Flashcards in Medical Physiology Block 4 Week 1 Deck (58):
State the four major functions of the kidney.
regulation of water and electrolyte balance; filtering (removing metabolic products and toxins from the blood and excreting them through the urine); regulation of arterial blood pressure; Produce or activate hormones (Renin, erythropoeitin, vitamin D, prostaglandins and kinins)
Explain mass balance and how it applies to the kidney.
For any solute (X) that the kidney does not synthesize, degrade, or accumulate, the only route of entry to the kidney is the renal artery, and the only two routes of exit are the renal vein and the ureter
What is the renal pelvis? what are calyxes? renal pyramids?
renal pelvis and its extensions, the major and minor calyces sit in the renal sinus; The medulla is subdivided into 8 to 18 conical renal pyramids, whose bases face the cortical-medullary border; the tip of each pyramid (papilla) terminates in the renal pelvis (urine flows from the tip into the minor calyxes of the renal sinus through perforations)
Describe the renal medulla. What is the renal papilla?
Lacks glomeruli and consists of a parallel arrangement of tubules and small blood vessels; The renal papilla is the location where the medullary pyramids empty urine into the minor calyx in the kidney. Histologically it is marked by medullary collecting ducts converging to form a duct of Bellini to channel the fluid.
Define nephron, renal corpuscle, glomerulus, and tubule.
Nephron = glomerulus + tubule; Renal corpuscle = glomerulus, Bowman's space, and Bowman's capsule + mesangium; Glomerulus (vascular)= cluster of blood vessels from which the plasma filtrate originates; The tubule is an epithelial structure consisting of many subdivision, designed to convert the filtrate into urine.
Draw the relationship between glomerulus, Bowman’s capsule, and the proximal tubule.
plasma flows from the glomerular capillaries into Bowman's space, which is contiguous with the lumen of the proximal tubule
Describe the three layers separating the lumen of the glomerular capillaries and Bowman’s space.
glycocalyx covering the luminal surface of endothelial cells (negatively charged proteins); endothelial cells; glomerular basement membrane (two thin exterior layers and a thick layer in the middle); epithelial podocytes (foot processes cover glomerular capillaries; filtration slits are spaces in between interdigitations of podocytes that cover GBM; connected together to form slit diaphragm surrounded by negatively charged glycoproteins)
Define glomerular mesangial cells and state their function.
similar to smooth muscle; secrete the extracellular matrix; contraction of mesangial cells reduces renal permeability; filtration occurs away from mesangial cells
List the individual tubular segments in order; state the segments that make up the proximal tubule, Henle’s loop, and the collecting duct system
proximal tubule (S1 & S2 = proximal convoluted tubule reabsorbs the bulk of the filtered fluid; S3 = proximal straight tubule; Henle's loop (thin descending, thin ascending, thick ascending: tall interdigitations and numerous mitochondria maintain the hyperosmotic nature of the medullary interstitium); collecting duct (distal convoluted tubule, initial collecting tubule, and cortical collecting tubule) and medullary collecting tubule
Define principal and intercalated cells
cells found in the initial collecting tubule and cortical collecting tubule; Principal cells reabsorb sodium chloride and secrete potassium; Intercalated A cells secrete hydrogen ion and reabsorb potassium; Intercalated B cells secretes bicarbonate
List in order the vessels through which blood flows from the renal artery to renal vein; contrast the blood supply to the cortex and the medulla; define vasa recta and juxtame-dullary nephrons.
a high resistance arteriole (afferent), followed by a high-pressure glomerular capillary network for filtration, followed by a second high resistance arteriole (efferent), which is followed by a low-pressure capillary network that surrounds the renal tubules (peritubular capillaries) and takes up the fluid absorbed by these tubules (followed by the renal vein); Some 90% of the blood entering the kidney perfuses superficial glomeruli and cortex; only ∼10% perfuses juxtamedullary glomeruli and medulla; efferent arterioles of juxtamedullary nephrons descend into the medulla and form capillaries and hairpin vessel structures
Define juxtamedullary apparatus and describe its three cell types; state the function of the granular cells.
a region where each thick ascending limb contacts its glomerulus (extraglomerular mesangial cells, macula densa, and granular cells); When the afferent arteriole senses decreased stretch in its wall (baroreceptor), neighboring granular cells increase the release of renin into the circulation
Define the basic renal process: glomerular filtration, tubular reabsorption, and secretion.
