Potassium Homeostasis 5w1o2h

POTASSIUM HOMEOSTASIS AND ETIOLOGY OF HYPO/HYPERKALEMIA

By Dr. Mayuresh

03/05/2012

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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 03/05/2012

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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.

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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 03/05/2012

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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 03/05/2012

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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 imbalance o Changes in osmolarity o Exercise o Cell lysis 03/05/2012

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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. 03/05/2012

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Hormonal control of K+ homeostasis

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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 lysis o 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. 03/05/2012

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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.

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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+ . Potassium homeostasis

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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 Potassium homeostasis

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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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………….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

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………….Cont’d

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……………..Cont’d

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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.

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……………..Cont’d • 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

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……………..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.

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……………..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 Potassium homeostasis

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……………..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 Potassium homeostasis

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……………..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

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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. (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 . 33

……………….cont’d

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………..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.

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………..cont’d • 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.

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………..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 istration 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.

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………..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. Potassium homeostasis

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………..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. Potassium homeostasis

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………..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) Potassium homeostasis

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………….Cont’d 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.

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