MNE: Diabetes Insipidus
MRI diagnosis of Central DI
1. disappearance of bright spot (for pituitary) = indicates a loss of neurons in the pituitary 2. thickened pituitary stalk = indicates inflammatory cause of Central DI (Lymphocytic infundibuloneurohypophysitis)
Hyperosmolar manifestations
1. dry mouth 2. thirst 3. decreased sweating 4. lethargy 5. disorientation 6. obtundation 7. coma 8. venous thrombosis (DVT, PE, CVA, death)
causes of Nephrogenic (Renal) DI
1. familial = mutations in either the AVP V2-receptor or the aquaporin-2 channel 2. acquired = result of hypercalcemia, hypokalemia, use of certain drugs (lithium and demeclocycline)
benefits of DDAVP
1. has a much longer half-life than AVP = can be administered only 2-3 times a day 2. intranasal and oral bioavailability 3. does NOT stimulate V1a receptors (in blood vessels)
Causes of Central (Neurogenic) DI
1. hypothalamic lesion (40-50% of cases) 2. idiopathic (20-30% of cases) = caused by an inflammatory attack on the posterior pituitary 3. genetic (5% of cases)
AVP
9-amino acid peptide located at the amino terminal end of a large precursor hormone (Vasotocin) the rest of the protein is secreted into the blood and has no biological effect
How do V2 receptors help retain water in kidney?
AVP binding V2 receptor activates a signal transduction cascade mediated by cAMP = causes insertion of Aquaporin water channels into the membrane of the collecting duct = allows for passage of water from collecting duct back into the bloodstream
Uosm increase of greater than 50% following AVP administration
indicates Central DI
Uosm increase of <10% following AVP administration
indicates Nephrogenic DI
Lymphocytic infundibuloneurohypophysitis
inflammatory attack on the posterior pituitary (neurohyophysis) resulting in Central DI often shows swelling of the pituitary stalk as a result of inflammatory response and edema
Nephrogenic (Renal) DI
kidney does not react to AVP
volume homeostasis
maintenance of ECF and plasma volume at adequate levels for tissue perfusion
osmotic homeostasis
maintenance of body osmolality (normal levels = 280-295 mOsm/kg water)
Primary Polydipsia
most common cause of polyuria in Western countries
antidiuresis
movement of water from collecting duct of kidney tubule through aquaporins back into the bloodstream
screening criteria Diabetes Insipidus (DI)?
need to define hypotonic polyuria: 1. 24-hr urine volume >50 mL/kg (under conditions of ad lib intake) 2. Urine-specific gravity <1.010 & Uosm <300 mOsm/kg water 3. absence of solute diuresis (urine dipstick = negative for glucose)
Nephrogenic DI
occurs as a result of defect or deficiency of AVP receptors in the kidneys no response to AVP secretion
Central DI
occurs because of insufficient Vasopressin (AVP) production
effective plasma osmolality
osmolality that causes fluid shift between the intracellular and extracellular space BUN does NOT contribute to this equation (can cross membranes freely to equalize its concentrations)
Osmotic Diuresis
osmotic agent in the urine (like glucose) causes polyuria frequently seen in diabetes mellitus
Overnight (outpatient) stimulation tests
patient must withhold all fluids after dinner until the following morning physician measures serum [Na+] and urine osmolality
Formal (inpatient) stimulation tests
patient withholds all fluids until their body weight decreases by 3-5%, urine osmolality plateaus by 2-3 successive measurements, or serum [Na+] >145 mmol/L 1. AVP is administered 2. Uosm and urine volume are followed for 2 more hours
Psychogenic DI
people are drinking too much for reasons other than true thirst (believe it is healthy, mental diseases such as schizophrenia, religious beliefs)
How do we diagnose DI?
