Potassium Disturbances

Front 1

Normal K values

Back 1

• Plasma K 3.5-5.0
• ICF 150 mmol/L
• ECF 5 mmol/L
• ICF 25L
• ECF 15L
• Intracellular: 150 x 25 = 3750 mmol (98%)
• Extracellular: 5 x 15 = 75 mmol (2%)

Front 2

factors influencing cellular potassium uptake

Back 2

hormonal influences,
acid-base homeostasis, insulin, glucagon and ß and alpha adrenergic activity

Front 3

Why is potassium so tightly
regulated?

Back 3

• Resting membrane potential depends on ratio
between intracellular and extracellular
potassium (Nernst equation)
• Changes in extracellular potassium profoundly
affect this membrane potential
• Changes in membrane potential lead to
changes in polarisation and excitability of
nerve/muscle cells

Front 4

Distribution affected by

Back 4

• Na/K ATPase vs K channels
• Insulin
• Catecholamines – beta 2
• alkalosis

Front 5

Balance of intake and output

Back 5

• Intake
– Dietary K approx 1 mmol/kg (39 mg = 1 mmol)
– 80 (30-150) mmol/day (3200 mg/day)
• Output
– 90% urine
– 10% stool

Front 6

K transport in the nephron

Back 6

• Site 1:PT 65% K filtered is reabsorbed
• Site 2:TAH 25%
• Site 3:ED nil
• Site 4: LD/CCD K secreted 0-20% equivalent of
filtered load
• Site 5: MCD 5% reabsorbed (normally doesn’t
happen)

Front 7

Cortical collecting duct- K

Back 7

Front 8

Factors regulating LD/CCD K secretion

Back 8

• Blood
– Aldosterone*
– Plasma [K]
– Increased pH
• Luminal
– Na delivery e.g. diuretics at sites 1,2,3
– Flow rate by reducing luminal K concentration
– Negative lumen potential difference (note
amiloride)

Front 9

Potassium and aldosterone

Back 9

• Adrenal gland – increased plasma K increases
aldosterone secretion from zona glomerulosa
(outer segment of adrenal)
• Kidney – aldosterone increased K secretion at
site 4, causing increased K excretion
• This causes plasma K to fall, feeding back on
adrenal gland

Front 10

Regulation of Renin

Back 10

• Reduced ECF V and lower blood pressure ->
increased renin -> AI -> AII -> zona
glomerulosa – increased aldosterone secretion
• Aldosterone acts on kidney to increase sodium
reabsorption and reduce sodium excretion
• These effects on sodium negatively feedback
on ECF and BP

Front 11

Aldosterone MOA

Back 11

Aldosterone acts primarily in the distal nephron to increase the reabsorption of Na+ and Cl- and the secretion of K+ and H+. As with other steroid hormones, aldosterone acts by diffusing into the tubular cell and then attaching to a specific cytosolic receptor, The hormone-receptor complex then migrates to the nucleus, where it interacts with specific sites on the nuclear chromatin to enhance messenger RNA and ribosomal RNA transcription. This in turn is translated into the synthesis of new proteins called aldosterone-induced proteins (AIPs). The time required for these processes to occur accounts for the 30 to 90 minute latent period before electrolyte excretion is affected
How these proteins act is not well understood. Aldosterone increases the abundance of the alpha subunit and promotes the phosphorylation of the beta and gamma subunits of the luminal membrane Na+ channel through which luminal Na+ enters the cells.
- the AIPs help INC channel activity and stability

Front 12

When is aldosterone maladaptive?

Back 12

Dehydration with hypokalaemia – aldosterone
response is maladaptive

Front 13

Hypokalaemia K < 3.5 mmol/L

Back 13

– Effect on transmembrane potential rendered more
electronegative, leading to hyperpolarisation and
enhanced membrane excitability due to enhanced sodium
channel activation
– Skeletal muscle weakness
– Cardiac effects ECG – T wave height falls, U wave, ectopics
(ventricular – VT/VF)
– GIT – smooth muscle effects – ileus (pseudo-obstruction)
– Kidney – long term hypokalaemia causes polyuria –
nephrogenic diabetes insipidus and renal fibrosis

Front 14

Hypokalaemia - causes

Back 14

• Redistribution e.g. pH changes
• Reduced intake e.g. diet (must be extreme due to kidney’s ability to adapt)
• Excess loss
– Kidney
• diuretics (sites 1,2,3)
• Excess aldosterone (Conn’s syndrome)
– GIT
• Vomiting – GI loss, volume contraction with increased aldosterone
• Diarrhoea – as above
• Purgatives
– Use urine potassium unless hypovolaemic when aldosterone will
increase urine K despite GI loss

Front 15

Urine Potassium

Back 15

– Use urine potassium unless hypovolaemic when aldosterone will increase urine K despite GI loss

high= kidney
low = GIT

but its not that simple

Front 16

Conn’s syndrome

Back 16

• A cause of hypertension
• Usually associated with adrenal adenoma or
bilateral adrenal hyperplasia
• Hypokalaemia is a common (but not universal)
accompaniment -30%

Front 17

Hypokalaemia - treatment

Back 17

• Reverse cause
• Replace with KCL – oral (slow K) or IV
• amiloride & spironolactone

Front 18

Hyperkalaemia

Back 18

• > 5 mmol/L
• Effects
– Skeletal muscle – paralysis
– Heart – T wave peaking, QRS, cardiac arrest depending on K level
• Cell membrane potential rendered less
electronegative, leading to excessive depolarisation and reduced membrane excitability due to reduced sodium channel activity

Front 19

Hyperkalaemia - causes

Back 19

• Spurious – e.g. haemolysed – pink blood (sample error)
• Redistribution – e.g. low pH, no insulin, beta-blockade
• Increased intake in individuals with kidney disease
• Renal retention
– Reduced GFR (AKI and CKD) – not enough K to distal tubule
in filtrate and not enough Na as well
– Normal GFR – tubular secretory failure e.g. Addisons,
amiloride, diseases of tubules

Front 20

Addison’s disease

Back 20

• Classically an autoimmune disease
• Adrenal insufficiency
• Lack of aldosterone
• Hyperkalaemia
• Hyponatraemia
• Hypotension

Front 21

Hyperkalaemia - treatment

Back 21

• Stabilise cell membrane – Ca gluconate
• Shift K into cells
– insulin + glucose
– B2 agonist
– Bicarbonate
• Remove potassium
– Diuretic
– Resin in gut
– Dialysis