1. THE URINARY SYSTEM

2. Every day the kidneys filter nearly 200 liters of fluid from the bloodstream, allowing toxins, metabolic wastes, and excess ions to leave the body in urine while returning needed substances to the blood –Although the lungs and skin also participate in excretion, the kidneys are the major excretory organs –As the kidneys perform these excretory functions, they simultaneously regulate the volume and chemical makeup of the blood, maintaining the proper balance between water and salts and between acids and bases –Other renal (kidney) functions: Gluconeogenesis during prolonged fasting Produces enzyme renin which helps regulate blood pressure and kidney function Produces hormone erythropoietin which stimulates red blood cell production Metabolizing vitamin D to its active form

3. Urinary System Kidneys: urine forming Urinary bladder: temporary storage reservoir for urine Paired ureters: transport urine from kidneys to urinary bladder Urethra: void urine to exterior

4. KIDNEY ANATOMY

5. Location and External Anatomy The kidneys are bean- shaped organs that lie retroperitoneal (between the dorsal wall and the parietal peritoneum) in the superior lumbar region –From T 12 to L 3 –Receive some protection from the lower rib cage

6. POSTERIOR VIEW OF KIDNEYS

7. Kidney Anatomy Right kidney is crowded by the liver and lies slightly lower than the left Adult kidney is about 150 g (5 ounces) and its dimensions are 12 cm long, 6 cm wide, and 3 cm thick (size of a large bar of soap) Lateral surface is convex The medial surface is concave and has a cleft called the renal hilus that leads into a renal sinus –Ureters, renal blood vessels, nerves, and lymphatics all join the kidney at the hilus and occupy the sinus Atop each kidney is an adrenal gland (endocrine gland) Three layers of supportive tissue surround each kidney: –Renal capsule: a fibrous, transparent capsule that prevents infections in surrounding regions from spreading to the kidneys –Adipose capsule: a fatty mass that attaches the kidney to the posterior body wall and cushions the organ –Renal fascia: an outer layer of dense fibrous connective tissue that anchors the kidney and adrenal gland to surrounding structures

8. POSTERIOR VIEW OF KIDNEYS

9. HOMEOSTATIC IMBALANCE Hydronephrosis: backup of urine from ureteral obstruction –Loss of fat resulting in the kidney dropping to a lower position (renal ptosis) resulting in kinked ureter –Can severely damage the kidney, leading to necrosis (tissue death) and renal failure

10. KIDNEY ANATOMY

11. Internal Anatomy There are three distinct regions of the kidney: the cortex, the medulla, and the renal pelvis –Renal cortex: most superficial region Granular appearance

12. Internal Anatomy Renal medulla: –Cone-shaped tissue masses called medullary or renal pyramids Base of pyramid faces the cortex/apex points internally Each pyramid and its surrounding cortical tissue constitutes one of approximately eight lobes of a kidney

13. Internal Anatomy Renal pelvis: flat, funnel-shaped tube –Continuous with the ureter leaving the hilus –Branching extensions of the pelvis form 2 or 3 major calyces (calyx), each of which subdivides to form several minor calyces, cup-shaped areas that enclose the papillae Calyces collect urine, which drains continuously from the papillae, and empties into the renal pelvis-ureter-urinary bladder Walls of calyces, pelvis, and ureter contain smooth muscle that contracts rhythmically to propel urine along its course by peristalsis

14. INTERNAL ANATOMY OF KIDNEY

15. HOMEOSTATIC IMBALANCE Pyelitis: –Infection of the renal pelvis and calyces Pyelonephritis: –Infections or inflammations that affect the entire kidney Kidney infections in females are usually caused by fecal bacteria that spread from the anal region to the urinary tract Infections (less often) can be the result of blood borne bacteria

16. Blood and Nerve Supply Kidneys continuously cleanse the blood and adjust its composition The renal arteries branch at right angles from the abdominal aorta: –Blood supply into and out of the kidneys progresses to the cortex through renal arteries to segmental, lobar, interlobar, arcuate, and interlobular arteries, and back to renal veins from interlobular, arcuate, and interlobular veins Renal veins empty into the inferior vena cava The renal plexus (autonomic nerve fibers and ganglia) regulates renal blood flow by adjusting the diameter of renal arterioles and influencing the urine-forming role of the nephrons –Offshoot of the celiac plexus

