1. ADVANCED PHYSIOLOGY FLUID & ELECTROLYTES PART 2 Instructor Terry Wiseth
NORTHLAND COLLEGE

2. Na+ K+ K+ Na+ Na+ Na+ K+ K+
ELECTROLYTE BALANCE
The exchange of interstitial and intracellular fluid is controlled mainly by the presence of the electrolytes sodium and potassium
Na+ K+ K+
Na+
Na+
Na+ K+ K+

3. K+ Na+ ELECTROLYTE BALANCE
Potassium is the chief intracellular cation and sodium the chief extracellular cation
Because the osmotic pressure of the interstitial space and the ICF are generally equal, water typically does not enter or leave the cell K+
Na+

4. ELECTROLYTE BALANCE Na+ K+ K+ Na+ K+ Na+ Na+ K+
A change in the concentration of either electrolyte will cause water to move into or out of the cell via osmosis
A drop in potassium will cause fluid to leave the cell whilst a drop in sodium will cause fluid to enter the cell
Click to see animation
Na+ K+ K+
H2O
H2O
Na+
H2O
H2O K+
Na+
Na+ K+
H2O
H2O
H2O
H2O

5. ELECTROLYTE BALANCE Na+ K+ K+ Na+ Na+ K+ Na+ K+
A change in the concentration of either electrolyte will cause water to move into or out of the cell via osmosis
A drop in potassium will cause fluid to leave the cell whilst a drop in sodium will cause fluid to enter the cell
Click to see animation
Na+ K+ K+
H2O
Na+
H2O
H2O
H2O
Na+ K+
Na+ K+
H2O
H2O
H2O
H2O

6. Na+ K+ ELECTROLYTE BALANCE
Aldosterone, ANP and ADH regulate sodium levels within the body, while aldosterone can be said to regulate potassium
Na+
ADH
ANP K+
aldosterone

7. Na+ Cl- HCO3- ELECTROLYTE BALANCE
Sodium (Na+) ions are the important cations in extracellular fluid
Anions which accompany sodium are chloride (Cl-) and bicarbonate (HCO3-)
Considered an indicator of total solute concentration of plasma osmolality
Cl-
HCO3-

8. ELECTROLYTE BALANCE
Sodium ions are osmotically important in determining water movements
A discussion of sodium must also include
Chlorine
Bicarbonate
Hydrogen ions
Potassium and calcium serum concentrations are also important electrolytes in the living system
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O

9. ELECTROLYTE BALANCES Click Click
Hypernatremia - elevated sodium levels
Hyponatremia -- lowered sodium levels
Hyperkalemia -- elevated potassium levels
Hypokalemia ---- lowered potassium levels
Click
Hypercalcemia - elevated calcium levels
Hypokalcemia -- lowered calcium levels
Click

10. HYPERNATREMIA
Normal range for blood levels of sodium is app meq/liter
Hypernatremia refers to an elevated serum sodium level ( meq/liter)
Increased levels of sodium ions are the result of diffusion and osmosis
Na+

11. SODIUM PRINCIPLES
1) Sodium ions do not cross cell membranes as quickly as water does
H2O
H2O
H2O
H2O
H2O
Na+
Na+

12. SODIUM PRINCIPLES
2) Cells pump sodium ions out of the cell by using sodium-potassium pumps
Na+
Na+
Na+
Na+

13. SODIUM PRINCIPLES
3) Increases in extracellular sodium ion levels do not change intracellular sodium ion concentration
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+

14. RESULTS OF HYPERNATREMIA
1) Water is osmotically drawn out of the cells
Resulting in dehydration
2) Increase in extracellular fluid volume
Intracellular
fluid
volume
Extracellular
fluid
volume

15. CNS REACTION TO HYPERNATREMIA
In the CNS tight junctions exist between endothelial cells of the capillary walls
These junctions restrict diffusion from capillaries to the interstitium of the brain
blood-brain barrier
Increased levels of sodium ions in the blood does not result in increased sodium ions in brain interstitial fluid

16. CNS REACTION TO HYPERNATREMIA
As the result of an osmotic gradient, water shifts from the interstitium and cells of the brain and enters the capillaries
The brain tends to shrink and the capillaries dilate and possibly rupture
Result is cerebral hemorrhage, blood clots, and neurological dysfunction
H2O

17. CNS PROTECTIVE MECHANISM
There is an unknown mechanism that protects the brain from shrinkage
Within about 1 day
Intracellular osmolality of brain cells increases in response to extracellular hyperosmolality ?

