HEPATOLOGY Flashcards

Question 1

Q

What is acute liver failure?

Answer

A

severe acute liver injury for fewer than twenty-six weeks duration with encephalopathy and impaired synthetic function (INR of 1.5 or higher) in a patient without cirrhosis or preexisting liver disease

Question 2

Q

How is acute liver failure categorised?

Answer

A

Hyperacute - hepatic encephalopathy within 7 days of noticing jaundice. Best prognosis as much better chance of survival and spontaneous recovery.
Acute - hepatic encephalopathy within 8-28 days of noticing jaundice
Subacute - hepatic encephalopathy within 5-12 weeks of noticing jaundice. Worst prognosis as usually associated with shrunken liver and limited chance of recovery

Question 3

Q

How is acute liver failure characterised?

Answer

A

Coagulopathy of hepatic origin (INR >1.5)
Altered levels of conciousness due to hepatic encephalopathy
Also usually accompanied by transaminitis and hyper bilirubinaemia

Question 4

Q

Whats the most common cause of acute liver failure in Europe?

Answer

A

Drug-induced liver injury

Question 5

Q

How can drug-induced liver injury be divided?

Answer

A

Paracetemol DILI
Non-paracetamol DILI

Question 6

Q

What is what is transaminitis?

Answer

A

Deranged LFTs - high transaminases e.g. AST and ALT

Question 7

Q

What is acute liver injury?

Answer

A

severe acute liver injury from a primary liver aetiology.
It is characterised by liver damage (i.e. elevated transaminases) and impaired liver function (e.g. jaundice and coagulopathy with INR > 1.5).
Hepatic encephalopathy is absent.

Question 8

Q

What is secondary liver injury?

Answer

A

Severe acute liver injury but with no evidence of a primary liver insult e.g. sepsis or ischaemic hepatitis

Question 9

Q

Worldwide, what is the most common cause of acute liver failure?

Answer

A

Viral - hepatitis

Question 10

Q

What are the primary causes of acute liver failure?

Answer

A

Hepatitis
Paracetamol
No paracetemol meds - statins, carbamazepine, Ecstacy
Toxin induced - death cap mushrooms
Budd-chiari sundrome
Pregnancy related
Autoimmune hepatitis
Wilsons disease

Question 11

Q

What are the secondary causes of acute liver failure?

Answer

A

Ischaemic hepatitis
Liver resection
Severe infection e.g. malaria
Malignant infiltration
Heat stroke
Haemophagocytic syndromes

Question 12

Q

Whats the pathophysiology of acute liver failure?

Answer

A

Depends on underlying aetiology but most cases = direct insult to the liver = massive hepatocytes necrosis = prevents normal liver function = release of toxins and cytokines = severe systemic inflammation
As the condition progresses it can lead to a hyper dynamic circulatory state with low systemic vascular resistance. This causes poor peripheral perfusion and multi-organ failure.
Also at high risk of infections due to decrease immunity
Marked cerebral oedema occurs due to hyperammonaemia causing cytotoxic oedema and increased cerebral blood flow that disrupts cerebral auto regulation = hepatic encephalopathy

Question 13

Q

What are the clinical features of acute liver failure?

Answer

A

Jaundice
Hepatic encephalopathy - confusion, altered mental status, asterixis, coma
Features of chronic liver disease - spider naevi, palmar erythema, leuconychia (may suggest first presentation of decompensated cirrhosis rather than ALF)
RUQ pain
Hepatomegaly
Ascites
Bruising and bleeding - coagulopathy
Hypotension and tachycardia
Raised intracranial pressure - papilloedema, bradycardia, hypertension, low GCS

Question 14

Q

How is the severity of hepatic encephalopathy graded?

Answer

A

Using the West Haven criteria

Grade 1 - change in behaviour with minimal change in level of consciousness. May have mild asterixis or tremor.
Grade 2 - gross disorientation, drowsiness, asterixis and inappropriate behaviour
Grade 3 - marked confusion, incoherent speech, sleeping most of the time but rousable to verbal stimuli. Asterixis less noticeable, elements of rigidity.
Grade 4 - coma that is unresponsive to verbal or painful stimuli. Evidence of decorticate or decerebrate posturing.

Question 15

Q

What urgent blood tests are needed for ALF?

Answer

A

FBC
U&Es
LFTs including conjugated and unconjugated bilirubin
Bone profile
BG
Arterial ammonia
Arterial blood gas (pH and lactate)
Coagulation-urgent INR
Lactate dehydrogenase
Lipase/amylase: pancreatitis complication of ALF
Blood cultures: sepsis is major cause of morbidity and mortality

Question 16

Q

What is done for a non-invasive liver screen?

Answer

A

A series of tests that are critical to determine the aetiology.

Serum/urine tox screen
Paracetemol serum level
Autoimmune markers - ANA, autoantibodies, immunoglobulins, ANCA
Viral screen

If they are all negative then an alternative cause for ALF needs to be determined.

Question 17

Q

How do you screen for hep A?

Answer

A

Check for anti-HAV IgM (hep A virus)
Be aware this may be positive for up to 6 months after clinical features subside
IgG antibody indicates past exposure

Question 18

Q

How do you screen for hep B?

Answer

A

HBsAg - for active infection
HBcAb (core antibody) - for previous infection

If these are positive then do further testing for HbeAg and viral load with HBV DNA

Question 19

Q

How do you screen for Hep C?

Answer

A

Anti-HCV
If positive then do hep C RNA testing.

Question 20

Q

How do you screen for Hep E?

Answer

A

Anti-HEV IgM
HEV RNA levels

Question 21

Q

Other than hepatitis, what viruses should you screen for when considering acute liver failure?

Answer

A

CMV
EBV
Herpes simplex virus
Varicella zoster virus
Parvovirus

Question 22

Q

What imaging should you do for acute liver failure?

Answer

A

Doppler ultrasound to assess the patency of hepatic and portal veins and for evidence of pre-existing cirrhosis
CT abdomen and pelvis may be required to examine the liver architecture, volume, vascular integrity and to exclude complications such as pancreatitis

Question 23

Q

What are contraindications to liver transplant?

Answer

A

Previous cirrhosis which would indicate decompensated cirrhosis rather than ALF
Heavy alcohol use
Significant comorbidities
Terminal illness

Question 24

Q

Whats the overal 1 year survival following an emergency liver transplantation?

Question 25

Q

What are the predictors of poor prognosis for acute liver failure?

Answer

A

Encephalopathy
Extrahepatic organ failure - particularly AKI
Indeterminate aetiology
Subacute ALF
Certain biochemical markers

Question 26

Q

What is the King’s college criteria?

Answer

A

clinical criteria that are used to select patients to undergo emergency liver transplantation

Question 27

Q

Whats the King’s college criteria for ALF secondary to paracetemol?

Answer

A

Arterial pH: < 7.3 after resuscitation and > 24 h since ingestion
Lactate: > 3 mmol/L after resuscitation

OR

The 3 following criteria:
Hepatic encephalopathy ≥ grade 3
Serum creatinine > 300 umol/L
INR > 6.5

Question 28

Q

Whats the King’s college criteria for ALF not secondary to paracetemol?

Answer

A

INR: > 6.5

OR

3 out of 5 following criteria:
Aetiology: indeterminate aetiology hepatitis, drug-induced hepatitis
Age: < 10 years or > 40 years
Jaundice: Interval jaundice-encephalopathy > 7 days
Bilirubin: > 300 umol/L
INR: > 3.5

Question 29

Q

How should pt with ALF be managed?

Answer

A

Manage in ICU at a transplant centre
Medications to reverse any poisonings
Liver transplant
Managing organ systems - fluid resuscitation, intubation and entail action, nutrition, manage GI bleeds, sort metabolic abnormalities, manage AKI, sort imbalance of coagulation, sepsis 6, management of raised ICP

Question 30

Q

What are the complications of acute liver failure?

Answer

A

Sepsis
Hypoglycaemia
Raised ICP
Bleeding
AKI

Question 31

Q

What proportion of pt with hepatic encephalopathy grade 3 and grade 4 will have cerebral oedema?

Answer

A

Grade 3 - 30%
Grade 4 - 70%

Question 32

Q

What is hepatitis?

Answer

A

Inflammation of the liver

Question 33

Q

What can cause hepatitis?

Answer

A

Alcoholic hepatitis
Non alcoholic fatty liver disease (steatohepatitis)
Viral hepatitis (hep viruses, CMV, EBV)
Autoimmune hepatitis
Drug induced hepatitis (e.g. paracetamol overdose)
Ischaemic hepatitis

Question 34

Q

How does hepatitis present?

Answer

A

Hepatitis may be asymptomatic or could present with non-specific symptoms:
Abdominal pain
Fatigue
Pruritis (itching)
Muscle and joint aches
Nausea and vomiting
Jaundice
Fever (viral hepatitis)
RUQ pain, Hepatomegaly

Question 35

Q

What are the typical biochemical findings of hepatitis?

Answer

A

Deranged LFTs - high AST/ALT with a proportionally less of a rise in ALP
Raised bilirubin

Question 36

Q

Why does ALT and AST rise in hepatitis?

Answer

A

ALT, AST, GGT, ALP are enzymes found within the liver. Hepatocellular injury will typically cause elevated transaminases (AST/ALT) that are released into the serum as a result of liver cell injury or death

Question 37

Q

Whats the most common viral hepatitis worldwide?

Answer

A

Hepatitis A (relatively rare in UK)

Question 38

Q

What is the hepatitic picture?
What is the biliary picture?

Answer

A

Raised AST and ALT with a proportionally less of a rise in ALP

Biliary - predominant rise in GGT and ALP

Question 39

Q

What are the characteristics of a hep A virus?

Answer

A

RNA picornavirus
Incubation period is 2-4 weeks

Question 40

Q

How is Hep A transmitted?

Answer

A

Transmitted via faecal oral route
Can also be spread with men who have sex with men or IV drug users

Question 41

Q

How does hep A present?

Answer

A

Prodromal flu-like stage
RUQ pain, tender hepatomegaly, nausea, vomiting, anorexia and jaundice. It can cause cholestasis which presents with dark urine (bilirubin excreted in urine) and pale stools (bilirubin doesnt manage to enter gut) and moderate hepatomegaly.

