Chapter 101 Flashcards
When water is lost, even a 1% increase in plasma osmolality stimulates hypothalamic osmoreceptors to release ________ from the posterior pituitary.
antidiuretic hormone = ADH, vasopressin, AVP (all the same thing)
What is the normal range of plasma osmolality?
285-290 mOsm/kg
Stimulation of the osmoreceptors on the hypothalamus stimulates the release of ADH from the posterior pituitary, BUT WHAT ELSE DOES IT STIMULATE??
THIRSTTTTT
THe ability of ADH to stimulate water reabsorption is mediated by kidney ________, which are ADH responsive water channels.
what is the major one?
aquaporins
aquaporin-2 is the major one
A lesion in any portion of the osmoregulatory system described earlier in the cards can result in Diabetes Insipidus and its attendant water diuresis*. _____ and _____ may ensue unless the thirst mechanism remains intact and access to water is adequate.
Dehydration and hypertonicy
HERES YO TEST:
CLINCIALLY…Diabetes Insipidus is characterized by what?
READY..SET..GO!!
excretion of large volumes of dilute urine in conjunction with *excessive thirst and polydipsia.
Urinary frequency must be defined from true polyuria, which is generally defined as the excretion of more than _____ or ____ per day.
3 L/day or 50 ml/kg
Stephanie comes into the clinic and Heather, the PA is torn in her differential diagnosis between Diabetes Insipidus or Primary polyuria. Stephanie tells Heather that she is CRAVING SOME ICE COLD WATER!!!! lightbulb* whats ur diagnosis?
Diabetes Insipidus (especially with central DI) - due to stimulation of osmoreceptors in the back of the throat. *Nocturia is also common
What is the color of urine in patients with Diabetes Insipidus?
Urine Osmolality?
Plasma Osmolality?
- Urine is almost always colorless, even in the morning because of its dilute nature.
- Urine osmolality is inappropriately low (<250 mOsm/kg).
- Serum Osmolality may be INCREASED! especially if the thirst mechanism is impaired
- **testin yah…. what is the normal plasma osmolality in a NORMAL patient (not with DI)? 285-290 mOsm/kg
__________ is an autosomal dominant disease caused by mutation in the arginine vasopressin gene.
Familial central diabetes insipidus
*** this is different from secondary (central) diabetes insipidus and nephrogenic diabetes insipidus which are due to deficient secretion of ADH.
_______ is characterized by normal ADH secretion but impaired renal response to ADH.
Nephrogenic Diabetes Insipidus
________ results from conditions or medications that damage renal tubulointerstitial function and concentrating ability (most commonly hypercalcemia, hypokalemia, sickle cell disease, lithium use)
Nephrogenic Diabetes Insipidus
In Nephrogenic Diabetes Insipidus, is the onset of polydipsia gradual or abrupt?
gradual!!!!!
________ produces POLYURIA and the condition appears to originate with AN ALTERED PERCEPTION OF THIRST and a primary* increase in water intake.
Primary Polydipsia
In what patients do you normally find Primary Polydipsia?
patients with chronic psychiatric disturbances (especially schizophrenia) but is also seen with organic brain disease (multiple sclerosis)
Is the onset of polydipsia gradual or abrupt in patients with primary polydipsia?
Are the symptoms episodic or continual in patients with primary polydipsia?
GRADUAL!
*like neprogenic diabetes insipidus :)
-SYMPTOMS are EPISODIC!
A patient with primary polydipsia has a fall in serum osmolality (<285 mOsm/kg) may be accompanied by what???
Hyponatremia = a deficiency of sodium in the blood
Patient comes in with diuresis (excessive discharge of urine) caused by a tumor in the sellar region?
-Will this be caused by Central DI, Nephrogenic DI, or Primary Polydipsia?
Central Diabetes Insipidus
A patient with sarcoidosis or tuberculosis is more at risk for Central DI, Nephrogenic DI, or Primary Polydipsia?
