Chapter 17. Lecture Outline. See separate PowerPoint slides for all figures and tables pre-inserted into PowerPoint without notes.

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1 Chapter 17 Lecture Outline See separate PowerPoint slides for all figures and tables pre-inserted into PowerPoint without notes. Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

2 I. Structure and Function of the Kidneys

3 A. Kidney Functions 1. Regulation of the extracellular fluid environment in the body, including: a. Volume of blood plasma (affects blood pressure) b. Wastes c. Electrolytes d. ph

4 B. Gross structure of the urinary system 1. Introduction a. Urine made in the kidney drains into the renal pelvis, then down the ureter to the urinary bladder. b. It passes from the bladder through the urethra to exit the body. c. Urine is transported using.

5 Organs of the urinary system Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Inferior vena cava Renal artery Renal vein Kidney Renal vein Renal artery Abdominal aorta Ureter Urinary bladder Urethra

6 2. Kidney Structure a. The kidney has two distinct regions: 1) Renal cortex 2) Renal medulla, made up of renal pyramids and columns b. Each pyramid drains into a minor calyx major calyx renal pelvis.

7 Radiograph of the urinary system Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Twelfth thoracic vertebra Twelfth rib Minor calyx Renal pelvis Kidney Ureter Urinary bladder SPL/Photo Researchers

8 C. Control of Micturition 1. Detrusor muscles line the wall of the urinary bladder. a. Gap junctions connect smooth muscle cells. b. Innervated by parasympathetic neurons, which release acetylcholine onto muscarinic ACh receptors 2. Sphincters surround urethra. a. Internal urethral sphincter: smooth muscle b. External urethral sphincter: skeletal muscle

9 Control of Micturition, cont 3. Stretch receptors in the bladder send information to S2 S4 regions of the spinal cord. a. These neurons normally inhibit parasympathetic nerves to the detrusor muscles, while somatic motor neurons to the external urethral sphincter are stimulated. b. Called the guarding reflex c. Prevents involuntary emptying of bladder

10 Control of Micturition, cont 4. Stretch of the bladder initiates the voiding reflex. a. Information about stretch passes up the spinal cord to the micturition center of the. b. Parasympathetic neurons cause detrusor muscles to contract rhythmically c. Inhibition of sympathetic innervation of the internal urethral sphincter causes it to relax. d. Person feels the need to urinate and can control when with external urethral sphincter.

11 D. Microscopic Kidney Structure 1. : functional unit of the kidney a. Each kidney has more than a million nephrons. b. Nephron consists of small tubules and associated blood vessels. c. Blood is filtered, fluid enters the tubules, is modified, then leaves the tubules as urine

12 Kidney Structure Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Renal cortex Renal medulla Renal pyramid Minor calyx Major calyx Renal cortex Nephron Renal column Renal pelvis I Renal artery Renal vein Renal medulla Ureter Renal papilla (a) Renal papilla Minor calyx Glomerular capsule (b) Distal convoluted tubule Collecting duct Proximal convoluted tubule Loop of Henle (c)

13 2. Renal Blood Vessels Renal artery Interlobar arteries Arcuate arteries Interlobular arteries Afferent arterioles Glomerulus Efferent arterioles Peritubular capillaries Interlobular veins Arcuate veins Interlobar veins Renal vein Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Interlobular artery and vein Renal cortex Arcuate artery and vein Interlobar artery and vein Renal medulla Renal artery Renal pelvis Renal vein Ureter

14 3. Nephron Tubules a. Glomerular (Bowman s) capsule surrounds the glomerulus. Together, they make up the. a. Filtrate produced in renal corpuscle passes into the. b. Next, fluid passes into the descending and ascending limbs of the. c. After the loop of Henle, fluid passes into the. d. Finally, fluid passes into the. e. The fluid is now urine and will drain into a minor calyx.

