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HPB Patho Flashcards

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1
Q

What is cholestasis?

A

Systemic retention of bilirubin and other solutes eliminated in bile, caused by impaired bile formation and flow

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2
Q

What is bile?

A

bilirubin and other non-water soluble waste products + bile salts

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3
Q

What is the term for yellow discoloration of the sclera?

A

Icterus

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4
Q

What are 5 symptoms of cholestasis?

A

1) Jaundice
2) Icterus
3) Pruritis (itch)
4) Skin xanthomas (Fat bumps)
5) Intestinal malabsorption (fat-soluble vit ADEK deficiencies)

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5
Q

What are 5 causes of jaundice?

A

Pre-hepatic
1) excess bilirubin prod. (eg. haemolysis, ineffective erythropoeisis)

Hepatic
2) ↓ hepatic uptake (eg. drugs)
3) impaired conjugation (eg. neonatal, genetic, diffuse hepatocellular change)
4) Impaired bile flow (eg. autoimmune cholangiopathies)

Post-hepatic
5) Impaired bile flow (eg. cholelithiasis, cancer)

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6
Q

What is the difference between unconjugated and conjugated bilirubin?

A

Unconjugated:
- ↑ in prehepatic jaundice
- water-insoluble, bound to albumin in circulation
- diffuse into tissues (eg. kernicterus)

Conjugated:
- ↑ in hepatic/post-hepatic jaundice
- water-soluble, non-toxic
- excess excreted in urine (“tea-coloured urine”)

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7
Q

What are the features of obstructive patterned jaundice?

A

1) ↑ conjugated bilirubin
2) tea-coloured urine
3) Pale stools
(Likely post-hepatic)

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8
Q

What are the features of hepatitic patterned jaundice?

A

1) ↑ conjugated bilirubin
2) ↑ unconjugated bilirubin
3) ↑ AST/ALT
4) ±tea coloured urine
5) Normal stools

(likely hepatic)

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9
Q

What is the clinical importance of localising the problem precipitating jaundice?

A

Extrahepatic biliary obstruction: surgical alleviation
Intrahepatic cholestasis: does not benefit from surgery/can be worsened

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10
Q

What are 3 examples of cholestatic diseases?`

A

1) Large bile duct obstruction
2) Primary hepatolithiasis
3) Neonatal cholestasis & biliary atresia

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11
Q

What are 5 common associations of large bile duct obstruction?

A

1) Gallstones (extrahepatic)
2) Malignancies (of biliary tree/pancreas head)
3) Inflammatory bile duct strictures
4) Porta hepatis lymphadenopathy
5) Children: Bile duct malformations/loss

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12
Q

What are the categories for large bile duct obstruction etiologies?

A

1) Intraluminal (eg. stones, parasites)
2) Mural (eg. strictures, malignancies)
3) Extramural (eg. HOP cancers, Portal LNs)

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13
Q

What are 3 sequelae of large bile duct obstruction?

A

1) Acute: reversible with obstruction removal

2) Subtotal/intermittent obstruction:
- ↑ ascending cholangitis risk → intrahepatic cholangitic abscesses/sepsis

3) Chronic: Biliary cirrhosis

4) Acute on Chronic Liver Failure (by superimposed ascending cholangitis)

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14
Q

When is feathery degeneration seen?

A

Hepatocyte damage secondary to cholestasis

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15
Q

When are dilated bile ducts seen?

A

Cholestasis

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16
Q

What is primary hepatolithiasis?

A

Intrahepatic biliary stone formation

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17
Q

What are 3 sequelae of primary hepatolithiasis?

A

Repeated bouts of:
1) Ascending cholangitis
2) Progressive inflammatory destruction/collapse
3) Scarring of hepatic parenchyma (recurrent pyogenic/oriental cholangitis)

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18
Q

Primary hepatolithiasis predisposes a px to ___________________________.

