Anatomical and Functional Organization of Kidneys Gross structure 3 regions o Cortex smooth curvature outside o Medulla o Pelvis Nephrons functional unit of the kidneys o Glomerular apparatus o Renal tubules o Loops of Henle Nephrons Glomerular Apparatus found only in cortex o Bowman s capsule o Glomerular capillaries o Basement membrane o Major function ultrafiltration Normal GFR 125 mL min 180 L day Renal Tubules found mostly in inner or upper cortex with some in cortex o Proximal tubules o Distal convoluted tubules o Collecting tubules o Major function transport resorptive and secretory Loops of Henle o Ascending limbs thick vs thin o Descending limbs permeable to water no ion movement o Function countercurrent multiplier mechanism Renal Function How urine is formed Filtration Resorption Secretion Fluid and Electrolyte Balance Intracellular water 40 of body weight Total Body Water TBW 60 of body weight Extracellular Water ECF 20 of body weight Plasma water 4 of body weight Interstitial Fluid ICF 16 of body weight Regulation of ECF Volume Extrarenal Processes High pressure baroreceptors in carotid sinus and aortic arch o Direct Effect increased sympathetic activity increases renal FF filtration fraction o Indirect Effect cardiovascular reflexes Low pressure baroreceptors in cardiac atria o Artial Natruiretic Peptide ANP o Released from atrial wall when stretched by volume o Vasodilates glomerular vessels to increase GFR o Reduces Na reabsorption in terminal segments o Inhibits renin release from macula densa o Inhibits vasopressin ADH release ECF solute concentration is determined by volume of water excreted by the Regulation of ECF Osmolarity kidneys Vasopressin ADH o Released by small 1 increases in osmolarity o Released by large 10 decreases in plasma volume o Surgical stress can also induce ADH release causing water retention o Promote the retention of water in kidneys and increases the blood and hyponatremia volume Diuretics Diuresis increase in urine volume Increase release of Na and water follows Natriuresis increase in renal Na excretion Diuretic Drugs o Decrease tubular reabsorption of Na o Promote water excretion Diuretic Drugs Pharmacologic Groups Osmotic agents Carbonic anhydrase inhibitors acetazolamide Thiazides Loop diuretics K sparking diuretics o Tiamterene like drugs o Aldosterone receptor antagonists Diuretic Sites of Action Proximal Tubule o Osmotic Agents must have adequate GFR to be safe and effective o Proximal tubule descending limb of loop collecting tubules o Carbonic anhydrase inhibitors o Mannitol Thick Ascending Limb of Loop of Henle o High ceiling loop diuretics Distal Tubule o Thiazides must have adequate GFR to be safe and effective o K Sparing Agents distal tubule and collecting ducts Thiazides Hydrochlorthiazide Most widely prescribed group Chemically related to CAI s and sulfonamides Low ceiling if patient takes too much the consequences aren t severe Mechanism of Action o Inhibit NaCl reabsorption from luminal side of epithelial cells in distal convoluted tubules weak diuretic effect o Act on an electrically neutral NaCl cotransporter All are secreted by the organic acid transport system and compete with uric acid consequently uric acid excretion is reduced and blood urate levels may rise Also enhance Ca reabsorption in distal convoluted tubule rarely cause hypercalcemia Thiazides Action Increased Na and K excretion o No change in acid base balance Loss of K Reduced peripheral vascular resistance o Caused by relaxation of arteriolar smooth muscle Acts on kidney and on vascular smooth muscle First line for an initial diagnosis of hypertension Thiazides Major Indications Hypertension CHF Nephrolithiasis due to idiopathic hypercalcemia Nephrogenic diabetes Insipidus o Paradoxical antidiuretic action o Only diuretics that can cause a hyperosmolar urine in this condition o Believed to enhance actions of ADH as a consequence of Na depletion Thiazides Contraindications Severe renal impairment Anuria urine output 250 mL day Hepatic coma Hypersensitivity to sulfa drugs Thiazides Adverse Effects Due to fluid loss or electrolyte imbalances Hypokalemia calf pain muscle weakness o Most frequent problem measure serum K o Add K supplements or change dietary intake o Combine with K sparing diuretic o Can predispose patients to digitalis toxicity arrhythmias Hyperruricemia gout can be secondary to hyperuricemia Volume Depletion orthostatic hypotension or light headedness Hyperglycemia impaired CHO tolerance due to impaired insulin release and reduced tissue utilization of glucose Hypersensitivity and Photosensitization like sulfas Decrease renal clearance of lithium ions exchanged for sodium and increases Thiazides Drug Interactions risk of lithium toxicity Loop Diuretics Very powerful Furosemide Mechanism of Action o Ascending limb of loop of Henle o Pump takes 1 Na 1 K and two fluorides and transport them o Results in increased sodium potassium and chloride excretion Other actions o Increase excretion of Mg and Ca don t usually cause hypocalcemia because Ca is actively reabsorbed in the distal convoluted tubule o Prevent reabsorption of Br F and I in anion overdosage requires concurrent saline administration to prevent ECF volume depletion Rapidly absorbed orally Eliminated by glomerular filtration and tubular secretion Almost immediate onset IV Duration of action is 1 4 hours Loop Diuretics Indications Acute pulmonary edema of CHF Hypercalcemia increase tubular secretion of Ca Hyperkalemia can significantly increase K excretion especially with concurrent administration of NaCl and water Edema feet and ankles Acute Renal Failure increase urine flow and K excretion Loop Diuretics Contraindications Anuria Hypersensitivity to sulfonamides Loop Diuretics Adverse Effects Ototoxicity dose related hearing loss Hypokalemia enhanced excretion of K Metabolic Alkalosis due to enhanced excretion of H Hyperuricemia can precipitate gouty attack Hypomagnesia reversed by oral supplements of Mg Acute Hypovolemia dehydration o Can cause severe and rapid reduction in blood volume hypotension shock and cardiac arrhythmias Sulfonamide Type Allergy less likely with ethacrynic acid Directly interfere with Na entry through sodium selective ion channels in Because K secretion is coupled to Na entry in collecting tubule these drugs Triamterene and Amiloride collecting tubule are K sparing Spironolactone Competitive antagonist at aldosterone receptor o Slow onset and several days