Urinary System

1. Chapter 26 Urinary System

2. Urinary System Functions Removal of metabolic waste products from the blood and their excretion in the urine Removal of foreign chemicals from the blood and their excretion in the urine. Regulation of Blood volume Concentration of blood solutes: Na+, Cl-, K+, Ca2+, HPO4-2 Acid-base balance Blood cell synthesis Production of hormones (EPO) and enzymes (Renin) Production of 1,25-dihydroxyvitamin D3

3. Nephron Functions: Overview

9. Filtration Movement of fluid, derived from blood flowing through the glomerulus, across filtration membrane Filtrate: water, small molecules, ions that can pass through membrane Pressure difference forces filtrate across filtration membrane Renal fraction: part of total cardiac output that passes through the kidneys. Varies from 12-30%; averages 21% Renal blood flow rate: 1176 mL/min Renal plasma flow rate: renal blood flow rate X fraction of blood that is plasma: 650 mL/min Filtration fraction: part of plasma that is filtered into lumen of Bowman�s capsules; average 19% Glomerular filtration rate (GFR): amount of filtrate produced each minute. About 125 ml/min = 180 L/day (45 gallons/day!!) Average urine production/day: 1-2 L. Most of filtrate must be reabsorbed

11. Filtration Pressure

12. Glomerular Filtration Rate (GFR) Defined as: The volume of filtrate produced by both kidneys per min Averages 115 ml/min in women; 125 ml/min in men Totals about 180L/day (45 gallons) So most filtered water must be reabsorbed or death would ensue from water lost through urination GFR is directly proportional to the NFP Increase GFR leads to an increase in NFP Decrease in GFR leads to a decrease in NFP Changes in GFR normally result from changes in glomerular blood pressure (Gcp)

13. Regulation of GFRGlomerular Filtration Rate If the GFR is too high: Fluid flows through tubules too rapidly to be absorbed Urine output rises Creates threat of dehydration and electrolyte depletion If the GFR is too low: Fluid flows sluggishly through tubules Tubules reabsorb wastes that should be eliminated Azotemia develops (high levels of nitrogen-containing substances in the blood) Only way to adjust GFR moment to moment is to change glomerular blood pressure

15. Renal Autoregulation Renal autoregulation: the ability of nephrons to adjust their own blood flow and GFR IF there were no renal autoregulation and MAP rose from 100 mmHg to 125 mmHg, urine output would rise from 1.5 L/day to 45 L/day!! Two mechanisms used to �renal autoregulate�: Myogenic Response When average BP drops to 70 mm Hg afferent arteriole dilates When average BP increases, afferent arterioles constrict Allows kidney to maintain a constant GFR over wide range of BPs Tubuloglomerular feedback Increased flow of filtrate sensed by macula densa (MD) Macula densa signals afferent arterioles to constrict

16. Extrinsic Control of GFR When the sympathetic nervous system is at rest: Renal blood vessels are maximally dilated Autoregulation mechanisms prevail Under stress: Norepinephrine is released by the sympathetic nervous system Epinephrine is released by the adrenal medulla Afferent arterioles constrict and filtration is inhibited Note: during fight or flight blood is shunted away from kidneys The sympathetic nervous system also stimulates the renin-angiotensin mechanism

17. Sympathetic Effects Sympathetic activity constricts afferent arteriole Helps maintain BP & shunts blood to heart & muscles

19. Tubular Reabsorption(In Reference to Previous Slide) Filtered loads are enormous E.g. only 40 L of water in body, but 180 L filtered per day Reabsorption of waste products is relatively incomplete Thus, large fractions of their filtered load are excreted in the urine Reabsorption of most useful plasma components is relatively complete Thus, amounts excreted in urine represent very small fraction of filtered load

20. Tubular Reabsorption: Overview Tubular reabsorption: occurs as filtrate flows through the lumens of proximal tubule, loop of Henle, distal tubule, and collecting ducts Processes used in reabsorption include: Diffusion Facilitated diffusion Active transport Cotransport Osmosis Reabsorbed substances are transported to interstitial fluid and reabsorbed into peritubular capillaries.

