TOPIC 10 Urinary System

1. TOPIC 10 Urinary System Chapter 26 pp. 1004-1036

2. Main Function Regulates the composition and volume of blood by: Regulating water content Maintaining ionic concentrations Maintaining pH balance Removing metabolic wastes (especially urea)

3. Other Functions: Regulates blood pressure secretes renin ? renin-angiotensin pathway (results in formation of angiotensin II - a potent vasoconstrictor) Regulates red blood cell (erythrocyte) formation erythropoietin (stimulates formation of RBCs in red bone marrow) Gluconeogenesis during prolonged fasting

4. Overview of Components Kidneys located posteriorly; superior lumbar region, below diaphragm; retroperitoneal perform functions of urinary system Ureters extend from kidney to urinary bladder transport urine to urinary bladder Urinary Bladder located in pelvic cavity stores urine before micturition Urethra extends from bladder to urethral oriface transports urine to outside

5. Gross Anatomy: Kidney Coverings renal fascia - dense fibrous CT that anchors kidney to posterior abdominal wall adipose capsule - fatty tissue surrounding and cushioning kidney outside of renal capsule renal capsule - connective tissue covering

6. Gross Anatomy: Kidney Regions Regions cortex - outer region medulla - middle region renal sinus - inner open area

7. Gross Anatomy: Ureters Mucosa � transitional epithelium (allows stretching) Muscularis � smooth muscle (propels urine by peristalsis) Adventitia � fibrous connective tissue (anchors ureters)

8. Gross Anatomy: Urinary Bladder Mucosa transitional epithelium designed to withstand stretching Muscularis smooth muscle contracts to expel urine

9. Gross Anatomy: Urethra Lining varies from transitional to pseudostratified columnar to stratified squamous epithelium Internal sphincter of smooth muscle (ANS control) External sphincter of skeletal muscle (voluntary control)

10. Kidney: Internal Anatomy Renal cortex renal columns � extend down into medulla between medullary pyramids Renal medulla medullary (renal) pyramids � formed from collecting tubules papilla � ends of pyramid

11. Kidney: Internal Anatomy Renal pelvis � part of urine collection system; sits in renal sinus major calyces (singular = calyx) � branches of pelvis minor calyces � branches of major calyces that receive urine from renal papillae

12. Nerve Supply Renal plexus - autonomic nervous control sympathetic nerve fibers control vasomotor tone of renal arterioles

13. Blood Supply Arterial blood supply: Renal Artery* Venous drainage: Renal Vein* *divisions covered in lab

14. Microvasculature: Afferent Arteriole Leads to (�feeds�) glomerulus Arises from interlobular artery Larger diameter than efferent arteriole (increases pressure in glomerulus)

15. Microvasculature: Glomerulus Fenestrated capillaries - have pores in walls to increase filtration Surrounded by Bowman�s (glomerular) capsule of nephron filtration membrane = capillary wall plus visceral (inner) layer of Bowman�s capsule plus basement membrane (fused basal laminas of capillary and capsule)

16. Microvasculature: Efferent Arteriole Drain glomerulus Give rise to peritubular capillaries and vasa recta

17. Microvasculature: Peritubular Capillaries Arise from efferent arteriole Follow renal tubules (around proximal and distal convoluted tubules) Low pressure Porous � better for absorption of water and solutes

18. Microvasculature: Vasa Recta Arise from efferent arteriole Follow loop of Henle� toward medulla (loops and vasa recta of juxtamedullary nephrons extend into medulla)

19. Nephrons: Overview Functional unit of the kidney Consist of: Glomerular (Bowman�s) capsule Proximal convoluted tubules (PCT) Loop of Henle� Distal convoluted tubules (DCT)

20. Nephrons: Glomerular Capsule a.k.a. Bowman�s capsule Found in cortex Cup-shaped blind sac surrounding glomerulus Renal corpuscle = Bowman�s capsule + glomerulus Parietal layer of Bowman�s capsule outer wall of capsule simple squamous epithelium

21. Nephrons: Glomerular Capsule Visceral layer (of BC) � in contact with glomerulus modified simple squamous epithelium with branched epithelial cells called podocytes filtration slits � openings between �feet� of podocytes; permit filtrate to enter capsular space Capsular space space between visceral and parietal layers space into which plasma is filtered

22. Nephrons: Proximal Convoluted Tubule (PCT) Proximal portion of nephron; found in cortex Designed for absorption and secretion Simple cuboidal epithelium microvilli increase area for absorption

23. Nephrons: Loop of Henle� Important to concentrated urine Most are entirely cortical (located in cortex) Loops of juxtamedullary nephrons extend into medulla � very important to concentrated urine

