Fluid, Electrolyte, and Acid - Base Homeostasis

Fluid Compartments Body Fluids are separated by semi-permeable 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 Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 Regulation: 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 Alkalosis 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 Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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+ Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Acid–Base Balance The Role of Amino Acids in Protein Buffer Systems. Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 PCO2 is rising or falling Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Acid–Base Balance Carbonic Acid–Bicarbonate Buffer System Cannot protect ECF from changes in pH that result from elevated or depressed levels of CO2 Functions only when respiratory system and respiratory control centers are working normally Ability to buffer acids is limited by availability of bicarbonate ions Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Acid–Base Balance Maintenance of Acid–Base Balance Requires balancing H+ gains and losses Coordinates actions of buffer systems with Respiratory mechanisms Renal mechanisms Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Acid–Base Balance Respiratory and Renal Mechanisms Support buffer systems by Secreting or absorbing H+ Controlling excretion of acids and bases Generating additional buffers Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Acid–Base Balance Respiratory Compensation Increasing or decreasing the rate of respiration alters pH by lowering or raising the PCO2 When PCO2 rises pH falls Addition of CO2 drives buffer system to the right When PCO2 falls pH rises Removal of CO2 drives buffer system to the left Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Acid–Base Balance Hydrogen Ions Are secreted into tubular fluid along Proximal convoluted tubule (PCT) Distal convoluted tubule (DCT) Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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: Carbonic acid–bicarbonate buffer system Phosphate buffer system Ammonia buffer system Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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 Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Acid–Base Balance Renal Responses to Acidosis Secretion of H+ Activity of buffers in tubular fluid Removal of CO2 Reabsorption of NaHCO3 Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Acid–Base Balance Renal Responses to Alkalosis Rate of secretion at kidneys declines Tubule cells do not reclaim bicarbonates in tubular fluid Collecting system transports HCO3- into tubular fluid while releasing strong acid (HCl) into peritubular fluid Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Acid–Base Balance Disturbances Disorders: Circulating buffers Respiratory performance Renal function Cardiovascular conditions: Heart failure Hypotension Conditions affecting the CNS: Neural damage or disease that affects respiratory and cardiovascular reflexes Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Acid–Base Balance Disturbances Figure 27–11a Interactions among the Carbonic Acid–Bicarbonate Buffer System and Compensatory Mechanisms in the Regulation of Plasma pH. Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Acid–Base Balance Disturbances Figure 27–11b Interactions among the Carbonic Acid–Bicarbonate Buffer System and Compensatory Mechanisms in the Regulation of Plasma pH. Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings