Unit 4 urinary system

Based on the syllabus of Purbanchal University for the third semester B.Pharmacy Students

1. Biswash Sapkota ( M.Pharm ) ( B.Pharm ) Lecturer, MBAHS Unit IV URINARY SYSTEM

2. Introduction It is one of the excretory systems of the body. It consist of following structures 2 kidneys , which secrets urine 2 ureter which convey urine from kidney to the urinary bladder 1 urinary bladder where urine collects and is temporarily stored 1 urethra through which urine is discharged from urinary bladder to exterior .

3. Functions of Urinary system Removes the metabolic waste Regulates the blood volume and blood pressure Regulates the plasma concentration of sodium, potassium, chloride etc Helps to stabilize blood pH Conserves valuable nutrients

4. Regulation of Acid-Base Balance. contribute to acid-base regulation, along with lungs and body fluid buffers, by excreting acids by regulating the body fluid buffer stores. kidneys are the only means of eliminating certain types of acids, such as sulfuric acid and phosphoric acid, generated by the metabolism of proteins. Regulation of Arterial Pressure. long-term regulation by excreting variable amounts of sodium and water. 5

5. short-term regulation by secreting vasoactive substances- renin , that lead to the formation of vasoactive products (e.g. angiotensin II) Regulation of Erythrocyte Production. secrete erythropoietin, which stimulates the production of RBC, account for almost all the erythropoietin secreted into the circulation. In people with severe kidney disease or people with kidney removal, and have been placed on hemodialysis , severe anemia develops as a result of decreased erythropoietin production. 6

6. Regulation of 1,25–Dihydroxyvitamin D3 Production. produce the active form of vitamin D- 1,25- dihydroxyvitamin D3 ( calcitriol ). Calcitriol plays an important role in calcium and phosphate regulation. Glucose Synthesis Kidneys synthesize glucose from amino acids and other precursors during prolonged fasting, by the process known as gluconeogenesis . The kidneys’ capacity to add glucose to the blood during prolonged periods of fasting rivals that of the liver. 7

7. Functions of kidney Regulation of: body fluid osmolarity and volume electrolyte balance acid-base balance blood pressure Secretion of : erythropoietin 1,25-dihydroxy vitamin D3 (vitamin D activation) Renin prostaglandin Excretion of : metabolic products foreign substances (pesticides, chemicals etc.) excess substance (water, etc) 8

8. Kidneys Lies on the posterior abdominal wall, one on each side of vertebral column, behind the peritoneum and below the diaphragm. They extend from 12 th thoracic to the 3 rd lumbar vertebra The right is usually slightly lower then the left, because of the considerable space occupied by the liver. They are bean shaped organ about 11 cm long, 6cm wide, 3cm thick and weigh 150g They are embedded in held in position by a mass of fat. A sheat of fibroelastic renal fascia encloses the kidney and renal fat.

9. Gross structure of kidney When longitudinal section of kidney is viewed with naked eyes following reasons and structure are observed. A Fibrous capsule , surrounding the kidney The Cortex a reddish brown layer of the tissue immediately below the capsule and outside of pyramids The Medulla , the innermost layer consisting of pale conical shaped striations, the renal pyramids The Hilum is the concave medial border of kidney where the renal blood and lymph vessels, the ureter and nerves enter

10. The renal pelvis is funnel shaped structure which acts as a receptacle for urine formed by kidney . It has the number of branches called calyces, which surround the pyramids. Urine formed in the kidney passes through the papilla at the apex of pyramid into minor calyx , then to major calyx before passing through the pelvis into ureter. Pelvis has smooth muscle and lined with transitional epithelium so this acts as the pacemaker cells in the walls of the calyces propels urine through the pelvis and the ureters to the bladder .

11. Microscopic structure of Kidney The kidney is composed of about 1-2 million of functional units, the nephrons and a smaller number of collecting ducts The collecting ducts transport the urine through the pyramids to the calyces and renal pelvis The collecting ducts are supported by small amount of connective tissue, containing blood vessels, nerves and lymph nodes .

