PHYSIO EXAM 4 STUDY GUIDE
PHYSIO EXAM 4 STUDY GUIDE PGY 451LEC
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This 15 page Study Guide was uploaded by Ndidiamaka Okorozo on Wednesday December 9, 2015. The Study Guide belongs to PGY 451LEC at University at Buffalo taught by Baizer, J S in Fall 2015. Since its upload, it has received 269 views. For similar materials see Human Physiology I in Physiology at University at Buffalo.
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PHYSIO EXAM 4 STUDY GUIDE LECTURE 1 Functions of a kidney: *Water balance (homeostasis) by moving sodium (most abundant molecule in the body). 1. Transport: a. Regulation of water and inorganic ion balance: Na+, K+, Cl, etc. b. Removal of waste products from the blood: urea, ammonia, creatinine, etc. 2. Hormonal: a. Renin: dominant long term regulator of renal function by the Renin Angiotensin System (RAS). b. 1,25dihydroxyvitamin D3 c. Gluconeogenesis d. Erythropoietin Hypertension Treatment: 1. Diuretics: block Na+ transporters and prevent absorption of sodium therefore hindering the absorption of water too. 2. ACE/AngII inhibitors: moderate the RAS. 3. ARB: affect flow to and from kidney, control excretion, 4. Adrenergic Blockers 5. Vasodilators C.O. = cardiac output, amount pumped per min (56L) C.O. = S.V. x H.R. (Fluid homeostasis) S.V. = stroke volume, amount pumped per beat. H.R. = heart rate. C.O. is the driving force of flow into the kidneys. Renal Blood Flow (RBF): amount of blood that enters by kidney 1200mL (25% of C.O.) Renal Plasma Flow (RPF): amount of plasma in blood that enters kidney ½ of RBF = 600mL ↑flow ↑excretion Increase U x V, and/or Uv Na Renal ensures that input volume = output, regulation of pressure in vasculature (hydrostatic pressure) is the main mechanism of regulating renal function. Body Fluid distribution: Water makes up 60% (40L) of our body weight. Intracellular fluid (ICF) = 25L (40%), majority of water Extracelular fluid (ECF) = 15L (20%) a) Interstitial fluid volume = 12L, 80% ECF, Interstitium is the space between cells b) Plasma volume = 3L, 20% ECF (maintained), plasma is in the blood in the blood vessels. Water and electrolytes have to travel from the cell, past the cell’s membrane into the interstitium and then past the capillary’s membrane into the capillary. Specific Fluid Composition (mEq) Plasma Interstitial Intracellular Na+ 135145 135145 1030 Cl 95105 95105 1020 K+ 35 35 120145 Ca++ 12 12 0.0001 Protein 1020 <1 50 Osmolarity 295 295 295 (SAME) *Same osmolarity in plasma, ICF and interstitium homeostasis Isotonic: no net movement of water between compartments. Ca : high in ICF.Movement of water betwween the interstitium and ICF is done by protein and ion imbalance. Sodium is the most abundant ion in the body. LECTURE 2 Electrolyte Composition: as Na+ increased in ICF and interstitium, K+ (the counter cation) decreased. They have reversed concentrations. Movement of water in the body follows sodium! You move sodium to move water in the diretion of that sodium. Pressure difference is the driving force of water between compartments. a) Hydrostatic pressure (HP): always present when there is fluid in a compartment. The hydirstatic pressure in capillaries is from the blood pressure of the heart. b) Osmotic pressure (OP): the measure of the tendency of a solution to take in water. If it is proteins that are concentrated in the solution and causing water to be taken in, it is reffered to as oncotic pressure. For this class, osmotic ppressure is synanamous to oncotic pressure. Osmolarity: the amount of solute dissolved in a solution. Higher number of solutes means greater osmolarity. Osmolarity in plasma of the peritubular capillaries: is 295 but is slightly <295 in the nephron becasue not all the protein filter. Renal Daily Filtration, excretion and Reasorption: Substanc Re (% Resorbed) Water(L) 180 1.5 178.5 99.2 + Na (mEq) 25,200 150 25,050 99.4 K (mEq) 720 100 620 86.1 ++ Ca (mEq) 540 10 530 98.2 HCO (3Eq) 4,320 2 4,318 >99.9 Cl(mEq) 18,000 150 17,850 99.2 Glucose(mM) 800 0 800 ~100 Urea (g) 56 28 28 50 Osmolarity <295 501000 *Concentrate on the bold ones. 99% of the water, chloride and