Gastroenterology Flashcards

Question

micro organisms related to Crohns

Answer 1

**Mycobacterium paratuberculosis** as well **Pseudomonas and Listeria species**

Answer 2

**fistulae**, abscess, bowel obstruction, perforation, **toxic megacolon**, kidney stones, Bowel cancer (adenocarcinoma), gallstones

Answer 3

AUTOIMMUNE Th2 mediated rxn, where cytotoxic T cells target abnormal gut bacteria or p-ANCA antibodies, thus eroding the lining of the intestines, and ulceration The circumferential inflammation can destroy the haustras of the colon leading to a smooth section of colon which is called the “lead pipe” sign. Prevalent in non-smokers/ex-smokers\*

Answer 4

* **Proctitis:** Just the rectum * **Proctosigmoiditis:** Involves the rectum and sigmoid colon * **Left sided Colitis:** Involves the descending colon up to the splenic flexure * **Extensive Colitis:** Extending to the hepatic flexure * **Pancolitis/Universal colitis:** The entire colon is affected, associated with Backwash Ileatis (inflammation of the terminal ileum)

Answer 5

**Inflammation of abnormal pouches called diverticula** (can develop on the walls of the large intestine, or any other hollow structure). Usually 0.5c,-1cm large True Diverticula: involve all layers of the intestine Pseudo diverticula: Muscle layers are not included **MOST COMMON**

Answer 6

diverticulosis

Answer 7

Obesity, lack of exercise, low fibre diet, Smoking, Connective tissue disorders (genetic), Family history, NSAIDs, Common in the western world, Elderly, Females

Answer 8

Symptoms: MOST CASES ARE ASYMPTOMATIC * Lower abdominal pain (sudden onset)- mostly affects the Sigmoid colon- LLQ pain and tenderness * Erratic bowel habits * Symptoms of infection (fever, tachycardia), Nausea, Diarrhea, Constipation, Fever, blood/mucus in the stool

Answer 9

Raised CRP and ESR, USS, CT, Barium enema, Sigmoidoscopy Treatment If less severe: analgesia, Fibre, Antibiotics, Fluid resus Surgical resection if acutely unwell

Answer 10

An AUTOIMMUNE DISORDER where exposure to **gluten** causes an autoimmune reaction that causes **inflammation in the small bowel**. It usually develops in early childhood but can start at any age. 1 in 100 people have it. Family History increases risk to 1 in 10.

Answer 11

Gluten is a large molecule, that is broken down to smaller ones in the gut, and it is the **breakdown products that are toxic (gliadins).** The main toxic peptide is **α-Gliadin.** **Autoantibodies** are created in response to exposure to gluten, which target the epithelial cells of the intestines, leading to inflammation in the small bowel (particularly jejunum) It causes **atrophy of the intestinal villi, and crypt hypertrophy,** so the surface of the bowel becomes flattened, and the surface area for absorption becomes greatly reduced (malabsorption)

Answer 12

1. Anti-TTG (anti-tissue transglutaminase)- attacks TTG, which is responsible for gluten breakdown 2. Anti-EMA (Anti-endomysial) 3. DGP (deaminated gliadin peptide)

Answer 13

**Often asymptomatic** (can be mistaken for IBS), Steatorrhea, failure to lose/gain weight, **abdo pain,** cramps, **bloating,** distension, diarrhoea, fatigue, mouth ulcers, anaemia, **dermatitis herpetiformis**, osteomalacia, Vit D and calcium deficiency, neurological (ataxia, epilepsy)

Answer 14

Check for total IgA levels whilst on gluten diet * Raised Anti-TTG antibodies serology (FIRST LINE) * Raised anti-endomysial antibodies * deaminated gliadin peptide (DGP) – in cases of patients who have a IgA deficiency Duodenal Biopsy to confirm Genetic testing for HLADQ2 and HLADQ8

Answer 15

- Irritable bowel syndrome (IBS) is a group of symptoms—including abdominal pain and changes in the pattern of bowel movements without any evidence of underlying damage (like inflammation, ulcers etc). - It has been classified into four main types depending on whether diarrhoea is common, constipation is common, both are common, or neither occurs very often

Answer 16

IBD has structural damage to the bowel (ie inflammation, ulceration) in ADDITION to IBS symptoms

Answer 17

Other pathology should be excluded: * Normal FBC, ESR and CRP blood tests * Faecal calprotectin negative to exclude inflammatory bowel disease * Negative coeliac disease serology (anti-TTG antibodies) * Cancer is not suspected or excluded if suspected **Symptoms should suggest IBS:** Abdominal pain / discomfort pain for ≥12wks which has 2 of: * Relieved by defecation * Change in stool frequency (D or C) * Change in stool form: pellets, mucu AND 2 of: * Abnormal stool passage: incomplete/urgency * Bloating/Distention * Worse symptoms after eating * PR mucus **ROME CRITERIA**

Answer 18

Female, stress, gastroenteritis (nota/rotavirus)

Answer 19

* A low FODMAPS diet: F- fermentable O- oligosaccharides 🡪 sucrose (Wheat, rye, legumes and various fruits and vegetables, such as garlic and onions.) D- disaccharides 🡪 lactose (Milk, yogurt and soft cheese) M- monosaccharides 🡪 fructose (Various fruit including figs and mangoes, and sweeteners such as honey Andmitriptyline P- polyols 🡪 sugar free sweeteners ( Certain fruits and vegetables including blackberries and lychee, as well as some low-calorie sweeteners like those in sugar-free gum.) * Avoid caffeine and alcohol * Probiotics, regular small meals, reduced processed food, physical activity, for constipation: soluble fibres, laxatives, stool softeners**,** for pain**: anti-diarrhoeals (ie loperamide), antimuscarinics, antispasmodics (mebeverine)** * Manage stress, anxiety and depression- **CBT** * Amitriptyline

Answer 20

Genetic connections: HLA-DQ2 gene (90%) HLA-DQ8 gene

Answer 21

Formation of hard stones in the gallbladder Incidence increases with age. More common in women. F – Fat F – Fair F – Female F – Forty Most are asymptomatic and are discovered when they cause biliary colic etc

Answer 22

* Cholesterol gallstones are the most common stones -supersaturation of bile with cholesterol --Gallbladder stasis -cannot been seen on X-RAY . However if they have enough CaCO3 * Bilirubin gallstones are the 2nd most common stones: AKA pigmented - can be seen on X-RAY as the bilirubin binds to calcium --associated with : hemolytic disease, E.coli

Answer 23

- sign of infection (caused by bacteria Ecoli) - causes calcium + UBC - browness is due to hydrolysed phospholipid too in it.

Answer 24

Biliary colic, also known as symptomatic cholelithiasis, a gallbladder attack or gallstone attack, is when a colic (sudden pain) occurs due to a gallstone temporarily blocking the cystic duct. * Intermittent RUQ pain that comes in waves * Pain MAY radiate to R shoulder tip * Typically starts in the evening and lasts till the morning * Recurring condition, usually managed with diet adjustment

Answer 25

* Inflammation of the cystic duct due to gallstone obstruction * Prolonged colicky pain which MAY radiate to the shoulder tip * Inflammation-\>Fever + leucocytosis * Murphy’s Sign. There will be **RUQ pain** that is usually worse on inspiration.

Answer 26

* Common bile duct obstruction * No inflammation -\> no fever or leucocytosis * Obstructive jaundice * Dilated hepatic ducts * RUQ pain\> 6h

Answer 27

Infection of the gallbladder and CBD Charcot triad-\> fever, jaundice and RUQ pain Reynolds triangle -\> hypotension (shock) +altered mental status + Charcoat triangle. This occurs when the infection becomes more advanced RUQ pain Murphy sign

Answer 28

* Cholecystitis , Acute cholangitis + Mirizzi syndrome * Empyema +perforation * Jaundice -\> obstructive jaundice * Acute pancreatitis -\> epigastric pain, radiates to the back , curling makes it better * Cancer of the gallbladder * Gallstone ileus A bowel obstruction requires immediate medical treatment. If it's not treated, there's a risk that the bowel could split open (rupture).

Answer 29

Primary (not caused by something else) Sclerosing (hardening/fibrosis of tissue) Cholangitis (inflammation of bile ducts) Disorder caused due to the chronic inflammation of the intra hepatic and extra hepatic bile ducts leading to fibrosis More commonly occurs in males (around 30-50 years)

Answer 30

The exact cause is unknown but it has a strong association with autoimmune disesases, especially inflammatory bowel disease (most commonly UC). In most patients, there is presence of antibodies such as pANCA and ANA antibodies but these are not specific for the disease. It is linked to HLA DR3 and HLA B8

Answer 31

UC Crohn’s (much rarer) AIH HIV

Answer 32

Disorder caused due to the chronic inflammation of the **intra hepatic** bile ducts leading to fibrosis More commonly occurs in females (around 30-65 years)

Answer 33

* Often asympto and Dx incidentally (↑ALP) * Jaundice occurs **late** * **P**ruritus and fatigue * **P**igmentation of face * **B**ones: osteoporosis, osteomalacia (↓vit D) * **B**ig organs: HSM * **C**irrhosis and coagulopathy (↓vit K) * **C**holesterol↑: xanthelasma, xanthomata * **S**teatorrhoe

Answer 34

Inflammation of the appendix Can occur at any age but most commonly in the elderly or in the 2nd decade of life. It is due to the obstruction of the appendix lumen by hyperplasia of the lymphoid tissue, feces, worms, foreign body etc.

