About this Chapter Fluid and electrolyte homeostasis Water

About this Chapter § Fluid and electrolyte homeostasis § Water balance § Sodium balance and ECF volume § Potassium balance § Behavioral mechanism in salt and water balance § Integrated control of volume and osmolarity § Acid-base balance Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings

Fluid and Electrolyte Homeostasis § Na+ and water: ECF volume and osmolarity § K+: cardiac and muscle function § Ca 2+: exocytosis, muscle contractions, and other functions § H+ and HCO 3–: p. H balance § Body must maintain mass balance § Excretion routes: kidney and lungs Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings

Fluid and Electrolyte Homeostasis The body’s integrated response to changes in blood volume and

Fluid and Electrolyte Homeostasis Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin

Water Balance in the Body Copyright © 2007 Pearson Education, Inc. , publishing as

Water Balance A model of the role of the kidneys in water balance Copyright

Urine Concentration Osmolarity changes as filtrate flows through the nephron Copyright © 2007 Pearson

Water Reabsorption Water movement in the collecting duct in the presence and absence of

Water Reabsorption Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure

Water Reabsorption The mechanism of vasopressin action Cross-section of kidney tubule Collecting duct lumen Medullary interstitial fluid Collecting duct cell 600 m. Os. M Filtrate 300 m. Osm 600 m. Os. M H 2 O 4 Vasa recta H 2 O 700 m. Os. M Storage vesicles Second 2 messenger signal Exocytosis of vesicles 3 Aquaporin-2 water pores 1 c. AMP Vasopressin receptor 1 Vasopressin binds to membrane receptor. 2 Receptor activates c. AMP second messenger system. 3 Cell inserts AQP 2 water pores into apical membrane. Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings 4 Water is absorbed by osmosis into the blood. Figure 20 -6

Water Reabsorption Cross-section of kidney tubule Collecting duct lumen Filtrate 300 m. Osm Collecting duct cell Medullary interstitial fluid Vasa recta 600 m. Os. M 700 m. Os. M 1 Vasopressin receptor 1 Vasopressin binds to membrane receptor. Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -6, step 1

Water Reabsorption Cross-section of kidney tubule Collecting duct lumen Filtrate 300 m. Osm Medullary interstitial fluid Collecting duct cell Vasa recta 600 m. Os. M 700 m. Os. M Second 2 messenger signal c. AMP 1 Vasopressin receptor 1 Vasopressin binds to membrane receptor. 2 Receptor activates c. AMP second messenger system. Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -6, steps 1– 2

Water Reabsorption Cross-section of kidney tubule Collecting duct lumen Medullary interstitial fluid Collecting duct cell Vasa recta 600 m. Os. M Filtrate 300 m. Osm 600 m. Os. M 700 m. Os. M Storage vesicles Second 2 messenger signal Exocytosis of vesicles 3 Aquaporin-2 water pores 1 c. AMP Vasopressin receptor 1 Vasopressin binds to membrane receptor. 2 Receptor activates c. AMP second messenger system. 3 Cell inserts AQP 2 water pores into apical membrane. Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -6, steps 1– 3

Water Reabsorption Cross-section of kidney tubule Collecting duct lumen Medullary interstitial fluid Collecting duct cell 600 m. Os. M Filtrate 300 m. Osm 600 m. Os. M H 2 O 4 Vasa recta H 2 O 700 m. Os. M Storage vesicles Second 2 messenger signal Exocytosis of vesicles 3 Aquaporin-2 water pores 1 c. AMP Vasopressin receptor 1 Vasopressin binds to membrane receptor. 2 Receptor activates c. AMP second messenger system. 3 Cell inserts AQP 2 water pores into apical membrane. Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings 4 Water is absorbed by osmosis into the blood. Figure 20 -6, steps 1– 4

Factors Affecting Vasopressin Release Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin

Water Balance The effect of plasma osmolarity on vasopressin secretion by the posterior pituitary

Countercurrent Heat Exchanger Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings

Water Balance Countercurrent exchange in the medulla of the kidney Copyright © 2007 Pearson

Ion reabsorption Active reabsorption of ions in the thick ascending limb creates a dilute

Fluid and Electrolyte Balance § Vasa recta removes water § Close anatomical association of the loop of Henle and the vasa recta § Urea increase the osmolarity of the medullary interstitium Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings

Sodium Balance Homeostatic responses to salt ingestion PLAY Animation: Urinary System: Late Filtrate Processing

Sodium Balance Aldosterone action in principle cells Interstitial fluid P cell of distal nephron Lumen of distal tubule 3 Translation and protein synthesis New channels K+ secreted 5 Na+ reabsorbed K+ Na+ Transcription 2 m. RNA New pumps 4 Proteins modulate existing channels and pumps. Blood Aldosterone 1 Aldosterone receptor 1 Aldosterone combines with a cytoplasmic receptor. 2 Hormone-receptor complex initiates transcription in the nucleus. ATP 3 New protein channels and pumps are made. ATP 4 Aldosteroneinduced proteins modify existing proteins. K+ K+ Na+ Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings 5 Result is increased Na+ reabsorption and K+ secretion. Figure 20 -13

Sodium Balance Interstitial fluid P cell of distal nephron Lumen of distal tubule Blood 1 Aldosterone combines with a cytoplasmic receptor. Aldosterone 1 Aldosterone receptor Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -13, step 1

Sodium Balance Interstitial fluid P cell of distal nephron Lumen of distal tubule Transcription 2 m. RNA Blood Aldosterone 1 1 Aldosterone combines with a cytoplasmic receptor. 2 Hormone-receptor complex initiates transcription in the nucleus. Aldosterone receptor Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -13, steps 1– 2

Sodium Balance Interstitial fluid P cell of distal nephron Lumen of distal tubule 3 Translation and protein synthesis New channels Transcription 2 m. RNA New pumps Blood Aldosterone 1 Aldosterone receptor ATP Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings 1 Aldosterone combines with a cytoplasmic receptor. 2 Hormone-receptor complex initiates transcription in the nucleus. 3 New protein channels and pumps are made. Figure 20 -13, steps 1– 3

Sodium Balance Interstitial fluid P cell of distal nephron Lumen of distal tubule 3 Translation and protein synthesis New channels Transcription 2 m. RNA New pumps 4 Proteins modulate existing channels and pumps. Blood Aldosterone 1 Aldosterone receptor 1 Aldosterone combines with a cytoplasmic receptor. 2 Hormone-receptor complex initiates transcription in the nucleus. ATP 3 New protein channels and pumps are made. ATP 4 Aldosteroneinduced proteins modify existing proteins. Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -13, steps 1– 4

Sodium Balance Interstitial fluid P cell of distal nephron Lumen of distal tubule 3 Translation and protein synthesis New channels K+ secreted 5 Na+ reabsorbed K+ Na+ Transcription 2 m. RNA New pumps 4 Proteins modulate existing channels and pumps. Blood Aldosterone 1 Aldosterone receptor 1 Aldosterone combines with a cytoplasmic receptor. 2 Hormone-receptor complex initiates transcription in the nucleus. ATP 3 New protein channels and pumps are made. ATP 4 Aldosteroneinduced proteins modify existing proteins. K+ K+ Na+ Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings 5 Result is increased Na+ reabsorption and K+ secretion. Figure 20 -13, steps 1– 5

Sodium Balance The renin-angiotensin-aldosterone pathway Copyright © 2007 Pearson Education, Inc. , publishing as

Sodium Balance Decreased blood pressure stimulates renin secretion Copyright © 2007 Pearson Education, Inc.

Sodium Balance Action of natriuretic peptides Copyright © 2007 Pearson Education, Inc. , publishing

Potassium Balance § Regulatory mechanisms keep plasma potassium in narrow range § Aldosterone plays a critical role § Hypokalemia § Muscle weakness and failure of respiratory muscles and the heart § Hyperkalemia § Can lead to cardiac arrhythmias § Causes include kidney disease, diarrhea, and diuretics Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings

Behavioral Mechanisms § Drinking replaces fluid loss § Low sodium stimulates salt appetite § Avoidance behaviors help prevent dehydration § Desert animals avoid the heat Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings

Disturbances in Volume and Osmolarity PLAY Animation: Fluid, Electrolyte, and Acid/Base Balance: Water Homeostasis Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -17

