HBIO420 FINAL EXAM

In terms of phototransduction, what are the different types of photoreceptive cells involved and what function(s) does each serve in terms of visual processing? How are they different in terms of their convergence with bipolar and ganglion cells and of what consequence is this? Know the different types of opsins. Be familiar with the signal transduction pathways for photoreception and the molecular events involved at the level of detail presented in my slide deck.

*RODS: - respond to any photon regardless of energy content - dim light activation - high in concentration outside of the fovea (periphery) - information about general SHAPE, MOTION, and SHADOWS - very sensitive *CONES - characteristics sensitivities to 98 specific ranges - color vision, ACUITY, FINE DETAILS - concentrated in the macula and especially in the fovea - fovea has primarily RED & GREEN - takes more photons to activate CONVERGENCE inevitable when going from rods/cones to ganglion cells - cones have far LESS convergence especially at fovea where they reach one to one ratio with ganglionic cells - convergence also compensated for by on/off center signaling RHODOPSIN = RODS AND PHOTOPSIN = CONES RETINAL + OPSIN = PHOTORECEPTOR - Retinal: light absorbing/ photon binding, synthesized from vitamin A - Opsin: inactive when bound to retinal, specific variant determines color of light absorbed Rhodopsin = 498 NM - activated by DIM LIGHT, shades of gray THREE photopsins, bright light - BLUE = SHORT @ 420NM - GREEN = MEDIUM @ 534 NM - RED = LONG @564 NM [BGR in alphabetical order] overlap allows for perception of intermediate hues from differential activation of more than one type of cone MELANOPSIN: found intrinsically in retinal GANGLION cells - circadian rhythm - peak @ 488nm DARK CURRENT: tonic release of glutamate in the absence of light - Cyclic Nucleotide Gated CNG CHANNELS open in dark lead to a constant influx of CA2+ and NA+ - RMP slightly depolarized at ~40 mv w/light - absorption of photon: 1. Rhodopsin is activated and 11-CIS RETINAL CONVERTED TO 11-TRANS RETINAL AND OPSIN IS RELEASED 2. Opsin activates G-protein TRANSDUCIN which activates PHOSPHODIESTERASE 3. PDE BREAKS DOWN cGMP which CLOSES CNG channels 4. Reduction in Na+ and Ca2+ decreases glutamate release, reduces dark current, and HYPERPOLARIZES the cells to -70 - change in activity relayed to adjacent bipolar cell and then one or more ganglion cells BLEACHING: breaking down of rhodopsin into retinal and opsin - requires time and ATP to regenerate! - also a mechanism for light/dark adaptation

In what chemical forms is CO2 carried to the lungs from tissue? What carriers are involved and what is responsible for interconversions in its chemical forms?

- 7% CO2 DISSOLVED in plasma - CARBAMINOHEMOGLOBIN/ carbamate = 23% of CO2 where it is an allosteric effector of Hb, carried via RBC - 70% as BICARBONATE after conversion to carbonic acid via carbonic anhydrase in the RBC and then dissolving in plasma (gets reconverted into CO2 before diffusing into a cell)

Metabolism Random Facts

- Positive peptides involved in food intake: NPY, Ghrelin, Orexin - Negative peptides involved in food intake: CCK, GLP-1, PYY, Leptin

Be familiar with the pathways and mechanisms for digesting and the enterocyte absorption of carbohydrates, proteins, and fats.

- Upper 40%: carbs, lipids, and proteins absorbed - Lower 60%: vitamin B12, water, electrolytes, bile salts, remaining nutrients - Water soluble compounds are absorbed into the intestinal fenestrated capillaries -> portal vein system -> liver - Fat soluble compounds are absorbed into lymphatic vessels called lacteals w/ minivalve pores -> lymph system -> general circulation - Both transcellular and paracellular absorption Fat Absorption: - bile salts emulsify lipid droplets into micelles and make them accessible to enzymes - phospholipase: break down phospholipids into free fatty acids and monoglycerides - colipase: co-factor of lipase that allows it to bind to bile salt covered TG, allowing the lipase to access fats inside - FA and monoglycerides enter enterocytes through diffusion, cholesterol enters via NPCL2 channel - inside the FA get remanufactured into TGs in the smooth ER and then combine with cholesterol and apolipoproteins (APOA-4/1, APOB-48) to become nascent chylomicrons - chylomicrons exchange components with HDL and receives APOC2 and ApoE, converting it to a mature chylomicron -- APOC2 is coenzyme required for lipoprotein lipase activity in capillaries, which frees TG from chylomicron to be taken up - after distributing TGs, returns the ApoC2 to an HDL and becomes a remnant chylomicron, with the ApoB48 and ApoE markers for endocytosis and breakdown Carbohydrate Absorption: - amylase breaks down starch and glucose into disaccharides - maltase breaks maltose into 2 glucose, sucrase breaks sucrose down into glucose and fructose, and lactase breaks lactose down into glucose and galactose - glucose and galactose enter cell through SGLT, leave into bloodstream via GLUT2 (also a basolateral Na+/K+ pump) - fructose enters through GLUT5 and leaves via GLUT2 Enterocytes use GLUTAMINE for energy and important processes Protein Absorption: - 30-60% of proteins in lumen are from sloughed off enterocytes - low acidity leads to denaturation - zymogens that are activated into active proteases break down proteins - Endopeptidases digest internal peptide bonds: -- pepsin: many AAs -- trypsin: Lys, Arg -- chymotrypsin: Trp, Tyr, Phe - Exopeptidases: digest terminal peptide bonds (amino vs carboxypeptidase) - Free amino acids absorbed, di and tripeptides co-transported with proton (leaves via NHE, supported by Na+/K+ ATPase), small peptides carried through transcytosis

Immunity Random Facts

- antibodies secreted by B lymphocytes - T-cell receptors recognize and bind antigen presented by MHC receptors - tumor necrosis factors: cytokines that can cause cells to self destruct - Some APCs can take up and present extracellular antigens on MHC I (cross presentation) to stimulate CD8+ cytotoxic cells (cross priming): important to still induce cytotoxic immunity when APCs are not infected but peripheral are - Follicular dendritic cells present native antigens to B cells for eventual interaction with CD8+ cells, allowing for antigen trapping even if not previously exposed

Digestion Random Facts

- increased particle size or increased energy content = slower gastric emptying - gastro-ileal reflex: distension of ileum -> decreased release of chyme - chemoreceptors detect macromolecules that should've been digested -> slow down gastric activity - enterocytes also have immune function (xenobiotic agents) - review last diagrams - NSAIDS are non-selective cyclooxygenase inhibitors which can inhibit cytoprotective and inflammatory prostaglandins and over long term can result in peptic ulcers - Few substances absorbed in stomach (ethanol is one of them), most happens in small intestine - Two forms of gut motility: 1. Unidirectional (forward) movement of material (via peristalsis [2 - 25 cm/s cyclic contractions]) - outer longitudinal muscles -- interstitial cells of Cajal, Pacemakers responsible for slow wave potential -- Gap junctions allow for coordination - single unit smooth muscles 2. Mixing of gut contents: bidirectional (via segmental contractions) - inner circular muscles

Be familiar with excitation-contraction coupling in cardiac muscle. How do these steps compare to that in the other types of muscles? What differences are observed in terms of the release and sequestration of calcium?

1. AP on cell membrane, depolarization enters T-tubule 2. Contraction cycle initiated by calcium (sparklet) from ECF via the voltage gated calcium channel CaV1.2 DHPR (10%) and SR via the RyR2 activated by calcium induced calcium release (90%) - not physical tethering 3. Calcium spark diffuses into sarcomeres to bind to troponin and subsequent contractile events similar to skeletal muscles 4. Relaxation via NCX ANTIPORTER (exchanges Ca2+ out with Na+ in following its gradient set up by Na/K pump) and SERCA 2&3 (2 Ca2+ per ATP for 2 H+) PHOSPHOLAMBAN-PO3: changes the overall activity in response to beta adrenergic agonists - non-phosphorylated = usually an inhibitor of SERCA - phosphorylated via agonists = disinhibition - LUSITROPIC (relaxation) effects by getting rid of calcium and increasing speed at which cardiomyocytes relax and also increasing contractility (+ INOTROPIC)

Be able to compare and contrast differences in the characteristics and functions of the 3 types of muscles.

1. SMALLER than striated cells, MONOnucleated, spindle shaped 2. ONLY AUTONOMIC 3. NO sarcomeres, troponin, or T-tubules, SR associated with caveolae 4. Different thick filament arrangement - UNIFORM MYOSIN heads per length) - much MORE ACTIN: 12-15 thin filaments surround a thick filament! - extensive EXOSKELETON: DENSE BODIES that actin is bound to and intermediate filaments that connect the dense bodies wrapped all around -> leads to a SQUISHING of the cell upon contraction 5. LESS ENERGY used than striated, can maintain TONIC CONTRACTION (like urinary and esophageal sphincters) AT LOW ENERGY cost 6. Contraction and Relaxation are much SLOWER in smooth muscle Myocardial show blend of smooth and skeletal: - shorter than skeletal muscle fiber - MONONUCLEATED - mix of contractile + AUTORHYTHMIC cells - STRIATED: contractile elements in sarcomeres - no direct innervation (NMJ) involved in initiating contraction - EXTRACELLULAR calcium important in contraction initiation smaller SR than skeletal, no triads, LOTS OF MITOCHONDRIA - single twitch duration much LONGER than in skeletal muscle - T tubule system larger than skeletal and branched - contractile cells electrically and mechanically linked in a network (branched) - joined together via INTERCALATED DISKS that contain: -- DESMOSOMES: mechanical linkages, transfer force -- GAP JUNCTIONS: electrical linkages

Be familiar with the mechanism of hearing from sound wave transduction, the detection of pitch and volume, hair cell polarization to IPSP or EPSP to spiral ganglion, the inferior colliculi, thalamus, and the auditory cortex.

1. Sound waves in the air enter the external auditory canal and vibrates the tympanic membrane 2. Tympanic membrane vibrates the malleus, incus, and then the stapes 3. The stapes vibrates the oval window, which creates waves in the perilymph in the scala vestibuli of the cochlea 4. Pressure waves DISTORT the basilar membrane on their way to the round window of the scala tympani, causing hair cell cilia to brush against the tectorial membrane and become distorted - INNER hair cells: responsible for DETECTION - OUTER hair cells 3X more and AMPLIFY outer wave (motor function 5. Flexion of the stereocilia TOWARDS THE TALLEST member results in the opening of the ion channels via the connective tip links and INFLUX OF K+ resulting in depolarization and increase in APs - TONIC RELEASE of glutamate at rest (due to calcium influx) - flexion away from kinocilium = hyperpolarization and no APs or GABA/dopamine release 6. Ca 2+ ENTERS through voltage gated channels and opens K+ channels, which then re-polarizes the cell 7. An EPSP is transmitted to the sensory neurons of the SPIRAL GANGLION 8. Axons of spiral ganglion transmit APs along the vestibulocochlear nerve (VIII CRANIAL NERVE) to be diverged to the SUPERIOR OLIVARY NUCLEUS of pons (localization and reflexive to both middle ear muscles) and the INFERIOR COLLICULI of mesencephalon (unconscious motor reaction) - both get ipsilateral and contralateral input from branches off VIII nerve after decussation at medulla 9. This goes to the medial geniculate nucleus of the THALAMUS and the AUDITORY CORTEX of temporal lobe (different mapping for frequencies) Streams: dorsal-where; ventral-what [I never know where the dorsal fin is, and don't even know what a ventral fin is]

Be familiar with the polypeptides that make up antibodies (2 light and 2 heavy chains, the Fab and Fc). What cells have receptors for the Fc region? Be familiar with the various functions of antibodies (e.g., opsonization, agglutination, complement activation, phagocyte attraction, disruption of viral or bacterial adhesion).

2 light and 2 heavy chains that are identical mirror images and connected by disulfide bonds - Fab (fragment antigen binding): V region, variable, binds antigen - Fc (fragment crystallizable): stem region, constant region, determines biological activity, has complement and macrophage binding sites B cells, NK cells, follicular dendritic cells, macrophages, neutrophils, eosinophils, basophils, mast cells have Fc receptors Antibodies act indirectly, recognize antigens and neutralize them or tag for destruction - precipitation and agglutination of antigen: clumping and inactivation/neutralizing of bacterial toxins - act as opsonins to tag antigens for phagocytosis (and attract phagocytes) - prevention of bacterial and viral adhesion - triggers degranulation and inflammation - activation of complement and B cells

Be familiar with the overall anatomy of the stomach and the function (secretion & stimulus) of mucous surface & neck cells, parietal cells, enterochromaffin-like cells, and chief, D & G cells.

