1. Potassium Homeostasis Ch4

3. ELECTROLYTE BALANCE K+ Na+
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+
Potassium Homeostasis Ch4

4. Potassium Homeostasis Ch4
ELECTROLYTE BALANCE
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. Potassium Homeostasis Ch4
ELECTROLYTE BALANCE
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. Potassium Homeostasis
Potassium Homeostasis Ch3
Potassium Homeostasis
Potassium is the major intracellular cation
Plasma potassium is about mmol/L.
In tissue cells, its average concentration is 150 mmol/L.
High intracellular concentrations are maintained because K+ diffuses only slowly outward through the cell membrane, whereas the Na+-K+ ATPase pump continually transports K+ into the cells.
The body requirement for K+ is satisfied by a dietary intake of to 150 mmol/day.
Potassium absorbed from GIT  is rapidly distributed; a small amount is taken up by cells,
but most is excreted by the kidneys.

7. The amount of K+ excreted in urine varies relative to intake.
Potassium filtered through the golmeruli is almost completely reabsorbed in the proximal tubules and then secreted in the distal tubule.
The amount of K+ excreted in urine varies relative to intake.
The renal secretory system respond immediately to K+ loading with an increase in K+ output
Intracellular stores of K+ maintain the K+ concentration in the extracellular compartment at a near normal level until K+ depletion is severe.
Potassium Homeostasis Ch3

8. 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+
Potassium Homeostasis Ch4

9. Potassium homeostasis
Kidney is the main regulator of total body K+. It depends on GFR
Plasma [K+] is a poor indicator of total body K+
ECF [K+] Dependent upon:-
K intake/load
Redistribution between ECF and ICF depend on:
Hormones
Acid base status
3. Output (excretion and loss)
Urine 90%
Gut and Skin 10%
Potassium Homeostasis Ch3

10. POTASIUM DISTRIBUTION
K content = 50 meq/kg
In 70 kg
Total body K = 3500 meq
Potassium Homeostasis Ch3

11. Regulation of Potassium Balance
Potassium Homeostasis Ch3
Relative ICF-ECF potassium ion concentration  affects a cell’s resting membrane potential
Excessive ECF potassium decreases membrane potential
Too little K+ causes hyperpolarization and nonresponsiveness
Hyperkalemia and hypokalemia can:
Disrupt electrical conduction in the heart
Lead to sudden death
Hydrogen ions shift in and out of cells
Leads to corresponding shifts potassium in the opposite direction
Interferes with activity of excitable cells
Cellular uptake of potassium is stimulated by insulin

12. Potassium Homeostasis
Urinary potassium excretion depends upon several factors:
The amount of sodium available for reabsorption in the distal convoluted tubules and collecting ducts: The active reabsorption of sodium  generates a membrane potential which is ----> neutralised by the movement of potassium and hydrogen ions from the tubular cells into the lumen.
The circulating concentration of aldosterone.
Aldosterone stimulates potassium excretion both :
directly, by increasing active potassium secretion in distal part of the distal convoluted tubules.
Indirectly, by increasing the active reabsorption of sodium in the distal convoluted tubules and the collecting ducts,
Potassium Homeostasis Ch3

13. ELECTROLYTE BALANCE Na+ K+
Aldosterone, ANP and ADH regulate sodium levels within the body, while aldosterone can be said to regulate potassium
Na+
ADH
ANP K+
aldosterone
Potassium Homeostasis Ch4

14. Potassium Homeostasis Ch3

15. Potassium Homeostasis
Disturbances of K+ homeostasis has serious consequences.
Decrease of extracellular K+ is characterized by:
Clinical features related primarily to disturbances of neuromuscular function;  muscular weakness, constipation and paralytic ileus (Non mechanical obstruction of the bowel from paralysis of the bowel)
Irritability and paralysis
Fast heart rate and specific conduction effects that are apparent on electrocardiographic examination
Cardiac arrhythmias.
Plasma K+ levels less than 3.0 mmol/L are associated with marked neuromuscular symptoms and are evidence of a critical degree of intracellular depletion.
Potassium Homeostasis Ch3