Question 42

Q

Whats the prognosis of hep A?

Answer

A

It resolves without treatment in around 1-3 months.

Question 43

Q

How is hep A treated?

Answer

A

it is commonly a mild self-limiting illness
Good oral hydration, rest, avoid alcohol, antiemetics, chlorphenamine for pruritus, stay home, avoid unnecessary contact, avoid unprotected sex for 7 days after onset of jaundice, analgesia

Notifiable disease so notify public health

Question 44

Q

Who should be vaccinated against hepatitis A?

Answer

A

Vaccination against hepatitis A isn’t routinely offered in the UK because the risk of infection is low for most people

Those at increased risk:
- close contacts of someone with hep A
- people planning to travel/live in parts of the world where hepatitis A is widespread
- people who inject illegal drugs
- you have chronic liver disease
- you have clotting disorders
- men who have sex with men
- people who may be exposed to hepatitis A through their job e.g. sewage workers, institutions where levels of personal hygiene may be poor, people working with monkeys, apes and gorillas

Question 45

Q

How would you know if hepatitis has developed into acute liver failure?

Answer

A

There would be a development of jaundice, asterixis, confusion, GI bleeds, ascites or bruising.
This is because ALF is defined as abnormal transaminases, development of coagulopathy and hepatic encephalopathy within 28 weeks of disease onset

Question 46

Q

What are a reflection of liver injury and what are reflections of liver function?

Answer

A

Liver injury - check ALT, AST, ALP, GGT
Liver function - check bilirubin, albumin and INR

Question 47

Q

What are the risk factors for hep A?

Answer

A

Those travelling to endemic areas
High risk sex, multiple partners
Factor VIII and factor IX deficiencies
Lab or sewage workers
IVDU

Question 48

Q

What are the 4 clinical phases of hepatitis A?

Answer

A

Incubation: Hepatitis A as a relatively long incubation period that may last from 2 - 6 weeks (mean 28-30 days).
Prodromal: Early part of the disease, characterised by fever, joint pain and rash. Flu-like symptoms may be present
Icteric: In addition to jaundice, the icteric phase is characterised by anorexia, abdominal pain and change in bowel habit.
Convalescent: Recovery phase as the body returns to normal and symptoms subside. Symptoms like malaise may last months.

Question 49

Q

Outline how hepatitis A can impact pregnancy and breast feeding?

Answer

A

Hep A is thought to increase the risk of miscarriage or pre-term labour when it occurs in the 2nd or 3rd trimester
Breastfeeding is not known to transmit the virus

Question 50

Q

What is post-hepatitis syndrome?

Answer

A

Post infection fatigue and feeling ill for months - common with hep A and B (a functional disease)

Question 51

Q

Whats the Hep A vaccine schedule?

Answer

A

Initial dose 4-6 weeks before travel
Provides protection for 12 months
Booster 6-12 months later
Provides immunity for 10 years (often considered life-long)

Question 52

Q

What are the characteristics of hepatitis B?

Answer

A

Enveloped DNA virus
Belongs to the family of hepadnaviridae
Incubation period is 6-20 weeks

Question 53

Q

How is Hep B transmitted?

Answer

A

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 abrasions.
It can also be passed from mother to child during pregnancy and delivery (known as “vertical transmission”).

Question 54

Q

Whats the prognosis of hep B?

Answer

A

Most people fully recover from the infection within 2 months, however 10% go on to become chronic hepatitis B carriers. In these patients the virus DNA has integrated into their own DNA and so they will continue to produce the viral proteins.

Question 55

Q

What are the viral markers of hepatitis B?

Answer

A

Surface antigen (HBsAg) – active infection
E antigen (HBeAg) – marker of viral replication and implies high infectivity
Core antibodies (HBcAb) – implies past or current infection
Surface antibody (HBsAb) – implies vaccination or past or current infection
Hepatitis B virus DNA (HBV DNA) – this is a direct count of the viral load

Question 56

Q

How can HBcAb distinguish between acute, chronic and past infections?

Answer

A

We can measure IgM and IgG versions of the HBcAb.
IgM implies an immediate response to an active infection and will give a high titre with an acute infection and a low titre with a chronic infection.
IgG indicates a past infection where the HBsAg is negative. (surface antigen is cleared but they have a clear immune response to a previous infection)

Question 57

Q

How do we interpret hep B e antigen (HBeAg)?

Answer

A

Indicates viral load
Where the HBeAg is present it implies the patient is in an acute phase of the infection where the virus is actively replicating. The level of HBeAg correlates with their infectivity. If the HBeAg is higher, they are highly infectious to others. When they HBeAg is negative but the hepatitis B e antibody is positive this implies they have been through a phase where the virus was replicating and but the virus has now stopped replicating and they are less infectious.

Question 58

Q

Outline the schedule for hep B vaccine?

Answer

A

All babies in the UK born on or after 1 August 2017 are given 3 doses of hepatitis B-containing vaccine as part of the NHS routine vaccination schedule. These doses are given at 8, 12 and 16 weeks of age.
It involves injecting the hepatitis B surface antigen (hepatitis B surface antibodies form against this and this is checked to ensure vaccine has worked)

Question 59

Q

How is hepatitis B managed?

Answer

A

Most acute cases are self-limiting
Notifiable disease so it must be reported
If profound acute hepatitis or even fulminant hepatic failure then urgent admission and assessment should be sorted.
Screen for other blood born viruses (hepatitis A and B and HIV) and other STD
Refer to gastroenterology, hepatology or infectious diseases for specialist management
Notify Public Health
Stop smoking and alcohol
Education about reducing transmission and informing potential at risk contacts
Testing for complications: FibroScan for cirrhosis and ultrasound for hepatocellular carcinoma
Antiviral therapy can be used to slow the progression of the disease and reduce infectivity only in chronic cases!
Liver transplantation for end-stage liver disease

Question 60

Q

What type of liver disease can hepatitis B lead to?

Answer

A

Acute and chronic

Question 61

Q

What can chronic hepatitis B lead to?

Answer

A

cirrhosis and hepatocellular carcinoma

Question 62

Q

What is an anicteric illness?

Answer

A

No evidence of jaundice

Question 63

Q

What is chronic hepatitis B?

Answer

A

failure to clear the virus after acute infection. Defined as persistence of serum hepatitis B surface antigen (HBsAg) for >6 months

Question 64

Q

Which age group are most at risk of hepatitis B progressing to chronic infection?

Answer

A

Perinatal transmission 90%

Risk of progression to chronic infection has an inverse relationship with age.

Answer 64

A

subclinical hepatitis
Anicteric hepatitis
Icteric hepatitis
Fulminant hepatic failure (rare)

Answer 65

A

Because for pt who clear the virus, HBV can persist at low levels and so can reactivate in the presence of immunosuppression

Answer 66

A

Phase 1 - HBeAg +ve chronic infection - minimal liver inflammation and high viral replication
Phase 2 - HBeAg +ve chronic hepatitis - moderate-severe liver inflammation and accelerate progression to fibrosis. Usually occurs many years after first phase. May skip this phase
Phase 3 - HBeAg -ve chronic infection - significant viral suppression and absence of significant liver disease. Favourable prognosis if minimal liver injury developed before immune clearance. Fibrosis may be present on biopsy despite low levels of HBV DNA.
Phase 4 - HBeAg -ve negative chronic hepatitis - moderate to severe liver inflammation, low rate of spontaneous clearance and genetic mutations in the HBV genome that impair expression of HBeAg.
Phase 5 - HBsAg negative phase - recovery.

Answer 67

A

Patients will be asymptomatic and unlikely to be identified unless blood tests are taken for an alternative problem. Patients will not realise they are infected. If acquired during adulthood, very low risk of chronic hepatitis B.

Answer 68

A

Typically presents with a non-specific illness in the absence of jaundice.

Malaise
Anorexia
Nausea
Fever
Right upper quadrant pain
Vomiting

Answer 69

A

Features similar to anicteric hepatitis but also present with jaundice.

Answer 70

A

A clinical syndrome of severe liver function impairment, which causes hepatic coma and the decrease in synthesizing capacity of liver, and develops within eight weeks of the onset of hepatitis.

Answer 71

A

Majoritively asymptomatic
Fatigue, RUQ pain, anorexia, nausea, fever, vomiting, jaundice
Exacerbations which may mimic acute hepatitis B
Complications of chronic hepatitis e.g. cirrhosis, hepatocellular carcinoma
Cirrhosis findings - stigmata of chronic liver disease
Decompensated cirrhosis - ascites, encephalopathy, jaundice, coagulopathy and GI bleeds

Answer 72

A

Skin rash, arthritis, arthralgia, glomerulonephritis, polyarteritis nodosa, Cryoglobulinaemia, and papular acrodermatitis

Answer 73

A

IgG anti-HBC positive
Anti-HBS positive or negative
HBsAg positive

Answer 74

A

IgG Anti-HBc (-), Anti-HBs (+), HBsAg (-)

Answer 75

A

Up to 20%

Answer 76

A

Entecavir, peginterferon alfa, tenofovir alafenamide, and tenofovir disoproxil

Answer 77

A

RNA flavivirus
Incubation period 6-9 weeks

Answer 78

A

Parenteral
Permucosal
Vertical

Answer 79

A

1 in 4 fights off the virus and makes a full recovery
3 in 4 it becomes chronic

Answer 80

A

liver cirrhosis and associated complications and hepatocellular carcinoma

Answer 81

A

Screen for other blood born viruses (hepatitis A and B and HIV) and other sexually transmitted diseases
Refer to gastroenterology, hepatology or infectious diseases for specialist management
Notify Public Health (it is a notifiable disease)
Stop smoking and alcohol
Education about reducing transmission and informing potential at risk contacts
Testing for complications: FibroScan for cirrhosis and ultrasound for hepatocellular carcinoma
Antiviral treatment with direct acting antivirals (DAAs) is tailored to the specific viral genotype. They successfully cure the infection in over 90% of patients. They are typically taken for 8 to 12 weeks
Liver transplantation for end-stage liver disease

Answer 82

A

After exposure to the hepatitis C virus only around 30% of patients will develop features such as:
a transient rise in serum aminotransferases / jaundice
fatigue
arthralgia

Answer 83

A

defined as the persistence of HCV RNA in the blood for 6 months.

