Kidney By Dr Abdel Aziz M Hussein Lecturer
Kidney By Dr. Abdel Aziz M. Hussein Lecturer of Medical Physiology
Proximal Tubules
1. Glucose, amino acids, vitamins, protein → 100% 2. HCO 3 - → 90% 3. inorganic phosphate → 80% 4. Na+ & water → 2/3 or 65% 5. K+, Ca 2+, Mg 2+ & urea → Variable amount Reabsorption
Organic solutes as PAH, drugs, various amines and ammonia. Secretion
Overall Functions of Proximal Tubules a) Reabsorption of: 1. All filtered glucose, amino acids, vitamins, protein and Kreb’s cycle intermediates. 2. About 2/3 of filtered load of Na+ & water. 3. About 90% of the filtered load of HCO 3 -. 4. About 80% of the filtered inorganic phosphate. 5. Variable amount of K+, Ca 2+, Mg 2+ & urea. b) Secretion of • Organic solutes as PAH, drugs, various amines and ammonia.
Loop of Henle
Loop of Henle Descending LH: Starts: • At junction ( ) outer and inner strips of outer medulla Epithelium: 1. Very thin endothelial –like cells. 2. Few microvilli 3. Few mitochondria 4. Permeability (high to water, hard to solutes)
Outer Strip Inner Strip
Loop of Henle Ascending LH: Thin ALH: • Presents only in long loops Epithelium: 1. Similar to DLH 2. Permeability • Impermeable to water • Permeable to solutes → allow Na reabsorption, and Urea secretion
1120 = Na. Cl 80 = Urea 600 = Na. Cl 600 = Urea
Loop of Henle Ascending LH: Thick ALH: Epithelium: 1. 2. 3. 4. 5. Tall epithelium Numerous microvilli Much mitochondria Basolateral border rich in Na-K pump Apical border contain Na-K-Cl 2 transporter
Apical border Basolateral border
Tight Junctions
Hypotonic fluid TEPD + 5 to +15 mv Na, Ca, Mg + + +
Overall Functions of LH 150 - 200 mosm/L 30% Ca 65% Mg 10 % K 25% Na (6000 -900 meq/day) 15% Water Urea
Distal Segment of Nephron
Distal Segment of Nephron • a) Distal convoluted tubule (early distal tubules • b) Connecting tubules (late distal tubule) • c) Collecting ducts
DCT CT CD
Overall Functions of Distal Segment 1. 2. 3. 4. 5. Final adjustment of urine formation. Reabsorption of 7 -10% of filtered load of Na+. Reabsorption of 10 -15% of filtered lead of water. Secretion of variable amount of H+ & K+. Major control site for Na+, K+, Ca 2+ & acid-base balance of body. • Many of these functions are controlled by hormones.
Distal Convoluted Tubules
Characters of DCT 1. Represent early 2/3 of distal tubules. 2. Reabsorbs 4% of filtered load of Na+. 3. Na. Cl is transported by a Na+ - Cl- transporter located at apical border. 4. This transporter is inhibited by thiazide diuretics. 5. The basolateral Na+- K+ ATPase together with that of thick ALH has highest activity of any nephron segment. 6. The osmolarity of tubular fluid leaving DCT is 100 m. Osm/L (i. e. more hypotonic) so, the diluting segments of the nephron are: thick ALH and early DCT.
Connecting Tubules • It is the late 1/3 of distal tubules. • As the collecting duct, its cell types are principal and intercalated cells. • Has variable water permeability according to ADH level. • Its TEPD is negative (about -45 m. V).
Collecting Ducts • Important site for final adjustment of urine volume, reaction (p. H) and composition. • Include: cortical (CCD), outer medullary (MCD) & inner medullary (papillary) (PCD). • Have 2 major cell types: • 1. Principal cells. • 2. Intercalated cells.
CCD MCD PCD
Proximal segment Distal segment The main site of reabsorption of No reabsorption of nutritional substances Reabsorption of large quantities Less absorption and smaller of salt & water capacity: 9% of filtered Na. Cl & 17% Transport of salt and water occurs Steep gradient in early distal tubule along small gradient so, fluid and the fluid leaving collecting leaving PT is isotonic. duct is usually hypertonic. Na+ concentration in urine is about Na+ concentration in urine can be 140 meq/L as plasma. as low as 1 meq/L. Leaky tight junction. Tight tight junction between the epithelial cells causing the steep gradient. p. H 6. 9 p. H as low as 4. 6 Na+ reabsorption is coupled to Na+ and water reabsorption are water. uncoupled. Not affected by aldosterone & Affected by Aldosterone & ADH.
