Differential diagnosis of obstructive liver function tests

Obstructive liver function tests, characterized by elevated conjugated bilirubin and alkaline phosphatase, can be caused by various conditions. Here are some possible differential diagnoses:

– Stone in common bile duct: This can obstruct the flow of bile and cause jaundice, as well as dilate the bile duct. The absence of urobilinogen in urine and the correction of prothrombin time with vitamin K support the diagnosis.
– Haemolytic anaemia: This can lead to increased breakdown of red blood cells and elevated unconjugated bilirubin, but usually does not affect alkaline phosphatase.
– Hepatitis: This can cause inflammation of the liver and elevated transaminases, but usually does not affect conjugated bilirubin or alkaline phosphatase.
– Liver cirrhosis: This can result from chronic liver damage and fibrosis, but usually does not cause obstructive liver function tests unless there is associated biliary obstruction or cholestasis.
– Paracetamol overdose: This can cause liver damage and elevated transaminases, but usually does not affect conjugated bilirubin or alkaline phosphatase unless there is associated liver failure or cholestasis.

Therefore, a careful clinical evaluation and additional tests may be needed to confirm the underlying cause of obstructive liver function tests and guide appropriate management.

Common Liver Disorders and Their Characteristics

Wilson’s Disease: A rare genetic disorder that results in copper deposition in various organs, including the liver, cornea, and basal ganglia of the brain. It typically presents in children with hepatic problems and young adults with neurological symptoms such as dysarthria, tremor, involuntary movements, and eventual dementia. Kayser-Fleischer rings may be present.

Alpha-1-Antitrypsin Deficiency: A genetic disorder that results in severe deficiency of A1AT, a protein that inhibits enzymes from inflammatory cells. This can lead to cirrhosis, but is typically associated with respiratory pathology and does not present with Kayser-Fleischer rings.

Haemochromatosis: A genetic disorder that results in iron overload and is typically described as bronze diabetes due to the bronzing of the skin and the common occurrence of diabetes mellitus in up to 80% of patients.

Primary Biliary Cholangitis: An autoimmune condition that typically presents in middle-aged females with itching, jaundice, and Sjögren’s syndrome.

Autoimmune Hepatitis: An autoimmune disorder that often affects young and middle-aged women and is associated with other autoimmune disorders. Around 80% of patients respond well to steroids.

The only definitive treatment for advanced hepatic disease in primary sclerosing cholangitis (PSC) is orthotopic liver transplantation (OLT). Patients with intractable pruritus and recurrent bacterial cholangitis are specifically indicated for transplant. Although there is a 25-30% recurrence rate in 5 years, outcomes following transplant are good, with an 80-90% 5-year survival rate. PSC has become the second most common reason for liver transplantation in the United Kingdom. Other treatments such as steroids, azathioprine, methotrexate, and pentoxifylline have not been found to be useful. Antibiotic prophylaxis with ciprofloxacin or co-trimoxazole can be used to treat bacterial ascending cholangitis, but it will not alter the natural course of the disease.

Differential diagnosis for a man with abdominal pain, nausea, and periumbilical bruising

The man in question presents with classic symptoms of pancreatitis, including abdominal pain that radiates to the back and worsens on lying down. However, his periumbilical bruising suggests retroperitoneal haemorrhage, which can also cause flank bruising. Given his alcohol consumption, coagulopathy is a possible contributing factor. Hepatic cirrhosis could explain coagulopathy, but not the rapid onset of abdominal pain or the absence of ecchymosis elsewhere. A ruptured duodenal ulcer or bleeding oesophageal varices are less likely causes, as there is no evidence of upper gastrointestinal bleeding this time. A pancreatic abscess is a potential complication of pancreatitis, but would typically have a longer onset and more systemic symptoms. Therefore, the differential diagnosis includes pancreatitis with retroperitoneal haemorrhage, possibly related to coagulopathy from alcohol use.