Answer 35

Once the lumen is obstructed, it can lead to bacterial overgrowth, ischemia, inflammation etc. If untreated, it can lead to necrosis, peritonitis, gangrene, perforation etc

Answer 36

n the early stages, the pain will be poorly localized to the periumbilical or epigastric region. This is because the organ is poorly innervated by the lesser splanchnic nerves which localise the pain to the centre of the abdomen.

Answer 37

In the later stages, as the inflammation becomes worse, it spreads to the parietal peritoneum in that area, so the pain can be localized. This is because the peritoneum is supplied by the same nerve as the respective dermatome. So, initial pain will be in the periumbilical region and then will localize to the RIF as the inflammation becomes worse

Answer 38

It is described as constant and sharp

Answer 39

2/3’s of the way along an imaginary line from the umbilicus to the anterior superior iliac spine on the right hand side

Answer 40

pain felt in the LRQ when the LLQ is palpated

Answer 41

increased pain during passive extension of the right hip

Answer 42

pain felt on passive internal rotation of the flexed hip

Answer 43

This shows that there is peritonitis. the pain is exacerbated by the slightest movement (e.g. rolling, coughing, even breathing) as this moves the peritoneum.

Answer 44

* **Increased IgG levels** * **Antibodies against:** Liver specific proteins Non-live specific proteins **Mononuclear infiltrate within the liver:** Monocytes, macrophages, lymphocytes, plasma cells, macrophages and mast cells

Answer 45

* **Cholestasis:** blockage to the flow of bile * **Cholelithiasis:** gallstone(s) are present * **Choledocholithiasis:** gallstone(s) in the bile duct * **Biliary colic:** intermittent right upper quadrant pain caused by gallstones irritating bile ducts * **Cholecystitis:** inflammation of the gallbladder * **Cholangitis:** inflammation of the bile ducts * **Gallbladder empyema:** pus in the gallbladder * **Cholecystectomy:** surgical removal of the gallbladder * **Cholecystostomy:** inserting a drain into the gallbladder

Answer 46

LFTs- raised bilirubin, ALP USS- first line

Answer 47

cholestasis an"obstructive picture”

Answer 48

a problem inside the liver with hepatocellular injury “a hepatitic picture”

Answer 49

A raised ALP is consistent with **biliary obstruction** in presence of right upper quadrant pain and/or jaundice.

Answer 50

A magnetic resonance cholangio-pancreatography (MRCP) is an MRI scan with a specific protocol that produces a detailed image of the biliary system. It is very sensitive and specific for biliary tree disease, such as stones in the bile duct and malignancy. MRCP is used in a number of scenarios for gaining a detailed picture of the biliary system, such as identifying biliary strictures or congenital abnormalities. With gallstone disease, MRCP is typically used to investigate further if the ultrasound scan does not show stones in the duct, but there is bile duct dilatation or raised bilirubin suggestive of obstruction.

Answer 51

An endoscopic retrograde cholangio-pancreatography (ERCP) 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. The main indication for ERCP is to clear stones in the bile ducts. Key complications of ERCP are: * Excessive bleeding * Cholangitis (infection in the bile ducts) * Pancreatitis

Answer 52

* Bleeding, infection, pain and scars * Damage to the bile duct including leakage and strictures * Stones left in the bile duct * Damage to the bowel, blood vessels or other organs * Anaesthetic risks * Venous thromboembolism (deep vein thrombosis or pulmonary embolism) * Post-cholecystectomy syndrome

Answer 53

Post-cholecystectomy syndrome involves a group of non-specific symptoms that can occur after a cholecystectomy. They may be attributed to changes in the bile flow after removal of the gallbladder. Symptoms often improve with time. Symptoms include: * Diarrhoea * Indigestion * Epigastric or right upper quadrant pain and discomfort * Nausea * Intolerance of fatty foods * Flatulence

Answer 54

Wilson disease is the excessive accumulation of copper in the body and tissues. It is caused by a mutation in the **“Wilson disease protein”** on **chromosome 13**. The Wilson disease protein also has the catchy name “**ATP7B copper-binding protein”** and is responsible for various functions, including the removal of excess copper in the liver. Genetic inheritance is **autosomal recessive.**

Answer 55

**Cornea** * Kayser-Fleischer rings (70%, may need slit-lamp) **Liver Disease** * Children usually present c̄acute hepatitis. * Fulminant necrosis may occur * →cirrhosis **Arthritis** * Chondrocalcinosis * Osteoporosis **Neurology** * Parkinsonism:bradykinesia,tremor, chorea, tics * Spasticity, dysarthria, dysphagia * Ataxia * Depression, dementia, psychosis **Kidney** * Fanconi’s syn. (T2 RTA)→osteomalacia **Abortions** **Haemolytic anaemia** * Coombs’ negative

Answer 56

Copper deposition in the liver leads to **chronic hepatitis** and eventually liver cirrhosis. Copper deposition in the **central nervous system** can lead to neurological and psychiatric problems.

Answer 57

* **Bloods:**↓Cu,↓caeruloplasmin NB. Caeruloplasmin is an acute-phase protein and maybe high during infection. It may also be low protein-deficient states: nephroticsyndrome, malabsorption * ↑24h urinary Cu * **Liver biopsy**:↑hepatic Cu * **MRI**:basal-ganglia degeneration

Answer 58

Treatment is with copper chelation using: * Penicillamine (lifelong) * Trientene

Answer 59

eating typically worsens the pain of **gastric** ulcers and improves the pain of **duodenal** ulcers.

Answer 60

Peptic ulcers are diagnosed by **endoscopy.** During endoscopy a **rapid urease test** (CLO test) can be performed to check for **H. pylori**. Biopsy should be considered during endoscopy to **exclude malignancy** as cancers can look similar to ulcers during the procedure. Medical treatment is the same as with **GORD**, usually with high dose **proton pump inhibitors**. Endoscopy can be used to monitoring the ulcer to ensure it heals and to assess for further ulcers

Answer 61

**First Line Medication:** * **Loperamide** for diarrhoea * Laxatives for constipation. Avoid lactulose as it can cause bloating. **Linaclotide** is a specialist laxative for patients with IBS not responding to first-line laxatives * **Antispasmodic**s for cramps e.g. hyoscine butylbromide (Buscopan) **Second Line Medication:** * Tricyclic antidepressants (i.e. amitriptyline 5-10mg at night) **Third Line Medication:** * SSRIs antidepressants

Answer 62

A hiatus hernia is when part of your stomach moves up into your chest. It's very common if you're over 50. It does not normally need treatment if it's not causing you problems

Answer 63

**Sliding (80%)** * Gastro-oesophageal junction slides up into chest * Often assoc. c̄GORD **Rolling (15%)** * Gastro-oesophageal junction remains in abdomen but abulge of stomach rolls into chest alongside theoesophagus * LOS remains intact so GORD uncommon * Can→strangulation **Mixed (5%)**

Answer 64

* **CXR**:gas bubble and fluid level in chest * **Ba swallow:** diagnostic * **OGD:** visualises the mucosa but can’t exclude hernia * **24h pH** + manometry:exclude dysmotility or achalsia

Answer 65

* Lose wt. * Rx reflux * Surgery if intractable symptoms despite medical Rx.-Should repair rolling hernia (even if asympto) as it may strangulate

Answer 66

Hereditary hemochromatosis (he-moe-kroe-muh-TOE-sis) causes your body to absorb too much iron from the food you eat. Excess iron is stored in your organs, especially your liver, heart and pancreas. Too much iron can lead to life-threatening conditions, such as liver disease, heart problems and diabetes ## Footnote **AR** **HFE gene (High FE) on Chr6 (C282Y**

Answer 67

* Inherited, multisystem disorder resulting from abnormaliron metabolism. * ↑intestinal Fe absorption (↑enterocyte DMT +↓hepatocyte hepcidin)→deposition in multiple organ

Answer 68

**Myocardial** * Dilated cardiomyopathy * Arrhythmias **Endocrine** * Pancreas: DM * Pituitary: hypogonadism→amenorrhoea, infertility * Parathyroid: hypocalcaemia, osteoporosis **Arthritis** * 2ndand 3rdMCP joints, knees and shoulders **Liver** * Chronic liver disease→cirrhosis→HCC * Hepatomegaly **Skin** * Slate grey discolouration

Answer 69

* **Bloods:**↑LFT,↑ferritin,↑Fe,↓TIBC, glucose, genotype * **X-ray:**chondrocalcinosis * **ECG, ECHO** * **Liver biopsy:**Pearl’s stain to quantify Fe and severity * **MRI:**can estimate iron loading

Answer 70

Iron removal * Venesection: aim for Hct \<0.5 * Desferrioxamine is 2ndline General * Monitor DM * Low Fe diet Screening * Se ferritin and genotype * Screen 1stdegree relatives Transplant in cirrhosis

