FLUID, ELECTROLYTE, AND ACID-BASE BALANCE

1. FLUID, ELECTROLYTE, AND ACID-BASE BALANCE

2. FLUID, ELECTROLYTE, AND ACID-BASE BALANCE • Cell function depends not only on a continuous supply of nutrients and removal of metabolic wastes, but also on the physical and chemical homeostasis of the surrounding fluids

3. BODY FLUIDSBody Water Content • Total body water is a function of age, body mass, and body fat • Due to their low body fat and bone mass, infants are about 73% water • The body water content of men is about 60%, but since women have relatively more body fat and less skeletal muscle than men, theirs is about 50% • Of all body tissues, adipose tissue is least hydrated (up to about 20% water) • Skeletal muscle is about 65% water • Body water declines throughout life, ultimately comprising about 45% of total body mass in old age

4. BODY FLUIDSFluid Compartments • There are two main fluid compartments of the body: • Intracellular fluid compartment: ICF • Contains slightly less than two-thirds by volume • Cells • Extracellular fluid compartment: ECF • The remaining third • Outside cells • Constitutes the body’s internal environment but external environment of the cell • Two Sub-compartments: • Blood plasma: fluid portion of blood • Interstitial fluid (IF): fluid in the microscopic spaces between tissue cells • Numerous other examples that are distinct from both plasma and interstitial fluid—lymph, cerebrospinal fluid, humors of the eye, synovial fluid, serous fluid, secretions of the gastrointestinal tract—but most of these are similar to interstitial fluid (IF) and are usually considered part of it

5. FLUID COMPARTMENTS OF THE BODY

6. Composition of Body FluidsElectrolytes and Nonelectrolytes • Water serves as the universal solvent in which a variety of solutes are dissolved: • Solutes may be classified broadly as: • Electrolytes: dissociate in water to ions • Include inorganic salts, both inorganic and organic acids and bases, and some proteins • Conduct electric current • Nonelectrolytes: do not dissociate in water • Have bonds (usually covalent) that prevent them from dissociating in solution • Include most organic molecules • Carry no net electrical charge when dissolved in water • Although all dissolve solutes contribute to the osmotic activity of a fluid: • Electrolytes have greater osmotic power because they dissociate in water and contribute at least two particles to solution • Examples: • NaCl → Na+ + Cl- (electrolyte: two particles) • MgCl2 → Mg2+ + 2Cl- (electrolyte: three particles) • Glucose → Glucose (nonelectrolyte: one particle)

7. Composition of Body FluidsElectrolytes and Nonelectrolytes • Regardless of the type of solute particle, water moves according to osmotic gradients—from an area of lesser osmolality (less dissolved substancesper unit of solvent) to an area of greater osmolality (more dissolved substances per unit of solvent) • Osmolality: the number of solute particles dissolved in one liter (1000g) of water • Reflects the solution’s ability to cause osmosis • Osmolarity: total concentration of all solute particles in a solution • Thus, electrolytes have the greatest ability to cause fluid shifts • Electrolyte concentrations of body fluids are usually expressed in milliequivalents per liter (mEq/L) • A measure of the number of electrical charges in 1 liter of solution

8. Comparison of Extracellular and Intracellular Fluids • Extracellular fluids: • The major cation in is sodium (Na+), and the major anion is chloride (Cl-) • Intracellular fluid: • The major cation is potassium (K+), and the major anion is phosphate (HPO42-) • Electrolytes are the most abundant solutes in body fluids, but proteins and some nonelectrolytes (phospholipiuds, cholesterol, and neutral fats) are also dissolved and account for 60-97% of the mass of dissolved solutes

9. ELECTROLYTE COMPOSITION OF BLOOD PLASMA, INTERSTITIAL FLUID, AND INTRACELLULAR FLUID

10. Fluid Movement Among Compartments • The continuous exchange and mixing of body fluids are regulated by osmotic pressure (pressure that develops when two solutions of different concentrations are separated by a semipermeable membrane) andhydrostatic pressures (pressures exerted on liquids) • Although water moves freely between the compartments along osmotic gradients, solutes are unequally distributed because of their size, electrical charge, or dependence on active transport • Anything that changes solute concentration in any compartment leads to net water flows

11. Fluid Movement Among Compartments • Exchanges between plasma and Interstitial Fluid (IF) occur across capillary membranes • Nearly protein-free plasma is forced out of the blood by hydrostatic pressure, and almost completely reabsorbed due to colloid osmotic (oncotic) pressure of plasma proteins(review blood capillaries Chapter) • Movement of water between the interstitial fluid and intracellular fluid is more complex because of the selective permeability of cell membranes • As a rule: • Involves substantial two-way osmotic (water) flow that is equal in both directions • Ion fluxes are restricted and , in most cases, ions move selectively by active transport • Movement of nutrients, respiratory gases, and wastes are typically unidirectional