sodium that are filtered are reabsorbed. ALL of glucose and amino acids are reabsorbed. Urea: some are recycled to increase volume in the nephron. HCO3: all absorbed to enable excretion of secreted H+ acid base balance. Anatomy of the kidney Basic functioning unit nephron fragile to changes in prsure Nephrons have varying depths with the cortical one being shallow and medullary one being deep. There about a million nephrons to a kidney. Pathway of the kidney: Afferent arteriole (A.A.) Glomerulus (capillaries) Efferent arteriole (E.A.) Peritubular capillaries (P.C.). Renal Flow: Arterial input (by AA) = Venous Output + Urine Output Amount = concentration x flow Concentration: the quantity of an electrolyte in proportion to the amount of fluid in a compartment. Amount: the quantity of an electrolyte in a compartment. Therefore, two compartments can have the same amount of salt but different concentrations of it. 10mL of water 5mL of water 5mEq of sodium 5mEq of sodium Lower concentration Higher concentration *Both compartments have same amount of sodium nonetheless. Glomerulus Filtration Rate (GFR): about 120mL. From CO to GFR: CO = 5L, ¼ of 5000L ~ 1200mL, RBF is 1200mL to both kidneys. RPF (renal plasma flow) = ½ of RBF = 600mL. (Plasma is about 50% of total blood) GFR = FR x RPF = 0.2 x 600 = 120mL, FR= filtration factor, normally 0.2 a) Men: 125 ± 15mL/min/1.73m 2 b) Women: 110 ± 15mL/min/1.73m 2 c) GFR decreases with exercise and at night d) It increases with high protein diet e) Renal reserve = ½ of normal GFR Determinants of GFR: Indirect: age, gender, race, size, etc. Should have relatively same amount of creatinine in the body. More direct (still indirect): amount of creatinine in renal artery, vein and urine can help calculate GFR. * As you decrease GFR, it takes higher change in creatinine to cause GFR change. Until you get to as low as 6070 GFR, GFR depletion shouldn’t affect the kidneys because of the renal reserve. LECTURE 3 So renal plasma flow enters the kidneys via the AA and then flows into the first capillary bed (glomerulus site of filtration). Fluid then filters into the Bowman’s capsule which is the starting point of the nephron. However, in order for anything to move from the glomerulus to the Bowman’s capsule, it needs pass three barriers: know these! a) Glomerular Barrier (endothelial cells): has fenestrated membranes, 7090nm pores that prevent the filtration/passage of blood cells b) Basement membrane: excludes molecules >8nm and negative charged ones c) Filtration slits: created by the pedicels on podocytes of the glomerular capsule. Does not allow particles > 3nm and negatively charged molecules to pass. Filtered molecules must be able to pass through these three barriers from a c. Small solutes like Na+, Cl, K+, etc. will freely filter. Charge and Size Exclusion: index of 0 does not filter at all. Excluded proteins that do not filter are important in determining water movement. Forces affecting filtration: a) Hydrostatic pressure from the pressure in the capillaries is driving for filtration = 55mm Hg b) Osmotic/oncotic pressure from the proteins that did not filter in the glomerulus is against filtration = 15mm Hg c) Hydrostatic pressure from the fluid already in the Bowman’s capsule is pushing back against filtration = 30mm Hg If anyone of these changes, filtration changes GFR changes Net filtration pressure = 55 – 15 – 30 = 10mm Hg in the favor of filtration. ΔP is needed for flow, 10mm Hg leads to a GFR of 180L/day, about 1% excreted. GFR = ΔP x (K . P /X, K = P ltration coefficient, A= area, X= thickness of corpuscle Osmolarity: the concentration of an osmotic solution when measured in osmoles. Simply put, it is the number of solutes in a concentration. More solute higher osmolarity. Water tends to go to compartments with higher osmolarity. Osmotic Pressure: develops due to water movement. Water moves to the area with glucose to equalize the osmolarity in the two compartments. Equalization of osmolarity between two compartments doesn’t mean the same amount of water and electrolytes are in both. It means that both have the same proportion/ratio of water to electrolytes. Example: 40mEq of