Answer 71

* Mutation of Cu transporting ATPase * Impaired hepatocyte incorporation of Cu intocaeruloplasmin and excretion into bile. * Cu accumulation in liver and, later, other organ

Answer 72

Symptoms * Jaundice * Pruritus and fatigue * Abdo pain Signs * Jaundice: dark urine, pale stools * HSM

Answer 73

Bacterial cholangitis ↑Cholangiocarcinoma ↑CRC

Answer 74

* **LFTs:**↑ALP initially, then↑BR * **Abs**:pANCA (80%), ANA and SMA may be +ve * **ERCP/MRCP**:“beaded” appearance of ducts * **Biopsy**:fibrous, obliterative cholangitis

Answer 75

rimary biliary cholangitis is associated with metabolic or immune system disorders, including thyroid problems, limited scleroderma (CREST syndrome), rheumatoid arthritis, and dry eyes and mouth (Sjogren's syndrome)

Answer 76

**ALT-** Markers of hepatocellular damage, localised to liver **AST**- Markers of hepatocellular damage, synthesised by liver, heart, skeletal muscle and brain **Billirubin**- Assessing degree of jaundice **gGT-** Cholestasis **ALP-** Cholestasis – sources are bone and liver **Albumin**- Synthetic function **Prothrombin time** - Synthetic function

Answer 77

* **USS-** Ultrasound is usually first line. Identifies any obstructive pathology present or gross liver pathology * **Fibroscan** * **MRI** * **MRCP-** Used to visualise the biliary tree. Usually performed if obstructive jaundice is suspected or US is inconclusive * **X rays – hepatic angiogram** * **CT** * **Biopsy-** Performed when the diagnosis has not been made despite the above investigations

Answer 78

yellow appearance of the skin, sclerae and mucous membranes resulting from an increased bilirubin concentrations in body fluids

Answer 79

* Pre-hepatic * Hepatic/ intrahepatic/ hepatocellular * Post-hepatic

Answer 80

haemolytic jaundice

Answer 81

Excessive red cell breakdown which overwhelms the liver’s ability to conjugate bilirubin 🡪 unconjugated hyperbilirubinemia Any bilirubin that manages to become conjugated is excreted normally Unconjugated bilirubin in the blood causes jaundice ALT, AST, ALP will be normal

Answer 82

* Examples * Haemolytic anaemia * Malaria * Sickle cell thalassemia * SLE

Answer 83

* Due to dysfunction of the hepatic cells * Liver loses the ability to conjugate bilirubin * Liver may become cirrhotic 🡪 compromises the intra-hepatic portions of the biliary tree to cause some obstruction * Both unconjugated and conjugated bilirubin are found in blood * High ALT, AST and ALP (higher ALT&AST)

Answer 84

* Alcoholic liver disease * Viral hepatitis * Primary biliary cirrhosis * Hepatocellular carcinoma

Answer 85

* AKA obstructive jaundice * Due to obstruction of biliary drainage * Bilirubin that has been conjugated by the liver is not excreted * Excess conjugated bilirubin = conjugated hyperbilirubinemia * High ALP, AST and ALT (higher ALP)

Answer 86

Onset of hepatic decompensation within 6 months, results in loss of function in 80-90%

Answer 87

* **Drugs** 50% of cases in the UK due to paracetamol overdose others inc NSAIDs and ecstasy * **Infection** Viral hepatitis, CMV, HSV, EBV * **Acute fatty liver in pregnancy** Unmetabolized fetal fatty acids enter maternal circulation and accumulate in mothers liver * **Wilsons disease** AR, copper accumulates in the liver * **Budd-Chiari** Occlusion of hepatic vein Abdo pain + ascites + liver enlargement

Answer 88

* Jaundice * Bruising (coagulation disturbance) * Ascites * Tachycardia and hypotension * Due to reduced systemic vascular resistance * Signs of encephalopathy * Sweet smell on breath

Answer 89

* Hepatic encephalopathy = altered level of consciousness * Impaired protein synthesis = measured by serum albumin + prothrombin time in blood

Answer 90

Progressive destruction/regeneration of liver parenchyma leading to fibrosis and cirrhosis (\> 6 months

Answer 91

* **Metabolic** Hereditary haemochromatosis -Accumulation of iron, reacts with H2O2 to form free radicals NAFLD Wilsons disease * **Toxic and drugs** Alcohol Drug induced is rare 🡪 methotrexate, amiodarone * **Infections – hep b & c** * **Autoimmune** Primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis

Answer 92

* Nail clubbing * Palmar erythema * Spider nevi * Gynaecomastia * Feminising hair distribution * Small irregular shrunken liver * Anaemia * Caput medusae

Answer 93

* Portal hypertension * Synthetic dysfunction * Hepatopulmonary syndrome * Hepatorenal syndrome * Encephalopathy * Hepatocellular carcinoma

Answer 94

* Increased blood pressure in the hepatic portal system (portal venous system) usually due to hepatic cirrhosis * Obstruction may prevent the blood flow from the portal vein into the IVC * Causes the blood to accumulate in the hepatic portal system 🡪 increasing the pressure 🡪 PORTAL HYPERTENSION * Portosystemic Shunts- anastomoses between portal and systemic systems, due to portal HTN the blood backs up and varices form- these can rupture * Features (ABCDE)- ascites, bleeding, caput medusae, diminished liver function and enlarged spleen

Answer 95

Reduced blood to liver 🡪 reduced liver function Increased ammonia crosses BBB Can be gradual or sudden In advanced stages 🡪 coma

Answer 96

Asterixis, lethargy, movement problems, changes in mood or changes in personality, altered consciousness, seizures

Answer 97

Treatment = Oral lactulose

Answer 98

Syndrome of shortness of breath and hypoxemia caused by vasodilation in lungs of patients with liver disease

Answer 99

Due to formation of microscopic intrapulmonary arteriovenous dilations Thought to be due to increased liver production or decreased liver clearance of vasodilators, e.g. NO Dilation of blood vessels 🡪 over-perfusion relative to ventilation 🡪 V/Q mismatch Increased gradient between the partial pressure of O2 in alveoli and adjacent arteries

Answer 100

Life-threatening medical condition that consists of rapid deterioration of kidney function in individuals with cirrhosis or fulminant liver failure Occurs due to portal hypertension

Answer 101

Malignant tumour of the liver which occurs primarily in patients with pre-existing liver cirrhosis or chronic hepatitis Most common type of primary liver cancer Malignant tumour of the liver which occurs primarily in patients with pre-existing liver cirrhosis or chronic hepatitis Most common type of primary liver cancer

Answer 102

A stepwise pattern; of mutational activation of oncogenes ( ie Kras) and inactivation of tumour suppressor genes (eg p53) that results in cancer

Answer 103

* Smoking * Alcohol * Diet; processed meat ( especially red meat), increased obesity risk, green vegetables and diet high in fibre protective against colorectal cancer * Chronic inflammation ie patients with ulcerative colitis have increased risk of developing colorectal cancer * Upper GI cancer; H pylori infection?

Answer 104

* Smoking * Alcohol * Diet; processed meat ( especially red meat), increased obesity risk, green vegetables and diet high in fibre protective against colorectal cancer * Chronic inflammation ie patients with ulcerative colitis have increased risk of developing colorectal cancer * Upper GI cancer; H pylori infection?

Answer 105

1. Inactiviation of APC 2. Activation of Kras 3. Inactivation of p53

Answer 106

Same genes different order 1. P53 2. Kras 3. APC

Answer 107

Same genes different order 1. P53 2. Kras 3. APC

Answer 108

1. Inactiviation of APC 2. Activation of Kras 3. Inactivation of p53

Answer 109

APC and P53

Answer 110

APC and P53

Answer 111

Oesophageal cancers Gastric cancers

Answer 112

colorectal cancers

Answer 113

Most common : adenocarcinoma ( a malignant tumour formed from glandular structures of the epithelial tissue) Less common; mucinous adenocarcinoma, signet ring cell carcinoma, small cell carcinoma Glandular dysplasia is the premalignant lesion, when it forms a poly it is commonly referred to as an adenoma Adenomas classified as tubular, tubulovillous and villous (the is the worst one) Adenomas are also graded in terms of dysplasia (low or high)

Answer 114

Most common : adenocarcinoma ( a malignant tumour formed from glandular structures of the epithelial tissue) Less common; mucinous adenocarcinoma, signet ring cell carcinoma, small cell carcinoma Glandular dysplasia is the premalignant lesion, when it forms a poly it is commonly referred to as an adenoma Adenomas classified as tubular, tubulovillous and villous (the is the worst one) Adenomas are also graded in terms of dysplasia (low or high)

Answer 115

**Gallstones** - Obstruct sphincter of Oddi causing reflux . Bile salts irritates pancreatic duct **Ethanol** - Increases acinar cell secretion, decreases ductal cell secretion → thickened pancreatic juice . ROS damages the cells **Trauma** - Usually ruptured duct in the body of the pancreas from direct trauma (vertebral column) **Drugs** - sodium valporate, furosemide, thiazides, Azathioprine

