Gastroenterology Flashcards

Question

Examination Findings with Excess Alcohol

Answer 1

Signs suggestive of excessive alcohol consumption include: Smelling of alcohol Slurred speech Bloodshot eyes Dilated capillaries on the face (telangiectasia) Tremor

Answer 2

Blood test results suggesting alcohol-related liver disease include: Raised mean cell volume (MCV) Raised alanine transaminase (ALT) and aspartate transferase (AST) AST:ALT ratio above 1.5 particularly suggests alcohol-related liver disease Raised gamma-glutamyl transferase (gamma-GT) (particularly notable with alcohol-related liver disease) Raised alkaline phosphatase (ALP) later in the disease Raised bilirubin in cirrhosis Low albumin due to reduced synthetic function of the liver Increased prothrombin time due to reduced synthetic function of the liver (reduced production of clotting factors) Deranged U&Es in hepatorenal syndrome Liver ultrasound may show early fatty changes with “increased echogenicity”. Later, it can show changes related to cirrhosis. Ultrasound is used to screen for hepatocellular carcinoma in patients with cirrhosis. Transient elastography (“FibroScan”) can be used to assess the elasticity of the liver using high-frequency sound waves. It helps determine the degree of fibrosis (scarring). Endoscopy can be used to assess for and treat oesophageal varices when portal hypertension is suspected. CT and MRI scans can be used to look for fatty infiltration of the liver, hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes and ascites. Liver biopsy can be used to confirm the diagnosis of alcohol-related hepatitis or cirrhosis, particularly in patients where steroid treatment is being considered for alcohol-related hepatitis.

Answer 3

Stop drinking alcohol permanently (drug and alcohol services are available for support) Psychological interventions (e.g., motivational interviewing or cognitive behavioural therapy) Consider a detoxication regime Nutritional support with vitamins (particularly thiamine – vitamin B1) and a high-protein diet Corticosteroids may be considered to reduce inflammation in severe alcoholic hepatitis to improve short-term outcomes (but not long-term outcomes) Treat complications of cirrhosis (e.g., portal hypertension, varices, ascites and hepatocellular carcinoma) Liver transplant in severe disease (generally 6 months of abstinence is required)

Answer 4

The CAGE questions can be used to quickly screen for harmful alcohol use: C – CUT DOWN? Do you ever think you should cut down? A – ANNOYED? Do you get annoyed at others commenting on your drinking? G – GUILTY? Do you ever feel guilty about drinking? E – EYE OPENER? Do you ever drink in the morning to help your hangover or nerves?

Answer 5

The Alcohol Use Disorders Identification Test (AUDIT) was developed by the World Health Organisation to screen people for harmful alcohol use. It involves 10 questions with multiple-choice answers and gives a score. A score of 8 or more indicates harmful use.

Answer 6

Alcohol dependence involves a risk of withdrawal symptoms. These range from mild and uncomfortable to delirium tremens. Symptoms occur at different times after alcohol consumption ceases: 6-12 hours: tremor, sweating, headache, craving and anxiety 12-24 hours: hallucinations 24-48 hours: seizures 24-72 hours: delirium tremens

Answer 7

Delirium tremens is a medical emergency associated with alcohol withdrawal. There is a 35% mortality rate if left untreated. Alcohol is a depressant substance. It stimulates GABA receptors in the brain. GABA receptors have a relaxing effect on the rest of the brain. Alcohol also inhibits glutamate receptors (also known as NMDA receptors), causing a further relaxing effect on the electrical activity of the brain (glutamate is an “excitatory” neurotransmitter). Chronic alcohol use results in the GABA system becoming down-regulated and the glutamate system becoming up-regulated to balance the effects of alcohol. When alcohol is removed, the GABA system under-functions and the glutamate system over-functions, causing extreme excitability of the brain and excessive adrenergic (adrenalin-related) activity. This presents with: Acute confusion Severe agitation Delusions and hallucinations Tremor Tachycardia Hypertension Hyperthermia Ataxia (difficulties with coordinated movements) Arrhythmias

Answer 8

The CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol, revised) tool can be used to score the patient on their withdrawal symptoms and guide treatment. Chlordiazepoxide (Librium) is a benzodiazepine used to combat the effects of alcohol withdrawal. Diazepam is a less commonly used alternative. It is given orally as a reducing regime titrated to the required dose based on the local alcohol withdrawal protocol (e.g., 10 – 40 mg every 1 – 4 hours). The dose is reduced over 5-7 days. High-dose B vitamins (Pabrinex) is given intramuscularly or intravenously, followed by long-term oral thiamine. This is used to prevent Wernicke-Korsakoff syndrome.

Answer 9

Alcohol excess leads to thiamine (vitamin B1) deficiency. Thiamine is poorly absorbed in the presence of alcohol. Alcoholics often have poor diets and get many of their calories from alcohol. Thiamine deficiency leads to Wernicke’s encephalopathy and Korsakoff syndrome. Features of Wernicke’s encephalopathy include: Confusion Oculomotor disturbances (disturbances of eye movements) Ataxia (difficulties with coordinated movements) Features of Korsakoff syndrome include: Memory impairment (retrograde and anterograde) Behavioural changes Wernicke’s encephalopathy is a medical emergency with a high mortality rate. Korsakoff syndrome is often irreversible and results in patients requiring full-time institutional care. Prevention and treatment involve thiamine supplementation and abstaining from alcohol.

Answer 10

Non-alcoholic fatty liver disease (NAFLD) is characterised by excessive fat in the liver cells, specifically triglycerides. These fat deposits interfere with the functioning of the liver cells. The early stages of NAFLD can be asymptomatic. However, it can progress to hepatitis and liver cirrhosis. Around 25% of adults are estimated to have non-alcoholic fatty liver disease.

Answer 11

Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis (NASH) Fibrosis Cirrhosis

Answer 12

Non-alcoholic fatty liver disease shares the same risk factors as cardiovascular disease and diabetes: Middle age onwards Obesity Poor diet and low activity levels Type 2 diabetes High cholesterol High blood pressure Smoking It is associated with metabolic syndrome, which is a combination of hypertension, obesity and diabetes. Metabolic syndrome is common and dramatically increases the risk of cardiovascular disease and other health problems.

Answer 13

Raised alanine aminotransferase (ALT) on the liver function blood tests is often the first indication that a patient has NAFLD. Liver ultrasound can confirm the diagnosis of hepatic steatosis (fatty liver), seen as increased echogenicity. Ultrasound does not indicate the severity, function of the liver or presence of fibrosis. It can be normal in NAFLD. The enhanced liver fibrosis (ELF) blood test is the first-line investigation for assessing fibrosis in non-alcoholic fatty liver disease. It measures three markers (HA, PIIINP and TIMP-1) and uses an algorithm to provide a result that indicates whether they have advanced fibrosis of the liver: 10.51 or above – advanced fibrosis Under 10.51 – unlikely advanced fibrosis (NICE recommend rechecking every 3 years in NAFLD) NAFLD Fibrosis Score (NFS) is another option for assessing liver fibrosis in NAFLD. It is based on an algorithm of age, BMI, liver enzymes (AST and ALT), platelet count, albumin and diabetes. Fibrosis 4 (FIB-4) score is another option for assessing liver fibrosis in NAFLD. It is based on an algorithm of age, liver enzymes (AST and ALT) and platelet count. Transient elastography (“FibroScan”) can be used to assess the stiffness of the liver using high-frequency sound waves. It helps determine the degree of fibrosis (scarring) to test for liver cirrhosis. It is used where the enhanced liver fibrosis (ELF) test indicates advanced fibrosis. Liver biopsy may be required to confirm the diagnosis and exclude other causes of liver disease. TOM TIP: Both the NFS and FIB-4 scores use the AST:ALT ratio to assess the severity of liver fibrosis. The normal ratio is less than 1. A ratio greater than 0.8 in NAFLD suggests advanced fibrosis. An AST:ALT ratio greater than 1.5 (meaning a disproportionately high AST) indicates alcohol-related liver disease rather than NAFLD.