Central Diabetes Insipidus
A patient has just had her pituitary adenoma removed. Is she more at risk for Central DI, Nephrogenic DI, or Primary Polydipsia?
Central Diabetes Insipidus
A patient comes in with Sheehan’s syndrome (postpartum pituitary necrosis, syndrome results from sudden infarction of the anterior lobe precipitated by obstetric hemorrhage or shock … in pregnancy, pituitary enlarges to almost twice its normal size, compressing blood supply). Is this patient more at risk for Central DI, Nephrogenic DI, or Primary Polydipsia?
** this is one of the vascular causes
Central Diabetes Insipidus
* also stroke could be a vascular cause of Central DI
What 3 drugs can cause Nephrogenic Diabetes Insipidus?
- Lithium
- Demeclocycline
- Amphotericin
Pyelonephritis Polycystic kidney disease sickle cell disease obstructive uropathy A patient comes into the clinic with one of the four diseases listed above and diuresis. Is this patient more at risk for Central DI, Nephrogenic DI, or Primary Polydipsia?
Nephrogenic Diabetes Insipidus
What are two metabolic causes of Polyuria/ Polydipsia?
Hypercalcemia & Hypokalemia
A schizophrenia patient comes into the clinic with polyuria and diuresis. Is this patient more at risk for Central DI, Nephrogenic DI, or Primary Polydipsia?
Primary Polydipsia
***** Psychogenic disorders always this
If a patient presents to your clinic with a central nervous system disease like MULTIPLE SCLEROSIS. Is this patient more at risk for Central DI, Nephrogenic DI, or Primary Polydipsia?
Primary Polydipsia
Urinary frequency that is NOT accompanied by polydipsia (excessive or abnormal thirst) can be caused by what?
urinary tract infection (UTI)
bladder dysfunction
**(NOT KIDNEY :)…kidney = nephrogenic DI)
—–just to add a little extra… so inorder for us to consider DI or Primary Polydipsia… we have to have a patient who is PEEING ALOT with DILUTE URINE and THIRSTYYYYY
DIFFERENTIAL DIAGNOSIS —
Patient with a history of freq. voiding LARGE VOLUMES of DILUTE (colorless or pale) urine both day and night, suggests _________.
Patient that is frequently voiding SMALL VOLUMES of CONCENTRATED urine suggests _________.
- True Polyuria
2. Bladder dysfunction caused by infection
_________ provides objective conformation of true polyuria when volume exceeds 3L or 50mL/kg
****24 hour urine collection
NOW… we know how to decide if our patient has true polyuria or just urinary freq due to an infection….HOW do we decide if this if the true polyuria is due to a WATER DIURESIS OR SOLUTE DIURESIS?
- measure the urine osmolality and total solute excretion
- patients with >350 mOsm/L = Solute diuresis
- patients with
Patient has urine osmolality less than 250 mOsm/L which confirms DILUTE URINE which tells you its WATER DIURESIS and not solute….. NOW we have water diuresis causing this increased urine freq in large volumes.. Does our patient have Diabetes Insipidus or Primary Polydipsia???? How do you decide??
Measurement of serum osmolality.
- a clearly *elevated SERUM osmolality >290 mOsm/L, WITH *dilute urine
Holly, the PA, has confirmed that her patient with frequent voiding of large volumes of urine that is dilute (
Direct Measurement of the Serum ADH
- Very low levels = Central DI
- Very high levels = Renal DI
- inappropriately elevated = Primary Polydipsia
- *** this is not the most reliable test
Clinical Context:
A patient with other manifestations of pituitary disease or has a condition that may damage the central nervous system like trauma, cancer, granulomatous disease would suggest Central DI, Renal DI, or Primary Polydipsia?
Central Diabetes Insipidus
Clinical Context:
A patient who presents with a mental illness raises the probability that Central DI, Renal DI, or Primary Polydipsia?
Primary Polydipsia
What about the rate of onset of polyuria… How does this differ between Central DI, Renal DI, and Primary Polydipsia?
