HEPATOBILIARY Flashcards

Question

What are some complications of acute liver injury?

Answer 1

- Acute kidney injury/ hepatorenal syndrome - Metabolic disturbance (electrolyte imbalance) - Hypoglycaemia - Haemorrhage (e.g. GI Bleeding) - Cerebral dysfunction (e.g. seizures, irreversible brain injury). - Patients are at risk of high output cardiac failure due to low vascular resistance from the widespread inflammatory response. - Sepsis

Answer 2

because the liver is responsible for producing a number of proteins that help regulate blood pressure, and when the liver fails, these proteins are no longer produced. This can lead to a decrease in blood pressure, causing the kidneys to not receive enough blood and oxygen, leading to renal failure. ***Also Liver failure====> Leads to drop in BP - poor peripheral perfusion leading to multi organ failure***

Answer 3

Portal hypertension in cirrhosis is due to to a rise in intrahepatic vascular resistance because massive structural changes associated with fibrosis and increased vascular tone in the hepatic microcirculation.

Answer 4

Liver cirrhosis leads to portal hypertension In response to this, **portal blood vessels dilate,** stretched by large amounts of blood pooling there. This leads to a loss of blood volume elsewhere, including kidneys. Leads to **hypotension in the kidney and activation of the RAAS.** This causes renal vasoconstriction, which combined with low circulation volume leads to starvation of blood to the kidney *Hepatorenal syndrome is fatal within a week or so unless liver transplant is performed*

Answer 5

Repeated damage to liver tha leads to inflammation, fibrosis and eventually cirrhosis. CLD is generally defined as **progressive liver dysfunction for six months or longer**. The end result of chronic liver disease is cirrhosis, which describes irreversible liver remodelling.

Answer 6

- **Alcohol** - **Viral** (Hepatitis B, C) - **Inherited** (Alpha-1-antitrypsin deficiency, Wilson’s disease, Hereditary haemochromatosis) - **Metabolic** (Non-alcohol fatty liver disease / Non-alcoholic steatohepatitis) - **Autoimmune** (Autoimmune hepatitis) - **Biliary** (Primary biliary cholangitis, primary sclerosing cholangitis) - **Vascular** (Ischaemic hepatitis, Budd-Chiari syndrome, congestive hepatopathy) - **Medication** (Drug-induced liver injury)

Answer 7

Overtime, progressive insults to the liver leads to **inflammation (hepatitis), **fatty deposits (steatosis)** and scarring (fibrosis)**. The normal liver architecture is replaced by **fibrotic tissue and regenerative nodules.** The end result of this process is cirrhosis, which describes **irreversible liver remodelling**

Answer 8

Two types are **Compensated** - despite injury, liver can carry out normal function - aka asymptomatic Decompensated - liver injury leads to inadequate function

Answer 9

- **Coagulopathy** (reducing clotting factor synthesis) - **Jaundice** (impaired breakdown of bilirubin) - **Encephalopathy** (poor detoxification of harmful substances) - **Ascites** (poor albumin synthesis and increased portal pressure due to scarring) - **Gastrointestinal bleeding** (increase portal pressure causing varices)

Answer 10

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

Answer 11

a) (redness of thenar and hypothenar eminences) b) blanch on pressure and spider-like branches fill from a central arteriole c) engorged superficial epigastric veins

Answer 12

LFTs- Raised AST and ALT FBC (thrombocytopenia) Also could see Hyperbilirubinaemia, raised INR, low albumin - in decompensated liver disease. ***ALT IS MORE SPECIFIC TO LIVER FAILIURE THAN AST, AS AST CAN BE FOUND IN OTHER ORGANS BESIDE LIVER***

Answer 13

AST (aspartate aminotransferase) is an enzyme that is found mostly in the liver, but it's also in muscles and other organs in your body. When cells that contain AST are damaged, they release the AST into your blood. An AST blood test measures the amount of AST in your blood.

Answer 14

alanine transaminase. It is an enzyme found mostly in the liver. An ALT test measures the amount of ALT in the blood. When liver cells are damaged, they release ALT into the bloodstream. High levels of ALT in your blood may be a sign of a liver injury or disease.

Answer 15

portal hypertension and hypersplenism

Answer 16

- Transabdominal Ultrasound - first, CT - more specifc MRI - most specific/the best **USS:** US is quick, inexpensive, and has a sensitivity of 65-95% for detection of CLD. - **CT:** Provides a more detailed view of the abdominal viscera and is good for secondary findings (e.g. features of portal hypertension). - **MRI:** Is emerging as a highly sensitive and specific modality for liver fibrosis.

Answer 17

- **Liver biopsy -** invasive so usually reserved for specific cases: - Liver disease of unknown aetiology - Differentiating between acute and chronic disease

Answer 18

Treat underlying pathology e.g. alcohol cessation, removal of offending medications or use of anti-viral therapies in chronic hepatitis. Transplantation based on patient’s ‘United Kingdom model for end-stage liver disease’ (UKELD) score Correct any electrolyte/glucose imbalances

Answer 19

- . Constipation is the main driver of HE. - **First line treatments:** Involves laxatives (i.e. lactulose 15-20 mls QDS) to maintain bowel motions **Correct electrolytes. - **Second-line treatments:** Involves the long-term use of antibiotics ***rifaximin:***

Answer 20

i.e. rifaximin), as this lowers the amount of *nitrogen producing bacteria in the gut flora*

Answer 21

In Alcoholic liver disease - AST higher than ALT 2:1 ratio In Hepatitis and Non Alcoholic fatty liver disease , ALT is higher

Answer 22

-- **Ascites -** develops due to a combination of portal hypertension and loss of oncotic pressure (hypoalbuminaemia). - **Aldosterone antagonists:** e.g. spironolactone (can be combined with loop diuretics i.e. furosemide). - **Paracentesis:** percutaneous drainage of ascites

Answer 23

- **GI bleeding -** due to oesophageal varices secondary to portal hypertension - **Beta blockers** to reduce portal hypertension - **Endoscopic variceal band ligation -** for variceal haemorrhage

Answer 24

fatty liver (steatosis), alcoholic hepatitis (inflammation and necrosis), and alcoholic liver cirrhosis.

Answer 25

A UK unit is 8 grams or 10ml of pure alcohol

Answer 26

Strength of the drink (% ABV) x Amount of liquid (Litres) 1 Bottle wine = 0.75L x 13.5% ABV = 10 units

Answer 27

- **Prolonged and heavy alcohol consumption** - Hepatitis C - increased risk of cirrhosis - Female sex - ALD develops more rapidly and occurs at lower drinking levels in women than in men. *However, most patients with ALD are male.* - Genetic predisposition - genes encoding enzymes that metabolise both alcohol and acetaldehyde, and pro-inflammatory (tumour necrosis factor [TNF]-alpha) and anti-inflammatory cytokines (interleukins 6 and 10), may influence the predisposition to ALD and cirrhosis. - Increasing age >65 - Obesity

Answer 28

2 ways: Alcohol =Alcohol Dehydrogenase=> Acetaldehyde == Acetaldehyde Dehydrogenase=> Acetate ==> CO2 and H2O Chronic alcohol use **upregulates cytochrome P450 2E1** = more free radicals produced as there is **more oxidation of NADPH to NADP**

Answer 29

hepatic macrophages, which produce tumour necrosis factor (TNF)-alpha and induce the production of reactive oxygen species in the mitochondria.

Answer 30

Alcoholic patients are often deficient in antioxidants like **Gluthathione and Vitamin E,** so oxidative stress caused can lead to further hepatocyte necrosis and apoptosis

Answer 31

When acetaldehyde is bound to cellular proteins, it produces **antigenic adducts which are recognised as foreign** and can be ***attacked by the immune system,*** causing further damage. At this point, the patient develops hepatitis.

