BIO 3520 Notes, 4/06/09

RENAL PHYSIOLOGY
I. Introduction. pp. 486-487] [Widmaier,

A. Urinary system is involved in production, storage, and elimination of urine. B. Organization (fig. 14-1). 1. Kidneys -- remove water and waste products to form urine. 2. Ureters -- drain urine from kidneys. 3. Bladder -- storage of urine. 4. Urethra -- elimination of urine.

II. Kidneys. [pp. 486-492] A. Functions (table 14-1). 1. Control of body water balance. a. Control of urine volume is most important mechanism.

b. What is second most important?

2. Control of electrolyte balance. a. Na+, Cl-, Ca++, and others. 3. Excretion of metabolic waste products (ex. urea). 4. Elimination of foreign chemicals (ex. drugs, poisons). B. Anatomy (fig. 14-4). 1. Cortex. 2. Medulla. 3. Renal pelvis drains into ureter. C. Microscopic anatomy of the kidney. 1. Functional unit = nephron (fig. 14-2a). a. One million nephrons in each kidney. b. Made up of a tuft of capillaries and a tubule. 2. Tuft of capillaries -- glomerulus. a. Function -- filtration of plasma. 3. Plasma filtrate enters blind end of tubule -Bowman's capsule. 4. Plasma filtrate travels through tubule and is converted to urine. a. Function of tubule -- selective secretion and reabsorption of substances.

b. Structures. 1. Bowman's capsule. 2. Proximal tubule. 3. Loop of Henle. a. Descending limb -- dips into medulla. b. Ascending limb -- returns to cortex. 4. Distal tubule. 5. Collecting duct -- shared by many nephrons. 5. Final product (urine) drains into renal pelvis. D. Renal circulation. 1. Blood enters via renal artery, which branches off aorta (figurea). 2. Renal vein drains into inferior vena cava. 3. Renal blood flow is more than 1 liter/min. 3. Renal artery branches into smaller arteries (figurea), then afferent arterioles (figurea). 4. Tufts of capillaries -- glomeruli. 5. Efferent arterioles.

6. Peritubular capillaries surround tubules. 7. Venules and veins return blood to renal vein. E. Overview of renal processes (fig. 14-6). 1. 2. 3. 4.
a

Glomerular filtration. Tubular secretion. Tubular reabsorption. Urine concentrating mechanism.

Fox, S.I. Human Physiology, 7th ed., McGraw-Hill, New York, 2002. Copyright restrictions apply.

III. Glomerular Filtration.

[pp. 492-494]

A. Glomerular filtration is the starting point for the production of urine. B. Glomerular filtration = Passage of protein-free plasma from the glomerular capillaries into Bowman's capsule. C. Filtration apparatus (figs. 14-3 and 14-5). 1. Glomerular capillaries have single epithelial cell layer. 2. Bowman's capsule lined by a single epithelial cell layer. 3. Capillary walls and lining of capsule contain large pores.

D. Mechanism of filtration (figurea). 1. Glomerulus and capsule are freely permeable to water and most molecules. a. Impermeable to cells or proteins. 2. Net movement of water and ions is out of capillaries into Bowman's capsule. a. Driving force is hydrostatic pressure in glomerulus (i.e. capillary blood pressure). b. Glomerular capillary BP = 50 mmHg. c. Higher than in most capillaries due to large diameter of afferent arterioles and resistance in efferent arterioles. 3. Analyze contents of capsule by micropuncture. a. Filtrate has same composition as blood plasma, except it contains no proteins. D. Glomerular filtration rate (GFR) = Volume of fluid filtered from plasma per minute. 1. Normal GFR = 120 ml/min = 180 L/day. E. Determination of GFR -- clearance of creatinine.

IV. Renal Clearance. 498]

[pp. 497-

A. Renal clearance = Volume of plasma from which a substance is completely removed per minute. B. Amount of substance removed from plasma = amount excreted in urine. Cl = UV P C. Example: Clearance of creatinine. 1. Creatinine is a breakdown product of creatine in muscle. 2. Freely filtered. 3. Neither reabsorbed nor secreted. U = 60 mg/dl V = 2 ml/min P = 1 mg/dl

Clcreatinine =

D. Clearances of different substances will vary, depending on the degree to which they are reabsorbed or secreted by the tubules.

