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Physiology of kidney zamala.pdf

  1. Iman sarhan Prof of nephrology Ain Shams university
  2. ILO’s • To know the gross external anatomy of the kidney. • To recognize the site of kidney in abdomen. • To understand the arterial supply and venous drainage and innervations. • To understand the histological structure of the kidney. • To understand the functional unite (nephron). • To list different factor affecting glomerular filtration. • To know the molecular structure of glomerular BM. • To recognize different types of kidney tubule. • To understand the function of different parts of nephron. • To understand the endocrinal function of kidney. 2
  3. Gross External Anatomy of the Kidney • The kidneys are paired organs, 11–14 cm in length in adults, 5–6 cm in width and 3–4 cm in depth. • The kidneys lie retroperitoneally on either side of the vertebral column at the level of T12 to L3. • The renal parenchyma comprises an outer cortex and an inner medulla.
  4. Gross External Anatomy of the Kidney  Near the center of the concave medial border of the kidney is a vertical fissure called the hilum, through which the ureter leaves and blood vessels, lymphatic vessels and nerves enter and exit.
  5. External Anatomy of Kidney Three layers of tissue surround each kidney: 1. The innermost renal capsule 2. The adipose capsule 3. Outer renal fascia.  Both kidneys rise and descend several centimeters with respiration  Innervations : renal capsule and ureters are innervated via T10–12 and L1 nerve roots.
  6. Internal Anatomy of Kidney • Gross Anatomy of the Kidney
  7. Internal Anatomy of the Kidney The nephron is the functional unit of the kidney.Each kidney contain 1 million nephron.
  8. 9 Renal vasculature
  9. The Nephron • Kidney has over 1 million nephrons composed of a corpuscle and tubule • Renal corpuscle = site of plasma filtration – glomerulus is composed of capillaries where filtration occurs – glomerular (Bowman’s) capsule is double walled epithelial cup that collects filtrate • Renal tubule – proximal convoluted tubule – loop of Henle dips down into medulla – distal convoluted tubule • Collecting ducts and papillary ducts drain urine to the renal pelvis and ureter.
  10. Juxstaglomerular apparatus Consists of 1. Macula densa cells lining early DCT between aff. & eff. arterioles - stimulated by Nacl - Important in auto-regulation 2. Juxtaglomerular cells - Modified muscle cells in the media of aff. arterioles - Stimulated by blood pressure - Secret renin 3. Lacis cells - Between aff & eff arterioles - Contain renin
  11. Basic Processes of Urine Formation • Nephrons and collecting ducts perform 3 basic processes 1. Glomerular filtration a portion of the blood plasma is filtered into the kidney Filtration is a function of size of the molecules 2. Tubular reabsorption • water & useful substances are reabsorbed into the blood 3. Tubular secretion • Secretion is important because not all wastes are moved into the filtrate at filtration. • Secretion is often the main mechanism by which some compounds like drugs are removed from the blood.
  12. Glomerular filtration of plasma  Tubular reabsorption Tubular secretion Glomerular filteration rate GFR volume of glomerular filtrate formed by both kidneys per minute 125ml/min - 7.5 L/h - 180L/ day Excretion of any substance= filtration –reabsorption + secretion
  13. Net Filtration Pressure Net filtration pressure (10)=Glomerular hydrostatic pressure (55)-capillary hydrostatc pressure (15) -blood osmotic pressure (30)
  14. Determination of the Glomerular Filtration Rate • Clearance is the amount of substance that cleared from circulation per min. • GFR is measured by determining the plasma concentration and excretion of a substance  • 1. Neither absorbed nor secreted by the renal tubules. 2. Freely filterable across the glomerular membranes. 3. Not metabolized or produced by the kidneys. Inulin, 5Kda is the classic marker substance infused to measure GFR. GFR= Ui XV /Pi • 17
  15. • iothalamate and iohexol, and these compounds can be administered to patients to measure GFR. • Creatinine clearance. – The clearance of creatinine is slightly greater than GFR (15% to 20%) because some creatinine is secreted. • Cystatin. • Typical normal values for GFR in adults are 100 mL/min for women and 120 mL/min for men. 18
  16. Normal Glomerular Capillary • Urine formation begins at the glomerular filtration barrier. • The glomerular filter through which the ultrafiltrate has to pass consists of three layers: the fenestrated endothelium, the intervening glomerular basement membrane, and the podocyte slit diaphragm. • The normal thickness of the basement membrane equals about 250–300 nm. • The spaces between foot processes, with diameters of 20–60 nm, are called filtration pores, by which filtered fluid reaches the urinary space
  17. 21 Normal Glomerular Capillary Permeable to Water Small solute Myoglobin (16.9 kDa) Inuline 5 Kda Albumin 70 KDa Impermeable to
  18. Reabsorption Routes Active and Passive Transport Processes • Paracellular reabsorption – 50% of reabsorbed material moves between cells by diffusion in some parts of tubule • Transcellular reabsorption – material moves through both the apical and basal membranes of the tubule cell by active transport
  19. • There are four major types of carrier-mediated transporters: – Facilitated diffusion: carrier proteins expend no energy moving a molecule along its concentration gradient. – Active transport: energy is expended by a carrier protein to move a molecule against its concentration gradient. – Cotransport: multiple molecules are moved along at least one of the molecule's concentration gradient. – Countertransport: at least two molecules are moved in opposite directions following one of their concentration gradients. 23
  20. Reabsorption in the PCT • Glucose, amino acids, lactic acid, water-soluble vitamins and other nutrients are completely reabsorbed in the first half of the proximal convoluted tubule
  21. PCT 26 These solutes are present at the same concentration in proximal tubular fluid as in plasma. Approximately 60% of the filtered Na+, Cl−, K+, Ca2+, and H2O and more than 90% of the filtered HCO3 − are absorbed along the proximal tubule.
