Main syndromes

A compilation of the main syndromes in medical practice.
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Julio Libman, Astrid L. Libman

 

Is a condition that results from the deficient release antidiuretic hormone or arginine-vasopressin (AVP), in response to physiological stimuli, or from a lack of renal response to said hormone, which translates into a decrease in the kidney's ability to preserve Water.

Pathophysiology

Under normal conditions, the concentration of osmotically active solutes in organic fluids is kept constant between 285 and 290 mOsm / kg, despite large fluctuations in the intake of water and solutes. Renal excretion of free water is regulated by the action of an antidiuretic hormone, AVP, on the distal tubule and collecting ducts of the nephron. Normally, AVP is formed in the cells of the supraoptic nucleus and to a lesser extent the paraventricular, located in the hypothalamus, and it is transported along the neuronal axons together with a protein, neurophysin, to the nerve terminals of the infundibular stem and the neurohypophysis, from where, in response to appropriate stimuli, it is released into circulation. Even though AVP, a 1080 molecular weight octapeptide, in high doses it can determine an increase in blood pressure, in physiological concentrations its basic function is to promote antidiuresis. It exerts its effect by binding to renal receptors in the distal portion of the nephron, generating cAMP, which activates a protein kinase bound to the membrane, increasing its permeability and producing an increase in passive water reabsorption through an osmotic gradient along the collecting tubule.

AVP is released into the circulation in response to a wide variety of stimuli. Under physiological conditions, plasma osmolarity is the main regulator of its secretion. Osmoreceptor neurons are capable of detecting minimal changes in plasma osmolarity and transforming them into appropriate signals to the neuropituitary system, which increases or decreases AVP secretion in response to an increase or decrease in osmolarity, respectively.

Alterations in intravascular volume affect AVP release; a depletion of plasma volume lowers the threshold for AVP release; conversely, hypervolemia increases the osmolar threshold for its release. Distention receptors in the great vessels of the chest and in the left atrium inhibit AVP secretion via impulses that travel through the vagus nerve. Stimulation of carotid baroreceptors by hypotension results in increased release of the hormone. Pain, emotion, and stress can increase circulating AVP through poorly defined pathways. Various drugs can stimulate or inhibit AVP secretion, either by direct action on the neurohypophyseal system or by affecting the neurotransmitter system. They stimulate its secretion, for example, acetylcholine, nicotine, morphine, vincristine, etc., and inhibited by ethanol, phenytoin, atropine, etc. On the other hand, various cations and drugs influence its peripheral action. Calcium and lithium inhibit the adenyl cyclase response to AVP. Demethylchlortetracycline inhibits the stimulation of adenyl cyclase and cAMP-dependent protein kinase. On the contrary, chlorpropamide potentiates the action of AVP on the activation of adenyl cyclase.

Diabetes insipidus can be caused by a variety of hypothalamoneurohypophyseal lesions. Any injury involving the hypothalamus or the infundibular stalk at or above the median eminence can produce this condition. Consequently, diabetes insipidus may be the result of a series of infiltrative abnormalities or neurologic surgery in the hypothalamoneurohypophyseal area. It can be complete or incomplete. Destruction of the supraoptic nuclei or the section of the supraoptic-pituitary tract above the median eminence is associated with permanent and complete diabetes insipidus: lesions that sit below the median eminence, or destruction of the neurohypophysis, often lead to diabetes tasteless partial or transitory.

Patients with incomplete diabetes insipidus release enough AVP to avoid severe polyuria and usually have a diuresis of 3-6 liters / day, with a decreased but not absent response to water deprivation. Diabetes insipidus can be caused by a reduced renal response to AVP, which is seen in a variety of renal disorders, congenital or acquired, characterized by the insensitivity of the renal tubule to AVP; in these cases the circulating hormone is at levels significantly higher than normal.

In this type of diabetes insipidus, called nephrogenic, the basic abnormality lies in the inability of the collecting tubes to increase their permeability to water in response to antidiuretic hormone (ADH). In the most common form, X-linked familial diabetes insipidus, there is a mutation in the V2 receptor subtype for HAD. In other types, the abnormality resides in the aquoporin gene, which produces abnormal aquoporin channels and the inability to increase water permeability in response to HAD.

Table 63-1 lists the main etiologies of diabetes insipidus.

