Gastroenterology September 2022 MRCP Part – 1

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From the scenario most probably he is suffering from cystic fibrosis (CF). It is autosomal recessive condition and affecting 1-in-2500 live births and 1-in-25 adults is carrier of the gene. The gene is localised at chromosome 7 (long arm). Due to mutation of CFTR (Cystic Fibrosis Transmembrane conductance Regulator protein). It (CFTR) acts as chloride channel (cAMP-activated) and present in secretary epithelial cell. The affected person will have dry protein rich secretions which ultimately causes pulmonary and gastrointestinal complications. It also exerts exocrine pancreatic insufficiency which manifests clinically as steatorrhea, bloating and abdominal pain with failure to thrive (due to malabsorption) and diabetes mellitus in earlier part of the life. Approximately 15% CF sufferers manifest with fatty liver and cholelithiasis. The incidence of secondary biliary cirrhosis and portal hypertension (due to mucus plugging of biliary trees) are quite common. The diagnosis is done by family history, pulmonary and gastrointestinal clinical features, positive sweat chloride test. Genetic studies are the gold standard for diagnosis. Therapy includes supportive care of recurrent pulmonary infections with antibiotics, analgesics, hydration and nutrition. For gastrointestinal complications – pancreatic enzyme supplementation, correction of vitamin and nutrient deficiency, control of diabetes mellitus and symptomatic management of hepato-biliary system disorders. Lung and liver transplants and targeted gene therapy are the main cornerstone of therapy.

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As per data, females are usually more prone to be carrier in Salmonella infection among the population. The exact cause is unknown. Children are usually less susceptible to become chronic carrier. Gall bladder may act as source of recurrent infection. In first week of infection faecal culture of Salmonella typhi is about 50% only

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From the clinical scenario most probably she is suffering from coeliac disease. So, the lesions are suggestive of dermatitis herpetiformis. So, deposition of IgA is hall mark findings at the dermo-epidermal junction. It is managed by control of severity of coeliac disease by gluten free diet and administration of dapsone.

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T-cell mediated hypersensitivity reaction to gliadin component of gluten present in diet can evoke severe intestinal inflammation with villous atrophy which results malabsorption and associated malnutrition. This is how coeliac disease presents. The onset of disease is in early 20-30 years of age with slight female preponderance. Chronic diarrhoea, steatorrhea and nutritional deficiency anaemia are usual presentation of it. Some may present with abnormal liver function, thrombocytosis and hypovitaminosis. Presence of IgA anti-endomysial antibodies and anti TTG antibodies almost confirm the diagnosis initially. Biopsy from the small intestine is gold standard for diagnosing the disease. 

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The classical spectrum of iron deficiency anaemia composed of microcytosis in peripheral blood smear. But if other nutritional deficiencies are associated with anaemia like folate or vitamin B12 deficiencies, the peripheral blood smear does not correspond with typical microcytosis alone. Iron deficiency anaemia is usually diagnosed by low serum iron raised iron binding capacity.

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Howell-Jolly bodies are found in peripheral blood smear in hyposplenism. In coeliac disease, hyposplenism can be seen.

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Coeliac disease can be diagnosed with appropriate history and clinical features and presence of circulating antibodies, but definitive diagnosis is done by intestinal biopsy and corresponding features. So, biopsy proven coeliac disease doesn’t require estimation of serological antibody titre routinely.

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Presence of thrombocytosis may signify acute inflammatory state, bone marrow diseases, acute haemorrhage and other various causes.

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HNPCC or Lynch Syndrome is an autosomal dominant condition characterised by any kind of cancer mentioned below: colon, endometrial, small intestine, hepatobiliary, ovary, urinary tract or even skin cancer. It happens due to inherited mutations that alters DNA mismatch repair. Affected individuals have lifetime risk for colorectal cancer is around 50-70%. The person who was diagnosed with HNPCC should undergo colonoscopy every 2 years from the age of 25. If family history is positive for HNPCC in earlier part of life, colonoscopy screening should be started before the age of 25 for affected other family members. The most affected part in colorectal cancer is proximal part of the colon. That’s why colonoscopy is always recommended for screening of cancer than sigmoidoscopy. Recurrent CT scan is not sensitive like colonoscopy to detect the cancer in earlier stages, radiation hazards is also a crucial factor for CT screening.

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Most probably she is suffering from lymphoid tissue tumour (gastric lymphoma) which is restricted to gastric mucosa only. Studies have suggested there is strong relation between gastric lymphoma and associated H. pylori infection. So, to eradication of H. pylori will help to reduce the further occurrence of gastric lymphoma as well as recurrent mucosal ulcers. Chemo therapy and surgery can be initiated after the eradication therapy.

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In haemochromatosis, if therapy can be initiated early, certain features are reversible like cardiomyopathy and dermal pigmentation while the other affected features including cirrhosis, diabetes, arthropathy and hypogonadism remain unchanged.

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Toxic Megacolon is diagnosed with adequate history and appropriate clinical symptoms and signs in combination with radiologic evidence. Usually, the risk factors are presence of inflammatory bowel disease (IBD), recent history of Clostridium difficile, Salmonella, Shigella, Campylobacter infections, use of loperamide following Amoebic colitis, disseminated CMV infection or HIV with IBD. Presence of electrolyte imbalance can potentiate the pathogenesis of toxic megacolon. Some chemical agents like glucocorticoids (sudden stopping), antimotility agents, opioids, sulfasalazine, 5-ASA agents can precipitate formation of toxic megacolon. Diagnosis is done by (Jalan et al) radiologic evidences of colonic distension along with following criteria:

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1. Fever

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2. Tachycardia (more than 120/minute)

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3. Neutrophilic leucocytosis (TLC more than 11000)

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4. Anaemia

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Along with signs of dehydration, altered mental status, electrolyte imbalance, unstable vitals.