18. CNS PROTECTIVE MECHANISM
Idiogenic osmoles accumulate inside brain cells
K+, Mg+ from cellular binding sites and amino acids from protein catabolism
These idiogenic osmoles create an osmotic force that draws water back into the brain and protects cells from dehydration
H2O

19. CAUSES OF HYPERNATREMIA
1) Water loss
2) Sodium ion overload
Most cases are due to water deficit due to loss or inadequate intake
Infants without access to water or increased insensible water loss can be very susceptible to hypernatremia

20. WATER LOSS
Diabetes insipidus caused by inadequate ADH or renal insensitivity to ADH results in large urinary fluid loss
Increased fluid loss also occurs as the result of osmotic diuresis (high solute loads are delivered to the kidney for elimination)

21. WATER LOSS
Diabetes mellitus results in loss of fluids as well by creating an osmotic pull (increased urine solute concentration) on water into the tubules of the kidney
H2O
H2O
H2O
Glucose
Glucose
Glucose
H2O
Glucose
H2O
Click to animate
H2O
Glucose
Glucose
H2O
H2O
Glucose
Glucose
H2O
H2O
Glucose
Glucose
H2O
H2O
Glucose

22. WATER LOSS
High protein feedings by a stomach tube create high levels of urea in the glomerular filtrate producing an osmotic gradient the same as glucose does and increased urinary output results

23. SODIUM EXCESS Occurs less frequently than water loss
Retention or intake of excess sodium
ex: IV infusion of hypertonic sodium ion solutions
Aldosterone promotes sodium and water retention by the kidney
High levels of aldosterone may result in mild hypernatremia

24. CAUSES OF HYPERNATREMIA

25. TREATMENT OF HYPERNATREMIA
Re-hydration is the primary objective in most cases
Decreases sodium concentrations
A point of concern is when and how rapid the re-hydration occurs

26. TREATMENT OF HYPERNATREMIA
After 24 hours the brain has responded by producing idiogenic osmoles to re-hydrate brain cells
If this adaptation has occurred and treatment involves a rapid infusion of dextrose for example
There is danger of cerebral edema with fluid being drawn into brain tissues

27. TREATMENT OF HYPERNATREMIA
Treatment is best handled by giving slow infusions of glucose solutions
This dilutes high plasma sodium ion concentrations

28. TREATMENT OF HYPERNATREMIA
Ideally the goal is to avoid overloading with fluid and to remove excess sodium
Diuretics can be used to induce sodium and water diuresis
However if kidney function is not normal peritoneal dialysis may be required

29. HYPONATREMIA
Defined as a serum sodium ion level that is lower than normal
Implies an increased ratio of water to sodium in extracellular fluid
Extracellular fluid is more dilute than intracellular fluid
Results in a shift of water into cells
Na+

30. CNS RESPONSE TO HYPONATREMIA
Brain cells lose osmoles creating a higher extracellular solute concentration
Effect is to protect against cerebral edema by drawing water out of the brain tissue

31. GENERAL RESPONSE TO HYPONATREMIA
Suppression of thirst
Suppression of ADH secretion
Both favor decreasing water ingestion and increasing urinary output

32. SYMPTOMS OF HYPONATREMIA
Primarily neurological (net flux of water into the brain)
Sodium ion levels of 125 meq / liter are enough to begin the onset of symptoms
Sodium ion levels of less than 110 meq / liter bring on seizures and coma

33. Na+ HYPONATREMIA H O 2 Produced by: 1) A loss of sodium ions
2) Water excess
Water excess can be due to:
Ingestion
Renal retention
H O 2

34. DILUTIONAL EFFECT 1) Isotonic fluid loss
2) Antidiuretic hormone secretion
3) Acute or chronic renal failure
4) Potassium ion loss
5) Diuretic therapy
H2O
H2O
H2O
Na+
Na+
H2O
H2O
H2O
H2O
Na+
H2O
H2O
H2O
H2O
H2O
H2O
Na+
Na+
Na+
Na+
H2O
H2O
H2O
H2O
H2O
H2O
Na+

