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 H 2 O & 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 HPO 4 2- 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 HCO 3 - 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 - ] [H 2 O]  [K + ] Atrial Natriuretic Peptide (opposite effect) Antidiuretic Hormone  [H 2 O] (  [solutes]) Parathyroid Hormone  [Ca ++ ]  [HPO 4 - ] Calcitonin (opposite effect) Female sex hormones  [H 2 O]

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 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

20. Electrolytes Calcium (Ca 2+ ) –Most abundant ion in body plasma 4.6-5.5 mEq/liter most stored in bone (98%) –Regulation: Parathyroid Hormone (PTH) -  blood Ca 2+ Calcitonin (CT) -  blood Ca 2+ –Homeostatic imbalances: Hypocalcemia - muscle cramps, convulsions Hypercalcemia - vomiting, cardiovascular symptoms, coma; prolonged  abnormal calcium deposition, e.g., stone formation

21. Electrolytes Phosphate (H 2 PO 4 -, HPO 4 2-, PO 4 3- ) –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 Ca 2+ 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 (Mg 2+ ) –2 nd 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 Mg 2+ 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 CO 2 - 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 + + HCO 3 -  H 2 CO 3  H 2 O + CO 2 Phosphate Buffer –NaOH + NaH 2 PO 4  H 2 O + Na 2 HPO 4 –HCl + Na 2 HPO 4  NaCl + NaH 2 PO 4 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 [NH 4 + ] Decreased [H + ] causes immediate hypoventilation and later decreased renal secretion of [H + ] and [NH 4 + ]

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 (pCO 2 > 45 mm Hg) –Respiratory Alkalosis (pCO 2 < 35 mm Hg) –Metabolic Acidosis (HCO 3 - < 23 mEq/l) –Metabolic Alkalosis (HCO 3 - > 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