17. INTERNAL ANATOMY OF KIDNEY

18. Nephrons Nephrons are the structural and functional units of the kidneys that carry out processes that form urine Each nephron consist of a renal corpuscle composed of a tuft of capillaries (the glomerulus), surrounded by a glomerular capsule (Bowman’s capsule): –The glomerular endothelium is fenestrated (penetrated by many pores), which makes these capillaries exceptionally porous: Allows large amounts of solute-rich, virtually protein- free fluid to pass from the blood into the glomerular capsule (Bowman’s capsule) This plasma-derived fluid or filtrate is the raw material that the renal tubules process to form urine

19. Nephrons Glomerular capsule (Bowman’s capsule) membrane has filtration pores (slit pores) which allow the filtrate to enter the capsular space inside the glomerular capsule (Bowman’s capsule) The renal tubule begins at the glomerular capsule (Bowman’s capsule) as the proximal convoluted tubule, continues through a hairpin loop, the loop of Henle, and turns into a distal convoluted tubule before emptying into a collecting duct –The meandering nature of the renal tubule increases its length and enhances its filtrate processing capabilities

20. Nephrons The collecting ducts collect filtrate from many nephrons, and extend through the renal pyramid to the renal papilla, where they empty into a minor calyx

21. Nephrons Walls of the proximal convoluted tubule (PCT) are formed by cuboidal epithelial cells with large mitochondria –Large exposed surfaces bear dense microvilli (brush border) which increases their surface area and capacity for reabsorbing water and solutes from the filtrate and secreting substances into it The descending limb, called the thin segment, is a simple squamous epithelium that is freely permeable to water

22. Nephrons The epithelial cells of the distal convoluted tubule (DCT) are thinner and almost entirely lack microvilli –May play a larger role in secreting solutes into the filtrate than in reabsorbing substances from it –Maintains a major role in maintaining the acid- base balance of the blood –Maintains the body’s water and Na + balance

23. Nephrons There are two types of nephrons: –Cortical nephrons: 85% Located almost entirely within the cortex Small parts of their loops of Henle dips into the outer medulla –Juxtamedullary nephrons: 15% Located near the cortex- medulla junction Play an important role in the kidney’s ability to produce concentrated urine Loops of Henle deeply invade the medulla

24. LOCATION AND STRUCTURE OF NEPHRONS

25. COMPARISON OF THE TUBULAR AND VASCULAR ANATOMY OF CORTICAL AND JUXTAMEDULLARY NEPHRONS

26. NEPHRON

27. Nephron Capillary Bed Every nephron is closely associated with two capillary beds: –Glomerulus capillaries: (a) Capillaries run in parallel Specialized for filtration –Produces filtrate Differs from all other capillary beds in the body in that it is both fed and drained by arterioles (afferent and efferent arterioles) –Afferent arteriole has a larger diameter than the efferent High-resistance vessels Blood pressure in the glomerulus is extraordinarily high for a capillary bed and easily forces fluid and solutes out of the blood into the glomerular capsule (Bowman’s capsule) Most of this filtrate (99%) is reabsorbed by the renal tubule cells and returned to the blood in the peritubular capillary beds

28. COMPARISON OF THE TUBULAR AND VASCULAR ANATOMY OF CORTICAL AND JUXTAMEDULLARY NEPHRONS

29. Nephron Capillary Bed Peritubular capillaries: (b) –Arise from efferent arterioles draining the glomerulus –Cling closely to adjacent renal tubules and empty into nearby venules –Low-pressure, porous capillaries that readily absorb solutes and water from the tubules cells as these substances are reclaimed from the filtrate –Reclaims most of the filtrate

30. Nephron Capillary Bed Note: (b) –Efferent arterioles serving the juxtamedullary nephrons tend not to break up into peritubular capillaries –They form bundles of long straight vessels called vasa recta that extend deep into the medulla paralleling the longest loops of Henle –The thin-walled vasa recta play an important role in forming concentrated urine

