patholophysiology of water electrolytes Pathophysiology（病理生理学） Pathology uploaded by prabesh 杰诗

1. 1
Water and Electrolytes BalanceWater and Electrolytes Balance
and Imbalanceand Imbalance
 Physiological Basis of Water and SodiumPhysiological Basis of Water and Sodium
MetabolismMetabolism
 Disorder of Potassium MetabolismDisorder of Potassium Metabolism
 Regulation of Water and Sodium BalanceRegulation of Water and Sodium Balance
 Disorder of Water and Sodium MetabolismDisorder of Water and Sodium Metabolism

2. 2
Disorder of Potassium
Metabolism
Normal Potassium Metabolism
Disturbance of Potassium Metabolism

3. Potassium (K+
):
Distribution and Normal Functions
ECF
ICF
(bone)
4.2 mmol/L
(1.4%)
150 mmol/L
(90%)
K+
Distribution
Serum [KSerum [K++
] 3.5~5.5 mmol/L] 3.5~5.5 mmol/L

4. Normal Metabolism of PotassiumNormal Metabolism of Potassium
1. IntakeIntake ：： FoodFood
2. Absorption:Absorption: IntestineIntestine
3.3. Excretion:Excretion:
UrineUrine 80%80% ～～ 9090 ％％
StoolStool 1010 ％％

5. Regulation of Potassium Balance
Transcellular Kidney
Two Mechanisms:

6. Transcellular Transfer
Pump-leak Mechanism
Na+
-K+
ATPase
(Active)
Leak
(Passive)
[K+
]i ： 150
mM
[K+
]e ： 3.5-5.5
mM
Na+
K+

7. Factors Affecting Transcellular Transfer of K+
(1) ECF K+
（↑ Na+
-K+
pump activity ）
(2) Acid-base balance
(3) Insulin （↑ Na+
-K+
pump activity ）
(4) Catecholamines （ -receptor: ↑ Na+
-K+
pump
activity ）
(5) ECF Osmosis
(6) Exercise

8. Reabsorption and Excretion of Potassium
Na+
K+
K+
H+
Principal Cell
K+
BloodVessel
DistalTubule
Intercalated Cell

9. 11
Physiological Functions of K+
Cell metabolism
Regulation of osmosis and pH
Generation of resting potential

10. Generation of Resting Potential
← Resting Potential
= K+
potential
At resting:
Plasma membrane
permeability
K +
>> Na+

11. 14
Disorder of Potassium
Metabolism
Normal Potassium Metabolism
Disturbance of Potassium Metabolism

12. 15
Serum K+
conc. < 3.5 mmol/L
Disturbance ofDisturbance of
Potassium MetabolismPotassium Metabolism
Hypokalemia ( 低 血症钾 )
Serum K+
conc. > 5.5 mmol/L
Hyperkalemia ( 高 血症钾 )

13. Hypokalemia
( 低 血症钾 )
Serum [K+
] < 3.5mmol/L
PotassiumPotassium deficiencydeficiency

14. ECF ICF
K+
Food
K+
HypokalemiaHypokalemia
 ①

15. ECF ICF
K+
Urine ↑
Food
K+
Stool ↑ ②
 ①
HypokalemiaHypokalemia

16. ECF ICF
K+
Urine ↑
Food
K+
Stool ↑ ②
③ ①
HypokalemiaHypokalemia

17. 1. Excessive Loss (most common)
Through digestive tract
Vomiting
Through kidney
K+
↓H+
DistalTubule
K+
Diuretics (urineDiuretics (urine ↑↑))
ADSADS ↑↑ → K↑↑ → K++
excretionexcretion
(?)(?)
Renal Tubular AcidosisRenal Tubular Acidosis
- H- H++
secretionsecretion↓↓
Causes and Mechanisms
Hypokalemia
Through skin
Too much sweatingToo much sweating
- workers at high temperature- workers at high temperature

18. 2. Decreased K+
intake
↓K+
Source
Excretion
(even w/o
intake)
Hypokalemia
Hypokalemia

19. 3. K ＋
goes into the cells
 Insulin therapy
- ↑ Na+
-K+
Pump
 Alkalosis
 Hypokalemic periodic paralysis
- Periodic muscle weakness or paralysis
- K+
goes into the cells during paralysis
- Caused by defects in ion channels
 Poisons - K+
channel blockers
(Barium ion, gossypol [ 棉子酚 ])
Pump
K+
H+
K+
Na+