Answer 84

A

heumatological problems: arthralgia, arthritis
eye problems: Sjogren’s syndrome
cirrhosis
hepatocellular cancer
cryoglobulinaemia: typically type II
porphyria cutanea tarda, especially if there are other factors such as alcohol abuse
Glomerulonephritis
Non-Hodgkin lymphoma

Answer 85

A

sustained virological response (SVR), defined as undetectable serum HCV RNA six months after the end of therapy

Answer 86

A

a combination of protease inhibitors (e.g. daclatasvir + sofosbuvir or sofosbuvir + simeprevir) with or without ribavirin are used

Answer 87

A

haemolytic anaemia, cough. Women should not become pregnant within 6 months of stopping ribavirin as it is teratogenic

Answer 88

A

Single stranded RNA virus that is transmitted parenterally

It can only survive in patients who also have a hepatitis B infection as its an incomplete RNA virus. It attaches itself to the HBsAg to survive and cannot survive without this protein

There are very low rates in the UK.

Answer 89

A

Hepatitis D increases the complications and disease severity of hepatitis B.

Answer 90

A

There is no specific treatment for hepatitis D. It is a notifiable disease and Public Health need to be notified of all cases.

Answer 91

A

Co-infection: Hepatitis B and Hepatitis D infection at the same time.
Superinfection: A hepatitis B surface antigen positive patient subsequently develops a hepatitis D infection.

Answer 92

A

associated with high risk of fulminant hepatitis, chronic hepatitis status and cirrhosis.

Answer 93

A

RNA hepevirus
Incubation period 3-8 weeks

Answer 94

A

Faecal oral route

Answer 95

A

Mild illness

Answer 96

A

the virus is cleared within a month and no treatment is required.

Can only cause chronic disease in immunocompromised individuals

Answer 97

A

Central and South-East Asia, North and West Africa, and in Mexico

Answer 98

A

carries a significant mortality (about 20%) during pregnancy

Answer 99

A

It’s currently in development but is not yet in widespread use

Answer 100

A

Acute - <6 months, causes nausea, vomiitng, RUQ pain, jaundice and hepatomegaly
Chronic - >6 months, sometimes asymptomatic, fever, fatigue, anorexia, extrahepatic symptoms, may not have hepatomegaly but may have a lower margin that feels irregular if there is cirrhosis

Answer 101

A

6-monthly abdominal ultrasound and alpha-fetoprotein

Answer 102

A

Paracetemol overdose

Answer 103

A

Greater elevation in AST than ALT
Associated with reduced albumin and protein levels due to reduced hepatic synthetic function

Answer 104

A

Human normal immunoglobulin (HNIG)
Hepatitis A vaccine may be used

Answer 105

A

if the person exposed is a known responder to the HBV vaccine then a booster dose should be given
if they are a non-responder (anti-HBs < 10mIU/ml 1-2 months post-immunisation) they need to have hepatitis B immune globulin (HBIG) and a booster vaccine

Answer 106

A

monthly PCR - if seroconversion then interferon +/- ribavirin

Answer 107

A

The acute onset of symptomatic hepatitis due to heavy alcohol consumption

Answer 108

A

> 100g per day for 15-20 years (about 88 units a week)

Answer 109

A

A spectrum of conditions that result from alcohol mediated liver damage
Alcoholic fatty liver -> alcoholic hepatitis -> cirrhosis (irreversible)

Answer 110

A

9 per 100,000 in those under 75

Answer 111

A

It can be metabolised by alcohol dehydrogenase in the cytosol. Uses the conversion of NAD+ to NADH. (most common)
It can be metabolised by catalase in peroxisome
It can be metabolised by CYP2E1

All 3 lead to the conversion of alcohol to acetaldehyde

Answer 112

A

Jaundice
Anorexia
Fever
Tender hepatomegaly

Others - abdo pain, ascites, muscle wasting, confusion, asterixis, tremor, bruising, stigmata of chronic liver disease
The pt may also have the features of alcohol withdrawal

Answer 113

A

FBC
U&Es
LFTs
Bone profile
CRP
Magnesium
Coagulation
Non-invasive liver screen to determines the possible cause of liver disease
Liver ultrasound with Doppler
Liver biopsy in cases of severe alcoholic hepatitis where steroid treatment is being considered
Septic screen
Endoscopy - varices
CT/MRI be be used

Answer 114

A

AST/ALT ratio >2
Elevated bilirubin
Elevated GGT
Elevated neutrophil count
Elevated INR
Low albumin due to reduced synthetic function
Elevated prothrombin time due to reduce synthetic function
U&Es may be deranged in hepatorenal syndrome

Answer 115

A

Steatosis
Neutrophil infiltration
Hepatocytes ballooning
Fibrosis
Cholestasis
Mallory-denk bodies

Answer 116

A

eosinophilic accumulations of proteins within the cytoplasms of hepatocytes.
No pathological role in disease but a marker of alcohol-induced liver disease.

Answer 117

A

Maddrey discriminant function
Model for end-stage lover disease
Glasgow alcoholic hepatitis score

Answer 118

A

Patients with mild-to-moderate alcoholic hepatitis are usually managed conservatively with good nutrition, attention to adequate hydration and managing alcohol withdrawal. It is important to screen for underlying chronic liver disease, but the mainstay of treatment is alcohol cessation.

Patients with severe alcoholic hepatitis can be extremely unwell with multi-organ failure and require referral to an ICU. Corticosteroids are often given

Answer 119

A

stratifies patients already receiving steroids for alcoholic hepatitis treatment for 7 days to predict which will not improve and should be considered for other management strategies

Answer 120

A

Hepatic encephalopathy
Systemic infection: including spontaneous bacterial peritonitis
GI bleeding: variceal bleeding (oesophageal/rectal)
Coagulopathy and thrombocytopaenia
Ascites
Multi-organ failure

Answer 121

A

not regularly drink more than 14 units per week for both men and women. If drinking 14 units in a week, this should be spread evenly over 3 or more days and not more than 5 units in a day.

Answer 122

A

breast, mouth and throat.

Answer 123

A

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

Answer 124

A

Used to check the elasticity of the liver by sending high frequency sound waves into the liver. It helps assess the degree of cirrhosis.

Answer 125

A

Chronic inflammation damaged liver cells and they are then replaced with scar tissue which tends to form nodules. This fibrosis affects the structure and blood flow through the liver, which causes increased resistance in the vessels leading in to the liver = portal hypertension

Answer 126

A

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

Others: autoimmune hepatitis, primary biliary cirrhosis, haemochromatosis, Wilson’s disease, alpha 1 anti trypsin deficiency, cystic fibrosis, drugs e.g. amiodarone or methotrexate

Answer 127

A

Type 1 - typically women with peak incidence at 16-30 years. Acute presentations are rare
Types 2 - seen more commonly in children with average age presentation at 10. Female predominance. More aggressive with 80% developing cirrhosis.

Answer 128

A

Type 1 - ANA, Anti-smooth muscle antibodies (anti-actin)
And raised IgG is typical

Ttype 2 - Anti-liver/kidney microsomal type 1 antibodies (LKM1)

Type 3 - Soluble liver-kidney antigen

Answer 129

A

Anti-liver kidney microscopes 1
Anti-liver cytosol antigen type 1

Answer 130

A

Scoring systems
Routine bloods
Non-invasive liver screen
Liver imaging
Liver biopsy

Answer 131

A

High dose steroids and other immunosuppressants e.g. azathioprine
Liver transplantation may be required in end stage liver disease but the disease can recur in transplanted livers

Answer 132

A

Jaundice – caused by raised bilirubin
Hepatomegaly – however the liver can shrink as it becomes more cirrhotic
Splenomegaly – due to portal hypertension
Spider Naevi – these are telangiectasia with a central arteriole and small vessels radiating away
Palmar Erythema – caused by hyperdynamic cirulation
Gynaecomastia and testicular atrophy in males due to endocrine dysfunction
Bruising – due to abnormal clotting
Ascites
Caput Medusae – distended paraumbilical veins due to portal hypertension
Asterixis – “flapping tremor” in decompensated liver disease

Answer 133

A

FBC - hyponatraemia due to fluid retention
U&Es - for hepatorenal syndrome
LFTS - ALT, AST, ALP and bilirubin will all be deranged
Albumin and prothrombin time
Noninvasive liver screen
Alpha fetoprotein every 6 months to check for hepatocellular carcinoma
Enhanced liver fibrosis blood test if its available

Answer 134

A

Ultrasound and alpha-fetoprotein - to check for hepatoceullar carcinoma

Answer 135

A

Nodularity of the surface of the liver
A “corkscrew” appearance to the arteries with increased flow as they compensate for reduced portal flow
Enlarged portal vein with reduced flow
Ascites
Splenomegaly

Answer 136

A

Child-Pugh score

Answer 137

A

The factors included are bilirubin, albumin, INR, ascites and encephalopathy
Each score is given 1,2 or 3 so the minimum score is 5 and maximum is 15
The score then indicates the severity of the cirrhosis and prognosis

Answer 138

A

NICE recommend retesting every 2 years in patients at risk of cirrhosis:
Hepatitis C
Heavy alcohol drinkers
Diagnosed alcoholic liver disease
Non alcoholic fatty liver disease and evidence of fibrosis on the ELF blood test
Chronic hepatitis B (although they suggest yearly for hep B)

Answer 139

A

Model for End-stage liver disease score
Stratifies severity of end-stage liver disease and helps guide referral for liver transplant
Should be used every 6 months in pt with compensated cirrhosis

Answer 140

A

High protein, low sodium diet

Answer 141

A

Malnutrition
Portal hypertension, varices, variceal bleeding
Ascites and spontaneous bacterial peritonitis
Hepatorenal syndrome
Hepatic encephalopathy
Hepatocellular carcinoma

Answer 142

A

Cirrhosis affects metabolism of proteins in the liver and reduces the amount of protein produced
It disrupts the liver’s ability to store glucose as glycogen

Answer 143

A

Liver cirrhosis increases the resistance of blood flow in the liver. As a result, there is increased back-pressure into the portal system. This is called “portal hypertension”.

