) and 36 ATP are made via AEROBIC METABOLISM (with
oxygen) or OXIDATION, 2 from the KREBS CYCLE or TRICARBOXYLIC ACID CYCLE
(TCA) and 34 from OXIDATIVE PHOSPHORYLATION. 277 kcal from 686 kcal results in
40% efficiency (all the about the same with starting materials), with remainder given
off as heat, higher body temperature makes higher metabolic rate. ATP is the universal
energy currency of most cellular processes, in the form of high-energy phosphate Pi.
With sufficient O2, aerobic respiration supplies ATP energy via the Krebs cycle and
oxidative phosphorylation. METABOLIC ACIDOSIS is which LACTATE (an acid)
dissociates to increase [H+] inside cells and blood, thus the decreasing O2 supply slows
aerobic respiration.
 GLYCOLSIS (ANEROBIC): A muscle cell or liver cell stores energy in the form of
glycogen, converted to glucose (6 carbons), converted to 2 pyruvates (3 carbons),
during which 2 NADH (energy rich compound) is produced from NAD+ and 2 ATP
formed (from ADP and Pi). Without oxygen, pyruvate build up is converted to
lactate/lactic acid (METABOLIC ACIDOSIS) and NAD is converted back to NADH, which
builds up and causes a pH depression within cell and body overall. With oxygen,
pyruvate diffuses into mitochondria with an outer membrane and an inner membrane
(with infoldings, called cristae). Cells that are active had lots of mitochondria because
they have to produce a lot of ATP. KREBS CYCLE: Pyruvate enters matrix, converted to 3
carbon compound Acetyl-CoA, 2 ATP produced, lots of NADH produced, CO2 produced
(before O2 is consumed). OXIDATE PHOSPHORLATION: Inner mitochondria membrane
have CYTOCHROME PROTEIN ENZYMES in reversible states, NADH diffuses and drives
ELECTRON/PROTON FLOW in CYTOCHROME CHAIN, coupled with movement of
protons out into matrix, which builds up proton gradient, ATP SYNTHASE CHANNEL
forms ATP from ADP and Pi from diffusion of H+ down concentration gradient. 2 NADH
+ 2 e- + ½ O2  NAD+ + H2O. 3 ATP for each NADH oxidized. If oxygen is available and
 diffuses to mitochondria, then Kreb’s Cycle and Oxidative Phosphorylation can occur.
Proteins/amino acids come in and can be converted to pyruvate or acetyl CoA, fatty
acids come in and are converted to Acetyl CoA or glycerol as an intermediate in
glycolysis.
 Glucose metabolism is regulated through a system of GLUCOSE HOMEOSTASIS in the
ENDOCRINE SYSTEM and involving CORTISOL (CNS needs energy rich glucose). An
increase in PLASMA GLUCOSE causes an increase in INSULIN secretion in PANCREATIC
ISLET BETA CELLS, which increases PLASMA INSULIN, which then causes an uptake of
glucose in adipocytes and muscle, and net glucose uptake via transmembrane protein
receptors (cessation of glucose output) in the liver, which results in the restoration of
plasma glucose to normal level. A decrease in plasma glucose levels causes an increase in
GLUCAGON secretion in the pancreatic islet alpha cells, which increases the PLASMA
GLUCAGON, which increases GLYCOGENOLYSIS (the breakdown of glycogen to glucose),
GLUCONEOGENESIS (generation of glucose), and KETONE SYNTHESIS in the liver,
which results in an increase in plasma glucose and PLASMA KETONES. DIABETES is the
failure of glucose homeostasis (failure of beta cells to produce adequate insulin) or the
resistance by cells to respond to insulin (through cell-membrane receptors and
secondary messaging). Glucose levels can increase or decrease the number of
transmembrane protein transporters. TYPE 1 diabetes is insulin deficiency or JUVENILE
DIABETES. TYPE 2 Diabetes is insulin resistance or ADULT-ONSET DIABETES by eating
(studied on rats). Diabetes and obesity are major public health problems. In 2012 in the
USA more than 66% of US adult population is over-weight or obese with a BMI of
greater than or equal to 30 kg/m2, and 1/3 of school age children are considered obese,
doubling since the 1970s.
 (1) Anaerobic metabolism provides energy rapidly, but causes METABOLIC ACIDOSIS
(excessive lactate production and decrease of pH) plus fatigue. Thus it is suited for the
onset and short bursts of activity (i.e. sprinting), versus reliance on aerobic respiration
for sustained activity without net production of lactate of time, no decrease in pH. (2)
Although 1 mole of lipids yields considerably more energy, fat and carbohydrate
oxidation has similar metabolic efficiencies (fat molecules have many more carbon
bonds than glucose) (3) Glycogen is readily converted into glucose, and can increase
aerobic metabolism. Because glycogen require more water, its energy storage/unit
weight is much less than for fat. Thus lipids are the principal energy store in the body
(double the energy storage of carbohydrates or proteins, more effective as from
biological and evolutionary habits from hunting). (4) Enzymes exist to convert glucose
into fat but not the reverse. Excessive carbs become fat. (5) All tissues, except the CNS,
can metabolize lipids and protein for energy. The CNS requires glucose and aerobic ATP
supply (thus HYPOXIA or insufficient oxygen is most critical to CNS function, i.e. as
during the metabolic crisis of birth). GLUCOSE SPARING is the use of fats or proteins for
fuel (i.e. by liver and muscle cells) to spare glucose for the brain and nervous system.
GLUCONEOGENSIS is the resynthesize of glucose from pyruvate or protein amino acids,
but not from fats. The liver converts ACETYL-COA to KETONES, which can be converted
to glucose and metabolized for energy. (6) Metabolic energy needs are linked to oxygen
delivery and carbon dioxide elimination. (7) There is a match between metabolic capacity
and cardiopulmonary design (linked to activity or traits, or a species behavioral
 strategy). (8) One can measure energy metabolism by measuring oxygen consumption
(and/or carbon dioxide production) under STEADY STATE CONDITIONS. VO2 is the
VOLUME RATE of O2 consumed (for an adult human at rest, it is about 250 ml O2/min).
The RESPIRATORY QUOTIENT is VCO2 (production)/ VO2 (consumption).
 One can measure the energetics of locomotion by walking and running using an OPEN
FLOW RESPIROMETRY, a measurement of steady state VO2, which is expired gas
sampled and pumped to O2 analyzer. One can measure the effect of incline, or
comparative animal energetics (domestic vs. wild, body size). Training and species
differences reflect reliance on anaerobic vs. aerobic ATP supply. Metabolic rate is also
linked to size, temperature and activity level. The respiratory quotient provides
information about the fuel the body is oxidizing for energy. Carbohydrate metabolism
RQ is 1, fat metabolism RQ is .7, and protein metabolism RQ is .9. The STEADY STATE
METABOLISM is steady VO2 at a certain exercise level. It is the point at which aerobic
ATP supply matches constant energy demand (which takes 1-2 minutes in humans).
 What are the sources and time-course of anaerobic and aerobic pathways of cellular
metabolism that supply ATP for activity? If exercise is immediate, how is ATP supplied
to enable an immediate onset of activity?

LECTURE #13: ENERGETICS 2 ACTIVITY METABOLISM

 What are the sources of ATP supply (anaerobic vs. aerobic) in relation to exercise
intensity and behavior? How does this vary across species and thermoregulatory
physiology? How does metabolic rate vary with activity level and the time course of
energy supply? VO2 max or MAXIMAL OXYGEN CONSUMPTION defines AEROBIC
CAPACITY. How do genetics and training affect aerobic capacity? Evolution of
endurance running in human ancestors (hominids).
 When O2 is available lactate can be reconverted to pyruvate and oxidized.
 Locomotion is the dominant way that the human body uses energy, with ATP for the
contraction of muscle. Exercise is an immediate demand for energy, which is the start of
exercise, then a relatively constant rate of exercise and then an end (on a graph of
energy demand against time). The first source of energy is the pools of ATP already
available, next is phosphocreatine (PCr), which is a high-energy store in muscle, which
splits, supplies ADP and resynthesizes ATP for 30 seconds. Then glycolysis begins and
peaks within the first minute anaerobic ATP synthesis, thus keeping ATP at a constant
level with the energy demand by supplementation, until aerobic supply via oxidative
phosphorylation with increase of respiratory rate and increase in aerobic metabolism
which is then able to be maintained by aerobic metabolism which is STEADY STATE.
Creatine does not enhance aerobic performance. There is a delay (of 1 to 2 minutes)
before ATP can be supplied fully via aerobic metabolism, thus there is a time-course of
ATP supply following onset of exercise. ATP splits to power muscle contraction and ATP
resynthesizes. During contraction, ATP splits into ADP plus Pi for energy. ADP and PCr
are regenerated back to ATP and Cr (resynthesize by PCr). ATP and lactate are
generated through glycolysis or anaerobic respiration (always some amount of lactate
formed with glycolysis). ATP, CO2 and H2O are generated aerobic respiration in
mitochondria. ADP from muscle contraction diffuses into mitochondria and ATP
 synthesized diffuses back out to myofilaments. In an expanded timetable the periods of,
(1) OXYGEN DEFICINCENY reflects depletion of ATP and PCr and the initial anaerobic
supply of ATP prior to steady state aerobic ATP supply (2) OXYGEN DEBT reflects post-
exercise elevated VO2 to payback depleted ATP and PCR pools, and metabolize
anaerobic end products (i.e. lactic acid), thus reestablishing resting physiological state
(slow decline), approximately equal out. SUSTAINABLE EXERCISE is within aerobic
capacity, when oxygen consumption VO2 is less than VO2 max (sustainable because no
lactate is produced). SPRINT EXERCISE is non-sustainable due to metabolic acidosis and
is large anaerobic ATP supply that require prolonged elevated recovery metabolism
(lactate produced by ongoing glycolysis for O2 deficit about VO2 max, exceeding VO2
max with demand for energy). SUSTAINED PERFORMANCE is limited by VO2 max
(although other cardiopulmonary factors involved in O2 transport also contribute)
though in actuality no one can exercise exactly at VO2 max) and depletion of glycogen
stores, or shifting shores of energy substrates (from glucose stores to fat with a more
limiting rate, and unsustainable as quickly or as high demand), such as “hitting the wall”
which muscle glycogen is depleted and reliance on lipid oxidation fails to meet ATP
demands despite adequate O2 supply to mitochondria. SPRINT PERFORMANCE is
limited by the anaerobic threshold, when lactate produced causes metabolic acidosis,
which cells and body when released into bloodstream.
 The biological extremes of maximal aerobic energy expenditure between animals, such
as python which has a maximum energy expenditure occurs when it’s digesting its meal
(with nutrient uptake), rather than moving, unlike humans and most animals.
 V is volume rate or CC/min.
 Species differ in exercise performance (i.e. antelope with high aerobic capacity,
sustained activity and short recovery, and cheetahs with low aerobic capacity, brief
bursts of activity and prolonged recovery, VO2 max of dog is higher than VO2 max of
cat). ENDOTHERMS have an elevated body temperature and metabolic rate, because heat
from the metabolism keeps the body warm, thus enabling endurance exercise in birds
and mammals (oxygen debt is small). Higher temperatures result in higher rates of
reactions with enzymes, representing evolution selection for broader ranges of
temperature and active for longer periods of time, high-energy strategy. ECTOTHERMS
have variable body temperature and limited aerobic performance, because heat from
external sources like the sun warms the body, thus having non-sustained, burst exercise
in fish, amphibians and reptiles (oxygen debt is large). Approach is economical with
food intake less often, low-energy strategy (can increase capacity with increase in
muscle mass). Energetics of LOCOMOTION are the effects of speed, gait and body size,
with studies based on measurements of steady state VO2 (inhaled/expired, CO2
production, etc.). One can measure steady state VO2 while a person walks and runs on a
treadmill, measuring the effect of speed on rate of energy use, as on a graph of VO2 vs.
speed (m/s) on which oxygen consumption increases linearly with speed, until leveling
off of oxygen consumption at VO2 max. If the line is extrapolated downwards, there is a
start up cost slightly above the individual’s resting MR; if the line is extrapolated
upwards (above VO2) max, represents increase in lactate by glycolysis in unsustainable
activity. AEROBIC SCOPE is VO2 max/ resting MR (metabolic rate), factorial increase of
metabolism above resting level. Aerobic capacity is defined by VO2 max. The cost of
 transport is energy/time//distance/time, which is energy/distance in mlO2/m or J/m.,
which is how much energy is used to move a given distance and can be used to compare
efficiency. The slope of the graph is the net transport cost. Aerobic scope varies across
species with humans and average endotherms at 10. Economical transport comes with
walking, rather than running (the cost of running is higher), when measures the effect
of gait on human energy cost. Waking cost of transport is non-linear and variable, at
greatest distance per energy use at lowest point, walking too fast can make it less
economical than running. Studies have shown that VO2 capacity is also hereditable
(possibly HR and glycolytic capacity of kinds of enzymes as well) and varies with
training. Genetic ancestry determines 50-85% of endurance aerobic performance and
training enables 6-30% increase in individual performance. Mass-specific VO2 max
(VO2/weight, mlO2/kg/min) demonstrates that gender difference reflects relatively
greater body fat in females than men (and have lower metabolic rate, but not oxygen
capacity) and thus must be controlled when comparing sports training of various
individuals, by gender or weight. Endurance training increases aerobic capacity. There
is also an effect of size (and age) on energy cost of running, thus smaller animals (or
children compared to adults) have higher mass specific metabolic rates as a function of
activity intensity (higher mass-specific slopes). Endurance running is a derived
capability of the genus Homo originating about 2 million years ago, including adaption
of skeleton, springy tendons, economical bipedal walking.

LECTURE #14: ENERGY BALANCE AND STARVATION

 Outline: Principles of energy allocation; mechanisms of energy allocation; starvation

physiology; obesity.
 METABOLISM consists of catabolism (burned), anabolism (building) and storage.
Energy is the process by which energy comes into the body and is utilized. POSITIVE
ENERGY BALANCE is more energy in than out, which produces weight gain (i.e.
obesity). NEGATIVE ENERGY BALANCE is more energy out than in, which results in
weight loss (i.e. starvation). NEUTRAL ENERGY BALANCE is when energy going in and
out is well matched, and body weight stays approximately the same (i.e. homeostasis,
cellular processes working properly). There are negative consequences of being too far
out of neutral balance. The LIMITING RESOURCES of energy (food to eat) and time (to
acquire it), are devoted to (in order) maintenance/staying alive (i.e. immune function,
basic cellular processes), growth and development (i.e. skeletal, lean tissue; how much
growth during lifetime differs between species), reproduction (i.e. babies; natural
selection cares about reproduction of genes for oneself and/or relatives), and storage
(i.e. somatic insurance; buffer for nutritional or environmental problems). In the event
of collapse of available resources, storage is diverted to the other three, sometimes
preferentially (i.e. preferential allocation of body fat on mothers to their own survival in
order to reproduce in the future, rather than to milk for one child, but terminally ill
mice allocate energy to reproduction). Carrying body fat storage has costs. Storage, or
somatic insurance, determined by how much can be carried when measured in percent
body fat, varies among species, of which humans are the highest, and among human
populations, such as UK vs. Gambia. Capital or income breeders are determined by
 capacity to store fat on body. It also varies between genders, as females have a higher
percent of fat and absolute fat mass, but weigh less than males. Some storage of fat has
to do with androgens, but also because females have to be pregnancy and lactate which
are both mobilization of fats and sugars, so substantial storage in case of shorter
nutritional insult.
 The principles of energy allocation are NEWTON’S PRINCIPLE of trade-offs, when you
can only spend a calorie once, and DARWIN’S PRINCIPLE of hierarchy when first things
come first (i.e. staying alive during pregnancy rather than milk production; adaptions
have been shaped to maximize survival or reproduction, which differ at various life
stages). Tsimane are hunter gathers in Bolivia. C-REATIVE PROTEIN (CRP) is a non-
specific immune system protein, elevated by a broad range of immune system
challenges, a biomarker of inflammation usually in response to some kind of pathogen.
Elevated CRP in TSIMANE children is associated with slower growth in the succeeding
three months, particularly in younger children (i.e. lower growth in height and fat
mass), and particularly in those with already low fat reserves, demonstrating
preference for survival or body maintenance for growth. Growth stunting for fatter
children in moderately malnourished areas grow less and preserve somatic stores to
maximize survival. Food becomes oxidizable metabolic fuels (glycogen and fatty acids),
which go to (1) essential processes (cell maintenance, circulation, and neural activity;
maintain of body and function of the brain first), (2) reducible processes
(thermoregulation, locomotion, and growth can be reduced within certain parameters,
but not turned off) and expendable processes (reproduction, and fat storage).
 Pancreas maintains balance in energy storage. In the PANCREATIC ISLET there are
ALPHA CELLLS that produce GLUCAGON and BETA CELLS that produce INSULIN. An
increase in blood glucose stimulates the pancreas to secrete insulin which goes into
circulation and is taken up by the cells to be removed from blood stream, which is going
to be used for metabolic energy, fat synthesis and glucagon synthesis, resulting in a
decrease in blood glucose. Decrease in blood glucose stimulates pancreas to secrete
glucagon, which goes into circulation, causes breakdown of glycogen in the liver, which
releases glucose to blood. Tow systems are linked to maintain homeostasis of blood
sugar of body. The actions of insulin include: glucose uptake, glycogen synthesis,
protein anabolism, fat storage, release of free fatty acids for uptake by adipocytes,
glycogen synthesis and fatty acid synthesis. The actions of glucagon include:
glycogenolysis, gluconeogenesis, and ketone formation. Type 2 diabetes is when beta
cells not producing insulin so body cells cannot respond to elevated blood sugar. Before
insulin was available to buy, juvenile diabetes was a terminal illness and every child
died. Type 1 diabetes was once treated with personalized nutrition, controlling every bit
of food to minimize amount of blood sugar, small amounts of protein and fat and
miniscule sugar, while tracking urine and blood, functionally starving children to
prevent HYPERGLYCEMIC SHOCK. Type 1 is now a manageable disease. Glucose uptake
is not mediated through insulin are in the brain or in fetuses. Energy out is spent or
burned by basal metabolism, thermogenesis and physical activity. There are numerous
factors influencing metabolic rate (i.e. sleep, age, gender, length of fasting state, height,
weight, body surface area, growth, reproductive state, infection/disease, body
temperature, ingestion of food, muscular activity, emotional state, ambient
 temperature, hormonal circulation, etc.). Humans have lower BASAL METABOLIC RATE
than other primates. The basal metabolic rate also varies between various human
populations, decreasing from rhesus macaque, chimpanzee, to human, as you grow
bigger, basal metabolic rate decrease per unit mass. Percent of BMR varies across age,
and areas (highest to lowest, brain, muscles, organs to fat). Women can shift metabolic
rate depending on where they live. Women in The Gambia women have to be physically
activity during planting and harvest season also shift metabolic rate lower so that they
don’t take energy away from reproduction, British women do not have same limiting
energy so increase. Also varies between individuals, based on resources and energy
needs of time of pregnancy. The THYROID HORMONE AXIS increases metabolism and
important for growth and development, which releases THYROTROPIN-RELEASING
HORMONE (TRH) from the hypothalamus, and THYROID-STIMULATING HORMONE
(TSH) from the anterior pituitary gland, causes the release of THYROID HOMORES
(T3/T4) from the THYROID GLAND (negative feedback to hypothalamus and anterior
pituitary), which increases metabolism for growth and development. T3 and T4
THRYOXINE require a lot of salt and thus salt is vital to thyroid function (dysfunction is
GOITER, inflamed thyroid). T3 uncouples protein within mitochondria, critical for use
of energy in making energy available. THERMOREGULATION is how much energy you
have to burn to maintain body heat. YUKUTE PEOPLE have an increasing T4 as it
becomes colder, T4 to maintain body temperature which takes more energy to
maintain, thyroid maintains body temperature in response to environmental
temperature. NENETS have higher T4 than comparable Russians in coldest months
because they spend more time outdoors, higher BMR by up regulation of T4 production
from thyroid. PHYSICAL ACTIVITY requires energy. Metabolic chambers to measure
baseline energy of daily lives can help understand how oxygen usage to energy
turnover and mobile oxygen VO2 max measures how heart rate is related to oxygen
usage, only have to collect heart rate to infer how much energy is allocated behavioral
activity, useful for human behavioral ecologists, thus better understand how using
energy out. Heart rate depends on what they’re doing through out day. TEE is totally
energy expenditure, comparison between males and females between world
populations, can understanding variation among peoples to see how their allocating
energy. Also differences in body mass cyclically in Senegal, variation in rainfall and
harvesting crops, depending on energy out in from crops and energy out for harvesting,
results in annual fluctuation in body mass.
 Minnesota starvation research during WWII in America, intended to understand what
happens to the body during starvation and to help facilitate recovery after liberation of
prison camps to optimize return to health after period of starvation. Reduced subjects
body fat by 25% and used various methods in recovery period. Small glucose buffer
within liver, more protein and a lot of energy storage with fat. STARVATION
PHYSIOLOGY by strategy through mechanism: by reducing activity through behavior,
by reduce BMR through lower thyroid hormones (T3/T3), by reducing glucose
utilization through lower insulin, by restricting anabolism through lower GH/sex
steroids, by increasing fat utilization through increasing cortisol and by prioritize brain
metabolism by shifting to ketone bodies.