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As per Rockall Score the following variables are there to assess the severity of GI bleeding:

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• age (higher the age more the severity)

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• presence of shock (less the blood pressure more the severity)

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• presence of commodities (chronic heart failure, ischemic heart disease, renal failure, liver failure, metastatic cancers etc can worsen the severity)

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• Endoscopic findings (presence of active bleeding, adherent blood clots, spurting vessels carries the more severity)

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The culture of gastric biopsy for Helicobacter pylori is more standard method for diagnosis though the sensitivity is still low (72%). In contrast, the (¹³C) urea breath test has more sensitivity (95%) and specificity (98-100%). But rapid urease test on gastric biopsy has 80-95% sensitivity with specificity around 95-100%. Histological demonstration of bacteria is inferior to the (¹³C) urea breath test as it has 80-90% sensitivity and 95% specificity.

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Aged gentleman with multiple co-morbidities with having new onset weakness, weight loss and change of bowel habits should be investigated to rule out colorectal carcinomas. As per the recent data, it is the third most leading cause of cancers among UK populations following breast and lung cancers. Cancer related poor survival or death rate is quite high in colorectal carcinomas. So as per national screening programme, age more than 60 years, presence of occult or frank blood in stool, new onset altered bowel habits, history of weight loss, presence of anaemia and related complications should be investigated to rule out colorectal carcinomas by sigmoidoscopy or colonoscopy for tissue diagnosis as well as macroscopic evaluation. As he is aged enough with multiple co-morbidities, so flexible sigmoidoscopy will be much more appropriate and easier than colonoscopy.

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Computed Tomography (CT) Colonography requires adequate colon preparation and availability of skilled systems. It is almost non-invasive so medical clearance and requirement of anaesthesia are not required here. But once diagnosed with presence of mass again invasive sigmoidoscopy or colonoscopy to be needed for tissue diagnosis.

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Barium Enema can hardly diagnose feeling defect into the gut secondary to the presence of tumour mass only. Here also tissue diagnosis to be done by invasive procedures.

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Computed Tomography (CT) scan of abdomen and thorax to be done once presence of tumour mass has been done to rule out presence of metastasis.

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In liver unconjugated bilirubin is metabolised into conjugated bilirubin and glucuronic acid. The conjugated bilirubin then enters into enterohepatic circulation. The residual bilirubin which is not absorbed into the enterohepatic circulation is metabolised by bacteria present in the large intestine and forms urobilinogen and subsequently stercobilinogen. Stercobilinogen is further oxidised to stercobilin and excreted through stools.

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Secretin releases from small intestine in response of entry of acid mixed, semi digested food from stomach. It can cause decrease gastric motility and acid production. Main function of secretin is to secrete bicarbonate from pancreas and liver.

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Gastrin enhances gastric acid secretion and gastric motility.

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Vasoactive Intestinal Peptide (VIP) causes smooth muscle relaxation, increase secretion of water and electrolytes into the intestinal lumen, decrease gastric acid secretion and increase secretion of water pancreatic and biliary juice.

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Motilin causes increase in intestinal peristalsis.

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Cholecystokinin (CCK) helps to contract gall bladder for emptying with increase pancreatic exocrine secretion.

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All other drugs from the options except warfarin, follow hepatic first-pass metabolism.

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Islet B Cells secrets insulin, amylin and C peptide. It also secrets GABA and proinsulin. Islet D Cells secrets somatostatin. Islet A Cells secrets glucagon. Islets F Cells secrets pancreatic polypeptide. Gastric Chief Cells secrets pepsin and Gastric Parietal Cells secrets intrinsic factor and hydrochloric acid.  

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Coeliac disease is diagnosed through several steps. Firstly, adequate clinical history (symptoms and signs of malabsorption secondary to diarrhoea after gluten rich diet and disappearance of symptoms and signs due to administration of gluten free diet) with demonstration of antibody through serology and histopathological findings (corroborative of clinical history). The histology of duodenal mucosa will show –

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• Flat to atrophic mucosal fold depending upon severity of the disease – Villous atrophy

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• Nodular or scalloped folds

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• Increased intraepithelial lymphocytosis

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• Crypt hyperplasia

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• Chronic inflammatory cell infiltration in lamina propria

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Peutz-Jeghers Syndrome is associated with mutation of STK11/LKB1 Gene.

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Neurofibromatosis is associated with following mutations NF1-neurofibromin, NF2-merlin.

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Tuberous Sclerosis is associated with TSC1 and TSC2 gene mutation.

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Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is associated with defective mismatch repair genes hMLH1 and hMSH2.

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Familial Adenomatous Polyposis is associated with APC gene mutation.

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Oral iron in ferrous sulphate form has significant amount of elemental iron than other formulations. Iron is mainly absorbed from duodenum. Presence of ascorbic acid enhances its absorption from duodenum. Sustained release oral iron preparation can improve the iron tolerance not the rate of absorption. Oral iron has intestinal irritant property. Parenteral iron does not work faster than oral preparations. It is only indicated when oral iron cannot be tolerated or absorbed from the gut.

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Pseudopolyps are characteristically seen in both Ulcerative Colitis and Crohn’s Disease during barium studies. Other lesions mentioned above are usually found in Crohn’s Disease mainly.

