BIO 169 FLUID, ELECTROLYTE, AND ACID-BASE BALANCE Chapter 27

1. BIO 169 FLUID, ELECTROLYTE, AND ACID-BASE BALANCE Chapter 27 created by Dr. C. Morgan

2. TOPICS Introduction Fluid and Electrolyte Balance Acid-Base Balance Disturbances in Acid-Base Balance Age Related Considerations Resource: IPCD Fluid, Electrolyte, and Acid/Base Balance

3. Introduction Objectives Review the importance of water to cellular life. Distinguish between extracellular and intracellular fluids. Discuss the meaning of fluid balance. Discuss the meaning of electrolyte balance. Discuss the meaning of acid-base balance.

4. Introduction Cellular life consists of an unending chain of chemical reactions we collectively call metabolism. These chemical reactions occur in an aqueous medium. If cells are to survive, the volume and composition of the fluids within and outside cells must be maintained within tolerable limits. Extracellular fluids (ECF) are those present outside cells (blood, lymph, interstitial fluid, kidney filtrate, etc). Intracellular fluids (cytosol, mitochondrial matrix, nucleoplasm, etc) are those present within cells. Exchanges of water and solutes regularly occur between the two fluid compartments.

5. Introduction (cont) Homeostasis of all systems depends upon the daily maintenance of fluid, electrolyte, and acid-base balance. Fluid balance is achieved when water gain = water loss along with the proper allocation to ECF and ICF. Electrolyte balance is achieved when ion gain = ion loss which is mostly influenced by activities of the digestive and renal systems. Acid-base balance refers to the maintenance of H+ concentration in body fluids within normal limits. Proteins will denature if there is an extensive acid-base imbalance. Without functional proteins (enzymes), our cells will not survive.

6. TOPICS Introduction Fluid and Electrolyte Balance Acid-Base Balance Disturbances in Acid-Base Balance Age Related Considerations

7. Fluid and Electrolyte Balance Objectives Discuss the composition of the human body with respect to water and other components. Describe the distribution of fluids in the ECF and ICF. Show the main cations and anions in body fluids. Present four principles that apply to fluid and electrolyte balance. Discuss the main regulatory hormones. Discuss fluid balance. Discuss electrolyte regulation of Na+, K+, Ca2+, and Cl–.

8. Fluid and Electrolyte Balance Our body consists of liquids and solids. Water comprises about 50% (females) to 60% (males) of the total body weight with the gender differences attributed to variations in adipose tissue versus muscle mass. Proteins comprise most of the solids with lipids second. About ⅔ of the body H2O is present in the ICF. Most of the ECF is interstitial fluid with plasma second. Fluid exchanges between the ICF and ECF occur by both passive and active transport processes. Osmotic concentrations of the ICF and ECF are equal.

9. Fluid and Electrolyte Balance (cont) Solid components of the body. solids = 31.5 kg Fig. 1 a

10. Fluid and Electrolyte Balance (cont) Fluid components of the body (H2O + ions) water = 38.5 l Fig. 1 b

11. Fluid and Electrolyte Balance (cont) ICF and ECF contain similar ions but they differ in concentrations. Among the cations, Na+ is high in ECF and K+ is high in the ICF compartment. Fig. 2 a 11

12. Fluid and Electrolyte Balance (cont) Among the anions, Cl– is the most important in the ECF while phosphate ions predominate in the ICF. Proteins are abundant in the ICF and many are present in ECF. Fig. 2 b 12

13. Fluid and Electrolyte Balance (cont) Important principles: *Homeostatic mechanisms respond to conditions in the ECF (not the ICF). *Receptors monitor plasma volume and osmotic concentration which reflect fluid and electrolyte balance in the entire body. *Water moves by osmosis between the ECF and ICF. *Water content and / or electrolytes will vary with intake and the effects of circulating hormones – especially antidiuretic hormone (ADH), aldosterone, and atrial natriuretic peptide (ANP).

14. Fluid and Electrolyte Balance (cont) Osmoreceptors in the hypothalamus are sensitive to even slight changes in the osmotic concentration of the ECF. The rate of ADH release from hypothalamic neurons varies directly with ECF osmotic concentration. ADH results in increased reabsorption of water by the kidneys and stimulates thirst to increase H2O volume. Aldosterone is secreted when K+ rises, Na+ falls, or by the RAA response. Renin is secreted by the JGA when BP drops,  filtrate osmotic concentration in the DCT, or the K+ / Na+ concentration changes as noted above. Aldosterone results in enhanced Na+ reabsorption with Cl– following along with water by osmosis.

