potassium homeostasis - lisa bailey

8/12/2019 Potassium Homeostasis - Lisa Bailey

1/40

Potassium

Homeostasis, Disorders & Management


2/40

Introduction

Fluid spaces:

Intracellular Fluid (ICF)

Extracellular Fluid (ECF)

- Intravascular space (plasma volume)

- Interstitial space (lymph)

- Transcellular fluid (pleural, pericardal, CSF,

gastrointestinal)


3/40

Body Fluid Distribution

Infant 1

year

Adult Male Adult

Female

Weight (Kg) 7 70 60

Total Body

Water (L)

4.9 42 30

ICF (L) 3.15 28 18

ECF (L) 1.75 14 12

Intravascular

(L)

0.35 2.8 2.4


4/40

Molal Concentration of Electrolytes In Body

Fluid Spaces

Electrolyte ECF (mmol/kg) ICF (mmol/kg)

Sodium 152 10

Potassium 4.3 160

Calcium 2.7 1.0

Magnesium 1.1 13

Chloride 109 10Bicarbonate 29 10

Phosphate 1.5 50


5/40

Fluid composition of extrarenal fluids

Sodium

(mmol/L)

Potassium

(mmol/L)

Chloride

(mmol/L)

Bicarbonate

(mmol/L)

Gastric

Juice

20-70 5-15 80-160 0

PancreaticJuice

140 6-9 110-130 25-45

Bile 130-165 3-12 90-120 30

Ileal fluid 105-144 6-29 42-60 50-70

Stool water 32-40 75-90 12-18 30-40

Sweat 5-80 5-15 5-70 -


6/40

Extracellular & Intracellular Potassium

Pathology Harmonisation Reference Range

= 3.55.3 mmol/L (serum)

Physiological control:- total body content

- distribution between ECF and ICF

Significant losses or increases in K+ alter membrane

potential, increased with K+ depletion and decreased

with excess.


7/40

Potassium Homeostasis


8/40

Factors influencing distribution of

Potassium

Decrease plasma potassium:

- insulin

- catecholamines -adrenergic

- alkalosis

Increase plasma potassium:

- hypertonicity- acidosis

- catecholamineadrenergic


9/40


10/40

Renal Control of Potassium Output

Ann Inter Med 2009, Vol 50, Number 9 pg 619-626


11/40

Aldosterone and potassium

homeostasis


12/40

Renal Control

Extracellular K+ balance occurs mainly in the kidney

(95% in proximal tubule)

Predominant control is in the distal tubule

Hypokalaemia (reduced renal excretion) Acidosis (preferential excretion of H+)

Aldosterone (high K+ stimulates aldo production)

Obligatory losses of 10-20 mmol/24hrs (renal)

Obligatory losses of 20 mmol/24hrs (extrarenal)


13/40

Extrarenal

Evidence of potassium control in the colon

Most reabsorbed in small intestine


14/40

Hypokalaemia

Signs & Symptoms:

- Cardiovascular

- ECG changes (depresed ST, inverted T waves,

prominent U waves)

- Arrhythmias, myocardial necrosis (extreme)

- Neuromuscular

- Weakness,pain,tenderness, cramps, rhabdomyolysis

- Neuropsychiatric- Lethargy, apathy, depression,confusion


15/40

ECG pattern in Hypokalaemia

Normal ECG pattern


16/40

Hypokalaemia

Signs & Symptoms:

- Renal

- Polyuria, sodium retention

- Gastrointestinal- Constipation, decreased gastric acid secretion


17/40

Causes of hypokalaemia

Redistribution

in vitro redistribution

in vivo redistribution

Extrarenal

inadequate intake

increased loss

Renal

renal hypokalaemia acidosis

renal hypokalaemia alkalosis with normotension renal hypokalaemic alkalosis with hypertension

renal hypokalaemia without specific acid-base disorder


18/40

Causes of hypokalaemia

Redistribution

In vitro

Uptake by white cells, heat,

In vivo Alkalosis, insulin, beta adrenergic agonists, chemicals

Hypokalaemic periodic paralysis


19/40

Hypokalaemic Periodic Paralysis

Familial hypokalaemic periodic paralysis (FHPP)