24. Nephrons: Loop of Henle� Descending limb � carries filtrate toward medulla thin segment = simple squamous or very low cuboidal ET Ascending limb � carries filtrate back into cortex thick segment = upper part is low columnar

25. Nephrons: Distal Convoluted Tubule (DCT) Found in cortex Last part of nephron Designed for absorption & secretion simple cuboidal epithelium microvilli increase area of cells

26. Types of Nephrons Cortical nephrons (~ 85% of all nephrons) located entirely in cortex (or almost entirely, loops of some dip into upper medulla) Juxtamedullary nephrons renal corpuscle located in cortex close to border with medulla loops of Henle� extend far into medulla important to forming concentrated urine

27. Juxtaglomerular Apparatus Consists of parts of afferent and efferent arterioles (called JG cells) and part of DCT (called macula densa) Juxtaglomerular (JG) cells consist of modified smooth muscle in the walls of the afferent and efferent arterioles respond to decreased blood pressure (BP) by secreting renin

28. Juxtaglomerular Apparatus Macula densa � cells of distal convoluted tubule contains osmoreceptors respond to changes in solute concentration of filtrate in lumen of tubule secrete local vasoconstrictor to decrease flow into glomerulus when solute concentration in filtrate is high

29. Mechanisms of Urine Formation Approx. 1-1.2 l of blood passes through kidney per minute of this, about 120-125 ml is filtered Approx. 99% of filtrate (liquid in lumen of nephron) is reabsorbed (taken back from filtrate back to blood, via interstitial fluid) Filtrate is processed in nephron to become urine that leaves through collecting ducts

30. Three Main Processes � Overview Glomerular Filtration � initial movement of fluid from blood into the capsular space of Bowman�s capsule of nephron Tubular Reabsorption � moves desirable substances from tubule to blood Tubular Secretion � moves undesirable substances from blood into tubule for removal from body

31. Glomerular Filtration Occurs at glomerulus Approx. 120-125 ml filtered into glomerular space per minute (~180 L per day!) Filtrate resembles blood, but normally lacks proteins and formed elements, ions and other solutes are in proportion to concentration in blood

32. Net Filtration Pressure (NFP) Provides force for movement of fluid into capsular space NFP = difference between pressures forcing fluid into glomerular space and pressures resisting filtration Uses forces similar to those involved in movement of fluid between blood and interstitial fluid at other capillaries

33. Net Filtration Pressure (NFP) NFP = forces into nephron � forces out of nephron NFP = HPg + OPc � (OPg + HPc) HPg = glomerular (capillary) hydrostatic pressure within glomerulus OPg = osmotic pressure of the filtrate within capsular space (normally near 0) OPg = glomerular osmotic pressure of the blood within the glomerulus (due to solutes inc., protein) HPc = hydrostatic pressure of fluid within capsular space

34. NFP: Forces Supporting Filtration factors supporting filtration move fluid out of blood into filtrate (within nephron) Glomerular hydrostatic pressure (HPg) main force supporting filtration blood pressure within glomerulus normally approx. 55 mm Hg higher than in most capillaries because efferent arteriole is narrower (smaller diameter) than afferent arteriole

35. NFP: Opposing Forces factors opposing filtrate push/pull fluid out of filtrate, back into blood (Glomerular) blood colloid osmotic pressure (OPg) osmotic pressure created primarily by proteins (albumins) in blood draws fluid back into blood normally 28-30 mm Hg Capsular hydrostatic pressure (HPc) physical pressure of fluids in glomerular space pushes fluid back into blood normally approx. 15 mm Hg

36. Net Filtration Pressure (NFP) NFP = forces into nephron � forces out of nephron NFP = HPg � (OPg + HPc) = 55 mm Hg � (28 mm Hg + 15 mm Hg) = 12 mm Hg range is normally 10-12 mm Hg

37. Glomerular Filtration Rate (GFR) Total amount of filtrate formed per minute (120-125 ml/min) Based on: total surface area available for filtration (number of functioning glomeruli) * permeability of filtration membrane * net filtration pressure varies with systemic blood pressure main part that is controlled Normally, total surface area available and permeability of filtration membrane do not change; can be changed by disease

38. Intrinsic Control (Autoregulation) of GFR Kidney adjusts resistance to blood flow to maintain normal, adequate filtration rate by regulating diameter of afferent (and efferent) arterioles myogenic mechanism (stretch response) = involves changes in vasomotor tone in response to changes in blood pressure tubuloglomerular feedback mechanism � involves macula densa cells of DCT in response to filtrate osmolarity

