potassium homeostasis and its renal handling

04/08/2023

Addis Ababa UniversityCollege of Health Science

Department of Medical Physiology

Presentation on Potassium Homeostasis and its Renal Handling

By Girmay F

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04/08/2023 Potassium homeostasis and its renal handling

presentation out line

1.Objectives

2. Introduction

3. Physiological roles of potassium

4. Potassium homeostasis

4.1 Hormonal control of K+ homeostasis

4.2 Miscellaneous factors

5.Renal handling of potassium

5.1 K+ secretion by the principal cells

5.2 regulation of K+ excretion

6. Clinical correlations Hyperkalemia Hypokalemia

7. References

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1.Objectives

At the end of this presentation students will able to:-• Mention the major physiological role of potassium.• Explain the main mechanisms of potassium

homeostasis.• Elaborate renal handling of potassium.• Identify factors that affect potassium excretion.• List the homeostatic disturbance of potassium.

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2.Introduction

• The total body stores are approximately 50 to 55 meq/kg.

• The main intracellular cation.• 98% located ICF,150 meq/L.• 2% located ECF,4meq/L.• 90% readily exchangeable• 10% non exchangeable• Amount ingested = up to 100meq/d = 2.5 gm/d• 92% urinary excretion• 8% GIT excretion

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Introduction ..cont’d

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3.Physiological roles of potassium

1.Roles of intracellular K+:• Cellular volume maintenance• Intracellular pH regulation• Cell enzyme function• DNA/protein synthesis• Cell growth

2.Roles of transcellular K+ ratio: Resting cell membrane potential Neuromuscular excitability Cardiac pacemaker rhythmicity

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4.Potassium homeostasis

1.Internal balance ( ICF and ECF K+ distribution)

2. External balance ( Renal excretion of K+)

1.Internal balance

Physiological and pathological conditions can influence this process.

o Hormones like insulin , catecholamines ,aldosterone o Acid base imbalanceo Changes in osmolarityo Exerciseo Cell lysis

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4.1 Hormonal control of K+ homeostasis

• Insulin and beta 2agonsists shifts K+ to the cell, by increase the activity of Na+,K+-ATPase, the 1Na+-1K+-2Cl- symporter, and the Na+-Cl- symporter.

• Aldosterone acting on uptake of K+ into cells and altering urinary K+ excretion.

• Stimulation of α-adrenoceptors releases K+ from cells, especially in the liver.

• insulin and epinephrine act within a few minutes, aldosterone requires about an hour to stimulate uptake of K+ into cells.

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Hormonal control of K+ homeostasis


4.2 Miscellaneous factors …..

1.Acid base imbalance • Metabolic acidosis increases the plasma [K+].

• Metabolic alkalosis decreases the plasma [K+] .2.Plasma osmolarity Hyperosmolarity associated with hyperkalemia . A fall in plasma osmolality has the opposite effect.

3.Cell lysiso Crush injury,burns,tumor lysis syndrome, rhabdomyolysis

associated with destruction of cells and release of K+ to ECF.

4. Exercise

vigorous exercise, plasma [K+] may increase by 2.0 mEq/L.

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…………Cont’d

• Physiological: Keep Plasma [K+] Constant

Epinephrine

Insulin

Aldosterone• Pathophysiological: Displace Plasma [K+] from Normal

Acid-base balance

Plasma osmolality

Cell lysis

Exercise• Drugs That Induce Hyperkalemia Dietary K+ supplements

ACE inhibitors

K+-sparing diuretics

Heparin

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5.Renal handling of potassium

• The PCT reabsorbs about 67% of the filtered K+ under most conditions by K+-H+ exchanger and K+-Cl- symport.

• 20% of the filtered K+ is reabsorbed by the TALH.

• The distal tubule and collecting duct are able to reabsorb or secrete K+.

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……….cont’d

• The rate of K+ reabsorption or secretion by the distal tubule and collecting duct depends on a variety of hormones and factors.

