Phase 2a Liver + friends diseases

Question 1

What are some functions of the liver and what are associated diseases should there be a problem with those functions?

Answer 1

• Oestrogen level regulation - Gynecomastia, palmar erythema, spider naevi

Albumin - Ascites + oedema

Clotting factors - bleeding disorders

Storage (vitamins, iron, copper fat) – Wilson’s haemachromatosis, A1AT deficiency

Immune system response - Kuppfer cells –> Spontaneous bacterial peritonitis

Detoxification - Hepatic encephalopathy

Bilirubin metabolism - Jaundice

Question 2

What is the normal AST:ALT
(Aspartate transaminase:Alanine transaminase)

What does a ratio of:
>2:1
>4.5:1
<0.9:1

Suggest

Answer 2

1:1 - normal

> 2:1 - Alcoholic liver disease (esp with increased GGT)

> 4.5:1 - Wilson’s/hyperthyroidism

<0.9:1 - NAFLD

Question 3

Where is ALT and AST usually found?

Answer 3

Liver, heart, kidney and muscles

Question 4

What does increased ALP (Alkaline phosphatase) suggest?

Answer 4

Increased biliary tree specific damage

Question 5

Acute liver failure

RF
Path
Symptoms
Investigations
Treatments

Answer 5

Rare, life threatening condition with a rapid decline in hepatic function. Characterised by Jaundice, coagulopathy (INR >1.5) and hepatic encephalopathy in patients with NO EVIDENCE of prior liver disease.

(if it occurs in patients with previous liver disease –> acute on chronic liver failure

RF - Chronic alcohol misuse, females, >40 years, fasting

PATHOLOGY
Acute liver failure - results in massive hepatocyte necrosis and can result in organ failure

Most common cause - PARACETAMOL OVERDOSE

Other causes: Autoimmune hepatitis, Hepatitis E, A and B, Budd chiari syndrome (obstruction of hepatic venous outflow)

SYMPTOMS
- Jaundice
- Coagulopathy
- Malaise, n+v
- Signs of hepatic encephalopathy
(West Haven criteria. Grade 1 - subtly impaired awareness, 2 - personality change, lethargy 3- somnolent, marked confusion 4 - coma

INVESTIGATIONS
First - Liver function test
- Increased bilirubin, increased PT/INR and decreased serum albumin
- Increased ALT and AST

Additional but not really required?
- FBC - (for haemolytic anaemia associated with Wilson’s disease)
- Abdominal ultrasound - to eliminate budd chiari syndrome
- EEG - electroencephalogram - assess hepatic encephalopathy

MANGEMENT
1st - Intensive care management
- Tracheal intubation
- Analgesia
- IV fluids

Then treat underlying cause
- Paracetamol causes - N acetylcysteine
- Budd chiari syndrome - LMWH

Treat complications
- Cerebral oedema - IV mannitol
- HE - Lactulose
- Ascites - Spironolactone
- Haemorrhage - vitamin K

Definitive - Liver transplant

Question 6

Symptoms of sepsis and treatment for sepsis

Answer 6

Sepsis - chills, confusion, fever, tachycardia, hypotension

Treatment with sepsis 6
Give 3 - Oxygen, antibiotics, fluids
Take 3 - cultures, lactate measurement and urine output

Question 7

Alcoholic Liver disease

RF
Path
Symptoms
Investigations
Treatments

Answer 7

Liver disease caused by chronic heavy alcohol ingestion

RF - heavy Alcohol consumption, female sex, smoking, hep C

PATHOLOGY
- Metabolism of alcohol produces FAT in the liver (through alcohol dehydrogenase and NADH)
- Reactive oxygen species are also produced which can damage hepatocytes (cause necrosis and apoptosis)

3 stages
Fatty liver undamaged (steatosis - initial fatty deposits) –> Alcoholic hepatitis (inflammation and necrosis) - mallory bodies –> Alcoholic liver cirrhosis (micronodular and irreversible)

SYMPTOMS
Early - RUQ discomfort, hepatomegaly

Later - more severe - Jaundice, ascites, palmar erythema, dupuytren’s contracture, asterixis

INVESTIGATIONS
First - LIVER FUNCTION TEST
- Increased bilirubin, decreased albumin, increased PT
- AST:ALT >2

FBC - Macrocytic anaemia (increased deposition of cholesterol on RBC membrane)

GS - Liver biopsy - shows extent of alcoholic liver disease

(Can do AUDIT and CAGE questionnaire)

TREATMENT
1st - STOP DRINKING ALCOHOL + give diazepam for alcohol withdrawal symptoms (delirium tremens)

• Consider prednisolone based on Maddrey’s discriminant function (>32 positive, poor prognosis)

Tranexamic acid (to reduce/prevent bleeding)- reduces mortality risk in GI bleeds

Definitive - Liver transplant

Complications - HE, Acites, hepatocellular carcinoma, Wernicke krsakoff syndrome

Question 8

2 questionnaires you use for alcoholic liver disease

Answer 8

First line - AUDIT questionnaire (10 MCQs)

CAGE questionnaire
- Do you ever think you should Cut down
- Do you get Annoyed at others commenting on your drinking?
- Do you ever feel Guilty about drinking?
- Do you drink in the morning (Eye opening)

2 or more considered dependent

Question 9

What does a patient need to do to be eligible for consideration for liver transplant?

Answer 9

Abstain from alcohol for at least 3 months.

Question 10

What is wernicke korsakoff syndrome?

Answer 10

Alcohol excess leads to thiamine (B1) deficiency as thiamine is poorly absorbed in the presence of alcohol.

