Chemical Pathology - Sodium Flashcards
How much sodium is freely exchanged, and where is the rest found?
- 70% freely exchangable
- The rest is complexed in bone
What is sodium?
Predominantly an extracellular cation, largely maintained by active pumping from ICF to ECF by Na/K ATPase
What is ECF volume directly dependent on?
Sodium
What is the treatment of mild/moderate hyponatraemia?
Treat underlying cause (unless severe and symptomatic)
How are mild and severe hyponatraemias defined?
Mild = 130-135 mmol/L
Moderate = 125-130 mmol/L
Severe = <125 mmol/L
What are the symptoms of Symptomatic hyponatraemia and when do they arise?
- Nausea + Vomiting: <134 mmol/L
- Confusion: <131 mmol/L
- Seizures, non-cardiogenic pulmonary oedema: <125 mmol/L
- Coma: <117 mmol/L + eventual death
MEDICAL EMERGENCY
What is the pathogenesis of true hyponatraemia?
Increased extracellular water
What are some causes of hyponatraemia with a high osmolality?
- Glucose/mannitol
- Infusion
What are some causes of hyponatraemia with a normal osmolality?
- Spurious
- Drip arm sample
- Pseudohyponatraemia (hyperlipidaemia/paraproteinaemia)
What is the cause of hyponatraemia with a low osmolality
True hyponatraemia
What is TURP syndrome (transurethral resection of the prostate)?
Hyponatraemia from irrigation aborbed through damaged prostate
What is used to irrigate during TURP (transurethral resection of the prostate)?
Glycine 1.5%
How is the clinical presentation of TURP caused?
Due to metabolism of glycine and hyponatraemia caused by dilution
What is the process of water reabsorption?
ADH acts on V2 receptors in the collecting duct, thus inserting Aquaporin-2 into the cell membrane, causing water reabsorption
What processes cause an increase in ADH release?
- An increased osmolality is detected by osmoreceptors causing an increase in ADH release
- A decrease in blood volume/pressure is detected by baroreceptors in the heart causing an increase in ADH release
What is the cause of hyponatraemia with elevated plasma osmolality?
An excess of osmotically active solutes into the plasma
- Often glucose (in HHS), can be mannitol
- Solutes draw water from ceclls into plasma, which dilutes the sodium
What are some symptoms of hypovolaemia?
- Tachycardia
- Postural hypotension
- Dry mucous membranes
- Reduced skin turgor
- Confusion/drowsiness
- Reduced urine output
What are some symptoms of hypervolaemia?
- Raised JVP
- Bibasasl crackles
- Peripheral oedema
What is the basic MoA of cardiac failure in causing hyponatraemia?
The heart pumps less so the BP is lowered
What is the basic MoA of liver cirrhosis in causing hyponatraemia?
There is an increase in release of vasodilators which causes the BP to drop
What is the basic MoA of renal failure in causing hyponatraemia?
There is reduced water excretion
What are initial steps of treating a hyponatraemic patient?
Assess volume status, urine sodium + osmolality
If a patient has hypovolaemic hyponatraemia, how are they managed?
- Fluid replacement with 0.9% NaCl (isotonic saline)
- Treat the cause
If a patient has hypervolaemic hyponatraemia, how are they managed?
Fluid restriction +/- diuresis
- Treat the cause
- Cirrhois usually requries specialist input
If a patient has euvolaemic hyponatraemia, what further investigations would you consider?
- TFTs
- Short Synacthen test
- Paired urine and serum osmolalities
If a patient has euvolaemic hyponatraemia, how are they managed?
- Dependent on the cause
What are some causes of hypovolaemic hyponatraemia, with a urine osmolality >20?
- Adrenocortical deficiency
- Renal failure/disease
- Diuretics
- Cerebral salt wasting
What are some causes of hypovolaemic hyponatraemia, with a urine osmolality <20?
- Vomiting
- Diarrhoea
- Skin loss (sweat/burns)
What are some causes of hypervolaemic hyponatraemia, with a urine osmolality >20?
- Renal failure
What are some causes of hypervolaemic hyponatraemia, with a urine osmolality <20?
- Heart Failure
- Cirrhosis
- Nephrotic syndrome
- Primary polydipsia
What are some causes of euvolaemic hyponatraemia, with a urine osmolality <100?
- Acute water load
- Psychogenic polydipsia
- Tea + toast/beer diets
What are some causes of euvolaemic hyponatraemia, with a urine osmolality >100?
- SIADH
- Glucocorticoid deficiency
- Chronic hypothyroidism
- Acute water load
When can hypertonic (3%) saline be used in a hyponatraemic patient?
If they have status epilepticus secondary to hyponatraemia (only on advice of specialist, usually in ITU)
What can happen with rapid correction of hyponatraemia, and how can this be avoided?