12. The nephron The nephron consists of a tubule closed at one end, the other end opening into a collecting tubule. The closed end is indented to form cup shaped glomerular capsule ( Bowmans Capsule) which almost completely encloses a network of tiny arterial capillaries the glomerulus After glomerulus, the remainder of nephron is about 3cm long and is described as : The proximal convoluted tubule The medullary loop (loop of Henle) The distal convoluted tubule, leading into a collecting duct . Collecting ducts unite forming larger ducts that empty into minor calyces

13. The kidney receives 20% of cardiac output After entering the kidney at hilum the renal artery divides into smaller arteries and arterioles . In cortex an arteriole, the afferent arteriole enters each glomerular capsule and then subdivides into cluster of tiny arterial capillaries forming glomerulus. The blood vessels leading away from glomerulus is efferent arteriole. The afferent arteriole has a larger diameter than efferent arteriole which increase the pressure inside the glomerulus and drives filtration across glomerular capillary walls.

14. The efferent arteriole divides into a second peritubular capillary network which wraps around the reminder of tubule allowing between the fluid in tubule and blood stream. The blood vessels of the kidney are supplied by both sympathetic and parasympathetic nerves. The presence of both the branches of ANS controls renal blood vessel diameter and renal blood flow independently and autoregulation

15. NOTE (IMP) Glomerulus has fenestrated capillaries in endothelium cells. Glomerulus basement membrane has middle layer of lamina dense and the upper and lower region has heparin sulfate (lamina rera interna and externa). Basement membrane is negatively charged. The lower region is attached with podocytes. Bowmans capsule has viscearal and parietal layer Visceral region has podocytes (leg like structure). The space between podocytes is called filtration slit and contain nephrin protein.

16. Formation of urine The kidneys form urine which passes through the ureters to the bladder for storage prior to excretion. The composition of urine reflects the activities of nephrons in maintenance of homeostasis. Waste products of protein metabolism are excreted, electrolyte balance is maintained and pH is maintained by the excretion of hydrogen ions. There are three processes involved in formation of urine: Simple filtration Selective reabsorption Secretion

17. 1. Simple filtration Filtration take place through the semipermeable walls of glomerulus and glomerulus capsule. Water and large number of small molecules pass through, although some are reabsorbed later. Blood cells, plasma proteins, and other large molecules are unable to filter through and remain in the capillaries. The filtrate in glomerulus is very similar in composition to plasma with the important exception of plasma proteins. The filtration occurs due to difference in blood pressure in glomerulus and pressure of filtrate in glomerulus capsule .

18. The volume of filtrate formed by both kidneys each minute is called the glomerular filtration rate (GFR). In a healthy adult the GFR is about 125ml/min ie 180litres of dilute filtrate are formed each day by two kidneys. In one minute around 1200ml of blood enters the glomerulus, out of this only 625ml undergoes filtration process while 575ml goes to efferent arterioles. Out of 625ml only 20% get filtered which is 125ml of the blood.

19. GFR depends upon Net Filtration Pressure (NFP) and filtration coefficient (KF). NFP = Pressure forcing out- pressure pulling in Pressure forcing out depends upon Glomerular hydrostatic pressure (GHP) : 55mm/Hg capsular osmotic pressure (COP) : 0mm/Hg Pressure pulling in depends upon Colloid osmotic pressure (COP): 30mm/Hg Capsular hydrostatic pressure (CHP): 15mm/Hg NFP is 10mm/Hg

20. The filtration coefficient depends upon the surface area of the glomerulus and the permeability of glomerulus .

21. Principal regulators of GFR: Renal autoregulation of GFR The kidneys are able to maintain a relatively constant internal blood pressure and GFR despite changes in systemic arterial pressure. There is negative feedback from the juxtaglomerular apparatus adjusting blood pressure and blood volume. Angiotensin I & II Activated by renin released from JG cells and further by ACE in the lungs 5 important functions direct systemic vasoconstriction  Na + reabsorption in PCT (H 2 O follows passively)

