Renal Physiology PDF

Renal Physiology Dr Mahdy AbuRagheif Figure 27-1; Guyton and Hall Primary Active Transport of Na+ Figure 27-2; Guyton and Hall Mechanisms of Secondary Active Transport Figure 27-3; Guyton and Hall Absorptive c...

Renal Physiology Dr Mahdy AbuRagheif Figure 27-1; Guyton and Hall Primary Active Transport of Na+ Figure 27-2; Guyton and Hall Mechanisms of Secondary Active Transport Figure 27-3; Guyton and Hall Absorptive capability of different tubular segments: Proximal segment: , Proximal Convoluted Tubule (PCT) Highly active → 65% of all absorptive and secretory functions. Water and Na ions are reabsorbed at this segment (65%). Also Cl are absorbed passively in the second half of the tubule. K, Ca, Mg, sulfate are absorbed actively. In Proximal Convoluted Tubule (PCT) –A thick, constantly actively segment of the nephron that reabsorbs most of the useful substances of the filtrate: sodium (65%), water (65%), bicarbonate (90%), chloride (50%), glucose (nearly 100%!), etc. –The primary site for secretion (elimination) of drugs, waste and hydrogen ions Proximal segment: Glucose and amino acids are absorbed by secondary active transport in the early half of proximal tubule. Proteins are absorbed by pinocytosis. Active secretion of drugs (penicillin & acetyl salicylic acid). Osmolarity at this segment remains isoosmolar. Thin segment of Henle:. The descending portion is highly permeable to water and very low to sodium, urea and others leading to hypertonic fluid; while, the ascending thin is impermeable to water. Descending Limb of the Loop of Henle –A part of the counter current multiplier –freely permeable to water and relatively impermeable to solutes (salt particles) –receives filtrate from the PCT, allows water to be absorbed and sends “salty” filtrate on the next segment. “Saves water and passes the salt” The thick ascending is also impermeable to water and permeable to ions through Na-K-2Cl co-transport mechanism, whereby Na is absorbed by secondary active cotransport system. Also Na ions are absorbed by secondary active counter-transport system through Na-H system. All this leads to hypotonic fluid. Ascending Limb of the Loop of Henle – a part of the counter current multiplier – impermeable to water and actively transports (reabsorbs) salt (NaCl) to the interstitial fluid of the pyramids in the medulla. “Saves salt and passes the water.” – the passing filtrate becomes dilute and the interstitium becomes hyperosmotic Distal tubule:. Distal Convoluted Tubule (DCT) It is divided into the diluting segment (thick ascending and ½ the distal convoluted) functions as active transport of sodium and chloride (Na-K-2Cl) and is impermeable to water and urea. In Distal Convoluted Tubule (DCT) – receives dilute fluid from the ascending limb of the Loop of Henle – Variably active portion of the nephron – When aldosterone hormone is present, sodium is reabsorbed and potassium is secreted. Water and chloride follow the sodium.  The principal cells reabsorb sodium and water from the lumen and secrete potassium ions into the lumen The intercalated cells secrete hydrogen ions and reabsorb bicarbonate and potassium ions The late distal functions for active transport of sodium and chloride under the effect of aldosterone Na reabsorption & K secretion occurring at the Principal cells (P-cells). The Intercalated cells (I-cells) are under aldosterone control for H+ secretion & K+ reabsorption. It is also very impermeable to water and urea and is under ADH. The collecting duct:. The cortical and medullary segments. Both portions function for active transport of Na, K, O2, Ca and others.  The cortical is impermeable to urea, while the / medullary is permeable to urea under ADH.  Water permeability is under ADH control.  Absorption of glucose and amino acids is nearly 100% done at the proximal portion by secondary co-transport with sodium.  Proteins are also reabsorbed completely at the proximal portion, and the mechanism of absorption is through endocytosis (pinocytosis). In Collecting Duct-- – receives fluid from the DCT – variably active portion of the Nephron – when antidiuretic hormone (ADH) is present, this duct will become porous to water. Water from the collecting duct fluid then moves by osmosis into the “salty” (hyperosmotic) interstitium of the medulla. – The last segment to save water for the body  Renal mechanism for concentrating and diluting urine:  Diluting mechanism: depends on ADH.  The osmolality at the proximal portion is 300 mOsm/l as in the cortex;  The descending loop is permeable to water and impermeable to electrolytes and no active transport. The ascending loop permits active. absorption of Na-K-2Cl and no water permeability, leaving the fluid hypotonic, Then the diluting segment of Henle also impermeable to water and active transport for electrolytes.  Late distal and collecting ducts are under ADH. and if not present, water remains and the urine is diluted.  