A 23-year-old male was seen in the emergency department after suffering a concussion and head trauma from a motor vehicle accident. The patient was stabilized in the emergency department and transferred to the intensive care unit (ICU) for observation. The patient had computed tomography(CT) scan of the head that revealed a small amount of cerebral edema but was otherwise normal. During the second day in the ICU, the nurse informed that the patient had a large amount of urine output in the last 24 hours. The nursing records reported his urine output over the previous 24 hours to be 5000 cc. He had not been given any diuretic medications. A urine osmolality was ordered and was found to be low. His physician remarked that the kidneys were not concentrating urine normally.
What is the most likely diagnosis for the increasing dilute urine output?
Which biochemical mediator is responsible for this disorder ?
Case discussion- The patient is suffering from Diabetes Insipidus. Excessive excretion of diluted urine with a low osmolarity and history of head injury are all suggestive of diabetes Insipidus. Head trauma is one of the most common causes of diabetes Insipidus, particularly if the posterior pituitary stalk is disrupted.
Polyuria, Polydipsia, high plasma osmolarity and a low urinary osmolarity are hall marks of diabetes Insipidus. Diabetes Insipidus is not the same as diabetes mellitus (“sugar” diabetes). Diabetes Insipidus resembles diabetes mellitus because the symptoms of both diseases are increased urination and thirst. However, in every other respect, including the causes and treatment of the disorders, the diseases are completely unrelated. Sometimes diabetes Insipidus is referred to as “water” diabetes to distinguish it from the more common diabetes mellitus or “sugar” diabetes.
The regulation of urine production occur in the hypothalamus, which produces ADH in the supraoptic and Para ventricular nuclei. After synthesis, the hormone is transported in neuro secretory granules down the axon of the hypothalamic neuron to the posterior lobe of the pituitary gland where it is stored for later release ( figure-1).
Figure-1- Synthesis, storage and release of ADH
In addition, the hypothalamus regulates the sensation of thirst in the ventromedial nucleus by sensing increases in serum osmolarity and relaying this information to the cortex (figure-2).
Figure-2- Excessive water intake leads to dilutional effect with the resultant decease in plasma osmolality that leads to decreased release of ADH. There is less water reabsorption and diuresis is promoted. Reverse occurs with a decreased intake of water, a concentrated urine is excreted due to more water reabsorption under the effect of ADH.
The main effector organ for fluid homeostasis is the kidney. ADH acts by increasing water permeability in the collecting ducts and distal convoluted tubule, specifically it acts on proteins called aquaporins which open to allow water into the collecting duct cells(figure-3).This increase in permeability allows for reabsorption of water into the bloodstream, thus concentrating the urine.
Figure-3- Under the effect of ADH aquaporins open up to allow reabsorption of water, a concentrated urine is excreted. Reverse occurs in the absence of ADH.
Signs and symptoms
- Excessive urination and extreme thirst are typical for DI. Symptoms of diabetes Insipidus are quite similar to those of untreated diabetes mellitus, with the distinction that the urine does not contain glucose and there is no hyperglycemia.
- Signs of dehydration may also appear in some individuals since the body cannot conserve much of the water it takes in.
- The extreme urination continues throughout the day and the night.
- In children, DI can interfere with appetite, eating, weight gain, and growth as well.
- They may present with fever, vomiting, or diarrhea.
- Adults with untreated DI may remain healthy for decades as long as enough water is consumed to offset the urinary losses. However, there is a continuous risk of dehydration and loss of potassium.
Biochemical defect –Diabetes Insipidus is divided into four types, each of which has a different cause and must be treated differently.
1) Central or neurogenic DI- The most common type of DI is caused by a lack of vasopressin, a hormone that normally acts upon the kidney to reduce urine output by increasing the concentration of the urine. This type of DI is usually due to the destruction of the “posterior” part of the pituitary gland where vasopressin is normally produced. Hence, it is commonly called pituitary DI.
The posterior pituitary can be destroyed by a variety of underlying diseases including tumors, infections, head injuries (as in the given patient), infiltrations, and various inheritable defects. The later can be recognized by the onset of the DI in early childhood and a family history of parents, siblings or other relatives with the same disorder. Nearly half the time, however, pituitary DI is” idiopathic” (that is, no cause can be found despite a thorough search including magnetic resonance imaging or MRI of the brain) and the underlying cause(s) is (are) still unknown.
2) Gestagenic or gestational DI –Occasionally, a lack of vasopressin can also develop during pregnancy if the pituitary is slightly damaged and/or the placenta destroys the hormone too rapidly.
3) Nephrogenic DI -The third type of DI is caused by an inability of the kidneys to respond to the “antidiuretic effect” of normal amounts of vasopressin. The kidneys’ ability to respond to ADH can be impaired by drugs—like lithium, for example—and by chronic disorders including polycystic kidney disease, sickle-cell disease, kidney failure, partial blockage of the ureters, and inherited genetic disorders.
4) Dipsogenic DI –The fourth form of DI occurs when vasopressin is suppressed by excessive intake of fluids. The latter is usually referred to as primary polydipsia and is most often caused by an abnormality in the part of the brain that regulates thirst. This subtype is difficult to differentiate from pituitary DI particularly since the two disorders can result from many of the same brain diseases.
Diagnosis is based on a series of tests, including urinalysis and a fluid deprivation test.
Urine analysis –The urine of a person with DI will be less concentrated.
A fluid deprivation test helps determine whether DI is caused by one of the following:
- excessive intake of fluid
- a defect in ADH production
- a defect in the kidneys’ response to ADH
This test measures changes in body weight, urine output, and urine composition when fluids are withheld. Sometimes measuring blood levels of ADH during this test is also necessary.
Desmopressin stimulation Test –To distinguish between the main forms,desmopressin stimulation is also used; desmopressin can be taken by injection,a nasal spray, or a tablet. While taking desmopressin, a patient should drink fluids or water only when thirsty and not at other times, as this can lead to sudden fluid accumulation in the central nervous system. If desmopressin reduces urine output and increases osmolarity, the pituitary production of ADH is deficient, and the kidney responds normally. If the DI is due to renal pathology, desmopressin does not change either urine output or osmolarity.
In order to distinguish DI from other causes of excess urination, blood glucose levels, bicarbonate levels, and calcium levels need to be tested. Measurement of blood electrolytes can reveal a high sodium level (hypernatremia as dehydration develops).
In some patients, a magnetic resonance imaging (MRI) of the brain may be necessary as well.
Central DI and gestational DI respond to desmopressin, a synthetic analogue of ADH. Gestational DI tends to abate on it sown 4 to 6 weeks following labor, though some women may develop it again in subsequent pregnancies. In dipsogenic DI, desmopressin is not usually an option. Desmopressin is ineffective in nephrogenic DI.
Again, adequate hydration is important for patients with DI, as they may become dehydrated easily.
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