22.  thirst generated at the hypothalamus  aldosterone secretion causes Na + reabsorption  ADH secretion – stimulates water reabsorption in distal tubules and collecting duct Net Effect  increased blood pressure and blood volume

23. 2) Hormonal regulation of GFR Atrial Natriuretic Peptide (ANP) Secreted by cells in atria of heart in response to stretch  GFR, promotes excretion of H 2 O, Na + , but retention of K + Suppresses output of ADH, aldosterone , and renin Net Effect  decreased blood pressure and blood volume Aldosterone Secreted by cells in adrenal cortex in response to angiotensin I & II (and ACTH ( Adrenocorticotropic  hormone))  GFR, promotes retention of H 2 O, Na + , but excretion of K + Antagonist to atrial natriuretic peptide Net Effect  increased blood pressure and blood volume

24. 3) Neural regulation Kidney’s blood vessels supplied by vasoconstrictor fibers from Sympathetic Division of the ANS which release norepinephrine . Strong sympathetic stimulation causes JG cells to secrete renin and the adrenal medulla to secrete Epinephrine

25. 2. Selective reabsorption Selective reabsorption is the process by which the composition and volume of the glomerular filtrate are altered during its passage through convoluted tubules, medullary loop and collecting tubule. The general purpose of this process is to reabsorb into the blood those filtrate constituents needed by the body to maintain fluid and electrolyte balance and pH of blood. Active transport is carried out at carrier sites in epithelial membrane using chemical energy to transport substances against the concentration gradients.

26. Some constituents of glomerular filtrate (glucose, amino acid) do not normally appear in urine because they are completely reabsorbed unless they are present in blood in excessive quantities. The kidney has its own renal threshold ie its maximum capacity for reabsorption. For eg glucose level is 2.5 to 5.3 mmol/l, if the level rise above the transport of about 9 mmol/l glucose appears in the urine because all the carrier sites are occupied and the mechanism for active transfer out of tubules is overloaded. The substances reabsorbed by active transport include amino acids and sodium, calcium, potassium, phosphate and chloride.

27. Parathyroid hormone from parathyroid gland and calcitonin from thyroid gland together regulates renal absorption of calcium and phosphate. Antidiuretic hormone from posterior lobe of pituitary gland increases the permeability of DCT and CD increasing water reabsorption . Aldosterone secreted by adrenal cortex increase the reabsorption of sodium and excretion of potassium . Nitrogenous waste product are only slightly reabsorbed to slight extent .

28. More on Reabsorption

29. PCT is site of most electrolyte reabsorption ~100% of the filtered glucose and other sugars, AA's, lactic acid, and other useful metabolites are reabsorbed Reabsorption in PCT

30. The Na + / K + - ATPase on basolateral side is fundamental Requires ATP for energy Concentration of Na + inside the tubular cells is low Interior of the cell negatively charged Na+ concentration is greater in the filtrate than in the tubular cells Na + symporters in the apical membrane power secondary active transport systems Why secondary? They rely on the Na + / K + ATPase pump. Reabsorption of Na + in PCT

31. Reabsorption of Glucose in PCT Glucose is actively transported from the filtrate in tubule lumen into tubular cells as Na + moves down its concentration gradient

32. Reabsorption of H 2 O in PCT H 2 O follows Na + passively by osmosis from the filtrate through the tubular cells into the peritubular capillaries The movement of water back to the bloodstream concentrates the remaining solutes in the filtrate. [H 2 O]  [solutes] 

33. The new concentration gradients increase the diffusion of some of the other remaining solutes in the filtrate from lumen to the blood stream. Reabsorption of Nutrients in PCT

34. Renal Thresholds The Renal Threshold is the plasma concentration at which a substance begins to spill into the urine because its T m (transport maximum) has been surpassed. If the plasma filtrate concentration is too high, all of the substance cannot be reabsorbed. For example, glucose spills into the urine in untreated diabetics. Tm for glucose = 375 mg/min If blood glucose > 400 mg/100 mL , large quantities of glucose will appear in the urine

