1. 1 Chapter 2 Normal Water, Electrolytes, and Acid-base Balance Professor A. S. Alhomida Disclaimer The texts, tables, figures and images contained in this course presentation (BCH 376) are not my own, they can be found on: References supplied Atlases or The web King Saud University College of Science Department of Biochemistry

2. 2 Total body water (60 – 70%) 36 – 49 Liter Intracellular Fluid (ICF) (50%) 35 L Extracellular Fluid (ECF) (20%) 14 L Interstitial Tissue Fluid (ITF) (15%) 11 L Plasma; Intravascular (Fluid (IVF) (5%) 3 L

3. 3 Darrow’s semipermealbe membrane (Cell membrane) Darrow’s permealbe membrane (Capillary membrane) A B C 35 L11 L3 L A = Plasma; B = Tissue Fluid; A + B = Extracellular Fluid (ECF); C = Intracellular Fluid (ICF) Figure 2. Showing distribution of body water in three compartments ICFECF Capillary and Cell Membrane

4. 4 Colloid Osmotic Pressure ECF Interstitial Plasma Capillary Membrane Capillary membrane freely permeable to water and electrolytes, but not to large molecules such as proteins (albumin) The albumin on the plasma side gives rise to a colloid osmotic pressure gradient favouring movement of water into the plasma This is balanced out by the hydrostatic pressure difference H2OH2O H2OH2O 120/80 H2OH2O H2OH2O

5. 5 Cell Membrane ICF Cell Membrane Na + K+K+ Interstitial H2OH2O H2OH2O Cell membrane is freely permeable to H 2 0, but Na and K are pumped across this membrane to maintain a gradient [K + ] =4 [K + ] =150 Na + = 144 Na + = 10

6. 6 Body Fluid 1.Intracellular (within the cell) Fluid (ICF) All fluids inside cells of body About 40% of total body weight 2.Extracellular Fluid (ECF) All fluids outside cells About 20% of total body weight Subcompartments Interstitial fluid (between cells) and plasma; lymph, CSF, synovial fluid

7. 7 Body Fluid Compartments

8. 8

9. 9 Normal Daily Inputs and Outputs: Water Input mLOutput mL Drink1500Urine1500 Food750Faeces100 Metabolic350Lungs400.Skin600 Total2600Total2600

10. 10 Movement of Fluid 1.Movement of Fluid and Solutes They are allowed by membrane permeability, pressures, active and passive transport 2.Diffusion Movement of molecules from area of higher concentration to area of low concentration Membrane must be permeable, requires no energy, most efficient

11. 11 Movement of Fluid, Cont ’ d 1.Facilitated Diffusion Molecules move from area of high concentration to low concentration, but combines with another substance to facilitate movement or increase speed of diffusion, example: Glucose combined with insulin increases rate of diffusion across cell membrane

12. 12 Movement of Fluid, Cont ’ d 1.Osmosis Process by which only water molecule move through a selectively permeable membrane Membrane must be impermeable to solute Concentration gradient must exist

13. 13 Movement of Fluids, Cont ’ d 3.Active Transport Cell must use extra energy to transport a substance across the cell membrane and uphill or against the concentration gradient

14. 14 Osmosis 1.Osmotic Pressure Describes movement of water (force) Osmolality measures osmotic force of solute per unit of weight of solvent (amount of solute in solution) The more solute the higher the osmolality 2.Unit Measured in millimoles, measured by number of dissolved particles per kilogram

15. 15 Osmosis, Cont ’ d 1.Osmolarity Measures total millimoles of solute per unit of total volume of solution 2.Osmolality and Osmolarity They are used interchangably, but osmolality is usually performed on plasma and urine 3.Fluid of High Osmolality They tend to pull water across a membrane to reduce the ratio of solute to solvent

16. 16 Osmosis, Cont ’ d 1.Normal value: 275-295 mmol/kg 2.Na +, glucose, and urea are major determinants with Na + as primary 3.Kidneys are mainly responsible for maintaining this narrow range

17. 17 Water Content Regulation 1.Content Regulated Total volume of water in body remains constant 2.Kidneys Primary regulator of water excretion 3.Regulation Processes Osmosis Osmolality Baroreceptors Learned behavior

18. 18 Water Content Regulation, Cont’d 1.Sources of Water Ingestion Cellular metabolism 2.Routes of Water Loss Urine Evaporation Perspiration Respiratory passages Feces