31. COMPARISON OF THE SOURCE AND PATTERN OF THE VASCULATURE OF CORTICAL AND JUXTAMEDULLARY NEPHRONS

32. Juxtaglomerular Apparatus Each nephron has a region called: JGA: –The juxtaglomerular apparatus is a structural arrangement between the afferent arteriole and the distal convoluted tubule that forms juxtaglomerular cells and macula densa cells In the arteriole walls are the granular juxtaglomerular (JG) cells—enlarged smooth muscle cells with prominent secretory granules containing renin –Act as mechanoreceptors that sense the blood pressure in the afferent arteriole Macula densa: a group of tall, closely packed distal convoluted tubule (DCT) cells that lie adjacent to the JG cells –Chemoreceptors (osmoreceptors) that respond to changes in the solute content of the filtrate –Both cells (JG + macula densa) play important roles in regulating the rate of filtrate formation and systemic blood pressure

33. JUXTAGLOMERULAR APPARATUS OF A NEPHRON

34. Filtration Membrane The filtration membrane lies between the blood and the interior of the glomerular capsule (Bowman’s capsule) It is a porous membrane that allows free passage of water and solutes smaller than plasma proteins

35. FILTRATION MEMBRANE

37. Filtration Membrane Three layers: –1.Fenestrated endothelium of the glomerular capillaries: Capillary pores allow passage of all plasma components but not blood cells

38. FILTRATION MEMBRANE

40. Filtration Membrane 2.Intervening basement membrane composed of the fused basal laminae of the other layers: –Restricts all but the smaller proteins while permitting most other solutes to pass –Confers electrical selectivity on the membrane: Negative glycoproteins repel anions (+) and hinder their passage into the tubule

41. FILTRATION MEMBRANE

43. Filtration Membrane 3.Visceral membrane of the glomerular capsule made of podocytes: –Engulf and degrade macromolecules that are caught in the membrane

44. FILTRATION MEMBRANE

46. KIDNEY PHYSIOLOGY: MECHANISMS OF URINE FORMATION The kidneys filter out your entire plasma volume more than 60 times each day consuming 20-25% of all oxygen used by the body at rest Filtrate contains everything found in the blood plasma except proteins, but by the time filtrate has percolated into the collecting ducts, it has lost most of its water, nutrients, and ions –What remains is called urine Contains mostly metabolic wastes and unneeded substances Urine formation and the adjustment of blood composition involve three major processes: –1.Glomerular filtration by the glomeruli –2.Tubular reabsorption in the renal tubules –3.Secretion in the renal tubules

47. Glomerular Filtration Is a passive, nonselective process in which hydrostatic pressure forces fluids and solutes through the glomerular membrane –Does not consume metabolic energy More efficient filter than other capillary beds because: –1.Its filtration membrane has a large surface area and is thousands of times more permeable to water and solutes –2.glomerular blood pressure is much higher than that in other capillary beds, resulting in a much higher net filtration pressure Molecules smaller than 3nm in diameter— such as water, glucose, amino acids, and nitrogenous wastes—pass freely from the blood into the renal tubule –Larger molecules pass with greater difficulty, and those larger than 7-9 nm are generally barred from entering the tubule Presence of proteins or blood cells in the urine usually indicates a problem with the filtration membrane

48. Single nephron

49. Net Filtration Pressure (NFP) Glomerular hydrostatic pressure (HP g ) (glomerular blood pressure) is the chief force pushing water and solutes out of the blood and across the filtration membrane HP g is opposed by two forces that drive fluids back into glomerular capillaries (filtration-opposing forces) –1.Colloid osmotic (oncotic) pressure of glomerular blood (OP g ) –2.Capsular hydrostatic pressure (HP C ) exerted by fluids in the glomerular capsule (Bowman’s capsule) –NFP = HP g – (OP g + HP C ) – = 55mmHg - ( 30mmHg + 15mmHg) – = 10mmHg

50. Glomerular Filtration Rate (GFR) The glomerular filtration rate is the volume of filtrate formed each minute by all the 2 million glomeruli of the kidneys combined Because the GFR is directly proportional to the NFP, any change in any of the pressures acting at the filtration membrane changes both the NFP and the GFR: –An increase in arterial (and glomerular) blood pressure in the kidneys increases the GFR, whereas dehydration (which causes an increase in glomerular osmotic pressure) inhibits filtrate formation