V. Tubular Secretion. 496, 517, 520-521]

[pp.

A. About 80% of renal blood flowing through the kidneys passes through the glomerulus without being filtered. 1. Blood that is not filtered enters the efferent arteriole and peritubular capillaries. 2. Opportunity for exchange of substances between filtrate (in tubules) and plasma (in peritubular capillaries). 3. Function of the tubules is to separate substances that are to be conserved in the body from those that are to be eliminated in the urine. B. Tubular secretion = Selective transfer of substances from blood into tubular fluid (figurea). C. Purpose is to more rapidly eliminate certain substances from the body. D. Clearance is greater than GFR. E. Example 1: Para-aminohippuric acid (PAH). 1. Freely filtered, totally secreted (substance X in fig. 14-7).

2. Inject PAH

> find almost none in renal vein.

3. ClPAH = 625 ml/min. 4. ClPAH is used to measure renal plasma flow. 5. GFR is about 20% of RPF -- i.e. about 20% of blood flowing through the kidneys is filtered. F. Example 2: Penicillin. 1. Filtered at glomerulus. 2. Secreted with high efficiency (figure). 3. Results in rapid elimination of penicillin from the body. G. Example 3: Hydrogen ion (H+). 1. Secretion rate is variable. 2. Important in control of acid-base balance. H. Renal control of acid-base balance. 1. Important to maintain normal H+ concentration in the body fluids. 2. Normal pH of arterial blood is 7.4. a. Increase [H+] > acidosis. b. Decrease [H+] > alkalosis. 3. Urine pH is about 6. > decrease > increase

pH pH

4. H+ concentration is regulated by kidneys and lungs. 5. Feedback control of acid-base balance. a. Controlled variable = H+ concentration in blood.

b. To correct an acidosis

>

c. To correct an alkalosis

>

VI. Tubular Reabsorption. 506-507, 523]

[pp. 494-496, 501-502,

A. Opposite of tubular secretion (figurea).

B. Tubular reabsorption = Selective transfer of substances from tubular fluid into blood. 1. Substances that were originally filtered move back into blood. C. Purpose is to conserve substances that would otherwise be excreted in the urine. D. Substances that are to be conserved are reabsorbed, while substances that are to be eliminated are often secreted. 1. Amount excreted = Amt filtered + amt secreted amt reabsorbed E. Clearance is less than the GFR. F. Example 1: Sodium. 1. 99% reabsorbed (substance Y in fig. 14-7). 2. ClNa = 1 ml/min. 3. Mechanism -- primary active transport. a. Responsible for 80% of kidney's total energy requirement. 4. Amount of reabsorption varies in different parts of the tubule. Segment

Proximal tubule Descending limb Ascending limb Distal tubule Total Reabsorption 5. Rate of Na+ reabsorption is regulated in order to maintain plasma Na+ levels. 6. As Na+ is reabsorbed, so is water. 7. Diuretics (ex. furosemide, Lasix) increase urine volume. a. Block tubular reabsorption of Na+. b. Useful in treatment of hypertension. G. Example 2: Glucose. 1. 100% reabsorbed (substance Z in fig. 14-7). 2. Normally, no glucose in urine. a. Clglucose = 3. Site -- proximal tubule. 4. Mechanism -- secondary active transport (cotransport with Na+). 5. Exhibits saturation. a. When blood glucose concentration is abnormally high (ex. diabetes

mellitus), rate of filtration exceeds maximum rate of reabsorption (fig. 14-11). b. Transport maximum (Tm) = Maximal rate of reabsorption of a substance by the renal tubular cells. c. Excess glucose "spills over" into urine (glucosuria). H. Example 3: Urea. 1. 50% reabsorbed. 2. Mechanism -- simple diffusion. 3. Lower rate of reabsorption allows for significant excretion of urea. I. Summary of three renal processes (figurea). J. Summary of range of clearances.

