1. Urine Formation

3. The kidney produces urine through 4 steps.

4. Glomerular Filtrate Tubular fluid Urine

5. 1) Glomerular Filtration

6. The Filtration Membrane From the plasma to the capsular space, fluid passes through three barriers. fenestrated epithelium basement membrane foot processes

7. The Filtration Membrane Almost any molecule smaller than 3 nm can pass freely through the filtration membrane into the capsular space. These include: Water, electrolytes, glucose, amino acids, lipids, vitamins, and nitrogenous wastes Kidney infections and trauma commonly damage the filtration membrane and allow plasma proteins or blood cells to pass through.

8. Blood cells in urine Plasma proteins

9. Filtration Pressure Glomerular filtration follows the same principles that govern filtration in other capillaries.

10. Glomerular Filtration Rate (GFR) - is the amount of filtrate formed per minute by the two kidneys combined. - For the average adult male, GFR is about 125 ml/min. - This amounts to a rate of 180 L/day. - An average of 99% of the filtrate is reabsorbed, so that only 1-2 L of urine per day is excreted.

11. GFR must be precisely controlled. a.If GFR is too high - increase in urine output - threat of dehydration and electrolyte depletion. b.If GFR is too low - insufficient excretion of wastes. c.The only way to adjust GFR from moment to moment is to change glomerular blood pressure.

12. Renal Autoregulation - the ability of the kidneys to maintain a relatively stable GFR in spite of the changes (75 - 175 mmHg) in arterial blood pressure.

13. The nephron has two ways to prevent drastic changes in GFR when blood pressure rises: 1) Constriction of the afferent arteriole to reduce blood flow into the glomerulus 2) Dilation of the efferent arteriole to allow the blood to flow out more easily. Change in an opposite direction if blood pressure falls

14. Mechanisms of Renal Autoregulation 1) myogenic response 2) tubuloglomerular feedback

15. Myogenic response This refers to inherent tendency of vascular smooth muscle cells to contract when stretched. Stretching the arteriole wall(increasing blood pressure) causes a reflexive vasoconstriction. As long as pressure continues, the vessel will stay constricted. When pressure against the vessel wall is reduced(decrease in blood pressure), the vessel dilates. Changes in blood pressure therefore directly affect the constriction or dilation of the arteriole, and so glomerular blood flow.

16. 2) tubuloglomerular feedback A second regulatory mechanism is the sensitivity of the macula densa cells of the juxtaglomerular apparatus to the concentration of sodium chloride in the filtrate, which is proportional to the rate of filtrate flow in the terminal portion of the ascending loop of Henle.

17. Low Osmolarity and Low Rate of Filtrate Flow in Tubule A low rate of filtrate flow and, therefore, low sodium chloride in the terminal portion of the ascending loop of Henle is also sensed by the macula densa cells. This condition is usually the result of low GFR caused by low blood pressure. In response, these cells initiate two effects: 1) They decrease secretion of the vasoconstrictor chemicals. This leads to dilation of the arteriole and so increases blood flow, glomerular hydrostatic pressure, and the GFR 2) The macula densa cells signal the granular cells of the afferent and efferent arterioles to release renin into the bloodstream. What is the Effect of Renin on the Regulation of the GFR ? 1- angiotensin II formed from renin causes constriction of the efferent arteriole 2- release of the hormone aldosterone

18. GFR Regulation Mechanisms: Sympathetic Nervous System Control Sympathetic nerve fibers innervate all blood vessels of the kidney as an extrinsic regulation mechanism. During normal daily activity they have minimal influence. However, during periods of extreme stress or blood loss, sympathetic stimulation overrides the autoregulatory mechanisms of the kidney. Increased sympathetic discharge causes intense constriction of all renal blood vessels. Two important results occur: 1) The activity of the kidney is temporarily lessened or suspended in favor of shunting the blood to other vital organs 2) The lower GFR reduces fluid loss, thus maintaining a higher blood volume and blood pressure for other vital functions. Reduction in filtration cannot go on indefinitely, as waste products and metabolic imbalances increase in the blood. Autoregulation mechanisms are now ineffective in preventing acute renal failure. When fluid is given intravenously, the blood volume increases. With increasing blood volume there will be gradual rise in blood pressure, reduction in sympathetic discharge, and restoration of renal functioning.

19. 1) Glomerular Filtration 2) Tubular Reabsorption 3) Tubular Secretion 4) Concentrating Urine by Collecting Duct

20. Renal clearance Definition- The renal clearance of a substance is: “The VOLUME of plasma rendered free of a given substance in one minute” Rate of excretion = U x.V Substance x: Plasma concentration = P x Clearance of x (C x ) = U x.V PxPx = ml/min liters/day gallons/second

21. P urea = 0.2 mg/ml U urea = 6 mg/ml V = 2ml/min Questions: How much urea is excreted per min? What is the clearance of urea? Answers: Urea excretion = 6 mg/ml x 2 ml/min = 12 mg/min Urea clearance = 12 mg/min = 60 ml/min 0.2 mg/ml i.e. 60 ml of plasma loses its urea into the urine in one minute

22. About 99% of Water and other useful small molecules in the filtrate are normally reabsorbed back into plasma by renal tubules.