A

1) Biliary Intraepithelial Neoplasia (BilIN)
2) Cholangiocarcinoma

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19
Q

What kind of jaundice does neonatal cholestasis cuase?

A

Prolonged conjugated hyperbilirubinaemia in neonates (>14-21days after birth)

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20
Q

What are 5 major causes of neonatal cholestasis?

A

1) Cholangiopathies (extrahepatic biliary atresia → surgery)
2) Toxins: drugs, parenteral nutrition
3) Metabolic: Tyrosinaemia
4) Infectious: CMV, sepsis
5) Idiopathic

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21
Q

What histological changes are expected in neonatal cholestasis?

A

Multinucleated hepatocyte giant cells

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22
Q

What is extrahepatic biliary atresia?

A

Complete/partial obstruction of the extrahepatic biliary tree lumen < 1st 3 mths of life
- cause of neonatal cholestasis

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23
Q

True or false: Extrahepatic biliary atresia can extend to involve intrahepatic ducts?

A

True, usually requires transplantation

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24
Q

How does extrahepatic biliary atresia present?

A

1) Jaundice (↑conj. bil)
2) Pale stools
3) Tea-coloured urine
(obstructive jaundice)

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25
Q

True or false: Extrahepatic biliary atresia is the #3 cause of death from liver disease in early childhood.

A

False. #1 cause (death <2yrs w/o transplant)

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26
Q

What are the 2 forms of extrahepatic biliary atresia patheogenesis?

A

By presumed timing of obstruction:
1) Fetal form
- aberrant intrauterine development of extrahepatic biliary tree (±other abnormalities eg. situs inversus, CHD)

2) Perinatal form
- normal biliary tree destroyed after birth (eg. viral infection, autoimmune)

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27
Q

What are 2 types of autoimmune cholangiopathies?

A

1) Primary biliary cholangitis
- assoc.: Sjogren’s, thyroid disease, 50F
- Histo: Florid duct lesions, loss of small/medium bile ducts

2) Primary sclerosing cholangitis
- assoc.: IBS/D, 30M
- histo: Inflammatory destruction of large ducts, fibrotic obliteration of small/medium ducts
- radio: strictures/beading of large ducts, pruning of small bile ducts

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28
Q

What are 2 structural anomalies of biliary tree that can lead to cholestasis?

A

1) Choledochal cyst
2) Fibropolycystic disease

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29
Q

What is a choledochal cyst?

A

Developmental malformation of biliary tree (usually CBD)
- predispose to stones, stenosis, strictures, pancreatitis, cholangiocarcinoma

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30
Q

What is fibropolycystic disease?

A

Heterogenous group of lesions (primary abnormalities are congenital ductal plate malformations)
eg.
1) Von Meyenburg complex (small bile duct hamartomas)
2) Single/multiple intra/extrahepatic biliary cysts
3) Congenital hepatic fibrosis
4) ±polycystic renal disease
↑ risk of cholangiocarcinoma

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31
Q

What is the difference between Caroli disease and Caroli syndrome?

A

Caroli disease: Biliary cysts 2° to fibropolycystic disease
Caroli syndrome: “ w congenital hepatic fibrosis

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32
Q

What are 3 types of gallstones?

A

1) Cholesterol
- supersaturation of cholesterol
- radiolucent
- Fat, Female, Forty, Fertile

2) Pigment
- Unconj. bil + insoluble Ca salts
- radio-opaque
- Black: Chronic Haemolytic Anemia; Brown: Biliary infections

3) Mixed

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33
Q

What are the clinical presentations of cholelithiasis?

A

1) >80% asymptomatic
2) Symptomatic:
- RUQ/epigastic pain
- biliary colic
- worse after fatty meal

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34
Q

What are 4 sequelae of cholelithiasis?

A

1) Acute cholecystitis, empyema (pus), hydrops (fluid distension)
2) CBD obstruction/pancreatitis
3) Perforation, fistulas, gallstone ileus (SI obstruction)
4) ↑gall bladder carcinoma

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35
Q

What are the features of acute and chronic cholecystitis?

