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Study Guide Questions Exam #1 1) What is “normal” in terms of biological parameters? What are some examples of sources of variation on “normal.” Sources of variation on “normal” Genetics Age...
Study Guide Questions Exam #1 1) What is “normal” in terms of biological parameters? What are some examples of sources of variation on “normal.” Sources of variation on “normal” Genetics Age ○ HR for 3 y/o is tachycardic for an adult Gender (Sex) ○ Hormone level – testosterone, [estrogen, progesterone] ○ Testosterone = higher RBC count Situational ○ Living at sea level (lower RBC count) vs high altitude (more RBC count) Time ○ Hormone levels Testosterone levels highest in morning Female hormone levels diff based on ovulation cycle Laboratory conditions ○ Every lab has their own reference values based on their tests There is no single value for any biological parameter that is normal. There is a distribution of normal within a population. 2) How has “race” been used in medicine as a source of variation in biological parameters? Why is this problematic? Race: historically used as source of variation in normal values Problematic because the way race is defined does not tie it to something biological Race is self-identified with very broad categories (African American, non-Hispanic, Hispanic) Does not translate to what people think it does ○ BELIEF: People THINK race = ancestry-related genes → r/t variation in biological parameters & disease Ancestry-related genes correspond to only 0.1% of genes differences between ppl ○ Ancestry-related genes represent only minuscule part of genome ○ REALITY: race ≠ ancestry-related genes Race = social category Race is only used as a very poor substitute for ancestry-related genes Medicine ○ Repeatedly weaponized throughout history to justify & rationalize enslavement of black people ○ Still used to obfuscate incidents of racial injustice ○ Used race as sorting tool w/ profound impacts on diagnostics & treatments of disease Inaccurate, not true, and perpetuates idea that individuals in different racial categories are biologically different ○ When in fact, people from different racial categories are biologically the same ○ Reinforces racial stereotypes ○ Leads to bad medicine ○ Implicit bias ○ Use of harmful standards of care that have gone unexamined When we find differences in disease incidence and health outcomes, it is a difference in social determinants (from oppression) → it shows disparities and NOT differences in genetics 1 3) What are the key concepts behind the biology of skin color? (18 min documentary) Skin color primarily determined by amount & type of Melanin (pigment) produced by Melanocytes in skin Melanin 2 types of melanin ○ Pheomelanin (reddish) ○ Eumelanin (black/brown) Packaged into melanosomes that position themselves above nucleus of skin cells Function: absorb UV light (esp. damaging UVB-(UV blue light emitted from the sun that has significant effects on living organisms) to prevent DNA damage Type & amount produced by individuals indigenous to regions (around equator & high altitude) = correlated to amount of UV exposure endemic to that region Individuals w/ more melanin = absorb less UVB = more prone to vitamin D deficiency UVB Too much UVB = breakdown of folic acid in circulation = inc risk birth defects & poor reproductive success Too little UVB = vitamin D deficient = can’t absorb calcium = brittle bones ○ Vitamin D supplements can be taken 4) Define and explain: Etiology, Pathogenesis, and Clinical Manifestations Etiology: cause of a disease Pathogenesis: development of the disease state How the disease affected body function and how the body reacts to it Factors of pathogenesis: ○ Time exposed to injury ○ Quantity ○ Location ○ Morphological changes Etiology → pathogenesis → clinical manifestations 5) What are the terms used to describe the clinical manifestations of disease….how are these terms different? Think of an example of each Clinical Manifestations: clinical observations that are a result of the disease 2 categories ○ Signs: objective; observable, measurable ○ Symptoms: subjective; reported 6) What are the terms used to describe the time course of a disease process? How are those terms different? Think of an example of each? Time Course ○ Latent period: time between injury and time you see s/sx ○ Prodromal period: time when you first see s/sx (usually nonspecific, eg fever) ○ Acute period: time when clinical manifestations most severe. s/sx can be more specific (jaundice) 2 7) What is a differential diagnosis? Differential diagnosis Identifies list of possible conditions or diseased that be causing pt’s s/sxà then narrows down the list via testing analysis and evaluation to most likely or definitive diagnosis ○ Clinical methods s/sx ○ Laboratory methods Urinalysis (fecal analysis) Blood analysis Blood count Blood chemistry Blood culture Serology Tissue diagnosis EKGs Radiology 8) What is meant by the idea: interdependence of cells and systems? How does this relate to the idea of a “cellular basis of disease?” Function of entire organism depends on function of cells Cells are also dependent on larger systems ○ Eg: circulatory system brings O2 to cell to function Cell (smallest living unit) → tissues (epithelial, connective, nervous) → organs → organ systems → organism Cells are found in ECFà maintained by body systems because they don’t have direct access to O2 9) What is Total Body Water? What is it composed of? To what extent does it contribute to body weight? Total body water = ICF + ECF=60% Intracellular fluid (40% body weight) ○ Inside cells ○ Indirect maintained via direct maintained of ECF Extracellular fluid (20% body weight) ○ Environment for cells to fxn ○ Plasma (intravascular; 5% body weight) Intravascular =w/in blood vessels ○ Interstitial fluid (fluid between cells) – third space (15% body weight) Inc Adipose tissue = dec total body water (fat contains little water) In reverse relationship 3 10) Explain the differences in Total body water in relation to body weight by age and gender. What factor contributes the most to these differences? Why? Inc age = lose muscle mass & inc fat = dec total body water Biological male = more lean muscle mass, less fat = higher total body water Biological female = less lean muscle mass, more fat = less total body water 11) How is cell volume controlled systemically? How is it controlled at the cellular level? Cell volume - Swelling- volume to high - Shrinking- volume too low o Both can cause cell death Controlled by water & osmolyte balance (sodium & potassium) ○ Water Balance Any loss or gain of water Primary Gains ○ Water- via consumption alone or w/ food ○ Metabolic processes Primary Loses ○ Urine ○ Feces Significant if person has diarrhea ○ Sweat Controlled by ADH/thirst system (low blood volume = inc ADH) Hypothalamus detects blood conc. à As osmolarity Û¯BVÛ blood conc. Depending on if de- or overhydrate a signal will be sent to promote or decrease the sensation of thirst ○ Dehydration ADH release from posterior pituitary glandà water retention via kidneysà restoration of normal water volumeà hypothalamus shuts off system ○ Overhydration Opposite ○ Osmolytes (sodium & potassium) Controlled by: Renin-angiotensin system (systemically) ○ Maintains Na+ and K+ ○ Liver makes angiotensinogenà SNS trigger by BP change, stress event, or Na fluctuation àkidneys release renin to convert to A1à lungs and kidneys then release ACE to convert A1 to A2. Kidneyà ¯ UOà BP Posterior Pituitary- ADH secretedà water retentionà BP Vascular smooth muscle- vasoconstriction à BP Hypothalamus- stimulates water thirstà water intakeà BP Adrenal cortex- aldosterone secretes (steroid hormone)à water, Na and ¯K+à BP Sodium-potassium ATPase pumps (intracellularly) ○ K inside and Na outside cell ○ Accounts for 50% of cells energy production 4 12) What controls the distribution of fluids between ICF and ECF? What controls the distribution of fluids between the Intravascular and Interstitial compartments? ICF ECF (Plasma/Intravascular + Interstitial) K+ Na+ Mg+ Ca2+ Proteins Cl- HCO! - Major shiftà cell death Distribution of fluids between ICF & ECF Controlled by osmolarity Distribution of fluid between intravascular and interstitial space Controlled by Starling Forces 13) What is capillary bulk flow and starling forces? Explain how they work. Capillary bulk flow Movement of fluid between intravascular and interstitial space Usually occur between capillaries Caused by Starling Forces ○ Passive Forcesà determined by the sum of the forces between cap and interstitial spaces 1. Capillary BP i. Pressure that comes from inside the capillary ii. Pushingà Ultrafiltration (out) 2. Capillary Oncotic (Osmotic) Pressure i. Pressure exerted by plasma proteins in blood that can’t get out cap. ii. Pulling à Reabsorption (In) 3. Interstitial Hydrostatic Pressure i. Pressure that any fluid can exert against any container it is found in ii. PushingàReabsorption (In) 4. Interstitial Oncotic (Osmotic) Pressure i. Only occurs is plasma proteins leak into the interstitial spaces’ b/c of break in capillary wall or acute inflammation 1. Usually, zero ii. Pullingà Ultrafiltration (Out) 5 14) Explain the common causes of Edema. Explain third space fluid accumulation. Accumulation of fluid in the interstitial spaces Decreased plasma oncotic pressure → dec reabsorption ○ Caused by lost or diminished production of albumin Increased interstitial oncotic pressure → inc ultrafiltration ○ Caused by increased capillary permeability or vascular injury → albumin escapes and pulls fluid Increased capillary blood pressure → ultrafiltration ○ Caused by hypertension, venous obstruction (blockage or volume overload) Lymphatic obstruction → impairs clearance of interstitial fluidà causing lymphedema ○ Lymphatic capillaries are neat blood vesselsà to drain excess interstitial fluid to be redistributed into blood Water follows Albumin à albumin has a higher pulling pressure Oncotic = pulling Plasma/Interstitial Oncotic à what is doing the pulling force Third space fluid accumulation Transcellular compartment (body cavities lines w/ serous membranes) ○ Eg: pericardial sac, peritoneal cavity, pleural cavity Cause: imbalance in starling forces Eg: ○ Ascites Cause: hypoalbuminemia (liver failure, starvation) ○ pleural effusion 15) What is isotonicity, hypertonicity, and hypotonicity? Review common causes of each. Conditions affecting ECF Isotonic alterations: alteration to ECF (fluid conc.) but osmolarity between ICF and ECF is same Causes ○ Isotonic volume depletion: hemorrhage, severe wound drainage ○ Isotonic volume excess: excess IV fluids, hypersecretion of aldosterone Hypertonic alterations: osmolarity of ECF elevated due to increased conc of solutes Causes ○ Hypernatremia: inadequate water intake, inappropriate administration of hypertonic saline ○ Water deficit: inadequate water intake, impaired renal conservation of water ○ Hyperchloremia: accompanies w/ excess of sodium or deficit of bicarbonate, excess ammonium chloride diuretic Hypotonic alterations: osmolarity of ECF less than normal due to decrease in solute conc. Causes ○ Hyponatremia: diuretics, vomiting, diarrhea, burns, dilutional hyponatremia (inc [glucose] or [cholesterol] pulls water from interstitial space) ○ Water excess: decreased urine formation (eg renal failure), SIADH (excessive ADH) ○ Hypochloremia: accompanies any deficit of sodium or excess of bicarbonate, vomiting (loss of HCL) 6 16) What factors cause potassium to shift between ICF and ECF? What consequences can that have? Potassium Balance à Change in ECF/ECF pH ○ Acidosis: H+ increases & enters cells → potassium swapped out from cell = inc potassium level (hyperkalemia) ○ Alkalosis: H+ leaves cell & K+ enters cells = dec potassium levels (hypokalemia) Insulin ○ Inc insulin = K+ moves into cell (to produce glycogen) Why? Insulin allows glucose to enter cell to form glycogen. K+ is cofactor needed to convert glucose to glycogen Emergency drug for acute hyperkalemia (+ give glucose) ○ Dec insulin = K+ stays outside cell Catecholamines (dopamine, epinephrine, norepinephrine) ○ Bind to B2 adrenergic receptors = K+ moves into cell E.g.: epi pen shot ○ Bind to Alpha 2 adrenergic = K+ moves out cell 1) What is an acid? What is a base? Acid Compound that can donate an H+ to a solution ○ High concentration of free H+ ions Base Compound that can absorb an H+ to a solution ○ Low concentration of free H+ ions 2) Explain the pH scale. (Acidic) 0 – 7 – 14 (Alkaline) pH = - log [H+] Measure of relative acidity/alkalinity of a solution r/t [H+] in solution 7=neutralà body fluids (Blood, CSF, interstitial fluids) 7 3) What is a buffer? What are the major buffering systems in the body? Buffer Weak acids and weak bases that can absorb excess H+ or OH-, preventing fluctuations in pH Primarily regulated by lungs & kidneys ○ But there are limits to this system Major buffering systems in body Bicarbonate (HCO3- / H2CO3) ○ Primary buffer- most CO2 in the blood is in this form ○ ○ Respiratory-Rapid à minutes to hours RR and depth effects PCO2à effects availability of CO2 for H2CO3 production Tachypneaà CO2 releaseà¯PCO2à ¯H2CO3àpHà alkalosis Bradypnea à¯CO2 releaseàPCO2à H2CO3à¯pHàacidosis ○ Kidneys- Slowà hour to days Regulates plasma levels HCO3- and H+ by controlling HCO3- reabsorption and H+ excretion via the urine Hemoglobin (Hb- / HHB) Proteins (Pr- / HPr) (both intracellular & extracellular) Phosphate (HPO4= / H2PO4-) ○ Form of energy (ATP) Mass action- the number of products on hand determine the direction of the reaction 4) What are the differences between and causes of respiratory vs. metabolic