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Chapter 27: Fluid, electrolyte, and acid-base homeostasis Copyright 2009, John Wiley & Sons, Inc. Body fluid all the water and dissolved solutes in the body’s fluid compartments Mechanisms regulate total volume distribution concentration of solutes and pH Regulatory mechanisms insure homeostasis of body fluids since their malfunction may seriously endanger nervous system and organ functioning. 2 Balance Between Fluid Compartments About 55%(female) or 60%(male) of total body mass Intracellular fluid (ICF) –about 2/3 of body fluid Extracellular fluid (ECF): -Interstitial fluid- about 80% of ECF - Plasma in blood- about 20% of ECF - Also includes lymph, CSF, synovial fluid, aqueous humor, vitreous body, endolymph, perilymph, pleural, pericardial and peritoneal fluids Volume of fluid in each is kept constant. Since water follows electrolytes, they must be in balance as well Only 2 places for exchange between compartments: Cell/plasma membranes separate intracellular from interstitial fluid. only in capillaries are Principles walls thin enough for exchange between plasma of Human Anatomy and 3 Physiology, 11e and interstitial fluids Fluid Balance Fluid balance means that the various body compartments contain the required amount of water, proportioned according to their needs. Fluid balance = water balance = electrolyte balance → inseparable. Osmosis is the primary way in which water moves in and out of body compartments. Solute concentration in the fluids is therefore a major determinant of fluid balance. Most solutes in body fluids are electrolytes, compounds that dissociate into ions. 2 barriers separate ICF, interstitial fluid and plasma Plasma membrane separates ICF from surrounding interstitial fluid Blood vessel wall divide interstitial fluid from plasma Water- largest single component of the body≈ 45-75% of total body mass Infants have low body fat, low bone mass, and are 73% or more water Total water content declines throughout life≈ 60%(males) & 50%(females) Difference due to > body fat & < amount of skeletal muscle in females In old age, only about 45% of body weight is water Continual exchange of water and solutes among compartments via filtration, reabsorption, diffusion, and osmosis Copyright 2009, John Wiley & Sons, Inc. Sources of Body Water Gain and Loss Fluid balance related to electrolyte balance Intake of water and electrolytes rarely proportional Kidneys excrete excess water through dilute urine or excess electrolytes through concentrated urine Body can gain water by Ingestion of liquids and moist foods (2300mL/day) Metabolic synthesis of water during cellular respiration and dehydration synthesis (200mL/day) Body loses water through Kidneys (1500mL/day) Evaporation from skin (600mL/day) Exhalation from lungs (300mL/day) Feces (100mL/day) Normally loss = gain Copyright 2009, John Wiley & Sons, Inc. Daily Water Gain and Loss Copyright 2009, John Wiley & Sons, Inc. Regulation of body water gain Metabolic water volume depends mostly on the level of aerobic cellular respiration, which reflects the demand for ATP in body cells. The main way to regulate body water balance is by adjusting the volume of water intake. Dehydration – when water loss is greater than gain Decrease in volume, increase in osmolarity of body fluids Stimulates thirst center in hypothalamus Regulation of fluid gain is by regulation of thirst Copyright 2009, John Wiley & Sons, Inc. Regulation of water and solute loss Although increased amounts of water & solutes are lost through sweating & exhalation during exercise, loss of body water or excess solutes depends mainly on regulating how much is lost in the urine Main factor that determines body fluid osmolarity is extent of urinary water loss 3 hormones regulate renal Na+ and Cl- reabsorption (or not) ADH(Vasopressin) & Angiotensin II-Aldosterone promote urinary Na+ and Cl- reabsorption of (and water by osmosis) when dehydrated Atrial natriuretic peptide (ANP) promotes natriuresis, excretion of Na+ and Cl- followed by water excretion to decrease blood volume Major hormone regulating water loss is antidiuretic hormone (ADH) - stimulates thirst - increases permeability of principal cells of collecting ducts to assist in water reabsorption→ very concentrated urine is formed - ADH secretion shuts off after the intake of water - ADH secretion is increased when BP drops due to ↓blood volume; dehydration, vomiting, diarrhea, sweating …. Copyright 2009, John Wiley & Sons, Inc. Hormonal Regulation of Blood Osmolality 27-9 Hormonal Regulation of Blood Volume Hormonal Regulation of Blood Volume 27-11 27_table_01 “water follows salt” Fluid imbalance between the intracellular and interstitial fluids can be caused by a change in their osmolarity. Most often a change in osmolarity is due to change in Na+ concentration: