Renal physiology-1

Renal physiology-1

1. Renal Physiology Dr. Osama El- Shahat Consultant Nephrologist Head of Nephrology Department New Mansoura General Hospital (international) ISN Educational Ambassador

2. BASIC AGAIN AND AGAIN

3. Lecture Outline Introduction Functions of the kidney Renal circulation & renal blood flow Physiological anatomy of the kidney Nephron & its types

4. Introduction – the kidney A retroperitoneal organ T11-L3 Normal size: 11-15cm in adults. located in the upper region of the abdominal cavity just above the waistline. protected by the ribcage. Right kidney usually shorter than the left (upper limit of variation in length between right & left 1.5 cm)

5. Functions of the kidney 1- Execratory function: a . Metabolites b . drugs c. toxins 2- Homeostatic function: Maintenance of water balance. Maintenance of electrolyte balance. Maintenance of acid-base balance.

6. Functions of the kidney 3- Endocrine (hormonal) secretory function: Renin by the juxtaglomerular cells (JG) Erythropoietin hormone by endothelial cells of peritubular capillaries of renal cortex Prostaglandins . 4- Endocrine (hormonal) metabolic function: The kidney converts vitamin D3 → active 1,25­dihydroxycholecalciferol by alpha one hydroxylase enzyme in cells of PCT under effect of PTH.

7. Urinary system consists of: Kidneys Ureters Urinary Bladder Urethra – The functional unit of the system Conducting & Storage components

8. The Kidney Diagram

9. Kidneys and their structures The Renal Arteries transport oxygenated blood from the heart and aorta to kidneys for filtration The Renal Veins Transport the filtered, deoxygenated blood from kidneys to the posterior vena cava and finally the heart

10. Kidneys and their structures Renal Capsule (inferior/superior) Outer membrane which encloses and protects kidneys against infections and trauma. The Renal Cortex Outer layer (granulated) of the kidney that contains most of the nephrons .

11. Kidneys and their structures The Renal Medulla Inner layer ( radially striated) of the kidney contains renal pyramids, renal papillae, renal columns, renal calyces (minor/major),renal pelvis and part of nephron , not located in the cortex Site for salt, water and urea absorption

12. Kidneys and their structures The Renal Pyramid Triangular shaped unit in the medulla houses the loop of Henle and collecting duct of the nephron The Renal Column Area between the pyramids, located in the medulla Used as a space for blood vessels

13. Kidneys and their structures The Renal Papillae The tips of the renal pyramids release urine into the calyces The Renal Calyces Collecting sacs that surround the renal papillae Transport urine from renal papillae to renal pelvis

14. Kidneys and their structure The Renal Pelvis Cavity which lies in the centre of the kidney and which extends into the ureter Collects urine from all of the calyces in the kidney

15. Kidneys and their structures The Ureters (right/left) Tubes that transports urine from the renal pelvis to the bladder The Urinary Bladder Hollow, expandable, muscular organ located in the pelvic girdle Functions as a temporary reservoir for urine

16. Kidneys and their structures Nephron Most basic microscopic structures of the kidneys Inside each kidney, there are about 1 million nephrons Physiological unit of the kidney used for filtration of blood, and reabsorption and secretion of materials

17. The Nephron Simplified view of its functions Glomerular Filtration Tubular Reabsorption Tubular Secretion Excretion

18. The Nephron Locations for filtration, reabsorption, secretion & excretion

19. The Kidney Nephron Diagram

20. Nephron structures and functions Afferent Arteriole Transport arterial blood to glomerulus for filtration Efferent Arteriole Transports filtered blood from glomerulus through the peritubular capillaries and the vasa recta, and to the kidney venous system

21. Nephron structures and functions Glomerulus The site for blood filtration operates as a nonspecific filter - removes both useful and non-useful material the product of the glomerulus – filtrate Bowman’s Capsule A sac that encloses glomerulus transfers filtrate from the glomerulus to the Proximal Convoluted Tubule (PCT)

22. Nephron structures and functions Proximal Convoluted Tubule ( PCT ) A thick, constantly active 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%) The primary site for secretion (elimination) of drugs, waste and hydrogen ions.

23. Nephron structures and functions The loop of Henle U-shaped tube that consists of a descending limb and an ascending limb. begins in the cortex, receiving filtrate from the PCT, extends into the medulla, and then returns to the cortex to empty into the distal convoluted tubule(DCT). Its primary role is to concentrate the salt in the interstitium , the tissue surrounding the loop.