23. Reabsorption in Proximal Convoluted Tubules

24. - The proximal convoluted tubule (PCT) is formed by one layer of epithelial cells with long apical microvilli. - PCT reabsorbs about 65% of the glomerular filtrate and return it to the blood.

25. 1) transcellular route 2) paracellular route Routes of Proximal Tubular Reabsorption PCT peritubular capillary

26. Mechanisms of Proximal Tubular Reabsorption 1) Solvent drag 2) Active transport of sodium. 3) Secondary active transport of glucose, amino acids, and other nutrients. 4) Secondary water reabsorption via osmosis 5) Secondary ion reabsorption via electrostatic attraction 6) Endocytosis of large solutes

27. Osmosis Water moves from a compartment of low osmolarity to the compartment of high osmolarity. low osmolarity ( high H 2 O conc.) high osmolarity ( low H 2 O conc.) H2OH2O

28. 1)Solvent drag - driven by high colloid osmotic pressure (COP) in the peritubular capillaries - Water is reabsorbed by osmosis and carries all other solutes along. - Both routes are involved. Proteins stay H2O Proteins

29. 2) Active transport of sodium Sodium pumps (Na-K ATPase) in basolateral membranes transport sodium out of the cells against its concentration gradient using ATP. capillary PCT cellTubular lumen Na + K+K+

30. There are also pumps for other ions capillary PCT cellTubular lumen Ca ++

31. - Various cotransporters can carry both Na+ and other solutes. For example, the sodium- dependent glucose transporter (SDGT) can carry both Na+ and glucose. 3) Secondary active transport of glucose, amino acids, and other nutrients Na + Glucose capillaryPCT cell Na + K+K+

32. Amino acids and many other nutrients are reabsorbed by their specific cotransporters with sodium. Na + capillaryPCT cell Na + K+K+ amino acids 3) Secondary active transport of glucose, amino acids, and other nutrients

33. Sodium reabsorption makes both intracellular and extracellular fluid hypertonic to the tubular fluid. Water follows sodium into the peritubular capillaries. 4) Secondary water reabsorption via osmosis H2O Na + capillary PCT cellTubular lumen

34. Negative ions tend to follow the positive sodium ions by electrostatic attraction. 5) Secondary ion reabsorption via electrostatic attraction Na Na + Cl - capillary PCT cellTubular lumen

35. The glomerulus filters a small amount of protein from the blood. The PCT reclaims it by endocytosis, hydrolzes it to amino acids, and releases these to the ECF by facilitated diffusion. 6) Endocytosis of large solutes protein capillary PCT cellTubular lumen amino acids

36. The Transport Maximum - There is a limit to the amount of solute that the renal tubule can reabsorb because there are limited numbers of transport proteins in the plasma membranes. - If all the transporters are occupied as solute molecules pass through, some solute will remain in the tubular fluid and appear in the urine. Na + Glucose Example of diabetes

37. Glucose in urine high glucose in blood high glucose in filtrate Exceeds Tm for glucose

38. Reabsorption in the Nephron Loop

39. - The primary purpose is to establish a high extracellular osmotic concentration. - The thick ascending limb reabsorbs solutes but is impermeable to water. Thus, the tubular fluid becomes very diluted while extracellular fluid becomes very concentrated with solutes. mOsm/L

40. The high osmolarity enables the collecting duct to concentrate the urine later.

41. Reabsorption in Distal Convoluted Tubules

42. - Fluid arriving in the DCT still contains about 20% of the water and 10% of the salts of the glomerular filtrate. - A distinguishing feature of these parts of the renal tubule is that they are subject to hormonal control.

43. Aldosterone a.secreted from adrenal gland in response to a  Na + or a  K + in blood b.to increase Na + absorption and K + secretion in the DCT and cortical portion of the collecting duct. c.helps to maintain blood volume and pressure.

44. Atrial Natriuretic Factor - secreted by the atrial myocardium in response to high blood pressure. - It inhibits sodium and water reabsorption, increases the output of both in the urine, and thus reduces blood volume and pressure.

45. 1) Glomerular Filtration 2) Tubular Reabsorption 3) Tubular Secretion 4) Concentrating Urine by Collecting Duct

46. Tubular Secretion - Renal tubule extracts chemicals from the blood and secretes them into the tubular fluid. - serves the purposes of waste removal and acid-base balance. H+H+ H+H+ capillary PCT cellTubular lumen

47. 1) Glomerular Filtration 2) Tubular Reabsorption 3) Tubular Secretion 4) Concentrating Urine by Collecting Duct

48. 1.The collecting duct (CD) begins in the cortex, where it receives tubular fluid from numerous nephrons. 2.CD reabsorbs water. Cortex collecting duct urine

49. 1. Driving force The high osmolarity of extracellular fluid generated by NaCl and urea, provides the driving force for water reabsorption. 2. Regulation The medullary portion of the CD is not permeable to NaCl but permeable to water, depending on ADH. Cortex mOsm/L medulla urine

50. a.In a state of full hydration, antidiuretic hormone (ADH) is not secreted and the CD permeability to water is low, leaving the water to be excreted. Cortex mOsm/L medulla Control of Urine Concentration depends on the body's state of hydration. urine b. In a state of dehydration, ADH is secreted; the CD permeability to water increases. With the increased reabsorption of water by osmosis, the urine becomes more concentrated.