15. Fluid and Electrolyte Balance (cont) Fluid Balance water constantly moves between cells, cavities and compartments pericardial thoracic peritoneal 80% in interstitium+ compartments 20% in plasma synovial blood / CSF blood / interstitium 15 Fig. 3

16. Fluid and Electrolyte Balance (cont) Fluid Balance (cont) Net filtration pressure determines fluid exchanges between the blood and interstitium. Inability to return adequate amounts of fluid from the interstitium may result in edema (tissue swelling). Fluids also exchange with the outside environment. Ideally, water losses will be balanced by water gains. You lose about 2500 ml / day of water in urine, feces, insensible perspiration (lungs and skin), and sensible perspiration (sweat gland activity). Water is gained by intake (2200 ml / day) and during metabolism (300 ml / day). TABLE 1 summarizes fluid gains and losses.

17. Fluid and Electrolyte Balance (cont) Body water varies with the amount of Na+ present in the ECF which is ideally around 136 – 142 mEq / l. When the Na+ level rises above 150 mEq / l, the body is in a state of hypernatremia. When the Na+ level falls below 130 mEq / l, the body is in a state of hyponatremia. The Na+ rise and fall in concentration is due the loss or gain of water respectively. Dehydration will cause Na+ concentration to rise while overhydration will dilute the Na+ concentration The interdependence of solute concentration and fluid volume is evident. Fluid Balance (cont)

18. Fluid and Electrolyte Balance (cont) Fluid Balance (cont) Fluid shifts between the ICF and ECF are due to changes in the osmotic concentration of the ECF. The ICF represents a water reserve. When the ECF becomes hypertonic to the interior of cells, water will move from the ICF to the ECF by osmosis. Conversely, when the ECF becomes hypotonic to the interior of cells, water will move into cells from the ECF. Within volume limits, homeostasis with regard to the osmotic concentration of the ICF and ECF is constantly maintained by fluid shifts.

19. Fluid and Electrolyte Balance (cont) Electrolyte balance is important since electrolytes affect water balance and cell functions depend on a balance of electrolytes, especially Na+ and K+. At 136 – 142 mEq / l, Na+ salts (NaCl and NaHCO3) account for more than 90% of the ECF solutes. ICF Na+ is only about 10 mEq / l. At 160 mEq / l, K+ predominates in the ICF and in the ECF it is present from 3.8 – 5 mEq / l. *Most electrolyte imbalances involve Na+ *K+ problems do occur and are more dangerous than Na+ balance problems. Electrolyte Balance

20. Fluid and Electrolyte Balance (cont) Electrolyte Balance (cont) – Na+ issues Total ECF Na+ is determined by absorption across the intestinal villi epithelium (48 – 144 mEq / day) and kidney function in reabsorption and excretion plus other losses such as in sweat. Osmosis and hormonal regulation of fluid shifts keep the ECF concentration of Na+ within normal limits. Kidney function in the presence of the regulatory hormones ADH and aldosterone is the most important homeostatic regulatory mechanism for sodium balance and ECF fluid volume. ANP inhibits mechanisms that elevate blood pressure. The ECF Na+ concentration and fluid volume are closely integrated.

21. Fluid and Electrolyte Balance (cont) Response mechanisms to rising Na+ in the ECF. Fig. 4 21

22. Fluid and Electrolyte Balance (cont) Response mechanisms to falling Na+ in the ECF. Fig. 4 22

23. Fluid and Electrolyte Balance (cont) Fig. 5

24. Fluid and Electrolyte Balance (cont) Electrolyte Balance (cont) – Na+ issues Other hormonal effects: Estrogens have aldosterone-like effects. Progesterones block aldosterone. Glucocorticoids may mimic aldosterone.

25. Fluid and Electrolyte Balance (cont) Electrolyte Balance (cont) – K+ issues 98% of the potassium in the body is contained in the ICF. The ECF K+ level is due to absorption across the digestive epithelium (50 – 150 mEq / day) and urinary losses. There are no other routes of appreciable K+ losses. Renal tubular secretion varies *directly with K+ ECF concentration, *preferential H+ secretion for pH maintenance rather than K+ secretion (meaning K+ is retained), and *aldosterone levels which influence Na+ reabsorption and K+ secretion.

26. Fluid and Electrolyte Balance (cont) Electrolyte Balance (cont) – K+ issues K+ imbalances cause numerous physiological problems. Hypokalemia, a plasma K+ level < 2 mEq / l, may result from inadequate dietary intake, diuretic administration, excessive aldosterone secretion, or the renal response to  pH of the ECF. Muscular weakness and paralysis may result. Hyperkalemia, a plasma K+ level > 8 mEq / l, may result from renal failure, diuretics that block Na+ reabsorption, and a  in pH. Cardiac arrhythmias accompany hyperkalemia.

