26

1. 26 Fluid, Electrolyte, and Acid-Base Balance

2. Body Water Content • Infants: 73% or more water (low body fat, low bone mass) • Adult males: ~60% water • Adult females: ~50% water (higher fat content, less skeletal muscle mass) • Water content declines to ~45% in old age

3. Total body water Volume = 40 L 60% body weight Extracellular fluid (ECF) Volume = 15 L 20% body weight Intracellular fluid (ICF) Volume = 25 L 40% body weight Interstitial fluid (IF) Volume = 12 L 80% of ECF Figure 26.1

4. Composition of Body Fluids • Water: the universal solvent • Solvent = substances in which solutes are dissolved • Solutes: • Nonelectrolytes • Electrolytes

5. Composition of Body Fluid • Nonelectrolytes: have bonds that do not dissociate in water (no electrical charge) • most are organic • e.g., glucose, lipids, creatinine, and urea • Electrolytes: dissociate into ions in water (have an electrical charge) • E.g., inorganic salts, inorganic and organic acids and bases, some proteins

6. Composition of Body Fluids • Electrolytes • The most abundant (most numerous) solutes • Have greater osmotic power than nonelectrolytes because they dissociate and form two molecules, so may contribute to fluid shifts • E.g., NaCl  Na+, Cl- vs. glucose • Determine the chemical and physical reactions of fluids

7. Extracellular and Intracellular Fluids • Each fluid compartment has a distinctive pattern of electrolytes • ECF (interstitial fluid and plasma) • Similar compostion except higher protein content of plasma • Major cation: Na+ • Major anion: Cl–

8. Extracellular and Intracellular Fluids • ICF: • Low Na+ and Cl– • Major cation: K+ • Major anion HPO42– (hydrogen phosphate) • K, Mg, phosphate ions are the predominant electrolytes ICF

9. Blood plasma Interstitial fluid Intracellular fluid Na+ Sodium K+ Potassium Calcium Ca2+ Mg2+ Magnesium HCO3– Bicarbonate Cl– Chloride HPO42– Hydrogen phosphate SO42– Sulfate Figure 26.2

10. Fluid Movement Among Compartments • Osmotic and hydrostatic pressures regulate the continuous exchange and mixing of body fluids • Exchange between plasma and IF occur across capillary walls • Exchanges between the IF and ICF occur across plasma membranes

11. Lungs Gastrointestinal tract Kidneys Blood plasma H2O, Ions O2 CO2 Nutrients H2O, Ions Nitrogenous wastes O2 CO2 H2O Nitrogenous wastes Nutrients Ions Interstitial fluid Intracellular fluid in tissue cells Figure 26.3

12. Water Balance and ECF Osmolality • Water intake = water output = 2500 ml/day • Water intake: beverages, food, and metabolic water • Water output: urine, insensible water loss (skin and lungs), perspiration, and feces

13. 100 ml Feces 4% 250 ml Metabolism 10% Sweat 8% 200 ml Insensible losses via skin and lungs 28% Foods 30% 750 ml 700 ml 2500 ml Urine 60% 1500 ml 1500 ml Beverages 60% Average output per day Average intake per day Figure 26.4

14. Regulation of Water Intake • Thirst mechanism is the driving force for water intake • The hypothalamic thirst center osmoreceptors are stimulated by • Increase in plasma osmolality of 2–3% • Dry mouth • Substantial decrease in blood volume or pressure

15. Regulation of Water Intake • Drinking water creates inhibition of the thirst center • Inhibitory feedback signals include • Relief of dry mouth • Activation of stomach and intestinal stretch receptors • These signals inhibit the thirst center before water is absorbed to prevent overhydration

16. Plasma osmolality Plasma volume* Blood pressure Saliva Granular cells in kidney Osmoreceptors in hypothalamus Renin-angiotensin mechanism Dry mouth Angiotensin II Hypothalamic thirst center Sensation of thirst; person takes a drink Water moistens mouth, throat; stretches stomach, intestine Initial stimulus Physiological response Result Water absorbed from GI tract Increases, stimulates Reduces, inhibits Plasma osmolality (*Minor stimulus) Figure 26.5

17. Regulation of Water Output: Influence of ADH • Water reabsorption in collecting ducts is proportional to ADH release •  ADH  dilute urine and  volume of body fluids •  ADH  concentrated urine and  volume of body fluids

18. Osmolality Na+ concentration in plasma Plasma volume BP (10–15%) Stimulates Osmoreceptors in hypothalamus Inhibits Negative feedback inhibits Baroreceptors in atrium and large vessels Stimulates Stimulates Posterior pituitary Releases ADH Antidiuretic hormone (ADH) Targets Collecting ducts of kidneys Effects Water reabsorption Results in Osmolality Plasma volume Scant urine Figure 26.6