Increasing IF osmolarity draws water out of cells→cells shrink Decreasing IF osmolarity causes cells to swell When water is consumed faster than the kidneys can excrete it, water intoxication may result. Repeated use of enemas can increase the risk of fluid and electrolyte imbalances. Series of Events in Water Intoxication ELECTROLYTES IN BODY FLUIDS Electrolytes serve four general functions in the body. Because they are more numerous than nonelectrolytes, electrolytes control the osmosis of water between body compartments. Maintain the acid-base balance required for normal cellular activities. Carry electrical current, which allows production of action potentials and graded potentials and controls secretion of some hormones and neurotransmitters. Electrical currents are also important during development. Serve cofactors needed for optimal activity of enzymes. Concentration expressed in mEq/liter or milliequivalents per liter for plasma, interstitial fluid and intracellular fluid The chief difference between plasma and interstitial fluid is that plasma contains quite a few protein anions→ blood colloid osmotic pressure Plasma also contains slightly more sodium ions but fewer chloride ions than the interstitial fluid. Principles of Human Anatomy and Physiology, 11e 15 ICF differs considerably from ECF ECF most abundant cation is Na+, anion is Cl Sodium Impulse transmission, muscle contraction, fluid and electrolyte balance Chloride Regulating osmotic pressure, forming HCl in gastric acid Controlled indirectly by ADH and processes that affect renal reabsorption of sodium ICF most abundant cation is K+, anion are proteins and phosphates (HPO42-) Potassium Resting membrane potential , action potentials of nerves and muscles Maintain intracellular volume Regulation of pH Controlled by aldosterone Na+ /K+ pumps play major role in keeping K+ high inside cells and Na+ high outside cell Copyright 2009, John Wiley & Sons, Inc. Regulation of ICF and ECF Regulation of ECF Volume Electrolyte and protein anion concentrations Copyright 2009, John Wiley & Sons, Inc. Sodium Na+ Most abundant ion in ECF - accounts for 1/2 of osmolarity of ECF 90% of extracellular cations Plays pivotal role in fluid and electrolyte balance Level in blood controlled by Aldosternone – increases renal reabsorption ADH – if sodium too low, ADH release stops Atrial natriuretic peptide – increases renal excretion Excess Na+ in the body can result in edema → generally due to renal failure & hyperaldosteronemia Excess loss of Na+ causes excessive loss of water, which results in hypovolemia, an abnormally low blood volume→ generally due to inadequate secretion of aldosterone or too many diuretics Copyright 2009, John Wiley & Sons, Inc. Chloride Cl Most prevalent anions in ECF Moves relatively easily between ECF and ICF because most plasma membranes contain Cl- leakage channels and transporters - Passively follows Na+ Can help balance levels of anions in different fluids - ex. Chloride shift – in RBCs - plays role in HCl production in stomach Regulated by ADH – governs extent of water loss in urine Processes that increase or decrease renal reabsorption of Na+ also affect reabsorption of Cl- Copyright 2009, John Wiley & Sons, Inc. Potassium K+ Most abundant cation in ICF Key role in establishing resting membrane potential in neurons and muscle fibers Also helps maintain normal ICF fluid volume Helps regulate pH of body fluids when exchanged for H+ Controlled by aldosterone – stimulates principal cells in renal collecting ducts to secrete excess K+ Abnormal plasma K+ levels adversely affect cardiac and neuromuscular function Copyright 2009, John Wiley & Sons, Inc. Potassium Ion Regulation in ECF Bicarbonate HCO3 Second most prevalent extracellular anion Concentration increases as blood flows through systemic capillaries due to CO2 released from metabolically active cells CO2 combines with H2O to form carbonic acid which dissociates Concentration decreases as blood flows through pulmonary capillaries and CO2 is exhale Chloride shift helps maintain correct balance of anions in ECF and ICF Kidneys are main regulators of blood HCO3 intercalated cells form more HCO3- if levels are too low excrete excess in the urine Copyright 2009, John Wiley & Sons, Inc. Calcium Ca2+ Most abundant mineral in body 99% of calcium in adults in skeleton and teeth – contributes to hardness In body fluids mainly an extracellular cation Plays important roles in blood clotting, neurotransmitter release, muscle tone, and excitability of nervous & muscle tissue Regulated by parathyroid hormone Stimulates osteoclasts to release calcium from bone – resorption Also enhances reabsorption from glomerular filtrate Increases production of calcitriol to increase absorption for GI tract Calcitonin lowers blood calcium levels Copyright 2009, John Wiley & Sons, Inc. Regulation of