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In Primary Biliary Cirrhosis (PBC) almost all the time (approx. 95%) AMA antibodies are found to be positive. Even in person without features of PBC, AMA can be positive and later on patient may develop PBC. Anti-Nuclear Antibody (ANA) found to be positive in PBC approximately 70-75%. PBC is auto immune liver disease, usually presents as features of chronic cholestasis, raised AMA, non-suppurative destructive cholangitis along with inter lobular bile duct damage (in liver biopsy). The classical history of the disease in middle aged female complaints with fatigue, pruritis, jaundice, dyslipidaemia, xanthomata and osteoporosis. Management is mainly done by ursodeoxycholic acid. Liver transplant for advanced disease with 10-year survival rate around 70% (post transplantation state).

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Hepatitis B surface antigen (HBsAg) serves as a crucial marker in the serologic diagnosis of hepatitis B virus (HBV) infection. Following acute exposure to hepatitis B virus (HBV), HBsAg becomes detectable in the bloodstream within one to 10 weeks, even before the onset of symptoms or an increase in serum alanine aminotransferase (ALT) levels.

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For individuals who successfully recover from hepatitis B virus (HBV) infection, HBsAg typically becomes undetectable within four to six months. However, if HBsAg persists in the bloodstream for more than six months, it indicates a chronic infection. It is important to note that less than 1% of individuals with a healthy immune system and acute hepatitis B progress to chronic infection.

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Among patients with chronic hepatitis B virus (HBV) infection, the rate of clearance of HBsAg is approximately 0.5% per year. This means that a small percentage of individuals with chronic infection may eventually eliminate HBsAg from their bloodstream over time.

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Understanding the presence or absence of HBsAg and its duration in the serum is crucial for the accurate diagnosis and management of hepatitis B virus infection.

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From the above list Amyloidosis is the most suitable answer here. In Peutz-Jeghers Syndrome characteristic mucocutaneous pigmentation, perioral freckling is found. In Crohn’s disease usually aphthous ulceration is common finding in oral cavity. Aphthous ulcer and glossitis are common features of coeliac disease. In tuberous sclerosis gingival fibromas are common finding not macroglossia

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Obesity, diabetes mellitus, dyslipidaemia and deranged hepatic enzymes are common associations in Non-Alcoholic Steatohepatitis (NASH). It is diagnosed by histological assessment from liver biopsy where features of hepatopathies are found with history of alcohol consumption usually less than 40 gm/week.

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Tylosis or Hyperkeratosis Palmaris / Plantaris is a condition where focal thickening of the skin of palms and soles is found. It is also known as diffuse non epidermolytic palmoplantar keratoderma. In oesophageal cancer, it is found and known as Howel-Evans syndrome.

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Necrolytic Migratory Erythema is associated with glucagonoma.

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Acanthosis Nigricans is associated with insulin resistance, pregnancy, gastric adenocarcinoma.

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Ichthyosis is associated with lymphoma.

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VIPoma is Vasoactive Intestinal Polypeptide (VIP) secreting endocrine tumour found mostly in pancreas. It originates from non-beta islet cells of pancreas. It may be associated with MEN-1. In VIPoma syndrome following features are more commonly found:

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• Profound and chronic secretory diarrhoea (‘pancreatic cholera‘)

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• weight loss

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• dehydration and hypotension

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• hypokalaemia

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• achlorhydria

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• abdominal colic

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• cutaneous flushing

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• raised plasma VIP level

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• raised urea

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• hypercalcemia

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• acidosis

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• raised plasma pancreatic polypeptide

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• hyperglycaemia

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VIP acts via following mechanism:

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• increases intestinal secretion of water and electrolytes

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• peripheral vasodilation

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• inhibition of gastric acid secretion

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• helps to increase action of acetylcholine on salivary glands.

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Transferrin is a glycoprotein formed in the liver and contains binding site of two Fe⁺³ ions. TF gene encoding its production. Iron is carried tightly but reversibly by it. Fe⁺² ion is oxidised to Fe⁺³ ion by ceruloplasmin for binding with transferrin. Transferrin saturation helps to assess iron stores in the body. Its value decreases in iron overload like hemochromatosis and increases in pregnancy, OCP use and iron deficiency state. 

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In PiZZ, Alpha-1-Antitrypsin levels are lowest.

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Somatostatin is produced by paracrine cells present throughout the gastrointestinal tract. It is chiefly secreted from the delta cells in the islet of pancreas.  It is a strong inhibitor of insulin and glucagon secretion and has multiple neuroendocrine effects in the body.

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Right-sided upper quadrant tender abdomen after chronic staying at third world country with features of evolving sepsis suggestive of liver pathology most likely. Amoebic/pyogenic liver abscess might be the probable aetiology. So, to diagnose it next best investigation would be ultrasound scan of the abdomen. High grade variable temperature, right upper quadrant pain and tenderness of abdomen, leucocytosis (neutrophilic), raised inflammatory markers along with septicaemia are the hall mark features of liver abscess. Serological diagnosis also has important role.

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Typhoid serology is not appropriate to do here.

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The clinical condition does not suggestive of hepatitis E infection.

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Stool Microscopy for ova, cysts, and parasites may have some clue for diagnosis but not at all a confirmatory tool.

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Sigmoidoscopy may demonstrate ulcerative lesions in amoebic liver abscess but not regarded as diagnostic tool. 