21. Tubular Reabsorption and Secretion

23. Peritubular Capillaries Blood has unusually high COP here, and BHP is only 8 mm Hg This favors reabsorption Water absorbed by osmosis and carries other solutes with it (solvent drag)

24. Reabsorption of Salt & H20 The PCT returns most molecules & H20 from filtrate back to peritubular capillaries About 180 L/day of ultrafiltrate produced; only 1�2 L of urine excreted/24 hours Urine volume varies according to needs of body Minimum of 400 ml/day urine necessary to excrete metabolic wastes (obligatory water loss)

25. PCT Filtrate in PCT is isosmotic to blood (300 mOsm/L) Thus reabsorption of H20 by osmosis cannot occur without active transport (AT) Is achieved by AT of Na+ out of filtrate Loss of + charges causes Cl- to passively follow Na+ Water follows salt by osmosis

27. Glucose & Amino Acid Reabsorption Filtered glucose & amino acids are normally 100% reabsorbed from filtrate Occurs in PCT by carrier-mediated cotransport with Na+ Transporter displays saturation if ligand concentration in filtrate is too high Level needed to saturate carriers & achieve maximum transport rate is transport maximum (Tm) Glucose & amino acid transporters don't saturate under normal conditions

28. Tubular Maximum Tubular Maximum (TM: Defined as Maximum rate at which a substance can be actively absorbed Each substance has its own tubular maximum Normally, glucose concentration in the plasma (and thus filtrate) is lower than the tubular maximum and all of it is reabsorbed. In diabetes mellitus, tubular load exceeds tubular maximum and glucose appears in urine. Urine volume increases because glucose in filtrate increases osmolality of filtrate reducing the effectiveness of water reabsorption

29. Significance of PCT Reabsorption �65% Na+, Cl-, & H20 is reabsorbed in PCT & returned to bloodstream An additional 20% is reabsorbed in descending limb of the loop of Henle Thus 85% of filtered H20 & salt are reabsorbed early in tubule This is constant & independent of hydration levels Energy cost is 6% of calories consumed at rest The remaining 15% is reabsorbed variably, depending on level of hydration

30. Medullary Concentration Gradient In order to concentrate urine (and prevent a large volume of water from being lost), the kidney must maintain a high concentration of solutes in the medulla Interstitial fluid concentration (mOsm/kg) is 300 in the cortical region and gradually increases to 1400 at the tip of the pyramids in the medulla Maintenance of this gradient depends upon Functions of loops of Henle Vasa recta flowing countercurrent to filtrate in loops of Henle Distribution and recycling of urea

31. Descending Limb Is permeable to H20 Is impermeable to salt Because deep regions of medulla are 1400 mOsm, H20 diffuses out of filtrate until it equilibrates with interstitial fluid This H20 is reabsorbed by capillaries

32. Ascending Limb LH Has a thin segment in depths of medulla & thick part toward cortex Impermeable to H20 Permeable to salt Thick part ATs salt out of filtrate AT of salt causes filtrate to become dilute (100 mOsm) by end of LH

33. AT in Ascending Limb NaCl is actively extruded from thick ascending limb into interstitial fluid Na+ diffuses into tubular cell with secondary active transport of K+ and Cl-

34. Na+ is AT across basolateral mem-brane by Na+/ K+ pump Cl- passively follows Na+ down electrical gradient K+ passively diffuses back into filtrate AT in Ascending Limb continued

35. Countercurrent Multiplier System Countercurrent flow & proximity allow descending & ascending limbs of LH to interact in way that causes osmolarity to build in medulla Salt pumping in thick ascending part raises osmolarity around descending limb, causing more H20 to diffuse out of filtrate This raises osmolarity of filtrate in descending limb which causes more concentrated filtrate to be delivered to ascending limb As this concentrated filtrate is subjected to AT of salts, it causes even higher osmolarity around descending limb (positive feedback) Process repeats until equilibrium is reached when osmolarity of medulla is 1400