51. FORCES THAT DETERMINE GLOMERULAR FILTRATION AND THE EFFECTIVE FILTRATION PRESSURE

52. Regulation of Glomerular Filtration Maintenance of a relatively constant glomerular filtration rate is important because reabsorption of water and solutes depends on how quickly filtrate flows through the tubules: –If massive amounts of filtrate form the flow too rapid for needed substances to be reabsorbed fast enough and some are lost in urine –If filtrate flows slowly, nearly all of it is reabsorbed, including most of the wastes that are normally disposed of Glomerular filtration rate is held relatively constant through intrinsic (renal autoregulatory) mechanisms, and extrinsic hormonal and neural mechanisms

53. Intrinsic Controls: Renal Autoregulation Renal autoregulation uses: –1.A myogenic control: Reflects the tendency of vascular smooth muscle to contract when stretched Increasing systemic blood pressure causes the afferent arterioles to constrict, which restricts blood flow into the glomerulus and prevents glomerular blood pressure from rising to damaging levels Declining systemic blood pressure causes dilation of afferent arterioles and raises glomerular hydrostatic pressure Both responses help maintain a normal glomerular filtration rate (GFR)

54. Intrinsic Controls: Renal Autoregulation 2.A tubuloglomerular feedback mechanism that responds to the rate of filtrate flow in the tubules, directed by the macula densa cells of the juxtaglomerular apparatus (respond to filtrate flow) –Exposed to slowly flowing filtrate or filtrate with low osmolality, their signals promote vasodilation of the afferent arteriole Allows more blood to flow into the glomerulus –Exposed to rapidly flowing and/or it has a high sodium and chloride content or high osmolality, generates vasoconstictor chemical that causes intense vasoconstriction Hinders blood flow into the glomerulus

55. MECHANISMS REGULATING THE GLOMERULAR FILTRATION RATE (GFR) IN THE KIDNEYS

56. Extrinsic Controls: Neural and Hormonal Mechanisms Sympathetic nervous system controls: During extreme stress or emergency when it is necessary to shunt blood to vital organs, neural controls may overcome renal autoregulatory mechanisms –Stress-included sympathetic responses that inhibit filtrate formation by constricting the afferent arterioles –Inhibiting filtrate formation The renin-angiotensin (potent vasoconstrictor) mechanism causes an increase in systemic blood pressure and an increase in blood volume (reabsorbing water) by increasing Na + reabsorption

57. MECHANISMS REGULATING THE GLOMERULAR FILTRATION RATE (GFR) IN THE KIDNEYS

58. Tubular Reabsorption Tubular reabsorption begins as soon as the filtrate enters the proximal convoluted tubule, and involves near total reabsorption of organic nutrients (glucose and amino acids), and the hormonally regulated reabsorption of water and ions –May be passive or active

59. ACTIVE/PASSIVE TRANSPORT PROCESSES

60. Tubular Reabsorption The most abundant cation of the filtrate is Na +, and reabsorption is always active

61. REABSORPTION BY PCT CELLS

62. Reabsorption of water, Ions, and Nutrients Passive tubular reabsorption is the passive reabsorption of negatively charged ions (Cl - and HCO 3 - ) that travel along an electrical gradient created by the active reabsorption of Na + Obligatory water reabsorption occurs in water-permeable regions of the tubules in response to the osmotic gradients created by active transport of Na +

63. REABSORPTION BY PCT CELLS

64. Reabsorption of water, Ions, and Nutrients Secondary active transport is responsible for absorption of glucose, amino acids, vitamins, and most cations, and occurs when solutes are cotransported with Na + when it moves along its concentration gradient Substances that are not reabsorbed or incompletely reabsorbed remain in the filtrate due to a lack of carrier molecules, lipid insolubility, or large size (urea, creatinine, and uric acid)

65. Absorptive Capabilities of the Renal Tubules and Collecting Ducts Different areas of the tubules have different absorptive capabilities: The proximal convoluted tubule is most active in reabsorption, with most selective reabsorption occurring there The descending limb of the loop of Henle is permeable to water, while the ascending limb is impermeable to water but permeable to electrolytes The distal convoluted tubule and collecting duct have Na + and water permeability regulated by the hormones aldosterone, antidiuretic hormone, and atrial natriuretic peptide