VII. Regulation of Sodium Excretion.

[pp. 506-509]

A. The renin-angiotensin-aldosterone system is a complex mechanism for regulation of plasma sodium levels. B. Aldosterone. 1. Hormone secreted by adrenal cortex (figureb). 2. Stimulates Na+ reabsorption from distal tubules. 3. Aldosterone secretion is stimulated by angiotensin II. C. Renin-angiotensin system. 1. Juxtaglomerular apparatus (fig. 14-5). a. Region of nephron where afferent arteriole and distal tubule come into contact. b. Juxtaglomerular cells in afferent arteriole secrete the enzyme, renin, into blood. 2. Stimuli to renin secretion. a. Decreased renal arteriolar pressure. 1. JG cells act as stretch receptors. b. Decreased distal tubular sodium. 1. Detected by macula densa cells in distal tubule.

c. Stimulation of renal sympathetic nerves. 3. Renin causes cleavage of circulating protein, angiotensinogen, to produce angiotensin I. a. Angiotensinogen and angiotensin I are both inactive. 4. Angiotensin I is cleaved by angiotensin converting enzyme in lung capillaries to produce angiotensin II. 5. Angiotensin II is a potent stimulator of aldosterone secretion (fig. 14-21, figure). D. Feedback control of sodium excretion. 1. Controlled variables. a. Renal arteriolar pressure (reflects MAP). b. Distal tubular Na+ concentration (reflects plasma Na+ conc). 2. Example: Na+ deficiency (fig. 14-22).

b Sherwood, L. Human Physiology: From Cells to Systems, 5th ed., Brooks/Cole, Belmont, CA, 2004. Copyright restrictions apply.

VIII. Urine Concentrating Mechanism. 503, 510-511] A. Introduction.

[pp. 501-

1. Water intake must equal water output in order to maintain body water balance. 2. When water is scarce, an animal must be able to concentrate the urine and thus limit water loss. 3. Minimum volume of urine that must be produced is 0.3 ml/min. B. Function of the collecting duct is to concentrate the urine by reabsorbing water. C. Fluid leaving distal tubule has the composition of very

dilute urine. 1. Mechanism responsible for dilute tubular fluid in the distal tubule (fig. 14-17, figurea). a. Ascending limb of loop of Henle is permeable to Na and Cl-, but impermeable to water.
+

b. As filtrate ascends, Na+ and Cl- are actively reabsorbed, but H2O does not follow. c. By the time the filtrate reaches the distal tubule, it is very dilute (100 mosmol/L). 2. Gradient is established in interstitial fluid of kidney. a. Descending limb is permeable to water, but not to Na and Cl-.
+

b. Counter-current exchange mechanism concentrates the interstitial fluid in the medulla (1400 mosmol/L near renal pelvis). c. Osmolarity in cortex is similar to plasma (300 mosmol/L). D. Reabsorption of water from collecting duct depends on antidiuretic hormone (ADH, vasopressin) secreted by posterior pituitary.

1. ADH causes insertion of aquaporins into membrane of collecting duct cells (figure). 2. In presence of ADH, collecting duct is permeable to water > water is reabsorbed > urine is concentrated. 3. In absence of ADH, collecting duct is not permeable to water > water is not reabsorbed > urine is dilute. 4. Urine volume is low in presence of ADH and high in absence of ADH. 5. Alcohol blocks ADH secretion. E. Renal control of body water balance. 1. Controlled variable = plasma osmolarity. 2. Sensor = osmoreceptors in hypothalamus. 3. Control center = hypothalamus. 4. Example: Dehydration (increased plasma osmolarity).

I. Comparison of urine concentrating abilities of various mammals. 1. Corresponds to availability of water in the environment (figure). 2. No differences in posterior pituitary or ability to secrete ADH. 3. Differences are in the lengths of the loops of Henle. a. Beaver -- all short loops. b. Human -- combination of short loops and long loops. c. Kangaroo rat (figure) -- all long loops.

IX. Urination. 487, 498-499]

[pp.

A. Urine passes from collecting ducts into renal pelvis, then ureters (fig. 14-1). 1. No further changes in urine composition. B. Ureters, urinary bladder, and urethra are all lined with smooth muscle. 1. Wave of smooth muscle contraction moves urine to bladder in a few sec. C. Walls of bladder can be stretched as it fills. 1. Holds about 500 ml when full. D. Two sphincters at opening to urethra (fig. 14-13). 1. Internal urethral sphincter -- smooth muscle. 2. External urethral sphincter -- skeletal muscle. E. Urine is usually sterile. F. Micturition reflex is an example of a spinal reflex (figureb). 1. Bladder wall contains stretch receptors. 2. When stretched, impulses are sent to lower spinal cord. 3. Activates parasympathetic neurons going to bladder and urethra. 4. Bladder wall contracts involuntarily and internal urethral sphincter

relaxes

> urge to urinate.