volume of fluid filtered into Bowman's capsule per unit time (the amount of X that appears in the urine per unit time is the same as the amount of X that the glomerulus filters per unit time); amount of solute filtered - amount of solute reabsorbed + amount of solute secreted = amount of solute excreted
Define renal blood flow, renal plasma flow, glomerular filtration rate, and filtration fraction and give normal values.
renal blood flow is 20% of the cardiac output (1 L/min); renal plasma flow = (1-hematocrit) x renal blood flow (600 mL/min); glomerular filtration rate- 125 mL/min or 180 L/day; filtration fraction = GFR/RPF (0.2)
State the formula relating flow, pressure, and resistance in an organ.
Flow = delta P/R
Describe the effects of changes in afferent and efferent arteriolar resistance on renal blood flow.
constriction of afferent arteriole and relaxation of efferent arteriole decreases glomerular capillary pressure; Constriction of only afferent arteriole decreases capillary pressure, renal plasma flow, and GFR; Constriction of only efferent arteriole increases capillary pressure and decreases renal plasma flow following administration of angiotensin II decreases renal plasma flow (Initially GFR increases because rising capillary pressure dominates; Later, GFR decreases because falling renal plasma flow dominates)
Describe the relative resistance of the afferent arterioles and efferent arterioles.
selective constriction or relaxation of the afferent and efferent arterioles allows for highly sensitive control of the hydrostatic pressure in the intervening glomerular capillary and thus of glomerular filtration.
Describe how molecular size and electrical charge determine filterability of plasma solutes; state how protein binding of a low-molecular weight substance influences its filterability.
The glomerular filtration barrier limits large, negatively charged, globular or rigid (non-deformable) solutes from entering into Bowman's space; solutes bound to proteins have reduced filtration
State the formula for the determinants of glomerular filtration rate, and state, in quantitative terms, why the net filtration pressure is positive.
glomerular ultrafiltration depends on the product of the ultrafiltration coefficient (K f ) and net Starling forces (GC pressure is very high throughout the capillary; BS pressure is 10 mm Hg along the capillary; Oncotic pressure of the glomerular capillary increases along the capillary; there is virtually no oncotic pressure for Bowman's space)
Define ultrafiltration coefficient and state how mesangial cells might alter the filtration coefficient; state the reason why glomerular filtration rate is so large relative to filtration across other capillaries in the body
Kf is the product of the hydraulic conductivity of the capillary (Lp) and the effective surface area available for filtration (very large compared to other capillary beds); contraction of mesangial cells reduces Kf
Describe how changes in renal plasma flow influence average glomerular capillary oncotic pressure.
At higher plasma flow (normal physiology), a hypothetical filtration equilibrium would be reached at a site actually beyond the end of the capillary (Capillary oncotic pressure rises more slowly along the length of the capillary)
Describe how arterial pressure influences peritubular capillary pressure.
Volume expansion inhibits the renin angiotensin system; Significant decrease in efferent arteriole resistance (increase in hydrostatic pressure entering peritubular capillary); Increases GFR, pGC, and RBF; decreases filtration fraction (renal plasma flow increases more relative to GFR, which saturates); Decreases oncotic pressure entering peritubular capillary; final outcome: decreased uptake by peritubular capillaries
Define autoregulation of renal blood flow and glomerular filtration rate.
