Neurohypophysial disorders Flashcards
1
Q
Recall the pathophysiology of diabetes insipidus
A
- Central (cranial): absence/lack of circulating vasopressin
- Nephrogenic: end-organ (kidneys) resistance to vasopressin
Cycle:
- Lack of VP
- Increased urine excretion (polyuria)
- Reduction in EC fluid volume
- Increase in plasma osmolarity
- Osmoreceptors trigger VP release
- Triggers thirst
- Increased drinking (polydipsia)
- Decrease in plasma osmolarity
- Expansion of EC fluid volume
- Increased urine excretion (polyuria)
2
Q
What are the principle causes of diabetes insipidus?
A
Cranial:
- Damage to neurohypophysial system: injury, surgery, cerebral thrombosis, tumours, granulomatous infiltration of median eminence
- Idiopathic
- Familial (rare) - receptor gene mutations
Nephrogenic:
- Familial (rare)
- Drugs - lithium, dimethyl chlortetracycline
3
Q
What are the clinical features of diabetes insipidus?
A
- Polyuria
- Hypo-osmolar urine (v dilute)
- Polydipsia
- Dehyration if fluid intake not maintained (can –> death)
- Possible sleep disruption
- Possible electrolyte imbalance
4
Q
How is diabetes insipidus diagnosed?
A
- Water deprivation test - should stimulate VP system - no/little change in urine osmolarity/VP
- Desmopressin (DDAVP) - like giving extra VP
- Central - urine osmolarity increases bc VP receptors work fine and are stimulated by DDAVP
- Nephrogenic - no effect bc they have VP anyway, it just has no effect
5
Q
How is diabetes insipidus treated?
A
- Desmopressin (DDAVP) for cranial - oral
- Thiazide diuretics for nephrogenic
6
Q
Recall the pathophysiology of SIADH
A
- Plasma [VP] is inappropriately high for existing plasma osmolarity
- Increased water reabsorption
- Decreased plasma osmolality (hyponatraemia)
- Decreased urine volume
- Compensatory “escape” phenomenon - natriuresis + attempted restoration of urine output?
7
Q
What are the principle causes of SIADH?
A
- Tumours (ectopic secretion)
- Neurohypophysial malfunction (meningitis, cerebrovascular disease)
- Thoracic disease (pneumonia)
- Endocrine disease (Addison’s)
- Physiological (hypovolaemia, pain, surgery)
- Drugs (carbamezapine, SSRI)
- Idiopathic
8
Q
What are the principle clinical features of SIADH?
A
Signs:
- Raised urine osmolarity
- Decreased urine volume (initially)
- ***Hyponatraemia - decrease in plasma [Na] due to increased water reabsorption
Symptoms:
- Can be asymptomatic
- When [Na] falls <120mM - generalised weakness, poor mental function, nausea
- When <110mM - confusion, coma, death
9
Q
How is SIADH treated?
A
- Once cause is identified, provide appropriate treatment, e.g. surgery
- If someone already hyponatraemic, must treat this immediately: immediate fluid restriction; longer term, use drugs that prevent VP action in kidneys (lithium, dimethyl chlortetracycline, V2R antagonist - vaptans)
10
Q
What are the principle actions of vasopressin?
A
- Acts on renal cortical and medullary CDs
- Stimulates synthesis and assembly of aquaporin 2
- Increased water transport
- Increased water reabsorption
- Anti-diuretic effect
- All above = V2
- Vasoconstrictor activity - V1a
- ACTH release - V1b
- Factor VIII + VWF - V2
- Central effects
11
Q
Which receptors does vasopressin act on
A
V2 receptors
12
Q
What are the neurohypophysial hormones?
A
Vasopressin
Oxytocin