Na Handling
Na Handling
Na Reabsorp. in Proximal Tubules General characters 1. About 2/3 (67%) of the filtered Na+ with the same percentage of water i. e. iso-osmotic reabsorp. 2. TFNa / PNa ratio at the end of PT is one as it is isoosmotic 3. In early PT, Na+, water, glucose, HCO 3, amino acids and organic anions as lactate, pyruvate, and phosphate …. all are absorbed 2 ry to Na+. 4. In the late PT: Na+ is absorbed with chloride mainly.
Transcellular and Paracellular Transport Transcellular Transport
Transcellular Transport • Occurs mostly at early segment of PT a) Carrier –mediated transport Symport Antiport Na-K pump
Transcellular Transport b) Channel –mediated transport Na Channels Na-K pump
Transcellular Transport Na-K pump Electrogenic symport Electoneutral symport
Transcellular Transport Na-K pump Electoneutral antiport
Transcellular Transport Cl ions Na-K pump Na channels
Paracellular Transport • Occurs mostly at late segment of PT a) Cl- derived Na Reabsorp. Early PT HCO 3 Cl = 105 meq/L Cl = 132 meq/L Na+ - Late PT
Paracellular Transport a) Solvent drag Reabsorp. 3 -5 mosmol/L Water Na. Cl PTC
Absorptive and Secretory + Function in PT Related to Na Reabsorption
Glucose Reabsorption
Glucose Reabsorption • % : 100% of glucose is reabsorbed in PT 2 ry active transport Na-K ATPase Facilitated diffusion
Glucose Reabsorption
Glucose Reabsorption
Glucose Reabsorption • This process is saturable and rate limited, due to saturation of the carrier, and it has a Tm. • The excess filtered glucose is excreted in urine as in DM. • Also; phlorizin competes with glucose for this transporter, thereby inhibiting glucose reabsorption • Galactose can compete with glucose at the luminal border, so increase plasma glucose as in pregnancy glucose appears in urine
Amino acids Reabsorption • Amino acids e. g. glutamate and glycine are absorbed Na-dependent 2 ry active transport • The transport is limited due to saturation of the carrier
Amino acids Reabsorption • Proteins are reabsorbed after digestion by brush border enzymes into amino acids or they may be absorbed by endocytosis • This process is easily saturated, so large leakage of proteins in glomeruli → proteinuria
Reabsorption of Organic acids • They are absorbed by Na-dependent 2 ry active transport. • There are 2 transport systems; 1. One for monocarboxylates as lactate, pyruvate. 2. Other for di-carboxylates as malate, succinate and for tri-carboxylates as citrate.
Secretion of Organic anions and cations • As PAH, oxalate, urate, creatinine and drugs as penicillin and aspirin. • Secretion occurs by a Tm-limited process using transporters with low specificity (i. e. some anions and cations compete with each others for same transport system).
Secretion of PAHA Primary Secondary Tertiary
Na Handling
Na Reabsorption in Thick ALH
Reabsorption of Na by Thick ALH • About 25% of the filtered load of Na+ • Is actively reabsorbed by a common transporter for Na+ - k+ - 2 Cl-. • This transporter is inhibited by the loop diuretics as frusemide and edecrine. • This process plays a key role in counter current multiplier system, responsible for medullary gradient.
Hypotonic
+ Na Reabsorption in the DT and CD
Na Handling in distal tubule CT and CDs reabsorb about 8% of the filtered load of Na+.
Na Handling in DCT • • 4% of filtered Na+ By common carrier with Cl-. Is inhibited by thiazide diuretics. Is impermeable to water, and the fluid leaving it is more hypotonic • So, thick ALH and early distal tubules are called the diluting segments of the nephron.
Late distal tubule (connecting tubule) and CD • Types of cells; 1. Principle cell: a. Reabsorbs Na+ via special channels. • Is influenced by aldosterone (2% filtered Na ) b. Reabsorbs water (under control of ADH). c. Secrete K+: • K+ secretion is influenced by aldosterone hormone.
Late distal tubule (connecting tubule) and CD
Late distal tubule (connecting tubule) and CD • Na+ is actively reabsorbed by the principal cell of the CT and cortical CD mainly and to less extent by the outer MCD • Na+ diffuses passively from tubular fluid into the cell via apical epithelial Na+ channel (blocked by amiloride diuretics) • It is actively pumped through the basolateral side, to the interstitium by Na+ - K+ ATPase. • K+ enters the cell by the basolateral Na+ - K+ ATPase • High intracellular K+ → exits the cell via a basolateral K+ channel to the interstitium (recycling) or secreted via apical K+ channels to tubular fluid.