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There is presence of Coeliac Disease in diagnosed Type 1 Diabetes Mellitus cases (approximate prevalence is 6-8%). In most cases of both associations, the symptoms and features of coeliac disease are silent. So, it is recommended for screening of coeliac disease after diagnosing type 1 diabetes mellitus. Coeliac Disease may present with altered bowel habit after having gluten rich diet. There are occasions patients may present with normal bowel habit in coeliac disease. The atrophic intestinal villi (due to the disease process) can cause severe malabsorption resulting in iron deficiency, nutrient deficiency anaemia. In the above clinical scenario, she is anaemic (microcytic) secondary to malabsorption of iron not from blood loss (as menstrual history is normal).

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Bacterial overgrowth can cause significant diarrhoea and vitamin B12 deficiency (due to consumption by bacteria). So, macrocytic anaemia will be more prominent here.

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Crohn’s Disease always presents with symptoms (abdominal pain, diarrhoea-with or without blood mixed, fever, weight loss, abdominal distension, anaemia, skin rashes, arthritis, features of bowel obstructions, inflammation of eyes etc). So, it can’t be asymptomatic.

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Beta-Thalassaemia Minor is associated with iron deficiency anaemia.

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There is no other clinical history and features of Anorexia Nervosa.

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The correct answer is D. Laxative abuse. This is a condition where someone uses laxatives excessively or inappropriately to lose weight or purge after binge eating. It can cause diarrhoea, dehydration, electrolyte imbalance, and organ damage. Laxative abuse is more common in young, female individuals with eating disorders such as bulimia or anorexia. Patients may present with chronic watery diarrhoea, abdominal pain, and bloating, and may deny taking any laxatives.

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The other options are incorrect for the following reasons:

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• A. Microscopic colitis: This is a condition where the colon becomes inflamed and causes chronic watery diarrhoea, abdominal pain, and bloating. The diagnosis is confirmed by taking a biopsy of the colon tissue and examining it under a microscope. However, microscopic colitis is usually associated with abnormal blood tests such as low albumin and high C-reactive protein, which reflect the inflammation and malnutrition caused by the disease. This lady has normal blood tests, which makes microscopic colitis unlikely.

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• B. Small bowel bacterial overgrowth: This is a condition where there is an excessive growth of bacteria in the small intestine, which can cause diarrhoea, malabsorption, and weight loss. However, small bowel bacterial overgrowth is usually associated with risk factors such as previous abdominal surgery, structural abnormalities, or motility disorders, which this lady does not have. Moreover, small bowel bacterial overgrowth does not typically produce a raised C-reactive protein level, as the inflammation is mainly confined to the small intestine.

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• C. Intestinal tuberculosis: This is a rare form of extrapulmonary tuberculosis that affects the gastrointestinal tract, usually the ileocecal region. It can cause diarrhoea, abdominal pain, fever, weight loss, and intestinal obstruction or perforation. However, intestinal tuberculosis is more common in regions with high prevalence of tuberculosis, and usually presents with abnormal blood tests such as anaemia, elevated C-reactive protein, and abnormal liver function tests, which this lady does not have. Additionally, intestinal tuberculosis may cause blood in the stool or melaena, which this lady has not noticed.

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• E. Crohn’s disease: This is a type of inflammatory bowel disease that causes inflammation and ulceration of the digestive tract, usually the terminal ileum and colon. It can cause diarrhoea, abdominal pain, fever, weight loss, and complications such as fistulas, abscesses, or strictures. However, Crohn’s disease is more common in younger age groups, and usually presents with abnormal blood tests such as anaemia, elevated C-reactive protein, and low albumin, which this lady does not have. Furthermore, Crohn’s disease may cause blood in the stool or melaena, which this lady has not noticed.

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According to King’s College criteria, patient should be considered for liver transplantation in acute liver failure (secondary to paracetamol/ acetaminophen overdose) if –

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• pH < 7.30

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• INR > 6.5 (prothrombin time > 100 seconds)

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• Serum creatinine > 300 µmol/L (> 3.4 mg/dL)

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• Grade 3 or 4 hepatic encephalopathy

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Serum bilirubin will only be considered in acute liver failure not due to paracetamol overdose. The criteria are more specific for mortality but sensitivity as well as negative predictive value is very less. Post liver transplantation usually graft rejection, complications of infection secondary to immune suppression are hallmark complications.

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As per NICE guideline, Oesophageal manometry and 24 hours oesophageal pH study is investigation of choice to assess the severity of GERD in spite of PPI therapy. So, prior to consider for surgical therapy endoscopic evaluation of oesophagus and Gastro-Esophageal Junction (GEJ) is recommended to rule out metaplasia or neoplastic disease. Laparoscopic fundoplication is the surgical treatment in the refractory GERD cases

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Cyclosporin has following side effects:

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• Hypertension

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• Tremor

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• Nephrotoxicity

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• Superadded infection

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• Hypertrichosis

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• Hirsutism

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• Gum hyperplasia

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• Diarrhoea, nausea, vomiting, abdominal discomfort

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• Hypertriglyceridemia

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• Leg cramps, parathesia

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Uses of Cyclosporin:

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• Post solid organ transplantation – kidney, liver, heart transplantation

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• Rheumatoid arthritis

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• Eczema

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• Psoriasis

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• Nephrotic Syndrome

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The most likely electrolyte abnormality responsible for this condition of this lady is D. Hypophosphataemia. Hypophosphataemia is a low level of phosphate in the blood, which can cause various symptoms such as muscle weakness, fatigue, paraesthesia, confusion, and vision problems. Hypophosphataemia can occur in patients receiving parenteral nutrition, especially if they have refeeding syndrome, a metabolic complication that occurs when severely malnourished patients are fed too rapidly. Refeeding syndrome can cause a shift of phosphate from the blood to the cells, resulting in hypophosphataemia and other electrolyte imbalances. The diagnosis of hypophosphataemia can be confirmed by measuring the serum phosphate level, which is usually less than 0.8 mmol/L in symptomatic cases. The treatment of hypophosphataemia depends on the severity and the underlying cause, and may include oral or intravenous phosphate supplementation, adjustment of parenteral nutrition, and correction of other electrolyte disturbances.

