POTASSIUM

BY; Dr BASHARDOUST

POTASSIUM Control of normal K+ homeostasis

Hypokalaemia

Hyperkalaemia

[Na+] = 20

[K+] = 150 [K+] = 4

[Na+] = 140

K+ gradient across cell membranes sets cell voltage

(Na+ gradient can be usefully linked to solute transport)

Regulation of K+ balance

Normal dietary intake: 40-120 mmol/day

3 components to maintain (‘defend’) homeostasis:

Cell shifts

Renal excretion

GI loss (weak and poorly regulated)

K+

K+

K+

K+

K+

K+

90%K+

Renal K+ handling

K+

(CCD)

(PT)

(LOH)

2K+

3Na+

K+ K+

Na+ 3Na+

2K+

Principal cell

Cortical collecting duct (CCD)

Amiloride

BariumBarium

Ouabain

-70mV

Lumen Blood

Cell shifts

2% of total body K+ in ECF

= ~50 mmol/l (= a good steak meal!)

- insulin (Na+,K+-ATPase) – goes up when you eat

- sympathetic - 2 (uptake) vs. (brake)

(*insulin has as much to do with K+ homeostasis as with glucose)

So ‘defence’ needed to prevent So ‘defence’ needed to prevent hyperkalaemia:hyperkalaemia:

What determines CCD K+ secretion?

1.1. Mineralocorticoid activity

2.2. Distal delivery of Na+ (and flow rate)

- nonreabsorbable(NR) anions, e.g. HCO3-

2K+

3Na+

K+ K+

Na+ 3Na+

2K+

Principal cell

Control of CCD K+ secretion

-70mV

Distal delivery of Na+

Mineralo-corticoids

K+

Lumen Blood

K+ secretion in CCD

Aldosterone Distal Na+ delivery K+ secretion

ECV

ECV Conn’s (ECV )

Diuretics (ECV )

Addison’s (ECV )

(CCD)

HYPOKALEMIA Hypokalemia is defined as a serum

potassium concentration less than 3.5 meq/L (3.5 mmol/L).

The serum potassium concentration may be a misleading marker of the degree of a patient’s serum potassium deficit, as patients with normal or even increased serum concentrations of potassium may have significant total body potassium depletion.

The exact cause of hypokalemia can usually be established by evaluating the history, blood pressure, acid-base balance, and urine potassium concentration

Hypokalaemia

Pseudo- (leukaemia, but only at room temp)

Cell shifts

Dietary intake (not usually a problem unless another source of K+ loss, e.g. diarrhoea or malabsorption)

GI loss

Renal loss

Hypokalaemia - cell shifts

Alkalosis - minor

Barium toxicity – remember CCD principal cell

Rapid cell growth - anabolism

Hypokalaemic periodic paralysis – Ca2+

channel mutation (presents at 10-19 years of age)

Thyrotoxicosis – Asian males

Extrarenal K+ loss

•Bowel K+ loss

•Diarrhoea is the most common

cause

•Urinary K+ excretion is typically <20

mmol/day

•Renal K+ loss

•Vomiting-associated hypokalaemia

Renal K+ loss

Diagnosis-Urinary K+ excretion >20 mmol/day -No diarrhoea (but remember to consider

laxative abuse)

A primary in mineralocorticoid

versusversus

A primary in distal Na+ delivery

- ECV expansion- BP elevation

A primary increase in mineralocorticoid

Primary hyper-reninism – renin and aldosterone

(not corrected by i.v. saline)- Malignant hypertension (~50%)-Renal artery stenosis (~15%)

- Renin secreting tumour

Primary hyperaldosteronism – renin - Conn’s syndrome (adrenal adenoma)- Bilateral adrenal hyperplasia- GRA (glucocorticoid remediable aldosteronism)

Primary increase in a non-aldosterone mineralocorticoid – renin and aldosterone - Cushing’s syndrome- CAH (congenital adrenal hyperplasia)- AME (apparent mineralocorticoid excess)- Liddle’s syndrome

