USMLE Step 1 Review

1. USMLE Step 1 Review James Paparello, M.D. Department of Nephrology Northwestern University Email: JPaparello@nmff.org

2. Renal Physiology and Tubular function

3. Body Water 50-60 % of body weight Total Body Water Intracellular Water Extracellular Water (2/3 total body water) (1/3 total body water) Intravascular(1/4) Extravascular (3/4) (Plasma)

4. Body Water Calculation Body Weight = 70 kg (154 lbs) Total Body Water (TBW) = 60 % of Weight = 42 Kg • Intracellular Water = 2/3 of TBW = 28 Kg • Extracellular Water (ECV) = 1/3 of TBW = 14 Kg • Extravascular water = ¾ of ECV = 10.5 Kg • Intravascular water = ¼ of ECV = 3.5 Kg = Plasma water Blood Volume = Plasma Water/(1 – Hct) = 6.4 Kg (assign Hct of .45)

5. First Aid: • TBW = ICF + ECF • 60 – 40 – 20 rule (% of Total body weight) Inulin • ECF = Plasma volume + Interstitial volume ¼ ¾ Albumin

6. Edema Two requirements: • Alteration in capillary hemodynamics favoring movement of fluid out of vascular space (into interstitium) • Renal retention of Na+ and water Starling’s Law: LpS[(Pcap – Pif) – σ(πcap – πif)] Lp = porosity, S = surface area, σ = reflection coefficient of proteins Differences are between hydrostatic and oncotic pressures (capillary and interstitial)

7. Capillary Fluid Exchange Filtration pressure = LpS[(Pcap – Pif) – σ(πcap – πif)] Increased Pcap: Heart failure Decreased πcap: Nephrotic syndrome, liver failure Increased Capillary permeability (Kf = LpS): infections, toxins, burns Increased πif : Lymphatic blockage

8. Remember: • The glomerulus is a specialized capillary network: • GFR = Kf [(Pgcap – Pbowman) – σ(πgcap – πbowman)]

9. Remember: • The glomerulus is a specialized capillary network: • GFR = Kf [(Pgcap – Pbowman) – σ(πgcap – πbowman)] • GFR = Amount excreted = Urine concentration x V Plasma conc. Plasma conc.

10. GFR calculation GFR = Uinulin x V/Pinulin = Cinulin We use creatinine instead of inulin (only a small amount of creatinine is secreted) Normal GFR ~ 120 cc/min

11. Clearance Calculations Px * Cx = Ux * V Cx = (Ux * V)/Px If Cx < GFR, then tubular reabsorption of x If Cx > GFR, then tubular secretion of x If Cx = GFR (e.g. inulin), there is not net absorption or secretion

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13. You develop a drug that blocks tubular reuptake of urea. What happens to urea clearance ? • It increases • It decreases • No change, as the GFR does not change

14. Glucose Clearance • At plasma glucose of > 200-300 mg/dl, tubular reabsorption is saturated, and glycosuria occurs. • Tm = maximal transport (for glucose, reabsorption) of a solute. • If glycosuria, blood sugar concentration > 200, so patient may have diabetes.

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16. Plamsa Glucose: 95 mg/dL Filtered glucose = 95 Reabsorbed Glucose = 95 Glucose in urine = 0

17. Plamsa Glucose: 375 mg/dL Filtered glucose = 375 If max tubular absorption is 200 mg/dL: Reabsorbed Glucose = 200 Glucose in urine = 175

18. Clearance of Free Water • CH2O = V – Cosm • V = urine flow rate • Cosm = (Uosm * V)/Posm • So if CH2O is positive, the kidney is excreting free water (dilute urine) • If CH2O is negative, the kidney is retaining free H2O (excreting concentrated urine)

19. Renal Plasma Flow Renal plasma flow = Plasma flow glomerulus + plasma flow tubules PAH is actively secreted by the tubules, so PAH in the blood that does not go through the glomerulus (1 – FF = 0.8) is cleared by tubular excretion. Therefore, PAH clearance accounts for both blood through the glomerulus (FF) and the blood through the tubules. Therefore: Effective renal plasma flow = (UPAH * V)/PPAH Renal Blood Flow = Renal Plasma Flow/(1 – HCT)

