​Kembara Xtra - Medicine - Malabsorption of Bile Acid

​Kembara Xtra - Medicine - Malabsorption of Bile Acid 

Introduction
​Increased primary bile acids in the colon cause persistent diarrhea and abdominal symptoms including pain and bloating, which are signs of bile acid malabsorption.

Defining Terms
- Type 1: Radiation injury, Crohn's disease, or ileal resection as a result of ileal dysfunction
Idiopathic, Type 2
- Type 3: Secondary to gastrointestinal conditions other than ileal dysfunction, such as chronic pancreatitis, postcholecystectomy, celiac disease, bacterial overgrowth, and others.
- Type 4: elevated bile acid production brought on by metformin (does not result in bile acid malabsorption, but may produce symptoms comparable to bile acid malabsorption due to impact of elevated bile acid levels in colon).

statistics and Epidemiology  

Prevalence

In Western nations, the prevalence is thought to be around 1% overall.
With ileal resection, prevalence in Crohn's disease patients may reach 90%.

 Thirty to forty percent of patients with functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS-D) have abnormal bile acid production.

Up to 43% of individuals with microscopic colitis have bile acid malabsorption, albeit the results are inconsistent and this finding was not confirmed in additional trials.
Unknown type 3 and type 4 bile acid malabsorption prevalence 


Pathophysiology and Etiology 

Primary bile acids are produced in the liver from cholesterol and secreted in bile after being stored in the gallbladder, where they emulsify lipids and aid in the creation of micelles.

In the colon, secondary bile acids are formed by modification of primary bile acids by intestinal bacteria; these modifications increase passive absorption of secondary bile acids in the colon. 95% of bile acids are actively absorbed in the terminal ileum via the apical sodium bile acid transporter. After passive reabsorption in the ileum or colon, primary and secondary bile acids travel back to the liver via the portal vein for reuse. Eventually, a tiny amount of bile acids is reabsorbed in the colon. Increased bile acid concentrations in the colon are caused by bile acid malabsorption in the ileum. There, the bile acids stimulate the secretion of water, electrolytes, and mucus; they also stimulate intestinal motility; and they modify the microbiome.

Genetics In mouse models, bile acid malabsorption may be caused by genetic variations in proteins involved in the enterohepatic circulation of bile acids.


Risk factors include Crohn's disease (ileal resection or ileal illness), an inflammatory bowel disorder (IBD), cholecystectomy, radiation therapy-associated ileitis (e.g., pelvic radiation therapy), and microscopic colitis.

Prevention 

There are no specific preventative methods.

associated with functional diarrhea, IBS-D, Crohn's disease, and celiac disease.

Introducing History 

The primary symptom of bile acid malabsorption is diarrhea. Other symptoms include bloating, fecal urgency, and discomfort in the abdomen.



clinical assessment 

On physical examination, there were no specific findings.

Multiple Diagnoses 

IBD, celiac disease, lactase deficiency, small intestinal bacterial overgrowth, parasite infection, cancer, microscopic colitis, endocrine dysfunction, and other conditions are other causes of persistent diarrhea.

Understanding test results 

Diagnostic testing may find decreased hepatic feedback inhibition, decreased ileal bile acid absorption, and/or increased hepatic bile acid production.
Initial examinations (lab, imaging)
Check first for additional reasons of persistent watery diarrhea; the following list is not all-inclusive.

 Upper endoscopy and colonoscopy with biopsies (to check for microscopic colitis, IBD, and celiac disease).
Giardia antigen, stool ova, and parasites (parasitic disorders)
Testing of thyroid function (hyperthyroidism)
Breath test for small intestine bacterial overgrowth; thorough medication review for diarrhea brought on by medicine.
Hemoglobin A1c (diabetes mellitus) and dietary history (sorbitol, for example, might cause osmotic diarrhea)

Tests in the Future & Special Considerations

 As many of the below tests have restricted availability or are still under research, an empiric trial with bile acid sequestrant (cholestyramine, colesevelam, or colestipol) may be taken into consideration in place of diagnostic testing. Various response rates to a first-line cholestyramine trial have been reported; in cases of severe bile acid malabsorption, the response rate reached 96%.

75SeHCAT (75-selenium homocholic acid taurine) (3) measures ileal reabsorption of a radiolabeled bile acid after seven days; decreased retention may signify type 1 bile acid malabsorption.
– For illness, thresholds of 15% retention (mild), 10% (moderate), or 5% (severe) are used.
- A finite amount of stock
● 7-hydroxy-4-cholesten-3-one (C4) in fasting serumLow ileal reabsorption may be indicated by high fasting serum C4 levels (cutoff value >48 ng/mL), which are a direct indicator of bile acid production.
48-hour fecal bile acid test (1) is commercially accessible through Mayo Clinic and is favored over fecal testing. Patients follow a high-fat diet for 4 days and collect stool for the previous 48 hours. Total and primary bile acids are measured, as well as the amount of fecal fat. Total fecal bile acids 2,337 mol/48 hr, primary bile acids >10%, or total fecal bile acids 1,000 mol/48 hr + primary bile acids >4% are the diagnostic standards for bile acid malabsorption.
Serum fasting fibroblast growth factor 19 (FGF-19) assesses bile acid production and has an inverse correlation with serum fasting C4. Lackluster test qualities and little usage.

Bile acid sequestrants are the cornerstone of treatment and may lessen gastrointestinal discomfort and stooling.

Chronic diarrhea caused by bile acid malabsorption is treated with a short course of cholestyramine in 70–96% of patients; dosage is started at 4 g once daily and increased up to 4 times daily.

Initial Line
Initiate at 4 g once daily and increase frequency up to 4 times daily for a short course of cholestyramine to treat chronic diarrhea caused by bile acid malabsorption in 70-96% of patients. Colesevelam and colestipol are the additional bile acid sequestrants that are readily available.
To prevent adverse effects (such as constipation, nausea, and abdominal discomfort), gradually increase the bile acid sequestrant dosage.
Other drugs should be administered 1 hour before or 4 to 6 hours after bile acid sequestrants since they may interfere with the absorption of other drugs.
Next Line
Primary bile acids increase the amount of electrolyte discharge in the colon, which is decreased by farnesoid X receptor (FXR) agonists. These are still being looked into.

entry into a hospital 
Rarely does the treatment of bile acid malabsorption require hospitalization.


Constant Care 
Treatment for IBD may lessen the symptoms of bile acid malabsorption in people who have it.

A follow-up 

No specific recommendations for further action
patient observation
When using long-term bile acid sequestrants, patients should be watched for malabsorption of fat-soluble vitamins (e.g., monitor vitamin A and E levels and prothrombin time) (1).
DIET A low-fat diet may enhance pharmacological therapy and lessen symptoms.

With the right diagnosis and treatment, the prognosis is favorable.

Complications 
Volume depletion brought on by watery diarrhea is rare not unlikely.
Patients taking bile acid sequestrants as a long-term treatment may experience malabsorption of fat-soluble vitamins (1).