-AD, caucasion, M:F 3:1,- flaccid paralysis on limbs & trunk

- attacks can last for up to 24 hrs

- cardiac arrhythmias may also be present

- attacks can be provoked by exercise, high CHO diet,hypothermia, high sodium intake

- mutation in the skeletal muscle voltage-gated calcium channel-1 subunit

Hypokalaemic periodic paralysis with thyrotoxicosis

(HPP)- Chinese or Japanese population, M:F 20:1

- - clinical presentation identical to FHPP but condition remitswhen patient becomes euthyroid


20/40

Extrarenal Causes of Hypokalaemia

Evident from clinical history

Urine potassium (


21/40

Extrarenal Causes of Hypokalaemia

Inadequate intake

Anorexia

Fluid replacement without potassium

Rapid cell synthesis (anaemia, rapid increasein reticulocyctes)

Increased loss

Excessive sweating (sweat 10 mmol/L) Gastrointestinal (stool water 90 mmol/L)


22/40

Investigation of hypokalaemia

Hypokalaemia

Spurious Redistribution

Potassium depletion

Extrarenal loss Renal loss(urine K10 mmol/L)

normal metabolic metabolic metabolic variable

acid base acidosis acidosis alkalosis acid/base

poor intake diarrhoea RTA (type 1&2) magnesium depletion

anorexia fistula carbonic anhydrase antibiotics

sweating villous adenoma inhibitor cisplatin

cell synthesis urinary tract diversion aminoglycosideslaxative abuse DKA leukaemia

diuretic phase ARF


23/40

Investigation of hypokalaemia


24/40

Causes of hypokalaemia Renal Losses

Hypokalaemic acidosis

RTA type 1 and type 2

Acetazolamide (carbonic anhydrase inhibitor)

induced RTA

Urinary tract diversion (into colon)

Hypokalaemic with specicific acid/base abnormaility

Drugs, diuretic phase ARF, Mg depletion


25/40

Causes of hypokalaemiaRenal Losses

Renal hypokalamic alkalosis

Low urine chloride

Vomiting/gastric loss

Diuretic that act on loop of Henle (frusemide) ordistal collecting ducts (thiazides)

Chloride losing diarrhoea (congenital, Zollinger-Ellison syndrome)

Cystic fibrosis

High Urine chloride Hypertensive

Normotensive


26/40


Metabolic alkalosis Normotensive

Bartters syndrome Hyperreninaemic hyperaldosterism

Usually presents in childhood

Mutations of genes encoding proteins that transport ionsacross renal cells in the thick ascending limbof thenephron

Gitelmans syndrome hypochloremic metabolic alkalosis, hypokalemia, and

hypocalciuria. Hypomagnesemiais present in many but not

all cases inactivating mutations in the SLC12A3gene resulting in a

loss of function of the encoded thiazide-sensitive sodium-chloride co-transporter(NCCT). This cell membraneprotein participates in the control of ion homeostasisat thedistal convoluted tubuleportion of the nephron.
http://en.wikipedia.org/wiki/Thick_ascending_limb_of_loop_of_Henlehttp://en.wikipedia.org/wiki/Thick_ascending_limb_of_loop_of_Henlehttp://en.wikipedia.org/wiki/Metabolic_alkalosishttp://en.wikipedia.org/wiki/Hypokalemiahttp://en.wikipedia.org/wiki/Hypocalciuriahttp://en.wikipedia.org/wiki/Hypomagnesemiahttp://en.wikipedia.org/wiki/SLC12A3http://en.wikipedia.org/wiki/Thiazidehttp://en.wikipedia.org/wiki/Sodium-chloride_symporterhttp://en.wikipedia.org/wiki/Sodium-chloride_symporterhttp://en.wikipedia.org/wiki/Homeostasishttp://en.wikipedia.org/wiki/Distal_convoluted_tubulehttp://en.wikipedia.org/wiki/Nephronhttp://en.wikipedia.org/wiki/Nephronhttp://en.wikipedia.org/wiki/Distal_convoluted_tubulehttp://en.wikipedia.org/wiki/Homeostasishttp://en.wikipedia.org/wiki/Sodium-chloride_symporterhttp://en.wikipedia.org/wiki/Sodium-chloride_symporterhttp://en.wikipedia.org/wiki/Sodium-chloride_symporterhttp://en.wikipedia.org/wiki/Sodium-chloride_symporterhttp://en.wikipedia.org/wiki/Sodium-chloride_symporterhttp://en.wikipedia.org/wiki/Thiazidehttp://en.wikipedia.org/wiki/SLC12A3http://en.wikipedia.org/wiki/Hypomagnesemiahttp://en.wikipedia.org/wiki/Hypocalciuriahttp://en.wikipedia.org/wiki/Hypokalemiahttp://en.wikipedia.org/wiki/Metabolic_alkalosishttp://en.wikipedia.org/wiki/Thick_ascending_limb_of_loop_of_Henle