When it comes to distinguishing between ulcerative colitis and Crohn’s disease, one key factor is the presence of crypt abscesses. These are typically seen in ulcerative colitis, which is the more common of the two inflammatory bowel diseases. In ulcerative colitis, inflammation starts in the rectum and spreads continuously up the colon, whereas Crohn’s disease often presents with skip lesions. Patients with ulcerative colitis may experience left-sided abdominal pain, cramping, bloody diarrhea with mucous, and unintentional weight loss. Colonoscopy typically reveals diffuse and contiguous ulceration and inflammatory infiltrates affecting the mucosa and submucosa only, with the presence of crypt abscesses being a hallmark feature. In contrast, Crohn’s disease is characterized by a transmural inflammatory phenotype, with non-caseating granulomas and stricturing of the bowel wall being common complications. Patients with Crohn’s disease may present with right-sided abdominal pain, watery diarrhea, and weight loss, and may have a more systemic inflammatory response than those with ulcerative colitis. Barium enema and colonoscopy can help to differentiate between the two conditions, with the presence of multiple linear ulcers in the bowel wall (rose-thorn appearance) and bowel wall thickening being suggestive of Crohn’s disease.

Extraintestinal Clinical Features Associated with IBD

Inflammatory bowel disease (IBD) is often accompanied by joint pain and inflammation, with migratory polyarthritis and sacroiliitis being common arthritic conditions. Other extraintestinal clinical features associated with IBD include aphthous ulcers, anterior uveitis, conjunctivitis, episcleritis, pyoderma gangrenosum, erythema nodosum, erythema multiforme, finger clubbing, primary sclerosing cholangitis, and fissures. However, aortic aneurysm is not known to be associated with IBD, as it is commonly linked to Marfan syndrome, Ehlers-Danlos syndrome, and collagen-vascular diseases. While peripheral arthropathy of the hands is associated with IBD, it is typically asymmetrical and non-deforming. Deforming arthropathy of the hands is more commonly associated with psoriatic arthritis and rheumatoid arthritis. Heberden’s nodes and Bouchard’s nodes, bony distal and proximal interphalangeal joint nodes, are found in osteoarthritis and are not associated with IBD. Prostatitis, a bacterial infection of the prostate gland, is not associated with IBD and is typically caused by Chlamydia or gonorrhoeae in young, sexually active men, and Escherichia coli in older men.

Effects of Gastrectomy on Nutrient Absorption and Digestion

Gastrectomy, whether partial or complete, can have significant effects on nutrient absorption and digestion. One of the most important consequences is the loss of intrinsic factors, which are necessary for the absorption of vitamin B12 in the ileum. Intrinsic factor is produced by the gastric parietal cells, which are mostly found in the body of the stomach. Without intrinsic factor, vitamin B12 cannot be absorbed and stored in the liver, leading to megaloblastic anemia and potentially serious complications such as dilated cardiomyopathy or subacute degeneration of the spinal cord.

Another consequence of gastrectomy is the loss of storage ability, which can cause early satiety and abdominal bloating after meals. This is due to the fact that the stomach is no longer able to hold as much food as before, and the remaining small intestine has to compensate for the missing stomach volume.

Achlorohydria is another common problem after gastrectomy, as the parietal cells that produce hydrochloric acid are also lost. This can lead to a range of symptoms such as abdominal bloating, diarrhea, indigestion, weight loss, malabsorption, and bacterial overgrowth of the small intestine.

Failed gastric emptying is not a major concern after gastrectomy, as it is unlikely to cause vitamin B12 deficiency. However, increased upper GI gut transit can affect the rate of nutrient absorption and lead to symptoms such as diarrhea and weight loss. Overall, gastrectomy can have significant effects on nutrient absorption and digestion, and patients should be closely monitored for any signs of malnutrition or complications.