Answer 144

A

This back-pressure causes the vessels at the sites where the portal system anastomoses with the systemic venous system to become swollen and tortuous = varices

Gastro-oesophageal junction, ileocaecal junction, rectum and anterior abdominal wall via the umbilical vein

Answer 145

A

Varices at the anterior abdominal wall via the umbilical vein
The portosystemic shunt causes the round ligament to re-chanell, allowing blood from the portal system to pass into the abdominal veins = veins dilate

Answer 146

A

Propranolol to reduce portal hypertension
Elastic band ligation at 2 weekly intervals until all varices have been eradicated
Injection of sclerosant (second line to ligation)
TIPS if above are all unsuccessful in preventing further episodes

Answer 147

A

Transjugular Intra-hepatic portosystemic shunt - inserting a wire into the jugular vein under X-ray guidance down the vena cava and into the liver via the hepatic vein. They then make a connection between hepatic vein and portal vein and put a stent in place to allow blood to flow directly from the portal vein to the hepatic vein and relieve the pressure in he portal system and varices

Answer 148

A

Resuscitation - Terlipressin, correct any coagulopathy, prophylactic broad spectrum antibiotics, consider intubation and intensive care
Urgent endoscopy - elastic band ligation or injection of sclerosant
Sengstaken-Blakemore tube if endoscopy fails

Answer 149

A

Abnormal accumulation of fluid in the abdomen/peritoneal cavity

In men, no fluid should be present. In women, up to 20 mls may be considered normal depending on the timing of their menstrual cycle.

Answer 150

A

Cirrhosis -> The increased pressure in the portal system causes fluid to leak out of the capillaries in the liver and bowel and into the peritoneal cavity. The drop in circulating volume caused by fluid loss into the peritoneal space causes a reduction in blood pressure entering the kidneys. The kidneys sense this lower pressure and release renin, which leads to increased aldosterone secretion and reabsorption of fluid and sodium in the kidneys. Cirrhosis causes a transudative, meaning low protein content, ascites.

Answer 151

A

Transudate: due to the ultrafiltration of plasma (i.e. removal of fluid). It does not contain large proteins and only few cells.
Exudate: due to leakage of whole contents of plasma (i.e. fluid, cells and proteins). Largely due to an inflammatory process.

Answer 152

A

Serum-ascites albumin gradient <11g/L or a gradient >11g/L

Answer 153

A

Liver disorders - cirrhosis, alcoholic liver disease, ALF, liver mets
Cardiac - right heart failure, constrictive pericarditis
Others - Budd-Chiari syndrome, portal vein thrombosis, veno-occlusive disease, myxoedema

Answer 154

A

Hypoalbuminaemia - nephrotic syndrome, severe malnutrition
Maliganncy - peritoneal carcinomatosis
Infection e.g. tuberculous peritonitis
Others - pancreatitis, bowel obstruction, biliary ascites, postoperative lymphatic leak, serositis

Answer 155

A

Reduce dietary sodium
Fluid restriction is sodium <125mmol/L
Aldosterone antagonists - spironolactone
Paracentesis (ascetic tap or drain)
Prophylactic antibiotics to reduce risk of SBP
TIPS may be considered
Consider transplantation in refractory ascites

Answer 156

A

This occurs in around 10% of patients with ascites secondary to cirrhosis and can have a mortality of 10-20%.

Answer 157

A

an infection developing in the ascitic fluid and peritoneal lining without any clear cause (e.g. not secondary to an ascitic drain or bowel perforation).

Answer 158

A

Can be asymptomatic so have a low threshold for ascitic fluid culture
Fever
Abdominal pain
Deranged bloods (raised WBC, CRP, creatinine or metabolic acidosis)
Ileus
Hypotension

Answer 159

A

Escherichia coli
Klebsiella pnuemoniae
Gram positive cocci (such as staphylococcus and enterococcus)

Answer 160

A

Take an ascitic culture prior to giving antibiotics
Usually treated with an IV cephalosporin such as cefotaxime

Answer 161

A

Hypertension in the portal system leads to dilation of the portal blood vessels, stretched by large amounts of blood pooling there. This leads to a loss of blood volume in other areas of the circulation, including the kidneys. This leads hypotension in the kidney and activation of the renin-angiotensin system. This causes renal vasoconstriction, which combined with low circulation volume leads to starvation of blood to the kidney. This leads to rapid deteriorating kidney function

Answer 162

A

fatal within a week or so unless liver transplant is performed.

Answer 163

A

functional impairment of the liver cells prevents them metabolising the ammonia into harmless waste products. Secondly, collateral vessels between the portal and systemic circulation mean that the ammonia bypasses liver altogether and enters the systemic system directly.
(Ammonia is produced by intestinal bacteria when they break down proteins!)

Answer 164

A

Acutely, it presents with reduced consciousness and confusion. It can present in a more chronically with changes to personality, memory and mood.

Answer 165

A

Lactulose to promote excretion of ammonia
And consider Rifaximin to reduce number of ammonia-producing bacteria

Answer 166

A

Serum albumin - ascitic fluid albumin

Answer 167

A

Direct spread - bacterial translocation across the bowel wall
Haematogenous spread - bacteria enter ascites via the bloodstream

Answer 168

A

SBP: >250/mm3 of WCC, predominantly neutrophils, cultures positive
Culture negative SBP: >250/mm3 of WCC, predominantly neutrophils, cultures negative
Bacterascites: <250/mm3 of WCC, culture-positive (suggests early-stage SBP or colonisation)
Secondary bacterial peritonitis: multiple organisms on culture, seen in 5%. Suggestive of intra-abdominal pathology (e.g. perforation).

Answer 169

A

Non-alcoholic fatty liver disease
(30% of adults in the uk have it)
It’s expected to become the leading indication for liver transplantation in the near future

Answer 170

A

Non alcoholic fatty liver (aka simple steatosis)
Non-alcoholic steatohepatitis (steatosis coexisting with hepatocellular injury and inflammation = NASH)
Fibrosis
Cirrhosis

Answer 171

A

Strongly linked to obesity and metabolic syndrome
Poor diet and low activity levels
Type 2 diabetes or impaired glucose regulation
Hyperlipidaemia
Middle age onwards
Smoking
Hypertension
Sudden weight loss/starvation
Obstructive sleep apnoea
Endocrine e.g. PCOS, hypothyroidism
FHx
Higher risk in Hispanic and asian people

Answer 172

A

USS
Hep B and C serology
Autoantibodies for autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis
Immunoglobulins for autoimmune hepatitis and primary biliary cirrhosis
Caeruloplasmin for Wilson’s disease
Alpha 1 anti-trypsin levels for alpha 1 anti-trypsin deficiency
Ferritin and transferrin saturation for hereditary haemochromatosis

Answer 173

A

LFTs, FBC, clotting, hep B and C viral serology, autoantibodies, ferritin serum caeruloplasmin, alpha-1 antitrypsin deficiency, HbA1c, lipid profile. Renal function test, TFTs
Assess persons risk of CVD
Liver USS to confirm hepatic steatosis
Enhanced liver fibrosis blood test if available
NAFLD fibrosis score if not available
Fibroscan is 3rd line and should be performed if ELF or NAFLD fibrosis score indicates fibrosis

Answer 174

A

Drug treatment - amiodarone or tamoxifen
Hep C virus infection
PCOS

Answer 175

A

Portal hypertension
Variceal haemorrhage
Liver failure
Hepatocellular carcinoma
Sepsis
Hypertension, CKD, impaired glucose regulation, type 2 diabetes
Cardiovascular disease

Answer 176

A

a non-invasive blood test that measures three direct markers of fibrosis:
hyaluronic acid (HA)
procollagen III amino-terminal peptide (PIIINP)
tissue inhibitor of matrix metalloproteinase 1 (TIMP-1)

Answer 177

A

No treatment but advise pt that the aim of management is to reduce the risk of progression of NAFLD
Lifestyle modification - diet, physical activity, regular exercise, weight loss, minimal alcohol, optimally manage comorbidities

Pioglitazone may be used off-label in NASH
Vitamin E supplementation for non-diabetic pt with NASH

Answer 178

A

If they are at high risk of advanced liver fibrosis
If there are signs of advanced liver disease on examination
If there is uncertainty about the diagnosis

Answer 179

A

paracetamol
sodium valproate, phenytoin
MAOIs
halothane
anti-tuberculosis: isoniazid, rifampicin, pyrazinamide
statins
alcohol
amiodarone
methyldopa
nitrofurantoin

Answer 180

A

combined oral contraceptive pill
antibiotics: flucloxacillin, co-amoxiclav, erythromycin*
anabolic steroids, testosterones
phenothiazines: chlorpromazine, prochlorperazine
sulphonylureas
fibrates
rare reported causes: nifedipine

Answer 181

A

methotrexate
methyldopa
amiodarone

Answer 182

A

Nonalcoholic fatty liver disease
Excess fat in the liver. It’s defined as >5% of hepatocytes containing fat

It requires exclusion of a significant alcohol intake (>30g/day in men and >20g a day in women) whic would be suggestive of alcohol-related liver disease

Answer 183

A

A group of risk factors associated with an increased risk of CVD and stroke
Abdominal obesity - waist circumference >94cm in men or >80 cm in women
Hypertension (>130/85 or treated for hypertension)
Impaired fasting blood glucose (>5.6mmol/L or treated for type 2 diabetes mellitus)
High triglycerides (>1/7mmol/L serum level)
Low HDL cholesterol (<1.0mg/dl men or <1.3mmol/L in women)

Answer 184

A

Insulin resistance -> promotes increased breakdown of peripheral adipose tissue + increased synthesis of triglycerides + increased uptake of fatty acids -> accumulation of toxic lipids in the liver -> hepatic steatosis

The accumulation of fat within the liver can promote inflammatory changes, liver injury and eventually scarring leading to fibrosis and in its most severe form cirrhosis

Answer 185

A

Typically asymptomatic
Non-specific RUQ pain
Fatigue
Hepatomegaly
Obesity
Hypertension
Stigmata of chronic liver disease
Features of decompensated cirrhosis - jaundice, ascites, bruising, encephalopathy

Answer 186

A

15 per 100,000
Most common in women
Type 1 has a 4:1 female predominance
Type 2 has a 10:1 female predominance
Affects all ages and ethnicities

