Biochemistry Mbchb4



1. Hypovolaemic - ↓ Na, ↓↓ H20
a. Excessive sweating
b. Diuretics
c. Diarrhea
2. Euvolaemic – Ø∆ Na, ↓ H20
a. Inadequate intake
b. Diabetes insipidis (ADH impaired)
3. Hypervolaemic - ↑↑ Na, ↑ H20
a. IV or oral salt administration
b. Enteral or parenteral nutrition
c. CRF during water restriction
d. Intake of hypertonic solutions


1. Psuedohyponatremia - glucose, lipids, proteins, drip arm (displacement)
2. Hypovolaemic -↓↓ Na, ↓ H20
a. Vomiting
b. Diarrhea
c. Diuretics
d. Aldosterone deficiency (Addisons)
3. Euvolaemic (diluational) – Ø∆ Na, ↑ H20
a. Primary polydipsia
b. Excess IV dex
i. Pulmonary – small cell lung tumour, TB, pn
ii. CVS – stroke, head trauma
iii. Post op – nausea, pain, stress
iv. Drugs – eg carbazemapine
v. Idiopathic
4. Hypervolaemic (edematous) - ↑ Na, ↑↑ H20
a. CHF
b. Cirrhosis
c. Nephrotic syndrome, Nephrosis
d. CRF during free water intake


1. Artefact
a. Delayed processing
b. Hemolysis
c. High wcc or platelets
2. Excess K intake – oral or IV
3. Excess release from cells
a. Acidosis
b. Hemolysis
c. Trauma
d. Hypoxia
4. Impaired renal K excretion
a. RF (↑ creatinine, oliguria)
b. Aldosterone deficiency
c. K sparing diuretics

1. <5.5 → Salbutamol (shifts K into cells)
2. 5.5 – 6.5 → Salbutamol + Calcium Gluconate (stabilises membrane)
3. >6.5 → Add insulin + glucose (shifts K into cell)
4. ECG if worried or >5.5 → look for peaked or wide t waves


1. Deficient intake – dietary or IV
2. Redistribution into cells
a. Alkalosis
b. Insulin excess
c. B2 agonists
3. Excessive renal loss
a. + HTN →hyperaldosteronism (Conns, Cushings, Ectopic ACTH)
b. – HTN → diuretics (Ø k sparing)
4. GI tract
a. ?M.acidosis → diarrhea, laxatives
b. M.alkalosis → vomiting
5. Drugs (diuretics, b-agonists)


Marked slowing of AP when K >7 mmol/L → ↑ risk cardiac arrest
Pres progr mus weakness (but sometimes no sxs until arrest occurs)
ECG T wave peaking, QRS widening

Causes of Hyperkalemia
1. Artefact – delayed processing, hemolysis, high wcc, high platelets count
2. Excess intake – eg oral/IV K supplements
3. Excess release from cells – eg hemolysis, acidosis, trauma, hypoxia
4. Impaired renal excretion – oliguria (acute/severe CRF), aldosterone deficiency, K+ sparing diuretics

Dx Decision Tree Hyperkalemia

Spurious (IV hemolysis or v high wcc/platelet counts)
Redistribution out of cells
Acidosis, Insulin deficiency, B-blockers, severe hyperglycemia
↑ K intake
Exogenous (diet (unlikely), IV therapy) or Endogenous (hemolysis, rhabdomyolysis)
Renal Retention of K

Plasma Creatinine >500 umol/L (↓ GFR) Plasma creatinine <500 umol/L (GFR preserved)
- ARF (severe) w low aldosterone adrenocortical failure (addisons)
- CRF (advanced) adrenal enzyme defects
drugs – NSAIDs, ACEI, B-blockers
w normal/high ald tubular transport defects
tubulointerstitial dis – SLE, amyloidosis, obstruction, inf
drugs – amiloride, spironolactone

No ECG of neuromusc changes → ↓ K intake and correct underlying abnormalities may be sufficient
Acute/Severe hyperkalemia →
• Calcium gluconate infusion – stabilizes conductive tissue membranes (calcium opp eff of K on AP conduction)
• Shift K into cells – inhaled b agonist, IV glucose, insulin, IV na-bicarb
• Remove K from body – IV furosemide + normal saline (if normal ren func + hypovol), ion exchange resin (if RF), dialysis


• Na >150 mmol/L (inability to concentrate urine)