39. Myogenic mechanism Increase in systemic BP would be expected to increase filtration, kidney counteracts by myogenic mechanism (to a degree) to maintain normal (or near normal) GFR Increased systemic BP, smooth muscles are stretched resulting in reflexive constriction of afferent arterioles decreases filtration pressure (compared to what it would be without change) minimizes increase in pressure due to increased systemic BP to prevent damage to glomerulus With a large increase in systemic BP, filtration increases ? increases fluid loss ? decreases blood volume ? decreases BP

40. Myogenic mechanism Decrease in systemic BP stretches afferent arteriole less resulting in dilation of afferent arterioles, which allows more blood to pass through glomerulus thus increasing filtration pressure (compared to doing nothing) maintains filtration even when BP decreases in order to maintain removal of wastes

41. Tubuloglomerular Feedback Mechanism Macula densa cells of distal convoluted tubules DCT secrete a potent locally-acting vasoconstrictor when: lots of filtrate is present and flow is high osmolarity (solute concentration, especially Na+ and Cl- content) of filtrate is high because not as many ions are being reabsorbed in PCT Vasoconstrictor constricts afferent arterioles which decreases flow ? decreases filtration slows movement of filtrate through nephron thus allowing increased time for reabsorption

42. Tubuloglomerular Feedback Mechanism (con�t) When flow or osmolarity is low, vasoconstrictor is not secreted afferent arteriole remains at normal size (i.e., not constricted) ? more blood enters glomerulus ? greater pressure allows maintenance of filtration rate

43. Extrinsic Controls: ANS � Sympathetic Division rapid control of filtration sympathetic stimulation results in vasoconstriction of afferent arterioles (and to a lesser extent, efferent arterioles) ? less blood enters glomerulus ? lower HPg (lowers NFP) ? decreases filtration ? less filtrate produced ? decreases volume loss to maintain blood pressure

44. Extrinsic Controls: Renin-Angiotensin Pathway Slower method of control Renin (enzyme) secreted by juxtaglomerular cells (of afferent and efferent arterioles) when: BP in arterioles drops and they are no longer stretched as much reduced filtrate flow stimulates macula densa cells (of DCT) next to JG cells sympathetic nervous system stimulates JG cells directly

45. Renin-Angiotensin Pathway (con�t) Renin hydrolyses angiotensinogen to angiotensin I which is then converted to angiotensin II, which: is a potent vasoconstrictor that directly raises BP by increasing peripheral resistance (? increased glomerular hydrostatic pressure) causes greater constriction of efferent than afferent arterioles (restores filtration to normal level when systemic BP decreases)

46. Renin-Angiotensin Pathway (con�t) Renin also stimulates release of aldosterone from adrenal cortex aldosterone acts on DCT to increase Na+ reabsorption leading to increased obligatory water reabsorption

47. Tubular Processing Tubular reabsorption � brings water and solutes back from filtrate into blood Tubular secretion � adds solutes to filtrate Reabsorption and secretion occur simultaneously

48. Tubular Reabsorption (TR) Absorption of solutes from filtrate and subsequent return to blood Takes place in PCT, loop of Henle� and DCT, but substances moved varies through nephron

49. Reabsorbed Substances Most organic nutrients (e.g., glucose, amino acids, vitamins) Most ions Na+ and K+ highly regulated (by aldosterone) H+ regulated to maintain pH balance minerals (e.g., Ca2+) regulated by hormones (PTH) Water reabsorption is highly regulated Aldosterone (indirectly) & antidiuretic hormone (directly)

50. �Nonreabsorbed� Substances Substances that are not reabsorbed or reabsorbed only in small amounts lack carriers, limited lipid solubility, large some substances are partially reabsorbed then later secreted into the DCT Nitrogenous wastes urea: 50% to 60% of urea is reabsorbed because it is small creatinine (from creatine phosphate in skeletal muscle) � large, not lipid soluble uric acid is reabsorbed by PCT, but most is secreted again later

51. Reabsorption Pathways Transcellular materials move through tubule cells materials must cross apical (near lumen) and basolateral membranes transport of some substances requires presence of membrane channels or carriers Paracellular materials go between cells held together by tight junctions limited to very small substances

52. Reabsorption: Passive Transport Uses energy of concentration gradient set up by active reabsorption of Na+ Simple diffusion thru lipid bilayer of membrane fat-soluble substances, urea Facilitated diffusion requires membrane proteins some ions (e.g., Cl-, HCO3-) and polar molecules

53. Reabsorption: Passive Transport Osmosis obligatory water reabsorption (follows osmotic gradient) facultative water reabsorption (controlled by ADH) Solvent drag pulls substances (especially fat-soluble substances and urea) as water moves

