Physiology 5th Ed.

Chapter 6. Renal Physiology

 

The kidneys function in several capacities. As excretory organs, the kidneys ensure that those substances in excess or that are harmful are excreted in urine in appropriate amounts. As regulatory organs, the kidneys maintain a constant volume and composition of the body fluids by varying the excretion of solutes and water. Finally, as endocrine organs, the kidneys synthesize and secrete three hormones: renin, erythropoietin, and 1,25-dihydroxycholecalciferol.

ANATOMY AND BLOOD SUPPLY

BODY FLUIDS

RENAL CLEARANCE

RENAL BLOOD FLOW

GLOMERULAR FILTRATION

REABSORPTION AND SECRETION

TERMINOLOGY ASSOCIATED WITH THE SINGLE NEPHRON

SODIUM BALANCE

POTASSIUM BALANCE

PHOSPHATE, CALCIUM, AND MAGNESIUM BALANCE

WATER BALANCE—CONCENTRATION AND DILUTION OF URINE

SUMMARY

ent Total body water is distributed between ICF and ECF. As percentages of body weight, 60% is total body water, 40% is ICF, and 20% is ECF. ECF consists of plasma and interstitial fluid. Volumes of the body fluid compartments are measured by dilution of marker substances.

ent ECF and ICF osmolarity are always equal in the steady state. When there is a disturbance of body fluid osmolarity, water shifts across cell membranes to reestablish the equality of ECF and ICF osmolarity. These shifts produce changes in ECF and ICF volume.

ent Renal clearance is the volume of plasma cleared of a substance per unit time and is determined by its renal handling. Substances with the highest clearances are both filtered and secreted. Substances with the lowest clearances either are not filtered or are filtered and subsequently reabsorbed. Inulin is a glomerular marker whose clearance equals the GFR.

ent RBF is autoregulated over a wide range of arterial pressures by changes in the resistance of the afferent arterioles. Effective RPF is measured by the clearance of PAH, and RBF is calculated from the RPF.

ent GFR is determined by the permeability of the glomerular capillary barrier (Kf) and the net ultrafiltration pressure. Net ultrafiltration pressure is the sum of three Starling pressures across the glomerular capillary: PGC, πGC, and PBS. If any of the Starling pressures change, net ultrafiltration pressure and GFR are altered.

ent Reabsorption and secretion modify the ultrafiltrate that is produced by glomerular filtration. The net reabsorption or secretion rate of a substance is the difference between its filtered load and its excretion rate. Glucose is reabsorbed by a Tm-limited process: When the filtered load of glucose exceeds the Tm, then glucose is excreted in the urine (glucosuria). PAH is secreted by a Tm-limited process.

ent Na+ reabsorption is greater than 99% of the filtered load and occurs throughout the nephron. In the proximal tubule, 67% of the filtered Na+ is reabsorbed isosmotically with water. In the early proximal tubule, Na+ is reabsorbed by Na+-glucose cotransport, Na+-amino acid cotransport, and Na+-H+ exchange. In the late proximal tubule, NaCl is reabsorbed. ECF volume expansion inhibits proximal tubule reabsorption, and ECF volume contraction stimulates it. In the thick ascending limb of the loop of Henle, a water-impermeable segment, 25% of the filtered Na+ is reabsorbed by Na+-K+-2Cl cotransport. Loop diuretics inhibit the Na+-K+-2Cl cotransporter. In the distal tubule and collecting ducts, 8% of the filtered Na+ is reabsorbed. In the early distal tubule, the mechanism is Na+-Cl cotransport, which is inhibited by thiazide diuretics. In the late distal tubule and collecting ducts, the principal cells have aldosterone-dependent Na+ channels, which are inhibited by K+-sparing diuretics.

ent K+ balance is maintained by shifts of K+ across cell membranes and by renal regulation. The renal mechanisms for K+ balance include filtration, reabsorption in the proximal tubule and thick ascending limb, and secretion by the principal cells of the late distal tubule and collecting ducts. Secretion by the principal cells is influenced by dietary K+, aldosterone, acid-base balance, and flow rate. Under the conditions of low K+ intake, K+ is reabsorbed by α-intercalated cells of the distal tubule.

ent Body fluid osmolarity is maintained at a constant value by changes in water reabsorption in the principal cells of the late distal tubule and collecting duct. During water deprivation, ADH is secreted and acts on the principal cells to increase water reabsorption. During water drinking, ADH secretion is suppressed and the principal cells are impermeable to water.


