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Addis Ababa UniversityCollege of Health ScienceDepartment of Medical Physiology Presentation on Potassium Homeostasis and its Renal Handling By Girmay F 10/8/2011 1
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
7. References 10/8/2011 2 Potassium homeostasis and its renal handling
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. 10/8/2011 Potassium homeostasis and its renal handling 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 10/8/2011 4 Potassium homeostasis and its renal handling
Introduction ..cont’d 10/8/2011 5 Potassium homeostasis and its renal handling
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:
10/8/2011 7 Potassium homeostasis and its renal handling
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. 10/8/2011 8 Potassium homeostasis and its renal handling
10/8/2011 9 Potassium homeostasis and its renal handling
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.
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. 10/8/2011 11 Potassium homeostasis and its renal handling
…………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 10/8/2011 12 Potassium homeostasis and its renal handling
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+. 10/8/2011 Potassium homeostasis and its renal handling 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. 10/8/2011 Potassium homeostasis and its renal handling 14
……………cont’d 10/8/2011 Potassium homeostasis and its renal handling 15
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
The activity of Na+,K+-ATPase . The driving force (electrochemical gradient) for movement of K+ across the apical membrane. The permeability of the apical membrane to K+ . 10/8/2011 Potassium homeostasis and its renal handling 16
……..cont’d 10/8/2011 Potassium homeostasis and its renal handling 17
………….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. 10/8/2011 Potassium homeostasis and its renal handling 18
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 10/8/2011 Potassium homeostasis and its renal handling 19
…………….cont’d 10/8/2011 Potassium homeostasis and its renal handling 20
…..cont’d 3.Acid–Base Acidosis decreases K+ secretion. Alkalosis increases K+ secretion Metabolic acidosis may either inhibit or stimulate excretion of K+ . 10/8/2011 Potassium homeostasis and its renal handling 21
………….cont’d 10/8/2011 Potassium homeostasis and its renal handling 22
………….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 10/8/2011 Potassium homeostasis and its renal handling 23
………….Cont’d 10/8/2011 Potassium homeostasis and its renal handling 24
10/8/2011 Potassium homeostasis and its renal handling 25 ……………..Cont’d
6.Clinical correlations 10/8/2011 Potassium homeostasis and its renal handling 26 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
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 .
29 ………..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
30 ……………cont’d Decreased intake of K+ Increased K+ loss Diuretics Metabolic alkalosis Trauma and stress Conn’s diseases Redistribution between ICF and ECF.
31 ………….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.
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 10/8/2011 Potassium homeostasis and its renal handling 32