Neurohypophysial Disorders Flashcards
Which neurons that originate in the hypothalamus project to the neurohypophysis
PVN and supraoptic nucleus
What are the neurohypophysis hormones
Oxytocin and VP
Where are oxytocin and vasopressin originally synthesised
In the hypothalamus
Difference in posterior pituitary and anterior in pituitary MRI?
Bright spot in the neurohypophysis
Where does VP act
collecting duct cells
What receptor does VP stimulate
V2
What does VP cause to happen to a collecting duct cell
Stimulates synthesis and assembly of aquaporin 2 at the luminal/apical membrane.
Overall effect of VP? And on urine?
Increased water transport
Concentrates urine
Other non-diuresis linked effects of VP? What receptors (3)
Vasoconstrictor Activity -‐ V1a
Corticotrophin (ACTH) Release -‐ V1b
Releases Factor VIII and von Willebrand Factor -‐ V2
Vasopressin - osmoreceptors within the BBB are sensitive to the C/D of plasma and have neurons the project into the hypothalamic paraventricular nucleus and supraoptic nucleus to stimulate VP release
BBB = circumventricular organum vasculosom C/D = concentrations/osmolality
How do osmoreceptors detect osmolality
High osmolality -> Osmoreceptors detect this as water will flow out of it due to the concentration gradient and the osmoreceptor shrink
What happens when an osmoreceptor shrinks to its firing rate
As it shrinks it neuronal firing increases
Oxytocin causes constriction of X at Y
myometrium at parturition
2 forms of Diabetes Insipidus
CENTRAL (or CRANIAL)
NEPHROGENIC
What is the problem in CENTRAL (or CRANIAL) diabetes Insipidus
Absence or lack of circulating vasopressin, neurohypophysis does not make enough vasopressin/ADH.
What is the problem in NEPHROGENIC diabetes Insipidus
End‐organ (kidneys) resistance to vasopressin. Less common.
Which form of diabetes insipidus is more common
Central/cranial
What causes acquired DI? (6)
Damage to neurohypophysial system through:
• Traumatic brain injury to neurohypophysis
• Pituitary surgery
• Cerebral thrombosis
• Tumours (intrasellar and suprasellar, craniopharyngioma)
• Metastasis to the pituitary gland (e.g. through breast cancer).
• Granulomatous infiltration of median eminence (e.g. TB and sarcoidosis
can you get congenital DI?
Yes
What causes Nephrogenic Diabetes Insipidus (2)
Congenital mutation in gene for V2 receptor or AQP2 water channel
Or acquire through through drugs (e.g. lithium which is used for BPD).
What drug for what disorder can cause DI
Lithium which is used for BPD
Signs and symptoms of DI? (5)
Large volumes of urine (polyuria)
Very dilute urine (hypo-osmolar)
Nocturia
Thirst and increased drinking (polydipsia)
Dehydration (and consequences like death) if fluid intake is not maintained
Possible disruption of sleep with associated problems
Possible electrolyte imbalance
How does DI cause thirst?
lack vasopressin -> can’t reabsorb water -> increase in urine excretion volume -> hypotonic urine and a reduction in extracellular fluid volume
This leads to an increase in plasma osmolarity (and sodium) so that will lead to osmoreceptors triggering vasopressin release and it will trigger thirst (polydipsia).
Why might a patient with DI have a normal plasma osmolarity
They are well hydrated
What is polydipsia
Thirst excessively
What is psychogenic polydipsia
increased drive to drink by psychiatric patients
What population is psychogenic polydipsia frequently seen in and why
Frequently seen in psychiatric patients, anti-cholinergic medications can cause a dry mouth
Difference between psychogenic polydipsia and DI?
Ability to secrete VP is not impaired
Results of a normal hydrated urine osmolarity test in: Normal people Psychogenic polydipsia Nephrogenic DI Central DI
All normal between 290-270mOsm/kg H2O
Normal range of urine osmolarity?
290-270mOsm/kg H2O
Results of a fluid deprived urine osmolarity test in: Normal people Psychogenic polydipsia Nephrogenic DI Central DI
Normal people will have high urine osmolarity as they will release AVP (arginine vasopressin) and concentrate the urine to preserve plasma osmolarity
In psychogenic polydipsia, the vasopressin system is working fine as so will have almost the same but justt slightly lower With central and nephrogenic diabetes insidus they have no/little change
Results of a DDAVP administered urine osmolarity test in: Normal people Psychogenic polydipsia Nephrogenic DI Central DI
You are giving extra vasopressin so this will concentrate the urine of a
normal person and the person with polydipsia
The person with CENTRAL diabetes insipidus will also be able to concentrate their urine because their vasopressin receptors are working
fine and can be stimulated by DDAVP
The NEPHROGENIC diabetes insipidus patient will not respond because they have vasopressin anyway it just doesn’t have any effect
Biochemical features of DI?
Hypernatremia
Raised urea levels
Increased plasma osmolality.
Dilute (hypo-osmolar) urine
What is the problem with using biochemical markers to test for DI? which biochemical marker is immune to this?
may be hidden if the patient is drinking a shit tonne of water
Dilute (hypo-osmolar) urine will always be hyperosmolar in DI
Treatment for central DI?
Desmopressin (DDAVP)
Which receptor are you trying to stimulate with argipressin? which is stimulated unwantlingly?
V2 in kidney
V1 in VSMC and NVSMC, pituitary, liver, platelets will however all be stimulated to
What drug stimulates only V2 receptors
Desmopressin (DDAVP)
Desmopressin (DDAVP) stimulates …
V2 receptors
RoA for DDAVP?
nasally, orally, subcutaneous injection
What should you tell a patient to do after giving them DDAVP?
Not drink as much water
Treatment for nephrogenic DI?
Thiazide Diuretics
What is The Syndrome of Inappropriate ADH (SIADH)
The plasma vasopressin concentration is INAPPROPRIATE for the existing plasma osmolarity
Too much ADH secretion is known as…
The Syndrome of Inappropriate ADH (SIADH)
What does The Syndrome of Inappropriate ADH (SIADH) cause
hyponatraemia
euvolaemia
How does excess VP cause hyponatremia and euvolaemia (mention ANP)
Increased VP Increased H20 reabsorption from renal collecting ducts Expansion of ECF volume ( Hyponatremia directly caused) Atrial natriuretic peptide (ANP) released from right atrium in response to increased ECF volume which causes Natriuresis (loss of sodium in urine) Loss of water along with sodium Euvolaemia AND hyponatremia
3 signs of SIADH
Raised urine osmolarity
Decreased urine volume (initially)
HYPONATRAEMIA -‐ decrease in plasma sodium concentration due to increased water reabsorption
MAIN CONSEQUENCE of SIADH?
Hyponatraemia
Symptoms caused by SIADH? (7)
Generalised weakness Poor mental function Nausea When Na+ concentration falls <110 mM you get: CONFUSION COMA DEATH
Causes of SIADH? (3, (3/2/1/2/0)
- CNS: SAH, stroke, tumour, TBI - Pulmonary disease: Pneumonia, bronchiectasis - Malignancy: Lung (small cell) - Drug related: Carbamezapine, SSRI - Idiopathic
Medical treatment and treatment target for SIADH?
Vaptans
Non-competitive V¬2 inhibitors
How do vaptans work
Non-competitive V¬2 inhibitors
Inhibit AQP2 synthesis and transport to collecting duct apical membrane, preventing renal water absorption
Short term treatment for SIADH?
Address the hyponatraemia, you would immediately restrict fluid, and in the long term use drugs which prevent vasopressin action in kidneys.
