Renal System Diuretics Overview of the Renal System o Anatomical Functional Organization of Kidneys Gross structure Nephrons Urine formation o Fluid Electrolyte Balance Body fluid compartments Electrolyte composition of the ECF Regulation of extracellular fluid ECF volume Regulation of ECF tonicity osmolarity o Anatomical Functional Organization of Kidneys Gross structure 3 regions cortex medulla pelvis Nephrons functional unit of the kidneys glomerular apparatus o responsible for glomular filtration renal tubules loops of Henle Glomerular apparatus found only in cortex Bowman s capsule major function ultrafiltration glomerular capillaries basement membrane o normal GFR 125 ml min 180 L day Renal tubules found mostly in inner or upper cortex with some in cortex major function transport resorptive secretory proximal tubules sodium reabsorption distal convoluted tubules collecting tubules Loops of Henle ascending limbs only water permeable no solute reabsorption o thick vs thin descending limbs Na and Cl are coupled in reabsorption function countercurrent multiplier mechanism o Renal Function How urine is formed filtration resorption secretion Fluid Electrolyte Balance o Body Fluid Compartments total body water TBW 60 of body weight intracellular water 40 of body weight extracellular water ECF 20 of body weight o plasma water 4 of body weight o interstitial fluid ICF 16 of body weight Electrolyte Composition of ECF Plasma Anions Cl 104 meq L HCO3 27 HPO4 2 organic acids 3 Proteins 15 Total Anions 152 ICF 118 meq L 31 149 Plasma Electrolyte Composition of ECF Ions Cations Na 141 meq L K 4 Ca 5 Mg 2 Total cations 151 ICF 144 meq L 4 148 Regulation of ECF Volume o Intrarenal Mechanisms renin angiotensin II reduces RPF GFR resulting in increased filtration fraction GFR RPF enhances Na reabsorption in proximal tubules angiotensin II exerts direct effects on Na transport in proximal tubules o low conc s increase Na reabsorption o hi conc s inhibit it angiotensin II stimulates aldosterone release o aldosterone increases Na reabsorption in collecting ducts o Extrarenal processes high pressure baroreceptors in carotid sinus aortic arch direct effect increased sympathetic activity increases renal FF filtration fraction indirect effect via cardiovascular reflexes low pressure baroreceptors in cardiac atria atrial natriuretic 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 Regulation of ECF Osmolarity o ECF solute conc is determined by volume of water excreted by the kidneys o Vasopressin ADH DIURETICS released by small 1 increases in osmolarity released by large 10 decreases in plasma volume surgical stress can also induce ADH release causing water retention hyponatremia o Normally work together to promote water excretion by reducing sodium reabsorption Diuresis increase in urine volume Natriuresis increase in renal Na excretion Diuretic Drugs o decrease tubular reabsorption of Na o promote water excretion Diuretic Drugs Pharmacologic Groups o Osmotic agents o Carbonic anhydrase inhibitors acetazolamide o Thiazides o Loop diuretics o K sparing diuretics triamterene like drugs aldosterone receptor antagonists Diuretic Sites of Action o Proximal tubule osmotic agents must have adequate GFR to be safe effective carbonic anhydrase inhibitors 3 sites proximal tubule descending limb of loop collecting tubules o Thick ascending limb of loop of Henle high ceiling loop diuretics highest efficacy must be used careful because so powerful an effect o Distal tubule thiazides must have adequate GFR to be safe effective K sparing agents distal tubule collecting ducts THIAZIDES o Thiazides hydrochlorthiazide Hydrodiuril o Thiazide like chemically like but not thiazide indapamide Lozol quinethazone Aquamox o Characteristics Low ceiling diuretics even if the patient doubled the does not likely to have a life threatening reaction Most widely prescribed group chemically related to CAI s sulfonamides mechanism of action inhibit NaCl reabsorption from luminal side of epithelial cells in distal convoluted tubules weak diuretic effect act on an electrically neutral NaCl cotransporter all are secreted by the organic acid transport system compete with uric acid consequently uric acid excretion is reduced blood urate levels may rise also enhance Ca reabsorption in distal convoluted tubule rarely cause hypercalcemia o Actions Increased Na K excretion no change in acid base balance Loss of K Reduced peripheral vascular resistance caused by relaxation of arteriolar smooth muscle o Major indications hypertension congestive heart failure CHF nephrolithiasis due to idiopathic hypercalcemia nephrogenic diabetes insipidus o paradoxical antidiuretic action o Contraindications severe renal impairment anuria urine output 250 ml day hepatic coma hypersensitivity to sulfa drugs o Adverse Effects mostly due to fluid loss or electrolyte imbalances hypokalemia calf pain muscle weakness tremendous amount of urinary excretion is caused by this disease and this drug causes only diuretics that can cause a hyperosmolar urine in this condition to a hyperosmolar condition o a lot less fluid will be lost believed to enhance actions of ADH as a consequence of Na depletion o most frequent problem therefore measure serum K add K supplements or change dietary intake or combine with K sparing diuretic o can predispose pts to digitalis toxicity arrythmias hyperuricemia volume depletion o orthostatic hypotension or light headedness hyperglycemia impaired CHO tolerance o due to impaired insulin release reduced tissue utilization of glucose o Drug Interactions hypersensitivity photosensitization like sulfas orthopedic hypotension decrease renal clearance of lithium ions exchanged for sodium increases risk of lithium toxicity LOOP DIURETICS o Furosemide Lasix Most potent o Mechanism of action inhibit the coupled Na K 2Cl cotransporter of the thick ascending limb of loop of Henle site of 25 reabsorption of filtered sodium can significantly increase K excretion especially with concurrent administration of NaCl water results in increased sodium potassium chloride excretion o Other actions increase Mg and Ca excretion don t usually cause hypocalcemia because Ca is actively reabsorbed in the distal convoluted tubule prevent reabsorption of Br F and I in anion