4 layers: - mucosa: lines lumen - submucosa - Inner circular muscular layer + Outer longitudinal muscular layer - stomach has additional innermost diagonal layer - serosa Mucous surface cell: secretes mucus, physical barrier between lumen and epithelium, tonic secretion Mucous neck cell: secretes bicarbonate, buffers gastric acid to prevent epithelial damage, secreted w mucus Parietal cells: secretes gastric acid (HCl) to activate pepsin and kill bacteria and intrinsic factors to complex with vitamin B12 to permit absorption, triggered by ACh, gastrin, and histamine Enterochromaffin-like cell: secretes histamine, stimulates gastric acid secretion, triggered by ACh and gastrin Chief cells: secretes pepsinogen to digest proteins and gastric lipase to digest fats, triggered by ACh and acid secretion (pepsinogen -> pepsin) D cells: secretes somatostatin, inhibits gastric acid secretion, triggered by acid in stomach G cells: secrete gastrin, stimulates gastric acid secretion, triggered by ACh, peptides, and AAs

What distinguishes the special sense from somatic senses such as mechanoreception (pressure, vibration and proprioception), pain (nociception) and heat (thermoreception)? How is the modality of a sense encoded in the CNS? How is the intensity and duration of the stimulus encoded?

5 special sense: olfaction (smell), gustation (taste), vision, equilibrium, hearing all involve special sensory receptors/ distinct receptor cells, typically have systems and their own cortices/ unique epithelial structure Modality (form of sensory perception) is encoded by neuronal pathway = labeled-line coding (chemo, mechano, thermo, and photo) - incoming information comes across in lines specific to the receptors they are bringing in information from - each receptor is sensitive to a specific stimulus modality and sends this information to the brain - not typically reliant on stimulus, just whatever triggers that line coding (cannot tell between real and false signal from receptor) -sensory receptors act as transducers (unless photo or olfactory), usually in form of AP, to CNS which then goes to mostly involuntary and some voluntary processes Intensity is encoded by the number of receptors activated and frequency of action potentials = rate/frequency coding Duration is encoded by DURATION OF APs = temporal coding Location: encoded by which receptive fields are activated - lateral inhibition: increases contrast between activated fields and inactivated neighbors - population coding in which multiple receptors work together to increase info content Sensitive receptive fields have many small but overlapping fields (area monitored by a single receptor cell)

What are the five antibody classes, what are their different roles and where are they found?

5 types of heavy chain constant segments IgG: most abundant in serum, produced in both primary and secondary responses, crosses placenta, reacts with complements IgA: found in mucosal area (gut, GI, urogenital) and in external secretions (saliva, tears, mucus, milk) IgE: bind to allergens triggering release of histamine from mast cells and basophils, protect against GI worms [allerg"E"] IgM: monomers act as B cell receptors, secreted pentamers are 1st line defense against pathogens before IgG but less effective, reacts strongly with complements IgD: antigen receptor on B cells, helps activate basophils and mast cells

What are the functional differences between cortical and juxtamedullary nephrons? What features of the glomerulus make it an "unusual" fenestrated capillary? Be familiar with "typical" values for the glomerular and capsular hydrostatic pressures and the blood colloid osmotic pressure. What is the composition of the initial filtrate? What in blood is not typically part of the filtrate? What are the three filtration barriers? Which is most selective and which least? What is the slit diaphragm?

80% cortical nephrons: outer part of kidney, short loops of Henle, lower concentration - have peritubular capillaries: sites of secretion and reabsorption, pick up substances from peritubular space 20% juxtamedullary nephrons: extend deep into medulla, responsible for hyperosmotic urine, necessary for CONCENTRATING ability - medullary peritubular capillaries are called vasa recta - drier the environment = longer loop = more concentrated urine + conservation of water possible Glomerulus is fenestrated = LEAKY, has pores that pass most plasma components 3 filtration barriers from plasma to tubule: 1. ENDOTHELIAL CELLS in glomerular capillaries: large (100 nm) fenestration pores, least selective 2. BASAL LAMINA: basement membrane (~20 nm) 3. FILTRATION SLITS FORMED BY PODOCYTES: specialized epithelial cells in Bowman's capsule, most selective (6-9 nm), zipper like slits Mutations in PODOCIN and NEPHRIN proteins, which form SLIT DIAPHRAGM on podocytes that function as the size selective final filtration barrier, allow pathological LEAKAGE of plasma proteins - proteinuria - serum hypoalbuminemia which causes edema due to decrease in colloid oncotic pressure of plasma = water retention in tissue Hydrostatic (blood) pressure: 55-60 mm Hg Fluid (capsular) pressure in Bowman's capsule: 15 mm Hg Colloid osmotic pressure:30 mm Hg Cells (including RBCs) and large proteins (not albumin) are retained in blood if normal functioning) Inorganic ions, water, glucose, amino acids, some vitamins, some hormones, albumin (reabsorbed by megalin) - fluid and small solutes basically

Be familiar with hormonal regulation of kidney functions by the renin-angiotensin- aldosterone system, ADH, and ANP & BNP.

ADH (arginine vasopressin): regulation of urine volume - produced by SUPRAOPTIC NUCLEUS (and paraventricular nucleus) of HYPOTHALAMUS Adjusts water reabsorption from CD and distal DCT by increasing APICAL INSERTION OF AQP2 into principal cells - increases permeability to water and therefore increases amount of water reabsorbed by vasa recta because the renal tubules equilibrate with increasing osmolarity in medulla = concentrated urine With no ADH, DCT and CD are not very permeable to water and urine stays diluted (~100 mOsm) after it leaves the loop of henle Vasopressin binds to basolateral membrane V2R receptor -> activates Gs -> adenylyl cyclase -> cAMP -> PKA -> phosphorylates Ser256 of AQP2-> storage vesicles insert AQP2 into apical membranes -> water absorbed and leaves through AQP3+4 Recycling of AQP2 via clathrin dependent endocytosis Released when OSMOLARITY HIGH OR BP LOW (bc increasing water reabsorption) sensed by: - ATRIAL STRETCH RECEPTORS: low stretch = low blood volume - CAROTID/AORTIC BARORECEPTORS: sense low BP - HYPOTHALAMIC OSMORECEPTORS: greater than 290 mOSM As plasma osmolarity increases, secretion of ADH + hypothalamic thirst level increases Effects: VASOCONSTRICTION, thirst, water reabsorption = BP/BV increases, blood osmolarity decreases Ingesting salt with no change in volume (so increasing osmolarity only) = vasopressin release + increased thirst = conservation of water by kidneys + increased ECF = vasodilation in response to increased BP Aldosterone: INCREASED NA+ REABSORPTION IN DCT AT EXPENSE OF K+ SECRETION, retain fluid - controls overall salt balance - endocrine hormone synthesized in adrenal cortex - can be released in response to hyperkalemia OR a decrease in blood volume/BP detected by stretch receptors - acts on PRINCIPAL CELLS IN DCT - controls via negative feedback - triggered by increased [angiotensin II] Fast response: INCREASE OPEN TIME OF ENAC & ROMK, INCREASE NA+/K+ ATPASE Activity - ROMK = Renal Outer Medulla K+ channel on apical side that lead to secretion of K+ that comes from sodium potassium pump Slow response: INCREASED TRANSCRIPTION of ROMK, ENaC, and NaK ATPase Other hormones: INCREASE in Na+ reabsorption = aldosterone, cortisol, estrogen, cortisol, estrogen, thyroid, insulin - often stimulate angiotensin production DECREASE in Na+ reabsorption = ANO, Parathyroid, Glucagon, Progesterone Aldosterone: promotes Na+ reabsorption and K+ secretion and responds to: - elevated [K+]: hyperkalemia protection - triggered by LOW BP via the RAAS - inhibited by high ECF osmolarity or high [Na+] UNLIKE ADH! Angiotensinogen = plasma protein constantly produced by liver in its inactive form, also increased by glucocorticoids, T3/T4, and estrogens RENIN: enzyme produced by GRANULAR CELLS of the juxtaglomerular apparatus that converts angiotensin into ANG I - released in response to DECREASE IN AFFERENT ARTERIOLE PRESSURE IN JUXTAGLOMERULAR APPARATUS --- beta adrenergic receptors that respond to sympathetic input: low BP increases sympathetic activity and triggers release of renin --- macula densa cells that detect sodium concentration: lower [Na+] indicates decrease in GFR (going slow), usually due to lower hydrostatic pressure -> paracrine signaling to release renin (higher [Na+] = LESS RENIN) ACE = angiotensin converting enzyme converts ANG I to ANG II, released by blood vessel and lung endothelium - ACE INHIBITORS = REDUCE HYPERTENSION ANGII stimulates: - ALDOSTERONE to increase sodium reabsorption - ADH to increase water reabsorption - thirst to increase volume - vasoconstriction and increased cardiovascular responses (through cardiovascular control centers) to increase blood pressure - decreased GFR and urine output to maintain blood volume ANP/BNP PROMOTES WATER + NaCl LOSS in urine ANP produced by atrial myocardial cells in response to atrial stretch (caused by increased atrial stretch) Triggers: - hypothalamus to decrease ADH - kidney to increase GFR and decrease renin - adrenal cortex to decrease aldosterone (also decreased by decreased renin) - medulla oblongata to decrease BP Effects: - increase NaCl and water excretion - decreased blood volume and pressure B-type produced in ventricles in response to ventricular filling pressure

What are the differences between active and passive immunity and by what mechanisms can each be acquired?

Active Immunity: antibodies develop after exposure to antigen - natural: infection - artificial: vaccine Passive Immunity: antibodies transferred from another source - natural: through placenta or breast milk - artificial: immunoglobulin injections

In regard to the Hb-O2-dissociation curve, how does temperature, pH, pCO2, and 2,3-DPG affect the curve?

All indicative of higher metabolic rates so ALL LOWER O2 AFFINITY AND SHIFT CURVE TO RIGHT (Bohr effect, greater Km = lower affinity) and FACILITATE UNLOADING of O2 from Hb to metabolic tissue - right shifted curve drops Hb saturation during exercise from 54% to 34% (80 ml to 130 ml O2) 1. low pH/ high [H+]: protons often as result of hydrolysis of ATP or CO2 dissolving into plasma, bind to histidine residue in Hb and lower O2 affinity by stabilizing tense state 2. increased CO2: binds to 4 amino terminals to form carbamate, more CO2 production = more metabolism 3. increased 2,3DPG (byproduct of glycolysis) binds to center of tetramer - chronic hypoxia (increased altitude) leads to hyperventilation = lowered CO2/ higher pH (alkaline) = typically left side shift and increased O2 binding affinity - increased DPG levels to offset/ correct the left hand shift of respiratory alkalosis and increase O2 tissue delivery 4. increased temperature: heat released during metabolism CADET: CO2, Acidosis, DPG, Exercise, Temperature forces RIGHT shift Automatic adjustment in tissue O2 delivery according to need, especially important for exercise - oxygen consumption increases 10 fold - cardiac output only changes 4-5 fold - need to account for difference through oxygen extraction from blood

Be familiar with the differences in the anterior and posterior pituitary in terms of their tissue origin, the way in which they are connected and respond to the hypothalamus, and the hormones each produces.

Anterior pituitary = adenohypophysis/ endocrine or glandular tissue, connected to hypothalamus via portal vein system - receives direct blood circulation/instruction from hypothalamus, synthesize and secrete hormones in response - Closed direct one-way circulation - Hormones: FLAT PEG · Posterior Pituitary = neurohypophysis/neural tissue, extension of hypothalamus essentially - has axon terminals of neurosecretory cells in nuclei of hypothalamus - Hormones produced by hypothalamus but stored in posterior until release - Peptide hormones: 1. ADH (increases amount of solute of free water that gets reabsorbed by regulating AQP2 in distal convoluted tubules and collecting duct, often increases blood pressure) 2. oxytocin (uterine contractions + milk letdown)

What is average resting membrane potential in human cells? Know all of the major components that contribute to the resting membrane potential and the importance of the Na/K-ATPase pump in maintaining it.

Average resting membrane potential: -70mV Depolarization: decreased separation of charge across membrane (typically by making the inside of the cell more positive (or the loss of negative) or losing some of the established concentration gradient) Hyperpolarization: increased separation of charge across membrane (typically by making the inside more negative (or loss of positive) or furthering the ion concentration gradients) Repolarization: reestablishment of the separation of charge and coming back to membrane potential Na+/K+ ATPase establishes gradient by increasing concentration of Na+ outside and K+ inside Leak channels for all cations exist that result in a constant ion flux across membrane at rest, but permeability for each is different - Potassium permeability is a dominant factor in membrane potential (highest) - Really low permeability of sodium - Permeability + ion concentration determine membrane potential

Be familiar with the different steps involved in the immune response to viral invader (see Fig. 24.13) and the immune response to extracellular bacterial infection (Fig. 24.12)

Bacterial Invasion: humoral - inflammation: degranulation of mast cells and release of chemotaxins - complement cascade - attract phagocytes to area to engulf immediately/post-opsonization - alert acquired immunity response: primary and secondary 1. activation of complement system - formation of MAC - activation of mast cells, w production of chemotaxins to attract circulating leukocytes and histamine to increase permeability - opsonization to enhance phagocytosis 2. activation of phagocytes - complement proteins, antibodies, acute phase proteins act as opsonins and coat pathogens 3. Acquired Immune Response - antigen presenting cells stimulate other lymphoid tissue to produce antibodies and cytokines - present antigens to helper T cells, activate B lymphocytes to release antibodies Viral Invasion: cell mediated - innate and antibody mediated defense - cytotoxic T cells and NK cells 1. Antibodies act as opsonins, enhancing phagocytosis by macrophages 2. Macrophages ingest virus and present on MHC II molecules + secrete cytokines for inflammatory response + interferons to block viral replication 3. Helper T cells activated by binding to MHC II and stimulate B cells + cytotoxic T cells 4. B cells (including memory) become plasma cells and release antibodies 5. Cytotoxic T cells release perforins + granzymes to attack infected host cell by binding to MHC I (also apoptosis)

Be familiar with ß-oxidation, lipogenesis, and differences in the composition and function of the 4 classes of lipoproteins the liver produces and the one class that enterocytes produce.