Answer 32

- Hepatomegaly - Abdominal pain - Haematemesis Venous collaterals - engorged para-umbilical veins (caput medusae), - Jaundice - Palmar erythema - Asterixis - Ascites - Weight loss - Fatigue - Confusion - Bruising - coagulopathy - Withdrawal symptoms - high pulse, low BP, tremor, confusion, fits, hallucinations

Answer 33

- Patients can be very well with few symptoms - On examination there are usually signs of chronic liver disease - **ascites, bruising, clubbing and Dupuytren’s contracture** palmar erythema spider naevi, - There are features of alcohol dependency

Answer 34

Dupuytren’s contracture is a progressive hand condition, leads to **tightening of the palmar fascia**, so fingers pull inward, leading to a claw-like deformity. It is often seen in individuals with liver disease, as it is thought that the accumulation of toxins in the liver may cause the fascia to become thicker, leading to the contracture.

Answer 35

**CAGE QUESTIONAIRE** C – CUT DOWN? Ever thought you should? A – ANNOYED? Do you get annoyed at others commenting on your drinking? G – GUILTY? Ever feel guilty about drinking? E – EYE OPENER? Ever drink in the morning to help your hangover/nerves? **AUDIT QUESTIONAIRE** *(Alcohol Use Disorders Identification Test)* 10 MCQs, a score of 8 or more shows harmful alcohol use

Answer 36

Raised Serum Aspartate aminotransferase AST, and alanine aminotransferase ALT **The classic ratio of AST/ALT >2 is seen in about 70% of cases** Raised Billirubin, Lowered Serum albumin reduced platelets, *raised prothrombin time/INR*

Answer 37

Alcohol Cessation - eg Alcoholic anonymous **Disulfiram** - causes negative effects for patients due to **acetaldehyde buildup - aversion therapy** Good Hydration Good nutrition, diet high in vitamins and protein

Answer 38

- **Diazepam** - **IV Thiamine** to prevent Wernicke-Korsakoff encephalopathy (presents with ataxia, confusion and nystagmus) which occurs from alcohol withdrawal,

Answer 39

-Good diet of proteins and minerals **Steroids eg Prednisolone** can be beneficial short term, - **Screen for infections** (ascitic fluid tap) and treat spontaneous bacterial peritonitis

Answer 40

- Reduce salt intake - Avoid aspirin and NSAIDs - Liver transplantation

Answer 41

- Liver cirrhosis and related complications e.g. liver failure, hepatocellular carcinoma - CNS - self neglect, low memory and cognition, cortical atrophy, retrobulbar neuropathy, fits, falls, neuropathy, hepatic encephalopathy, Wernickes - Gut - obesity, diarrhoea and vomiting, **gastric erosions, peptic ulcers, varices, pancreatitis,** cancer, oesophageal rupture

Answer 42

Delirium tremens is a rapid onset of confusion usually caused by withdrawal from alcohol. Acute confusion , severe agitation, delusions and hallucinations, tremor, tachycardia, hypertensio, hyperthermia, ataxia, arrhythmias

Answer 43

- Blood - coagulopathy, thrombocytopenia, anaemia from: marrow depression, GI bleeding, alcoholism related folate deficiency, haemolysis, sideroblastic anaemia - Heart - arrhythmias, high BP, cardiomyopathy, sudden death - Reproduction - testicular atrophy, low testosterone and progesterone, high oestrogen, fetal alcohol syndrome

Answer 44

A fatty liver that cannot be attributed to alcohol or viral causes Spectrum of disease - steatosis, steatohepatitis, fibrosis, cirrhosis (least to most severe)

Answer 45

- Older age - Obesity - Hypertension - Diabetes - Hypertriglyceridemia - Hyperlipidemia

Answer 46

**Insulin resistance plays a key role** Overtime, insulin receptors are less responsive to insulin so **liver increases fat storage and decreases fatty acid oxidation** There is also **increased synthesis and uptake of free fatty acids from the blood** (known as steatosis).

Answer 47

The fat in the hepatocytes causes them to swell. These fats, **especially unsaturated fats**, are vunverable to ROS and form fatty acid radicals, which can further react with **other fatty acids and oxygen** - These reactions **damage the lipid membrane,** leads to cell death

Answer 48

It generates inflammation - **inflammation + steatosis = steathepatitis** Damage also attracts neutrophils to the liver. Chronic steatoheptitis can trigger ***stellate cells*** **to lay down fibrotic tissue (fibrosis).** The architecture then changes to the point where disease is now classed as cirrhosis

Answer 49

Sometimes symptoms are vague: - Fatigue - Malaise Sufficient damage presents with: - Hepatomegaly - Pain in RUQ - Jaundice - Ascites - Bruising - Pruritis - *itchiness/irritation of skin*

Answer 50

**Serum AST and ALT:** Increase in ALT and sometimes AST. ***(Different to alcoholic liver disease where AST>ALT)*** **LFT:** raised bilirubin, ALP, GGT, prothrombin time, low serum albumin **FBC:** anemia and thrombocytopenia due to hypersplenism **Imaging:** US, CT, MRI to look for fatty infiltrates **Biopsy:** used to diagnose and assess severity *think non alcoholic fatty liver disease when patients don't drink lots of alcohol

Answer 51

*Steatosis and steatohepatitis is reversible if underlying cause is addressed. Cirrhosis is not reversible.* - Avoid alcohol consumption - Reverse factors that contribute to insulin resistance - Healthy diet - Active lifestyle - Medication to control blood glucose - Control risk factors e.g. bariatric surgery for obesity - **Address cardiovascular risk** (commonest cause of death) - **Vitamin E** may improve histology of fibrosis

Answer 52

Alcoholic hepatitis Non alcoholic fatty liver disease Viral hepatitis Autoimmune hepatitis Drug induced hepatitis (e.g. paracetamol overdose)

Answer 53

Abdominal pain Fatigue Pruritis (itching) Muscle and joint aches Nausea and vomiting Jaundice Fever (viral hepatitis)

Answer 54

Herpes viruses e.g., EBV (Epstein-Barr virus) CMV (Cytomegalovirus), VZV (Varicella Zoster Virus)

Answer 55

The Hepatitis A virus is a non-enveloped single-stranded RNA virus, Belongs to the Picornaviridae family. **is a (picornavirus)**

Answer 56

Spread via the faeco-oral route (contaminated food and water) Endemic in Africa and South America. It is uncommon in the UK. Most infections are in children

Answer 57

- **Travel**: those travelling to endemic areas - **Sexual**: high risk activities, multiple partners - **Occupational risks**: for example laboratory or sewage workers - **IV drug users**: known to be at increased risk

Answer 58

1. **Incubation** 2. **Prodromal** 3. **Icteric** 4. **Convalescent**

Answer 59

a) Hepatitis A incubation period, may last from 2 - 6 weeks b) Prodromal: Early part of the disease, characterised by fever, joint pain and rash. Flu-like symptoms may be present

Answer 60

a) Phase with **jaundice, as well as abdo pain, changes in bowel habit** -- ***MOST INFECTIOUS JUST BEFORE JAUNDICE ONSET*** b) Convalescent: Recovery phase as the body returns to normal and symptoms subside.

Answer 61

- **Jaundice** - **RUQ tenderness** - **Hepatomegaly (85%)** - **Abdominal discomfort** - **Nausea** - **Arthralgia** - **Anorexia** - **Diarrhoea** - **Flu-like illness**

Answer 62

SEROLOGY - Hepatitis A virus Antibodies, **IgG and IgM** - **+ve HAV-IgM, +ve HAV-IgG**: ****Likely acute hepatitis A infection - **+ve HAV-IgM, -ve HAV-IgG**: ****May indicate acute infection or false positive IgM - -**ve HAV-IgM, +ve HAV-IgG**: ****Indicates previous infection or vaccine based immunity

Answer 63

**Supportive management:** - **General points**: advise good oral hydration and rest. Alcohol should be avoided. **Antiemetics** - **Reduce transmission**: ****stay at home, good hygiene, avoid unnecessary contact and unprotected sex for 7 days after jaundice appears or symptoms began.

Answer 64

- **Fulminant liver failure:** is rare, if so then give interferon alfa given. Relapsing hepatitis (may occur in 5-15%) Patients should be reviewed on a weekly basis for clinical review and repeat LFTs. Refer to specialist services if clinically worsening or persistently abnormal LFTs. - **Hep A vaccine** Hepatitis A vaccine is recommended to those at risk of infection and at risk of complications of infection.

