MS1 Physiology Review of Na+, K+, H + /HCO 3. /Acid-base, Ca+² and PO 4 physiology

Transcription

1 MS1 Physiology Review of,, / /Acidbase, Ca+² and PO 4 physiology I. David Weiner, M.D. Professor of Medicine and Physiology University of Florida College of Medicine

2 Basic principles Proximal tubule Majority of transport Transport is linked Loop of Henle Thin descending limb transport for countercurrent multiplication Essentially no active ion transport Thick ascending limb Moderate ion transport capacity Major site for regulated Ca+² transport Distal convoluted tubule NaCl reabsorption, no transport Generates urine substantially more dilute than plasma Collecting duct Quantitatively less transport, but more regulation Major site of regulated,, titratable acid and ammonia transport Specialized cells transport each molecule independently, or almost so

3 Proximal tubule Lumen 70 mv Peritubular 140 mm 4 mm 55.5 M 24 mm Glucose PO 4 = Amino acids i i Fanconi syndrome if defect in all

4 Proximal tubule reabsorption Lumen ~ 70 mv Peritubular H 2 CO 3 CA IV H 2 CO 3 CO 2 CA II ( ) 3 Carbonic anhydrase inhibitors decrease both and reabsorption (acetazolamide) CO 2

5 Proximal tubule reabsorption Lumen Peritubular (very slight) 70 mv osmolality [] AQP1 AQP1 The change in osmolality is below measureable change, resulting effectively in isosmotic fluid reabsorption

6 Proximal tubule Lumen Formic Acid 0 Formic Acid 0 70 mv Peritubular [Cl ] Formate Cl Formate Cl Cl

7 Proximal tubule phosphate transport Lumen 70 mv Peritubular PTH Glucose ()₃ PO 4 = Amino acids Hyperphosphatemia increases PTH PTH inhibits NaPI2a transport Decreased NaPi2a transport decreases phosphate reabsorption Increased phosphate excretion Correction of the hyperphosphatemia NaPi2a i i

8 Proximal tubule paracellular transport Lumen 70 mv Peritubular [Cl ] Ca+² +13 mv Ca+² Cl

9 Thick ascending limb of loop of Henle NaK2Cl cotransporter (NKCC2) Cl 2Cl 2Cl ROMK Cl Cl ClC1 Ca+² +13 mv Ca+²

10 Distal convoluted tubule NaCl, but not, reabsorption Cl NaCl cotransporter (NCC) osmolality As low as 150 mosm (kg ) ¹

11 Collecting duct principal cell transport ENaC inhibitors are also termed sparing diuretics ENaC mv AQP2 ADH regulates reabsorption by regulating AQP2 AQP3, AQP4

12 HCO₃ reabsorption in the collecting duct ~ Cl Cl ~ Cl Cl AE1 H 2 CO 3 H 2 CO 3 CO 2 CO 2 Atype intercalated cell

13 Bicarbonate secretion by the collecting duct Pendrin Cl ~ With Cl depletion, i.e., intravascular volume depletion, all Cl is reabsorbed in more proximal segments, and you cannot secrete Btype intercalated cell

14 New HCO₃ generation why not just H+ secretion Kidneys can acidify urine to ph 4.4 Normal serum ph is 7.4 H+ gradient is 1,000:1 What volume of urine is needed to excrete normal endogenous acid production? Endogenous H+ production, 0.8 mmol/kg/d, ~56 mmol/d (70 kg) Maximally acidic urine, ph 4.4 [H+], 40 µmol/l Necessary urine volume = amount concentration = 56 mmol/d 40 µmol/l = 1.4 L = 1,400 L 1440 minutes in a day

15 Components of net acid excretion (new HCO₃ generation) Net acid excretion Ammonia, Titratable acids, Urinary bicarbonate Basal contribution: Ammonia, ~55% Titratable acid, ~45% Bicarbonate, <1% Increment, mmol per day Changes in net acid excretion after acidloading of ~125 mmol per day Ammonia Titratable Acids Bicarbonate Day of Acid Loading (data from: Elkinton JR, et al, Am J Medicine 36:55475, 1960)

16 Titratable acids and the collecting duct Titratable Acid n ~ ~ Cl Cl Cl Cl AE1 Titratable Acid n+1 H 2 CO 3 The exiting across the basolateral membrane is new bicarbonate CO 2 CO 2 Atype intercalated cell

17 Renal ammonia metabolism

18 Key features in ammonia metabolism Major component of basal net acid excretion (NAE) Major component of increase with acidosis Stimulated by: Acidosis Aldosterone AngII Hypokalemia

19 Key features in ammonia metabolism Takes days to develop Renal response has two phases Initial (rapid), minimal increase Delayed, 35 days, maximal increase Requires increased ammoniagenesis Requires increase glutamine availability Requires muscle cell catabolism to generate the glutamine Body balances need for strong muscles versus need for longterm acidbase regulation Clinical adverse effects of acidbase disorders mostly longterm, not shortterm Urine acidification is ratelimiting step to ammonia excretion