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Fluid, Electrolyte, and Acid Base Homeostasis Fluid Compartments • Body Fluids are separated by semipermeable membranes into various physiological (functional) compartments • Two Compartment Model – Intracellular = Cytoplasmic (inside cells) – Extracellular (outside cells) • The Two Compartment Model is useful clinically for understanding the distribution of many drugs in the body Fluid Compartments • Three Compartment Model – [1] Intracellular = Cytoplasmic (inside cells) – [Extracellular compartment is subdivided into:] – [2] Interstitial = Intercellular = Lymph (between the cells in the tissues) – [3] Plasma (fluid portion of the blood) • The Three Compartment Model is more useful for understanding physiological processes • Other models with more compartments can sometimes be useful, e.g., consider lymph in the lymph vessels, CSF, ocular fluids, synovial and serous fluids as separate compartments Fluid Compartments • Total Body Water (TBW) - 42L, 60% of body weight – Intracellular Fluid (ICF) 28L, 67% of TBW – Extracellular Fluid (ECF) 14L, 33% of TBW • Interstitial Fluid - 11L, 80% ECF • Plasma - 3L, 20% of ECF Fluid Balance • Fluid balance – When in balance, adequate water is present and is distributed among the various compartments according to the body’s needs – Many things are freely exchanged between fluid compartments, especially water – Fluid movements by: • bulk flow (i.e., blood & lymph circulation) • diffusion & osmosis – in most regions Water • General – Largest single chemical component of the body: 45-75% of body mass – Fat (adipose tissue) is essentially water free, so there is relatively more or less water in the body depending on % fat composition – Water is the solvent for most biological molecules within the body – Water also participates in a variety of biochemical reactions, both anabolic and catabolic Water • Water balance – Sources for 2500 mL - average daily intake • Metabolic Water • Preformed Water – Ingested Foods – Ingested Liquids – Balance achieved if daily output also = 2500 mL • GI tract • Lungs • Skin – evaporation – perspiration • Kidneys Regulating Fluid Intake - Thirst • Recall the role of the Renin-Angiotensin System in regulating thirst along with the Autonomic NS reflexes diagramed below Regulating Fluid Intake Thirst Quenching • Wetting the oral mucosa (temporary) • Stretching of the stomach • Decreased blood/body fluid osmolarity = increased hydration (dilution) of the blood is the most important Regulation of Fluid Output • Hormonal control – AntiDiuretic Hormone (ADH) [neurohypophysis] – Aldosterone [adrenal cortex] – Atrial Natriuretic Peptide (ANP) [heart atrial walls] • Physiologic fluid imbalances – – – – – – – Dehydration: blood pressure, GFR Overhydration: blood pressure, GFR Hyperventilation - water loss through lungs Vomiting & Diarrhea - excessive water loss Fever - heavy perspiration Burns - initial fluid loss; may persist in severe burns Hemorrhage – if blood loss is severe Concentrations of Solutes • Non-electrolytes – molecules formed by only covalent bonds – do not form charged ions in solution • Electrolytes – Molecules formed with some ionic bonds; – Disassociate into cations (+) & anions (-) in solutions (acids, bases, salts) – 4 important physiological functions in the body • essential minerals in certain biochemical reactions • control osmosis = control the movement of water between compartments • maintain acid-base balance • conduct electrical currents (depolarization events) Distribution of H2O & Electrolytes • Recall Starling’s Law of the Capillaries which explains fluid and solute movements Distribution of Electrolytes Cations and Anions in Body Fluids Distribution of Major Electrolytes • Na+ and CL- predominate in extracellular fluids (interstitial fluid and plasma) but are very low in the intracellular fluid (cytoplasm) • K+ and HPO42- predominate in intracellular fluid (cytoplasm) but are in very low concentration in the extracellular fluids (interstitial fluid and plasma) • At body fluid pH, proteins [P-] act as anions; total protein concentration [P-] is relatively high, the second most important “anion,” in the cytoplasm, [P-] is intermediate in blood plasma, but [P-] is very low in the interstitial fluid Distribution of Minor Electrolytes • HCO3- is in intermediate concentrations in all fluids, a bit lower in the intracellular fluid (cytoplasm); it is an important pH buffer in the extracellular comparments • Ca++ is in low concentration in all fluid compartments, but it must be tightly regulated, as small shifts in Ca++ concentration in any compartment have serious effects • Mg++ is in low concentration in all fluid compartments, but Mg++ is a bit higher in the intracellular fluid (cytoplasm), where it is a component of many