Autoimmune Liver Diseases: Differentiating PBC, PSC, and AIH

Autoimmune liver diseases, including primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH), can present with non-specific symptoms and insidious onset. However, certain demographic and serological markers can help differentiate between them.

PBC is characterized by chronic granulomatous inflammation of small intrahepatic bile ducts, leading to progressive cholestasis, cirrhosis, and portal hypertension. It is often diagnosed incidentally or presents with lethargy and pruritus. AMA M2 subtype positivity is highly specific for PBC, and treatment involves cholestyramine for itching and ursodeoxycholic acid. Liver transplantation is the only curative treatment.

PSC is a disorder of unknown etiology characterized by non-malignant, non-bacterial inflammation, fibrosis, and strictures of the intra- and extrahepatic biliary tree. It is more common in men and frequently found in patients with ulcerative colitis. AMA is negative, and diagnosis is based on MRCP or ERCP showing a characteristic beaded appearance of the biliary tree.

AIH is a disorder of unknown cause characterized by autoantibodies directed against hepatocyte surface antigens. It can present acutely with signs of fulminant autoimmune disease or insidiously. There are three subtypes with slightly different demographic distributions and prognoses, and serological markers such as ASMA, anti-LKM, and anti-soluble liver antigen antibodies can help differentiate them.

A hepatitis screen is negative in this case, ruling out hepatitis C. A pancreatic head tumor would present with markedly elevated bilirubin and a normal autoimmune screen.

Causes of Dysphagia: Understanding the Underlying Disorders

Dysphagia, or difficulty in swallowing, can be caused by various underlying disorders. Mechanical obstruction typically causes dysphagia for solids more than liquids, while neuromuscular conditions result in abnormal peristalsis of the oesophagus and cause dysphagia for liquids more than solids. However, oesophageal dysmotility is the only condition that can cause more dysphagia for liquids than solids due to uncoordinated peristalsis.

Achalasia is a likely underlying disorder for oesophageal dysmotility, which causes progressive dysphagia for liquids more than solids with severe episodes of chest pain. It is an idiopathic condition that can be diagnosed through a barium swallow and manometry, which reveal an abnormally high lower oesophageal sphincter tone that fails to relax on swallowing.

Oesophageal cancer and strictures typically cause dysphagia for solids before liquids, accompanied by weight loss, loss of appetite, rapidly progressive symptoms, or a hoarse voice. Pharyngeal pouch causes dysphagia, regurgitation, cough, and halitosis, and patients may need to manually reduce it through pressure on their neck to remove food contents from it.

Gastro-oesophageal reflux disease (GORD) may cause retrosternal chest pain, acid brash, coughing/choking episodes, and dysphagia, typically where there is a sensation of food getting stuck (but not for liquids). Benign oesophageal stricture is often associated with long-standing GORD, previous surgery to the oesophagus, or radiotherapy.

Differentiating Hereditary Haemochromatosis from Other Liver Diseases

Raised serum ferritin levels and increased transferrin saturation, with or without abnormal liver function tests, are indicative of hereditary haemochromatosis. On the other hand, abnormal serum ferritin and iron saturation are not observed in alpha-1 antitrypsin deficiency. Diagnosis of the latter involves measuring serum alpha-1 antitrypsin levels and pi-typing for mutant alleles.

In primary biliary cirrhosis (PBC), liver function abnormalities follow a cholestatic pattern, and it typically affects middle-aged females. However, serum ferritin and iron studies are normal in PBC. Primary sclerosing cholangitis (PSC) is characterized by a disproportionate elevation (4-10 times normal) in serum alkaline phosphatase, and patients with PSC usually have a history of inflammatory bowel disease.

Finally, Wilson’s disease is a condition that primarily affects young people, usually in their second or third decade of life. It is rare for Wilson’s disease to manifest after the age of 40. By the unique characteristics of each liver disease, healthcare professionals can make an accurate diagnosis and provide appropriate treatment.