5. Urination can be prevented by voluntarily contracting the external urethral sphincter. 6. Relax external urethral sphincter bladder are released out urethra > urination. > contents of

G. Urinary incontinence = Inability to control urination. 1. Infants. 2. Spinal cord injury. 3. Some elderly people.

X. Kidney Disorders. 525] A. Kidney stones (figure).

[pp. 523-

1. Formation of calcium crystals in renal pelvis. 2. Painful passage through ureters (figure). B. Renal failure. 1. Damage to kidneys so that glomeruli fail to filter blood. 2. Causes. a. Infection of the kidneys (nephritis). b. Inadequate blood flow to kidneys.

c. Complete obstruction of urinary tract. 3. Consequences. a. Decreased GFR. b. Leakage of proteins into tubular > proteinuria. c. Buildup of toxic substances in > uremia. 4. May be temporary or permanent. 5. Treatment. a. Dialysis (artificial kidney) (fig. 14-34). 1. Needles in one artery and one vein. 2. Blood flows through dialyzer. 3. Contains dialyzing solution -- same concentration of ions and small molecules as normal plasma. 4. Semipermeable membrane separates dialyzing solution from blood flowing through dialyzer. 5. Permeable to ions and small molecules, but not blood cells and proteins. 6. Large surface area provides maximum exchange of molecules. 7. Waste products move into dialyzing

filtrate blood

fluid

> discarded. 8. Must be dialyzed every few days. b. Kidney transplant (figure). 1. Most common type of organ transplant. 2. Only one kidney is transplanted. 3. Donor may be an accident victim or a close

relative.

XI. Urinalysis. pp. 496, 523] A. Urine is a body fluid that is easily and painlessly obtained. B. The measurement of chemical substances in urine (urinalysis) can be important in the diagnosis of a variety of diseases. 1. 2. 3. 4. Diseases of the kidney and urinary tract. Metabolic diseases (ex. diabetes). Diseases of other organs (ex. liver). Presence of drugs and their metabolites.

C. Urinalysis using reagent strips (figure). 1. Blood. a. Red blood cells are too large to be filtered. b. Positive test indicates hemoglobin in the urine (hematuria).

c. Positive test is produced by: 1. 2. 3. 4. Damage to glomerular capillaries. Bleeding elsewhere in the urinary system. Strenuous exercise. Contamination from menstrual bleeding.

2. Ketones. a. Ketone bodies are intermediates of fatty acid metabolism. b. Present in blood, but not usually found in urine. c. Levels will be elevated when there is a high rate of fat metabolism. 1. Starvation. a. Body depends heavily on fat metabolism as a primary energy source. b. Excess ketones in blood appear in the urine (ketonuria). 2. Diabetes mellitus. 3. Glucose. a. Glucose is normally 100% reabsorbed. b. Diabetes mellitus. 1. Inadequate amounts of insulin are secreted

by the pancreas. 2. Elevated blood glucose level (hyperglycemia). 3. Blood glucose level exceeds the reabsorptive capacity of renal tubules (Tm) > glucose will appear in the urine (glucosuria) (fig. 14-11). 4. Protein. a. Proteins are very large molecules that are not normally filtered by the glomeruli. b. Protein in the urine (proteinuria) indicates that the permeability of glomerular capillaries is abnormally high. c. Causes: 1. Renal failure. 2. Infection of the kidneys (nephritis). 3. Urinary tract infections. d. About 5% of the normal population show slight proteinuria due to the presence of small protein fragments. 5. Urine pH. a. Urine is typically more acidic than blood. b. Tubular secretion of H+ is a mechanism by which the acidity of blood is regulated.

c. pH of urine is highly variable (normal range = 4.5 - 8.0). D. Regulation of body water balance. 1. Water intake must equal water output in order to maintain body water balance. 2. Body water balance is maintained through the production of a concentrated or dilute urine. 3. The solute concentration of a urine sample is estimated using a urinometer. a. Specific gravity is a measure of the density of a solution compared to water. b. Specific gravity is proportional to solute concentration. c. Normal urine specific gravity is between 1.010 and 1.025.