BLOCK REVIEW Renal Physiology Lisa M. HarrisonBernard, Ph.D. May 9, 2011 Koeppen & Stanton EXAM May 12, 2011 Tubular Epithelium Reabsorption Secretion 1
1. 20, 40, 60 rule for body fluid volumes 2. ECF = ISF + PV. JGA 4. Basic renal processes Filtration, reabsorption, secretion, excretion 5. Damage to filtration barrier results in glomerular disease ECF17L TBW = 42L ICF25L 1. Filtrate formation filtration barrier & Starling forces 2. Clearance of certain substances index of renal function. Plasma creatinine tool for diagnosing and following renal function GFR = K f (P UF ) GFR = (Cl Cr ) =. (U Cr V)/ P Cr GFR ml/min P Cr mg/dl 120 1 60 2 0 4 15 8 2
Substance CLEARANCE (ml/min) Glucose 0 0.9 12 Inulin 125 Creatinine 140 PAH 560 Glomerular Ultrafiltration GFR = K f [(P GC P BS ) ( GC BS )] P UF Rate of glomerular ultrafiltration = product of ultrafiltration coefficient (K f ) & net Starling forces (P UF )
Mechanism for Achieving Selective & Independent in GFR & RBF (assuming RAP is constant) GFR mainly driven P GC R A RBF & GFR parallel R E RBF & GFR opposite directions Summary Renal Hormones Vasoconstrictors/ Antinatriuretic Sympathetic nerves Angiotensin II Endothelin AVP Norepinephrine Vasodilators/ Natriuretic Prostaglandins Nitric Oxide Bradykinin ANP RBF GFR excretion RBF GFR excretion 4
and H 2 O Reabsorption reabsorption active H 2 O reabsorption passive Proximal tubule 2/ reabsorb NaCl & H 2 O Isosmotic to lumen AQP1 water channels Descending limb LOH highly permeable H 2 O impermeable NaCl Reabs NaCl Passive Reabs H 2 O and H 2 O Reabsorption Ascending limb LOH (TAL) relatively impermeable H 2 O Na/K/2Cl cotransporter Collecting duct ENaC permeability H 2 O under physiological control = ADH Reabs NaCl Passive Reabs H 2 O 5
Apical aa,gluc etc. 2Cl H + Cl H + Transporters PT TAL DCT CD principal cell PT HCO BASOLAT ATP 2 Peritub bular capillary/va asa recta Solute Composition Along the Proximal Tubule ~ Fig 4 Ratio increases if 1 NOT reabsorbed same as H 2 O, or secreted 1. High for Inulin 2. Low for Glucose, Amino acids, HCO 2. Unchanged, isosmotic ~ 1 6
Cl Cotransport Late Proximal Tubule Fig 44 Lumen 1. High [Cl ] lumen relative to blood Cl 1 driving force chemical gradient passive diffusion of Cl paracellular 2. Lumenpositive transepithelial 2 Cl Cl voltage b/c paracellular Cltransport. Chemical gradient overcomes electrical gradient Distribution of in Body Hormones that uptake into cells: Insulin βadrenergic agonists (epinephrine) Aldosterone Acidbase disturbances: Acidemia = ph = uptake into cells Alkalemia = ph = uptake into cells 7
Apical Transporters BASOLAT 2Cl ATP H + Cl PT (min) TAL CCT intercalated CCT principal PT Cl ATP Na + 2 Peritub bular capillary/va asa recta LOW DIETARY INTAKE NORMAL HIGH INTAKE FILTER & REABSORB ONLY FILTER & REABSORB & SECRETE 8
How to Make Concentrated Urine Generate hypertonic interstitial fluid in confined compartment renal medulla CD fluid exposed interstitial hyperosmolality passive reabsorption H 2 O in presence AVP = Conc urine You Are Here [ADH] low [ADH] low Dilute Urine 9
[ADH] high [ADH] high Conc Urine Aquaporin Water Channels PROXIMAL TUBULE AQP1 Apical & Basolateral Thin Ascending Limb Thick Ascending Limb LOOP of HENLE DISTAL TUBULE NO AQP ~WATER IMPERMEABLE Descending Thin Limb Descending Thin Limb LOOP OF HENLE AQP1 Apical & Basolateral COLLECTING DUCT AQP2 Apical [AVP Control] AQP & AQP4 Basolateral 10
Apical H + Transporters BASOLAT H + ATP ATP H + H + ATP H + PT TAL DCT CCT Intercalated MCD Early PT HCO PT TAL HCO CCT MCD Cl Peritub bular capillary/va asa recta NET Urinary Acid Excretion pg 12 NET URINARY ACID EXCRETION (NAE) EQUALS Excreted H + bound phosphate (as HPO 2 4, divalent),h 2 PO 4, (monovalent), creatinine, uric acid = titratable acid PLUS Excreted H + bound NH (as NH 4+ ) MINUS Excretion filtered HCO 11
% FILTERED LOAD REABSORBED PROXIMAL TUBULE 50% Urea 67%, Cl,, H 2 O 70% Ca 2+ 80% HCO, HPO 2 4 98% Glucose 99% AA, Oligopeptides LOOP OF HENLE 10% HCO 15% H 2 O 20%, Ca 2+ 25%, Cl [SECRETE UREA 60%] % FILTERED LOAD REABSORBED DISTAL TUBULE % [SECRETE 1050%] 5%, Cl 6% HCO 10% HPO 2 4 COLLECTING DUCT 15%C 1.5% Ca 2+ %, Cl 4% HCO 9% [SECRETE 5 0%] 70% Urea H 2 O ADH dependent 12
% FILTERED LOAD EXCRETED EXCRETED 0% HCO, Glucose, AA, Oligopeptides 1 % H 2 O 0.6% 0.8% Ca +2 1 80% 10% HPO 2 4 50% Urea {70 mmol/d H + } Volume Contraction Effective Circulating Volume 2 + Fig 65 + Volume contraction SNS 1 + + Renin ANP AngII + ADH 4 Aldo hemodynamics & transport UNaV = GFR X P Reabsorption 1
The End Good Luck on the Exam! ** Renal Failure Patient ** Patient Data Normal Plasma K+ P Urea BP P PO4 Hematocrit P HCO P ph P Ca2+ 14