Liver Pathology Flashcards
(128 cards)
1
Q
Pathogenesis of liver disease
A
Insult to hepatocytes → grading (degree of inflammation) → staging (degree of fibrosis) → cirrhosis
2
Q
Causes of acute liver failure
A
Viruses, alcohol, drugs, bile duct obstruction
3
Q
Outcomes of acute liver failure
A
Complete recovery, chronic liver disease, death
4
Q
What is jaundice?
A
Yellowing of the skin due to bilirubin
5
Q
Pre-hepatic jaundice:
- Why does it occur?
- Examples of causes
- Is bilirubin conjugated or unconjugated?
A
- When there is too much haem to break down
- Haemolytic anaemia
- Unconjugated bilirubin
6
Q
Hepatic jaundice:
- Why does it occur?
- Examples of causes
- Is bilirubin conjugated or unconjugated?
A
- When liver cells are injured or dead
- Pregnancy, acute liver failure, alcoholic hepatitis, cirrhosis, bile duct loss
- Both unconjugated and conjugated bilirubin
7
Q
Post-hepatic jaundice:
- Why does it occur?
- Examples of causes
- Is bilirubin conjugated or unconjugated?
A
- Bile cannot escape the bowel
- Congenital biliary atresia, gallstones in common bile duct, strictures of common bile duct, tumours
- Conjucated
8
Q
What is liver cirrhosis defined by?
A
Bands of fibrosis separating regenerative nodules of hepatocytes
9
Q
2 types of liver cirrhosis
A
Macronodular and micronodular
10
Q
Causes of liver cirrhosis
A
Alcohol, gallstones, hepatitis B and C, iron overload, autoimmune liver disease
11
Q
Complications of liver cirrhosis
A
Portal hypertension, ascites, liver failure
12
Q
Clinical features of chronic liver disease
A
Oedema, ascites, haematemesis, gynaecomastia, spider naevi, purpura and bleeding, coma, infection
13
Q
What causes oedema in chronic liver disease?
A
Hypoalbuminaemia
14
Q
What causes ascites in chronic liver disease?
A
Hypoalbuminaemia, secondary hypoaldosteronism, portal hypertension
15
Q
What causes haematemesis in chronic liver disease?
A
Ruptured oesophageal varices due to portal hypertension
16
Q
What causes gynaecomastia in chronic liver disease?
A
Hyperoestrogenism
17
Q
What causes spider naevi in chronic liver disease?
A
Hyperoestrogenism
18
Q
What causes purpura and bleeding in chronic liver disease?
A
Reduced clotting factor synthesis
19
Q
What causes coma in chronic liver disease?
A
Failure to eliminate toxic gut bacterial metabolites
20
Q
What causes infection in chronic liver disease?
A
Reduced Kupffer cells and numbers
21
Q
Pathogenesis of alcoholic liver disease
A
o Increased peripheral release of fatty acids and increased synthesis of fatty acids within liver cells
o Acetaldehyde, a product of alcohol metabolism, is probably responsible for liver cell injury, manifested by the formation of Mallory’s hyaline
o There is increased collagen synthesis by fibroblasts and by the perisinusoidal cells of Ito
22
Q
Duration of liver disease and alcoholic liver disease:
- 2-3 days
- 4-6 weeks
- Months-years
- Years
A
2-3 days → fatty liver → reversible
4-6 weeks → hepatitis → reversible
Months-years → fibrosis → irreversible
Years → cirrhosis → irreversible
23
Q
Weekend binge drinking:
- Pathology in hepatocytes
- Outcome
- Differential diagnoses
A
- Fat vacuoles in hepatocytes
- Reversible outcome
- NASH, pregnancy, drugs, nutritional, diabetes, hepatitis C
24
Q
Heavy drinking for weeks to months:
- Histological features
- Outcome
A
- Hepatocyte necrosis, neutrophils, mallory bodies, pericellular fibrosis
- Reversible if drinking stops
25
Heavy drinking for months to years:
- Histological features
- Outcome
- Collagen is laid down around cells, bands of fibrosis separating regenerative nodules
- Irreversible
26
Outcomes for alcoholic liver disease
Cirrhosis, portal hypertension, varices, ascites, malnutrition, hepatocellular carcinoma
27
Non-alcoholic steatohepatitis:
- Which patients does it occur in?
