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Learning Objectives: 1) Define the components of the CNS and PNS. CNS: Brain and spinal cord. PNS: All peripheral nerves. (Dorsal and ventral rami and everything lateral; cranial nerves.) 2) Describe the differences between the somatic and autonomic nervous system. Somatic: Innervates limbs and structures of body wall. Autonomic: Innervates internal organs, smooth muscle and sweat glands. 3) Describe the gross morphological features of the spinal cord.
Dorsal
Ventral Blue nerves: Sensory Dorsal horn: Sensory Red nerves: Motor Ventral horn: Motor
4) Know the nerve components found in a primary ramus based on the tissue it innervates (i.e. muscle or skin)
5) Know the nerve components of a dorsal vs ventral root. Dorsal Root: Somatosensory neurons Ventral Root: Somatomotor neurons Dorsal Root Ganglion: Somatosensory neuronal cell bodies
6) Define a dermatome: Answer: The area of skin innervated by the SENSORY fibers of a single spinal nerve.
Blue and red path is a voluntary response. It is processed in the cerebral cortex. Yellow path is a non-voluntary spinal reflex. An efferent signal is sent by the spinal cord before the afferent signal is processed by the brain.
a. b. Simple clinical scenarios (see question 3) 2. Define feedback regulation and its importance in homeostasis a. Feedback regulation= controller. Aka, a mechanism that uses the results of a process to regulate the rate at which the process occurs i. InputPlantOutput Controller ii. Input example: brain senses thirst, vasopressin released iii. Plant: kidneys, where vasopressin acts (In general, a plant accepts an input and makes it an output) iv. Output: low volume high osmolality urine produced NOTE: For this lecture, ECF constituents= output v. Controller: kidneys, which no longer stimulated NOTE: For this lecture, nervous and hormonal systems that act on a plant to regain homeostasis b. Importance to homeostasis: feedback control is responsible for specific normal ranges of ions, amongst other important functions in the body that keep us alive 3. Define the main organ systems responsible for rapid and for long term homeostatic regulation of each of the following: plasma sodium/volume, plasma potassium, plasma pH, plasma osmolality (For efficacy, I have combined objective 1 in here, regarding simple clinical scenarios) a. Rapid response in homeostasis (this fuses with the next lecture on acids and bases) i. ECF buffering: bicarbonate, proteins, etc. (fastest) ii. IF buffering: bone, protein, organic and inorganic phosphates (2nd fastest) b. Long term homeostasis i. Respiratory compensation (in minutes, not seconds, so its not really long term, but its not the mere seconds of the previous two) ii. Renal adjustment: takes days to reach full efficacy
Which organ systems at work Cardiovascular system (to sense changes), renal, brain (thirst response) Cardiovascular system (to sense changes), renal, brain (thirst response)
Atria stretch receptors release atrial natriuretic peptide inhibit renal Na+ and volume reabsorption increased output (slow)
OR
Na+
Dietary Na+ sensed in GI tract factors releasedincrease urine Na+ excretion (fast) Cardiovascular stretch receptors and baroreceptors sense decreased Na+
Nervous signals simulated, increasing Na+ retaining hormones angiotensin II and aldosterone (fast) Increased sympathetic nervous system outflow to increase Na+ and volume reabsorption by kidney
Hyponatremia <138 mM
(slow) K+ Muscle and renal Increased insulin increases Na+ pump activity in muscle and fat K+ pumped into ICF (fast) OR Increased K+ secreted into urine via K+ channels and increased aldosterone (which increases K+ channel activity) (unsure) Increased renal K+ reabsorption and transfer of K+ out of muscle ICF into the ECF (slow) ECF buffering decreases CO2 (hyperventilate) (slow) OR Kidneys increase net acid output and increase reabsorption of HCO3 for further ECF buffering (slow) ECF buffer increases CO2 (hypoventilate) (slow) OR Decrease renal acid output and decrease renal HCO3 reabsorption (slow) Osmoreceptors release vasopressin from pituitary produce low volume high osmolality urine (slow) Osmoreceptors also stimulate thirst (fast) Lack of vasopressin production of high volume dilute urine (unsure) Hyperkalemia >5 mM
K+ H+
H+
Alkalemia >7.4 pH
Osmolality
Osmolality
Dehydration, profound sweating <280 mOsm/kg Too much water or beer, >290 mOsm/kg
there it is.