Answer 65

YES Clinicians should contact their local Health Protection Unit to allow contact tracing and monitoring of outbreaks. In England hepatitis A is a ‘notifiable disease’, meaning you must notify a Proper Officer of the local authority. At risk contacts should be reviewed, if they have not been vaccinated, immunoglobulin should be considered. Typically the hepatitis vaccine will be offered.

Answer 66

Hepatitis B is caused by the hepatitis B virus (HBV). It is an **enveloped DNA virus** that belongs to the Hepadnaviridae family and can cause acute or chronic hepatitis:

Answer 67

It is transmitted by direct contact with **blood or bodily fluids, such as during sexual intercourse or sharing needles** (i.e. IV drug users or tattoos). It can also be passed through sharing contaminated household products such as toothbrushes or contact between minor cuts or abrasion

Answer 68

1. Surface Antigen - **HBsAg** *present in active infection, and 6 months after exposure* 2. E Antigen - **HBeAg** - released during replications, indicates acute infection 3. Core Antigen - **HBcAg** - not in the blood but in the core of the virus. *implies past or current infection*

Answer 69

**HBsAg persisting for >6 months** defines carrier status and occurs in 5–10% of infection

Answer 70

**Hepatitis B c antibodies (HBcAb) can help distinguish acute, chronic and past infections.** measure IgM and IgG versions of the HBcAb. a) **Anti-Hbc IgM** implies an active infection, so **high in acute infection and low in chronic infection** b) **Anti- HBc IgG** indicates a past infection **where the HBsAg (antigen) is negative.** *taken from OHCM 9th edition*

Answer 71

Positive HBcoreAntibody **IgG**, and a negative HB surface antigen ***HB surface antigen*** - indicates active disease

Answer 72

Anti-HBsAg (Antibody to the surface antigen on Hep B virus) Vaccinated patients are tested for HBsAb to confirm their response to the vaccine. The vaccine requires 3 doses at different intervals.

Answer 73

Hepatitis B e antigen Where present, implies the patient is in an acute phase of infection, **where virus is actively replicating.** ***The level of HBeAg correlates with their infectivity.*** aka high HBeAg = highly infectious. When they HBeAg is negative but the hepatitis B e antibody is positive = **implies they have been through phase of viral replication**, but it has stopped replicating now, **aka less infectious**

Answer 74

Supportive, so Monitor liver function Fulminant hepatic failure (0.1% - 0.5%) **Antiviral if severe** Liaise with hepatology/liver transplant centre Management of contacts (HV vaccine ± HBIG)

Answer 75

Consider oral nucleoside analogue, like **Entecavir, tenofovir,** They are **incorporated into the DNA chain, causing the chain to terminate** when the virus attempts to replicate

Answer 76

Pegylated **interferon-α 2a** Liver Transplant Do this along side your antivirals, like Tenofovir and entecavir

Answer 77

It's an RNA flavivirus Infection may be acute and chronic.

Answer 78

7 genotypes; genotype 1a and 1b account for 70% cases in USA and 50% in Europe *Rapid mutations so envelope proteins change rapidly so its hard to develop a vaccine*

Answer 79

Acute - Most patients are asymptomatic - 10% have mild influenza-like illness with jaundice and a rise in serum aminotransferases (ALT and AST) b) Chronic - Signs of cirrhosis, liver failure and hepatocellular carcinoma

Answer 80

**HCV antibodies** - confirms prior exposure (remember there is no vaccine for Hep C) **HCV PCR** - if this is positive, implies an active/current infection Serum aminotransferases may be elevated

Answer 81

Directly acting anti-virals (DAAs) Combination of DAAs - eg **Entecavir** from two or more of three drug classes, usually combined with **ribavirin (RBV)** so eg Ledipasvir, Sofosbuvir, Grazoprevir, Ribavirin

Answer 82

It is a unique RNA virus - **Requires HBV for assembly**

Answer 83

Hep D virus is an incomplete RNA particle **enclosed in a shell of HBsAg Virus** is unable to replicate on its own but is **activated by the presence of HBV** It attaches itself to the HBsAg to survive and cannot survive without this protein. If acquired simultaneously with HBV (co-infection) causes increased severity of acute infection

Answer 84

Co infection - When you get HVD and HBV at same time - indistinguishable from normal Hep B infection Superinfection When you have chronic Hep B infection, and get HDV on top of it. == *Speeds up scarring* It attaches itself to the HBsAg to survive and cannot survive without this protein.

Answer 85

**Anti-HDV antibody** (only ask for it if HBsAg +ve)

Answer 86

As interferon-a has limited success, liver transplantation may be needed Most common in eastern Europe, eg Romania

Answer 87

RNA virus and acute only (can be chronic in immunosuppressed) Route of Transmission Faeco-oral route – water or food-borne Found in undercooked pork

Answer 88

None!! All cases of Hepatitis A,B,C,D,E you need to notify public health for

Answer 89

Serology – HEV antibodies Nucleic acid amplification test

Answer 90

Management Supportive, liver transplant eg **Entecavir** **Consider ribavirin – anti-viral medication** Most likely see chronic HEV in immunocompromised

Answer 91

Chronic infection (immunosuppressed) Reverse immunosuppression (if possible) If HEV RNA persists, treat with ribavirin

Answer 92

An Ultrasound of the foetus and test for it - to make sure foetus doesn't get fulminant Hepatitis

Answer 93

Hep B and Hep C

Answer 94

Hep A - faeco-oral route (contaminated food and water) Hep B - direct contact with **blood or bodily fluids, such as during sexual intercourse or sharing needles* Hep C - contact with infected blood - sharing needles and razors Hep D- only with Hep B so also blood/bodily fluids Hep E - Faeco-oral route – water or food-borne Found in undercooked pork

Answer 95

Always can say supportive, and avoid alcohol Hep A - INTERFERON ALPHA - Entercavir Hep B - Entecavir, Tenofovir Hep C - Entecavir, combined with Ribavirin Hep D - Interferon a, liver transplant Hep E - transplant Entecavir, Consider ribavirin basically if in doubt say Entecavir - its a **Direct acting antiviral**

Answer 96

We are not sure of the exact cause, however it could be associated with a genetic predisposition and triggered by environmental factors such as a viral infection that causes a T cell-mediated response against the liver cells. There are 2 types

Answer 97

Adults Type 1 typically affects women in their late forties or fifties. It presents around or after the menopause with fatigue and features of liver disease on examination. It takes a less acute course than type 2.

Answer 98

In type 2, patients in their teenage or early twenties present with acute hepatitis with high transaminases and jaundice.

Answer 99

Anti-nuclear antibodies (ANA) Anti-smooth muscle antibodies (anti-actin) Anti-soluble liver antigen (anti-SLA/LP)

Answer 100

Anti-liver kidney microsomes-1 (anti-LKM1) Anti-liver cytosol antigen type 1 (anti-LC1)

Answer 101

**High dose steroids (prednisolone)** that are tapered over time, as other immunosuppressants, particularly **azathioprine,** are introduced. Immunosuppressants are normally life long Liver transplant may be required in end stage liver disease, however the autoimmune hepatitis can recur in transplanted livers.

Answer 102

Change in normal liver architecture due to repeated insult to **abnormal nodules, and fibrotic tissue**

Answer 103

Chronic alcohol use Chronic HBV or HCV Genetic disorder like **haemochromatosis, A1AT Deficiency** Autoimmune hepatitis Non alcoholic fatty liver disease Drugs eg Amiodarone *(An anti-arrhythmic medicine)*

Answer 104

Liver injury results in inflammation, necrosis which leads to the release of ROS ROS activates Heptaic Stellate cells and Tissue macrophages (Kupffer cells) **Stellate cells release cytokines** that attract neutrophils and macrophages to the liver 🡪 further inflammation and necrosis 🡪 fibrosis

Answer 105

Compensated – when the liver can still function effectively and there are no (or few) noticeable clinical symptoms Decompensated – when the liver is damaged to the point that it cannot function adequately and overt clinical complications (such as jaundice, ascites, variceal haemorrhage and hepatic encephalopathy) are present

Answer 106

- Clubbing - Palmar erythema - Dupuytren’s contracture - Spider naevi - Xanthelasma - yellow fat deposits under skin usually around eyelids - Gynaecomastia - Loss of body hair - Hepatomegaly - Splenomegaly - Bruising - Ankle swelling and oedema - Abdominal pain due to ascites

Answer 107

**Liver Function tests** - Alaine aminotransferase (ALT) and and Aspartate aminotransferase, (AST) Alkaline phosphatase (APT) and gamma-glutamyl transferase (GGT) will be raised Serum Albumin will be lowered Serum Sodium will be lowered Serum Potassium will be raised Prothrombin time prolonged Platelet count low

Answer 108

Gamma-GT indicates damage to the liver and bile ducts. GGT is particularly associated with alcohol use.