16. Factors favouring K+ secretion
The relative availability of hydrogen and potassium ions in the cells of the distal convoluted tubules and collecting ducts.
Since both hydrogen and potassium ions can neutralise the membrane potential generated by active sodium reabsorption  There is close relationship between potassium and hydrogen ion homeostasis.
in a state of acidosis, hydrogen ions will tend to be secreted in preference to potassium;
in alkalosis, fewer hydrogen ions will be available for excretion and there will be an increase in potassium excretion.
Thus, there is a tendency to hyperkalaemia in acidosis and to hypokalaemia in alkalosis.
The relationship between the excretion of hydrogen and potassium ions also explains why potassium depletion tends to produce alkalosis If there is insufficient potassium available for excretion as sodium is reabsorbed, then the excretion of hydrogen ions will be increased.
Potassium Homeostasis Ch3

17. 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+
Potassium Homeostasis Ch4

18. 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+
Potassium Homeostasis Ch4

19. K+ HYPOKALAEMIA Causes: (K ion less than 3.5 meq/L)
1-Inadequate k intake.
2-Intercompartmental shift of K.
3-Increase k loss.
a. Renal loss
b. Body fluid’s loss
4- Others
Potassium Homeostasis Ch3

20. Hypokalaemia
Causes of hypokalaemia (decreased plasma K+ concentration) can be grouped into:
Decreased intake: Include chronic starvation and postoperative therapy with K+ poor fluids.
Redistribution of extracellular K+ into intracellular fluid: When insulin therapy of diabetic hyperglycemia starts  cellular uptake of glucose is accompanied by uptake of K+ and water. Hypokalaemia
Hypokalaemia is a feature also of alkalosis, …….where K+ moves from extracellular fluid into the cell as H+ moves in the opposite direction; thus, all other things being equal, alkalosis itself causes hypokalaemia.
3. Renal loss of K+ can also be caused by the use of thiazides, loop diuretics, and chronic anhydrase inhibitors
Renal losses  renal tubular acidosis, primary or secondary aldosteronism, or Cushing’s syndrome
Potassium Homeostasis Ch3

21. 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+
Potassium Homeostasis Ch4

22. H+ HCO3- ALKALOSIS K+ 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-
Potassium Homeostasis Ch4

23. 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+
Potassium Homeostasis Ch4

24. 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+
Potassium Homeostasis Ch4

25. The effect of hypokalemia
Hypokalaemia
4. Increased loss of K+ rich body fluids.
Gastrointestinal loss in the case of vomiting, diarrhoea.
5. Other conditions may be associated with low serum K+ levels include cirrhosis, Conn’s syndrome, and digitalis toxicity.
The effect of hypokalemia
Most of the patients are asymptomatic until K level below 3 meq/L
Cardiovascular effects are most prominent
Effect on the ECG
Venticular repolarization is prolonged ECG changes include
a prominent U wave.
The T wave represents ventricular repolarization
Potassium Homeostasis Ch3

26. Effects of hypokalamia
As K+ level decreases, ectopic impulses form and conduction disturbances increase. Atrial and venticular arrhythmias may develop.
As ectopy becomes more frequent, the patient is at risk for potentially fatal arrythmias.
Prominent U -
wave
Flat T
Depressed ST
segment
Normal
Decreasing Serum K +
Cardiovascular
ECG changes
T wave flattening
Prominent U wave
ST segment depression
Increase P wave amplitude
Prolongation of PR interval
Potassium Homeostasis Ch3

27. Potassium Homeostasis Ch4

28. Potassium Homeostasis Ch3

29. Treatment Is not urgent UNLESS complications
Oral is preferable to IV therapy
The K+ shortage is almost entirely from the ICF and since administered potassium first enters the ECF, replacement must be undertaken with care, particularly when intravenous route is used When treating hypokalaemia, plasma concentrations should be monitored during treatment.
If unusually large amounts of potassium are necessary and particularly if there is impaired renal function, electrocardiograph (ECG) monitoring is useful since= characteristic changes in the wave form occur with changing plasma potassium concentrations.
Potassium Homeostasis Ch3

30. Potassium Homeostasis Ch3

31. HYPERKALEMIA K+ Normal serum potassium level (3.5-5 mmol / liter)
As compared to Na+ (142 mmol / liter)
Intracellular levels of potassium ( mmol / liter)
This high intracellular level is maintained by active transport by the sodium-potassium pump K+
Potassium Homeostasis Ch4