Beta-Oxidation: - occurs in mitochondria - for each 2 carbon fragment removed from FA: 12 ATP from acetyl coA in TCA and 5 ATP from NADH and FADH2 - 18 carbon FA actual yield would be ~120 ATP, equivalent to 1.5 times the energy of an 18C carb - fats are further reduced = more energy & yield per gram Lipogenesis: - FA synthesis starts with acetyl coA and builds with addition of 2C at a time - occurs in cytoplasm - TG synthesis: FAs esterified with glycerol - some FA essential aka we cannot produce it/ enough: linoleic acid/omega-6 (nut oils) and linolenic/omega 3 (marine oils) Chylomicrons: enterocyte-produced, fats from food - largest and least dense (so more fats than protein) - ApoA1/4 & ApoB48, matures w/ addition of ApoC2 and ApoE - enters lacteals and travels through thoracic duct Very Low Density Lipoproteins: - transport triglycerides to muscles and adipose tissue fo fat storage (typically after a meal) Intermediate Density Lipoproteins and Low Density Lipoproteins - deliver cholesterol to peripheral tissues - can lead to arterial plaques (oxidized LDL taken up by macrophages) High Density Lipoproteins: - equal amounts protein and lipid - transports excess cholesterol from peripheral tissues to liver for storage or excretion in bile

Be familiar with the different classes of T cells. Which classes bind to antigens displayed on MHC class I proteins and which CD marker must these cells have to interact with such cells? For MHC class II? By what different mechanisms are antigens processed and displayed by MHC I and II proteins? What is an antigen-presenting cell?

CD8+ Cytotoxic T cells: attack infected or mutated cells, responsible for cell mediated immunity, bind to MHC I target cells for activation (which presents peptides from within itself - normal or virus/mutated) CD4+ Helper T cells: stimulate function of B and T cells via cytokines, bind to MHC II target cells (which presents peptides from engulfed pathogen) Suppressor (Regulatory) T cells: inhibit function of T and B cells Others: NKT, mucosal, GDT Antigen Presenting Cells: responsible for activating T cells against foreign cells and proteins - phagocytic cells such as free and fixed macrophages CD markers: antigen recognition in T cells - CD3 found in all cells - CD4: helper T cells + TREGs + memory cells, respond to MHC II presented antigens - CD8: cytotoxic T cells + TREGs + memory cells, respond to MHC I presented antigens

What factor(s) determine the metabolic pathway(s) by which ATP will be made to fuel skeletal muscle contractions? What role does creatine phosphate play in skeletal muscle contraction? Know the relative amounts of different energy sources that can fuel skeletal muscle contractions and the duration over which each can support contractions.

COMPETITION FOR ADP AND CHANGES IN ADP BINDING AFFINITIES OF ENZYMES INVOLVED IN PHOSPHORYLATION DICTATES WHICH METABOLIC PATHWAYS - either PK/PGK win or ADP/ATP translocase + ATP synthase wins RESTING muscle: - use of blood borne substrates (glucose, oxygen, and FATTY ACIDS) - any excess goes to bolster supplies of ATP, CP, or glycogen MAX EXERTION: - ATP and CP used up rapidly and ENERGY CHARGE begins to crash - low energy charges ACTIVATE GLYCOLYSIS - w/high ATP demand and low energy charge, glycolysis enzymes will outcompete all other enzymes that us ADP - if ATP demand remains high and O2 gets used up - fermentation MODERATE activity: moderate to low myosin ATPase activity - ATP and CP used up - blood borne fatty acids and muscle glycogen are tapped into to generate ATP AEOROBICALLY - ATP levels never dip low enough to fully activate PK and PGK and so ADP/ATP translocase and ATP synthase outcompete thereby ensuring oxidative phosphorylation ATP needed for myosin ATPase, SERCA, and normal ion channels ATP is very minimal and NOT stable/supportive - phosphocreatine stores reserve energy 4x more than ATP but even this is short - in resting muscle, ATP used to create phosphocreatine - in working muscle that is reversed to obtain ATP via creatine phosphate kinase Adenylate kinase: AMP + ATP <-> 2 ADP (shifts depending on if you need ATP) Energy for Fueling Contractions - glycolysis: fast and powerful bc doesn't use O2 but energetically inefficient = used at HIGH EXERCISE INTENSITY - aerobic respiration: efficient and sustainable but slower and less powerful bc needs O2 = lower intensity exercise but LONGER duration (so SUSTAINED exercise) - fat catabolism is SLOW but does have a very high energy output and can last long (larger than glycogen for both) - High intensity NEEDS GLUCOSE (from glycogen of which there is a high availability) - Phosphocreatine power output only advantageous if high intensity repetitive, explosive exercise

Know what ion channels are involved in all of the phases of an action potential in both a cardiomyocyte and an autorythmic cardiac cell. How are they different from each other? Which channels account for the pace-maker potential? By what specific mechanisms do norepinephrine and acetylcholine affect the pace-maker potential?

Cardiomyocytes AP: 1. depolarization via voltage gated Na+ channels 2. partial repolarization initiated by opening fast K+ channels 3. PLATEAU from increased Ca 2+ through CaV1.2 channels DHPR and decreased K+ permeability (fast K+ channels close) 4. rapid repolarization occurs following closing of Ca2+ channels and slow K+ channels opening Autorhythmic AP: spontaneous, adjustable, 1% of cells - PACEMAKER POTENTIAL due to funny, non-selective IF CHANNELS = leak Na+ (more bc electro + chemical gradient) and K+ = slowly drifting towards threshold - If channels are HCN CHANNELS: HYPERPOLARIZATION-activated cyclic nucleotide gated channel (cAMP and cGMP) - If channels open at -60mV - at ~-55 mV, T-type Ca2+ channels open (LOW voltage activated, transient opening) + If channels close - at threshold = -40mV many L-type Ca2+ channels open = high voltage, long opening - repolarization due to Ca 2+ channels closing and K+ channels opening - at -60 mV, K+ channels close, If channels open SYMPATHETIC (norepinephrine) INCREASES FREQ and PM POTENTIAL - NE binds B1 adrenergic receptors = increase in cAMP = If channels open = faster depolarization due to influx of Na+ (If channels) and Ca2+ (T-type channels) PARASYMPATHETIC (acetylcholine) DECREASES FREQ and PM POTENTIAL - activates muscarinic (M2) receptors that open G-protein mediated inward rectifying K+ channels (KACh) - indirectly decrease cAMP leading to fewer If channels open = hyperpolarization / slower depolarization

In regard to the regulation of breathing, what are the roles of the dorsal respiratory group, ventral respiratory group and pontine respiratory group? Be familiar with the central chemoreceptors in terms of their location and what they specifically respond to.

Cerebral cortex: voluntary/ behavioral breathing Pons/ Medulla Oblongata: involuntary/ metabolic breathing, sensory feedback from central (in CSF) and peripheral (aortic/carotid) chemoreceptors - increased ventilation provoked by increase in pCO2 and decrease in pH DRG - contains INSPIRATORY neurons that fire to activate diaphragm and external intercostal muscle (primarily inspiratory muscles) via the phrenic and intercostal nerve for inspiration during eupnea - receive sensory input from central + peripheral CHEMORECEPTORS that is relayed to pontine group VRG - contains PACEMAKER neurons in PRE-BOTZINGER complex that inhibits DRG inspiration to begin EXPIRATION - VRG neurons also innervate expiratory + some inspiratory muscles used during HYPERPNEA (abdominals, sternocleidomastoids) and muscles of pharynx, larynx, and tongue required to keep airway passages OPE PRG - provides feedback from higher brain sensors and interprets central + peripheral chemoreceptor/ mechanoreceptor info from DRG that is used to modulate DRG and VRG - alters breathing rate and depth - limits inspiration via PNEUMOTAXIC center or promotes inhalation via APNEUSTIC center [want to prevent sleep apnea] Activity of inspiratory neurons increase during inspiration (positive feedback) until inspiration stops (cease all neuronal activity), expiration occurs mainly as result of elastic recoil of lungs - rate of cycling driven by Pre-Botzinger complex pacemaker neurons Cerebral Cortex: motor cortices + limbic system - can OVERRIDE pons and medulla oblongata during voluntary control of breathing, elevated ventilation, breath control, sudden gasp (emotions) receptors in muscles and joints can also activate respiratory centers stretch and irritant receptors in lungs can inhibit respiratory centers

Have good understanding of how chemical, electrical and electrochemical gradients determine the movement of ions (e.g., Na+ and K+) during an action potential. Know the "anatomy" of an AP and the steps involved in terms of ion channel gating and ion movement for the depolarization, repolarization and hyperpolarization. Understand the kinetics and mechanistic of Na+ and K+ channel gating and what is responsible for both the absolute and relative refractory periods. What is a graded potential?

Change in ion permeability + concentration gradients determine movement - Change in Na+ permeability is what drives MP towards Ena and is the basis of all electrical signaling - Na+: concentration and charge wants it to go in - K+: concentration wants it to go out but negative charge keeps it in Graded potentials: local current wave that can be depolarizing or hyperpolarizing usually in dendrites or cell body (varying locations from axon hillock) Conduction: high speed movement of action potential along an axon at constant amplitude 1. Membrane potential at -70 mV 2. Depolarizing stimulus that reaches threshold: Na+ channels open up for ½ msec before inactivation gates close and depolarizes the cell 3. During all that K+ channels being to open and move out of the cell: repolarization 4. K+ channels remain open and the cell hyperpolarizes (-80 mV) 5. Cell returns to resting ion permeability and resting membrane potential Ion Channel Gating: - Activation gates: voltage sensors (arginine and lysine residues) detect threshold and open to let Na+ in - Inactivation gate: hydrophobic residue on channel, takes 0.5 msec to close after activation gates open - Both gates require 2 msec post threshold to reactivate Sodium Channel - Alpha subunit: 4 homologous domains w/ 6 transmembrane segments form a channel - S4 has positive amino acid residues that forms part of voltage sensor - S5-S6 segments form channel lining - S5-S6 linkage is the pore selective filter - DIII-DIV linkage: inactivation gates Absolute refractory period: No Aps possible, to prevent overlap of Aps or backward propagation Relative Refractory Period: - Aps can be triggered by very large graded potentials - K+ channels are still open - Aps smaller than normal - Really need something huge though

Be able to explain the characteristics and differences between each of the following transport mechanisms, the steps involved in each and to provide an example of each. a. channel-mediated vs. carrier-mediated transport b. active vs. passive vs. secondary active transport c. uniport vs. symport vs. antiport

Channel-mediated: water filled pore that can be gated (with an inactivation gate or affected by cofactor) or not gated (like a leak channel or aquaporin) - mechanical, chemical, or voltage - Primarily passage of ions and water - Variable specificity: one or more substances, based on diameter of pore and charges of amino acids in the pore or hydration sphere - Saturation limits: max rate depends on number of channels - Regulated by gating Carrier-Mediated: undergo conformational changes as they bind to their substrates which are usually ions or organic substrates and transport them across the membrane - High specificity: one transport protein, one substrate or set of similar substrates - Saturation limits: max rates depend on number of transport proteins, lower than # of channels themselves, try to increase surface area (ex. microvilli) to allow for more transport proteins - Regulated by cofactors like hormones - Uniport, symport, antiport - Passive OR active! (depends on direction/gradient) 1. Uniport: transport of single molecule (ex. Glucose transporters) 2. Symport: transport of two or more dissimilar solutes together in the same direction (ex. Sodium-glucose linked transporters) - Cotransport - Can sometimes utilize the concentration gradient of one substrate for the other that is going against 3. Antiport: transport of one or more solute for another (opposite direction): ex. Na+/K+ ATPase or ADP/ATP translocase - Counter transport/ "exchange diffusion"/ "ping pong" kinetics Passive Transport: no ATP/energy required - Facilitated diffusion: use of channels or carrier proteins (depending on size usually) - Receptor site, conformational change Primary Active Transport: directly requires energy to carry a substrate(s) against their concentration gradient - Ex. Na+/K+ ATPase - both against concentration gradient, exchange pump Secondary Active Transport: transport mechanism doesn't require energy but uses a pre-existing gradient created using ATP - Ex. Sodium glucose linked transporter uses created Na+ concentration gradient to drive glucose transport

CDs and MHCs

Clusters of Differentiation: (CD4/8) transmembrane glycoprotein cell surface molecules that serve as co-receptors for T cell receptor, allowing TCR to interact with specific MHCs - CD8: CYTOTOXIC T cells, NK T Cells, and dendritic cells, binds MHC I - CD4: HELPER T Cells, macrophages, dendritic cells, binds MHC II Major Histocompatibility Complexes: cell surface proteins essential for acquired immunity - MHCI: all nucleated cells have, displays epitope peptides from intracellular pathogens - MHCII: only APCs have, displays epitope peptides from extracellular pathogens

What are the functions of the conducting and respiratory zones of the respiratory tract? In which portions of the respiratory tract is gas exchange possible? What cell types are found in the respiratory zone and what are their functions? What structures are responsible for keeping the alveoli open? What is the role of surfactant? What muscles are involved during eupnea? During hyperpnea?

