1. Water, Electrolyte, and Acid-Base Balance

2. Function of Water:
Most of cellular activities are performed in water solutions.

3. Body Fluid 4% TBW 40% TBW - makes up ~60% of total body weight (TBW)
- distributed in three fluid compartments.
16% TBW

4. 4% TBW
40% TBW
Fluid is continually exchanged between the three compartments.
16% TBW

5. 4% TBW
40% TBW
Exchange between Blood & Tissue Fluid
- determined by four factors:
capillary blood pressure
plasma colloid osmotic pressure
interstitium Hydrostatic Pressure
Interstitium colloid osmotic pressure
16% TBW

6. 4% TBW
40% TBW
Exchange between Blood & Tissue Fluid
- not affected by electrolyte concentrations
- Edema = water accumulation in tissue fluid
16% TBW

7. Exchange between Tissue Fluid & Intracellular Fluid
4% TBW
40% TBW
Exchange between Tissue Fluid & Intracellular Fluid
- determined by two:
1) intracellular osmotic pressure
electrolytes
2) interstitial osmotic pressure
16% TBW

8. Water Gain Water is gained from three sources. 1) food (~700 ml/day)
2) drink – voluntarily controlled
3) metabolic water (200 ml/day) --- produced as a byproduct of aerobic respiration

9. Routes of water loss
1) Urine – obligatory (unavoidable) and physiologically regulated, minimum 400 ml/day
2) Feces -- obligatory water loss, ~200 ml/day
3) Breath – obligatory water loss, ~300 ml/day
4) Cutaneous evaporation -- obligatory water loss, ~400 ml/day
5) Sweat – for releasing heat, varies significantly

10. Regulation of Water Intake - governed by thirst.
blood volume and osmolarity 
peripheral volume sensors central osmoreceptors
hypothalamus
thirst felt

11. Regulation of Water Output
- The only physiological control is through variations in urine volume.
- urine volume regulated by hormones

12. blood volume and/or osmolarity
1) ADH
dehydration 
blood volume and/or osmolarity
hypothalamic receptors / peripheral volume sensors
posterior pituitary to release ADH
 H2O reabsorption
Water retention

13. inhibits Na+ and H2O reabsorption
2) Atrial Natriuretic Factor
 blood volume 
atrial volume sensors
atria to release ANF
inhibits Na+ and H2O reabsorption
 water output

14. Dehydration
- decrease in body fluid
Causes
the lack of drinking water
2) excessive loss of body fluid due to:
overheat
diabetes
overuse of diuretics
diarrhea

15. Edema
- the accumulation of fluid in the interstitial spaces
caused by:
increased capillary filtration, or
2) reduced capillary reabsorption, or
3) obstructed lymphatic drainage

16. ELECTROLYTE BALANCE

17. Electrolytes = small ions that carry charges

18. Major cations
Na+ K+
Ca++ H+
Major anions
Cl-
HCO3-
PO4---

19. Distribution of Electrolytes
Na+ K+
Ca++
Cell
PO4---
Cl-
Extracellular
space

20. Sodium Na+ Na+ K+ Ca++ Cell PO4--- Cl- Functions
- involved in generating action membrane potential of cells
make a major contribution to extracellular osmolarity.

21. Regulation of plasma Na+
Aldosterone
Na+
plasma Na+ 
 aldosterone
renal Na + excretion
 plasma Na +
plasma

22. Renin-angiotensin-II
angiotensin-II
 aldosterone
 renal Na+ excretion
 plasma Na+
Na+
plasma

23. increases water reabsorption in kidneys
3) ADH
increases water reabsorption in kidneys 
water retention
dilute plasma Na+
H2O
Na+
plasma

24. eliminate more sodium and water
Atrial Natriuretic Factor
inhibits renal reabsorption of Na+ and H2O and the excretion of renin and ADH 
eliminate more sodium and water
 plasma Na +
Na+
plasma
Na+