Calcium Ions Phosphate About 85% in adults present as calcium phosphate salts in bone & teeth Remaining 15% ionized – H2PO4-, HPO42-, and PO43- are important intracellular anions HPO42- important buffer of H+ in body fluids and urine Same hormones governing calcium homeostasis also regulate HPO42- in blood Parathyroid hormone – stimulates resorption of bone by osteoclasts releasing calcium and phosphate but inhibits reabsorption of phosphate ions in kidneys Calcitriol promotes absorption of phosphates and calcium from GI tract Copyright 2009, John Wiley & Sons, Inc. Regulation of Blood Phosphate Regulation of Phosphate Ions Under normal conditions, reabsorption of phosphate occurs at maximum rate in the nephron An increase in plasma phosphate increases amount of phosphate in nephron beyond that which can be reabsorbed; excess is lost in urine Magnesium Second most common intracellular cation In adults, about 54% of total body magnesium is part of bone as magnesium salts Remaining 46% as Mg2+ in ICF (45%) or ECF (1%) Cofactor for certain enzymes and sodium-potassium pump Essential for normal neuromuscular activity, synaptic transmission, and myocardial function Secretion of parathyroid hormone depends on Mg2+ Regulated in blood plasma by varying rate excreted in urine Copyright 2009, John Wiley & Sons, Inc. Regulation of Blood Magnesium 27_table_02 Acid-Base Balance The overall acid-base balance of the body is maintained by controlling the H+ concentration of body fluids, especially extracellular fluid. Homeostasis of H+ concentration is vital Proteins’ 3-D structure sensitive to pH changes normal plasma pH must be maintained between 7.35 - 7.45 diet high in proteins tends to acidify the blood 3 major mechanisms to regulate pH buffer system exhalation of CO2 (respiratory system) kidney excretion of H+ (urinary system) Principles of Human Anatomy and Physiology, 11e 35 3 Types of Acids in the Body Volatile acids - Can leave solution and enter the atmosphere Carbonic acid is an important volatile acid in body fluid Fixed acids - Are acids that do not leave solution. Once produced they remain in body fluids until eliminated by kidneys Sulfuric Acid and Phosphoric Acid are most important fixed acids in the body generated during catabolism of AA’s, phospholipids, & nucleic acids Organic acids : Produced by aerobic metabolism are metabolized rapidly & do not accumulate Produced by anaerobic metabolism (e.g., lactic acid) build up rapidly Buffer systems Act to quickly temporarily bind H+ Raise pH but do not remove H+ Most consist of weak acid and salt of that acid functioning as weak base Change either strong acid or base into weaker one Work in fractions of a second Found in fluids of the body 3 principal buffer systems protein buffer system carbonic acid-bicarbonate buffer system phosphate buffer system Copyright 2009, John Wiley & Sons, Inc. Regulation of Acid-Base Balance Regulation of Acid-Base Balance 27-40 Buffer Systems Buffer systems Protein buffer system - Most abundant buffer in ICF & blood plasma Hemoglobin in RBCs & Albumin in blood plasma Hemoglobin acts as a buffer in blood by picking up CO2 or H Free carboxyl group acts like an acid by releasing H+ Free amino group acts as a base to combine with H+ Side chain groups on 7 of 20 amino acids also can buffer H+ Copyright 2009, John Wiley & Sons, Inc. Buffer Systems Carbonic acid / bicarbonate buffer system Based on bicarbonate ion (HCO3-) acting as weak base & carbonic acid (H2CO3) acting as weak acid HCO3- is a significant anion in both ICF and ECF Because CO2 and H2O combine to form this buffer system cannot protect against pH changes due to respiratory problems in which there is an excess or shortage of CO2 Copyright 2009, John Wiley & Sons, Inc. Buffer Systems Phosphate buffer system Dihydrogen phosphate (H2PO4-) and monohydrogen phosphate (HPO42-) Phosphates are major anions in ICF and minor ones in ECF Important regulator of pH in cytosol but also acts to buffer acids in urine Copyright 2009, John Wiley & Sons, Inc. Exhalation of carbon dioxide The pH of body fluids may be adjusted by a change in the rate & depth of respirations, which usually takes from 1 to 3 minutes Increase in the rate & depth of breathing = more CO2 exhaled = ↑ blood pH. Decrease in respiration rate & depth= less CO2 exhaled = ↓blood pH . The pH of body fluids, in turn, affects the rate of breathing Increase in carbon dioxide in body fluids lowers pH of body fluids The kidneys excrete H+ and reabsorb HCO3- to aid in maintaining pH. Because H2CO3 can be eliminated by exhaling CO2 it is called a volatile acid Copyright 2009, John Wiley & Sons, Inc. Regulation of blood pH by the respiratory system pH modified by changing rate & depth of breathing: faster breathing rate, blood pH rises slow breathing rate, blood pH drops H+ detected by chemoreceptors in medulla