36. Vasa Recta Is important component of countercurrent multiplier Permeable to salt, H20 (via aquaporins), & urea Recirculates salt, trapping some in medulla interstitial fluid Reabsorbs H20 coming out of descending limb Descending section has urea transporters Ascending section has fenestrated capillaries

37. Effects of Urea Urea contributes to high osmolality in medulla Deep region of collecting duct is permeable to urea & transports it

38. Osmotic Gradient in the Renal Medulla

39. Urine Concentrating Mechanisms

41. Collecting Duct (CD) Plays important role in water conservation Is impermeable to salt in medulla Permeability to H20 depends on levels of ADH

42. ADH Is secreted by posterior pituitary in response to dehydration Stimulates insertion of aquaporins (water channels) into plasma membrane of CD When ADH is high, H20 is drawn out of CD by high osmolality of interstitial fluid & reabsorbed by vasa recta

43. Formation of Concentrated Urine ADH-dependent water reabsorption is called facultative water reabsorption ADH is the signal to produce concentrated urine ADH stimulates formation of aquaporins in membrane of tubule cells. Increases water reabsorption from filtrate The kidneys� ability to respond depends upon the high medullary osmotic gradient

44. Urine Movement Hydrostatic pressure forces urine through nephron Peristalsis moves urine through ureters from region of renal pelvis to urinary bladder. Occur from once every few seconds to once every 2-3 minutes Parasympathetic stimulation: increase frequency Sympathetic stimulation: decrease frequency Ureters enter bladder obliquely through trigone. Pressure in bladder compresses ureter and prevents backflow

45. Composition and Properties of Urine Appearance almost colorless to deep amber; yellow color due to urochrome, from breakdown of hemoglobin (RBC�s) Odor - as it stands bacteria degrade urea to ammonia Specific gravity density of urine ranges from 1.001 -1.028 Osmolarity - (blood - 300 mOsm/L) ranges from 50 mOsm/L to 1,200 mOsm/L in dehydrated person pH - range: 4.5 - 8.2, usually 6.0 Chemical composition: 95% water, 5% solutes urea, NaCl, KCl, creatinine, uric acid

46. Neural Control of Micturition

47. Micturition Reflex

48. Micturition Reflex Filling of bladder stimulates stretch receptors. Stimulate parasympathetic fibers which: inhibits contraction of the external urethral sphincter stimulates contraction of the detrusor muscle of the bladder

49. Urine Volume Normal volume - 1 to 2 L/day Polyuria > 2L/day Oliguria < 500 mL/day Anuria - 0 to 100 mL/day

50. Diuretics Effects ? urine output ? blood volume Uses hypertension and congestive heart failure Mechanisms of action ? GFR ? tubular reabsorption

51. Kidney Diseases In acute renal failure, ability of kidneys to excrete wastes & regulate blood volume, pH, & electrolytes is impaired Rise in blood creatinine & decrease in renal plasma clearance of creatinine Can result from atherosclerosis, inflammation of tubules, kidney ischemia, or overuse of NSAIDs Glomerulonephritis is inflammation of glomeruli Autoimmune attack against glomerular capillary basement membranes Causes leakage of protein into urine resulting in decreased colloid osmotic pressure & resulting edema

52. In renal insufficiency, nephrons have been destroyed as a result of a disease Clinical manifestations include salt & H20 retention & uremia (high plasma urea levels) Uremia is accompanied by high plasma H+ & K+ which can cause uremic coma Treatment includes hemodialysis Patient's blood is passed through a dialysis machine which separates molecules on basis of ability to diffuse through selectively permeable membrane Urea & other wastes are removed Kidney Diseases continued

53. Diabetes Chronic polyuria of metabolic origin With hyperglycemia and glycosuria diabetes mellitus I and II, insulin hyposecretion/insensitivity gestational diabetes, 1 to 3% of pregnancies ADH hyposecretion diabetes insipidus; CD ? water reabsorption