Answer 14

The diagnosis requires the presence of ultrasound findings of a fatty liver, risk factors and excluding other causes of liver disease with a careful alcohol history and full non-invasive liver screen. Liver biopsy is the gold standard test.

Answer 15

Weight loss Healthy diet (Mediterranean diet is recommended) Exercise Avoid/limit alcohol intake Stop smoking Control of diabetes, blood pressure and cholesterol Refer patients where scoring tests indicate liver fibrosis to a liver specialist Specialist management may include vitamin E, pioglitazone, bariatric surgery and liver transplantation

Answer 16

Type of Virus Transmission Vaccine Treatment Hepatitis A RNA Faecal-oral route Yes Supportive Hepatitis B DNA Blood/bodily fluids Yes Supportive/antivirals Hepatitis C RNA Blood No Direct-acting antivirals Hepatitis D RNA Always with hepatitis B No Pegylated interferon alpha Hepatitis E RNA Faecal-oral route No Supportive All viral hepatitis infections are notifiable diseases. The UK Health Security Agency need to be notified of all cases.

Answer 17

Alcoholic hepatitis Non-alcoholic steatohepatitis (NASH) Autoimmune hepatitis Drug induced hepatitis (e.g. paracetamol overdose)

Answer 18

Viral hepatitis may be asymptomatic or present with non-specific symptoms of: Abdominal pain Fatigue Flu-like illness Pruritus (itching) Muscle and joint aches Nausea and vomiting Jaundice

Answer 19

A “hepatitic picture” on liver function tests refers to high transaminases (AST and ALT) with proportionally less of a rise in ALP. Transaminases are liver enzymes released into the blood due to inflammation of the liver cells. Bilirubin can also rise as a result of inflammation of the liver cells. High bilirubin causes jaundice.

Answer 20

Hepatitis A is the most common viral hepatitis worldwide but relatively rare in the UK. It is an RNA virus transmitted via the faecal-oral route, usually in contaminated water or food. Vaccination is available to reduce the chance of developing the infection. It can cause cholestasis (slowing of bile flow through the biliary system), with pruritus, significant jaundice, dark urine and pale stools. Diagnosis is based on IgM antibodies to hepatitis A. It usually resolves without treatment. Rarely it can lead to acute liver failure (fulminant hepatitis). Management is supportive, with basic analgesia.

Answer 21

Hepatitis B is a double-stranded DNA virus. It is transmitted by direct contact with blood or bodily fluids, such as during sexual intercourse or sharing needles (e.g., IV drug users or tattoos). It can also be passed through sharing toothbrushes, razors or contact with open cuts. It can be passed from mother to child during pregnancy and delivery (known as vertical transmission). Most people fully recover from the infection within 1-3 months. However, 5-15% become chronic hepatitis B carriers. In carriers, the virus DNA has integrated into the cell nucleus. They continue to produce viral proteins. Antibodies are produced by the immune system against pathogen proteins. Antigens are proteins that are targeted by the antibodies. Antibodies are part of the immune system. Antigens are part of the virus. There are key viral markers to remember with hepatitis B: Surface antigen (HBsAg) – active infection E antigen (HBeAg) – a marker of viral replication and implies high infectivity Core antibodies (HBcAb) – implies past or current infection Surface antibody (HBsAb) – implies vaccination or past or current infection Hepatitis B virus DNA (HBV DNA) – a direct count of the viral load Screening for hepatitis B involves testing for HBcAb (for previous infection) and HBsAg (for active infection). When these are positive, further testing is performed for HBeAg and viral load (HBV DNA). HBsAb demonstrates an immune response to HBsAg. The HBsAg is given in the vaccine, so having a positive HBsAb may indicate they have been vaccinated and created an immune response. The HBsAb may also be present in response to an infection. The other viral markers are necessary to distinguish between the presence of HBsAb due to previous vaccination and infection. HBcAb can help distinguish acute, chronic and past infections. We can measure IgM and IgG versions of the HBcAb. IgM implies an active infection and will give a high titre with an acute infection and a low titre with a chronic infection. IgG indicates a past infection where the HBsAg is negative. HBeAg correlates with infectivity. Where the HBeAg is present, it implies the patient is in the acute phase of infection, where the virus is actively replicating. When the HBeAg is high, they are highly infectious to others. When the HBeAg is negative, but the HBeAb is positive, this implies they have been through a phase where the virus was replicating but has now stopped replicating and are less infectious. Vaccination is available and involves injecting the hepatitis B surface antigen (HBsAg). Vaccinated patients are tested for HBsAb to confirm their response to the vaccine. The vaccine requires 3 doses at different intervals. Vaccination for hepatitis B is included as part of the UK routine vaccination schedule (as part of the 6-in-1 vaccine).

Answer 22

A low threshold for screening patients at risk of hepatitis B Screen for other viral infections (e.g., HIV, hepatitis A, C and D) Referral to gastroenterology, hepatology or infectious diseases for specialist management Avoid alcohol Education about reducing transmission Contact tracing and informing potential at-risk contacts Testing for complications (e.g., FibroScan for cirrhosis and ultrasound for hepatocellular carcinoma) Antiviral medication can be used to slow the progression of the disease and reduce infectivity Liver transplantation for liver failure (fulminant hepatitis)

Answer 23

Hepatitis C is an RNA virus. It is spread by blood and body fluids (e.g., semen). No vaccine is available. Hepatitis C is now curable with direct-acting antiviral medications (e.g., sofosbuvir and daclatasvir). Without treatment: 1 in 4 fight off the virus and make a full recovery 3 in 4 develop chronic hepatitis C Complications of hepatitis C include: Liver cirrhosis and associated complications of cirrhosis Hepatocellular carcinoma Testing involves: Hepatitis C antibody is the screening test Hepatitis C RNA testing is used to confirm the diagnosis of hepatitis C, calculate the viral load and identify the genotype Management involves the same general principles as hepatitis B (described above). Antiviral treatment with direct-acting antivirals (DAAs) is tailored to the specific viral genotype. They successfully cure the infection in over 90% of patients. The duration of treatment is typically 8 to 12 weeks.

Answer 24

Hepatitis D is an RNA virus. It can only survive in patients who also have a hepatitis B infection. It attaches itself to the HBsAg and cannot survive without this protein. There are very low rates in the UK. Hepatitis D increases the complications and disease severity of hepatitis B. Hepatitis D can be treated with pegylated interferon alpha over at least 48 weeks. This treatment is not very effective and has significant side effects.

Answer 25

Hepatitis E is an RNA virus transmitted by the faecal-oral route. It is very rare in the UK. It usually produces only a mild illness, the virus is cleared within a month, and no treatment is required. Rarely it can progress to chronic hepatitis and liver failure, usually in immunocompromised patients. There is no vaccination.

Answer 26

There are two types of autoimmune hepatitis, with different age distributions and autoantibodies. Type 1 typically affects women in their late forties or fifties. It presents around or after menopause with fatigue and features of liver disease on examination. It takes a less acute course than type 2. Type 2 usually affects children or young people, more commonly girls. It presents with acute hepatitis with high transaminases and jaundice.

Answer 27

Investigations will show high transaminases (ALT and AST) and minimal change in ALP levels (a “hepatitic” picture). Raised immunoglobulin G (IgG) levels are an important finding. Autoantibodies in type 1 autoimmune hepatitis are: Anti-nuclear antibodies (ANA) Anti-smooth muscle antibodies (anti-actin) Anti-soluble liver antigen (anti-SLA/LP) Autoantibodies in type 2 autoimmune hepatitis are: Anti-liver kidney microsomes-1 (anti-LKM1) Anti-liver cytosol antigen type 1 (anti-LC1) Liver biopsy forms part of the diagnosis. Key histology findings are interface hepatitis and plasma cell infiltration.