- What can it lead to?
- Non drinkers, diabetes, obesity, hyperlipidaemia
| - Fibrosis and cirrhosis
28
Viruses that can cause:
- Hepatitis A
- Hepatitis B
- Hepatitis C
- Hepatitis D
- Hepatitis A = Epstein Barr virus
- Hepatitis B = yellow fever virus
- Hepatitis C = herpes simplex virus
- Hepatitis D = cytomegalovirus
29
Hepatitis A:
- Spread
- Incubation period
- Is there a carrier state?
- Outcome
- Faecal-oral spread
- Short incubation period
- No carrier state
- Mild illness with usually full recovery
30
Hepatitis B:
- Spread
- Incubation period
- How does it cause liver disease?
- Is there a carrier state?
- Outcomes
- Spread by blood, blood products, sexually, vertically
- Long incubation period
- Causes liver disease by antiviral immune response
- Carriers exist
- Death, chronic hepatitis, cirrhosis, hepatocellular carcinoma, asymptomatic
31
Hepatitis C:
- Spread
- Incubation period
- Outcomes
- Blood, blood products
- Short incubation period
- Chronic hepatitis, cirrhosis
32
Aetiology of chronic hepatitis
Hepatitis B, hepatitis C, primary biliary cirrhosis, autoimmune hepatitis, drug induced hepatitis, primary sclerosing cholangitis
33
Primary biliary cirrhosis:
- What is it caused by?
- More common in males or females?
- Outcome
- Autoimmune disease associated with autoantibodies to mitochondria
- Females (90%)
- Bile duct loss leads to cholestasis, liver injury, inflammation, fibrosis and cirrhosis
34
Autoimmune hepatitis:
- More common in males or females?
- Which cells are numerous?
- What are autoantibodies to?
- Females
- Plasma cells are numerous
- Autoantibodies to smooth muscle, nuclear or LKM, raised IgG
35
Primary sclerosing cholangitis:
- What is it?
- What can it lead to?
- What disease is it associated with?
- Which gender is it more common in?
- What does histological staining show?
- Chronic inflammatory process affecting intra- and extra-hepatic bile ducts
- Leads to periductnal fibrosis, duct destruction, jaundice and fibrosis
- Ulcerative colitis
- Femakes
- Periductnal onion-skinning fibrosis
36
Haemochromatosis:
- What is it?
- Primary causes
- Secondary causes
- Excess of iron in the liver
- Genetic condition, increased absorption of iron
- Iron overload from diet, transfusions, iron therapy
37
Is primary haemochromatosis autosomal dominant or recessive?
Recessive
38
Where in the liver does iron accumulate?
Hepatocytes
39
Which staining is used to confirm iron?
Perls staining
40
Wilson's disease:
- What is it?
- Where does copper accumulate?
- Signs
- What can it cause?
- Inherited autosomal recessive disorder of copper metabolism
- Liver and brain
- Kayser-Fleischer rings at corneal limbus and low serum caeruloplasmin
- Chronic hepatitis and neurological deteriorateion
41
Alpha-1-antitrypsin deficiency:
- What is it?
- What does it cause?
- Inherited autosomal recessive disorder of an enzyme inhibitor
- Empyema, cirrhosis
42
Primary tumours of the liver
Hepatocellular adenoma, hepatocellular carcinoma
43
Where can liver cancer metastasise from?
Colon, pancreas, breast, lung, etc
44
Hepatocellular carcinoma:
- What is it associated with?
- How does it present?
- HBV, HCV, cirrhosis
| - Mass, pain, obstruction
45
What is acute liver disease?