Volume and Osmolarity Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings

Volume and Osmolarity Homeostatic compensation for severe dehydration Blood volume/ Blood pressure DEHYDRATION CARDIOVASCULAR MECHANISMS Osmolarity accompanied by RENIN-ANGIOTENSIN SYSTEM RENAL MECHANISMS HYPOTHALAMIC MECHANISMS Hypothalamic osmoreceptors + Carotid and aortic baroreceptors CVCC + Granular cells + Flow at macula densa + Volume conserved Renin Angiotensinogen Parasympathetic output Heart GFR + Atrial volume receptors; carotid and aortic baroreceptors Sympathetic output Arterioles + ANG I Vasopressin release from posterior pituitary + ACE + Hypothalamus ANG II + + Thirst + Adrenal cortex Vasoconstriction Rate osmolarity inhibits Force Aldosterone Peripheral resistance Distal nephron Na+ reabsorption Cardiac output Blood pressure H 2 O intake H 2 O reabsorption Volume Osmolarity Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -18

Volume and Osmolarity DEHYDRATION Blood volume/ Blood pressure CARDIOVASCULAR MECHANISMS Carotid and aortic baroreceptors CVCC Parasympathetic output Sympathetic output Heart Arterioles Vasoconstriction Rate Force Peripheral resistance Cardiac output Blood pressure Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -18 (1 of 6)

Volume and Osmolarity DEHYDRATION Blood volume/ Blood pressure Osmolarity accompanied by HYPOTHALAMIC MECHANISMS Hypothalamic osmoreceptors Atrial volume receptors; carotid and aortic baroreceptors Hypothalamus + Vasopressin release from posterior pituitary + Thirst Distal nephron H 2 O intake Blood pressure H 2 O reabsorption Volume Osmolarity Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -18 (2 of 6)

Volume and Osmolarity DEHYDRATION Blood volume/ Blood pressure RENIN-ANGIOTENSIN SYSTEM RENAL MECHANISMS + Granular cells + Flow at macula densa Volume conserved Renin Angiotensinogen GFR ANG I ACE ANG II Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -18 (3 of 6)

Volume and Osmolarity Blood volume/ Blood pressure DEHYDRATION Osmolarity accompanied by RENIN-ANGIOTENSIN SYSTEM + Granular cells CVCC + Renin Angiotensinogen ANG I Vasopressin release from posterior pituitary + ACE Arterioles + ANG II + Thirst + Adrenal cortex osmolarity inhibits Aldosterone Distal nephron Na+ reabsorption Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -18 (4 of 6)

Volume and Osmolarity Blood volume/ Blood pressure DEHYDRATION Osmolarity accompanied by RENIN-ANGIOTENSIN SYSTEM RENAL MECHANISMS + + CVCC Granular cells + Flow at macula densa + Volume conserved Renin Angiotensinogen Parasympathetic output GFR + Sympathetic output Arterioles ANG I Vasopressin release from posterior pituitary + ACE + ANG II + Thirst + Adrenal cortex Vasoconstriction osmolarity inhibits Aldosterone Distal nephron Na+ reabsorption Blood pressure H 2 O intake H 2 O reabsorption Volume Osmolarity Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -18 (5 of 6)

Volume and Osmolarity Blood volume/ Blood pressure DEHYDRATION CARDIOVASCULAR MECHANISMS Osmolarity accompanied by RENIN-ANGIOTENSIN SYSTEM RENAL MECHANISMS HYPOTHALAMIC MECHANISMS Hypothalamic osmoreceptors + Carotid and aortic baroreceptors CVCC + Granular cells + Flow at macula densa GFR + Atrial volume receptors; carotid and aortic baroreceptors + Volume conserved Renin Angiotensinogen Parasympathetic output Sympathetic output Heart Arterioles + ANG I Vasopressin release from posterior pituitary + ACE + Hypothalamus ANG II + + Thirst + Adrenal cortex Vasoconstriction Rate osmolarity inhibits Force Aldosterone Peripheral resistance Distal nephron Na+ reabsorption Cardiac output Blood pressure H 2 O intake H 2 O reabsorption Volume Osmolarity Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -18 (6 of 6)

Acid-Base Balance § Normal p. H of plasma is 7. 38– 7. 42 § H+ concentration is closely regulated § Changes can alter tertiary structure of proteins § Abnormal p. H affects the nervous system § Acidosis: neurons become less excitable and CNS depression § Alkalosis: hyperexcitable § p. H disturbances § Associated with K+ disturbances Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings

Acid-Base Balance Hydrogen balance in the body Copyright © 2007 Pearson Education, Inc. ,