Answer 28

Treatment is with high-dose steroids (e.g., prednisolone). Other immunosuppressants are also used, particularly azathioprine. Immunosuppressant treatment is usually successful at inducing remission (controlling the disease). Liver transplant may be required in end-stage liver disease. Autoimmune hepatitis can reoccur in the new liver.

Answer 29

Haemochromatosis is an autosomal recessive genetic condition resulting in iron overload. There is excessive total body iron and deposition of iron in tissues. It is an iron storage disorder. The human haemochromatosis protein (HFE) gene is located on chromosome 6. The majority of cases of haemochromatosis relate to C282Y mutations in this gene. Mutations are required in both copies of the gene (homozygous) since it is an autosomal recessive condition. This gene is important in regulating iron metabolism.

Answer 30

Haemochromatosis usually presents after age 40 when the iron overload becomes symptomatic. It presents later in females due to menstruation acting to eliminate iron from the body regularly. It presents with: Chronic tiredness Joint pain Pigmentation (bronze skin) Testicular atrophy Erectile dysfunction Amenorrhoea (absence of periods in women) Cognitive symptoms (memory and mood disturbance) Hepatomegaly

Answer 31

Serum ferritin is the initial investigation. The causes of a raised ferritin are: Haemochromatosis Infections (it is an acute phase reactant) Chronic alcohol consumption Non-alcoholic fatty liver disease Hepatitis C Cancer Transferrin saturation helps distinguish between high ferritin caused by iron overload (transferrin saturation is high) and other causes (transferrin saturation is normal). Genetic testing for mutations in the HFE gene is used when the serum ferritin and transferrin saturation are both high. Liver biopsy with Perl’s stain can be used to establish the iron concentration in the liver. Genetic testing means that a liver biopsy is not usually necessary for establishing a diagnosis. It may help stage the fibrosis and exclude other liver pathology. MRI can give a detailed picture and quantify the iron concentration in the liver (avoiding a biopsy).

Answer 32

Secondary diabetes (iron affects the functioning of the pancreas) Liver cirrhosis Endocrine and sexual problems (hypogonadism, erectile dysfunction, amenorrhea and reduced fertility) Cardiomyopathy (iron deposits in the heart) Hepatocellular carcinoma Hypothyroidism (iron deposits in the thyroid) Chondrocalcinosis (calcium pyrophosphate deposits in joints) causes arthritis

Answer 33

Venesection (regularly removing blood to remove excess iron – initially weekly) Monitoring serum ferritin Monitoring and treating complications

Answer 34

Wilson’s disease is an autosomal recessive genetic condition resulting in the excessive accumulation of copper in the body tissues, particularly in the liver. It is caused by mutations in the Wilson disease protein gene on chromosome 13 (also called the ATP7B copper-binding protein). This copper-transporting protein is important in helping remove excess copper from the body via the liver. Copper is excreted in the bile.

Answer 35

Wilson’s disease typically presents in teenagers or young adults. It is rare for symptoms to start after age 40. The presenting features vary significantly between individuals. Liver problems usually arise first. Rarely it can present initially with neurological or psychiatric problems, although these typically occur with more advanced disease. Copper deposition in the liver leads to chronic hepatitis, eventually leading to cirrhosis. Copper deposition in the central nervous system can lead to neurological and psychiatric problems. Neurological symptoms can include tremor, dysarthria (speech difficulties) and dystonia (abnormal muscle tone). Copper deposition in the basal ganglia causes Parkinsonism (tremor, bradykinesia and rigidity). Psychiatric symptoms can include abnormal behaviour, depression, cognitive impairment and psychosis. Kayser-Fleischer rings in the cornea (deposition of copper in Descemet’s membrane) may be seen in Wilson’s disease. These are green-brown circles surrounding the iris of the eye. They can usually be seen by the naked eye but proper assessment is made using slit lamp examination. Haemolytic anaemia (low haemoglobin caused by red blood cell destruction) may also be a feature.

Answer 36

Serum caeruloplasmin is the initial screening test for suspected Wilson’s disease. A low serum caeruloplasmin is suggestive of Wilson’s disease. Caeruloplasmin is the protein that carries copper in the blood. It can be falsely normal or elevated in cancer or inflammatory conditions. A 24-hour urine copper assay will show high urinary copper. Liver biopsy can be used to assess the liver copper content and assess liver disease. Scoring systems that consider various features and laboratory results are used to establish the diagnosis. Other investigations: Kayser-Fleischer rings on slit lamp examination MRI brain may show changes, including the characteristic “double panda sign” Low haemoglobin with haemolytic anaemia (negative Coombs test) Genetic testing (including screening family members)

Answer 37

Treatment is with copper chelation using either: Penicillamine Trientine Other treatments include: Zinc salts (inhibit copper absorption in the gastrointestinal tract) Liver transplantation

Answer 38

Alpha-1 antitrypsin deficiency is a genetic condition caused by low levels of alpha-1 antitrypsin. Two main organs are affected by alpha-1 antitrypsin deficiency: Chronic obstructive pulmonary disease and bronchiectasis in the lungs (typically after 30 years old) Dysfunction, fibrosis and cirrhosis of the liver (depending on the specific genotype)

Answer 39

The SERPINA1 gene coding for alpha-1 antitrypsin is found on chromosome 14. The gene has many potential variations, each with different effects on the quantity and functionality of alpha-1 antitrypsin. Alpha-1 antitrypsin deficiency is inherited in an autosomal co-dominant pattern. Co-dominant refers to when both gene copies are expressed and contribute to the outcome (neither is dominant or recessive over the other). The disease severity results from the combination of both copies of the gene. Alpha-1 antitrypsin is a protease inhibitor. One critical protease enzyme is neutrophil elastase. This enzyme, secreted by neutrophils, digests elastin (elastolysis), a protein in connective tissue that helps keep the tissues flexible. Alpha-1 antitrypsin (AAT) offers protection by inhibiting the action of neutrophil elastase. In the lungs, the lack of a normal, functioning alpha-1 antitrypsin protein leads to excess protease enzymes attacking the connective tissues. Destruction of elastic tissue in the lungs leads to bronchiectasis and emphysema. Smoking dramatically accelerates this process. Alpha-1 antitrypsin is produced in the liver. In specific genotypes of alpha-1 antitrypsin deficiency, an abnormal mutant version of the protein is made that gets trapped and builds up inside the liver cells (hepatocytes). These mutant proteins are toxic to the hepatocytes, causing inflammation. Over time this progresses to fibrosis, cirrhosis and potentially hepatocellular carcinoma. Liver pathology can occur at any age, including childhood. Less commonly, it can be associated with: Panniculitis (tender skin nodules caused by inflammation of the subcutaneous fat) Granulomatosis with polyangiitis (a small and medium vessel vasculitis)

Answer 40

Diagnosis is based on: Low serum alpha-1 antitrypsin (the screening test) Genetic testing Lung damage is assessed with: Chest x-ray High-resolution CT thorax Pulmonary function tests Liver biopsy shows periodic acid-Schiff positive staining globules in hepatocytes, resistant to diastase treatment. These represent a buildup of the mutant proteins.

Answer 41

Stop smoking Symptomatic management (e.g., standard treatment of COPD) Organ transplant for end-stage liver or lung disease Monitoring for complications (e.g., hepatocellular carcinoma) Screening of family members Giving an infusion of alpha-1 antitrypsin to boost the levels is possible, but there is doubt about the clinical benefit and cost. The NICE guidelines on COPD (updated 2019) recommend against using replacement alpha-1 antitrypsin.

Answer 42

Primary biliary cholangitis is an autoimmune condition where the immune system attacks the small bile ducts in the liver, resulting in obstructive jaundice and liver disease. It was previously known as primary biliary cirrhosis.