27/40


Metabolic alkalosis

Hypertensive

Measure renin/aldo

See chart


28/40



29/40

Management

Medics guidelines

Every 1 mmol below 4 mmol/l = deficit of 300 mmol

Oral/IV - Remember 40 mmol/day will only replace

obligatory losses

K+ >2.5 mmol/L give oral max 80 mmol/day

K+


30/40


31/40

ECG Hyperkalaemia

Normal ECG


32/40

Causes of hyperkalaemia

Redistribution

in vitro redistribution

in vivo redistribution

Increased intake

Decreased Output

Syndromes of hypoaldosteronism


33/40


Redistribution

In vitro

haemolysis, release from WBC & platelets, cold

In vivo

Acidosis

Insulin deficiency with high glucose (DKA)

Drugs (beta-blockers)

Acute tissue damage

Hyperkalaemic periodic paralysis


34/40

Hyperkalaemic Periodic Paralysis

(HYPP)

Rare AD condition present with muscle weakness

and K+ up to 8.0 mmol/L

Attacks variable, provoked by high K+ intake,

glucocorticoids, hypothermia & recovery after

exercise

ECG show tall T waves but cardiac arrhythmias are

rare

Disorder due to mutations in skeletal muscel voltage-

gated sodium channel X subunit (SCN4A)

Management salbutamol inhalers


35/40


Potassium retention

Increased intake (iv fluids)

Decreased output

Decreased GFR

Potassium sparing diuretics

ACE inhibitors

Syndromes of hypoaldosteronism

Primary/secondary hypoaldosteronism

CAH Type IV RTA


36/40

Drug Effects on Potassium

Homeostasis


37/40

Syndromes of Hypoaldosteronism

Syndrome Renin AldoPrimary hypoaldosteronism

- Addisons Disease

- isolated aldosterone deficiency

- heparin treament Congenital adrenal hyperplasia N to N to

ACE inhibitors N to N to

Hyporeninaemic hypoaldosteronism

Secondary tubular disorders N N

Pseudohypoaldosteronism

- type I

- type II (Gordons syndrome) N to


38/40

Laboratory Investigation

Exclude spurious causes

Assess acid-base status, glucose

Assess eGFR

Check drug therapy

Check renin & aldosterone

Cautionhigh K+ stimulates aldosterone but

suppresses reninAs eGFR fallsaldo increases & renin

decreases


39/40

MANAGEMENT

If plasma K>6.0mmol/l, check for EDTA contamination. Plasma K>6.0mmol/l needs urgent treatment but first ensure it is not an

artefact. Ask for ECG to be done urgently in such patients.

10ml of 10% calcium gluconate i.v. over a period of 10min. Repeat ifnecessary until the ECG changes improves.

10units of soluble insulin in 250ml of 10% dextrose over 30-60min is

given. If potassium remains high a continuous infusion of insulin andglucose may be required.

Calcium resonium 15g four times daily or 30g enema in 100ml may begiven in asymptomatic hyperkalemia. This takes a few days to takeeffect.

Haemodialysis may be required in: Persistent hyperkalemia (>7mmol/l)

Severe or worsening metabolic acidosis (pH


40/40

References

Understanding Bartter syndrome and Gitelman syndromeWorld J Paed 2012;

Feb 8 (1): 25-30

Periodic Paralysis - Adv Genetics 2008; 63: 3-23

Liddles syndromeNEJM; 330: 178-181

Mineralcorticoid hypertensionLancet 1999: 353:1341

potassium homeostasis - lisa bailey

Documents