66. Tubular Secretion Tubular secretion is important for: –Substances not already in the filtrate, such as certain drugs –Elimination of unwanted substances or end products that have been reabsorbed by passive processes Urea, uric acid –Rids the body of excess K + –Controls blood pH Tubular secretion is most active in the proximal convoluted tubule, but occurs in the collecting ducts and distal convoluted tubules, as well

67. Regulation of Urine Concentration and Volume One of the critical functions of the kidney is to keep the solute load of body fluids constant by regulating urine concentration and volume Osmolality: is the number of solute particles dissolved in one liter (1000g) of water and reflects the solution’s ability to cause osmonsis –For any solution interfacing with a semipermeable membrane, this ability called osmotic activity, is determined only by the number of nonpenetrating solute particles (solute particles unable to pass through the membrane) and is independent of their type 10 sodium ions have the same osmotic activity as 10 glucose molecules or 10 amino acids in the same volume of water

68. Regulation of Urine Concentration and Volume The osmolality of the filtrate entering the PCT is identical to that of plasma (300mOsm; milliosmol) –Because of PCT reabsorption of water and solutes, the filtrate when reaching the loop of Henle increases to 1200 mOsm in the deepest part of the medulla

69. Regulation of Urine Concentration and Volume The countercurrent mechanism involves: –Flowing in opposite directions through adjacent channels –Interaction between filtrate flow through the loops of Henle (the countercurrent multiplier) of juxtamedullary nephrons and the flow of blood through the vasa recta (the countercurrent exchanger)

70. Regulation of Urine Concentration and Volume Since water is freely absorbed from the descending limb of the loop of Henle, filtrate concentration increases and water is reabsorbed: –The descending limb of the loop of Henle is relatively impermeable to solutes and freely permeable to water Water passes out of the filtrate The ascending limb is permeable to solutes, but not to water –Impermeable to water and selectively permeable to salt Na + and Cl - in the filtrate entering the ascending loop is very high Reabsorption takes place in the thicker portion of the ascending loop

71. Regulation of Urine Concentration and Volume Although the two limbs of the loop of Henle are not in direct contact with each other, they are close enough to influence each other’s exchanges with the interstitial fluid they share Water diffusing out of the descending limb produces the increasingly salty filtrate that the ascending limb uses to raise the osmolality of the medullary interstitial fluid The more NaCl the ascending limb extrudes, the more water diffuses out of the descending limb and the saltier the filtrate in the descending limb becomes –This establishes a positive feedback mechanism

72. Regulation of Urine Concentration and Volume –In the collecting duct, urea diffuses into the deep medullary tissue, contributing to the increasing osmotic gradient encountered by filtrate as it moves through the loop –The vasa recta (capillary branches) aids in maintaining the steep concentration gradient of the medulla, by cycling salt into the blood as it descends into the medulla, and then out again as it ascends toward the cortex

73. OSMOTIC GRADIENT

74. COUNTERCURRENT MECHANISM FOR ESTABLISHING AND MAINTAINING THE MEDULLARY OSMOTIC GRADIENT

75. Formation of Dilute Urine (a) Since tubular filtrate is diluted as it travels through the ascending limb of the loop of Henle, production of a dilute urine is accomplished by simply allowing filtrate to pass on to the renal pelvis Because the filtrate by the workings of the countercurrent mechanism, all that is needed to secrete dilute urine is to allow the filtrate reaching the Distal Convoluted Tubule to be excreted

76. Formation of Concentrated Urine (b) Formation of a concentrated urine occurs in response to the release of antidiuretic hormone, which makes the collecting ducts permeable to water and increases water uptake from the urine Concentrated urine is excreted in the presence of ADH (Antidiuretic Hormone-Posterior Pituitary: vasopressin) which causes insertion of aquaporins (water moves freely and reversibly through water-specific channels constructed by transmembrane proteins called aquaporins) in luminal membranes of principal cells of the late Distal Convoluted Tubule and collecting duct –Release of ADH is the signal to produce concentrated urine –Consequently water rapidly leaves the filtrate in the collecting duct