Answer 109

Liver biopsy - *gold standard* Abdominal ultrasound Abdominal CT Abdominal MRI

Answer 110

Treat underlying cause!! ==> *aka Antivirals Ledipasvir, Ribavirin* Good nutrition is vital. Alcohol abstinence Avoid NSAIDS, sedatives, and opiates. **Treat side effects - eg Treat ascites, Pruritus,** *(Cholestyramine)* ***Give Hep A and Hep B vaccination to those that are at risk!!***

Answer 111

Ascites - fluid restriction and reduced salt intake, spironolactone Pruritus - Cholestyramine *(Itchy skin is causes by failure to eliminate bile salts due to liver failure)* **Cholestyramine binds to bile acid in GI tract to prevent reabsorption** Spontaneous bacterial peritonitis - antibiotics **Hepatocellular carcinoma - need an ultrasound every 6 months to screen for it**

Answer 112

There are vaccines available for hepatitis A and hepatitis B. The hepatitis B vaccine is also available in combination with the hepatitis A vaccine.

Answer 113

Because the liver produces **Thrombopoietin, the hormone that stimulates bone marrow to make platelets.** When the liver is damaged less of this is made leading to a reduction in platelet production

Answer 114

Coagulopathy – fall in clotting factors II, VII, IX and X Encephalopathy – liver flap (flapping tremor with wrist extended) and confusion/coma When toxins e.g. ammonia make it into the brain and cause mental deficits Thrombocytopenia **Hepatocellular carcinoma - need an ultrasound every 6 months to screen for it** Hypoalbuminaemia Portal hypertension - leads to Ascites, Oesophageal varices

Answer 115

Haemoglobin= Haem *=(Hemoxygenase)=>* Biliverdin Billverdin => Reduced to Unconjugated Bilirubin, **travels In blood to bound to albumin to liver**

Answer 116

Unconjugated Bilirubin **undergoes Glucuronidation into Conjugated Bilirubin**, *(by enzyme glucuronosyltransferase)* Conjugated Billirubin is released in Bile and becomes **Urobilinogen** 90% of Urobilinogen becomes **Stercobilin (faeces)** and 10% becomes **Urobilin (recycled back to bile or urinated out)**

Answer 117

Biliverdin and Fe2+

Answer 118

Albumin as it is not soluble it needs to travel to the liver

Answer 119

Urobilinogen/Stercobilinogen

Answer 120

Intestinal bacteria

Answer 121

It can go back to the liver It can go to the kidneys and form urinary urobilin, to be urinated out Can form stercobilin which is secreted in faeces 90%

Answer 122

**Problem before the liver** is caused by increased haemolysis. This results in the increased presence of unconjugated bilirubin in the blood as the liver is unable to conjugate it all at the same rate.

Answer 123

Pre hepatic jaundice: high in blood, but normal in urine. **(so stools brown and urine normal)** Enlarged Spleen, (due to excess breakdown) Seen in: Malaria. Sickle Cell anaemia. Gilbert’s syndrome,

Answer 124

is caused by liver impairment. This causes the decreased ability of the liver to conjugate bilirubin, resulting in the presence of conjugated and unconjugated bilirubin in the blood.

Answer 125

Hepatitis/B/C, alcoholic liver disease, drug misuse.

Answer 126

is caused by the blockage of bile ducts. This results in backflow of conjugated bilirubin into the blood as it cannot move past the obstruction.

Answer 127

Gall stones, pancreatitis, Gall/pancreatic cancer

Answer 128

Conjugated bilirubin

Answer 129

Stercobilinogen

Answer 130

Unconjugated bilirubin

Answer 131

Dark urine and pale stools

Answer 132

UDP-gluconoryltransferase, due a fault in the UGT1A1 gene

Answer 133

This faulty gene results in slower conjugation of bilirubin in the liver, causing it to build up in the blood stream. ==> **Prehepatic jaundice**

Answer 134

is a neurological emergency resulting from thiamine deficiency with varied neurocognitive manifestations.

Answer 135

Hypothalamic damage & cerebral atrophy due to thiamine (vitamin B1) deficiency (eg in alcoholics). Wernicke's encephalopathy is the acute, reversible stage of the syndrome, and if left untreated it can later lead to Korsakoff syndrome, which is chronic and irreversible.

Answer 136

Thiamine is typically stored in the liver and absorbed in the duodenum in the brain thiamine helps maintain normal amino acid and neurotransmitter levels.

Answer 137

- **Alcohol abuse** - **Malnutrition** - **Anorexia** - **Malabsorption due to stomach cancer and IBD** - **Prolonged vomiting e.g. due to chemotherapy, hyperemesis**

Answer 138

It **block the phosphorylation of thiamine**, stopping it from being converted into its active form Ethanol **reduces gene expression of Thiamine transporter**, so can stop it getting absorbed in the duodenum. Alcoholic tend to have a poor diet, relying on alcohol for calories so will not get enough Thiamine (b1) anyway

Answer 139

- Thiamine deficiency impairs glucose metabolism and this leads to a decrease in cellular energy. - The brain is particularly vulnerable to impaired glucose metabolism since it utilises so much energy.

Answer 140

1 confusion 2 ataxia (wide-based gait; fig 2) 3 **ophthalmoplegia** (nystagmus, lateral rectus or conjugate gaze palsies).

Answer 141

- Mainly targets the limbic system, causing severe memory impairment: - **Anterograde amnesia:** inability to create new memories - **Retrograde amnesia:** inability to recall previous memories. - **Confabulation:** creating stories to fill in the gaps in their memory which they believe to be true. - **Behavioural changes**

Answer 142

- Diagnosis is typically made **based on clinical presentation** - **Bloods including LFTs**: measure thiamine levels, measure blood alcohol levels, liver function may be deranged in alcoholism - **Red cell transketolase test:** rarely done, thiamine is a co-enzyme to transketolases so transketolase activity will be low - **MRI/CT:** can confirm diagnosis by showing degeneration of the mammillary bodies Lumbar puncture to rule out other causes of the symptoms of wernickes

Answer 143

Urgent replacement to prevent irreversible Korsakoff’s syndrome (p718). Give thiamine (Pabrinex®) Oral supplementation (100mg OD) should continue until no longer ‘at risk’, *give other B vitamins as well* Correct Magnesium deficiency as well If there is coexisting hypoglycaemia, correct it

Answer 144

it’s important to normalise the thiamine levels first, because without thiamine pyrophosphate, **most of the glucose will become lactic acid and that can lead to metabolic acidosis.** (often the case in this group of patients), make sure **thiamine is given before glucose**, as Wernicke’s can be caused by glucose administration to a thiamine-deficient patient - ***NOT GIVING THIAMINE AS YOU JUST THINK ITS HYPOGLYCAEMIA IS A COMMON MISTAKE DOCTORS MAKE***

Answer 145

Biliary Colic is the name given to the **pain experienced from gallstones**, it is not a condition itself. Gallstones are often described as biliary colic though so this can be confusing.