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The other options are less likely because:

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• A. Hyperkalaemia is a high level of potassium in the blood, which can cause cardiac arrhythmias, muscle weakness, and paralysis. Hyperkalaemia can occur in patients with renal failure, acidosis, tissue breakdown, or excessive potassium intake. It does not cause double vision or paraesthesia.

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• B. Hypocalcaemia is a low level of calcium in the blood, which can cause muscle spasms, tetany, seizures, and cardiac arrhythmias. Hypocalcaemia can occur in patients with hypoparathyroidism, vitamin D deficiency, renal failure, or sepsis. It does not cause double vision or peripheral sensory loss.

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• C. Hypermagnesaemia is a high level of magnesium in the blood, which can cause hypotension, bradycardia, respiratory depression, and coma. Hypermagnesaemia can occur in patients with renal failure, excessive magnesium intake, or magnesium-containing laxatives or antacids. It does not cause double vision or paraesthesia.

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• E. Hyperphosphataemia is a high level of phosphate in the blood, which can cause hypocalcaemia, soft tissue calcification, and renal damage. Hyperphosphataemia can occur in patients with renal failure, tumour lysis syndrome, or excessive phosphate intake. It does not cause double vision or peripheral sensory loss.

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Peutz-Jeghers syndrome (PJS) is a rare genetic disorder that causes the development of hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation. Peutz-Jeghers syndrome (PJS) is associated with an increased risk of various cancers, especially gastrointestinal, breast, and gynaecological cancers. The estimated prevalence of Peutz-Jeghers syndrome (PJS) is 1 in 25,000 to 300,000 births.

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Peutz-Jeghers syndrome (PJS) is caused by mutations in the STK11 gene, which encodes a tumour suppressor protein that regulates cell growth, polarity, and metabolism. The STK11 gene is located on chromosome 19p13.3. The mode of inheritance of Peutz-Jeghers syndrome (PJS) is autosomal dominant, meaning that one copy of the mutated gene in each cell is sufficient to increase the risk of developing polyps and tumours. In about half of all cases, an affected person inherits a mutation in the STK11 gene from one affected parent. In the remaining cases, the mutation occurs for the first time in the affected person.

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The other options for the mode of inheritance of Peutz-Jeghers syndrome (PJS) are incorrect for the following reasons:

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• X linked dominant: This means that the mutated gene is located on the X chromosome, and that one copy of the mutated gene in each cell is sufficient to cause the disorder. This is not the case for Peutz-Jeghers syndrome (PJS), as the STK11 gene is located on an autosome (chromosome 19), and both males and females can be affected equally.

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• Polygenic: This means that the disorder is influenced by multiple genes, often in combination with environmental factors. This is not the case for Peutz-Jeghers syndrome (PJS), as the disorder is caused by a single gene mutation in the STK11 gene.

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• Mitochondrial: This means that the mutated gene is located in the mitochondrial DNA, which is inherited from the mother only. This is not the case for Peutz-Jeghers syndrome (PJS), as the STK11 gene is located in the nuclear DNA, which is inherited from both parents.

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• Autosomal recessive: This means that two copies of the mutated gene in each cell are required to cause the disorder. This is not the case for Peutz-Jeghers syndrome (PJS), as one copy of the mutated gene in each cell is sufficient to increase the risk of developing polyps and tumours.

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The most plausible diagnosis for this 31-year-old primigravida is B. Gilbert’s Syndrome. This is a benign genetic condition that causes mild elevations of serum bilirubin, especially during periods of stress, fasting, or illness. Gilbert’s syndrome does not affect the other liver function tests, and does not cause any symptoms or complications. It is estimated that about 5% to 10% of the general population have Gilbert’s syndrome.

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The other diagnoses are less likely because they either cause more severe abnormalities of the liver function tests, or have other clinical features that are not present in this case. For example:

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• Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the bile ducts that causes progressive scarring and obstruction of the bile flow. Primary sclerosing cholangitis (PSC) usually causes elevated levels of alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), which are markers of bile duct damage. Primary sclerosing cholangitis (PSC) is also associated with inflammatory bowel disease, especially ulcerative colitis, and increases the risk of cholangiocarcinoma and colorectal cancer.

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• Cholestasis of pregnancy is a condition that occurs in the second or third trimester of pregnancy, and causes itching and elevated levels of serum bile acids. Cholestasis of pregnancy can also affect the other liver function tests, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. Cholestasis of pregnancy can cause complications for the mother and the foetus, such as preterm delivery, foetal distress, and stillbirth.

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• Dubin-Johnson syndrome (DJS) is a rare genetic disorder that causes impaired excretion of conjugated bilirubin into the bile. Dubin-Johnson syndrome (DJS) causes chronic elevation of serum bilirubin, mainly the conjugated fraction, which can be detected by a direct (van den Bergh) test. Dubin-Johnson syndrome (DJS) does not affect the other liver function tests, and does not cause any symptoms or complications, except for a black pigmentation of the liver.

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• Primary biliary cirrhosis (PBC) is an autoimmune disease that causes progressive destruction of the small bile ducts in the liver. Primary biliary cirrhosis (PBC) causes elevated levels of alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), as well as antimitochondrial antibodies (AMA), which are specific for the diagnosis of primary biliary cirrhosis (PBC). Primary biliary cirrhosis (PBC) can also cause symptoms such as fatigue, pruritus, dry eyes, and dry mouth, and complications such as cirrhosis, portal hypertension, and hepatocellular carcinoma.

