TOPIC 11 Fluid & Electrolyte Balance

1. Biology 221 Anatomy & Physiology II TOPIC 11 Fluid & Electrolyte Balance Chapter 27 pp. 1041-1066 E. Lathrop-Davis / E. Gorski / S. Kabrhel

2. Fluid Compartments • Intracellular fluid (ICF) is the fluid within the cell. • Extracellular fluid (ECF) is fluid outside the cell. There are two major ECF compartments: • Plasma is the fluid matrix of blood. • Interstitial fluid (IF) is the fluid matrix of other tissues. Fig. 27.1, p. 1041

3. Composition of Body Fluids • Water is the universal solvent. That is, most things (except lipids) dissolve in water. • Solutes are substances that dissolve in a solvent. Solutes can be classified as nonelectrolytes and electrolytes. • Nonelectrolytes are solutes with or without electrical charge that do not ionize in water. Nonelectrolytes include polar and nonpolar compounds. • Polar compounds such as carbohydrates, proteins are hydrophilic and dissolve in water. Polar compounds have charged areas within the molecule.

4. Composition of Body Fluids • The other group of nonelectrolytes is the hydrophobic compounds. • lipids and other nonpolar molecules (e.g., O2, CO2) are hydrophobic solutes that either do not dissolve in water or are only slightly soluble in water. • Electrolytes are particles that ionize in water to form anions (ions with a negative [-] charge) and cations (ions with a positive [+] charge).

5. Electrolytes • Electrolytes include inorganic salts, inorganic and organic acids, and inorganic and organic bases. • Inorganic salts (e.g., NaCl, NaHCO3, MgCl2, KCl, CaCO3) do not form H+ or OH- when they dissociate. Examples include: • HCO3- = bicarbonate; CO3= = carbonate • NaHCO3  Na+ + HCO3- • CaCO3  Ca2+ + CO3=

6. Electrolytes - Acids • Acidsare molecules that dissociate to form H+ and an anion. Acids lower pH when added to solution.. • Inorganic acids (e.g., HCl) do not include carbon in the molecule. • Inorganic acids tend to be very strong; that is, they dissociate readily.

7. Electrolytes - Acids • Acidsare molecules that dissociate to form H+ and an anion. • Organic acids (e.g., H2CO3, amino acids, lactic acid, fatty acids, ketone bodies) generally include carbon-hydrogen bonds in the molecule. • Organic acids tend to be weak; that is, they do not dissociate readily.

8. Electrolytes - Bases • Bases are molecules that dissociate to form OH- and a cation (e.g., NaOH), or accept H+ (e.g, NH3). Bases raise pH when added to solution. • Inorganic bases (e.g., NaOH, NH3) do not include carbon in the molecule. • Inorganic acids tend to be very strong; that is, they dissociate readily or they take up H+ readily. • NaOH: NaOH  Na+ + OH- • NH3: NH3 + H+ NH4+

9. Electrolytes - Bases • Bases can also be organic, that is, they contain carbon in the molecule. • Organic bases tend to be weak; that is, they do not dissociate readily or take up H+ as readily as inorganic bases, therefore, they have less of an effect on pH. • Examples include the nitrogen bases of DNA and RNA, and certain amino acids.

10. ECF versus ICF ECF and ICF differ in ion composition. • ECF is higher in Na+, Cl-, HCO3-; • ICF is higher in K+, PO42- (phosphate), Mg2+, and protein. Fig. 27.2, p. 1043

11. Water Balance • Sources of water in the body include: • ingested water (from food or liquids); and • metabolic water (from aerobic respiration of glucose in mitochondria). • glucose + 6 O2 6 CO2 + 6 H2O • Loss of water occurs through: • urine (accounts for approximately 60% of water outflow. This is where loss is controlled.); • sweat (controlled for thermoregulation); • lungs (through humidification of air. More is lost if you breathe through your mouth.); See also Fig. 27.3, p. 1044 Fig. 27.4, p. 1044

12. Water Balance • Loss of water occurs through: • feces (some is always lost to keep feces from being to hard); and • skin (some water is lost directly through the skin even though it is keratinized and has glycoproteins between the cells). See also Fig. 27.3, p. 1044 Fig. 27.4, p. 1044

13. Water Balance: Regulating Intake • The thirst response by hypothalamus regulates intake. • Thirst is stimulated by: • dry mouth (sensation carried to hypothalamus via sensory cranial nerves); and/or • increased osmolality of the ECF in the hypothalamus. • The blood-brain barrier is missing from the thirst center so that it can detect ion changes. • The result of stimulation of the thirst center is an urge to drink liquids. Fig. 27.5, p. 1045

14. Water Balance: Obligatory Output Obligatory water loss is not controlled. • Loss through lungs. Air is humdified during inhalation (this is necessary for gas exchange in the alveoli); some water is lost with exhalation. More is lost through the mouth than through the nose. • Some always lost through feces. • Diarrhea due to irritation of the GI tract decreases residence time in the large intestine. Therefore, there is less reabsorption and greater loss through feces. • Loss across the skin which is not completely water tight.