• Most of the daily variations in potassium excretion is caused by changes in potassium secretion in the distal and cortical collecting tubules.

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……………cont’d

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5.1 K+ SECRETION BY PRINCIPAL CELLS

• Secretion from blood into the tubule lumen is a two-step process:

1.uptake of K+ from blood across the basolateral membrane by Na+,K+-ATPase and

2. diffusion of K+ from the cell into tubular fluid via K+ channels.

Three major factors that control the rate of K+ secretion by the distal tubule and the collecting duct

A. The activity of Na+,K+-ATPase .

B. The driving force (electrochemical gradient) for movement of K+ across the apical membrane.

C. The permeability of the apical membrane to K+ .

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……..cont’d

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………….Cont’d

• Intercalated cells reabsorb K+ via an H+,K+-ATPase transport mechanism located in the apical membrane .

• This transporter mediates uptake of K+ in exchange for H+. This phenomena only occur during low potassium dietary intake.

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5.2 REGULATION OF K+ SECRETION ..

1.Dietary K+ • A diet high in K+ increases K+ secretion .a diet low in K+

decreases K+ secretions.

2. Aldosterone• Increases K+ secretion.• Hyperaldosteronism increases K+ secretion and causes

hypokalemia .• Hypoaldestronism decreases K+ secretion and causes

hyperkalemia • MOA

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…………….cont’d

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…..cont’d

3.Acid–Base • Acidosis decreases K+ secretion.• Alkalosis increases K+ secretion • Metabolic acidosis may either inhibit or stimulate

excretion of K+ .

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………….cont’d

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4.Flow of Tubular Fluid • A rise in the flow of tubular fluid (e.g., with diuretic treatment,

ECF volume expansion) stimulates secretion of K+ within minutes.

• A fall (e.g., ECF volume contraction caused by hemorrhage, severe vomiting, or diarrhea) reduces secretion of K+ by the distal tubule and collecting duct.

• MOA

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……………..Cont’d


6.Clinical correlations

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1.Hyperkalemia• plasma concentration of K+ > 5.5 mEq / L

Causes

a. Reduced excretion- acute renal failure

-potassium –sparing diuretics.

b. Increased intake or release .

-potassium supplements

- Rhabdomyolysis

-Hemolytic sates


………………..cont’d

c. Trans cellular shifts of potassium Acidosis Beta blockers ,cell destruction Insulin deficiency Addison’s disease Cell lysis

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……………….cont’d

Clinical manifestation • Early – hyperactive muscles , paresthesia• Late - Muscle weakness, flaccid paralysis• Dysrhythmias• Bradycardia , heart block, cardiac arrest

• Change in ECG pattern Appearance of tall, thin T waves on the ECG. prolong the PR interval, depress the ST segment Lengthen the QRS interval of the ECG. As plasma [K+] approaches 10 mEq/L, the P wave

disappears, the QRS interval broadens, the ECG appears as a sine wave, and the ventricles fibrillate .

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………..cont’d

2.Hypokalemia• Serum K+ < 3.5 mEq /L

Causes • In diabetic patient – Insulin gets K+ into cell– Ketoacidosis – H+ replaces K+, which is lost in urine

• β – adrenergic drugs or epinephrine

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……………cont’d

• Decreased intake of K+

• Increased K+ loss– Diuretics– Metabolic alkalosis – Trauma and stress– Conn’s diseases – Redistribution between ICF and ECF.

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Clinical manifestation • Neuromuscular disorders– Weakness, flaccid paralysis, respiratory arrest, constipation

• Dysrhythmias• Cardiac arrest • Prolongs the QT interval, inverts the T wave, and lowers the

ST segment of the ECG.


7.References

• Berne and levy physiology, sixth edition Bruce M.Koeppen, Bruce A. Stanton

• Guyton and Hall Textbook of Medical Physiology, 12th Edition.

• Human physiology: The Basis of Medicine, 3rd Edition.

• Institutional websites

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potassium homeostasis and its renal handling

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