What Is Chloride-Losing Diarrhea?
It is a rare, genetic intestinal condition marked by chronic, possibly fatal water diarrhea, hypochloremia (low level of body chloride), hyponatremia (low sodium level in the bloodstream), hypokalemia (low blood potassium level), and metabolic alkalosis, all leading to chronic dehydration. It can manifest in patients of all ages, from newborns to adults, with an incidence within the first weeks or months of life.
What Causes Chloride-Losing Diarrhea?
Some causes of chloride-losing diarrhea are:
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Genetic: A mutation in the CLD gene is the root cause of this extremely uncommon disease. In scientific circles, the CDL gene is often referred to as the solute carrier family of 26 members 3 genes (SLC26A3). This is because, it triggers the apical epithelial chloride and HCO3 exchanger in addition to the intestinal loss, both of which result in diarrhea, which is abundant in chloride.
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Inheritance: Due to the existence of two copies of the genes, the disease may be inherited. The person with the inherited disease would have copies of the gene that contains the disease-causing variation they received from their parents.
Which Are the Diagnostic Method?
Most typically, the diagnosis is recommended for newborns with excessive watery diarrhea and other accompanying symptoms.
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Personal History: A thorough patient history should be obtained to determine the condition. This history should include demographic information, such as the patient's age at the time of diagnosis, gender, and gestational age, and clinical information, including the patient's neonatal record, clinical features, disease progression, and family medical history.
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Laboratory Test: The electrolyte content of the stool and urine, the pH of the blood, uric acid test, sodium bicarbonate test, renal function, plasma renin activity, and aldosterone level should be determined utilizing a test.
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Ultrasonography: During the antenatal follow-up, fetal ultrasonography is performed to diagnose conditions such as abdominal distension, dilated bowel loop, edematous hypoechoic intestine wall, bowel peristalsis, intrauterine growth restriction, excessive amniotic fluid accumulation in the uterus during pregnancy (polyhydramnios).
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Renal Ultrasound: Calcium deposit in the kidney and renal size are the conditions that an ultrasound of the kidney can diagnose.
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Doppler Sonography: The test would rule out the passage of diarrhea, which uses an ultrasound image of the fetal pelvis that often reveals a rectum packed with fluid.
What Are the Management Methods?
The management of the condition would include the following:
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Salt Substitution: Sodium chloride and potassium chloride are added to the intravenous maintenance fluid as a substitution therapy in neonates at a rate of 120 to 300 mL/day (milliliters per day) within the first few days after birth. Then, the dose is increased, and the therapy switches from intravenous to peroral within the following weeks. Chloride-free urine would result from an increase in intestinal absorption during salt replacement. There will be a reduction in the development of hypochloremic and hypokalaemia and aggressive reabsorption of the chloride in the distal colon and nephron.
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Proton Pump Inhibitor: The intervention with a proton pump inhibitor would decrease the volume and frequency of stool and a recess in the bowel activity in chloride-losing diarrhea. In addition, since there is an inhibition of the gastric chloride secretion, this would protect endogenous chloride storage and even help in the amount of chloride present in the intestine by lowering the concentration. As a consequence, it would lead to a reduction in the amount of chloride that is not absorbed, the quantity of water, and cations found in the stool. As a result, the electrical and osmotic equilibrium would finally be established.
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Metabolite of Anaerobic Bacteria: Oral Butyrate is a metabolite produced by anaerobic bacteria. It is a four-carbon short-chain fatty acid that helps alleviate chloride diarrhea. It also helps prevent severe dehydration episodes and can be used in long-term treatments for rare and severe illnesses. It would stimulate intestinal water and ion absorption by working in tandem with the chloride and sodium exchange in the intestines. And the protective impact it has on the mucosa of the intestinal tract would help lessen the intensity of diarrhea.
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Bile Acid Sequestrant: It binds bile acid and lowers intestinal output, which contributes to a reduction in diarrheal symptoms.
What Are the Complications?
The complications of chloride-losing diarrhea are:
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Renal Injury: It is a condition that develops due to improper management during childhood and manifests as a complication. Alterations in the levels of renin and angiotensin, along with secondary hyperaldosteronism, generate vascular changes in the kidney. In addition, in the absence of potassium synthesis, the renal system and the cells responsible for the body's internal absorption of nutrients would negatively impact their functions.
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Elevated Uric Acid: The condition that results when there is an increase in the level of uric acid in the body due to excessive production of the uric acid combined with an inability of the body to eliminate the uric acid is referred to as hyperuricemia.
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Gout: It is a sudden, severe attack of pain, swelling, redness, and tenderness in the joint; it is a form of arthritis that is common, and is an associated condition caused by hyperuricemia.
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Sweat: Patients who suffer from chloride-losing diarrhea see an increase in the amount of chloride that is found in their sweat. Therefore, they must take in salt substitution when they experience excessive sweating.
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Male Subfertility: The term "subfertility" refers to a decline in fertility accompanied by an extended period of unintended infertility. It involves a high concentration of abnormally structured and insufficiently motile sperm in the seminal plasma, with a low pH and a high chloride concentration. Large bilateral spermatocytes are the root of the male reproductive system's problem, resulting in an inability to absorb salt and water properly.
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Diarrhea: The loss of chloride through diarrhea and increased water in the stool are both lifelong conditions associated with this condition.
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Fecal Inconsistency: It is a condition in which the individual is not able to regulate the motions of their bowels. As a result of the watery consistency of the condition, there are more chances of soiling, mostly by the patient. This condition affects children more frequently than it does the elderly, and in the elderly, it manifests itself most frequently during periods of physical activity and at night.
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Urinary Tract Complications: Patients frequently experience uncontrollable urination and hospitalization due to infections in the urinary tract. Therefore, it is recommended that these symptoms be treated with potassium and sodium chloride substitution to keep the system in equilibrium.
What Are the Follow-ups for the Patients?
The monitoring of the patient's condition includes adjustments to the salt substitution of sodium chloride and potassium chloride throughout their lifetime. Improper patient care can lead to poor conformity, and dehydration can raise the risk of various systemic complications for the patient, such as renal failure and gastrointestinal tract infections.
The dosage of the salt replacement would rely on the serum electrolyte level and the blood gas analysis for patients with an age range of fewer than three years. Therefore, patients in this age range should be followed up between intervals of three months.
In the case of an adult patient, the subsequent care would consist of a blood test to assess the acid-base and electrolyte balance, the glomerular filtration rate to ascertain that the kidneys are functioning, the recognition of any additional symptoms, and the selection of an appropriate course of treatment.
Conclusion
The loss of chloride can commence at any point in a human's life, including the later phases of childhood and even later in life when the individual is aged. The clinical signs would include hypovolemia and hypoelectrolytemia, in addition to the persistent manifestation of the disease. A better prognosis can be expected in cases of chloride-losing diarrhea if an early diagnosis and adequate salt substitution therapy consisting of sodium chloride and potassium chloride are administered. The potential kidney and urinary tract damage would increase if correct therapy were not administered. In the event of a later diagnosis, a higher dosage of salt replacement would be required. The disease's symptoms may be alleviated if optimal treatment, a healthy diet, and consistent clinic follow-ups are performed.