35. DILUTIONAL EFFECT 1) Isotonic fluid loss Burns, fever, hemorrhage
Indirect cause of hyponatremia
Any volume loss stimulates thirst and leads to increased water ingestion
Thus isotonic fluid loss can cause hyponatremia not because of sodium loss but because of increased water intake

36. DILUTIONAL EFFECT 2) Antidiuretic hormone secretion
Enhances water retention
3) Acute or chronic renal failure
The kidney fails to excrete water
Can lead to hyponatremia

37. DILUTIONAL EFFECT 4) Potassium ion loss
Potassium ions are the predominant intracellular cations
When they are lost they are replaced by diffusion of intracellular potassium into extracellular fluid
Electrical balance is maintained by the diffusion of sodium ions into the cells in exchange for potassium ions
Thus a loss of extracellular sodium is realized and hyponatremia may ensue

38. POTASSIUM ION LOSS cell K+ Na+ Na+ K+ K+ K+ interstitial fluid plasma
1) extracellular
potassium loss
3) intracellular electrical balance
is maintained by diffusion of
sodium ions into cells
Na+
Na+
cell K+
2) diffusion of potassium
ions into extracellular
compartments K+ K+
interstitial fluid
plasma

39. POTASSIUM ION LOSS Cell Na+ Na+ K+ Na+ K+ K+ K+ K+ K+
Click to see animation K+ K+ K+
Interstitial fluid
Plasma

40. DILUTIONAL EFFECT 5) Diuretic therapy Common cause of hyponatremia
Loss of sodium and potassium often occurs in addition to fluid loss

41. CAUSES OF HYPONATREMIA

42. REACTIONS TO HYPONATREMIA
Increased ADH release
Increased Thirst
Decreased urinary H2O loss
Increased H2O gain
Osmoreceptors stimulated
Click to view increased Na+
Increased Na+
Additional H2O dilutes Na+
Homeostasis Normal Na+
H2O loss concentrates Na+
Decreased Na+
Click to view decreased Na+
Decreased ADH release
Decreased Thirst
Increased urinary H2O loss
Decreased H2O gain
Osmoreceptors inhibited

43. K+ HYPERKALEMIA Normal serum potassium level (3-5 meq / liter)
As compared to Na+ (142 meq / liter)
Intracellular levels of potassium ( meq / liter)
This high intracellular level is maintained by active transport by the sodium-potassium pump K+

44. Na+ / K+ Pump
Cells pump K+ ions in and Na+ ions out of the cell by using sodium-potassium pumps K+ K+
Na+ K+ K+
Na+
Na+
Na+

45. HYPERKALEMIA
Hyperkalemia is an elevated serum potassium (K+) ion level
A consequence of hyperkalemia is acidosis
an increase in H+ ions in body fluids
Changes in either K+ or H+ ion levels causes a compartmental shift of the other K+

46. HYPERKALEMIA
When hyperkalemia develops potassium ions diffuse into the cell
This causes a movement of H+ ions out of the cell to maintain a neutral electrical balance
As a result the physiological response to hyperkalemia causes acidosis H+ K+
HYPERKALEMIA H+ K+ H+ K+ H+ K+ H+ H+ K+ H+ H+ K+ H+

47. HYPERKALEMIA The reverse occurs as well
The body is protected from harmful effects of an increase in extracellular H+ ions (acidosis)
H+ ions inside the cells are tied up by proteins (Pr -)
This causes a shift of potassium ions out of the cells H+ H+
ACIDOSIS K+ H+ K+ H+ K+ H+ K+ H+ H+ K+ H+ H+ K+

48. HYPERKALEMIA Summarized: Hyperkalemia causes acidosis
Acidosis causes hyperkalemia
HYPERKALEMIA H+ K+
ACIDOSIS

49. HYPERKALEMIA Summarized: Hyperkalemia causes acidosis
Acidosis causes hyperkalemia
HYPERKALEMIA H+ K+
ACIDOSIS

50. SYMPTOMS OF HYPERKALEMIA
Muscle contraction is affected by changes in potassium levels
Hyperkalemia blocks the transmission of nerve impulses along muscle fibers
Causes muscle weakness and paralysis
Can cause arrhythmia's and heart conduction disturbances