Answer 146

sudden onset, severe but constant and has a crescendo characteristic Pain is temporary and stops when gallstone dislodges

Answer 147

May be present at any age but unusual <30 Increasing prevalence with age More common in females More common in Scandinavians, S. Americans and Native North Americans

Answer 148

The common bile duct *credit - teach me anatomy*

Answer 149

The common bile duct goes onto to join the pancreatic duct. they meet at the major duodenal papilla (known as the ampulla of vater) , just as they enter the duodenum *picture credit - unknown*

Answer 150

In the descending part of the duodenum. The Spinchter of Oddi controls its opening and closing

Answer 151

blockage to the flow of bile

Answer 152

the preasence of gall stones

Answer 153

gallstone(s) in the **common bile duct**

Answer 154

* Bile salts * Cholesterol * Electrolytes * Phospholipids * Bilirubin It is Amphipathic - has both Hydrophobic and hydrophilic parts

Answer 155

Digestion of Dietary fats, Facilitates Protein absorption, Has anti-microbial properties, Prevents Calcium Gallstones

Answer 156

Stones form from supersaturation of bile - 2 ways 1. From build up of excess cholesterol, and cholesterol crystals 2. From build up of pigment from excess bilirubin - seen in patients with chronic haemolysis (e.g. hereditary spherocytosis and sickle cell disease) **Reduced stasis and motility of Gall bladder.**

Answer 157

The 5Fs: Fat, Fertile, Forty, Female, Fair, (Caucasian) FHx rapid weight loss CROHN'S DISEASE can result in terminal ileitis, the part of the bowel where gall stones are absorbed - leads to bile salts not being absorbed - so **Crohns can be a risk factor for galls stones**

Answer 158

Classically ‘colicky’ RUQ pain that is worse after eating large or fatty meals (triggers gallbladder to contract against the blockage). May also radiate to epigastrium and back **Murphys sign negative** May have no symptoms!

Answer 159

Murphy's sign is a maneuver used by physicians to diagnose the presence of gallstones. Seen by patient inhaling while the physician palpates the right upper quadrant of the abdomen. Pain in this area indicates the presence of gallstones. **Present in Cholecystitis, but not biliary colic**

Answer 160

**Abdominal ultrasound** Liver function tests Billirubin levels **Raised Alkaline Phosphatase** - raised in biliary obstruction - ***!!!!!!!!!!!!!!!!!!!!!!*** **Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)** levels

Answer 161

In patients with cholestasis (e.g., due to gallstones), ALT and AST can increase slightly, with a **higher rise in ALP (“an obstructive picture”).**

Answer 162

High ALT and AST, comapred with level of ALP

Answer 163

Analgesia An anti-spasmodic (e.g., hyoscine) **Ursodeoxycholic acid** – decreases cholesterol If the patient has symptomatic gallbladder stones but does not have features of cholecystitis, offer the patient elective laparoscopic cholecystectomy

Answer 164

Inflammation of the gallbladder

Answer 165

When the GB has a gallstone in it, the squeezing of the GB can get it lodged in the cystic duct *(aka when you have meal)* --**Therefore bile gets stuck** **Bile stasis becomes a chemical irritant** so causes mucosa to release mucus and inflammatory enzymes 🡪 **inflammation, distension and pressure build up** Bacteria can start to grow e.g. E. coli and invade into gallbladder wall 🡪 peritonitis

Answer 166

E.Coli -ve rod Enterococci - +ve Coci Klebseilla - -ve Rod Clostridium +ve rod

Answer 167

The main difference from biliary colic is the inflammatory component (local peritonism, fever, **raised White Cell count**) Murphy's sign is present in Cholecystitis, absent in biliary colic!!

Answer 168

RUQ pain Fever Nausea and vomiting **Murphy’s sign** – *tenderness that is worse on inspiration* Muscle guarding

Answer 169

**CT/MRI** of abdomen Ultrasound: Thicc gallstone walls from inflammation Inflammatory markers - FBCs, CRP - raised white blood cells, raised billirubin, elevated Alkaline Phosphatase Positive Murphy’s Sign = Severe pain on deep inhalation with examiners hand pressed into the RUQ.

Answer 170

Antibiotics IV, heavy analgesia, IV fluids and an eventual Cholecystectomy if needed. Antibiotic should have anaerobic cover, such as **cefuroxime (cephlasporin) and metronidazole (DNA)**

Answer 171

Acute SAAG refers to infection of the biliary tree characteristically resulting in pain, jaundice and fevers

Answer 172

Obstruction of common bile duct 🡪 stasis of bile 🡪 invasion of bacteria from duodenum High pressure on the CBD (due to the obstruction) can cause spaces between the cells do widen which allows the bacteria and the bile access to the blood stream 🡪 bacteraemia and jaundice E.Coli is the most common pathgogenic cause *(aerobic, gram negative, bacilli, lactose fermenting)*

Answer 173

Choledocholithiasis, stones in the bile duct, is the most common cause of acute cholangitis A **Benign structure** - - Chronic pancreatitis, Iatrogenic injury (during cholecystectomy), Radio / chemo-therapy, Idiopathic - **Malignant stricture:** e.g. cholangiocarcinoma, pancreatic cancer and gallbladder cancer. - **Other:** - **Post-ERCP** (normally related to inadequate drainage) - **Blocked biliary stent** Parasites **(e.g. Ascaris lumbricoides)** can cause blockage E.Coli is the most common pathgogenic cause

Answer 174

- **Gallstones:** the most common predisposing factor - **Stricture of the biliary tree:** benign or malignant - **Post-procedure injury** of the bile ducts e.g. post-ERCP

Answer 175

Charcots Triad Jaundice *(Dark urine, pale stools)* RUQ pain Fever Reynold’s Pentad - Those 3 and also **Shock** – (hypotension and tachycardia) and **Confusion**

Answer 176

- **FBC:** leukocytosis with neutrophilia - **LFTs:** obstructive jaundice with raised ALP > ALT, and bilirubin - **U&Es**: pre-renal acute kidney injury in sepsis - **CRP**: acute-phase protein and marker of inflammation Blood Cultures - **MRCP:- Magnetic Resonance Cholangiopancreatography** gold-standard for diagnosis and used for pre-intervention planning and has the highest sensitivity. However, not as readily available so CT tends to be performed first - **ERCP:** Endoscopic Retrograde Cholangiopancreatography) (basically a biliary tree contrast x-ray) Usually preceded by imaging

Answer 177

The sepsis 6 protocol should be implemented when indicated - **Intravenous antibiotics**: broad-spectrum antibiotics with gram-negative and anaerobic cover e.g. cefotaxime and metronidazole for 4-7 days - **IV fluids**: patients are often septic and require rehydration - **Analgesia:** if needed, and tailored to patients' needs. Srugery if needed

Answer 178

ERCP Endoscopic Retrograde Cholangiopancreatography: first-line procedure usually performed within 24-48 hours. Allows for endoscopic exploration of the biliary tract with the removal of gallstones to facilitate drainage. Elective cholecystectomy:

Answer 179

Biliary colic - YES RUQ, NO Fever/raised WCC, NO Jaundice Acute Cholecystitis - YES RUQ, YES fever/raised WCC, NO jaundice Cholangitis - YES RUQ, YES fever/raised WCC, YES jaundice

Answer 180

Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, Autoimmune condition, **with granulomatous destruction** of intrahepatic biliary ducts *(the bile ducts that drain the liver)* . ===> It can lead to fibrosis, cirrhosis, and portal hypertension

Answer 181

Unknown environmental triggers (?pollutants, xenobiotics, non-pathogenic bacteria) + genetic predisposition (eg IL12A locus) leading to loss of immune tolerance to self-mitochondrial protein **Antimitochondrial antibodies (AMA) are the hallmark of PBC**

Answer 182

The inflammatory process coupled with trapping of bile acids in the liver leads to progressive fibrosis, cirrhosis, and eventually liver failure.

Answer 183

Up to 50% of PBC patients have at least one associated autoimmune condition, such as: - Sjögren's syndrome (25%) - Raynaud’s phenomenon (25%) - Autoimmune thyroid disease (25%) - Rheumatoid arthritis (20%) - Systemic sclerosis(10% Far more common in women, middle aged!