• ↓ cerebral func – dehydration of cerebral neurons → shrinkage
• In presence of intact thirst mechanism and preserved capacity to obtain water – hypernatremia may not progress very far as water intake ↑
• Where adequate water not obtained → dizziness, confusion, weakness and ultimately coma and death can result
• Uncommon - ~1% cf Hyponatremia 10-20%

Causes of hypernatremia
1. Hypovolaemic
2. Euvolaemic
3. Hypervolaemic

1. Hypovolaemic
Na deficit w a relatively greater water deficit
a. Renal Na loss – diuretic therapy (esp loop diuretics during water restriction); polyuria of any cause
b. GI – diarrhea
c. Skin – excessive sweating, burns

2. Euvolaemic
Water deficit only
a. Diabetes insipidus (central or nephrogenic) – inadequate ADH
b. Inadequate fluid intake – eg thirst defect

3. Hypervolaemic
Na retention w relatively less water retention
a. Enteral or parental alimentation
b. IV or oral salt administration
c. CRF (during water restriction)
d. Intake of hypertonic fluids ie. Salt water drowning or hypertonic saline

Acute hypernatremia – correct with appropriate volumes IV hypotonic fluid
Chr pts – correct slowly to avoid cerebral edema
Address underlying cause
Problems managing hypernatremia
• Thirst and mobility problems are chronic and hard to treat
• Fluid depletion → RF
• Excess fluids → HF
• Rapid correction of Na → cerebral edema


• Plasma K <3.5 mmol/L

• Muscular weakness, tiredness
• Cardiac effects - ventricular ectopics, arrhythmias, potentiation of digoxin adverse effects
• ECG: Flat t wave or ST depr/u wave
• Bowel obstruction (due to paralytic ileus – low k)

Complications of longstanding hypokalemia
• damages renal tubular structures (hypokalemic nephropathy)
• interferes w tubule response to ADH (acquired neprhongenic diabetes insipidis) → polyuria + polydipsia

Summary of causes of hypokalemia
1. Deficient intake
2. Drugs – diuretics, b-agonists
3. GI losses – diarrhea, laxatives, vomiting
4. Renal losses – diuretics, tubule disease, mineralcorticoid excess, Mg2+ deficiency
5. Redistribution – insulin, alkalosis, rapid growth

Diagnostic Decision tree for Hypokalemia (davidsons pg 433)


Redistribution into cells? → alkalosis, insulin excess, catecholamine b2 agonists

↓ K intake? → dietary, IV therapy

Excessive K loss (either through kidnes or GI sys)

Urine K >20-30 mmol/day Urine K <20-30 mmol/day
With HT → excess mineralcorticoid activity With m.alkalosis – vomiting, nasogastric aspiration (upper GI loss > pylorus)
- hyperaldosteronism – 1’ conn’s syndr / 2’ renal ischemia With m.acidosis – diarrhea, laxative abuse, rectal adenoma,
- other forms mineral corticoid activation bowel osbstruction/fistula (lower GI loss < pylorus)
Cushings Syndr / Ectopic ACTH
Corticosteroid therapy
With normal or low BP
- with alkalosis – diuretic therapy (loop or thiazides)
- with acidosis – renal tubular acidosis (rare)
- variable pH – post-obstructive diuresis, recovery post ATN

Plasma electrolytes, bicarb, urine k
Calcium and Mg2+ (sometimes useful)
Plasma renin activity + aldosterone (identify pts w 1’ hyperaldosteronism)

Correction of cause of hypokalemia – may require must redistribution from cells (eg correction of alkalosis) or may require K supplement
KCl tablets – slow release
IV KCl – acute situations
K bicarb oral – when pt acidotic

Case Hx 1 – Vomiting
• Na ↓, K ↓ Cl ↓, HCO3- ↑ (metabolic alkalosis) – mechanism; na losses with vomiting stimulates na absorption at the expense of k secretion??