- Central pontine myelinolysis (pseudobulbar palsy, paraparesis, locked-in syndrome)
- Aim to increase sodium by no more than 8-10mmol/L per 24hrs
What can cause hyponatraemia post-surgery?
- Overhydration with hypotonic IV fluids
- Transient increase in ADH due to stress of the surgery
What does demeclocycline do?
Reduces the cells responsiveness to ADH
What does tolvaptan do?
Antagonist to V2 receptor
What is the diagnostic criteria for SIADH?
- True hyponatraemia (<135)
- Low plasma/serum osmolality (<270)
- High urine sodium (>20)
- High urine osmolality (>100)
- No adrenal/thyroid/renal dysfunction
What is SIADH?
An inappropriate ADH secretion, not in response to a stimulus
What is the mechanism of SIADH?
Increased ADH causes increased water reabsorption leading to a low plasma osmolality (secondary to dilution) causing less water to be excreted in the urine and causing a high urine osmolality
How do you confirm the diagnosis of SIADH?
- Normal 9am cortisol
- Normal TFTs
Diagnosis of exclusion
What are some causes of SIADH?
- Malignancy: SMALL CELL LUNG CANCER (most common), pancreas, prostate, lymphoma
- CNS disorders: meningoencephalitis, haemorrhage, abscess
- Chest disease: TB, pneumonia, abscess
- Drugs: opiates, SSRIs, TCAs, carbamazepine, PPIs
What is the treatment of SIADH?
- Fluid restriction
- Treat the cause
- Demeclocycline + tolvaptan can induce state of DI that may help correct SIADH (cost is prohibitive)
- IF SEVERE: slow IV hypertonic 3% saline
What would be some concurrent investigation findings in a hypernatraemic patient?
Raised urea, albumin + PCV
Which is more common - hyponatraemia or hypernatraemia?
Hyponatraemia
Which type of patients are usually hypernatraemic?
- ITU patients
- Elderly
- Infants
What is the pathogenesis of hypernatraemia?
Decreased extracellular water
How can the symptoms progress in a hypernatraemic patient?
Thirst leads to confusion, leading to seizures and ataxia leading to a coma
What are some causes of a hypovolaemic hypernatraemic patient with a urinary sodium <20
- GI loss (vomiting, diarrhoea)
- Skin loss (excessive sweating, burns)
What are some causes of a hypovolaemic hypernatraemic patient with a urinary sodium >20?
- Loop diuretics
- Osmotic diuresis (uncontrolled DM, gluce, mannitol)
- Diabetes insipidus
- Renal disease
What are some causes of a euvolaemic hypernatraemic patient?
- Respiratory (tachypnoea)
- Skin (sweating, fever)
- Diabetes insipidus
What are some causes of a hypervolaemic hypernatraemic patient?
- Mineralocorticoid excess (Conn’s syndrome)
- Inappropriate saline
What is the management of hypernatraemia?
Slow fluids/replace water (5% dextrose)
- IF really dry, replace initially with 0.9% NaCl
What are some clinical features of diabetes insipidus?
- Hypernatraemia (lethargy, thirst, irritability, confusion, coma, fits)
- Clinically euvolaemic
- Polyuria + polydipsia
- Urine plasma osmolality <2
What are some causes of cranial diabetes inspidius?
- Surgery
- Trauma
- Tumours (craniopharyngioma)
- Autoimmune hypophysitis
- Irradiation
What is the management of cranial diabetes insipidus?
Desmopressin
What is cranial diabetes insipidus?
Lack of/no ADH production
What is nephrogenic diabetes insipidus?
Receptor defect - insensitivity to ADH
What are the causes of nephrogenic diabetes insipidus?
- Inherited channelopathies
- Drugs: litium, demeclocycline
- Electrolyte disturbances: hypokalaemia, hypercalcaemia
What is the management of nephrogenic diabetes insipidus?
Thiazide diuretics (e.g. bendroflumethiazide)
What are the five steps to diagnose diabetes insipidus?
- Serum glucose (exclude DM)
- Serum potassium (exclude hypokalaemia)
- Serum calcium (exclude hypercalcaemia)
- Plasma + urine osmolality
- 8-hour water deprivation test (DIAGNOSTIC)
What is the exclusion criteria for diabetes insipidus?
Urine : Plasma osmolality ratio > 2:1
- Plasma osmolality <296mOsmol/kg
How can you distinguish between cranial and nephrogenic diabetes insipidus?
8-hour water deprivation test
- Cranial: urine osmolality increases >600mOsmol/kg ONLY after desmopressin administration
- Nephrogenic: no increase in urine osmolality, even after desmopressin
- Primary polydipsia: urine concentrates but less than normal (400-600mOsmol/kg)