Acid and Base Input Acid § Organic acids § Diet and intermediates § Under extraordinary conditions § Metabolic organic acid production can increase § Ketoacids § Diabetes § Production of CO 2 § Acid production Base § Few dietary sources of bases Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings

p. H Homeostasis § Buffers moderate changes in p. H § Cellular proteins, phosphate ions, and hemoglobin § Ventilation § Rapid § 75% of disturbances § Renal regulation § Directly excreting or reabsorbing H+ § Indirectly by change in the rate at which HCO 3– buffer is reabsorbed or excreted Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings

p. H Disturbances The reflex pathway for respiratory compensation of metabolic acidosis Copyright ©

p. H Disturbances Overview of renal compensation for acidosis Copyright © 2007 Pearson Education,

Renal Compensation: Transporters § Apical Na+-H+ antiport § Basolateral Na+-HCO 3– symport § H+-ATPase § H+-K+-ATPase § Na+-NH 4+ antiport Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings

Renal Compensation Proximal tubule H+ secretion and the reabsorption of filtered HCO 3– 1 Na+-H+ antiport secretes H+. Bowman’s capsule Filtration HCO 3– Interstitial fluid Peritubular capillary Glomerulus 3 CO 2 diffuses into cell and combines with water to form H+ and HCO 3–. Proximal tubule cell Na+ 1 Na+ Secreted H+ 4 4 H+ is secreted again and excreted. Na+ H+ Na+ HCO 3– Filtered HCO 3– + H+ 2 H 2 O + CO 2 3 CO 2 + H 2 O CA H+ + HCO 3– 5 HCO 3– is reabsorbed. Na+ HCO 3– 5 Reabsorbed 7 NH 4+ Na+ a. KG 6 Glutamine is metabolized to ammonium ion and HCO 3–. 7 NH 4+ is secreted and excreted. 6 Glutamine Secreted H+ and NH 4+ will be excreted 2 H+ in filtrate combines with filtered HCO 3– to form CO 2. HCO 3– Na+ Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings HCO 3– Na+ 8 8 HCO 3– is reabsorbed. Figure 20 -22

Renal Compensation 1 Na+-H+ antiport secretes H+. Bowman’s capsule Filtration Peritubular capillary Glomerulus Proximal tubule cell Na+ 1 Na+ Secreted H+ Interstitial fluid Na+ H+ Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -22, step 1

Renal Compensation 1 Na+-H+ antiport secretes H+. Bowman’s capsule Filtration HCO 3– Peritubular capillary Glomerulus Proximal tubule cell Na+ 1 Na+ Secreted H+ Interstitial fluid 2 H+ in filtrate combines with filtered HCO 3– to form CO 2. Na+ H+ Filtered HCO 3– + H+ 2 H 2 O + CO 2 Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -22, steps 1– 2

Renal Compensation 1 Na+-H+ antiport secretes H+. Bowman’s capsule Filtration HCO 3– Glomerulus Proximal tubule cell Na+ 1 Na+ Secreted H+ Filtered HCO 3– + H+ 2 H 2 O + CO 2 Interstitial fluid Peritubular capillary 2 H+ in filtrate combines with filtered HCO 3– to form CO 2. 3 CO 2 diffuses into cell and combines with water to form H+ and HCO 3–. Na+ H+ 3 CO 2 + H 2 O CA H+ + HCO 3– Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -22, steps 1– 3

Renal Compensation 1 Na+-H+ antiport secretes H+. Bowman’s capsule Filtration HCO 3– Glomerulus Proximal tubule cell Na+ 1 Na+ Secreted H+ Filtered HCO 3– + H+ 2 H 2 O + CO 2 Interstitial fluid 4 3 Peritubular capillary 2 H+ in filtrate combines with filtered HCO 3– to form CO 2. 3 CO 2 diffuses into cell and combines with water to form H+ and HCO 3–. 4 H+ is secreted again and excreted. Na+ H+ CO 2 + H 2 O CA H+ + HCO 3– Secreted H+ will be excreted Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -22, steps 1– 4

