Potassium Homeostasis

By Dr. Mayuresh

03/05/2012 1

POTASSIUM HOMEOSTASISAND ETIOLOGY OF

HYPO/HYPERKALEMIA

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 factors5.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

03/05/2012 2Potassium homeostasis

1.Objectives

At the end of this presentation we 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.

03/05/2012 Potassium homeostasis 3

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


Introduction ..cont’d


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


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


4.1 Hormonal control of K+ homeostasis

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



10

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.


…………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

12Potassium homeostasis

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+.

Potassium homeostasis 13

……….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.


……………cont’d


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+ .


……..cont’d


………….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.


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


…………….cont’d


…..cont’d

3.Acid–Base

• Acidosis decreases K+ secretion.

• Alkalosis increases K+ secretion

• Metabolic acidosis may either inhibit or stimulate excretion of K+ .


………….cont’d



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





……………..Cont’d

04/11/23 Potassium homeostasis and its renal handling 26

6.Clinical correlations


1.Hyperkalemia

• plasma concentration of K+ > 5.5 mEq / L

Causes

There are usually several simultaneous contributing factors, including increased K intake, drugs that impair renal K excretion, and acute or chronic kidney disease. It can also occur in metabolic acidosis as in diabetic ketoacidosis.

• The most common cause of increased serum K concentration is probably pseudohyperkalemia caused by hemolysis of RBCs in the blood sample.

• Normal kidneys eventually excrete K loads, so sustained, nonartifactual hyperkalemia usually implies diminished renal K excretion. However, other factors usually contribute. They can include increased K intake, increased K release from cells, or both


……………..Cont’d

• Hyperkalemia due to total body K excess is particularly common in oliguric states (especially acute renal failure) and with rhabdomyolysis, burns, bleeding into soft tissue or the GI tract, and adrenal insufficiency.

• In chronic renal failure, hyperkalemia is uncommon until the GFR falls to < 10 to 15 mL/min unless dietary or IV K intake is excessive.


……………..Cont’d

• Factors Contributing to Hyperkalemia• Examples• Increased K intake (usually iatrogenic)• Dietary• Oral K supplements• Blood transfusions• IV fluids with supplemental K• K citrate solutions• K-containing drugs (eg,penicillin G)• TPN


……………..Cont’d

• Increased K movement out of cells• β-Blockers• Digoxin toxicity• Acute tumor lysis• Acute intravascular hemolysis• Bleeding into soft tissues or GI tract• Burns• Rhabdomyolysis• Diabetes mellitus• Fasting• Hyperkalemic familial periodic paralysis (rare)• Exercise• Metabolic acidosis


……………..Cont’d

• Decreased K excretion• Drugs• ACE inhibitors• Angiotensin II receptor

blockers• Direct renin inhibitor

(aliskiren)• Cyclosporine andtacrolimus• Heparin• K-sparing diuretics• Lithium• NSAIDs• Trimethoprim

• Hypoaldosteronism• Adrenal insufficiency• Kidney disorders• Acute renal failure• Chronic kidney disease• Obstruction• Renal tubular acidosis, type IV• Other• Decreased effective circulating

volume


……………..Cont’d

33

……………….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. (5.5-6.5 meq/l) prolong the PR interval, depress the ST segment (6.5-7.5 meq/l) Lengthen the QRS interval of the ECG. (7-8 meq/l) As plasma [K+] approaches 10 mEq/L, the P wave disappears, the QRS

interval broadens, the ECG appears as a sine wave, followed by ventricular fibrillation .


……………….cont’d


……………….cont’d


……………….cont’d


Potassium homeostasis and its renal handling 38

39

………..cont’d

2.Hypokalemia

• Serum K+ < 3.5 mEq /L

Causes

• Hypokalemia can be caused by decreased intake of K but is usually caused by excessive losses of K in the urine or from the GI tract.

• GI tract losses• Abnormal GI K losses occur in all of the following:• Chronic diarrhea, including chronic laxative abuse and bowel

diversion• Clay (bentonite) ingestion, which binds K and greatly decreases

absorption• Vomiting• Protracted gastric suction (which removes volume and HCl, causing

the kidneys to excrete HCO3 and, to electrically balance lost HCO3, K)

• Rarely, villous adenoma of the colon, • concomitant renal K losses due to metabolic alkalosis and

stimulation of aldosterone due to volume depletion.


………..cont’d

• Intracellular shift• The transcellular shift of K into cells may also cause hypokalemia. This

shift can occur in any of the following:• Glycogenesis during TPN or enteral hyperalimentation (stimulating insulin

release)• After administration of insulin• Particularly with β2-agonists (eg, albuterol, terbutaline), which may

increase cellular K uptake• Thyrotoxicosis (occasionally) due to excessive β-sympathetic stimulation

(hypokalemic thyrotoxic periodic paralysis)• Familial periodic paralysis, a rare autosomal dominant disorder

characterized by transient episodes of profound hypokalemia thought to be due to sudden abnormal shifts of K into cells. Episodes frequently involve varying degrees of paralysis. They are typically precipitated by a large carbohydrate meal or strenuous exercise.


………..cont’d

• Renal losses• Excess mineralocorticoid effect can directly increase K secretion by

the distal nephrons and occurs in any of the following:• Cushing's syndrome, • Primary hyperaldosteronism, • Rare renin-secreting tumors, • Glucocorticoid-remediable aldosteronism, and• Congenital adrenal hyperplasia.• Ingestion of substances such as glycyrrhizin (present in natural

licorice and used in the manufacture of chewing tobacco), inhibit(11β-HSDH), preventing the conversion of cortisol, which has some mineralocorticoid activity, to cortisone, which does not, resulting in high circulating concentrations of cortisol and renal K wasting.


………..cont’d

• Bartter and Gitelman's syndromes, characterized by renal K and Na wasting, excessive production of renin and aldosterone, and normotension.

• Liddle syndrome) is a rare autosomal dominant disorder characterized by severe hypertension and hypokalemia

• Renal K wasting can also be caused by numerous congenital and acquired renal tubular diseases, such as the renal tubular acidoses and Fanconi syndrome.

• Hypomagnesemia is a common correlate of hypokalemia. Much of this is attributable to common underlying causes (ie, diuretics, diarrhea), but hypomagnesemia itself may also result in increased renal K losses.


………..cont’d

• Drugs• Diuretics are by far the most commonly used drugs that cause hypokalemia. K-wasting diuretics that block Na reabsorption proximal to the distal nephron

include• Thiazides• Loop diuretics• Osmotic diuretics• By inducing diarrhea, laxatives, especially when abused, can cause hypokalemia.

• Other drugs that can cause hypokalemia include• Amphotericin B• Antipseudomonal penicillins (eg, carbenicillin)• Penicillin in high doses• Theophylline intoxication (both acute and chronic)


………..cont’d

45

………….Cont’dClinical 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.


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Potassium Homeostasis