Potassium

Homeostasis, Disorders & Management

Introduction
Fluid spaces:
Intracellular Fluid (ICF)
Extracellular Fluid (ECF)
- Intravascular space (plasma volume)
- Interstitial space (lymph)
- Transcellular fluid (pleural, pericardal, CSF,
gastrointestinal)

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
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 10
Bicarbonate 29 10
Phosphate 1.5 50
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
Pancreatic
Juice
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 -
Extracellular & Intracellular Potassium
Pathology Harmonisation Reference Range
= 3.5 5.3 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.
Potassium Homeostasis

Factors influencing distribution of
Potassium
Decrease plasma potassium:
- insulin
- catecholamines - adrenergic
- alkalosis

Increase plasma potassium:
- hypertonicity
- acidosis
- catecholamine adrenergic




Renal Control of Potassium Output


Ann Inter Med 2009, Vol 50, Number 9 pg 619-626
Aldosterone and potassium
homeostasis

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)


Extrarenal
Evidence of potassium control in the colon
Most reabsorbed in small intestine
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
ECG pattern in Hypokalaemia
Normal ECG pattern
Hypokalaemia
Signs & Symptoms:
- Renal
- Polyuria, sodium retention
- Gastrointestinal
- Constipation, decreased gastric acid secretion




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


Causes of hypokalaemia
Redistribution
In vitro
Uptake by white cells, heat,
In vivo
Alkalosis, insulin, beta adrenergic agonists, chemicals
Hypokalaemic periodic paralysis

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 remits
when patient becomes euthyroid

Extrarenal Causes of Hypokalaemia
Evident from clinical history
Urine potassium (<10 mmol/L)
Acid Base Status
diarrhoea is high in bicarbonate (hypokalaemic
metabolic alkalosis)

Extrarenal Causes of Hypokalaemia
Inadequate intake
Anorexia
Fluid replacement without potassium
Rapid cell synthesis (anaemia, rapid increase
in reticulocyctes)
Increased loss
Excessive sweating (sweat 10 mmol/L)
Gastrointestinal (stool water 90 mmol/L)
Investigation of hypokalaemia
Hypokalaemia

Spurious Redistribution


Potassium depletion


Extrarenal loss Renal loss
(urine K<10 mmol/L) (urine K>10 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 aminoglycosides
laxative abuse DKA leukaemia
diuretic phase ARF


Investigation of hypokalaemia

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

Causes of hypokalaemia Renal Losses
Renal hypokalamic alkalosis
Low urine chloride
Vomiting/gastric loss
Diuretic that act on loop of Henle (frusemide) or
distal collecting ducts (thiazides)
Chloride losing diarrhoea (congenital, Zollinger-
Ellison syndrome)
Cystic fibrosis
High Urine chloride
Hypertensive
Normotensive
Causes of hypokalaemia Renal Losses
Metabolic alkalosis
Normotensive
Bartters syndrome
Hyperreninaemic hyperaldosterism
Usually presents in childhood
Mutations of genes encoding proteins that transport ions
across renal cells in the thick ascending limb of the
nephron
Gitelmans syndrome
hypochloremic metabolic alkalosis, hypokalemia, and
hypocalciuria. Hypomagnesemia is present in many but not
all cases
inactivating mutations in the SLC12A3 gene resulting in a
loss of function of the encoded thiazide-sensitive sodium-
chloride co-transporter (NCCT). This cell membrane
protein participates in the control of ion homeostasis at the
distal convoluted tubule portion of the nephron.

Causes of hypokalaemia Renal Losses
Metabolic alkalosis
Hypertensive
Measure renin/aldo
See chart
Causes of hypokalaemia Renal Losses
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+ <2.5 IV K+ 40 mmol/L in NS over 6 hours (normal
rate 10 mmol/hr to max 240 mmol/day)
Plan 48 hr/72 hr replacement, check K+ regularly
Replace slowly never bolus
Higher rates maybe given in an ITU setting with
cardiac monitoring

Hyperkalaemia
Signs & Symptoms
Cardiovascular
Tall T waves, prolonged PR interval, flat P waves,
widening of QRS complex, VF, asystole
Neuromuscular
Parasthesia weakness, paralysis
Renal
Natiuresis, decreased reabsorption of HCO3

ECG Hyperkalaemia
Normal ECG
Causes of hyperkalaemia
Redistribution
in vitro redistribution
in vivo redistribution
Increased intake
Decreased Output
Syndromes of hypoaldosteronism

Causes of hyperkalaemia
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



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
Causes of hyperkalaemia
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
Drug Effects on Potassium
Homeostasis
Syndromes of Hypoaldosteronism
Syndrome Renin Aldo
Primary 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
Laboratory Investigation
Exclude spurious causes
Assess acid-base status, glucose
Assess eGFR
Check drug therapy
Check renin & aldosterone
Caution high K+ stimulates aldosterone but
suppresses renin
As eGFR falls aldo increases & renin
decreases
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 if
necessary 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 and
glucose may be required.
Calcium resonium 15g four times daily or 30g enema in 100ml may be
given in asymptomatic hyperkalemia. This takes a few days to take
effect.
Haemodialysis may be required in:
Persistent hyperkalemia (>7mmol/l)
Severe or worsening metabolic acidosis (pH <7.2)
Uraemic pericarditis, encephalopathy, refractory pulmonary oedema.

References
Understanding Bartter syndrome and Gitelman syndrome World J Paed 2012;
Feb 8 (1): 25-30
Periodic Paralysis - Adv Genetics 2008; 63: 3-23
Liddles syndrome NEJM; 330: 178-181
Mineralcorticoid hypertension Lancet 1999: 353:1341