The rapid development of hepatic dysfunction without prior liver disease
46
Functions of the liver
- Protein metabolism
- Carbohydrate metabolism
- Lipid metabolism
- Bile acid metabolism
- Bilirubin metabolism
- Hormone and drug metabolism
- Immunological defence
47
Liver function tests
ALT/AST, Alk phos, GGT, bilirubin, albumin, prothrombin time
48
Duration of acute liver disease
<6 months duration
49
Acute liver failure
Causing encephalopathy and prolonged coagulation
50
Clinical features of acute liver disease
Jaundice, lethargy, nausea, anorexia, pain, itch, arthralgia, abnormal liver function tests
51
Causes of acute liver disease
Viral A, B, C, D, E, CMV, EBV, drugs, shock to liver, cholangitis, alcohol, malignancy, chronic liver disease, overuse of paracetamol, Budd Chiari, acute fatty liver or cholestasis of pregnancy
52
Investigations for acute liver disease
LFTs incl. albumin and bilirubin, prothrombin time, US, virology
53
Treatment of acute liver disease
Rest (3-6 months), fluids, no alcohol, sodium bicarbonate bath for itch, cholestyramine for itch, ursodeoxycholic acid for itch, observation for fulminant hepatic failure
54
Antibiotics that can cause liver injury
Co-amoxiclav, flucloxacillin, NSAID
55
Fulminant hepatic failure:
| - What is it?
Acute episodes of severe liver dysfunction (jaundice and encephalopathy) in a patient with a previously normal liver
56
Causes of fulminant hepatic failure
Paracetamol, viral, drugs, HBV, mushrooms, malignancy, Wilson's, Budd Chiari
57
Clinical cause and complications of fulminant hepatic failure
- Encephalopathy
- Hypoglycaemia
- Coagulopathy
- Circulatory failure
- Renal failure
- Infection
58
Treatment for fulminant hepatic failure
Supportive, inotropes and fluids, renal replacement, management of raised ICP, liver transplant
59
What is chronic liver disease?
Liver disease of a duration > 6 months
60
Pathology in chronic liver disease
Recurrent inflammation and repair with fibrosis of the liver and regeneration of hepatocytes
61
Outcome of chronic liver disease
Progression to cirrhosis
62
Causes of chronic liver disease
Alcohol, NAFLD, hepatitis C, primary biliary cholangitis, autoimmune hepatitis, hepatitis B, haemochromatosis, primary sclerosing cholangitis, Wilson's disease, alpha-1 anti-trypsin, Budd Chiari, drugs
63
How much of the population have non alcoholic fatty liver disease?
20-30%
64
How much of the population with NAFLD have non-alcoholic steatohepatitis?
20-30%
65
Spectrum of pathology in non-alcoholic steatohepatitis
Steatosis → steatohepatitis → steatohepatitis with fibrosis → cirrhosis
66
Steatohepatitis:
- What is it?
- Describe inflammation
- Describe hepatocyte degeneration
- Describe fibrosis
- Inflammation and concurrent fat accumulation of the liver
- Usually mild, lobular and mixed mononuclear and neutrophilic infiltrate
- Mallory bodies and ballooning
- Initially pericellular fibrosis, later bridging
67
Metabolic risk factors for non-alcoholic fatty liver disease
Type II diabetes, obesity, HDL cholesterol <40mg/dL in men and <50mg/dL in women, hypertension, triglycerides ≥150mg/dL
68
Diagnosis of simple steatosis
Ultrasound
69
Treatment for simple steatosis
Weight loss and exercise
70
Diagnosis of non-alcoholic steatohepatitis
Liver biopsy
71
Treatment for non-alcoholic steatohepatitis
Weight loss and exercise and other treatments are experimental
72
Examples of autoimmune liver diseases
Primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis
73
Primary biliary cholangitis - which cell mediates it?
T-cell, CD4 cells reactive to M2 target
74
Symptoms of primary biliary cholangitis
Itch without rash, fatigue, xanthelasma and xanthomas
75
Diagnosis of primary biliary cholangitis
2 of 3:
- Positive AMA (antimitochondrial antibodies)
- Cholestatic LFTs (alkaline phosphate and gamma GT are elevated more than ALT)
- Liver biopsy
76
Treatment for primary biliary cholangitis
Urseo-deoxycholic acid (first line), obeticholic acid
77
How does urseo-dexycholic acid work?