perform stimulation tests = see if the patient still produces hypotonic urine in situations where they have high plasma osmolality
Sir Thomas Willis
person responsible for discovering that patients with diabetes mellitus had sweet tasting urine (because of glucose in urine) while urine of diabetes insipidus patients had no taste
Gestational DI
rare disorder that can occur during pregnancy
Dispogenic DI
reset thirst threshold due to lesions, granulomatous disease, idiopathic causes, or aging
Total plasma osmolality
sodium, chloride, and bicarbonate can calculate by multiplying the [Na+] by 2 (because equal amount of anions and cations)
Thirst
solely a neural mechanism
osmolality
solute (osmoles)/water (kg)
aquaporins
specific channel just for water (other molecules can't pass through)
diabetes insipidus CAN'T be diagnosed until?
the patient is shown to excrete a hypotonic urine despite the presence of a hyperosmolar serum
Fasting blood glucose labs
used to rule out Diabetes mellitus as a cause for the polyuria and polydipsia
V2 receptors
vasopressin receptor located in the kidney that causes water reabsorption in the collecting duct of the kidney
V1a receptors
vasopressin receptor that is located in blood vessels and causes vasoconstriction of blood vessels to maintain BP
Types of Diabetes Insipidus (DI)
1. Central Diabetes Insipidus 2. Nephrogenic Diabetes Insipidus 3. Gestational Diabetes Insipidus
TWO types of Primary Polydipsia
1. Dipsogenic DI 2. Psychogenic DI
mechanisms that stimulate Vasopressin production/secretion
1. Hyperosmolarity 2. decreased atrial receptor firing 3. Angiotensin II 4. Sympathetic stimulation
Hypovolemic manifestations
1. Orthostatic dizziness 2. Tachycardia 3. Hypotension 4. Syncope 5. loss of consciousness 6. death
Disorders causing Polyuria
1. Osmotic Diuresis 2. Diabetes Insipidus (DI) 3. Primary Polydipsia 4. Osmoreceptor Dysfunction
TWO major components of body fluid homeostasis
1. Osmotic homeostasis 2. Volume Homeostasis
AVP
"Arginine-Vasopressin" produced in Hypothalamus (SON and PVN) and secreted from the posterior pituitary acts on the kidney (both a neural and renal response)
Diabetes meaning
"passing water like a siphon"
mellitus meaning
"sweetened with honey"
insipidus meaning
"without taste"
mechanisms to preserve osmotic homeostasis during hyperosmolarity and dehydration
1. AVP secretion 2. Thirst
BUN
Blood Urea Nitrogen can cross cell membrane feely in order to equalize its concentrations between the intracellular and extracellular compartment
Is Diabetes Mellitus or Diabetes Insipidus more prevalent?
Diabetes mellitus is more prevalent affects 1.6% of the population for ages 20-39 affects 19.3% of the population for ages 75+
Why are pituitary lesions not sufficient enough to cause DI?
Vasopressin is produced in the hypothalamus and travels to the posterior pituitary for secretion lesions on the posterior pituitary will cause decreased release of Vasopressin but will not impact its synthesis
polyuria
abnormal production of large amounts of dilute urine
polydipsia
abnormal thirst resulting in excessive fluid intake
prevalence of Diabetes Insipidus
affects 1 in 10-15,000 people number of cases is less than 0.1% of Diabetes mellitus cases has not increases in incidence over the last 50 years
When do many Central DI cases occur?
after neurosurgery = neurons can be damaged around the base of the brain
DDAVP
analog of AVP with 2 different modifications: 1. D-Arg at position 8 (instead of L-Arg in AVP) 2. amino group is removed from the amino terminal end
Treatment for DI
antidiuretic agents (AVP or DDVAP)
normal pituitary on a MRI
appears as a bright spot
Why do most patients with DI not present with hypovolemia or hyperosmolar manifestations
because of their intact thirst mechanism
Why did the patient crave cold water?
cold water relieves thirst much better/faster than warm or room-temp water
if a patient was given AVP and their polyuria did not improve?
consider Nephrogenic DI as cause (problem with AVP receptor V2) not with AVP production
Osmoreceptor dysfunction
damage to osmoreceptors in the hypothalamus that stimulate AVP production results in Diabetes Insipidus (DI) and a lack of thirst patients reach hyperosmolality quickly and are difficult to control
urine osmolality (Uosm) >600 mOsm
effectively eliminates a diagnosis of DI in most cases
urine osmolality (Uosm) >800 mOsm
eliminates a diagnosis of DI