15 Nephron Tubules & Associated Blood Vessels Glomerulus Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Peritubular capillaries Distal convoluted tubule Glomerular capsule Efferent arteriole Afferent arteriole Interlobular artery Proximal convoluted tubule Interlobular vein Arcuate artery and vein Interlobar artery and vein Nephron loop (of Henle) Descending limb Ascending limb Peritubular capillaries (vasa recta) Collecting duct

16 4. Two Types of Nephrons a. Juxtamedullary: better at making concentrated urine b. Cortical Cortical nephron Juxtamedullary nephron (a) Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Renal cortex Glomerulus Renal medulla Blood flow (b) Collecting duct

17 II. Glomerular Filtration

18 A. Glomerular Corpuscle 1. Capillaries of the glomerulus are fenestrated. a. Large pores allow water and solutes to leave but not blood cells and plasma proteins. 2. Fluid entering the glomerular capsule is called filtrate

19 Glomerular Corpuscle, cont 3. Filtrates must pass through: a. Capillary fenestrae b. Glomerular basement membrane c. Visceral layer of the glomerular capsule composed of cells called podocytes with extensions called pedicels

20 Glomerular Capillaries & Capsule Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Podocyte cell body Primary process of podocyte Branching pedicels Professor P.M. Motta and M. Sastellucci/SPL/Photo Researchers

21 Glomerular Corpuscle & Filtration Barrier Afferent arteriole Blood flow Efferent arteriole Parietal layer of glomerular capsule Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glomerulus Proximal convoluted tubule Glomerular (Bowman s) capsule Podocyte of visceral layer of glomerular capsule Filtrate Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Slit diaphragm Foot processes Fenestrae Pedicel (foot process) Basement membrane Fenestrae Capillary endothelium Glomerular basement membrane Slit diaphragm Filtration slits Plasma Capillary lumen Erythrocyte Fenestra Podocyte foot process Donald Fawcett & D. Friend/Visuals Unlimited, Inc

22 Glomerular Corpuscle, cont d. Slits in the pedicels called slit diaphragm pores are the major barrier for the filtration of plasma proteins. 1) Defect here causes proteinuria = proteins in urine. 2) Some albumin is filtered out but is reabsorbed by active endocytosis.

23 B. Glomerular Ultrafiltrate 1. Fluid in glomerular capsule gets there via hydrostatic pressure of the blood, colloid osmotic pressure, and very permeable capillaries. 2. These forces produce a net filtration pressure of about 10mmHg

24 Formation of Glomerular Ultrafiltrate Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glomerular (Bowman s) capsule Protein Afferent arteriole Glomerular ultrafiltrate Other solutes Efferent arteriole

25 3. Filtration Rates a. Glomerular filtration rate (GFR): volume of filtrate produced by both kidneys each minute = ml. 1) 180 L/day (~45 gal) 2) Total blood volume is filtered every 40 minutes 3) Most must be reabsorbed immediately

26 C. Regulation of Glomerular Filtration Rate 1. Vasoconstriction or dilation of afferent arterioles changes filtration rate. a. Extrinsic regulation via sympathetic nervous system b. Intrinsic regulation via signals from the kidneys; called renal autoregulation

27 2. Sympathetic Nerve Effects a. In a fight/flight reaction, there is vasoconstriction of the afferent arterioles. b. Helps divert blood to heart and muscles c. Urine formation decreases to compensate for the drop in blood pressure

28 Sympathetic Nerve Effects Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Stimuli Blood pressure Exercise Baroreceptor reflex Sympathetic nerve activity Cardiac output Vasoconstriction of afferent arterioles in kidneys Vasoconstriction in skin, GI tract GFR Total peripheral resistance Urine production Blood volume Negative feedback corrections

29 3. Renal Autoregulation a. GFR is maintained at a constant level even when blood pressure (BP) fluctuates greatly. 1) Afferent arterioles dilate if BP < 70. 2) Afferent arterioles constrict if BP > normal. b. Myogenic constriction: Smooth muscles in arterioles sense an increase in blood pressure.

30 Renal Autoregulation, cont c. Tubuloglomerular feedback: Cells in the ascending limb of the loop of Henle called sense a rise in water and sodium as occurs with increased blood pressure (and filtration rate). 1) They send a chemical signal (ATP) to constrict the afferent arterioles.

31 Regulation of Glomerular Filtration Rate

32 III. Reabsorption of Salt and Water

33 A. Introduction 1. return of filtered molecules to the blood L of water is filtered per day, but only 1 2 L is excreted as urine. a. This will increase when well hydrated and decrease when dehydrated. b. A minimum 400 ml must be excreted to rid the body of wastes = obligatory water loss. c. 85% of reabsorption occurs in the proximal tubules and descending loop of Henle. This portion is unregulated.