Symptoms: Memory impairment and behavioural changes, ataxia, nystagmus, confusion

Medical emergency which can be treated with IV thiamine. (and abstain from alcohol)

Question 11

Non Alcoholic Fatty Liver Disease

RF
Path
Symptoms
Investigations
Treatments

Answer 11

Evidence of hepatic steatosis in the absence of significant alcohol consumption

NAFLD - Hepatic steatosis without evidence of hepatocellular injury
–>
NASH (non alcoholic steatohepatitis) - hepatic steatosis and inflammation with hepatocyte injury
–>
Fibrosis
–> Cirrhosis
(Associated with hypertension, obesity and diabetes)

Symptoms
Typically asymptomatic initially
- Obese patients may present with : fatigue, malaise, RUQ discomfort, hepatosplenomegaly

INVESTIGATIONS
Liver function test - Increased ALT (but ALT:AST <0.9)

GS - Liver biopsy

Liver ultrasound - use fibrosis 4 score to estimate risk of advanced fibrosis and need for liver biopsy

TREATMENT
First - Lifestyle modification- Healthy diet and exercise for weight loss (no smoking and alcohol)

Vitamin E to improve histological fibrotic liver appearance.

(Can lead to HCC, HE, Ascites, portal hypertension)

Question 12

Liver Cirrhosis

RF
Path
Symptoms
Investigations
Treatments

Answer 12

The result of chronic inflammation and damage to liver cells. –> characterised by fibrosis and replacement of functional liver cells with scar tissue - nodules of scar tissue form within the liver

RF - Alcohol misuse, IVDU, obesity

PATHOLOGY
Most common causes
- Alcohol related liver disease
- NAFLD
- Chronic viral hepatitis (B and C)

Hepatic fibrosis activates hepatic stellate cells –> they contract and increase portal resistance –> leading to portal hypertension. (leads to complications)

Compensated cirrhosis - early stage where liver can still perform functions despite fibrosis

Decompensated cirrhosis - Advanced stage where liver can’t compensate for extensive damage which leads to development of complications. (jaundice, ascites, HE)

SYMPTOMS
Abdominal features - hepatomegaly, splenomegaly, abdominal distension

Hand and nail features - leukonychia, palmar erythema, spider naevi, finger clubbing, dupuytren’s contracture

INVESTIGATIONS
LFT - low albumin, raised bilirubin, raised prothrombin time
- Platelet count reduced (liver has impaired ability to produce thrombopoietin)

Abdominal ultrasound - liver surface nodularity, ascites, splenomegaly

(Transient elastography for determining degree of fibrosis)

GS - Liver biopsy
(Use child pugh score for prognosis of patients with chronic liver failure/cirrhosis - severity of liver cirrhosis)

TREATMENT
3 things
1) Treat underling cause
- avoid alcohol, NSAIDS, high dose paracetamol, treat any hep B and C

2) Monitor complications
e.g. use ultrasound to monitor ascites and endoscopy to monitor oesophageal varices

3) Manage complications e.g. spironolactone/diuretics for ascites

2nd line - Liver transplant

Question 13

Chronic liver failure

Causes
Symptoms
Investigations
Treatment
What is it a huge risk factor of developing

Answer 13

Main cause: Alcoholic liver disease

Other causes:
- NAFLD
- Hepatitis B a. nd C
- Budd chiari
- Autoimmune

Symptoms
- Ascites, asterixis
- Clubbing, Coagulopathy
- Dupuytren’s contracture
- Palmar Erythema
- Gynaecomastia
- Hepatomegaly, HE, portal Hypertension
- Increase in size of parotid gland
- Jaundice
- Spider naevi

INVESTIGATIONS
- LFT (increased AST, ALT), ascitic tap culture (eliminates SBP/Identifies bacteria causing SBP)

• GS - Liver biopsy
  Assessing hepatic function –> Prothrombin time

Treatment
- Lifestyle modification prevents progression (decrease alcohol, decrease BMI)

Definite - liver transplant

Manage complication
HE - Lactulose
Ascites - diuretics
SBP

HUGE RISK OF DEVELOPING HEPATIC CELLULAR CARCINOMA

Question 14

Hepatitis A

RF
Path
Symptoms
Investigations
Treatments

Answer 14

• An RNA virus with a faecal-oral mode of transmission (not associated with Chronic liver disease like B and C)

PATHOLOGY
- Faeco-oral route of transmission (can be via foods - SHELLFISH)
- After oral inoculation –> virus enters hepatocytes and replicates –> virus particles secreted into bile and blood –> virus is either excreted in stool or reabsorbed via enterohepatic circulation –> (Liver injury occurs when cytotoxic T cells lyse the infected hepatocytes)

SYMPTOMS
Takes 1-2 weeks after infection.
Initial : (pre-jaundice) - fever, N+V, malaise

Afterwards: Jaundice, dark urine + pale stools (obstruction of bile duct due to liver inflammation), hepatosplenomegaly

Investigations
First - LFT - increased bilirubin, increased transaminase (high ALT than AST)

Hepatitis A viral serology –> Positive for IgM antibodies for hep A

TREATMENT
Supportive treatment (pain/itch relief)
(6 weeks self limiting)

For high risk/prevention –> Vaccine is available

Question 15

Hepatitis B

RF
Path
Symptoms
Investigations
Treatments

Answer 15

Double stranded DNA virus - transmitted by blood or bodily fluids
(Sex, vertical transmission, needles)

RF: IVDU, born in endemic region, healthcare workers

PATHOLOGY

SYMPTOMS
- Mostly asymptomatic till jaundice onset
–> Jaundice, hepatosplenomegaly, (possible hepatocellular carcinoma/cirrhosis + complications)

INVESTIGATION
FIRST - Serology
- Screening involves testing for HbcAb (core antibody) and HbsAg (surface antigen)
- Measuring IgM and IgG of HbcAb:
+ IgM - active infection (higher in acute, lower in chronic)
+ IgG - Past infection (where HbsAg is negative)

• If HbeAG is present –> patient is in an acute phase of infection where virus is actively replicating

MANAGEMENT
First (chronic) - Pegylated interferon alfa 2a

In severe symptoms - Antiviral therapy with entecavir

Acute –> supportive treatment e.g. fluids, healthy diet. (can achieve seroconversion without treatment)

Can use vaccine for PREVENTION

Question 16

What do these help to indicate?