Answer 184

- Skin hyperpigmentation: due to increased melanin - Clubbing - Mild hepatosplenomegaly - **Xanthelasma and xanthomata (late sign)** - due to leakage of cholesterol - Jaundice in eyes - Pruritis (itchy skin) - leakage of bile salts - Fatigue and weight loss - Obstructive jaundice (late sign) - due to leakage of bile and conjugated bilirubin - Icteric (Jaundice) - Pale stool and dark urine **Far more common in women, middle aged!**

Answer 185

- **Antimitochondrial antibodies (AMA):** present in 95% of patients (highly specific) - **Antinuclear antibodies (ANA):** present in 50% of patients - **Raised serum cholesterol** - **LFTs:** an obstructive picture is seen with a raised ALP, GGT and bilirubin. AST and ALT may be mildly raised - **Serum immunoglobulin:** elevated IgM - **Transabdominal ultrasound**: excludes other extrahepatic causes of cholestasis e.g. gallstones MRCP: if the above tests are inconclusive, an MRCP should be conducted to look for intrahepatic biliary duct stenosis

Answer 186

- **Ursodeoxycholic acid** - First-line agent in all patients - A bile acid analogue which dampens the inflammatory response, acts as an anti-apoptotic agent, and improves cholestasis This may be combined with Obeticholic acid, As well as **Cholestyramine**: bile acid sequestrant for symptomatic relief of **pruritus (itching)** Fat-soluble vitamin supplementation: cholestasis impairs fat absorption; vitamins A, D, E and K must be supplemented Codeine phosphate: for diarrhoea Liver transplantation if V severe

Answer 187

Liver transplantation: indicated in end-stage disease with liver cirrhosis

Answer 188

It's a condition where the intrahepatic or extrahepatic ducts become narrowed, stiffened and fibrotic. This causes an obstruction to the flow of bile out of the liver and into the intestines

Answer 189

The main difference between primary biliary cholangitis and primary sclerosing cholangitis is the cause of the disease. PBC is caused by an autoimmune disorder, while PSC is caused by inflammation, from a number of causes Primary Bilialry cholangitis affects **intrahepatic ducts only** Primary Sclerosing Cholangitis affects **affects intrahepatic and extrahepatic ducts** - Additionally, PBC is more likely to affect women, while PSC is more likely to affect men. - PSC is associated with Ulcerative Collitis

Answer 190

The cause is mostly unclear although there is likely to be a combination of genetic, autoimmune, intestinal microbiome and environmental factors. There is an established association with ulcerative colitis, with around 70% of cases being alongside established ulcerative colitis.

Answer 191

Irrespective of cause, the damage to bile ducts leads to: - **Cholestasis** - **Bile and toxin build up in the liver** - **Bile duct strictures** All of the above contribute to **liver fibrosis, cirrhosis** and progression to **end-stage liver disease.** PSC is associated with Ulcerative Collitis

Answer 192

***PSC is often asymptomatic in the early stages and detected on routine blood tests.*** - Jaundice - Signs of complications: - **Ascending Cholangitis:** Charcot’s triad - **Chronic liver disease:** rare at first presentation, e.g. ascites or encephalopathy

Answer 193

- Pruritis - Fatigue - RUQ/ epigastric abdominal pain - Symptoms of underlying bowel disease: bloody stools, tenesmus, diarrhoea, steatorrhoea

Answer 194

LFTs - raised ALP *(Alkaline phosphatase)* and raised bilirubin, raised GGT *(gamma-glutamyl transferase)* , raised ALT and AST if liver damage present, decreased albumin. Viral hepatitis screen: screen for HBsAg and anti-HCV in all patients **Antimitochondrial antibody, will be negative**, but ANA, SMA, and ANCA may be +ve; **GOLD STANDARD - ERCP (Endoscopic Retrograde Cholangio-Pancreatography)**

Answer 195

You insert a small cameria in persons throat - goes through **oesophagus, stomach and duodenum to the a point in the duodenum where the bile ducts empty into the GI tract.** Then goes through **Ampulla of Vater** where they can now enter the bile ducts and use **X-rays and injecting contrast to identify different structures** These structures can be **Stented/widened using the same technique**, to help relieve symptoms **So can be used to view and diagnose/investigate, and can also fit stents with it, so can be used for treatment too**

Answer 196

Observation and lifestyle optimisation, healthy diet, reduce alcohol etc Cholestyramine: a bile acid sequestrant that is the first-line treatment for relief of pruritus Fat-soluble vitamin supplementation: cholestasis leads to impaired fat absorption; to ensure the absorption of fat-soluble vitamins (ADEK), supplementation Supplent calcium/vit D to prevent hepatic osterporosis endoscopic retrograde cholangiopancreatography (ERCP), if severe **Liver transplant if end stage liver disease** No set definite cure for PSC!

Answer 197

Main are **Gall Stones Ethanol** - *aka alcohol abuse* **Trauma** Steroids Mumps/malignancy Autoimmune e.g. SLE Scorpion stings Hyperlipidaemia and hypercalcaemia **Endoscopic Retrograde Cholangiopancreatography** Drugs – azathioprine, metronidazole, tetracycline, furosemide **GET SMASHED**

Answer 198

Gall stones can get stuck, and block the **ampulla of vater** - leading to back flow of Bile and Pancreatic enzymes up into the pancreas. This leads to **increased Intracellular Ca2+, causes the early activation of trypsinogen** ***into trypsin*** Trypsin causes *increased enzymatic digestion of the pancreas and inflammation leading to extensive acinar damage*

Answer 199

Increases zymogen secretion, but also decreased fluid bicarbonate in duct 🡪 **thick and viscous pancreatic juice** which can obstruct the pancreatic duct This backs up and leads to enzymatic degrading of pancreas cells. Alcohol also stimulates cytokine release 🡪 immune response 🡪 neutrophils release superoxides and proteases

Answer 200

**Epigastric pain radiating to the back – relieved by sitting forwards Nausea and vomiting**

Answer 201

Cullen’s sign – bruising around periumbilical region Grey Turner’s sign – bruising on flanks Tachycardia Abdominal guarding and tenderness Distension

Answer 202

Serum amylase/Lipase - >3 times the upper limit of the normal range - **Lipase is more sensitive and specific for pancreatitis.** **CRP >150mg/L** at 36h after admission is a predictor of severe pancreatitis **Elevated alanine aminotransferase (ALT) levels strongly suggest gallstones as the cause.** Abdo xray - : No psoas shadow (retroperitoneal fluid is increased) Chest Xray Abdominal ultrasound

Answer 203

**Amylase** Amylase is produced in the pancreas and is used to digest carbohydrates. It is released into the blood in large quantities in pancreatic disease.

Answer 204

**Gauge severity - Using PANCREAS pneumonic** Supportive treatment IV fluid and maintain electrolyte balance - **Give lots of fluids**!! Pain relief Insert a urinary catheter, monitor urine Oxygen supplementation if needed Treat complications **Regular CT or CRPs to gauge progress** ERCP + gallstone removal may be needed if there is progressive jaundice

Answer 205

3 or more positive factors detected within 48h of onset suggest severe pancreatitis, and should prompt transfer to ITU/HDU. Mnemonic: PANCREAS PaO2 <8kPa Age >55yrs Neutrophilia WBC >15 x 109/L Calcium <2mmol/L Renal function Urea >16mmol/L Enzymes LDH >600iu/L; AST >200iu/L Albumin <32g/L (serum) Sugar blood glucose >10mmol/L *Severity can also be assessed with the help of CT (Computed Tomography Severity Index).1 CRP can be a helpful marker.*

Answer 206

Each round of pancreatitis = increased chance of dilation of ducts and permanent damage. - Stellate cells lay down fibrotic tissue - causes narrowing of ducts, acinar cell atrophy - In Acute Alcohol PCT, Calcium deposits can plug ducts Healthy tissue is replace by misshaped ducts, together with fibrosis and calcium plugs = chronic pancreatitis **It results in fibrosis and reduced function of the pancreatic tissue**

Answer 207

Alcohol abuse Also Cystic Fibrosis – main cause in children Tumours Pancreatic trauma – knife wounds Repeated bouts of acute pancreatitis Epigastric pain that radiates to back – may be linked to eating meals N+V ==> *symptoms tend to be less intense and longer-lasting*

Answer 208

± CT (pancreatic calcifications confirm the diagnosis), MRCP + ERCP (risks acute attack); AXR: speckled calcification; raised glucose

Answer 209

Alcohol and smoking cesscation - **first line** Pain relief Pancreas enzymes **eg creon** and Proton Pump Inhibitor Insulin for diabetes

Answer 210

Chronic epigastric pain Loss of exocrine function, resulting in a lack of pancreatic enzymes (particularly lipase) secreted into the GI tract Loss of endocrine function, resulting in a lack of insulin, leading to diabetes Damage and strictures to the duct system, resulting in obstruction in the excretion of pancreatic juice and bile Formation of pseudocysts or abscesses

