Total Body Potassium

Transcription

1 Potassium Kate Driver BMLSc MAACB Immunochemistry Product Manager ANZ PI Diasorin Australia AACB QLD Branch Education Representative Australasian Association of Clinical Biochemists

2 AACB Curriculum

3 AACB questions

4 Total Body Potassium Total body potassium concentration is ~ 3000 mmol Potassium is the major intracellular cation ~ concentration of 150 mmol/l Potassium is tightly regulated in the extracellular fluid at mmol/l

5 Fluid Space Potassium

6 Why is Potassium so important? Potassium is the major intracellular ion and the difference between the ICF/ECF concentrations is responsible for the difference in potential across the cell membrane. This potential is referred to as the Resting Membrane Potential (RMP). Changes in the RMP cause Hyper ( K+) or Hypoexcitability ( K+) of cells and is a significant issue in myocytes where contraction and relaxation cycles are altered (twitch). Clinical sequalae arise mainly due to changes in twitch.

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8 Potassium Homeostasis Major factors in maintaining potassium homeostasis Adequate Dietary Intake Due to compulsory renal and GI loss, dietary intake is important Daily losses are more or less equal to daily dietary intake Intracellular/Extracellular shifts Potassium is the major intracellular cation, but is constantly redistributed. Certain drugs, physiological conditions and acid base balance all contribute to the ICF/ECF concentration of K. Renal regulation Two most important physiological determinants of potassium excretion are the serum aldosterone concentration and the delivery of sodium to the distal nephron.

9 Potassium Homeostasis Intracellular/Extracellular shifts Potassium redistributed between the ECF and ICF can occur quickly and is important in the daily maintenance of ECF eg. during ingestion of K+ Potassium shifts occur in: Alkalosis/Acidosis Insulin and catecholamines (Normal physiology or pathological) Rapid Cellular proliferation disorders Thyrotoxicosis Via the activation of the NaKATPase pump or NaH Transporter Electrolyte Quintet - Potassium - Mitchell L Halperin, Kamel S Kamel

10 Potassium Homeostasis Renal Regulation Renal regulation of potassium is a slower acting mechanism and fine tunes the extracellular concentration Renal Potassium reabsorption/secretion is dependent on the following factors: Amount of Na available for transportation or excretion Relative availability of Hydrogen and Potassium ions in the distal convoluted tubules Ability of the distal convoluted tubules to excrete Hydrogen ions Circulating Concentration of Aldosterone The flow rate of tubular fluid - high flow rate favours transfer of potassium to lumen Clinical Chemistry - William J Marshall, Stephen K Bangert

11 Potassium Homeostasis Renal Regulation

12 Potassium Homeostasis Renal Regulation Aldosterone Harrisons Principles of Internal Medicine - 19th Edition

13 Potassium Homeostasis Renin Angiotensin Aldosterone (RAA) The Renin, Angiotensin, Aldosterone (RAA) system is an important regulator of Na+ and K+ and assessment of this system is an important part of investigating dyskalaemia Aldosterone is produced in response to angiotensin II, but also in response to Hyperkalaemia. These two mechanisms are a selective process to retain NaCl or to promote kaliuresis.

14 Potassium Homeostasis Actions of Aldosterone Electrolyte Quintet - Potassium - Mitchell L Halperin, Kamel S Kamel

15 Potassium Homeostasis RAA system

16 Urine analysis - Investigating Dyskalaemia The investigation of any electrolyte imbalance without an obvious cause will probably require urine analysis. Tests that are immediately useful are K+ Na+ Cl- Osmolality, ph (Calculate anion gap from plasma results) It is important to establish if the nephron s are handling K+ appropriately regardless of the initial presentation. Eg. A patient who has been sweating excessively who displays persistent hypokalaemia after fluid correction may demonstrate inappropriate renal excretion of potassium, suggesting an underlying renal handling issue.

17 Urinary Potassium tests Electrolyte Quintet - Potassium - Mitchell L Halperin, Kamel S Kamel

18 Urine Potassium Testing Trans-Tubular Potassium Gradient (TTKG) The TTKG calculation reflects the conservation or lack there of of Potassium in the CCD. It is useful in identifying the causes of hyperkalaemia or hypokalemia and indirectly assesses the action of mineralocorticoid in the CCD. It is a ratio/index that estimates the amount of potassium in the lumen of the CCD compared to that in peritubular capillaries. The following is the formula for calculating the TTKG: Note that this formula is valid only when Uosm >300 and UNa >25 The validity of this measurement falls on three assumptions: (1) Few solutes are reabsorbed in the medullary collecting duct (MCD) (2) Potassium is neither secreted nor reabsorbed in the MCD (3)The osmolality of the fluid in the terminal CCD is known

19 Urine Potassium Testing Trans-Tubular Potassium Gradient (TTKG) Significant reabsorption or secretion of K in the MCD seldom occurs, except in profound K depletion or excess, respectively. A typical TTKG in a normal person on a normal diet is 8-9. During hyperkalemia or high potassium intake, more potassium should be excreted in the urine and the TTKG should be above 10. Low levels (<7) during hyperkalemia may indicate mineralocorticoid deficiency, especially if accompanied by hyponatremia and high urine Na. During potassium depletion or hypokalemia, the TTKG should fall to less than 3, indicating appropriately reduced urinary excretion of potassium.