25. Sodium imbalance
hypernatremia
plasma sodium > 145 mEq/L,
hyponatremia
plasma sodium < 130 mEq/L

26. Potassium Na+ K+ K+ Ca++ Cell Functions PO4--- Cl-
- the greatest contributor to intracellular osmosis and cell volume
- determines the resting membrane potentials
- an essential cofactor for protein synthesis and some other metabolic processes. K+

27. secretion by the kidneys
Regulation of Potassium
by aldosterone
Aldosterone 
stimulates K+
secretion by the kidneys
 Plasma K+ K+
plasma K+

28. Potassium Imbalance
hyperkalemia (> 5.5 mEq/L)
hypokalemia (< 3.5 mEq/L)

29. Chloride Na+ K+ Ca++ Cell PO4--- Cl-
- makes a major contribution to extracellular osmolarity
- required for the formation of stomach acid (HCl)

30. Regulation of Cl–
No direct regulation
indirectly regulated as an effect of Na+ homeostasis. As sodium is retained or excreted, Cl– passively follows.
Chloride Imbalance
hyperchloremia (> 105 mEq/L)
hypochloremia (< 95 mEq/L).

31. Calcium
Na+ K+
Ca++
Cl-
PO4---
Cell

32. Functions of Ca++
- lends strength to the skeleton

33. [ Ca++ ]i Contraction Excitation Functions of Ca++
- lends strength to the skeleton
- activates muscle contraction
[ Ca++ ]i
Excitation
Contraction
(Action Potentials)
(shortening)

34. Functions of Ca++
- lends strength to the skeleton
- activates muscle contraction
- serves as a second messenger for some hormones and neurotransmitters

35. Functions of Ca++
- lends strength to the skeleton
- activates muscle contraction
- serves as a second messenger for some hormones and neurotransmitters
- activates exocytosis
of neurotransmitters and
other cellular secretions

36. Functions of Ca++
- lends strength to the skeleton
- activates muscle contraction
- serves as a second messenger for some hormones and neurotransmitters
- activates exocytosis of neurotransmitters and other cellular secretions
- essential factor
in blood clotting.

37. Functions of Ca++
- lends strength to the skeleton
- activates muscle contraction
- serves as a second messenger for some hormones and neurotransmitters
- activates exocytosis of neurotransmitters and other cellular secretions
- essential factor in blood clotting.
- activates many cellular
enzymes

38. Dynamics of Calcium
Ca++
Ca++
Ca++
plasma
Ca++

39. Regulation of calcium
1) parathyroid hormone (PTH):

40. Regulation of calcium
1) parathyroid hormone (PTH):
- dissolving Ca++ in bones
- reducing renal excretion of Ca++
Ca++
Ca++
plasma

41. 2) calcitonin (secreted by C cells in thyroid gland):

42. 2) calcitonin (secreted by C cells in thyroid gland):
depositing Ca++ in bones
Ca++
Ca++
plasma

43. 3) calcitrol (derivative of vitamin D):
- enhancing intestinal absorption of Ca++ from food
Ca++
Ca++
plasma
Ca++

44. Calcium imbalances
hypocalcemia (< 4.5 mEq/L)
hypercalcemia (> 5.8 mEq/L).

45. Phosphates needed for the synthesis of: ATP, GTP DNA, RNA
phospholipids

46. Regulation of Phosphate
by parathyroid hormone
PTH 
increases renal excretion of phosphate
decrease plasma phosphate
- no real phosphate imbalances
PO4---
plasma
PO4---

47. ACID-BASE BALANCE

48. Acid Base An acid is any chemical that releases H+ in solution.
A base is any chemical that accepts H+.

49. pH
is the negative logarithm of H+ concentration, and an indicator of acidity.
  pH = - log [H+ ]
Example: [H+ ] = 0.1 M = 10 –7 M

50. pH
is the negative logarithm of H+ concentration, and an indicator of acidity.
  pH = - log [10 –7 ]
= 7 log 10 = 7
Example: [H+ ] = 0.1 M = 10 –7 M