Answer 211

abnormal accumulation of fluid within the abdominal cavity Physiologically, in men, no fluid should be present. In women, up to 20 mls may be considered normal depending on the timing of the menstrual cycle

Answer 212

- Normal portal pressure - Raised portal pressure

Answer 213

Malignancy Cirrhosis Low albumin Pancreatitis Bowel obstruction Portal hypertension

Answer 214

abdominal distention, Shifting dullness, flank dullness, Fluid thrill, Bulging flanks

Answer 215

SAAG the serum ascites-albumin gradient

Answer 216

High SAAG >1.1g/dl or 11 g/l= raised portal pressure and cirrhosis (transudate) Low SAAG <1.1g/dl or 11g/l= normal portal pressure (exudate)

Answer 217

A shunt Spironolactone to increase sodium excretion Paracentesis

Answer 218

Severe hypovolemia Peritonitis

Answer 219

Elevated pressure in the portal venous system. **It is defined as pressure 5 mm Hg greater than the pressure in the inferior vena cava** (normal pressure 5-10)

Answer 220

THINK VENOUS BLOCKAGE! Pre-hepatic – due to blockage of portal vein before liver Portal vein thrombosis Intra-hepatic – resulting from distortion of liver architecture Cirrhosis – most common cause Schistosomiasis Post-hepatic – due to venous blockage outside of liver Right HF

Answer 221

**Schistosomiasis** a parasitic disease caused by tiny worms known as Schistosoma.

Answer 222

Endothelin-1 production increased in cirrhosis 🡪 more vasoconstriction NO production reduces in cirrhosis 🡪 less vasodilation Reduced radius 🡪 increases resistance 🡪 higher pressure in portal system

Answer 223

Symptoms Often symptomatic GI bleeding from oesophageal or gastric varices Signs Ascites Hepatic encephalopathy Splenomegaly Oesophago-gastric varices

Answer 224

- Abdominal ultrasound - dilated portal vein - Doppler ultrasound - slow velocity and dilated portal vein - Endoscopy - for presence of oesophageal varices

Answer 225

- Treat underlying cause - Salt reduction and diuretics - Beta-blockers and nitrate to reduce blood pressure

Answer 226

- Varices and variceal haemorrhage - Ascites - Hepatopulmonary syndrome - Liver failure - Hepatic encephalopathy - Cirrhotic cardiomyopathy

Answer 227

Oesophageal varices are abnormal, dilated veins that occur at the lower end of the oesophagus; they account for 10-20% of upper GI bleeds

Answer 228

Veins of the oesophagus drain into the portal vein. Due to hypertension there is backflow from the portal vein causing the veins to enlarge and dilate

Answer 229

Hypotension Tachycardia Pallor Signs of chronic liver damage – jaundice, easy bruising (liver not produced coagulation factors) and ascites Splenomegaly Ascites

Answer 230

Haematemesis - *vomiting blood* Abdominal pain Rectal bleeding

Answer 231

**ABCDE approach** Resuscitation and supportive care, IV fluids **Terlipressin:** ADH analogue and causes splanchnic vasoconstriction **Blood Transfusion** Vitamin K, to correct bleeding abnormality then surgery: **endoscopic variceal band ligation** within 24hr

Answer 232

diagnostic endoscopy + non-selective beta-blocker - **propranolol** Nitrate to cause vasodilation 🡪 to reduce portal pressure Terlipressin (ADH analogue) 🡪 reduce portal pressure endoscopic variceal band ligation

Answer 233

Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae. **Escherichia Coli is the most common**

Answer 234

A – Appendicitis – umbilicus to RIF pain E – Ectopic pregnancy – low abdominal pain, sudden onset, tachycardia, low BP I – Infection (bacteria) O – Obstruction – colicky pain, history of abdominal surgery U – Ulcer – epigastric pain radiating to shoulder VOWELS

Answer 235

intravenous third-generation cephalosporin cefotaxime, ceftriaxone Following an episode of SBP, patients require prophylactic oral antibiotics e.g. rifaximin.

Answer 236

Is an iron storage disorder that results in excessive total iron and deposition of iron in tissues.

Answer 237

The human haemochromatosis protein (HFE) gene is located on chromosome 6. It is an autosomal recessive allele on this gene that causes disease

Answer 238

Family history Alcoholism History of chronic transfusion: only relevant inacquiredhaemochromatosis, for example in patients with thalassaemia

Answer 239

There is unregulated absorption of iron from the gut causing iron overload This results in iron deposition on multiple tissues most commonly affecting liver, pancreas, and the heart

Answer 240

Chronic tiredness Joint pain Bronze pigmentation of skin Hair loss Erectile dysfunction Amenorrhoea Cognetive symptoms

Answer 241

Serum ferritin will be high but can also be high in other conditions Serum transferrin if this is high as well then likely to be hemochromatosis

Answer 242

Liver biopsy with Perl’s stain can be used to establish the iron concentration in the parenchymal cells used to be the gold standard Now genetic testing is gold standard

Answer 243

venesection involves draining small amounts of blood around 500ml Iron chelation can be used Deferoxamine Patients should avoid alcohol

Answer 244

Endocrine - Diabetes Mellitus due to destruction of islet cells Liver - cirrhosis, and hepatocellular carcinoma Cardiac - Dilated cardiomyopathy, and congestive cardiac failure MSK- Gout and pseudogout Derma - Skin hyperpigmentation GREY SKIN INFERTILITY

Answer 245

An excessive accumulation of copper in the body and tissue.

Answer 246

Due to Mutation of the **ATP7B gene on chromosome 13,** resulting in dysfunction in ATP-mediated hepatocyte copper transport. It is an autosomal recessive disease

Answer 247

Total body copper content is ~125mg. Intake≈ 3mg/day (absorbed in proximal small intestine). In the liver, copper is **incorporated into caeruloplasmin** - the main copper carrying protein in the blood

Answer 248

Wilson’s disease, intestinal copper absorption and transport into the liver are intact, while copper incorporation into caeruloplasmin in hepatocytes and its excretion into bile are impaired. Therefore, copper accumulates in liver, and later in other organs

Answer 249

Hepatic problems (40%) Neurological problems (50%) Psychiatric problems (10%

Answer 250

*In children/young adults* Hepatosplenomegaly Hepatitis and cirrhosis Jaundice Ascites

Answer 251

*In children/young adults* Dysarthria (speech difficulties) Dystonia Parkinsonism (tremor, rigidity) - Similar presentation to Parkinson's Awful handwriting Motor symptoms often asymmetric

Answer 252

Depression Psychosis Poor Memory; quick to anger; slow to solve problems; low IQ; delusions; mutism

Answer 253

Kayser-Fleischer rings in cornea yellow-brown deposits of copper in the cornea - They form a ring around the edge of the iris, the colored part of the eye.

Answer 254

Reduced ceruloplasmin and increased 24 hour urinary copper excretion is highly suggestive of Wilson’s disease.

Answer 255

**Liver biopsy** to test for copper content. - **Genetic testing:** ATP7B mutation; perform for all patients to confirm the diagnosis and facilitate family testing

Answer 256

Copper chelation: usually the first-line treatment. Chelators bind copper and facilitate renal excretion; **D-penicillamine** is most commonly used

Answer 257

Autosomal recessive genetic disorder, on A1AT gene on chromosome 14

Answer 258

Produced in liver Function is to inhibit neutrophil elastase, which is a proteolytic enzyme (produced by neutrophils in the presence of inflammation, infection, smoking)

Answer 259

If there is A1AT deficiency, elastase from neutrophils can break down elastin unchecked Deficiency affects lung (alveolar wall destruction) and liver Without this there is destruction of cells leading to emphysema and lung dysfunction

Answer 260

In the liver as the protein is misfolded it gets stuck in the hepatocyte. This causes cell death leading to liver damage (Jaundice, hepatitis, cirrhosis and hepatocellular carcinoma) ***This only happens in certain genotypes of the disease***

Answer 261

Respiratory early onset COPD and SOB Liver symptoms will only occur in certain subtypes but will be the symptoms of liver failure e.g., hepatic encephalopathy , Jaundice, coagulopathy, ascites

Answer 262

Serum A1AT levels:reduced with levels < 20 micromol/L Genetic testing

Answer 263

Smoking cessation: COPD treatment: A1AT augmentation: **intravenous A1AT** - **Alcohol avoidance** - **Hepatitis A and B vaccinations** - **Liver transplantation**: for end-stage, refractory liver disease

Answer 264

A hernia is a condition in which an organ or tissue pushes through a weak spot in a muscle or the surrounding tissue wall. In most cases, the hernia causes a bulge or lump in the abdomen.