oblongata, carotid & aortic bodies Respiratory centers inhibited or stimulated by changes is pH Copyright 2009, John Wiley & Sons, Inc. Respiratory Regulation of Acid-Base Balance 27-47 Kidney Regulation of Acid-Base Balance Kidney Excretion of H+ Metabolic reactions produce 1mEq/liter of nonvolatile acid/kg BW Excretion of H+ in the urine is only way to eliminate huge excess In the PCT, Na+/H+ antiporters secrete H+ as they reabsorb Na+ Intercalated cells of collecting duct include proton pumps→ secrete H+ into tubule fluid; reabsorb K+ & HCO3Urine can be up to 1000 times more acidic than blood Kidneys synthesize new bicarbonate and save filtered bicarbonate Renal failure can cause death rapidly due to its role in pH balance 2 other buffers can combine with H+ in collecting duct: - HPO42- and NH3 49 Hydrogen Ion Buffering Regulation of Acid-Base Balance Cells in the PCT and collecting ducts secrete H+ into the tubular fluid. In the PCT Na+/H+ antiporters secrete H+ and reabsorb Na+ The apical surfaces of some intercalated cells include proton pumps (H+ ATPases) that secrete H+ into the tubular fluid and HCO3– antiporters in their basolateral membranes to reabsorb HCO3– Other intercalated cells have proton pumps in their basolateral membranes and Cl–/HCO3– antiporters in their apical membranes. These two types of cells help maintain body fluid pH by excreting excess H+ when pH is too low or by excreting excess HCO3– when the pH is too high. Normal pH range of arterial blood 7.35-7.45 Acidosis – blood pH below 7.35 ; Alkalosis – blood pH above 7.45 Major physiological effect of : Acidosis – depression of synaptic transmission in CNS Alkalosis – overexcitability of CNS and peripheral nerves Principles of Human Anatomy and Physiology, 11e 51 27_table_03 Physiological responses to normalize arterial blood pH Changes in blood pH may be countered by compensation Complete – brought within normal range Partial – still too low or high Respiratory compensation – hyperventilation or hypoventilation Renal compensation – secretion of H+ and reabsorption of HCO3Respiratory acidosis / alkalosis are primary disorders of blood PCO2. Metabolic acidosis/alkalosis are primary disorders of HCO3- concentration Copyright 2009, John Wiley & Sons, Inc. Respiratory acidosis Abnormally high PCO2 in systemic arterial blood Inadequate exhalation of CO2 Any condition that decreases movement of CO2 out – emphysema, pulmonary edema, airway obstruction Kidneys can help raise blood pH Goal to increase exhalation of CO2 – ventilation therapy Respiratory Alkalosis - Abnormally low PCO2 in systemic arterial blood Cause is hyperventilation due to O2 deficiency from high altitude or pulmonary disease, stroke, severe anxiety, aspirin overdose Renal compensation involves decrease in excretion of H+ and increase reabsorption of bicarbonate - One simple treatment to breathe into paper bag for short time Copyright 2009, John Wiley & Sons, Inc. Metabolic Acidosis Results from changes in HCO3- concentration Metabolic acidosis – abnormally low HCO3- in systemic arterial blood Loss of HCO3- from severe diarrhea or renal dysfunction Accumulation of acid (ketosis with dieting/diabetes) Kidney failing to remove H+ from protein metabolism Respiratory compensation by hyperventilation Administer IV sodium bicarbonate and correct cause of acidosis Metabolic Alkalosis Abnormally high HCO3- in systemic arterial blood Non-respiratory cause: vomiting acidic stomach contents, gastric suctioning Excessive intake of alkaline drugs (antacids) & use of certain diuretics Severe dehydration Respiratory compensation is hypoventilation Give fluid solutions to correct Cl-, K+ and other electrolyte deficiencies and correct cause of alkalosis Copyright 2009, John Wiley & Sons, Inc. 27_table_04 Diagnostic Chart for Acid-Base Disorders Figure 27–15 (1 of 2) Copyright 2009, John Wiley & Sons, Inc. Diagnosis of Acid-Base Imbalances Evaluate systemic arterial blood pH concentration of bicarbonate (too low or too high) PCO2 (too low or too high) Solutions if problem is respiratory, the pCO2 will not be normal if problem is metabolic, the bicarbonate level will not be normal Principles of Human Anatomy and Physiology, 11e 59 End of Chapter 27 Copyright 2009 John Wiley & Sons, Inc. All rights reserved. Reproduction or translation of this work beyond that permitted in section 117 of the 1976 United States Copyright Act without express permission of the copyright owner is unlawful. Request for further information should be addressed to the Permission Department, John Wiley & Sons, Inc. The purchaser may make back-up copies for his/her own use only and not for distribution or resale. The Publishers assumes no responsibility for errors, omissions, or damages caused by the use of theses programs or from the use of the information herein. Copyright 2009, John Wiley & Sons, Inc.