Conduction Zone: NO gas exchange - trachea, bronchioles - can change diameter to increase velocity of air and dislodge something - humidification + warming of air - particle filtration (mucus lining) - immunoglobulins (in mucus) fight pathogens - mucus moved by cilia Respiratory Zone: GAS EXCHANGE - surface for gas exchange - surfactant production - pH regulation - blood clotting regulation - endocrine function 23 DIVISIONS OF BRONCHIOLES - 1-16 is conduction zone (trachea to bronchioles) - 17-23 is respiratory zone (respiratory bronchioles to alveolar sacs) Gas exchange possible in respiratory bronchiole + alveoli (majority) Pores of Kohn: inter-alveolar pores that allow for equalization of pressures within alveoli Respiratory membrane = 0.5 MICRONS (extremely thin tissue to allow for rapid diffusion) - two thin endothelial cells and fused basement membrane - surfactant TYPE 1 alveolar cells: - path for diffusive GAS EXCHANGE - squamous cells that make up the alveoli TYPE 2 alveolar cells - SECRETE SURFACTANT to reduce surface tension but NOT necessarily to keep from collapsing inwards TYPE 3 alveolar cells - dust cells or alveolar macrophages INGEST PATHOGENS and foreign material - majority phospholipids + surfactant protein DIAMETER OF ALVEOLI = 200-500 microns Alveoli are POLYGONAL in shape so laplace's law doesn't even apply - alveoli are more like FOAM than grapes on a wine Alveoli do not collapse because of: 1. suspension in a matrix of connective tissue cables (elastic and collagen fibers) that keep them open 2. share common perforated walls with pores of Kohn so there is no pressure differential Surfactant important along PLANAR surfaces of the alveolar wall and in mitigating forces that tend to close small airways LEADING IN towards alveolo but not specifically alveoli Muscles of INSPIRATION: eupnea and hyperpnea - STERNOCLEIDOMASTOID - SCALENES - less role of external intercostal as thought - diaphragm - paternal intercostals - ribs also lift (maybe counts?) Muscles of EXPIRATION: hyperpnea only (during eupnea, the ones above just relax - internal intercostals - OBLIQUES + ABDOMINIS (external, internal, transverse, rectus) At rest, there is a slight negative pressure in the intrapleural space but pleural fluid cannot expand due to surface tension (why IPP becomes more negative during inhalation) PNEUMOTHORAX = air entering pleural space due to the pleural cavity somehow - can cause partial or full lung collapse - ATELECTASIS due to high number of elastic and collagen fibers - can be fixed by pulling that air out

When at rest at sea level, how saturated is Hb at the alveoli? In the aorta? In the vena cavae? How many ml of O2 is carried in our blood per liter in each of these locations?

Cooperative binding: sigmoidal saturation curve - large range of intermediate average saturations at different PO2 97% SATURATION AT SEA LEVEL AT ALVEOLI (100 mm Hg) RESTING cell can drop to 74% SAT = 46 ml O2/L EXERCISE - tissue PO2 drops 30 torr: 57% SAT = 80 mL O2/L - decreasing binding affinity/ increasing Km good because you want to dump oxygen when it is needed Alveoli: 100 mm Hg PO2, 97% saturation, 194 mL Aorta: 95 mm Hg PO2, 97% saturation, 194 mL Vena cava: 40 mm Hg PO2, 74% saturation, 148 mL Exercise: 30 mm Hg PO2, 57% saturation, 114 mL Total oxygen carrying capacity - 200 mL Reserve built in to dump O2 to tissue when metabolic tissue increases to ensure that we never reach zero saturation

In regard to the HPA axis and the release specifically of cortisol, know the hormone cascade (CRH - ACTH - cortisol) and mechanism of feedback regulation, the function/action of glucocorticoids, and the effects and diseases associated with hypo- and hyper-cortisolism. Be familiar with the therapeutic use of glucocorticoids and precautions for their iatrogenic abuse.

Corticotropin Releasing Hormone -> Adrenocorticotropic Hormone (stimulates the growth of the adrenal cortex and the synthesis/secretion of glucocorticoids) -> Cortisol (negatively feedbacks to pituitary and hypothalamus via long loop) Cortisol: influence metabolism, stress response, etc - Prevents hypoglycemia!!: end goal is to increase plasma glucose levels - Has a permissive effect on glucagon and catecholamine (Epi) - Critical for responding to stress - All nucleated cells have glucocorticoid receptor - Increase gluconeogenesis in liver, lipolysis, increased protein breakdown in skeletal muscle - Tries to limit the amount of calcium that is building bone and so it throws it all out -- Increases breakdown of bone -- Increase renal excretion of Ca2+ -- Decrease intestinal absorption of Ca 2+ - Suppresses immune system (prevents cytokine release and antibody) and inflammation - Effects mood cognition and behavior Hypercortisolism = Cushing's syndrome - Adrenal cortex tumor or pituitary tumor that secretes - Hyperglycemia, increased muscle breakdown and catabolism in general (body feeding on itself), increased appetite, increased bone breakdown (osteoporosis), decreased inflammation but possible immune dysregulation - Depression, cognitive impairments - Decreased gonadotropin release hormone - Buffalo hump, moon face, striations Hypercortisolism: Addison's Disease - Not common - Deficiencies in mineralocorticoids and glucocorticoids (autoimmune destruction) - Moon face Therapeutic drugs: hydrocortisone, prednisone, dexamethasone (short to long acting) - Topical creams for allergies or bee stings, longer term would be epidurals - Suppress immune system and inhibit inflammatory response - Over long term, can lead to iatrogenic hypercortisolism: excess exogenous causes the effects of hypercortisolism (like osteoporosis) but also hard for your HPA axis to go back to functioning as normal (can lead to adrenal atrophy)

What is the relative power output from glucose oxidation vs. glucose fermentation vs. fat oxidation vs. creatine phosphate utilization? Which substrates do we store in our body for catabolic use and why?

Creatine phosphate has highest power output because it is a one step enzymatic reaction Glucose fermentation has high power output (almost 2x that of glucose oxidation) because it is really fast and has same energy availability because the lactate that is produced does eventually get converted into ATP (same net amount of glucose is being utilized) Fats have highest energy availability hence why they stored for catabolic use

Be familiar with the general mechanism of inflammation and the specific roles of acute- phase proteins, histamine, interleukins, bradykinin, and the complement pathway, and other chemical-mediators of the immune response listed on Table 24.1 (slide 31).

Cytokine Induced Inflammation: nonspecific defense, hallmarked by swelling, redness, heat, and pain 1. attracts immune cells and chemical mediators to site 2. produces physical barrier to slow spread of infection 3. promotes tissue repair once infection is under control - blood flow increases, phagocytes activated, capillary permeability increases, complement activated, clotting reaction, regional temperature increases, adaptive defenses activated Acute phase proteins: act as opsonins by coating pathogens - anti-proteases: protect tissue - produced by liver - ex. C reactive protein activated complement pathway, indicates chronic inflammation Histamine: released by mast cells and basophils, general inflammation - attract leukocytes, opens capillaries, and dilated blood vessels - works with prostaglandins and leukotrienes - vasodilator but bronchoconstrictor Interleukins: cytokines secreted by leukocytes - IL-1 is major modulator of immune response 1. alters blood vessel endothelium to ease passage of WBCs and proteins 2. stimulates production of acute phase proteins 3. endogenous pyrogen: fever inducing Bradykinin: vasodilator of blood vessels, inflammatory mediator, promotes pain sensation Complements: many different plasma and cell membrane proteins that are part of cascade (complement pathway) - intermediates in cascade act as opsonization, chemotaxins, and cause mast cell degranulation - terminates in formation of membrane attack complex (MAC) --> C9s opens large pore in pathogen causing lysis upon entrance of water and ions

Be familiar with T cell antigen recognition, stimulation and activation, clonal expansion, intruder destruction (perforin, lymphotoxin, granzymes and Fas activation).

Cytotoxic T cells (CD8+): recognize MHC I proteins on infected cell -> activation and clonal expansion 1. release perforins and granzymes (like NK cells) to lyse and digest 2. activate Fas (death receptor) to induce apoptosis 3. some subtypes secrete poisonous lymphotoxin - fairly slow response (2 days post antigen exposure) Memory T cells (CD8+): produced along with cytotoxic T cells during clonal expansion, stay in circulation Helper T Cells (CD4+): recognize MHC II proteins on APCs and divide into - Memory T cells: remain in reserve - Active Helper T Cells: secrete cytokines to stimulate both cell mediated and humoral immunity (HIV destroys these) 1. stimulate T cell divisions (produce memory TH and accelerate cytotoxic maturation) 2. attract and stimulate macrophages 3. attract and stimulate NK cells 4. promote activation of B cells Co-stimulation: for a T cell to be activated, must be co-stimulated by binding of 2nd, antigen nonspecific site Regulatory T Cells (TREGs) CD4+/CD25+: inhibit the function of T and B cells after initial immune response t limit response

Be familiar with the conducting system of the heart, the spontaneous depolarization rates of autorhythmic cells in each location and the influence of sympathetic and parasympathetic input. Also, know the steps in Wigger's diagram and factors involved in changing hemodynamics.

Depolarization of AP from autorhythmic pacemaker cells spreads to contractile cells through GAP JUNCTIONS in the intercalated cells 1. SINOATRIAL NODE: cluster of autorhythmic cells in right atrium is main pacemaker 2. Internodal pathways (non-contractile) send depolarization to ATRIOVENTRICULAR NODE 3. 130 MSEC DELAY at AV node before atrial contraction begins! - Bachman's bundle helps out 4. Depolarization moves from AV node through AV BUNDLE in the interventricular septum (non-conducting) down the right and left bundle branches to the PURKINJE FIBERS + through the moderator band to papillary muscles attached to valves 5. Depolarization up through the Purkinje fibers and ventricular contraction begins Spontaneous depolarization rates: - SA Node: 80-100 AP/min* - AV Node: 40-60 AP/min** - Purkinje fibers: 30-40 AP/min *our HR not 80-100 at rest, so there is a parasympathetic tone slowing down intrinsic rate of contraction caused by tonic release of acetylcholine (KAch channels = hyperpolarization) via vagus nerve **if SA node fails (which normally overrides to set HR), the AV node controls HR but doesn't beat fast enough to provide adequate CO 1. Atrial contraction/systole begins, both AV valves remain open 2. Atria eject blood into ventricles: "topping off" of ventricular volume 3. Atrial systole ends: AV valves close, ventricles at EDV 4. Isovolumetric ventricular contraction (systole begins) - no volume change but pressure in ventricles rises with AV valves shut 5.Ventricular ejection/systole occurs - semilunar valves open (pressure in ventricles high enough), blood flows into pulmonary and aortic trunks - Stroke volume (SV) = 55-70% of EDV ventricular pressure increases until it hits systolic pressure level 6. Semilunar valves close - ventricular pressure falls lower than in aortic arch so valves close - ventricles contain ESV, about 30-45% of EDV 7. Isovolumetric relaxation occurs: ventricular diastole - ventricular pressure still > atrial pressure - all heart valves closed 8. AV valves open, passive ventricular filling occurs when ventricular pressure falls below atrial pressure - blood flows from atria into ventricles while both in diastole: refilling until new contraction Autonomic innervation of SA + AV node, atrial myocardium - sympathetic dominates in ventricles - cardiac centers of MEDULLA OBLONGATA monitor BP via baroreceptors and arterial O2/CO2 levels via chemoreceptors - dual innervation maintains resting tone (NE + ACh) CARDIOACCELERATORY center (in MO) controls sympathetic neurons and has positive chronotropic (HR) effect --B1 receptors of autorhythmic cells lead to opening of If channels via increased [cAMP] = greater calcium and Na+ influx = increased rate of depolarization = increased HR CARDIOINHIBITORY center (in MO) controls parasympathetic neurons and has negative chronotropic effect -- muscarinic receptors in autorhythmic cells lead to indirect decrease in [cAMP] and closing of IF channels, increased K+ efflux and possible decreased Ca 2+ influx = hyperpolarization/ decrease in rate of depolarization = decreased HR PARASYMPATHETIC (ACh) decrease contractility - vagus nerve INOTROPIC agents affect contractility and thus stroke volume CHRONOTROPIC agents affect heart rate - catecholamines (NE + Epi) are POSITIVE inotropic and chronotropic agents because they increase contractility (more forceful) - glucagon and thyroid hormones also positive inotropic + chronotropic - caffeine increases HR - all 3 act on SA node - nicotine stimulates sympathetic neurons - changes in K+, Ca2+, temperature can also affect - B1 receptor mimetics increase contractile strength and pacing - B1 receptor blockers often used to treat myocardial infarction, tremors, hypertension, rhythmic disorders bc they block an increase in cardiac output - other drugs affect calcium, such as digoxin inhibiting Na+/K+ ATPase and slowing NCX = increase calcium to restore circulation

What is diffusion, what are its characteristics and what factors affect the diffusion of molecules in our bodies? According to Fick's law of diffusion, the rate of diffusion of a substance across a plasma membrane is proportional to what 3 factors?

