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Chapter 17.2. Physiology of the Kidneys. 17-1. Chapter 17.2 Outline Renal Clearance Hormonal Effects Na + , K + , H + , and HCO 3 - Relationships Clinical Aspects. 17-2. Renal Clearance. 17-50. Renal Clearance.
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Chapter 17.2 Physiology of the Kidneys 17-1
Chapter 17.2 Outline • Renal Clearance • Hormonal Effects • Na+, K+, H+, and HCO3- Relationships • Clinical Aspects 17-2
Renal Clearance 17-50
Renal Clearance • Refers to ability of kidney to remove substances from blood and excrete them in urine • Occurs by filtration and by secretion • Secretion is opposite of reabsorption--substances from vasa recta are transported into tubule and excreted • Reabsorption decreases renal clearance; secretion increases clearance 17-51
Renal Clearance • Excretion rate = (filtration rate + secretion rate) - reabsorption rate 17-52
Secretion of Drugs • Many drugs, toxins, and metabolites are secreted by membrane transporters in the PCT • These transport organic anion and cation molecules • And determine the half-life of many therapeutic drugs • Many foreign molecules (xenobiotics) are eliminated by this system at a more rapid rate than by glomerular filtration 17-53
Inulin Measurement of GFR • Inulin, a fructose polymer, is useful for measuring GFR because is neither reabsorbed or secreted • Rate at which a substance is filtered by the glomeruli can be calculated: • Quantity filtered = GFR x P • P = inulin concentration in plasma • Quantity excreted (mg/min) = V x U • V = rate of urine formation; U = inulin concentration in urine • Amount filtered = amount excreted GFR = V x U P 17-54
Renal Plasma Clearance (RPC) • Is volume of plasma from which a substance is completely removed/min by excretion in urine • If substance is filtered but not reabsorbed then all filtered will be excreted RPC = GFR • If substance is filtered and reabsorbed then RPC < GFR • If substance is filtered but also secreted and excreted then RPC will be > GFR (=120 ml/ min) RPC = V x U P 17-56
Clearance of Urea • Urea is freely filtered into glomerular capsule • Urea clearance calculations demonstrate how kidney handles a substance: RPC = V X U/P • V = 2ml/min; U = 7.5 mg/ml of urea; P = 0.2 mg/ml of urea • RPC = (2ml/min)(7.5mg/ml)/(0.2mg/ml) = 75ml/min • Urea clearance is 75 ml/min, compared to clearance of inulin (120 ml/min) • Thus 40-60% of filtered urea is always reabsorbed • Is passive process because of presence of carriers for facilitative diffusion of urea 17-57
Measurement of Renal Blood Flow • Not all blood delivered to glomerulus is filtered into glomerular capsule • 20% is filtered; rest passes into efferent arteriole and back into circulation • Substances that aren't filtered can still be cleared by active transport (secretion) into tubules 17-58
Total Renal Blood Flow Using PAH • PAH clearance is used to measure total renal blood flow • Normally averages 625 ml/min • It is totally cleared by a single pass through a nephron • So it must be both filtered and secreted • Filtration and secretion clear only molecules dissolved in plasma • To get total renal blood flow, amount of blood occupied by erythrocytes must be taken into account • 45% blood is RBCs; 55% is plasma • total renal blood flow = PAH clearance • = 625/0.55 = 1.1L/min 0.55 17-59
Glucose and Amino Acid Reabsorption • Filtered glucose and amino acids are normally 100% reabsorbed from filtrate • Occurs in PCT by carrier-mediated cotransport with Na+ • Transporter displays saturation if ligand concentration in filtrate is too high • Level needed to saturate carriers and achieve maximum transport rate is transport maximum (Tm) • Glucose and amino acid transporters don't saturate under normal conditions 17-61
Glycosuria • Is presence of glucose in urine • Occurs when glucose > 180-200mg/100ml plasma (= renal plasma threshold) • Glucose is normally absent because plasma levels stay below this value • Hyperglycemia has to exceed renal plasma threshold • Diabetes mellitus occurs when hyperglycemia results in glycosuria 17-62
Hormonal Effects 17-63
Electrolyte Balance • Kidneys regulate levels of Na+, K+, H+, HCO3-, Cl-, and PO4-3 by matching excretion to ingestion • Control of plasma Na+ is important in regulation of blood volume and pressure • Control of plasma of K+ is important in proper function of cardiac and skeletal muscles 17-64