Answer 43

Primary biliary cholangitis affects the small bile ducts inside the liver (the intrahepatic ducts). There is inflammation and damage to the epithelial cells of the bile ducts (the cholangiocytes). Over time, this can lead to obstruction of bile flow through these ducts. Reduced flow of bile is called cholestasis. The back-pressure of bile and the overall disease process ultimately lead to liver fibrosis, cirrhosis and failure. Bile acids, bilirubin and cholesterol are excreted through the bile ducts into the intestines. When obstruction to the outflow of these chemicals means they are not being excreted, they build up in the blood. Raised bile acids cause itching, and raised bilirubin causes jaundice. Raised cholesterol causes cholesterol deposits in the skin called xanthelasma. Xanthomas are larger nodular deposits of cholesterol in the skin or tendons. Raised cholesterol increases the risk of atherosclerosis and cardiovascular disease. Bile acids help with the digestion of fats. Reduced or absent bile acids in the gastrointestinal tract cause abdominal symptoms, malabsorption of fat and greasy stools. Bilirubin is responsible for the darker colour of stools. A lack of bilirubin results in pale stools. Excretion of bilirubin via the urine causes dark urine.

Answer 44

The typical patient is a white woman aged 40-60 years. Often patients are asymptomatic at diagnosis, with the problem picked up on abnormal liver function tests. However, they may present with: Fatigue Pruritus (itching) Gastrointestinal symptoms and abdominal pain Jaundice Pale, greasy stools Dark urine On examination, there may be: Xanthoma and xanthelasma (cholesterol deposits) Excoriations (scratches on the skin due to itching) Hepatomegaly Signs of liver cirrhosis and portal hypertension in end-stage disease (e.g., splenomegaly and ascites)

Answer 45

Liver function tests show: Raised alkaline phosphatase (the most notable liver enzyme as with most “obstructive” pathology) Other liver enzymes and bilirubin are raised later in the disease Autoantibodies relevant to primary biliary cholangitis are: Anti-mitochondrial antibodies (AMA) are the most specific to PBC and form part of the diagnostic criteria Anti-nuclear antibodies are present in about 35% of patients Raised immunoglobulin M (IgM) is a non-specific blood result finding. Ultrasound does not show specific changes with primary biliary cholangitis but helps exclude other pathology. Liver biopsy may be used in diagnosing and staging the disease. TOM TIP: The two results for primary biliary cholangitis to remember are anti-mitochondrial antibodies and alkaline phosphatase. In your exams, a middle-aged white woman presenting with itching, a positive AMA and a raised alkaline phosphatase almost certainly has primary biliary cholangitis.

Answer 46

Ursodeoxycholic acid is the most essential treatment to remember in primary biliary cholangitis. It is a non-toxic, hydrophilic bile acid that protects the cholangiocytes from inflammation and damage. It makes the bile less harmful to the epithelial cells of the bile ducts. It slows the disease progression and improves outcomes. Other treatments include: Obeticholic acid (where UDCA is inadequate or not tolerated – although it can have significant adverse effects) Colestyramine for symptoms of pruritus (a bile acid sequestrant that reduces intestinal absorption of bile acids) Replacement of fat-soluble vitamins Immunosuppression (e.g., with steroids) is considered in some patients Liver transplant in end-stage liver disease

Answer 47

Disease course and symptoms vary significantly. Some people live decades without symptoms. The most crucial result is liver cirrhosis with the associated complications (e.g., portal hypertension and hepatocellular carcinoma). Other complications and associations include: Fat-soluble vitamin deficiency (A, D, E and K) Osteoporosis Hyperlipidaemia (raised cholesterol) Sjögren’s syndrome (dry eyes, dry mouth and vaginal dryness) Connective tissue diseases (e.g., systemic sclerosis) Thyroid disease

Answer 48

Primary sclerosing cholangitis is a condition where the intrahepatic and extrahepatic bile ducts become inflamed and damaged, developing strictures that obstruct the flow of bile out of the liver and into the intestines. Sclerosis refers to the stiffening and hardening of the bile ducts, and cholangitis is inflammation of the bile ducts. Chronic bile obstruction eventually leads to liver inflammation (hepatitis), fibrosis and cirrhosis.

Answer 49

The cause is unclear and thought to be combined genetic and environmental factors. There is a strong association with ulcerative colitis, with around 70% of cases occurring alongside pre-existing ulcerative colitis. Less commonly, it can be associated with Crohn’s disease. The key risk factors for primary sclerosing cholangitis are: Male Aged 30-40 Ulcerative colitis Family history

Answer 50

Often patients are asymptomatic at diagnosis, with the problem picked up on abnormal liver function tests. However, they may present with: Abdominal pain in the right upper quadrant Pruritus (itching) Fatigue Jaundice Hepatomegaly Splenomegaly

Answer 51

Liver function tests show: Raise alkaline phosphatase (the most notable liver enzyme as with most “obstructive” pathology) Other liver enzymes and bilirubin are raised later in the disease Autoantibodies are not helpful in diagnosis or assessment. No antibodies are particularly sensitive or specific to primary sclerosing cholangitis. The main autoantibodies are: Perinuclear antineutrophil cytoplasmic antibody (p-ANCA) Antinuclear antibodies (ANA) Anti-smooth muscle antibodies (anti-SMA) Magnetic resonance cholangiopancreatography (MRCP) is the diagnostic imaging investigation. It involves an MRI scan that gives a detailed view of the bile ducts, showing bile duct strictures in primary sclerosing cholangitis. Colonoscopy should be performed to assess for ulcerative colitis. Liver biopsy is not usually required but may be used where there is diagnostic uncertainty.

Answer 52

There are no treatments proven to be effective for primary sclerosing cholangitis. Endoscopic retrograde cholangio-pancreatography (ERCP) may be used to treat dominant strictures. This involves inserting an endoscope down the oesophagus, past the stomach, to the duodenum and the opening of the common bile duct (the sphincter of Oddi). This gives the operator access to the biliary system. Strictures can be dilated. Stents can be inserted to keep the ducts open. Antibiotics are given alongside ERCP to reduce the risk of infection (bacterial cholangitis). Liver transplant is used in advanced disease, with around 80% survival at five years post-transplantation. Other aspects of management include: Colestyramine for symptoms of pruritus (a bile acid sequestrant that reduces intestinal absorption of bile acids) Replacement of fat-soluble vitamins Monitoring for complications such as cholangiocarcinoma, cirrhosis and oesophageal varices

Answer 53

Biliary strictures Acute bacterial cholangitis Cholangiocarcinoma develops in 10-20% of cases Cirrhosis and the related complications (e.g., portal hypertension and oesophageal varices) Fat-soluble vitamin deficiency (A, D, E and K) Osteoporosis Colorectal cancer in patients with ulcerative colitis TOM TIP: The association between ulcerative colitis, primary sclerosing cholangitis and cholangiocarcinoma is commonly tested in exams.

Answer 54

IgG4-related sclerosing cholangitis is similar to primary sclerosing cholangitis. Elevated IgG4 levels in the blood are the distinguishing feature. Unlikely primary sclerosing cholangitis, IgG4-related sclerosing cholangitis responds well to treatment with steroids. It is associated with autoimmune pancreatitis.

Answer 55

Primary liver cancer is cancer that originates in the liver. The main type of primary liver cancer is hepatocellular carcinoma. Secondary liver cancer originates outside the liver and metastasises to the liver. Metastasis to the liver can occur with almost any cancer that spreads. It is common to have liver metastases of unknown primary. There is a poor prognosis when there is cancer with liver metastasis.