cellular enzymes Electrolyte Balance • Aldosterone [Na+] [Cl-] [H2O] [K+] • Atrial Natriuretic Peptide (opposite effect) • Antidiuretic Hormone [H2O] ( [solutes]) • Parathyroid Hormone [Ca++] [HPO4-] • Calcitonin (opposite effect) • Female sex hormones [H2O] Electrolytes • Sodium (Na+) - 136-142 mEq/liter – Most abundant cation • major ECF cation (90% of cations present) • determines osmolarity of ECF – Regulation • Aldosterone • ADH • ANP – Homeostatic imbalances • Hyponatremia - muscle weakness, coma • Hypernatremia - coma Electrolytes • Chloride (Cl-) - 95-103 mEq/liter – Major ECF anion • helps balance osmotic potential and electrostatic equilibrium between fluid compartments • plasma membranes tend to be leaky to Cl- anions – Regulation: aldosterone – Homeostatic imbalances • Hypochloremia - results in muscle spasms, coma [usually occurs with hyponatremia] often due to prolonged vomiting • elevated sweat chloride diagnostic of Cystic Fibrosis Electrolytes • Potassium (K+) – Major ICF cation • intracellular 120-125 mEq/liter • plasma 3.8-5.0 mEq/liter – Very important role in resting membrane potential (RMP) and in action potentials – Regulation: • Direct Effect: excretion by kidney tubule • Aldosterone – Homeostatic imbalances • Hypokalemia - vomiting, death • Hyperkalemia - irritability, cardiac fibrillation, death Electrolytes • Calcium (Ca2+) – Most abundant ion in body • plasma 4.6-5.5 mEq/liter • most stored in bone (98%) – Regulation: • Parathyroid Hormone (PTH) - blood Ca2+ • Calcitonin (CT) - blood Ca2+ – Homeostatic imbalances: • Hypocalcemia - muscle cramps, convulsions • Hypercalcemia - vomiting, cardiovascular symptoms, coma; prolonged abnormal calcium deposition, e.g., stone formation Electrolytes • Phosphate (H2PO4-, HPO42-, PO43-) – Important ICF anions; plasma 1.7-2.6 mEq/liter • most (85%) is stored in bone as calcium salts • also combined with lipids, proteins, carbohydrates, nucleic acids (DNA and RNA), and high energy phosphate transport compound • important acid-base buffer in body fluids – Regulation - regulated in an inverse relationship with Ca2+ by PTH and Calcitonin – Homeostatic imbalances • Phosphate concentrations shift oppositely from calcium concentrations and symptoms are usually due to the related calcium excess or deficit Electrolytes • Magnesium (Mg2+) – 2nd most abundant intracellular electrolyte, 1.3-2.1 mEq/liter in plasma • more than half is stored in bone, most of the rest in ICF (cytoplasm) • important enzyme cofactor; involved in neuromuscular activity, nerve transmission in CNS, and myocardial functioning – Excretion of Mg2+ caused by hypercalcemia, hypermagnesemia – Homeostatic imbalance • Hypomagnesemia - vomiting, cardiac arrhythmias • Hypermagnesemia - nausea, vomiting Acid–Base Balance Terms • Acid – Any substance that can yield a hydrogen ion (H+) or hydronium ion when dissolved in water – Release of proton or H+ • Base – Substance that can yield hydroxyl ions (OH-) – Accept protons or H+ Terms • pH – Negative log of the hydrogen ion concentration – Represents the hydrogen concentration Acid-Base Imbalances • Acidosis – High blood [H+] – Low blood pH, <7.35 • Alkalosis – Low blood [H+] – High blood pH, >7.45 – Note: Normal pH is 7.35-7.45 Terms • Buffer – Combination of a weak acid and /or a weak base and its salt – What does it do? • Resists changes in pH – Effectiveness depends on • pK of buffering system • pH of environment in which it is placed Acid-Base Balance • Normal metabolism produces H+ (acidity) • Three Homeostatic mechanisms: – Buffer systems - instantaneous; temporary – Exhalation of CO2 - operates within minutes; cannot completely correct serious imbalances – Kidney excretion - can completely correct any imbalance (eventually) • Buffer Systems – Consists of a weak acid and the salt of that acid which functions as a weak base – Strong acids dissociate more rapidly and easily than weak acids Acid–Base Balance • Buffer System – Consists of a combination of • A weak acid • And the anion released by its dissociation – The anion functions as a weak base – In solution, molecules of weak acid exist in equilibrium with its dissociation products Acid–Base Balance • Buffers – Are dissolved compounds that stabilize pH • By providing or removing H+ – Weak acids • Can donate H+ – Weak bases • Can absorb H+ Acid–Base Balance • Three Major Buffer Systems – – Protein buffer systems: • Help regulate pH in ECF and ICF • Interact extensively with other buffer systems Carbonic acid–bicarbonate buffer system: • – Most important in ECF Phosphate buffer system: • Buffers pH of ICF and urine Acid–Base Balance • Protein Buffer Systems – Depend on amino acids – Respond to pH changes by accepting or releasing H+ – If pH rises • Carboxyl group of amino acid dissociates • Acting as weak acid, releasing a hydrogen ion • Carboxyl group becomes carboxylate ion Acid–Base Balance • Protein Buffer Systems – At normal pH (7.35–7.45) • Carboxyl groups of most amino acids have already given up their H+ – If pH drops • Carboxylate ion and amino group act as weak bases • Accept H+ • Form carboxyl group and amino ion Acid–Base Balance The Role of Amino Acids in Protein Buffer Systems. Acid–Base Balance • The Hemoglobin Buffer System – CO2 diffuses across RBC membrane • No transport mechanism required – As carbonic acid dissociates • Bicarbonate ions diffuse into plasma • In exchange for chloride ions (chloride shift) – Hydrogen ions are buffered by hemoglobin molecules Acid–Base Balance • The Hemoglobin Buffer System – Is the only intracellular buffer system with an immediate effect on ECF pH – Helps prevent major changes in pH when plasma PCO is rising or falling 2 Oxygen Dissociation Curve Curve B: Normal curve Curve A: Increased affinity for hgb, so oxygen keep close Curve C: Decreased affinity for hgb, so oxygen released to tissues Bohr Effect • It all about oxygen affinity! Acid–Base Balance • Carbonic Acid–Bicarbonate Buffer System – Carbon Dioxide • Most body cells constantly generate carbon dioxide • Most carbon dioxide is converted to carbonic acid, which dissociates into H+ and a bicarbonate ion – Is formed by carbonic acid and its dissociation products – Prevents changes in pH caused by organic acids and fixed acids in ECF Acid–Base Balance • Carbonic Acid–Bicarbonate Buffer System 1. Cannot protect ECF from changes in pH that result from elevated or depressed levels of CO2 2. Functions only when respiratory system and respiratory control centers are working normally 3. Ability to buffer acids is limited by availability of bicarbonate ions Acid–Base Balance • Phosphate Buffer System – Consists of anion H2PO4- (a weak acid) – Works like the carbonic acid–bicarbonate buffer system – Is important in buffering pH of ICF Acid–Base Balance • Maintenance of Acid–Base Balance – Requires balancing H+ gains and losses – Coordinates actions of buffer systems with • Respiratory mechanisms • Renal mechanisms Acid–Base Balance • Respiratory and Renal Mechanisms – Support buffer systems by • • • Secreting or absorbing H+ Controlling excretion of acids and bases Generating additional buffers Acid–Base Balance • Respiratory Compensation – Is a change in respiratory rate • That helps stabilize pH of ECF – Occurs whenever body pH moves outside normal limits – Directly affects carbonic acid–bicarbonate buffer system Acid–Base Balance • Respiratory Compensation – Increasing or decreasing the rate of respiration alters pH by lowering or raising the PCO2 – When PCO rises • pH falls 2 • Addition of CO2 drives buffer system to the right – When PCO falls 2 • pH rises • Removal of CO2 drives buffer system to the left Acid–Base Balance • Renal Compensation – Is a change in rates of H+ and HCO3- secretion or reabsorption by kidneys in response to changes in plasma pH – The body normally generates enough organic and fixed acids each day to add 100 mEq of H+ to ECF – Kidneys assist lungs by eliminating any CO2 that • Enters renal tubules during filtration • Diffuses into tubular fluid en route to renal pelvis Acid–Base Balance • Hydrogen Ions – Are secreted into tubular fluid along • Proximal convoluted tubule (PCT) • Distal convoluted tubule (DCT) Acid–Base Balance • Buffers in Urine – The ability to eliminate large numbers of H+ in a normal volume of urine depends on the presence of buffers in urine: 1. Carbonic acid–bicarbonate buffer system 2. Phosphate buffer system 3. Ammonia buffer system Acid–Base Balance • Major Buffers in Urine – Glomerular filtration provides components of • Carbonic acid–bicarbonate buffer system • Phosphate buffer system – Tubule cells of PCT • Generate ammonia Acid–Base Balance • Renal Responses to Acidosis 1. 2. 3. 4. Secretion of H+ Activity of buffers in tubular fluid Removal of CO2 Reabsorption of NaHCO3 Acid–Base Balance • Renal Responses to Alkalosis 1. Rate of secretion at kidneys declines 2. Tubule cells do not reclaim bicarbonates in tubular fluid 3. Collecting system transports HCO3- into tubular fluid while releasing strong acid (HCl) into peritubular fluid Acid–Base Balance Disturbances 1. Disorders: – – – Circulating buffers Respiratory performance Renal function 2. Cardiovascular conditions: – – Heart failure Hypotension 3. Conditions affecting the CNS: – Neural damage or disease that affects respiratory and cardiovascular reflexes Acid–Base Balance Disturbances Figure 27–11a Interactions among the Carbonic Acid–Bicarbonate Buffer System and Compensatory Mechanisms in the Regulation of Plasma pH. Acid–Base Balance Disturbances Figure 27–11b Interactions among the Carbonic Acid–Bicarbonate Buffer System and Compensatory Mechanisms in the Regulation of Plasma pH.