LECTURE #15: ENERGY BALANCE AND STARTVATION II, BRAIN I

 KETONE BODIES are small enough to cross the blood-brain barrier thus can travel to
the brain, come from broken down fatty acids to be utilized in absence of glucose (very
little glucose stored on body, rather an protein muscle and fat), critically important to
fuel brain in starvation conditions, increasing percentage as starvation period
continues, because there is no beta-oxidation, anaerobic glycolysis is insufficient but it
can utilize ketone bodies. Ketone bodies can go into the Krebs cycle as Acetyl Coenzyme
A when further broken down. The psychological effects of starvation include behavioral
reduction such as depression, reduced sexual interest, preoccupation with food, social
withdrawal, reduced concentration, but cognition intact (perception that cognitively
comprised but not manifested in testing).
 Fat, sugar and salt was rare commodity in ancestral environment (Africa) all critically
important for body processes (i.e. salt for thyroid, fat for storage). Mechanisms in brain
that trigger higher probability of gorging when encountering any of them, taste
delicious because were so critically important for survival in ancestral environment, but
still with us today regardless that our environment has ubiquitous amounts of each.
Obesity is a growing epidemic in developed world, health of people is more threatened
by obesity than malnutrition for first time in evolutionary history. Numerous health
problem that derive from surplus of consummation of unhealthy food in combination
with lack of physical activity. Increasing in time. High amount of obesity in adults, but
also obesity in teenager, which has long-term affects. More people spend less time being
physically activity, correlated between overweight people and time sedentary activities.
Current energy balance is unique in evolutionary history.
 Summary: Long-term energy balance has been a challenged during our evolutionary
past, and continues to be a challenge today for different reasons (challenge to get
energy in past, too much in present). Energy allocation involves trade-offs between
essential and more fungible categories. Fat storage provides an essential buffer for
meeting essential metabolic needs. Our physiology and our behavioral dispositions
have evolved to guard against negative energy balance and to exploit opportunities for
positive energy balance. We have no mechanisms to protect against excessive positive
energy balance.
 PHRENOLOGY, brain phenotypes with grooves in skull to determine personality, is
false. Improved experimental designs have gradually shown that many brain areas are
specialized for particular function, and the brain is part of the CNS (100 billion neurons
and 1x10^13 connections). Beyond neurons, GLIAL CELLS (supporting function of
brain) are at least as numerous as neurons. NEUROGLIAL CELLS of the CNS include
ASTROCYTES which regulate neurotransmitters at synapses and other aspects of
neuron’s environment (including energy), OLIGODENDROCYTES coat the CNS neuron in
MYELIN, EPENDYMAL CELLS secrete CSF, and MICROGLIA are immune cells
(macrophages).
 Brain helps to integrate information and coordinate movement. SEA SQUIRTS have tow
life stages, one where they move around and have a brain, the other when they are
sedentary and consume most of their own brain and absorb brain (no purpose for
energy allocation). Brains are expensive and will only invest in them if actually need
them. Most of BMR in humans allocated to big brains. The brain grow as neurons near
 the center of the neural tube proliferate and migrate outwards, RADIAL GLIA CELLS
contributing to this organizational development.
 FISH have a big brainstem (with mostly autonomic functions), a small forebrain (with
mostly olfaction and vision) and a big cerebellum (mostly motor control). The general
evolution trend is that the hindbrain is relatively smaller, the midbrain is relatively
smaller, and the forebrain is relatively larger (especially the neocortex or cerebrum).
Evolution is constantly occurring, not progressive. As on a graph of log of body mass
and brain mass, there is a linear correlation between the two meaning as animals get
bigger, brains get bigger. Deviations means brain relative to body is bigger or smaller,
humans are bigger. Major deviations means something must have happened in
evolutionary time. Primates as a group have bigger brains relative to body size than
expected for mammals, systematic increasing pressure during evolution to have bigger
brains relative to body size. Humans are biggest of group. Earliest human ancestors did
not show derived brain size. Expansion of hominid brain size dates back to less than 2
million years ago during split with chimpanzee, from where relative brain size
increases exponentially. Brains were not just getting bigger and becoming more
complex with increasing of folding (SULCI), which increases surface area and facilitates
greater network connections. Organization, number of neurons and number of
connections are important
 In NEUROANATOMY, there is the HORIZONTAL PLANE, the SAGITTAL PLANE, and the
CORONAL PLANE (most biological research).
 The BRAINSTEM has parts of MIDBRAIN and hindbrain, the PONS and the MEDULLA.
Its main functions are (1) to receive sensory information from cranial structures and
control muscles of the head and eye via 12 pairs of cranial nerves; (2) contains neurons
that transmit info from the spinal cord to other brain regions and down from the brain
to the spinal cord and cerebellum; (3) contains neurons that regulate arousal and sleep-
wake cycle via diffuse projections to many brain regions including the cerebral cortex;
(4) the MEDULLA is essential for control of blood pressure and respiration; (5) contains
nuclei (clusters of cells bodies), that control autonomic functions (i.e. breathing, HR, BP,
swallowing, coughing/sneezing etc.). Damage is usually fatal. The MIDBRAIN is involved
in controlling eye movements (SUPERIOR COLLICULI) and body movements, reward
and addiction (SUBSTANTIA NIGRA). PARKINSON’S DISEASE is associated with a steady
loss of dopamine producing cells in the substantial nigra. The HINDRAIN is composed of
the cerebellum and the medulla, the pons and the MEDULLA OBLONGATA. The
CEREBELLUM (little brain) has as many neurons as the rest of the brain (the amount of
neurons is not linked to absolute size of structure). Paleontologists only have access to
fossils and fossil crania only tell size of the brain, not neuronal density or neuronal
architecture, which is a challenge for understanding minor changes in brain complexity,
so closest ancestor to examine is chimpanzee, but many stages that we can’t know too
much about so difficult aspect of studying human evolution. The cerebellum monitors
sensory input from the body and coordinates with outgoing motor commands from
cerebrum and brainstem, controls gross motor function (i.e. posture/balance, muscle
tone, coordination; first thing impacted with high blood alcohol content), and damage
leads to loss of control on the contralateral side. The FOREBRAIN consists of the
thalamus, the hypothalamus, and the cerebral cortex. The thalamus and the
 hypothalamus (important for endocrine regulation and reproduction) both make up the
DIENCEPHALON or “twin brain,” which is a cluster of ancient regulatory regions atop
the brainstem, which also includes the outgrowths of optic stalks to the eyes. The
THALAMUS or “inner chamber” relays all sensory information (except smell) to the
cerebrum and is involved in awareness and learning. The HYPOTHALMUS controls the
release of hormones by the pituitary gland, the homeostasis of thirst, heart rate and
blood pressure, and interacts with the limbic system to help control emotions. The
EPITHALAMUS “on top of thalamus” controls circadian rhythms. Increasing degree of
how critical to survival brain region is, moving from brainstem upward, differences in
staying alive versus being optimally productive.

LECTURE #16: BRAIN II

 The CEREBRUM or “telencephalon” is the biggest part of the brain, much of which is the
cerebral cortex; the cerebrum accomplishes most of the complex cognitive functions,
especially thinking and awareness; it receives and processes sensory information,
controls complex cognitive processes (i.e. language, thinking, awareness, memory,
consciousness, etc.) and also controls non-localized, associative function. Biggest part of
the brain, and most evolved/derived from other mammals, so what makes us human.
WHITE MATTER consists mostly of axons with white myelin sheaths. GRAY MATTER
contains more cell bodies and dendrites, lacking myelin. Human specifically have a large
degree of folding. In the CEREBRAL CORTEX surface area in creased by SULCI and GYRI
(the folds), and is mostly highly developed in mammals (especially primates, especially
humans), thus the grey matter of the outer cortex is 2-5 mm thick (in humans) but
2,400 cm2 of surface area due to the deep foldings. Specifically increases surface area
and density of neurons. Cerebral cortex is divided into six distinct layers (with some
areas having only four or five) and two hemispheres with parallel structures on both
but not identical.
 The LOBES OF CORTEX in the forebrain consists of the frontal, parietal, occipital,
temporal and insular or limbic. There is interaction between forebrain and deeper part
of the brain to form the limbic system. The two hemispheres of the brain are linked by
the CORPUS CALLOSUM, a think bundle of myelinated axons and consisting of 200-250
million contralateral axonal projections, it is the largest white matter structure in the
brain. Main area of communication between the two hemispheres, and damage slowly
down brain function. The two hemispheres are also linked by the ANTERIOR
COMMISSURE, which is 1/10 the size of the corpus collosum, deeper in emotional part
of the brain, near the limbic system. The FRONTAL LOBE controls cognitive processes,
planning future action, anticipating future outcomes/consequences (i.e. chess) and
movement, the motor functions are in the posterior part, but also includes memory,
recognition, behavioral regulation, and motor aspects of speech. Limbic system has a lot
of emotion (i.e. passion), frontal is reason and cognitive process, which allow to
suppress certain urges. Individuals with damaged (or developmental problems)
PREFRONTAL cortex have challenges, such as inability to plan or organize daily
(anticipate or understand consequences), but often score very well on intelligence and
memory tests (not cognitively impaired). This area is specifically developed in humans.
Phineas Gage, recreation of injury shows that damage probably occurred in one side, so
 that he could maintain his personality. The brain is very good at recovering, within a
certain margin of time, age and extent of damage. The PAREITAL LOBE controls somatic
sensation and forms body image (proprioception: where your body is in relation to other
parts of your body), including representations of the body in the MOTOR CORTEX and
SOMATOSENSORY CORTEX, shown in a SENSORY HOMUNCULUS and MOTOR
HOMUNCULUS (significant portions assigned to hands, feet, mouth, and face). Neuronal
dedication reflects importance, rather than size. Evolutionarily, these are the critically
important to survival and we must be sensitive when these are hurt. There are times
when sensory and motor align, other times when one is more important (i.e. face in
both, hands in motor). The OCCIPITAL LOBE controls vision, eyes project contra
laterally. Vision processing part of the brain is actually in the back, acting like a
projector that is then sent to the front lobe to process the meaning of what is visually
perceived in occipital. The TEMPORAL LOBE controls hearing and language,
WENICKE’S AREA processes sound, travels to BROCA’S AREA to respond, travels to
motor cortex to generate sound. The INSULAR or LIMBIC LOBE (only four or five
layers), which is deeper, controls emotional response learning (i.e. fear, love, gambling).
The HIPPOCAMPUS of the forebrain plays an important role in long-term memory, and
damage to it during a stroke or heart attack can lead to cognitive deficits. Hippocampus
interacts directly with HPA axis. The LIMBIC SYSTEM is the cortical and subcortical
structures around the brainstem (deep structures in the cerebrum), generating and
regulation emotions, memory and emotional learning, by interacting with the endocrine
and autonomic system. Interface between deep, emotional, ancient areas to more
involved areas like frontal, prepares various areas for fight or flight. In the limbic
system, the thalamus relays sensory information to the cortex, the HIPPOCAMPUS
controls memory and navigations, the amygdala controls reward, fear and mating
urges, the hypothalamus controls heart rate, blood pressure, etc., and is also related to
olfactory bulbs, pituitary, other deep structures and the prefrontal cortex. The
AMYDALA is a highly complex brain region involved in processing emotional
information, damage to which inhibits ability to recognize fearful facial expressions
(comprises ability to recognize danger and respond to threat). Hippocampus learns
what the amygdala processes. While the amygdala seems to be important for learned or
experiential fear, innate or instinctual fear seems to be less dependent. Many animals
have particular brain areas that recognize and fear certain patterns. In the limbic
system, emotional and learning states are very sensitive to and affected by external
stimuli (i.e. exercise elevates BRAIN DERIVED NEUROTROPHIC FACTORS (BDNF) in
hypothalamus, which promotes memory), therefore condition of body affects brain and
can impair brain functioning. The BASAL GANGLIA controls conscious motor control,
and has a number of direct connections/projections into limbic system.
 The brain communicates neutrally with the rest of the body via spinal and cranial
nerves. The 12 CRAIN NERVES (although CN1 isn’t a real nerve) mostly arise from the
brainstem (except CN1 and CN2), control mostly motor and sensory innervation of head
(except CN10 and CN11) and some are very complex (i.e. CN5, 7, and 10). Some are
mainly motor, some are mainly sensory and some are mixed. The divisions of the brain
can be divided into EVOLUTION, which is the neocortex (cerebrum), paleocortex
(olfactory and limbic systems), and non-cortical brain and cerebellum. DEVELOPMENT,
which is the prosencephalon (the telencephalon/cerebrum and the diencephalon), the
 mesencephalon and the rhomb encephalon (mesencephalon/cerebellum and pons, and
myelencephalon/medulla), and FUNCTION, which is the forebrain (cerebrum, thalamus,
hypothalamus), midbrain, and hindbrain (pons, medulla, cerebellum).
 FMRI scans show relative real-time blow flow In the brain, or which region O2
consumption is highest, demonstrating that some areas get used more than other and
areas are linked within the brain and to the rest of the body (darker the area, the more
oxygen is used, how hard the brain is working during scan). Glucose levels can also be
monitored. The problem is whenever it is excitatory (making something go) or
inhibitory (making something stop) processes cannot be determined from
neuroimaging, but can tell which area of the brain is being used. ASCENDING
PATHWAYS go from afferent neurons to sensory regions in the brain. DESCENDING
PATHWAYS go from motor regions in the brain to the brainstem to efferent neurons. The
four categories of systems are autonomic system which regulates and controls the
visceral organs (PNS), sensory system which monitors and interprets environmental
stimuli (i.e. sights, sounds, etc.), motor system, which initiates and coordinates muscles
to generate movement, and the limbic system which coordinates autonomic functions
with consciousness, regulating emotion and learning. In the ANS, the sympathetic
system is thoracic-lumbar with ganglia near the spinal cord, and the parasympathetic is
cranio-sacral with ganglia near the organ.
 In feeding the brain, the brain is an expensive organ (possibly most expensive tissue),
with 20-25% of resting metabolism and 300-420 kcal/day, because of neuronal
processes (i.e. the Na/K pumps and neurotransmitter synthesis and transport). Another
cause is the BRAIN-BLOOD BARRIER (BBB), as the blood and the brain are mostly
separated by CEREBROSPINAL FLUID (CSF) that bathes the entire CNS, and is
synthesize by CHOROID PLEXUS in VENTRICLES (cavities in the brain, remnants of the
neural tube center) in EPENDYMAL CELLS (glial cells). BBB, which is important for
protecting the brain, is tight junctions between endothelial cells forming blood vessels
in the brain prevent large molecules from passing from the blood into the brain, and
helps prevent infections and toxin from coming in contact with brain cells (may also
prevent many hormones and drugs from accessing neural cells, meth users interferes
with this system). BBB cannot allow passage of RBCs, however permits passage of
plasma, glucose, gasses, hormones, ketone bodies and other small lipid soluble
substances. Non-diffusible substances need to be pumped in an out. In draining the
brain, many SINUSES (valve less) drain the brain, keeping the fluid balance appropriate
(neither too high nor too low). The entire CNS is suspended within the 3 DURAL
MEMBRANES: outer, or DURA MATER, inner or PIA MATER, and the middle, or
ARACHNOID MATER (SUBARACHNOID SPACE filled with CSF). The CSF circulates
through the ventricles and in dural spaces around the brain and spinal cord before
draining. HYDROCEPHALUS is cause by excess CSF, too much production or blocked
drainage; fluid pressure can damage neurons and tissues. In keeping the brain
cool/warm, 37 degrees C is normal. Less than 35 or above 39 leads to impaired function.
Less than 30 leads to slow cell death, greater than 40 leads to rapid cell death. If body
temperature rises above normal, the nervous system signals dermal blood vessels to
dilate and sweat glands to secreted so body heat is lost to its surroundings and body
temperature drops towards normal. When body temperature drops below normal, the
 nervous system signals dermal blood vessels to constrict and sweat glands to remain
inactive so that body heat is conserved, and if body temperature continues to drop, the
nervous system signals muscles to contract involuntarily, so that muscle activity
generates body heat (mammals cools by panting, we cool by sweating, to protect cells
and function). We sweat so much on our scalps and faces due to COUNTERCURRENT
COOLING. In protecting the brain, the cranial vault is 5-10 mm thick, and its domed
structure is very strong, dissipating stress over a large area without stress
concentrations. CONCUSSIONS occur with a blunt force trauma, first impact with
instrument is COUP, primary impact, and a CONTRECOUP, secondary impact with
opposite wall of skull, can cause blood pooling. A basic layer of protection is the
meninges. Human brains are especially big, which means brains generally take more
time to grow, with slower growth compared to other animals and rapid growth
compared to the rest of the body, which is costly in energy. It also causes a long period
of adolescence with extended parental care. Humans are especially evolved in social
interactions, diet, and neurobiological evolutions.

LECTURE #17 SENSORY BIOLOGY

 A major task of the nervous system is to sense environment via environmental stimuli
such as movement, temperature, color, etc. Acquisition of energy is a driving force in
natural selection. Getting and evaluating information on food, predators and prey was a
major selective force on many sensory adaptations in evolutionary history. Our lives
today and usual compared to our ancestral history because our food is plentiful,
prepared and pleasing, unlike past when food was hard to acquire. Pleasing means that
foods we ingest trigger reward pathways in the brain. We are rarely hungry, we have
lots of food choices and we spend little time getting preparing and eating food
(consumption is quick). We have a high probability of becoming overweight, in part
because we love foods rich in fat, and starch/sugar, neuron pathways implicated in
ingesting food via reward processes, which overlaps with neurobiology of selective
romantic bonds. Behaviors that are reward motivate us to do them more, and if those
behaviors have a fitness advantage, more individuals will display them in the
population. 2/3 of US adults over 20 are overweight and/or obese. Percentage
overweight individuals have remained relatively constant, while obesity has increased.
This relationship to food is very recent and very unusual; we spent millions of years
foraging, the only last 12000 years (still fairly recently) farming and the last few
hundred years in non-agrarian societies. Environments today are radically different
than we were evolved, leading to distinctive mismatches. Traces of the importance of
procuring food during our evolutionary past are abundant in our biology, especially in
the organs of sense. Food technology and food modification has been designed to
maximally appeal to our senses (i.e. organic wild strawberries vs. greenhouse grown
juicy, red strawberries so makes a challenge between senses and cognitively know what
is best).
 Touch features cells within skin MECHANORECPTORS that sense pressure and
communicate to spinal cord via afferent nerve cell, various degrees of pressure. Also an
emotional component to how touch is perceived. MEISSNER’S CORPUSCLES for light
 touch, MERKLE’S CORPUSCLES for touch, PACINIAN CORPUSCLES for vibration and
pressure, and RUFFINI CORPUSCLES for temperature. Meissner’s corpuscles sense
pressure from surface to under the skin. Most sensory systems are in the head. This
sense is unusual in that it requires contact.
 Most sensory systems are specific to the head, rather than periphery as touch. The NEW
HEAD HYPOTEHSIS that the reason is that arose originally in a ancient worm that head
was only part exposed and vulnerable to predators so perception of predators had to be
located in the head. What are the challenges that they have evolved to respond to? The
origin of vertebrates (525 x 10^6 years ago), when FILTER FEEDING PRIMITIVE
CHORDATES evolved into EARLY VERTEBRATE PREDATOR, with a nose to smell, eyes to
see, ears to hear, and a tongue to taste, all of which are derived from neural crest cells
during embryonic development. The general pathway for sensory systems is STIMULUS
(photons, chemicals, sound waves and pressure) to RECEPTOR (photoreceptor,
chemoreceptor, mechanoreceptor) to AFFERENT NEURON (receptor potential, action
potential, change in stimulus to change in frequency) to BRAIN (ascending pathway
from brainstem to thalamus to cerebral cortex).
 Eyes sense ripe food (i.e. food, leaves), movement speed, health, rank (i.e. reproductive
status) and danger (i.e. predators or threatening species). The range of visible light is
narrow for humans. One perceives light because it comes in and refracts differently off
different colors. Eye is an exquisitely complex organ (often used against arguments for
evolution). By experiment, one can start out with three layers of cells sensitive to light,
and after generations of selective pressure favoring greater perception of light, one that
can generate what is comparable to the mammalian eye (small changes over light can
generate complex systems). Light sensitivity cells are thought to be a single time point
evolution but from there, there has evolved many different derivations that perceive
the world and utilize light in different ways (i.e. insect eyes). Eyes are mostly an
outgrowth of forebrain (diencephalon) induced by a special group of ectodermal cells
(lens placcode), three layers with increasing complexity, specification and
differentiation to generate all components and form eye. The basic anatomy of the
eyeball is the iris, cornea, pupil, aqueous humor, lens, vitreous humor, 3-layered capsule
(sclera, choroid, retina) and all which concentrate light on optic nerve, which
communicates to brain. The path of light: (1) focusing by CORNEA, the curved change in
velocity converges light through the pupil of the iris onto lens. The IRIS is a tinted, fan
shaped muscle, DILATORS are radial and CONSTRICTORS are concentric, depends on
amount of light desired to be allowed in (i.e. nighttime is dilate, and daytime is contract)
(2) focusing by LENS, the lens is suspended by 1000s of filaments called ZONULES
attached to ciliary muscles which tense and flatten the lens, the muscle contractions
slacken the zonules. The contraction of ciliary muscles relaxes zonules, permitting focus
on near objects; the relaxation of ciliary muscles allows zonules to tense lens, flattering
it to focus on far objects. As we age, lens mineralizes so relaxation of zonules fails to
allow lens to regain convexity (harder time to look at things up close).
NEARSIGHTEDNESS (MYOPIC) is when the visual image is focus in front of the retina,
FARSIGHTEDNESS is when visual image is focused behind the retina (creating fuzzy
images), NORMAL VISION occurs when light is focused directly on the retina rather
than in front or behind it. (3) PHOTORECEPTION light detection occurs at the back of
 the retina. BIPOLAR CELLS receive input from MULTIPLE ROD CELLS and SINGLE CONE
CELLS that transmit information to GANGLION CELL which are linked by HORIZONTAL
CELLS and AMACRINE CELLS. Light detection occurs at the back of the retina. The
OPTIC NERVE carries action potentials from GANGLIA to the brain. The initial
processing of visual information occurs in the VISUAL CORTEX in the occipital lobe.
Image transmitted back to frontal lobe.
 Human vision is special due to being able to see red-spectrum color and stereoscopy
(depth-perception) from our primate heritage. RHODOPSIN RODS are about 120 million
per eye, distributed all over the retina, with 6 to 600 rods synapses per bipolar cell.
They have low acuity and high sensitivity, with little color perception. OPSIN CONES are
about 6 million per eye, mostly in MACULA (a derived feature of monkeys to have fewer
cones then rods), especially FOVEA (a small pit in the center of macula without vessels),
with 1 cone per bipolar cell. They have high acuity and high sensitivity, with color
perception. This is a tradeoff between nocturnal vision and diurnal visions; color vision
is not as sensitive to light, so color seers cannot see nocturnally as well and vice versa.
Seeing blues and greens are common to most mammals but high-end red is derived in
monkeys. TRICHROMATIC VISION is useful fro selecting ripe fruits and tender leaves
(i.e. leaves that are not young and toxic or old and innutritious) so must have red-green
spectrum to look at fine gradations, and MACULA and FOVEA are useful for seeing detail
and rich color. STEREOSCOPY is the ability to perceive depth. MONOCULAR CUES show
relative size (more distant things are smaller), clarity (more distant things are fuzzier),
and parallax (more distant objects appear to move less when we change position).
BINOCULAR VISION has a narrower range, with more stereoscopy, or overlapping visual
field (humans have more than monkeys), PANORAMIC VISION has a wider range with
less stereoscopy. DEPTH PERCEPTION is useful for leaping, hunting and aggression. Eyes
on the side of the head have small overlapping visual field and thus low depth
perception, fully frontated eyes have big overlapping visual field and thus high depth
perception (i.e. zebras need wide field of vision for predator but not depth perception
for grass, lions need depth perception for leaping during hunting or else miss food or
have injury). Primates had a long arboreal history, moved quickly through the trees,
and thus needed depth perception for leaping between trees. Also aggressive
encounters in fighting because same species interactions. Chimpanzees hunt their prey
once every three days, provided a significant contribution in form of protein, which is
important for energy for many organizations. A derived human feature is the VISIBLE
SCLERA, also derived in orangutan.
 Smell and taste is chemoreception. There are about 10,000 taste buds, mostly on the
tongue. BUDS are groups of cells, arranged like organs segments around a central pore.
(1) Food particles dissolve in liquid (ingested with saliva), (2) enter pore, (3) bind to the
receptor causing depolarization (communicates into brain, perceiving taste). There is
no tongue map, but only 5 different kinds of taste (bitter, salty, sweet, MSG, and sour).
The more rich things perceived from taste (80%) of flavor comes from smell (i.e. jelly
bean taste, can identify which 5 kinds, but not what it is). OLFACTION is accomplished
by ODORANTS, which are air-born molecules with a molecular weight of less than 300,
which then bind to the receptor. (1) Odorant dissolves in mucous, (2) binds to receptors
on olfactory nerve dendrite (3) action potential travels to synapse in olfactory bulb
 (glomerulus 10-100 neurons), (4) approx. 12-36 glomeruli synapse per mitral cell (5)
olfactory nerve carries stimulus to various parts of the brain. Communicates with other
areas of the brain, can also be associated with other aspects of brain such as memory
(i.e. social recognition queued by olfaction along with reward processing in
monogamous prairie dogs) Human are poor at olfaction (rely to a greater extent on
vision) because we have (1) relatively smaller olfactory bulbs (30% volume relative to
brain size), (2) fewer olfactory neurons (3), fewer functioning olfactory receptors.
Humans as biped has removed our noses from the ground, we only sniff things deeply
when we want to do so, also less need to do so, and we are quite good at perceiving
odorants when we try. One possible explanation is that the human nose is especially
turbulent and complex to brain. Odorants have two pathways in humans, the
ORTHNASAL and the RETRONASAL (through throat), normally 10& of air hits the
OLFACTORY EPITHELIUM (another reason why food can taste so good). Much of flavor
perception is in the NEOCORTEX in the retro nasal olfactory flavor system. Many parts
of the brain are used to perceive flavor: taste, smell, mouth texture and visual (i.e. food
science in vegetarian recreation). These result in a highly integrated sensory
experience.
 Hearing is important for predator and prey. Sound is the pressurized waves of
molecules, where amplitude is VOLUME (dB), frequency is PITCH (Hz) and harmonics is
character or TIMBRE. Stage #1 is the outer ear: (1) sound is reflected by the earlobe (i.e.
satellite dish) of PRINNA into the ear canal, (2) is amplified and filtered in ear canal (i.e.
tunnel) or RESONATOR, where longer tubes amplify lower frequencies and narrow
tubes filter lower frequencies, (3) sounds cause vibrations of TYMPANIC MEMBRANE.
Stage #2 is middle ear: (4) EAR OSSICLES (MALLEUS, INCUS, and STAPES, i.e. hammer,
anvil and stirrup) amplify sound, bent lever amplifier is 10 to 20x amplification, which
is important because the inner ear is filled with fluid and requires more energy to
propagate a wave, (5) movements of ossicles vibrate OVAL WINDOW of inner ear. Stage
#3 is the inner ear with liquid: (6) Vibrations pass up COCHLEA, the spiral shaped tube
of bone with 3 tubes- vibrations will go up SCALA VESTIBULI, and down SCALA
TYMPANI, lower frequencies travel farther slower (higher travel faster), vibrations in
scalae cause vibrations of BASILAR MEMBRANE that separates the central COCHLEAR
DUCT, (7) vibrations in basilar membrane displace hair cells in ORGAN OF CORTI, (8)
organ of corti hair cells end in STEROCILIA which touch station TECTORIAL
MEMBRANE which is then bent by vibrations, which open K+ channels to depolarize
cell, opening voltage-gated CA++ channels that trigger neurotransmitter glutamate
release to cochlear nerve (communicate with the brain, and interpret sound).
FREQUENCY is when air cells are activated, distal is lower. Different species have
various ranges of hearing (i.e. lower frequencies detected by elephants, move further,
can communicate further away, mouse uses high frequency imperceptible to humans).
Human hearing is 20Hz – 20,000Hz, best at 2,000Hz-4,000Hz, speech at 100Hz-7000Hz.
Ears on either side of the head can allow for localization of sound. AMPLITUDE is the
rate at which given hair cells vibrate. Is human hearing special? SOUND LOCALIZATION
is the INTERAURAL LEVEL DIFFERENCE and the INTERAURAL TIMING DIFFERENCE.
The VESTIBULAR SYSTEM is another use of hair cells in the ear for balance.
SEMICIRCULAR CANALS measure angular rotation, which have pitch roll and yaw.
 SACCULE and UTRICLE measure VERTICAL ACCELERATION and HORIZONTAL
ACCELERATION.
 Summary: Most organs of sense are in the head because selection for early predators
favored new sues of neural crest cells. Vision is photo sensory pigments and lens. Smell
and taste has chemosensory receptors. Hearing and balance have mechanosensory
cells.