Answer 116

**Gallstones** - Obstruct sphincter of Oddi causing reflux . Bile salts irritates pancreatic duct **Ethanol** - Increases acinar cell secretion, decreases ductal cell secretion → thickened pancreatic juice . ROS damages the cells **Trauma** - Usually ruptured duct in the body of the pancreas from direct trauma (vertebral column) **Drugs** - sodium valporate, furosemide, thiazides, Azathioprine

Answer 117

4th rectum 2nd

Answer 118

family history, those that have FAP or HNPCC, diet with lack of fibre, inflammatory bowel disease (ie ulcerative colitis)

Answer 119

Classic familial adenomatous polyposis, called FAP or classic FAP, is a genetic condition. It is diagnosed when a person develops more than 100 adenomatous colon polyps. An adenomatous polyp is an area where normal cells that line the inside of a person's colon form a mass on the inside of the intestinal trac

Answer 120

Autosomal dominant inheritance

Answer 121

Autosomal dominant inheritance

Answer 122

Mutations in the DNA mismatch repair genes (MSH2 (60%)) and MLH1 (30%)), causing microsatellite instability. These genes normally maintain stability of DNA during replication

Answer 123

Mutations in the DNA mismatch repair genes (MSH2 (60%)) and MLH1 (30%)), causing microsatellite instability. These genes normally maintain stability of DNA during replication

Answer 124

* Unintentional / unexplained weight loss * Rectal bleeding * Change in bowel habit * Abdominal masses * Iron deficiency anaemia * In history; ask about family history- family members with ovarian and bowel cancer can be significan

Answer 125

* Unintentional / unexplained weight loss * Rectal bleeding * Change in bowel habit * Abdominal masses * Iron deficiency anaemia * In history; ask about family history- family members with ovarian and bowel cancer can be significan

Answer 126

Autosomal dominant inheritance

Answer 127

Autosomal dominant inheritance

Answer 128

Classic familial adenomatous polyposis, called FAP or classic FAP, is a genetic condition. It is diagnosed when a person develops more than 100 adenomatous colon polyps. An adenomatous polyp is an area where normal cells that line the inside of a person's colon form a mass on the inside of the intestinal trac

Answer 129

Epigastric pain; may be relieved by food and antacids Dysphagia especially if tumour involves stomach fundus Anaemia Nausea, vomiting and weight loss Can have Liver, bone , brain and lung involvement

Answer 130

Zollinger–Ellison syndrome is a disease in which tumours cause the stomach to produce too much acid, resulting in peptic ulcers. A gastrin secreting tumour (gastrinoma) - Excess gastric acid secretion leads to (unusual/severe peptic ulceration, oesophagitis, diarrhoea and

Answer 131

* Neuroendocrine tumours * Gastrin secreting * Cause severe peptic ulcer disease and diarrhoea (referred to as the Zollinger Ellison Syndrome) * Can either be sporadic (75-80% of cases) or associated with Multiple endocrine neoplasia type 1 (20-30% of cases)

Answer 132

Sudden inflammation, haemorrhage of pancreas due to autodigestion from inappropriate activation of zymogen (trypsinogen → trypsin) Reversible

Answer 133

Sudden inflammation, haemorrhage of pancreas due to autodigestion from inappropriate activation of zymogen (trypsinogen → trypsin) Reversible

Answer 134

Elevated serum amylase \>1000 IU/L **Elevated serum lipase (2-5x normal value)** LFTs: gallstones aetiology (jaundice) Imaging CT: swollen gland with inflammation, necrosis, pseudocyst USS: gallstones

Answer 135

- Chronic inflammation causing irreversible structural damage Atrophy of acinar cells Fibrosis Calcification Dilation of ducts/ narrowing - Formation of chronic pseudocysts, intrapancreatic cysts

Answer 136

Obstruction in the pancreatic ducts Ductal dilatation and damage to tissue (atrophy of acinar cells) Stellate cells lay down fibrotic tissue Further resulting in atrophy of acinar cells, intraluminal calcification, narrowing of ducts

Answer 137

- Recurrent episodes of acute pancreatitis (alcohol) - Duct obstruction: tumour, gallstones, structural abnormalities (annular pancreas, pancreas divisum), traumatic strictures - Cystic fibrosis

Answer 138

Serum lipase and amylase may or may not be elevated Glucose tolerance test (endocrine function) Imaging CT : calcification, intrapancreatic cysts or chronic pseudocysts ERCP: dilated and strictured ducts (chain of lakes pattern) To differentiate from carcinoma Pancreatic imaging + EUS + targeted needle biopsy

Answer 139

Increased risk of pancreatic carcinoma Pancreatic pseudocysts, fistula, ascites Biliary obstruction Malnutrition Diabetes mellitus

Answer 140

Western lifestyle Cigarette smoking High-fat diet Liver cirrhosis Chronic pancreatitis Obesity Family history/genetic factors (BRCA1/BRCA2/FAP/HNPCC)

Answer 141

Hirschprung’s Disease Meckel’s Diverticulum Omphalocele Gastroschisis

Answer 142

Agangliosis of myenteric and submucosal plexus in the distal colon and rectum which causes lack of peristalsis Functional obstruction from spasms in denervated colon Severe constipation within first 2 months Investigations X ray: colon distension Biopsy to identify transition zone Management: surgical removal of affected segment

Answer 143

**Persistence of vitellointestinal duct** **_Rule of 2s_** 2% of population Present in first 2 years 2 inches in length Approximately 2 ft from ileocaecal valve

Answer 144

Herniation of intestines (sometimes liver and other organs) out of umbilicus at birth due to abdominal wall defects Failure to return to abdomen after natural protrusion during development Covered by peritoneal membrane and amnion Investigations: USS antenatal scan shows herniated loop contained within peritoneum Associated with severe malformations, 25% mortality

Answer 145

Herniation of bowel loops (sometimes stomach and liver) through para-umbilical wall defect (lateral to the umbilicus) Not covered by surrounding membrane Investigations: Antenatal USS show herniation to lateral of umbilicus, free-floating

Answer 146

Alcoholic liver disease results from the effects of the long term excessive consumption of alcohol on the liver. The onset and progression of alcoholic liver disease varies between people, suggesting that there may be a **genetic predisposition** to having harmful effects of alcohol on the liver.

Answer 147

**1. Alcohol related fatty liver** Drinking leads to a build-up of fat in the liver. If drinking stops this process reverses in around 2 weeks. **2. Alcoholic hepatitis** Drinking alcohol over a long period causes inflammation in the liver sites. Binge drinking is associated with the same effect. Mild alcoholic hepatitis is usually reversible with permanent abstinence. **3. Cirrhosis** This is where the liver is made up of scar tissue rather than healthy liver tissue. This is irreversible. Stopping drinking can prevent further damage. Continued drinking has a very poor prognosis.

Answer 148

That latest recommendations (Department of Health, 2016) are to **not regularly drink more than 14 units per week** for both men and women. If drinking 14 units in a week, this should be spread evenly over 3 or more days and not more than 5 units in a day. The government guidelines also state that any level of alcohol consumption increases the risk of cancers, particularly breast, mouth and throat. Pregnant women should avoid alcohol completely.

Answer 149

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 gives an indication of harmful use.

Answer 150

* Alcoholic Liver Disease * Cirrhosis and the complications of cirrhosis including hepatocellular carcinoma * Alcohol Dependence and Withdrawal * Wernicke-Korsakoff Syndrome (WKS) * Pancreatitis * Alcoholic Cardiomyopathy

Answer 151

* Jaundice * Hepatomegaly * Spider Naevi * Palmar Erythema * Gynaecomastia * Bruising – due to abnormal clotting * Ascites * Caput Medusae – engorged superficial epigastric veins * Asterixis – “flapping tremor” in decompensated liver disease

Answer 152

**Bloods** FBC – raised MCV LFTs – elevated ALT and AST (transaminases) and particularly raised gamma-GT. ALP will be elevated later in the disease. Low albumin due to reduced “synthetic function” of the liver. Elevated bilirubin in cirrhosis. Clotting – elevated prothrombin time due to reduced “synthetic function” of the liver U+Es may be deranged in hepatorenal syndrome. **Ultrasound** An ultrasound of the liver may show fatty changes early on described as **“increased echogenicity”**. It can also demonstrate changes related to cirrhosis if present. _“FibroScan”_ can be used to check the elasticity of the liver by sending high frequency sound waves into the liver. It helps assess the degree of cirrhosis. **Endoscopy** Endoscopy can be used to assess for and treat oesophageal varices when portal hypertension is suspected. **CT and MRI scans** CT and MRI can be used to look for fatty infiltration of the liver, hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes and ascites. **Liver Biopsy** Liver biopsy can be used to confirm the diagnosis of alcohol-related hepatitis or cirrhosis. NICE recommend considering a liver biopsy in patients where steroid treatment is being considered.

Answer 153

* Stop drinking alcohol permanently * Consider a **detoxication regime** * Nutritional support with vitamins (particularly **thiamine**) and a high protein diet * **Steroids** improve short term outcomes (over 1 month) in severe alcoholic hepatitis but infection and GI bleeding need to be treated first and do not improve outcomes over the long term * Treat complications of cirrhosis **(portal hypertension, varices, ascites and hepatic encephalopathy)** * **Referral for liver transplant** in severe disease however they must abstain from alcohol for 3 months prior to referral

Answer 154

* 6-12 hours: tremor, sweating, headache, craving and anxiety * 12-24 hours: hallucinations * 24-48 hours: seizures * 24-72 hours: “delirium tremens”

Answer 155

Delirium tremens is a medical emergency associated with **alcohol withdrawal** with a mortality of 35% if left untreated. Alcohol 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**) having a further inhibitory effect on the electrical activity of the brain.