32. 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+
Potassium Homeostasis Ch4

33. 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+
Potassium Homeostasis Ch4

34. 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+
Potassium Homeostasis Ch4

35. HYPERKALEMIA Summarized: Hyperkalemia causes acidosis
Acidosis causes hyperkalemia
HYPERKALEMIA H+ K+
ACIDOSIS
Potassium Homeostasis Ch4

36. HYPERKALEMIA Summarized: Hyperkalemia causes acidosis
Acidosis causes hyperkalemia
HYPERKALEMIA H+ K+
ACIDOSIS
Potassium Homeostasis Ch4

37. Hyperkalaemia Increased plasma K+ concentration
It is the commonest and most serious electrolyte emergency encountered in clinical practice
May be precipitated by intravenous infusion of K+ at high rate.
Over treatment is unlikely to produce hyperkalaemia so long as renal function is normal, because excess K+ is readily excreted in the urine.
Transfer of intracellular K+ into extracellular fluid may occur in cases of dehydration and shock with tissue hypoxia, diabetic ketoacidosis, thrombocytosis, and in leukocytosis (damaged cells).
Decreased excretion of K+ in acute renal failure or end-stage renal failure with oliguria or anuria and acidosis is a common cause of hyperkalaemia.
Potassium Homeostasis Ch3

38. Hyperkalaemia The hyperkalaemia in acidosis is the result of
K+ moving from intracellular fluids into  the plasma as H+ moves ….into the cells from extracellular fluid.
Hyperkalaemia occurs along with Na+ depletion in adrenocortical insufficiency, because in the absence of adequate amounts of aldosterone and other mineralocorticoids,…. diminished Na+ reabsorption and Na+_K+ exchange and decreased K+ secretion lead to retention of K+.
Other causes of hyperkalaemia include administration of diuretics that block distal tubular K+ secretion (e.g., amiloride, triamterene and spironolactone)
Artifactually hyperkalaemia (Pseudohyperkalemia) Movement of K+ out of cells during or after blood drawing  is commonly seen if hemolysis has occurred in collecting the sample, or there has been a delay in separating the serum from the clotted blood sample.
Potassium Homeostasis Ch3

39. Hyperkalemia: Disorders of External Balance
Excessive
K+ intake
Acute & chronic
renal failure
Pseudo
hyperkalemia
 Distal tubular
flow
Distal tubular
dysfunction
Mineralocorticoid
deficiency
Potassium Homeostasis Ch3

40. It lowers the resting membrane potential
Clinical features
Hyperkalaemia can kill without warning
It lowers the resting membrane potential
Shortens the cardiac action potential and
Increases the speed of repolarization.
Cardiac arrest with ventricular fibrillation
(condition in which there is
uncoordinated contraction of the
cardiac muscle of the ventricles
in the heart, making them tremble
rather than contract properly)
may be the
first sign of hyperkalaemia.
Characteristic ECG changes precede the onset of ventricular fibrillation.
Potassium Homeostasis Ch3

41. The effect of hyperkalemia on ECG
Excess K+ alters the heart’s electrical activity and leads to depressed conduction.
Among the earliest signs is a tall, tented T wave.
AV or venticular block may develop.
If left untreated, sever hyperkalemia causing a P wave to disappear and the QRS complex to widen.
Potassium Homeostasis Ch3

42. Treatment is URGENT if K > 7.0 mmol/L
Management
Treatment is URGENT if K > 7.0 mmol/L
Intravenous calcium gluconate (10 ml of a 10% solution, given over one minute and repeated as necessary) affords some degree of immediate protection to the myocardium by antagonizing the effect of hyperkalaemia on myocardial excitability.
Intravenous glucose and insulin promotes intracellular potassium uptake.
Salbutamol, which  activates Na+-K+ ATPase, has similar effect.
In the acidic patient, hyperkalaemia can be controlled temporarily by bicarbonate infusion.
When there is slow rise in the plasma potassium this may be stopped or reversed by oral administration of a cation exchange resin such as Resonium A.
ECG monitoring can be valuable in patients with hyperkalaemia. Changes in the plasma potassium concentration are reflected by changes in the ECG wave form more rapidly than could be determined by biochemical measurements.
Potassium Homeostasis Ch3

43. Potassium Homeostasis Ch3