15. Water Balance: Regulating Output • Sweat is controlled for body temperature regulation, not fluid balance. • When the body is hot, it will sweat regardless of whether it is sufficiently hydrated. • Urine output is the point of control for water balance, electrolyte balance, pH balance and blood pressure.

16. Regulating Urine Output: ADH Antidiuretic hormone • ADH is a protein hormone produced by the hypothalamus and secreted by posterior pituitary in response to: • impulses from the hypothalamus; • The hypothalamus responds to increased osmolality of ECF (resulting in increased osmolality of IF in hypothalamic cells). • presence of aldosterone in plasma. • ADH increases the water permeability of collecting ducts. • Water follows the osmotic gradient back into plasma; this is facultative water reabsorption. Fig. 27.7, p. 1049

17. Regulating Urine Output: Aldosterone • Aldosterone is a steroid hormone secreted by zona glomerulosa of the adrenal cortex. • Steroid hormones are derivatives of cholesterol. • Aldosterone increases Na+ reabsorption in the DCTs and CDs of the kidney. • Reabsorption of Na+ adds to the osmotic gradient in IF around the nephron. • Increased solute causes water to follows by osmosis. This is obligatory water reabsorption since water must reenter IF due to osmotic draw by Na+. Fig. 27.8, p. 1050

18. Regulating Urine Output: Diuretics • Diuretics enhance urinary output, that is, they decrease water reabsorption from the filtrate back into the blood. Two main mechanisms are used: • inhibition of ADH secretion as is done by alcohol. • This prevents water from reentering through the CDs of the nephron. • inhibition of Na+ reabsorption as is done by caffeine and most other drugs. • This decreases the osmotic draw within the IF around the nephron.

19. Disorders of Fluid Balance • Dehydration occurs when water loss exceeds water intake over a period of time. The result is that solute concentration gets too high. • Dehydration leads to thirst and secretion of very concentrated urine. • Hypotonic Hydration occurs when cells have too much water, that is, the concentrations of cellular solutes becomes too dilute. • This may be due to excessive water intake or, more often, renal insufficiency Fig. 27.6, p. 1046

20. Disorders of Fluid Balance: Edema See Topics 4 - 6 Accumulation of fluid in IF is caused by: • increased BP – which increases movement of fluid from the plasma into the IF; • decreased lymphatic drainage – which fails to remove excess fluid from the tissue; • inflammation – caused by histamine and other chemicals resulting in vasodilation, increased capillary permeability, and loss of proteins to the IF; • This increases the osmotic pressure of the IF and draws more water out.

21. Disorders of Fluid Balance: Edema Accumulation of fluid in IF is caused by: • decreased blood proteins due to decreased liver function, protein malnutrition, loss of proteins at glomerulus • This results in lower blood (capillary) osmotic pressure to draw fluid back into blood.

22. Electrolyte Balance • Electrolytes are charged particles that dissociate to form cations (+ charge) and anions (- charge). • Electrolytes include salts, acids, and bases. • Salts are ionic compounds that form cations and anions other than H+ and OH- (hydroxide) when dissolved in solution. • Sources of salts include: foods, fluids (e.g., sodas), small amounts from metabolism.

23. Electrolytes: Salt Losses Salt is lost through: • perspiration in a hot environment; • hotter environment means more sweat which contains ions; more sweat means more salts lost with water. • normal loss with feces; • GI upset increases loss • During diarrhea there is a shorter retention time of the feces so that there is less time for reabsorption, therefore, greater loss of salts as well as water • During vomiting salts are lost as well as water and H+ ions.

24. Electrolytes: Salt Losses • Urine production is the point of control for the concentrations of most important electrolytes.

25. Important Electrolytes: Na+ • Na+ (sodium) is the main cation in ECF and accounts for 90-95% of all solutes in the ECF. • Na+ is the most important electrolyte in creating significant osmotic pressure. • Na+ essential to neural and muscular function. • Na+ is responsible for the depolarization associated with graded potentials and action potentials in neurons and muscles.