54. Reabsorption: Primary Active Transport Requires direct use of ATP Sodium-potassium pump at basal end of cell (basolateral membrane) moves Na+ into interstitial fluid creates Na+ and K+ gradients

55. Reabsorption: Primary Active Transport Na+ gradient forms as Na+ moves from filtrate into cells because of gradient created by active transport of Na+ into interstitial fluid K+ returns to interstitial fluid through K+ channels in basolateral membrane due to gradient created by pumping it into filtrate

56. Reabsorption: Secondary Active Transport (Cotransportation) Cotransport of substance is by same protein that carries Na+ from lumen of tubule into cells of tubule wall Substances cotransported: simple sugars (glucose, galactose, fructose), amino acids some ions vitamins

57. Reabsorption: Secondary Active Transport (Cotransportation) Transport maximum (Tm) � maximum amount of substance that can be reabsorbed per minute depends on number of carrier proteins in membrane solute is lost if availability exceeds Tm or if filtrate moves too fast

58. Sites of Reabsorption Proximal convoluted tubule (PCT) 65% to 99% of desirable solutes reabsorbed about 65% of the filtrate fluid reabsorbed Loop of Henle� � reabsorption of water and NaCl Distal convoluted tubule (DCT) reabsorption of water, NaCl (controlled by aldosterone) Collecting ducts (CD) � NaCl, water, urea water reabsorption is influenced by ADH (antidiuretic hormone) which increases permeability of duct walls to water

59. Control of Tubular Reabsorption: Aldosterone made mainly by zona glomerulosa of adrenal cortex secreted when: K+ levels rise (hyperkapnia) Na+ levels drop (hyponatremia) blood pressure or blood volume drop (renin-angiotensin pathway) ACTH is secreted by adenohypophysis targets cells of collecting ducts to increase Na+ reabsorption and K+ secretion water follows Na+ by osmosis (obligatory reabsorption) ? increases blood volume ? increases blood pressure

60. Control of Tubular Reabsorption: Antidiuretic Hormone (ADH) produced in hypothalamus secreted from posterior pituitary gland when hypothalamic cells detect increase in blood osmotic pressure (solute concentration) acts on DCT and collecting ducts to increase water permeability, thus allowing increased reabsorption of water = facultative water reabsorption

61. Control of Tubular Reabsorption: ANP and PTH Atrial natriuretic peptide (ANP) inhibits reabsorption of Na+ (thus decreasing water reabsorption) decreased water reabsorption ? decreased blood volume ? decreased blood pressure secreted by atria when BP rises Parathyroid Hormone (PTH) secreted by parathyroid glands when blood Ca2+ drops increases Ca2+ reabsorption in DCT

62. Control of Tubular Reabsorption: Diuretics any solute that exceeds its transport maximum acts as an osmotic diuretic e.g., glucose in diabetes mellitus e.g., glucose in steroid diabetes chemicals that inhibit ADH release e.g., alcohol chemicals that inhibit Na+ reabsorption e.g., caffeine

63. Tubular Secretion Movement of solutes from blood (via interstitial fluid) INTO filtrate Solutes secreted include: H+ K+ NH4+ (ammonium ions) organic acids and bases urea and uric acid certain drugs (transported by same carriers as organic acids and bases)

64. Tubular Secretion Important to: disposal of solutes not normally filtered (e.g., penicillin, phenobarbitol) eliminating undesirable substances (urea, uric acid) ridding body of excess K+ maintaining blood pH (by secreting H+)

65. Conserving Water While Removing Wastes Living in dry environment means we constantly lose water --> must conserve water Kidneys conserve water while concentrating undesirable solutes by removal of water (and NaCl) from filtrate

66. Concentration Amount of solute per volume of solution (or solvent) Changed by: changing amount of solute adding solute (tubular secretion) increases concentration removing solute (tubular reabsorption) decreases concentration changing amount of solvent (water) adding solvent decreases concentration removing solvent increases concentration Concentration is measured as osmolality or osmolarity

67. Osmolarity vs Osmolality Osmolality = number of solute particles per kilogram of solvent (water; 1 L water weighs 1 kg at 20o C) filtrate (urine) concentration measured in osmolality unit = milliosmols (mosm) Osmolarity = number of solute particles in 1 liter of solution (e.g., plasma) unit = mg/L

68. Mechanism of Water Conservation Countercurrent multiplier in loop of Henle� and vasa recta Key factors: direction of flow in ascending limb of loop is opposite that of flow in descending limb filtrate entering and exiting loop of Henle� is approximately isotonic with plasma BUT, urea is concentrated relative to blood because water, NaCl and nutrients have been removed