3. Explain the unique role of the CO2- HCO3- system in regulating body fluid pH a. CO2 + H2O H2CO3 HCO3- + H+ b. why is this is a good buffer
i. [HCO3-] is in great quantity ii. CO2 and HCO3- are well regulated by respiration and renal systems iii. CO2 is volatile, so it readily leaves the body iv. HCO3- is easily removed via renal system or absorbed back c. Conclusion: pH can be quickly and easily be regulated using the above buffer system 4. Learn the changes in blood pH, [HCO3-], and Pco2 that occur in the following uncompensated acid-base disturbances: metabolic acidosis, metabolic alkalosis, respiratory acidosis, respiratory alkalosis a. Acidosis and alkalosis: interplay of respiratory and renal (metabolic) regulation of CO2 and HCO3b. This is different from acidemia and alkalemia, which is the term describing the pH in blood and does not describe whether respiration or metabolism resulted in the academia or alkalemia
pH
[H+]
compensatory response PCO2, respiratory PCO2, respiratory [HCO3-], renal production [HCO3-], renal loss
d. Patterns to help remember this stuff i. metabolic acidosis/alkalosis is compensated via respiration regulation, and vice versa ii. if [HCO3-] is disturbed, it is compensated by PCO2, and vice versa 5. Explain how the kidney compensates for acid-base disturbances induced by the respiratory system, and how the respiratory system compensates for metabolic disturbances a. Respiratory acidosis- caused by hypoventilation or lung diseases that decrease respiration rate i. Kidneys secrete and excrete H+ b. Respiratory alkalosis-caused by hyperventilation, hypoxia, pain, or hysteria i. Kidney will attempt to hold onto HCO3 c. Metabolic acidosis- caused by diarrhea, diabetes, renal failure i. Lungs will reduce pCO2 breath faster d. Metabolic alkalosis- caused by ingestion of strong base or loss of acid (vomiting) i. Reduced breathing
c.
Epidemiology 1
Prevalence The proportion of people who have the disease at a given point in time=(Diseased)/(Total Population) Example: There are 180 medical students in class today. 18 have cholera. Therefore, prevalence=18/180=0.1 of the population is sick Units: number of sick people over total population Cumulative Incidence The proportion of cases that develop over a specified period of time. Example: There are 180 medical students. In the next year, 36 develop anality retentiveness. Therefore, the cumulative incidence of anality retentiveness is (36 new cases)/(180 total people)=0.2 Note: The study population at risk (denominator must be free of disease). Example: There are 180 medical students. 120 of them already have anality retentiveness. In the next year, 15 develop anality retentiveness. Therefore, the cumulative incidence of this population is (15 new cases)/(180-120 students without disorder)=15/60=0.25. Units: number of new cases over population without disorder over a certain amount of time. Incidence Rate The rate at which individuals develop a disease in a population. Person-time is the total amount of time all subjects contribute to the study. Example: 120 students are followed for 1 year, 30 students are followed for 2 years, and 50 students are followed for 3 years. Therefore, total person-time=120(1 year)+30(2 years)+ 50(3 years)=330 person-years. When calculating person-time, the people who get sick are considered to have served only half the amount of time. Example: Let's say you a have a study spanning one year and 10 people get sick. On average, half of these people will have gotten sick before the halfway point and half after so that they average out. So each person would have contributed an average of 0.5 person-years. Therefore, total person-time=10(0.5 years)=5 person-years. Units: number of new cases over population without disorder over a certain amount of time or number of new cases per person-time Mortality Rate
A measure of the rate at which individuals in a population die over a specific amount of time. Example: 200 people are followed over the next year. 30 of them die. Mortality rate=30/200 person-years Cause-Specific Rates The number of new events over a specified amount of time. Example: 180 medical students are followed over 2 years. 60 develop cholera. The cause-specific rate is 60 new cases/[120(1 year)+60(0.5 years)]=60/150 person-years. Sex-Specific Rates Event rates within gender. Example: In a class of 180 medical students, 75 are women and 105 are men. Over the next year, 10 women develop cholera and 20 men develop cholera. Therefore: Sex-specific rate for women is 10/[65(1 year)+10(0.5 years)]=10/70 personyears. Therefore: Sex-specific rate for men is 20/[85(1 year)+20(0.5 years)]=20/95 personyears. Race-Specific Rates Same as sex-specific rates but with race used instead of sex. Case Fatality Rate (not an actual rate) The proportion of people who die from a specific disease. Example: There are 180 medical students. 