Potassium Homeostasis Ch4 1

Potassium Homeostasis Ch4 1

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Potassium Homeostasis Ch4



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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+


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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

K+

H2O

H2O

H2O H2O

H2O

H2O

H2O H2O

K+

K+

K+

Na+

Na+

Na+

Na+

Click to see

animation


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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

K+

H2O

H2O

H2O H2O

H2O

H2O

H2O H2O

K+

K+

K+

Na+

Na+ Na+

Na+

Click to see

animation


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Potassium Homeostasis

Potassium is the major intracellular cation

Plasma potassium is about 3.5-5.0 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 50 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.

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.


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Na+ / K+ Pump • Cells pump K+ ions in and Na+ ions out

of the cell by using sodium-potassium

pumps

Na+

Na+

Na+

Na+

K+

K+

K+

K+


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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:-

1. K intake/load

2. Redistribution between

ECF and ICF depend on:

Hormones

Acid base status

3. Output (excretion and loss)

Urine 90%

Gut and Skin 10%


Potassium Homeostasis: 3.5-5.0 mmol/L

ECF [K+] Dependent upon:-

K Intake/Load

Redistribution between ECF and ICF

Output

Excretion & Loss

Urine 90% Gut and Skin 10%

Kidney = Main Regulator of total body K+

Plasma [K+] is a poor indicator of total body K+

Redistribution: ECF and ICF

–Hormones

–Acid base status

–Plasma tonicity

–Plasma [K+]

9 Potassium Homeostasis Ch4

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Regulation of Potassium Balance • 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


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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,



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ELECTROLYTE BALANCE

• Aldosterone, ANP and ADH regulate

sodium levels within the body, while

aldosterone can be said to regulate

potassium

K+

Na+

aldosterone

ADH

ANP


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* 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.


Factors favouring K+ secretion

Increased intra-cellular K+: High K+ Intake

• Stimulates renal cell uptake and secretion of K+.

• Stimulation of aldosterone secretion.

Increased fluid delivery to lumen causes

increased K+ excretion

– Wash out.

• diuretics

• poorly absorbed anions

• osmotic diuresis


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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.


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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

K+

K+

K+

K+

K+

K+ H+

H+

H+

H+

H+ H+

H+ H+

H+

HYPERKALEMIA


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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+

H+

H+

H+

H+ H+

H+

H+

K+

K+ K+

K+ K+

K+

ACIDOSIS


POTASIUM DISTRIBUTION

In 70 kg

Intracellular 98%

3430 meq

K content = 50 meq/kg

Total body K = 3500 meq

Extracellular 2%

70 meq

Plasma

20%

15 meq

Na-K ATPase


Plasma potassium concentration

Potassium

Intake

Intercompartmental

distribution

Potassium

Excretion


HYPOKALAEMIA

(K ion less than 3.5 meq/L)

Causes:

1-Inadequate k intake.

2-Intercompartmental shift of K.

3-Increase k loss.

a. Renal loss

b. Body fluid’s loss

4- Others 21 Potassium Homeostasis Ch4

K+

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Hypokalaemia

* Causes of hypokalaemia (decreased plasma K+ concentration) can be

grouped into:

1. Decreased intake: Include chronic starvation and

postoperative therapy with K+ poor fluids.

2. 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 Ch4

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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

Cariovascular effects are most prominent

Effect on the ECG

Venticular repolarization is prolonged.

ECG changes include

a prominent U wave.


ventricular The T wave represents

repolarization

http://www.cvphysiology.com/Arrhythmias/A006.htm

http://www.cvphysiology.com/Arrhythmias/A006.htm

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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+ K+

Click to view

animation Potassium Homeostasis Ch4

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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

K+

H+

HCO3-


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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-

HCO3-

HCO3-

H+

H+ H+

H+ H+

H+

H+ H+


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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-

HCO3-

HCO3-

HCO3-

H+

H+ H+

H+ H+

H+

H+ H+

K+ K+

K+

K+

K+

K+

K+

K+



Effects of hypokalamia

Cardiovascular

ECG changes

T wave flattening

Prominent U wave

ST segment depresion

Increase P wave amplitude

Prolongation of PR interval

Prominent U - wave

Flat T - wave

Depressed ST - segment

Normal D

ecre

asin

g S

eru

m K

+

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.

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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.


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HYPERKALEMIA

• Normal serum potassium level

(3.5-5 mmol / liter)

– As compared to Na+ (142 mmol / liter)

• Intracellular levels of potassium

(140-150 mmol / liter)

– This high intracellular level is maintained by

active transport by the sodium-potassium pump

K+ Potassium Homeostasis Ch4

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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+


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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

K+

K+

K+

K+

K+

K+ H+

H+

H+

H+

H+ H+

H+ H+

H+

HYPERKALEMIA


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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+

H+

H+

H+

H+ H+

H+

H+

K+

K+ K+

K+ K+

K+

ACIDOSIS


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HYPERKALEMIA • Summarized:

– Hyperkalemia causes acidosis

– Acidosis causes hyperkalemia

HYPERKALEMIA

H+

H+

H+

H+

H+

H+

H+ H+

K+

K+

K+

K+

K+

K+

K+ K+

ACIDOSIS Potassium Homeostasis Ch4

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HYPERKALEMIA • Summarized:

– Hyperkalemia causes acidosis

– Acidosis causes hyperkalemia

HYPERKALEMIA

H+

H+

H+

H+

H+

H+

H+ H+

K+

K+

K+

K+

K+

K+

K+ K+

ACIDOSIS Potassium Homeostasis Ch4

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Hyperkalaemia

Increased plasma K+ concentration

It is the commonest and most serious electrolyte emergency encountered in

clinical practice

1. 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.

2. 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).

3. 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 Ch4

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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.


Hyperkalemia: Disorders of

External Balance

Excessive

K+ intake

Distal tubular

flow

Mineralocorticoid

deficiency

Acute & chronic

renal failure

Distal tubular

dysfunction

Pseudo

hyperkalemia


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.


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http://en.wikipedia.org/wiki/Cardiac_muscle

http://en.wikipedia.org/wiki/Ventricle_(heart)

http://en.wikipedia.org/wiki/Heart

42

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.


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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.


Laboratory assessment of potassium

Proper collection and handling of samples for K analysis is extremely importantbecause there are many causes of artfactual hyperkalemia:

1. The coagulation process releases K from platelets, so that serum K may be 0.1-0.5 mmol/L higher than plasma K concentrations. If the patient’s platelet count is elevated, serum K may be further elevated.

2. If a tourniquet is left on the arm too long during blood collection or if patients excessively clench their fists or otherwise exercise their forearms before venipuncture, cells may release K into the plasma.

The first situation may be avoided by using heparinized tube to prevent clotting of specimen and the second by using proper care in the drawing of blood.

3. storing blood on ice promotes the release of K from cells, whole blood samples for K determinations should be stored at room temp. (never iced) and analyzed promptly or centrifuged to remove cells.

4. If hemolysis occurs after the blood is drawn, K may be falsely elevated-the most common cause of artifactual hyperkalemia.

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Specimens • Serum, heparinised plasma, and urine (24 hr).

• Hemolysis must be avoided because of high K+ content of

erythrocytes

• Urine specimens should be collected over 24-hour period to

eliminate the influence of diurnal variations.

• Potassium is determined electrochemically with an ion-selective

electrode (ISE) or by flame emission spectrophotometry (FES).

Reference intervals

The interval for serum K+ is 3.4 to 5 mmol/L from infancy

throughout life.



Potassium Homeostasis Ch4 1

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