Surface antigen (HbsAg)

E antigen (HbeAg)

Core antibodies (HbcAb)

Surface antibodies (HbsAb)

Hepatitis B virus DNA

Answer 16

Surface antigen - is an indication of active infection

E antigen - is a marker of viral replication and implies high infectivity

Core antibodies.- implies past or current infection

Surface antibodies - implies vaccination/past infection/
(possibly current infection also)

Hepatitis B virus DNA - a direct count of viral load

Question 17

Hepatitis C

RF
Path
Symptoms
Investigations
Treatments

Answer 17

An RNA virus causing inflammation of the liver

RF - Alcohol, White populated countries

PATHOLOGY
ALCOHOL CULTURE CAUSES IT)

Transmitted by: percutaneous blood exposure and bodily fluids: IVDU, sex

(Unsafe injection practices during medical treatment, IVDU, blood transfusion)

SYMPTOMS
Acute - often asymptomatic
Chronic - possible chronic liver disease symptoms - HEPATOSPLENOMEGALY, (ascites, jaundice, HE)

INVESTIGATIONS
1st - Screen for hepatitis C antibody and hepatitis C RNA virus
(some people would have cleared the virus without treatment - positive C antibody, negative C RNA virus)

MANAGEMENT
Direct Acting Antivirals
- Sofosbuvir + Ribavarin

Question 18

Hepatitis D

RF
Path
Symptoms
Investigations
Treatments

Answer 18

Defective RNA virus that requires hepatitis B virus surface antigen in order to propagate

RF- HBV infection, IVDU, sex

PATHOLOGY
Can infect susceptible hosts (with HBV) via:
1) Simultaneous co infection with HBV
2) Superinfection of an individual with chronic HBV infection
3) Blood, bodily fluids, sexual routes
(It increases the complications and disease severity of HBV)

SYMPTOMS
Initially- asymptomatic

(After incubation of 3-7 weeks –> Jaundice, ascites)

INVESTIGATION
Serology for:
- HBV surface antigen, surface antibody, core antibody, e antigen, e antibody,
- Serum HBV DNA
- Serum HDV RNA

MANAGEMENT
Supportive treatment + pegylated interferon alfa 2a

Question 19

Hepatitis E

Path
Symptoms
Investigations
Treatments

Answer 19

RNA virus transmitted by faecal oral route

PATHOLOGY
Spread via faecal oral route:
- Contaminated drinking water
- Consumption of UNCOOKED PORK/deer meat

RF - PREGNANT LADIES

Mostly self limiting

(May progress to chronic hepatitis and liver failure - in immunocompromised patients) - with mortality in pregnant ladies being 10-20%

SYMPTOMS
Initially - fever, nausea and vomiting

Later stage - abdominal pain, jaundice and hepatomegaly

INVESTIGATION
Serology
HEV IgM - acute infection
HEV RNA - viral load

TREATMENT
Supportive treatment - self limiting virus

Question 20

Autoimmune hepatitis

RF
Path
Symptoms
Investigations
Treatments

Answer 20

Chronic inflammatory disease of the liver. Characterised by the presence of circulating auto-antibodies with high serum globulin

RF - Females, other autoimmune diseases (SLE), genetic predisposition (HLA DR3/DR4), measles

PATHOLOGY
Type 1 - affects women in late 40s to 50s (less acute)
- Anti nuclear antibodies (ANA)
- Anti smooth muscle antibodies
- Anti soluble liver antigen (anti-SLA)

Type 2 - affects children or younger people (Acute hepatitis)
- Anti liver kidney microsomes (anti-LKM1)
- Anti liver cytosol antigen (Anti-LC1)

Symptoms
Some are asymptomatic, some present with
- ABD discomfort
- Hepatomegaly
- Jaundice

INVESTIGATIONS
Serology for:
- Anti nuclear antibodies (ANA)
- Anti smooth muscle antibodies (ASMA)
- (Anti soluble liver antigen (anti-SLA)
and)
- Anti liver kidney microsomal type 1 (anti-LKM1)
- Anti liver cytosol antigen (Anti-LC1)

MANAGEMENTS
High dose corticosteroid + immunosuppressant
Prednisolone + Azathioprine

Last resort liver transplant

Question 21

Symptoms and treatment of Crigler Najjar syndrome

Answer 21

Extremely rare

Symptoms - Severe jaundice with N+V
Persistent yellowing of eyes and skin which become apparent SHORTLY AFTER BIRTH

TREATMENT - Phototherapy (which helps breakdown unconjugated bilirubin)

(can result in kernicterus if untreated - bilirubin induced neurological damage - mostly in infants)

Question 22

Gilbert syndrome

RF
Path
Symptoms
Investigations
Treatments

Answer 22

An autosomal recessive disorder where there is decreased levels of the enzyme UDP glucuronosyltransferase resulting in impaired conjugation of bilirubin. (Non haemolytic unconjugated hyperbilirubinaemia)