35. Reabsorption in the PCT By the end of the PCT the following reabsorption has occurred: 100% of filtered nutrients (sugars, albumin, amino acids, vitamins, etc.) 80-90% of filtered HCO 3 - 65% of Na + ions and water 50% of Cl - and K + ions

36. Cells in the thin descending limb are only permeable to water. H 2 O reabsorption is not coupled to reabsorption of filtered solutes in this area as it had been in the PCT. Reabsorption in Loop of Henle

37. Cells in the thicker ascending Loop feature Na + /K + /2Cl - symporters Reabsorb 1 Na + , 1 K + , 2 Cl - Depend on low cytoplasmic Na + concentration to function No H 2 O is reabsorbed from the thick ascending Loop Loop reabsorbs 30% of K + , 20% of Na + , 35% of Cl - , and 15% of H 2 O Reabsorption in Loop of Henle

38. Reabsorption in DCT and Collecting Ducts Filtrate reaching the DCT has already had ~80% of the solutes and H 2 O reabsorbed Fluid now has the characteristics of “urine” DCT is the site of final adjustment of urine composition Less work to do, so no need for microvilli (brush border) to increase surface area for transporters Na + /K + / Cl - symporter is a major DCT transporter DCT reabsorbs another 10% of filtrate volume

39. Reabsorption in DCT and Collecting Duct Principal cells are present in the distal DCTs and collecting ducts Three hormones act on principal cells to modify ion and fluid reabsorption : [1] Anti-Diuretic Hormone (ADH) (from neurohypophysis )  H 2 O reabsorption by increasing permeability to H 2 O in the DCT and collecting duct

40. Reabsorption in DCT and Collecting Duct [2] Aldosterone (from adrenal cortex)  Na + reabsorption ; Cl - and H 2 O follow passively;  K + reabsorption  number & activity of basolateral Na + /K + ATPases  number of luminal Na + & K + channels Germann & Stanfield, 2005

41. Reabsorption in DCT and Collecting Duct [3] Atrial Natriuretic Peptide (ANP) is the antagonist to Aldosterone  K + reabsorption ;  Na + reabsorption ; Cl - and H 2 O follow passively; adding “salt” and water to urine

42. 3. Secretion Filtration occurs as the blood flows through glomerulus Substances not required and foreign materials eg drugs including penicillin and aspirin are not cleared by filtration . They remain in blood for short time and cleared by secretion into convoluted tubules and excreted from body in urine. Tubular secretion of H+ is important in maintaining homeostasis of blood pH.

43. More on secretion

44. Secretion of K + ions Principal cells in collecting ducts secrete variable amount of K + in exchange for reabsorbed Na + Most animal diets contain excess K + but scarce Na + Na + /K + ATPases are the “ion pumps” Controlled by Aldosterone and Atrial Natriuretic Peptide Aldosterone is released from the adrenal cortex in response to angiotensin I & II With excess K+, aldosterone secretion predominates: Na+ (and Cl - ) are reabsorbed while considerable K + is secreted Atrial Natriuretic Peptide is released from the atrial walls in the heart in response to stretching when blood volume or blood pressure increase With excess Na+, atrial natriuretic peptide secretion predominates: K + is reabsorbed while considerable Na+ (and Cl - ) are secreted

45. Secretion of H + ions Cells of the renal tubule can elevate blood pH in three ways: Secrete H + ions into the filtrate Reabsorb filtered HCO 3 - Produce more HCO 3 - The key is the chemical relationship between H + ions and HCO 3 - ions: H 2 O + CO 2  H 2 CO 3  H + + HCO 3 - This reaction occurs spontaneously and it is also catalyzed by the enzyme carbonic anhydrase .