LECTURE #18: RESPIRATION AND OXYGEN TRANSPORT

 Overview: expiratory design for molecular diffusion and matching oxygen transport in
linked steps of diffusion and bulk flow; the branching architecture of lung airways,
alveoli, and pulmonary circulation facilitate diffusive exchange (lung anatomy); air
versus water as respiratory media and partial pressure of gases (effect of altitude);
mechanics of breathing, tidal ventilation and its control; health related issues.
 The 4 linked transport processes are ventilation, diffusion, convection and diffusion. How
well are these transport processes matched to the rate of oxygen use? They aren’t
necessarily ideally matched. (1) VENTILATION, the exchange of air between
atmosphere and alveoli by bulk flow (tidal volume of inspiration and expiration), (2)
GAS EXCHANGE, the exchange of O2 and CO2 between alveolar air and blood in lung
capillaries by diffusion, (3) GAS TRANSPORT, the transport of O2 and CO2 through
pulmonary and systemic circulation by bulk flow (4) GAS EXCHANGE, the exchange of
O2 and CO2 between blood in tissue capillaries and cells in tissues by diffusion, (5)
CELLULAR RESPIRATION, the cellular utilization of O2 and production of CO2.
DIFFUSION is effective over short distances, the DIFFUSION RATE EQUATION = KA(C
out – C in)/L. K is the diffusivity constant (1/molecular weight, larger molecules diffuse
more slowly), A is surface area (larger surface area, faster), ^C is the concentration
difference (must have a gradient), L is barrier thickness or diffusion distance (thinner the
thickness, faster), ^C/L is the concentration gradient (higher concentration gradient,
faster rate). Ventilation during respiration and circulation maintain concentration
difference with movement of oxygen. Diffusion is designed to maximize surface area for
exchange, minimize diffusion path, and maximize concentration difference (hence ^C/L
is concentration gradient).
 Human lung anatomy is the branching tree-like distribution of airways, alveoli and
blood vessels (trachea to bronchi to bronchioles). ALVEOLI (alveolus) are tiny sac-like
endings that inflate and deflate during breathing to exchange gasses with blood flow
through capillaries in alveolar wall via diffusion. Alveoli create big internal surface area
with thin walls. Pulmonary arteries are shown in blue (deoxygenated blood) to lungs
and veins are shown in red (oxygenated blood) to body (reverse relative to systemic
circulation). The branching distribution of airways supply extremely small alveoli,
enabling extreme increase in surface area (large surface area) and short diffusion path
to enhance diffusive gas exchange (thin air-blood barrier) to maximize diffusive gas
exchange. DIAPHRAGM is a muscle that separates contracts and depresses to expand
cavity, increases in volume create negative pressure relative to atmospheric air for air
to flow in, and vice versa.
 SEM and TEM, electron micrograph, images show alveoli. TYPE 1 EPITHETIAL CELLS
forms border, TYPE 2 EPITHELIAL CELLS produce PULMONARY SURFACTANT,
 lipoprotein complex that wets the surface of alveoli, reducing their surface tension,
important for uniform inflation. Small radius of alveoli makes it hard to expand; larger
alveoli are easier to expand naturally. This makes it easier to inflate alveoli at low lung
volumes (small alveolar size), which increases lung compliance. NEWBORN
RESPIRATORY DISTRESS SYNDROME has lack of surfactant product (didn’t need to
breathe because mother performed gas exchange) and cannot breathe on its own (a
mechanical ventilator), which is a common and leading cause of mortality in premature
babies. The branching architecture of airways and pulmonary circulation provide
hierarchical subdivision into millions of small alveoli for increase in surface area and
decrease in diffusion path. Corresponding arterial structure to airways. Lung is delicate
and lightweight.
 Air is far superior to water for O2 supply. Air has lower density and weight, lower
viscosity, higher O2 content, and lower respiratory effort (how many liters to ventilate to
make a given amount of oxygen available for diffusion) than water. This enables high
metabolic rates of birds and mammals, but have to worry about gravity and desiccation
(i.e. loss of water from breathing). The PARTIAL PRESSURE OF GASES has implications
for respiratory physiology. Atmospheric pressure is about 760 mmHg at sea level,
creating pressure in a given volume container. Partial pressure is the fractional
concentration of gases relative to atmospheric pressure (atmospheric pressure
multiplied by decimal percentage). Air is 100% humidified when inhaled into lungs by
airway pathway, reducing lung PO2 by PH2O, water vapor pressure. Accounting for
dead space (stale air trapped in non-exchange airways, percentage that is not expired),
alveolar PO2 at sea level is 105 mmHg (less than 160 mmHg at room air, also
respiratory water loss). Due to solubility, concentration of oxygen in air is 30x more
than in water, even when two pressure are the same.
 A SOLUTION is a mixture of water and solutes dissolved in and associate with the water
(or other fluid). NaCl dissociates when added to water H2O into its constituent ions Na+
and Cl- creating loosely charged bonds with H2O molecules. The ability to dissolve into
solution also applies to respiratory gasses. CO2 dissolves much more readily than O2
and N2 in water.
 The effect of altitude greatly limits oxygen extraction as summit is approached (PO2 <
30 mmHg). VO2max is just barely above resting, the implication for climbing ability is
that one must climb very slow, minimal activity (critical activity that cannot sustain life
for extended periods of time). PO2 in lung alveoli (105 mmHg) is less than PO2 of air
(160 mmHg) because of dead space of airways that causes stale air to ix with freshly
inhaled air. TIDAL RESPIRATION involves a near equilibration of PO2 and PCO2 of air
relative to blood in the lung alveoli and throughout circulation, making CONCURRENT
EXCHANGE. Over vertebrates have evolved similar designs with comparable or greater
gas exchange capacity, facilitated by large surface area and thin diffusion barrier. The
mammal lung is COLLAPSIBLE, tidal, discontinuous airflow, the bird lung is RIGID,
allows unidirectional, semicontinous “cross current” flow, without dead space (more
oxygen at a higher rate, can fly over mountains). Fish gills have SECONDARY LAMELLAE
allows large surface area and short diffusion path, water goes in through mouth and
PERICULAR PUMPS, uniform flow of water past gills, and blood flow goes in opposite
direction (from low oxygen to high oxygen). COUNTERCURRENT of water versus blood
 flow via secondary lamellae allow greater than 90% O2 extraction versus less than 50%
extraction for tidal ventilation of mammals.
 Change in volume of lungs controls breathing. INSPIRATION is active, increasing
thoracic volume, the expansion of the thorax creates NEGATIVE PLEURAL PRESSURE,
drawing air into the lungs, and depression via the diaphragm and EXTERNAL
INTERCOSTAL MUSCLES elevate and expand ribs. EXPIRATION is active during
exercise, normally passive at rest, when active, the abdominal muscles assist INTERNAL
INTERCOSTALS creating POSITIVE PLEURAL PRESSURE forcing air out of lungs. Elastic
recoil of stretched ligaments and connective tissue of thorax and diaphragm reduces
respiratory work. F = Palv – Patm/ Resistance of Airway. The THORACIC WALL contains
the INTRAPLEURAL FUILD, bordered by PARIETAL PLEURA and VISCERAL PLEURA.
Lung ventilation is driven by changes in lung volume (inhaled or exhaled in one breath)
or TIDAL VOLUME. Negative TRANSPULMONARY PRESSURE keeps lungs inflated.
PNEUMOTHORAX is air the pleural space usually via a wound, creating a COLLAPSED
LUNG due to the equilibration of pleural and air pressures. RESIDUAL VOLUME keeps
alveoli and lungs inflated, so that even maximum expiration does not reach zero.
INSPIRATORY CAPATCITY is total maximum volume of lungs above tidal volume. VITAL
CAPACITY is total amount from maximum expiration to maximum inspiration.
VENTILATION RATE (L/min) = Respiratory frequency (breaths/min) x tidal volume
(liters/breath). Breathing unique in that it is controlled by both involuntary and
voluntary pathways. CO2 partial pressure levels is sensed to control breathing, not O2,
by CHEMORECEPTORS and BARORECPTORS (blood pressure) located in AORTIC and
CAROTID BODIES. The higher cerebral centers voluntarily control breathing, with the
BRAINSTEM INTEGRATING RESPIRATORY CENTER in the medulla monitor respiratory
rate, and has neuron that monitor magnitude and rate.
 The high surface area of lung alveoli provides design for developing effective drug
delivery strategies via pulmonary exchange to bloodstream, which confers an
advantage over oral medications by avoiding digestive breakdown prior to gut
absorption and being more rapid. ASTHMA is bronchiole constriction due to smooth
muscle contraction associated with inflammation (steroid relaxes muscles and keeps
radius large), a reaction to a variety of airborne particles. FLOW RESISTANCE is
inversely proportionally to radius^4, which applies to blood vessels. Effort to breathe
goes up when resistance goes up. Particle accumulation in the lungs is a significant
underlying problem of lung disease; lung cancer is the most concern and leading cause
of death by cancer in the US. Smoking is a high risk factor for lung cancer in addition to
other environmental pollutants.
 Summary: Gas exchange involves a linked series of transport steps, involving bulk flow
and diffusion ad tied to the rate of O2 use; branching airways, alveoli and pulmonary
circulation greatly increase SA and reduce L for diffuse gas exchange; design for
diffusion is linked to ventilation and cardiovascular transport of oxygen and nutrients;
tidal respiration is facilitated by superior properties of air as a respiratory medium, in
contrast to gas uptake by aquatic animals, such a fish, that rely on elegant
countercurrent design for effective gas exchange; lung ventilation produced by negative
pressure created through thorax expansion; breathing is under voluntary as well as
involuntary control, with ventilation rate changing to meet energy demand, rest versus
 exercise. To learn: Understand how gas exchange involves a linked series of transport
steps, involving bulk flow and diffusion that are tied to rate of cellular respiration (O2
use) should these be matched rates? Understand how/why design for gas exchange is
linked to ventilation and cardiovascular transport of oxygen and nutrients; Understand
lung and respiratory anatomy: branching distribution of airways, alveoli and
pulmonary circulation greatly increases SA and reduces L for diffusive gas exchange;
Understand the mechanism of lung ventilation (via negative pressure produced by
thorax expansion) and why tidal respiration benefits from superior properties of air as
a respiratory medium versus water; Understand how breathing is controlled and how it
is regulated in relation to changes in energy demand (i.e. rest versus exercise);
Understand health related issues (smoking, asthma, drug delivery).

LECTURE #19: HEART STRUCTURE AND FUNCTION

 Overview: heart circulation has two divisions of pulmonary deoxygenated low-pressure

flow and systemic oxygenated high pressure (fully divided in mammals and birds), low-
pressure atria, high-pressure ventricles. Heart anatomy and flow, heart physiology,
activation and regulation of heartbeat, and cardiac cycle and pressure
 Capillaries are embedded in the walls of the lung alveoli; pulmonary circulation
pressure must be lower than systemic circulation pressure. High blood pressure can be
caused by obstructed flow, lung cannot handle high pressure, RBC squeezed through
barrier. Blood fluid goes into lung, causes fluid in the lungs or lung edema, which makes
it hard to breathe with fluid layer.
 Heart disease is a major medical concern. As of 2004, it causes 20% of deaths, 1.2
million new heart attacks each year in the US and high blood pressure affects about
50M people in the US. Risk factors for heart attacks include genetics, age (more time for
other underlying factors to take affect), smoking, alcohol abuse and diabetes, as well as
obesity, inactivity and psychological stress, which contribute to high blood pressure.
Signs of heart attack include chest pain, which is hallmark sign, but also nausea,
indigestion, and shoulder aches. Women have less obvious signs (often lacking chest
pain, often default to diagnosis). Most heart attacks occur on Mondays. The average
time to seek hospital assistance is 2 hours after the heart attack (50% of victims die
before reaching the hospital).
 CT scan is non-invasion, with a cross section. The lungs are located in the PLEURAL
CAVITY of the thorax, the heart is located anteriorly in the PERICARDIAL CAVITY which
is fluid filled to allow the heart to beat (expand and contract) without friction located
between the lungs and the pleural cavity and shifted to the left side of the body. The
RIGHT VENTRICLE project anteriorly, but is smaller than the more posterior LEFT
VENTRICLE (more blood, higher pressure, more muscle). The right ventricle supplies
PUMONARY CIRCULATION (lungs); the left ventricle supplies SYSTEMIC CIRCULATION
(body). Atria have less muscle than the ventricles. The human has surface anatomy have
consists of the superior vena cava (head upper extremities), inferior vena cava (up
through lower extremities), the systemic aorta (LV to superior carotid circulation, inferior
to trunk), the pulmonary artery (RV to lung), the left atrium, the right atrium, the right
ventricle, the left ventricle and the coronary arteries and veins. The CORONARY BLOOD
 FLOW that supplies blood to the heart is 4 to 5% of the total systemic flow, CORONARY
ARTERIES often become obstructed, often precipitating heart attack in left ventricle.
 (1) Superior (upper extremities)/inferior (lower extremities) vena cava go to right
atria, deoxygenated systemic blood through ATRIO VENTRICLULAR VLAVE (tricuspid)
into right ventricle (2) Atria contract, ventricles contract, blood pumped to left atrial
through PULMONARY SEMILUNAR VAVLVE to lungs (3) Pulmonary veins bring in
oxygenic respiratory blood to atria (4) Atria contract, ventricles contract. VALVES also
prevent backflow because based on pressure (5) Papillary muscles stabilize valves,
keep them close. Left ventricle is very high pressure, compounded by high blood
pressure so AORTIC VALVE is often needs reconstructed or pig valve replaced. Valves
are reinforced and stabilized by PAPILLARY MUSCLES to prevent blood from going the
wrong way or leaving through the wrong valve.
 The VALVES within the heart open and close depending on the pressure difference
between heart chambers and vessels. Circulation is divided between ARTERIAL
DEOXYGENATED in the pulmonary circulation and ARTIERIAL OXYGENATED in the
systemic circulation. PAPILLARY MUSCLES and PAPILLARY TENDONS keep valves
closed during forceful ventricular contraction. Valves are designed to ensure ONE-WAY
FLOW. Flow (through chamber or pipe) = Pressure/ Resistance, AV valves open when
Atrial Pressure > Ventricle Pressure, AV valves close when Atrial Pressure < Ventricle
Pressure (important to prevent backflow). Aortic Valves open when Left Ventricle
Pressure > Aortic Pressure. Pulmonary valves open when Right Ventricle Pressure >
Pulmonary Arteries. These also close when pressure falls below. Pressure difference
goes against resistance. Pressure difference must exist, nothing can go to zero,
maintained pressure but all about exceeding. Pulmonary semilunar valve (tricuspid) is
most anterior, aortic semilunar valve (tricuspid), left AV (bicuspid) and right AV
(tricuspid) valves most posterior (from superior view). The blood doesn’t leave until
the valve is open by pressure.
 FETAL CIRCULATION has systemic and umbilical circulation only (without pulmonary).
Deoxygenated blood goes through umbilical arteries and back into via umbilical vein,
while mother’s blood and lungs supplies oxygen and nutrients. Blood to the blood of the
fetus mixes with deoxygenated blood when going to the heart (with portal vein and
inferior vena cava), so not fully oxygenated. Lungs are collapsed in baby, resistance
prevents pulmonary circulation (already oxygenated), two ducts circumvent: The 2
SHUNTS are the FORAMEN OVALE that goes from the right to left atrium and the
DUCTUS ARTERIOSUS that goes from the pulmonary artery to the aorta. The foramen
ovale normally closes and seals immediately at birth when pressure increases in left
versus right atrium, and baby breathes so lungs expand functional pulmonary circuit.
Ligaments arteries are a remnant in adult. Birth defects in foramen ovale must be
closed via surgery to prevent deoxygenated blood
 CARDIAC OUTPOUT (ml blood/min) = heart rate (beats/min) x stroke volume
(volume/beat). Exercise increases both components but majority is heart rate. ^VO2 =
cardiac output x ^blood O2 = 12x difference in AEROBIC SCOPE; three factors
contribute to changes in overall oxygen consumption with various level of activity in an
individual. The A-V blood O2 concentration difference (^O2) is based on change in
oxygen concentration between arterial and venous circulation reflects arterial PO2 –
 venous PO2, the more oxygen demanded by increased activity of the cell
(mitochondria), can increase oxygen extracted through tissues.
 The regulation of heart rate is made by 2 inputs to the SINOATRIAL NODE (SA) from the
VAGUS NERVE (from the parasympathetic nervous system, decreases HR) and the
SYMPATHETIC NERVE (with epinephrine or adrenaline, increases HR).
AUTORHYTHMIC SA and AV NODE are PACEMAKER CELLS produce phasic activation
that maintains resting heart beat independent of other inputs. Heart can beat on its own
because of SA node baroreceptor and chemoreception. Input from SA has basic rhythm,
activities contracting of atria, transmitted to AV, conducted down to ventricles via
conducting fibers at the base called BUNDLE OF HIS. Contracting at base is best for
effective and timing. Depolarization of muscle is modulated by shortening time or
slowing by blocking movement of Na+ for depolarization.
 Cardiac muscle cell membrane properties underlying heart beat, muscles and nerves are
excitable cells that produce electrical action potential. Na+ channels are fast, Ca+ are
slower and last longer which causes a delay, single pulse of force development or
pressure increase, similar to “twitch” contractions which relax and allow it eject blood
effectively and to be filled again during longer refractory period. The slow Ca2+ current
broadens action potential within cardiac muscle cells, which leads to a longer refractory
period, ensuring a single heart beat, allowing heart to relax after contraction which is
necessary for the heart to fill properly after emptying. The GAP JUNCTIONS of
INTERCALATED DISCS allow spread of depolarization between cardiac muscle cells,
which results in coordinated contraction of atria and then ventricles; all muscle cells
contract in unisons. ECG is the ELECTROCARDIOGRAM which measures the
ELECTROPHYSIOLOGY or function of the heart, peak is QRS wave depolarization of
ventricles and smaller P wave is contraction of atria (measure by chest wall), T wave is
repolarization during relaxation. The SINUS RHYTHM is key to the proper timing of
atrial contraction followed by ventricular contraction. Various ARRHYTHMIAS indicate
improper timing of ventral contraction relative to the atria or poorly coordinated
ventricular contractions, which reduces the efficiency of the heart for cardiac output
and muscle work.
 The control of heart rate is done by AORTIC and CAROTIDE BODIES, which are
CHEMORECEPTORS that sense CO2, levels (and a little oxygen). BARORECEPTOS sense
blood pressure and relay sensory information about cardiovascular state to the
hypothalamus and brain stem (which is under feedback) and generates motor output to
control heart rate via autonomic NS via the parasympathetic vagus nerve and
sympathetic nerves. As a muscular pump, the heart fills and empties each cycle. The
CARDIAC CYCLE or each heart beat is defined by 2 ventricular phases: DIASTOLE (the
filling phase at low pressure when ventricles are relaxed and atria contract, blood enter
from right and left atria into right and left ventricles), and SYSTOLE (the emptying
phase at high pressure when ventricles contract and atria relax, blood ejected from
right ventricle into pulmonary artery, left ventricle into aorta and systemic circulation
and atria fill). Blood only leaves the heart during phase 3. Work = Pressure x Volume
(Force x Length).
 STARLING’S LAW states to adjust cardiac output to venous return. More blood
returning to the heart stretches the cardiac muscle cells more (increased volume)
 which affects the force-length properties of the heart muscle. This causes the heart to
beat strong, pumping out more blood from the heart (STROKE VOLUME). All animals
have approximately the same number of heartbeats per lifetime.
 Divided circulation of mammals and birds, enables separation of oxygenated from
deoxygenated blood (high pressure systemic versus low pressure pulmonary
circulation). Timing of atrial and ventricular contraction regulated by sinoatrial node.
Heart displays auto rhythmicity: SA firing can be slowed by parasympathetic or sped up
by sympathetic neural input. Heart muscle cells electrically connected to spread
depolarization and synchronize cardiac muscle contract. The cardiac cycle is divided
into 2 ventricular phases diastole filling at low pressure and systole emptying at high
pressure. Cardiac output (= HR x SV) measures heart performance or blood flow
pumping. Starling’s Law ensures match of cardiac output to venous return. Hear scaling
shows fairly constant working life (approximately 1 to 2 million heart beats in an
animal’s lifetime).