51. CAUSES FOR HYPERKALEMIA
1) Increased input of potassium
2) Impaired excretion of potassium
3) Impaired uptake of potassium by cells

52. INCREASED INPUT A) Intravenous KCl infusion
B) Use of K+ containing salt substitutes
C) Hemolysis of RBC during blood transfusions with release of K+
D) Damaged and dying cells release K+
Burns, crush injuries, ischemia
E) Increased fragility of RBC

53. CELLULAR-EXTRACELLULAR SHIFTS
Insulin deficiency predisposes an individual to hyperkalemia
Cellular uptake of K+ ions is enhanced by insulin, aldosterone and epinephrine
Provides protection from extracellular K+ overload
Insulin K+ K+ K+ K+ K+
Click to view animation K+

54. CELLULAR-EXTRACELLULAR SHIFTS
Insulin deficiency represents decreased protection if the body is challenged by an excess of K+ ions
In the absence of aldosterone there is loss of Na+ in the urine and renal retention of K+

55. HYPERKALEMIC PERIODIC PARALYSIS
Inherited disorder in which serum K+ level rise periodically
Caused by a shift of K+ from muscle to blood in response to ingestion of potassium or exercise
Reasons for the shift are not clear
Attacks are characterized by muscle weakness

56. RENAL INSUFFICIENCY Aldosterone has a primary role in promoting:
Conservation of Na+
Secretion of K+ by the nephrons of the kidney
Addison’s disease is characterized by aldosterone deficiency
Thus the kidney is unable to secrete potassium at a normal rate

57. OLIGURIC RENAL FAILURE
Kidney loses the ability to secrete K+

58. SPINOLACTONE
Diuretic that is antagonistic to the effects of aldosterone
Causes some rise in serum K+ levels by interfering with K+ secretion in the kidneys
Increases may not be significant
But individuals taking the diuretic are at risk if potassium is administered

59. TREATMENT
1) Counteract effects of K+ ions at the level of the cell membrane
2) Promotion of K+ ion movements into cells
3) Removal of K+ ions from the body

60. SALT INFUSIONS Infusion of calcium gluconate or NaCl solutions
Immediately counteract the effects of K+ ions on the heart
Effective for only 1-2 hours

61. SODIUM BICARBONATE
NaHCO3 also reverses hyperkalemic effects on the heart
If acidosis is a factor also raises the pH of body fluids

62. INSULIN-GLUCOSE INFUSION
Insulin given with glucose
Effective in about 30 minutes
Has a duration of action of up to 6 hours
Insulin promotes the shift of K+ ions into cells
Glucose prevents insulin-induced hypoglycemia

63. KAYEXALATE Kayexalate (cation exchange resin)
Removes K+ ions from the body by exchanging K+ for Na+
Exchange time is about 45 minutes
Effective for up to 6 hours

64. DIALYSIS Peritoneal dialysis or hemodialysis
Effectively clears the blood of high K+ levels as well

65. CAUSES OF HYPERKALEMIA

66. HYPOKALEMIA
Defined as a serum K+ level that is below normal (< 3 meq / liter)
Serum concentrations will decrease if:
There is an intracellular flux of K+
K+ ions are lost from the gastrointestinal or urinary tract K+

67. H+ HCO3- K+ ALKALOSIS Alkalosis causes and is caused by hypokalemia
Alkalosis is defined as a decrease of hydrogen ions or an increase of bicarbonate in extracellular fluids
Opposite of acidosis H+ K+
HCO3-

68. ALKALOSIS
Alkalosis elicits a compensatory response causing H+ ions to shift from cells to extracellular fluids
This corrects the acid-base imbalance
HCO3-
HCO3-
HCO3-
HCO3- H+ H+ H+
HCO3- H+ H+ H+
HCO3- H+ H+

69. ALKALOSIS H+ ions are exchanged for K+ (potassium moves into cells)
Thus serum concentrations of K+ are decreased
And alkalosis causes hypokalemia
HCO3-
HCO3-
HCO3- K+ K+ K+
HCO3- H+ K+ H+ K+ H+ K+
HCO3- H+ H+ H+
HCO3- K+ H+ H+ K+

