Neurohypophysial Disorders Flashcards
Where are the Osmoreceptors that regulate Vasopressin Release Located?
Organum Vasculosum; neurones located here project to Hypothalamus Paraventricular and Supraoptic nuclei
How does an Osmoreceptor work?
Very sensitive to changes in osmolality of ECF.
Increase in EC Na+ (during dehydration) causes osmosis of water out of osmoreceptor neurone.
Cells shrink which causes excitation and increased firing of neurone
Leads to increased production of VP from PP.
Define osmolality:
The concentration of all solutes in a given weight of water.
Describe the sequence of events that occurs when you are water-deprived:
- Increased serum osmolality
- Stimulation of osmoreceptors
- Thirst/Increased VP release
- Increased water reabsorption from Renal collecting ducts
- Reduction in urine volume/serum osmolality
What is a basic definition of Diabetes Insipidus?
When there is insufficient ADH, or ADH doesn’t work, leading to chronic polydipsia and dehydration.
What are the two types of Diabetes Insipidus, and what characterises them?
Cranial (central) - Absence or lack of circulating vasopressin
Nephrogenic - End organ (kidney) resistance to vasopressin
What is the Aetiology of Cranial DI?
3 ways from most to least common:
Acquired
Damage to neurohypophysial system
Congenital
What types of damage to the Neurohypophysial system can cause Cranial DI?
- Traumatic brain injury
- Pituitary surgery
- Pituitary tumours, craniopharyngioma
- Metastasis to the pituitary gland eg breast
- Granulomatous infiltration of median eminence eg TB, sarcoidosis
What are the aetiologies of Nephrogenic DI?
Acquired - via drugs like Lithium
Congenital - mutation in V2 receptor
What are the signs and symptoms of DI?
Polyuria
Hypo-osmolar urine (Dilute)
Polydipsia
Dehydration
Disruption to sleep from symptoms (nocturia)
Describe what happens during dehydration in patients with DI?
Increased firing of Osmoreceptors, but no ADH increase/release
Continued production of large volumes of dilute urine
Increase in plasma osmolality
Reduction in EC fluid volume
Thirst still present so drinking
EC fluid volume expansion
What is Psychogenic Polydipsia?
Excess water intake - excess urine output
Usually in psychiatric patients, possibly due to dry-mouth side effect.
Can be bc of medical advice to drink plenty of water
Describe what happens upon increased drinking in patients with Psychogenic Polydipsia
The normal homeostatic mechanism
ADH functions correctly
What is the normal range for Plasma Osmolality?
270-290 mOsm/kg H2O
What can be diagnosed when Plasma Osmolality is above the normal range?
Diabetes insipidus
What can be diagnosed when Plasma Osmolality is below the normal range?
Psychogenic polydipsia
Describe a Water Deprivation Test:
Patient not given water, mass constantly measured
Urine osmolality measured to see response to water deprivation
DDAVP administered at the end to see response to artificial vasopressin
Describe what you would you see on a Water Deprivation test in patients with DI, P Polydispia and Normal Patients
In normal and P Polydipsia patients, urine osmolality increases as normal, but in DI patients, osmolality remains low.
When DDAVP administered, cranial DI patients will begin to retain water and Urine osmolality will increase
What is the marker of clinical dehydration?
A 3% loss of bodymass upon fluid deprivation.
Stop test then and give DDAVP or water
How do you differentiate between Central and Nephrogenic DI in a Water deprivation test?
DDAVP will cause an increase in Urine osmolality in cranial DI patients, but not nephrogenic, as they are insensitive to VP
When should you suspect DI?
Polyuria
Polydipsia
ONE . MORE
These symptoms suggest Diabetes Mellitus which is much more common and should be investigated first.
What are the biochemical features of DI?
- Hypernatraemia
- Raised urea
- Increased plasma osmolality
- Dilute (hypo-osmolar) urine - ie low urine osmolality
What are the biochemical features of Psychogenic Polydipsia?
- Mild hyponatraemia – excess water intake
- Low plasma osmolality
- Dilute (hypo-osmolar) urine - ie low urine osmolality
How is Central DI treated?
Desmopressin (DDAVP) given
It is a V2 specific agonist
How can Desmopressin be administered?
Nasal spray (could be mistaken for unimportant medicine)
Can be given orally
What should you tell a patient who is starting Desmopressin?
Patients must be told not to continue to drink large volumes of water, or they risk Hyponatraemia
How do you treat Nephrogenic DI?
Thiazides
What does SIADH stand for?
Syndrome of inappropriate ADH
Define what SIADH is:
“the plasma vasopressin concentration is inappropriately high for the existing plasma osmolality”
What are the possible signs of SIADH?
Raised Urine Osmolality
Decreased urine volume
Hyponatraemia
What are the possible symptoms of SIADH?
Can be asymptomatic
If p[Na+] <120 mM; weakness, poor mental function and nausea
If p[Na+] <110 mM; Confusion leading to Coma and ultimately death
What are the possible causes of SIADH
Often idiopathic, otherwise:
•CNS
–SAH, stroke, tumour, TBI
•Pulmonary disease
–Pneumonia, bronchiectasis
•Malignancy
–Lung (small cell)
•Drug-related
–Carbamazepine, SSRI
What is the normal treatment of SIADH?
Immediate fluid restriction
Appropriate treatment for cause, e.g. surgery for tumour excision
Demeclocycline to induce nephrogenic DI
What drugs can be given to treat SIADH and how does this work?
Vaptans: non-competitive V2 receptor antagonists.
Very expensive, rarely used
Inhibit AQP2 synthesis - aquaresis - solute sparing excretion of water