51. Cortex medulla urine No more reabsorption after tubular fluid leaving CD urine

52. Composition and Properties of Urine Fresh urine is clear, containing no blood cells and little proteins. If cloudy, it could indicate the presence of bacteria, semen, blood, or menstrual fluid. Urine Properties

53. SubstanceBlood Plasma (total amount) Urine (amount per day) Urea4.8 g25 g Uric acid0.15 g0.8 g Creatinine0.03 g1.6 g Potassium0.5 g2.0 g Chloride10.7 g6.3 g Sodium9.7 g4.6 g Protein200 g0.1 g HCO 3 - 4.6 g0 g Glucose3 g0 g

55. Urine Volume An average adult produces 1-2 L of urine per day. a.Excessive urine output is called polyuria. b.Scanty urine output is oliguria. An output of less than 400 mL/day is insufficient to excrete toxic wastes.

56. Diabetes - is chronic polyuria resulting from various metabolic disorders, including Diabetes mellitus and Diabetes insipidus

57. Diabetes mellitus - caused by either 1) deficiency of insulin (Type I) or 2) deficiency of insulin receptors (Type II). - Diabetes mellitus features high glucose in the blood (hyperglycemia) glucose cell blood insulin receptors insulin pancreatic  cell glycogen

58. - When glucose in tubular fluid exceeds the transport maximum (180 mg/100 ml), it appears in urine (glycosuria). - Glucose in tubular fluid hinders water reabsorption by osmosis, causing polyuria. high urine volume high glucose high glucose in filtrate Retain H 2 O by osmosis

59. Diabetes insipidus - is caused by inadequeate ADH secretion. - Due to the shortage of ADH, water reabsorption in CD is compromised, leading to polyuria.  urine

60. Diuresis refers to excretion of large amount of urine. Natriuresis refers to enhanced urinary excretion of sodium

61. Diuretics - are chemicals that increase urine volume. They are used for treating hypertension and congestive heart failure because they reduce overall fluid volume. - work by either increasing glomerular filtration or reducing tubular reabsorption. Caffeine falls into the former category; alcohol into the latter (alcohol suppresses the release of ADH).

62. Many diuretics produce osmotic diuresis by inhibiting sodium reabsorption

63. Renal Function Tests

64. Renal Clearance a.the volume of blood plasma from which a particular waste is removed in 1 minute. b.can be measured indirectly by measuring the waste concentration in blood and urine, and the urine volume.

65. 2.Glomerular Filtration Rate a.Measuring GFR requires a substance that is not secreted or reabsorbed at all. Inulin, a polymer of fructose, is suitable. b.Inulin filtered by the glomeruli remains in the renal tubule and appears in the urine; none is reabsorbed, and the tubule does not secrete it. For this solute, GFR is equal to the renal clearance.

66. Hemodialysis artificially clearing wastes from the blood

67. 1) Dialysis machine - efficient - inconvenient

68. 2) Continuous ambulatory peritoneal dialysis (CAPD) Dialysis fluid - The peritoneal membrane is a natural dialysis membrane - convenient - less efficient

69. Urine Storage and Elimination

70. The Ureters The ureters are muscular tubes leading from the renal pelvis to the lower bladder.

71. The Urinary Bladder - is a muscular sac on the floor of the pelvic cavity. - is highly distensible and expands superiorly.

72. The openings of the two ureters and the urethra mark a triangular area called the trigone on the bladder floor.

73. The Urethra - conveys urine from the urinary bladder to the outside of the body. Females male 3-4 cm ~18 cm greater risk of urinary tract infections

74. The male urethra has three regions: 1)prostatic urethra 2) membranous urethra 3) penile urethra. Difficulty in voiding urine with enlarged prostate

75. In both sexes: - internal urethral sphincter- under involuntary control. - external urethral sphincter - under voluntary control internal urethral sphincter external urethral sphincter

76. Spinal cord Voiding Urine in infants micturition reflex When the bladder contains about 200 ml of urine, stretch receptors in the wall send impulses to the spinal cord. Parasympathetic signals return to stimulate contraction of the bladder and relaxation of the internal urethral sphincter.

77. 2.Once voluntary control has developed, emptying of the bladder is controlled predominantly by a micturition center in the pons. This center receives signals from stretch receptors and integrates this information with cortical input concerning the appropriateness of urinating at the moment. It sends back impulses to stimulate relaxation of the external sphincter. Once voluntary control has developed, emptying of the bladder is controlled predominantly by a micturition center in the pons. This center receives signals from stretch receptors and integrates this information with cortical input concerning the appropriateness of urinating at the moment. It sends back impulses to stimulate relaxation of the external sphincter. Voiding Urine in adults Voluntary control

78. SUMMARY 1) General Introduction 2) Anatomy of Urinary System 3) Urine Formation 4) Urine Storage and Elimination