70. ALKALOSIS
Conversely when K+ ions are lost from the cellular and extracellular compartments
Sodium and hydrogen ions enter cells in a ratio of 2:1 as replacement
This loss of extracellular H+ causes alkalosis
HCO3-
HCO3- H+ H+ H+
HCO3-
HCO3-
Na+
Na+ H+ H+
Na+
HCO3- K+ K+ H+
Na+
HCO3- K+ K+
Na+
HCO3-
Na+ K+ H+ K+
Na+ K+ K+

71. KIDNEY FUNCTION NORMAL Kidney function is altered by hypokalemia
Na+ ions are reabsorbed into the blood when K+ ions are secreted into the urine by kidney tubules
NORMAL
Peritubular fluid
Tubular lumen K+
Na+ K+
Na+
Na+ K+
Na+ K+ K+
Na+
Na+
Na+ K+ K+

72. KIDNEY FUNCTION HYPOKALEMIA Kidney function is altered by hypokalemia
If adequate numbers of K+ are not available for this exchange
H+ ions are secreted instead
HYPOKALEMIA
Peritubular fluid
Tubular lumen H+
Na+ K+
Na+
Na+ K+
Na+ H+ H+
Na+
Na+
Na+ H+ K+

73. KIDNEY FUNCTION
Hypokalemia promotes renal loss of H+ ions and thus results in alkalosis

74. NORMAL NEPHRON Normal nephron function is to secrete H+ and K+ in
exchange for Na+
capillary
distal tubule H+ K+
Na+
Blood
Urine

75. NEPHRON ACTION IN HYPOKELEMIA
In Hypokalemia the kidney
selectively secretes
H+ ions in preference
to K+ ions
The loss of H+ ions
may lead to alkalosis H+ K+
Na+
distal tubule
capillary
Blood
Urine

76. ALKALOSIS
3) the kidney then eliminates K+ ions which can lead to Hypokalemia
1) in alkalosis there is a
decrease in extracellular
fluid H+ H+
retained K+ K+
Na+
excreted
distal tubule
capillary
Blood
2) the kidney retains
hydrogen ions to
correct the alkalosis
Urine

77. CAUSES OF HYPOKALEMIA

78. TREATMENT OF HYPOKALEMIA
Replacement of K+ either by:
Oral K+ salt supplements
Diet
Intravenous administration of K+ salt solution
Diuretic (spinolactone) if renal loss is at work

79. CALCIUM HOMEOSTASIS Ca++ plays an important role in:
Muscle contraction
Nerve impulse transmission
Hormone secretion
Blood clotting

80. Ca++ = 4.9 meq / liter CALCIUM HOMEOSTASIS
Normal range for serum calcium is mg/dl ( meq / liter)
The range for proper function has narrow limits
Ca++ =
4.9 meq / liter

81. VITAMIN D
Vitamin D is involved in maintaining serum Ca++ levels

82. VITAMIN D
Source of vitamin D is either dietary or is synthesized by the body
Cholesterol is converted in the skin by exposure to sunlight into a precursor product which is converted to an active form of vitamin D by the liver and kidneys

83. VITAMIN D Vitamin D enhances serum Ca++ levels by:
1) Directly promoting bone resorption with the release of chemical salts
2) Potentiating the effects of parathormone (PTH) on bone reabsorption
3) Increasing absorption of Ca++ ions from the intestine
4) Reabsorption by the kidney tubules

84. PARATHORMONE Secreted into the bloodstream by the parathyroid glands
Essential part of the Ca++ homeostatic mechanisms

85. PARATHORMONE ACTION PTH
1) Increases calcium ion absorption from the intestine
Enhances the synthesis of the active form of vitamin D
2) Favors reabsorption of calcium

86. PARATHORMONE ACTION PTH
3) Favors excretion of phosphate (PO4 -3) by kidney tubules
4) Enhances bone reabsorption with the release of Ca++

87. PARATHORMONE SECRETION
PTH secretion is:
Stimulated by decreased serum level of Ca++
Inhibited by increased serum levels of Ca++
Ca++
PTH
Ca++
PTH