RF - post pubertal age, family history of Gilbert syndrome, T1DM

PATHOLOGY
- UDP glucuronosyltransferase is an enzyme responsible for the rate limiting step of bilirubin conjugation
- Because of an autosomal recessive mutation in the UGT1A1 gene - enzymatic function becomes defective resulting in unconjugated hyperbilirubinemia

SYMPTOMS
- Painless jaundice
- Crigler Najjar syndrome - more severe jaundive with N+V (persistent yellowing of the skin and whites of eyes which become apparent shortly after birth)

INVESTIGATION
- Unconjugated bilirubin - elevated

(UGT1A1 genotyping - presence of mutation)

TREATMENT
No need treatment, just patient education (they may become jaundiced in certain situations of increased stress: fasting, sleep deprivation, heavy physical exertion)

For Crigler Najjar syndrome (another flash card ) - but phototherapy

Question 23

Causes of prehepatic jaundice - 2

Answer 23

Jaundice - result of accumulation of bilirubin in the bloodstream and subsequent deposition in the skin, sclera and mucous membranes.

Pre hepatic causes
- An increase in unconjugated bilirubin due to increased bilirubin production –> HAEMOLYTIC ANAEMIAS (sickle cell, autoimmune, thalassemia, G6PD deficiency, malaria)
- Portal vein stenosis
- Gilbert’s syndrome - mutation to UGT1A1 gene - decreased conjugation of bilirubin

Question 24

Causes of hepatic jaundice - 5

Answer 24

intrahepatic/hepatic causes
- Conditions which DAMAGE the structure/function of hepatocytes e.g infections, toxin, cancer, autoimmune conditions
- Viral hepatitis, alcohol, drugs, hepatocellular carcinoma, liver cirrhosis, ALD/NAFLD
- Haemochromatosis, A1AT deficiency, wilson’s disease

Question 25

Causes of post hepatic jaundice

What changes in your stools do you see?

Answer 25

• Occurs due to obstruction of bile drainage - conjugated hyperbilirubinaemia

1) Choledocholithiasis (stones in the Common bile duct)
2) Pancreatic cancer (palpable gallbladder) - pancreas head
3) Cholangiocarcinoma
4) Mirizzi syndrome - gallstones stuck externally compressing the CBD and causing obstruction

Stool changes:
1) Darker urine - conjugated bilirubin builds up in the blood and passes out as dark urine
2) Pale stools - conjugated bilirubin is not able to leave the common bile duct due to an obstruction

Question 26

How would you differentiate between biliary colic, cholecystitis and ascending cholangitis based on a patient’s presentation?

Answer 26

Charcot’s triad
1) Biliary colic (stone in cystic/common bile duct) –>RUQ pain
2) Cholecystitis (inflammation of the gallbladder) –> RUQ pain and fever
3) Ascending cholangitis (ascending bacterial infection of the biliary tree) –> RUQ pain, fever and jaundice

Question 27

Briefly talk about the process of the breakdown of RBC

Answer 27

1) Haemoglobin is broken down –> to form haem and globin (globin is broken down and transported to the bone marrow to make more haemoglobin)
2) Haem –> biliverdin (via heme oxgenase)
3) Biliverdin –> unconjugated bilirubin (via biliverdin reductase) which is lipid soluble and can cross cell membranes to enter blood.
4) Unconjugated bilirubin is taken up by hepatocytes and conjugated with glucuronic acid –> conjugated bilirubin (water soluble)
5) Conjugated bilirubin –> released into biliary system and excreted in bile
6) Conjugated bilirubin is hydrolysed by bacteria in the intestines –> urobilinogen or it is oxidised into stercobilin

(Urobilinogen - excreted in urine and stercobilin excreted in stool)

Question 28

Definition of cholestasis

Answer 28

Blockage to the flow of bile

Question 29

Cholelithiasis

RF
Path
Symptoms
Investigations
Treatments

Answer 29

Presence of gallstones in the gallbladder

RF - Increasing age, females, obesity, diabetes, family history (Fair-caucasion, Forty, Fat, Female, fertile)

PATHOLOGY and symptoms
Due to the presence of gallstones which could block or irritate the cystic duct/bile duct, –> There is COLICKY RUQ pain - pain is worse after a fatty meal and may radiate to the back.

Pain intensifies over time, peaks in severity and gradually subsides in a cyclical manner. CONSTANT SEVERE EPISODES OF PAIN >30 MINS.

INVESTIGATION
Abdominal ultrasound - where you may find:
- Gallstones in the gallbladder/ducts
- Dilation of the ducts
- Acute cholecystitis

LFT - show a large increase in ALP (in an obstructive picture) - maybe slight increase in transaminases

Can do Endoscopic retrograde cholangiopancreatography - if stone in bile duct(ERCP_= endoscope inserted through oesophagus and stomach to sphincter of oddi. (can inject contrast)

TREATMENT
Analgesia - diclofenac/paracetamol + LAPAROSCOPIC CHOLECYSTECTOMY

Question 30

Choledocholithiasis

Answer 30

Gallstones in the bile duct

Question 31

Biliary colic

Answer 31

Intermittent (coming and going) RUQ pain caused by gallstones blocking the cystic duct (or bile duct) - typically occurs after eating a large fatty meal which causes contraction of the gallbladder.

Question 32

Cholecystitis and cholangitis

Answer 32

Inflammation of the gall bladder

Cholangitis - inflammation of the bile ducts

Question 33

What do gallstones consist of?