34 Filtration and Reabsorption Reabsorption Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Filtration Glomerular (Bowman s) capsule Glomerulus

35 B. Reabsorption in the Proximal Tubule 1. The osmolality of filtrate in the glomerular capsule is equal to that of blood plasma (isoosmotic). 2. Na + is actively transported out of the filtrate into the peritubular blood to set up a concentration gradient to drive osmosis.

36 3. Active Transport a. Cells of the proximal tubules are joined by tight junctions on the apical side (facing inside the tubule). b. The apical side also contains microvilli. c. These cells have a lower Na + concentration than the filtrate inside the tubule due to Na + /K + pumps on the basal side of the cells and low permeability to Na +. d. Na + from the filtrate diffuses into these cells and is then pumped out the other side.

37 4. Passive Transport a. The pumping of sodium into the interstitial space attracts negative Cl out of the filtrate. b. Water then follows Na + and Cl into the tubular cells and the interstitial space. c. The salts and water diffuses into the peritubular capillaries.

38 Salt and Water Reabsorption in the Proximal Tubule Cl transport (passive) Reabsorption Na + transport (active) Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. H 2 O follows salt by osmosis Filtration Glomerular (Bowman s) capsule Fluid reduced to 1 / 3 original volume, but still isosmotic

39 5. Significance of proximal tubule reabsorption a. 65% of the salt and water is reabsorbed, but that is still too much filtrate b. An additional 20% of water is reabsorbed through the descending limb of the Loop of Henle. 1) Happens continuously and is unregulated 2) The final 15% of water (~27 L) is absorbed later in the nephron under hormonal control. 3) Fluid entering loop of Henle is isotonic to extracellular fluids.

40 C. Countercurrent Multiplier System 1. Water cannot be actively pumped out of the tubes, and it will not cross if isotonic to extracellular fluid. a. The structure of the loop of Henle allows for a concentration gradient to be set up for the osmosis of water. b. The ascending portion sets up this gradient.

41 2. Ascending Limb of the Loop of Henle a. Salt (NaCl) is actively pumped into the interstitial fluid from the thick segment of the limb 1) Movement of Na + down its electrochemical gradient from filtrate into tubule cells powers the secondary active transport of Cl and K +. 2) Na + is moved into interstitial space via Na + /K + pump. Cl follows Na + passively due to electrical attraction, and K + passively diffuses back into filtrate.

42 Transport of Ions in the Ascending Limb of the Loop of Henle Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ascending limb of loop Filtrate (tubular lumen) Interstitial space Apical membrane 2 Cl 2 Cl 2 Na + Na + ATP ADP Na + 1 Na + K + K + K + K + 3 K + Cl Cl K + Cl K + Cl Basolateral membrane

43 Ascending Limb of the Loop of Henle, cont b. Walls are not permeable to water, so osmosis cannot occur from the ascending part of the loop. c. Surrounding interstitial fluid becomes increasingly solute concentrated at the bottom of the tube. d. Tubular fluid entering the ascending loop of Henle becomes more hypotonic as it ascends the loop.

44 3. Descending Limb of the Loop of Henle a. Is not permeable to salt but is permeable to water b. Water is drawn out of the filtrate and into the interstitial space where it is quickly picked up by capillaries. c. As it descends, the fluid becomes more solute concentrated. 1) This is perfect for salt transport out of the fluid in the ascending portion.

45 1, Countercurrent Multiplier System Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 300 mosm Loop of Henle Cortex Medulla 2 H 2 O H 2 O H 2 O ,000 Na + Cl Na + Cl Na + Cl Na + Cl 1 Na + Cl Na + Cl Na + Cl Na + Cl Capillary 3 1,400 Descending limb Passively permeable to water Ascending limb Active transport of Na +, Cl follows passively; impermeable to water

46 4. Countercurrent Multiplication a. Positive feedback mechanism is created between the two portions of the loop of Henle. 1) The more salt the ascending limb removes, the saltier the fluid entering it will be (due to loss of water in descending limb).

47 b. Steps of countercurrent mechanism 1) Interstitial fluid is hypertonic due to NaCl pumped out of the ascending limb 2) Water leaves descending limb by osmosis, making the filtrate hypertonic going into the ascending limb 3) More NaCl in the ascending limb can now be pumped out into the interstitial fluid 4) The greater concentration of the interstitial fluid draws more water from the descending limb 5) Filtrate in ascending limb now more concentrated 6) Continues until the maximum NaCl concentration of the inner medulla is reached.

