Physiology 441

1. Physiology 441 The Renal System, Chp. 14 Text: Human Physiology (Sherwood), 6th Ed. Julie Balch Samora, MPA, MPH jbsamora@hsc.wvu.edu 293-3412, Room 3145

2. Renal Processes 1

3. Tubular Reabsorption • All plasma constituents (except proteins) are filtered through the glomerular capillaries, including needed nutrients and electrolytes • Tubular reabsorption is the discrete transfer of substances from the tubular lumen into the peritubular capillaries (to be returned to the body) • VERY SELECTIVE PROCESS

4. Tubular Reabsorption • Tubules have a high reabsorptive capacity for substances needed by the body • Only excess amounts of essential materials (eg elctrolytes) end up being excreted in the urine • Out of the 125 ml/min filtered, ~124 ml/min are reabsorbed! (178.5/180 L filtered/day are reabsorbed) • 99% of filtered water, 100% filtered sugar, and 99.5% of filtered salt gets reabsorbed

5. Steps of Transepithelial Transport A Substance must: • Cross luminal membrane of tubular cell • Pass through cytosol from one side of tubular cell to the other • Cross the basolateral membrane of the tubular cell to inter the IF • Diffuse through the intersitial fluid • Penetrate the capillary wall to enter the blood plasma

6. Interstitial fluid Peritubular capillary Tubular lumen Tubular epithelial cell Filtrate Plasma Tight junction Lateral space Luminal membrane Basolateral membrane Capillary wall Fig. 14-14, p. 515

7. Active Reabsorption • Major substances are reabsorbed via active transport. These are substances that are needed by the body (e.g. Na+, glucose, aa’s, other elctrolytes) • Sodium reabsorption- 99.5% of filtered sodium is absorbed • Proximal tubules (67%) • Loop of Henle (25%) • Distal/Collecting tubules (8%)

8. Sodium Reabsorption • Na+-K+ ATPase located at the basolateral membrane of tubular cells. • Pumps Sodium out of cell into lateral space. • Keeps tubular cell ICF [Na+] low, creating concentration gradient for Na+ to diffuse in from lumen. • Keeps lateral space [Na+] high creating concentration gradient for Na+ to diffuse into blood (against gradient)

9. Mechanism of Na+ reabsorption Peritubular capillary Lumen Tubular cell Interstitial fluid Diffusion Na+ channel Active transport Basolateral Na+– K+ ATPase carrier Lateral space Diffusion Fig. 14-15, p. 516

10. Control of Na+ Absorption • Renin-Ang II-Aldo – goal to keep Na+ • If ↓ NaCl, ECF volume, arterial blood pressure, the JGA secretes renin into blood • Ang I Ang II in lung • Ang II stimulates release of Aldo from Adrenal Cortex • Aldo stimulates distal/collecting tubules to reabsorb sodium, thereby conserving it

11. Aldosterone • Only the sodium reabsorbed in the distal and collecting tubules is subject to hormonal control • The amount of this sodium depends on amt of Aldo secreted • Without Aldo, can excrete lots of NaCl daily • However, maximum Aldo secretion leads to complete reabsorption of sodium

12. RAAS

13. Diuretics • Drugs/drinks that increase urinary output • Promote loss of fluid from body • Function by inhibiting tubular reabsorption of sodium • Examples include thiazide, loop and potassium-sparing diuretics (medicinal-used for ↑ BP, CHF, Edema, Diabetes insipidus), coffee, sodas, and alcohol

14. Atrial Natriuretic Peptide (ANP) • Goal to rid body of Sodium • ANP released from cardiac atria when senses ↑ECF • Decreases sodium reabsorption and increases sodium loss in urine • Result- decrease sodium load and ECF volume • (not nearly as powerful as renin-Ang-Aldo system!)

