Diabetes insipidus

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Diabetes insipidus

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Questions

USMLE® Step 1 style questions USMLE

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A 36-year-old man comes to the clinic because of increased urination and thirst for the past three months. He mentions that he urinates approximately 10 times per day, including 3-4 times at night, and he drinks about 6 liters of water per day. Past medical history is noncontributory, and the patient does not take any medications. Vitals are within normal limits. Physical examination is unremarkable. Laboratory studies are as follows:  
 
Laboratory value  Result 
Sodium  150 mEq/L 
 Serum osmolality  309 mOsmol/kg 
 Urine osmolality  187 mOsmol/kg 

There is inadequate change in the values after two hours of water deprivation. Desmopressin (antidiuretic hormone analog) is then administered. Laboratory studies one hour later revealed serum osmolality of 282 mOsmol/kg and urine osmolality of 500 mOsmol/kg. Which of the following is the most likely diagnosis?

External References

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Amiloride p. 627

for diabetes insipidus p. 349

Antidiuretic hormone (ADH) p. 338, 606

in diabetes insipidus p. 342

Demeclocycline p. 360

diabetes insipidus and p. 248, 349

Diabetes insipidus p. 349

antidiuretic hormone in p. 338

demeclocycline and p. 362

desmopressin acetate for p. 362

drug reaction and p. 248

lithium p. 592

lithium toxicity p. 587

potassium-sparing diuretics for p. 627

thiazides for p. 627

Hydrochlorothiazide (HCTZ) p. 627

for diabetes insipidus p. 342

Hypercalcemia p. 609

diabetes insipidus p. 349

Indomethacin p. 495

for diabetes insipidus p. 349

Lithium p. 592

diabetes insipidus and p. 248, 349

Nephrogenic, diabetes insipidus

Pituitary tumors

diabetes insipidus p. 342

Polyuria p. 618

diabetes insipidus p. 349

Transcript

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With diabetes insipidus, “diabetes” means an increased passing of urine, and “insipidus” means tasteless; so diabetes insipidus is a condition characterized by the production of large quantities of dilute and tasteless urine.

The tasteless urine of diabetes insipidus distinguishes it from diabetes mellitus which describes sweet tasting urine- and, yes, urine was really tasted at one point in time to make that distinction!

Now, in the brain there’s a region called the hypothalamus.

Inside the hypothalamus are osmoreceptors, which can sense the osmolality of the blood, or how concentrated it is.

Osmolality is the concentration of dissolved particles in the blood plasma, or the liquid portion of blood.

There are a number of dissolved particles in the blood plasma, but the major ones are glucose, sodium, and blood urea nitrogen, and a normal osmolality is between 285 and 295 milli Osmoles per kilogram.

During periods of dehydration there is an increase in concentration of these particles in the blood and osmolality increases.

The osmoreceptors in the hypothalamus detect the increased osmolality and that triggers the sensation of thirst, which tells us to drink more water. The water then gets absorbed and dilutes the blood, bringing the osmolality back to normal.

In addition to osmoreceptors, the hypothalamus also contains a cluster of neurons that are found in a specific spot called the supraoptic nucleus.

These neurons produce a hormone called antidiuretic hormone, or ADH. ADH is also called vasopressin because it causes smooth muscle around the blood vessels to contract, which increases blood resistance and raises blood pressure.

When the osmoreceptors detect high osmolality, they signal the supraoptic nucleus to send ADH down the supraoptico-hypophyseal tract, which runs through the infundibulum or pituitary stalk, and into the posterior pituitary gland, where it is then released into the blood.

ADH travels to the kidneys, specifically to the distal convoluted tubule and collecting ducts of the nephrons and binds to a receptor called vasopressin receptor 2, or AVPR2.

When AVPR2 is bound, proteins called aquaporins, which usually sit in vesicles inside the cells of the distal convoluted tubule and collecting ducts, start to embed themselves in the apical surface of the cells, which is the side facing the lumen of the tubule.

Summary

Diabetes insipidus is when the body cannot regulate its fluid levels properly and loses a lot of water in the urine. There are two major types of diabetes insipidus, which are central and nephrogenic diabetes insipidus. Central diabetes insipidus occurs when the hypothalamus is not producing enough antidiuretic hormone (ADH). ADH ensures that the kidneys produce less urine and reduce water loss. On the other hand, nephrogenic diabetes insipidus results from the kidneys failing to respond to ADH. People with diabetes insipidus present with excessive quantities of diluted urine (polyuria), resulting in excessive thirst (polydipsia).

Sources

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Harrison's Endocrinology, 4E" McGraw-Hill Education / Medical (2016)
  6. "THE PATHOGENESIS OF DIABETES INSIPIDUS." Journal of the American Medical Association (1907)
  7. "Management of Hypopituitarism" Journal of Clinical Medicine (2019)
  8. "Post-Traumatic Hypopituitarism—Who Should Be Screened, When, and How?" Frontiers in Endocrinology (2018)
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