Answer 56

The main risk factor for hepatocellular carcinoma (HCC) is liver cirrhosis due to: Alcohol-related liver disease Non-alcoholic fatty liver disease (NAFLD) Hepatitis B Hepatitis C Rarer causes (e.g., primary sclerosing cholangitis) Patients with liver cirrhosis are offered screening for hepatocellular carcinoma every 6 months with: Ultrasound Alpha-fetoprotein

Answer 57

Liver cancer often remains asymptomatic for a long time, presenting late and making the prognosis poor. There are non-specific presenting features associated with liver cancer: Weight loss Abdominal pain Anorexia Nausea and vomiting Jaundice Pruritus Upper abdominal mass on palpation

Answer 58

Relevant investigations in assessing liver cancer are: Alpha-fetoprotein (tumour marker for hepatocellular carcinoma) Liver ultrasound is the first-line imaging investigation CT and MRI scans are used for further assessment and staging of the cancer Biopsy is used for histology

Answer 59

Hepatocellular carcinoma has a very poor prognosis unless diagnosed early. Surgery may be possible in early disease. Resection can be used when the tumour is isolated in a removable liver area. A liver transplant is an option when the tumour is isolated to the liver and the patient meets specific criteria. Other options for treating liver cancer include: Radiofrequency ablation (destroying the tumour cells with heat) Microwave ablation (destroying the tumour cells with heat) Transarterial chemoembolisation (TACE) Radiotherapy Targeted drugs (e.g., kinase inhibitors and monoclonal antibodies) Transarterial chemoembolisation (TACE) is an interventional radiology procedure. A chemotherapy drug is injected into the hepatic artery feeding the tumour, delivering the dose directly to the tumour. This is followed by embolisation of the vessel to block the tumour’s blood supply.

Answer 60

Cholangiocarcinoma is a type of cancer that originates in the bile ducts. The majority are adenocarcinomas. It may affect the bile ducts inside the liver (intrahepatic ducts) or outside the liver (extrahepatic ducts). The most common site is in the perihilar region, where the right and left hepatic ducts have joined to become the common hepatic duct just after leaving the liver. Cholangiocarcinoma is associated with primary sclerosing cholangitis. However, only 10% of patients with cholangiocarcinoma have primary sclerosing cholangitis. Cholangiocarcinoma usually presents in patients over 50 years old unless related to primary sclerosing cholangitis. Obstructive jaundice is the key presenting feature to remember. Obstructive jaundice is associated with: Pale stools Dark urine Generalised itching CA19-9 is a tumour marker for cholangiocarcinoma. Cholangiocarcinomas have a very poor prognosis unless diagnosed early. Surgical resection is potentially successful in early disease. TOM TIP: Painless jaundice should make you think of cholangiocarcinoma or cancer of the head of the pancreas. Pancreatic cancer is more common, so this is likely the answer in your exams.

Answer 61

Haemangiomas are common benign tumours of the liver. They are often found incidentally. They cause no symptoms and have no potential to become cancerous. No treatment or monitoring is required.

Answer 62

Focal nodular hyperplasia is a benign liver tumour made of fibrotic tissue. This is often found incidentally. It is usually asymptomatic and has no malignant potential. It can be related to oestrogen and is more common in women and those on the oral contraceptive pill. No treatment or monitoring is required.

Answer 63

When an entire liver is transplanted from a deceased donor to a recipient, it is known as an orthotopic transplant. This translates as straight (ortho-) in place (-topic). The liver has the ability to regenerate. Therefore, it is possible to take a portion of the liver from a living donor, transplant it into a patient and have both regenerate to become two fully functioning organs. This is known as a living donor transplant. It is also possible to split the liver of a deceased person into two and transplant it into two patients and have them regenerate to function normally in each recipient. This is known as a split donation.

Answer 64

Indications for liver transplants fall into two categories: acute liver failure and chronic liver failure. They may also be used in specific cases of hepatocellular carcinoma. Acute liver failure usually requires an immediate liver transplant, and these patients are placed at the top of the list. The most common causes are acute viral hepatitis and paracetamol overdose. Chronic liver failure patients can wait longer for their liver transplant and are put on a standard transplant list. It is usual for it to take around 5 months for a liver to become available.

Answer 65

Contraindications include: Significant co-morbidities (e.g., severe kidney, lung or heart disease) Current illicit drug use Continuing alcohol misuse (generally 6 months of abstinence is required) Untreated HIV Current or previous cancer (except certain liver cancers)

Answer 66

The liver transplant surgery is carried out in a specialist transplant centre. It involves a “rooftop” or “Mercedes Benz” incision along the lower costal margin for open surgery. The liver is mobilised away from the other tissues and excised. When an entire donor liver is implanted, the donor liver’s inferior vena cava, hepatic artery, portal vein and common bile duct are anastomosed with the recipient’s. With a split donation, the remaining branches of the donated portion of liver are anastomosed with the recipient. For example, with a left lobe liver transplantation, the left hepatic vein, left hepatic artery, left portal vein and left hepatic duct are anastomosed with the recipient’s inferior vena cava, hepatic artery, portal vein and common bile duct.

Answer 67

Patients will require lifelong immunosuppression (e.g., steroids, azathioprine and tacrolimus) and careful monitoring of these drugs. They are required to follow lifestyle advice and require monitoring and treatment for complications: Avoid alcohol and smoking Treating opportunistic infections Monitoring for disease recurrence (e.g., autoimmune hepatitis or primary biliary cholangitis) Monitoring for cancer, as there is a significantly higher risk in immunosuppressed patients Monitoring for evidence of transplant rejection: Abnormal LFTs Fatigue Fever Jaundice

Answer 68

Gastro-oesophageal reflux disease (GORD) is where acid from the stomach flows through the lower oesophageal sphincter and into the oesophagus, where it irritates the lining and causes symptoms. The oesophagus has a squamous epithelial lining that makes it more sensitive to the effects of stomach acid. The stomach has a columnar epithelial lining that is more protected against stomach acid.

Answer 69

Greasy and spicy foods Coffee and tea Alcohol Non-steroidal anti-inflammatory drugs Stress Smoking Obesity Hiatus hernia

Answer 70

Dyspepsia is a non-specific term used to describe indigestion. It covers the symptoms of GORD: Heartburn Acid regurgitation Retrosternal or epigastric pain Bloating Nocturnal cough Hoarse voice

Answer 71

Patients with symptoms suspicious of cancer get a two week wait referral for further investigation. It is possible to refer from primary care for an urgent direct-access endoscopy. The NICE guidelines on suspected cancer (2021) have criteria for when to refer urgently or routinely. The key red flag features are: Dysphagia (difficulty swallowing) at any age gets an immediate two week wait referral Aged over 55 (this is generally the cut-off for urgent versus routine referrals) Weight loss Upper abdominal pain Reflux Treatment-resistant dyspepsia Nausea and vomiting Upper abdominal mass on palpation Low haemoglobin (anaemia) Raised platelet count TOM TIP: Remember dysphagia as a critical red flag. Any patient presenting with the feeling that food is getting stuck on the way down needs an urgent two week wait referral for an endoscopy.

Answer 72

An oesophago-gastro-duodenoscopy (OGD) involves inserting a camera through the mouth down to the oesophagus, stomach and duodenum. It can be used to assess for: Gastritis Peptic ulcers Upper gastrointestinal bleeding Oesophageal varices (in liver cirrhosis) Barretts oesophagus Oesophageal stricture Malignancy of the oesophagus or stomach Patients with evidence of upper gastrointestinal bleeding (e.g., melaena or coffee ground vomiting) need admission and urgent endoscopy.