acidosis/alkalosis? Respiratory acidosis causes: Hypoventilation or poor gas exchange (accumulation of CO2 & carbonic acid) ○ Ex: COPD Respiratory alkalosis Hyperventilation (depletion of CO2 & carbonic acid) Metabolic acidosis Increased non-carbonic acids ○ Ketoacidosis, uremia, ingestion Bicarbonate loss ○ Diarrhea, renal failure, proximal tube acidosis Metabolic alkalosis Excess loss of non-carbonic acids ○ Prolonged vomiting (loss of HCl), GI suctioning, hyperaldosteronism, diuretics Excess bicarbonate intake 8 5) What data can be used to determine a patient’s acid/base balance? What are the normal ranges for these data? ABG- Arterial Blood Gas ○ pH: 7.35-7.45 ○ pCO2: 35-45 ○ HCO3: 21-28 6) Work through case study #1 (below) 7) What is the primary difference between aerobic and anaerobic metabolism? Aerobic metabolism: O2 is required Anaerobic metabolism: O2 is not required Cellular metabolism= break down of proteins, fats, and carbs into ATP (energy for the cell) via 3 processes - Glycolysis o Occurs in the cytosol - Citric/Krebs Cycle o Mitochondria - Oxidative Phosphorylation+ ETC o Mitochondria o Yields the most ATP o Requires O2 to produce ATP à¯O2à ¯ATP productionàcell death (if occurs long periods) - Byproducts of ATP formation in mitochondria is ROS (Reactive Oxygen Species)à normally neutralized and protect against oxidative damage by antioxidants (apart of cells defense mechanisms) o Theses species can interact will various cellular componentsà if produced in excess can cause oxidative stress (cellular damage) § DNA § Proteins § Lipids o Benefits: § In moderate levels plays roles in: Cell signaling Immune responseàto help kill pathogens Regulation of cell growth **Slide NoteàKnow These Forms of Cellular Transport - Passive o Simple diffusionà molecules move from high à low conc o Osmosis- water molecule diffusion o Facilitated Diffusion- using proteins to help cross membrane - Active o Primary- uses ATP o Secondary- doesn’t use ATP directly 9 8) Explain hypoxic and free radical cellular injury Hypoxic injury Caused by low O2à Glycolysis ramps up → lactic acid byproduct → acidosis ○ Ischemia- most common ○ Anoxia Reperfusion injuryà blood supply return after a period of ischemiaà return of flow important but sudden influx of O2 can cause formation f ROS and free radicalsà which can cause damage to cell membranes proteins and DNA. Free radical cellular injury Damaged causes by free radicalsà highly ROS unpaired electrons break bondsà causing cellular dysfunction or death ○ Lipid peroxidation- steal electrons from membrane lipids 1. Membrane damage due to alter permeability and damage to enzymes and other protein 2. Protein damage 3. DNA damage ○ Disruption of polypeptide chains ○ DNA damage Increases number of free radicals- 10 9) What intracellular events lead to Hydropic swelling because of hypoxic injury? Hypoxia - Lack of O2à oxidative phosphorylation not able to and ETC not able to operateàcannot produce large amount ATP (normally produced)à cells are not able to function without an energy sourceà Na+/K+ ATPase pumps stopà Sodium accumulates in cellàwater followsàcell swells 10) What are the morphologic cellular changes that can be observed caused by cell stress or injury? Morphologic cellular changes caused by cell stress/injury Know the definition Metaplasia: Changes from terminal differentiated (mature) cells to less mature cellsà type changes but stability is maintained ○ Terminal differentiated cellsàmature cellsàmost functional and lose ability to divide when replacements are needed ○ Less mature cells divide faster and don’t lose their ability to divide even after loss if function Lead to pathology/problems Cause: chronic injury ○ Smokers → no mature ciliated cells → smoker’s cough Common in epithelial cells (skin, GI, GU, respiratory) Adaptive Reversible (when injury goes away) Dysplasia - precancerous Changes to diff cell type & divides rapidly (precancerous)à tumors ○ W/ increased cellular division there is an increased risk for mutations Cause: persistent severe cell injury Not adaptive Not reversible Accumulations (Infiltrations) – altered cellular storage Water → Hydropic swelling ○ Hypoxic injury Lipids ○ Tay-Sachs Disease deficiency in gene to digest certain type of lipid → accumulate in brain ○ Fatty liver disease Chronic injury from ETOH exposure 11 11) What is the difference between hypertrophy and hyperplasia? Under what circumstances do you get one but not the other? Atrophy Decrease size of cells (not number) Causes: ○ Decreased functional demand ○ Decreased hormonal stimulation ○ Examples: Lack of hormonal stimulation Protein/Calorie deficiencyà starvation Hypertrophy Inc size of cells (not number) Causes: ○ Increased functional demand ○ Increased hormonal stimulation Can be performed by cells that don’t divide ○ Eg: cardiac cells Hyperplasia Inc number of cells (not size) Causes: ○ Increased functional demand ○ Increased hormonal stimulation ○ Chronic injury/tissue repair Often occurs w/ hypertrophy Cardiac muscle does not divide (no hyperplasia), but may get bigger (hypertrophy) 12 12) What are the visual signs of cellular (coagulative) necrosis? General tissue death because of cellular necrosis Visuals: - Blebbing of plasma membrane - Cell & organelle swelling - Ribosomes detaches - Nuclear Changes 1. Pyknosis: nucleus shrinks 2. Karyorrhexis: nucleus in many pieces 3. Karyolysis: no nucleus Types of Necrosis: - Liquefactive o Tissue cells die and liquify o Occurs in tissue that has little to no connective tissue (like the brain) - Caseous o Occurs when cells die and there is a network of connective tissue holding it together o Looks like cottage cheese - Fat o Intracellular contents die and get releasedà react with fatty deposits and undergo saponification § Soapy deposits of tissue Cells have unique look o Occurs in tissues rich in fatty deposits (like pancreas or breast tissue) 13 13) Among the cellular responses to injury we learned in lecture (atrophy, hyperplasia, etc), which one is never adaptive and is considered “pre-neoplastic”? Dysplasia - “pre-neoplastic” = pre-cancer 14) Compare and contrast cell necrosis vs. apoptosis. Cell necrosis Unintentional cell death Look swollen & exploding Cell apoptosis Cell death Programmed cell death Look: imploding (collapsing on itself); shrinkage Triggered by ○ Viral infection ○ DNA damage ○ Certain kinds of membrane/mitochondrial damage ○ Cell stress (endoplasmic reticulum) ○ Induction by immune cells Both: Versions of cell death 14 Case Studies Question 1: A 66-year-old male with insulin-dependent diabetes mellitus, tobacco use, and COPD (FEV1 1.65 L, 50% predicted) presents to the emergency department with a 3-day history of diarrhea, fatigue, and lightheadedness. He recently returned from a cruise and both he and his wife are ill. He reports minimal oral intake over the past 2 