Answer 187

A

Environmental trigger in a genetically predisposed individual

Genetics:
Dysfunctional Treg cell response.
HLA DR3 and HLA DR4
Other genes

Precipitants:
Herbal chemicals, drugs or viral infections include hep A and human herpes viruses)

Answer 188

A

Interface hepatitis (i.e. between the lobules of hepatocytes and portal tracts)
Lymphoplasmacytic infiltrates into portal tracts and extending to lobules
Hepatocytes necrosis usually in periportal area (may see bridging necrosis where necrosis extends between terminal venues and portal tracts)
Hepatic rosette formation (pseudoacini which are glandlike formations develop due to chronic inflammation)

Answer 189

A

The presence autoimmune hepatitis with another autoimmune liver disease (PBC or PSC)

Answer 190

A

Autoimmune hepatitis and PBC are female predominant. PSC is male predominant.
Can all present asymptmatically. Autoimmune hepatitis can be acute or chronic. PBC can present with marked fatigue and Pruritis. PSC can present with features of cholangitis
AIH has raised ALT/AST (liver picture). PBC and PSC have raised ALP and GGT (cholestatic picture)
AIH has raised IgG.
PBC has raised IgM
Autoantibodies in AIH are ANA, SMA and LKM. In PBC its AMA.
AIH and PBC have excellent prognoses. PSC once symptomatic will have a need for transplant within 15 years at 50% of cases

Answer 191

A

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

Answer 192

A

Mutations in human haemachromatosis protein gene on chromosome 6. This genetic mutations is autosomal recessive and is important in regulating iron metabolism. Variants in this gene lead to excess iron absorption by enterocytes and ultimately, iron overload in vital organs.

There is also non-HFE haemachromatosis which is rare. Caused by other genetic variants.

Acquired haemachromatosis is often due to frequent transfusions of RBCs or excessive intake of iron

Answer 193

A

It may be as low as 1% in women and 28% in men
This means the vast majority of pt with abnormal gene will not develop HH

Answer 194

A

About 4g of iron with 3G stored in haemoglobin of RBC

Answer 195

A

1mg iron lost a day from desquamation of GI cells each day
15-40mg lost with each menstrual cycle
We required 1-2mg of dietary iron a day

Answer 196

A

Iron is absorbed from the upper gastrointestinal tract and enters the body via the ferroportin receptor on the basolateral surface.
It is then transferred within the body by carrier protein transferrin. Transferrin is able to transport iron from body stores to tissues by interacting with the transferrin receptor.
Once in tissue, iron is stored as ferritin that is a readily available soluble iron store. A small amount of ferritin is found within the serum and can be measured.
Many immune cells of the reticuloendothelial system can also store large sums of iron in the form of ferritin - this is why its known as an acute phase reactant

Answer 197

A

Hepcidin - a protein made by the liver
This inhibits the efflux of iron from enterocytes and the reticuloendothelial system by induced degradation of ferroportin

Answer 198

A

Genetic variants in HFE gene -> reduced levels of hepcidin -> increased absorption of iron to 2-4mg a day -> increased stores of iron -> increased serum ferritin and transferrin saturation -> iron deposition in key organs which causes major dysfunction

Answer 199

A

Secondary hypothyroidism - Chronic tiredness, weakness, cold intolerance, constipation, weight gain
Type 2 diabetes mellitus - polyuria, polydypsia, weight loss
Joint pain from chronic arthropathy
Pigmentation - bronze/slate-grey
Hair loss
Secondary hypogonadism - Erectile dysfunction and amenorrhoea
Cognitive symptoms (memory and mood disturbances)
Chronic liver disease stigmata
Cardiomyopathy -> HF symptoms

Early symptms are typically fatigue, ED and arthralgia

Answer 200

A

Usually after the age of 40 when iron overload becomes enough to cause sympotms

Answer 201

A

menstruation acts to regularly eliminate iron from the body.

Answer 202

A

Liver
Heart
Pituitary gland - affects sex hormone and TSH production
Pancreas
Joints
Skin

Answer 203

A

Second and third metacarpophalangeal joints

Answer 204

A

FBC, LFTs
Serum ferritin
Transferrin saturation (determines whether high ferritin is caused by iron overload or high ferritin due to inflammation)
If serum ferritin and transferrin saturation are high…
Genetic testing for HFE variants (and rarer genetic variants if not positive)
CT abdomen
MRI / Liver biopsy with perl’s stain can establish iron concentration in parenchymal cells
HbA1c for diabetes
X-rays for joint arthropathy

Answer 205

A

Type 1 Diabetes
Liver Cirrhosis
Iron deposits in the pituitary and gonads lead to endocrine and sexual problems - hypogonadism, impotence, amenorrhea, infertility)
Cardiomyopathy
Hepatocellular Carcinoma
Hypothyroidism
Arthropathy

Answer 206

A

Weekly venesection (about 500ml of blood which is about 350mg of iron)
Alternatively iron chelation therapy e.g. deferasirox
Monitor FBC weekly , serum ferritin monthly and transferring saturation 1-3 monthly
Avoid alcohol
Genetic counselling
Monitoring and treating complications

Answer 207

A

the excessive accumulation of copper in the body and tissues

Answer 208

A

a mutation in the “Wilson disease protein” on chromosome 13.
The Wilson disease protein is also known as “ATP7B copper-binding protein” and is responsible for various functions, including the removal of excess copper in the liver.
Genetic inheritance is autosomal recessive.

Answer 209

A

Most patients with Wilson disease present with one or more of:

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

Answer 210

A

Copper deposition in the liver leads to chronic hepatitis and eventually liver cirrhosis

Answer 211

A

The most common neurologic symptoms of WD are movement disorders including tremor, dystonia, parkinsonism, ataxia and chorea which are associated with dysphagia, dysarthria and drooling

Answer 212

A

Can range from mild depression to full psychosis

Answer 213

A

Chronic hepatitis
Neurological and psychiatric features
Kayser-fleischer rings in Cornea
Haemolytic anaemia
Renal tubular acidosis
Osteopenia

Answer 214

A

Brown circles surrounding the iris caused by deposition of copper in Descemet’s corneal membrane
Can eventually be seen by the naked eye but proper assessment is made using slit lamp examination

Answer 215

A

serum caeruloplasmin
Slit lamp examination for Kayser-Fleischer rings
Liver biopsy for liver copper content is definitive gold standard test
24 hour urine copper assay
Scoring systems
Serum copper
Genetic analysis of ATP7B gene

Answer 216

A

This is the protein that carries copper in the blood. It can be falsely normal or elevated in cancer or inflammatory conditions. It is also not specific to Wilson disease.

Answer 217

A

Treatment is with copper chelation using:
Penicillamine
Trientene

Answer 218

A

10-25
Children usually present with liver disease whereas the first sign of disease in young adults is often neurological diseases

Answer 219

A

Untreated Wilson’s disease is fatal. The majority of patients die due to liver complications, though a minority will die from neurological complications.

Prognosis is dependent, in part, on time of diagnosis, with those diagnosed and treated early having better long-term outcomes. Specialist treatment and adherence to therapy is key to improving survival.

Answer 220

A

An abundant enzyme produced by the liver and acts as a protease inhibitor
Inhibits neutrophil elastase enzyme

Answer 221

A

Autosomal recessive with co-dominant expression (both alleles are expressed but the clinical phenotype is only seen with inheritance of 2 abnormal genes)
defect in the SERPINA1 gene that codes for A1AT on chromosome 14. There are many genetic mutations that can affect the gene and each mutation refers to an allele which is subsequently linked to a letter code which described their electrophoretic mobilities such as the 3 major ones… M (medium), S (slow) or Z (very slow).
M allele is normal and is found in >95% of the general population
S allele is found in 2-3% of the population
Z allele is the most severe and is found in 1% of the population

Answer 222

A

Liver cirrhosis after 50
Bronchiectasis and emphysema - in pt who are young and non-smokers

Answer 223

A

The mutant alpha-1-antitrypsin protein gets trapped in the liver/can’t leave, builds up, and causes liver damage which can progress to cirrhosis over time
It can also lead to hepatocellular carcinoma

Answer 224

A

The lack of a normal, functioning alpha-1-antitrypsin protein leads to an excess of neutrophil elastase that attack the connective tissue in the lungs.
Elastase breaks down elastin which is vital for the integrity of alveoli. This leads to bronchiectasis and emphysema over time.

Answer 225

A

Pt with COPD who are young, non-smokers or have a positive FHx, those with chronic liver disease and adult-onset asthma with poor response to bronchodilators

Answer 226

A

Underrecognised conditions with >1 million carriers of the abnormal AAT gene
Most common in white Northern Europeans
M=F
Bimodal distribution in clinical presentation - neonates it causes hepatitis and children it causes decompensated cirrhosis, its most commonly seen in 5th decade of life with features of liver or lung disease

Answer 227

A

PiMM - homozygous for normal alleles
PiZZ - homozygous for abnormal Z allele (only has 10% normal A1AT levels)
PiSZ - compound heterozygous, 2 abnormal recessive alleles, variable phenotype
PiMZ - heterozygous - only 1 abnormal gene so unlikely to have the clinical phenotype

Answer 228

A

PiZZ (likely to only have 10% normal A1AT levels so good chance of manifesting disease)
There is an 80-100% chance of developing COPD with PiZZ

Answer 229

A

15% of adult pt will develop cirrhosis and 75% will hae respiratory problems
Dyspnoea, cough, wheeze, ankle swelling
Jaundice, bruising, spider naevi, palmar erythema, hepatomegaly, ascites, leuconychia, confusion, asterixis, cachexia

Answer 230

A

Low serum-alpha 1-antitrypsin (screening test of choice)
Spirometry and other pulmonary function tests will show an obstructive picture
Chest X-ray/CT to look for emphysema and bronchiectasis
LFTs

Others to consider:
Phenotyping and genotyping
Gene sequencing
Liver USS and possibly liver biopsy
Abdominal CT

(Family members should also be investigated)

Answer 231

A

By using an acid-Schiff-positive staining (this stain is also used for glycogen storage disease)

Answer 232

A

Normal is 0.9-1.9g/L
Minimum amount is about 0.8g/L
(Patients with PiZZ usually have levels <0.3)