glucose 20mEq of glucose 20 mL of water 10 mL of water *Not the same amount but same proportions so they are isosmotic (same osmolarity). NaCl in water 2 Osmo, cuz Na+ and Cl Glucose 1 Osmo LECTURE 4 Osmotic Regulation between fluid compartments: Red blood cells (RBC) are isotonic and permeable to water (but not NaCl). Hypertonic: RBCs shrink when put in a hypertonic solution. Isotonic: no net water movement (0.9 NaCl solutions) Hypertonic: cell bursts as water enters *If the RBC was impermeable to water, there would be NO volume change. NaCl is an effective osmolite because it has a reflexive coeff and it drives water movement. Reflexive coefficient of 1 impermeable, of 0 means you are permeable. Diseases affecting GFR and Filtration Proteinuria: presence of large amounts of proteins in the urine such as albumin and creatinine. hematuria: blood in the urine reduced glomerular filtration rate: inefficient filtering of wastes from the blood hypoproteinemia: low blood protein edema: swelling in parts of the body Hydrostatic Pressures across the renal vasculature Filtration regulation occurs at the level of hydrostatic pressure Change in resistance changes diameter of the vessel changes hydrostatic pressure The AA and EA control the flow of blood into the glomerulus and peritubular capillaries. Mean arterial pressure; algebraic sum of time of diastoles and systole. It is the average pressure accounting for time. Conductance (g) = 1/R, R = resistance π.r 4 Change in resistance Pressure g = 8n.l ) , r = radius of the vessel, n= viscosity, l= length ¿ Control of GFR: done by three mechanisms 1. Renal autoregulation (intrinsic system 2. Hormonal/Paracrine mechanisms (Renin, Angiotensin II, Prostaglandins, ANP) 3. Neural controls (autonomic) largely sympathetic NS Hydrostatic Regulation of GFR At about 80mm Hg renal arterial pressure, GFR levels at about 120 mL/min. As renal arterial pressure increases to 80mm Hg, RBF increases and levels off at 1200mL. As RAP increases, AA resistance gradually increases to prevent further increases in pressure and EA resistance decreases slightly to counter AA restriction. Mechanical Forces Affecting Filtration 1. Autoregulation: Myogenic: Stretch (stretch in an arteriole causes constriction and increased resistance) and 4 nonlinear R (2 =16). In first scenario, arterial pressure is 100, AA resistance (1.0) reduces it to 60 in glomerulus and EA resistance of 1 uses up pressure reducing it to 20 in the peritubular capillaries. AP: arterial pressure. In the second scenario, AP is 150 and it is increased by ½ so everything will increase/decrease by ½ to compensate. AA resistance increases by ½ making it 1.5. The pressure in Glomerulus which should have been 90 (60 + ½ of 60 = 90) in this case, is decreased from 90 to 70 in an attempt to bring it down to 60 as in normal condition. Constriction of AA causes EA to relax/dilate so it has a resistance of 0.5 (as opposed to 1.0). Because AA constricted a lot, pressure has fallen so much to 15 in peritubular capillaries and the EA dilation increases it back closer to 20, making it 25. Third scenario is same concept as the second. TGF/JGA (Juxtaglomerular Apparatus) The distal convoluted tubule slots between the AA and the EA. The Macula densa (MD): osmotic sensor for Na+, K+, Cl, affects AA resistance. Juxtaglomerular(JG) cells: does a lot of regulation of AA and EA. Respond to MD cell’s osmotic signal and affect the AA resistance. They also release renin in response to change in the input pressure. Renin activates the Reninangiotensin II system (RAS). LECTURE 5 Single effect of Constriction on GFR As renin is released by the JG cells, it sends signals to constrict AA and EA however, EA vessels are more sensitive so they constrict first before the AA constrict. Constriction of only EA: when EA constricts, flow goes back toward to glomerulus increasing the glomerular pressure (P GCso GFR increases back to normal. However, if EA constricts too much, renal plasma flow begins to decrease causing the GFR to go back down. Constriction of only AA: when AA constricts, RPF decreases and so P andGCFR decrease. In this case you will want to conserve water