Table 63-1. Etiology of Diabetes Insipidus

  • Insufficient secretion of HAD (central diabetes insipidus)
    • Primary
      • Idiopathic
      • Hereditary (dominant or recessive)
    • High school
      • Postraumatic
      • Neurosurgery
      • Tumors
        • Pituitary or suprasellar
        • Metastatic (mainly lung and breast)
    • Rare causes
      • Sarcoidosis
      • Histiocitosis
      • Tuberculosis
      • Syphilis
      • Encephalitis
  • Adequate secretion of HAD (nephrogenic diabetes insipidus)
    • a. Congenital nephrogenic tasteless diabetes
    • b. Acquired nephrogenic diabetes insipidus
      • Drugs (lithium, demethylchlortetracycline, methoxyfluorane, etc.)
      • Chronic kidney disease
      • Obstructive uropathy
      • Multiple myeloma
      • Amyloid disease
      • Hypokalemia
      • Hypercalcemia
      • Polyuric phase of acute tubular necrosis
      • Sickle Red Cell Anemia

Signs and symptoms

The most important manifestation is polyuria, which can reach 10 or more liters in 24 hours with consequent polydipsia. This sign appears suddenly. In the partial forms, the diuresis is lower. Patients have a marked predilection for cold water. If they do not have the possibility of ingesting adequate amounts of fluids, the patients develop a severe picture of dehydration, with asthenia, fever, prostration, mental disorders and death. These clinical features are associated with increased plasma osmolarity and Na levels.

Study methodology

It includes the diagnosis of diabetes insipidus and, when this has been done, the investigation of the determining cause of the condition.

Plasma osmolarity . It is normally kept within a narrow range of 280-295 mOsm / kg. Na is one of the most important contributors to it and can be used to determine it through the following formula, which gives a rough estimate:

insipid01

It is an easy calculation to perform and correlates well with direct determination of osmolarity. It is important to remember that the blood must be drawn without a tourniquet and that the osmolarity must be determined as soon as possible to obtain valid results.

Urinary osmolarity . A normal individual can dilute urine to approximately 50 to 90 mOsm / kg, and concentrate it to 800 to 1500 mOsm / kg. Its isolated determination is not very useful if the plasma osmolarity is not evaluated simultaneously.

Dehydration test. The classic method for the diagnosis of central or neurogenic diabetes insipidus consists of fluid restriction followed by exogenous administration of AVP, a method that generally allows the identification of patients with complete diabetes insipidus and differentiating them from those with nephrogenic diabetes insipidus or primary polydipsia . The test is carried out by restricting fluid intake until urinary osmolarity measured with hourly intervals reaches a plateau, which usually occurs after 8 to 10 hours of liquid deprivation, which can result in the loss of 3 to 5 % of body weight. It is very important to emphasize that it is a risky test, since the patient with marked polyuria and water restriction can develop hypovolemia and vascular collapse,

The protocol is as follows:

  1. The patient is weighed at the beginning of the test and then at regular intervals.
  2. Plasma and urinary osmolarities are determined.
  3. Urinary osmolarity is then evaluated every hour, until it reaches a plateau with a change of less than 30 mOsm / kg in two consecutive samples.
  4. When this plateau occurs, blood is drawn without a tourniquet to determine plasma osmolarity.
  5. DDAVP [1- (3-mercaptopropionic acid) -8- D-arginine vasopressin], a synthetic analog of HAD, is administered 1 ug subcutaneously.
  6. Plasma and urinary osmolarity are assessed at 30, 60, and 120 minutes after injection.

In normal individuals, urinary osmolarity is greater than that of plasma after aqueous deprivation, and since AVP release is in itself maximal due to dehydration, no changes occur following exogenous administration. Thus, urinary osmolarity after AVP shows a change of less than 9% compared to the maximum prior to its administration. In circumstances where there is partial diabetes insipidus, even though urinary osmolarity may be somewhat higher than plasma after dehydration, the addition of exogenous AVP can further increase urinary osmolarity, by 9% to 50%. Patients with severe neurogenic diabetes insipidus demonstrate much lower urinary osmolality than plasma before injection of AVP, with an increase of at least 50% after it. Those with nephrogenic diabetes insipidus will not have an adequate urinary concentration during the dehydration test, and the increase in urinary osmolality following AVP administration will be zero or minimal.

Once the existence of a central diabetes insipidus has been confirmed, the necessary steps will be taken to determine its etiology, including an MRI of the brain, etc. The same applies to cases of nephrogenic diabetes insipidus.