Chapter 26

Fluid, Electrolyte, and Acid - Base Homeostasis

James F. Thompson, Ph.D.

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 from Ch. 19

Distribution of Electrolytes

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-, PO4

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 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• 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• 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)

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

+]

Acid-Base Imbalances• Acidosis

– High blood [H+]– Low blood pH, <7.35

• Alkalosis– Low blood [H+]– High blood pH, >7.45

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

Causes of Acid-Base Imbalances• Respiratory Acidosis

– Chronic Obstructive Pulmonary Diseases e.g., emphysema, pulmonary fibrosis

– Pneumonia

• Respiratory Alkalosis– Hysteria– Fever– Asthma

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)

End Chapter 26