77. FORMING URINE

78. Diuretics Chemicals that enhance urinary output Osmotic diuretic: –A substance that is not reabsorbed and that carries water out with it Example: high glucose levels of a diabetes mellitus patient Alcohol: –Essentially a sedative, encourages diuresis (urination) by inhibiting release of ADH Caffeine: –Increases urine flow by inhibiting Na + reabsorption and the obligatory water reabsorption that normally follows

79. Renal Clearance Renal clearance refers to the volume of plasma that is cleared of a specific substance in a given time, usually 1 minute –Provides information about the amount of functioning renal tissue and detects glomerular damage –Renal clearance rate (RC: ml/min) = UV/P U=concentration of the substance in urine (mg/ml) V=flow rate of urine formation (ml/min) P=concentration of the substance in plasma (mg/ml) –Inulin (polysaccharide) is used as a clearance standard to determine glomerular filtration rate (GFR) since it is not reabsorbed, stored, or secreted Inulin’s clearance value is equal to the GRF –If the clearance value for a substance is less than that for inulin, then some of the substance is being reabsorbed; if the clearance value is greater than the inulin clearance rate, then some of the substance is being secreted Knowing a drug’s renal clearance value is essential because if it is high, the drug dosage must also be high and administered frequently to maintain a therapeutic level A clearance value of zero indicates the substance is completely reabsorbed –Such as for glucose in healthy individuals

80. SUMMARY (a): Proximal Tubule: –Filtrate that enters the PCT from the glomerular capsule has about the same osmolality as blood plasma –Reabsorption of certain solutes from filtrate back into the blood Nearly all nutrients 65% of Na + –Cl - and water follow –Secreted into the filtrate Ammonium ion Nitrogenous wastes Helps maintain a constant pH in blood and interstitial fluid by the controlled secretion of H + and reabsorption of HCO 3 - –By the end of the proximal tubule, the filtrate volume has been reduced by 65%

81. SUMMARY (b): Descending Limb: –Freely permeable to water but not NaCl –As filtrate in this limb descends into the medulla, the filtrate loses water by osmosis to the interstitial fluid, which is increasingly hypertonic Consequently, salt and other solutes become more concentrated in the filtrate

82. SUMMARY (c): Ascending Limb: –Impermeable to water –Permeable to Na + and Cl - These ions, which became concentrated in the descending limb, move passively out of the thin portion of the ascending limb, are actively pumped out of the thick portion of the ascending limb, and contribute to the high osmolality of interstitial fluid in the inner medulla K + is cotransported with Na + and Cl - Filtrate becomes more and more dilute as the exodus of salt from the filtrate continues

83. SUMMARY (d): Distal Tubule: –Na + and Cl - are cotransported Na + may be reabsorbed in the presence of aldosterone (mineralocorticoid hormone secreted by adrenal cortex) –H + may be secreted into tubule –Water permeability is extremely low Almost no further H 2 O absorption occurs

84. SUMMARY (e): Collecting Duct: –Urine, normally quite dilute at this point, begins its journey via the collecting duct back into the medulla, with its increasing osmolality gradient –Cortical collecting duct: K +, H +, and/or HCO 3 - ions may be reabsorbed or secreted depending on what is required to maintain blood pH –The wall of the medullary region of the collecting duct is permeable to urea and is made more so by the presence of ADH (Vasopressin: Antidiuretic Hormone that effects water content of urine) Some urea diffuses out of the collecting duct and contributes to the high osmolality of the inner medulla Urea is much less toxic than ammonia; therefore, organisms that cannot easily and quickly remove ammonia usually have to convert it to some other substance, like urea or uric acid.urea uric acid

85. SUMMARY (e): Collecting Duct: –In the absence of ADH, the collecting duct is nearly impermeable to water, and the dilute urine passes out of the kidney –In the presence of ADH, more aquaporins are inserted into the collecting ducts, and the filtrate loses water by osmosis as it passes through medullary regions of increasing osmolality Consequently, water is conserved, and concentrated urine is excreted

86. SUMMARY Urea Cycling Critical in the reabsorption of water Urea reabsorbed into inner medullary interstitium down concentration gradient—water follows –Urea osmotically pulls water with it Ascending limbs of Vasta Recta pick up urea (and water) carry urea to outer regions of the medulla In outer regions of medulla, high concentration of urea diffuses from the ascending limb of the Vasa Recta into the interstitium where it is picked up: –By the descending limb of Vasta Recta returning some of the urea to inner medulla—countercurrent exchange of urea between ascending and descending limbs of Vasta Recta –By the descending limbs of Loop of Henle of the Cortical Nephrons