48 c. Vasa Recta 1) Specialized blood vessels around loop of Henle, which also have a descending and ascending portion 2) Help create the countercurrent system because they take in salts in the descending region but lose them again in the ascending region a) Keep salts in the interstitial space

49 Vasa Recta, cont 3) High salt concentration (oncotic pressure) at the beginning of the ascending region pulls in water, which is removed from the interstitial space. a) Also keeps salt concentration in the interstitial space high 4) There are also urea transporters and aquaporins to aid in the countercurrent exchanges

50 Countercurrent Exchange in the Vasa Recta Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Blood flow Capillary 300 Tissue fluid Renal cortex Outer renal medulla ,075 Inner renal medulla 1,025 1,200 Diffusion of NaCl and urea Osmosis of water

51 5. Effects of Urea a. Urea is a waste product of protein metabolism b. Contributes to countercurrent system 1) Transported out of collecting duct and into interstitial fluid 2) Diffuses back into ascending limb and cycles around continuously 3) Helps set up solute concentration gradients

52 Role of Urea in Urine Concentration Cortex Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Distal tubule H 2 O Outer medulla H 2 O Collecting duct H 2 O Inner medulla H 2 O H 2 O H 2 O NaCl Urea Water Loop of Henle H 2 O

53 Renal Tubule Transport Properties

54 Renal Tubule Osmolality Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Proximal tubule Distal tubule Collecting duct Cortex Vasa recta H 2 O Outer medulla H 2 O Descending limb of loop H 2 O Ascending limb of loop H 2 O Inner medulla 1,200 1,200 1,200 1,400 1,400 1,400 H 2 O

55 D. Collecting Duct and ADH 1. Last stop in urine formation 2. Impermeable to NaCl but permeable to water a. Also influenced by hypertonicity of interstitial space water will leave via osmosis if able to b. Permeability to water depends on the number of aquaporin channels in the cells of the collecting duct c. Availability of aquaporins determined by ADH (antidiuretic hormone)

56 Collecting Duct and ADH, cont 3. ADH binds to receptors on collecting duct cells camp Protein kinase Vesicles with aquaporin channels fuse to plasma membrane. a) Water channels are removed without ADH. 4. ADH is produced by neurons in the hypothalamus but stored and released from the posterior pituitary gland a) Release stimulated by an increase in blood osmolality

57 ADH Stimulation of Aquaporin Channels Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Extracellular fluid Cytoplasm ADH Vesicle Aquaporin channels Fusion of exocytotic vesicle (a) No ADH (b) ADH No ADH Plasma membrane with aquaporin channels (d) Formation of endocytotic vesicle (c)

58 Homeostasis of Plasma Concentration by ADH Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Stimulus Stimulus Low water intake (dehydration) High water intake (over-hydration) Plasma osmolality Plasma osmolality Osmoreceptors in hypothalamus Sensor Integrating center Effector Posterior pituitary ADH ADH Kidneys Water reabsorption Water reabsorption Negative feedback correction Less water excreted in urine More water excreted in urine Negative feedback correction

59 ADH Secretion and Action

60 IV. Renal Plasma Clearance

61 A. Transport processes affecting renal clearance 1. Kidneys must also remove excess ions and wastes from the blood. a. Sometimes called renal clearance b. Filtration in the glomerular capsule begins this process. c. Reabsorption returns some substances to the blood (decreases renal clearance) d. Secretion finishes the process when substances are moved from the peritubular capillaries into the tubules. (increases renal clearance)

62 2. Excretion Rate a. Excretion rate = (filtration rate + secretion rate) reabsorption rate b. Used to measure glomerular filtration rate (GFR), an indicator of renal health

63 Secretion is the reverse of reabsorption Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Secretion Reabsorption Filtration Excretion

64 3. Secretion of Drugs a. Membrane carriers specific to foreign substances transport them into the tubules. b. Called organic anion transporters (OATs) or organic cation transporters (OCTs) c. Carriers are polyspecific overlap in function d. Very fast; may interfere with action of therapeutic drugs

65 B. Clearance of Inulin 1. Inulin is a compound found in garlic, onion, dahlias, and artichokes. a. Great marker of glomerular filtration rate because it is filtered but not reabsorbed or secreted V X U GFR = P V = rate of urine formation U = inulin concentration in urine P = inulin concentration in plasma

66 Renal Clearance of Inulin Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Inulin (a) (b) Renal artery with inulin To peritubular capillaries Renal vein inulin concentration lower than in renal artery (c) Ureter urine containing all inulin that was filtered