27. Fluid and Electrolyte Balance (cont) Calcium, the most abundant body mineral, is absorbed across the intestinal mucosa, deposited and released from bone, reabsorbed from the filtrate as it is processed in the kidneys, and slightly lost in the bile. The normal serum range is 4.5 – 5.3 mEq / l (plasma range is 8.5 – 11 mEq/l) (why the difference?) Parathyroid hormone and calcitriol stimulate absorption across the intestinal mucosa and reabsorption from the DCT. Hypercalcemia exists when the ECF concentration exceeds 11 mEq / l with hyperparathyroidism the most common cause. Severe cardiac arrhythmias may result. Electrolyte Balance (cont) – other regulated ions

28. Fluid and Electrolyte Balance (cont) Electrolyte Balance (cont) – other regulated ions Hypocalcemia exists when the ECF serum concentration is less than 4 mEq / l with hypoparathyroidism, vitamin D deficiency, or renal failure the main causes. The condition results in cardiac arrhythmias and decreased contractility , osteoporosis, muscle spasm, and possibly convulsions. Magnesium, an enzymatic cofactor, is present in the ICF at about 26 mEq / l and at 1.5 – 2.5 mEq / l in the ECF. The skeleton contains 60% of the Mg2+ in the body.

29. Fluid and Electrolyte Balance (cont) Phosphate ions are used in bone mineralization, as cofactors, in making ATP and other high energy compounds, and for the synthesis of nucleic acids. The serum concentration of PO43¯ is 1.8 – 2.6 mEq / l. Calcitriol stimulates reabsorption along the PCT but some is lost in urine and feces. Chlorideion serum concentration is from 100 – 108 mEq / l and only 3 mEq / l in the ICF. Cl– moves with Na+ and provides electrical balance. You only need 48 – 146 mEq / day (1.7 – 5.1 g). TABLE 2 lists normal ECF range of the ions discussed. Electrolyte Balance (cont) – other regulated ions

30. TOPICS Introduction Fluid and Electrolyte Balance Acid-Base Balance Disturbances in Acid-Base Balance Age Related Considerations

31. Acid – Base Balance Objectives Review some terms related to acid – base balance. Discuss the importance of pH control in body fluids. Describe the types of acids in the body. Discuss the mechanisms of pH control by buffer systems. Discuss the maintenance of acid – base balance.

32. Acid – Base Balance By definition, an acid releases H+ ions into solution and a base removes H+ from solution usually by supplying OH– which combines with the H+ to form H2O. The strongest acids and bases dissociate completely; weaker acids and bases do not have all molecules dissociated. Salts dissociate to release ions that are not H+ or OH– . Buffers are substances that oppose pH changes by supplying or removing H+ from body fluids (TABLE 3). The normal pH of ECF is 7.35 – 7.45. Deviations from the normal pH range threaten life and mechanisms constantly operate to maintain pH homeostasis.

33. Acid – Base Balance (cont) Acidemia is a plasma pH < 7.35 resulting in acidosis. Alkalemia is a plasma pH > 7.45 resulting in alkalosis. The CNS and cardiovascular system are very sensitive to pH fluxuations. Acidosis is a more prevalent deviation from normal. There are three types of acids in the body. *A volatile acid will leave the body as a gas. Carbonic acid is our only volatile acid. CO2 + H2O  H2CO3  H+ + HCO3– The CO2 you exhale is the key component of the volatile acid that may leave the body and enter the atmosphere.

34. Acid – Base Balance (cont) The CO2 – pH balancing act Fig. 6 34

35. Acid – Base Balance (cont) *Fixed acids do not leave solution and are eliminated by the kidneys. Sulfuric and phosphoric acid are the main fixed acids which are generated during metabolism of amino acids and compounds containing phosphate groups. *Organic acids are those that participate in the TCA cycle or evolve as byproducts of metabolism. Lactic acid and ketone bodies are the main forms. Lactic acid builds up as an end product of anaerobic metabolism and excess ketone bodies are generated during prolonged lipid and amino acid catabolism (as in starvation).

36. Acid – Base Balance (cont) Buffer systems exist to maintain acid–base balance. Buffers are able to donate H+ to solution or remove H+ from solution. H+ ions are absorbed across the intestinal villi and are generated during metabolism. H+ ions are eliminated by the kidneys and indirectly by the lungs as CO2 is exhaled and water is formed. There are three major buffer systems: *the protein buffer system *the carbonic acid–bicarbonate buffer system *the phosphate buffer system

37. Acid – Base Balance (cont) The three buffer systems Fig. 7

38. Acid – Base Balance (cont) Protein Buffers Amino acids are able to donate an H+ from their carboxyl end or bind an H+ on their amino end. Peptides have buffering ability only at the ends of their amino acid chain or side groups of histidine and cysteine. If pH rises If pH falls Fig. 8 In the ECF, plasma proteins and hemoglobin are buffers. In the ICF, intracellular proteins are efficient buffers.

