Chapter 26

1. Chapter 26 Fluid, Electrolyte, and Acid - Base Homeostasis James F. Thompson, Ph.D.

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. Regulating Fluid Intake - Thirst • Recall the role of the Renin-Angiotensin System in regulating thirst along with the Autonomic NS reflexes diagramed below

9. 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

10. 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

11. 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)

12. Distribution of H2O & Electrolytes • Recall Starling’s Law of the Capillaries which explains fluid and solute movements from Ch. 19

13. Distribution of Electrolytes

14. 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

15. 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

16. 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]

17. 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

18. 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

19. Electrolytes • Potassium (K+) • Major ICF cation • intracellular 120-125 mEq/liter • plasma 3.8-5.0 mEq/liter • Very importantrole 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

20. 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

21. 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

22. 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

23. 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

24. Acid-Base Balance • Carbonic Acid - Bicarbonate Buffer • A weak base (recall carbonic anhydrase) • H+ + HCO3- H2CO3 H2O + CO2 • Phosphate Buffer • NaOH + NaH2PO4 H2O + Na2HPO4 • HCl + Na2HPO4 NaCl + NaH2PO4 • Protein Buffer (esp. hemoglobin & albumin) • Most abundant buffer in body cells and plasma • Amino acids have amine group (proton acceptor = weak base) and a carboxyl group (proton donor = weak acid)

25. Acid-Base Balance • CNS and peripheral chemoreceptors note changes in blood pH • Increased [H+] causes immediate hyperventilation and later increased renal secretion of [H+] and [NH4+] • Decreased [H+] causes immediate hypoventilation and later decreased renal secretion of [H+] and [NH4+]

26. Acid-Base Imbalances • Acidosis • High blood [H+] • Low blood pH, <7.35 • Alkalosis • Low blood [H+] • High blood pH, >7.45

27. Acid-Base Imbalances • Acid-Base imbalances may be due to problems with ventilation or due to a variety of metabolic problems • Respiratory Acidosis (pCO2 > 45 mm Hg) • Respiratory Alkalosis (pCO2 < 35 mm Hg) • Metabolic Acidosis (HCO3- < 23 mEq/l) • Metabolic Alkalosis (HCO3- > 26 mEq/l) • Compensation: the physiological response to an acid-base imbalance begins with adjustments by the system less involved

28. Causes of Acid-Base Imbalances • Respiratory Acidosis • Chronic Obstructive Pulmonary Diseases e.g., emphysema, pulmonary fibrosis • Pneumonia • Respiratory Alkalosis • Hysteria • Fever • Asthma

29. Causes of Acid-Base Imbalances • Metabolic Acidosis • Diabetic ketoacidosis, Lactic acidosis • Salicylate poisoning (children) • Methanol, ethylene glycol poisoning • Renal failure • Diarrhea • Metabolic Alkalosis • Prolonged vomiting • Diuretic therapy • Hyperadrenocortical disease • Exogenous base (antacids, bicarbonate IV, citrate toxicity after massive blood transfusions)

30. End Chapter 26