Causes increased flow of bile from the liver and washes toxic bile salts out
78
Type I immunology in autoimmune hepatitis:
- When does it present?
- Which antibodies are associated?
- Which antigen is associated?
- Presents in adult, commonly affecting teenage girls and adults
- ANA antibody, ASMA antibody
- Soluble liver antigen
79
Type II immunology in autoimmune hepatitis:
- When does it present?
- Which antibodies are associated?
- Children and young adults
| - Liver-kidney-microsomal-1 antibody, AMA may also be present
80
Clinical presentation of autoimmune hepatitis
Jaundice, general fatigue, elevated AST and ALT, elevated PT, malaise, nausea, abdominal pain, anorexia
81
Diagnosis of autoimmune hepatitis
Elevated AST and ALT, elevated IgG, rule out other causes, presence of autoimmune antibodies, liver biopsy
82
Genetic predisposing factors to autoimmune hepatitis
HLA-DR3 (severe form), HLA-DR4
83
Drugs associated with autoimmune hepatitis
- Oxyphenisatin, Methyldopa, Nitrofurantoin, Diclofenac, Minocycline, Statins
84
Combination therapy for treatment of autoimmune hepatitis
Prednisolone (30g daily then taper down to 15mg at week 4 then maintain on 5mg daily) + azothioprine (50-100mg daily)
85
Primary sclerosing cholangitis:
- What is it?
- Clinical presentation
- Diagnosis
- Treatment
- Autoimmune destructive disease of large and medium sized bile ducts
- Recurrent cholangitis
- Imaging of biliary tree
- Maintain bile flow, monitor for cholangiocarcinoma and colorectal cancer
86
Treatment for haemochromatosis
Venesection weekly or 2 weekly
87
Clinical presentation of Wilson's disease?
Chorea-athetoid movements, cirrhosis or sub-fulminant liver failure, Kaiser Fleischer rings
88
Treatment for Wilson's disease
Copper chelation drugs
89
Clinical presentation of alpha-1 anti-trypsin deficiency
Lung emphysema (exacerbation by smoking), liver disposition of mutant protein, cell damage
90
Treatment for alpha 1 anti-trypsin deficiency
Supportive management
91
Where is the genetic mutation in alpha 1 anti-trypsin deficiency?
A1AT gene
92
Budd Chiari:
- What is it?
- Clinical presentation
- Diagnosis
- Mangement
- Thrombosis of the hepatic veins
- Acute - jaundice, tender hepatomegaly, chronic - ascites
- Ultrasound of hepatic veins
- Recanilisation or TIPS
93
Most common liver tumour
Haemangioma
94
What is haemangioma?
Hypervascular tumour that is usually a single, small, well demarcated capsule
95
Diagnosis of haemangioma
Ultrasound - echogenic spot, well demarcated
CT - venous enhancement from periphery to centre
MRI - high intensity area
96
Focal nodal hyperplasia:
| - What is it?
Benign nodule formation of normal liver tissue. Classically, but not always, central scar containing a large artery, radiating branches to the periphery
97
Histology of focal nodal hyperplasia
Sinusoids, bile ductules and Kupffer cells
98
Diagnosis of focal nodal hyperplasia
Ultrasound - nodule with varying echogenicity
CT - hypervascular mass with central scar
MRI - iso or hypo intense
FNA - normal hepatocytes and Kupffer cells with central core
99
What is hepatic adenoma?
Benign neoplasm composed of normal hepatocytes, no portal tract, central veins or bile ducts
100
What medication is hepatic adenoma associated with?
Contraceptive hormones and anabolic steroids
101
Presentation of hepatic adenoma
Usually asymptomatic, RUQ pain, may present with rupture, haemorrhage or malignant transformation
102
Where in the liver are hepatic adenomas most commonly found?
