1. صدق الله العظيم الاسراء اية 58

2. By Dr. Abdel Aziz M. Hussein Lecturer of Medical Physiology

9. 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

10. Organic solutes as PAH, drugs, various amines and ammonia. Secretion

11. 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.

13. 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)

14. Outer Strip Inner Strip

16. 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

17. 1120 = NaCl 80 = Urea 600 = NaCl 600 = Urea

18. Ascending LH: Thick ALH: Epithelium: 1.Tall epithelium 2.Numerous microvilli 3.Much mitochondria 4.Basolateral border rich in Na-K pump 5.Apical border contain Na-K-Cl2 transporter

19. Basolateral border Apical border

20. Tight Junctions

21. TEPD + 5 to +15 mv Hypotonic fluid Na, Ca, Mg ++++++

22. 15% Water 25% Na (6000-900 meq/day) 30% Ca 65% Mg 10 % K Urea 150- 200 mosm/L

24. a) Distal convoluted tubule (early distal tubules b) Connecting tubules (late distal tubule) c) Collecting ducts

25. DCT CT CD

26. 1.Final adjustment of urine formation. 2.Reabsorption of 7-10% of filtered load of Na +. 3.Reabsorption of 10-15% of filtered lead of water. 4.Secretion of variable amount of H + & K +. 5.Major control site for Na +, K +, Ca 2+ & acid-base balance of body. Many of these functions are controlled by hormones.

29. 1.Represent early 2/3 of distal tubules. 2.Reabsorbs 4% of filtered load of Na +. 3.NaCl 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 mOsm/L (i.e. more hypotonic)  so, the diluting segments of the nephron are: thick ALH and early DCT.

31. 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 mV).

33. Important site for final adjustment of urine volume, reaction (pH) and composition. Include: cortical (CCD), outer medullary (MCD) & inner medullary (papillary) (PCD). Have 2 major cell types: 1. Principal cells. 2. Intercalated cells.

34. CCD MCD PCD

35. Proximal segmentDistal segment The main site of reabsorption of nutritional substances No reabsorption of nutritional substances Reabsorption of large quantities of salt & water Less absorption and smaller capacity: 9% of filtered NaCl & 17% Transport of salt and water occurs along small gradient so, fluid leaving PT is isotonic. Steep gradient in early distal tubule and the fluid leaving collecting duct is usually hypertonic. Na + concentration in urine is about 140 meq/L as plasma. Na + concentration in urine can be as low as 1 meq/L. Leaky tight junction.Tight tight junction between the epithelial cells causing the steep gradient. pH 6.9pH as low as 4.6 Na + reabsorption is coupled to water. Na + and water reabsorption are uncoupled. Not affected by aldosterone & ADH. Affected by Aldosterone & ADH.

38. General characters 1.About 2/3 (67%) of the filtered Na + with the same percentage of water i.e. iso-osmotic reabsorp. 2.TF Na / P Na ratio at the end of PT is one as it is iso- osmotic 3.In early PT, Na +, water, glucose, HCO 3, amino acids and organic anions as lactate, pyruvate, and phosphate …. all are absorbed 2ry to Na +. 4.In the late PT: Na + is absorbed with chloride mainly.

39. Paracellular Transport Transcellular Transport

40. Na-K pump Symport Antiport Occurs mostly at early segment of PT a) Carrier –mediated transport

41. Na Channels Na-K pump b) Channel –mediated transport

42. Na-K pump Electoneutral symport Electrogenic symport

43. Na-K pump Electoneutral antiport

44. Na-K pump Na channels Cl ions

45. Occurs mostly at late segment of PT Cl = 132 meq/L Cl = 105 meq/L a) Cl- derived Na Reabsorp. Early PT Late PT HCO3- ---------- Na+

46. Water a) Solvent drag Reabsorp. 3-5 mosmol/L NaCl PTC

49. % : 100% of glucose is reabsorbed in PT Na-K ATPase 2ry active transport Facilitated diffusion

53. 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

54. Amino acids e.g. glutamate and glycine are absorbed Na-dependent 2ry active transport The transport is limited due to saturation of the carrier

55. 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

56. They are absorbed by Na-dependent 2ry 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.

57. 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).

58. Primary Secondary Tertiary

63. About 25% of the filtered load of Na + Is actively reabsorbed by a common transporter for Na + - k + - 2Cl -. 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.

65. Hypotonic

67. CT and CDs reabsorb about 8% of the filtered load of Na +.

68. 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.

70. 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.

72. 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.

73. 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.

75. Types of cells; 2. Intercalated cell : a.Secretion of H + by either; H + ATPase K + - H + ATPase b. Reabsorb K +

79. Electrolyte balance Na homeostasis K homeostasis Water balance Regulation of water output pH regulation Reabsorption of filtered HCO3 Secretion of H

82. Intracellular 98% concentration of 130 - 150 meq/L Extracellular 2% concentration of 130 - 150 meq/L. Distribution:

83. 1. Regulation of protein and glycogen synthesis. 2. Control of cell volume3. Regulation of intracellular pH 4. RMP & action potential of neurons and muscles; thus affecting their excitability

84. InputOutput Shift of K between ICF and ECF K excretion by kidney Shift between ICF and ECF K intake

85. 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

86. 1.Na + - K + ATPase activity. 2.H + ion concentration 3.Body fluid osmolarity. 4.Vitality of the cell membrane

87. 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

88. 1.Increase H +  exchange with intra cellular K +  K + efflux  hyperkalemia 2.Decrease H +  opposite effect  hypokalemia

89.  Decrease ECF osmolarity  shift of water ICF together with K +  hypokalemia.  Increase ECF osmolarity  shift of water ECF together with K +  hyperkalemia.

90.  Exercise and cell lysis  K + efflux  hyperkalemia

91. 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 +.

97. K + secretion occurs 2ry 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 – 45mvolt).

98. 1.Plasma K + Increase K + concentration  increase K + secretion via: a.Activation of Na + - K + ATPase  increase intracellular K + b.Stimulation of aldosterone hormones.

99. 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 +

100. 3) Acid - base status: Acidosis  decrease K + secretion. Alkalosis  increase K + secretion.

101. 4) Aldosterone : Aldosterone induced proteins (AIP)

102. 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.

103. THANKS