69. Counter-current Multiplier (con�t) Osmotic gradient exists between cortex and medulla Osmolality in cortex ~ 300 milliosmols (mosm) Osmolality in inner (deep) medulla ~ 1200 mosm Descending limb of loop is relatively impermeable to solutes, but freely permeable to water --> water leaves as filtrate descends into medulla

70. Counter-current Multiplier (con�t) Ascending limb of loop is impermeable to water but NaCl is actively reabsorbed from filtrate into interstitial fluid --> creates and maintains osmotic gradient in medulla Vasa recta removes excess water and solute Lower portion of the collecting ducts is permeable to urea, which adds to the high medullary osmolality

71. Mechanism of Concentration (How it works) NaCl is actively reabsorbed from filtrate in ASCENDING LIMB of loop ? NaCl enters interstitial fluid (IF) Entrance of NaCl into IF increases osmolality of IF this exerts an osmotic pressure that draws water out of loop BUT, ascending limb is impermeable to � water cannot leave!! Permeable descending limb is close by and also subject to increased osmolality of IF Water flows out of descending limb of loop of Henle� into IF (i.e., water leaves filtrate)

72. Mechanism of Concentration Loss of water from filtrate increases concentration of solutes remaining in filtrate in descending limb Water and excess NaCl are removed from IF around descending limb by vasa recta? solute concentration in IF stays high Active transport of NaCl out of ascending limb lowers osmolality of filtrate remaining in nephron Urea is more concentrated (as are other remaining solutes) because the amount of urea has not changed while the amount of water (and NaCl) has decreased

73. Mechanism of Concentration Portion of collecting duct deep in inner medulla is permeable to urea, which diffuses out and adds to high osmolality in medulla --> pulls more water out of descending limb into interstitial fluid

74. Role of the Vasa Recta Vasa recta acts does countercurrent exchange Vasa recta (VR) parallel loop of Henle� of juxtamedullary nephrons and descends into inner medulla Freely permeable to both water and NaCl --> preserves osmotic gradient of IF Water leaves vasa recta as it descends into medulla, and reenters as vasa recta ascends into cortex Salt enters as VR descends into medulla, leaves as vasa recta ascends into cortex

75. Formation of Dilute Urine Response to excess fluid intake or decreased secretion of ADH or aldosterone Normally, collecting ducts (CDs) are not very permeable to water, therefore, lots of water leaves with filtrate, resulting in a dilute urine Reabsorption of solutes from DCT and CDs further dilutes urine

76. Formation of Concentrated Urine Response to dehydration or increased ADH or aldosterone secretion Urine is concentrated by reabsorption of water Water reabsorption increases when water permeability of CDs increases Water permeability of CDs increases when ADH is present ADH secreted by posterior pituitary in response to signal from hypothalamus Hypothalamus stimulated by: increase in plasma solute concentration (especially Na+) aldosterone

77. Characteristics & Compositionof Urine Normal constituents include: substances that are only partially reabsorbed (e.g., NaCl, water) substances that are secreted (e.g., organic acids, organic bases, K+, H+) Abnormal constituents include: blood cells (white or red) organic nutrients (e.g., simple sugars, amino acids -- normally completely reabsorbed) hemoglobin bile pigments proteins

78. Micturition (Urination) Distension of bladder activates stretch receptors when ~ 200 ml of urine has accumulated ? visceral reflex arc Sensory impulses to sacral spinal cord segments Result in parasympathetic impulses to smooth muscle of bladder and internal urethral sphincter results in contraction of bladder and relaxation of internal urethral sphincter

79. Micturition (Urination) Sensory input to brain allows conscious recognition of need to urinate and conscious control of external urethral sphincter Reflexive contractions of bladder cease after ~ 1 minute if urine is not voided Cycle begins again after an additional ~ 200-300 ml of urine have accumulated

80. Disorders Incontinence � inability to control micturition voluntarily Bladder infection � invasion of bladder by bacteria Cystitis � inflammation of the bladder Renal calculi (kidney stones) � crystallization of calcium, magnesium or uric acid salts in renal pelvis Nephritis � inflammation of the nephrons Pyelonephritis � inflammation of the kidney caused by bacterial infection Anuria � abnormally low urinary output caused by low glomerular blood pressure or renal failure

81. Disorders: Diabetes Excessive production of urine; differ in cause Insipidus � due to failure of ADH secretion Mellitus � due to lack of insulin (results in excess glucose in urine, which pulls water out) Steroid diabetes � excess of glucocorticoids cause persistent hyperglycermia that results in excess glucose in urine