50 develop anality retentiveness. 40 die from it. The case fatality rate=40/50=0.8 Proportional Mortality The proportion of deaths attributed to a specific cause. Example: A medical class had 100 deaths in 2008. 40 were caused by anality retentiveness. The proportional mortality of anality retentiveness in 2008 = 40/100=40%. Crude-Rates vs. Age-Adjusted Rates Crude rates measure the total amounts of death while age-adjusted rates stratify by age. See PM 4-8. The age-adjusted rates for 1990 are lower than for 1960 but the crude rate is higher. Simpson's Paradox! Annual Rate
Miscellaneous Incidence rates are more helpful when studying the etiology of the disease. An incidence rate could show a change in causative factors of the effect of a preventive program. Prevalence is more helpful when planning public health programs. A change in prevalence could reflect a change in incidence rate, a change in duration, or a change in immigration/emigration rate of sick people. Relationships
Incidence Rate * Time = Cumulative Incidence Prevalence = Incidence Rate * Average Duration of Disease
o o o o
Career aspirations vs. achievements Relationships in the middle & feeling pressure from spouse, children, parents Social divorce Financial pressures saving for kids, retirement
4. Discuss the relationship between age and timing regarding smooth vs tumultuous transitions in adult development. Unexpected events may or may not invoke crisis depending on timing Age norms and expectations change with society, and timing of these changes may impact development Biological early puberty can be difficult, particularly for females Social young adults waiting longer to enter job market, women choosing to postpone marriage & having kids Midlife crisis may arise if o Dramatic emotional upheaval & turmoil for individ or others o Abrupt changes o Limited insight o Person feels unwell 5. Discuss the major biological, psychological, and social issues characteristic of early, middle, and late adulthood Early adulthood o Biological: peak of biological development o Psychological intimacy vs isolation (see #2) o Social assumption of major roles (education, job, marriage, parenthood) Middle adulthood o Bio climacterium (decreased bio fxn) o Psycho Generativity vs stagnation (see #2) o Social re-evaluation of roles Relationships, family, career Midlife transition vs crisis Late adulthood o Bio aging o Psycho integrity vs despair (see #2) o Social economics, retirement, social/sexual activity Vulnerable to stress & dealing with loss
2.
3. 4.
Apoptosis: mito releases cytochrome c and activates a caspase cascade to induce apoptosis *NOT the same as necrosis (inflammation, uncontrolled release of cell contents) Other: Inner membrane is impermeable to small ions Tubular and can form networks Acetyl CoA Citric Acid cycle ETC (ATP synthase) Mt protein import (general): proteins contain mt targeting sequence 1. Proteins bind the TOM and TIM (transfer protein of outer/inner mitochondrial membrane) and binding allows import into mito 2. There are also secondary sequences which target inner membrane, intermembrane space, outer membrane Identify peroxisomes and mitochondria in electron micrographs. Compare and contrast the structure, function, and genetics of peroxisomes and mitochondria. Peroxisomes 0.5-1m Lipid bilayer; single membrane Granular matrix; oxidase, catalase Nonhumans have a nucleoid structure in the middle (big black spot) Biosynthesis (bile acid, cholesterol, myelin) Detoxification of alcohol and purines oxidation of fatty acids (very long chain) breakdown H2O2 Binary fission replication Membranes from the ER No endogenous DNA biogenesis disorders are more severe Neurological myelination diseases Zellweger syndrome (no peroxisome; buildup of very long chain fatty acids) X linked adrenoleukodystrophy (no fatty acid transport into peroxisomes) Mitochondria 0.5-10m Inner membrane (cristae etransport) Outer membrane Intermembrane space (high H+) Matrix: mtDNA, ribosome, tRNA, TCA enzymes ATP synthesis Ca homeostasis Regulation of apoptosis oxidation of fatty acids Binary fission replication Inherited from egg (gamete) mtDNA (can have defects) autosomal mtprotein defects Mt enzyme deficiency Mitochondrial DNA defects Autosomal DNA defects for mt proteins Lebers hereditary optic neuropathy (loss of central vision, affects mostly males, optic nerve degeneration)
Structure
Function
Genetics
Disease
5.