Right lobe
103
Symptoms of hepatic adenoma
Pain, bleeding. Size related
104
Diagnosis of hepatic adenoma
Ultrasound - filling defect
CT - diffuse arterial enhancement
MRI - hypo or hyper intense lesion
FNA may be needed
105
Treatment for hepatic adenoma
Stop hormones, weight loss, for males: surgical excision, for females: imaging after 6 months - <5cm or reducing in size annual MRI, >5cm or increasing in size surgical excision
106
Simple cyst
Liquid collection lined by epithelium
107
What are symptoms of simple cyst related to?
Intracystic haemorrhage, infection, rupture, compression
108
Hydatid cyst:
- What is it caused from?
- Management
- Echinococcus granulosus
| - Surgery, albendazole, percutaneous drainage
109
Polycystic liver disease:
- What is it?
- What does it result in?
- 3 types
- Embryonic ductal plate malformation of the intrahepatic biliary tree
- Results in numerous cysts throughout liver parenchyma
- Von Meyenburg complexes, polycystic liver disease, autosomal dominant polycistic kidney disease
110
Another name for Von Meyenburg complexes
Microhamartomas
111
Symptoms of polycystic liver disease
Asymptomatic, abdominal pain, abdominal distension, atypical symptoms due to voluminous cysts resulting in compression of adjacent tissue or failure of the affected organ
112
Management of polycystic liver disease
Care of symptoms, conservative treatment to halt cyst growth, somatostatin analogues, surgery in selective patient group with PCLD, ADPKD or liver failure
113
Clinical features of liver abscess
High fever, leucocytosis, abdominal pain, complex liver lesion, history of abdominal or biliary infection or dental procedure
114
Management of liver abscess
Broad spectrum antibiotics, aspiration/drainage percutaneously, echocardiogram, operation if no clinical improvement
115
Hepatocellular carcinoma:
- Risk factors
- Clinical features
- On examination
- Cirrhosis of any cause (alcohol, hepatitis B/C, aflatoxin)
- Weight loss and RUQ pain, asymptomatic, worsening of pre-existing chronic liver disease, acute liver failure
- Signs of cirrhosis, hard enlarged RUQ mass, liver bruit (rare)
116
Where can hepatocellular carcinoma metastasise to?
Rest of liver, portal vein, lymph nodes, lung, bone, brain
117
What value of AFP is highly suggestive of hepatocellualr carcinoma?
>100mg/L
118
Diagnosis of hepatocellular carcinoma
Clinical presentation, elevated AFP, ultrasound, triphasic CT scan, MRI, biopsy
119
What does prognosis with hepatocellular carcinoma depend on?
Tumour size, extrahepatic spread, underlying liver disease, patient performance status
120
Best available treatment for hepatocellular carcinoma
Liver transplant
121
When is liver transplant for hepatocellular carcinoma given?
Single tumour <5cm or less than 3 tumours less than 3cm each
122
When is resection feasible for hepatocellular carcinoma?
Small tumours with preserved liver function. No jaundice or portal hypertension
123
In which patients is local ablation given as treatment for hepatocellular carcinoma?
When resection is not feasible, patient with advanced liver cirrhosis
124
Process of chemoembolisation in hepatocellular carcinoma
Transarterial chemoembolisation, chemotherapy is selectively injected into hepatic artery, then an embolic agent is injected
125
Which patients can receive chemoembolisation as treatment for hepatocellualr carcinoma?
Those with early cirrhosis
126
Systemic therapy for hepatocellular carcinoma:
- Name of drug
- What does it do?
- Sorafenib
| - Multikinase inhibitor of vascular endothelial gf receptor
127
Fibro-lamellar carcinoma:
- When does it present?
- AFP
- CT
- Management
- Young patients (5-35 years old)
- Normal AFP
- CT shows stellate star with radial septa showing persistent enhancement
- Surgical resection or transplantation, transarterial chemoebolism if unresectable
128
Diagnosis of metastases to the lvier
Imaging or fine needle aspiration