Answer 156

* Acute confusion * Severe agitation * Delusions and hallucinations * Tremor * Tachycardia * Hypertension * Hyperthermia * Ataxia (difficulties with coordinated movements) * Arrhythmias

Answer 157

(Clinical Institute Withdrawal Assessment – Alcohol revised) tool can be used to score the patient on their withdrawal symptoms and guide treatment.

Answer 158

Chlordiazepoxide (“Librium”) Diazepam

Answer 159

Alcohol excess leads to **thiamine (vitamin B1)** deficiency. Thiamine is poorly absorbed in the presence of alcohol and alcoholics tend to have poor diets and rely on the alcohol for their calories. **Wernicke’s encephalopathy** comes before **Korsakoffs syndrome**. These result from thiamine deficiency.

Answer 160

* Confusion * Oculomotor disturbances (disturbances of eye movements) * Ataxia (difficulties with coordinated movements)

Answer 161

* Memory impairment (retrograde and anterograde) * Behavioural changes *

Answer 162

Non alcholic fatty liver disease (NAFLD) forms part of the **“metabolic syndrome”** group of chronic health conditions relating to processing and storing energy that increase risk of heart disease, stroke and diabetes. It is estimated that up to 30% of adults have NAFLD. It is characterised by fat deposited in liver cells. These fat deposits can interfered with the functioning of the liver cells. NAFLD does not cause problems initially, however it can progress to **hepatitis** and **cirrhosis.** Non-alcoholic steatohepatitis (NASH) is most extremeform and→cirrhosis in 10%

Answer 163

1. Non-alcoholic Fatty Liver Disease 2. Non-Alcoholic Steatohepatitis (NASH) 3. Fibrosis 4. Cirrhosis

Answer 164

* **Obesity** * Poor diet and low activity levels * **Type 2 diabetes** * **High cholesterol** * Middle age onwards * Smoking * **High blood pressure**

Answer 165

**Liver Ultrasound** can confirm the diagnosis of hepatic steatosis (fatty liver). It does not indicate the severity, the function of the liver or whether there is liver fibrosis. **Enhanced Liver Fibrosis (ELF)** blood test. This is the first line recommended investigation for assessing fibrosis but it is not currently available in many areas. It measures three markers (HA, PIIINP and TIMP-1) and uses an algorithm to provide a result that indicates the fibrosis of the liver: * \< 7.7 indicates _none to mild fibrosis_ * ≥ 7.7 to 9.8 indicates _moderate fibrosis_ * ≥ 9.8 indicates _severe fibrosis_ **NAFLD fibrosis** score is the **second line** recommended assessment for liver fibrosis where the ELF test is not available. It is based on an algorithm of age, BMI, liver enzymes, platelets, albumin and diabetes and is helpful in ruling out fibrosis but not assessing the severity when present. **Fibroscan** is the third line investigation. It involves a particular ultrasound that measures the stiffness of the liver and gives an indication of fibrosis. This is performed if the ELF blood test or NAFLD fibrosis score indicates fibrosis. * **BMI** * **Glucose, fasting lipids** * **↑transaminases: AST:ALT \<** * **Liver biopsy**

Answer 166

* Weight loss * Exercise * Stop smoking * Control of diabetes, blood pressure and cholesterol * Avoid alcohol Refer patients with **liver fibrosis** to a liver specialist where they may treat with **vitamin E or pioglitazone.**

Answer 167

Liver cirrhosis is the result of chronic inflammation and damage to liver cells. When the liver cells are damaged they are replaced with scar tissue (fibrosis) and nodules of scar tissue form within the liver.

Answer 168

portal hypertension

Answer 169

* Alcoholic liver disease * Non Alcoholic Fatty Liver Disease * Hepatitis B * Hepatitis C

Answer 170

* **Genetic**:Wilson’s,α1ATD, HH, CF * **AI**:AH, PBC, PSC * **Drugs:**Methotrexate, amiodarone, methyldopa,INH * **Neoplasm:**HCC, mets * **Vasc**:Budd-Chiari, RHF,constrict. pericarditis

Answer 171

Hands * Clubbing (± periostitis) * Leuconychia (↓albumin) * Terry’s nails (white proximally, red distally) * Palmer erythema- caused by hyperdynamic cirulation * Dupuytron’s contracture * **Asterixis** – “flapping tremor” in decompensated liver diseas Face * Pallor: ACD * Xanthelasma: PBC * Parotid enlargement (esp. c̄EtOH) * **Jaundice** – caused by raised bilirubin Trunk * Spider naevi (\>5, fill from centre)- these are telangiectasia with a central arteriole and small vessels radiating away * Gynaecomastia- in males due to endocrine dysfunction * Loss of sexual hair * Brusing- due to abnormal clotting Abdo * Striae * Hepatomegaly (may be small in late disease) * Splenomegaly- due to portal hypertension * **Caput Medusa**e – distended paraumbilical veins due to portal hypertension * Testicular atrophy- in males due to endocrine dysfunction

Answer 172

**Bloods** * FBC:↓WCC and↓plats indicate hypersplenism * ↑LFTs * ↑INR * ↓Albumin **Find Cause** * EtOH:↑MCV,↑GGTNASH:hyperlipidaemia,↑glucose * Infection:Hep, CMV, EBV serology * Genetic:Ferritin,α1AT, caeruloplasmin (↓in Wilson’s) * Autoimmune:Abs (there is lots of cross-over) * AIH:SMA, SLA, LKM, ANA * PBC:AMA * PSC:ANCA, ANA * Ig:↑IgG – AIH,↑IgM – PBC * Ca:α-fetoprotein **Abdo US + PV Duplex** * Small / large liver * Focal lesions * Reversed portal vein flow * Ascites **Ascitic Tap + MCS** PMN \>250mm3indicates SBP **Liver biopsy**

Answer 173

adenocarcinomas

Answer 174

Post Hepatic Obstructive jaundice

Answer 175

liver, then to the peritoneum, lungs and bones.

Answer 176

* **Painless Obstructive jaundice** * **Yellow skin and sclera** * **Pale stools** * **Dark urine** * Generalised itching * Non-specific upper abdominal or back pain * Unintentional weight loss * Palpable mass in the epigastric region * Change in bowel habit * Nausea or vomiting * New‑onset diabetes or worsening of type 2 diabetes

Answer 177

Pancreatic cancer

Answer 178

* Over 40 with jaundice – referred on a **2 week wait referral** * Over 60 with weight loss plus an additional symptom (see below) – referred for a **direct access CT abdomen**

Answer 179

if a patient has **weight loss** plus any of: * Diarrhoea * Back pain * Abdominal pain * Nausea * Vomiting * Constipation * New‑onset diabetes

Answer 180

Courvoisier’s law suggests cholangiocarcinoma or pancreatic cancer

Answer 181

refers to **migratory thrombophlebitis** as a sign of malignancy, particularly **pancreatic adenocarcinoma**. **Thrombophlebitis** is where blood vessels become inflamed with an associated blood clot (thrombus) in that area. **Migratory** refers to the thrombophlebitis reoccurring in different locations over time.

Answer 182

Diagnosis is based on **imaging** (usually CT scan) plus **histology** from a biopsy. **Staging CT scan** involves a full **CT thorax, abdomen and pelvis (CT TAP)**. This is used to look for metastasis and other cancers. **CA 19-9 (carbohydrate antigen)** is a tumour marker that may be raised in pancreatic cancer. **Magnetic resonance cholangio-pancreatography (MRCP**) may be used to assess the biliary system in detail to assess the obstruction. **Endoscopic retrograde cholangio-pancreatography (ERCP)** can be used to put a stent in and relieve the obstruction, and also obtain a biopsy from the tumour. **Biopsy** may be taken through the skin (percutaneous) under ultrasound or CT guidance, or during an endoscopy under ultrasound guidance.

Answer 183

Surgery * Total pancreatectomy * Distal pancreatectomy * Pylorus-preserving pancreaticoduodenectomy (PPPD) (modified Whipple procedure) * Radical pancreaticoduodenectomy (Whipple procedure) In most cases, curative surgery is not possible. Palliative treatment may involve: * Stents inserted to relieve the biliary obstruction * Surgery to improve symptoms (e.g., bypassing the biliary obstruction) * Palliative chemotherapy (to improve symptoms and extend life) * Palliative radiotherapy (to improve symptoms and extend life) * End of life care with symptom control

Answer 184

A Whipple procedure (pancreaticoduodenectomy) is a surgical operation to remove a tumour of the head of the pancreas that has not spread. A Whipple procedure is a massive operation so patients need to be in good baseline health.