Identify maternal inheritance by pedigree analysis; explain how mitochondrial diseases can be maternally or autosomally transmitted; explain heteroplasmy. Maternal inheritance: Mitochondrial DNA defects (13 mt proteins, 22 tRNA, 2rRNA) Autosomal inheritance: nuclear DNA defects that code for mt proteins Heteroplasmy: mixture of mutated and normal mitochondria redistribute unevenly during development, so this is the occurrence of cells having different mitochondria and may occur within one individual Eg: Lebers hereditary optic neuropathy (loss of central vision, affects mostly males, optic nerve degeneration because not enough functional mito produce energy to maintain cells)
germ layers (pluripotency). Progenitor cells have a limited number of divisions and do not maintain their ability to self-renew, are considered to be at a further stage of differentiation than stem cells, and are more limited in the variety of cell types into which they can differentiate (multipotency or oligopotency).
*Note: These two terms are sometimes used interchangeably, and the distinction between the two is still contested, since some stems cells (ex. adult stem cells) are also only multipotent, oligopotent, or unipotent. The best criterion to go by for distinguishing the two seems to be the self-renewal aspect, which is exclusive to stem cells.
3. Distinguish determination and differentiation. Differentiation = the process by which different, specialized cells (morphologically, biochemically and functionally) arise from a homogeneous group of unspecialized cells. Determination = the commitment of a cell to differentiate into a certain cell type at some later time. Determination generally occurs as a step (or a series of steps) that is prior to, and separate from, differentiation. Cells can be determined a long time before they differentiate (at least by histological criteria). Two major ways that cells can become committed are by: 1) possession of special cytoplasmic determinants localized within the egg or early embryo, and 2) interaction with other cells or the factors secreted by other cells. Cytoplasmic determinants are components localized to a particular region of the egg or embryo that, when segregated to a cell or cell lineage cause those cells to become determined, i.e., to adopt a particular cell fate.
First column: Normal pattern of differentiation; cells in region A differentiate into one type of cell, cells in region B into another type Second column: Sample of region B cells labeled and transplanted into region A early on, before they have become determined transplanted cells differentiate into region A type cells Third column: Sample of region B cells labeled and transplanted into region A later on, when they are already determined transplanted cells differentiate into region B type cells [Fourth column is not relevant to this objective, but is basically demonstrating that region B cells that are specified (specification = early, reversible/changeable step of determination, so not fully determined) will still differentiate into region B type cells in an isolated environment.]
4. Explain the potency of stem cells and understand it in the context of differentiation stages. Cell potency = amount of differentiation potential; the following are listed from least differentiated stage (have the most differentiation potential) to most differentiated stage (have the least differentiation potential) Definition Can differentiate into any cell type (ectoderm, mesoderm, and endoderm) as well as extra-embryonic tissue such as the placenta Can differentiate into any cell type (ectoderm, mesoderm, and endoderm), but cannot produce full embryo Can differentiate into a limited number of cell types Example Human zygote is totipotent up through the 8-cell stage.