19. Disorders of Water Balance: Dehydration • Negative fluid balance • ECF water loss due to: hemorrhage, severe burns, prolonged vomiting or diarrhea, profuse sweating, water deprivation, diuretic abuse • Signs and symptoms: thirst, dry flushed skin, oliguria (less than 400ml output of urine) • May lead to weight loss, fever, mental confusion, hypovolemic shock, and loss of electrolytes

20. 1 2 Excessive loss of H2O from ECF 3 ECF osmotic pressure rises Cells lose H2O to ECF by osmosis; cells shrink (a) Mechanism of dehydration Figure 26.7a

21. Disorders of Water Balance: Hypotonic Hydration • Cellular overhydration, or water intoxication • Occurs with renal insufficiency or rapid excess water ingestion • ECF is diluted  hyponatremia  net osmosis into tissue cells  swelling of cells  severe metabolic disturbances (nausea, vomiting, muscular cramping, cerebral edema)  possible death

22. 3 1 2 H2O moves into cells by osmosis; cells swell ECF osmotic pressure falls Excessive H2O enters the ECF (b) Mechanism of hypotonic hydration Figure 26.7b

23. Disorders of Water Balance: Edema • Atypical accumulation of IF fluid  tissue swelling • Due to anything that increases flow of fluid out of the blood or hinders its return • Blood pressure •  Capillary permeability (usually due to inflammatory chemicals) • Incompetent venous valves, localized blood vessel blockage • Congestive heart failure, hypertension,  blood volume

24. Edema • Hindered fluid return occurs with an imbalance in colloid osmotic (oncotic) pressures, e.g., hypoproteinemia ( plasma proteins) • Fluids fail to return at the venous ends of capillary beds • Results from protein malnutrition, liver disease, or glomerulonephritis, PPIs/acid blockers

25. Edema • Blocked (or surgically removed) lymph vessels • Cause leaked proteins to accumulate in IF •  Colloid osmotic (oncotic) pressure of IF draws fluid from the blood • Results in low blood pressure and severely impaired circulation

26. Electrolyte Balance

27. Electrolyte Balance • Generally refers to salt balance • Important in controlling fluid movement and provide minerals essential for excitability, secretory activity, and membrane permeability • Most important: Na • In ECF, main cation that contributes to osmotic pressure • REMEMBER: WATER FOLLOWS SALT • Kidneys regulate balance of Na, K

28. Regulation of Sodium Balance: Aldosterone • Na balance is key in blood pressure/volume • Na+ reabsorption • 65% is reabsorbed in the proximal tubules • 25% is reclaimed in the loops of Henle •  Aldosterone  active reabsorption of remaining Na+ in DCT and collecting duct • Water follows Na+ • Through aquaporins if ADH is present • Or from ICF

29. Regulation of Sodium Balance: Aldosterone • Renin-angiotensin mechanism is the main trigger for aldosterone release • Granular cells of JGA secrete renin in response to • Sympathetic nervous system stimulation •  Filtrate osmolality •  Stretch (due to  blood pressure)

30. Regulation of Sodium Balance: Aldosterone • Renin catalyzes the production of angiotensin II, which prompts aldosterone release from the adrenal cortex • Aldosterone release is also triggered by elevated K+ levels in the ECF • Aldosterone brings about its effects slowly (hours to days)

31. K+ (or Na+) concentration in blood plasma* Renin-angiotensin mechanism Stimulates Adrenal cortex Negative feedback inhibits Releases Aldosterone Targets Kidney tubules Effects Na+ reabsorption K+ secretion Restores Homeostatic plasma levels of Na+ and K+ Figure 26.8

32. Regulation of Sodium Balance: ANP • Released by atrial cells in response to stretch ( blood pressure) • Effects • Decreases blood pressure and blood volume: •  ADH, renin and aldosterone production •  Excretion of Na+ and water • Promotes vasodilation directly and also by decreasing production of angiotensin II

33. Stretch of atria of heart due to BP Releases Negative feedback Atrial natriuretic peptide (ANP) Targets Hypothalamus and posterior pituitary JG apparatus of the kidney Adrenal cortex Effects Effects Renin release* Aldosterone release ADH release Inhibits Angiotensin II Inhibits Collecting ducts of kidneys Vasodilation Effects Na+ and H2O reabsorption Results in Blood volume Results in Blood pressure Figure 26.9

34. Influence of Other Hormones • Estrogens:  NaCl reabsorption (like aldosterone) •  H2O retention during menstrual cycles and pregnancy • Progesterone:  Na+ reabsorption (blocks aldosterone) • Promotes Na+ and H2O loss • Glucocorticoids:  Na+ reabsorption and promote edema