in later parts of the nephron. Autoregulation: no input from external parts. Increase in the perfusion rate in the late proximal tubule causes JGA to alter the diameter of AA in order to decrease excretion and conserve electrolytes and water. This is done by paracrine mediator such as adenosine and NO. Shifting to the left (less perfusion rate) causes more sensitivity to ANG II while shifting to higher perfusion rate leads to less sensitivity. High protein diet causes les sensitivity so they operate at high pressure. ↑electrolyte conc force electrolytes in ↑Na+ in ICF increases turnover(capacity rate) of Na+ ↑AMP production from ATP usage of the pump AMP (adenosine) diffuses into renal interstitium & binds to receptor ↑Ca2+ that enters cell contraction of AA!!! Then there is decreases in renin secretion. So ↑ electrolytes or ↓osmolarity ↓ GFR Hormonal Regulation (RAS) ↑B.P. ↓C.O ,↓S.V. and ↓ pressure in AA. Capillaries in the kidney have a higher temperature than any other capillaries in the body. Decrease in bp ANG II cleaved by renin ANG I (acted upon by ANG converting enzyme – ACE) ANG II heart constricts EA and AA, hypothalamus increases thirst, kidney produces aldosterone bp goes back up Atrial Natriuretic Peptic (ANP): released by the heart when it stretches due to increased bp. It reduces bp and blood vol by preventing vasoconstriction and Na+ and water retention. So it leads to water and sodium excretion and inhibits ANG II production. Stretch ANP release adrenal cortex reduces aldosterone release, ADH release in hypothalamus decreases and JGA releases renin release and therefore ANG II release. Reduced sodium and water reabsorption and vasodilation occurs diuresis and naturesis blood vol decreases and bp decreases. ANS regulation of GFR Largely sympathetic and causes antidiuresis (prevent water excretion) by arteriole vasoconstriction and renin. Vol depletion stimulates SNS to give vol conservation and flow is shunted away from the kidneys to legs excretion decreases. There is little baseline for SNS because it is a backup plan and not the main regulatory system. Reabsorption & Secretion along the nephron: the sum of starling forces (hydrostatic pressure and osmotic pressure) dictate reabsorption or filtration. 99% of GFR filtered in reabsorbed. Amount excreted = amt filtered – amt reabsorbed + amt secreted Amt filtered = GFR x P x(plasma conc of electrolyte, not proteins!) Amt excreted = UV x U (xrinary vol and urine conc of electrolyte) Difference oftwo is; sum of the secreted and reabsorbed. Kidneys consume an incredibly high amount of oxygen. Clearance: amount of a substance that is removed from urine, it is specific to each solute (vol/time). of albumin 0, not filtered Ux .V Cx = Px ,V= vol of urine Inulin and creatinine: filtered by not reabsorbed or secreted therefore, amount filtered is amount excreted in urine. So the GFR reflects the amount of them that is excreted. Uinulin .V C inulin Pinulin = GFR = 125mL/min (standard) PAH is filtered and secreted so amount that is excreted is even more than that is filtered and is equal to the renal plasma volume. UPAH .V C PAH = PPAH = RPF = 600mL/min LECTURE 6 Free Water clearance: reflection of amt of water you must subtract or add to urine to make it isosmotic to plasma (295Osm/kg). C H2Oreflects the ability of the kidneys to excrete dilute or concentrated urine. CH2O > 0 indicates hypoosmotic urine, Osmo <295 diluting and trying to get rid of excess water CH2O < 0 indicates hyperosmotic urine Osmo >295 concentrating the urine if Uosm >Posm (295), then C Osm s negative. Renal Diseases: 1. Volume Expansion release of renin and ANG II ↓resistance of EA ↑/↓ GFR (↑RPF) ↓Filtration Fraction (FF) forcing less of RPF to become GFR ↓oncotic pressure in PT capillaries (cuz proteins are dilute due to less filtration) & ↑HP in PT capillaries (more fluid in PT cap ↓ absorption (Naturesis and diuresis). 