46. Secretion of H + ions In PCT [1] Na + /H + antiporter puts H + ions into the filtrate H + ions combine with HCO 3 - in lumen to form CO 2 and H 2 O H + 1 1

47. Secretion of H + ions [2] CO 2 from the filtrate or plasma enters the tubular cell where it combines with H 2 O to form H 2 CO 3 2 2 CO 2

48. Secretion of H + ions [3] H + is pumped into the lumen [4] HCO 3 - follows pumped Na+ back to the bloodstream HCO 3 - H + HCO 3 - 3 4

49. Secretion of H + ions Collecting ducts also secrete H + ions H + pumps are a primary active transport process powered by ATPs new bicarbonate ions are reabsorbed by the basolateral HCO 3 - / Cl - antiporter adding new HCO 3 - buffer to the bloodstream H + HCO 3 -

50. Secretion of NH 3 and NH 4 + Liver converts ammonia to urea, a much less toxic nitrogenous waste PCT cells can also deaminate certain amino acids and secrete additional NH 4 + with a Na + /NH 4 + antiporter when blood pH becomes acidic

51. Composition of urine Urine is clear and amber in color due to presence of urobilin, a bile pigment altered in intestine . pH is around 6 1000 to 1500 ml per day.

52. Water balance and urine output Water is taken in body through alimentary tract and a small amount is formed by metabolic processes. Water is excreted as the constituent of the faeces , through skin as a sweat and as a constituent of urine. The amount lost in expired air and in faeces is fairly constant and amount of sweat produced is associated with maintenance of normal body temperature. The balance between fluid intake and output is there fore controlled by kidneys . The minimum urinary output ie the smallest volume required to excrete body waste is about 500ml per day. The amount produced in excess is controlled by antidiuretic hormone (ADH) released by posterior lobe of pituitary gland.

53. The osmoreceptors stimulate the posterior lobe of pituitary gland which detects the change in osmotic pressure of blood and causes the release of ADH. The ADH output is increased and as a result water reabsorption by cells in DCT and CD is increased reducing the osmotic pressure.

54. Electrolyte balance Sodium is most common cation in extracellular fluid and potassium is most common intracellular cation. Sodium is a normal constituent of urine and the amount excreted is regulated by hormone aldosterone , secreted by adrenal cortex . The afferent arteriole in nephron are stimulated to produce enzyme renin by low blood volume or low arterial pressure . Renin converts the plasma protein angiotensinogen produced by liver to angiotensinogen 1 . Angiotensin converting enzyme (ACE) formed in lungs, PCT and other tissues converts Angiotensin 1 to angiotensin 2 which is potent vasoconstrictor and increased blood pressure.

55. Renin and raised potassium level stimulate the adrenal gland to secret aldosterone. Water is reabsorbed with sodium and together they increase blood volume and leading to reduce renin secretion. When sodium reabsorption is increased the potassium excretion is increased indirectly reducing intracellular potassium .

56. When there is excess imbalance in the electrolyte level of blood the cells of the PCT secret Hydrogen ion.

57. Additional notes on acid base balance

58. Role of kidneys in acid-base balance Kidneys helps in acid-base balance by: Reabsorption of bicarbonate ions(HCO 3 - ) Excretion of this much HCO3- in urine will affect the acid-base balance of body fluids. So, HCO3 must be taken back from the renal tubule by reabsorption . Secretion of hydrogen ions(H + ) Sodium-hydrogen antiport pump ATP-driven proton pump Removal of hydrogen ions & acidification of urine. Bicarbonate mechanism Phosphate mechanism Ammonia mechanism

59. Acid-base balance Normally,urine is acidic in nature. Metabolic activities in the body produce lot of acids which threaten to push the body towards acidosis. However, kidneys prevent this by excreting hydrogen ions (H + ) and conserving bicarbonate ions (HCO 3 - ). Conservation or reabsorption of HCO 3 - is an important process because of the high quantity of filtered HCO 3 - . Excretion of much HCO 3 - through urine will affect the acid-base balance of body fluids. So, HCO 3 - must be taken back from the renal tubule by reabsorption . The reabsorption of filtered HCO 3 - utilizes secretion of H + in the renal tubules.