Diffusion: passive transport down a concentration gradient (high to low concentrations) until an equilibrium is formed, rapid over short distances (why we need to keep distances small because of the limitations of diffusion) and very slow over long distances The diffusion coefficient is directly related to temperature (higher temperature is better for diffusion, but only weakly dependent), and inversely related to viscosity and molecular size/radius (smaller and less viscous is faster) - R^2 = 6Dt (r = distance traveled) - Fick's Law states that the rate of diffusion across the membrane depends on: -- Membrane surface area (more is better) -- Concentration gradient across the membrane (more is better) -- Membrane permeability (can be affected by cholesterol = more rigid)

Be familiar with both the endocrine and exocrine functions of the pancreas. Which cells are involved in each and which cells secrete sodium bicarbonate to neutralize the acids secreted by parietal cells (and by what mechanism)? By what mechanism is trypsinogen activated to trypsin and what does it then do?

Endocrine functions: insulin and glucagon from islet cells Exocrine functions: - DUCT CELLS secrete majority of of bicarbonate needed to neutralize stomach acid - acinar cells: digestive enzymes - stimulated by cholecystokinin (CCK) (synthesized by duodenum triggers release of pancreatic enzymes), small intestine digestion, stomach distension, and neural control Pancreatic secretions of inactive zymogens including trypsinogen into lumen of small intestine -> ENTEROPEPTIDASE in brush border of intestinal mucosa activates it into trypsin -> TRYPSIN ACTIVATES ALL OTHER ZYMOGENS into activated enzyme form Pancreatic Duct and Duodenal Cells: BASOLATERAL: - Na/H+ exchanger pumps H+ in produced by carbonic anhydrase - NKCC channel - Na+/K+ ATPase sets up gradient for both - K+ channel to release K+ coming in APICAL: - HCO3-/ Cl- exchanger pumps HCO3- produced by carbonic anhydrase out into lumen - CFTR (Cl-) channel to release Cl- coming in, important for keeping mucus fluid and allowing for enzymatic secretion

Which antibodies are produced during the first encounter with an antigen, how long does it take from them to reach a high titer, and which is more effective? How does the secondary immune response differ from a primary response? Why do some vaccinations require "booster" shots and others not?

First exposure/ primary response - takes up to two weeks - antigens activate B cells, plasma cells differentiate - antibody titer slowly rises and then declines - primarily IgM and IgA initially: produced faster but at lower concentrations and is less effective - IgG peaks at around 3/4 weeks to higher concentration and lasts longer Secondary response - activates memory B cells at lower antigen concentrations - secretion of massive quantities of antibodies - IgM production quicker and slightly extended - IgG levels rise really high and very quickly for extended periods of tiems some need continual exposure to boost the antibody titer to appropriate level or if some are particularly deadly viruses its better to keep those levels maintained (pathogenicity)

By what different stimuli are G cells activated?

G cells are stimulated by either: 1. stomach distension 2. peptides and amino acids 3. Gastrin releasing peptide (GRP) from postganglionic fibers of Vagus nerve (parasympathetic innervation) Gastrin released into bloodstream -> stimulates enterochromaffin-like cells (ECL) and parietal cells via cholecystokinin type B receptors ECL release histamine -> stimulates parietal cells at H2 receptors (G protein) along w ACh and gastrin -> parietal cells produce H+ ions for acid secretion - H2 receptor antagonists can treat acid reflux Excess H+ stimulates D cells to release somatostatin to negative feedback G cells and downregulate acid

By what mechanisms is the glomerular filtration rate (GFR) regulated on a local level (autoregulation)? What sensors are involved in regulating both the myogenic response and tubuloglomerular feedback systems? By what global mechanisms is autoregulation overridden and how do these mechanisms work?

GFR: volume of initial filtrate entering nephrons per unit time, dependent on - filtration pressure - total surface area of glomerular capillaries (can be changed by mesangial cells - permeability of capillary-Bowman's interface - CONSTANT over wide range of BP (80-180 mm Hg) but low blood pressure will lead to reduced GFR to increase the BP - downstream tubular reabsorption of fluid is more often adjusted than GFR Autoregulation: - upstream afferent vasoconstriction = reduced GFR - upstream afferent vasodilation = increased GFR - downstream efferent vasoconstriction = increased pressure = increased GFR - downstream efferent vasodilation = decreased pressure = decreased GFR 1. MYOGENIC RESPONSES: ADJUSTING BLOOD FLOW through renal arterioles *smooth muscle constriction/dilation in afferent/efferent arterioles - mediated by afferent arteriole STRETCH receptors that tell about BP (stretch leads to depolarization = contraction) - HIGH systemic BP = stretch = let LESS blood into glomerulus (by constriction) to offset - LOW systemic BP = relax = let MORE blood in glomerulus (by vasodilation) to offset 2. TUBULOGLOMERULAR FEEDBACK: PARACRINE SIGNALS *negative feedback loop that maintains GFR through paracrine signals - macula densa cells in DCT sense salt concentration as a function of GFR and release paracrine signaling to affect afferent arteriole diameter - ATP and adenosine = vasoconstriction - Nitric Oxide = vasodilation - high [NaCl] means going too fast and GFR is large = CONSTRICT arterioles and mesangial cells to decrease GFR (and vice versa) via ATP/adenosine - low GFR also triggers renin release because low BP usually triggers low GFR 3. Primary cilia in renal tubules also detect flow directly Global Regulation 1. ENDOCRINE SIGNALS: ANP (atria), BNP (ventricles) - natriuretic peptides lead to a INCREASE GFR and decrease in blood volume/BP - stimulus: increase in blood volume/pressure detected by atrial wall stretching - heart releases ANP --> inhibits renin release from granular cells -> decreased angiotensin II production -> relaxation of mesangial cells + vasodilation of afferent arterioles -> increased GFR 2. SYMPATHETIC INNERVATION - stressor causes sympathetic stimulation of kidneys -> granular cells release renin + increased production of angiotensin II -> contraction of mesangial cells and vasoconstriction of afferent and efferent arterioles -> decreased GFR and MAINTENANCE of blood volume

Be familiar the regulation, release and effects of prolactin, GH, insulin and glucagon and effects or diseases that are associated with their dysregulation.

GH: - Tonic secretion, circadian rhythm - Under antagonistic control: growth hormone releasing hormone (somatotropin) vs growth hormone inhibiting hormone (somatostatin) - Negative feedback from IGF to somatotropin - Acts on liver and other tissues - Stimulates secretion of GIFs and bone, cartilage, muscles to grow - Promotes protein synthesis - Abnormalities due to pituitary tumors: -- GH deficiency in childhood: dwarfism -- GH excess in childhood: gigantism -- GH excess in adulthood: acromegaly (appositional bone growth) Prolactin: - Inhibited primarily by dopamine = prolactin inhibiting hormone - Shit ton of effects: mainly milk synthesis/ secretion - Works with oxytocin (milk let down) which leads to brain functions down regulating PIH allowing for increase in prolactin Insulin/Glucagon - Beta islet cells: secrete insulin (increased after a meal for uptake of glucose) -- Dominates in a fed state and promotes anabolic effects and lowers blood glucose levels -Alpha islet cells: glucagon (increased when hungry to increase blood sugar) -- Dominates in a fasted state and promotes catabolic effects -- Kinda like cortisol - Delta cells: somatostatin

Be familiar with the general function of leukocytes and lymphocytes and their different classifications (e.g., granulocytes, phagocytes, cytotoxic, or antigen presenting - see Figure 24.5). What are the primary physical and chemical lines of defense against pathogens?

Granulocytes: have granules (antibacterial compounds / acid hydrolases they can secrete), found in blood and tissues - NEUTROPHILS: most abundant, phagocytes*, release cytokines and inflammatory mediators - BASOPHILS: rare, release heparin (anticoagulant) and histamine*, similar to mast cells (fixed cells), inflammation - EOSINOPHILS: rare, cytotoxic*, important in parasitic and allergic reactions Antigen Presenting Cells (APCs): insert fragments of processed antigens on cell surface - MONOCYTES: precursors of macrophages, larger phagocytes* than neutrophils - LYMPHOCYTES: B cells, T cells, NK cells, some cytotoxic, acquired immunity, antibody production - DENDRITIC CELLS: in skin (Langerhans) and other organs, recognize pathogens and migrates to 2ndary lymph tissue for presentation,phagocytic Physical and Chemical Barriers: - skin: hair, sebaceous secretions - epithelial membranes: mucosal secretions, resident sentinel macrophages - microflora on skin

Be familiar with the different transporters for organic molecules, protons, bicarbonate and ammonium in the nephrons. What is the renal threshold?

H+ ATPase: active transport of H+ into urine H+/K+ ATPase: active transport of H+ into urine, K+ reabsorption APICAL NHE = H+/Na+ exchanger: exports H+ into tubule in exchange for Na+ NH4+/Na+ antiport: exports NH4+ into urine in exchange for Na+ BASOLATERAL Na+/HCO3- symport: exports both out into IF using [HCO3-] gradient In CD: HCO3-/Cl- ANTIPORTER (aka Pendrin) PCT Control: 1. SECRETION OF H+, REABSORPTION OF HCO3- - Uses APICAL NHE = H+/Na+ exchanger: exports H+ into tubule in exchange for Na+ - that H+ in urine combines with bicarbonate to become CO2 and water - water leaves and CO2 diffuses back in to combine with water to form HCO3- and become reabsorbed via BASOLATERAL Na+/HCO3- symport 2. DEAMINATION OF GLUTAMINE to form ammonium - glutamine metabolized into ammonium and excreted via NH4+/Na+ antiport - and alpha-ketoglutarate which is converted into HCO3- and leaves through BASOLATERAL Na+/HCO3- symport Type A intercalated cells = Acid Secretion - SECRETE H+ AND REABSORB HCO3- AND K+ - acidosis more frequently encountered, combined with hyperkalemia - APICAL: --- H+/K+ ATPase (active transport of H+ into urine, K+ reabsorption) --- H+ ATPase (active transport of H+ into urine) - BASOLATERAL --- HCO3-/Cl- ANTIPORTER (bicarbonate out, Cl- in) --- K+ leak channels to complete reabsorption - bicarbonate buffer in IF helps to bring in protons to intercalated (by converting to water and CO2) - carbonic anhydrase within the cell converts back to H+ to be kicked out through the apical transporters Type B Intercalated Cells = Base Secretion during alkalosis, combined with hypokalemia often - SECRETE K+ and HCO3- AND REABSORB H+ - FLIPPED TRANSPORTERS - APICAL: --- HCO3-/Cl- ANTIPORTER (bicarbonate out, Cl- in) --- K+ leak channels cause excretion - BASAL: --- H+/K+ ATPase (active reabsorption of H+ into urine, K+ into principal cell) --- H+ ATPase (active transport of H+ into urine) - H2O and CO2 come into cell and get converted into bicarbonate (secreted) and H+ (reabsorbed) - Other transporters: --- apical NDCBE: Na+ driven Cl- and HCO3- exchanger brings bicarbonate in and Cl- out --- basal anion exchanger drives NDCBE by transporting Na+ and bicarbonate into IF TRANSPORT MAXIMUM = saturation of transporters - beyond threshold -> excess secretion in pee - can occur when [plasma glucose] is very high: - reabsorption is proportional until Tm, and then the rest is lost in urine (sweet pee) For glucose: Tm is 375 mg/min and RENAL THRESHOLD IS ~180 mg/dl - slightly elevated in people with type 2 diabetes (some compensation)

What is homeostasis, who championed its definition and why is it important to maintain a homeostatic state?