The kidney autoregulates RBF by responding to a rise in renal arterial pressure with a proportional increase in the resistance of the afferent arterioles (changes in posture, sleeping, and light to moderate exercise)
Describe the myogenic mechanisms of autoregulation
The afferent arterioles have the inherent ability to respond to changes in vessel circumference by contracting or relaxing—a myogenic response. The mechanism of contraction is the opening of stretch-activated, nonselective cation channels in vascular smooth muscle. The resultant depolarization leads to an influx of Ca 2+ that stimulates contraction
Describe the tubuloglomerular feedback mechanisms of autoregulation
(mediated by juxtaglomerular appartus) the macula densa cells in the thick ascending limb sense an increase in GFR (NaCl) and, in classic feedback fashion, translate this to a contraction of the afferent arteriole, a fall in pGC and RPF, and hence a decrease in GFR. The rise in [Cl − ]i , in conjunction with a Cl − channel at the basolateral membrane, apparently leads to a depolarization, which activates a nonselective cation channel, which, in turn, allows Ca 2+ to enter the macula densa cell. The result is an increase in [Ca 2+ ]i that causes the macula densa cell to release paracrine agents (ATP, adenosine, thromboxane, or other substances) that may trigger contraction of nearby vascular smooth muscle cells. A1 adenosine receptors on the smooth muscle cells may be particularly important in this response. The net effect is an increase in afferent arteriolar resistance and a decrease in GFR, thereby counteracting the initial increase in GFR; Blocking the Na/K/Cl cotransporter with furosemide (a diuretic) blocks this feedback mechanism
Describe how each of the following concepts relates to fluid homeostasis in health: molarity and equivalence; osmosis and osmotic pressure; osmolarity and osmolality; tonicity.
Concentration can be expressed in terms of either molarity or equivalence; Molarity is the amount of a substance relative to its molecular weight; Differences in osmotic pressure drive water across cell membranes; Osmolality is a test that measures the concentration of all chemical particles found in the fluid part of blood.
Explain how effective osmolytes drive fluid movement between the extracellular and intracellular fluid compartments.
Na + is the most important contributor to the osmolality of the ECF; hence, where Na + goes, water follows.
Explain why the amount of Na+, and not Na+ concentration, determines the volume of extracellular fluid.
The total amount of Na+ in the ECF determines ECF volume (ECF volume is regulated by renal excretion of sodium)
Discuss the concept of extracellular fluid osmolality and its relationship to plasma Na+ concentration.
The total amount of water in ECF determines ECF osmolality (ECF osmolality is regulated by renal excretion of water); an increase in the amount of Na + in the body leads to an increase in ECF volume, blood volume, and blood pressure
Define the term “effective circulating volume” and discuss its importance in fluid homeostasis.
Effective arterial blood volume (EABV) is best defined as adequacy of perfusion of arterial tree. EABV is that portion of the ECF volume contained in the arteries and is the volume “effectively” perfusing the tissues; Your body can not sense the volume of ECF. Instead, effectors of volume homeostasis are controlled by effective arterial blood volume
Describe renal handling of Na+ (i.e., filtration and reabsorption) along the nephron and the transporters/channels involved.
movement of sodium into the proximal tubule from the lumen- electroneutral Na-H exchanger ( NHE3 ) and Na/AA cotransporter (The Na-K pump and, to a lesser extent, the electrogenic Na/HCO cotransporter (NBC) are responsible for moving sodium from cell to blood; sodium leaks back into the lumen paracellularly); movement of sodium into the TAL- Na/K/2 Cl cotransporter (NKCC2; loop diuretics) and paracellular transport (accounts for half of reabsorption of TAL); distal tubule- Na/Cl cotransporter (NCC; thiazide diuretics); initial collecting tubule and cortical collecting tubule- epithelial apical sodium channel (ENaC; controlled by aldosterone)
Compare and contrast how the renin-angiotensin system and atrial natriuretic hormone control renal Na+ excretion in response to changes in effective circulating volume.
angiotensin II: net reabsorption (through PKC stimulates apical NHE3s in proximal tubule; stimulates Na/H exchange in TAL and stimulates apical sodium channels in initial collecting tubule); Aldosterone stimulates sodium reabsorption by the initial tubule and the cortical collecting tubule, and by medullary collecting duct; Of the four parallel effectors that control effective circulating volume, ANP is the only one that promotes natriuresis (cGMP;even though it increases GFR and solute load, it increases the overall sodium load to the distal nephron (inhibits passive reabsorption) thus increasing urinary sodium excretion
What are characteristics of decreased reabsorption rates?
less brush border (apical), diminished complexity of lateral cell interdigitations (basolateral), a lower basolateral cell membrane area, and a decrease in the number of mitochondria (oxidative phosphorylation)
How is the structure of the nephron different in superficial nephrons and juxtamedullary nephrons?
superifical nephrons have abbreviated loop of Henle; juxtamedullary nephrons have a loop of Henle that reaches the inner medulla to the tip of the papilla
The tightness of tight junctions increases or decreases from the proximal to the medullary collecting tubule?
increases (decreased paracellular transport)
Does the kidney receive parasympathetic innervation?