Renal Compensation 1 Na+-H+ antiport secretes H+. Bowman’s capsule Filtration HCO 3– Filtered HCO 3– + H+ 2 H 2 O + CO 2 Peritubular capillary Glomerulus 3 CO 2 diffuses into cell and combines with water to form H+ and HCO 3–. Proximal tubule cell Na+ 1 Na+ Secreted H+ Interstitial fluid 4 4 H+ is secreted again and excreted. Na+ H+ Na+ HCO 3– 3 2 H+ in filtrate combines with filtered HCO 3– to form CO 2 + H 2 O CA H+ + HCO 3– Na+ HCO 3– 5 HCO 3– is reabsorbed. 5 Reabsorbed Secreted H+ will be excreted Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -22, steps 1– 5

Renal Compensation 1 Na+-H+ antiport secretes H+. Bowman’s capsule Filtration HCO 3– Filtered HCO 3– + H+ 2 H 2 O + CO 2 Peritubular capillary Glomerulus 3 CO 2 diffuses into cell and combines with water to form H+ and HCO 3–. Proximal tubule cell Na+ 1 Na+ Secreted H+ Interstitial fluid 4 4 H+ is secreted again and excreted. Na+ H+ Na+ HCO 3– 3 2 H+ in filtrate combines with filtered HCO 3– to form CO 2 + H 2 O CA H+ + HCO 3– Na+ HCO 3– 5 HCO 3– is reabsorbed. 5 Reabsorbed 6 Glutamine is metabolized to ammonium ion and HCO 3–. 6 Glutamine Secreted H+ will be excreted NH 4+ a. KG HCO 3– Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -22, steps 1– 6

Renal Compensation 1 Na+-H+ antiport secretes H+. Bowman’s capsule Filtration HCO 3– Interstitial fluid Glomerulus 3 CO 2 diffuses into cell and combines with water to form H+ and HCO 3–. Proximal tubule cell Na+ 1 Na+ Secreted H+ 4 4 H+ is secreted again and excreted. Na+ H+ Na+ HCO 3– Filtered HCO 3– + H+ 2 H 2 O + CO 2 3 CO 2 + H 2 O CA H+ + HCO 3– 7 NH 4+ Na+ a. KG Na+ HCO 3– 5 HCO 3– is reabsorbed. 5 Reabsorbed 6 Glutamine is metabolized to ammonium ion and HCO 3–. 7 NH 4+ is secreted and excreted. 6 Glutamine Secreted H+ and NH 4+ will be excreted Peritubular capillary 2 H+ in filtrate combines with filtered HCO 3– to form CO 2. HCO 3– Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings Figure 20 -22, steps 1– 7

Renal Compensation 1 Na+-H+ antiport secretes H+. Bowman’s capsule Filtration HCO 3– Peritubular capillary Interstitial fluid Glomerulus 3 CO 2 diffuses into cell and combines with water to form H+ and HCO 3–. Proximal tubule cell Na+ 1 Na+ Secreted H+ 4 4 H+ is secreted again and excreted. Na+ H+ Na+ HCO 3– Filtered HCO 3– + H+ 2 H 2 O + CO 2 3 CO 2 + H 2 O CA H+ + HCO 3– 5 HCO 3– is reabsorbed. Na+ HCO 3– 5 Reabsorbed 7 NH 4+ Na+ a. KG 6 Glutamine is metabolized to ammonium ion and HCO 3–. 7 NH 4+ is secreted and excreted. 6 Glutamine Secreted H+ and NH 4+ will be excreted 2 H+ in filtrate combines with filtered HCO 3– to form CO 2. HCO 3– Na+ Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings HCO 3– Na+ 8 8 HCO 3– is reabsorbed. Figure 20 -22, steps 1– 8

Intercalated Cells Role of intercalated cells in acidosis and alkalosis Copyright © 2007 Pearson

Acid-Base Balance PLAY Animation: Fluid, Electrolyte, and Acid/Base Balance: Acid/Base Homeostasis Copyright © 2007

Summary § Fluid and electrolyte homeostasis § Water balance § Vasopressin, aquaporin, osmoreceptors, countercurrent multiplier, and vasa recta § Sodium balance § Aldosterone, principal cells, ANG I and II, renin, angiotensinogen, ACE, and ANP § Potassium balance § Hyperkalemia and hypokalemia Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings

Summary § Behavioral mechanisms § Integrated control of volume and osmolarity § Acid-base balance § Buffers, ventilation, and kidney § Acidosis and alkalosis § Intercalated cells Copyright © 2007 Pearson Education, Inc. , publishing as Benjamin Cummings