Patho-physiology of Diabetes Insipidus

Patho-physiology of Diabetes Insipidus

Introduction

Diabetes Insipidus DI is a rare disorder that comes as a result of kidney failure to concentrate urine (Shapiro, 2013). It is estimated that the daily urine production for patients suffering from this disease is 121 urines per day. The large volume of urines produced creates a need for constant replenishment through water intake. The disease disrupts the norm of life with the patients planning their day and nights with logistics of frequent urination and continuous water intake. The condition is either caused by decreased release or response to antidiuretic hormone. It results in electrolyte imbalance.

Epidemiology

Diabetes Insipidus is a rare disease with a very low prevalence of 1:25000. The condition can affect every age and has an equal incidence among males and females. The disease is found less than 10% of patients’ cases, with only 10% of the total cases of DI being hereditary. 90% of cases are the X-linked nephrogenic DI.

Etiology

DI is caused by an imbalance of fluids level in the body. For a healthy person, the kidneys help maintain the balance of fluids in the body. Excess fluids in the bloodstream are removed via the kidney. They are then temporarily stored in the bladder as urine before on urinates. Other mechanisms of removing excess fluids include breathing, sweating, and diarrhea.

The antidiuretic hormone is responsible for controlling the rate at which fluids are excreted. ADH is made in the hypothalamus and stored in the pituitary glands. When a person is suffering from DI, the body cannot balance the fluids properly. The causes vary with the type of DI on is suffering.

First, Central Diabetes Insipidus is caused by damage to the hypothalamus or pituitary gland. The damage may be from the head injury, a neuro-surgery, a tumor, or other brain illness, which causes may affect average production, release, and storage of ADH. An inherited genetic condition also causes it. The ADH deficiency caused by damage to the hypothalamus or pituitary gland can be treated by injecting a synthetic hormone called desmopressin. The hormone can also be taken via nasal spray and or as a pill. It is advised that any person under this medication should strictly take water only when thirsty. The drug prevents water excretion, and water can build up now that the kidneys are making less urine.

Secondly, Nephrogenic Diabetes Inspidus is caused by a defect in the kidney tubules. Tubules are structures in the kidney that causes re-absorption and excretion of water (Moeller et al., 2013). The abnormalities lead to the patient’s kidney’s incorrect response to ADH. The disorder may be inherited or a chronic kidney disorder. Chronic disorders include sickle cell diseases, partial blockage of the uterus, kidney failure, polycystic kidney disease, and an inherited genetic disorder. Also, certain drugs can cause NDI; they include antiviral and lithium medications.

In some cases, the cause of NDI is not discovered. A person is given indomethacin or hydrochlorothiazide to treat the condition. It may also be combined with an amiloride drug. It is also advised that the person should strictly take water only when thirsty.

nal diabetes insipidus is very rare and occurs during pregnancy. It happens when enzymes produced by the placenta damages the mother’s ADH. The placenta is a system of blood vessels and other tissues that develop with the fetus and allow the exchange of nutrients and waste products between the fetus and the mother. l

Finally, dipsogenic diabetes insipidus is caused by damage to the thirst-regulating mechanism in the hypothalamus. The condition is often linked with mental conditions such as schizophrenia. Therefore, due to excessive liquid intake, there is the production of excessive dilute urine.

Pathophysiology and molecular basis of the disease

The water balance in the body is regulated by thirst, ADH, and kidney functions. The posterior pituitary produces ADH, which is then released to the bloodstream through inferior hypophyseal arteries. What follows is the binding of ADH to V2-receptors on the renal collecting tubule. It then signals the Gs-adenyl cyclize system, which activates hence increasing cyclic 3′,5′- adenosine monophosphate. It then leads to phosphorylation of the preformed AQP2 water channel. The AQP2 helps in water flow by an osmotic gradient from the lumen into the cells of collecting duct. There is a deficiency of ADH in central diabetes insipidus while there is the availability of ADH in nephrogenic diabetes insipidus; the kidneys are not –responsive.

Types/ Classification

Central Diabetes Insipidus

The disease occurs as a result of impaired production, transportation, and release of ADH. It equally affects both females and males, and it occurs in all ages. It is, however, most frequent in ages between 10 and 20 years. The main signs of the disease are polydipsia and polyuria. The patients have rapid dehydration and compulsive thirst in case of a lack of water even for shorter periods. The thirst highly affects the patients causing sleep deprivation hence a lack of quality sleep. Most patients suffer from the complete form of the disease more than the moderate and partial form.