LECTURE #20: CIRCULATORY DESIGN AND REGULATION

 Overview: Heart function, cardiac cycle and heart work (pressure-volume changes);
pipe flow design; structural organization of arteries (strength and elasticity: collagen
and elastin proteins), health related issues; regulation of blood flow, local and extrinsic
factor that adjust regional blood flow patterns.
 There are 2 inputs to sinoatrial (SA) node: the VAGUS NERVE via the parasympathetic
nervous system and the SYMPATHETIC NERVE via epinephrine. AUTORHYTHMIC SA
and AV node PACEMAKER CELLS produce phasic activation that maintains resting heart
beat independent of other inputs. There is gradual membrane depolarization (Na+ and
Ca++ ions leak into cell) and conducting fibers are modified MYOCARDIAL CELLS, not
nerves. As a muscular pump, the heart fills and empties each cycle. The CARDIAC CYCLE
(each heart beat) is defined by 2 ventricular phases: DIASTOLE (filling phase at low
pressure when ventricles relax and atria contract) when blood enters from R and L atria
into R and L ventricles, and SYSTOLE (emptying phase at high pressure when ventricles
contract and atria relax) when blood is ejected from R ventricle into the pulmonary
artery and the L ventricle into aorta and systemic circulation and atria fill. A healthy
measurement is 120/80 (systole/diastole mmHg), HYPERTENSION is 160/100, can
cause edmena, increase in either is a problem. Blood only leaves heart during phase 3 of
the cardiac cycle. In cardiac cycle, left atrial pressure is always slightly above left
ventricular pressure to open AV valve, left ventricle contracts and decreases pressure
while ventricular volume stays the same until ventricular pressure exceed aortic
pressure and blood flows out (stroke volume is amount of blood during this phase) with
opening of valves. On a graph of pressure (mmHg) vs. volume (mL) for heart work, the
area between systole and diastole is work. Work is pressure x volume or force x length.
Obstructions increase work of heart.
 STARLING’S LAW (regulation of blood flow) is adjusting cardiac output to venous
return, with more blood returning to the heart (END DIASTOLIC VOLUME from atria to
ventricles) stretches the cardiac muscle cells more (increased volume), which affects
the force-length properties of the heart muscle. Amount of blood going in has to equal
 amount of blood going out. As heart fills more blood, heart muscles get stretched to a
longer length, (self regulating) produces a higher force, produces a high stroke volume
(as heart fills less blood, lower stroke volume). This causes the heart to beat stronger,
pumping out more blood from the heart and increasing stroke volume. All animals have
approximately the same number of heartbeats per lifetime (humans have more because
of modern medicine), because heart muscle and connective properties are basically the
same working life cycle. Scaling reflects exponential relationship, heart frequencies
scales inversely with size, life span inversely with mass.
 Blood flow requires a pressure difference to overcome vessel resistance. Flow
(volume/time)= P1-P2/R = ^P/R, where pressure 1 occurs before the resistance. Pipe
flow is LAMINAR FLOW, meaning fluid moves in parallel fashion. O at surface, maximal
in middle. The Poiseuille Equation is Flow (ml/min) = ((pi)(^P)(r^4))/(8nl), so
Resistance = 8nl/pi r^4, when ^P is pressure difference, r is vessel radius, n is viscosity, l
is vessel length, which applies both to blood and respiratory airflow. Flow resistance for
laminar flow is inversely proportional to r^4, turbulent flow is inversely proportional to
r^5. Circulation is regulated throughout the body via changes in flow by changes in
resistance with radius, because radius is so effective. This also applies to respiratory
system. Changes in vascular resistance provide an effective mechanism to control blood
flow. Cardiovascular health can be affected by a resistance such as ATHEROSCLEROSIS
(obstructions and stiffening of the arteries), resulting in high blood pressure, which
may lead to heart damage. How is blood flow maintained moving from large to smaller
vessels where diffusive exchange can occur? The continuity of flow is conservation of
mass and momentum, must have same volume of blood going in as flowing out. To
maintain CONTINUITY OF FLOW, flow velocity must be same in arteries and veins of
bigger diameter, so faster in smaller capillaries. (1) Flow out (10 ml/s), #2 flow velocity
is 1 cm/s, #3 V2 = 10 cm/s, volume flow = velocity x area. To reduce diffusion path one
needs to move blood and RBCs through small diameter vessels but this tends to greatly
increase flow velocity and resistance and thus MANIFOD DESIGN of branching
architecture of circulatory system (airways and blood vessels in lungs) reduces flow
resistance and also reduces flow velocity in small diameter vessels where diffusion
occurs, satisfies conversation of fluid momentum, allowing rapid low resistance
transport in large diameter vessels over long distances and slow transport for effective.
Cross sectional area increase and is maximal of capillaries, allowing velocity of blood
flow to decrease velocity of flow because overall cross sectional area is decreases,
sufficient time for exchange of nutrients and waste products via diffusion and bulk flow
at big. Summary x area of daughter vessels is greater than X – A of parent vessel. As
diameter of pipes decreases, increase in number of pipes, increase in total cross
sectional area. Circulatory and lung airways systems follow 2 design principles: (1)
large pipes for transport via bulk flow and small pipes for exchange via diffusion (2)
total X-A of small pipes is bigger than large pipes via manifold design. How are arteries
vs. veins built? Arteries have lumen of endothelium with many layers of smooth muscle
and connective tissues; veins have wider lumen, fewer elastic layers and fewer muscle
layers (thin walled for less pressure). Arterioles regulated by hormones or for contract
diameter to regulate blood flow expansion with smooth muscle cells to supply
capillaries bed, venule just endothelium and connective tissue for low pressure.
Capillaries just single endothelial cell layer that allow diffusion but keep blood separate.
 ELASTIN and COLLAGEN are key proteins that give arteries elasticity and strength
(resistance to deformation and tearing), also smooth muscle to allow contraction and
nerve cells that provide innervation. Changes in vascular resistance regulate blood flow,
VASODILATION increases flow with smooth muscle relaxation, and
VASOCONSTRICTION decreases flow with smooth muscle contraction. The
ENDOTHELIUM is surrounded by smooth muscle and ELASTIC LAMIN (layers of
collagen and elastin), surrounding by nerve cells, collagen and elastin. The folding of
endothelium and wall layers occurs due to absence of internal arterial pressure.
 An ANEURYSM is the localized weakening, damage over time, and blowout of arterial
wall, wall tension as radius increases which collagen and elastin attempt to prevent.
Most common and most dangerous in arties at the base of the brain (CIRCLE OF
WILLIS), internal carotid and descending aorta. Graph of STRESS-STRAIN CURVE or
collagen load-deformation on a force or stress (force/area) versus deformation or
strain (% change) plot is J-shaped, so as collagen is stretched, becomes increasing stiff,
helps prevent blow out. Increased slope signals increased stiffness, which helps
collagen resist tendency of arterial wall to balloon out. ARTERIAL WALL ELASTICITY
stores and returns energy to smooth out pressure pulses of beating heart, smoothing
blood flow. Systole, primaries arteries stretch out, store energy, pulse decrease, can
elastin and collagen recoil producing pressure, which helps to damp fluctuation in
pressure pulses. Thus BP is damped by arterial elasticity and by pressure wave
reflection/cancellation. ATHEROSCLEROSIS is a major cause of coronary heart disease.
Abnormal deposition of smooth muscle cells, macrophages, lymphocytes, cholesterol
(lipoproteins) creates dense connective tissue, under endothelial layer and closes off
lumen of artery, increasing vascular resistance, reducing blood flow and stiffing arteries
wall so ability to stretch and expand with pressure pulse from heart is lost created
ATHEROSCLEROTIC PLAQUE, which is hardening of the arteries. Reduced radius
increases arterial resistance and loss of arterial elasticity, resulting in high blood
pressure. Risk factors include smoking, high plasma cholesterol, hypertension, diabetes,
obesity, inactivity and stress.
 Arteries and arterioles respond through smooth muscle contraction or relaxation by
changing their diameter to regulate vascular resistance and blood flow in response to
three main regulatory signals (1) sympathetic nervous system (excite and contract,
vasoconstrictor, or inactive and relaxed, increasing lumen parasympathetic unknown)
and (2) hormones via epinephrine and norepinephrine, both EXTRINCSIC (larger
vessel) and resulting in CASOCONSTRICTION, and (3) local chemical factors (H+, O2,
CO2, K+) which most often enhance blood flow and affect smaller arterioles that
regulate flow to local capillary beds in the tissues, INTRINSIC and resulting in
VASODILATION.
 AUTOREGULATION of local blood flow (i.e. HYPEREMIA, increased flow in response to
increased metabolism of local tissues or vasodilation in response to reduced local blood
flow, tissue injury to inflammation, or local signaling via H+, O2, CO2, K+, through
arteriole smooth muscle relaxation. Changes in blood flow distribution during exercise
is regulated by vascular resistance and vasoconstriction. During exercise brain and
skeletal muscle percentage of blood flow increases, heart amount increases but
percentage stays the same, and other less important decreased.
 Summary: Changes in vascular resistance is a very effective way to control regional
blood flow (flow resistance 1/r^4); A branching hierarchy from large to small vessels
(manifold design) satisfies continuity of flow, achieving effect bulk flow over long
distances and diffusion over short distances; Elastin and collagen are proteins found in
the walls of arterioles that provide elasticity and strength (smooth out pressure pulses
of heart beat and reduce risk of arterial wall blowout under high pressure (aneurysm);
contraction and relaxation of smooth muscle in arterial walls controls blood flow via
changes in vessel radius, in response to local factors (hyperemia, auto regulation and
extrinsic factors (sympathetic nervous system and hormones).

LECTURE #21: BLOOD AND HEMOGLOBIN

 Overview: Composition and multiple roles of blood; formation of red blood cells;
hemoglobin, oxygen transport carrier molecules, protein structure and function;
myoglobin (skeletal muscle), facilitated diffusion; factors that affect Hb binding affinity
for oxygen; carbon dioxide transport; blood clotting; sickle cell anemia (balancing
evolution for malaria resistance).
 Functions of blood/circulation: (1) gas exchange (major, O2 and CO2), (2) metabolism
(metabolites, ions, fuels), (3) waste elimination (renal filtration), (4) hormone
transport, (5) body defense: immune system, (6) fluid and ion balance, (7) heat transfer
(storage and dissipation): temperature regulation. Blood is 55% plasma, less 1%
leukocytes and platelets, and re HEMATOCRIT measure RBC count, low hematocrit is
anemia (low hemoglobin and Fe), caused by hemorrhage, vitamin B defiency,
abnormalities, etc. ERYTHROCYTES are red blood cells, nucleus, biconcave with big
surface area for diffusion of gasses; majority of volume is protein hemoglobin and
water, all anaerobic metabolism (don’t use carried oxygen). HEMATOPOIESIS is blood
cell formation that occurs in the red bone marrow (pelvic girdle, shoulder girdle, heads
of humerus and femur): HEMOCYTOBLAST (stem cell in red bone marrow) 
PROEYTHROBLAST (committed cell)  developmental pathway phase #1: EARLY
ERYTHROBLAST (ribosome synthesis)  phase #2: (hemoglobin accumulation by
ribosomes) LATE ERYTHROBLAST  NORMOBLAST (ejects nucleus)  phase #3:
RETICULOCYTE (no nucleus)  ERYTHROCYTE. Hormones control erythropoiesis by
blood oxygen levels, (1) when a decrease in normal blood oxygen levels stimulated by
HYPOXIA due to decreased RBC count, decrease availability of oxygen to blood or
increased tissue demands for oxygen, (2) kidneys release ERYTHROPOIETIN, (3)
erythropoietin stimulates red bone marrow, (4) enhanced erythropoiesis increases RBC
count, (5) increase oxygen carrying ability of blood, restoring normal blood oxygen
levels (negative feedback). There are 4 HEME (Fe) SUBGROUPS in hemoglobin, each
which binds oxygen, plus globin. The PORPHYRIN RING changes conformation, altering
heme-binding affinity for oxygen, fully bound or saturated Hb is Hb4O2, oxygen binds to
iron, which gives it red. Oxygen is not very soluble in water of plasma, enters plasma by
diffusion from lungs, and goes into RBCs from blood plasma. Hemoglobin binds oxygen;
taking oxygen out of solution, maintain concentration gradient, increasing blood
transport capacity by over 100x. Hb changes color, blood with CO2 is darker red than
blood with O2, percent saturation curve with Hb displays the property of
 COOPERATIVE REVERSIBLE BINDING, Hb affinity for oxygen is affected by bound state
of oxygen to 4 heme groups, increasing until 3 oxygen’s (1 and 4th are hard). The
OXYGEN-HEMOGLOBIN DISSOCIATION CURVE has a characteristic sigmoidal shape,
with increased binding affinity when few oxygen bound (low PO2) by changing
conformation, with low to moderate exercise about 50% of O2 dissociates from Hb to
supply tissues (50-100% PO2 from veins to arteries). The molecular structural model
has 2 alpha and 2 beta subunits. MYOGLOBIN is a 1 heme oxygen carrier found in
muscle cells, which provides facilitated diffusion of oxygen from RBC into muscle cells.
Myoglobin curve is shifted left with stronger binding affinity of myoglobin for oxygen
cause oxygen to be released from Hb. Mb has a greater binding affinity than Hb at a
given PO2. Myoglobin binds O2 as it diffuses into the muscle cell, keeping the
concentration gradient for diffusion elevated in muscles where it is used, the partial
pressure gradient pulls oxygen off Mb and into mitochondria, because PO2mit < PO2
cytosol. Factors that affect Hb-O2 binding affinity are: (1) fetal vs. maternal Hb-O2
affinity (molecular structure, gene expression), (2) pH (metabolic state, biochemical
effect), (3) temperature (metabolic heat production) and (4) altitude (biochemical
effect). Horizontal shift in oxygen dissociation curve reflects changes in Hb binding
affinity, left-shift increases oxygen affinity, and right-shift decreases oxygen affinity
(encouraging oxygen to be released), can observe various hB% saturation at a given
PO2. The left-shit in maternal vs. fetal Hb reflects difference in molecular structure,
change in gene expression at birth changes from fetal to maternal Hb form. Fetal Hb has
increase oxygen affinity by facilitating oxygen dissociation from maternal Hb, enabling
oxygen to diffuse across placenta and bind to fetal Hb (made in liver, different
molecule). The BOHR EFFECT is a right shift in oxygen dissociation curve, when
reduced pH and elevated CO2 levels decrease Hb binding affinity, as oxygen dissociates
more readily to enter tissues, facilitating its diffusion into metabolically active cells for
oxygen use. Hemoglobin shifts dependent where it is, highly dynamic situation, capable
of responding to immediate environment to maximize oxygen carrying capacity for
what it needs. Reduced pH results from lactate and H+ as end products of anaerobic
glycolysis and CO2 of aerobic metabolism. Increased temperature (heat from
metabolism) end altitude (via production of DPG) also causes a right shift in oxygen
dissociation curve and decreases in Hb binding affinity. These and pH represent
allosteric effects on Hb, change in Hb conformation changes its oxygen binding affinity.
Dissolve CO2 can contribute to metabolic acidosis, but it’s effect on pH is reduced by
reacting with H2) via CARBOINC ANHYDRASE in RBCs to produce BICARBONATE and
weakly acidic H+ ions. Anaerobic glycolysis produces lactate and H+, which also lowers
pH.
 Carbon dioxide is transported in the blood in three forms (1) dissolved in plasma, (2)
chemically bound to hemoglobin, (3) bicarbonate ion in plasma. CO2 + H2O  H2CO3
(carbonic acid)  H+ + HCO3- (bicarbonate ion). HCO3- goes out, but Cl- goes in to
balance negative charge in and outside of RBC. Standard buffer system in affect in
metabolic ion changes in blood.
 Blood flow driven by heart pressure requires a mechanism to plugs leaks, thus
PLATELETS, which produce FIBRIN, perform blood clotting which WBCs have immune
of body defense. Vessel damage exposes collagen under endothelium, causes activation
 of platelets to discharge mediates a synthesis thromboxine, which constricts vascular
smooth muscle for vasoconstriction and aggregation of platelets to form platelet plug.
Normal levels are 250,000 platelets per microliter, if platelet count falls below 50,000
per microliter, bleeding becomes a problem. NO (nitrous oxide) and PROTAGLANDIN
inhibit platelet aggregation and limit clotting to localized area of damage.
HAEMOPHILIA is los of critical clotting factors, which leads to uncontrolled bleeding,
which is a rare recessive trait that affects most often males. SICKLE CELL ANEMIA is
when a single AA mutation in the beta submit gene. HbSS is homozygous for sickle cell
anemia, HbSA is heterozygous or sickle cell trait, a condition selected for resistant to
malaria. HbA is normal Hb. HbS is sickled RBCs that clump and aggregate, blocking
small vessels. Sickled RBCS also die more quickly, leading to severe anemia, and cannot
bind oxygen as well. Malaria is caused by parasitic microorganisms transmitted by
mosquitoes that feed on RBCs. Normal RBCs are particularly susceptible, heterozygotes
are less vulnerable and allow partial resistance because it cannot infect sickle cells. 90%
of cases of 10% of world population infected by malaria in are sub-Saharan Africa.
Treatment of homozygous is activated fetal hemoglobin.
 Outside of RBCS are antibodies, particularly antibodies that determine blood type. In
humans there are 4 major blood types: A, B, AB, O. The immune system produces anti-
bodies against the opposite markers on the RBC, so: B, A, zero, and AB antibodies
respectively. Thus, for blood transfusions, patients can have: A/O, B/O, A/B/O/AB, and
O respectively. O individuals are considered universal donors, and AB universal
recipient. Bad blood transfusions can cause antibodies will bind to foreign RBC, causing
them to aggregate and seriously affect function of kidneys and liver. +Rh have no
antibodies against Rh factor, -Rh initially have no antibodies until immune system
produces antibodies (first time, +Rh has so no affect but second time will cause
aggregation and anemia).
 Summary: Multiple roles of blood reflect multiple cell populations carried within blood;
Hematocrit measures quantity of RBCs in blood (40-45%), RBCs are made in the bone
marrow by a process under hormonal control; hemoglobin is produced and carried in
RBCs which display cooperative reversible binding of 4 O2 molecules, greatly increasing
the blood’s oxygen transport capacity by 100x; Hb oxygen dissociation curve has
sigmoidal shape reflecting cooperative bind of 4 oxygens; myoglobin produced in
muscle has high affinity for oxygen, facilitating oxygen diffusion into muscle cells;
several factors (fetal/maternal, altitude) affect Hb-O2 binding affinity (left vs. right
shifts); CO2 is primarily carried in the blood as bicarbonate and acts as a major buffer in
the blood; clotting initiated by platelets in response to blood vessel damage; sickle-cell
Hb heterozygous trait (homozygous: anemia) reflects balancing selection for resistance
to malaria.

LECTURE #22: SCALING AND SIZE

 OUTLINE: Scaling and allometry: the importance of size; Scaling basics (the allometric
equation, geometric similarity, isometric expectations); 4 examples: metabolic rate
scaling, COT during swimming, flying and running, respiratory system scaling and
elephants and LSD.
 SIZE varies enormously and has a significant impact on function. Size has many
important consequences for how we understanding physiology function; changing size
may change function; Major variation in size between species. SCALING is how
organismal structure and function changes with size. ALLOMETRY is the study of size
and its consequences for organismal function (i.e. the bones of very large animals must
be scaled out of proportion to their linear dimension, such as diameter, in order to
support the weight of the animal, which increases with the third power of the linear
dimensions (between species); during growth, humans change shape as well as size,
head makes up less and limbs make up more of its overall height (in development)).
Studies of scaling usually quantify changes in organismal anatomy or function with size
using the ALLOMETIC EQUATION Y = aX^b, where Y is the TRAIT OF INTEREST or
RESPONSE VARIABLE (i.e. limb mass, metabolic rate, running speed, #mitochondria,
lung volume, body surface area, heart rate, leaf area, etc.), a is a constant, b is the
exponent (the “allometic”/”scaling” coefficient) and X is another trait of interest
(usually a measure of body size, i.e. body mass (Mb), bone mass, volume or length when
body mass can’t be measured, i.e. dinosaurs). This is a logarithmic relationship, which
can be made linear by taking the logs of the values measure for each trait, becoming log
Y = log (a) + b x log (X) or Y = (a) x (b)(X). This describes a straight line with b being the
slope and the intercept is log, which is a constant. One point can be a value for a species,
or point in development. ISOMETRIC EXPECTATION is a hypothesis of slope under
certain conditions. As a NULL CONDITIONS, if large animals were just bigger versions of
smaller animals, what would we expect that slope to be for various variables. Large
organisms could be but are not necessarily just geometrically scaled up versions of
smaller organisms or XEROX ENGLARGEMENT where if we double length, SA increases
4x and volume or mass 8x (i.e. surface area of elephant versus mouse). If
ISOMETRIC/GEOMETIC SCALING, body mass is proportional to length cubed and
surface area is proportional to length squared. In a graph of log lung surface area versus
log of body mass, for children in development, by geometric scaling or Xerox
enlargement, isometric expectation for slope or exponent should be 2/3 (or .67) if
GEOMETRIC SIMILARITY is true. POSITIVE ALLOMETRY is data with a slope above
isometric expectation; NEGATIVE ALLOMETRY is data with a slope blow isometric
expectation of Xerox enlargement. MASS SPECIFIC or VOLUME SPECIFIC SCALING is
usually negative slope (-1/3), on a graph of SA vs. volume, thus as animals are bigger,
bones should increase by cross sectional area to account for support of mass. Brain
mass versus body mass is negative allometry for reptiles, still negative allometry in
humans but largest for body size compared to mammal. Other non-geometric models
for predicting allometric exponents are possible, such as a FRACTAL NETWORK
MODEL, which makes different predictions of scaling exponents from geometric
similarity model. Animal and plant functional design is modeled as a branching network
to generate predicted scaling exponents.
 METABOLIC RATE SCALING can be observed by measure metabolic rates in many
animals, plotting metabolic rates versus body mass, measuring slope of relationship,
and observing how metabolic rate scales with size? On a graph of log metabolic rate
(lO2/hour) versus log body mass, if one were to make a “mass mass” (depending on
mass) hypothesis, the slope would be 1, if one were to make a “surface area-mass”
 (depending on surface area, i.e. heat dissipating through sweating in skin), the slope
would be .67. However, it has been shown in various mammals and birds, on log-log
axes the KLEIBER CURVE has exponents of .75, even among many different groups of
organisms. COST OF TRANSPORT SCALING (J/ kg m) (in running, swimming and flying)
is classically done with mammals (dog), birds (seagull) and fish, results have found
negative allometry (less cost than expected to move tissue), but various intercepts so
less energetically costly at same body mass. The problem is difference in the respiratory
systems of these animals in different media. Comparing only amount mammals (aquatic
mammals and bats) in each group shows that the slopes are actually very similar and
COT differences vanish. RESPIRATORY SYSTEM SCALING, scaling lung volume versus
body mass, and capillary volume versus body mass both have a slope of about 1, thus
isometric scaling (in volume/mass-mass). When comparing alveolar surface area the
slope is still about 1, but SA-mass isometric prediction is .67, so positive allometry.
When comparing alveolar diffusion distance the slope is .05 (when predicted .33),
because alveolar distances is approximately constant between species. An elephant,
given the LSD dosage based on what was an appropriate for a cat by body weight.
Maybe should have been scaled by metabolic rates, or either in humans, or brain size.
Allometric studies have help discover why differences in size occur.