Homeostasis: maintenance/regulation of internal functional equilibrium/ stability in the face of perturbations using passive/active mechanisms Walter Cannon's Postulates: - Nervous system has over-reaching control and works to preserve homeostasis - Some systems are under tonic control: some base level of a physiological variable that can be increased or decreased by a single factor (ex. TSH on T3/T4, amount of neurotransmitter on heart rate diameter) - Antagonistic Control: up-regulation and down regulation by two opposing factors on a physiological variable (ex. Sympathetic/ parasympathetic on heart rate; glucagon and insulin on blood sugar) - Same chemical can have different effects in different parts of the body (ex. Epinephrine can cause vasodilation or constriction depending on which adrenergic receptor it binds to)

Be familiar with the mechanism of B-cell sensitization, their activation by helper T-cells and their subsequent clonal expansion and differentiation.

Humoral/Antibody Mediated Immune Response: B Cell 1. Sensitization: Naive B cell takes up FREE antigens (not displayed on MHCs) in secondary lymphoid tissue that correspond to specific BCRs --> antigen degraded and processed --> antigen presentation on MHC II 2. Activation: CD4+ Helper T Cells typically activated by same antigen binds to MHC II complex and secretes cytokines that promote B cell activation and division (cytokine co-stimulation) 3. Clonal Expansion: Activated B cells divides into 1. Effector cells that carry out immediate response 2. Plasma cells that secrete antibodies into IF (peak [antibody] at around 2 weeks) 3. Memory B cells that remain in a reserve to respond to next infection

Be familiar with the input and output of the liver, the anatomical arrangement of the liver's lobules, enterohepatic circulation and the hepatic portal system.

Inputs: - HEPATIC ARTERY: supplies oxygenated blood to liver + pylorus of stomach, duodenum, and pancreas, carries metabolites and drugs from peripheral tissue - HEPATIC PORTAL VEIN: carries nutrient filled deoxygenated blood from digestive tract Outputs: - HEPATIC VEIN: blood returning to heart, carries metabolites to peripheral tissue - COMMON HEPATIC DUCTS: bile flow to gall bladder, secreted into duodenum Lobules: hexagonal stacks of hepatocytes - each lobule centered around a central vein that drains blood into the hepatic vein - portal triad on periphery: hepatic artery, hepatic portal vein, and bile ductule - bile secreted by hepatocytes are picked up by canaliculi, which coalesce into ductules, then ducts, and then common hepatic duct for storage in gall bladder (which eventually releases to small intestine) - sinusoids are tiny branches of hepatic portal vein that allows for mixing with hepatic artery Functions: - glucose and fat metabolism/ glycogen production/ gluconeogenesis - detoxification via cytochrome P450s - production of bile salts for lipid digestion - protein and hormone synthesis - urea production Bile salts are recycled by enterohepatic circulation - some synthesized daily from cytochrome P450 mediated oxidation of cholesterol - malabsorption decreases absorption of ingested materials + lose large amounts of bile salts

What do interferons do?

Interferons: interfere with viral replication - chemical messenger cytokines that trigger production of antiviral proteins - don't kill viruses, but block their replication - alpha interferons: produced by virus infected host cells, stimulate NK cells - beta interferons: secreted by fibrocytes and monocytes, slow inflammation - gamma interferons: secreted by T cells and NK cells, stimulate macrophage activity

How much filtrate do the kidneys make per day, how much is typically excreted as urine and what is the highest and lowest osmolarity observed for urine?

Kidney collects ~180 L per day Can excrete from 500 mL/day to 2.5 L/ day Hypoosmotic urine = ~50-100 mOsm (less concentrated than IF/blood) Osmolarity of our blood = 290 mOsm Hyperosmotic urine = ~1200 mOsm (4x concentrated than blood/IF) numbers dependent on length of nephron and channels

What is a pattern recognition receptor (PRR), what cells have such receptors and what is a pathogen-associated molecular pattern (PAMP)? How do phagocytes recognize "uninvited guests", how are they dealt with, and by what mechanism will their future encounter be ever so brief?

Leukocytes have pattern recognition receptors (PRR) that recognize pathogen associated molecular patterns (PAMPs) - antibody coated (IgG, IgE, IgA, and IgM) particles - mannose receptor (binds yeast) - C3b (complement) - opsonins: coat surface of encapsulated bacteria before recognition - scavenger receptors - peptide receptors, various types - cell wall components Phagocytes: first line of innate defense - monitor peripheral tissue and phagocytize invaders by recognizing PAMPs --> lysosomal digestion via enzymes and oxidants (H2O2, O2-, NO) - exhibit positive chemotaxis: follow bacterial toxins, cell wall components, and fibrin + collagen from damaged tissue - APCs (macrophages and dendritic cells) display ingested antigenic fragments on MHCII surface receptors for future recognition

In a clinical setting, how is metabolic rate estimated? What is basal metabolic rate and what factors influence it? What is the respiratory quotient and how can it be used to determine what kind of substrate is fueling metabolism and also measure metabolic rate?

Metabolic Rate: sum of all anabolic and catabolic processes in body - estimated clinically through thyroxine concentration (via a T4 assay), since it controls overall metabolism Basal Metabolic Rate: minimum resting energy expenditure of an awake and alert person, affected by: - age - sex - conditioning - muscle mass - genetics - hormones - diet induced thermogenesis Respiratory Quotient: ratio of CO2 produced per O2 consumed - measuring BMR involves monitoring respiratory activity because energy utilization is proportional to oxygen consumption - RQ =1 for carbs, RQ = 0.7 for fat, RQ = 0.8 for proteins - both carbs and protein have 4 kcal/g energy storage, fat has 9 kcal/g

Be familiar with the transporters responsible for salt and water reabsorption in the nephron and the typical water balance input from food/drink & metabolism as compared to loss through the lungs & integument and in urine and feces.

Na+ reabsorbed by active transport Electrochemical gradient drives anion reabsorption Water moves by osmosis via aquaporins CLAUDINS: PARACELLULAR TRANSPORT very important for reabsorption - tight junction membrane proteins that function as pores and barriers - in proximal tubule, claudins have a role in the bulk reabsorption of salt and water - ABOUT 30% of water and salt reabsorption (of the 70%) comes through CLAUDIN-2* - in ascending thick loop, other claudins absorb calcium and magnesium - in MANY LOCATIONS Water Gain: - 2.2 L/day from food and drink (highly variable) - 0.3 L/day (12%) from metabolism: ETC (somewhat variable) Water Loss: - 0.9 L/day from skin/sweat + lungs (insensible water loss, highly variable) - 1.5 L/day from urine (highly variable) - 0.1 L/day from feces (fairly constant except during diarrhea) Role of Kidney/Urine is to control that water loss and keep total body water content within acceptable limits while also controlling osmolarity - linked to blood pressure - if blood volume too low, then GFR slows to maintain BP

How does a NK cell recognize a cancerous or virus-infected cell? By what mechanism is such a cell lysed (A: perforins).

Natural Killer cells constantly monitor tissue for virus infected or cancerous cells - don't need to be sensitized to attack - can detect in the absence of MHCs, cells displaying low MHCI (tumor cells), r cells opsonized w/antibodies as they have Fc receptors - formulated antigen specific immunological memory - functions similar to cytotoxic T cells but NK cells are more general and faster 1. identify and attach to abnormal cells 2. golgi apparatus in NK cell relaligns and secretes PERFORINS and GRANZYMES *Perforins: lyse *Granzymes: digest

Be familiar with differences and similarities of the body's two primary lines of defense: Non- Specific (Innate) & Specific (Adaptive/Acquired)

Non-Specific Defense: innate blocks ANY potential infectious organism, cannot distinguish one attacker from another, and includes both physical/chemical barriers and innate immune response - epithelium / mucous membrane - glandular secretions - stomach acidity - connective tissue - recognition of pathogen associated molecular patterns (PAMP) - inflammation, cytokine mediated - fast acting, general Specific Defense: adaptive immune response 1. detection and identification of foreign substances 2. communication with other immune cells to organize response 3. recruitment and coordination of response 4. Destruction or suppression of invader - slow first response takes days to weeks - memory cells enable response to 2nd exposure rapidly - cell mediates + humoral immunity Overlaps because inflammatory cytokines attract all players!

What is the difference between obligatory water reabsorption and facultative water reabsorption? Where in the nephron does each occur?

Obligatory water reabsorption: water follows salt via osmosis; dependent on reabsorption of solutes - PCT, Loop of Henle Facultative water reabsorption: facilitated by hormones - in distal DCT and CD - facilitated by ADH

What is unique about olfaction as compared to other special senses in terms of its neural transduction pathways to the cerebral cortex? Know the general morphology of the olfactory receptor cells. In terms of signal transduction, after binding of an odorant molecule be able to describe the molecular and electrical events in relaying this information.

Odorants bind to specific receptors in dendrites of highly modified bipolar neurons = olfactory neuron - binding activates G PROTEIN COUPLED RECEPTOR which activates ADENYLYL CYCLASE and STIMULATES [cAMP] - cAMP binds to nonspecific CATION CHANNELS (or sodium channels) causing opening and leading to membrane DEPOLARIZATION - each sensory neurons likely has only one type of receptor, and axons with SAME RECEPTOR TYPE CONVERGE on a few secondary neurons in olfactory BULB (some processing) - axons leave olfactory bulb via the olfactory TRACT = reach olfactory CORTEX, HYPOTHALAMUS, and parts of LIMBIC SYSTEM (emotional memory) Olfaction is unique in that it is the only type of sensory info that reaches the cerebral (olfactory) cortex WITHOUT SYNAPSING AT THALAMUS FIRST (with an exception of few fibers) Hypothalamus and limbic system: - elicit emotional, behavioral, and memory responses to odors - signaling can also stimulate reflexes of salivation, digestive secretion, sneezing and coughing Olfactory receptors = neurons!! (highly modified bipolar neurons) themselves, regularly replace themselves, and don't go through the thalamus before going to olfactory cortex located within the olfactory epithelium in the nasal cavity *OLFACTORY EPITHELIUM: - contain olfactory chemoreceptor neurons - basal cells (stem cells that replace receptors every 30-60 days) - supporting cells: simple columnar epithelium *LAMINA PROPRIA: areolar connective tissue - contain olfactory glands that secrete mucus [not proper to wipe your nose] Vomeronasal organ (VNO) in macrosmatic animals, pheromones

Be familiar with the roles of opsonins, chemotaxins, and toll-like receptors.

Opsonins: antibodies and plasma proteins that tag particles or cells to be ingested, enhances phagocytosis (it's where the phagocyte binds_ - necessary if bacteria is encapsulated Chemotaxins: molecules that attract phagocytes to site of infection - bacterial toxins, cell wall components, fibrin and collagen from damaged tissue Toll-like Receptor (TLRs 1-10): activate macrophages to secrete inflammatory cytokines - single membrane spanning non-catalytic receptors usually expressed on sentinel cells - recognize PAMPs, type of PRR

Be familiar with the anatomy of structures involved with hearing and equilibrium. What is unique about the composition of endolymph as compared to other extracellular fluids and how does this unique composition affect the way that hair cells are depolarized?

Organs = ears; Receptor = mechanoreceptors *Outer/ External Ear: - auricle (pinna): basically actual ear - external auditory canal/ acoustic meatus: the ear canal, lined with hairs and seruminous glands - tympanic membrane (ear drum): thin semitransparent sheet of connective tissue and epithelium, separates external ear from middle ear, TRANSMITS SOUND ENERGY TO OSSICLES *Middle Ear: - aka Tympanic Cavity: air filled mucosa lined chamber between tympanic membrane and oval window - AUDITORY OSSICLES = MALLEUS, INCUS, STAPES TRANSMIT SOUND ENERGY TO OVAL WINDOW (in that order) - Acoustic Impedance Mismatch between mediums! - total amplification of pressure wave of sound to liquid filled cochlea is 22X: occurs because of DIFFERENCE IN SAs between tympanic membrane and oval window - Tensor tympani and Stapedius muscles: can uncouple sound wave, important to filter out low frequencies and be attuned to delicate high frequencies *Inner Ear: - VESTIBULE (gravity and acceleration): saccule and utricle - SEMICIRCULAR CANAL (rotation) - COCHLEA: spiral conical chamber beginning at oval window and ending at round window, containing spiral ORGAN OF CORTI COCHLEA: SCALAE (one long perilymphatic chamber) - Scala vestibuli: begins at oval window [oVal Vestibuli] - Scala tympani: ends at round window - they're "going in opposite directions" - in between them is the COCHLEAR DUCT which is filled with endolymph and the mechanoreceptors Endolymph is unique in that it has an extremely high extracellular K+ concentration set up by fibrocytes and other channels The inward flux of potassium from the endolymph upon deflection of the stereocilia causes depolarization and glutamate release

What is osmosis and what would be required for osmosis to occur across the plasma membrane of a cell? What is osmotic pressure? What is the difference between osmolarity and tonicity? What is the average osmolarity of fluids in our body as provided in lecture?