19. 19 Extracellular Fluid Osmolality 1.Osmolality Adding or removing water from a solution changes this 2.Increased Osmolality Triggers thirst and ADH secretion 3.Decreased Osmolality Inhibits thirst and ADH secretion

20. 20 Hormonal Regulation of Blood Osmolality

21. 21 Regulation of ECF Volume Mechanisms 1.Neural 2.Renin-angiotensin-aldosterone 3.Atrial natriuretic hormone (ANH) 4.Antidiuretic hormone (ADH)

22. 22 Regulation of ECF Volume, Cont’d Increased ECF Results in: 1.Decreased aldosterone secretion 2.Decreased ADH secretion 3.Decreased sympathetic stimulation 4.Increased ANH secretion

23. 23 Regulation of ECF Volume, Cont’d Decreased ECF results in: 1.Increased aldosterone secretion 2.Increased ADH secretion 3.Increased sympathetic stimulation 4.Decreased ANH secretion

24. 24 Hormonal Regulation of Blood Volume Increase

25. 25 Hormonal Regulation of Blood Volume Decrease

26. 26 Regulation of ECF Volume

27. 27 Regulation of ICF and ECF

28. 28 Regulation of ECF Electrolytes Electrolytes 1.Molecules or ions with an electrical charge Water ingestion adds electrolytes to body Kidneys, liver, skin, lungs remove from body 2.Concentration changes only when growing, gaining or losing weight

29. 29 Regulation of ECF Electrolytes, Cont ’ d 1.Sodium Ions Dominant ECF cations Responsible for 90-95% of osmotic pressure Regulation of Na + ions Kidneys major route of excretion Small quantities lost in sweat Terms Hypernatremia Hyponatremia

30. 30 Mechanisms Regulating Blood Sodium

31. 31 Mechanisms Regulating Blood Sodium

32. 32 Abnormal Plasma Levels of Sodium Ions

33. 33 Regulation of Chloride and Magnesium Ions 2.Chloride Ions Predominant anions in ECF 3.Magnesium Ions Capacity of kidney to reabsorb is limited Excess lost in urine Decreased extracellular magnesium results in greater degree of reabsorption

34. 34 Regulation of Blood Magnesium

35. 35 Abnormal Plasma Levels of Magnesium Ions

36. 36 Regulation of Potassium Ions 4.Potassium Ions Maintained in narrow range Affect resting membrane potentials Aldosterone increases amount secreted Terms Hyperkalemia Hypokalemia

37. 37 Potassium Ion Regulation in ECF

38. 38 Abnormal Concentrations of Potassium Ions

39. 39 Regulation of Calcium Ions 5.Calcium Ions Regulated Within Narrow Range Elevated extracellular levels prevent membrane depolarization Decreased levels lead to spontaneous action potential generation Terms Hypocalcemia Hypercalcemia

40. 40 Regulation of Calcium Ions, Cont’d PTH Increases Ca 2+ extracellular levels Decreases extracellular phosphate levels Vitamin D Stimulates Ca 2+ uptake in intestines Calcitonin Decreases extracellular Ca 2+ levels

41. 41 Regulation of Calcium Ions, Cont’d

42. 42 Regulation of Phosphate Ions 5.Phosphate Ions Under normal conditions Reabsorption of phosphate occurs at maximum rate in the nephron An increase in plasma phosphate Increases amount of phosphate in nephron beyond that which can be reabsorbed; excess is lost in urine

43. 43 Regulation of Blood Phosphate Ions

44. 44 Abnormal Plasma Levels of Phosphate Ions

45. 45 Acids, Bases and Buffers 1.Acids Release H + into solution 2.Bases Remove H + from solution 3.Acids and Bases Grouped as strong or weak

46. 46 4. Buffers Resist changes in pH When H + added, buffer removes When H + removed, buffer replaces 5. Types of Buffer Systems Carbonic acid and bicarbonate Protein Phosphate Acids, Bases and Buffers, Cont ’ d

47. 47 Regulation of ECF pH Buffering MechanismsBuffering Mechanisms 1.Chemical buffers in ECF, ICF and bone Phosphate Proteins Bicarbonate and CO 2 system Hemoglobin 2.Lungs 3.Kidneys

