--- module: 017-01 language: en chapter: 17 title: "Glomerular Filtration, Tubular Transport, Concentration, and Clearance" module_title: "Foundations" source_sha256: df7f2d06dd2fb16204cbcac48ef462b5f02d72d17abd43e959f7cc1818f892d3 --- # Glomerular filtration, tubular transport, concentration, and clearance ## Renal roles and endocrine functions ### Filter plasma, reabsorb, secrete, regulate electrolytes ### Acidity, pressure, erythropoietin, vitamin D ### Erythropoietin follows hypoxia-inducible signalling #### Chronic disease gives hypoproliferative anaemia ### Proximal cells activate vitamin D #### Parathyroid hormone and low phosphate stimulate it #### Failure brings hyperparathyroidism and bone disease ## Circulation and nephron organisation ### Afferent arteriole supplies each glomerular tuft ### Blood leaves through an efferent arteriole #### Peritubular capillaries surround cortical tubules #### Vasa recta descend into the medulla ### Capsule, proximal, loop, distal, collecting duct ### Juxtamedullary long loops allow urine concentration ### Cortex takes most flow, medulla little #### Sodium transport drives medullary oxygen demand ## Glomerular filtration barrier ### Fenestrated endothelium, basement membrane, podocyte slits ### Size, shape, and charge govern passage ### Albumin restricted, small amounts reclaimed proximally ### Injury gives haematuria, proteinuria, filtration loss #### Dysmorphic cells and casts mean glomerular bleeding #### Nephrotic: oedema, hypoalbuminaemia, lipids, thrombosis #### Inflammatory: haematuria, hypertension, low filtration ## Filtration pressure and autoregulation ### Glomerular hydrostatic pressure favours filtration ### Bowman's and plasma oncotic pressures oppose it ### Rate equals net pressure times filtration coefficient #### Coefficient reflects permeability and surface area ### Moderate efferent constriction raises glomerular pressure #### Severe constriction lowers flow and filtration ### Myogenic response constricts stretched afferent muscle ### Macula densa senses sodium chloride delivery #### Delivery sets afferent tone and renin release ## Proximal tubule ### Reclaims most sodium, water, bicarbonate, phosphate ### Nearly all glucose and amino acids normally ### Sodium-potassium pump powers apical transport #### Water follows solute, reabsorption is iso-osmotic ### Bicarbonate reclaimed, no new bicarbonate made ### Transport maximum exceeded gives osmotic diuresis ### Secretes organic acids and bases, including drugs ### Injury: bicarbonate, phosphate, glucose, amino acids ## Loop and countercurrent system ### Thin descending limb concentrates tubular fluid ### Thick ascending limb moves sodium, potassium, chloride #### Water impermeable, so tubular fluid is diluted ### Opposing flow multiplies a small transverse gradient ### Urea recycling adds to the inner medulla ### Vasa recta supply tissue and limit washout ## Distal nephron and collecting duct ### Early distal tubule takes sodium and chloride ### Principal cells reabsorb sodium, secrete potassium #### Aldosterone raises channel and pump activity ### Antidiuretic hormone inserts aquaporin two channels #### Without it, dilute urine is excreted ### Alpha cells secrete acid, beta cells bicarbonate ### Distal acid and ammonium make new bicarbonate ## Clearance and filtration markers ### Virtual plasma volume cleared per unit time ### Equals filtration for an unhandled filtered marker #### Inulin approximates the ideal experimentally #### Creatinine is filtered and partly secreted ### Small creatinine rise can mean large filtration loss ### Acute change defeats steady-state equations ### Filtration fraction is filtration over plasma flow ### Fractional excretion shifts with diuretics and illness ## Urine testing and sediment ### Dipstick: pH, blood, protein, glucose, nitrite #### False positives and negatives both occur ### Microscopy: cells, casts, crystals, organisms #### Hyaline casts can occur normally #### Red-cell casts support glomerulonephritis #### Muddy granular casts support tubular injury ### Albumin and protein ratios adjust for concentration ## Diuretic sites as physiology probes ### Carbonic-anhydrase inhibitors cut proximal reclamation ### Loop diuretics weaken the medullary gradient #### Calcium and magnesium excretion rise ### Thiazides reduce distal sodium chloride uptake #### Calcium excretion falls