Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings 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 – : pH 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 blood pressure Figure 20-1a

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20-1b Fluid and Electrolyte Homeostasis

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20-2 Water Balance in the Body

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20-3 Water Balance A model of the role of the kidneys in water balance

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20-4 Urine Concentration Osmolarity changes as filtrate flows through the nephron

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20-5a Water Reabsorption Water movement in the collecting duct in the presence and absence of vasopressin

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20-5b Water Reabsorption

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20-6 Water Reabsorption The mechanism of vasopressin action Collecting duct lumen Filtrate 300 mOsm H2OH2O Exocytosis of vesicles Cross-section of kidney tubule Collecting duct cell Second messenger signal H2OH2O cAMP Storage vesicles Aquaporin-2 water pores 600 mOsM H2OH2O Medullary interstitial fluid Vasopressin receptor 600 mOsM Vasa recta H2OH2O 700 mOsM Vasopressin binds to mem- brane receptor. Receptor activates cAMP second messenger system. Cell inserts AQP2 water pores into apical membrane. Water is absorbed by osmosis into the blood

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

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20-6, steps 1–2 Water Reabsorption Collecting duct lumen Filtrate 300 mOsm Cross-section of kidney tubule Collecting duct cell Second messenger signal cAMP Medullary interstitial fluid Vasopressin receptor Vasa recta Vasopressin binds to mem- brane receptor. Receptor activates cAMP second messenger system mOsM 700 mOsM

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20-6, steps 1–3 Water Reabsorption Collecting duct lumen Filtrate 300 mOsm Exocytosis of vesicles Cross-section of kidney tubule Collecting duct cell Second messenger signal cAMP Storage vesicles Aquaporin-2 water pores Medullary interstitial fluid Vasopressin receptor Vasa recta Vasopressin binds to mem- brane receptor. Receptor activates cAMP second messenger system. Cell inserts AQP2 water pores into apical membrane mOsM 700 mOsM

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20-6, steps 1–4 Water Reabsorption Collecting duct lumen Filtrate 300 mOsm H2OH2O Exocytosis of vesicles Cross-section of kidney tubule Collecting duct cell Second messenger signal H2OH2O cAMP Storage vesicles Aquaporin-2 water pores 600 mOsM H2OH2O Medullary interstitial fluid Vasopressin receptor 600 mOsM Vasa recta H2OH2O 700 mOsM Vasopressin binds to mem- brane receptor. Receptor activates cAMP second messenger system. Cell inserts AQP2 water pores into apical membrane. Water is absorbed by osmosis into the blood

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20-7 Factors Affecting Vasopressin Release

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20-8 Water Balance The effect of plasma osmolarity on vasopressin secretion by the posterior pituitary

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20-9 Countercurrent Heat Exchanger

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure Water Balance Countercurrent exchange in the medulla of the kidney

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure Ion reabsorption Active reabsorption of ions in the thick ascending limb creates a dilute filtrate in the lumen

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings 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 Figure Animation: Urinary System: Late Filtrate Processing PLAY Sodium Balance Homeostatic responses to salt ingestion

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

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

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

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

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

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

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

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure Sodium Balance Decreased blood pressure stimulates renin secretion

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure Sodium Balance Action of natriuretic peptides

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

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

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

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

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

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

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

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

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

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

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

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Acid-Base Balance  Normal pH of plasma is 7.38–7.42  H + concentration is closely regulated  Changes can alter tertiary structure of proteins  Abnormal pH affects the nervous system  Acidosis: neurons become less excitable and CNS depression  Alkalosis: hyperexcitable  pH disturbances  Associated with K + disturbances

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure Acid-Base Balance Hydrogen balance in the body

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings 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 pH Homeostasis  Buffers moderate changes in pH  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 Figure pH Disturbances The reflex pathway for respiratory compensation of metabolic acidosis

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure pH Disturbances Overview of renal compensation for acidosis

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings 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 Figure Renal Compensation Proximal tubule H + secretion and the reabsorption of filtered HCO 3 – Peritubular capillary Interstitial fluid Reabsorbed Filtration Proximal tubule cell Glomerulus HCO 3 – H + + HCO 3 – HCO 3 – CO 2 + H 2 O H+H+ Na + Secreted H + Na + HCO 3 – Na + Bowman’s capsule H 2 O + CO 2 Filtered HCO 3 – + H + Secreted H + and NH 4 + will be excreted Na +  KG HCO 3 – Na + NH 4 + HCO 3 – Na + Glutamine CA Na + -H + antiport secretes H +. H + in filtrate combines with filtered HCO 3 – to form CO 2. CO 2 diffuses into cell and combines with water to form H + and HCO 3 –. H + is secreted again and excreted. HCO 3 – is reabsorbed. Glutamine is metabolized to ammonium ion and HCO 3 –. NH 4 + is secreted and excreted. HCO3– is reabsorbed

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

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

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

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

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

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

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

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 20-22, steps 1–8 Renal Compensation Peritubular capillary Interstitial fluid Reabsorbed Filtration Proximal tubule cell Glomerulus HCO 3 – H + + HCO 3 – HCO 3 – CO 2 + H 2 O H+H+ Na + Secreted H + Na + HCO 3 – Na + Bowman’s capsule H 2 O + CO 2 Filtered HCO 3 – + H + Secreted H + and NH 4 + will be excreted Na +  KG HCO 3 – Na + NH 4 + HCO 3 – Na + Glutamine Na + -H + antiport secretes H +. H + in filtrate combines with filtered HCO 3 – to form CO 2. CO 2 diffuses into cell and combines with water to form H + and HCO 3 –. H + is secreted again and excreted. HCO 3 – is reabsorbed. Glutamine is metabolized to ammonium ion and HCO 3 –. NH 4 + is secreted and excreted. HCO3– is reabsorbed CA

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure Intercalated Cells Role of intercalated cells in acidosis and alkalosis

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Acid-Base Balance Animation: Fluid, Electrolyte, and Acid/Base Balance: Acid/Base Homeostasis PLAY

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