Osmosis: diffusion of water across the cell membrane towards the side with more solute concentration = less water For osmosis to occur, the membrane must be freely permeable to water = have aquaporins and be selectively permeable to solutes Osmotic pressure: the pressure that must be applied to oppose osmosis from happening Osmolarity: osmoles of solute particles (makes difference if dissociation occurs) per liter - Average osmolarity of fluids is 290 mOsm (rounded is 300) Tonicity: the osmotic effect of a solution (shrinking, swell, no change) that occurs because of the concentration of nonpenetrating solutions

Be familiar with what is filtered, reabsorbed or secreted in each segment of the nephron, to level of detail as presented on slide #24 (Table 26-4).

PCT: - 70% of water and salt (NaCl) reabsorbed (AQP1 channels) - 99-100% of nutrients reabsorbed - phosphate reabsorption inhibited by PTH - active reabsorption: glucose (secondary active transport w/ Na+), amino acids, vitamins, most (70%) electrolytes like Na+, K+, Ca2+, Mg2+, phosphate, bicarbonate - passive reabsorption: water, urea, Cl- - secretion: creatinine, drugs, toxins, H+, NH4+, organic cations, anions (nitrogenous wastes + drugs) - isoosmotic fluid Descending Loop: - AQP1 channels reabsorb water passively (to equilibrate with increasing osmolarity as you go down): 25% of water Ascending Loop: - reabsorption: salt active transporter Na+/K+/2 Cl- in apical membrane (20-25% of salts reabsorbed in whole loop) DCT: - facultative reabsorption - AQP2 controlled by ADH - Sodium reabsorption/ potassium excretion controlled by aldosterone - secretion: H+, NH4+, creatinine, drugs, toxins - hypoosmotic fluid but high concentration of urea and nitrogenous waste Collecting Duct: - facultative reabsorption - AQP2 controlled by ADH - salt + urea reabsorption dependent on hormones - intercalated cells: acid/ base via bicarbonate - principal cells: calcium (regulated by PTH) - both principal + intercalated: potassium (controlled by aldosterone) - variable osmolarity

Be familiar with the mechanism of HCl secretion by parietal cells.

Parietal cells secrete HCl: APICAL: - obligatory active H+/K+ ATPASE pumping H+ into the lumen - K+ channel to release the K+ being pumped in - Cl- channel to release the Cl- being pumped in and to create HCl BASOLATERAL: - HCO3-/Cl- exchanger pumps HCO3- produced via carbonic anhydrase (which also produces the H+) into IF - can create "alkaline" tide during meal absorption proton pump blockers can treat acid reflux and stomach ulcers more than histamine blockers

What are the different structural classes of hormones? Be familiar with the general pathways for their synthesis and storage.

Peptides: water soluble - largest class - Synthesized as a preprohormone: contains a signal sequence that directs it into the lumen of the rough ER -> signal sequence is cleaved -> prehormone -> prohormone with proteolytic enzymes (to cleave the pre- when needed) packaged by Golgi and stored in secretory vesicles (which they can do because they are water soluble) until calcium dependent exocytosis releases the mature hormone - Peptide hormones are made continuously and stored in secretory vesicles until they are needed - Peptide hormones are transported in the blood through plasma (water soluble) by hopping onto plasma proteins - Bind to receptors on the membrane (hydrophilic so cannot permeate) - Can gate or open a channel, affect target cells by activating 2nd messenger systems and signal transduction pathways via adenylyl cyclase/cAMP), some have genomic effects -- Fast response: can modify proteins (most commonly) -- Long response: alter protein synthesis - Half-life is short: rapidly degraded via peptidases or excreted - Examples: leptin, insulin, parathyroid hormone Steroids: lipid soluble - All steroid hormones are derived through cholesterol, with a common intermediate being pregnenolone - Made in steroidogenic tissues: adrenal cortex, gonads, placenta, nervous system (mostly glial cells) - Can be interconverted elsewhere - Made as needed in the smooth ER because they cannot be stored in vesicles - Transported in blood via carrier proteins (inactive when bound) because they are lipophobic -> dissociate from CPs at target cell -> enter membrane easily for the same reason -> hormone binds to receptor in cytoplasm anchored by HSP 90 -> dimerization -> hormone receptor complex travel to nuclear receptor -> genomic effects (activation/suppression) -> inactivated in liver - Have nuclear receptors mostly, but some have cytoplasmic receptors - Long lived, especially because they most commonly have slow overall /genomic effects -- Activate or repress genes for protein synthesis -- Affects gene transcription! (slow response: takes time to affect/regulate transcription and show results in translation) -- Can also have some short response effects Amines: - Catecholamines - water soluble - Indoleamines - amphipathic - Thyroid Hormones - lipid soluble - All amine hormones are made from tyrosine or tryptophan -- Catecholamines and thyroid hormones are from tyrosine -- Indoleamines are from tryptophan - Catecholamines: epinephrine, norepinephrine, dopamine (neurohormones) - Water soluble, stored in secretory vesicles, released via calcium dependent exocytosis, dissolved in plasma and bind to receptors on membrane where they activate 2nd messenger systems, short half life and no genomic effects -- Basically act like protein hormones -- Synthesized by adrenal medulla - Thyroid Hormones: T3 and T4 -- Lipid soluble, use carrier proteins to travel through plasma -- Pre-made and stored but not released as true form until required --Thyroglobulin made -> exocytosed out of thyroid follicular cell into lumen -> iodinated -> iodine is oxidized making a colloid -> upon binding of TSH -> Tg endocytosed and proteolytically cleaved into T4 (prohormone, in much higher proportions) and T3 (true hormone) --At target cell, deiodinases convert remaining T4 to T3 which induces the expression of genes via nuclear receptors (long half life) -- Sodium iodine symport brings iodine in for synthesis of Tg -- Monocarboxylate transporter 8: export and import of T3 and T4

What is positive and negative feedback and what components are required for setting up such systems? What is the difference between local (intrinsic or autoregulation) and reflexive (extrinsic)? Which physiological processes are regulated by positive feedback regulation as compared to negative feedback or feedforward control? What is feed-forward regulation?

Positive feedback: response of the effector further induces the signal/ amplifies the stimulus, moving away from set point to speed up certain processes (ex. Oxytocin and uterine contractions during Childbirth, damaged cells attracting clotting factors in blood clotting), need outside factor to shut off the feedback loop Negative feedback: variable falls outside setpoint range, response decreases or eliminates the stimulus, negates to bring back to homeostasis/normal range (ex. Body temperature) Components required: receptor (ex. Temperature receptors), control center (ex. Thermoregulatory center in brain), effector (sweat glands, blood vessels) Local/intrinsic/autoregulation: automatic response initiated at local site of disturbance Reflexive/extrinsic regulation: system wide mechanisms such as nervous or endocrine control Feedforward control: responses in anticipation of changes (ex. Visual acuity before blink, saliva release when smelling food, heart rate before exercise)

What is the functional difference between primary and secondary lymphoid tissues and where are these tissues located? Be familiar with the structure/function of lymph nodes and the spleen.

Primary: site of lymphocyte production - B cells: bone marrow - T cells: thymus Secondary: site of lymphocyte activation - lymph nodes, spleen

Be familiar with the negative and positive allosteric modulators of glycolysis and gluconeogenesis, and the concept of "push-pull" regulation of opposing catabolic and anabolic pathways. Yields.

Push-pull regulation of opposing catabolic and anabolic pathways: - one set of enzymes control the forward direction (glycolysis) and a different set control the reverse (gluconeogenesis) - when one's activated the other gets inhibited! Global control of gluconeogenesis through glucagon: triggers signal transduction pathways via PKA resulting in inhibition of glycolysis and stimulation of gluconeogenesis - Glycogen synthase: active a form dephosphorylated - Glycogen phosphorylase: active b form phosphorylates Glycolysis: - used when ATP is needed and glucose is present - activated by F26BP and AMP - inhibited by citrate, ATP, H+ Gluconeogenesis: - used when ATP is present and glucose needed - activated by citrate and acetyl coA - inhibited by F26BP and ADP/AMP

Be familiar with the anatomy of different blood vessels. At rest, where is most of the blood found? How does this change during exercise? What controls blood flow into a capillary bed? Be familiar with the different types of pressures that occur in a capillary bed and the functional consequences of changes in these pressures?

Rapid movement of large volumes of blood in large diameter vessels + effective exchange of gases and nutrients in capillaries Arteries = high flow at high pressure, large diameter, thick muscular ELASTIC walls Arterioles: smaller thin, muscular walls Capillaries: very small diameter + very thin walls - 35 mmHg in, 16-20 mmHg out Venules: low pressure, thin walls Veins; high flow at LOW pressure, very large diameter, fairly thin walls Total relaxed volume in circulatory system larger than actual volume of blood - need to control so venous return doesn't drop 64% (1/3) IN SYSTEMIC VENOUS SYSTEM due to its HIGH CAPACITANCE (ability to accomodate large blood volumes w/o large increase in BP) via distension Elastic properties of arteries maintain blood pressure (and flow) in diastole - SPHINCTERS IN ARTERIOLES control radius and thereby the amount of blood going through capillaries at a given time = MAIN CONTROL OF FLOW DISTRIBUTION - not enough blood for all capillary beds to be open = need episodic blood flow dependent on metabolic needs - distribution of flow a function of CO and arteriole resistance METARTERIOLE: bypasses/shunts that can route flow directly from an arteriole to venule w/o passed through capillaries when sphincters are closed - function of capillary resistance Exercise: goes to skeletal muscle (nearly 90% of CO) some to skin: temperature regulation CO to Liver/kidneys/ digestive tract reduced to 1/4 or 1/5 of resting values - why long term marathon runners can get kidney problems Globalized vasoconstriction (NE) but localized vasodilation at active tissue sites (released by active muscle, RBCs, vascular epithelial cells) - Adenosine - ATP - Nitric Oxide (most potent vasodilator) - increase in PCO2 and release of O2 - Endothelium derived hyperpolarization factors (EDHs) - prostaglandins Filtration: bulk flow of fluid out of capillary walls due to hydrostatic blood pressure Absorption of EC fluid back into capillary due to colloid osmotic pressure from proteins, peptides, etc in plasma on the venule side Net pressure = hydrostatic pressure - colloid osmotic pressure BP in capillaries goes from 32-35 mmHg in beginning of capillary to 15-18 by end

In addition to salivary amylase and lingual lipase, what other compounds are released in saliva that help to mitigate harmful bacteria?

Salivary Amylase (from parotid salivary glands): breaks down amylose from starch Lingual Lipase (in pre-weaned infants): breaks down milk fat droplets LYSOZYMES: enzymatically punch holes in bacterial cell walls by catalyzing hydrolysis of 1,4 B-linkages in peptidoglycan walls LACTOFERRINS: high affinity Fe-binding protein that has antimicrobial properties by competing with bacteria for iron that it needs - present in milk (especially colostrum), saliva, tears, and nasal secretions = innate defense - iron deficiency anemia associated w high [lactoferrin]

How does a muscle shorten according to the sliding filament model or theory? Know all of the steps involved in excitation contraction coupling as well as those involved in the contraction cycle, cross-bridge formation, and muscle relaxation. What factors contribute to muscle fatigue?