51. pH  [ H+ ] =  pH  [ H+ ] =  pH
is the negative logarithm of H+ concentration, and an indicator of acidity.
  pH = - log [10 –8 ]
Example: [H+ ] = 0.01 M = 10 –8 M
= 8 log 10 = 8
0.01 M [ H+ ] = pH 8
0.1 M [ H+ ] = pH 7
 [ H+ ] =  pH
 [ H+ ] =  pH

52. Normal functions of proteins (especially enzymes) heavily depend on an optimal pH.
pH7.35-pH7.45

53. Regulation of acid-base balance
1) Chemical Buffers
2) Respiratory Control of pH
3) Renal Control of pH

54. Buffer
is any mechanism that resists changes in pH.

55. acid
acid
H2O
pH 7.0
Buffer
pH 7.0
pH 3.0
pH 6.8

56. base
base
H2O
pH 7.0
Buffer
pH 7.0
pH 11.0
pH 7.2

57. Chemical Buffers
There are three major buffers in body fluid.
1) The Bicarbonate (HCO3-) Buffer
2) The Phosphate Buffer
3) The Protein Buffer

58. The Bicarbonate (HCO3-) Buffer System
H + HCO H2CO H2O CO2
- reversible depending on the equilibrium between the substrates and products.
- The lungs constantly remove CO2.

59. 2) The Phosphate Buffer System
H + HPO42– H2PO4– + H
H3PO4

60. 3) The Protein Buffer System
more concentrated than either bicarbonate or phosphate buffers
- accounts for about three-quarters of all chemical buffering ability of the body fluids.
The carboxyl groups release H+ when pH rises and amino groups bind H+ when pH falls. H+ H+
NH2-CH2-CH2 CH2-CH2-COOH

61. Properties of Chemical Buffers
- respond to pH changes within a fraction of a second.
- Bind to H but can not remove H out of the body
- Limited ability to correct pH changes

62. H + HCO H2CO H2O CO2 10 1) 20 10 2)
H + HCO H2CO H2O CO2 10 20 3)
H + HCO H2CO H2O CO2
H2CO H2O CO2 10 20

63. Respiratory Control of pH
H + HCO H2CO CO2 + H2O
H + HCO H2CO CO2 + H2O

64. stimulate peripheral/central chemoreceptors  pulmonary ventilation
stimulate peripheral/central chemoreceptors
 pulmonary ventilation
removal of CO2 and  pH
H + HCO3-
H2CO3
H2O + CO2

65. Limit to respiratory control of pH
The respiratory regulatory mechanism cannot remove H+ out of the body. Its efficiency depends on the availability of HCO3- .
H + HCO H2CO H2O CO2

66. Renal Control of pH
The kidneys can neutralize more acid or base than both the respiratory system and chemical buffers.
a. Renal tubules secrete hydrogen ions into the tubular fluid, where most of it combines with bicarbonate, ammonia, and phosphate buffers.
b. Bound and free H+ are then excreted in urine.

67. The kidneys are the only organs that actually expel H+ from the body
The kidneys are the only organs that actually expel H+ from the body. Other buffering systems only reduce its concentration by binding it to another chemical.
3. Tubular secretion of H+ continues as long as a sufficient concentration gradient exists between the tubule cells and the tubular fluid.

68. Disorders of Acid-Base Balance
Acidosis: < pH 7.35 , Alkalosis: > pH 7.45
Mild acidosis
depresses CNS, causing
confusion, disorientation, and coma.
Mild alkalosis
CNS becomes hyperexcitable.
Nerves fire spontaneously and overstimulate skeletal muscles.
- Severe acidosis or alkalosis is lethal.

69. Respiratory acidosis / alkalosis
Respiratory vs Metabolic Cause
Respiratory acidosis / alkalosis
- caused by hypoventilation or hyperventilation
Initial change
H + HCO H2CO H2O CO2
Emphysema

70.  production of organic acids
Respiratory acidosis / alkalosis
- caused by hypoventilation or hyperventilation
Metabolic acidosis or alkalosis
- result from any causes but respiratory problems
Diabetes 
 production of organic acids
metabolic acidosis
Chronic vomiting 
loss of stomach acid
metabolic alkalosis