67 2. Renal Plasma Clearance Calculation a. Volume of plasma from which a substance is completely removed by the kidneys in 1 minute 1) Inulin is filtered only. Clearance = GFR 2) Anything that can be reabsorbed has a clearance < GFR. 3) If a substance is filtered and secreted, it will have a clearance > GFR. 4) Renal plasma clearance uses same formula as GFR. b. Clearance of urea is less than GFR means some is reabsorbed

68 Renal Plasma Clearance

69 C. Clearance of PAH 1. Not all blood delivered to the glomeruli is filtered in each pass, so blood must make several passes to completely clear a substance. 2. PAH (para-aminohippuric acid) is an exogenous molecule injected for measurement of total renal blood flow. 3. Substances not filtered must be secreted into the tubules by active transport from the peritubular capillaries 4. All PAH in the peritubular capillaries will be secreted by OATs, so the time it takes to clear all PAH injected indicates blood flow to these capillaries.

70 Renal Clearance of PAH Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. PAH Filtration (a) To peritubular capillaries Renal artery containing PAH Renal vein almost no PAH (c) Peritubular capillaries To renal vein Filtration plus secretion (d) Ureter urine containing almost all PAH that was in renal artery

71 D. Reabsorption of Glucose 1. Glucose (and amino acids) is easily filtered out into the glomerular capsule 2. Completely reabsorbed in the proximal tubule via secondary active transport with sodium, facilitated diffusion, and simple diffusion

72 Mechanism of Reabsorption in the proximal tubule Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Lumen of kidney tubule Glucose Apical membrane Na + 1 Cotransport Proximal tubule cell Basolateral membrane ATP ADP K + 3 Facilitated diffusion Primary active transport 2 Simple diffusion Glucose K + Na + Capillary

73 Reabsorption of Glucose, cont 3. Glucose/Na + cotransporters have a transport maximum (T m ). a. If there is too much glucose in the filtrate, it will not be completely reabsorbed because all the carriers are in use (saturated). b. Extra glucose spills over into the urine = glycosuria and is a sign of diabetes mellitus. c. Extra glucose in the blood also results in decreased water reabsorption and possible dehydration.

74 V. Renal Control of Electrolyte and Acid-Base Balance

75 A. Introduction 1. Kidneys match electrolyte (Na +, K +, Cl, bicarbonate, phosphate) excretion to ingestion. a. Control of Na + levels is important in blood pressure and blood volume. b. Control of K + levels is important in healthy skeletal and cardiac muscle activity. c. Aldosterone plays a big role in Na + and K + balance.

76 B. Role of Aldosterone in Na + /K + Balance 1. About 90% of filtered Na + and K + is reabsorbed early in the nephron. a. This is not regulated. 2. An assessment of what the body needs is made, and aldosterone controls additional reabsorption of Na + and secretion of K + in the distal tubule and collecting duct.

77 3. Potassium Secretion a. Aldosterone independent response: Increase in blood K + triggers an increase in the number of K + channels in the cortical collecting duct. 1) When blood K + levels drop, these channels are removed. b. Aldosterone-dependent response: Increase in blood K + triggers adrenal cortex to release aldosterone. 1) This increases K + secretion in the distal tubule and collecting duct.

78 Potassium is Reabsorbed and Secreted Filtered Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Reabsorbed K + Secreted K + K + Cortical portion of collecting duct Proximal convoluted tubule Excreted

79 c. Sodium and Potassium 1) Increases in sodium absorption drive extra potassium secretion. 2) Due to: a) Potential difference created by Na + reabsorption driving K + through K + channels b) Stimulation of renin-angiotensin-aldosterone system by water and Na + in filtrate c) Increased flow rates bend cilia on the cells of the distal tubule, resulting in activation of K + channels

80 4. Control of Aldosterone Secretion a. A rise in blood K + directly stimulates production of aldosterone in the adrenal cortex. b. A fall in blood Na + indirectly stimulates production of aldosterone via the renin- angiotensinaldosterone system.

