Renal Physiology Part I Bio 219 Napa Valley College Dr. Adam Ross Renal System • 1. osmoregulation = water and solute balance • a. ECF osmolarity (~290 mOsm) • b. ECF volume (total H2O) • 2. ion (electrolyte) balance (Na+, K+, Ca2+, etc.) • 3. acid-base regulation (H+, HCO3-) • 4. excretion - urea + other soluble waste products • 5. endocrine function - erythropoietin The Kidneys and associated structures Renal Anatomy Nephron Functions of the Nephron • Three primary processes: • Flitration • Filtering stuff from blood • Reabsorption • From nephron back into blood • Secretion • From blood into urine Basic Renal Processes • Filtration : Water and solutes move from the blood through the filtration barrier into Bowman’s space • Reabsorption : Moving substances from the lumen to the surrounding interstitium and generally back into the blood • Secretion : Moving substances into the tubular lumen • Excretion : Substances are removed in the urine Filtration • Happens at the glomerulus/ glomerular capillaries (GC) • Formation of protein-free filtrate • Contains water, ions and small to medium sized solutes (glucose, urea, etc) • Filtration depends on three pressures: • PGC: Blood pressure in the GC (favors filtration) • πGC: Colloid osmotic pressure in GC (opposes filtation) • PBS: Hydrostatic pressure in Bowman’s Capsule (opposes filtration) For a good website on filtration- http://faculty.stcc.edu/AandP/AP/AP2pages/Units24to26/urinary/filtrati.htm Net filtration pressure • Balance of blood pressure, πGC, and Hydrostatic pressure in bowman’s capsule. • Body can easily regulate blood pressure in afferent or efferent arterioles to change net filtration pressure (NFP) • Increases in NFP increase Glomerular Filtration Rate (GFR), which is normally about 125mL/min • GFR can be estimated by measuring the clearance of a substance that is filtered into the nephron but not secreted or reabsorbed • GFR = creatinine clearance = [creatinine]urine x urine flow (ml/min) / [creatinine]plasma Tubular Reabsorption • Glomerulus filters ~180L per day, but most of this fluid is reabsorbed to conserve essential substances (water, ions, glucose….) • 99% water reabsorbed • 100% sugar reabsorbed • 99.5% of NaCl reabsorbed • At normal body pH, almost all of the filtered bicarbonate is reabsorbed • Reabsorption can occur by: • Passive Reabsorption: flux using electrochemical or osmotic gradient • Active Reabsorption: flux through the addition of an energy source to move a substance against its electrochemical gradient • Both require epithelial transport across two membranes Transport Mechanisms for Reabsorption • Na+ - diffusion through channels in the apical membrane • - primary active transport: Na+/K+ ATPase in the basolateral membrane • glucose- secondary active transport with Na+ (SGLT) across apical membrane • - facilitated diffusion (GLUT) across basolateral membrane • amino acids - cotransport with Na+ similar to glucose • H2O - via osmosis, follows movement of solutes Glucose Reabsorption in PCT • - normally, all glucose filtered into nephrons is reabsorbed. • - at very high glucose levels, glucose transporters become saturated. • transport maximum - maximal rate of glucose reabsorption • renal plasma threshold - minimum plasma [glucose] at which glucose appears in urine • normal plasma [glucose] 90 mg/dL << renal plasma threshold ~ 180 mg/dL. • In diabetes mellitus - high plasma [glucose] > renal plasma threshold → glucose in urine • → osmotic diuresis Loop of Henle: A vertical osmotic gradient Loop of Henle • Three parts: • Descending Limb • Permeable to water but impermeable to solutes • Thin ascending limb • Impermeable to water, passive reabsorption of salt • Thick Ascending limb • Impermeable to water, active reabsorption of salt Countercurrent Exchange Mechanism: • A. active transport of NaCl • NaCl pumped out of ascending limb (thick region) • ↓ osmolarity of tubular fluid and ↑ osmolarity of surrounding ECF Countercurrent Exchange: • B. osmotic movement of H2O • - H2O moves out of descending limb due to ↑ ECF osmolarity • - differential permeability properties along the loop of Henle: descending limb ascending limb permeable to H2O impermeable to H2O impermeable to NaCl permeable to NaCl (active transport) Countercurrent Exchange • C. countercurrent flow • - opposite direction of flow in descending and ascending limbs • - concentrated fluid (1200 mOsm) formed at base of loop and surrounding ECF • - dilute fluid (100 mOsm) at top of ascending limb enters DCT • - vasa recta around loop of Henle helps maintain vertical osmotic gradient Tubular Secretion • Active transport of ions and waste products (H+, K+, organic acids) into tubules • Occurs in PCT and DCT Collecting Duct: Regulated Reabsorption of Water • - hypotonic fluid (~100 mOsm) enters collecting duct (CD) from DCT • - as CD passes down the medulla, it encounters high osmolarity of surrounding ECF • - permeability of the CD to H2O is variable and regulated • antidiuretic hormone (ADH) (vasopressin) secreted by the posterior pituitary gland • - ADH stimulates insertion of aquaporins into the membrane of the CD epithelial cells • → promotes reabsorption of H2O from the CD back into the ECF .