24. Nephron structures and functions Decending Limb of the Loop of Henle A part of the counter current multiplier fully permeable to water and completely impermeable to solutes (salt particles) receives filtrate from the PCT, allows water to be absorbed and passes “salty” filtrate to the next segment. “Saves water and passes the salt”

25. Nephron structures and functions 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

26. Nephron structures and functions Distal Convoluted Tubule (DCT) Variably active portion of the Nephron receives dilute fluid from the ascending limb of the loop of Henle

27. Nephron structures and functions Collecting Duct variably active portion of the Nephron receives fluid from the DCT The last segment to save water for the body

28. Nephron structures and functions Peritubular Capillaries transport reabsorbed materials from the PCT and DCT into kidney veins and eventually back into the general circulation help complete the conservation process (reabsorption) that takes place in the kidney

29. PHYSIOLOGY

30. I am happy that now you know more about me!!!

31. Questions ?

32. Kidney nephron The nephrons are the functional units of the kidney and are the site of: 1. Filtration of blood 2. Maintainance of Renal blood pressure 3. Formation of urine 4. Counter current mechanism 5. Acid-base balance 6. Regulation of electrolytes 7. Reabsorption of materials 8. Secretion of materials( production of hormones) 9. Excretion of wastes

33. 1. Filtration of Blood The glomerulus is the site of filtration of blood

34. The Bowman’s capsule (basement membrane + podocytes ) filters blood, hold back large molecules such as proteins, passes through small molecules such as water, salts, and sugar Aids in the formation of urine

35. Podocytes : Also known as visceral epithelial cells Cells in the Bowman's capsule in the kidneys that wrap around the capillaries of the glomerulus leaving slits between them. They are involved in regulation of glomerular filtration rate (GFR). When podocytes contract, they cause closure of filtration slits. This decreases the GFR by reducing the surface area available for filtration.

36. 2. Maintainance of Renal Blood Pressure This process is achieved by the Juxtaglomerular apparatus.

37. The three cellular components of the apparatus are the juxtaglomerular cells macula densa , extraglomerular mesangial cells .

38. The Juxtaglomerular Apparatus

39. Function of the JC cells 1. Release of Renin Stimulus : Low blood pressure Action : Release of Renin Angiotensin Angiotensin I Angiotensin II Angiotensin II It acts as a vasoconstrictor to raise blood pressure. It stimulates the release of aldosterone hormone from the adrenal cortex.

40. 2. Release of Aldosterone hormone It stimulates the DCT to reabsorb salt. 3. Reabsorption of salt ( NaCl ) Salt reabsorption induces the movement of water to the blood by osmosis thereby raising the blood volume and hence increasing the blood pressure .

41. Function of the Macula Densa Cells It monitors the salt content of the blood. If concentration of salt is raised, the macula densa cells inhibit the release of renin from the JC cells. No release of renin No angiotensin II , No aldosterone . Blood pressure decreases until it is sent back to normal.

42. Function of the extra glomerular mesangial cells It secretes erythropoietin Erythropoietin is a glycoprotein hormone which controls erythropoiesis or red blood cell production.

43. 3. Formation of urine Takes place in 3 main steps; 1 . Ultrafiltration seeping of fluid from glomerular capillaries to the Bowman’s capsule along with useful substances (e.g. glucose, vitamins ,amino acids) 2 . Reabsorption along the nephron PCT; selective reabsorption of useful substances LOH, DCT and CD Reabsorption of water and salts 3 . Secretion from blood to tubule

44. 4.Counter Current Multiplier Down the descending limb of the LOH, fluid becomes more concentrated due to loss of water. Na + and Cl - concentration increase as fluid turns and heads on towards the ascending limb. All the way up osmotic pressure of fluid in LOH is almost equal to the osmotic pressure in interstitial fluid. The fluid again passes through hypertonic interstitial fluid loosing water again until into the collecting duct. The final product in the CD is urine!!!!

45. Counter current Multiplier Interstitial fluid should be hypertonic for water to be reabsorbed

46. 5 . Regulation of electrolyte Electrolytes are substances that become ions in solution and acquire the capacity to conduct electricity. The primary ions of electrolytes are sodium (Na + ), potassium(K + ), calcium (Ca 2+ ), magnesium (Mg 2+ ), chloride ( Cl − ), hydrogen phosphate (HPO 4 2− ), and hydrogen carbonate (HCO 3 − ). Maintenance of an electrolyte balance occurs so that the osmolarity of both the body fluids and the urine is the same. Maximum electrolyte balance is maintained by the release of hormones which are going to trigger the reabsorption of certain ions thereby preventing electrolyte disbalances .

47. ADH Also known as vasopressin Released by hypothalamus Stimulus: Low blood level Prevents the production of dilute urine Helps in reabsorption of water in kidneys Maintains osmolarity of plasma levels normal

48. 6 . Acid-base balance Forms part of human homeostasis Is important to maintain cellular stability Alterations in the acid-base balance are resisted by extracellular and intracellular chemical buffers and by respiratory and renal regulation. In acid-base balance, the kidney is responsible for 2 major activities : Reabsorption of filtered bicarbonate: 4,000 to 5,000 mmol /day Excretion of the fixed acids (acid anion and associated H + ): about 1 mmol /kg/day.

49. Formation of H+ Secretion from the organic acid and base secretory system (uric acid, antibiotics and diuretics). H 2 CO 3 H + + HCO 3 - In case of high H + H + is bound to ammonia, phosphate and bicarbonate to form NH 4 + , H 2 PO 4 - , CO 2 and H 2 O.