20. ◣Automaticity
◣Contractibility ( severe)
◣Excitability
◣Conductivity
Effects on Myocardial
Cells
Hypokalemia

21. Effects of Acute Hypokalemia on
Myocardial Electrophysiology

22. 25
◣Excitability
KK++
Permeability AcrossPermeability Across
Cell Membrane↓Cell Membrane↓
K+
Outflow↓
Em value ↑
Difference with the Threshold ↓

23. Delayed
repolorization
Flat T wave, Suppressed ST
Q-T interval prolonged
U wave (abnormal)
Changes of ECG in Hypokalemia

24. Arrhythmias (Tachycardia)
(because of ↑ Automaticity)
↑ Sensitivity to the toxicity of Digitalis
- A drug used to treat atrial fibrillation (for
congestive heart failure)
- Affinity with Na+
-K+
ATPase ↑
- Lowering its therapeutic efficiency
◣Manifestations of Myocardial Injury
Hypokalemia

25. Effect on Skeletal Muscle
Rhabdomyolysis ( 横 肌溶解纹 )
K+
↓ (<2 mmol/L) → necrosis of muscle
cells
Hypokalemia

26. Effect on renal function
Hypokalemia
↓ cAMP
PolyuriaPolyuria
Damage to Cells of Collecting Duct
↓ Response to ADH

27. Metabolic Alkalosis
K+
H+
Effect on Acid-base Balance
Hypokalemia
Q: Urine pH?

28. Pathophysiological Basis of
Treatment
1. Treat the causative disorder1. Treat the causative disorder
Hypokalemia
2. Principles for supplying K+
：
(1) Oral administration preferred （ KCl)
(2) Not too early （ Urine >500 ml/d ）
- No urine, no K+
.
(3) Not too concentrated （ <40 mmol/L ）
(4) Not too fast （ 10~20 mmol/h ）
(5) Not too much （ <120 mmol/d)
(6) Supply Mg2+
(↓K+
→ ↓ Mg2+
)

29. 32
Serum K+
conc. < 3.5 mmol/L
Disturbance ofDisturbance of
Potassium MetabolismPotassium Metabolism
Hypokalemia ( 低 血症钾 )
Serum K+
conc. > 5.5 mmol/L
Hyperkalemia ( 高 血症钾 )

30. Hyperkalemia (Hyperkalemia ( 高 血钾高 血钾
症症 ))
Concept
Serum [K+
] > 5.5 mmol/L
Hyperkalemia may be lethal, primarily because
of its effect on cardiac conduction.
Clinically, it requires urgency treatment.

31. Causes
1. Renal Excretion↓
(1) GFR↓↓
Acute or Chronic Renal Failure
Hemorrhage, Shock
(2) Impaired K+
secretion
ADS↓ (Addison disease) → ↓ Na+
-K+
ATPase
activity (in renal tubule).
Hyperkalemia

32. 2. Export of K+
from the cells
(1) Acidosis
(2) Hypoxia (↓ATP)
(3) Tissue damage and hemolysis
(4) ↓ Insulin (+ hyperglycemia)
- ↓ Insulin → ↓ Na+
-K+
ATPase activity
- ↑ Glucose → ↑ Osmosis → H2O and K+
export
(5) Drugs ：
Digitalis and β-receptor blockers
(propranolol and pronethalol)
- ↓Na+
-K+
ATPase activity
(6) Hyperkalemic periodic paralysis
Hyperkalemia
K+
H+
Acidosis

33. 3. ↑Intake (medical)
– infusion of K+
-containing fluid
– infusion of stored blood
Hyperkalemia

34. ◣Automaticity
◣Contractibility
◣Excitability ( ( severe)
◣Conductivity
Effects on Myocardial
Cells
Hyperkalemia

35. Changes of ECG in Hyperkalemia
Delayed
repolorization
Flat T wave
U wave
Suppressed ST
Speeded
repolorization
Peaked T wave
Shortened Q-T

36. Metabolic Acidosis
H+
K+
Effect on Acid-base Balance
Hyperkalemia
Effect on Renal Function
Urine pH?

37. Pathophysiological Basis of Treatment
1. Treat the causative disorder1. Treat the causative disorder
Hyperkalemia
2. Principles for lowering serum K+
：
(1) Intracellular transfer:
G.S. + Insulin (→ activate ADS)
(2) Dialysis
3. Oppose the myocardial toxicity of K+
：
I.V. injection of Calcium and Sodium salt