Answer 185

* Head of the pancreas * Pylorus of the stomach * Duodenum * Gallbladder * Bile duct * Relevant lymph nodes

Answer 186

pylorus-preserving pancreaticoduodenectomy (PPPD). leave pylorus in place

Answer 187

Symptoms * GI bleeding (May contain gastric mucosa → gastric ulcerations) * Abdominal pain and cramping * Tenderness near the belly button * Obstruction of bowels

Answer 188

Excess (billirubin) BR production * Haemolytic anaemia * Ineffective erythropoiesise.g. thalassaemia

Answer 189

**↓BR Uptake** * Drugs: contrast, RMP * CCF **↓BR Conjugation** * Hypothyroidism * Gilbert’s (AD) * Crigler-Najjar (AR) Neonatal jaundice is both ↑production +↓conju

Answer 190

**Hepatocellular Dysfunction** * **Congen:**HH, Wilson’s,α1ATD * **Infection**:Hep A/B/C, CMV, EBV * **Toxin:**EtOH, drugs * **AI**:AIH * **Neoplasia**:HCC, mets * **Vasc:**Budd-Chiari **↓Hepatic BR Excretion** * Dubin-Johnson * Rotor’

Answer 191

Obstruction * **Stones** * **Ca pancreas** * Drugs * PBC * PSC * Biliary atresia * Choledochal cyst * Cholangio Ca

Answer 192

BR-UDP-glucuronyl transferase in live

Answer 193

* Normal BR = 3-17uM * Jaundice visible @ 50uM (3 x ULN

Answer 194

* Normal BR = 3-17uM * Jaundice visible @ 50uM (3 x ULN

Answer 195

In Gilbert's syndrome, slightly higher than normal levels of a substance called bilirubin build up in the blood. * Auto dom partial UDP-GT deficiency * 2% of the population * Jaundice occurs during intercurrent illness * Dx:↑uBR on fasting, normal LFTs

Answer 196

* Rare auto rec total UDP-GT deficiency * Severe neonatal jaundice and kernicterus * Rx:liver Transplant

Answer 197

**Child-Pugh Grading of Cirrhosis** * Predicts risk of bleeding, mortality and need for Tx * Graded A-C using severity of 5 factors * Albumin * Bilirubin * Clotting * Distension: Ascites * Encephalopathy * Score \>8 = significant risk of variceal bleeding

Answer 198

**Child-Pugh Grading of Cirrhosis** * Predicts risk of bleeding, mortality and need for Tx * Graded A-C using severity of 5 factors * Albumin * Bilirubin * Clotting * Distension: Ascites * Encephalopathy * Score \>8 = significant risk of variceal bleeding

Answer 199

* Inflammatory disease of unknown cause characterisedby Abs directed vs. hepatocyte surface antigens * Predominantly young and middle-aged women

Answer 200

Classified according to Abs * T1:Adult, SMA+ (80%), ANA+ (10%),↑IgG * T2:Young, LKM+ * T3:Adult, SLA+

Answer 201

Autoimmune thyroiditis DM Pernicious anaemia PSC UC GN AIHA (Coombs +ve)

Answer 202

* ↑LFTs * ↑IgG * Auto Abs: SMA, LKM, SLA, ANA * ↓WCC and↓plats = hypersplenism * Liver biopsy

Answer 203

Immunosuppression * Prednisolone * Azathioprine as steroid-sparer Liver transplant (disease may recur)

Answer 204

Immunosuppression * Prednisolone * Azathioprine as steroid-sparer Liver transplant (disease may recur)

Answer 205

* ↑LFTs * ↑IgG * Auto Abs: SMA, LKM, SLA, ANA * ↓WCC and↓plats = hypersplenism * Liver biopsy

Answer 206

Autoimmune thyroiditis DM Pernicious anaemia PSC UC GN AIHA (Coombs +ve)

Answer 207

Classified according to Abs * T1:Adult, SMA+ (80%), ANA+ (10%),↑IgG * T2:Young, LKM+ * T3:Adult, SLA+

Answer 208

* Inflammatory disease of unknown cause characterisedby Abs directed vs. hepatocyte surface antigens * Predominantly young and middle-aged women

Answer 209

* Rare auto rec total UDP-GT deficiency * Severe neonatal jaundice and kernicterus * Rx:liver Transplant

Answer 210

In Gilbert's syndrome, slightly higher than normal levels of a substance called bilirubin build up in the blood. * Auto dom partial UDP-GT deficiency * 2% of the population * Jaundice occurs during intercurrent illness * Dx:↑uBR on fasting, normal LFTs

Answer 211

BR-UDP-glucuronyl transferase in live

Answer 212

Obstruction * **Stones** * **Ca pancreas** * Drugs * PBC * PSC * Biliary atresia * Choledochal cyst * Cholangio Ca

Answer 213

**Hepatocellular Dysfunction** * **Congen:**HH, Wilson’s,α1ATD * **Infection**:Hep A/B/C, CMV, EBV * **Toxin:**EtOH, drugs * **AI**:AIH * **Neoplasia**:HCC, mets * **Vasc:**Budd-Chiari **↓Hepatic BR Excretion** * Dubin-Johnson * Rotor’

Answer 214

**↓BR Uptake** * Drugs: contrast, RMP * CCF **↓BR Conjugation** * Hypothyroidism * Gilbert’s (AD) * Crigler-Najjar (AR) Neonatal jaundice is both ↑production +↓conju

Answer 215

Excess (billirubin) BR production * Haemolytic anaemia * Ineffective erythropoiesise.g. thalassaemia

Answer 216

Symptoms * GI bleeding (May contain gastric mucosa → gastric ulcerations) * Abdominal pain and cramping * Tenderness near the belly button * Obstruction of bowels

Answer 217

pylorus-preserving pancreaticoduodenectomy (PPPD). leave pylorus in place

Answer 218

* Head of the pancreas * Pylorus of the stomach * Duodenum * Gallbladder * Bile duct * Relevant lymph nodes

Answer 219

A Whipple procedure (pancreaticoduodenectomy) is a surgical operation to remove a tumour of the head of the pancreas that has not spread. A Whipple procedure is a massive operation so patients need to be in good baseline health.

Answer 220

Surgery * Total pancreatectomy * Distal pancreatectomy * Pylorus-preserving pancreaticoduodenectomy (PPPD) (modified Whipple procedure) * Radical pancreaticoduodenectomy (Whipple procedure) In most cases, curative surgery is not possible. Palliative treatment may involve: * Stents inserted to relieve the biliary obstruction * Surgery to improve symptoms (e.g., bypassing the biliary obstruction) * Palliative chemotherapy (to improve symptoms and extend life) * Palliative radiotherapy (to improve symptoms and extend life) * End of life care with symptom control

Answer 221

Diagnosis is based on **imaging** (usually CT scan) plus **histology** from a biopsy. **Staging CT scan** involves a full **CT thorax, abdomen and pelvis (CT TAP)**. This is used to look for metastasis and other cancers. **CA 19-9 (carbohydrate antigen)** is a tumour marker that may be raised in pancreatic cancer. **Magnetic resonance cholangio-pancreatography (MRCP**) may be used to assess the biliary system in detail to assess the obstruction. **Endoscopic retrograde cholangio-pancreatography (ERCP)** can be used to put a stent in and relieve the obstruction, and also obtain a biopsy from the tumour. **Biopsy** may be taken through the skin (percutaneous) under ultrasound or CT guidance, or during an endoscopy under ultrasound guidance.

Answer 222

refers to **migratory thrombophlebitis** as a sign of malignancy, particularly **pancreatic adenocarcinoma**. **Thrombophlebitis** is where blood vessels become inflamed with an associated blood clot (thrombus) in that area. **Migratory** refers to the thrombophlebitis reoccurring in different locations over time.

Answer 223

Courvoisier’s law suggests cholangiocarcinoma or pancreatic cancer

Answer 224

if a patient has **weight loss** plus any of: * Diarrhoea * Back pain * Abdominal pain * Nausea * Vomiting * Constipation * New‑onset diabetes

Answer 225

* Over 40 with jaundice – referred on a **2 week wait referral** * Over 60 with weight loss plus an additional symptom (see below) – referred for a **direct access CT abdomen**

Answer 226

Pancreatic cancer

Answer 227

* **Painless Obstructive jaundice** * **Yellow skin and sclera** * **Pale stools** * **Dark urine** * Generalised itching * Non-specific upper abdominal or back pain * Unintentional weight loss * Palpable mass in the epigastric region * Change in bowel habit * Nausea or vomiting * New‑onset diabetes or worsening of type 2 diabetes

Answer 228

liver, then to the peritoneum, lungs and bones.