Answer 33

Mainly cholesterol. (some bilirubin)
Some consist of pigment (black)

Question 34

Cholecystitis

RF
Path
Symptoms
Investigations
Treatments

Answer 34

Gallbladder inflammation - a major complication of cholelithiasis

RF - Gallstones, physical inactivity

PATHOLOGY
- Mostly caused by complete cystic duct obstruction due to a gallstone (neck of gallbladder/cystic duct) - 90% –> bile is trapped in the gallbladder causing irritation and increased pressure within the gallbladder.

SYMPTOMS
- RUQ pain (and tenderness)
- FEVER
- Positive MURPHY’s SIGN –> patient inhales while doctor palpates right subcostal area - if there is pain on contact with inflamed gallbldder or patient stops inspiring, murphy’s sign is positive.
(Pain may be referred to right shoulder (via phrenic nerve))

INVESTIGATIONS
- Abdominal ultrasound scan - shows evidence of cholecystitis:
+ Thickened gallbladder wall
+ Stones in gallbladder
+ Pericholecystic fluid (fluid around the gallbladder) - caused by the inflammation
GS - MRCP

FBC - leukocytosis (inflammation triggers immune response)

TREATMENT
Laparoscopic cholecystectomy - (should be done within 1 week of diagnosis according to NICE)
+
Analgesia - (ibuprofen/diclofenac)

(Antibiotics -Piperacillin and tazobactam….. Ciprofloxacin)

Question 35

Ascending Cholangitis

RF
Path
Symptoms
Investigations
Treatments

Answer 35

An infection of the biliary tree (most commonly caused by obstruction)

RF- >50 years, cholelithiasis, strictures

Pathology
2 main causes:
1) Obstruction of the bile duct (e.g. gallstones)

2) Infection introduced during ERCP procedure - E.coli, Klebsiella, enterococcus.

SYMPTOMS
Charcot’s triad
- RUQ pain
- Fever
- Jaundice (increased bilirubin)

(Reynold’s pentad: + changed mental state and hypotension)
+ possible pale stools

INVESTIGATION
First - Abdominal ultrasound - dilated bile duct, common bile duct stones

LFTs - increased conjugated bilirubin

GS - MRCP (magnetic resonance cholangiopancreatography) - non invasive (ERCP is invasive but can be used for treatment)

TREATMENT
1st - IV antibiotics (for E.coli ceftriaxone)

After 24 hours-
Endoscopic retrograde cholangiopancreatography (ERCP) - places a drainage stent to allow for biliary tree decompression and stone extraction.

(Consider cholecystectomy to prevent recurrence once stable)

Question 36

What is a main complication of Ascending cholangitis?

Answer 36

Sepsis

• Biliary obstruction causes increased backflow of biliary sludge which allows bacteria to move from the intestines through the ampulla of vater, and colonise the biliary tree

Question 37

Primary biliary cholangitis

RF
Path
Symptoms
Investigations
Treatments

Answer 37

An autoimmune condition of the small intrahepatic bile ducts.

RF - Females, 40-65 years, RA, systemic sclerosis, family history of PBC/autoimmune disease

PATHOLOGY
Inflammation and damage to the intrahepatic bile ducts can lead to obstruction of bile flow (CHOLESTASIS) - can lead to chronic inflammation –> liver fibrosis –> cirrhosis and failure

ASSOCIATED SJORGEN’s syndrome,

SYMPTOMS
Initially 50% of patients asymptomatic but have chance of Itching and fatigue

Followed by Jaundice, abdominal pain, hepatomegaly and steatorrhoea (reduced bile acids in GI tract result in malabsorption of fat, and greasy stools)
(Pale stools and dark urine)

Investigations
- LFT - increased ALP, increased conjugated bilirubin

Serology for autoantibodies
- Anti mitochondrial antibodies (AMA) - most specific to PBC
- (Anti nuclear antibodies present sometimes)

FIRST LINE IMAGINE - ABDOMINAL ULTRASOUND (to rule out other causes of cholestasis - obstructive mass, PSC)

TREATMENT
1st line - Ursodeoxycholic acid
(decreases toxicity thus decreasing inflammation and reducing cholestasis – and dampens immune response)

Cholestyramine - give for pruritus

(Consider liver transplant)

Question 38

Primary Sclerosing Cholangitis

RF
Path
Symptoms
Investigations
Treatments

Answer 38

Autoimmune destruction of intrahepatic and extrahepatic bile ducts (may not be considered a pure autoimmune condition as some genetics play a part) genetic predisposition

RF - Males, 40-50, IBD
(Strong association with ULCERATIVE COLITIS)

PATHOLOGY
Inflammation and injury of bile ducts lead to fibrosis and multi focal stricture formation –> leading to obstruction of the bile ducts –> which further leads to:
- Progressive fibrosis and obliteration of the small ducts
- Bile stasis
- Obstruction of the flow of the bile
(Chronic bile obstruction leads to hepatitis, fibrosis and cirrhosis)

SYMPTOMS
Often asymptomatic but symptoms include:
- RUQ pain
- Pruritus and fatigue
- Charcot’s triad (jaundice, fever, RUQ pain)

INVESTIGATIONS
- LFT - increased ALP, increased GGT supports liver origin rather than bone origin (for raise in ALP)

(pANCA positive but not helpful in diagnosis)

GS - MRCP - beaded appearance of bile ducts (look at any strictures of intra/extra hepatic ducts)

TREATMENT
- no proven effective treatment

Conservative treatment (lifestyle changes - maintain healthy wait, limit alcohol)
- ERCP can be used to treat strictures
- Colestyramine given for pruritus relief