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  23. Water Handling by the Human Kidney • Filtered Water…………………180 L/day • Reabsorbed Water……………178.5 L/day • Excreted Water…………………..1.5 L/day • Fractional Reabsorption.…..…..99.2% 28
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  26. Glucose handling by the kidney 31 The tubular transport maximum for glucose (TmG).When glucose delivery exceeds the TmG, the excess glucose is excreted in the urine There is a concentration of a molecule in the tubular fluid at which point the carriers for that molecule cannot reabsorb all of the molecule because they are saturated. This concentration is considered the Tm or the renal threshold, above which the molecule will be found in the urine.
  27. 32 Glucose handling by the kidney
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  29. Na handling © iman sarhan Urinary Na excreation 100-300 meq/l= intake 99 % reabsorped Filtered Na= plasma conc X GFR Na reabsorption is active process is derived from Na-K -ATPase All natriureteric drug act on tubules to inhibit Na reabsoption and increase the Na FE 20 to 25 % 60% 3-5%
  30. Fraction excretion of sodium (FENa ) 37 FENa is usually less than 1%. FENa can also exceed 1% in disease states in which the tubular transport of Na+ is impaired.
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  32. Renal Handling of Potassium 39 ADH, antidiuretic hormone;ALDO, aldosterone; CCT, cortical collecting tubule; DCT, distal convoluted tubule; ICT, initial collecting tubule; MCD, medullary collecting duct; PCT, proximal tubule; R, reabsorption;S, secretion; TAL, thick ascending limb.
  33. Physiology of Renal Acidification Proximal acidification : PCT absorption of HCO3 ( 85%) Distal Urinary acidification.  Reabsorption of HCO3 (15%)  Excretion of fixed acids through buffering & Ammonia recycling and excretion . The urine PH can be lowered to a max. 4.5-5 in presence of acid load. This maintained the plasma H+ and PH within a narrow limits The generated acid =50-100 meq/day The kidney filters approximately 4320 meq/day of HCO3- (24 meq/L ×180L/day). Secrete 4320 meq/day of hydrogen ions +the daily acid load.
  34. Renal autoregulation Regulation of renal blood flow (RBF) and glomerular filtration rate (GFR) 41 Autoregulation Hormonal Neural Sympathetic stimulation=>VC of blood vessls of kidney Noradrenaline and angiotensin II=> renal VC=>dec. RBF. Prostaglandins and Kallikrein-kinine system=>renalVD. Baroreceptor in afferent and efferent arteriol will detect the changes in pressure
  35. Autoregulation of GFR  The most important autoregulation response occurs upon decrease of systemic blood pressure:  The afferent arterioles dilate (to increase blood flow to the glomerulus), the supporting cells of the glomerulus capillaries relax (causing dilation and increased blood flow), and the efferent arterioles constrict (causing increased blood pressure by way of increased post-nephron resistance).  Upon increased blood pressure at the renal afferent arterioles, the walls are stretched and smooth muscles are triggered to contract, thus decreasing the diameter and decreasing the blood flow to the glomerulus. 42
  36. RAS and BP control 43
  37. Renin Angiotensin Aldosterone 44
  38. Hormonal control of renal function ADH 45
  39. Regulation of Body Fluid Osmolarity water intake is low or fluid is lost • Urine volume =1 L/day (<0.5 mL/min), • Uosm) may reach 1200 mOsm/kg H2O water intake is high • Urine volume=14 L/day (10 mL/min), • osmolality (75 to 100 mOsm/kg) 46 The hormone responsible for the regulatory changes in urine volume and tonicity is ADH (vasopressin).
  40. Effect of PTH on the kidney 47
  41. Renal Function  Filtration occurs exclusively in the renal corpuscle, across the filtration membrane.  Water and solute reabsorption occurs primarily along the proximal convoluted tubules, but also elsewhere along the renal tubule and within the collecting system.  Active secretion occurs primarily at the proximal and distal convoluted tubules.  Regulation of the final volume and solute concentration of the urine results from the interaction between the collecting system and the nephron loops–especially the long loops of the juxtamedullary nephrons. 48
  42. Hormonal functions  Erythropoietin is produced by interstitial peritubular cells in response to hypoxia.  In vitamin D metabolism, the kidneys hydroxylate 25- hydroxycholecalciferol to the active form, 1,25- dihydroxycholecalciferol.  Renin is secreted from the juxtaglomerular apparatus in response to reduced afferent arteriolar pressure, stimulation of sympathetic nerves, and changes in sodium content of fluid in the distal convoluted tubule at the macula densa. 49
  43. Summary  Kidney is bean shape located retro-peritoneal between T12-L3, measure 12x6x3cm.  Concave medial border of the kidney is a vertical fissure called the hilum, through which the ureter leaves and blood vessels, lymphatic vessels and nerves enter and exit.  Unit function of kidney is nephron (2million nephron receive 25% of cardiac output).  Main function :filtration through glomerulus, followed by tubular reabsorption and secretion, which lead to water and electrolyte regulation, excretion of waste product, toxins.  Filtration controlled by filtration pressure, and pores of glomerular cap membrane.  Endocrinal function: excretion of erothropoetin, activation of vit D, secretion of renin. 50