Late distal tubule (connecting tubule) and CD • K+ secretion by these segments is the primary determination of K+ secretion and excretion in urine; therefore regulating K+ balance • The absorption of Na+ across the apical border makes the TEPD –ve up to -45 mv • This help secretion of either K+ or H+ or reabsorption of Cl- to paracellular space.
Late distal tubule (connecting tubule) and CD • Types of cells; 2. Intercalated cell : a. Secretion of H+ by either; • H+ ATPase • K+- H+ ATPase b. Reabsorb K+
Transporters involved in movements of Na+ & Cl-
Role of Kidney in Homeostasis
Role of Kidney in Homeostasis Electrolyte balance Na homeostasis K homeostasis Water balance Regulation of water output p. H regulation Reabsorption of filtered HCO 3 Secretion of H
Role of Kidney in Na Homeostasis
Role of Kidney in K Homeostasis
K Balance Distribution: Intracellular 98% concentration of 130 - 150 meq/L Extracellular 2% concentration of 130 150 meq/L.
Functions of K 1. Regulation of protein and glycogen synthesis. 2. Control of cell volume 3. Regulation of intracellular p. H 4. RMP & action potential of neurons and muscles; thus affecting their excitability
Regulation of Extracellular Input Output K intake K excretion by kidney Shift between ICF and ECF Shift of K between ICF and ECF + K level
Shift of K between ICF and ECF • K+ is primary an intracellular cation • 80% of the ingested K+ is moved temporary ICF to prevent rapid elevation of ECF K+ concentration which is dangerous
Factors affecting Shift of K between ICF and ECF 1. Na+ - K+ ATPase activity. 2. H+ ion concentration 3. Body fluid osmolarity. 4. Vitality of the cell membrane
Na-K ATPase a) Activators: insulin, β agonist, aldosterone, high K • These factors increase K shift into ICF → hypokalaemia b) Inhibitors: digitalis • These factors decrease K shift into ICF → hyperkalemia
H ion concentration 1. Increase H+ exchange with intra cellular K+ efflux hyperkalemia 2. Decrease H+ opposite effect hypokalemia
Body fluid osmolarity v. Decrease ECF osmolarity shift of water ICF together with K+ hypokalemia. v. Increase ECF osmolarity shift of water ECF together with K+ hyperkalemia.
Vitality of Cell Membrane v. Exercise and cell lysis K+ efflux hyperkalemia
Renal Handling of K 1. At the PT: about 80% of the filtered K+ 2. At thick ALH: 10% of K+ 3. Connecting tubule and cortical collecting ducts where the actual K+ balance occurs: • K+ is secreted by the principle cells in amount ranging from 2% to 180% of the filtered K+.
Renal Handling of K
Renal Handling of K
K handling In PT
K handling in thick ALH
K handling In DCT and CDS
Renal Handling of K • K+ secretion occurs 2 ry to Na+ reabsorption→ help increase of the electrochemical gradient for K+ secretion • High gradient for K secretion is; 1. high K+ concentration inside the cell 2. –ve lumen (TEPD is – 45 mvolt).
Factors affecting K secretion in Principal Cells 1. Plasma K+ • Increase K+ concentration increase K+ secretion via: a. Activation of Na+ - K+ ATPase increase intracellular K+ b. Stimulation of aldosterone hormones.
Factors affecting K secretion in Principal Cells 2. Tubular flow rate: • Increase tubular flow rate increase K+ secretion via: a. Delivery of Na+ to the principle cell. b. Dilution of the secreted K+
Factors affecting K secretion in Principal Cells 3) Acid - base status: • Acidosis decrease K+ secretion. • Alkalosis increase K+ secretion.
Factors affecting K secretion in Principal Cells 4) Aldosterone : • Aldosterone induced proteins (AIP)
Factors affecting K secretion in Principal Cells • So, the delay of action of aldosterone for 1 -2 hours could be explained by the period necessary for the synthesis of AIP • The effectiveness of the kidney to control Na+ excretion is bitter than that for K+. • For example, in complete Na+ deprivation, only 0. 01% of the filtered Na+ is excreted in urine while in complete deprivation of K+, 2% of the filtered K+ is secreted and excreted in urine and so, hypokalemia can develop.
THANKS
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