26. Important Electrolytes: K+ • K+ (potassium) is the main cation in the ICF. • K+ is important to neuron and muscle function function due to its influence on membrane potential. • K+ is responsible for repolarization and hyperpolarization of cell membranes. • K+ also influences acid-base balance (to be discussed shortly).

27. Important Electrolytes: Ca2+ • Ca2+ is important to neuron and muscle function. • Ca2+ is important to maintaining correct Na+ permeability of neuronal membranes. • Ca2+ causes exocytosis of neurotransmitter by signaling the synaptic vesicle to fuse with the cell membrane of the axon terminal. • Ca2+ is an intracellular regulator of muscle contraction in all types of muscle (the exact mechanism varies; See A&P I, Unit 13). • Ca2+ is responsible for the rapid phase of the action potential in autorhythmic cardiac cells.

28. Important Electrolytes: Ca2+ • Other functions of Ca2+ include: • serving as clotting factor IV during coagulation; • If serum (blood) calcium levels decrease, clotting time increases. • serving as an important constituent of bone (calcium and magnesium salts form the inorganic part of the bone matrix).

29. Other Important Ions • Mg2+ (magnesium) serves as an: • enzyme cofactor for carbohydrate and protein metabolism; and • important component of bone • Cl- (chloride) is the main anion of the ECF and follows Na+ to balance charge.

30. Control of Selected Ions: Sodium Aldosterone • is a steroid hormone secreted by the zona glomerulosa of the adrenal cortex; • is secreted in response to: • high serum K+ or low serum Na+; • angiotensin II (renin-angiotensin pathway); and • ACTH from adenohypophysis. • increases active reabsorption of Na+ from DCT and CD (without aldosterone, little Na+ is reabsorbed from DCT or CD). Fig. 27.8 p. 1050

31. Control of Selected Ions: Sodium ADH • is released by the neurohypophysis (posterior pituitary) in response to increased Na+ detected by hypothalamus. • ADH is synthesized in hypothalamus. • increases water reabsorption to decrease plasma osmolality by increasing the membrane permeability of the cells of the collecting ducts. • affects the concentration BUT the not total amount of solute. Fig. 27.7, p. 1049

32. Control of Selected Ions: Sodium Atrial natriuretic peptide (ANP; a.k.a., atrial natriuretic factor) • is released from the right atrium in response to elevated BP; • blocks reabsorption of Na+ (by decreasing aldosterone release); • blocks ADH secretion; • inhibits renin release by kidney; • causes a decrease in systemic BP. Fig. 27.10, p. 1052

33. Control of Selected Ions: Sodium • Estrogens • are steroids produced by the ovaries and zona reticularis of adrenal cortex; • enhance Na+ reabsorption and, therefore, increase water retention. • Glucocorticoids • are steroids produced by the zona fasciculata of the adrenal cortex; • enhance Na+ reabsorption and, therefore, increase water retention.

34. Control of Sodium: Disorders • Hyponatremia, decreased blood Na+, leads to: • neurological dysfunction (brain swelling; mental confusion, irritability, convulsions, progresses to coma; muscular twitching) • systemic edema (less osmotic pressure in plasma) • Hypernatremia, increased blood Na+ leads to: • thirst; • CNS dehydration leading to confusion, lethargy, progressing to coma; • increased neuromuscular irritability leading to twitching and convulsions.

35. Control of Selected Ions: K+ • K+ concentration is regulated at CDs in cortex of kidney. • K+ secretion tied to Na+ reabsorption. • The most important factor in regulation is K+ concentration in plasma. • Increased K+ directly stimulates cells of CDs to secrete more of it. • Excess of K+ causes K+ to move into CD cells leading to secretion into filtrate. • Aldosterone stimulates active secretion of K+ coupled to reabsorption of Na+.

36. Control of Potassium: Disorders • Hypokalemia is decreased blood K+ and causes: • cardiac arrhythmias, including bradycardia; • muscular weakness; • alkalosis (K+ competes with H+ for secretion); • hypoventilation (to compensate for alkalosis); • mental confusion.

37. Control of Potassium: Disorders • Hyperkalemia is increased blood K+ and causes: • nausea, vomiting, and diarrhea; • at severely elevated levels causes bradycardia; cardiac arrhythmias, depression and arrest (at slightly elevated levels causes tachycardia. See Albasan et al.) • skeletal muscle weakness and flaccid paralysis; • neural dysfunction (paresthesia).