to 3 days. His serum glucose is 160 mg/dL, and his urinalysis shows no ketones present. He has a baseline creatinine level of 1.0 mg/dL. He is hypotensive on presentation with a blood pressure of 80/50 mm Hg, heart rate 110 bpm. Laboratory Data: ABG Basic Metabolic Panel pH 7.22 Na 135 mEq/L PaCO2 52 mm Hg K 3.0 mEq/L PaO2 80 mm Hg Cl 102 mEq/L HCO3 13 mEq/L CO2 12 mEq/L BUN 44 mg/dL Cr 2.3 mg/dL What is/are the primary acid-base disturbance(s) occurring in this case? A Metabolic acidosis only B Respiratory acidosis only C Metabolic acidosis and respiratory acidosis D Metabolic alkalosis and respiratory acidosis 15 1) What is a homeostatic feedback system? What do they do? Describe an example of one. What body systems serve as the “control systems of the body” and therefore control most homeostatic feedback systems? Homeostatic feedback system Negative feedback loops Controls some biological parameter that is important in the body ○ E.g. body temp Involves brain (hypothalamus), body receptors (thermoreceptors from skin) Control systems of the body: nervous system, endocrine system 2) Describe the structure of the Nervous system: Central vs. Peripheral, Afferent vs. Efferent. Etc. CNS – brain & spinal cord Peripheral – nerves that branch from brain & spinal cord Afferent nerves (carries sensory info to CNS) ○ Somatosensory stimuli Conscious stimuli from body – touch, heat, pain ○ Visceral stimuli Autonomic BP, blood volume, blood osmolarity, HR Efferent nerves (carries commands from CNS to body) ○ Somatic efferent motor neurons → skeletal muscle (voluntary motor function) ○ Autonomic nervous system – involuntary visceral function Sympatheticà Fight-or-flight Parasympatheticà Rest and digest Control: smooth muscle, cardiac muscle, glands → feedback loop 16 3) Describe the general structure of a neuronal cell. What is myelination? Neuronal cell Soma: cell body ○ Nucleus ○ Organelles ○ Protein synthesis originates Dendrites & dendritic tree ○ Received info from other cells (stimulatory or inhibitory) Axon Hillock ○ Where AP begins Axon ○ Fiber that connects soma & cells that the axon contacts ○ Myelinationà insulation covering (high in lipids) increases conduction speed of AP down axon, prevents loss of signal Schwann cells (in PNS) Nodes of Ranvier: exposed axon between Schwann cells, where AP occurs by jumping nodes Oligodendrocytes (in CNS) Form of glial cell Axon Terminal ○ Final point that contacts other neuronal cells 17 4) Compare and contrast the three basic types of neuronal cells: afferent, efferent, & interneuron. Efferent neurons Command Neurons Cell body located in CNS Axon extends into PNS → effector organ/cell Afferent neurons Sensory Neurons Cell body in PNS, but close to spinal cord (CNS) Somatosensory afferent neurons don’t have dendrites. They have a specialized receptor at organ ○ Receptor turns signal to AP → PNS → CNS Interneuron Connect & communicates between afferent/efferent neurons Found in CNS only 5) Define and explain equilibrium potential. In what direction will an ion move when a cell is at that ion’s equilibrium potential? Why? Equilibrium Potential An ion is the electrical potential difference across a cell membrane at which there is no net movement of that specific ion across the membrane. ○ No net movementà concentration and electrochemical gradients are equal and opposite Chemicalà driven by the concentration difference of the ion across the membrane Electrochemicalà force exert by membrane potentialà ions move towards the side of the membrane where the opposite charge exists Inside of cell mostly negatively charged (more amino acids & proteins) Outside of cell mostly positively charged (sodium) K+ equilibrium potential = -90 mV Greater concentration drives from K+ inside cell → out of cell Electrical gradient (negative intracellular charge) pulls K+ from outside cell → inside cell Na+ equilibrium potential = +60 Greater concentration Na+ outside cell → moves inside cell 18 6) What factors determine resting membrane potential? Resting membrane potential= -86 mV Determined by: ○ Ions present (K+, Na+, Cl-, Ca2+) ○ Ions’ equilibrium potential Electrical graduation = concentration gradient ○ Ions’ permeability Most permeable ion pulls cell closer to its equilibrium potential (K+ b/c there’s more leak channels for K+) 7) Review the changes in membrane potential that occur during an action potential. What are the underlying events involved? - Resting Potential: K⁺ leak channels maintain the resting potential. - Depolarization: Voltage-gated Na⁺ channels open, allowing Na⁺ to rush into the cell. - Repolarization: Voltage-gated Na⁺ channels close, and K⁺ channels open, allowing K⁺ to exit the cell. - Hyperpolarization: K⁺ channels stay open slightly longer, causing the membrane potential to overshoot. - Return to Resting: K⁺ channels close, and the Na⁺/K⁺ pump restores the resting potential. 8) What purpose does the myelin sheath serve? - Increases conduction speed of AP down axon, prevents loss of signal 9) What is a synapse? What types of synapses exist? Contact between presynaptic cell and postsynaptic cell 2 types: ○ Chemical synapse (most) Via excitatory or inhibitory neurotransmitters (amino acids, monoamines, catecholamines) ○ Electrical synapse 2 cells that are electrically coupled via gap junctions (allow ions & small molecules to pass from one cell to the other – direct electrical spread) Example: ○ NMJ: axon terminal between voluntary neuronal cells & skeletal muscle Neurotransmitter: acetylcholine Receptor: nicotinic receptors 19 10) What are the steps involved in synaptic transmission at a chemical synapse? Steps of chemical synaptic transmission 1. Neurotransmitter molecules synthesized & stored in vesicles in presynaptic cell 2. AP reaches presynaptic terminal 3. Voltage gated Ca2+ channels open; Ca2+ enters presynaptic cell terminal 4. Rise in Ca2+ triggers fusion of vesicles w/ presynaptic membrane 5. Neurotransmitters diffuse across synaptic cleft → bind to specific receptors on postsynaptic cell 6. Bound receptors activate postsynaptic cell 7. Neurotransmitter breaks down, taken up by presynaptic terminal, or other cells, or diffuses away from synapse 11) What is the difference between a neurotransmitter and a neuroactive peptide? Neurotransmitter Chemical messenger released by presynaptic cell that produces either excitation/inhibition of postsynaptic cell Neuroactive peptides Peptides co-released w/ neurotransmitters Function: Modify response to NT ○ Usually changes responsiveness of postsynaptic cell to neurotransmitter Stimulate postsynaptic cell to make more receptors → inc sensitivity/response to neurotransmitter; or vice versa 20 12) Describe, compare, and contrast the following categories of neurotransmitters: Amino acid, monoamines, and catecholamines. Amino Acids (Building blocks of protein) ○ Fast-acting, often influencing ion channels directly. ○ Localized, rapid effects on excitability or inhibition Glutamate (aka glutamic acid) – excitatory; CNS GABA – inhibitory, CNS Glycine – inhibitory, CNS Monoamines (NT derived from single AAs) ○ Modulatory effects, influencing mood, alertness, and sleep patterns, and they often act through G- protein coupled receptor Acetylcholine (modification of choline) Serotonin (modification of tryptophan) Histamine (modification of histidine) Catecholamines (Derived from AA tyrosine) ○ Derived from tyrosine, modulate physiological functions like the stress response and reward. ○ Slower, more modulatory effects. ○ Critical for motor control, attention, and autonomic functions Dopamine Norepinephrine Epinephrine Primarily a hormone 13) What are the predominant excitatory and inhibitory neurotransmitters found in the central nervous system? Glutamate (aka glutamic acid) – excitatory; CNS GABA – inhibitory, CNS Glycine – inhibitory, CNS 21 Case Study Jean was a 54-year-old woman recently hospitalized and diagnosed with congestive heart failure. Upon discharge from the hospital, she was given a prescription for Lasix (furosemide) 20 mg PO daily. After 1 week at home, she had lost 3 pounds of water weight. She was very excited about this weight loss and decided “If 1 pill is good, 2 pills are better” and so she began to take 40 mg of furosemide daily. A week later she presents to the emergency room with generalized weakness, leg cramps, constipation, and “strong” heartbeats. 1. What was the likely cause of Jean’s symptoms? 2. What is the major intercellular cation, and what is its role in the action potential of neurons and muscle cells? 3. What were the effects of Jean’s electrolyte imbalance on the resting membrane potential of her neurons and muscle cells and on the threshold for an action potential? 4. Relate what was occurring in Jean’s cells to her musculoskeletal and gastrointestinal symptoms. 5. How do cardiac and muscle cells respond differently to alterations in serum potassium levels? 22 1) What are the major divisions of the Central Nervous System and their basic functions? Major divisions of CNS Spinal cord Brain stem ○ Function: baseline vegetative functions (heart pumping, breathing) ○ (1) Medulla oblongata ○ (2) Pons ○ (3) Midbrain Cerebellum ○ Function: learned motor movement/patterns (stores muscle memory) & updates with info from muscles Regulate motor movement modifies movement from frontal lobe Diencephalon ○ (1) Thalamus Major relay circuit/station- Afferent & efferent messages & messages between brain structures pass through thalamus ○ (2) Hypothalamusà Connected to pituitary gland Other baseline functions- regulates body temp, appetite, feeding behavior, libido, sexual appetite, reproductive function Part of limbic system (emotional reactions) Cerebrum ○ (1) Left & right cerebral hemispheres Higher order brain functions: cognition (solving, sorting things, evaluating), Executive function (brain’s ability to regulate own activity): planning, focusing ○ (2) Basal ganglia Regulate motor movement makes them smooth, controls fine motor movement, edits message from frontal lobe prevents overshooting movement ○ (3) Hippocampus Part of limbic system (emotion) Short term memory ○ (4) Amygdala Part of limbic system (emotion) Alerts you to danger (note: NOT perceive fear) 23 Divided into lobes: ○ Occipital lobe Primary visual cortex (visual perception), vision ○ Temporal lobes (2) Surface: hearing, Auditory cortex Deep structures: Hippocampus Amygdala ○ Parietal lobes (2) Somatic sensations Forming body image & relating it to extra- personal space ○ Frontal lobe Short term memory Plan future action Control of movements Prefrontal cortex: detect threats & produce stress response or not 2) Describe, compare, and contrast the structure and function of the motor cortex vs. the somatosensory cortex. Motor cortex (L & R hemisphere) Output: voluntary movement originates here (controls contralateral side) Anterior to central sulcus Sensory cortex (L & R hemisphere) Input: perceives all conscious sensation (of contralateral side) Posterior to central sulcus 24 3) Review the brain system responsible for the production and comprehension of language. Review the structures, the location, and the sequence of events that occurs when a person is listening to someone else speak and then responds with speech. Language circuità Most language is generated on the L-side of the brain Wernicke’s area (L & R) Processes auditory input for language → understand speech Clinical condition: receptive aphasiaà difficulty comprehending language Angular gyrus Part of temporal lobe Combines auditory input (from primary auditory area) & other senses from somatosensory cortex & visual cortex → feeds into Wernicke’s area ○ I.e.: tone, body language (“I had a great weekend”) Broca’s area (L& R) Receives input from Wernicke’s area Controls production of intelligible speech (generates language) Location: near primary motor cortex that controls tongue movements that form words Connection between Broca’s and Wernicke’s is bidirectional (info goes back and forth) to facilitate integration of speech formation, comprehension, & editing ○ For most ppl language is generated on left side of Broca and Wernicke Clinical condition: expressive aphasiaà difficulty expression words but know what they want to say Circuit FlowàPrimary auditory area (temporal lobe) + primary visual cortex (occipital lobe) + somatosensory cortex (parietal lobe) → angular gyrus → Wernicke’s ⇄ Broca’s → motor cortex → speech 25 5) What is the difference between CSF and Brain extracellular fluid (BECF)? +6) How is CSF produced? What compartments in the CNS does CSF occupy? Where is it ultimately absorbed? CSF Located in ventricular system around larger structures ○ Lateral ventricles (L/R), third ventricle, fourth ventricle → → Central canal of spinal cord → subarachnoid space → (drains into arachnoid granulations) → sagittal vein/sinus → reenters the bloodstream TAKEAWAYà CSF circulates though all the ventriclesà exits through the ventricles via the median and lateral apertures Produced by choroid plexus (located in L/R lateral ventricle, fourth ventricle) by filtering blood ○ Choroid plexus (“kidneys of the brain”) Constant circulation of CSF helps keep the composition of CSF optimal ○ Involved in systemic circulation Provides physical protection and regulates intracranial pressure Brain extracellular fluid (BECF) Located directly surrounding the neurons and glial cells in the brain, filling the interstitial spaces between cells. Provides direct regulation of neuronal signaling and local homeostasis Produced by BBB filtering plasma in blood vessels Similarities Same composition 26 7) What are the major differences with respect to composition between CSF and plasma? What is the purpose of this difference? CSF Less ○ Na+ ¯concentration gradientà ¯ Na+ going into cellàcell resting potential more negativeà ¯ likelihood of AP ௠excitability of cell (eg: seizures) ○ K+ K+ concentration gradient → K+ moves out cell → cell more negative → ¯excitability ○ Amino acids AA are neurotransmitters ○ Proteins Proteins are neurotransmitters More ○ Mg2+ Reduces permeabilityà reduces AP firing 27 8) What is the Blood Brain Barrier? What purpose does it serve? What structures comprise the BBB? Selective permeability barrier that separates the circulating blood from the BECF in the (CNS). 