Answer 233

A

Stop smoking to slow down emphysema
Stop drinking alcohol completely if signs of chronic liver disease
Nutritional support, pulmonary rehabilitation and seasonal vaccinations
COPD management - beta agonists, Muscarinic antagonists and steroids.
Organ transplant for end-stage liver/lung disease
Monitoring for complications e.g. hepatocellular carcinoma

Answer 234

A

Patients with established cirrhosis need regular surveillance for hepatocellular carcinoma with 6-monthly liver ultrasound and alpha-fetoprotein (AFP) monitoring

Answer 235

A

Trials are ongoing into the use of intravenous human alpha-1-antitrypsin therapy (e.g. Zemaira) to treat AATD. However, in the UK this is currently not recommended by NICE

Answer 236

A

Aka hepatic vein thrombosis
A condition where there is obstruction to the venous outflow of the liver owing to occlusion of the hepatic vein. It can be caused by occlusion or partial occlusion to any, or all, of the 3 major hepatic veins
It usually seen in the context of underlying haematological disease or another procoagulant condition

Answer 237

A

abdominal pain: sudden onset, severe
ascites → abdominal distension
tender hepatomegaly

(It can present acutely with this + nausea and vomiting)
(It can also present chronically with hepatomegaly, mild jaundice, ascites, negative hepatojugular reflux and splenomegaly)

Answer 238

A

obstruction due to a predominantly venous process (e.g. thrombosis, phlebitis)

Answer 239

A

obstruction due to external compression or invasion of the hepatic veins/IVC (e.g. tumour)

Answer 240

A

also known as veno-occlusive disease.
It specifically refers to obstruction of the hepatic sinusoids and small hepatic venules.

Answer 241

A

This describes several conditions that result in hepatic congestion due to cardiac or pericardial disease. Commonly the result of right-sided heart failure, tricuspid regurgitation or constrictive pericarditis

Answer 242

A

a very specific condition where there is membranous obstruction in the IVC that predisposes to thrombosis. A thick fibrous band or web may develop blocking flow through the IVC. More frequently seen in Asian countries (e.g. Japan). Usually a milder version of BCS.

Answer 243

A

Myeloproliferative disorders (cause 50%)
combined oral contraceptive pill (20%)
Malignancy (10%)
thrombophilia: activated protein C resistance, antithrombin III deficiency, protein C & S deficiencies
pregnancy
Infection and benign liver lesions

Answer 244

A

Occlusion increases the pressure in hepatic sinusoids, which reduces blood flow, causes dilatation and leads to interstitial fluid accumulation. When the lymphatic capacity for clearing the interstitial fluid is exceeded, it passes through the liver capsule and causes ascites.
This global increase in pressure reduces portal flow and leads to hypoxic damage to hepatocytes. Due to poor portal flow, portal vein thrombosis may be seen in 10-20% of cases. As the condition progresses there is centrilobar necrosis (cell damage around the central veins in the liver architecture). This area is known as zone 3. Rapid progression to acute liver failure, or slow progression of fibrosis, depends on the speed of occlusion.

Answer 245

A

Acute occlusion: patients at risk of acute liver failure that can result in death within 2-3 weeks.

Subacute occlusion: more insidious onset over months compared to acute occlusion. Less severe due to collateral venous formation in portal and hepatic venous systems. At risk of rapid progression of fibrosis.

Chronic occlusion: development of chronic liver disease with features of portal hypertension. Usually present with complications of cirrhosis (e.g. ascites, encephalopathy)

Answer 246

A

The clinical features of BCS are highly variable. Up to 15% of patients may be asymptomatic, which is usually due to hepatic venous collaterals (patency of the last remaining hepatic vein)

Other pt:
Acute liver failure characterised by ascites, encephalopathy, jaundice and coagulopathy
Abdominal pain
Ascites
Nausea and vomiting
Bruising
GI bleeding
Hepatomegaly
Distended abdominal veins

Answer 247

A

Doppler ultrasound: first-line investigation.
CT/MRI: used if doppler ultrasound is not available, to confirm the diagnosis following ultrasound or when ultrasound is negative but the suspicion is still high.
Venography: involves transvenous insertion of a catheter via the internal jugular or femoral vein. Contrast is then injected to visualis the hepatic venous system once accessed. May be used if CT/MRI are inconclusive or to plan for therapeutic interventions. Considered the gold-standard.

Answer 248

A

FBC
U&E
LFTs
Bone profile
CRP
Coagulation
Non-invasive liver screen
Imaging to assess for underlying malignancy or tumour causing extrinsic compression
Thrombophilia screen
Haematological screen to assess for myeloproliferative disorders
Liver biopsy maybe

Answer 249

A

They should be referred to a specialist liver unit with access to interventional radiology and transplant services.

Treat underlying obstruction - medical management, interventional radiology, TIPSS and Oliver transplantation
Treat any consequences of portal hypertension e.g. varices and ascites
Treat underlying condition

Answer 250

A

Systemic anticoagulation - LMWH

Answer 251

A

Angioplasty with or without stenting
Catheter directed thrombolysis

Answer 252

A

Acute forms of BCS with acute liver failure is usually fatal without liver transplantation.
The use of TIPSS and liver transplantation has improved outcomes with 75% survival at 5 years.
Without treatment life expectancy is 3 years after first symptoms
Follow-up is important because patients are at risk of developing hepatocellular carcinoma following an episode of BCS.

Answer 253

A

progressive liver dysfunction for six months or longer

Answer 254

A

Alcohol
Viruses
Inherited conditions (AAT deficiency, Wilson’s disease, hereditary haemochromatosis)
Metabolic - NAFLD and NASH
Autoimmune
Biliary - PBC and PSC
Vascular - ischaemic hepatitis, BCS, congestive hepatopathy
Drug-induced liver injury
Cryptogenic (no known cause)

Answer 255

A

Chronic liver disease may result from repeated insults that cause inflammation or cholestasis. Excess deposition of fat in the liver can also promote an inflammatory response, which is seen in conditions like non-alcoholic fatty liver disease.
Over time, chronic damage can lead to fibrosis where the normal liver architecture is replaced by fibrotic tissue and regenerative nodules. If the aetiological factor is removed or treated then some reversibility in liver function can occur depending on the extent of fibrosis. If fibrogenesis continues then the end result is cirrhosis, which describes irreversible liver remodeling that is associated with significant morbidity and mortality.

Answer 256

A

Compensated and decompensated cirrhosis

Answer 257

A

patients are typically asymptomatic as a small amount of residual function allows the liver to continue carrying out normal function despite extensive damage.

Answer 258

A

in this state the liver no longer has the capacity to carry out its normal functions, which results in multiple complications. If the insult is removed, the liver may ‘recompensate’ over time to a state of compensated cirrhosis.
Characterised by coagulopathy, jaundice, encephalopathy, ascites and GI bleeding

Answer 259

A

Child-Pugh score

Answer 260

A

A way to grade the severity of cirrhosis using the clinical and biochemical features of decompensated cirrhosis: encephalopathy, ascites, bilirubin, albumin and INR
It puts your diagnosis into class A (5-6), class B (7-9) or class C (10-15).

The different classes reflect the severity of cirrhosis and provide an estimated one year survival.
Class A: mild disease, one year survival 100%
Class B: moderate disease, one year survival 80%
Class C: severe disease, one year survival 45%

Answer 261

A

Early clinical features are usually non-specific. They include anorexia, lethargy, weight loss, hepatomegaly, nausea or disturbed sleep pattern.
As patients develop more advanced disease, stigmata of chronic liver disease develop.

Answer 262

A

Caput medusa
Splenomegaly
Palmar erythema
Dupuytren’s contracture
Leuconychia
Gynaecomastia
Spider naevi

Answer 263

A

Encephalopathy (confusion +asterixis)
Ascites
Jaundice
GI bleeding
Coagulopathy

Answer 264

A

Liver biopsy - gold standard but high risk of complications so reservied for specific cases
LFTs (although cannot be used to exclude cirrhosis) - likely to see hyperbilirubinaemia, raised INR and low albumin
FBC - low platelets supportive of portal hypertension
Transient elastography - US to measure sound wave velocity and indicate the degree of fibrosis
USS, CT or MRI

Answer 265

A

Ask about alcohol intake, metabolic risk, hepatitis risk, hepatotoxic medications, FHx, previous jaundice, travel history

USS and other imaging

If <40 then check serum copper and caeruloplasmin

LFTs, FBC, renal function, coagulation tests

Virology - hep B, hep C , CMV< EBV

Biochemistry - alpha-1-antitrypsin, HbA1c, blood glucose, iron studies, alpha-fetoprotein (tumour marker)

Immunology - autoantibodies and coeliac, immunoglobulins

Answer 266

A

Liver fibrosis -> increased pressure in portal system -> splenomegaly -> hypersplenism
(Other causes - alcohol effects on bone marrow or DIC)

Answer 267

A

Remove aetiological factor e.g. alcohol cessation, stopping meds, anti-viral therapies
Diet - healthy, balanced diet as malnutrition is common, cutting down on salt and reduce oedema/ascites
Meds - diuretics, hypotensive agents, prescription creams to ease skin itching
Manage major complications
Liver transplantation

Answer 268

A

Hepatic encephalopathy
Ascites
Hyponatraemia
Gastrointestinal bleeding (i.e. variceal bleed)
Bacterial infections (i.e. SBP)
Acute kidney injury
Hepatocellular carcinoma
Hepatorenal syndrome
Hepatopulmonary syndrome
Acute-on-chronic liver failure

Answer 269

A

Caused by hyperammonaemia
One theory - portal hypertension, causes shunting of ammonia away from the liver into the systemic circulation at portosystemic collaterals -> encephalopathy

Answer 270

A

First-line treatments: involves laxatives (i.e. lactulose 15-20 mls QDS) to maintain bowel motions. Should aim for 2-3 bowel motions per day - this is because constipation is the main driver of encephalopathy
Second-line treatments: involves the long-term use of antibiotics (i.e. rifaximin) to reduce the proportion of ammonia-producing colonic bacteria.

Answer 271

A

It develops due to a combination of portal hypertension and loss of oncotic pressure due to hypoalbuminaemia.
Due to widespread vasodilatation and underperfusion of the kidneys, the RAAS is active leading to excess water and sodium reabsorption that exacerbates ascites.