12. Fluid Movement Among Compartments • Plasma circulates throughout the body and links the external and internal environments • Exchanges occur almost continuously in the lungs, gastrointestinal tract, and kidneys: • Although these exchanges alter plasma composition and volume, compensating adjustments in the other two fluid compartments (Interstitial Fluid/Intracellular Fluid) follow quickly so that balance is restored

13. CONTINUOUS MIXING OF BODY FLUIDS

14. WATER BALANCE AND ECF OSMOLALITY • ECF: extracellular fluid compartment • For the body to remain properly hydrated, water intake must equal water output • Typically 2500 ml/day • Most water enters the body through ingested liquids and food, but is also produced by cellular metabolism (metabolic water or water of oxidation) • Water output is due to evaporative loss from lungs in expired air and skin (insensible water loss: imperceptible ), sweating (perspiration), defecation, and urination

15. WATER INTAKE/OUTPUT

16. Regulation of Water Intake • The thirst mechanism is triggered by a increase in plasma osmolarity (2-3%), which results in a dry mouth (less fluid leaves the bloodstream) and excites the hypothalamic thirst center • Less saliva is produced • Hypothalamic thirst center is stimulated when its osmoreceptors lose water by osmosis to the hypertonic ECF, or are excited by baroreceptor (pressure receptors in blood vessels) inputs, angiotensin (vasopressor-antidiuretic produced when renin is released by the kidneys), or other stimuli • Cause a subjective sensation of thrist • Free salty snacks in bar

17. THIRST MECHANISM FOR REGULATING WATER INTAKE

18. Regulation of Water Intake • Thirst is quenched as the mucosa of the mouth is moistened, and continues with distention of the stomach and intestine, resulting in inhibition of the hypothalamus thirst center

19. THIRST MECHANISM FOR REGULATING WATER INTAKE

20. Regulation of Water Output • Drinking is necessary since there is obligatory water loss due to the insensible (imperceptible/gradual) water losses • Even the most heroic conservation efforts by the kidneys cannot compensate for zero water intake • Beyond obligatory water losses, solute concentration and volume of urine depend on fluid intake

21. Influence of Antidiuretic Hormone (ADH) • The amount of water reabsorbed in the renal collecting ducts is proportional to ADH release: • When ADH levels are low, most water in the collecting ducts is not reabsorbed, resulting in large quantities of dilute urine • When ADH levels are high, filtered water is reabsorbed, resulting in a lower volume of concentrated urine • Osmoreceptors of the hypothalamus sense the ECF solute concentration and trigger or inhibit ADH release from the posterior pituitary: • ADH secretions is promoted or inhibited by the hypothalamus in response to changes in solute concentration of extracellular fluid, large changes in blood volume or pressure, or vascular baroreceptors

22. MECHANISMS AND CONSEQUENCES OF ADH RELEASE

23. MECHANISMS REGULATING SODIUM AND WATER BALANCE HELP MAINTAIN BLOOD PRESSURE HOMEOSTASIS

24. Disorders of Water BalanceDehydration (a) • Occurs when water output exceeds water intake, and may lead to weight loss, fever, mental confusion, or hypovolemic (decreased blood volume due to bleeding, fluid loss or inadequate fluid intake) shock • Common sequel to hemorrhage, severe burns, prolonged vomiting or diarrhea, profuse sweating, water deprivation, and diuretic abuse • May also be caused by diabetes

25. Disorders of Water BalanceHypotonic Hydration (b) • Is a result of renal insufficiency, or intake of an excessive amount of water very quickly • ECF is diluted—its sodium content is normal, but excess water is present: • Hyponatremia (low ECF Na+): • Promotes net osmosis into the tissue cells, causing them to swell as they become abnormally hydrated • Resulting electrolyte dilution leads to severe metabolic disturbances evidenced by nausea, vomiting, muscular cramping, and cerebral edema (excess fluid) • Damaging to neurons • Uncorrected cerebral edema quickly leads to disorientation, convulsions, coma, and death

26. DISTURBANCES IN WATER BALANCE

27. Disorders of Water BalanceEdema • Is the accumulation of fluid in the interstitial space, which may impair tissue function: • Caused by any event that: • Steps up the flow of fluid out of the blood: • Blood pressure • Increased capillary permeability • Inflammation) • Or hinders its return: • Imbalance on the two sides of the capillary membranes • Hypoproteinemia: Low levels of plasma proteins • Fluids are forced out of the capillary beds at the arterial ends by blood pressure as usual, but fail to return to the blood at the venous end • Interstitial spaces become congested with fluid • Result of poor nutrition, liver disease, or renal failure