3 layers ○ Tight junctions of brain-capillary endothelial cells ○ Basement membrane (glycoproteins, connective tissue) ○ Astrocytes endfoot Able to cross BBB ○ Lipid soluble ○ Passive diffusionàWater, CO2 ○ Co-transportàNa+, K+, glucose Difficulty crossing ○ Water soluble Know the astrocytes/composition of blood brain barrier 9) What are the Circumventricular organs? What is so special about them? What purpose do they serve? Leaky regions of BBBà has a more permeable barrier that allows or substances in the blood to directly interact with brain tissue (direct access to circulating hormones). They are strategic places where circulating messengers & other things can interact w/ brain that’s safe for brain ○ Allows hormones to pass, which normally would not be able to pass BBB ○ Median eminence: allows passage to hypothalamus Allows cytokines released during infection to pass & bind to hypothalamus to produce fever 28 10) Explain the difference between a spatially focused vs. widely divergent pattern of synaptic connectivity. Spatially Focused Pattern of Synaptic Connectivity Neuron forms synaptic connections with a limited, localized group of neighboring neurons→ information is specially focused Task-oriented E.g.: language circuit, motor function Widely Divergent Pattern of Synaptic Connectivity Single neuron connects to broad neurons or regions of brainà allowing for widespread signal distribution Controls level of excitation Good for complex behaviors/traits ○ Sleep-wake cycles ○ Regulation of attention ○ Regulation of mood E.g.: Systems of Central Neurons Using Modulatory Transmitters ○ Norepinephrine system Origin- locus coeruleusà brainstem Effect: sleep/wake cycle, attention, regulates mood ○ Serotonin system Origin- raphe nucleià brainstem Effect- sleep/wake cycle, mood, temperature control, level of motor excitation ○ Dopamine system Origin- Substantia Nigra-part of basal gangliaà EFFECT-voluntary motor movement Ventral tegmental areaà EFFECT-reward pathway ○ Interacts with the prefrontal cortex which drives motivationsà pleasure, reinforcement, motivation Sex, eating food, addiction, etc. Fewer widespread connections ○ Acetylcholine system Effect- sleep/wake cycle, cognitive processing (perception and thinking) Blocking Ach leads to delirium 29 11) Review the 4 systems of central neurons using modulatory transmitters (specifically, review the transmitter used, the sites where the neurons originate, and the brain functions the system is thought to influence.) SEE ABOVE 12) What is a “cranial nerve”? What is a “spinal nerve”? How do they differ? Cranial nerve Extend from brainà 12 pairs Fully sensory (olfactory, optic, vestibulocochlear) Fully motor (oculomotor, trochlear, abducens) Mix (trigeminal, facial, glossopharyngeal) Part of PNS (efferent)à Vagus nerve Spinal nerves Extend from spinal cordà31 pairs ○ CI=100% sensory ○ All others are both sensory and motor Has protective coveringà Meninges Roots from ventral (anterior) root are motor/control of skeletal muscle or efferent Roots that come from dorsal (posterior) root are sensory ○ Dorsal root gangliaà located along the dorsal roots of spinal nerves, just outside the spinal cord Function: play a critical role in transmitting sensory information from the body to the central nervous system, allowing the brain to process and respond to various external stimuli. Vagus nerve from efferent branches off and becomes both somatosensory and motor 30 13) What are spinal nerves composed of? Explain the relationship between spinal nerves and Dermatomes and Myotomes. Spinal Nerves - Formed by the combination of two roots: a dorsal (posterior) root and a ventral (anterior) root Dermatomes Sensory map Mapping of surface of skin that’s innervated by a particular spinal nerve pair Segments ○ Cervical ○ Thoracic ○ Lumbar ○ Sacral Mapping is conserved from person to person ○ Sensory impairments/change can be mapped to which spinal pair & location on spinal cord is involved E.g.: shingles ○ Comes out a spinal nerve → Unilateral rash within a dermatome Myotome Motor/skeletal muscle map Mapping of motor nerves innervated by spinal nerve pairs 14) What is the difference between white and gray matter in the nervous system? What are the structural and functional subdivisions of both white and gray matter? Brain - Grey matterà Outside o Cell bodies, dendrites, synapse - White matteràInside o Axons – Fatty myelination makes it white 31 Spinal Cord Grey matteràInsideàHorizontal ○ Cell bodies, dendrites, synapses ○ Dorsal horn Where sensory fibers enter spinal cord → synapse w/ interneurons in spinal cord → some communicate with white matter & go up in brain, some communicate w/ ventral horn ○ Lateral horn Cell bodies of autonomic efferent nerve fibers → leave spinal cord thru ventral roots → autonomic functions (sympathetic/parasympathetic, depending where in spinal cord) Preganglionic neuronsàFound between T1-L1 ○ Ventral horn Cell bodies of motor (somatic) efferent neurons → axons leave spinal cord thru ventral roots → skeletal muscle (voluntary motor movement) White matteràOutsideà Vertical ○ Composed of: Ascending axon fibers (from body to brain) On dorsal surface (mostly sensory track) Descending axon fibers (from brain to body) On ventral surface (mostly efferent/motor track) 32 15) Sketch out, on a separate piece of paper, a simple map of the circuitry of the two branches of the autonomic nervous system. Include in your map: location of major synapses, neurotransmitters, and postsynaptic receptor subtypes. 33 16) What tissue types serve as the targets of the autonomic nervous system? ANS: Controls viscera (involuntary) ○ Smooth muscle ○ Glands Exocrine & Endocrine ○ Cardiac muscle 17) What neurotransmitter is used in all the synapses in the Celiac Ganglion? Celiac ganglionàPart of sympathetic nervous systemàNT-acetylcholineà Cholinergic Post-ganglionic neurons then release norepinephrine (NE) at the target organs à Adrenergic 18) Where are you likely to find muscarinic acetylcholine receptors? On target cells receiving input from PNS 34 19) Review the receptor subtypes on target organs involved in autonomic function. 35 20) Review the parts of the brain that control autonomic function. Are some of these brain regions sympathetic vs. parasympathetic? Controlled byàhypothalamus + brainstem - Hypothalamusà regulates temp, water balance appetite/feeding - Brainstemà bladder, respiratory, and cardiovascular control Hypothalamus + Brainstem decides efferent response from afferent (stimuli input) → they DECIEDE if you need sympathetic/parasympathetic responses 36 37 Neurons have short distances to travel to stimulate target organà resulting postganglionic neurons smaller 38 39 Normal Function of the Endocrine System 1) Compare and contrast the terms: endogenous ligand, agonist, partial agonist, and antagonist. - Endogenous Ligand: o Naturally occurring molecule w/in the bod that binds to a receptor § Hormones or NT - Agonist: o A substance that activates a receptor to produces a biological response § Mimics the effect of the endogenous ligand - Partial Agonist/Antagonist: o A substance that binds and activates a receptor with a weaker response, but can a produce an agonist or antagonist response § Drugs/Medications à acts like internal source (hormones) and enter bloodstream - Antagonist: o Substance that binds to receptor but blocks activation of the endogenous ligand 2) What is the difference between a central vs. a peripheral endocrine gland? What is the difference between dedicated endocrine glands vs. ones with mixed function? Endocrine gland- any gland that secretes hormones (chemical messenger) directly into the bloodstream Hormone- chemical messenger produced by glands o Two Types § Central endocrine glandà part of CNS Hypothalamus Pituitary gland Pineal gland § Peripheral endocrine glandà any gland outside CNS Dedicated Endocrine Glands ○ Endocrine functionàsecretes hormones parathyroid gland thyroid gland adrenal glands Mixed Function Endocrine Glands o Both primary and endocrine function § Kidney, etc. - Neurohormonal Cells o Neuronal cells that released hormones into the bloodstream § Neuronal cellà releases hormone directly onto neighboring cell § Hypothalamus § Pituitary Gland 40 3) What is (are) the primary difference (s) between a hormone and a neurotransmitter? - Hormone o Chemical messenger released by glands into the bloodstream o Acts on distant targets o Delayed onset action and longer duration - Neurotransmitter o Released by neuronal cells onto synapse o Acts on adjacent cell o Fast action and short duration 4) Describe the relationship between a hormone and its receptor? What are the possible intracellular effects that can be triggered? Endocrine Glandà Hormoneà Binding w/ Receptor à Target Cellà Physiologic Response - Binds a specific receptor onto target cellà triggers intracellular cascade o Crucial for physiological processes w/in the body o This relationship determines the effect of the hormone - 3 Possible Intracellular Effects o Alteration in ion channel permeability → change in membrane potential (depolarization/repolarization) o Acts through second-messenger system → alter activity of pre-existing proteins (turn off/on enzymes) o Activates specific genes → formation of new proteinsà turn on/off genes to increase or decrease expression of protein 5) Describe the differences in hormone synthesis, transport, and mechanism of action of target cells between water-soluble hormones and lipid-soluble hormones? Water Soluble Hormonesà Peptide, Protein, and AA Fat Soluble Hormonesà Steroids, derived Thyroid Hormone Synthesis Synthesized as prohormone & converted to active Synthesized from cholesterol structure (except T3, T4) Hormone Storage Usually stored in intracellular vesicles Often not stored Often made on demand Use of hormone binding proteins (intracellular or in circulation) Hormone Transport Usually travel free in plasma Bound to plasma protein to travel Interaction w/ Target Cell Binds to membrane receptorà can’t penetrate Usually binds to nuclear receptor membrane Regulates gene transcription Often uses second messenger 41 6) Of the three main categories of hormones (peptide, amino acid-derived, and steroid) which are water-soluble, and which are lipid-soluble? Water Solubleà Hydrophilic - Activates secondary messengers inside the cell when bound to hormone receptorà inhibits or amplifies effects of cell o Secondary messengers-à CAMP, IP3 and Ca2+ionsà changes function of protein or enzyme and cellular response - Peptide Hormones o Created by hypothalamus and released by posterior pituitary o Vasoconstrictor o Function: § V1à binds to smooth muscle/blood vesselsà constriction § V2à binds to kidneysà increase water reabsorption - Protein Hormones - AA-Derived Hormones o Exceptà T3 and T4= lipid soluble o Catecholamines § Epi and NE § Derived from tyrosine and released from adrenal medulla § Epi- NT and released as a hormone by SNS Depending on how it is released 42 Lipid Solubleà Hydrophobic - Influence gene expression and binds nuclear (receptors on the nucleus of a cell) receptors - Steroid Hormones o Derived from cholesterol From either diet or liver production Is a fat and unable to travel via bloodstreamà packages as LDL o LDL bind receptors of endocrine cellà cholesterol is freed and converted into pregnenoloneàproduces steroid hormones § Enzymes determine what hormone is produced from pregnenolone o Steroids are formed via intermediates that require enzymes § Deficiencyà no hormone production § Abundanceà too much of a particular hormone Both occur due to congenital abnormalities o Thyroid Hormones T3 and T4: § Derived from thyronine § T3- active form (3 represents # of iodine) § T4- inactive formà 4th iodine is removed to convert into active form Iodineà makes it non-polarà resulting in the hormone being lipid-soluble § Codes for protein that consume energy (Na/K pump)à connected to metabolic rate Increased THà Increased BMR - Example question how its asked: o Which hormone is most likely to bind to a nuclear receptor (lipid soluble)? § Vasopressin, aldosterone, brain naturistic peptide 43 7) Describe, compare, and contrast the connectivity between the hypothalamus and the anterior vs. the posterior pituitary gland. Hypothalamus Connected to pituitary gland functionally and physically by connecting stalk Produces hypothalamic hormoneàVasopressin (ADH) & oxytocin ○ Stored in axon terminals of posterior pituitary Pituitary gland Posterior: ○ Extension of hypothalamus ○ Neurosecretory cells of hypothalamus release oxytocin and vasopressin at axon terminalà into bloodstream ○ Store and releases: Vasopressinàreleased when plasma volume decreases Oxytocinàreleased w/ breastfeeding reflex, neurotransmitter for social bonding Anterior: ○ Separate structure – true endocrine gland ○ Hypothalamus releases hypothalamic hormone within connecting stalkà travel via circulatory loop to anterior pit. → hormone into bloodstream Hierarchical level of controlà has negative feedback regulation 44 ○ Hormones released: Thyroid stimulating hormone (TSH) → thyroid gland → T3/T4 → metabolic rate ACTH → adrenal cortex → cortisol → metabolic actions; stress response Prolactin → mammary glands → breast growth & milk secretion Growth hormoneà Bone and soft tissue growth via the liver; other tissuesà metabolic actions Luteinizing hormone (LH) +Follicle stimulating hormone (FSH) Gonads (F-ovaries, M-testes)à sex hormone secretions and gamete production 8) Where are Oxytocin and Vasopressin synthesized? From where are they released? See above 9) What is the relationship between the hypothalamus and the somatotrophs of the anterior pituitary? Hypothalamus releases 2 hormones that control the somatotroph’s release of growth hormone: Somatostatin ○ Inhibits release of GH GHRH (Somatotrophs) ○ Stimulates release of GH 45 10) What is the pattern of release of Growth Hormone? - Released in pulses (pulsatile manner) - Highest during sleep (non-REM sleep; deep sleep) - When GH spitsà IGF (Insulin Growth Factor) decrease and vice versa 11) What is the relationship between Growth Hormone and IGF-1 and IGF-2? What are the basic actions of GH and IGF-1 and 2? Relationship - GH released by anterior pituitaryà production of IGF 1+2 o Creates a negative feedback loop § If levels are highà signal sent to hypothalamus and Pituitaryà ¯ GH § If levels are lowà signal sent to hypothalamus and Pituitaryà GH Actions - GH has direct & indirect actions o Direct – § Acts on all tissues/organs Stimulates cell growth/division ¯ adiposity (dec fat) lean body mass BG via gluconeogenesis Inhibit insulin uptake of glucose o Indirect actions – § Acts on liver and other tissuesà produces IGF 1+2 → act on cellsà causing: organ size bone density ¯ BGà allowing for cells to uptake glucoseà energy allows for cellular growth and division 46 12) Consider the structure of the thyroid gland. How is thyroid hormone stored? Why is it necessary to store thyroid hormone this way? - Thyroid arranged into folliclesà a hollow structure that is lined with follicular cells w/ colloid cells inside (thyroid storage center) - C-cells=Parafollicular cellsà release calcitoninà regulates Ca level in the body o Iodine uptake from blood into follicular cellsà transported to colloidà converted into T3 and T4à Stored into colloid until needed o Hypothalamus releases TRHà Ant Pit releases TSHà TSH acts on follicular cellsà T3 and T4 are released - Necessary for storage w/in colloid b/c: o Allow for steady supply: § Ensured the body can maintain metabolic homeostasis § Respond quickly to body demands w/o need for constant synthesis 13) What component of thyroid hormone cannot be synthesized by the body? - Iodine § Obtained via diet § Crucial for synthesis of T3 and T4 47 14) What are the primary physiological effects of thyroid hormone? - Connected to overall metabolic activity and energy consumption - Stimulates many genes, which when expressedàmetabolizes a lot of energyà increases BMR o Formation of: Na-K pump Gluconeogenic enzymes Formation of glucose Respiratory enzymesàcellular respiration/metabolism Myosin heavy chainsàr/t muscle contraction B-adrenergic receptorsà SNS response Etc. 15) What are the two major zones of the adrenal glands? How do they differ? - Adrenal medulla – inside layer Part of SNS Produces catecholamines (epinephrine, norepinephrine) - Adrenal cortexà Outer layer Part of endocrine system Produces all steroid hormones + mineral-corticoids + glucocorticoids 48 - There are multiple layers different layers of the gland Zona glomerulosa, fasciculata and reticularis (outer most layer-> inner most layer o Glomerulosa specifically produces aldosterone (mineralocorticoid) 16) What is the difference between mineral- corticoids and gluco-corticoids? Where are they respectively synthesized? Mineralocorticoids Formed in adrenal cortexàspecifically zone glomerulosa Controlled RAAS system ○ Regulated BP and fluid balance When BP or Na+ dropsà kidneys release renin to converted angiotensin IIà stimulating formation of aldosterone in the glomerulosaà Na+ retention and K+ lossà in the kidneysà BP “Mineral-” àcausing Na+ retention and K+ loss Produces: ○ Aldosterone Glucocorticoids Formed in adrenal cortexà specifically fasciculata Controlled by the hypothalamus and anterior pituitary ○ Release during times of stress of low cortisolà signal release of hormones from hypothalamus (CRH) and anterior pituitary (ACTH)à stimulates adrenal cortex to form and secrete glucocorticoidsà cortisolà once levels are sufficientà negative feedback to the hypothalamus and anterior pituitary reduces release of their hormones “Gluco-” à blood glucose Produces ○ Corticosterone ○ Cortisol constantly produced à diurnal pattern (more during day) Highest right before waking up and lowest in the evening ○ Cortisone Sex Hormone Formed in the adrenal cortexà Specifically zona reticularis Controlled by the hypothalamus and anterior pituitary Produces: ○ Androgens and testosterone ○ Progesterone and estrogen 49 17) Describe the primary physiological effects of cortisol. Actions of Cortisol blood glucose levels ○ Breakdown muscle → AA → gluconeogenesis in liver → glucose ○ Antagonize insulin receptors-à inhibiting glucose uptake ○ Enhance glycogen breakdown in liver to form glucose calciumà for muscle contraction ○ Micro breakdown of bone → release Ca2+ calcium excretion à counterbalance calcium levels Na+ retention, K+ loss Vasoconstriction Immunosuppressant & anti-inflammatory response excitability of brain 18) Destruction of pancreatic Beta cells would result in a deficiency of which hormone? Insulinà Type I Diabetesà autoimmune condition 50 Case Study Hazel C. a 30-year-old female demonstrated a subtle onset of the following symptoms: dull facial expression; droopy eyelids; puffiness of the face and periorbital swelling; sparse, dry hair; dry, scaly skin; evidence of intellectual impairment; lethargy; a change of personality; bradycardia (50 b/min); a blood pressure of 90/70; constipation, and hypothermia. The patient does not complain of pain. Plasma concentrations of total and free T4 and T3 follow: T4 T3 Total 3 ug/dL (normal is 4-12 ug/dL) 0.14 ng/dL (normal is 75-195 ng/dL) A blood sample indicated elevated TSH levels. A TSH stimulation test did not increase the output of thyroid hormones from the thyroid gland. A biopsy of Hazel's thyroid revealed large numbers of lymphocytes in her thyroid gland (see micrographs below.) 1. How do Hazel's levels of T3 and T4 compare to normal? 2. What do Hazel's elevated levels of TSH reveal about the function of her anterior pituitary? about her thyroid glands? 3. What is a TSH stimulation test and how are the results interpreted? 4. Name the endocrine disorder in this case. 5. Diagram the feedback loop involved. 51 6. Why does Hazel have a lower-than-normal body temperature? 7. What is the most likely explanation for the bradycardia and low blood pressure in Hazel C? 52