THIN = ACTIN [tin = thin] THICK = MYOSIN [myosin is a thicker word] Sarcomeres can be aligned in series or parallel - SERIES: CONTRACTION VELOCITY proportional to fiber length - PARALLEL: FORCE proportional to SA I BAND: THIN ONLY (actin) - also counts the next sarcomere over! H ZONE: THICK ONLY (myosin) A BAND: THICK + THIN OVERLAP + Thick (inevitably) M LINE: CENTER of sarcomere where thick filaments attach w/ myomesin Z DISK: END of sarcomeres where thin filaments attach Thick filament: myosin molecules in repeating arrangement of groups of 3 heads at 120 angles - thick SURROUNDED by SIX THIN filaments in overlap - thin SEES THREE THICK filaments During overlap: - Thick filament: myosin molecules in repeating arrangement of groups of 3 heads at 120 angles - thick SURROUNDED by SIX THIN filaments - thin SEES THREE THICK filaments *Sliding Filament Model: Sarcomeres shorten with contraction and thick/thin filaments slide past each other but do NOT change LENGTH - A ZONE DOESN'T CHANGE - I BAND AND H ZONE SHORTEN: H zone can almost disappear, thin filaments come up all the way to the M line 1. Neural Stimulation: release of acetylcholine at the NMJ from myelinated alpha motor neurons triggered by voltage sensing (synaptotagmin) calcium channels 2. Excitation-Contraction Coupling: coupling of neural excitation with muscle contraction - dependent on if ENOUGH nicotinic ACh receptors have ACH BOUND to them on the motor end plate - AP transmission through T tubule system reaches a triad and activates a voltage sensor calcium channel dihydropyridine (DHPR) that links T tubules and SR, and is also mechanically tethered to ryanodine (RyR1) on the SR - triggers calcium release from SPR that binds troponin and UNMASKS binding sites on actin 3. Muscle Contraction: shortening of sarcomeres and muscles (look at contraction cycle) 4. Relaxation of muscle: - once neural stimulation has ended and all the Ca 2+ has been re-sequestered into SPR by SERCA with the help of CASQ - ACh degraded by AChE rapidly - both minimize LATENCY period before another cycle - ATP needed for SERCA and release of myosin from actin 1. Contraction Cycle Begins 2. Active-Site Exposure 3. Cross-Bridge Formation 4. Myosin Head Pivoting 5. Cross-Bridge Detachment 6. Myosin Reactivation 1. ATP binds myosin head = myosin releases actin but head is not cocked yet - only way for myosin to release from actin - essentially a reset 2. Cocking Phase: - Myosin HYDROLYZES ATP via myosin ATPase -> ROTATES MYOSIN TO COCKED position and myosin weakly binds to actin (high potential energy conformation) - Myosin head is COCKED (contains potential energy) but cannot bind to actin since tropomyosin blocks active sites on actin 3. Power Stroke: - Myosin RELEASES Pi -> myosin HEAD MOVES ACTIN filament to M LINE - occurs only when calcium is present - Ca 2+ comes in and binds to troponin, which moves tropomyosin off the binding sites and the myosin is able to bind to the actin - formation of CROSS BRIDGE and shortening of sarcomere 4. End of Power Stroke: - Myosin RELEASES ADP at the end of the power stroke and goes BACK TO RIGOR state with myosin tightly BOUND to G-actin until ATP available for release - occurs when Ca 2+ no longer bound to troponin C and contraction ends with actin sliding back to normal position If ATP is present and calcium signals continue, cycle repeats Muscle Fatigue can happen at CNS, PNS, NMJ, or muscle fiber level NOT: - LACTATE: not lactate buildup, which is serves a protective function of the proton load caused by the hydrolysis of ATP - not synaptic failure CAUSES: - DEPLETION OF GLYCOGEN in muscle especially in long duration sub-maximal exercise - ION IMBALANCES: - increased phosphate and H+ from hydrolysis of ATP - increased sodium inside and potassium inside because of APs that haven't been able to be re-set up by sodium potassium pump - increased reactive oxygen species - increased magnesium and ADP and decreased ATP: not able to use SERCA or myosin ATPase SUMMARY: anything indicatory of a loss of ability to have an AP or the hydrolysis of ATP leads to fatigue

Be familiar with the gustatory sensing and signal transduction pathways for salt (Type I) vs. sour (Type III) vs, sweet, umami, and bitter (type II) and the pathway from secondary neurons to the gustatory cortex.

TYPE 1 = SALT (support receptor) TYPE 2 = SWEET, UMAMI, OR BITTER TYPE 3 = SOUR *Salt and maybe sour: activate CHEMICALLY GATED ION CHANNELS that lead to depolarization *Bitter, sweet, and umami: - activate G PROTEIN (gustducin) COUPLED RECEPTORS > activates second messenger system -> increase the release of calcium from calcium stores in ER and mitochondria - TRPM5 channel also leads to increase in calcium, opened by partial depolarization - Ca2+ leads to ATP PRODUCTION/ RELEASE - ATP can act as a neurotransmitter - paracrine functioning Sour: more specifically - high acidity/ high [H+] -> protons enter the cell -> block K+ leak channel KIR2 -> increased [H+] and decreased [K+] lead to depolarization - signal transmission with SEROTONIN Primary sensory neurons extend to cranial NERVES VII and IX to the MEDULLA oblongata to THALAMUS to the GUSTATORY CORTEX in the ANTERIOR INSULA ON THE INSULAR LOBE and the frontal operculum on the inferior frontal gyrus of the frontal lobe [bad taste is an insult] Gustatory information correlated with other sensory input!! - - 70-80% of taste goes with olfactory - thermo (TRP channels), mechano, noci Also go to Hypothalamus and limbic system to elicit emotional reactions or memory Signaling can also trigger reflexes to stimulate digestive activity Gustation undergoes rapid CENTRAL ADAPTATION

Know the characteristics of the three types of skeletal muscle fibers (fast, slow, intermediate), how they differ from each other, and what each is designed to do.

TYPE IA: - SLOW-OXIDATIVE (using primarily FA but also glucose, adipose tissue, and AAs) - dark red due to myoglobin content (binds oxygen) and extensive blood supply w/ lots of mitochondria - Fatigue Resistant but slower to contract (slow cycling) and produce less tension - small - example: posture, endurance activities - MYH6, MYH7 TYPE IIA: - FAST-OXIDATIVE/GLYCOLYTIC - transitional fiber: qualities of both - red - Fast Fatigue Resistant so fact acting (medium rate of cycling) but performs aerobic respiration so slow to fatigue - example: walking, standing - mixture of different chain types TYPE IIX: - FAST-GLYCOLYTIC (anaerobic - few mitochondria) - white - Fast Fatiguable but very powerful (very fast cycling and fast SERCA) so last to be recruited - large in diameter, many myofilaments, high glycogen supply - ex: jumping jacks, quick and fine movements - ABSENCE of MYH6, MYH7 and MYL3 - MYH1, MYH2, MYH4 and MYL1 Fiber Type Switching: the switching of the different fiber types based on endurance and the building of stamina - to go from Type IIx (default type) to Type I, the muscle needs to start expressing MYH6, MYH7, and MYL3 - goes through intermediate fibers - vice versa also happens - it is NOT permanent - is a continuum also

What type of transporter is the Na+/K+-ATPase pump? How many Na+ and K+ atoms does it pump per ATP hydrolyzed to ADP and in which directions?

The Na+/K+ ATPase is antiport (carrier protein) that uses primary active transport to move 3 Na+ out of the cell and 2 K+ into the cell per ATP hydrolyzed 3 Na+ from ICF bind to high affinity states -> ATP hydrolysis -> Na+ binding sites lose their affinity and release them -> 2 K+ bind to high affinity states -> Pi is released -> K+ loses affinity -> ATP binds

In regard to the HPT axis, know the hormone cascade (TRH - TSH - T3/T4) and mechanism of feedback regulation, the function/action of T3/T4, and the effects and diseases associated with hypo- and hyper-thyroidism.

Thyrotropin Releasing Hormone -> Thyrotropin/ Thyroid Stimulating Hormone (stimulates growth of thyroid cells and synthesis/secretion of thyroid hormones) -> T3, T4 - T3/T4 negative feedbacks to both pituitary and hypothalamus (long loop) - T3/T4: increase O2 consumption, increase thermogenesis, majorly affects metabolic rate - Necessary for normal growth and development (esp nervous system) in children Hypothyroidism: too little T3/T4 - Hashimoto's: autoimmune thyroiditis (inflammation of thyroid) disease - Iodine deficiency: need iodine for TH - Pituitary tumor: just dysfunction - Decreased metabolic rate, cold intolerance, decreased protein synthesis (brittle nails and hair), fatigue, slow reflexes and speech - Myxedema: increase of connective tissue deposits - Goiter: low iodine = low T3/T4 -> lack of negative feedback -> TSH and TRH stimulation -> stimulation of thyroid -> inflammation - Cretinism: congenital defect or absence of thyroid gland -> impaired growth or retardation, infertility Hyperthyroidism: - Graves: TSI -> act like TSH and keep stimulating the release of TH - Thyroid or pituitary tumor - Increase metabolic rate, heat intolerance, protein catabolism = muscle weakness and weight loss, increased B-1 adrenergic receptors (so higher fast rate and muscle contractions) - Exophthalmos: bulging eyes - Goiter: overstimulation of the thyroid by TSI (if Graves) or a pituitary tumor will not listen to negative feedback to stop it either

Be familiar with the functions and characteristics of skeletal muscle fiber components, including the sarcolemma, t-tubule system, sarcoplasmic reticulum, triads, myofibrils, and the anatomy of the thick and thin filaments.

Tranverse Tubules (T-TUBULES): invaginations of the sarcolemma that reach deep inside cell to transmit APs and facilitates contraction of entire muscle fiber simultaneously (EXCITATION-CONTRACTION) SARCOLEMMA: cell membrane of the muscle fiber itself (not just the connective tissue) MYOFIBRILS: numerous subdivisions within muscle fiber, made up of bundles of protein myofilaments (thick and thin) responsible for muscle contraction SARCOPLASMIC RETICULUM: membranous structure surrounding each myofibril similar to SER, STORES CALCIUM and helps transmit AP - forms chambers (terminal cisternae) attached to T-tubules concentrated with Ca 2+ via ion pumps - releases Ca 2+ into sarcomeres to begin muscle contraction - high density off SERCA PUMPS (ca2+ pumps that keep [Ca2+] low within muscle) - TRIAD: 2 terminal SR cisterna + 1 T-tubule in between THIN FILAMENTS: actin 1. Filamentous (F)-Actin: 2 twisted rows of globular actin - ACTIVE SITES on strands of G-ACTIN bind to MYOSIN 2. NEBULIN: BINDS TO ACTIN and attaches to Z line to STABILIZE thin filament position - augments cross bridge interaction - dictates thin filament length during assembly (can control tension) - spans length of filament 3. TROPOMYOSIN: double stranded protein that COVERS THE ACTIVE SITES on actin thereby preventing actin-myosin interaction 4. TROPONIN: binds TROPOMYOSIN TO ACTIN (kinda holds it there) - has receptor for Ca 2+ - when 4 CA2+ BIND = CONFORMATIONAL CHANGE EXPOSING ACTIVE SITES on F-actin - T - locks, I - binds [troponin is the thumbtack] THICK FILAMENTS: myosin - contains 250 twisted myosin subunits - TITIN: ANCHORS TO Z DISK (tension can be modified by calcium - Myosin II: skeletal muscle motor protein containing light and heavy chains - 2 HEAVY chains: tadpole head w/ ATP AND ACTIN binding sites and the stiff neck - 4 LIGHT chains: bind heavy chains in neck region)

How is the gastric mucosa protected from the low acidity of the stomach lumen? What functions does the low acidity perform?

Two Protective Mechanisms: both produced by mucous neck cells - Mucus Layer (physical barrier) - Bicarbonate secretion to neutralize acid Stomach is acidic so that: 1. barrier to bacteria 2. protein digestion via denaturation to allow for absorption of beneficial cofactors and so more AA residues are exposed to proteases

Be familiar with the partial pressures of O2 and CO2 observed during eupnea at the alveoli and systemic capillaries. Why is there a decrease in PO2 from 100 mm Hg in the alveoli down to about 95 mm Hg at systemic arterioles?

Want to flow from high to low: - PO2 must be lower in cells than in air - PCO2 must be lower in air than in cells - Gradients generated by metabolism ALVEOLI: 100 mm Hg PO2, 40 mm Hg PCO2 PERIPHERAL TISSUE: 40 mm Hg PO2, 46 mm Hg PCO2 PO2 IN ARTERIOLES = 95 MM HG BC OF PULMONARY SHUNTING - portion of CO enters left side of heart without having undergone complete alveolar equilibration - anatomical shunting: enters left side of heart without traversing pulmonary capillaries (5% of CO), includes bronchial + thebesian veins - decreases PO2 in systemic circulation During exercise, ventilation can increase 10-20 fold depending on intensity - over wide range of ventilation rates, blood pH and amount of metabolic gases are remarkably constant - arterial PO2 constant - arterial PCO2 and venous PO2 decrease a tiny bit - arterial pH constant until VO2 max

How is total cholesterol calculated, what is an optimal level, is it different for males and females or as we age, and why are high LDLs "bad" but high HDLs "good"? Be familiar with the cholesterol lowering drugs and methods listed on slide #21.

cholesterol increases fluidity at [low] and decreases fluidity at [high], key precursor for synthesis of bile acids, steroid hormones, and vitamin d3 Total cholesterol = LDL + HDL + triglycerides/5 - increases with age - normal levels are slightly higher for females than males Optimal = less than 200 mg/dl - HDL > 40 mg/dl - LDL < 100 mg/dl Looking at ratio of ApoB100/ApoA1 is better predictor of myocardial infarction than high LDL-C levels Extremely high [HDL] can be bad too Drugs: - Statin (1st line therapy): inhibits rate limiting step of cholesterol biosynthesis - Ezetimibe: (2nd line therapy): inhibits NPC1L1 transporter - Fibrates: decrease LDL and increase HDL - Bile Acid Sequestrants: bind to bile acids preventing their absorption (leading to excretion) and causing increased bile synthesis/ decreasing plasma cholesterol

What are the functions of the large intestine?

mainly waste compaction, salt + water reabsorption, fiber digestion also absorption of nutrients not previously absorbed and vitamins: thiamine, folate, biotin, riboflavin, pantothenic acids, vitamin K no microvilli, no digestive enzymes secreted gut flora/ microbiome