LECTURE #23: PATTERNS OF GROWTH

 OUTLINE: General concepts; basic patterns of growth- centile charts; hormonal control
of growth (growth hormone, thyroid hormone, hormones and bone growth).
 The 3 universal characteristics of life are (1) metabolism, (2) reproduction, and (3).
Energy is partitioned in the body into maintenance, growth and reproduction. The
general principles of physical growth are directionality (how body proportions change,
generally cephalocaudal from head to tail, though also proximodistal from the center
outward), independence of systems (different parts of the body develop along different
timetables, i.e. the nervous system develops most rapidly in the first five years of life,
while sexual characteristics remain fairly stagnant until puberty is reached in early
adolescence; body size changes quickly from birth to age three before slowing but rapid
growth occurs again right around puberty in an ADOLESCENT GROWTH SPURT until
full adult height is reached in late adolescence such as compared on a graph of adult
status attained versus age), and canalization (many systems in the body follow a
standard, genetically pre-structured pathways of development; if something throws
development off course, a correction back on course occurs as soon as a change is
possible). Norms represent average outcomes where individual differences are the range
of variation within the normal range.
 On a graph of adult stats attained (percentage) vs. age, the nervous system grows
rapidly early then asymptotes out at 10-12 years (despite neuronal changes, just mass),
body size increases tapers then increase during puberty, sexual characteristics have
little growth than rapid growth. Various in trajectories between body systems.
Montebeillard scientifically measured his son’s absolute height over time but also
growth velocity or how much height changes at each age, thus how rapid growth is
during infancy. The fastest growth in childhood occurs in the first 2 years of life, and
 then spike at puberty. Poor growth during this critical period of fast growth from birth
to 2 years has life-long health and function consequences and is one of the justifications
for the focus of nutrition on the first 1000 days of life. The long period of relatively slow
growth between infancy and adolescence is unique to humans and is thought to be an
evolutionary adaptation to allow brain development a social learning and thereby
enhance the survival chances of humans. The adolescent growth spurt, which occurs
during puberty, is another period of rapid growth. The growth spurt occurs earlier n
girls than in boys, and girls also stop growing earlier than boys, and boys achieve a
taller maximum high. Humans have a unique pattern of growth, but similar in general to
the primate pattern (i.e. Guinea baboon), although noteworthy big drop in humans after
both and primate species peak (puberty) earlier than humans. Compared to the growth
curve in a wild mouse population, pattern of growth is quite different, slope goes up and
asymptotes out in growth vs. age, and growth rate (vs. age) increases and then drops
and tapers off (no adolescent growth spurt).
 Human growth is monitored using centile charts. This allows medical professionals to
monitor a child’s growth compared to a certain percentage of the population. Old CDC
charts showed formula-fed, so undergrowing and then heavier, new WHO charts show
breast-fed and much more representative and optimal of natural human population
growth. Charts are broken down in various categories, i.e. ethnicity, location. The age of
the child is taken into consideration as well as the spread of differences in the
population. Height, weight, BMI and head circumference (brain growth) are al
measured in this way. In a centile chart, with weight vs. age in percentages, the thicker
red line in the middle is the 50th percentile (average) which indicates that 50% of the
population of boys has weight heaver than the line and 50% are lighter, the 2nd and the
98th centiles are two standard deviations above and below the median. Each line at Nth
centile marks weight or height below N% of children of that age and gender fall.
Likewise, the 95% percentile line indicates the weight where 95% of the population of
boys is lighter. Growth charts are constructed using measurements from a large
number of children at different ages. A series of these cross sectional samples of
population measurements are then used to construct the chart by joining the dots
between key points at each age. When charts were first made this was done by hand but
now there are sophisticated mathematical techniques to do this. The distance between
each centile line is known as a centile space. The lowest centile, the, 4th has been
chosen to identify extreme low measurements, below which only 1/250 optimally
growing children will fall. Individuals tend to track centile lines during growth. Crossing
two centile lines can be cause for clinical concern. The major exception is at
adolescents. The growth curve of a boy with constitutional delay showing slower
growth in the peripubertal time and then achievement of the normal range by the end
of the growth process, due to acceleration through puberty, which is not unusual. The
growth velocity curve is shown with a more attenuated and lower increase at puberty.
In many countries, dramatic seasonal differences in the availability of foods and
incidence of infectious disease have significant effects on growth (can track people and
communities, variable of nutrition, types of growth rates among populations subject to
various environmental conditions). This figure shows the growth in weight of one child
from birth to 2 years. The child’s weight remains well within the normal range from
birth until the time of the first rainy season. Multiple infectious events during the rainy
 season slow and ultimately halt weight growth. Weight growth increases rapidly after
the first rainy season but the child’s weight remains well below the normal range. The
subsequent rainy season results in further disease events and poor growth.
MICROCEPHALY, when one’s head circumference is 2SD less than normal or impaired
head growth, has many possible causes.
 Many hormones control growth with principal actions. GROWTH HORMONE is a major
stimulation of postnatal growth, induces precursor cells to differentiate and secrete
IGF-1 (insulin-like growth factor I) which stimulates cell division, stimulates lives to
secret IGF-1, and stimulates protein synthesis (predominantly in muscle). It also has
ANTI-INSOLUIN EFFECTS particularly at high concentrations, rendering adipocytes
more responsive to stimuli that induce breakdown of triglycerides, releasing fatty acids
into the blood, stimulates gluconeogenesis, and reduces the ability of insulin to
stimulate glucose uptake by adipose and muscle cells, resulting in higher blood glucose
levels. INSULIN stimulates fetal growth, stimulates postnatal growth by stimulating
secretion of IGF-1, and stimulates protein synthesis. IGF-1 mediates GH action, secreted
primarily by liver, circulating bound to carrier proteins. During puberty, there is an
increase in IGF-1 production. THYROID HORMONES are permissive (two together are
greater than either individually) fro growth hormone’s secretion and actions and
permissive for development of the central nervous system. TESTOSTERONE stimulates
growth at puberty (in large part by stimulating the secretion of growth hormone),
causes eventual epiphyseal closure, and stimulates protein synthesis in male.
ESTROGEN stimulates the secretion of growth hormone at puberty and causes eventual
epiphyseal closure. CORTISOL inhibits growth and stimulates protein catabolism, the
catabolic action of which opposes insulin. Treatment, hormone therapy, can restore
someone back to his or her original growth trajectory (i.e. after anorexia).
 KIDNEY TRANSPLANTS can restore normal growth velocity to a patient with retarded
growth at the time of transplantation, while treatment with recombinant human growth
hormone can produce accelerated growth velocity. In a child, these two results can
produce substantive improvement in the height centile, despite insufficient growth
spurt during the early stages of puberty. Affect can depend on timing. PITUATIARY
GIANTS are caused by an increased production of GH that can occur at any time (i.e. by
tumor) when growth plates of bones are still open and continue to grow. PITUITARY
DWARFISM is caused by insufficient GH in childhood. ACROMEGALY is excess secretion
of GH in adult, when the bones of the hands, feet and face can thicken gradually but not
lengthen stature because growth plates are fused.
 PARATHYROID and THYROID GLAND regulate calcium. Disorders of the thyroid gland
include SIMPLE GOITER, CRETINISM, and EXOPTHALMOS. THYROID HORMONE is
important for the development of the central nervous system. Iodine is necessary for
the synthesis of thyroid hormone. THYRONINE HORMONES govern general metabolic
rate by increasing ATP production in mitochondria. Thyroid hormones act successful in
hormone treatment to increase growth when patients are below good centile levels
CALCITONIN (CT) is produced by the PARAFOLLICULAR CELLS in the thyroid and
regulates calcium levels in the blood. It acts directly on osteoclasts, which shrink in size
and slow calcium release. When calcium levels are high, the bones take up the thyroid
gland releases CT and calcium. PARATHYROID HORMONE (PTH) is produced by the
 PARATHRYOID GLANDS and also regulates calcium levels in the blood. PARATHYROID
HORMONE stimulates osteoclasts to degrade the bone matrix and release Ca2+ into the
blood. When levels of calcium are low, the parathyroid glands release PTH. In response,
calcium is released by bones, reabsorbed by the kidneys and absorbed by the intestines.
 Stages of ENDOCHONDRAL OSSIFICATION: (1) formation of bone collar around hyaline
cartilage model, (2) cavitation of the hyaline cartilage within the cartilage model, (3)
invasion of internal cavities by the periosteal bud and spongy bone formation, (4)
formation of the medullary cavity as ossification continues, appearance of secondary
ossification centers in the epiphyses in preparations for (5) ossification of the
epiphyses, when completed hyaline cartilage remains only in the epiphyseal plates and
articular cartilages. EPIPHYSAL GROWTH PLATES, where cartilage meets developing
bone, are central to growth.
 During infancy and childhood, epiphyseal plate activity is stimulated by growth
hormone/IGF-1 release by the anterior pituitary (using hormone receptors in cells).
Closure of epiphyseal plate can also show bone age, which is another way to measure
development (incomplete is younger than chronological age, is also cause for concern).
During puberty, testosterone and estrogens initially promote adolescent growth spurts;
cause masculinization and feminization of specific parts of the skeleton, and later
induce epiphyseal plate closure, ending longitudinal bone growth. Estrogen receptor
deficiencies in bone cells in men can result in continued growth of bones, because
estrogen signals close of epiphyseal plates.

LECTURE #25: IMMUNOLOGY I

 OUTLINE: Lymphatic system function and anatomy; Innate nonspecific immunity;

antigens and antibodies (part of the adaptive/specific immune system).
 Blind-ended in stumps, endothelial cells are leaky with mini valves that allow fluid in
but not out and anchored to connective tissue to restrict movement. The LYMPATHIC
CAPILLARIES play an absorptive (cell debris from damage cells, pathogens, cancer cells)
and transport role during inflammation with lymph nodes (where fluid transported is
monitored by cells of the immune system). Blind ended capillaries interweave between
the capillaries of the circulatory system, hydrostatic/osmotic forces pushes fluid from
the arterial side of capillary bed, lymphatic capillaries pick up fluid (not picked up by
venules) to return to heart after going through immune system bodies such as lymph
nodes. Although the lymphatic system lacks an organ that acts as a pump, it uses some
of the same methods as veins to propel lymph (muscle contraction by muscoskeletal
pump, valves and respiratory system pump, also run next to arteries so pulsation
pumps fluid back to heart). LYMPHOCYTES (type of WBC) include T-CELLS (divide in
bone marrow, migrate to thymus, manage immune system defenses and attack/kill
infected cells) and B-CELLS (innate, produce antibodies, made in bone marrow) that
protect the body against antigens. ANTIGENS are anything the body perceives as
foreign. Other LYMPHOID CELLS include MACROPHAGES (chief phagocytic cell in
immune system, engulf bacteria), DENDRITIC CELLS and RETICULAR CELLS (stroma
network within lymph nodes to help capture foreign material). LYMPH NODES are
LYMPHOID ORGANS have afferent and efferent lymphatic vessels, cortex, follicle,
 germinal center of follicle, capsule, subscapular sinus trabecular, hilus, and medullary
sinus and medullary cord. Lymph returns to heart via lymph nodes. Lymph nodes tend
to be found along blood vessels, bean shape, enter via afferent, migrate through cortex
and medulla, and exit through efferent. More afferent than efferent to cause stagnation
of lymph fluid, giving cells (WBCs, T-cells, B-cells) time to examine everything. Infection
cause lots of foreign material/pathogens in lymph nodes swell inflamed lymph nodes.
Nodes can also act as secondary cancer sites by cancer metastasizing and enter
lymphatic system (moving throughout body); nymph nodes become swollen because
cancer is reproducing at a rapid rate. Other lymphoid organs include the SPLEEN, the
THYMUS, and the TONSILS, but only lymph nodes filter lymph. Spleen is site of
lymphocyte proliferation, and filters blood by removing and storing iron from blood
(blood supply by splenic blood vessels), with relatively thin capsule, rupture by blows
causes susceptibility in immune system but also release of a lot of blood so hemorrhage
and shock. Thymus is site of T-cell maturation, very large in childhood as grows to
adolescent with T-cell maturation is prolific, and begins to atrophy or get smaller after
adolescence, although doesn’t fight infection directly without thymus, no innate
immune system. Tonsils trap pathogens that enter body through food or air, are blind-
ended caves and easy for pathogens to get trapped and become inflamed, important for
immune system because cells look at a lot of pathogens.
 Skin, mucous membranes, and their secretions make up the first line of defense of INNANE
IMMUNITY, including KERATIN and EPITHELIAL MEMBRANES. Skin is very thick with
multiple layers and keratin confers waterproof, allows skin to resist weak acids/bases
and prevents a lot of things from getting in. Other epithelial membranes produce
chemicals that actively destroy microorganisms (i.e. stomach with HCl, lacrimal glands
(tear/saliva) produce antimicrobial proteins, skin has antimicrobial protons and acidic
inhibits bacterial growth. Mucous can trap any type of pathogen entering the body.
Innate immunity is also conferred by nonspecific cells and chemicals, which have specific
cell types. PHAGOCYTES also include NEUTORPHILS tend to be partial to
bacterial/fungal pathogens; EOSINOPHILS are partial to parasitic worms and allergies.
Phagocytes absorb micro bacteria via endocytosis, forming a PHAGOSOME, fusing with
LYSOSOSME which destroy pathogen by enzyme by digestion or respiration burst
(PEROXISOMES with hydrogen peroxide), small pieces are released into or out of cells.
MAST CELLS or BASOPHILS (are WBCs) dotted with granules of HISTOMINE, chemical
released by cell responsible for symptoms of allergies with inflammatory response.
NATURAL KILLER CELLS are able to provide rapid responses and can destroy any virus
infected or cancer cells without activation, faster than B/T-cells (3 versus 10 days), by
causing them to undergo APOPTOSIS (programed cell death) by producing PERFORNIN
by perforating cell membrane that will decrease selective permeability, allowing water
in. INFLAMMATION I triggered whenever a body is exposed to a foreign entity or when
body is injured, prevents pathogens from spreading to nearby tissues gets rid of cell
debris and sets the stage for the repair process. The 4 signs are redness, heat swelling
and pain. Damage to tissue or foreign pathogen causes inflamed mediator to released
(complement, histamines, prostaglandins and cytokines) vasodilation which increases
blood flow to area which causes redness and heat, increased permeability of capillaries
so fluid flows out into tissue spaces causes swelling and pain (pressure on nerves),
pathogens that release toxins directly cause pain, phagocyte immigration into site to
destroy pathogen or chemotaxis and sets the stage for tissue repair (RBCs, WBCs, etc.).
The sequence of events in a nonspecific local inflammatory response to bacteria is: (1)
the entry of bacteria into tissue, injury to tissues causes release of chemical to initiate
the following events, (2) vasodilation of the microcirculation in the infected area,
leading to increased blood flow, (3) large increase in protein permeability of the
capillaries and venules in the infected area, with resulting diffusion of protein and
filtration of fluid into the interstitial fluid, (4) chemotaxis, movement of leukocytes from
venules into the interstitial fluid of the infected area, (5) destruction of bacteria in the
tissue either through phagocytosis or by other mechanism, (6) tissue repair. If the body
can’t destroy infection, it walls it off by ABSCESS with PUSS, mixture of dead or dying
WBCs, dead or dying tissue cells and pathogens. System can’t heal until elimination of
ABCESS (i.e. INFECTORUS GRANULA of TUBERCULUSIS, one of the ways it can stay as a
latent pathogen until depression immune system again. Treatment requires 60 to 90
days of antibiotics, which, if not followed properly, causing a lot of ANTIBIOTIC
RESITANT TB). ANTIMICROBIAL PROTEINS include INTERFERONS (has ability to
interfere with viral replication, when host cell is inflected stimulates production of
interferon, which exits the cell and binds to nearby cells, conferring resistant to viral
infection and can activate other immune cells (macrophages, T-cells) but causes
SORENESS) and COMPLEMENT PROTEINS (is a series of 20 or 25 proteins, found in
blood in inactive form, when activated by other parts of the immune system, it inserts
MEMBRANE ATTACK COMPELXS which puts holes in cell membrane, also amplify
inflammatory response, and increases nonspecific/specific response) both CYTOKINS.
FEVER is elevated body temperature in response to invaded microorganisms, thus body
produces PYROGYTE, which resets HYPOTHALAMUS thermostat higher. Mild fever is
beneficial to inhibit some organismal growth but anything about 103 is dangerous (can
cause seizes), above 105 is deadly (losing brain cells rapidly). ANTIGENS are any
substances that the body perceives as foreign and must be able to mobilize the immune
system and provoke and immune response (stimulate and react with lymphocytes and
antibodies). The ultimate targets of all immune responses, or antigens, are mostly large,
complex molecules not normally found in the body, and tend to be proteins because
they have lots of foreign cites (i.e. pollen grain, bacteria, fungi, viruses have foreign
proteins that can act as antigen determinants or OCMPLETE ANTIGENS which can
function on their own). COMPLETE ANTIGENS (Ags) and HAPTENS (small molecules,
peptides, nucleotides and some hormones, which can be recognized is foreign but don’t
generate an immune response until they link up with something else). SELF-ANTIGENS
allows our body to recognize cells as not foreign. Our cells are dotted with protein
molecules that are not antigenic to us but are strongly antigenic to others. One major
type is MAJOR HISTOCOMPATABILITY COMPLEX (MHC) protein, which mark a cell as
self. There are two classes of MHC proteins: MHC1 is found on all body cells except for
red blood cells and when bound with a VIRAL ANTIGEN is marked fro destruction,
MHC2 is found on ANTIGEN PRESENTING CELLS such as B-cells, macrophages,
dendritic, which then activate T-Helper cells to increase immune response. There are 5
major antibodies associated with B0cels that form gamma globin portion of blood
plasma, Antibodies are soluble protein produced by B-cells or plasma cells capable of
binding specifically to an antigen, so basic structure is a wide heavy chain with two
variable ends, with two antigen-binding cites. Stem region is conserved, and each end is
 variable region, which determines what antigen the antibody can bind to. B-cells can
make about a billion antibodies but only a hundred thousand genes so a lot of
recombination occurs to produce that huge diversity. Because antibodies are coded for
in genome, genetic capacity determines capability of producing antibody against a
certain antigen (i.e. people who survived Black Plague by producing antibodies against
it and have slight immunity to HIV because of the effects of CROSS-REACTIVITY)
ANTIBODIES (Ab) have specific antigen-binding sides at each PRONG, which are
composed of a LIGHT CHAINS and HEAVY CHAINS, and VARIABLE ENDS and
CONSTANT ENDS. The STERN REGION includes a complement biding site and
macrophage binding site. There is also a HINGE REGION. IgD is a monomer attached to
the surface of mature B cells, found in all vertebrates except for birds, signals B cell
activation and proliferation, may play a role in allergies because bind to basophils and
cause them to release histamine. IgM is a pentamer (largest, with 5 subunits capable of
binding to 10 antigens) released by plasma cells during the primary immune response,
first antibody produce in response to antigen expose and effective at activating
complement, can bind to RBCs during poor blood transfusion causing cells to
GLUTENATE or clump. IgG is a monomer that is the most abundant and diverse
antibody in primary and secondary response, makes up approximately 75% of all
immunoglobins and is capable of passing through the placenta to provide protection to
fetus, when performing ANTIBODY TITER testers are looking for exposure to antigens
to measure numbers of IgG against a particular antigen. IgA is a dimer that helps
prevent attachment of pathogens to epithelial cell surfaces (an antibody with a
secretory component), found in saliva, tears, gastrointestinal tract preventing
inflammation, activates other WBCs (i.e. macrophages, etc.) to increase the response.
IgE is a monomer that binds to MAST CELLS and basophils and binds to parasitic worms
(i.e. liver flukes, etc.) can trigger massive inflammation reaction. Mechanism of antibody
action: antigen + antibody = antigen-antibody complex can inactivate antigens by
NEUTRALIZATION by blocking binding cites or bacteria toxins (masks dangerous parts
of bacterial exotoxins, viruses), AGGLUTINATION or clumping (cell-bound antigens)
and PRECIPITATION taking soluble antigens out of solution, which enhances
PHAGOCYTOSIS by marking them; can activate COMPLEMENT which exchanges
PHAGOCYTOSIS and INFLAMMATION (chemotaxis) and leads to CELL LYSIS.

LECTURE #26: IMMUNOLOGY II

 SPECIFIC ADAPTIVE DEFENSES are the bodies’ built in defense system. Unlike, the
innate immune system it must be primed by an initial exposure to an antigen. The
adaptive immune system is a functional system that recognizes specific foreign
substances (encoded by genes), is system (body-wide, no regulated to a particular
system), and has memory. Adaptive immunity is a two-sided defensive system that uses
lymphocytes, APCs (antigen presenting cells), and specific molecules to identify and
destroy non-self particles. Its response depends upon the ability of its cells to recognize
foreign substances by binding to them and communicate with one another so that the
whole system mounts a response specific to those antigens (problems when not specific).
Specific immune defenses have two separate but overlapping arms: HUMORAL or
antibody-mediated immunity provided by antibodies that circulate freely, and
CELLULAR or cell-mediated immunity, where protective factor is lymphocytes, targets
are cellular and have helper and direct killing cells. Antibodies are good are attacking
extracellular, but not intracellular pathogens in the cells of the specific immune system.
There are two types of LYMPHOCYTES: B LYMPHOCYTES and T LYPHOCYTES, which
also are CYTOTOXIC T-CELLS and HELPER T-CELLS, all require APCs which process and
make capable for other cells to responses. In the specific immune system there are also
ANTIGEN-PRESENTING CELLS (APCs) that do not respond to specific antigens.
Lymphocytes are made in bone marrow, come from lymphoid stem cells, mature in
bone marrow and partially mature into B and T cells, T cells finish maturation in
thymus into helper and cytotoxic cells but activation occurs when activated by antigen
in secondary lymph organ (i.e. spleen, lymph nodes tonsils), B cells mature in bone
marrow, activate din lymph nodes and both circulate in blood and lymphatic system.
IMMUNOCOMPETENT B or T CELLS originate in the bone marrow as immature
lymphocytes, circulate in the blood to the thymus (T) or stay in the bone marrow (B) to
develop immunocompetence, and then migrate to lymphoid organs (lymph nodes,
spleen, etc.) which is the site of antigen challenge and differentiation to mater B or T
cells which recirculate in blood and lymph. In thymus, T-cells (i.e. antigen-presenting
cells) that are STRONGLY ANTI-SELF or ANTI-NOTHING result in NEGATIVE SELCTION
or death, while WEAKLY ANTI SELF results in POSITIVE SELECTION or self-tolerant
immunocompetent. Thus they must recognize a cell antigen but not recognize it too
strong or killed. ANTIGEN-PRESENTING CELLS (APCs) major rolls in immunity are to
engulf foreign particles and to present fragment of antigens on their own surfaces to be
recognized by T-cells. Major APCs are macrophages, dendritic cells, and Langerhans cells
and activated B-cells. Humoral immunity response is an ANTIGEN CHALLENGE, (the
first encounter between an antigen or an immunocompetent B-cell) if the lymphocyte is
a B-cell, the challenging antigen provokes a humoral immune response, causing
CLONAL SELECTION or proliferation occurs, B-cells’ antibodies bind to antigen which
stimulates B-cell to proliferate and majority of them turn into PLASMA CELLS which are
antibody-making factories producing large amounts of antibodies to be secreted into
the circulatory and lymphatic system to bind to foreign antigen. MEMROY B CELLS are
also produced, which don’t do anything in first exposure, but stay until second time
when response is larger, faster and longer lasting. In IMMUNOLOGICAL MEMORY, the
secondary immune response to an antigen after a secondary exposure is much larger than
the primary immune response after a first exposure. It takes 5 days after first exposure
to antigen before ay antibody response, peaking 7 days and then declining until day 28,
second exposure antibody production days 3 days. ACQUIRED IMMUNITY can be
NATURALLY ACQUIRED through ACTIVE means (infection, contact with pathogen,
having the virus) or PASSIVE (antibodies pass from mother to fetus via placenta, or to
infant in her milk, but not any memory cells so immune system affect lasts only so long
as the antibodies), or ARTIFICALLY AQUIRED through ACTIVE means (vaccine, dead or
attenuated pathogens) or PASSIVE (injection of immune serum with antibodies, gamma
globin for Hepatitis). VACCINES are a way of using a dead or weakened/attenuated
pathogen to cause humoral immune system to produce memory cells (i.e. chicken pox)
so that the body produces so many antibodies so quick when exposed you don’t feel the
symptoms. Why is vaccine development for certain viral diseases difficult? Because we
 can’t test them due to fatality. What was the first disease that a vaccine was developed
for? Smallpox, then cholera and rabies.
 Antibodies are useless for intraocular virus, so CELL-MEDIATED IMMUNE SYSTEM. In
cell-mediated immune response, two major populations of T cells mediate cellular
immunity: CD4 cells (T4 cells) are primarily helper T cells (Th) and CD8 cells (T8 cells)
are cytotoxic T cells (Tc) that directly destroy cells harboring foreign antigens, foreign
or infected. Other types of cells are DELAYED HYPERSITIVITY T-CELLS (Tdh),
SUPPRESSOR T-CELLS (Ts) and MEMORY T-CELLS. For CLASS 1 MHC PROTEINS: (1)
endogenous antigen degraded by protease after infection by intercellular virus protein,
(2) endogenous antigen peptides enter ER via TAP, (3) endogenous antigen peptide
loaded onto MHC Class 1, (4) loaded MHC protein migrates to the plasma membrane
where it displays the antigenic peptide, targeting itself for destruction by cytotoxic T-
cells. For CLASS II MHC PROTEINS: (1) bacterium pathogen is phagocytized, (2) after
synthesis at the ER, the MHC Class II Protein, with invariant chain still attached
migrants to the phagolysosome, (3) in phagolysosome, the antigen is degrade and
invariant chain removed for peptide loading, and (4) loaded MHC2 protein migrates to
the plasma membrane to display to helper T cells. This is not an infected cell, but
communicating to helper T cells that there is an exogenous (outside cell) antigen in the
system that needs response by amplifying the immune system response. Why is it
important to try to get a good MHC match prior to organ transplantation? Without MHC
match, immune system will attack cell as foreign. T-CELL ACTIVATION must occur by
first ANTIGEN BIDNING to MHC and must be COSTIMULATED by another factor.
COSTIMULATION done is CYTOKINES or chemical-mediating factors released by APCs
that enhance the immune response by activation the helper T-cells (i.e. TNF, IL-1), some
of which are stimulants of T cells and T cell proliferation. INTERLEUKIN 1 (IL-1) is
released by macrophased costimulates bound T-cells, costimulating to release
INTERLEUKIN 2 (IL-2) and synthesize more IL-2 receptors. IL-2 act as costimulates to
activated cytotoxic T-cells to release chemicals like perforin to destroy infected cell.
CYTOTOXIC T-CELLS (Tc) or KILLER T-CELLS is the only T cell that can directly attack
and kill other cells (i.e. cancer cells, foreign transplant cells, virus infected cells, cells
with intracellular parasites). They circulate throughout the body in search of body cells
that display the antigen to which they have been sensitized. In most cases Tc cells bind
to the target cells and release PERFORIN into its membrane. Other Tc cells induce cell
death by secreting LYMPHOTOXIN (fragmenting target cells DNA, releasing TUMOR
NECROSIS FACTOR (TNF, triggering APOPTOSIS) or secreting GAMMA INTERFERON.
HELPER T-CELLS (Th, stimulates PHAGOSYTOSIS via MACROPHAGE). Cytotoxic T-cells
need helper T-cells, activated by macrophages or activated B-cells. Helper T-cells can
also (in addition to activating cytotoxic T-cells) increase immune response, by activated
macrophages to release more cell-killing chemicals and activated NATURAL KILLER
CELLS, overlapping between specific and nonspecific immune systems. It is a positive
feedback loop, although the body shuts the system off.
 Nonspecific defense include anatomical barriers, inflammation and interferon, involving
body surface linings which provide physical barrier and antiviral chemicals, tissue
macrophages which provide phagocytosis of extracellular virus, and most cell types
after viruses enter them, for which interferon nonspecifically prevents viral replication
 inside host cells. Specific defenses include antibody mediated, involving plasma cells
(derived form B cells) that secrete antibodies, that neutralize viral and prevent entry
into cell, activate complement which leads to enhanced phagocytosis of extracellular
virus and recruit NK cells via antibody mediated cellular cytotoxicity, helper involving
helper t cells that secrete interleukins, keep NK cells/macrophages/cytotoxic T
cells/helper cells active and convert B cells to plasma cells, and direct killing, involved
cytotoxic T cells, NK cells and activated macrophages, that destroy host cells via
secreted chemicals and induce release of virus into extracellular fluid where it can be
phagocytized (activity stimulated by IL-3 and interferon-gamma.
 ORGAN TRANSPLANTS include AUTOGRAFTS (i.e. skin grafts, take a graft from a person
to move somewhere else, same tissue, no rejection), ISOGRAFTS (tissue in-between
genetic identical twins, same genetic code, no rejection), ALLOGRAFTS (non-genetically
identical individuals, ABO and blood group antigens must match, MHC antigen match,
even then immunosuppressive therapy for the rest of their lives, two exceptions are
blood transfusions, tendons and ligaments, and cornea transplants because cornea has
no blood supply) and XENOGRAFTS (graft between human and non-human species,
most common is pig, for tendons, heart valves, but no major organs, but also possible to
directly transfer pathogen, XENOTIC INFECTIONS directly from animals, i.e. HIV, bird
flu, swine flu, TB, SARS). IMMUNDEFICIENCIES occur when immune system is not
function or not producing immune cells, can be congenital (birth) or acquired conditions
in which the function or production of immune cells, phagocytes or complement is
abnormal. SEVERE COMBINE IMMUNODEFICIENCY (SCID) SYNDROMES are genetic
defects that produce a resulted deficient in B or T cells, or no cell receptors for IL, thus
susceptible to every pathogen without a way to fight them. SCID is fatal if untreated with
bone marrow transplants (to replace or supply what is wrong or isn’t there). Hairless
house bred without thymus (and thus without T-cells). Acquired immunodeficiency are
HODGKIN’S DIEASE, cancers of the lymph nodes, which leads to immunodeficiency by
depressing lymph node cells, and ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS).
Which cells do AIDS target that causes individuals to become susceptible to
opportunistic infections? Attacks helper T cells, virus or fungal infection. Is there
another disease that causes the body to become susceptible to opportunistic infections?
The 1918 flu resulted in a world pandemic of devastation proportions. It was also
unusual in the age and sex pattern or morality it caused. Mortality was particularly high
among those harboring tuberculosis, which had a young male biased distribution and
became an opportunistic infection. 1918 flu may have also prevented the body from
shutting the positive feedback loop down, massive respiratory system inflammation
due to CYOTOKINE STORM. AUTOIMMUNE DISEASES are the loss of the immune
system’s ability to distinguish self from non-self (i.e. GRAVES’ DISEASE, RHEUMATOID
ARTHRISTIS, TYPE 1 JUVENILE DIABETES MELLITUS (destroys cells in panaceas)),
which go after and destroy healthy functional cells. HYPERSENSITIVY are immune
responses that cause tissue damage. IMMUNE COMPLEX-MEDIATED ALLERGIES are
immediate/life-threatening and subacute hypersensitivities (inflammatory reaction
caused by systemic allergen that causes anaphylactic shock, i.e. bee stings and peanut
butter allergies. Immediate hypersensitivity reactions include runny nose, itching
reddened skin and water eyes, produced by excessive histamines, ANTIHISTAMINES
counteract these effects. ANAPHYLACTIC SHOCK is a systemic response to allergens that
 directly enter the blood which (i.e. insect bite, injection). SYTEMIC HISTAMINE release
may result in constriction of bronchioles, sudden vasodilation (off all blood vessels drops
blood pressure and must be treated with vasoconstrictors) and fluid loss from the
bloodstream, and hypotensive shock and death. IMMUNE-COMPLEX HYPERSENSITIVITY
has antigens that are widely distributed through the body or blood, insoluble antigen-
antibody complexes that form and intense inflammation, local cell lysis and death may
result against self cells and long lasting because not easy to remove from system (i.e.
lupis). DELAYED HYPERSENTITIVES have slow onset (1-3 days), mediated by
mechanisms involving delayed hypersensitivity T-cells and cytotoxic T cells (Tdh and
Tc cells), and cytokines from activated Tc are the mediators of the inflammatory
response (i.e. poison ivy, cortisol suppresses the immune system to eliminate reaction).
 Delayed hypersensitivity is mediated by helper T cells and macrophages independent of
antibodies, immune complex hypersensitivity is mediated by antigen antibody
complexes deposited in tissue and immediate hypersensitivity is mediated by IgE
antibodies, MAST CELLS and eosinophil.

