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بسم الله الرحمن الرحيم. SODIUM BALANCE. OVERALL HANDLING OF NA +. Na + Reabsorption. Of total energy spent by kidneys, 80% is used for Na + transport Na + is not reabsorbed in the descending limb of the loop of Henle. In the early proximal tubule, Na + is reabsorbed primarily with
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بسم الله الرحمن الرحيم SODIUM BALANCE
Na+ Reabsorption • Of total energy spent by kidneys, 80% is used for Na+transport • Na+ is not reabsorbed in the descending limb of the loop of Henle
In the early proximal tubule, Na+ is reabsorbed primarily with HCO3- ,Glucose and Amino acids. In the late proximal tubule, Na+ is reabsorbed primarily with Cl-,
What is Isosmotic Reabsorption • Solute and water reabsorption are coupled and are proportional to each other. Thus, if 67% of the filtered solute is reabsorbed by the proximal tubule, then 67% of the filtered water also will be reabsorbed.
Glomerulotubular Balance ? • Tubular reabsorption increases/decreases automatically as the filtered load increases/ decreases.
GlomerulotubularBalance----how? Increase in GFR Increase in filtration fraction Increase in concentration of protein in peritubular capillaries Increase in πc Increase reabsorption in proximal tubule
Effects of ECF volume expansion & ECF volume contraction on isosmotic fluid reabsorption in the proximal tubule
Late distal tubule • Principal cell : Na+ reabsorption & K+ secretion • α- inetercalted cells K+ reabsorption & H+ secretion
Potassium handling by nephron(continued) • Distal tubule & collecting ducts : • α -Intercalated cells : absorption of potassium if person is on low K+ diet • Principle cells : if person on normal or high K+ diet potassium is excreted by principle cells
Factors affecting K+secretion • Magnitude of K+ secretion is determined by the size of electrochemical gradient across luminal membrane • Diet: High K+ diet concentration inside thus principle cells increases electrochemical gradient across membrane
Factors affecting K+secretion(continued) • Aldosterone : • Aldosterone Na+ re absorption by principle cell by inducing synthesis of luminal membrane Na+ channels & basolateral membrane Na+- K+ channel • more Na+ is pumped out of the cell simultaneously more K+ pumped into the cell • Thus increasing the electrochemical gradient for K+ across the luminal membrane that leads to increase K+ secretion
Relationship between Na+ absorption & K+ secretion • High Na+ diet: • more Na+ will be delivered to principle cells ,more Na+ is available for Na+- K+ ATPase than more K+ is pumped into the cell which increases the driving force for K+ secretion
Factors affecting K+secretion(continued) • Acid base disturbances : • The exchange of H+ & K+ ion across membrane underlies these effect • Alkalosis H+ in ECF H+ leaves & K+ enters the cell intracellular K+contn driving force for K+ • Acidosis H+ in ECF H+ enters & K+ leaves the cell intracellular K+contn driving force forK+
Factors affecting K+secretion(continued) • Diuretics : • Loop diuretics & thiazide diuretics causes hypokalemia • By decreasing the sodium re absorption in upstream to the site of K+ secretion ,make more Na+ available for the principle cells ,so more Na+ will be given out & more K+ will be taken in by Na+ - K+ ATPase • Increase flow rate luminal K+ contndiluted driving force for K+ secretion
Loop diuretics: also contribute to hypokalemia • by inhibiting Na+ - K+ -2cl co transport & thus K+ re absorption in thick ascending limb • K+ sparing diuretics: • inhibits all of the action of aldosterone on principle cells & therefore inhibits K+ secretion
Role of PTH • In the DCT ,PTH , • Ca2+ reabsorption via basolateral receptor activation of adenylcyclase & generation of cyclic AMP • proximal tubule • PTH inhibits phosphate re absorption by inhibiting Na phosphate co transport As a result it causes phosphaturea
If substance is filtered , not reabsorbed or secreted , its plasma clearance rate equals GFR • E.g • Inuline
Clearance of Various Substances • Albumin – 0: normally albumin is not filtered across the membrane • Glucose – 0 :normally filtered glucose is completely reabsorbed back into the blood stream • Inulin – is equal to the GFR.(Glomerular Marker) Inulin is a Fructose polymer ; freely filtered across the membrane and neither reabsorbed nor secreted. • PAH – • Para Amino Hippuric Acid(& other organic acids).Has highest clearance since it is both filtered and secreted.
Clinically it is not convenient to use inline clearance so • Which substance is used instead • Creatinine
CLEARANCE RATIO • Clearance of any substance (x) compared with clearance of Inulin = C x ( glomerular marker) C inulin • C x = 1 (filtered & neither reabsorbed nor secreted) C inulin • C x < 1 (substance is not filtered/filtered & reabsorbed) C inulin • C x > 1 (substance is filtered as well as secreted ) C inulin
UPAH x V ERPF = PPAH PAH Clearance is use to Estimate ? Renal Plasma Flow ~ ~ 10 % PAH remains ERPF = Clearance PAH
Urine Concentration & Dilution • The final adjustment of the urine volume and osmolarity depends on the extent of facultative water reabsorption in the Collecting Ducts, which is depends on:- • The blood level of antidiuretic hormone (ADH). • The Medullary interstitium (MI) hypertonicity (Medullary concentration gradient).
Medullary Countercurrent system • Juxta medullary nephrons • vertical osmotic gradient in MI is estabilished by long loop of henle(Countercurrent multiplier) , • this gradient is preserved by vassarecta,( Countercurrent exchanger) • Which structure use the gradient in conjunction with the hormone vassopressin, to produce urine of varying concentration ? collecting ducts of all nephrones(osmotic equilibrating device) .
Countercurrent Multiplication • Comparing the descending and ascending limbs of the loop of Henle • The descending ling is highly permeable to water but does not extrude sodium for reabsorption. • The ascending limb actively transports NaCl out of the tubular lumen into the surrounding interstitial fluid. It is impermeable to water. Therefore, water does not follow the salt by osmosis. • There is a countercurrent flow produced by the close proximity of the two limbs.
Countercurrent Multiplication The descending limb The ascending limb It is impermeable to water. Therefore, water does not follow the salt by osmosis. actively transports NaClout of the tubular lumen into the surrounding interstitial fluid. • is highly permeable to water • but does not reabsorbs Na+
BENEFITS OF COUNTERCURRENT MULTIPLICATION • It establishes a vertical osmotic gradient in the medullary interstitial fluid. This gradient, in turn, is used by the collecting ducts to concentrate the tubular fluid so that a urine more concentrated than normal body fluids can be excreted. • Second, the fact that the fluid is hypotonic as it enters the distal parts of the tubule enables the kidneys to excrete a urine more dilute than normal body fluids.
Role of Vasopressin • Vasopressin-controlled, variable water reabsorption occurs in the final tubular segments. • 65 percent of water reabsorption is obligatory in the proximal tubule. In the distal tubule and collecting duct it is variable, based on the secretion of ADH. • The secretion of vasopressin increases the permeability of the tubule cells to water. An osmotic gradient exists outside the tubules for the transport of water by osmosis. • Vasopressin works on tubule cells through a cyclic AMP mechanism. • During a water deficit, the secretion of vasopressin increases. This increases water reabsorption. • During an excess of water, the secretion of vasopressin decreases. Less water is reabsorbed. More is eliminated.
Abnormalities of micturition Atonic Bladder Caused by Destruction of Sensory Nerve Fibers. • Micturition reflex cannot occur Person loses bladder control • overflow incontinence. • A common cause of atonic bladder is crush injury to the sacral region of the spinal cord.