Answer 73

A hiatus hernia refers to the herniation of the stomach up through the diaphragm. The diaphragm opening should be at the lower oesophageal sphincter level and fixed in place. A narrow opening helps to maintain the sphincter and stops acid and stomach contents from refluxing into the oesophagus. When the opening of the diaphragm is wider, the stomach can enter through the diaphragm, and the contents of the stomach can reflux into the oesophagus. There are four types of hiatus hernia: Type 1: Sliding Type 2: Rolling Type 3: Combination of sliding and rolling Type 4: Large opening with additional abdominal organs entering the thorax A sliding hiatus hernia is where the stomach slides up through the diaphragm, with the gastro-oesophageal junction passing up into the thorax. A rolling hiatus hernia is where a separate portion of the stomach (i.e., the fundus), folds around and enters through the diaphragm opening, alongside the oesophagus. Type 4 hiatus hernia refers to a large hernia that allows other intra-abdominal organs to pass through the diaphragm opening (e.g., bowel, pancreas or omentum). Hiatus hernias can be intermittent, meaning they may not be seen on investigations. Hiatus hernias may be seen on a: Chest x-ray CT scan Endoscopy Barium swallow test

Answer 74

Management of gastro-oesophageal reflux disease can be split into: Lifestyle changes Reviewing medications (e.g., stop NSAIDs) Antacids (e.g., Gaviscon, Pepto-Bismol and Rennie) – short term only Proton pump inhibitors (e.g., omeprazole and lansoprazole) Histamine H2-receptor antagonists (e.g., famotidine) Surgery Lifestyle changes include: Reduce tea, coffee and alcohol Weight loss Avoid smoking Smaller, lighter meals Avoid heavy meals before bedtime Stay upright after meals rather than lying flat Surgery for reflux is called laparoscopic fundoplication. This involves tying the fundus of the stomach around the lower oesophagus to narrow the lower oesophageal sphincter. TOM TIP: The usual medical strategy when someone presents for the first time is to exclude red flags, address potential triggers, offer a 1 month trial of a proton pump inhibitor and consider H. pylori testing.

Answer 75

Helicobacter pylori (H. pylori) is a gram-negative aerobic bacteria that can live in the stomach. It causes damage to the epithelial lining, resulting in gastritis, ulcers and an increased risk of stomach cancer. It avoids the acidic environment by forcing its way into the gastric mucosa, using flagella to propel itself. It creates gaps in the mucosa, exposing the epithelial cells underneath to damage from stomach acid. H. pylori produces ammonium hydroxide, which neutralises the acid surrounding the bacteria. It also produces several toxins. The ammonia and toxins lead to gastric mucosal damage. We offer a test for H. pylori to anyone with dyspepsia. They need 2 weeks without using a PPI before testing for H. pylori for an accurate result. Investigations for H. Pylori are: Stool antigen test Urea breath test using radiolabelled carbon 13 H. pylori antibody test (blood) Rapid urease test performed during endoscopy (also known as the CLO test) A rapid urease test involves taking a small biopsy of the stomach mucosa. This is added to a liquid medium containing urea. H. pylori produce urease enzymes that convert urea to ammonia. Ammonia makes the solution more alkaline. A pH indicator (e.g., phenol red) changes colour if the pH rises, giving a positive result. The H. pylori eradication regime involves triple therapy with a proton pump inhibitor (e.g., omeprazole) plus two antibiotics (e.g., amoxicillin and clarithromycin) for 7 days. Routine re-testing is not necessary after treatment.

Answer 76

Barrett’s oesophagus refers to when the lower oesophageal epithelium changes from squamous to columnar epithelium. This process is called metaplasia. It is caused by chronic acid reflux into the oesophagus. Patients may notice improved reflux symptoms after they develop Barrett’s oesophagus. Barrett’s oesophagus is a premalignant condition and a significant risk factor for developing oesophageal adenocarcinoma (cancer of the epithelial cells). There can be a stepwise progression from no dysplasia to low-grade dysplasia, high-grade dysphasia, and adenocarcinoma. Treatment of Barrett’s oesophagus is with: Endoscopic monitoring for progression to adenocarcinoma Proton pump inhibitors Endoscopic ablation (e.g., radiofrequency ablation) Ablation can be used to destroy abnormal columnar epithelial cells, which are then replaced with normal squamous epithelial cells. Ablation has a role in treating low and high-grade dysplasia to reduce cancer risk. TOM TIP: The histology of Barrett’s oesophagus is a common exam topic. Remember the term metaplasia, which means a change in the type of cell. This is different from dysplasia, which refers to the presence of abnormal cells. Remember that the normal epithelium is squamous, and in Barrett’s it changes to columnar.

Answer 77

Zollinger-Ellison syndrome is a rare condition where a duodenal or pancreatic tumour secretes excessive quantities of gastrin. Gastrin is a hormone that stimulates acid secretion in the stomach. Therefore, there is excess production of stomach acid, resulting in severe dyspepsia, diarrhoea and peptic ulcers. Gastrin-secreting tumours (gastrinomas) may be associated with multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant genetic condition, which can also cause hormone-secreting tumours of the parathyroid and pituitary glands.

Answer 78

Peptic ulcers involve ulceration of the mucosa of the stomach (gastric ulcer) or the proximal duodenum (duodenal ulcer). Duodenal ulcers are more common. Pathophysiology The mucosa, also known as the mucous membrane, is the inner lining of the stomach and duodenum. It secretes mucus that coats the surface and forms a barrier that protects it from the stomach’s contents, particularly stomach acid and digestive enzymes. It secretes bicarbonate into this mucus coating to neutralise the stomach acid. Factors that disrupt the mucus barrier or increase stomach acid increase the risk of mucosal ulceration.

Answer 79

The risk key factors that disrupt the mucus barrier are: Helicobacter pylori Non-steroidal anti-inflammatory drugs (NSAIDs) The key risk factors that increase stomach acid are: Stress Alcohol Caffeine Smoking Spicy foods

Answer 80

The risk of bleeding from a peptic ulcer is increased with the use of: Non-steroidal anti-inflammatory drugs (NSAIDs) Aspirin Anticoagulants (e.g., DOACs) Steroids SSRI antidepressants

Answer 81

Peptic ulcers present with non-specific symptoms of: Epigastric discomfort or pain Nausea and vomiting Dyspepsia The signs of upper gastrointestinal bleeding are: Haematemesis (vomiting blood) Coffee ground vomiting Melaena (black, tarry stools) Fall in haemoglobin on a full blood count Chronic microscopic bleeding can lead to iron deficiency anaemia, with low haemoglobin, low mean cell volume (MCV) and low ferritin. TOM TIP: Eating typically worsens the pain of gastric ulcers. The pain of duodenal ulcers tends to improve immediately after eating, followed by pain 2-3 hours later. Patients with gastric ulcers tend to lose weight due to the fear of pain on eating, whereas with duodenal ulcers, the weight is stable or increases. This helps you differentiate them in your MCQ exams.

Answer 82

Peptic ulcers can be diagnosed on endoscopy. During endoscopy, a rapid urease test (CLO test) can be performed to check for H. pylori. A biopsy is considered during endoscopy to exclude malignancy.

Answer 83

The core aspects of treating peptic ulcers are: Stopping NSAIDs Treating H. pylori infections Proton pump inhibitors (e.g., lansoprazole or omeprazole) Repeat endoscopy (at 4-8 weeks) may be performed to ensure the ulcer heals.

Answer 84

Bleeding from the ulcer is a common and potentially life-threatening complication. Perforation results in acute abdominal pain and peritonitis, requiring urgent surgical repair (usually laparoscopic). Scarring and strictures can lead to a narrowing of the exit of the stomach, causing difficulty in emptying the stomach contents. This is known as gastric outlet obstruction and presents with early fullness after eating as well as upper abdominal discomfort, abdominal distention and vomiting, particularly after eating. This may be treated with balloon dilatation during an endoscopy or surgery.