LECTURE #27: OSMOREGULATION

 OUTLINE: Overview of osmoregulation (general types: osmoconformers,

osmoregulators; water and ion homeostasis); Overview of the human kidney anatomy;
how the kidney works (structure and function of the nephron; hormonal control of
osmoregulation); Comparative osmoregulation (salt excreting glands in birds;
comparative nephrons; fish without glomeruli).
 Two fundamental strategies used by animals are OSMOCONFORMATION (plasma ionic
concentrates vary with environmental condition) and OSMOREGULATION (regulate to
maintain internal physiology) to interionic physiological. Advantages to osmoregulation
include that osmosregulators can live in a wide variety of habitats: marine, estuaries,
freshwater, land (can fine-tune physiology); organs don’t have to change function.
Disadvantages include that osmoregulation is energetically costly (especially kidneys)
depending on how different the animal’s internal osmolarity is from the environment,
how permeable the animal’s surfaces are to water and ion movement, and how costly it
is to pump ions across membranes. What is regulated? Water volume, through kidney
(taken in through food or metabolically produced; intake must equal outtake by
sweating, etc.) which is the largest constituent of the body (55-65% of body weight),
blood volume and pressure by adjusting volume of water lost in urine, plasma ion
concentrations sodium, potassium, chloride and calcium ion levels by controlling
quantities lost in urine, blood pH by controlling loss of hydrogen ions and bicarbonate
ions in urine, valuable nutrients (i.e. glucose) by preventing excretion of nutrients while
excreting organic waste products, and nitrogenous waste from protein catabolism by
excreting urea. Animals vary greatly considerably in their tissue osmolarity or ionic
blood plasma, 300 for mammals’ plasma concentration. OSMOLARITY is the total solute
concentration in a solution (mOsm/Liter) and OSMOSIS is the movement of water from
low to high solute concentration.
 The typical adult kidney is 10 cm long, 5.5 cm wide and 3 cm thick, weighing about 150
g. The paired KIDNEYS filtrates a large volume of FILTRATE from which substances
 (water and ions) of the blood that is modified by REABSORPTION (water) and
SECRETION (ions). Urine designated fro EXCRETION moves along the ureters to the
bladder. The kidneys are located on either side of the vertebral column. The left kidney
lies superior to the right. The superior surface is capped by the ADRENAL GLAND. The
position is maintained by overlying peritoneum, contact with adjacent visceral organs
and supporting connective tissues. The kidneys are RETROPERITONEAL (behind coelom
lining) and are not located with the body cavity proper, supplied by RENAL VEINS AND
ARTERIES. The kidneys receive about 20% of cardiac output. Kidney is divided into
CORTEX (surrounds medulla) and MEDULLA, with striated RENAL PYRAMIDS that
filters blood. The path of urine flow after filtration is dripping from the renal pyramid
tips to RENAL SINUS to collect and then exit. NEPHRONS are the functional units of the
kidney, including both the cortex and medulla and draining into sinus, including the
renal pyramids. The approximately 1 million nephrons drain into the RENAL PELVIS.
 [Diagram] Nephron and kidneys are divided into cortex and medulla. There is a
gradient of solute concentration from the cortex to medulla. 300 mOsm/L is
concentration in cortex, to a maximum of 1200 mOsm/L at the tip of the renal pyramid.
Each nephron has an afferent and efferent arteriole from the renal artery, forming an
arteriole ball of leaky capillaries called the GLOMERULUS, sitting in a hollow cup into
which the plasma will be filtered, called BOWMAN’s CAPSULE by small molecules (no
RBCs or big proteins). Filtrate moves down NEPHRON TUBULUE which has a wavy
section before it dives down into the medulla; the tubules in the cortex is call the
PROMIAL TUBULE, ascending tubule starts to thicken into cortex, then called the
DISTALE TUBULE in the cortex, flowing into the COLLECTING DUCT, which goes down
medulla to deposit in the renal sinus. The loop (DESCENDING, transverse and
ASCENDING LIMB) is called the LOOP OF HENLE. The ascending limb membrane is
impermeable to water and has sodium pumps to pump sodium out. In the proximal
tubule of the cortex the osmolarity is still 300 like plasma, and materials the body wants
to keep are reabsorbed actively using a lot of ATP by cells lining it such as sodium,
chloride and glucose, as well water passively. The interstitial fluid surrounding the
descending limb is increasingly salty, so by osmosis salt concentration increasing (1200
at transverse) and water decreasing. In ascending limb, the filtrate concentration is
decreasing, by being impermeable to water and allowing sodium out, so about 100 in
distal. If the collecting duct is permeable to water, water is lost by osmosis in salty
environment to become 1200. The filtrate is thus concentrated. The solute
concentration of the interstitial medullary region is maintained by ions lost from
proximal tubule to distal tubule, allowing the collecting duct to pull out water by
osmosis in the end to make it concentrated. Thus a counter current multiplier, because
filtrate moving down descending and up ascending and magnifying different between
input and output filtrate. Tubules are made up of single-cell lining. The blood vessels
themselves have a counter-current arrangement in VASA RECTA which enables the
circulatory to isolate the medullary concentration gradient without washing it out and
taking away the ions by osmosis, coming and leaving with 300, while provided the
services of vessels. Reabsorption in both proximal and distal tubules. Kidney does a lot
of blood flow management, i.e. by smooth muscles, many connection in vessels, vesa
recta not very separated from tubules. Loop of Henle length varies, CORTICAL
 NEPHRON is more important for reabsorption whereas JUXTAMEDULLARY NEPHRONS
are more important for concentrating urine. (???)
 There is FILTRATION of all molecules less than 60,000 mw at the BOWMAN’s CAPSULE
or CAPSULAR SPACE. FILTRATION SLIT, CAPILLARY LUMAN, PODOCYTE. Filtration
happens in filtration silts between oocytes, small enough to exclude. Blood pressure
drives filtrate of blood from glomerular capillaries to Bowman’s space, but opposed by
fluid pressure of Bowman’s space and osmotic force due to large proteins not filtered.
Formation of the GLOMERULAR FILTRATE in the Bowman’s capsule is the outcome of
opposing pressures, HYDROSTATIC PRESSURE from the heart favors filtration,
OSMOSTIC AND HYDROSTATIC pressure of the filtrate oppose it, resulting in NET
GLOMERULAR FILTRATION PRESSURE. COUNTER-CURRENT MULTIPLIER. The
ASCENDING LIMB is impermeable to water. The composition of the filtrate changes due
to SECRETION and ABSORPTION, urine contains urea, waste produce and little sodium
(filtrate is not just salty, also urea). Since plasma volume is about 3L, all plasma is
filtered about 60x a day. UREA is the main nitrogenous waste product, some is excreted
and some is retained as a solute within the medulla. Note the sides of absorption and
secretion. The geometry of the VASA RECTA parallels the renal counter-current
multiplier system, assuring that blood in these vessels does not “wash out” or dilute the
medullary osmotic gradient.
 ANTI-DIURETIC HORMONE (ADH) is VASOPRESSIN, which makes DISTAL TUBULES
and COLLECTING DUCTS permeable to water. It is secreted by the hypothalamus. It is
critical for allowing urine concentration, more permeable ducts via more AQUAPORNS
to let water out and results in more concentrated urine. The hormone ALDOSTERONE is
secreted by the adrenal cortex and stimulates Na+ absorption by the distal tubules and
collecting ducts (via a complex pathway). Aldosterone also stimulates K+ secretion. Low
blood Ca++ stimulates PARATHYROID HORMONE, released from 4 small parathyroid
glands on either side of the thyroid, which increase tubular Ca++ resorption.
 Birds have usually short LOOPS OF HENLE and cannot make very concentrated urine.
Some seas birds and reptiles (which cannot make a concentrated urine, have evolved
EXTRARENAL routes of salt excretion allow them to drink salt water. Sea birds use
NASAL GLANDS that release salt excretions into the nasal passages. Sea turtles have
modified TEAR DUCTS that secrete salt out around the eye. In fish, the large RENAL
CORPUSCLE (Bowman’s capsule) means more water in raw filtrate. The thick
intermediate segments indicate that many cilia are present to drive filtrate through the
tubule, which means less water will be reabsorbed (no glomerulus). MARINE BONY
FISHES have concentrated urine; FRESHWATER FISHES have copious dilute urine. Big
variety in osmoregulation system design.

LECTURE #28: THE UROGENITAL SYSTEM

 OUTLINE: Review and overview of early embryology (after gastrulation, 3 layer

formation, differentiation of the mesoderm); development of the genital and nephric
ridges (wolffian archinephric duct, mullerian ducts, formation of the testes and ovaries,
indifferent stage, early sexual differentiation); the three part kidney concept
(pronephros, mesonephros, metanephros, development of the kidney); evolution of the
 urogenital system. KEY POINTS: Development of the genital system and kidney are very
closely linked reflecting their evolutionary history; the urogenital system shows how
human anatomy s a mix of traits with obvious origins in our evolutionary history; the
development of the UG system shows how parts that evolved for one purpose can be
reused for a different purpose (not necessarily optimally designed).
 [Diagram] 3-4 weeks in development the embryo is at an indifferent stage, embryo is
sectioned with neural tube, notochord and dorsal aorta in a line. SCLEROTOM
(skeleton), MYOTOM (muscles), DERMATOM (skin) of somites on the side. Underneath
are GENITAL and NEPHRIC RIDGES and GUT. Dorsal aorta goes to a glomerulus, drains
to CARDINAL vein, and also is like a bowman’s capsule, tubule and duct in
MESONEPHRIC TUBULUE. In the dorsal mesentery PRIMORDIAL GERM CELLS will
differentiate, migrate via amoebic movement to genital ridge. In humans the
mesonephric tubules and glomerulus are non=functioning and do not become kidney,
just evolutionary origins. In men, at 8-12, the epithelium of the genital ridge will
thicken, the primordial sex cells with associate with and be nurtured by to the sex chord
which will be SEMINIFEROUS TBULUES, the site of sperm maturation. The mesonephric
tubules, which are disintegrated and reconstructed to connect to the woffian duct and
to the sex cords/ seminiferous tubules. Sperm will get to the outside in men by using
ancient structures that were originally intended for kidney function but have been
coopted by evolution for genital system. The mullerian duct with degenerated. In
female, at 8-12 weeks, also proliferation of epithelium, sex chord, migration of
primordial sex cells, associate with sex chords but also other surrounds cells that
nourish from proliferation of genital ridge (SECONDARY SEX CORDS), called a
FOLLICLE. The mullerian duct is open to the coelom at the top, become the OVIDUCT or
UNTERINE TUBLE. The mesonephric duct and tubule is degenerated, thus the ovary is
separated from the coelom, so must be ovulated from surface to make way into opening
of mullerian duct. All vertebrate ovulate into coelom before swept into mullerian duct.
 The initial formation of the 3 cell GERM LAYERS results in the ECTODERM, ENDODERM
and MESODERM. The INTERMEDIATE MESODERM differentiates into the urogenital
system. At 4 weeks the human embryo is SEXUALLY INDIFFERENT, no specific male or
female genital structures have developed. The PRIMORDIAL GERM CELLS, which will
develop into sperm and eggs as appropriate, are in the wall of the yolk sac and migrate
along the wall of the hindgut and dorsal mesentery in to the GENITAL RIDGE between
weeks 4-6. The WOLFFIAN DUCT is the ARCHINEPHRIC DUCT, which is the
MESONEPHRIC DUCT in the male, the OVIDUCT is the MULLERIAN DUCT in the female.
A section through the urogenital ridge shows the initial formation of an excretory
tubule of the mesonephric part of the kidney, much of which will ultimately disappear.
There is also a relationship of the development gonads to the mesonephros. A
schematic section shows the indifferent gonad with the primitive SEX CORDS, with the
invading primordial germ cells and the thickening genital ridge epithelium. There is
very early sexual differential at week 6, with degenerating excretory tubules in both. A
section through the testis at week 8 shows the cords with the primordial germ cells. At
the 4th month of development the TESTIS CORDS have made contact with the tubules
derived from the mesonephric duct. Also in the 4th month, the Mullerian duct has mostly
degenerated and the testes descend to their final position during months 3-9. At the end
 of the 2nd month in females, almost all of the mesonephric system degenerates and the
uterine tube are formed by the Mullerian duct. This tube is open at the end to the
coelom and ovulation involves release of the egg into the coelom.
 In early ancestral vertebrate, there was a long ridge of tissue with the genetic capability
to of kidneys, in a HOLONEPHROS a complete longitudinal kidney.
 The hypothetical complete longitudinal kidney in early vertebrates had SEGMENTAL
NEGPHRASE, ARCHINEPHRIC DUCT, and URINARY PAPILLA. The hypothetic
HOLONEPHROS or complete kidney all along the body in the retroperitoneal position.
The formation of the vertebrate kidney involves development at three regions along the
archinephric duct: the PRONEPHROS (near the head), the MESONEPRHORS (in the
middle) and the METANEPHROS (near the caudal/posterior end). Early fishes had a
PRONEPHROS. A salamander has a MESONEHPROS (proneprhos will develop then
degenerate), in which kidney tubules are utilized in sperm transport. Mammals have a
METANEPHROS (pronephros develops and degenerates, male humans mesonephros is
change, females develops then degenerates), using former kidney ducts in sperm
transport in mammals. The development of a mammalian kidney closely mirrors its
comparative anatomy. The development of the kidney in the human embryo has
considerable longitudinal differentiation of the intermediate mesoderm. The
degenerating pronehpros and mesonephros (genital in male) and the early
development of metanehpros (in a 5 week old embryo). Tissue buds off metanephric,
invade nephrogetic tissue, forms a kidney and induces the formation of tubules around
the kidney. The embryo grows down and around the kidney, so kidney ends higher up
than were originally formed. The mesonephros and the metanephros change positions
in an ascent of the kidney while most of the mesonephros degenerates. In both male
and female embryos the gonads descend from the site of original formation to a much
lower position in the body cavity. The division of the embryonic CLOACA into separate
urogenital and rectal openings (all vertebrates have a cloaca at some point in the
development). A PELVIC KINDEY can result from error in development if a kidney does
not ascend to meet up with the adrenal gland. Major feature of urogenital evolution are:
Achinephric duct, functional pronephros in adult, single gonad, urinary y bladder as
outgrowth from cloaca, seminiferous tubules in testes, cleidoic egg, metanephros,
ureter, lose archinephric duct (male) archinephric duct becomes deferent duct (female),
mammary glands, ovaries with extensive stroma, uterine tubes.