Answer 272

A

Aldosterone antagonists which may be combined with loop diuretics
Paracentesis

Answer 273

A

Lower oesophagus
Upper anal canal
Umbilicus
Bare area of the liver
Retroperitoneum

Answer 274

A

Infection in ascitic fluid.
It is defined as a predominantly neutrophilic ascitic white cell count (WCC) >250/mm3.

Answer 275

A

Antibiotics: Follow local guidance, should not be delayed, ascitic tap should be obtained prior.
Human albumin solution: Helps to prevent the development of acute kidney injury and hepatorenal syndrome.
Prophylaxis: Patients at risk of, or following confirmed, SBP should be managed with long-term prophylactic antibiotics (e.g. rifaximin).

Answer 276

A

United Kingdom model for end-stage liver disease (UKELD) score

Answer 277

A

Serum creatinine
Sodium
Bilirubin
INR

The minimum criteria for listing a patient for liver transplantation is a score ≥ 49, which represents a 9% one-year mortality without a transplant

Other indications for liver transplantation, outside the UKELD score, are based on the presence of hepatocellular carcinoma with specific criteria and variant syndromes (e.g. diuretic resistant ascites).

Answer 278

A

6th most frequently diagnosed cancer
3rd leading cause of cancer-released deaths
Incidence is highest in Asia due to burden of viral hepatitis
M:F 3:1

Answer 279

A

Cirrhosis is the largest risk factor (up to 1/3rd of pt will deve;op it in their lifetime)
Chronic hep B even in the absence of cirrhosis
Hep c usually with advanced fibrosis or cirrhosis

Others - hep D, aflatoxin, betel nut chewing (common in Asia), alcohol, smoking, NAFLD, AAT deficiency, hereditary haemachromatosis, androgenic steroids and a weak association with the contraceptive pill

Answer 280

A

A mycotoxin produced by certain moulds
Can contaminate food products

Answer 281

A

Chronic liver injury -> necrosis -> hepatocytes regeneration -> regenrative nodules can lead to hyperplasia -> dysplasia -> maliganncy

Answer 282

A

Because it can integrate its own DNA material into the host genome and promote replication

Answer 283

A

Due to cirrhosis nearly always being present in HCV

Answer 284

A

Bones, lymph nodes and lungs (via the hepatic or portal veins)

Answer 285

A

Many pt are asymptomatic
features of liver failure/cirrhosis (may present as de compensated liver disease)
Constitutional symptoms - fever, anorexia, night sweats, weight loss, fatigue
Localised symptoms - abdo pain, hepatomegaly, RUQ mass, jaundice
Paraneoplastic syndromes

Answer 286

A

Hypoglycaemia (due to tumours high metabolic rate or, rarely, secretion of insulin-like growth factor)
Erythrocytosis (due to secretion of EPO)
Hypercalcaemia (due to secretion of parathyroid-hormone related peptide)
Dermatological conditions e.g. dermatomyositis

Answer 287

A

There are 2 ways to make a formal diagnosis…
Imaging - CT or MRI using imaging criteria
Histology - liver biopsy or surgical specimen

(Also do routine liver biochemistry, FBC, U&Es, alpha-fetoprotein, USS)

Answer 288

A

Liver Imaging Reporting and Data System (LIRaDS)

Answer 289

A

a focal nodule >1cm with early enhancement on the arterial phase with rapid washout of contrast on the portal venous phase of a three-phase contrast scan

Answer 290

A

Pain
Bleeding
Needle track seeding (implantation of tumour cells along the tract created by an instrument when trying to take a sample)
Infection
Injury to a nearby organ e.g. Perforation of gallbladder

Answer 291

A

surgical resection in early disease
Liver transplantation
Radio frequency ablation
Transarterial chemoembolisation
For more advanced disease… Multikinase inhibitors e.g. Sorafenib

Answer 292

A

Assesses the suitability of pt for lover transplant with cirrhosis and hepatocellular carcinoma

It has three components:
Tumour size: A single lesion < 5 cm, OR, up to 3 lesions each < 3cm
Invasion: no evidence of macrovascular invasion
Other features: No extrahepatic features

Patients who meet the Milan criteria have a < 10% recurrence rate and 5-year survival of 70%.

Answer 293

A

Stage 0-A: > 5 years
Stage B: > 2.5 years
Stage C: > 1 year
Stage D: ~ 3 months

Overall 5-year survival for all stages is only 15%

Answer 294

A

> 12g
Doses of >150mg/kg associated with serious or fatal adverse effects
Doses <75mg/kg are unlikely to cause toxicity unless staggered

Answer 295

A

The ingestion of a potentially toxic dose of paracetamol within 1 hour or less.
Serious toxicity is unlikely if a patient has ingested <75 mg/kg. If a patient has ingested > 75 mg/kg, are symptomatic, or need urgent psychiatric assessment, hospital admission is warranted.

Answer 296

A

This refers to excessive ingestion of paracetamol over a period longer than one hour, usually in the context of self-harm.
Serious toxicity may occur in patients who have ingested > 150 mg/kg in any 24 hour period. Rarely, toxicity may occur for ingestions between 75-150 mg/kg. Doses consistently < 75 mg/kg in any 24 hour period are unlikely to be toxic. However, if paracetamol above the recommended daily dose (4g/24 hours in adults) is ingested for the two preceding days or more, the risk increases.
All patients that have taken a staggered overdose should be referred to hospital for assessment.

Answer 297

A

As a staggered overdose

Answer 298

A

Once ingested, paracetamol reaches peak concentration at 4 hours with an average half life of 2 hours. This may be significantly increased in the presence of hepatic dysfunction.

Answer 299

A

Paracetamol is primarily metabolised in the liver via conjugation with the addition of glucuronide to form a water soluble metabolite that can be excreted in the urine

Answer 300

A

When there is excess paracetamol ingestion, such as with overdose, conjugation in the liver become saturated and paracetamol is converted into the metabolite N-acetyl-p-benzoquinoneimine (NAPQI).
NAPQI has a short half-life and is usually conjugated by the addition of glutathione, which is then renally excreted. When glutathione stores are depleted, excess NAPQI binds to hepatocellular proteins and results in oxidative damage, mitochondrial dysfunction and ultimately hepatocellular injury.
Anything that effects glutathione reserves may increase the risk of severe hepatotoxicity such as fasting, excess alcohol consumption and certain drugs

Answer 301

A

Pt may be completely asymptomatic in the early stages. They may have nausea, vomiting and abdominal pain

Around 12-36 hours following the overdose pt typically experience abdominal pain
At 48-72 hours pt develop clinical features due to hepatic necrosis - RUQ pain, nausea, vomiting, jaundice, AKI, hepatic encephalopathy

Rarely, patients who have taken a significant overdose with very high plasma paracetamol concentrations may develop early metabolic acidosis, raised lactate and possibly coma.

Answer 302

A

History
FBC
U&Es
LFTs
Bone profile
Blood gas
BG
Paracetemol levels
Salicylates levels (always request in acute overdose)
Nomogram

Answer 303

A

A paracetemol ingestion graph
It plots paracetemol concentration against time from ingestion
If paracetemol concentration lies on or above the treatment line, then NAC should be administered

This is use for patient paracetamol over 1 hour or less and presented within 8 hours

Answer 304

A

It determines whether treatment with N-acetylcysteine (NAC) is needed

Answer 305

A

IV NAC
Standard 21 hour regimen which is based on the pt weight

Answer 306

A

First infusion at 1 hour - 200mls 5% dextrose or 0.9% NaCl with 150mg/kg of NAC
Second infusion at 4 hour - 500mls 5% dextrose or 0.9% NaCl with 50mg/kg of NAC
Third infusion at 16 hour -1000mls 5% dextrose or 0.9% NaCl with 100mg/kg of NAC

Answer 307

A

Take bloods in to look for signs of hepatic impairment
If there is any evidence of significant deranged LFTs or abnormal renal function. The patient should be discussed with the liver transplant centre.

Answer 308

A

It’s a precursor to glutathione so it increases glutathione concentration so more can bind to NAPQI

Answer 309

A

Anaphylactic reactions (30% of pt)

Answer 310

A

nausea, vomiting, urticarial rash, angioedema, tachycardia, and bronchospasm. Shock is uncommon.

Answer 311

A

Temporary stop of infusion
Consider chlorpromazine and nebulised salbutamol
Once reaction has settles and slowly restart the infusion with the first bag over 2 hours

Answer 312

A

If plasma paracetemol concentration is on or above the line on a nomogram
Any staggered overdose
If any doubt over time of paracetemol ingestion
patients who present > 24 hours if they are clearly jaundiced or have hepatic tenderness, their ALT is above the upper limit of normal

Answer 313

A

Consider - activated charcoal may help reduce absorption of the drug
4 hours post ingestion check bloods, paracetemol levels and assess nomogram. If at risk then give IV NAC

Answer 314

A

Arterial pH < 7.3, 24 hours after ingestion

or all of the following:
prothrombin time > 100 seconds
creatinine > 300 µmol/l
grade III or IV encephalopathy

Answer 315

A

vasoactive mediators cause splanchnic vasodilation which in turn reduces the systemic vascular resistance.
This results in ‘underfilling’ of the kidneys. This is sensed by the juxtaglomerular apparatus which then activates the RAAS, causing renal vasoconstriction which is not enough to counterbalance the effects of the splanchnic vasodilation.