Challenge Yourself

Answer each question with a word, phrase, sentence, or numerical solution. When a list of possible answers is supplied with the question, one, more than one, or none of the choices may be correct. Correct answers are provided at the end of the book.

1 Constriction of which arteriole leads to decreased renal plasma flow (RPF) and increased glomerular filtration rate (GFR)?

2 In what portion of, or at what point on, the glucose titration curve, is the renal vein glucose concentration equal to the renal artery glucose concentration?

3 What happens to the oncotic pressure of peritubular capillary blood following an increase in filtration fraction?

4 When the clearance of PAH is used to measure effective RPF, is the measurement done at plasma concentrations of PAH that are above or below the Tm for secretion?

5 A person with an ECF volume of 14 L, an ICF volume of 28 L, and a plasma osmolarity of 300 mOsm/L drinks 3 L of water and eats 600 mmoles of NaCl. In the new steady state, what is the plasma osmolarity?

6 If GFR is constant and there is an increase in urine flow rate, how does the plasma inulin concentration change: increased, decreased, or unchanged?

7 An increase in urine pH causes what change in the excretion of a weak acid: increased, decreased, or unchanged?

8 During water diuresis, where in the nephron is [TF/P]inulin lowest?

9 Where in the nephron is fractional excretion of Na+ highest?

10 What is the effect of a loop diuretic (inhibitor of Na+-K+-2Cl-cotransporter) on maximum urine osmolarity during production of hyperosmotic urine: increased, decreased, unchanged?

11 Which ADH disorder is represented by the following changes: increased plasma osmolarity, dilute urine, decreased ADH?

12 In a person who ingests a bag of potato chips (i.e., NaCl), what happens to intracellular volume: increased, decreased, or unchanged?

13 What are the units of glucose Tm?

14 What is the effect of dilation of the efferent arteriole on filtration fraction: increased, decreased, or unchanged?

15 Which of the following cause(s) hyperkalemia: lack of insulin, hyperaldosteronism, loop diuretics, spironolactone, hyperosmolarity, metabolic alkalosis?

16 Regarding the actions of parathyroid hormone (PTH) on the kidney, which of the following is/are seen: inhibition of Na+-phosphate cotransport, decreased urinary phosphate excretion, decreased urinary Ca2+ excretion, decreased urinary cyclic AMP?

17 GFR is 120 mL/min, the plasma concentration of X is 10 mg/mL, the urine concentration of X is 100 mg/mL, and urine flow rate is 1.0 mL/min. Assuming that X is freely filtered, is there net reabsorption or net secretion of X, and what is the rate?

18 During production of hyperosmotic urine, where in the nephron is [TF/P]osmolarity lowest?

19 Which is highest: clearance of PAH below Tm, clearance of glucose below threshold, or clearance of inulin?

20 Rank the following substances in order of fractional excretion from highest to lowest: inulin, Na+, glucose (below threshold), K+ on a high potassium diet, and HCO3.


SELECTED READINGS

Koeppen BM, Stanton BA: Renal Physiology, 3rd ed. St Louis, Mosby, 2001.

Seldin DW, Giebish G: The Kidney: Physiology and Pathophysiology, 2nd ed. New York, Raven Press, 1992.

Valtin H, Schafer JA: Renal Function, 3rd ed. Boston, Little, Brown, 1995.

Windhager EE: Handbook of Physiology: Renal Physiology, New York, American Physiological Society, Oxford University Press, 1992.