87. SUMMARY Urea Cycling ADH regulates permeability of late distal tubules, early and late collecting tubules: –Late distal tubules and early collecting ducts: ADH increases permeability of cells to water by insertion of water channels in membranes –However, if permeability of urea does not increase→increases urea concentration in tubular fluid –Deep collecting ducts: ADH increases permeability of cells to both water and urea –Increase in concentration of urea as a consequence of ADH increasing permeability to water but not urea in late distal tubules and early collecting ducts –Water follows urea: If urea reabsorbed in collecting ducts, water also reabsorbed If urea not reabsorbed in collecting ducts, water follows excretion of urea

88. SUMMARY OF NEPHRON FUNCTIONS

89. URINE Physical Characteristics: –Freshly voided urine is clear and pale to deep yellow due to urochrome, a pigment resulting from the destruction of hemoglobin (via bilirubin or bile pigment) –Fresh urine is slightly aromatic, but develops an ammonia odor if allowed to stand, due to bacterial metabolism of urea –Urine is usually slightly acidic (around pH 6) but can vary from about 4.5-8.0 in response to changes in metabolism or diet A predominantly acidic diet that contains large amounts of protein and whole wheat products produces acidic urine A vegetarian (alkaline) diet, prolonged vomiting, and bacterial infection of the urinary tract all cause the urine to become alkaline –Urine has a higher specific gravity than water, due to the presence of solutes Specific gravity is the weight of a substance compared to an equal volume of water Water has a specific gravity of 1

90. URINE Chemical Composition: –Urine volume is about: 95% water and 5% solutes: Urea: –Largest component of urine by weight, apart from water –Derived from the normal breakdown of amino acids Uric acid: –End product of nucleic acid metabolism Creatinine: –Metabolite of creatine phosphate, which stores energy for the regeneration of ATP –Found in large amounts in skeletal muscle tissue Ions: in order of decreasing concentration –Na +, K +, PO 4 3-, SO 4 2-, Ca 2+, Mg 2+, HCO 3 -

91. Abnormal Urinary Constituents Glycosuria: glucose –Nonpathological: excessive intake of sugary foods –Pathological: diabetes mellitus Proteinuria (albuminuria): proteins –Nonpathological: Excessive physical exertion Pregnancy High-protein diet –Pathological: over 250 mg/day Heart failure Severe hypertension Glomerulonephritis Renal disease

92. Abnormal Urinary Constituents Ketonuria: Ketone bodies –Excessive formation and accumulation of ketone bodies, as in starvation and untreated diabetes mellitus Hemoglobinuria: hemoglobin –Various causes: Transfusion reaction Hemolytic anemia Severe burns Etc Bilirubinuria: bile pigments –Liver disease: hepatitis, cirrhosis –Obstruction of bile ducts from liver or gallbladder Hematuria: erythrocytes –Bledding urinary tract (due to trauma, kidney stones, infection, or neoplasm: tumor/growth) Pyuria: leukocytes (pus) –Urinary tract infection

93. URETERS Ureters are tubes that actively convey urine from the kidneys to the urinary bladder –Descends behind the peritoneum and runs obliquely through the posterior bladder wall This arrangement prevents backflow of urine during bladder filling because any increase in bladder pressure compresses and closes the distal ends of the ureters

94. URETERS The walls of the ureters consist of a: –Inner mucosa continuous with the kidney pelvis and the urinary bladder –Double-layered muscularis (peristaltic contractions move urine to the urinary bladder) –Connective tissue adventitia covering the external surface

95. URETER WALL

96. HOMEOSTATIC IMBALANCE Renal calculi: kidney stones –Crystallized and precipitated salts of calcium, magnesium, or uric acid –Various sizes –Predisposing conditions: Frequent bacterial infections Urine retention High blood levels of calcium Alkaline urine

97. URINARY BLADDER The urinary bladder is a muscular sac that expands as urine is produced by the kidneys to allow storage of urine until voiding is convenient