A primary increase in distal Na+ delivery

- Diuretics that act upstream of the CCD

- Nonreabsorbed anions

- Mg2+ deficiency

- Bartter’s syndrome

- Gitelman’s syndrome

- Acidosis

NaNa++

NaNa++

NaNa++

NaNa++

2Cl-

Cl-

K+

H+

URINE

3Na3Na++

2K+

Proximal tubule

Thick ascending limb

Distal tubule

Collecting duct

Na+ transport along the nephronCELL

- Osmotic diuretics- CA inhibitors

- Loop diuretics- Bartter’s

- Thiazides- Gitelman’s

- Triamterene- Amiloride- Spironolactone

Nonreabsorbed(NR) anions

Failure to reabsorb in the proximal leads to an increase distal Na+ delivery

Failure to reabsorb in the CCD leads to increased cation (K+ or H+) secretion in ‘exchange’ for Na+ (absorption)

Examples:- HCO3

- (Urine pH high)

- keto-anions (DKA)- penicillins

Mg2+ deficiency/Metabolic acidosis

Mg2+ deficiency inhibits TAL Na+ absorption- hypokalaemia, alkalosis, hypocalcaemia

Acidosis inhibits proximal tubule Na+ reabsorption- urinary K+ loss in diarrhoea

Bicarbonaturia in proximal RTA causes urinary K+ loss

Hypokalaemia occurs in distal RTA

HYPOKALAEMIA - an algorithm

UK or

<20 mmol/day >20 mmol/day

Renin, aldosterone Plasma [HCO3-]

BP, ECV

High Low/Normal

RASConn’s/adrenal hyperplasiaGRACushing’sAMELiddle’s

Low HighRTA

Urine [Cl-]

Low HighGastric

NR anionDiureticsMg2+ deficiencyBartter’sGitelman’s

Diarrhoea

Risks of hypokalaemia

PK

‘Bad’ events

Post-MI

Hypokalaemia in this setting may be due to high adrenaline

BUT high adrenaline is a marker of poor outcome post-MI

Treatment of hypokalaemia

Chronic- KCl liquid or Slow K- deficit will be at least 100 mmol

Acute- i.v. KCl (no more than 20 mmol/h)

If hypokalaemic and acidotic- treat hypokalaemia first!

Hyperkalaemia

Pseudo- (high wbc, platelet counts and leaky rbc, but check that ECG is normal!)

Excess K+ intake

Cell shifts

Renal retention (sustained hyperkalaemia)

PERKALAEMIA

PSEUDOHYPERKALAEMIA

High K+ with a normal ECG, think of:

oRepeated fist clenching

o Haemolysis from a small gauge needle

o Sample stored on ice and/or delayed transfer (causing

efflux from red cells)

o Hyperventilation

o Release from leukaemic cells

o Interference with K+-ion sensitive electrode from

benzalkonium (topical antiseptic) or heparin

o Familial (chromosome 16)

Cell shifts

Cell damage - rhabdomyolysis, haemolysis, tumour lysis

Diabetic ketoacidosis, nonketotic hyperosmolar

Lactic acidosis

Toxins and drugs - digoxin, tetrodotoxin*

*Hyperkalaemic periodic paralysis

Acidosis and K+ shifts

INORGANIC acids do cause K+ to leave cells (H+ influx and

buffering)

ORGANIC acids do not cause K+ to leave cells

In DKA K+ exit from cells is due to lack of insulin

Hyperosmolarity also shrinks cells and the gradient for

K+ exit (loss) from cells

In lactic acidosis - cell ischaemia, ATP leads to K+ leak out of cells

Asymptomatic hyperkalaemia - think of a renal cause

Renal retention of K+

Primary decrease in mineralocorticoid- hyporeninaemic hypoaldosteronism (DM, cID)- heparin- Addison’s

Primary decrease in distal delivery of Na+

- oliguric ARF (cf. non-oliguric)- acute GN- Gordon’s syndrome (pseudohypoaldosteronism type II)

Abnormal CCD function- pseudohypoaldosteronism type Ia (ENaC) or Ib (MR)- cID (destroys CCD)- obstruction- amiloride, trimethoprim, pentamidine- spironolactone

Treatment of hyperkalaemia

Acute- CaCl2

- NaHCO3/glucose+insulin/b2 agonists

- Ca2+ resonium/dialysis

Chronic (assess aldosterone/ECV)

- if low give fludrocortisone

- if high (BP) give diuretic

-NaHCO3 useful in all patients- low K+ diet- Ca2+ resonium (beware, may actually K+ acutely!)

(slow!)