If ADH is present, then most of the water is reabsorbed because of the high osmolality at the medulla, leading to highly concentrated urine. The major factors buildup of solute concentration into the renal medulla are as follows: 1. Active transport of sodium ions and co- transport of potassium, chloride, and other ions out of the thick portion of the ascending limb of the loop of Henle into the medullary interstitium 2. Active transport of ions from the collecting ducts into the medullary interstitium 3. Facilitated diffusion of urea from the inner medullary collecting ducts into the medullary interstitium 4. Diffusion of only small amounts of water from the medullary tubules into the medullary interstitium— far less than the reabsorption of solutes into the medullary interstitium  Osmoreceptor– antidiuretic hormone (ADH) feedback mechanism for regulating extracellular fluid osmolarity Figure 28-8; Guyton and Hall  Countercurrent Multiplier Interstitial fluid should be hypertonic for water to be reabsorbed Countercurrent multiplier:.  is the mechanism for increasing deep medullary osmolality.  It is found at the juxta-medullary nephrons (1/3- 1/5 of nephrons) The reason for the high medullary concentration and osmolalities explained by Countercurrent Multiplier:.: Steps Involved in Causing Hyperosmotic Renal Medullary Interstitium. Step 1 assume that the loop of Henle is filled with fluid with a concentration of 300 mOsm/L, the same as that leaving the proximal tubule Step 2 the active ion pump of the thick ascending limb on the loop of Henle reduces the concentration inside the tubule and raises the interstitial concentration; this pump establishes a 200- mOsm/L concentration gradient between the tubular fluid and the interstitial fluid.  Step 3 is that the tubular fluid in the descending limb of the loop of Henle and the interstitial fluid quickly reach osmotic equilibrium because of osmosis of water out of the descending limb.  The interstitial osmolarity is maintained at 400 mOsm/L because of continued transport of ions out of the thick ascending loop of Henle.  Step 4 is additional flow of fluid into the loop of Henle from the proximal tubule, which causes the hyperosmotic fluid previously formed in the descending limb to flow into the ascending limb.  Step 5 Once this fluid is in the ascending limb, additional ions are pumped into the interstitium, with water remaining in the tubular fluid, until a 200-mOsm/L osmotic gradient is established, with the interstitial fluid osmolarity rising to 500 mOsm/L  Step 6 Then, once again, the fluid in the descending limb reaches equilibrium with the hyperosmotic medullary interstitial fluid, and as the hyperosmotic tubular fluid from the descending limb of the loop of Henle flows into the ascending limb, still more solute is continuously pumped out of the tubules and deposited into the medullary interstitium. Step 7 --These steps are repeated over and over, with the net effect of adding more and more solute to the medulla in excess of water; with sufficient time, this process gradually traps solutes in the medulla and multiplies the concentration gradient established by the active pumping of ions out of the thick ascending loop of Henle, eventually raising the interstitial fluid osmolarity to 1200 to 1400 mOsm/L. It depends on 1. Active Na-K-2Cl transport from the thick ascending loop. 2. Active sodium (& Cl) from distal convoluted and cortical collecting ducts. 3. When ADH is secreted, water is absorbed together with urea. 4. Passive diffusion of sodium from the thin ascending loop (600 inside and 300 outside). 5. All these processes cause an increase in the osmolality of the interstitium. Counter-current exchange:. depend on vasa recta where the descending absorb sodium and the ascending one excretes sodium maintaining the high osmolality of the interstitium and only minor quantities are removed.  So the mechanism for concentrating. urine depends on the high osmolality of the interstitium And the presence of ADH to remove water forming urine with 1200-1400 osmolality. Obligatory Urine Volume:.  The maximal concentrating ability of the kidney dictates how much urine volume must be excreted each day to rid the body of waste products of metabolism and ions that are ingested.  A normal 70-kilogram human must excrete about 600 milliosmoles of solute each day.  If maximal urine concentrating ability is 1200 mOsm/L, the minimal volume of urine that must be excreted, called the obligatory urine volume,  The limited ability of the human kidney to concentrate the urine to a maximal concentration of 1200 mOsm/L explains why severe dehydration occurs if one attempts to drink seawater can be calculated If the max. urine osmolarity is 1200 mOsm/L, [[ and 600 mOsm of solute must be excreted each day to maintain electrolyte balance, the obligatory urine volume is: 600 mOsm/d = 0.5 L/day 1200 mOsm/L Urea excretion: Body forms 25-30 gm/day and the normal level in blood is around 25mg/dl. The factors affecting excretion is (1)Plasma level (2)GFR. On low GFR, fluid remains for a long time in the tubules allowing much absorption and little excretion, while high GFR, much of the urea is excreted (100%).  