Answer 85

Bleeding from the upper gastrointestinal tract is a relatively common medical emergency. It involves bleeding from the oesophagus, stomach or duodenum. Causes The key sources of bleeding are: Peptic ulcers (the most common cause) Mallory-Weiss tear (a tear of the oesophageal mucosa) Oesophageal varices (secondary to portal hypertension in liver cirrhosis) Stomach cancers

Answer 86

The presenting features of an upper gastrointestinal bleed are: Haematemesis (vomiting blood) Coffee ground vomit (caused by vomiting digested blood with the appearance of coffee grounds) Melaena (tar-like, black, greasy and offensive stools caused by digested blood) Haemodynamic instability occurs with significant blood loss, causing low blood pressure, tachycardia and other signs of shock. Young, fit patients may compensate well with normal observations until they have lost a lot of blood. Peptic ulcers are associated with a history of epigastric pain and dyspepsia. They may be taking non-steroidal anti-inflammatory drugs (NSAIDs). Mallory-Weiss tears tend to occur after heavy retching or vomiting, which may be caused by binge drinking, gastroenteritis or hyperemesis gravidarum (in early pregnancy). Oesophageal varices are associated with liver cirrhosis and portal hypertension. The patient will have signs of these conditions, such as ascites, jaundice and caput medusae. Stomach cancer is associated with a history of weight loss, epigastric pain, treatment-resistant dyspepsia, low haemoglobin (anaemia) and a raised platelet count.

Answer 87

The Glasgow-Blatchford score is used at the initial presentation in suspected upper GI bleed. It estimates the risk of the patient having an upper GI bleed. A score above 0 indicates a high risk for an upper GI bleed. The NICE guidelines (updated 2016) suggest considering early discharge in patients with a score of 0. The easiest way to calculate the score is using an online calculator. It takes into account: Haemoglobin (falls in upper GI bleeding) Urea (rises in upper GI bleeding) Systolic blood pressure Heart rate Presence of melaena (black, tarry stools) Syncope (loss of consciousness) Liver disease Heart failure TOM TIP: Acid and digestive enzymes break down blood in the upper GI tract. One of the breakdown products is urea, which is then absorbed in the intestines, causing a rise in blood urea. The association between upper GI bleeding and increased blood urea is a key fact worth remembering.

Answer 88

The Rockall score is used after endoscopy to estimate the risk of rebleeding and mortality. It takes into account: Age Features of shock (e.g., tachycardia or hypotension) Co-morbidities Cause of bleeding (e.g., Mallory-Weiss tear or malignancy) Endoscopic findings of recent bleeding (e.g., clots and visible bleeding vessels)

Answer 89

As with any medical emergency, get senior support early and follow the local policies. The initial management can be remembered with the ABATED mnemonic: A – ABCDE approach to immediate resuscitation B – Bloods A – Access (ideally 2 x large bore cannula) T – Transfusions are required E – Endoscopy (within 24 hours) D – Drugs (stop anticoagulants and NSAIDs)

Answer 90

Haemoglobin (FBC) Urea (U&Es) Coagulation (INR and FBC for platelets) Liver disease (LFTs) Crossmatch 2 units of blood TOM TIP: “Group and save” is where the lab checks the patient’s blood group and saves a blood sample to match blood if needed. “Crossmatch” is where the lab allocates units of blood, tests that it is compatible, and keeps it ready in the fridge.

Answer 91

Blood, platelets and clotting factors (fresh frozen plasma) are given to patients with massive bleeding Transfusing more blood than necessary can be harmful Platelets are given in active bleeding plus thrombocytopenia (platelet count less than 50) Prothrombin complex concentrate can be given to patients taking warfarin that are actively bleeding

Answer 92

There are some additional steps if oesophageal varices are suspected (e.g., in patients with liver cirrhosis): Terlipressin Broad spectrum antibiotics Oesophago-gastro-duodenoscopy (OGD) (endoscopy) is required to diagnose and treat the source of the bleeding. Non-variceal bleeding can be treated in various ways, such as with clips or thermal coagulation. Variceal band ligation is used to treat bleeding oesophageal varices. The NICE guidelines (updated 2016) recommend against using a proton pump inhibitor until after endoscopy in patients with non-variceal upper GI bleeding.

Answer 93

Inflammatory bowel disease involves recurrent episodes of inflammation in the gastrointestinal tract. The two main types are ulcerative colitis and Crohn’s disease. They are associated with periods of exacerbation and remission. Inflammatory bowel disease is thought to be caused by a combination of factors related to genetics, environment and the gut microbiome. The typical patient presents in their 20s.

Answer 94

The general presenting features of inflammatory bowel disease are: Diarrhoea Abdominal pain Rectal bleeding Fatigue Weight loss

Answer 95

Differentiating features of Crohn’s can be remembered with the “crows” NESTS mnemonic: N – No blood or mucus (PR bleeding is less common) E – Entire gastrointestinal tract affected (from mouth to anus) S – “Skip lesions” on endoscopy T – Terminal ileum most affected and Transmural (full thickness) inflammation S – Smoking is a risk factor (don’t set the nest on fire) Crohn’s is also associated with strictures and fistulas. Differentiating features of ulcerative colitis can be remembered with the “you see (UC)” CLOSEUP mnemonic: C – Continuous inflammation L – Limited to the colon and rectum O – Only superficial mucosa affected S – Smoking may be protective (ulcerative colitis is less common in smokers) E – Excrete blood and mucus U – Use aminosalicylates P – Primary sclerosing cholangitis TOM TIP: It is common for exams to give you some features and ask you to determine whether the patient has Crohn’s or ulcerative colitis. This might be a finding of skip lesions on an endoscopy, transmural inflammation or mouth ulcers to suggest Crohn’s rather than ulcerative colitis.

Answer 96

Many associated conditions can occur in patients with inflammatory bowel disease: Erythema nodosum (tender, red nodules on the shins caused by inflammation of the subcutaneous fat) Pyoderma gangrenosum (rapidly enlarging, painful skin ulcers) Enteropathic arthritis (a type of inflammatory arthritis) Primary sclerosing cholangitis (particularly with ulcerative colitis) Red eye conditions (e.g., episcleritis, scleritis and anterior uveitis)

Answer 97

Blood tests include: Full blood count for haemoglobin (low in anaemia) and platelet count (raised with inflammation) C-reactive protein (CRP) indicates inflammation Urea and electrolytes (U&Es) indicate electrolyte imbalances and kidney function Liver function tests (LFTs) can show low albumin in severe disease (protein is lost in the bowel) Thyroid function tests for hyperthyroidism as a cause of diarrhoea Anti-tissue transglutaminase antibodies (anti-TTG) for coeliac disease as a differential diagnosis Stool microscopy and culture can be used to exclude infection as a differential diagnosis (e.g., Salmonella). Faecal calprotectin is around 90% sensitive and specific for inflammatory bowel disease in adults. It is used as an initial test before moving on to endoscopy. Colonoscopy with multiple intestinal biopsies is the investigation of choice for establishing the diagnosis. Imaging investigations (e.g., ultrasound, CT and MRI) can be used to look for complications such as fistulas, abscesses and strictures.

Answer 98

Management of inflammatory bowel disease can be separated into: Inducing remission during an acute exacerbation Maintaining remission Systemically unwell patients require hospital admission. Patients should be under the care of a gastroenterologist, with support from specialist nurses.

Answer 99

Mild to moderate acute ulcerative colitis is treated with: Aminosalicylate (e.g., oral or rectal mesalazine) first-line Corticosteroids (e.g., oral or rectal prednisolone) second-line Severe acute ulcerative colitis is treated with: Intravenous steroids (e.g., IV hydrocortisone) first-line Other options for severe acute ulcerative colitis include: Intravenous ciclosporin Infliximab Surgery Options for maintaining remission in ulcerative colitis are: Aminosalicylate (e.g., oral or rectal mesalazine) first-line Azathioprine Mercaptopurine Ulcerative colitis typically only affects the large bowel and rectum. Therefore, removing the entire large bowel and rectum (panproctocolectomy) will remove the disease. The patient has either a permanent ileostomy or an ileo-anal anastomosis (J-pouch). An ileostomy is where the end portion of the small bowel (ileum) is brought onto the skin with a spout that drains stools directly into a tightly fitting stoma bag. A J-pouch is where the ileum (small bowel) is folded back on itself and fashioned into a larger pouch, which is attached to the anus and functions like a rectum, collecting stools before the person opens their bowels.