28. ELECTROLYTE BALANCE • Sodium is the most important cation to regulation of fluid and electrolyte balance in the body due to its abundance and osmotic pressure: • Since all body fluids are in chemical equilibrium, any change in sodium levels causes a compensatory shift in water, affecting plasma volume, blood pressure, and intracellular and interstitial fluid volumes

29. HOMEOSTATIC IMBALANCE • Severe electrolyte deficiencies prompt a craving for salty foods and often exotic foods, such as smoked meats or pickled eggs: • Common in Addison’s disease • Disorder entailing deficient mineralocorticoid hormone (aldosterone: regulates the retention and excretion of fluids and electrolytes) production by the adrenal cortex • Pica: appetite for abnormal substances • When electrolytes other than NaCl are deficient, a person may even eat substances not usually considered foods, like chalk, clay, starch, and burnt match tips

30. The Central Role of Sodium in Fluid and Electrolyte Balance • Sodium holds a central position in fluid and electrolyte balance and overall body homeostasis • Regulating the balance between sodium input and output is one of the most important renal functions • The salts NaHCO3 and NaCl account for 90-95% of all solutes in ECF (extracellular fluid): • Na being the single most abundant • Cellular plasma membranes are relatively impermeable to Na+, but some does manage to diffuse in and must be pumped out against its electrochemical gradient • These two qualities give sodium the primary role in controlling ECF volume and water distribution in the body • It is important to understand that while the sodium content of the body may change, its ECF concentration normally remains stable because of immediate adjustments in water volume • Water follows salt

31. Regulation of Sodium BalanceInfluence of Aldosterone • Despite the critical importance of sodium, receptors that specifically monitor Na+ levels in body fluids have yet to be found • Influence of Aldosterone: Adrenal cortex • When aldosterone secretion is high, nearly all the filtered sodium is reabsorbed in the distal convoluted tubule and the collecting duct • Water follows if it can, that is, if the tubule permeability has been increased by ADH • The most important trigger for the release of aldosterone is the renin-angiotensin mechanism (kidneys), initiated in response to sympathetic stimulation, decrease in filtrate osmolality, or decreased blood pressure • The principal effects of aldosterone are to diminish urinary output and increase blood volume

32. MECHANISMS AND CONSEQUENCES OF ALDOSTERONE RELEASE

33. MECHANISMS REGULATING SODIUM AND WATER BALANCE HELP MAINTAIN BLOOD PRESSURE HOMEOSTASIS

34. HOMEOSTATIC IMBALANCE • People with Addison’s disease (hypoaldosteronism) lose tremendous amounts of NaCl and water to urine • As long as they ingest adequate amounts of salt and fluids, people with this condition can avoid problems, but they are perpetually teetering on the brink of hypovolemia (decreased blood volume) and dehydration

35. Regulation of Sodium BalanceCardiovascular Baroreceptors • Cardiovascular baroreceptors monitor blood volume so that blood pressure remains stable: • Because Na+ concentration determines fluid volume, the baroreceptors might be regarded as “sodium receptors”

36. MECHANISMS REGULATING SODIUM AND WATER BALANCE HELP MAINTAIN BLOOD PRESSURE HOMEOSTASIS

37. Regulation of Sodium BalanceInfluence of Atrial Natriuretic Peptide • Atrial natriuretic peptide (ANP) hormone reduces blood pressure and blood volume by inhibiting release of ADH, renin, and aldosterone, and directly causing vasodilation: • It reduces blood pressure and blood volume by inhibiting nearly all events that promote vasoconstriction and Na+ and water retention • Released by certain cells of the heart atria when they are stretched by the effects of elevated blood pressure • Potent diuretic (increasing urine secretion) and natriuretic (salt-excreting) effects • Promotes excretion of water and Na+ by the kidneys

38. MECHANISMS AND CONSEQUENCES OF ANP RELEASE

39. Regulation of Sodium BalanceInfluence of Other Hormones • Estrogens are chemically similar to aldosterone, and enhance reabsorption of salt by the renal tubules: • Because water follows, many women retain fluid as their estrogen levels rise during the menstrual cycle • The edema experienced by many pregnant women is also largely due to the effect of estrogen • Progesterone appears to decrease Na+ reabsorption by blocking the effect aldosterone has on the renal tubules: • Thus, progesterone has a diuretic-like effect and promotes Na+ and water loss • Glucocorticoids (cortisol and hydrocortisol) enhance tubular reabsorption of sodium, but increase glomerular filtration