Answer 229

Post Hepatic Obstructive jaundice

Answer 230

adenocarcinomas

Answer 231

**Bloods** * FBC:↓WCC and↓plats indicate hypersplenism * ↑LFTs * ↑INR * ↓Albumin **Find Cause** * EtOH:↑MCV,↑GGTNASH:hyperlipidaemia,↑glucose * Infection:Hep, CMV, EBV serology * Genetic:Ferritin,α1AT, caeruloplasmin (↓in Wilson’s) * Autoimmune:Abs (there is lots of cross-over) * AIH:SMA, SLA, LKM, ANA * PBC:AMA * PSC:ANCA, ANA * Ig:↑IgG – AIH,↑IgM – PBC * Ca:α-fetoprotein **Abdo US + PV Duplex** * Small / large liver * Focal lesions * Reversed portal vein flow * Ascites **Ascitic Tap + MCS** PMN \>250mm3indicates SBP **Liver biopsy**

Answer 232

Hands * Clubbing (± periostitis) * Leuconychia (↓albumin) * Terry’s nails (white proximally, red distally) * Palmer erythema- caused by hyperdynamic cirulation * Dupuytron’s contracture * **Asterixis** – “flapping tremor” in decompensated liver diseas Face * Pallor: ACD * Xanthelasma: PBC * Parotid enlargement (esp. c̄EtOH) * **Jaundice** – caused by raised bilirubin Trunk * Spider naevi (\>5, fill from centre)- these are telangiectasia with a central arteriole and small vessels radiating away * Gynaecomastia- in males due to endocrine dysfunction * Loss of sexual hair * Brusing- due to abnormal clotting Abdo * Striae * Hepatomegaly (may be small in late disease) * Splenomegaly- due to portal hypertension * **Caput Medusa**e – distended paraumbilical veins due to portal hypertension * Testicular atrophy- in males due to endocrine dysfunction

Answer 233

* **Genetic**:Wilson’s,α1ATD, HH, CF * **AI**:AH, PBC, PSC * **Drugs:**Methotrexate, amiodarone, methyldopa,INH * **Neoplasm:**HCC, mets * **Vasc**:Budd-Chiari, RHF,constrict. pericarditis

Answer 234

* Alcoholic liver disease * Non Alcoholic Fatty Liver Disease * Hepatitis B * Hepatitis C

Answer 235

portal hypertension

Answer 236

Liver cirrhosis is the result of chronic inflammation and damage to liver cells. When the liver cells are damaged they are replaced with scar tissue (fibrosis) and nodules of scar tissue form within the liver.

Answer 237

* Weight loss * Exercise * Stop smoking * Control of diabetes, blood pressure and cholesterol * Avoid alcohol Refer patients with **liver fibrosis** to a liver specialist where they may treat with **vitamin E or pioglitazone.**

Answer 238

**Liver Ultrasound** can confirm the diagnosis of hepatic steatosis (fatty liver). It does not indicate the severity, the function of the liver or whether there is liver fibrosis. **Enhanced Liver Fibrosis (ELF)** blood test. This is the first line recommended investigation for assessing fibrosis but it is not currently available in many areas. It measures three markers (HA, PIIINP and TIMP-1) and uses an algorithm to provide a result that indicates the fibrosis of the liver: * \< 7.7 indicates _none to mild fibrosis_ * ≥ 7.7 to 9.8 indicates _moderate fibrosis_ * ≥ 9.8 indicates _severe fibrosis_ **NAFLD fibrosis** score is the **second line** recommended assessment for liver fibrosis where the ELF test is not available. It is based on an algorithm of age, BMI, liver enzymes, platelets, albumin and diabetes and is helpful in ruling out fibrosis but not assessing the severity when present. **Fibroscan** is the third line investigation. It involves a particular ultrasound that measures the stiffness of the liver and gives an indication of fibrosis. This is performed if the ELF blood test or NAFLD fibrosis score indicates fibrosis. * **BMI** * **Glucose, fasting lipids** * **↑transaminases: AST:ALT \<** * **Liver biopsy**

Answer 239

* **Obesity** * Poor diet and low activity levels * **Type 2 diabetes** * **High cholesterol** * Middle age onwards * Smoking * **High blood pressure**

Answer 240

1. Non-alcoholic Fatty Liver Disease 2. Non-Alcoholic Steatohepatitis (NASH) 3. Fibrosis 4. Cirrhosis

Answer 241

Non alcholic fatty liver disease (NAFLD) forms part of the **“metabolic syndrome”** group of chronic health conditions relating to processing and storing energy that increase risk of heart disease, stroke and diabetes. It is estimated that up to 30% of adults have NAFLD. It is characterised by fat deposited in liver cells. These fat deposits can interfered with the functioning of the liver cells. NAFLD does not cause problems initially, however it can progress to **hepatitis** and **cirrhosis.** Non-alcoholic steatohepatitis (NASH) is most extremeform and→cirrhosis in 10%

Answer 242

* Memory impairment (retrograde and anterograde) * Behavioural changes *

Answer 243

* Confusion * Oculomotor disturbances (disturbances of eye movements) * Ataxia (difficulties with coordinated movements)

Answer 244

Alcohol excess leads to **thiamine (vitamin B1)** deficiency. Thiamine is poorly absorbed in the presence of alcohol and alcoholics tend to have poor diets and rely on the alcohol for their calories. **Wernicke’s encephalopathy** comes before **Korsakoffs syndrome**. These result from thiamine deficiency.

Answer 245

Chlordiazepoxide (“Librium”) Diazepam

Answer 246

(Clinical Institute Withdrawal Assessment – Alcohol revised) tool can be used to score the patient on their withdrawal symptoms and guide treatment.

Answer 247

* Acute confusion * Severe agitation * Delusions and hallucinations * Tremor * Tachycardia * Hypertension * Hyperthermia * Ataxia (difficulties with coordinated movements) * Arrhythmias

Answer 248

Delirium tremens is a medical emergency associated with **alcohol withdrawal** with a mortality of 35% if left untreated. Alcohol 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**) having a further inhibitory effect on the electrical activity of the brain.

Answer 249

* 6-12 hours: tremor, sweating, headache, craving and anxiety * 12-24 hours: hallucinations * 24-48 hours: seizures * 24-72 hours: “delirium tremens”

Answer 250

* Stop drinking alcohol permanently * Consider a **detoxication regime** * Nutritional support with vitamins (particularly **thiamine**) and a high protein diet * **Steroids** improve short term outcomes (over 1 month) in severe alcoholic hepatitis but infection and GI bleeding need to be treated first and do not improve outcomes over the long term * Treat complications of cirrhosis **(portal hypertension, varices, ascites and hepatic encephalopathy)** * **Referral for liver transplant** in severe disease however they must abstain from alcohol for 3 months prior to referral

Answer 251

**Bloods** FBC – raised MCV LFTs – elevated ALT and AST (transaminases) and particularly raised gamma-GT. ALP will be elevated later in the disease. Low albumin due to reduced “synthetic function” of the liver. Elevated bilirubin in cirrhosis. Clotting – elevated prothrombin time due to reduced “synthetic function” of the liver U+Es may be deranged in hepatorenal syndrome. **Ultrasound** An ultrasound of the liver may show fatty changes early on described as **“increased echogenicity”**. It can also demonstrate changes related to cirrhosis if present. _“FibroScan”_ can be used to check the elasticity of the liver by sending high frequency sound waves into the liver. It helps assess the degree of cirrhosis. **Endoscopy** Endoscopy can be used to assess for and treat oesophageal varices when portal hypertension is suspected. **CT and MRI scans** CT and MRI can be used to look for fatty infiltration of the liver, hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes and ascites. **Liver Biopsy** Liver biopsy can be used to confirm the diagnosis of alcohol-related hepatitis or cirrhosis. NICE recommend considering a liver biopsy in patients where steroid treatment is being considered.

Answer 252

* Jaundice * Hepatomegaly * Spider Naevi * Palmar Erythema * Gynaecomastia * Bruising – due to abnormal clotting * Ascites * Caput Medusae – engorged superficial epigastric veins * Asterixis – “flapping tremor” in decompensated liver disease

Answer 253

* Alcoholic Liver Disease * Cirrhosis and the complications of cirrhosis including hepatocellular carcinoma * Alcohol Dependence and Withdrawal * Wernicke-Korsakoff Syndrome (WKS) * Pancreatitis * Alcoholic Cardiomyopathy

Answer 254

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 gives an indication of harmful use.

Answer 255

That latest recommendations (Department of Health, 2016) are to **not regularly drink more than 14 units per week** for both men and women. If drinking 14 units in a week, this should be spread evenly over 3 or more days and not more than 5 units in a day. The government guidelines also state that any level of alcohol consumption increases the risk of cancers, particularly breast, mouth and throat. Pregnant women should avoid alcohol completely.

Answer 256

**1. Alcohol related fatty liver** Drinking leads to a build-up of fat in the liver. If drinking stops this process reverses in around 2 weeks. **2. Alcoholic hepatitis** Drinking alcohol over a long period causes inflammation in the liver sites. Binge drinking is associated with the same effect. Mild alcoholic hepatitis is usually reversible with permanent abstinence. **3. Cirrhosis** This is where the liver is made up of scar tissue rather than healthy liver tissue. This is irreversible. Stopping drinking can prevent further damage. Continued drinking has a very poor prognosis.

Answer 257

Alcoholic liver disease results from the effects of the long term excessive consumption of alcohol on the liver. The onset and progression of alcoholic liver disease varies between people, suggesting that there may be a **genetic predisposition** to having harmful effects of alcohol on the liver.