Central DI = gradual
Renal & Primary = abrupt
When the cause remains uncertain and in the absence of a reliable measure of ADH, it may be necessary to perform _______ test and administer ______.
Water Deprivation Test Administer Desmovasopressin (DDAVP), an ADH analog
How will the results of DDAVP (desmovasopressin) help to distinguish between the underlying mechanism of the water diuresis in trying to differentiate between Central DI, Nephrogenic DI, and Primary Polydipsia?
- In CENTRAL DI, urine osmolality increases greater than 50% (often greater than 100%) with a comparable 50% decrease in urine volume.
- Nephrogenic DI or Primary Polydipsia, unequivocal absence of change in urine concentration (
Baleigh, Heather, Holly, and Stephanie ALL MISSED THE DIAGNOSIS!!!!! A patient has had CONTINUED POLYDIPSIA for a long term. What is MOST LIKELY to occur??
*very bad
Hyponatremia = a deficiency of sodium in the blood
A patient with Central Diabetes Insipidus has a mass lesion or some other disease that is compromising the integrity of the pituitary. What should Heather order to determine whether the cause is a mass lesion or some other disease?
MRI with GADOLINIUM is the treatment of choice
but CT is a reasonable alternative if MRI is unavailable or cost is a major issue
Stephanie and Holly are NOT in agreement that this patient has Primary Polydipsia. How could Holly prove to Stephanie that this is DEFIANTLY Primary Polydipsia?
Primary Polydipsia = low-normal serum osmolality, polyuria, low urine osmolality, concurrent psychiatric disease.
AN INPATIENT WATER RESTRICTION TEST will CONFIRM hollys diagnosis.
- all parameters listed above should return to normal when water is restricted.
- this can be hazardous to a patient with DI, so CLOSE WATCH NEEDED
What is the treatment of choice for Central DI?
Desmopressin (ADH receptor AGONIST)
- intranasally, orally, or parenterally
In a patient with Central DI, Heather, being the smartest PA there is, prescribed Desmopressin. She FORGOT to educate the patient on when to take this medication. The patient calls the clinic the next day and Holly explained…… intranasal and oral directions
- The intranasally ADH is taken before bed to eliminate nocturnal polyuria.
- an initial 5 micrograms is taken at bedtime and is used, and the dose is adjusted to allow normal amounts of daytime urination.
- the usual maintenance dose is 5 to 20 micrograms once or twice a day. - 0.05 mg (not micro like with the intranasal) at BEDTIME, and teh usual maintenance is 0.1 to 0.8 mg in divided doses
Stephanie is always very concerned about her patients, therefore she ALWAYS makes a point to educate them on the risks of toxicity. What should Stephanie educate the patient on about the toxicity of Desmopressin?
- Excessive dose can lead to a DDAVP induced fluid retention and hyponatremia
- The oral preparation is one tenth of the potency of the nasal spray due to POOR GI absorption
- So steph really wants to patient to take oral prep :)
What are the 3 drugs that can be used to treat Central DI (enhance ADH secretion drugs)?
-Not Desmopressin - this is an ADH receptor agonist
Clofibrate
Chlorpropamide
Carbamazepine
**** somewhat paradoxically, thiazide diuretics and amiloride relieve the symptoms of central DI and can be used in nephrogenic DI
Treatment of Nephrogenic DI:
Because the kidneys are poorly responsive to ADH, the best treatment is ___________. (mechanism not drug)
volume contraction
Treatment of Nephrogenic DI:
What are the two drugs that can be helpful in nephrogenic DI by inducing a imld sodium diuresis, they enhance the proximal resorption of sodium and water, so the amount of water that reaches the distal tubule is reduced.
Thiazides and Amiloride
__________ are sometimes helpful in nephrogenic DI by inhibiting renal prostaglandins (which are active in settings of renal disease), they reduce water delivery to the distal tubule.
Nonsteroidal anti-inflammatory drugs = indomethacin
What is the treatment for Primary Polydipsia?
treatment of the underlying psychiatric disturbance