What are the effects of catecholamines on the nephron?
vasoconstriction; enhanced sodium reabsorption in the proximal tubule; increased renin secretion
What hormones are produced by the kidney?
renin (ang II); vitamin D (calcium and phosphate metabolism); erythropoetin (red blood cells); prostaglandins (generally vasodilators)
What is the formula for filtered load? fractional excretion?
filtered load = GFR x plasma concentration of x; FE = (concentration of solute x urine flow)/ filtered load or clearance/GFR
How are GFR and net Starling forces related?
GFR = ultrafiltration coefficient and net Starling forces
What is the effect of volume expansion and a high-protein diet on tubuloglomerular feedback?
decreases sensitivity (makes sense because the body wants to maintain homeostasis)
What is the effect of prostaglandins, leukotriences, and NO on renal plasma flow?
prostaglandins are protective (can modulate constriction); leukotrienes (also produced from arachidonic acid; vasoconstriction); NO- vasodilation
Why is sodium reabsorption in the proximal tubule iso-osmotic?
sodium salts are the dominant osmotically active solutes in the filtrate
What segments of the nephron transport sodium? describe the basic mechanism of transport.
proximal tubule (2/3), TAL (1/4), distal convoluted tubule, connecting tubule, initial collecting tubule, cortical collecting tubule, OMCD, and IMCD; passive movement of sodium intracellulary and transported out by Na/K pump
What is the voltage of the basolateral tubular membrane compared to the interstitial fluid? apical tubular membrane compared to lumen? What maintains this gradient?
negative; negative; Na/K pump
What segment of the nephron has a positive net driving force for paracellular sodium reabsorption? How can sodium move paracellularly in other segments?
S2 and S3 of proximal tubule and TAL; solvent drag
What cause sodium to leak back into the lumen in the early proximal tubule?
lumen negative transepithelial voltage (electrochemical driving force)
What is the mechanism for sodium reabsorption in the TAL? What happens to the potassium and why?
50% NKCC2 cotransporter (1 sodium, 1 potassium, and 2 chloride into the cell), NHE3 (sodium proton exchanger; also found in proximal tubule), also 50% paracellular (lumen-positive transepithelial voltage); gets recycled into the lumen by apical potassium channels (to maintain sodium chloride transport)
Why is does the TAL have a lumen-postive transepithelial voltage? is this common to other nephron segments?
most nephrogenic epithelia have a lumen-negative voltage because the apical membrane voltage is less than the basolateral membrane voltage (depolarization); because potassium channels dominate the apical membrane conductance, the voltage of the TAL apical membrane is more negative than that of the basolateral membrane (chloride reabsorption in S3 generates lumen-positive potential)
Is the TAL permeable to water?
Which diuretic blocks sodium reabsorption in the TAL? distal convoluted tubule? ICT and CCT?
furosemide (loop diuretic); thiazides; amiloride (blocks ENaCs)
What is the mechanism of sodium transport in the distal convoluted tubule? ICT, CCT and collecting ducts?
Na/Cl cotransporter; ENaCs on principal cells
How is chloride reabsorbed?
S1: paracellular (lumen-negative); S3: paracellular (favorable chemical gradient; bicarbonate absorbed in earlier segments) + transcellular (chloride/anion exchange); TAL = transcellular (some chloride enters the cell basolaterally as bicarbonate exits); DCT: NCC; ICT + CCT: beta intercalated cells- chloride/bicarbonate exchange and paracellular (lumen negative)
exits through chloride channels, K/Cl cotransporter (proximal tubule), and sodium/bicarbonate exchange (TAL)
Where is water permeability highest with hormonal intervention?
proximal tubule (high concentration of aquaporin channels)
oxygen consumption in the nephron is dependent on transport of what solute?
What is GT balance?
proximal tubules reabsorb a constant fraction of the sodium load in response to changing solute loads; increasing GFR increases the amount of sodium reabsorbed in the proximal tubule and also increases the amount of sodium left in the proximal tubule (may not be salient for the distal nephron)
What enzyme converts glucocorticoids to inactive metabolites? Why is this important?
11beta-hydroxy-steroid dehydrogenase (prevents glucocorticoids from binding to mineralocorticoid receptors)