LECTURE #29: BIOMECHANICS AND TERRESTRIAL LOCOMOTION

 OUTLINE: Biomechanics of materials and structures; Brief overview of vertebrate

locomotion evolution; Terrestrial gaits and the advantages of legs; Center of mass body
motion: PE and KE changes of the CM; Elastic energy savings in terrestrial locomotion;
Walking and running legged robots inspired by CM mechanics.
 In BIOMECHANICS its important to distinguish 2 levels, the MATERIAL PROPERITIES,
related to tissue composition and STRUCUTRAL PROPERITIES related the shape (i.e.
length, diameter, etc.). Material properties (stiffness, failure stress and strain) of
skeletal and connective tissues versus structural properties (shape of bones, muscles
and tendons). Both levels are important to how muscles, tendons and skeletons
 transmit force. Biomechanics is key to locomotion but also applies to manipulation,
chewing and sports, as well as cardiovascular and respiratory function. Structural
properties depend on size and shape. STRENGTH is fracture force. Applying a force to a
tissue (i.e. pulling on a tendon) the cross sectional area under load can be represented
as having been increased in length by a hanging weight. This is a structural relationship
between force and deformation, leading to a force deformation curve. The maximum
force is the greatest load it can bear or energy transmitted. Before breaking. On a force
versus deformation (or change in length) graph, the slope is STIFFNESS, and the area is
TOUGHNESS (energy absorption). The problem is that force and deformation do not
account for size differences, thus we need to normalize force and deformation to
account for size. Material properties are shape and size independent and thus stress
and strain normalize forces and deformations for size differences. STRENGTH is
maximum stress and FAILURE STRAIN is maximum strain at maximum stress. Dividing
force by area normalizes the stress on a given tissue. Dividing change in length by
original length is percent change in length or strain. The longer, larger structure is the
more it can deform but can be normalized as a material property. On a stress (F/A) over
strain (% change in L, normalized deformation is change in L over L) the slope is
SITFFNESS or ELASTIC MODULUS and area is ENERGY ABSORPTION PER VOLUME,
which is ½ the stress times the strain, how much it can compress. Comparing quality is
comparing material properties. Size differences occur during growth and across
species. Force is proportional to weight, and stress if F/A or W (or volume)/A.
Compression and bending loads. How is bone stress predicted to scale with size based
on isometry? Stress is going to go up proportion to the weight of the animal to the 1/3
power. Weight and the forces goes up disproportionally, thus risk of fracture goes up
with increasing size, tradeoffs to compensate include being not as active, less
acceleration or change in posture.
 Bending is most dominant form of loading and most likely to fracture. Bone must be
rigid and resist multiple forms of loading. Vertebrate biomaterials are (1) BONE
(CaPO4, 2/3 hydroxyapatite + 1/3 type 1 collagen fibers) which resist compression and
tension, bending, twisting (torsion); (2) TENDON (and LIGAMENT, type 1 collagen
arranged in parallel fiber arrays) which resists tension (flexible in bending), attach to
muscles and stabilize joints by wrapping around, transmit force from different
directions by pulling; (3) CARTILAGE (‘articular,’ or hyaline, 15% type 2 collagen, 15%
proteoglycan/ GAGs (enormous muscles, radiating outward from BOTTLEBRUSH
configuration because many negative charges bind H2O via H-bonds) and 70% H2O and
HYDRATED GEL for absorbing energy/water molecules, reducing friction at joints by
squeezing out water, fluid movement from cartilage into joint space and lubricating
movement) which resists compression. Bone is stiff/rigid and strong (greater than
tendon and much greater than cartilage, does not strain much), tendon is strong and
elastic (‘spring,’ stores and recovers elastic energy by stretching) and cartilage is
compliant and tough (‘shock-absorber’, absorbs and dissipates energy with water
movement, does not spring back). Tendons and ligaments act as springs to save energy
during running, thus muscles do less work (utilize less ATP). Elastic energy stored
during 1st half, elastic energy recovered via recoiled during 2nd half. Bones are tubular
(with cavity), have tubular design to increase their resistance to being bend and twisted
(torsion). They are also expanded at their ends or joint surfaces to reduce the stress on
 articular cartilage (cartilage is not as strong, needs a larger area to support load).
Bending moment (M) = Fb x L/2 (longer limb bones are loaded mainly bending (>90%
of strain). During bending, one side is stretched, once side is being compressed. Bending
produces a GRADIENT OF STRAIN/STRESS across the bone. MAXIMUM
STRAINS/STRESSES (COMPRESSING/TENSION) occur at the bone surfaces in the plane
of bending, with zero stress at the bone’s center (at NEUTRAL AXIS/PLANE). At the
surface is structurally advantageous, for a given weight, it takes more energy to move
away from neutral plane, because already away from neutral plane. The tubular shape
increases bending and torsional strength 50-100% (for given weight or size of a bone).
By being tubular in shape can increase strength, without any change in material or
weight: maximize stiffness, minimize weight.
 How do terrestrial animals support their weight and move over ground? Transition
from aquatic to land, first land vertebrate were amphibious: locomotion involved a
combination of lateral trunk undulation (retained from fish ancestor) with motion of
sprawled limbs (i.e. tiger salamander) over a greater distance but not very fast. The
triangles of limb support provide STATIC STABILITY, with tripod of support and CM
within. Terrestrial mammals and birds evolved locomotion with more upright planar
(parasagittal) limb motion (reduced lateral trunk undulation), resulting in faster speeds
and dynamically stable gaits (i.e. galloping horse quadruped, running ostrich biped).
Human are unusual bipeds, only birds, but also not primates. STRIDE (cycle of gait) =
STANCE PHASE + SWING PHASE. The stance phases are much longer in walking than
running (shorter periods of support state phases and aerial period), where they overlap
as opposed to non-overlapping stance in aerial phase. Speed and GAIT changes involve
changes in relative timing of limb movement and ground contact duration (which is
reduced at higher speeds). SPEED (m/sec) = STRIDE RATE (increased muscle
recruitment/movement, strides/sec) x STRIDE LENGTH (distance traveled, m/stride).
Gaits involve changes in stride duration and relative timing of limb support and swing
phases (i.e. quadrucept trot equals biped run, right and left coordinated). Quadruped
can gallop or canter, increase in stride length extension as well as stride rate.
 Why legs and not wheels? Wheels are difficult to evolve (muscles can’t produce rotary,
circular motion, only one kind of bacteria) and wheels only work well for movement
over smooth surfaces. Wheels cannot overcome obstacles bigger than its radius, so
much have big radius. Legs require ^PE and ^KE in CM of body, but allow animals to
step over and around obstacles which is good for negotiating uneven terrain. By
Newton’s 1st Law, the ground pushed up against your feet and your feet push back on
the ground with an equal force! How much weight (force) does each leg support when
you stand? [1/2 body weight] How much weight is supported when you stand on one
leg? [full body weight] If you jump or run, how does this affect the weight supported by
your legs? Why? Force of ground increases with jumping, so must produce acceleration
to above body weight to overcome acceleration due to gravity.
 What are the forces of locomotion? GROUND REACTION FORCE (GRF or G) results from
support of body weight due to gravity and represents the force acting on the foot, which
is transmitted via the limb during the stance phase of gait. MUSCLE FORCES (Fm)
contract to support body weight and generate movement by producing JOINT TORQUES
to balance torque from GRF. Joint torque (or MOMENT) T = G x R (out lever) = Fm x r (in
 lever, muscle moment arm/lever arm, where Achilles tendon attaches). Because r is
much smaller than R, the force of the muscles is much greater than the GRV, so this is
what determines the load of the muscle (Achilles tendon stretches until movement off
ground) and forces that have to be supported by the skeleton (dominant loading mode).
Doors have handle away from hinge axis, increases moment arm so low force to cause
rotation. A force can’t produce a rotation without a moment arm. The
MUSCULOSKELETAL SYSTEM consists of a series of JOINTED LEVERS. VERTICAL
GROUND FORCES (Gv, increases at faster speeds, because less time on the ground) and
HORIZONTAL GROUND FORCES (Gh, fore aft, that slows down) vs. time. At steady
speed, the acceleration and deceleration by horizontal forces, slow down at beginning
of support, then speed up. Faster speeds require shorter ground contact times (tc) and
higher peak forces. For STEADY LEVEL LOCOMOTION, IMPULSE is integral of force over
time, vertical direction is body weight force due to gravity (must be equal, so not flying
up or sinking down), horizontal is 0. Humans evolved an erect bipedal terrestrial gait
from quadrupedal (arboreal) primate ancestors. Shifted emphasis to hind limb support
and movement. Arboreal locomotion (climbing) linked to the evolution of human
bipedalism and grasping/manipulation. During every step the body’s CM moves up and
down (due to fluctuating Gv, and ground forces) changing PE and slows down and
speeds up (due to fluctuation Gh) changing KE. When force is equal to body weight,
greater than is gain of PE, and less than is loss of PE. PE is max when foot in on the
ground, min between. For running, increase in PE is decrease in KE (exchange between
two), at the same in running. Walking vs. running gaits has different CM mechanical
energy patters (therefore different mechanisms for conserving energy use, minimize
energy). Walking: PE and KE fluctuate OUT OF PHASE; RUNNING (also applies to
hopping and trotting): PE and KE fluctuate IN PHASE (spring-mass system, no
exchange). KE is lost in landing; energy is stored in ligaments of the feet (i.e. Achilles).
INVERTED PENDULAR motion of walking because human CM located between hips has
friction. Because PE and KE of body’s CM fluctuate every step, muscles energy is
recovered, it must be supplied by muscle work. 2 energy saving mechanisms to reduce
muscle work and metabolic energy cost. Walking is an INVERTED PENDULUM and
running is SPRING-MASS (bouncing gait, like trotting, galloping and hopping). Galloping
also involves flexion and extension of the trunk. During running, terrestrial animals
conserve energy by elastic storage and recovery of TENDON AND LIGAMENT SPRING
ENERGY. Center of mass PE and KE exchanged as spring energy in limbs. Hopping is like
a bouncing ball or a child on a pogo stick. Tendons, ligaments and muscles enable limbs
to act like springs. Elastic energy stored as joints flex and limb is loaded during 1st half
of step (stretching tendons, ligaments and muscles); Elastic energy returned as joints re-
extend and limb is unloaded during 2nd half of step (recoiling tendons, ligaments and
muscles). Tendons and ligaments act as springs to save energy during running. In
walking robots, or PASSIVE PENDULAR DYNAMICS, change in PE drives motion, with
dynamic robots that bounce.
 SUMMARY: Biological materials consist of different chemical components (mineral,
collagen, hydrostatic gels) that yield different mechanical properties: stiffness, strength
and energy absorption. Structural properties depend on shape (tubular design of bone
provides increased resistance to bending and torsion, with expanded ends for reducing
cartilage stress). Limbs evolved for support and movement over uneven terrain
 (upright, parasagittal limb motion improves economy). Animals increase speed by
increasing stride rate and stride length. Increased speed requires reduced limb support
time: increasing ground reaction forces, joint torques, and musculoskeletal forces.
Terrestrial animals conserve CM energy to reduce muscle work by 2 means: walking
pendulary exchange between PE and KE out of phase and running spring based elastic
energy storage and recovery PE and KE in phase. Primates exhibit diverse arboreal and
terrestrial locomotors specializations with human bipedalism likely evolving from an
ancestral arboreal habit. Humans are unusual bipeds!

LECUTRE #30: HUMAN GAITS

 Walking has most clinical importance. Robot on a downhill curve is an example of

passive pendulum dynamics with PE driving motion, although some PE is lost. Arm
motion relative to body CM is important to counter rotational energy of swinging legs
for stabilization. BIPEDALISM is rare, most terrestrial animals are QUADRUPEDS.
Human bipedalism is unusual; we are the only featherless, tailless, striding bipeds.
Bipedalism is an unusual way to move about, it is hard to learn, unsteady and slow.
Bipedalism is a key distinguishing feature of the human lineage versus KNUCKLE
WALKING like other primates (can walk bipedal). Why be a biped? Not to carry things
(walking before had big brains and using tools), wade, or see over tall grass. It saves
energy (humans have a lower cost of transport mlO2/kg/m lower than chimps), stand
to assist reach when feeding and possible advantage when fighting (male dominance
while fighting).
 How do we walk? A STRIDE is a full cycle from heel strike (HS) to heal strike. STANCE
PHASE (60% walking) is (1) heel strike, (2) foot flat, (3) heel off, (4) toe off to SWING
PHASE (40% walking). Stance is DOUBLE SUPPORT (two feet), single support, double
support in walking, no double support and aerial in running (less stable but faster). In a
walk, the foot is on the ground for more than 50% of the time. Biomechanical challenge
of gait is how to move the body’s CM (or center of gravity) forward economically and
with stability in legs? The CM is 2 cm anterior to 2nd sacral vertebrate. The
OSCILLATIONS of CM during walking is a distorted figure of 8. Movement up and down
(5 cm, PE= mgh) are PE fluctuations, side-to-side is left and right limb support. Walking
mechanics have inverted pendulum model changes of CM PE and KE to conserve
energy, COMPASS GAIT, as body vaults over leg. Determinants of walking gait function
to minimize oscillation of CM (smoothing elevations and depressions, and transitions),
vertical displacements (5), lateral displacements (2) and anterior-posterior
displacements (1). Determine (#1) PELVIC ROTATION, when stance side limb, pelvis
rotates via muscles 4 degrees medially (towards midline) at hip (about a vertical axis).
Function is to increase stride length (reduces minima of compass gait), effectively
elongating leading and trailing legs at heel strike, decreasing nadir of CM vertical
motion at heel strike by 1 cm, reducing ^PE of CM. (#2) PELVIC TILT, when pelvis on
swing side tilts inferiorly about 5 degrees (reduces elevation of CM), controlled by
ABDUCTION (away from middle) of stance side hip. Function is to decrease zenith of
trajectories arc by .5 cm, further reducing ^PE of CM. Medial rotation and abduction of
stance side hip are both made possible by SMALL GLUTEAL MUSCLES on side of hip
 (contraction of gluteus medius and minimus). Without hip abduction, have to throw
weight over leg. These key action are made possible by lateral (instead of posterior)
orientation of ILIUM in the hominin pelvis, shifting muscle fx to hip abduction vs. only
extension in chimps. Chimps lack determines 1 and 2 (waddle, trunk back and forth,
also DISEASE). (#3) KNEE FLEXION during stance, when knee is extended at heel
strikes but flexes 15 degrees by midstance and extends again at heel-off. Function is to
decrease zenith of trajectory by 1 cm, reducing ^PE of CM. This is caused by gravity and
hamstring muscles and controlled by QUADRICEPS (knee extensors). Quads peak early
in stance, drops and then peaks again, making legs compliant while walking. Compass
gait has no flexion of limb as a whole. (reduction in CM PE height maximum) (#4)
CONTROLLED PLANTARFLEXION at heel strike. At heel strike, foot plantar flexes to
ground, lowering trajectory of leg and lowering trajectory of CM between HS and FF,
smoothing transitions between right and left limb supports. Plantar flexion resisted and
controlled by DORSIFLEXOR SHIN MUSCLE (anterior tibialis raising for swing).
(smoothing transition and trajectory of the CM to reduce elevation) (SLAP FOOT) (#5)
POWERED PLANTARFLEXION from heel-off (raises heel) to toe off. Without plantar
flexion, the leg would rotate about ankle joint, cause CM to fall after HO, also contributes
to smoothing CM trajectory during limb support transition. Plantar flexors are calf
muscles (gastrocnemius and soleus to push off) (smoothing transition and reducing
elevation of CM in second half). Powered plantar flexion requires a stiff midfoot (ARCH
with ligaments as stabilized lever, in addition to stretch during running), which in
humans is stiffed by MID TARSAL maintaining arched (mid tarsal break in chimps
results in no arch). Putting gait determinants together, control of vertical fluctuations of
CM to smooth CM motion (^PE). Other determinants of walking gait include LATERAL
DISPLACMENT of CM (mideo-lateral trunk sway, with FEMORAL ANGLE knock-knees to
reduce lateway sway of CM) and ANTERO-POSTERIOR DISPLACEMNT of CM (antero-
posterior trunk sway). Knees are closer together than hips, feet closer to midline of CM.
Abdominal muscle help control mideo-lateral sway. Antero-posterior sway allows to
move trunk back, acceleration/deceleration of first half of stance to stabilize trunk, and
acceleration as push off (moving forward controlled by posterior and vice versa).
Women’s wider pelvis affects the way one walks, accentuating pelvic motions.
Ligaments/tendons in the leg/foot contribute about 50% of the energy required to
move CM otherwise produce by muscles, chimps lack thick but broader ranges of
motion important for arboreal habits but poor runners. Running is a bouncy gait, our
reliance on springs to conserve energy while running distinguishes us from other
primates but not other running mammals and birds. Humans also have long legs for
their size (longer strides, increase in speed), which help reduce energy costs. Humans
have good endurance for hunter gathers, capabilities facilitated through increase in
limb length (even relative to horses). Human running COT is 30-50% greater than
walking and higher than many other animals (though not chimps).

LECTURE #31: THERMOREGULATION

 OUTLINE: Why maintain and regulated an elevated body temperature (Tb)?

Evolutionary overview of thermoregulatory strategies; Hypothalamic regulation of Tb
(fever); Principles of thermoregulation: heat balance equation; Physiological and
 behavioral mechanisms underlying temperature regulation; Exercise and ecological
implications (human sweating and hair loss).
 Thermoregulation in vertebrates has evolved 2 strategies: ECTOTHERMS, with an
outside heat source (including aquatic animals with gills/cutaneous respiration) and
ENDOTHERMS with an inside heat source controlled by METABOLISM. Majority of
animals maintain do not maintain constant body. Similar to cost of regulating osmotic
balance. Ectoderms have an ECONOMICAL STRATEGY that limits heat gradient with
environment, especially in aquatic animals with gills/cutaneous respiration, also called
POIKILOTHERMS for changing temperature. HIGH ENERGY STRATEGY that is more
active and broader habitat range, similar to higher cost of being an osmoregulation.
HEAT is energy, but TEMPREAUTRE is a measure of heat (1 calorie is energy to heat 1
ml H2O to 1 C). Heat gain is temperature increase, heat loss is temperature decrease.
Heat flows from warmer to colder temperatures, down a TEMPERATURE GRADIENT.
CORE BODY TEMPERATURE (including CNS) for humans is about 37 degrees Celsius,
but is variable regionally and over time. CORE vs. PERIPHERY, the body allows the
periphery to get colder to reduce the temperature gradient and reduce heat loss.
Temperature of body varies on a CIRCADIAN RHYTHM, elevated during the day,
depressed at night while sleeping. Animals try to maintain a constant body temperature
because maintaining a stable biochemical and cellular function depends on constant
temperature. Increase in temperature, exponentially increases reaction rate. Must
maintain all cells at same reaction rate. Most cellular functions in your body have a
limited temperature range: too low body temperature limits oxygen transport and
reduces the metabolic rate (HYPOTHERMIA), too high denatures proteins, deteriorates
enzymes, lose of integrity for membranes, etc. Birds and mammals maintain an elevated
body, relative to environment, temperature because it is easier to regulate heat loss
than heat gain. HOMEOSTATIS includes regulation of a constant Tb or temperature set
point (Tset), which is normally 37 C for humans and mammals. Blood flows from body
to brain regulates heat to or from hypothalamus (central control of metabolism and
body temperature), affecting Thypothalamus with THERMOSENSORY NEURONS. Tset is
critical point the hypothalamus maintains. If the Thypo is less than the Tset, then the
hypothalamus stimulates heat production (shivering and activity) and reduces heat loss
(by PERIPHERAL VASOCONSTRICTION, i.e. fingers and toes to preserve heat for core of
body with organs). If the Thypo is greater than the Tset, the hypothalamus stimulates
heat loss (sweating and vasodilation, increases periphery temperate to encourage heat
loss through temperature gradient) and reduces heat gain (move to shade, reduce
activity). This is a NEGATIVE FEEDBACK SYSTEM, regulated by sympathetic and
voluntary. A FEVER is an increase in Tset, macrophages release ENDOGENOUS
PYROGENS as initial immune response to a pathogen, and the hypothalamus
synthesizes PROSTAGLANDINS, which elevate Tset. ASPIRIN inhibit prostaglandin
actions to reduce Tset and fever; VASOPRESSIN also counters affect of elevated set
point to limits affects of fever by negative feedback. Only time Tset is changed. This is
why you feel cold even when body temperature may be normal.
 To maintain a constant, balanced Tb, heat loss = heat gain. Thermoregulation involves
both PHYSIOLOGICAL and BEHAVIORAL MECHANISMS. The HEAT BALANCE
EQUATION is 0 = + Metabolism +/- Hconduction/convection +/- Hradiation –
 Hevaportation. The sources of heat loss and gain are METABOLISM (always heat gain),
CONDUCTION (heat gain or loss), CONVECTION (accelerates rate of heat gain or loss),
RADIATION (most often heat gain, i.e. solar radiation) and EVAPORATION (nearly
always heat loss). Metabolism is positive, as your muscles and organs produce heat as a
byproduct of inefficiency (metabolism is 38% efficient for usable ATP energy, other
62% lost as heat). Muscle contribution goes up a lot during exercise, with glycolysis and
other processes. Metabolism is balanced by sources of heat loss. Conduction is +/-
because heat flows down a temperature gradient by conduction (similar to diffusion).
HEAT FLOW = k A (Tb – Tenviron)/ L. A is surface area, Tb-Talt/L is temperature
between 2 locations (^T or thickness) and k is THERMAL CONUDCTIIVY or how easily
heat flows in a material (air (1) > fat > fur > water (500) for relative insulation, which is
inverse relationship of conductivity). Fur can trap air, so fur is fur plus air insulation.
Because water is high conductivity, it’s very hard to be an endotherm in water.
AQUATIC MAMMALS limit heat loss by effective SUBCUTANEOUS INSULATION, thick
layer of blubber as insulter. Also a SHUNT VASCULAR, shunt blood to surface in warm
water, can block blood flow to surface in cold water, way of dealing with high heat
conductance. Change conductance C to regulate heat gain or loss. The blubber of sea
mammals provides effective insulation, which can be shunted by circulation, which isn’t
possible with fur. Dolphins retain body heat by use of COUNTERCURRENT EXCHANGE
to reduce heat loss via flippers, warm blood leaving bodies core is cooled by venus
blood returning from surrounding cooler water, which is warmed. Wading birds do the
same via countercurrent exchange of heat in leg arteries and veins, reducing amount of
heat loss in feet. Humans reduce heat loss by allowing exposed fingers and feet to cool
via vasoconstriction but risk FROSTBITE with extended period of exposure. Convection
increases heat flow by conduction by maintaining temperature gradient movement of
air and water over body surface, by density differences or forced wind or pumped flow.
Air surrounding body is warm relative to surrounding in a layer, wind blows warm air
away with steeper temperature gradient and increase of heat loss (WIND CHILL).
Radiation is heat exchange by electromagnetic radiation. Head can be absorbed or
reflected. Practically, the main effect is heat gain from solar radiation. Clothing and fur
color affect absorbance or reflection of radiation energy (white reflects, dark absorbs).
Evaporation is nearly always a mechanism for heat loss, via respiration and sweating,
evaporation off skin surface. It is an extremely effective process (resulting from phase
shift of 1g of water from liquid to vapor for 580 cal/mL) but at the expense of water loss
and DEHYDRATION. Water has high heat capacity and conductance.
 Problems and solutions of body determined by environment. In HOT ENVIRONMENTS,
Tb < Tair + solar radiation, resulting in problems of heat gain and dehydration. COLD
ENVIRONMENTS, Tb > Tair, resulting in problems of heat loss. How do endotherms (i.e.
humans) regulate body temperature (Tb) in relation to changes in environmental
temperature (Tair)? Thermoregulation involves both PHYSIOLOGICAL and
BEHAVIORAL MECHANISMS. ADAPTATION is phenotypic traits selected for through
natural selection by environment. ACCLIMATION is a physiological adjustment to long-
term seasonal or geographic climate change. Heat acclimating includes improved
cutaneous blood flow; lowered threshold for sweating, increased sweat output and
reduced salt concentration of sweat (defending against electrolyte loss). Heat/Hmet = C
(Tb-Ta). A graph of endothermic responses to changes in environmental temperature,
in metabolic rate (Hmetbaolism) vs. environment temperature, Ta (C), where slope is
conductance C. Metabolic rate decreases until the LOWER CRITICAL TEMPERATURE
(LCT), and is in a THERMONEUTRAL ZONE at BMR until the UPPER CRITICAL
TEMPERATURE (UCT). Heat = C (Tb-Ta), C is a conductance constant. In thermo neutral
zone, conductance constant must be changing with change in temperature gradient to
maintain heat, because basal metabolic rate stays the same. Constant Tb is maintained
by physiological and behavioral mechanisms (so ^MR is 0). Below a LCT, metabolic rate
increases exponentially. Increase in metabolic rate above UCT represents a breakdown
in metabolic regulation, shouldn’t be increase while temperature is increases, so going
towards death. Effect of insulation (reduced conductance) on thermoregulation ecology
(on a graph of metabolic rate versus environmental temperature), is that COLD-
ADPATED with greater insulation has a lower LCT; C is reduced (increase in
temperature gradient less metabolic change), but lower UCT. TEMPERATE ADAPTED
with lower insulation has a higher LCT and UCT. Body size also affect conductance:
increased size, decreased surface area per volume/body mass, decreased conductance.
Endotherms rely on metabolism and ectoderms rely on conduction and convection and
radiation for sources of heat gain. Metabolism is change in activity,
conduction/convection is change in insulation, change in physiology and movement in
environment, radiation is movement in environment and evaporation is change in
physiology. Behavioral strategies for reducing heat loss in cold environments include
HUDDLING (which reduces surface area exposed to cold to limit heat loss, i.e. penguins),
BURROWING (ground below a certain depth doesn’t freeze), and, in human populations
BODY SHAPE (artic dwellers have higher body mass index, more fat, more squat,
compared to long slender, lower BMI in tropical regions). CULTURE allowed dispersal
of human population, clothing, fie and shelter was key to biogeographically dispersal of
early Homo from African origin. In response to exercise heat load and life in hot
environment, humans sweat profusely. Sweating is a highly effective evaporative heat
loss but works well only with exposed skin without hair (convection facilitates
evaporative heat loss, enhanced by upright bipedal posture). Necessarily causes
dehydrating, but there is much importance of maintaining fluid and electrolyte balance
during exercise, particularly in hot-dry environments. Humans sweat because heat
dissipation via nasal respiratory evaporation is lifted. Dogs don’t sweat (fur) but have
ability to lose substantial heat via nasal and oral evaporation, or PANTING to cool their
brain and body, which is also true of desert adapted animals and for exercise heat loads.
There are 3 EXCRETORY SKIN GLAND TYPES, ECCRINE SWEAT GLANDS (independent
of hair follicles, which are the main source of sweat production, loss of dilute water but
NaCl loss), SEBACEOUS (associated with hair follicles) and APOCRINE (secrete
moisturizing oils and fluid to keep skin and hair supple, also contribute to body odors
associated with sexual attraction/stimulation). What was the basis for evolutionary hair
loss in humans? Sexual selection for mate attraction, reduction of ectoparasites and
increased heat loss (upright in a warm environment). Hair los co-evolved with the
evolution of eccrine sweat glands in humans, and presumably their hominid ancestors.
Human running endurance and sweating is linked to PRESISTENCE HUNTING, large
animals, middle of the day is peak heat, running above animal’s trot/gallop transition
speed, combination of running/chasing and walking/tracking, 10-25 km is usually
 sufficient to drive prey into HYPERTHERMIA (past upper critical temperature). We
don’t know when humans became mostly furless but probably by genus homo.
 SUMMARY: Heat balance is required for maintaining a constant body temperature
(which is important for stabilizing metabolic reaction rates with heat balance equation).
Mammals (humans) and birds are endothermic, maintaining a constant elevated Tv
through metabolic heat production, which facilitates heat loss. Hypothalamus regulates
Tv via thermo sensory neurons that sense blood temperature the head (and brain).
Constant Tb is achieved through physiological and behavioral mechanisms (ectothermic
animals rely on external sources of heat gain, i.e. solar radiation). Heat flow depends on
conductance and temperature gradient between the body and surrounding
environment (larger size and greater insulation reduce heat loss relative to metabolic
heat production). Humans sweat via eccrine glands to dissipate exercise and
environmental heat loads, linked to the evolution of hair loss and upright bipedalism (in
contrast, many other mammals rely on respiratory evaporation to cool their brain and
body).