Answer 100

Inducing remission in an exacerbation of Crohn’s disease is with: Steroids (e.g., oral prednisolone or IV hydrocortisone) first-line Enteral nutrition as an alternative, particularly where there are concerns about steroids affecting growth Enteral nutrition involves a specially formulated liquid diet given orally or by NG feed that replaces the patient’s diet. This induces remission by: Treating nutritional deficiencies Improving the gut microbiome Removing inflammatory foods Where steroids alone are inadequate, adding other medications may be considered: Azathioprine Mercaptopurine Methotrexate Infliximab Adalimumab Maintaining remission in Crohn’s disease is tailored to the individual, based on risks, side effects, nature of the disease and patient wishes. This might involve no medications. First-line for maintaining remission in Crohn’s is with either: Azathioprine Mercaptopurine Methotrexate is an alternative for maintaining remission where first-line options are unsuitable. Surgical options for Crohn’s include: Resecting the distal ileum when the disease is isolated to this area Treating strictures Treating fistulas

Answer 101

Irritable bowel syndrome (IBS) is caused by a disturbance of the gut-brain interaction, resulting in troublesome abdominal and intestinal symptoms. Symptoms can significantly impact the patient’s life. Irritable bowel syndrome is a functional disorder. This means there is no identifiable bowel disease underlying the symptoms, and the symptoms result from the abnormal functioning of an otherwise normal bowel. It occurs in up to 20% of the population. It affects women more than men and is more common in younger adults.

Answer 102

The three key features can be remembered with the IBS mnemonic: I – Intestinal discomfort (abdominal pain relating to the bowels) B – Bowel habit abnormalities S – Stool abnormalities (watery, loose, hard or associated with mucus) The specific symptoms vary with individuals. Common symptoms include: Abdominal pain Diarrhoea Constipation Fluctuating bowel habit Bloating Worse after eating Improved by opening bowels Passing mucus

Answer 103

Anxiety Depression Stress Sleep disturbance Illness Medications Certain foods Caffeine Alcohol

Answer 104

Bowel cancer Inflammatory bowel disease Coeliac disease Ovarian cancer (often presents with vague symptoms, particularly bloating in women over 50 years) Pancreatic cancer

Answer 105

A thorough history and examination are required to identify the typical features of IBS and exclude red flags for other underlying pathology. Investigations can be used to assess for underlying differentials (normal in IBS): Full blood count for anaemia Inflammatory markers (e.g., ESR and CRP) Coeliac serology (e.g., anti-TTG antibodies) Faecal calprotectin for inflammatory bowel disease CA125 for ovarian cancer The NICE clinical knowledge summaries (updated 2022) suggest before a diagnosis, differentials need to be excluded, and the patient should have at least 6 months of abdominal pain or discomfort with at least one of: Pain or discomfort relieved by opening the bowels Bowel habit abnormalities (more or less frequent) Stool abnormalities (e.g., watery, loose or hard) For a diagnosis, patients also require at least two of: Straining, an urgent need to open bowels or incomplete emptying Bloating Worse after eating Passing mucus

Answer 106

The first step is making a positive diagnosis, explaining the condition and reassuring the patient that evidence of other pathology has been excluded. Lifestyle advice includes: Drinking enough fluids Regular small meals Adjusting fibre intake according to symptoms (more fibre if predominantly constipated, less with diarrhoea/bloating) Limit caffeine, alcohol and fatty foods Low FODMAP diet, guided by a dietician Probiotic supplements may be considered over-the-counter (discontinuing after 12 weeks if there is no benefit) Reduce stress where possible Regular exercise

Answer 107

First-line medications depend on the symptoms: Loperamide for diarrhoea Bulk-forming laxatives (e.g., ispaghula husk) for constipation (lactulose can cause bloating and is avoided) Antispasmodics for cramps (e.g., mebeverine, alverine, hyoscine butylbromide or peppermint oil) There is only weak evidence for the benefit of using antispasmodic medications, and they may cause side effects. Linaclotide is a specialist secretory drug for constipation in IBS when first-line laxatives are inadequate. Other options include where symptoms remain uncontrolled: Low-dose tricyclic antidepressants (e.g., amitriptyline) SSRI antidepressants Cognitive behavioural therapy (CBT) Specialist referral for further management

Answer 108

Coeliac disease is an autoimmune condition triggered by eating gluten. It can develop at any age and is thought to be caused by genetic and environmental factors. There is a link with other autoimmune conditions, particularly type 1 diabetes and thyroid disease. TOM TIP: Remember for your exams that we test all new cases of type 1 diabetes and autoimmune thyroid disease for coeliac disease, even if they do not have symptoms.

Answer 109

In patients with coeliac disease, autoantibodies are created in response to exposure to gluten. These autoantibodies target the epithelial cells of the small intestine, leading to inflammation. These antibodies relate to disease activity and will rise with more active disease and may disappear with effective management. There are three antibodies related to coeliacs (particularly worth remembering the first two): Anti-tissue transglutaminase antibodies (anti-TTG) Anti-endomysial antibodies (anti-EMA) Anti-deamidated gliadin peptide antibodies (anti-DGP) Inflammation affects the small bowel, particularly the jejunum. The surface of the small intestine is covered in projections called villi, which increase the surface area and help with nutrient absorption. Coeliac disease causes atrophy of the intestinal villi, resulting in malabsorption. It is associated with certain human leukocyte antigen (HLA) genotypes: HLA-DQ2 HLA-DQ8

Answer 110

Coeliac disease is often asymptomatic and is under-diagnosed, so have a low threshold for testing for coeliac disease in patients where it is suspected. Presenting symptoms can include: Failure to thrive in young children Diarrhoea Bloating Fatigue Weight loss Mouth ulcers Dermatitis herpetiformis is an itchy, blistering skin rash, typically on the abdomen, caused by coeliac disease. Anaemia occurs secondary to malabsorption and deficiency of iron, B12 or folate. Rarely coeliac disease can present with neurological symptoms: Peripheral neuropathy Cerebellar ataxia Epilepsy

Answer 111

The patient must continue eating gluten while being investigated. Antibodies and histology may be normal if the patient is gluten-free. The first-line blood tests are: Total immunoglobulin A levels (to exclude IgA deficiency) Anti-tissue transglutaminase antibodies (anti-TTG) Anti-endomysial antibodies (anti-EMA) are a second-line option where there is doubt (e.g., a borderline result). TOM TIP: Initial anti-TTG and anti-EMA antibody tests are IgA. Some patients have an IgA deficiency. When you test for these antibodies, it is important to test for total immunoglobulin A levels because if the total IgA level is low, the antibody test will be negative, even in a patient with coeliac disease. In this circumstance, you can test for the IgG version of anti-TTG or anti-EMA antibodies. Patients with a positive antibody test are referred to a gastroenterologist to confirm the diagnosis by endoscopy and jejunal biopsy. Typical biopsy findings are: Crypt hyperplasia Villous atrophy

Answer 112

A lifelong gluten-free diet should completely resolve the symptoms. Dietician input may be helpful. Relapse will occur upon consuming gluten. Coeliac antibodies may help monitor the disease.

Answer 113

Nutritional deficiencies Anaemia Osteoporosis Hyposplenism (with immunodeficiency, particularly to encapsulated bacteria such as Streptococcus pneumoniae) Ulcerative jejunitis Enteropathy-associated T-cell lymphoma (EATL) Non-Hodgkin lymphoma Small bowel adenocarcinoma