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Acute Budd-Chiari Syndrome (BCS) is clinically presented as abdominal pain and distension (secondary to ascites), tender hepatomegaly, features of portal hypertensive gastropathy (variceal bleeding – hematemesis, melaena). Rarely it can present lower extremity oedema, jaundice, fever and hepatic encephalopathy. Sub-acute or chronic Budd-Chiari Syndrome often remains asymptomatic. Signs of acute liver failure are very rare in this case. Usually, the common causes of acute liver failure in young females are associated with viral hepatitis (HAV, HBV, HEV in pregnancy), hepatic vein thrombosis (BCS) secondary to OCP use or hyper coagulable state, autoimmune hepatitis, drugs – paracetamol overdose etc.

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From the above options tender hepatomegaly is the most appropriate association in BCS. Other options like acute liver failure, ascites fluid protein of 37 g/L, ankle oedema and raised Alanine Aminotransferase (ALT) are not closely associated with BCS. They may or may not be present in acute BCS but may present in other causes of acute liver failure. So, other options are not diagnostic for acute BCS

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The above features are suggestive of Gluten sensitive enteropathy or Coeliac disease. It is T-cell mediated hypersensitivity reaction to the alpha-gliadin fraction of gluten molecule. The incidence is high among Western Ireland. HLA-B8, DRw3 is associated almost all Coeliac disease patient. The commonest clinical features are chronic diarrhoea, weight loss, growth retardation, abdominal pain, amenorrhoea, generalised weakness, paraesthesia and ataxia. Diagnosis is done by demonstration of raised Tissue Transglutaminase (TTG) antibody/ anti-endomysial antibody and duodenal biopsy. Treatment is mainly strict avoidance of gluten containing food, correction of anaemia with nutrient supplementation. GI malignancies like small bowel lymphoma have high chance of occurrence.

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The most likely reason for the anaemia in this lady is D. Parvovirus B19 infection.

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Parvovirus B19 is a virus that can infect the red blood cell precursors in the bone marrow and cause a temporary cessation of red blood cell production, leading to transient aplastic crisis (TAC). This condition is more severe in patients with chronic haemolytic disorders, such as hereditary spherocytosis (HS), which is a genetic disorder that causes the red blood cells to be abnormally shaped and prone to rupture.

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This lady in this scenario has a history of hereditary spherocytosis (HS) and presents with signs and symptoms of severe anaemia, such as extreme lethargy, shortness of breath, chest pain, and pallor. She also reports having a flu-like illness with a rash on her cheeks a few days before the onset of anaemia, which is consistent with the incubation period and clinical manifestations of parvovirus B19 infection. Her laboratory investigations show a very low haemoglobin level, indicating a profound reduction in red blood cell mass, and a high serum C-reactive protein level, indicating inflammation. Her white blood cell and platelet counts are normal, suggesting that the bone marrow suppression is selective for the erythroid lineage.

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The other options are less likely to cause such a severe anaemia in this lady with hereditary spherocytosis (HS). Influenza virus, rubella virus, Epstein Barr virus, and cytomegalovirus can all cause mild to moderate anaemia due to viral suppression of the bone marrow or immune-mediated haemolysis, but they usually affect multiple blood cell lines and do not cause transient aplastic crisis (TAC). Moreover, these viruses have different clinical features than parvovirus B19, such as respiratory symptoms, lymphadenopathy, splenomegaly, or mononucleosis-like syndrome. 

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Paracetamol poisoning has high grade probability of acute liver failure (irreversible). Usually, liver failure settles within 48 hours of ingestion of paracetamol. The condition may be associated with symptoms like jaundice, coagulopathy, encephalopathy, lactic acidosis and other organ failure like pancreas, kidney etc. Probability of death is high from 1^st to 3^rd week of onset of symptoms. N-acetyl-cysteine (NAC) are used as antidote. Blood level of paracetamol at specific time interval are plotted on the Rumack-Matthew nomogram to access the severity. Activated charcoal can be given within after few hours of ingestion. Induced vomiting is not recommended usually. Liver transplant may be required depending upon following criteria:

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• Low blood pH (< 7.3)

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• Hepatic encephalopathy

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• Hypotension (SBP < 80 mmHg)

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• High blood lactate

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• Poor blood clotting (INR > 2 within first 48 hours or > 3.5 after 48-72 hours)

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• Serum creatinine > 200 mmol/L

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From the clinical scenario, as there is no elevation of CRP, ESR most probably he is not suffering from recurrence of Crohn’s disease. Stool examination reveals no abnormality excludes the possibility of infectivity or recurrence of Crohn’s colitis. So, metronidazole, prednisolone, mesalazine will not be needed to treat his condition. As there is history of right sided hemicolectomy, the possibility of bile salt malabsorption (secondary to loss of terminal ileum) is high and may establish the cause of diarrhoea. So, the bile salt chelator cholestyramine is therapy of choice here.

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The most proper treatment of the clinical condition of this lady is A. Ciprofloxacin. This is because ciprofloxacin is an antibiotic that can treat bacterial infections that cause diarrhoea, especially in travellers who have visited high-risk areas such as Kenya. Ciprofloxacin can reduce the duration and severity of diarrhoea, and prevent complications such as dehydration and sepsis.