40. Regulation of Potassium Balance • Potassium, the chief intracellular cation, is required for normal neuromuscular functioning as well as for several essential activities • Potassium is critical to the maintenance of the membrane potentialof neurons and muscle cells, and is a buffer that compensates for shifts of hydrogen ions in or out of the cell • The heart is particularly sensitive to K+ levels • Both too much (hyperkalemia) and too little (hypokalemia) can disrupt electrical conduction in the heart, leading to sudden death

41. Regulation of Potassium BalanceRegulatory Site: The Cortical Collecting Duct • Like Na+ balance, K+ balance is maintained chiefly by renal mechanisms • Potassium balance is chiefly regulated by renal mechanisms, which control the amount of potassium secreted into the filtrate • The main thrust of renal regulation of K+ is to excrete it: • Because the kidneys have a limited ability to retain K+ it may be lost in urine even in the face of a deficiency • Consequently, failure to ingest potassium-rich substances eventually results in a severe deficiency

42. Regulation of Potassium BalanceInfluence of Plasma Potassium Concentration • The single most important factor influencing K+ secretion is the K+ concentration in blood plasma: • A high-potassium diet increases the K+ content of the ECF • This favors entry of K+ into the principal cells of the cortical collecting duct and prompts them to secrete K+ into the filtrate so that more of it is excreted • Conversely, a low-potassium diet or accelerated K+ loss depresses its secretion by the collecting ducts

43. Regulation of Potassium BalanceInfluence of Aldosterone • As it stimulates the principal cells to reabsorb Na+, aldosterone simultaneously enhances K+ secretion: • Thus, as plasma Na+ levels rise, K+ levels fall proportionately

44. MECHANISMS AND CONSEQUENCES OF ALDOSTERONE RELEASE

45. HOMEOSTATIC IMBALANCE • In an attempt to reduce NaCl intake, many people have turned to salt substitutes, which are high in potassium: • Heavy consumption of these substitutes is safe only when aldosterone release in the body is normal • In the absence of aldosterone, hyperkalemia is swift and lethal regardless of K+ intake • High levels of aldosterone cause potassium levels to fall so low that neurons all over the body hyperpolarize and paralysis occurs

46. Regulation of Calcium and Phosphate Balance • About 99% of the body’s calcium is found in bones in the form of calcium phosphate salts, which provide strength and rigidity to the skeleton • Ionic calcium in the ECF is important for: • Blood clotting • Cell membrane permeability • Secretory behavior • Neuromuscular excitability

47. Regulation of Calcium and Phosphate Balance • Calcium ion levels are closely regulated by parathyroid hormone and calcitonin; about 98% is reabsorbed • Parathyroid hormone (PTH: parathormone) is released when blood calcium levels decline, and targets the bones, small intestine, and kidneys: • Promotes an increase in calcium levels • Targets: • Bone: breaking down bone matrix and liberating Ca2+ • Small intestine: enhances intestinal absorption of Ca2+ indirectly by stimulating the kidneys to transform vitamin D to its active form, which is a necessary cofactor for Ca2+ absorption by the small intestine • Kidneys: increases Ca2+ reabsorption while decreasing phosphate ion reabsorption • Thus, calcium conservation and phosphate excretion go hand in hand • Hence, the product of Ca2+ and HPO42- remains constant, preventing calcium-salt deposit in bones or soft tissues

48. Regulation of Calcium and Phosphate Balance • Thyroid hormone (calcitonin) is an antagonist to parathyroid hormone, and is released when blood calcium rises, targeting bone: • Targets bone, where it encourages deposit of calcium salts and inhibits bone reabsorption (process of absorbing calcium again from the bone and transported to the interstitial fluid or blood)

49. Regulation of Anions • Chloride is the major anion reabsorbed with sodium, and helps maintain the osmotic pressure of the blood

50. ACID-BASE BALANCE • Because of the abundance of hydrogen bonds in the body’s functional proteins (enzymes, hemoglobin, cytochromes, and others) they are strongly influenced by hydrogen ion concentration: • It follows then that nearly all biochemical reactions are influenced by the pH of their fluid environment, and the acid-base balance of body fluids is closely regulated • Optimal pH varies from one body fluid to another: • When arterial blood pH rises above 7.45, the body is in alkalosis (alkalemia); when arterial pH falls below 7.35, the body is in acidosis (acidemia) • Between 7.0 and 7.35 is called physiological acidosis even though the value is slightly basic • Most hydrogen ions originate as metabolic by products, although they can also enter the body via ingested foods