Totipotent
Pluripotent
Multipotent
Can differentiate into very few cell types Can differentiate into only one cell type; however, unipotent stem cells can still self-renew Have fully differentiated
Embryonic stem cells (which originate from the inner cell mass of the human blastocyst) are pluripotent. Progenitor cells; also, hematopoietic stem cells (a type of adult stem cell) can differentiate into various blood cells (RBCs, white blood cells, platelets, etc.) but not other mesodermal cell types. Progenitor cells; some adult stem cells Skin cells
Neurons
differentiated
5. Explain inductive interactions and epigenetic controls in cell differentiation. Induction = process by which surrounding cell or environment guide the cell differentiate process; can be mediated through cell-cell, cell-matrix, or diffusible growth factor interactions; can be instructive (signal itself causes target cell to differentiate) or permissive (cell already committed, induction creates conducive environment for differentiation); timing of induction is crucial (see objective #6 on temporal specificity).
Epigenetic controls contribute to maintenance of differentiation through heritable alterations in chromatin structure (ex. DNA methylation) and transcription factor expression. 6. Draw a diagram that demonstrates the principle of temporal specificity in induction.
7. List the sources of stem cells for use in research and medicine. Type Adult stem cells Embryonic stem cells Pros Easily obtained; no controversy Pluripotent Cons Multipotent or unipotent, so have limited usefulness Political/ethical controversy; potential for aberrations leading to tumor formation during culturing stage (None mentioned in lecture)
Mostly multipotent (peripheral blood stem cells, or PBSCs), but also some pluripotent stem cells; less controversial Derived from nonpluripotent cell, ex. adult skin cells, so also no controversy; can be reprogrammed to regain pluripotency and even totipotency
Chances of aberrations tumor formation in origin cells, and during reprogramming and culturing stages; require more research
Intro to Imaging
MM, GA 3 1. To describe how a plain radiograph (x-ray) is made. Radiography is not like photography Photography reflects photons off of the subject and into camera lens Radiography transmits x-rays through the subject to a film, turning it from clear to black less dense matter appear darker/more dense matter appears lighter Dense matter absorbs more x-ray photons than non dense (radiolucent) Upright chest radiographs are performed with patient facing the film X-rays pass through the patient back (posterior) to front (anterior) PA chest x-ray standard - Posterior anatomy is a bit larger due to beam divergence Right side of radiograph is the left side of the patient 2. To identify the tissue densities seen on a plain radiograph Air, Fat, Water, Bone, Metal Remember: Air - Fat - Water/Soft Tissue - Bone - Metal. Least dense to more dense. darker to lighter 3. To recognize the following normal structures on a frontal chest radiograph (note: dont expect to accomplish this entire objective just from this onehour lecture! You will have opportunities to study examples of normal chest radiographs in you gross anatomy lab.) My Rendition of Objectives a. Heart i. Lateral margin of the right atrium ii. Lateral wall of the left ventricle b. Aortic knob (the radiographic name for the aortic arch) c. Left pulmonary artery d. Right pulmonary artery e. Trachea f. Left mainstem bronchus g. Right mainstem bronchus h. Right lung i. Left lung j. Location of the pleura (its too thin to see) k. Spine l. Ribs m. Clavicle Superimposed From Handout 1. Right brachiocephalic vessels arteries, veins 2. Ascending aorta 3. Lateral margin of the right atrium 4. Inferior vena cava (not always seen) 5. Left brachiocephalic vessels 6. Aortic knob / proximal descending aorta 7. Main pulmonary artery 8. Left atrial appendage (not always seen) 9. Lateral wall of Left ventricle
Intro to Tissues
Dr. Wood 9.1.2011 Generalities: All cells have: -Nuclei,EXCEPT RBCs or mitotic cells -Cytoplasm -Plasma membrane **They may be hard to see, due to abundance or plane or section Common cell shapes: Squamous Cuboidal Columnar Spherical Spindle Stellate When talking about tissues, dont forget to think about the ECM associated with the cells Epithelial tissue -Lines free surfaces, both externally and internally (i.e. skin, sweat glands, GI, kidney tubules) -Supported by connective tissue -Serves as barriers -Cells tend to be tightly packed (look for high density of nuclei) with little ECM -Avascular -Tend to be polarized Connective tissue -Provide structural support for many other types of tissue -Tend to have few cells (sparse density of nuclei) with lots of ECM -Fibroblasts are the most common type of connective cell >Stellate/spindle shape, constitutively secreting ECM (collagen) -Classified as loose (more cells/water, less protein/fibers) or dense (more protein/fibers, less water/cells) -Blood is connective tissue -Also fat, bone, tendon, cartilage Contractile tissue -Specialized for rapid movement, responsive to electrical signals -Striated (cardiac, skeletal) vs. smooth muscle -Voluntary (skeletal) vs. involuntary (cardiac, smooth) -Many tubular structures (vasculature, GI tract) have contractile tissue
*Smooth muscle can often look like connective tissue. Try looking at how many nuclei there are- more nuclei usually signals smooth muscle Nervous tissue -Neurons are large cells responsive for conveying electrical stimuli -Glia are smaller supporting cells (50:50 90:10) -Neuropil is cellular (not extracellular) material between cell bodies- cell processes of glia and neurons Origins of tissues from germ layers Ectodermal Origin Mesodermal Origin Epidermis of skin Dermis of skin
Circulatory (heart, vascular epithelia) Kidney tubule epithelia Skeletal muscle, skeleton Connective tissue Lymphatic systems Excretory system (kidneys and bladder, excluding lining of bladder) Lining of body cavity (mesothelium?)