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The other treatments are not appropriate for her condition, for the following reasons:

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• Loperamide is an anti-diarrhoeal drug that can slow down the movement of the bowel and reduce the frequency and volume of stools. However, loperamide is not recommended for diarrhoea that is caused by infection, as it can trap the bacteria in the gut and prolong the illness. Loperamide can also increase the risk of toxic megacolon, which is a serious complication of some infections such as shigella.

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• Metronidazole is an antibiotic that can treat certain types of infections that cause diarrhoea, such as giardia and amoeba. However, metronidazole is not effective against the most common bacteria that cause traveller’s diarrhoea, such as Escherichia coli, Campylobacter, Salmonella, and Shigella. Metronidazole can also cause side effects such as nausea, vomiting, and metallic taste.

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• Vancomycin is an antibiotic that can treat severe infections that cause diarrhoea, such as Clostridioides difficile. However, vancomycin is not indicated for traveller’s diarrhoea, as it is not effective against the most common bacteria that cause it. Vancomycin can also cause side effects such as kidney damage, hearing loss, and allergic reactions.

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• Prednisolone is a steroid that can reduce inflammation and suppress the immune system. However, prednisolone is not a treatment for diarrhoea, as it can worsen the infection and increase the risk of complications. Prednisolone can also cause side effects such as weight gain, mood changes, and increased blood pressure.

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The correct answer is D. Mallory-Weiss tear. A Mallory-Weiss tear is a split in the inner layer of the oesophagus caused by forceful vomiting, retching or straining. The tear can bleed into the mouth and cause vomiting blood. The bleeding is usually mild and self-limiting, but may require endoscopic treatment in some cases. A Mallory-Weiss tear can occur in anyone who experiences severe vomiting, such as people with alcoholism, bulimia, cyclic vomiting syndrome or hyperemesis gravidarum.

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The other answer options can be ruled out as follows:

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• A. Duodenal ulceration: An open sore in the first part of the small intestine, which can bleed into the stomach and cause vomiting blood. It is often caused by a bacterial infection or by the regular use of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin. The bleeding from a duodenal ulcer is usually more severe and persistent than from a Mallory-Weiss tear, and may be associated with abdominal pain, weight loss and anaemia.

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• B. Oesophageal varices: Enlarged, swollen blood vessels in the lining of the oesophagus or stomach. They are one of the possible complications of liver cirrhosis, which can result from excessive alcohol consumption. In cirrhosis, scarred liver tissue blocks blood flow through the liver, causing an increase in pressure in the portal vein, which takes blood from the gut to the liver. The increased pressure pushes back into the gut and causes the veins to swell in the oesophagus. The swellings are quite fragile and may bleed heavily into the oesophagus. The bleeding from oesophageal varices is usually massive and life-threatening, and may be accompanied by signs of liver failure, such as jaundice, ascites and encephalopathy.

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• C. Oesophagitis: Inflammation of the oesophagus, often due to acid reflux from the stomach. The inflamed oesophagus may bleed into the mouth and cause vomiting blood. The bleeding from oesophagitis is usually mild and intermittent, and may be associated with heartburn, regurgitation and dysphagia.

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• E. Haemorrhagic gastritis: Inflammation and bleeding of the stomach lining, which can cause vomiting blood. It can be caused by various factors, such as infections, alcohol, stress, medications, or autoimmune disorders. The bleeding from haemorrhagic gastritis is usually diffuse and persistent, and may be associated with abdominal pain, fever, and shock. This option can be ruled out because this gentleman’s symptoms are not consistent with haemorrhagic gastritis. He has a long history of excessive alcohol consumption, which is a risk factor for oesophageal varices, not haemorrhagic gastritis. He also vomited only a cupful of blood, which is more suggestive of a mild and localized bleeding source, such as a Mallory-Weiss tear, rather than a diffuse and severe bleeding source, such as haemorrhagic gastritis. Furthermore, he did not have any signs of infection, stress, or autoimmune disorder that could trigger haemorrhagic gastritis. Therefore, haemorrhagic gastritis is an unlikely cause of his haematemesis.

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Most probably he is suffering from haemolytic anaemia (spherocytic in nature). The above history is suggestive of possibility of immunogenic activity. To diagnose it, direct antiglobulin test (DAT) is required. If DAT is negative possibility of hereditary spherocytosis (HS) should be worked out. The osmotic fragility test is use to detect erythrocyte resistance to haemolysis. Increased value of osmotic fragility test (more prone of haemolysis of RBC’s) found in auto-immune spherocytosis, hereditary spherocytosis, poisoning and in burn cases. The value decreases in sickle cell anaemia, thalassemia, iron deficiency anaemia. But it cannot differentiate between HS and auto-immune spherocytosis. Osmotic gradient ektacytometry can be used to differentiate between HS and hereditary stomatocytosis.

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Most probably he is suffering from bacterial overgrowth syndrome. The positive hydrogen breath test, signs of severe malnutrition (raised MCV, anaemia, bilateral pedal oedema secondary to hypoalbuminemia), bloating, abdominal distension and diarrhoea are indicating so. As his ESR is not elevated, the possibility of Crohn’s disease exacerbation is unlikely. It is managed with metronidazole and tetracycline. 

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Behçet’s Syndrome is characterised by recurrent oral ano-genital aphthus ulcers. Mucous membrane of oral cavity, genitalia, gastrointestinal, ocular are predominant cites of involvement. In severe cases, skin lesions, neurologic involvement, vascular disease, arthritis also may be seen. Exact aetiology is unknown. Most probable cause is secondary to vasculitis. It is common in Eastern Asia (China. Japan, Korea), Mediterranean countries (Turkey, Arab, Iraq, Iran) and some states of North America. Males are more severely affected than females. Ocular involvement is more associated with severe outcomes. Management consisting of supportive care and administration of immunosuppressant agents only. In severe cases individual organ supports are needed.