20. Filtration Fraction Fraction of the material that enters the kidney and is filtered (normally 0.20) FF = GFR/RPF = 120/600 = 0.2

21. Netter, Atlas of Human Anatomy, 1989, Plate 322

22. Renal Hemodynamics

23. Glomerular Filtration Barrier Three components: • Fenestrated Capillary Endothelium (size barrier) • Fused basement membrane with heparan sulfate (negative charge barrier) • Epithelial layer consisting of podocyte foot processes

24. Afferent/Efferent Hemodynamics Glomerulus with capillary loops surrounded by Bowman’s space Afferent Arteriole Efferent Arteriole Blood Flow Proximal Tubule (continuation of urinary space)

25. Afferent/Efferent Hemodynamics:Dilation of Afferent Artery Glomerulus with capillary loops surrounded by Bowman’s space Afferent Arteriole  Efferent Arteriole Blood Flow Proximal Tubule (continuation of urinary space)

26. Renal Hemodynamics

27. Renal Hemodynamics

28. Dilation of Afferent Artery • Caused by: • Prostaglandins • Physiologic Changes •  Glomerular capillary pressure •  Nephron Plasma Flow,  GFR

29. Filtration fraction:Afferent Artery Dilation GFR So min. change in FF. RPF

30. Afferent/Efferent Hemodynamics: Constriction of Afferent Artery Glomerulus with capillary loops surrounded by Bowman’s space Afferent Arteriole  Efferent Arteriole Blood Flow Proximal Tubule (continuation of urinary space)

31. Renal Hemodynamics

32. Renal Hemodynamics

33. Constriction of Afferent Artery • Caused by • NSAIDs (decrease prostaglandin production) • Physiologic results: •  Glomerular capillary pressure •  Nephron plasma flow,  GFR N.B. Afferent arteriolar changes happen before the glomerulus, so no change in filtration fraction.

34. Filtration fraction:Afferent Arteriole Constriction GFR So no change in FF RPF

35. Afferent/Efferent Hemodynamics:Efferent Arteriole Dilation Glomerulus with capillary loops surrounded by Bowman’s space Afferent Arteriole Efferent Arteriole  Blood Flow Proximal Tubule (continuation of urinary space)

36. Renal Hemodynamics

37. Renal Hemodynamics

38. Efferent Arteriole Dilation • Caused by: • ACE-I, ARB • Physiologic results: •  Glomerular capillary pressure •  Nephron Plasma flow, but  GFR ( **N.B. Decreases filtration fraction)

39. Filtration fraction: GFR So filtration fraction decreases. RPF

40. Afferent/Efferent Hemodynamics:Efferent Arteriole Constriction Glomerulus with capillary loops surrounded by Bowman’s space Afferent Arteriole Efferent Arteriole Blood Flow Proximal Tubule (continuation of urinary space)

41. Renal Hemodynamics

42. Renal Hemodynamics

43. Efferent Arteriole Constriction • Caused by: • Angiotensin II • Physiologic results: •  Glomerular capillary pressure •  Nephron Plasma flow, but  GFR ( **N.B. Increases filtration fraction)

44. Filtration fraction: GFR so increased FF RPF N.B. efferent arteriole changes cause opposite effects on GFR and RPF

45. Which of the following would be expected to result in an increase in GFR soon after administration ? • ACE-Inhibitors • Angiotensin receptor blockers • Non-steroidal anti-inflammatory medications • Prostaglandins

46. Other Changes in Renal Function GFR FF(GFR/RPF) Increased Plasma Protein (πgcap) Decreased Plasma Protein (πgcap) Ureteral Blockage Note: None of the above change RPF, hence FF goes in the direction of the GFR

47. Remember: • The glomerulus is a specialized capillary network: • GFR = Kf [(Pgcap – Pbowman) – σ(πgcap – πbowman)] • GFR = Amount excreted = Urine concentration x V Plasma conc. Plasma conc.

48. Tubular Function

49. Renal Sodium Handling

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