Case Hx 2 – Diarrhea
• Na ↓, K ↓, Cl ↑, HCO3- ↓↓, AG 18, Ur K ↓, Ur Na ↓, Ur Osm ↑
• Low HCO3- in diarrheal fluid - reflects m.acidosis
• Low Na and K - due to loss in diarrhea and subsequent hypotonic repl
• High urine osm appropriate considering fluid loss, Na and K both conserved at kidneys


Def Plasma Na conc <135 mmol/L
Pres Asx or disturbances of cerebral func (anorexia, n+v, confusion, lethargy, seizures, coma) – cerebral cell swelling → ↑ ICP → ↓ c.perfusion
Rate of devt critical – gradual ↓ Na osmolality compensated by neurons ↓ intracell K + other osmolytes → ↓ intracellular osmolality

Causes of Hyponatremia
1. Pseudohyponatremia
2. Hyponatremia with hypovolaemia
3. Hyponatremia with euvolaemia
4. Hyponatremia with hypervolaemia

1. Pseudohyponatremia (artefactual)
• Artefacts – hyperlipidemia, hyperproteinemia, high blood sugar levels, drip arm
• Transient hyperosmolar states – acute hyperglycemia or mannitol infusion

2. Hyponatremia with hypovolaemia
• Sodium deficiency w relatively smaller water deficit
a. Renal salt loss - Diuretics or Addison’s dis (aldosterone deficiency – adrenocortical failure)
b. GI salt loss – vomiting or diarrhea
• ↓ urinary Na conc
• ↑ plasma rennin activity
Clin Feats Hypovolaemia
• Sxs - Thirst, dizziness on standing, weakness
• Signs- Low JVP, postural hypotension, tachycardia, dry mouth, ↓ skin turgor, ↓ urine output, weight loss, confusion, stupor

3. Hyponatremia with euvolaemia
• Dilutional hyponatremia – no major disturbance of body Na content + clinically euvolaemic
• Excess body water may be the result of abnormally high intake – oral (primary polydipsia) or via medical infusion (IV dextrose solutions)
a. Primary polydipsia
b. Excess electrolyte-free water infusion
c. SIADH (Dx of exclusion) – cerebral or tumor derived source ADH → water retention w/o appropr phys stim
Causes Tumor (esp small cell lung)
CNS disturbances (stroke, trauma, inf, psychosis)
Pulmonary d/os – pn, tb
Drugs – anticonvulsants (carbamazepine), psychotropics (haloperidol), antidepressants (amitriptyline)
Sustained pain, stress, nausea (eg post op)
Dx Low plasma Na (<130)
Low plasma osm (<270)
Urine osmolality not minimally low (>150)
Urine Na conc not minimally low (>30)
Low-normal plasma urea, creatinine, uric acid

4. Hyponatremia with hypervolaemia (edematous)
• Sodium retention with relatively greater water retention (fluid overload)
a. CHF
b. Cirrhosis/LF
c. Nephrotic syndr/Nephrosis
d. CRF – during free water intake

Clinical Approach to hyponatremia
• Exclude high lipids/protein/glucose and drip arm
• How severe and long lasting – prev results, known acute/chr dis, hx of sxs
• Fluid status – Hx, BP, skin turgor, edema / serum/ur creatinine, urine Na/osm
• Obvious organ path – liver, brain, adrenal, lung, thyroid, kidney
• Meds – diuretics, pschotropics, anticonvulsants, cytotoxics, NSAIDs, opiates, ecstasy

Plasma and urine electrolytes and osmolality
Doubt re clin signs ECF vol → measure renin activity
Plasma ADH assay (generally not helpful as ADH activated in both hypovolaemic and most chr hypervolaemic states)

Urine Na and Osmolality in the Diff dx of Hyponatremia
Urine Na (mmol/L) Urine osmolality (mmol/kg) Possible dx
Low (<30) Low (<100) Primary polydipsia
Low High (>150) Salt depletion, hypovolaemia
High (>40) Low Diuretic action (acute phase)
High High SIADH, adrenal insufficiency, cerebral salt wasting

Hyponatremia of rapid onset (hours-days) – morbidity high due to cerebral edema → correct plasma Na rapidly (infusion hypertonic NaCl)
Chr hyponatremia → correct slowly otherwise complications -
• Neuron shrinkage and possible detachment from myelin sheath – “central pontine myelinolysis” → permanent + fatal
• Worsening HF
Specific tx measures depending on cause of hyponatremia
• Hypovolaemic pts – control Na loss, IV saline
• Dilutional hyponatremia – fluid restriction (600-1000 ml/day), withdrawal of precipitating stimulus (eg drug causing SIADH)
• Hypervolaemic pts – tx underling condition + cautious use of diuretics + strict fluid restriction
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