15. Tubular Maximum (TM) • Represents the maximum amount of a substance that the tubular cells can actively transport within a given time period • Carriers become saturated • TM ONLY for active processes • Sodium only actively reabsorbed substance w/o transport max

17. Glucose • Normally no glucose should be in the urine • However, DM patients often has glucose due to TM being overcome • Amt of substance filtered = plasma concentration X GFR • e.g. [plasma glucose] = 100mg/100ml • Normal GFR = 125 ml/min • Therefore Filtered Load = (100mg/100ml)x125ml/min = 125 mg/min

18. Glucose- 2° active transport • Energy is not used directly to absorb glucose, even though it is being reabsorbed against its concentration gradient • Carrier is driven by the sodium concentration gradient established by the N +-K+ pump • TM for glucose carriers is 375 mg glucose/ minute

19. Glucose Reabsorption Renal Processes 2

20. Renal Threshold • Plasma concentration at which a substance reaches the TM and 1st starts appearing in the urine • Renal threshold for glucose is 300 mg glucose/100 ml plasma

21. Phosphate • Also exhibits a TM – Unlike glucose, kidneys DIRECTLY contribute to its regulation because the renal threshold for phosphate = nml plasma [phosphate] • Whenever ↑ [plasma phosphate], the kidneys immediately excrete the excess as the TM is exceeded

22. Passive Reabsorption • All passive reabsorption is ultimately linked to active sodium reabsorption. • Includes Cl-, H2O, and urea • Chloride moves via electrical gradient that was established by Na+ • Sodium creates an osmotic gradient for the passive reabsorption of H2O via osmosis

23. Urea • Waste product • At end of proximal tubule, urea is concentrated, creating a gradient favoring entrance into the blood • However, tubular cell membranes not very permeable and only ~50% of the filtered urea is passively reabsorbed • BUN- measured as a crude assessment of kidney function

24. Passive Reabsorption of Urea at the End of the Proximal Tubule

25. No Reabsorption of the other unwanted substances • The other waste products are too large or are not lipid soluble, so even though the gradient favors their return to the blood, they do not go. • Furthermore, there are no carriers to allow them passage. • Therefore, they remain in the tubule and pass into the urine in a highly concentrated form (e.g. uric acid, sulfate, nitrates, phenols, etc)

26. Urea Reabsorption Renal Processes 2

27. Tubular Secretion • Additional mechanism to eliminate certain substances • Secretion of H+, NH3, K+, organic anions and cations • Acid and ammonia secretion imp. in acid-base balance • Ammonia is secreted during acidosis in order to buffer the secreted H+

28. H+ and NH3 secretion • Hydrogen and ammonia secretion aid with acid-base balance • H+ secretion provides a highly discriminating mechanism for varying the amt of H+ excreted in the urine, depending on the acidity of the body fluids • NH3 is secreted in pronounced acidosis to buffer the H+ secreted into the urine

29. K+ Secretion • K+ is actively reabsorbed in the proximal tubule, but is also actively secreted in the distal tubule. • Allows fine degree of control over plasma K+ concentration • Secretion of K+ is variable and subject to aldosterone control • Even slight fluctuations in ECF [K+] can alter nerve and muscle excitability

30. Organic anion and cation secretion • The proximal tubule contains 2 different carriers for secreting organic ions • These systems aid in secreting foreign organic substances • The liver helps this process by converting many foreign substances into anionic metabolites

31. Process of Secretion Renal Processes 1

32. Urine excretion • The final quantity of urine formed averages about 1ml/min • This urine contains a high conc. of waste products & low or no conc. of substances needed by the body • Minimum volume of urine to eliminate wastes is 500ml/day

33. Plasma Clearance • The amount of plasma “cleared” of a substance • Plasma clearance for a substance that is FILTERED, but not REABSORBED or SECRETED == GFR == 125ml/min • EXAMPLE = INULIN

34. INULIN- Filtered, NOT reabsorbed, NOT secreted Renal Processes 2

35. Plasma Clearance • Plasma clearance for a substance that is FILTERED AND REABSORBED, but NOT SECRETED < GFR • EXAMPLE = GLUCOSE, UREA • Clearance rate can be anywhere from 0 up to normal clearance (125 ml/min) depending on amount reabsorbed

36. Plasma Clearance • Plasma clearance for a substance that is FILTERED AND SECRETED > GFR • EXAMPLE = PAH (Para-aminohippuric acid) • Not only is the plasma that is filtered cleared of that substance, but additional amt cleared from plasma which was not filtered • Plasma clearance rate for PAH=RENAL PLASMA FLOW

37. Plasma clearance rate for PAH = Renal Plasma Flow Renal Processes 2