Answer 258

Herniation of bowel loops (sometimes stomach and liver) through para-umbilical wall defect (lateral to the umbilicus) Not covered by surrounding membrane Investigations: Antenatal USS show herniation to lateral of umbilicus, free-floating

Answer 259

Herniation of intestines (sometimes liver and other organs) out of umbilicus at birth due to abdominal wall defects Failure to return to abdomen after natural protrusion during development Covered by peritoneal membrane and amnion Investigations: USS antenatal scan shows herniated loop contained within peritoneum Associated with severe malformations, 25% mortality

Answer 260

**Persistence of vitellointestinal duct** **_Rule of 2s_** 2% of population Present in first 2 years 2 inches in length Approximately 2 ft from ileocaecal valve

Answer 261

Agangliosis of myenteric and submucosal plexus in the distal colon and rectum which causes lack of peristalsis Functional obstruction from spasms in denervated colon Severe constipation within first 2 months Investigations X ray: colon distension Biopsy to identify transition zone Management: surgical removal of affected segment

Answer 262

Hirschprung’s Disease Meckel’s Diverticulum Omphalocele Gastroschisis

Answer 263

Western lifestyle Cigarette smoking High-fat diet Liver cirrhosis Chronic pancreatitis Obesity Family history/genetic factors (BRCA1/BRCA2/FAP/HNPCC)

Answer 264

Increased risk of pancreatic carcinoma Pancreatic pseudocysts, fistula, ascites Biliary obstruction Malnutrition Diabetes mellitus

Answer 265

Serum lipase and amylase may or may not be elevated Glucose tolerance test (endocrine function) Imaging CT : calcification, intrapancreatic cysts or chronic pseudocysts ERCP: dilated and strictured ducts (chain of lakes pattern) To differentiate from carcinoma Pancreatic imaging + EUS + targeted needle biopsy

Answer 266

- Recurrent episodes of acute pancreatitis (alcohol) - Duct obstruction: tumour, gallstones, structural abnormalities (annular pancreas, pancreas divisum), traumatic strictures - Cystic fibrosis

Answer 267

Obstruction in the pancreatic ducts Ductal dilatation and damage to tissue (atrophy of acinar cells) Stellate cells lay down fibrotic tissue Further resulting in atrophy of acinar cells, intraluminal calcification, narrowing of ducts

Answer 268

- Chronic inflammation causing irreversible structural damage Atrophy of acinar cells Fibrosis Calcification Dilation of ducts/ narrowing - Formation of chronic pseudocysts, intrapancreatic cysts

Answer 269

Elevated serum amylase \>1000 IU/L **Elevated serum lipase (2-5x normal value)** LFTs: gallstones aetiology (jaundice) Imaging CT: swollen gland with inflammation, necrosis, pseudocyst USS: gallstones

Answer 270

* Neuroendocrine tumours * Gastrin secreting * Cause severe peptic ulcer disease and diarrhoea (referred to as the Zollinger Ellison Syndrome) * Can either be sporadic (75-80% of cases) or associated with Multiple endocrine neoplasia type 1 (20-30% of cases)

Answer 271

Zollinger–Ellison syndrome is a disease in which tumours cause the stomach to produce too much acid, resulting in peptic ulcers. A gastrin secreting tumour (gastrinoma) - Excess gastric acid secretion leads to (unusual/severe peptic ulceration, oesophagitis, diarrhoea and

Answer 272

Epigastric pain; may be relieved by food and antacids Dysphagia especially if tumour involves stomach fundus Anaemia Nausea, vomiting and weight loss Can have Liver, bone , brain and lung involvement

Answer 273

family history, those that have FAP or HNPCC, diet with lack of fibre, inflammatory bowel disease (ie ulcerative colitis)

Answer 274

4th rectum 2nd

Answer 275

colorectal cancers

Answer 276

Oesophageal cancers Gastric cancers

Answer 277

A stepwise pattern; of mutational activation of oncogenes ( ie Kras) and inactivation of tumour suppressor genes (eg p53) that results in cancer

Answer 278

Malignant tumour of the liver which occurs primarily in patients with pre-existing liver cirrhosis or chronic hepatitis Most common type of primary liver cancer Malignant tumour of the liver which occurs primarily in patients with pre-existing liver cirrhosis or chronic hepatitis Most common type of primary liver cancer

Answer 279

Life-threatening medical condition that consists of rapid deterioration of kidney function in individuals with cirrhosis or fulminant liver failure Occurs due to portal hypertension

Answer 280

Due to formation of microscopic intrapulmonary arteriovenous dilations Thought to be due to increased liver production or decreased liver clearance of vasodilators, e.g. NO Dilation of blood vessels 🡪 over-perfusion relative to ventilation 🡪 V/Q mismatch Increased gradient between the partial pressure of O2 in alveoli and adjacent arteries

Answer 281

Syndrome of shortness of breath and hypoxemia caused by vasodilation in lungs of patients with liver disease

Answer 282

Treatment = Oral lactulose

Answer 283

Asterixis, lethargy, movement problems, changes in mood or changes in personality, altered consciousness, seizures

Answer 284

Reduced blood to liver 🡪 reduced liver function Increased ammonia crosses BBB Can be gradual or sudden In advanced stages 🡪 coma

Answer 285

* Increased blood pressure in the hepatic portal system (portal venous system) usually due to hepatic cirrhosis * Obstruction may prevent the blood flow from the portal vein into the IVC * Causes the blood to accumulate in the hepatic portal system 🡪 increasing the pressure 🡪 PORTAL HYPERTENSION * Portosystemic Shunts- anastomoses between portal and systemic systems, due to portal HTN the blood backs up and varices form- these can rupture * Features (ABCDE)- ascites, bleeding, caput medusae, diminished liver function and enlarged spleen

Answer 286

* Portal hypertension * Synthetic dysfunction * Hepatopulmonary syndrome * Hepatorenal syndrome * Encephalopathy * Hepatocellular carcinoma

Answer 287

* Nail clubbing * Palmar erythema * Spider nevi * Gynaecomastia * Feminising hair distribution * Small irregular shrunken liver * Anaemia * Caput medusae

Answer 288

* **Metabolic** Hereditary haemochromatosis -Accumulation of iron, reacts with H2O2 to form free radicals NAFLD Wilsons disease * **Toxic and drugs** Alcohol Drug induced is rare 🡪 methotrexate, amiodarone * **Infections – hep b & c** * **Autoimmune** Primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis

Answer 289

Progressive destruction/regeneration of liver parenchyma leading to fibrosis and cirrhosis (\> 6 months

Answer 290

* Hepatic encephalopathy = altered level of consciousness * Impaired protein synthesis = measured by serum albumin + prothrombin time in blood

Answer 291

* Jaundice * Bruising (coagulation disturbance) * Ascites * Tachycardia and hypotension * Due to reduced systemic vascular resistance * Signs of encephalopathy * Sweet smell on breath

Answer 292

* **Drugs** 50% of cases in the UK due to paracetamol overdose others inc NSAIDs and ecstasy * **Infection** Viral hepatitis, CMV, HSV, EBV * **Acute fatty liver in pregnancy** Unmetabolized fetal fatty acids enter maternal circulation and accumulate in mothers liver * **Wilsons disease** AR, copper accumulates in the liver * **Budd-Chiari** Occlusion of hepatic vein Abdo pain + ascites + liver enlargement

Answer 293

Onset of hepatic decompensation within 6 months, results in loss of function in 80-90%

Answer 294

* AKA obstructive jaundice * Due to obstruction of biliary drainage * Bilirubin that has been conjugated by the liver is not excreted * Excess conjugated bilirubin = conjugated hyperbilirubinemia * High ALP, AST and ALT (higher ALP)

Answer 295

* Alcoholic liver disease * Viral hepatitis * Primary biliary cirrhosis * Hepatocellular carcinoma

Answer 296

* Due to dysfunction of the hepatic cells * Liver loses the ability to conjugate bilirubin * Liver may become cirrhotic 🡪 compromises the intra-hepatic portions of the biliary tree to cause some obstruction * Both unconjugated and conjugated bilirubin are found in blood * High ALT, AST and ALP (higher ALT&AST)

Answer 297

* Examples * Haemolytic anaemia * Malaria * Sickle cell thalassemia * SLE

Answer 298

Excessive red cell breakdown which overwhelms the liver’s ability to conjugate bilirubin 🡪 unconjugated hyperbilirubinemia Any bilirubin that manages to become conjugated is excreted normally Unconjugated bilirubin in the blood causes jaundice ALT, AST, ALP will be normal

Answer 299

haemolytic jaundice

Answer 300

* Pre-hepatic * Hepatic/ intrahepatic/ hepatocellular * Post-hepatic

Answer 301

yellow appearance of the skin, sclerae and mucous membranes resulting from an increased bilirubin concentrations in body fluids

Answer 302

* **USS-** Ultrasound is usually first line. Identifies any obstructive pathology present or gross liver pathology * **Fibroscan** * **MRI** * **MRCP-** Used to visualise the biliary tree. Usually performed if obstructive jaundice is suspected or US is inconclusive * **X rays – hepatic angiogram** * **CT** * **Biopsy-** Performed when the diagnosis has not been made despite the above investigations

Answer 303

**ALT-** Markers of hepatocellular damage, localised to liver **AST**- Markers of hepatocellular damage, synthesised by liver, heart, skeletal muscle and brain **Billirubin**- Assessing degree of jaundice **gGT-** Cholestasis **ALP-** Cholestasis – sources are bone and liver **Albumin**- Synthetic function **Prothrombin time** - Synthetic function