Answer 316

A

Type 1 is rapidly progressive and has a very poor prognosis
Type 2 is slowly progressive and prognosis is poor but pt may liver for longer

Answer 317

A

Liver transplantion is ideal but pt are often too unwell to have surgery and there’s a shortage of donors
Vasopressin analogues e.g. Terlipressin, to cause vasoconstriction of splanchnic ciruclation
Volume expansion with 20% albumin
TIPPS

Answer 318

A

AKI in pt with liver disease
It represents the end-stage of a reduction in kidneys perfusion induced by increasingly severe hepatic injury
Diagnosis of exclusion

Answer 319

A

Ground-glass hepatocytes with flat, hazy and uniformly dull appearing cytoplasms

Answer 320

A

Portal vein thrombosis
Arteriovenous fistula
Increased splenic blood flow or splenic vein thrombosis

Answer 321

A

Cirrhosis
Schistomiasis
Polycystic liver disease
Metastatic maligannt disease
Drugs
Veno-occlusive disease
Sarcoidosis
Massive fatty change
Nodular regenerative hyperplasia
Alcoholic hepatitis

Answer 322

A

Budd-chiari syndrome
Veno-occlusive disease
Severe right sided HF or constrictive pericarditis (very rare now)

Answer 323

A

Usually asymptomatic and only present with splenomegaly
Complications can cause haematemesis or meleana, ascites and encephalopathy

Answer 324

A

Portal hypertension
Hypoalbuminaemia
Na+ and water retention due to peripheral arterial vasodilation
All can occur at once

Answer 325

A

A rare disorder affecting children up to the age of 15
characterised by an acute, life-threatening, non-inflammatory encephalopathy and fatty degeneration of the liver with minimal or no clinical signs of liver involvement. In classic Reye’s syndrome, there is a severe but self-limiting disturbance of mitochondrial structure and associated enzymatic disturbances usually lasting about six days. This is accompanied by an intense, acute catabolic state associated with cerebral oedema in the absence of encephalitis or meningitis.

The pathogenesis of Reye’s syndrome is unclear but it appears to involve mitochondrial dysfunction that inhibits oxidative phosphorylation and fatty-acid beta-oxidation in a virus-infected, sensitised host. The host has usually been exposed to mitochondrial toxins, most commonly salicylates (e.g. aspirin use). Histologically the mitochondria are seen to become swollen and reduced in number. The liver and kidney are both affected. Changes in the brain result in cerebral oedema and increased intracranial pressure (ICP).
A rare complication of common viral infections

Answer 326

A

a group of inherited diseases that result from a lack of, or abnormal functioning of, one of the enzymes involved in the conversion of glucose to glycogen or the breakdown of glycogen back into glucose. Because there are a number of different enzymes involved in glycogen production and breakdown, there are a number of different glycogen storage disorders

If the enzyme problem is with one of the enzymes involved in glycogen production (synthesis), this causes reduced amounts of normal glycogen to be produced and sometimes abnormal glycogen being produced.
If the enzyme problem is with one of the enzymes involved in glycogen breakdown back into glucose, this can lead to hypoglycaemia and a build-up of glycogen in your muscles and liver.

Answer 327

A

a clinical syndrome of severe liver function impairment, which causes hepatic coma and the decrease in synthesizing capacity of liver, and develops within eight weeks of the onset of hepatitis.

Answer 328

A

A pus-filled pocket of fluid within the liver

Answer 329

A

Staph aureus in children
E.coli in adults

Answer 330

A

Drainage
Amoxicillin + ciprofloxacin + metronidazole

Answer 331

A

Due to the dual blood supply via hepatic artery and portal vein

Answer 332

A

Hepatic artery occlusion - arteriosclerosis, thrombosis, emboli, hepatic artery aneurysm, polyarteritis nodes, sickle cell disease

Others - shock, trauma, hypercoagulable state, eclampsia, complications of anaesthesia

Answer 333

A

Liver ischaemia
Obstruction to hepatic vascular inflow - Portal vein thrombosis, hepatic artery thrombosis, presinusoidal causes of vascular obstruction
Obstruction to hepatic vascular outflow - Budd-chiari syndrome (hepatic vein thrombosis), thrombosis of retrohepatic inferior vena cava and vasoocclusive disease
Obstruction to blood flow through the liver - Sickle cell disease, DIC, intrasinuoidal malignancy, infection

Answer 334

A

A potentially life-threatening condition in which some small veins in the liver are obstructed
Also called sinusoidal obstruction syndrome

Answer 335

A

Stellate cells store retinoids in their resting state and contain the intermediate filament, desmin. When activated (to myofibroblasts), they are contractile and regulate sinusoidal blood flow.

Under appropriate conditions, stellate cells can also produce proteases that degrade the extracellular matrix, leading to reversal of fibrosis. The balance between collagen production and degradation is critical to the progression of liver scarring and cirrhosis development/resolution

Answer 336

A

Endothelin and nitric oxide play a major role in modulating stellate cell contractility. Stellate cells are activated by a wide variety of inflammatory cytokines

Answer 337

A

Reduce dietary sodium
Fluid restriction may be requires if Na+ is <125mmol/L
Aldosteron antagonists
Drainage if tense ascites with albumin cover
Prophylactic antibiotics to reduce risk of SBP
TIPS may be considered in some patients

Answer 338

A

Albumin administration reduces paracentesis-Induced Circulatory Dysfunction and renal failure

Answer 339

A

Human albumin solution - A solution containing protein derived from plasma, serum, or normal placentas

Answer 340

A

Apoptotic hepatocytes which are acidophilic globule of cells that represent a dying hepatocytes surrounded by normal parenchyma (necrosis of individual hepatocytes)

Answer 341

A

Hepatitis (viral, autoimmune or drug)

Answer 342

A

Necrosis of a minute cluster of hepatocytes. Macrophages and lymphocytes tend to accumulate around them in an effort to localise the damage.

Answer 343

A

Hepatitis (viral, autoimmune, drug)

Answer 344

A

Necrosis involving a particular zone of the acinus
Zone 3 is most typically affected

Answer 345

A

Zone 1 is periportal cells (closest to portal vessels so best oxygenated)
Zone 2 is mid lobular cells
Zone 3 is pericentral cells (closest to central vein where oxygenation is poor)

Answer 346

A

Zone 1 hepatocytes are specialized for oxidative liver functions e.g. gluconeogenesis, β-oxidation of fatty acids and cholesterol synthesis

zone III cells are more important for glycolysis, lipogenesis and cytochrome P-450-based drug detoxification (here there is the highest concentration of CYP2E1 and thus are most sensitive to NAPQI production in acetaminophen toxicity)

Answer 347

A

Portal vessel - autoimmune hepatitis, haemochromatosis, biliary cirrhosis

Central vein - NAFLD, drug/alcohol induced toxicity, parasite infection

Answer 348

A

It is characterized by inflammation extending from the portal tract (PT) into the periportal zone, with necrosis of periportal hepatocytes and disruption of the limiting plate
(A type of zonal necrosis)

Answer 349

A

Hepatitis (viral, autoimmune, drug)

Answer 350

A

necrosis involving multiple lobules
E.g. in localised ischaemic injury

Answer 351

A

Inferior portion of oesophagus
Superior portal of the anal canal
Round ligament of the liver (previous umbilical cord)

Answer 352

A

> 5-10mm/Hg

Answer 353

A

When blood is diverted away from the portal venous system and backs up into the systemic veins
(Less blood gets to liver -> decreased liver function and blood detoxification which causes a build up of toxic metabolites e.g. ammonia)

Answer 354

A

Blood backs up into the spleen causing congestive splenomegaly which leads to hypersplenism = anaemia, leukopenia and thrombocytopenia

Answer 355

A

Portal hypertension causes endothelial cells to release more NO -> arteries dilate -> hypotension -> stimulates release of aldosterone -> kidneys retain sodium and water -> fluid gets pushed a crossed tissues = ascites

Answer 356

A

Ascites (distended abdomen)
Bleeding (secondary to oesophageal varices)
Caput medusae
Diminished liver function (jaundice, hepatic encephalopathy, bleeding etc)
Enlarged spleen (anaemia, thrombocytopenia and leukopenia)

Answer 357

A

Take a hepatic venous pressure gradient measurement (catheter is inserted into IVC and then into portal vein to measure the difference in pressures)
Liver USS to look for cirrhosis
CT or MRI to look for ascites, cirrhosis and splenomegaly
FBC, liver enzymes, serology
OGD to look for oesophageal varices

Answer 358

A

Beta blockers can decrease portal venous pressured
Diuretics and sodium restriction for ascites
Manage oesophageal varices and prevent bleeding again with TIPPS (creates an internal bypass between portal and hepatic vein= relieves pressure)

Answer 359

A

A rare lung complication of liver disease
It’s hypoxaemia due to dilated intrapulmonary vasculature = somehow causes a ventilation-perfusion mismatch
Causes SOB, clubbing, spider angioma, cyanosis, low blood o2 sats

Answer 360

A

Chronic obstruction to flow within portal venous system = portal vein pressure builds up

Answer 361

A

Type 1 is a rapid onset hepatorenal syndrome (less than two weeks). This typically occurs following an acute event such as an upper GI bleed.
Type 2 is a more gradual decline in renal function and is generally associated with refractory ascites

Answer 362

A

Alcohol is converted to acetaldhyde by alcohol dehydrogenase using the conversion of NAD+ to NADH. This also produces reactive oxygen species.
As NADH levels increase, more fatty acids are produced
As NAD+ levels decrease, less fatty acid oxidation
Both lead to more fat production in the liver

Answer 363

A

Production of acetaldhyde from alcohol causes production of ROS
Reactive oxygen species can damage proteins, including DNA
Acetaldehyde can also inhibit anything they bind to and this causes acetaldhyde adducts to form = immune system recognises these as foreign = neutrophil clear up = destruction of hepatocytes by neutrophilic infiltration
At this point you may get painful hepatomegaly and neutrophil leukocytosis

Answer 364

A

Mallory bodies - Damaged intermediate filaments in the cytoplasm of hepatocytes

Answer 365

A

ALT exceeding AST

Answer 366

A

Yellow fever
Dengue fever
Lassa fever
Ebola

Answer 367

A

Spread by aedes mosquitos
Common in tropical and subtropical areas of Africa and South America

Answer 368

A

2-14 days incubation
may cause mild flu-like illness lasting less than one week
classic description involves sudden onset of high fever, rigors, nausea & vomiting. Bradycardia may develop. A brief remission is followed by jaundice, haematemesis, oliguria
if severe jaundice, haematemesis may occur

Answer 369

A

Acidosis
In one study, 95% of patients with an arterial pH <7.30 who didn’t receive a liver transplant died

Answer 370

A

Pneumococcal one off vaccine

Answer 371

A

Human Normal Immuniglobulin or hep A vaccine

Answer 372

A

If the person is a known responder to the HBV vaccine then give a booster dose
If they are a non-responder then give hep B immune globulin and a booster vaccine

Answer 373

A

monthly PCR - if seroconversion then interferon +/- ribavirin

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HEPATOLOGY Flashcards

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