Answers
Session 6
/Renal Physiology II
M.A.S.T.E.R. Learning Program, UC Davis School of MedicineRevised: February 21, 2002
Revised by: David Saito and Stephanie Eden1. Explain the changes in mean pressure from renal artery to renal vein (lec 23/8, 23/9)
The major resistances to flow within the kidney occur in the afferent arteriole, the efferent arteriole, and small veins. Thus, there are large decreases in hydrostatic pressure as blood flows through these segments and little or no decreases in the other segments. Note that because of the increased total cross sectional area that exists in the glomerular and peritubular capillary beds, there is little or no pressure drop as blood flows along the capillaries.
2. Explain changes in hydrostatic and oncotic pressures as blood flows through the glomerulus from afferent to efferent arteriole (lec 23/11).
At the point of the afferent arteriole and extending through the capillaries to the efferent arteriole, the hydraulic pressure of both compartments (GC and BS) remains stable. However, the oncotic pressure in the GC changes because as plasma progresses from the afferent side of the glomerular capillary to the efferent side, water is being removed by filtration, whereas protein remains in the capillary and is not filtered. Thus, the protein concentration will increase along the length of the glomerular capillary and therefore so will GC oncotic pressure (pGC).
3. What determines the rate of glomerular filtration (lec 23/10)?
The rate of glomerular filtration (or flow) is determined by the product of the net filtration pressure and the filtration coefficient of the glomerulus. The net pressure is the sum of the following:
· the glomerular capillary hydrostatic pressure
· pressure in Bowman's capsule (tubular hydrostatic pressure)
· colloid osmotic pressure in the glomerulus.
· GFR = Kf [(PGC – PBS) – (pGC – pBS)] (pBS is usually zero since no protein is filtered, or the small amounts of filtered albumin are subsequently absorbed. However, in pathological states where protein filtration does occur, pBS can significantly impact GFR.) Basically, Starling Forces!!!
Kf = filtration coefficient = Lp * surface area
(Lp = hydraulic conductivity)
4. What happens to GFR & RBF if: (lec 23/13)a. increase afferent arteriole resistance
b. increase efferent arteriole resistance
c. decrease efferent arteriole resistance
d. decrease afferent arteriole resistance
5. Describe autoregulation of the kidney and how it works (23/14,15).
Autoregulation is an intrinsic mechanism of the kidney which tends to maintain a constant RBF and GFR in the face of altered perfusion pressures. Two mechanisms are involved:
· Myogenic: This is the direct response of afferent arterioles and interlobular arteries to a decrease in blood pressure resulting in vasodilation. Vasoconstriction occurs in response to increased blood pressure.
· Tubulo-glomerular feedback: As blood pressure increases, GFR increases transiently. Thus the rate of fluid flow through the proximal tubule increase and the macula densa senses the increased delivery of Na+ and Cl-. The macula densa sends a signal that results in vasoconstriction of the afferent arterioles. The net effect is to reduce the GFR. With a decrease in blood pressure the opposite will occur resulting in vasodilation of the afferent arterioles.
6. What are the major physiologic factors which influence the afferent and efferent arterioles (lec 23/16)?
Renal nerves: The afferent and efferent arterioles are richly supplied with sympathetic neurons which cause arteriolar constriction (via alpha1 adrenergic receptors). Although, afferent arteriolar vasoconstriction predominates under sympathetic control.
Circulating humoral factors: Epinephrine, norepinephrine, angiotensin II, endothelin, and vasopressin (ADH) cause vasoconstriction. Atrial natriuretic peptide (ANP) & acetylcholine cause renal vasodilation.
Local factors: Renal prostaglandins and kinins cause vasodilation. Anglotensin II causes vasoconstriction.
7. A drug is noted to cause a decrease in GFR. What might the drug be doing? (seven possible actions) (lec 23/10,11)
1. Constricting glomerular mesangial cells (decrease Kf)
2. Lowering arterial pressure (decrease PGC)
3. Constricting afferent arteriole (decrease PGC)
4. Dilating the efferent arteriole (decrease PGC)
5. Causing obstruction in urinary system (increase PBS)
6. Increasing plasma albumin concentration (increase pGC)
7. Decreasing amount of blood flow to the kidneys resulting in steeper rise of pGC along the length of the glomerular capillaries.