50. 7. Reabsorption of materials Nutrients such as glucose, amino acids and other metabolites are reabsorbed in the medulla such that the body does not lose important nutrients. Location : proximal convoluted tubule situated in the cortex of the kidney

51. 8. Secretion of substances Release of several substances occur in order to aid in the functions of the kidney : Calcitriol ( activated form of vitamin D promotes intestinal absorption of calcium and the renal reabsorption of phosphate ) Renin Erythropoietin ADH Prostaglandins Kinins 1,25-dihydroxyvitamin D3

52. 9. Excretion of wastes The kidney is also involved in the excretion of wastes such as: Urea ( from protein metabolism) Uric acid ( from nucleic acid metabolism ) Creatinine ( from metabolic breakdown of creatine phosphate ) End-products of Hb metabolism Metabolites of hormones Foreign substances : drugs, pesticides, other chemicals ingested in food

53. Finding the amount of a substance excreted per unit time Given Amount filtered in NaCl g/day Amount reabsorbed in NaCl g/day Amount excreted in NaCl g/day Amount excreted = Amount filtered – Amount reabsorbed

54. 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.

55. 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

56. I am happy that now you know more about me!!!

57. Questions ?

58. 4.Counter Current Multiplier A system of limbs running in opposite directions Consists of; Descending limb and Ascending limb of the Loop of Henle. Helps in the absorption of water from fluid found in the LOH

59. Counter current multipier Down the descending limb of the LOH, fluid becomes more concentrated due to loss of water. Na + and Cl - concentration increase as fluid turns and heads on towards the ascending limb. All the way up osmotic pressure of fluid in LOH is almost equal to the osmotic pressure in interstitial fluid. The fluid again passes through hypertonic interstitial fluid loosing water again until into the collecting duct. The final product in the CD is urine!!!!

60. Kidney disorders Are diseases that affect the kidney. Usually affects both kidneys. The kidneys ability to remove waste products and control water balance is severely affected. This causes an accumulation of waste products and fluids causing severe uremia . Uremia=kidney failure

61. There is a rich blood supply surrounding each nephron, which is important for the reabsorption process. The cubical epithelial cells lining the tubule invaginates to form intercellular and subcellular spaces next to the basement membrane of the capillaries. Glucose and amino acids are absorbed into the blood by active transport across the infolded membranes and subcellular spaces. These solutes diffuse from the filtrate into the cells, then through to the subcellular spaces and then into the bloodstream. This sets up a concentration gradient which is maintained as the reabsorbed solutes are carried away by the flowing blood.

62. Other mineral ions are also actively reabsorbed the way glucose and amino acids are. As so many of the solutes are removed, the filtrate becomes hypotonic (lower concentration of solute molecules) than the surrounding blood, stimulating water to move via osmosis from the filtrate to the blood. This leads to the filtrate and the blood being isotonic (same solute concentrations) by the time the filtrate reaches the end of the tubule. However, since urea is not actively reabsorbed, its concentration in the filtrate is much higher than in the blood and some of the urea unavoidably diffuses back into the bloodstream and is taken away.

63. THE LOOP OF HENLE This hairpin-bend structure has a descending limb and an ascending limb and is found in the medulla of the kidney. The descending limb has thin walls permeable to water and penetrates deep into the medulla but the ascending limb has thicker, relatively impermeable walls that returns to the cortex. Surrounding the loop is a network of capillaries, one part of which has the same hairpin structure and is called the vasa recta.

64. Urine formation: Filtration from of plasma from the glomerular capillaries into the Bowman’s space. Movement from the tubular lumen to the peritubular capillaries is the process called tubular reabsorption Movement from the peritubular capillaries to the tubular lumen is the process known as tubular secretion BASIC RENAL PROCESS

65. Once in the tubule the substance need not be excreted , it can be reabsorbed. These processes do not apply to all substances. E.g. Glucose (completely reabsorbed.) Toxins ( Secreted and not reabsorbed)

66. Metabolism by Tubules The cells of the renal tubules synthesize glucose and add it to the blood. Cells also catabolize substances such as peptides which are taken from the tubular lumen or peritubular capillaries. Catabolism eliminates these substances from the body.

67. OSMOLARITY: Osmolarity is the measure of solute concentration, defined as the number of osmoles ( Osm ) of solute per liter (L) of solution( osmol /L or Osm /L). NOTE : Molarity measures the number of moles solute per unit volume of solution ,

68. Counter current multiplier Na+ is actively pumped out of the ascending limb into the interstitial fluid. Cl - follows Na+ passively Increases the Na+ and Cl - of interstitial fluid by about 4 times. Water seeps out of the of the descending limb into the interstitial fluid by osmosis

69. The two types of Nephrons Cortical The loop of Henle does not extend past the cortex of the kidney. Juxtamedullary Loop of Henle extends past the cortex and into the medulla of the kidney.