LECTURE #32: REPRODUCTION I

 OUTLINE: Evolution of reproduction; anatomy (male and female); physiology

(hormonal regulation); copulation  conception; variation amount reproductive
systems; reproductive ecology.
 ASEXUAL REPRODUCTION is the primary form of reproduction for single-celled
organisms (characteristic of most of the history of life on earth), with and without
nuclei (i.e. Achaea, bacteria, protists, some plants and fungi as well). Daughter cells
inherit genetic material from a single parent cell, so functionally clones. Asexual
reproduction is effective and efficient. SEXUAL REPRODUCTION is the primary form of
reproduction for multi-celled organisms. Combination of genes of two parents
minimizes the accumulation of deleterious mutations and produces much more
variation among progeny. Natural selection acts upon heritable variation leading to
ADAPTATIONS. Asexual reproduction leads to adaption too, but in sexual there is more
variation each generation upon which selection can act. In males, under the influence of
TESTIS DETERMINING FACTOR (TDF), a product of the SRY gene (SEX-DETEMRINING
REGION Y), the migrating germ cells in a male associate with the inner, medullary
portion of the sex cords, making organization. Then, these join to the Wolffian duct
system to form the seminiferous tubules, rete testis, epididymis and vas deferens of the
male reproductive tract, under direction of TDF. Sperm cells will eventually be shed
into this duct system in the interior of the gonad. In the absence of TDF, the germ cells
associate with the outer, cortical portion of the sex cords, which produce clusters of
GRANULOSA CELLS to surround each OOGONIUM (primordial oocyte). These
primordial follicles remain in the cortex of the gonad and will potentially be shed to the
exterior of the organ in ovulation. In GAMEOTOGENSIS, the chromosomes in MEIOSIS
undergo a recombination, which shuffles the genes producing a different genetic
combination in each game. The outcome of meiosis is four genetically unique haploid
cells (compared with the two genetically identical diploid cells produced from mitosis),
going from prophase I to anaphase II. SPERMATOGONIA and OOGONIA are mitotically
active. PRIMARY SPERMATOCYTES and OOCYTES have begun meiosis I. SECONDARY
SPERMATOCYTES and OOCYTES have complete meiosis I and begun meiosis II.
SPERMATIDS and OOTIDS have complete meiosis. SPERMATOZOA and OVA are
potentially ready for fertilization. Female birds and mammals have a finite oocyte
supply established early in fetal life. After that point the number of FOLLICLES declines
exponentially through ATRESIA. Any individual female who lives long enough will
outlive her egg supply. Humans do this regularly, as do many domestic species.
Menopause is unique to humans, unique endocrine, because of extended lifespan after
reproducing, unique among other mammals. Body does not shut down as abruptly.
Other primates usually die before exhausting their egg supply in the wild. Males don’t
start reducing sperm in quantity until puberty and continue to produce gametocytes
through mitosis until late in life (females peak in fetal development, density of follicles
dramatically declines). There are specific attributes of the environment that influencing
timing and development of sperm. Humans versus chimp ovary density are parallel in
slope, but humans have more follicles. Aspects of reproductive are under both
sympathetic and parasympathetic system. Route sperm take is fairly long and
circulating (going up and around bland). Within seminiferous tubules, cells nurse
primordial cells, maturing as they migrate in and combined with tails to become
functional sperm. (1) Basal lamina, (2) spermatogonia (3) spermatocyte (1st and second
order) (4) spermatid (5) mature spermatid (7) sertoli cell (8) tight junctions, shape
change and combination with tails for locomotion and can be mobilized at time of
copulation. Sertoli cells are on inside, leydig cells on outside. NUCLEUS contains DNA
material to combine with egg at conception, ACROSOME in head forms central role in
conception, MTIOHONDRIA provides energy for swimming to encounter egg, TAIL for
forward proportion. Sperm cells can be inideal by being giant, micro, two heads, two
tails, long head, rough head, and abnormal middle with subpar energy. Sperm motility
and shape issues contribute to difficulty in conceiving. Ovaries and testes have many
features of anatomy and physiology in common (originate from same development):
cooperation between cells inside and outside a BASEMENT MEMBRANE; outer cells
respond to LUTEINIZING HORMONE (LH) produce TESTOSTERONE (LEYDIG CELLS in
males, THECA CELLS in females); Inner cells respond to FOLLICLE-STIMULATING
HORMONE (FSH), nurture gametes, secrete inhibit (SERTOLI CELLS in males,
GRANULOSA cells in females); Once established, gamete maturation can proceed on
steroid supposed without much FSH. Hypothalamus secretes GONADOTRIPIN
RELEASING HORMON (GnRH), stimulates pituitary to release FSH and LH, enter blood
system, travel gonads in HYPOTHALAM PITUARY GONADAL AXIS (ordinates are same
as HPA but targets different). FSH and LH bind to receptor in ovaries, uterus and testes.
In males, LH communicates with LH receptor, Leydig cells release testosterone. FSH
communicates with sertoli cells on inside to release INHIBIN. These are under negative
feedback. In females, FSH communicates with Granulosa cells, LH communicates with
Theca cells, stimulating release of androgen and communicate with granulose which
facilitates oogenesis. INHIBIN has a negative feedback with FSH only. Estrogen has
negative feedback on FSK and GnRH. Midway through cycle, several follicles with be
stimulated by FSH in a competition to grow and release an egg, biggest winning,
releasing egg and follicle becomes CORPUS LUTEUM to release progesterone and
preparing uterus to receive egg in case of conception. Selection of dominant follicle is
 by: FSH stimulates granulosa cell proliferation, granulosa cell proliferation stimulates
estradiol production and inhibits production, estradiol production stimulates follicle
growth and oocyte maturation, inhibin production stimulates FSH suppression. The
first follicle to reach critical size produces enough E2 (estradiol) to support its own
growth, produces enough inhibit to suppress FSH, and thereby inhibits further growth
of smaller follicles. (1) If E2 crests at a high enough level it releases a surge of stored
LH; (2) the LH surge cause an extrusion of the ovum by the follicle; (3) the LH surge also
causes the follicle to be transformed in to a corpus luteum with no basement
membrane; (4) the corpeus luteum secretes progesterone in large quantities. After
ovulation, the basement membrane is disrupted, the theca and granulosa cells become
intermingled and in contact with an arterial blood supply, they start to produce
PROGESTERONE in massive quantities, maintaining the endometrial lining of the uterus
in a secretory state into which the blastocyst is implanted. Initial hormone-independent
stage of follicle and oocyte development. Hormonal deregulation contributes to
infertility (i.e. obesity). Various levels of hormones at various times. ESTRUS
SWELLINGS in non-human primates is determined by their hormonal fluctuation,
increase in size as ovulation approaches, signaling reproductive state. Humans have
CONCELEADED ovulation, without overt signal of current reproductive state.
 Ejaculation  cervical canal  uterus  fallopian tube. Of the millions of sperm that
are ejaculate into the vagina, only hundreds reach the fallopian tube, due to (1)
energetic constraints (misdirection until energy burns out), (2) physical and chemical
barriers (acidity of pH, to inhibit growth of pathogenic bacteria) and (3) immunological
barriers (immunoglobin is sensitive to hormonal cycle, attack sperm as foreign bodies).
CAPACITATION are secretions from the female that act upon the sperm in order for
fertilization to occur, (1) changing tail motion from smooth to fast whipping to
penetrate egg and (2) sperm’s plasma membrane is altered to be capable to fuse with
the surface membrane of the egg, acrosome is filled with enzymes that dismantle tissue
to allow insertion of sperm head (dissolving part of the egg surface) and separates form
midpiece. There is a POLYSPERMY BLOCK that the initial fusion of the sperm and egg
plasma membranes triggers exocytosis in cytosolic secretory vesicles at the membrane,
inactivating sperm-binding site and hardening the ZONA PELLUCIDA.

LECTURE #33: REPRODUCTION II

 OUTLINE: Evolution of reproduction; Anatomy (male and female); Physiology

(hormonal regulation); copulation  conception; variation among reproductive
systems; reproductive ecology.
 MALE MOURNING CUTTLEFISH (sepia plangon) mislead conspecifics during courtship
in a specific social context amenable to cheating 39% of the time, but never employed in
other social context. Smaller males deceive larger, rival males by displaying male
courtship patterns (in body colors) for receptive females on one side of the body and
simultaneously displaying female patterns to a single rival male on the other, thus
preventing the rival from disrupting courtship and from attack. In SEAHORSES, can
continually replace eggs (like sperm, no atresia), females transfers eggs to ventral
pouch on male, 2000 fertilizes eggs, reduced sperm, intrapouch fertilization,
impanation is immediate in male pouch, male testes weight is much smaller (less
investment in male reproductive organs). Complete reversal of sexual roles.
ANGLERRISH are benthic; deep-sea fish with lours to attract prey. Male anglerfish have
chemical receptors that cue into the presence of a female, leading male to female that he
starts biting her in arousal, at biting juncture enzymes start to dissolve her skin and his
mouth, causing the two to fuse (analog to acrosome head), blood systems become
intermingled and male receives nutrition from female. Over time, the male consumes
his body (some absorbed by female) until only single pair of gonads that fertilize the
female. This process can happen with multiple males, absorbing multiple males. . Sexual
rose reversal in hyena. Females are larger, more aggressive and dominant to adult
males. Social order by characterized by cooperation and group hunting, leading to
favoring of unique attributes. Female aggression not due to higher TESTERONE levels.
But females have ANDROSTENEDION, a precursor to testosterone, as high as
reproductive males. The highly masculinized genitalia of FEMALE SPOTTED HYENAS
(crocuta crocuta) is unique among mammals. Elongated clitoris and fused vaginas.
Crocuta have no external vagina so urination, penile intromission and parturition take
place through the clitoris, which mimics a fully erectile male penis. Females exercise
absolutely choice with male they mate with. Communal predation so substantial
competition within groups leading to high aggression and infant mortality. If females
could not compete with males they could not receive necessary nutrients for sustaining
reproductive activities due to limited resources. Normal ancestral females underwent
communal predation, which increased feeding, and competition and juvenile mortality,
leading to female dominance and enhanced aggression via androgenization, resulting in
masculine female genitalia and maternal and neonatal mortality through neonatal
aggression. Hyena babies have prolonged gestation, tooth eruption in utero, motor
development and large size in order to be less vulnerable to attack and more
independent and high rates of siblicide if limited food resources. Positive feedback loop
on aggression. 1-2 breeding males with a single breeding female (POLYANDRY).
Because infants are so big relative to maternal size and energetic requirement, MALE
TAMARINS carry and transport infants, relaxing energetic burden on mother, but
transfer infants to females for nursing. Although both males might not have copulated,
still demonstrate significant father tendencies. In Marmosets there is genetic
chimerism. Fraternal twins exchange cell lines through CHORIONIC FUSION during
early development. CHIMERISM was demonstrated to be present in germ line tissues
due to in utero exchanges. Chimeric MARMOSETS often transmit sibling alleles acquired
in utero to their own offspring. Thus an individual that contributes gametes to an
offspring is not necessarily the genetic parent of that offspring. The presence of
SOMATIC and GERMLINE CHIMERISM may have influence the evolution of the
extensive paternal and ALLOPATERNAL, cooperative paternal care, care system of this
taxon. During father, TESTOSTERONE is lower and PROLACTIN is increased. Father
may have lower testosterone while providing childcare (more time providing care,
lower testosterone, unsure directionality) and fathers may have higher prolactin than
non-fathers (also unsure directionality). MANTID MATING CANNIBALISM. If mantids
mount from behind, can’t copulate as long but don’t get eaten; if mantids mount from
front, copulate longer, and are eaten, demonstrates how important energy is for
reproduction. Reproduction is not necessary for survival but necessary for passing
 genes onto next generation. Individuals are not reproducing for survival of the species,
but on an individual level, but energy allocated for reproductive success and
evolutionary fitness. Maternal energy balance during gestation influences the number
of eggs that calves have when they’re born. If you are born with fewer, you may reach
the end of your egg supply at a younger age through decline, limiting your reproductive
success. During follicular development prior to ovulation, the number of simultaneously
developing follicles varies among individuals. If feed was reduced during gestation,
fewer follicles are activated for development. Limits on energy influence egg
development of offspring in utero. Better nutrition (more energy in diet) = Earlier age
of reproductive maturity (across time, population and women within populations),
earlier age of reproductive maturity (MENARCHY) = earlier age of 1st birth, energy
balance = ovarian function. The timing, investment and duration of life stages are
necessarily interrelated, what is happening at time point 1 will influence what happens
at time point 2. Greater access to food has lead to a linear decline of the age of first
menstruation. People living in more energy rich areas, start puberty earlier, later age in
agrarian or non-market goods communities. Usually, the firs few ovulatory cycles
involve release of hormones from the ovaries and shedding of uterine lining but do not
necessary involve the release of egg, EARLY PUBERTAL ONVAL CYCLES, without
sufficient follicular development. Linear relationship between females entering puberty
at younger ages, also conceive and give birth at younger ages. Under conditions of
weight loss, although pattern of reproductive hormones (peripheral progesterone,
estradiol) is same, the amplitude of the hormone is reduced, increased with increased
weight. There is also fluctuation in when infants are being conceived (fewer resources,
losing weight, less likely to conceive, more with weight gain). Differences are due to
differences in hormonal cycling, not rates of copulation. Timings peaks and depressions
with hormones that are necessary for ovarian function and uterine development, so
deregulation is disruptive. Being in negative energy balance reduces hormonal
regulation of ovaries. After birth, females have LACTATIONAL AMENORRIA when
ovaries are not cycling. During postpartum resumption of ovarian function, PROLACTIN
is critical for milk synthesis, and ovarian function is suppressed during lactation, thus
prolactin should be an ovarian suppressor but not necessarily. If you are gaining weight
while you are lactating, Prolactin will remain high but you will resume ovulation
because it is energy signaling of resources to allocate that determines cycling, number
one constraint is length of reproductive career and number of offspring we have (can
afford to be pregnant and lactating at the same time). Male mating efforts consist of
sperm production, muscle mass, and sex drive and male-male competition, all driven by
testosterone. Higher testosterone, more muscles, needs more energy. IN competition,
winners have higher testosterone soon after match, declines at same rate, but winners
are higher longer after match (losers is lower than starting).

LECTURE #34: FEEDING AND DIGESTION

 OUTLINE: Basic components of the GI tract; heat increment of digestion; embryology;

oral cavity (evolution, feeding and chewing); stomach; liver/pancreas; small and large
intestines; the appendix.
 The map of the digestive system or DIGESTIVE TRACT includes the BUCCAL CAVITY,
PHARYNX, and ALIMENTARY CANAL. This is essentially a tube through the body with
two openings. The alimentary canal is divided into the esophagus, stomach and
intestines. Many vertebrates have a CLOACA at some point in development, a common
opening for urinary, reproductive and digestive materials. The MOUTH receives food
and contains teeth and a tongue that manipulates food and monitors quality.
Mechanical digestions by teeth that tear and crush food into smaller pieces and
enzymes where digestion of carbohydrates begins. The PHARYNX is the area that both
foods and air pass through (no digestion). The ESOPHAGE is the tube that transports
food from mouth to stomach (no digestion). The STOMACH is a J-shaped muscular sac
for food storage. Mechanical digestion is churning of stomach that mixes food with
gastric juice creating fluid CHYME, chemical digestion is when protein digestion begins.
The SMALL INTESTINE is a log tube where digestion is complete and nutrients are
absorbed. Mechanical digestion is when segmental contractions mix food with
INTESTINAL ENZYMES, PANCREATIC ENZYMES and BILE, chemical digestion complete
carb, protein and fat digestion. LARGE INTESTINE is the final tubular region of GI tract
that absorbs water and ion, houses bacteria and forms/expels feces, with some
chemical digestion carried out by bacteria. ANUS is the terminal outlet of digestive tract
(no digestion). In the mouth, salivary amylase produced by salivary glands breaks down
polysaccharides into shorter molecules. In the stomach pepsin produced by the
stomach breaks down proteins into protein fragments. In the small intestine, secreted
by the pancreas, trypsin and chymotrypsin break down proteins and polypeptides into
smaller fragments, amylase breaks down polysaccharides into disaccharides,
carboxypeptidase breaks down polypeptide into amino acids, lipase breaks down
triglycerides (fats) into fatty acids and glycerol, and nucleases (deoxyribonuclease and
ribonuclease) breaks down DNA or RNA into nucleotides. In the small intestine,
secreted by the small intestine, maltase breaks down maltose in glucose units, sucrose
breaks down sucrose into glucose and fructose, lactase breaks down lactose into
glucose and galactose, and aminopeptidase breaks down peptides into amino acids.
 DIGESTION is a chemical process based on acid produced by the stomach, not just the
mechanical breakdown of food into smaller particles. Digestion of food and absorption
of nutrients are accomplished in a long tube connected to the external world at both
ends, secretion and motility in the tube are major themes in understanding the gut. IN
the later development of the digestive tract (after development of endoderm), the buds
off the GI tube form organs and he germs layers transition within the mouth cavity. The
four major processes carried out by the GI tract: DIGESTION (food are broken down
into smaller and smaller pieces), SECRETION (fluids synthesized and secreted),
ABSORPTION (energy extracted), and MOTILITY (movement and specialization).
Digestive tract is capability of a lot of change associated with digestion of food, resulting
in metabolic increase. SPECIFIC DYNAMIC ACTION (SDA) or HEAT INCREMENT of
feeding is the increase in metabolic rate that occurs after feeding. In humans, this
increase is typically about 10-20%, in some other animals it can be very large (about
200+%). Active GI tract (movement, synthesizing) requires. The increase in metabolic
rate, reflected by an increase in oxygen consumption, associated with the many cellular
processes involved with digestion, absorption, transport and assimilation of ingested
food. This THERMIC EFFECT or POST PRANDIAL INCREASE of food accounts for about
10% of our total energy expenditure per day. This is best observed in animals that eat
infrequent, large meals (i.e. snakes, one of functions of venom is injecting prolytic
enzymes into circulatory system which help to break down prey from inside out). The
FACTORIAL INCREASE of snakes is much more than mammals, from fasting levels to
peak levels of feeding, as well as increase in mass of organs upon feeding. Example of
regulating extreme changes. The functions of the heat include acquisition, chewing and
swallowing of food. We have a relatively simple head mechanically (complex motions in
restricted framework). Major evolutionary patterns to feeding system evolution in
vertebrates: (A) FILTER FEEDING (closes early evolutionary ancestor, elongated body
of amphioxus, capture food using tentacles, movement trough tract via villi), (B)
SUCTION FEEDING (in fishes the head expands to generate movement of water that
brings prey into the mouth, very versatile in terms of abilities to capture various prey in
water environment), (C) TONGUE BASED PREY CAPTURE SYSTEM (terrestrial system,
mucus laden tongue, tongue extended, air is less viscous than water, most lizards
without teeth to breakdown and swallow whole), (D) COMPLEX TEETH WITH
CHEWING (cusps, mammals have relatively few mechanical degrees of freedom
compared to other vertebrates, humans are relatively simple (no shearing, or bone
cracking)). From an evolutionary and historical perspective your diet is bizarre. We
spend much less time feeding than other species (even primates), even varying between
groups of humans, and also less time chewing or processing food. Muscles of
mastication move the MANDIABLE, with four major ADUCTORS or jaw elevators (series
of muscles to move up and down, side to side, rotate and twist, teeth must come into
OCCUSIAN where teeth must interact): the TEMPORALIS (side of vault  coronoid
process), MASSETER (zygotic arch  angle of mandible), MEDIAL PTERYGOID
(pterygoind wings inside of mandibular angle), and LATERAL PTERYGOID (side of
vault  mandibular condyle). In the ORAL CAVITY breaks down food and mixes in
saliva by CHEWING, has 3 pairs of SALIVARY GLANDS secrete into the oral cavity, wets
food for TASTE BUD sensory input and lubrication, and carbohydrate digestions starts
with AMYLASE from the salivary glands. Coordinated contraction and relaxation
(voluntary then involuntary) in the upper ESOPHAGEAL SPHINCTER, the ESOPHAGUS,
and the lower esophageal sphincter is necessary to deliver swallowed food to the
stomach. The esophagus is also lined with MUCUS CELLS and exhibits PERISTALISIS to
move food into the stomach. Specialized cells in the STOMACH synthesize and secrete
MUCUS, ENZYME PRECURSORS, HYDROCHLORIC ACID and HORMONES. The mixture of
small food fragments and HCl leaving the stomach is CHYME. Abundant smooth muscle,
three layers oriented in a different direction, in the stomach wall is responsible for
gastric motility, allowing the stomach to churn and mix food with digestive secretions.
CHIEF CELLS, within holes in stomach, synthesize and secrete the protease precursor
(cannot make a digesting enzyme within cells) known as PESINOGEN (converted and
activated by HCl). PARIETAL CELLS synthesize and secrete the HCl responsible for the
acidic pH in the gastric lumen. The SMALL INTESTINE is signaled that food is coming,
has three major parts for final breakdown and food absorption of particles:
DUODENUM, JEJUNUM, and ILEUM. The completion of protein fat and carb breakdown
into subunits that can be absorbed by intestinal cells. The GALLBLADDER and
PANCREASE empty into the small intestine and produce BILE, BICARBONATE (to
neutralize stomach HCl) and trypsin. It has had a very large surface area for and is
major location of absorption of nutrients, where mixing and peristalsis occurs. The
MUCOSA is a mucous membrane that lines the GI tract and secretes mucus that
lubricates and protects the GI tract. The SUBMUCOSA is a layer of connective tissue that
contains blood vessels, lymph vessels and nerves. The MUSCULARIS is made up of two
layers of smooth muscle (autonomic innervation), one circular and one longitudinal.
The SEROSA is a connective tissue covering that secretes a fluid to lubricate the outside
of the GI tract for facilitate movement of peristaltic transfer. The small intestine also has
absorbing and mucus secreting cells, VILLI with MICROVILLI with big surface area for
absorption, and capillary and lymphatic vessels. The VILLI project into the INTESTINAL
LUMEN. TIGHT JUNCTION between adjacent cells are important in the GI tract,
separating the lumen and blood sides, forcing fluid in lumen to pass through the cell via
absorption and preventing bypass (also in KIDNEY). Both the large and small intestines
contain glands, but only the small intestine contains villi and microvilli. The LIVER is
wrapped in a tough fibrous capsule divided into lobes, is the largest visceral organ
storing gat and glycogen, performs many essential metabolic and synthetic functions
(i.e. detoxifying), secretes bile (stored in gallbladder) contain salts that aid in fat
breakdown and absorption, and secretes bicarbonate into bile neutralizing stomach
HCl. In the HEPATIC PORTAL SYSTEM, one capillary bed flows into another capillary
bed via veins before returning to the heart. The GALLBLADDER hormonal signal
pathway, stores BILE made in the liver, absorbs salts (to make FAT GLOBULUES fro
absorption) and alters to concentrate bile, and contracts to release bile into the
duodenum. The LARGE INTESTINE or OCLOR stores waste matter, has 4 major sections,
has a larger diameter and thinner wall than the small intestine, wall of colon forms a
series of pouches HAUSTRA (storage for fecal matter), haustra permits expansion,
absorbs water and salts, and elongation often colon also does some absorption of water
and slat but little else. The APPENDIX is a specialized organ for harboring symbiotic
bacteria essential for health, reservoir to recolonize digestive tract after diarrhea cleans
it out (possible positive selection).