88. CALCITONIN Calcitonin is a hormone secreted by the thyroid gland
Effects of calcitonin are weak compared to PTH

89. CALCITONIN Decreases serum Ca++ level by:
1) Interfering with bone resorption
2) Favoring bone uptake of calcium
3) Promoting excretion of calcium by the kidney
CALCITONIN
Calcitonin stimulates calcium salt deposit in bone
Thyroid gland releases calcitonin
Falling blood Ca++ levels
Rising blood Ca++ levels
Osteoclasts degrade bone and release Ca++
PTH
Parathyroid glands release PTH

90. STORES OF CALCIUM
bone calcium
renal excretion
extracellular
calcium
intracellular
calcium
absorption from
intestine
There are exchangeable stores of calcium in bone and in cells
This total pool is in equilibrium with calcium in extracellular fluid
Serum calcium levels are also maintained by a balance between renal excretion and intestinal absorption

91. Ca++ Ca++ = = 10.5 Hypercalcemia 9.0 Hypocalcemia HYPERCALCEMIA
A serum calcium level of 10.5 mg / dl or above results in hypercalcemia
Ca++ =
10.5
Hypercalcemia
Ca++ =
9.0
Hypocalcemia

92. HYPERCALCEMIA High levels of Ca++: Interfere with nerve impulse
Interfere with muscle contraction
May cause kidney stones
May precipitate out of body tissues (at high levels)

93. CAUSES FOR HYPERCALCEMIA
1) Overactive parathyroid glands
2) Hyperthyroidism increases bone resorption
3) Large doses of vitamin D

94. CAUSES FOR HYPERCALCEMIA
4) Confinement to bed for weeks at a time
Bone reabsorption occurs at a more rapid rate than bone formation
5) Some malignancies secrete hormones that cause bone resorption

95. CAUSES FOR HYPERCALCEMIA
6) Milk-alkali syndrome
Excessive and prolonged ingestion of milk and alkaline antacids (peptic ulcer)
Sodium bicarbonate and calcium carbonate used as antacids
Metabolic acidosis results because of increased levels of plasma bicarbonate

96. MILK-ALKALI SYNDROME Alkalosis promotes hypercalcemia
1) Causes increased kidney resorption of calcium
2) Decreases the capacity of bone to take up additional calcium

97. CAUSES OF HYPERCALCEMIA

98. TREATMENT
Intravenous or oral administration of phosphate decreases plasma calcium levels by interfering with bone resorption
Calcitonin reduces activities of bone destroying cells (osteoclasts)
Glucocorticoids inhibit intestinal absorption of calcium

99. TREATMENT Some diuretics promote excretion of calcium by the kidneys
Infusion of saline (NaCl) or sodium sulfate (Na2SO4) increases urinary calcium excretion

100. Ca++ Ca++ = = 9.0 Hypocalcemia 10.5 Hypercalcemia HYPOCALCEMIA
Defined as a low serum calcium level
Less than 9 mg / dl
Ca++ =
9.0
Hypocalcemia
Ca++ =
10.5
Hypercalcemia

101. HYPOCALCEMIA Physiological response to low calcium serum levels
Increased secretion of PTH
Which increases calcium by favoring bone resorption
Intestinal absorption
Renal reabsorption

102. CAUSES FOR HYPOCALCEMIA
1) Inadequate vitamin D
a) Nutritional deficiencies
b) Impaired intestinal absorption
ex: partial gastrectomy
c) Liver or kidney dysfunction interferes with formation of active form of vitamin D

103. CAUSES FOR HYPOCALCEMIA
d) Inadequate exposure to sunlight
Reduction in formation of active vitamin D in the skin
e) Intestinal or bone unresponsiveness to action of vitamin D

104. CAUSES FOR HYPOCALCEMIA
2) Loss of parathyroid glands or loss of function
3) Pancreatitis
Defect in PTH secretion
Calcium deposits form in soft tissues

105. CAUSES FOR HYPOCALCEMIA
4) Renal failure
Reduction in the formation of an active vitamin D metabolite
Altered bone response to PTH is also a factor

106. CAUSES OF HYPOCALCEMIA

107. TREATMENT Calcium salts administered intravenously or orally
Calcium gluconate or calcium chloride solutions
Vitamin D may be given

108. END OF FLUID AND ELECTROLYTES PART 2