Nephrogenic Diabetes Insipidus

In NDI, the posterior pituitary is hyperstimulated and produces the required amount of ADH; however, the kidneys are non-responsive; hence they are unable to concentrate the urine. Three interruptions in the kidney functions characterize the disease: Generation or maintenance of the corticomedullary osmotic gradients is interrupted. Corticomedullary osmotic gradient acts as the driving force that allows osmotic water to flow from collecting duct into the interstitial tissues. Second, the osmotic equilibrium between the medullary interstitium and tubular content is interrupted due to a defect of the proximal component of ADH-cyclic adenosine monophosphate. Third, there are disturbances in the osmotic diuresis leading to the rapid production of tubular fluid hence preventing complete equilibrium between medullary interstitium and osmotic (Moeller et al., 2013). The degree of disease is varied.

The cases of NDI are divided into acquired and familial. In the acquired form, the kidney is functionally or structurally altered by disease or drugs. Some of the circumstances leading to acquired NDI are renal diseases, hypokalemia, hypercalcemia, and sickle cell anemia. Familial NDI is not very common and is caused by two genetic defects. The defects are V2 receptor mutation and aquaporin two mutations.

Signs and Symptoms

Symptom of all the diabetes insipidus cases is the need to pass a high volume of less concentrated urine. The amount of urine passed can be between 3 to 20 liters daily. In cases of Central diabetes insipidus on can give up to 30 liters of urine (Makaryus & McFarlane, 2006). Secondly, patients suffering from DI experience polydipsia that is excessive thirst. The thirst is as a result of dehydration due to excessive urination. The patients suffering from this condition have high water uptake.

Other secondary symptoms include fever, listlessness, diarrhea, and vomiting, especially in children who are unable to communicate their thirst. The aged may suffer from dementia face the risk of dehydration.

The patients may suffer from hypernatremia, a condition caused by extreme dehydration. Due to low water retention in the serum, sodium becomes is highly concentrated. It leads to cells losing water that is absorbed in the blood. Hypernatremia leads to neurological symptoms such as nerve and brain overactivity, seizures, confusion, and in extreme cases, coma.

The patient suffering from Central diabetes insipidus faces the risk of kidney failure if not treated; however, there are no severe complications for patients suffering from Nephorogenic diabetes inspidus if they maintain enough water intakes.

Diagnosis

DI has the same symptoms as DM; however, DI is not a common disorder. Therefore, doctors need to determine the correct diagnosis before beginning treatment.

First, doctors must undertake urinalysis. During this analysis, the physical and chemical properties of the urine are tested. A person suffering from DI should have his urine less concentrated. The salt and other waste concentration are low, and the amount of water is high. The level is determined by measuring particles per kg of urine (Makaryus & McFarlane, 2006).

Moreover, a fluid deprivation test is taken to determine the cause of DI. In a laboratory test, hourly measurement of urine osmolality and body weight is made. It is done continuously until the patients lose 5% of their body weight. The level of ADH in the serum is then measured, and five units of desmopressin are injected. A urine osmolality text then follows, which takes 30-60 minutes (Weiner, 2016). The following are the probable outcomes: caused by excessive fluid intake, caused by a defect in ADH production or responsiveness of kidney to ADH. The tests measure changes in urine output, body weight, and urine composition. It is also necessary to measure the blood levels of ADH. In extreme cases, MRI of the brain is essential to test damage in the hypothalamus.

References

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Boone, M., & Deen, P. (2009). Congenital nephrogenic diabetes insipidus: what can we learn from mouse models?. Experimental Physiology, 94(2), 186-190. https://doi.org/10.1113/expphysiol.2008.043000

Ma, T., Song, Y., Yang, B., Gillespie, A., Carlson, E. J., Epstein, C. J., & Verkman, A. S. (2000). Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels. Proceedings of the National Academy of Sciences, 97(8), 4386-4391. https://www.pnas.org/content/97/8/4386.short

Maghnie, M., Cosi, G., Genovese, E., Manca-Bitti, M. L., Cohen, A., Zecca, S., … & Severi, F. (2000). Central diabetes insipidus in children and young adults. New England Journal of Medicine, 343(14), 998-1007. https://www.nejm.org/doi/full/10.1056/nejm200010053431403

Makaryus, A., & McFarlane, S. (2006). Diabetes insipidus: diagnosis and treatment of a complex disease. Cleveland Clinic Journal Of Medicine, 73(1), 65-71. https://doi.org/10.3949/ccjm.73.1.65

Morello, J. P., & Bichet, D. G. (2001). Nephrogenic diabetes insipidus. Annual review of physiology, 63(1), 607-630.https://www.annualreviews.org/doi/abs/10.1146/annurev.physiol.63.1.607

Moeller, H., Rittig, S., & Fenton, R. (2013). Nephrogenic Diabetes Insipidus: Essential Insights into the Molecular Background and Potential Therapies for Treatment. Endocrine Reviews, 34(2), 278-301. https://doi.org/10.1210/er.2012-1044

Robertson, G. (2016). Diabetes insipidus: Differential diagnosis and management. Best Practice & Research Clinical Endocrinology & Metabolism, 30(2), 205-218. https://doi.org/10.1016/j.beem.2016.02.007

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