60. Secretion of Hydrogen ions Kidney is only route through which H + can be eliminated from body. Secretion of H + into the renal tubules occurs by the formation of carbonic acid. Carbonic anhydrase catalyses the production of carbonic acid(H 2 CO 3 )from CO 2 and H 2 O in renal tubular cell. H 2 CO 3 then dissociated to H + and HCO 3 - . PCT, thick segment of ascending loop of Henle and early distal tubule all secrete H + into tubular fluid by sodium-hydrogen counter-transport.

61. Removal of Hydrogen ions and Acidification of urine The H + , which enters the renal tubules by filtration and secretion, is removed by three mechanisms. Bicarbonate mechanism Phosphate mechanism Ammonia mechanism

62. Bicarbonate mechanism All the filtered HCO 3 - into the renal tubules is reabsorbed. About 80% reabsorbed in PCT,15% in Henle’s loop and 5% in DCT and collecting duct. The reabsorption of HCO 3 - utilizes the H + present in renal tubules,which combines with filtered HCO 3 - forming carbonic acid. H 2 CO 3 is cleaved by carbonic anhydrase into CO 2 and H 2 O. As CO 2 concentration gradient built,it diffuses into tubular cells,where CO 2 combines with H 2 O to form H 2 CO 3 ,which dissociates into HCO 3 - and H + . H + is secreted into lumen in exchange of Na + and HCO 3 - is reabsorbed into plasma. Reabsorption of HCO 3 - is an important factor in maintaining pH of the body fluids.

63. Phosphate mechanism The H + , which is secreted into renal tubules, reacts with phosphate buffer system. It combines with sodium hydrogen phosphate to form sodium dihydrogen phosphate which is excreted in urine. The H + , which is added to urine in the form of sodium dihydrogen , makes the urine acidic. This happens mostly in distal tubule and collecting duct.

64. Ammonia mechanism This is the most important mechanism by which kidneys excrete H + and make the urine acidic. In the tubular epithelial cells,ammonia is formed when the amino acid glutamine is converted into glutamic acid in presence of enzyme glutaminase . NH 3 secreted into tubular lumen in exchange for sodium ion combines with H + to form ammonium. The tubular cell membrane is not permeable to ammonium. So,it remains in the lumen and combines with sodium acetoacetate to form ammonium acetoacetate,which is excreted through urine. This process takes place mostly in the PCT.

65. Ureters The ureters are the tubes that convey urine from the kidneys to the urinary bladder. They are about 25-30cm long with a diameter of about 3mm The ureter is continuous with funnel shaped renal pelvis and passes obliquely through posterior wall of bladder. Because of this arrangement, when urine accumulates and pressure in bladder rises, the ureters are compressed and the openings occluded. This prevent the reflux of urine into the ureters as bladder fills and during micturition, when pressure increases as muscular bladder wall contracts.

66. Structure: The ureters has 3 layers outer covering of fibrous tissue The middle layer has smooth muscle fibre The inner layer mucosa, lined with transitional epithelium Functions: To propel the urine from kidneys into bladder by peristaltic contraction of smooth muscle layer.

67. Urinary Bladder It is the reservoir for urine. It lies in pelvic cavity and its size and position vary depending on the amount of urine it contains. When distended, the bladder rises into the abdominal cavity . It is roughly pear shaped, but become more oval as it fills with urine. The bladder open into the urethra at its lowest point the neck. The peritoneum covers the superior surface. .

68. The bladder has three layers: Outer layer of connective tissues containing blood and lymphatic vessels covered by upper surface by peritoneum. The middle layer of interlacing smooth muscle fibers and elastic tissue and this is called detrusor muscle and empties the bladder when it contracts. The inner layer is mucosa lined with transitional epithelium . When the bladder is empty the inner lining is arranged in folds or rugae and these gradually disappear as bladder fills. The bladder is distensible but when it contains 300 to 400ml , the awareness of need to pass urine is felt. The total capacity is rarely more than 600ml.

69. The three orifices in the bladder wall form a triangle or trigone . The upper two orifices on the posterior wall are the opening of the ureters. The lower orifice is the opening into the urethra. The internal urethral sphincter a thickening of urethral smooth muscle layer in upper part of urethra, controls outflow of urine from the bladder.