81 C. Juxtaglomerular Apparatus 1. Located where the afferent arteriole comes into contact with the distal tubule Glomerular capsule Glomerulus Region of the juxtaglomerular apparatus Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glomerulus Afferent arteriole Efferent arteriole Distal tubule Afferent arteriole Granular cells Efferent arteriole Macula densa Juxtaglomerular apparatus (a) Loop of Henle (b) Thick ascending limb

82 Juxtaglomerular Apparatus, cont 2. A decrease in plasma Na + results in a fall in blood volume. a. Sensed by juxtaglomerular apparatus b. Granular cells secrete renin into the afferent arteriole. c. This converts angiotensinogen into angiotensin I. d. Angiotensin-converting enzyme (ACE) converts this into angiotensin II.

83 Juxtaglomerular Apparatus 3. Stimulates adrenal cortex to make aldosterone a. Promotes the reabsorption of Na + from cortical collecting duct b. Promotes secretion of K + c. Increases blood volume and raises blood pressure

84 4. Regulation of Renin Secretion a. Low salt levels result in lower blood volume due to inhibition of ADH secretion. 1) Less water is reabsorbed in collecting ducts and more is excreted in urine. b. Reduced blood volume is detected by granular cells that act as baroreceptors. They then secrete renin. 1) Granular cells are also stimulated by sympathetic innervation from the baroreceptor reflex.

85 Homeostasis of Plasma Na + Sensor Integrating center Effector Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Stimulus Low Na + intake Negative feedback correction Na + retention in blood Low plasma Na + concentration Na + reabsorption in cortical collecting duct Hypothalamus Aldosterone Posterior pituitary Adrenal cortex ADH Angiotensin II Water reabsorption in collecting ducts Renin Urine volume Blood volume Juxtaglomerular apparatus Sympathetic nerve activity

86 5. Macula Densa a. Part of the distal tubule that forms the juxtaglomerular apparatus b. Sensor for tubuloglomerular feedback needed for regulation of glomerular filtration rate 1) When there is more Na + and H 2 O in the filtrate, a signal is sent to the afferent arteriole to constrict limiting filtration rate. 2) Controlled via negative feedback

87 Macula Densa, cont c. When there is more Na + and H 2 O in the filtrate, a signal is sent to the afferent arteriole to inhibit the production of renin. 1) This results in less reabsorption of Na +, allowing more to be excreted. 2) This helps lower Na + levels in the blood.

88 D. Atrial Natriuretic Peptide 1. Increases in blood volume also increase the release of atrial natriuretic peptide hormone from the atria of the heart when atrial walls are stretched. 2. Stimulates kidneys to excrete more salt and therefore more water 3. Decreases blood volume and blood pressure

89 Regulation of Renin and Aldosterone Secretion

90 E. Relationship Between Na +, K +, and H + 1. Reabsorption of Na + stimulates the secretion of other positive ions; K + and H + compete. 2. Acidosis stimulates the secretion of H + and inhibits the secretion of K + ions; acidosis can lead to hyperkalemia. 3. Alkalosis stimulates the secretion and excretion of more K Hyperkalemia stimulates the secretion of K + and inhibits secretion of H + ; can lead to acidosis

91 Reabsorption of Na + and Secretion of K +, and H + Blood Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Peritubular capillaries Na + K + or H + Na + Na + Na + Na + Na + Na + K + /H + Distal tubule Cortical collecting duct Na + K + K + H + Na+ Na + Na + K + H + K + Na + Ascending limb of Henle s loop Medullary collecting duct

92 F. Acid-Base Regulation 1. Kidneys maintain blood ph by reabsorbing bicarbonate and secreting H + ; urine is thus acidic. 2. Proximal tubule uses Na + /H + pumps to exchange Na + out and H + in. a. Some of the H + brought in is used for the reabsorption of bicarbonate. b. Antiport secondary active transport

93 Acid-Base Regulation, cont 3. Bicarbonate cannot cross the inner tubule membrane so must be converted to CO 2 and H 2 O using carbonic anhydrase. a. Bicarbonate + H + carbonic acid b. Carbonic acid (w/ carbonic anhydrase) H 2 O + CO 2 c. CO 2 can cross into tubule cells, where the reaction reverses and bicarbonate is made again. d. This diffuses into the interstitial space.

94 Acidification of the Urine Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. HCO 3 Na + Na + HCO 3 Proximal tubule CA H 2 CO 3 H 2 O + CO 2 Na + ATPase Distal tubule K + Blood H + H + Filtration Lumen Na + HCO 3 + H + CA Na + H + H + 2 O CO 2 2 HPO H 2 CO 4 3 NH 3 H + H 2 PO 4 NH 4 + Proximal tubule cell

95 Acid-Base Regulation, cont 4. Aside from the Na + /H + pumps in the proximal tubule, the distal tubule has H + ATPase pumps to increase H + secretion.