Definitive treatment - liver transplant

LEADS TO CHOLANGIOCARCINOMA

Question 39

Key differences between PSC and PBC

Answer 39

PBC - Women (typical autoimmune disease)
PSC - Men (Atypical autoimmune disease)

PBC - associated with other autoimmune conditions e.g. sjorgens, SLE
PSC - associated with Ulcerative colitis

Investigations
PBC - LFT, serology (AMA positive), abdominal ultrasound
PSC - LFT, MRCP
(This is because PBC is an autoimmune disease whereas PSC has genetic predisposition + UC)

Treatment
PBC - Ursdeoxycholic acid, colestyramine

PSC - conservative treatment (lifestyle changes) + colestyramine

Question 40

Acute pancreatitis

RF
Path
Symptoms
Investigations
Treatments

Answer 40

Inflammation of the pancreas associated with acinar cell injury

RF - Middle aged women, young-middle aged men, gallstones, alcohol

PATHOLOGY
Mostly caused by gall stones (UK). And excessive alcohol consumption (world wide)

I GET SMASHED
Idiopathic
Gallstones (most common? with heavy alcohol use)
Ethanol (Alcohol)
Trauma
Steroids
Mumps
Autoimmune
Scorpion sting
Hyperlipidaemia/hypercalcemia
ERCP
Drugs

Gallstone pancreatitis - gallstones are trapped at the end of the biliary system, blocking ampulla of vater –> blocking flow of bile and pancreatic juice into the duodenum –> bile refluxes into the pancreatic duct, preventing secretion of pancreatic juice –> which results in accumulation of digestive enzymes in the pancreas –> inflammation

(Alcohol is directly toxin to pancreatic cells)

SYMPTOMS
- Severe sudden onset epigastric pain radiating to the back (worsens with movement and eases with fetal position)
- N+V
- Grey Turner sign (lateral abdominal wall bruising)
- Cullen sign (bruising around umbilicus)

INVESTIGATIONS
GS - Blood test for serum lipase/serum amylase
(Lipase - elevated for longer
more specific) –> Leakage from pancreatic cells

LFT - Elevated ALT (suggests gallstone pathology)

Ultrasound - diagnostic for gallstones

Assess severity - using glasgow score

TREATMENT
ABCDE
- IV fluid resuscitation
- Analgesia
- IV antibiotics if infection
Nil by mouth

Use ERCP for gallstones
(Metronidazole for suspected bacterial infection)

Question 41

Complications of acute pancreatitis

Answer 41

ARDS - inflammatory mediators released during pancreatitis may damage alveolar capillary membrane and destroy pneumocytes

Acute renal failure

Question 42

Chronic pancreatitis

RF
Path
Symptoms
Investigations
Treatments

Answer 42

Chronic inflammation in the pancreas results in fibrosis and reduced function of the pancreatic tissue

RF - Alcohol, smoking, family history

PATHOLOGY
Mostly caused by alcohol
Caused by these also:
- Recurrent acute pancreatitis
- Idiopathic pancreatitis

SYMPTOMS
- Dull epigastric pain radiating to the back (diminished on sitting forwards and exacerbated by alcohol)

• Steatorrhoea (Exocrine), Diabetes Mellitus (Endocrine), weight loss and malnutrition

INVESTIGATIONS
1st - Faecal fat - increased (indicator of exocrine function)

GS - Abdominal US and CT scan –> shows pancreatic calcification + dilated pancreatic duct (diagnostic)

(unlikely to see increased lipase and amylase)

TREATMENT
1st - Alcohol and smoking cessation + analgesia (ibuprofen)

For patients with exocrine pancreatic insufficiency –> Pancreatin (pancreatic enzyme replacement therapy)
(Insulin regime for diabetes)

Question 43

Portal hypertension

RF
Path
Symptoms
Investigations
Treatments

Answer 43

Most commonly due to a complication of liver cirrhosis (pathological increase in pressure in the portal vein - abdominal organs to liver)

RF - Liver cirrhosis

PATHOLOGY
Causes include
1) Pre hepatic (increased pressure in the portal vein before reaching the liver)
- Portal vein thrombosis
- Splenic vein thrombosis

2) Hepatic (liver related factors contributing to increased pressure)
- Liver cirrhosis - most common in UK
- Schistosomiasis (parasitic infection) -> most common worldwide

3) Post hepatic (Conditions affecting outflow tract)
- Budd chiari syndrome (obstruction of hepatic venous flow)
- Constrictive pericarditis
- Valvular heart disease
(These conditions elevate pressure in the right side of the heart leading to increased resistance to blood flow from the liver)

Cirrhosis and hepatic fibrosis increases resistance to flow by activating stellate cells which become contractile, resulting in portal hypertension.
–> resulting in compensatory mechanisms (Splanchnic vasodilation and oesophageal varcies)

SYMPTOMS
Mostly asymptomatic
- Can present with oesophageal varices which can rupture

(Hepatosplenomegaly, ascites)

Investigations
For oesophageal varices –> oesophagogastroduodenoscopy

MANAGEMENT
- Carvedilol - beta blocker

Question 44

Ascites

RF
Path
Symptoms
Investigations
Treatments

Answer 44

A pathological collection of fluid in the peritoneal cavity

PATHOLOGY
- Most commonly caused by cirrhosis (75%)
(Sodium retention is a major factor)

Split into 2
1) Non peritoneal disease
- Cirrhosis, ALD, budd chiari, constrictive pericarditis, heart failure –> Conditions causing PORTAL HYPERTENSION - force fluid out of blood vessels into surrounding cavities
- Also NEPHROTIC SYNDROME - causing HYPOALBUMINEMIA

