1. 1 Brief overview of mammalian renal physiology Jason Williams University of Nevada Las Vegas 2-28-07

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3. 3 Outline for renal physiology lecture I. Specific functions of the kidney II. Kidney structure III. Nephron: the functional unit of the kidney IV. Basic renal process V. Specific renal process VI. How does the kidney create hyperosmotic urine? VII. Renal regulation of sodium, water, and potassium VIII. Hydrogen ion regulation IX. Diuretics and kidney disease

4. 4 What does the kidney do? Kidneys filter plasma to regulate the makeup of the interstitial fluid and blood.

5. 5 What is interstitial fluid?

6. 6 Where is Interstitial fluid located?

7. 7 I. Specific Functions of the Kidney: 1. Form urine: (95% water, 5% solutes) A. Removal of metabolic waste from plasma i. urea (protein breakdown) ii. uric acid (nucleic acid breakdown) - insoluble in blood - can precipitate out in blood and cause gout iii. creatinine (muscular creatine phosphate breakdown)

8. 8 B. Removal of foreign compounds - drugs, food additives, pesticides

9. 9 C. maintain water, inorganic ion concentrations i. important for proper fluid volume

10. 10 2. Other Functions of the kidney A. Acts as endocrine gland i. erythropoietin ii. Renin iii. 1,25 dihydroxyvitamin D3 B. Gluconeogenesis – during times of fasting i. amino acids → glucose

11. 11 II. Structure of the Kidney: 1. Location: - retroperitoneal - superior lumbar region - twelfth thoracic to the third lumbar vertebrae

12. 12 2. Part of the urinary system - ureters - bladder - urethra

13. 13 3. External anatomy of the kidney - Bean shaped - vertical cleft called the renal hilus - Ureters, renal blood vessels, lymphatics, and nerves enter and exit at the hilus

14. 14 4. Internal anatomy of a kidney: The kidney has three main regions: A. Renal Cortex - outer region (granular) B. Renal Medulla - inner region (striated) - consists of a number of triangular structures called renal pyramids C. Renal pelvis - major calyces

15. 15 III. Nephron: The functional unit of the kidney i. smallest unit capable of forming urine ii. microscopic, each kidney has about 1 million

16. 16 1. The nephron consists of two distinct regions: A. Renal corpuscle B. Tubule

17. 17 A. Anatomy of the renal corpuscle: i. Glomerulus - Afferent and efferent arterioles ii. Bowman’s capsule - Bowman’s space

18. 18 B. Anatomy of the tubule: i. Very narrow hollow tube of single celled epithelial tissue. ii. Contiguous with Bowman’s capsule

19. 19 C. Tubule consists of: 1. Proximal tubule (convoluted and straight) 2. Loop of Henle (descending and ascending) 3. Distal convoluted tubule 4. Connecting tubule 5. Collecting duct

20. 20 D. Vascularization of the nephron Two sets of capillaries: a. Glomerulus b. Peritubular capillaries Connected by efferent arteriole

21. 21 IV. Basic renal process 1. Urine formation: A. begins with glomerular filtration ends with urine formation.

22. 22 B. glomerular filtrate has essentially the same concentrations of solutes as blood plasma, minus proteins

23. 23 B. Glomerular filtrate ≠ Urine SubstanceAmount Filtered per day Amount excreted per day Water, L1801.8 Sodium, g6303.2 Glucose, g1800 Urea, g5430

24. 24 C. How is glomerular filtrate altered as it moves through the tubule? -Tubular reabsorption -Tubular secretion Excreted = filtered - reabsorbed + secreted

25. 25 B. Glomerular filtrate ≠ Urine SubstanceAmount Filtered per day Amount excreted per day Water, L1801.8 Urea, g5430 Penicillin310 Creatinine, g20~20

26. 26 V. Closer look at renal processes 1. glomerular filtration - glomerular filtrate has essentially the same concentrations of solutes as blood plasma, minus proteins

27. 27 A. Glomerular filtrate passes through three layers i. Single-celled capillary endothelium ↓ ii. Non-cellular proteinaceous layer of basement membrane. ↓ iii. Single-celled epithelium lining (podocytes)

28. 28 B. Forces involved in filtration Net glomerular filtration pressure= P GC -P BS -π GC 55 - 15 - 30 = 10mmHG

29. 29 C. Glomerular Filtration Rate (GFR) GFR = the volume of fluid/plasma filtered from the glomeruli to the Bowman’s space per unit time. GFR = 180 L/day for average adult blood volume filtered ~60 times per day GFR is under physiological regulation

30. 30 2. Clinical determination of GFR

31. 31 A. Introduction: i. Estimated glomerular filtration rate by measuring inulin and creatinine clearance. ii. Why?: Abnormal GFR may suggest renal disease (the leading cause of death in captive cheetahs)

32. 32 B. Brief Materials and Methods: i. measure of GFR 1. injected cats with known amount of inulin Inulin: - foreign polysaccharide - fully filtered - not reabsorbed

33. 33 B. Brief Materials and Methods: (Cont.) 2. Determine amount of inulin in serum and urine sample 3. Calculate GFR in milliliters: (Urine conc. of inulin) X (urine volume) (serum conc. of inulin) 4. Report final GFR as: ml min -1 kg -1

34. 34 C. Results: Ccr = creatinine clearance rate - Creatinine produced endogenously - typically only filtered - measured in same fashion as inulin GFR

35. 35 D. Conclusions:

36. 36 Tubular Reabsorption:

37. 37 3. Reabsorption A. Occurs in: proximal tubule and loop of Henle

38. 38 B. General process: i. Luminal membrane → basolateral membrane → interstitial fluid → peritubular capillary ii. Tight junction → interstitial fluid → peritubular capillary

39. 39 C. Tubular reabsorption occurs by: i. Diffusion – water, urea, other lipid soluble substances ii. Mediated transport – Move substances “uphill” against diffusion gradient. (glucose, amino acids, etc.)

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41. 41 D. Efficiency of tubular reabsorption: SubstanceAmount Filtered per day Amount excreted per day Percent reabsorbed Water, L1801.899.0 Sodium, g6303.299.5 Glucose, g1800100 Urea, g543044 Rates of reabsorption are under physiological control

42. 42 Tubular Secretion

43. 43 4. Tubular Secretion A. Moves substances from: - peritubular capillary → tubular lumen B. occurs by diffusion or mediated transport C. secreted substances: hydrogen ions, potassium, foreign chemicals, choline etc.

44. 44 5. Division of Labor in Nephron: A. Renal corpuscle = filtrate B. Proximal tubule = primary reabsorption C. Proximal tubule = primary secretion

45. 45 D. Renal D. Loop of Henle = reabsorption E. Distal segments = fine tuning, under homeostatic control