Endodermal Origin GI (stomach, intestines, epithelial lining) but NOT including muscle layers Lungs and epithelial lining Liver Pancreas Bladder/urethral lining
Epithelium
1) Explain how epithelia establish barriers and control exchange between different environments Epithelium lines the free surfaces of the body, so material (ions, proteins, oxygen, sugars) needing to pass between tissues of the body and luminal spaces (lungs, gut, ducts) needs to pass through the epithelium. Epithelial cells are densely packed and connected to neighboring epithelial cells through: a) Tight junctions: forms a ring around the cell that maintains polarity of transport proteins between apical and basolateral faces. Not anchored by cytoskeletal elements b) Adhering Junctions: forms a ring around the cell, connected to actin c) Desmosomes: Spot welds connected to intermediate filaments This most commonly happens in a transcellular pathway, although there are examples of paracellular transport through the tight and adhering junctions. Because of cell polarity, different transporters on apical and basolateral surfaces can regulate directionality of transport and create downhill gradients across the cell. The apical side of epithelium in the trachea are coated in cilia that facilitate transfer of mucus out of the airway Keratinized stratified squamous epithelium provides a particularly strong barrier with a thick layer of dead, denucleated squamous cells that are continuously regenerated as they are sloughed off. 2) Classify Epithelium based on cell layers and cell morphology Simple Squamous Epithelium: fried egg morphology, can have elongated cytoplasm. (endothelium, alveoli, mesothelium, portions of kidney tubule) Simple Cuboidal epithelium: cuboidal, regular (or just not columnar or squamous) morphologyshape. (kidney tubules and ducts) Simple Columnar Epithelium: Tall cells, usually with apical surface specialization (gut, intestine, respiratory tract, oviduct Stratified Squamous Epithelium: Only top living layer has to be squamous. Usually serves to protect underlying tissue. Can be keratinized (skin cells) or non-keratinized (mouth, vagina, esophagus) Transitional Epithelium: Stratified epithelium that lines urinary system from center of kidney (Renal calyx) to bladder. Allows stretching.
- rounded (bumpy) surface is identifying characteristic Pseudostratified epithelium (Respiratory Epithelium): All cells contact the basement membrane, but not all are exposed to the lumen 3) Explain replacement of epithelium: Determined cells can undergo mitosis to form new cells (liver, endothelium) or stem cells can undergo mitosis and determination (intestines, skin). In stratified epitheliums, the new cells are generated near the basement membrane and migrate to the top as cells are sloughed off. 4) Explain different types of glandular secretion: Merocrine: secretory granule fuses with the PM and dumps it contents into the ECF Apocrine: secretory granule leaves cell where its contents are still enclosed in plasma membrane (i.e. mammary glands secreting milk) Holocrine: Whole cell lyses and dumps contents (ex/ sebaceous gland) Paracrine: Cell releases contents that then signals nearby cells. Commonly, this occurs with signaling molecules that degrade quickly and can thus only act on nearby cells. Autocrine: Cell releases contents that then binds to same cell (B-cells)