2) Peritoneal disease
- Infectious peritonitis (tb, chlamydia, shistosoma) –> causing INFLAMMATION
- SLE
(Malignant ascites)

SYMPTOMS
- Abdominal distention (may have severe pain if SBP)
- Bloating
- Shifting dullness (also an investigation)

INVESTIGATION
1) Shifting dullness on exam
Percussing central abdomen when supine = resonant + tapping on flank = dull due to fluid
Next
Percussing opposite flank when patient lying on one side will be resonant as fluid shifted with gravity and bowel float up (fluid makes dull sound)

2) Ascitic tap (paracentesis) - culture to determine presence of bacterial/fungal infections

3) Serum ascites albumin gradient
- >1.1g/dl = ascites due to increased hydrostatic pressure (transudate)
- <1.1 g/dl = ascites due to inflammation mediated exudation (peritonitis, pancreatitis) - exudate

4) Ultrasound

TREATMENT
- Diuretics –> spironolactone

Paracentesis - drains fluid

Liver transplant (last resort)

Question 45

Peritonitis

RF
Path
Symptoms
Investigations
Treatments

Answer 45

An inflamed peritoneal cavity

RF - Decompensated liver cirrhosis, low ascitic protein, GI bleeding

PATHOLOGY
Primary –> Spontaneous bacterial peritonitis – associated with spontaneous infection of ascitic fluid in patients with liver disease
(Common bacteria: E.coli, S.aureus, Klebsiella pneumoniae)

Secondary –> Localised peritonitis (caused by organ inflammation) - appendicitis, cholecystitis

SYMPTOMS
- Severe abdominal pain
- Fever
- Guarding
- Rebound tenderness
- (Signs of ascites - shifting dullness)

INVESTIGATION
- Ascitic tap
Shows neutrophilia, and culture shows growth of causative organism

• Elevated ESR and CRP
• Imaging - CT scan (looking for perforated colon)

MANAGEMENT
ABCDE
- IV fluids for resuscitation, IV antibiotics (Cefotaxime, metronidazole)

Definitive - Peritoneal lavage (surgical cleaning out of peritoneum)

Question 46

A1AT deficiency

RF
Path
Symptoms
Investigations
Treatments

Answer 46

An autosomal recessive genetic disorder resulting in deficiency of A1AT enzyme
(Alpha 1 antitrypsin)

RF - Family history of A1AT deficiency, Males, 32-41

PATH -
A1AT is produced in the liver.
In A1AT deficiency there is a mutation of SERPINA 1 gene on chromosome 14.

A1AT is a protease inhibitor which inhibits neutrophil elastase which breaks down elastin–> in the LUNGS, A1AT deficiency leads to excess protease enzyme attacking the connective tissue –> leading to panacinar emphysema (lung tissue + alveolar damage) - accelerated with smoking.

A1AT is produced in the LIVER - abnormal mutant versions - the Z allele can get stuck and aggregate in the liver causing inflammation –> which can lead to fibrosis, cirrhosis and potentially HCC.

SYMPTOMS: (like COPD) - Chronic cough, dyspnoea, possible jaundice (if A1AT deficiency leads to liver failure), wheezing and chest hyperinflation (Barrel chest)

INVESTIGATION
- First Serum A1AT - low <20micromol
- Barrel chest on exam

Chest X-ray - shows emphysematous changes (destruction of alveoli)

Spirometry - showing reduced FEV1 (obstructive cause as there is loss of elastic recoil in the lungs, contributing to airway collapse)

Gene sequencing - Mutations in the SERPINA 1 gene

TREATMENT
1st - Stop smoking and manage emphysema (with SABA, LABA)

Question 47

Wilson’s disease

RF
Path
Symptoms
Investigations
Treatments

Answer 47

An autosomal recessive disease of copper overload caused by mutations in the ATP7B gene on chromosome 13

RF - teenagers 10-25, family history

PATHOLOGY
ATP7B encodes for an enzyme that facilitates transmemberane transport of copper (P type ATPase) .
–> A lack of the protein leads to decreased copper excretion from the liver –> copper overloads in the hepatocytes –> if hepatic storage capacity is exceeded –> copper is released into the circulation and deposited into organs like the liver and basal ganglia –> it can present as liver disease or neurological disorder.

SYMPTOMS
Hepatic - Chronic hepatitis –> jaundice, coagulopathy, renal failure (hypoalbuminemia)

Neurological - Cognitive impairment, dysdiadochokinesis, parkinsonism, memory impairment, dysarthria (speech difficulties)

Presence of Kayer Fleischer rings - gold brown pigments of copper deposition in the cornea.

INVESTIGATIONS
24 hour urinary copper - high (serum is low as they are deposited in tissue)

Serum ceruloplasmin - low (protein that carries copper around the body)

GS - Liver biopsy - increased copper content

(Slit lamp examination for kayer fleishcher rings)
(Genetic testing for ATP7B mutation)

TREATMENT
1st - Oral chelation therapy to remove excess copper from the body –> Penicillamine

zinc acetates (zinc inhibits intestinal absorption of copper)

(Dietary restriction of copper)
Last resort - liver transplant

Question 48

Haemochromatosis

RF
Path
Symptoms
Investigations
Treatments

Answer 48

An autosomal recessive disorder resulting in excessive total body iron and deposition of iron in tissues.