39. Acid – Base Balance (cont) Protein Buffers (cont) Proteins present in the plasma and interstitial fluids act as buffers. Intracellular functional and structural proteins serve to buffer acids produced during metabolism. Since ion exchanges occur between the ECF and ICF, intracellular functional and structural proteins are able to assist in buffering the ECF. H+ ions may be pumped from an acidic ECF into cells where intracellular proteins act as buffers. ECF K+ ions may also exchange for intracellular H+ ions when the ECF pH rises above normal. These buffering processes are relatively slow.

40. Acid – Base Balance (cont) Protein Buffers (cont) Hemoglobin molecules have the ability to bind H+ on their polypeptide chains and supply bicarbonate which moves into the plasma where it may buffer H+. The H+ evolves from the familiar equation: CO2 + H20  H2CO3  H+ + HCO3– Recall that in the lungs, the equation shifts to the left. The hemoglobin buffering system helps to maintain plasma pH homeostasis when there are fluxuations in PCO2. This is the only intracellular buffering system that is able to immediately change the pH of the ECF.

41. Acid – Base Balance (cont) Carbonic Acid – Bicarbonate Buffer System The main role of this system is to buffer organic and fixed acids that move into the ECF. The supply of bicarbonate ions may be quickly consumed so must be replaced from the bicarbonate reserve (NaHCO3) present in body fluids. Fig. 9 a

42. Acid – Base Balance (cont) As the bicarbonate is consumed in buffering the H+ from acids, more carbonic acid is formed driving the equation to the left when the blood reaches the lungs. The amount of available HCO3– ions is the limiting factor. replacement required lungs  The respiratory system is able to compensate for the metabolic generation of H+ ions. 42 Fig. 9 b

43. Acid – Base Balance (cont) Kidney Function Transport processes along the DCT result in the generation of bicarbonate while secreting H+ ions into the tubular fluid. This new bicarbonate becomes part of the plasma bicarbonate reserve. Fig. 26-14 c 43

44. Acid – Base Balance (cont) Phosphate Buffer System Dihydrogen phosphate (H2PO4–) is a weak acid that will dissociate to supply an anion that is able to buffer H+. H2PO4–  H+ + HPO4 2– As the monohydrogen phosphate is consumed during buffering, more is released from a phosphate reserve. Na2HPO4  2 Na+ + HPO4 2– This system has greatest importance in the ICF. This system is also employed as a buffer in the urine.

45. Acid – Base Balance (cont) Buffering is only a short term solution to pH imbalances. Long term maintenance of acid–base balance depends on eliminating excess H+ ions from the ECF so buffers are free to be used again. Likewise, if H+ ions need to be supplied to correct an alkalotic condition, the supply of H+ ions obtained from buffers may be rapidly exhausted unless the H+ ions are replaced. The solution is to integrate activities of the respiratory and urinary systems to eliminate or supply H+ ions to the ECF while buffers solve immediate pH imbalances. pH homeostasis is critically important in maintaining the integrity of functional and structural proteins.

46. Acid – Base Balance (cont) Respiratory compensatory mechanisms involve a change in respiratory rate and depth of ventilation which results in an alteration of the amount of CO2 leaving the body. This mechanism manipulates the carbonic acid – bicarbonate buffer system. CO2 + H20  H2CO3  H+ + HCO3– Recall that central and peripheral chemoreceptors send information to the respiratory center in the medulla oblongata which results in appropriate adjustments to ventilation for pH maintenance of the ECF.  pH   ventilation  pH   ventilation

47. Acid – Base Balance (cont) Renal compensatory mechanisms involve changing the rates of secretion or reabsorption of H+ and newly generated HCO3– ions. Kidney tubular cells are able to secrete H+ until the pH falls to about 4.0 to 4.5 after which buffering is required. The kidneys eliminate H+ in the form of ammonium ions (NH4+), dihydrogen phosphate (H2PO4– ), and utilizing the carbonic acid – bicarbonate system. When alkalosis develops, the kidneys decrease H+ secretion, reclaim fewer bicarbonates, and excrete HCO3– while reabsorbing H+ and Cl–.

48. Acid – Base Balance (cont) Acidosis response PCT Collecting duct Renal compensation using buffer systems 1.bicarbonate 2. monohydrogen phosphate 3. ammonia Fig. 10 a

49. Acid – Base Balance (cont) Acidosis response renal tubule cell of the PCT The amino acid glutamine supplies ammonia and bicarbonate for buffering. The toxic NH3 is detoxified to ammonium ion (NH4+) during buffering. Fig. 10 b

50. Acid – Base Balance (cont) Renal response to alkalosis Reclaim H+ Secrete HCO3– Fig. 10 c