Answer 265

- Irreducible - contents cannot be pushed back into place - Obstructed - bowel contents cannot pass as the intestine is obstructed

Answer 266

- Strangulated - ischaemia occurs as blood supply of the sac is cut off - this requires urgent surgery. - Incarceration - contents of the hernial sac are stuck inside by adhesions

Answer 267

Inguinal hernia The protrusion of abdominal contents through the inguinal canal - Account for 70% of all abdominal hernias - M>F

Answer 268

**Direct hernia:** hernia protrudes through the posterior wall of the inguinal canal. - Less common (20%) **Indirect hernia:** hernia protrudes through the deep inguinal ring and into the inguinal canal - More common (80%)

Answer 269

When assessing a hernia, always comment on the size of the neck/defect (narrow or wide), Hernias that have a wide neck, meaning that the size of the opening that allows abdominal contents through is large, are at lower risk of complications. While the contents can easily pass out of this opening, they can also easily be put back, which puts them at a lower risk of incarceration, obstruction and strangulation.

Answer 270

herniation of the abdominal contents through the femoral canal. This occurs below the inguinal ligament, at the top of the thigh. The opening between the peritoneal cavity and the femoral canal is the femoral ring. The femoral ring leaves only a narrow opening for femoral hernias, putting femoral hernias at high risk of: Incarceration Obstruction Strangulation

Answer 271

Incisional hernias occur at the site of an incision from previous surgery. They are due to weakness where the muscles and tissues were closed after a surgical incision

Answer 272

Umbilical hernias occur around the umbilicus due to a defect in the muscle around the umbilicus. Umbilical hernias are common in neonates and can resolve spontaneously. They can also occur in older adults

Answer 273

Epigastric hernia Being overweight, being pregnant, ascites, straining due to constipation

Answer 274

herniation of the stomach up through the diaphragm. The diaphragm opening should be at the level of the lower oesophageal sphincter and should be fixed in place.

Answer 275

Heartburn Acid reflux Reflux of food Burping Bloating Halitosis (bad breath)

Answer 276

Conservative (with medical treatment of gastro-oesophageal reflux) Surgical repair if there is a high risk of complications or symptoms are resistant to medical treatment

Answer 277

mild inherited disorder of the liver. It is characterized by episodes of elevated levels of bilirubin in the bloodstream - **its a common cause of unconjugated hyperbilirubinaemia**

Answer 278

Gilbert's Syndrome is caused by a **genetic mutation affecting the UGT1A1 gene,** which is responsible for encoding an enzyme involved in bilirubin metabolism. This mutation results in reduced activity of this enzyme, leading to higher levels of bilirubin in the blood.

Answer 279

The vast majority are adenocarcinomas, and most occur in the head of the pancreas (as opposed to the body and tail). tend to spread and metastasise early, particularly to the liver, then to the peritoneum, lungs and bones

Answer 280

Painless obstructive jaundice Yellow skin and sclera Pale stools Dark urine Generalised itching **New-onset diabetes or worsening of type 2 diabetes** -*think of PC in patients with this when they are trying to control it well* The presence of a palpable gallbladder and jaundice

Answer 281

Courvoisier’s law states that a palpable gallbladder along with jaundice is unlikely to be gallstones. The cause is usually cholangiocarcinoma or pancreatic cancer.

Answer 282

Trousseau's sign of malignancy - that in pancreatic cancer (and other things) , can **SEE MIGRATORY THROMBOPHLEBITIS** - this is **multiple venous thrombosis at different changing sites** (due to procoagulant factors made by cancer cells)

Answer 283

pancreatic protocol CT - ***indeed, suspected Pancreatic cancer is the only time a GP can directly refer for a CT*** **CA 19-9 (carbohydrate antigen)** is a tumour marker *that may be raised in pancreatic cancer. It is also raised in cholangiocarcinoma and a number of other malignant and non-malignant conditions.* Biopsy may be taken through the skin (percutaneous) under ultrasound or CT guidance,

Answer 284

surgical resection PLUS – pancreatic enzyme replacement CONSIDER – preoperative biliary stenting CONSIDER – neoadjuvant radiotherapy or chemoradiotherapy pallitative support

Answer 285

**CA 19-9 (carbohydrate antigen)** - a tumour marker raised in pancreatic cancer, and also cholangiocarcinoma

Answer 286

Cholangiocarcinoma *accounts for 10% of liver cancer*

Answer 287

- Palpation - enlarged, irregular, tender liver may be felt - Signs of chronic liver disease - Signs of decompensation - jaundice, ascites - Listen for bruit - murmur over the liver - Symptoms - Fever - Weight loss - Abdominal pain +/- ascites - Malaise

Answer 288

- **Surgery (not possible in 70% of patients at presentation)** - e.g. major hepatectomy, extrahepatic bile duct excision and caudate lobe resection - **Purcutaneous stenting or ERCP** - stenting of obstructed extrahepatic bililary tree improves QOL - **Liver transplantation**

Answer 289

- HBV - leading cause worldwide especially, if high viral load - HCV - Autoimmune hepatitis - Cirrhosis - NAFLD - Anabolic steroids

Answer 290

A small amount of paracetamol is metabolised by the P450 system into toxic ***N-acetyl-p-benzoquinone imine (NAPQI),*** a mitochondrial poison. Its normally **detoxified by conjugation with glutathione** In Paracetamol OD - NAPQI increases, **glutathione stores become depleted,** leaving NAPQI to remain unconjugated and resulting in hepatocellular damage.

Answer 291

- Signs - Jaundice - Encephalopathy - reduced GCS - consciousness - Tachycardia/ hypotension - Evidence of self-harm - Symptoms - Abdominal pain - Right upper quadrant pain - Nausea or vomiting - Confusion or coma

Answer 292

- **Date of ingestion**: is there a delay in presentation? - **Timing of ingestion**: single overdose or staggered - **Time since last ingestion** - **Weight**: if >110 kg, used 110 kg as the maximum weight for calculations. - **Pregnancy**: use pre-pregnancy weight to determine toxicity and current weight for treatment - **Total amount ingested** (mg/kg) - **Current suicidal risk**

Answer 293

- **Serum paracetamol:** levels should be measured at 4 hours post-ingestion. If presenting after 4 hours of ingestion, take levels immediately - **LFTs:** deranged liver function and rising INR - **Clotting screen:** PT and APTT prolonged in hepatocellular damage - **U&E:** severe toxicity results in renal failure - **Arterial blood gas:** s

Answer 294

- **Activated charcoal:** reduces intestinal absorption - Administered if the patient presents **within 1 hour** of ingestion - **N-acetylcysteine (NAC)**: *replenishes glutathione stores which bind NAPQI, the toxic metabolite*

Answer 295

- **Acute liver failure:** evidence of liver failure may warrant urgent liver transplantation, as per the King’s College Criteria - **Acute kidney injury -** due to acute tubular necrosis occurs in 25% of patients who have severe hepatic damage - **Anaphylactoid reaction**: NAC may cause an **anaphylactoid reaction** due to non-IgE mediated mast cell degranulation (10-50% of patients).

Answer 296

Because the liver produces **Thrombopoietin, the hormone that stimulates bone marrow to make platelets.** When the liver is damaged less of this is made leading to a reduction in platelet production

Answer 297

Unconjugated Bilirubin **undergoes Glucuronidation** (conjugated with glucuronic acid )to form Conjugated bilirubin, *(by enzyme glucuronosyltransferase)* Conjugated Billirubin is released in Bile and becomes **Urobilinogen** 90% of Urobilinogen becomes **Stercobilin (faeces)** and 10% becomes **Urobilin (recycled back to bile or urinated out)**

Answer 298

Alpha Fetoprotein is RIASED