(It is possible for a drug to increase GFR with no change in the net filtration pressure by increasing Kf)
8. What happens to urine formation in a patient with uncontrolled diabetes mellitus(lec 24/8)?
Osmotic Diuresis In these patients the filtered load of glucose exceeds the maximum transport capacity of the sodium/glucose cotransporter to reabsorb glucose. Thus glucose is retained and concentrated in the tubular fluid. This results in less water being reabsorbed due to the osmotic effects of glucose (for every 300 mOsm of glucose in the proximal tubular fluid 1 L of water is retained to maintain isoosmolarity). The extra water retained reduces the concentration of Na+ and other solutes (i.e. Cl-) in the tubular fluid. This decreases the gradient for Cl- diffusion from tubule to blood. The net result is the increased urinary output with increased excretion of solutes (i.e. glucose, Na+, etc.) and water.
Glucosuria will be seen once glucose concentration in the glomerulus reaches 200 mg/dL; the glucose transporters of the nephron are saturated at 300 mg/dL.
9. Describe the mechanism of fluid reabsorption (24/10).
Governed by Starling forces (net hydrostatic and colloid osmotic pressure difference). The peritubular capillaries have a low hydrostatic pressure due to resistance of glomerular arterioles. They also have a high oncotic pressure due to the removal of the protein free filtrate in the glomerulus. Therefore the net effect favors uptake of fluid from the interstitial space to the peritubular capillaries. They can be affected by a change in hydrostatic pressure by increasing or decreasing arteriolar constriction. Both angiotensin II and norepinephrine released with decreased circulating volume will lead to increased constriction of afferent and efferent arterioles, reduced RBF and therefore promote fluid reabsorption.
10. Where and how is K+ excretion regulated(lec 25/9)?
In the principal cells of the distal nephron. The Na+/K+ pump maintains high cell K+ concentration. The concentration difference favors potassium leakage into the lumen on the apical membrane, yet this is opposed by the membrane potential difference. Anything that increases the [K+] difference or increases the membrane potential will favor K+ secretion.
Increased plasma [K+] does two things:
1. It stimulates the Na+/K+ pump therefore increasing the intracellular [K+] and increasing the driving force for secretion to the tubule lumen.
2. Increased plasma [K+] concentration increases aldosterone secretion which increases Na+ and K+ permeability of the apical membrane and increased activity of the Na+/K+ pump.
The intercalated cells ( type A) of the distal nephron, which are interspersed among the principal cells, are responsible for K+ reabsorption. The net reabsorption of K+ in this segment occurs under situations of severe K+ depletion via a H+/K+-ATPase located on the apical membrane.
In addition, if the tubular fluid flow rate is increased due to decreased fluid reabsorption in the proximal tubule the [K+] remains low therefore more K+ will be secreted. If intracellular [Na+] increases, this makes the cell interior less negative therefore increasing the drive for K+ secretion.
11. Give three reasons why osmotic diuresis enhances potassium excretion (lec 25/10).
· It inhibits potassium reabsorption by the proximal tubule.
· It increases fluid delivery to the cortical collecting duct resulting in increased potassium secretion.
· It causes sodium depletion, which increases aldosterone secretion (via the renin - angiotensin system), and this hormone stimulates potassium secretion.
12. Why do the loops of Henle work as countercurrent multipliers and the vasa rectae function as a countercurrent exchanger (lec 26/4-6)?
Countercurrent multiplication:
a) The single step is the active reabsorption of NaCl in excess of water in the TAL. This active step allows the generation of a transverse gradient of ~200 mOsm/kg.
b) The thin descending limb has a high water permeability, allowing the tubular fluid to equilibrate with the interstitial fluid. This does not dissipate the osmotic gradient set up by the active transport in the TAL because it continues to "pump" until a steady state gradient is established and maintained.
c) The thin and thick ascending limbs are impermeable to water, allowing the single step to be maintained.
d) The small transverse gradient is multiplied into a large longitudinal gradient by the flow of fluid in the tubule and the countercurrent arrangement of the loop. As the loop becomes longer (relative to the size of the kidney), the longitudinal gradient can become very great.
Hence, the generation of the corticopapillary osmotic gradient is achieved. In desert rodents which have a tremendous capacity to concentrate their urine (as high as ~4000 mOsm/kg), the loops can be so long relative to the size of the kidney they begin to emerge from the renal pelvis.
Countercurrent exchange:
The outer and inner medulla are perfused by capillaries whose structure is of critical importance to the maintenance of the corticopapillary osmotic gradient set up by the countercurrent multiplication in the loop of Henle. These capillaries are known as the vasa rectae, and their specialized hairpin (i.e. countercurrent) structure permit them to function as countercurrent exchangers. In other words, the loop structure of the vasa rectae allows blood flow to reach the inner medulla but does not wash out the osmotic gradient. The vasa rectae are highly permeable to water and solutes which equilibrate across the capillary wall as it courses through the medulla. In addition to maintaining the osmotic gradient, the vasa rectae provide nutrients and O2 to the medullary tissues and remove the excess water and solutes being reabsorbed in the cortical and medullary nephron segments.
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