48. 48 Carbonic Acid–Bicarbonate Buffer 1.Operates in both the lung and the kidney 2.The greater the partial pressure of carbon dioxide, the more carbonic acid is formed At a pH of 7.4, the ratio of bicarbonate to carbonic acid is 20:1 Bicarbonate and carbonic acid can increase or decrease, but the ratio must be maintained

49. 49 3.If the amount of bicarbonate decreases, the pH decreases, causing a state of acidosis 4.If the amount of bicarbonate increases, the pH increases, causing a state of alkalosis Carbonic Acid–Bicarbonate Buffer, Cont’d

50. 50 5.The pH can be returned to normal if the ratio of bicarbonate to carbonic acid is maintained This type of pH adjustment is referred to as compensation Respiratory compensation Renal compensation Carbonic Acid–Bicarbonate Buffer, Cont’d

51. 51 6.The respiratory system compensates by increasing or decreasing ventilation 7.The renal system compensates by producing acidic or alkaline urine Carbonic Acid–Bicarbonate Buffer, Cont’d

52. 52 Other Buffering Systems 1.Protein Buffering Proteins have negative charges, so they can serve as buffers for H + 2.Renal Buffering Secretion of H + in the urine and reabsorption of HCO 3 – 3.Cellular Ion Exchange Exchange of K + for H + in acidosis and alkalosis

53. 53 Regulation of Acid-base Balance

54. 54 Regulation of Acid-base Balance, Cont’d

55. 55 Buffer Systems

56. 56 Transport of HCO 3 - and O 2 CO 2 is transported by the blood in three forms 1.Dissolved CO 2 in the plasma (7%) 2.Bound to Hb (23 %) 3.As HCO 3 - in the blood (70%)

57. 57 1.CO 2 diffuses into RBC, where carbonic anhydrase catalyzes a reversible reaction that converts CO 2 into HCO 3 - 2.H 2 CO 3 forms first but quickly dissociates to HCO 3 - and H + 3.HCO 3 - diffuses out of the RBC and into the blood plasma 4.H + attaches to Hb and other proteins, resulting in only a slight change in the pH 5.The process is reversed in the lungs Transport of HCO 3 - and O 2, Cont’d

58. 58 Transport of HCO 3 - and O 2, Cont’d In Lungs 1.Hb-H + binds to O 2 to form Hb- O 2 and releases H + which reacts with HCO 3 - to form H 2 CO 3 2.Hb-O 2 is transported into tissues 3.H 2 CO 3 dissociates to CO 2 and H 2 O 4.CO 2 is eliminated in the expired air

59. 59 Transport of HCO 3 - and O 2, Cont’d In Tissues 1.CO 2 from metabolic reactions is hydrated to H 2 CO 3 which dissociates to H + and HCO 3 - 2.Hb-O 2 releases O 2 and binds to H + to form Hb-H + which is transported to lungs 3.HCO 3 - is transported to lungs

60. 60 Respiratory Regulation of ECF pH 1.Respiratory Regulation of pH It is achieved through carbonic acid/bicarbonate buffer system As carbon dioxide levels increase, pH decreases As carbon dioxide levels decrease, pH increases Carbon dioxide levels and pH affect respiratory centers Hypoventilation increases blood carbon dioxide levels Hyperventilation decreases blood carbon dioxide levels

61. 61 Respiratory Regulation of ECF pH, Cont ’ d

62. 62 Mechanisms of Renal Regulation of ECF pH Renal Buffer Blood pH by: Urinary Excretion of H + (Urinary Acidification): 1.Mechanism of Renal Tubular Reabsorption of HCO 3 - 2.Mechanism of Renal Excretion of Titratable Acid Excretion of H + (as H 2 O) Excretion of H + (as H 2 PO 4 - ) 3.Mechanism of Renal Excretion of NH 4 +

63. 63 Mechanism of Renal Reabsorption of HCO 3 - 1.Secretion of H + into filtrate and reabsorption of HCO 3 - into ECF Cause extracellular pH to increase HCO 3 - in filtrate reabsorbed 2.Rate of H + secretion increases as Body fluid pH decreases or Aldosterone levels increase 3.Secretion of H + inhibited When urine pH falls below 4.5

64. 64 Mechanism of Renal Reabsortion of HCO 3 -

65. 65 Mechanism of Renal Excretion of Titratable Acid and NH 4 +

66. 66 THE END Any questions?