96 5. ph Disturbances a. Kidneys can help compensate for respiratory problems b. Alkalosis: Less H + is available to transport bicarbonate into tubule cells, so less bicarbonate is reabsorbed; extra bicarbonate secretion compensates for alkalosis.

97 ph Disturbances, cont c. Acidosis: Proximal tubule can make extra bicarbonate through the metabolism of the amino acid glutamine. 1) Extra bicarbonate enters the blood to compensate for acidosis. 2) Ammonia stays in urine to buffer H +.

98 Disturbances of Acid-Base Balance

99 G. Urinary Buffers 1. Nephrons cannot produce urine with a ph below To increase H + secretion, urine must be buffered. a. Phosphates and ammonia buffer the urine. b. Phosphates enter via filtration. c. Ammonia comes from the deamination of amino acids.

100 VI. Clinical Applications

101 A. Use of Diuretics 1. Used clinically to control blood pressure and relieve edema (fluid accumulation) a. Diuretics increase urine volume, decreasing blood volume and interstitial fluid volume. b. Many types act on different portions of the nephron.

102 2. Types of Diuretics a. Loop diuretics: most powerful; inhibit salt transport out of ascending loop of Henle 1) Example: Lasix 2) Can inhibit up to 25% of water reabsorption b. Thiazide diuretics: inhibit salt transport in distal tubule 1) Can inhibit up to 8% of water reabsorption c. Carbonic anhydrase inhibitors: much weaker; inhibit water reabsorption when bicarbonate is reabsorbed 1) Also promote excretion of bicarbonate

103 Types of Diuretics, cont d. Osmotic diuretics: reduce reabsorption of water by adding extra solutes to the filtrate 1) Example: Mannitol 2) Can occur as a side effect of diabetes e. Potassium-sparing diuretics: Aldosterone antagonists block reabsorption of Na + and secretion of K +.

104 Actions of Classes of Diuretics

105 Sites of Action of Clinical Diuretics Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Carbonic anhydrase inhibitors Proximal convoluted tubule Thick ascending limb Distal convoluted tubule Thiazide diuretics Na + NaCl Cortex Amino acids Glucose HCO 3 3, PO 4 Passive Potassium-sparing diuretics H 2 O (with ADH) H 2 O no ADH Cortical collecting duct Glomerulus Loop diuretics K + Na + Collecting duct Medulla Increasing NaCl and urea concentrations H 2 O H 2 O Descending limb Ascending limb H 2 O (with ADH) H 2 O no ADH Medullary collecting duct NaCl Passive Urea

106 B. Renal Function Tests 1. PAH and inulin clearance a. Can diagnose nephritis or renal insufficiency 2. Urinary albumin excretion rate: detects abovenormal albumin excretion a. Called microalbuminuria b. Signifies renal damage due to hypertension or diabetes 3. Proteinuria: overexcretion of proteins; signifies nephrotic syndrome

107 C. Kidney Diseases 1. Acute Renal Failure a. Ability of kidneys to regulate blood volume, ph, and solute concentrations deteriorates in a matter of hours/days. b. Usually due to decreased blood flow through kidneys due to: 1) Atherosclerosis of renal arteries 2) Inflammation of renal tubules 3) Use of certain drugs (NSAIDs)

108 2. Glomerulonephritis a. Inflammation of the glomerulus b. Autoimmune disease with antibodies produced in response to streptococcus infection c. Many glomeruli are destroyed, and others are more permeable to proteins. d. Loss of proteins from blood reduces blood osmotic pressure and leads to edema.

109 3. Renal Insufficiency a. Any reduction in renal activity b. Can be caused by glomerulonephritis, diabetes, atherosclerosis, or blockage by kidney stones c. Can lead to high blood pressure, high blood K + and H +, and uremia = urea in the blood. d. Patients with uremia are placed on a dialysis machine to clear blood of these solutes.

110 4. Dialysis a. Artificial kidney b. Hemodialysis blood cleansed of wastes as it passes through dialysis fluid c. CAPD continuous ambulatory peritoneal dialysis dialysis fluid introduced to the abdominal cavity where wastes can pass out of abdominal blood vessels; fluid is then pumped out of the abdominal cavity