Formation of a Concentrated Urine when Antidiuretic Hormone (ADH) Levels are High Figure 28-4; Guyton and Hall  In the presence of high concentrations of ADH, water is. reabsorbed rapidly from the cortical collecting tubule and the urea concentration increases rapidly because urea is not very permeate in this part of the tubule. Then, as the tubular fluid flows into the inner medullary collecting ducts, still more water reabsorption takes place, causing an even higher concentration of urea in the fluid. Glucose Reabsorption From tubular lumen to tubular cell: Sodium co-transporter (Carrier-mediated secondary active transport). Uphill transport of glucose driven by electro-chemical gradient of sodium, From tubular cell to peritubular capillary: Facilitated diffusion (Carrier-mediated passive 55 transport) 56 Glucose Transport Maximum Sodium excretion: At the proximal tubules, 65% is absorbed actively in addition to chloride. Water flows passively. In the thin descending, no sodium absorption occurs. The ascending thick, active Na-K-2Cl absorption occurs (25%). What remains is 10% at the late distal tubules and is under the effect of aldosterone. Aldosterone causes active sodium absorption coupled with active potassium secretion Normal Renal Tubular Na+ Reabsorption (16,614 mEq/day) 7% 65 % (1789 mEq/d) 25,560 mEq/d 25 % (6390 mEq/d) 2.4% (617 mEq/day) 0.6 % (150 mEq/day) Copyright © 2006 by Elsevier, Inc. Factors affecting Na+ excretion 1. Change in GFR: 2. Effect of hormones: / Aldosterone, Angiotensin II ↑ Na+ reabsorption , Circulating epinephrine, Glucocorticoids (cortisone), Estrogen [↑ during pregnancy], Atrial natriuretic hormone: 3. H+ secretion: // 4. K+ secretion: ↑ K+ secretion [in Hyperkalemia] → ↑ Na+ reabsorption → ↓ Na+ excretion, and vice versa. 5. Diuretics: most of diuretics ↓ Na+ reabsorption Potassium excretion:. Similar to sodium (65% at the proximal portion, 25% at the diluting ascending segment and only 10% remains at the late distal tubule. There, aldosterone affects the secretion of potassium at the late distal and early collecting ducts. This increases the remaining K to around 12% leading to excretion. There is also active K absorption at the late distal tubules but overshadowed by secretion. So in the absence of aldosterone, absorption occurs instead of secretion. Fluid volume excretion:. Depends on glomerulo-tubular balance. Glumerulo-tubular balance: means that if GFR increases, the tubular absorption increases to remove the extra amounts filtered. This balance is not exact and any factor affecting the GFR in addition to other factors affects fluid volume excretion. These factors are:. 1. Effect of tubular osmolar clearance:. The concept of osmolar diuresis. 2. Effect of plasma colloid osmotic pressure: sudden increase in plasma colloid osmotic pressure decreases the fluid excretion by: a- decreasing GFR b-increasing tubular re-absorption. 3. Effect of sympathetic stimulation: increased stimulation leads to afferent arteriole constriction leading to decreased GFR, and the opposite occurs. 4. Effect of arterial pressure: if all other factors remain constant, changes in arterial pressure markedly and this is due to:  a- hypertension increase glomerular pressure increasing GFR.  b- increasing the peritubular capillary pressure leading to a decrease in reabsorption and increasing urine output. 5. Effect of ADH: increased ADH leads to acute , water absorption, but chronic ADH loses its effect because of increasing arterial pressure, lower colloid osmotic pressure and concentration of osmolar substances in the glomerular filtrate will force water excretion according to intake.  Plasma clearance rate It is defined of the amount of blood cleaned of a substance per unit time. Clearance is a function of glomerular filtration, secretion from the peritubular capillaries to the nephron, and reabsorption from the nephron back to the peritubular capillaries.  Finding plasma clearance rate C = V x U/P C= plasma clearance rate in ml/min V=urine production rate in ml/min U=concentration of a substance in urine in mg/ml P=concentration of a substance in plasma in mg/ml Units of plasma clearance rate: ml/min Clinically, the clearance of another endogenous substance (normally present inside the body) called creatinine, is used in the measurement of GFR by the clearance concept. Mechanism if the kidney to regulate [. extra cellular fluid content: This depends on the presence of stretch reflexes in the atria and the presence of barorecpetors in the carotid, aortic and pulmonary arteries. In increase extra cellular fluid content, vascular fluid content increases, leading to stimulation of stretch and baroreceptors. These receptors lead to , A. Central nervous system reflexes →1- sympathetic inhibition → afferent arteriolar dilatation → increased GFR; →2- ADH inhibition → increased urine output). B. Atrial natriuretic factor (ANF) is released leading to increased Na excretion leading to increased water excretion. ?Questions I am happy that now you know more about me!!! THANK YOU