38. Control of Selected Ions: Calcium Parathyroid hormone (PTH) increases plasma Ca2+. • Parathyroid glands secrete PTH in response to decreased plasma Ca2+. • PTH acts on: • the gut, where it stimulates uptake by epithelial cells (PTH works by increasing Vita. D formation in kidney); • bones, where it stimulates osteoclasts, inhibits osteoblasts (see A&P I, Unit XII); • kidney, where it acts on DCT to increase active reabsorption of Ca2+ (also inhibits PO42- reabsorption to maintain balance between Ca2+ and PO42-).

39. Control of Selected Ions: Calcium Calcitonin from the thyroid: • is secreted by parafolliclar cells of thyroid in response to increased plasma Ca2+ • is generally, thought to be only really important during youth when bones are being remodeled; • stimulates osteoblasts, inhibits osteoclasts in bone (see A&P I; Unit XII); • results in decreased plasma Ca2+.

40. Control of Calcium: Disorders • Hypocalcemia is decreased blood calcium and causes: • tingling in fingers, tremors, convulsions, tetany; • depressed cardiac function; and • “bleeder’s disease”. • Hypercalcemia is increased blood calcium and causes: • bone wasting; • kidney stones; • nausea, vomiting; • cardiac arrhythmias and arrest; • depressed respiration; and • Coma.

41. Control of Selected Ions: Magnesium • Mg2+ is the second most abundant intracellular cation. • Mg2+ is an important cofactor of enzymes involved in protein and carbohydrate metabolism. • Mg2+ is an important component of bone. • Mg2+ reabsorption is inhibited by PTH.

42. Control of Selected Ions: Anions • Cl- is major anion • Cl- follows Na+ actively or passively in PCT, DCT and CD to balance charge. • Most other anions are passively reabsorbed by membrane transport proteins. • Hence, transport maxima exist for most anions. • Any concentration in excess of transport maximum is excreted in urine.

43. Acid-Base Balance • pH is a measure of the H+ concentration in a liquid. • The pH of distilled water (i.e., neutral) is 7.0. • Normal values for body fluids are: • arterial blood has an average of pH 7.4 • venous blood and interstitial fluid have an averages of pH 7.3. • intracellular fluid (ICF) has an average of pH 7.0 (neutral, but more acidic than other compartments). • Protein function depends on H+ concentration.

44. Acid-Base Balance • Acids dissociate to form H+ and an anion • Addition of H+ lowers pH. • Metabolic sources of acids include: • anaerobic respiration (produces lactic acid); • protein catabolism (produces amino acids and keto acids); and • fat metabolism (produces fatty acids and ketone bodies). • Bases dissociate to form OH- and a cation, or sequester H+ (e.g., NH3). • Removal of H+ or addition of OH- raises pH.

45. Strength of Acids/Bases • Strength refers to the ability to ionize (i.e., dissociate to form H+ or OH-). • Strong acids/bases: • dissociate readily and completely; • are usually inorganic (e.g., HCl, KOH, NaOH, NH3); • lead to large changes in pH when added to unbuffered solutions. Fig. 27.11, p. 1056

46. Strength of Acids/Bases (con’t) • Weak acids/base: • do not completely ionize (i.e., some of the molecular form remains); • are usually organic (e.g., H2CO3, NaHCO3, amino acids, fatty acids); • only change pH slightly when added to unbuffered solutions. Fig. 27.11, p. 1056

47. Acid-Base Balance: Chemical Buffer Systems • Chemical buffer systems act quickly. • These involve exchange of a strong acid/base for weaker one. • The reactions also produce either a salt or water. • The three major chemical buffer systems are: • the Bicarbonate buffer system; • the Phosphate buffer system; and • the Protein buffer system.

48. Chemical Buffers: Bicarbonate • Bicarbonate is the most important chemical buffer present in ECF; also buffers ICF • HCl (strong acid) + NaHCO3H2CO3 + NaCl • NaOH (strong base) + H2CO3NaHCO3 + H2O • Carbonic acid (H2CO3) levels are affected by carbon dioxide availability (which is controlled by ventilation). • Bicarbonate (NaHCO3) levels are regulated by kidney. When HCO3-is high, it is secreted; when low, it is reabsorbed.

49. Chemical Buffers: Phosphate • The phosphate buffer very important in ICF and urine. • HCl + Na2HPO4 NaH2PO4 + NaCl • NaOH + NaH2PO4 Na2HPO4 + H2O  Indicates a reversible reaction.

50. Chemical Buffers: Protein • Protein is very important in ICF and in plasma. • Protein activity as a buffer is based on presence of acidic (donate H+)and basic (accept H+) side chains of amino acids within the protein. • Reduced hemoglobin (hemoglobin without O2) takes on H+ (decreases free H+ and increases pH).