2. Volume Contraction: ANG II antinaturesis and antidiuresis, lower bp. GFR may ↑ or ↓ but RPF will ↓ and FF will ↑ ↑ ANG II ↑AA and EA resistance ↓RPF & ↑FF ↑ PT cap Osmo pressure ↑proximal NA+ reabsorption ↓ water and sodium excretion ↑ ANG II ↓ vasa recta (deep PT cap) blood flow ↑urea and ↓ sodium in the interstitium ↑ NaCl reabsorption ↓ water and sodium excretion Stages of Renal Dysfunction: until you get down to GFR of 30mL/min and below, it is not a problem because the kidneys can function off of the renal reserve. BLOCK II (STILL LECTURE 6) Water can’t be moved against its concentration gradient Driving force are HP and OP. Reabsorption and secretion are tied to the GFR, if GFR is too low, everything is reabsorbed to conserve including waste. If GFR is too high, needed substances cannot be reabsorbed quickly enough and are lost in urine. Factors affecting Reabsorption GFR it does so by affecting these: a) Peritubular capillary pressure: affects FF which determines HP in PT cap. b) Transporter numbers at the membrane c) Transporter activity d) Driving forces across nephron epithelial Cells *Renal has the HIGHEST oxygen delivery in the body. Cortical Nephrons: 85% and not deep Medulla nephrons: are deep with vasa recta capillaries, deep nephrons concentrate the urine. Epithelial Transport: epithelial Cells regulate transport through all tubule segments. They are single layer thick and are polarized. For solute to travel it can travel transcellularly through the apical/luminal (the membrane between the nephron and interstitium) or through the basolateral (b/w interstitium and nephron basolateral membrane) It can also travel paracellularly. Tubular transport: solute has to pass through three membranes: luminal membrane, basolateral and capillary mem. Direction of Tubular Transport: on basolateral mem, Na+/K pump sets up gradient for movement. Selectivity: there is no selectivity between PT cap and interstitium, the only selectivity is apical and basolateral membranes. Movement across epithelium is rate limiting. Active transport: slow, uses ATP and is highly selective, drives uphill too. Facilitated diffusion: no ATP but is selective, a bit slow. Uses one thing to move another. Passivechannel and Passive bilayer: least selective, fast, no ATP use. Passive bilayer moved lipid soluble substances which the channel moves other substances. Saturation: Transporters have finite rates, in saturation you have more solutes available than the number of transporters available for transport. LECTURE 7 Transport Maximum (Tm): the number of available transporters for an electrolyte transport. When T mf a substance is reached (saturation), the excess of that substance is excreted. Graphs: a) As more plasma is delivered to the kidneys, filtration rate of glucose is increasing (linear) b) When Tm is reached at 300 saturation excess are excreted c) After 300 glucose excretion increases d) All graphs in one plot Nonreabsorbed/excreted substances: a) Lack carriers b) Are not lipid soluble c) Are at tubular levels above Tm d) Are too large to pass through the epithelial junctions Oxygen consumption signifies reabsorption because the Na+ pump that drives other reabsorptions uses ATP which is produced by oxygen consumption. Tubular Secretion: opposite of reabsorption, electrolytes are put back into the lumen of the nephron. It is important for: a) Disposing of substances not already in the filtrate b) Eliminating toxic substances such as urea and uric acid c) Ridding the body of excess potassium ions d) Controlling blood pH How Water moves: hydrostatic, osmotic and being dragged by solute. Routes: by aquaporins (AQP1water channels) and through the lipid bilayer (little). Across cells, you need aquaporins & osmotic difference. Without aquaporins, water mov’t can happen by osmotic gradient set up by Na+. Proximal tubule: leaky, no need for aquaporins Reabsorption by capillaries: driven by sum of HP (against reabsorption) and OP (favors reabsorption) and diffusion. The specific protein for water transport is aquaporin! Epithelial water mov’t: sodium pumps on the lateral side of the cells (in b/w the two cells) pumps sodium into the space and driving water with it. The space already has a higher conc of water so it seems like water is going uphill. Water then enters the capillaries. LECTURE 8 Tubular Reabsorption: 1. Proximal Tubule: leaky epithelium with low voltage. Osmolarity is constant. Glucose