70. Urethra The urethra is a canal extending from the neck of the bladder to the exterior, at the external urethral orifice, it is longer in the male than in female. The male urethra is associated with the urinary and reproductive functions. Female urethra is approximately 4cm long and 6mm in diameter. It runs downwards and forwards and opens at the external urethral orifice just in front of vagina. The external urethral orifice is guarded by external urethral sphincter which is under voluntary control.

71. The wall of female urethra has two main layers: an outer muscle layer and an inner lining of mucosa, which is continuous with that of bladder . The muscle layer has two parts, an inner layer of smooth muscle that is under autonomic nerve control and outer layer of striated muscle surrounding it. The striated muscle forms the external urethral sphincter and is under voluntary control.

72. Micturition When 300 to 400ml of urine have accumulated in bladder, afferent autonomic nerve fibres in bladder wall sensitive to stretch are stimulated. In infant this initiates a spinal reflex and micturition occurs. Urine passed in the response to parasympathetic stimulation of the bladder, causing contraction of the detrusor muscle and relaxation of internal urethral sphincter and muscle of pelvic floor can inhibit micturition until it is convenient to empty the bladder.

73. In adult, urine is passed when detrusor muscle contracts and there is reflex relaxation of the internal sphincter and voluntary relaxation of the external sphincter. It can be assisted by increasing the pressure within the pelvic cavity, achieved by lowering the diaphragm and contracting abdominal muscles. Over distension of bladder is extremely painful and when this stage is reached there is tendency for involuntary relaxation of external sphincter to occur allowing a small amount of urine to escape, provided there is no mechanical obstruction. Involuntary loss of urine is known as incontinence.

74. Filling of bladder Stimulation of stretch receptors Afferent impulses pass through pelvic nerve Sacral segments of spinal cord Efferent impulses through pelvic nerve Contraction of detrusor muscle and relaxation of internal sphincter Flow of urine into urethra and stimulation of stretch receptors Afferent impulses through pelvic nerve Inhibition of pudendal nerve Relaxation of external sphincter Voiding of urine

75. Mechanism of urine concentration and dilution Presence of ADH-Urine osmolality as high as 1400mosm/L of water Kidney operates intrinsic mechanism to concentrate and dilute urine. Absence of ADH- Urine osmolality fall to as low as 30mosm/L of water Diabetes insipidus , ADH deficiency urine out put is more than 20 ltrs per day

76. With adequate H 2 O, the posterior pituitary releases little ADH The glomerular filtrate equilibrates with medullary conditions while passing down through the loop Meanwhile, tubular reabsorption of solutes continues Producing a Dilute Urine

77. As the filtrate enters the ascending limb of the loop, and the DCT, and then the collecting ducts, no water can diffuse out of the filtrate Meanwhile, continuing tubular reabsorption of solutes in the DCT & CDs creates a dilute = hypo-osmotic (hypotonic) urine Producing a Dilute Urine

78. Producing a Concentrated Urine With inadequate H 2 O, the posterior pituitary releases more ADH The glomerular filtrate equilibrates with medullary conditions while passing down through the loop Meanwhile, tubular reabsorption of solutes continues

79. Producing a Concentrated Urine The ascending limb of the loop remains impermeable to H 2 O However, as the filtrate enters the DCT, and then the collecting ducts, ADH causes the tubular cells to become permeable to H 2 O Water can diffuse in or out of the filtrate

80. Producing a Concentrated Urine The filtrate becomes hypo-osmotic (hypotonic) in the DCT while H 2 O and solutes are returned to the bloodstream However, the filtrate equilibrates with medullary conditions while passing down through the collecting ducts

81. Producing a Concentrated Urine Even though the filtrate is still losing urea and NaCl to active transport, the other solutes cannot leave The filtrate becomes hyper-osmotic (hypertonic) as it equilibrates with the osmotic gradient surrounding the collecting ducts Water is drawn into the vasa recta and back to the bloodstream

82. Producing a Concentrated Urine The effect of ADH is to create a concentrated = hyper-osmotic (hypertonic) urine