Role of Aldosterone in Na+/K+Balance • 90% filtered Na+ and K+ reabsorbed before DCT • Remaining is variably reabsorbed in DCT and cortical CD according to bodily needs • Regulated by aldosterone (controls K+ secretion and Na+ reabsorption) • In the absence of aldosterone, 80% of remaining Na+ is reabsorbed in DCT and cortical CD • When aldosterone is high all remaining Na+ is reabsorbed 17-65
K+ Secretion • Is only way K+ ends up in urine • Is directed by aldosterone and occurs in DCT and cortical CD • High K+ or low Na+ will increase aldosterone and K+ secretion 17-66
Juxtaglomerular Apparatus (JGA) • Is specialized region in each nephron where afferent arteriole comes in contact with thick ascending limb LH 17-67
Renin-Angiotensin-Aldosterone System • Is activated by release of renin from granular cells within afferent arteriole • Renin converts angiotensinogen to angiotensin I • Which is converted to Angio II by angiotensin-converting enzyme (ACE) in lungs • Angio II stimulates release of aldosterone 17-68
Regulation of Renin Secretion • Inadequate intake of NaCl always causes decreased blood volume • Because lower osmolality inhibits ADH, causing less H2O reabsorption • Low blood volume and renal blood flow stimulate renin release • Via direct effects of BP on granular cells and by Symp activity initiated by arterial baroreceptor reflex (see Fig 14.26) 17-69
Macula Densa • Is region of ascending limb in contact with afferent arteriole • Cells respond to levels of Na+ in filtrate • Inhibit renin secretion when Na+ levels are high • Causing less aldosterone secretion, more Na+ excretion 17-71
Atrial Natriuretic Peptide (ANP) • Is produced by atria due to stretching of walls • Acts opposite to aldosterone • Stimulates salt and H2O excretion • Acts as an endogenous diuretic 17-73
Na+, K+, and H+ Relationship • Na+ reabsorption in DCT and CD creates electrical gradient for H+ and K+ secretion • When extracellular H+ increases, H+ moves into cells causing K+ to diffuse out and vice versa • Hyperkalemia can cause acidosis • In severe acidosis, H+ is secreted at expense of K+ 17-75
Renal Acid-Base Regulation • Kidneys help regulate blood pH by excreting H+ and/or reabsorbing HCO3- • Most H+ secretion occurs across walls of PCT in exchange for Na+ (Na+/H+ antiporter) • Normal urine is slightly acidic (pH = 5-7) because kidneys reabsorb almost all HCO3- and excrete H+ 17-76
Reabsorption of HCO3- in PCT • Is indirect because apical membranes of PCT cells are impermeable to HCO3- 17-77
Reabsorption of HCO3- in PCT continued • When urine is acidic, HCO3- combines with H+ to form H2CO3 (catalyzed by CA on apical membrane of PCT cells) • H2CO3 dissociates into CO2 + H2O • CO2 diffuses into PCT cell and forms H2CO3 (catalyzed by CA) • H2CO3 splits into HCO3- and H+ ; HCO3- diffuses into blood 17-78
Urinary Buffers • Nephron cannot produce urine with pH < 4.5 • Excretes more H+ by buffering H+s with HPO4-2 or NH3 before excretion • Phosphate enters tubule during filtration • Ammonia produced in tubule by deaminating amino acids • Buffering reactions • HPO4-2 + H+ H2PO4- • NH3 + H+ NH4+ (ammonium ion) 17-79
Clinical Aspects 17-80
Diuretics • Are used to lower blood volume because of hypertension, congestive heart failure, or edema • Increase volume of urine by increasing proportion of glomerular filtrate that is excreted • Loop diuretics are most powerful; inhibit AT salt in thick ascending limb of LH • Thiazide diuretics inhibit NaCl reabsorption in 1st part of DCT • Carbonic anhydrase inhibitors prevent H2O reabsorption in PCT when HCOs- is reabsorbed • Osmotic diuretics increase osmotic pressure of filtrate 17-81
Kidney Diseases • In acute renal failure, ability of kidneys to excrete wastes and regulate blood volume, pH, and electrolytes is impaired • Rise in blood creatinine and decrease in renal plasma clearance of creatinine • Can result from atherosclerosis, inflammation of tubules, kidney ischemia, or overuse of NSAIDs 17-83
Kidney Diseases continued • Glomerulonephritis is inflammation of glomeruli • Autoimmune attack against glomerular capillary basement membranes • Causes leakage of protein into urine resulting in decreased colloid osmotic pressure and resulting edema 17-84
Kidney Diseases continued • In renal insufficiency, nephrons have been destroyed as a result of a disease • Clinical manifestations include salt and H2O retention and uremia (high plasma urea levels) • Uremia is accompanied by high plasma H+ and K+ which can cause uremic coma • Treatment includes hemodialysis • Patient's blood is passed through a dialysis machine which separates molecules on basis of ability to diffuse through selectively permeable membrane • Urea and other wastes are removed 17-85