98. URINARY BLADDER The wall of the bladder has three layers: an outer adventitia, a middle layer of detrusor muscle, and an inner mucosa that is highly folded to allow distention of the bladder without a large increase in internal pressure The smooth, triangular region of the bladder base outlined by these three openings is the trigone –Important clinically because infections tend to persist in this region

99. URINARY BLADDER/URETHRA IN MALE/FEMALE

100. RELATIVE POSITIONING AND SHAPE OF A DISTENDED AND AN EMPTY URINARY BLADDER IN AN ADULT MALE

101. URETHRA The urethra is a muscular tube that drains urine from the body; it is 3-4 cm long in females, but closer to 20 cm in males

102. URETHRA There are two sphincter muscles associated with the urethra: –Internal urinary sphincter: Which is involuntary and formed from detrusor muscle Keeps the urethra closed when urine is not being passed and prevents leaking between voidings –External urinary sphincter: Which is voluntary and formed by the skeletal muscle at the urogenital diaphragm

103. URETHRA The external urethral orifice lies between the clitoris and vaginal opening in females, or occurs at the tip of the penis in males

104. URINARY BLADDER/URETHRA IN MALE/FEMALE

105. HOMEOSTATIC IMBALANCE Because the female’s urethra is very short and its external orifice is close to the anal opening, improper toilet habits (wiping back to front after defecation) can easily carry fecal bacteria into the urethra Most urinary tract infections occur in sexually active women, because intercourse drives bacteria from the vagina and external genital region toward the urethral orifice and the urinary bladder –Spermicides may increase infections –40% of all women get urinary tract infections Urethritis: inflammation of urethra Cystitis: inflammation of urinary bladder Pyelitis (pyelonephritis): renal inflammation

106. MICTURITION Micturition, or urination, is the act of emptying the urinary bladder

107. MICTURITION Storage Reflexes As urine accumulates, distention of the urinary bladder activates stretch receptors (about 200 ml of urine), which trigger spinal reflexes, resulting in storage of urine

108. STORAGE REFLEXES

109. MICTURITION Voiding Reflexes Voluntary initiation of voiding reflexes results in activation of the micturition center of the pons, which signals parasympathetic motor neurons that stimulate contraction of the detrusor muscle and relaxation of the urinary sphincters –Because the external sphincter is voluntarily controlled, we can choose to keep it closed and postpone bladder emptying temporarily The urge to void eventually becomes irresistible and micturition occurs when urine volume exceeds 500-600 ml, whether one wills it or not

110. VOIDING REFLEXES

111. HOMEOSTATIC IMBALANCE Incontinence: –After toddler years, usually a result of emotional problems, physical pressure during pregnancy, or nervous system problems Overflow incontinence: –Urine dribbles from the urethra whenever the bladder overfills Urinary retention: unable to void –Hypertrophy of prostate (male) –Catheter: slender plastic tube inserted through urethra Drains the urine and prevents bladder trauma from excessive stretching

112. DEVELOPMENTAL ASPECTS OF THE URINARY SYSTEM In the developing fetus, the mesoderm-derived urogenital ridges give rise to three sets of kidneys: the pronephros, mesonephros, and metanephros –The pronephros forms and degenerates during the fourth through sixth weeks, but the pronephric duct persists, and connects later-developing kidneys to the cloaca –The mesonephros develops from the pronephric duct, which then is named the mesonephric duct, and persist until development of the metanephros –The metanephros develops at about five weeks, and forms ureteric buds that give rise to the ureters, renal pelvises, calyces, and collecting ducts –The cloaca subdivides to form the future rectum, anal canal, and the urogenital sinus, which gives rise to the urinary bladder and urethra

113. EMBRYONIC DEVELOPMENT OF URINARY SYSTEM

114. DEVELOPMENTAL ASPECTS OF THE URINARY SYSTEM Newborns void most frequently, because the urinary bladder is small and the kidneys cannot concentrate urine until two months of age From two months of age until adolescence, urine output increases until the adult output volume is achieved Voluntary control of the urinary sphincters depends on nervous system development, and complete control of the urinary bladder even during the night does nor usually occur before 4 years of age In old age, kidney function declines due to shrinking of the kidney as nephrons decrease in size and number; the urinary bladder also shrinks and loses tone, resulting in frequent urination