RF- Middle aged males, white ancestry

PATHOLOGY
- C282Y mutation in HFE gene on chromosome 6 (HFE gene regulates iron metabolism)
- In C282Y mutations, hepatic hepcidin which decreases the level of iron by reducing dietary absorption and inhibiting iron release from storage, is low. – meaning iron will continue to be absorbed despite full stores.
- Iron can accumulate in organs e.g. liver, heart, anterior pituitary, leading to organ damage.

SYMPTOMS
HYPOGONADISM (damage to anterior pituitary - loss of libido, impotence), bronze discolouration of skin (pigmentation), hepatomegaly, fatigue
Arthralgia!

INVESTIGATIONS
Iron studies- Increased serum ferritin, increased serum iron, increased transferrin saturation
(Increased ALT and increased ferritin should indicate haemochromatosis - iron accumulation in the liver can cause damage to it, increasing ALT)

Genetic testing for HFE mutation

GS - Liver biopsy (with perl’s stain) - to assess degree of liver damage. (shows raised iron content)

TREATMENT
Venesection + lifestyle modifications (decreased iron diet - red meat)

If CI
2nd line - iron chelation with desferrioxamine

Question 49

Pancreatic cancer

RF
Path
Symptoms
Investigations
Treatments

Answer 49

Adenocarcinoma of the exocrine pancreas

RF - Smoking, family history, chronic pancreatitis, alcohol)

PATHOLOGY
- Most cancers are located in the head (65%), then the body then tail.

A tumour in the head of the pancreas can grow large enough to compress bile ducts resulting in obstructive jaundice.

SYMPTOMS
- Positive Courvoisier’s sign - painless palpable gallbladder and jaundice
- Pale stools and dark urine
- Epigastric pain radiating to the back (relieved on sitting forward)
- Weight loss

INVESTIGATIONS
First line - Abdominal ultrasound (pancreatic mass, dilated bile ducts)

GS - Pancreatic CT - used to diagnose and stage cancer

Cancer antigen 19-9 biomarker - elevated (could be false positive)

TREATMENT
Poor prognosis (5 year survival - 3%)

Stage 1-2 –> Pylorus preserving pancreaticoduodenectomy (Modified whipple procedure) + chemotherapy (+ pancreatin)

Stage 3 - palliative care

Question 50

Where can pancreatic cancers metatasise?

Answer 50

Liver, peritoneum, lungs and bones

Question 51

Hepatocellular carcinoma

RF
Path
Symptoms
Investigations
Treatments

Answer 51

Primary cancer arising from hepatocytes (in predominantly cirrhotic liver)

RF- Liver cirrhosis, HBV, HCV, chronic heavy alcohol use

Primary liver cancer - Hepatocellular carcinoma (cancer originating in the liver)

Secondary liver cancer - Cancer originating outside the liver and metastasises to the liver. From GIT, lungs, breast

SYMPTOMS
- symptoms of decompensated liver failure : Jaundice, ascites, HE, abdominal pain, weight loss

INVESTIGATIONS
First line imaging - liver ultrasound

GS imaging - CT (also for staging)

Alpha fetoprotein - may be elevated (tumour marker for hepatocellular carcinoma)

TREATMENT
Early disease - surgical resection of tumour

Transarterial chemo-embolisation with doxorubicin (drug causes embolisation that blocks the vessel supplying blood to the tumour)

Definitive - Liver transplant

Question 52

Which cancers can spread to the liver?

Whats the treatment

Answer 52

Secondary liver cancer

From GIT, lungs, breast

Surgical resection of primary tumour + chemotherapy

Question 53

Cholangiocarcinoma

RF
Path - most common site
Symptoms
Investigations
Treatments

Answer 53

Cancer arising from the bile duct (biliary tree)

RF - >50 years, cholangitis, choledocholithiasis, cholecystolithiasis

PATHOLOGY
-(Can be divided into intrahepatic or extrahepatic)
- Mostly adenocarcinomas
- Most common side is perihilar region (where right an left hepatic ducts join to form common hepatic duct)

SYMPTOMS
- Symptoms of obstructive jaundice - painless jaundice, dark urine, pale stools, weight loss, pruritus, fever

INVESTIGATIONS
First line imaging
- Abdominal ultrasound (identifies lesions)
- CT - identifies any mass

Serum CA 19-9 – elevated
LFT - increased ALP and conjugated bilirubin

GS - ERCP

TREATMENT
- Poor prognosis unless diagnosed early – early disease –> surgical resection + chemotherapy

Question 54

Symptoms of chronic liver disease

Answer 54

Ascites, Bruising, Clubbing, Duputyren’s contracture, Erythema, foul breath, gynaecomastia, hepatomegaly, increased size of parotid gland, jaundice

Question 55

Irreversible and reversible complications of haemochromatosis

Answer 55

Reversible - Cardiomyopathy (conduction abnormalities due to iron infiltration into the heart –> arrhythmias)

Irreversible - Diabetes mellitus

Question 57

What is Maddrey’s discriminant function?

Answer 57

A score that helps to suggest which patients with alcoholic hepatitis may have a poor prognosis and benefit from steroid administration.

Question 58

Most common causes of liver cirrhosis

and

Acute liver failure

Answer 58

Most common causes of liver cirrhosis
- Alcohol related liver disease
- NAFLD
- Chronic viral hepatitis (B and C)

For acute liver failure
Most common cause - PARACETAMOL OVERDOSE

Other causes: Autoimmune hepatitis, Hepatitis E, A and B, Budd chiari syndrome (obstruction of hepatic venous outflow)

Question 59

Symptoms of functional dyspepsia (the ones that help to identify it)

Answer 59

• Epigastric burning pain
• Post prandial fullness
• Early satiety
  (Structurally normal endoscopy)