and Amino Acids (99%): they decrease because they are absorbed 67% of Filtered Sodium: conc increases a little but amt decreases cuz of reabsorption Inulin: amt is the same but conc increases, same as creatinine HCO3 (in the graph): decreases, almost all reabsorbed 65% of Filtered Water, 50% of Filtered Urea and Most of Filtered Potassium. Proton secretion is dependent on amount required for acid/base regulation. Transeptithelial membrane potential: really low and leaky. But it changes from 3 in early tubule to +3 at the late prox tubule. Process of secretion: organic anion (left) – PAH. Organic anion secretion in exchange for an organic cation. Citric concentration in lumen affects nucleation and crystallization of Na+. Organic cation OC (right): proton is secreted for absorbing HCO3 but it is later reabsorbed and OC is exchanged and secreted for the proton absorbed. Prox Tubule Transport Mechanism In proximal tubule, AQP 1 is found in the luminal mem while AQP 1 and AQP4 are found on basolateral. Water movement is driven by leaky mem and aquaporins. Other substances: a) Urea: has specific transporters. Water absorption concentrates urea in the tubule causing it to diffuse into PT cap via transporters and paracellularly. b) Glucose: Na+/glucose. In early prox tubule, 1 Na+ drives glucose along into the cell against its conc gradient via SGLT2. Then glucose diffuse on basolateral into interstitium via GLUT2. In prox tubule, 2 Na+ drives glucose via SGLT1 into the cell. c) Na+ recycling: in late prox tubule, the 3 voltage causes some Na+ to be leaked back into the lumen of the nephron. If FF increases driving force for absorption increases, if GFR increases amt of filtered Na+ increases. So in Pox tubule, if you absorb an increased amt of NA+, you absorb an increased amt of everything because it drives other along meaning that OP is higher than HP. LECTURE 9 Prox Tubule Balance: absorption needs a gradient. Proximal tubule absorbs molecules nearly at isosmolarity. Fluid entering and leaving the tubule also has same osmolarity but you absorb a lil more solutes than you do water. *You absorb solutes and water in the same proportion, not amount! PT Summary: the animal has water deficit because it cannot absorb water. Osmolites are more diluted in the nephron and water is lost. AQP 1 in prox tubule is essential for isosmolarity without it, water is not absorbed. Summary: absorption of water absorption of salt absorption of urea Loop of Henle Descending= high water permeability, AQP1 Ascending= low water, high salt permeability Overall absorbs ~ 25% of filtered NaCl Membrane is neither tight nor leaky Reabsorption of Electrolytes in the Loop: Active absorption of Na+ and Cl and K+, but K+ goes back into the lumen Ascending: NKCC – pump that pumps Na+ into the cell but it drives K+ and 2 Cl in too. Loop Diuretics: Acids related to PAH, e.g., Furosemide, Bumetanide, Block NKCC so prevent sodium and other solute to be absorbing and also preventing water reabsorption. Distal Tubule Transport: Absorbs 79% of NaCl and water NCC transporter: transports sodium and two chlorides Basolateral side doesn’t regulate absorption, luminal does. Thiazide diuretics block the NCC pump and prevent sodium reabsorption. It increases amount of sodium that travels to the next segment which causes more potassium to be secreted back into the lumen in that next segment. Increased K+ secretion hypokalemia Collecting Ducts: Has tight epithelium and does regulation of K+ excretion. Sparing diuretics like amiloride block Na+ channels. Renal Chloride transport: In early prox tubule, it travels paracellularly cuz of leaky membrane. In late prox tubule, it travels both paracellularly and with Na+. No Cl reabsorption in descending loop. In ascending loop, it travels with NKCC pump. In distal tubule, it travels with NCC channel and in collecting duct, it travels paracellularly. Urea Transport: Proximal tubule, it absorbs paracellularly and via a transporter. It only moves when the reabsorption of water has concentrated it in the tubule so it moves down its conc gradient. In thin descending limb, at the tip of the loop, urea is secreted back into the lumen (recycling). In the collecting duct, it is reabsorbed as the urine is concentrated but about 50% of filtered amt is excreted. *Ascending limb is impermeable to water Renal Na+ transport: Proximal tubule absorbs sodium using many different mechanisms and even paracellularly. Ascending: uses facilitated NKCC channel Distal tubule; NCC channel Collecting duct: diffusion through ion channels. Diuresis and Diuretics Diuretic: anything that causes diuresis: increased excretion of water. Osmotic diuresis: relating to osmolites in urine that is pulling water thereby increasing water excretion. Examples: glucose, alcohol, caffeine and Lasix. If you have same amt of the solute and the water you pulled zero free water clearance IF you have more solutes than water pulled negative free water clearance Water diuresis: trying to get rid of excess water. Increased excretion positive free water clearance *Things that block Na+ reabsorption are used as diuretics. Mechanisms of concentrating urine: interstitial osmolarity is the driving force of water reabsorption. It can concentrate urine to up to 1200 but can dilute to up to 60. Gradient not required for dilution because Na+ reabsorption is done actively. *Gradient doesn’t limit your diluting capacity, it limits the concentration. LECTURE 10 Facts: 1. There is osmotic gradient as you go from cortical to medullary region 2. Luminal and interstitial osmolarity mirror each other. 3. Osmolarity of nephron goes up and comes back down to hyposomotic when you get to distal tubule. 4. You are reducing volume and amount of everything by the time you get to distal. Hypervolumic (left): increase in vol, get rid of excess water, positive water clearance, no AQP and ADH, no absorption. Hypovolumic (right): decrease in vol, neg free water clearance , presence of ADH conserve water, most absorbed. Urine has 7090 osmo excreted. Distal tubule: regulation of water Interstitium and tip of loop: 1200 osmo; 300 from Na+, 300 from Cl and 600 from urea that was recycled back into the loop of Henle. Colleting duct: has regulated water permeability, done by ADH. Counterflow in tubules and finite permeability causes coupling. Multiples ability of the loop to reduce the volume and amt of NaCl and water. Counterflow also allows for different concentrations in diff tubules. Recycling of urea is essential to maintaining he high medullary osmolarity the 600 of the 1200 osmotic concentration at the tip of the loop of Henle. 50% of the urea is excreted however. Counterflow in vasa recta also maintains deep nephron amount of urea. In distal, you have about 110% of how much was filtered. In collecting duct, you secrete 70% of it and excrete about 40% approx. half. Countercurrent Multiplication; 200mOsmo gradient maintains 200 difference by acting on new segments end up with a capacity to produce 1200 by the end this is how you multiply ability. Active Na+ transport in descending and passive water transport in ascending. Countercurrent Exchange System 1. Formed by vasa recta provide blood supply to medulla does not remove NaCl from medulla 2. Descending capillaries water diffuses out of blood NaCl diffuses into blood 3. Ascending capillaries water diffuses into blood NaCl diffuses out of blood It ensures that osmolarity of fluid coming into and leaving the peritubular cap is nearly similar, so vasa recta enters and leaves with nearly isosmotic fluid. NaCl released by ascending loop is picked up by descending vasa recta & water released by descending loop is picked up by ascending vasa recta so osmolarity is kept same in vasa recta as it is leaving, *Vasa recta and interstitium are almost the same osmolarity. BLOCK 3 (STILL LECTURE 9) Block III Renal Homeostasis Regulation of Na+ and Water Balance Regulation of K+ Balance AcidBase Balance Sodium balance: GIT and urinary systems absorb almost all sodium that we take in. Majority are found in ECF. 0 sodium balance all have to be excreted Response to changes of Na+ Intake: when you sodium intake, excretion of sodium increases. There is imbalance of excretion and intake because it takes a few days for response to form. Increase in sodium intake increases body weight (increased sodium in body increases water retention which increases body weight). As you increase intake, sodium excretion and absorption both increase. Hypervolemia: volume expansion, need to get rid of excess water. PT absorbing more percentage of intake. You are absorbing 75% of sodium delivered to the collecting duct and excreting 25%. Hypernatremia: you take in high sodium. PT absorbs more sodium but less percentage of intake. Other parts absorb more percentages to compensate. In the collecting duct, you excrete 75%. Hypovolemia: similar to hypernatremia but you excrete 25% Hyponatremia is similar to hypervolemia except you excrete 0% and absorb all of the sodium. *Highest fractional change in activity in the collecting duct. Major determinants of Na+ excretion: 1. GFR: increase in GFR causes increased Na+ excretion. 2. Aldosterone: Na+ retention 3. RAS ANG II ADH and aldesterone 4. ANP: counteract ANG II 5. AVP or ADH: sodium absorption GFR – Pressure Natureis and Diuresis: ↑ Volume or Pressure: ↑ GFR ↑ Filtered Na+ (amount) ↑ Na+ Reabsorption (amount) ↓ Reabsorption (%): more absorbed but iis less percentage of Na+ intake ↑ Excretion (amount) Water Follows MORE IN MORE OUT! Glomerular tubular balance (GTB) imperfect Natriuresis Aldosterone: long term response of NA+ balance. It is the main hormone responsible for sodium regulation. Can be stimulated in the presence of high potassium concentration. Na+ absorption, Cl follows to and there is increased potassium excretion. Cellular Effects of Aldosterone: all steroid hormones have intracellular receptors. Aldosterone diffuses into the membrane and binds to the intracellular MR receptor AldoMR complex which initiates transcription proteins produced to make Na+/K+ channels more channels activated channel sets up gradient that drives absorption increased sodium absorbed and increased K+ excreted. Collecting duct has tight epithelium for Cl to follow Na+ paracrinely, by aldosterone changes that and Cl is able to travel paracrinely. RAS: long term ANGII Aldosterone decrease flow to kidneys ADH: main hormone responsible for change in balance. Operates in a narrow window of plasma osmolarity and plasma also operates in a narrow range of ADH. Volume contraction increases sensitivity to ADH while volume expansion decreases sensitivity to ADH. ADH/AVP and Water Channels: ADH binds to V receptor cAMP produces series of protein synthesis phosphorylation moves AQP2 to the membrane AQP2 in membrane allows for water absorption. Osmolarity: you need a little change in plasma ADH for you to change the urinary osmolarity. 0 is the least dilute urine, at about 6 in the ADH plasma, you have reached 1200 which is the peak of urine concentration. Urodilation: increase in volume and bp stretch produce ANP inhibits sodium absorption Potassium balance: potassium balance is highly determined by amt secreted. (810mmol/day (filtered) – 770 reabsorbed) = 40 filtered remaining 40 + 50 (secreted in collecting duct) = 90 excreted Response to Changes of Extracellular K+: maintained by a) Intracellular K+ stores b) Renal K+ handling Pathway: increase in glucose increase in ATP powers absorption of Sodium excretion of K+ increased potassium excretion Major Determinants of Increased K+ Excretion: a) Increased GFR or Filtration Fraction b) Increased K+ intake or Extracellular K+ ** c) Stimulation of the RAS Increased intake of K+: increase in osmolite constriction of AA increases in renin and ANG II increase in aldosterone increased sodium reabsorption increased K+ excretion Acid/Base Balance: Physiological pH: 7.4, normal range is 7.38 to 7.42 arterial pH >7.42 – alkalosis: could be in metabolism or respiratory <7.38 acidosis: could be in metabolism or respiratory Low abundance ion of H+ has effect everywhere. H+ can be excreted through the urine, feces and through expired air. H+ is secreted in exchange for HCO3 absorption Ammonia is the main buffer in the urine. HCO3 reabsorption occurs as: 1. H+ secretion or 2. HCO3 reabsorption In proximal tubule, hydration reaction od CO2 and H2O produces bicarbonate that is absorbed while the H+ is secreted.
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