20 Hypokalaemia Hypokalaemia - Results in an increase of the RMP, decreasing the excitability Muscle fatigue/weakness Constipation Paralytic Ilieus Hypotonia Depression Confusion Changes to ECG - S,T segment changes Potentiation of Digoxin therapy Arrythmia Inability to concentrate urine - polyuria

21 Hypokalaemia Causes of Hypokalaemia Inadequate Dietary intact Poor diet/alcoholism (Mg def) Parental nutrition Intracellular shifts Alkalosis Insulin therapy Excessive catecholamines Rapid cellular proliferation Increased K excretion Renal Renal failure - using diuretics Acute renal failure with diuresis Excess Mineralcorticoids/Glucocorticoids Primary aldosteronism Secondary aldosteronism Cushings Carbenoxolone - liquorice ingestion Renal tubular acidosis (types 1 and 2) Extrarenal Laxatives/diarrhoea Vomiting/gastric aspiration Sweating Villious Adenoma of the large bowel Subcutaneous fistula Clinical Chemistry - William J Marshall, Stephen K Bangert

22 Hypokalaemia Intracellular Shift During alkalosis, H+ is retained at the kidneys to buffer the excess HCO3 Mechanism Both the H+K+ATPase and H+ATPase both work to retain H+ ions H+K+ATPase results in direct exchange of H+ for K+ H+ only transports H+ the K+ moves to retain electroneutrality (refer back to slide demonstrating channels) Important concept as this is the mechanism for hypokalaemia during protracted vomiting where large amounts of HCL are lost from the gut. The kidneys waste the potassium to retain H+. Pylori stenosis in infants requires rapid diagnosis and treatment Hypokalemic Hypochloremic Metabolic Alkalosis.

23 Hypokalaemia Excess Mineralocorticoid

24 Mechanisms of High mineralocorticoid levels 3. Stimulation by ACTH - ectopic production - tumour 2. High Aldosterone -low renin Primary Aldosteronism 4. Exogenous steroids 1. High Renin, High Aldosterone Secondary Hyperaldosteronism 7. Increased permeability/channel availability for Transportation of Na Electrolyte Quintet - Potassium - Mitchell L Halperin, Kamel S Kamel 5. Fast uptake of Na - increased Lumen negative potential - 6. Inhibition of 11 bhsdh continued action of Cortisol promoting uptake of Na from the lumen

25 Hypokalaemia Renal Tubular Acidosis Characterised by hypokalaemia with a normal anion gap acidosis Type 1: Classical Distal RTA is failure to excrete hydrogen ions Genetic causes Autoimmune - eg. Sorjens or Lupus Type 2: Classical Proximal RTA is failure to absorb HCO3 Faconi s Disease Ifosfamide - chemotherapy Multiple Myeloma Chronic Kidney Rejection Type 4: Hyperkalemic RTA inability to excrete Ammonia (results in Non-anion gap metabolic acidosis) Many drugs in antibiotics, Diuretics, NSAIDs Structurally altered kidney HIV Diabetic Neuropathy Amyloid

26 Sonic Pathology Handbook Evaluation of Hypokalaemia

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28 Hypokalaemia Actions of Diueretics

29 Hyperkalaemia Clinical effects Hyperkalaemia results in a decrease in the RMP, leading to increased excitability of cells Clinical consequences/effects are all about myocardial function sinus bradycardia sinus arrest slow idioventricular rhythms ventricular tachycardia ventricular fibrillation asystole Requires rapid diagnosis and treatment

30 Hyperkalaemia Spurious Haemolysis Delay in separation Cold sample Patient preparation Excess intake Oral - rare - except with diuretics Parental nutrition Blood transfusion - old blood Redistribution Cellular death/damage Catabolic states Systemic acidosis Insulin lack Decreased excretion Renal Potassium sparing diuretics Addisons - not usually pituitary Hyporenemic hypoaldosteronism ACE inhibitors Clinical Chemistry - William J Marshall, Stephen K Bangert

31 Sonic Pathology Handbook Evaluation of Hyperkalaemia

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33 Recommended Reading

34 Useful Links and Sites The Electrolyte Quintet - The Utility of the Transtubular Potassium Gradient in the Evaluation of Hyperkalemia Michael J. Choi* and Fuad N. Ziyadeh *Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; and Departments of Internal Medicine and Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon AACB CPC 2013 Potassium disturbances - interpretation using bicarbonate Andrea Rita Horvath, SEALS Department of Clinical Chemistry Prince of Wales Hospital, Sydney