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The most likely underlying condition for this lady in this question is hereditary haemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome. This is a rare genetic disorder that causes abnormal blood vessel formation in various parts of the body, leading to bleeding episodes. The small red areas on her lips are called telangiectasias, which are dilated capillaries that can bleed easily. The history of her father having a bowel problem may also suggest a familial tendency for hereditary haemorrhagic telangiectasia (HHT), as the condition can affect the gastrointestinal tract and cause rectal bleeding.

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The inheritance pattern of hereditary haemorrhagic telangiectasia (HHT) is D. Autosomal dominant. This means that a person only needs to inherit one copy of the mutated gene from either parent to have the condition. The chance of passing the gene to each child is 50%, regardless of the child’s sex.

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Rectal bleeding is a common symptom that can have many different causes, ranging from benign to serious. Some of the common causes of rectal bleeding include haemorrhoids, anal fissures, diverticulosis, inflammatory bowel disease, and colorectal cancer. However, in this case, this lady has some features that suggest a rare and specific cause of rectal bleeding: hereditary haemorrhagic telangiectasia (HHT).

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Hereditary haemorrhagic telangiectasia (HHT) is a genetic disorder that affects the development and function of blood vessels in various parts of the body, such as the skin, mucous membranes, lungs, liver, brain, and gastrointestinal tract. People with hereditary haemorrhagic telangiectasia (HHT) have abnormal blood vessels that are fragile and prone to bleeding, resulting in episodes of haemorrhage that can be mild or life-threatening. The most common sites of bleeding are the nose and the gastrointestinal tract, but bleeding can occur anywhere in the body.

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The lady has two signs that are characteristic of hereditary haemorrhagic telangiectasia (HHT): telangiectasias and a family history of bowel problems. Telangiectasias are small, red, spider-like lesions that are caused by dilated capillaries near the surface of the skin or mucous membranes. They are usually found on the face, lips, tongue, mouth, fingers, and chest, but can also occur in other areas. They are painless and harmless, but can bleed easily when injured or irritated. This lady has telangiectasias on her lips, which disappear on pressure before refilling, indicating that they are vascular lesions.

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The lady also reports that her father had a bowel problem, which may indicate that he also had hereditary haemorrhagic telangiectasia (HHT) and suffered from gastrointestinal bleeding. Gastrointestinal bleeding is the second most common manifestation of hereditary haemorrhagic telangiectasia (HHT), affecting about 25% to 30% of patients. The bleeding can occur anywhere along the gastrointestinal tract, from the oesophagus to the anus, but is more common in the stomach and small intestine. The bleeding can be intermittent or chronic, and can range from mild to severe, depending on the size and location of the abnormal blood vessels. The lady describes a cupful of fresh red blood present in the toilet following defecation, which suggests a significant amount of bleeding from the lower gastrointestinal tract.

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The inheritance pattern of hereditary haemorrhagic telangiectasia (HHT) is autosomal dominant, which means that a person only needs to inherit one copy of the mutated gene from either parent to have the condition. There are at least five genes that have been identified to cause hereditary haemorrhagic telangiectasia (HHT), and each gene is responsible for a different type of hereditary haemorrhagic telangiectasia (HHT). The most common types are HHT1 and HHT2, which are caused by mutations in the genes ENG and ACVRL1, respectively. The chance of passing the gene to each child is 50%, regardless of the child’s sex. Therefore, the lady has a 50% chance of inheriting the gene from her father, and a 50% chance of passing it to her children.

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The other inheritance patterns are not consistent with hereditary haemorrhagic telangiectasia (HHT). Autosomal recessive means that a person needs to inherit two copies of the mutated gene, one from each parent, to have the condition. Mitochondrial means that the gene is inherited from the mother only, as the mitochondria are the organelles that contain their own DNA and are passed down from the egg cell. X-linked recessive means that the gene is located on the X chromosome, and males are more likely to have the condition than females, as males only have one X chromosome. X-linked dominant means that the gene is located on the X chromosome, and females are more likely to have the condition than males, as females have two X chromosomes.

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From the above clinical scenario most probably she is suffering from Campylobacter infection. It is associated with inflammatory diarrhoea, abdominal cramping pain (mostly in the iliac fossa), blood mixed stool and reactive arthritis (post remission phase). It may be associated with Acute Inflammatory Demyelinating Polyradiculopathy (AIDP) few weeks later. Other infections associated with reactive arthritis are Shigellosis, Salmonellosis and Yersinia infections.

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From the above clinical scenario most probably she is suffering from spontaneous rupture of oesophagus secondary to persistent projectile vomiting. The clinical diagnosis of spontaneous rupture of oesophagus is done by Mackler’s triad (profuse vomiting, chest pain, palpable surgical emphysema). But rarely it is present in most of the cases. A chest X-ray will reveal surgical emphysema while gastrografin swallow confirms the site of oesophageal perforation in most of the cases. Barium swallow is more sensitive than gastrografin swallow for detecting small perforations. But chances of mediastinitis is much higher in case of barium swallow. A CT scan with contrast can easily confirm the site of perforation and adjacent affected structures. But high radiation exposure and contrast induced allergic reactions are potential demerits (and cost too). Neck X-rays in lateral view may be helpful in earlier stages to detect surgical emphysema which is not evident in chest X-ray. Upper GI endoscopy may be performed once gastrografin swallow becomes negative.

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