35. Systemic blood pressure/volume Filtrate NaCl concentration in ascending limb of loop of Henle Inhibits baroreceptors in blood vessels Stretch in afferent arterioles (+) (+) (+) (+) Sympathetic nervous system Granular cells of kidneys Release (+) Renin Systemic arterioles Causes Catalyzes conversion Angiotensin I Vasoconstriction Angiotensinogen (from liver) Results in Converting enzyme (in lungs) (+) Peripheral resistance Angiotensin II Posterior pituitary (+) Releases (+) (+) ADH (antidiuretic hormone) Systemic arterioles Adrenal cortex Secretes Causes (+) Vasoconstriction Aldosterone Collecting ducts of kidneys Results in Targets Causes Peripheral resistance Distal kidney tubules H2O reabsorption Causes Na+ (and H2O) reabsorption Results in Blood volume (+) stimulates Renin-angiotensin system Blood pressure Neural regulation (sympathetic nervous system effects) ADH release and effects Figure 26.10

36. Potassium Balance • Chief intracellular cation • Required for normal neuromuscular functioning and metabolic activities • The heart is very sensitive to K balance

37. Regulation of Potassium Balance • Importance of potassium: • Affects RMP in neurons and muscle cells (especially cardiac muscle) •  ECF [K+] RMP  depolarization  reduced excitability •  ECF [K+] hyperpolarization and nonresponsiveness

38. Regulation of Potassium Balance • H+ shift in and out of cells • Leads to corresponding shifts in K+ in the opposite direction to maintain cation balance • Interferes with activity of excitable cells • ECF K levels rise with acidosis as K leaves and H+ enters the cell • ECF K levels fall with alkalosis as K enters the cell and H+ leaves the cell

39. Regulation of Potassium Balance • Influence of aldosterone • Stimulates K+ secretion (and Na+ reabsorption) by principal cells • Increased K+ in the adrenal cortex causes • Release of aldosterone • Potassium secretion

40. Regulation of Calcium • Ca2+ in ECF is important for • Neuromuscular excitability • Blood clotting • Cell membrane permeability • Secretory activities

41. Regulation of Calcium • Hypocalcemia  excitability and muscle tetany • Hypercalcemia  Inhibits neurons and muscle cells, may cause heart arrhythmias • Calcium balance is controlled by parathyroid hormone (PTH) and calcitonin

42. Influence of PTH • Bones are the largest reservoir for Ca2+ and phosphates • PTH promotes increase in calcium levels by targeting bones, kidneys, and small intestine (indirectly through vitamin D) • Calcium reabsorption and phosphate excretion go hand in hand

43. Hypocalcemia (low blood Ca2+) stimulates parathyroid glands to release PTH. Rising Ca2+ in blood inhibits PTH release. Bone 1 PTH activates osteoclasts: Ca2+ and PO43Sreleased into blood. Kidney 2 PTH increases Ca2+reabsorption in kidney tubules. 3 PTH promotes kidney’s activation of vitamin D, which increases Ca2+ absorption from food. Intestine Ca2+ ions Bloodstream PTH Molecules Figure 16.12

44. Influence of PTH • Normally 75% of filtered phosphates are actively reabsorbed in the PCT (follows Na) • PTH inhibits this by decreasing the Tm

45. Regulation of Anions • Cl– is the major anion in the ECF • Helps maintain the osmotic pressure of the blood • 99% of Cl– is reabsorbed under normal pH conditions • When acidosis occurs, fewer chloride ions are reabsorbed (more HCO3- reabsorbed to restore blood pH) • Other anions have transport maximums and excesses are excreted in urine

46. Acid-Base Balance • pH affects all functional proteins and biochemical reactions • Normal pH of body fluids • Arterial blood: pH 7.4 • Venous blood and IF fluid: pH 7.35 • ICF: pH 7.0 • Alkalosis or alkalemia: arterial blood pH >7.45 • Acidosis or acidemia: arterial pH < 7.35

47. Acid-Base Balance • Most H+ is produced by metabolism • Phosphoric acid from breakdown of phosphorus-containing proteins in ECF • Lactic acid from anaerobic respiration of glucose • Fatty acids and ketone bodies from fat metabolism • H+ liberated when CO2 is converted to HCO3– in blood

48. Chemical Buffer Systems • Chemical buffer: system of one or more compounds that act to resist pH changes when strong acid or base is added • Bicarbonate buffer system • Phosphate buffer system • Protein buffer system

49. Bicarbonate Buffer System • Mixture of H2CO3 (weak acid) and salts of HCO3– (e.g., NaHCO3, a weak base) • Buffers ICF and ECF • The only important ECF buffer

50. Physiological Buffer Systems • Respiratory and renal systems • Act more slowly than chemical buffer systems • Have more capacity than chemical buffer systems