Flashcards in Lecture 25: Diabetes Insipidus Case Deck (71)
What are the 3 vasopressin receptors?
1. Vasopressin V2
2. Vasopressin V1a
3. Vasopressin V1b
Where is Vasopressin V2 located? How does it work?
Location: kidney (distal and collecting tubules)
Allows for vasopressin to function as ADH to reabsorb water
Where is Vasopressin V1a located? How does it work?
Location: smooth muscle, CNS, liver
How do the osmoreceptor afferent magnocellular neurons detect high blood osmolality? How sensitive are they?
When body is hyperosmolar the fenestrations of hypo let solute go through, this shrinks the cells that have fenestrations and activates the magnocellular neurons
VERY sensitive: respond to changes in osmolality of less than 1%
How would you characterize the osmotic regulation of vasopressin secretion?
Linear: increases as osmolality increases AT ANY BP!
Describe the 8 steps that happens when vasopressin binds the V2 receptors? What is this process referred to as?
1. Vasopressin binds V2 on basolateral membrane
2. Binding releases GDP from the Gs part of the receptor and GTP binds instead
3. Gs bound to GTP binds to adenylyl cyclase to activate it
4. cAMP synthesis
5. Protein kinase A activation
6. Phosphorylation of vesicles in cytoplasm that contain aquaporins (AQP-2)
7. Insertion of aquaporins into apical/luminal membrane to reabsorb water
8. Water pumped back into the cell (because collecting duct cell medium is always hyperosmolar) and then interstitial space via the AQP3 and 4 aquaporins of the basolateral membrane
Where is Vasopressin V1b located? How does it work?
Location: corticotrophs of ant pit
Works with CRH to release ACTH
What is sarcoidosis
The growth of tiny collections of inflammatory cells in different parts of the body.
What is histiocytosis?
Abnormal increase in the number of immune cells
Can pituitary lesions cause DI?
Usually not but can decrease the amount of secreted ADH
How can central DI be confirmed with an MRI? 2 ways
1. Swelling of the pituitary stalk on an MRI = central DI due to idiopathic cause: lymphocytic infundibuloneurohypophysitis
2. No pituitary seen on an MRI (no bright spot)
How common is central DI compared to other DI types?
Rare: less than 1:25,000
Which is more rare: central or nephrogenic DI?
How can we SCREEN for DI?
ALL criteria for hypotonic polyuria must be met:
1. 24 hr urine volume > 50 mL/kg under conditions of ad lib intake
2. Urine specific gravity below 1.010 OR Uosm below 300 mOsm/kg
3. Absence of osmotic diuresis (dipstick test for glucose negative)
What does ad lib mean in medicine?
At one's own pleasure, desire
In what patients with polyuria do you see normal blood osmolarity and BP and why?
1. Osmotic diuresis
2. Central DI
3. Nephrogenic DI
4. Gestational DI
Because their thirst is intact and regulates blood osmolarity and BP
What are 2 tests to diagnose DI?
1. Overnight outpatient test: patient withholds drinking from after dinner until morning and plasma [Na+] and Uosm is measured: if below 800 (or even 600) mOsm DI is ruled out
2. Formal inpatient test: patient withholds drinking until body weight decreases by 3-5% OR until osmolality plateaus quickly OR until [Na+] is above 145 mmol/L. THEN: measure Uosm: if below 300 then DI!
To determine which DI type:
- If Uosm increases by more than 50% = central DI
- If Uosm increases by less than 10% = nephrogenic DI
- Intermediate results: inconclusive
How common is gestational DI?
What are 5 symptoms of hypovolemia?
1. Orthostatic dizziness: blood pressure falls significantly when you stand up quickly
2. Tachychardia: rapid heart rate
4. Syncope: temporary loss of consciousness caused by a fall in blood pressure
Hypovolemia vs hypotension?
Hypovolemia is low blood volume while hypotension is low blood pressure
What are 9 symptoms of hyperosmolarity?
1. Dry mouth
3. Decreased sweating
6. Obtundation: less than full alertness
8. Venous thrombosis (deep vein, pulmonary embolism, stroke)
Why can DI patients have a poor quality of life?
Cause they need to drink and pee all the time
Treatments for DI? How do they work?
2. Antidiuretic agents (for central DI only):
- Desmopressin (DDAVP): AVP analog 2/3 times/day either orally or intranasally
How does DDAVP differ from AVP? What is their purpose?
D-Arg instead of L-Arg at position 8 and amino group removed from N-terminal => much longer half-life than AVP and does not stimulate V1a receptors
What are the 2 major defenses for maintenance of osmotic homeostasis?
1. AVP (neural and renal)
2. Thirst (neural)
What does AVP stand for?
What is diuresis?
Collecting duct is impermeable to water (normal state)
What is psychosis-intermittent hyponatremia-polydipsia (PIP) syndrom?
Increased fluid intake by schizophrenic patients: type of psychogenic DI
How do we make a DI diagnosis?
Patient has to be shown to excrete a hypotonic urine despite the presence of a hyperosmolar serum (aka when the patient is dehydrated)