A

Chronic:
- often asymptomatic, ± antecedent attacks

Acute:
- Progressive pain (>6hrs) ± mild fever
- LOA
- Tachycardia, sweating, nausea, vomiting
- Hx of RUQ/perigastric/biliary colic

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36
Q

What are the 2 types/pathogenesis of acutecholecystitis?

A

1) Calculous (90%)
- obstruction by stone → irritation and inflammation

2) Acalculous (10%)
- severely ill px (eg. septic shock, trauma, burns, immunosuppressed, DM, infections)
- due to ischaemia (cystic artery is end-artery)

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37
Q

What is the pathogenesis of calculous cholecystitis?

A

Mucosal phospholipase hydrolyse luminal lecithins → toxic lysolecithins
→ disrupt protective glycoprotein mucus layer (exposed to detergent action of bile salts)
→ prostaglandin release
→ mucosal and mural inflammation
→ distension + ↑intramural P
→ ↓blood flow to mucosa

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38
Q

What is the pathogenesis of acalculous cholecystitis?

A

Ischaemia to cystic artery
→ inflammation + oedema of wall
→ ↓blood flow
→ gallbladder stasis, biliary sludge, mucus
→ cystic duct obstruction

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39
Q

What are 4 gross features of acute cholescystitis?

A

1) Enlarged, tense edematous and congested
2) Violaceous/green-black
3) Fibrinous/Fibrinopurulent serosal exudates
4) Ulcerated mucosa
± stones

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40
Q

What are 4 complications of acute cholecystitis?

A

1) Gangrene/empyema (eg. C. diff)
2) Pericholecystic/subdiaphragmatic abscesses
3) Ascending cholangitis/Liver abscess
4) Septicaemia

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41
Q

What are 2 gross features of chronic cholecystitis?

A

1) Contracted, thickened wall
2) Smooth mucosa
± calculi

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42
Q

What are 4 histological features of chronic cholecystitis?

A

1) Chronic inflammatory infiltrates
2) Fibromuscular hypertrophy
3) Rokitansky-Aschoff sinuses
4) Subserosal fibrosis

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43
Q

What is a porcelain gallbladder?

A

Form of chronic cholecystitis
- extensive dystrophic calcification in walls
- ↑risk of cancer

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44
Q

What is Xanthogranulomatous cholecystitis?

A

Form of chronic cholecystitis
- rupture of Rokitansky-Aschoff sinuses → accumulation of foamy macrophages
- massively thickened wall

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45
Q

What is a hydrops gallbladder?

A

Form of chronic cholecystitis
- atrophic
- dilated GB containing only clear secretions

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46
Q

What are 2 non-neoplastic liver masses?

A

1) Focal nodular hyperplasia (FNH)
2) Macro-regenerative nodule

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47
Q

What are 3 benign neoplasms of liver masses?

A

1) Hepatocellular adenoma (HCA)
2) Bile duct hamartoma/adenoma
3) Haemangioma

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48
Q

What are 3 malignant neoplasms of liver masses?

A

1) Hepatocellular carcinoma (90%)
2) Cholangiocarcinoma (10%)
3) Angiosarcoma

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49
Q

What is focal nodular hyperplasia?

A

Non-neoplastic liver mass
- due to focal alterations in hepatic blood supply

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50
Q

What are 2 gross features of focal nodular hyperplasia?

A

1) Well-demarcated but poorly encapsulated pale nodule (± central fibrous scar)
2) Background non-cirrhotic liver

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51
Q

What are

A

1) Fibrous scar w radiating fibrous septa containing large, misshapened arterial vessels
2) Ductular reaction
3) Separated hyperplastic hepatocytes
4) No normal ducts

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52
Q

What is the most common benign liver tumour?

A

Cavernous haemangioma

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53
Q

What is a cavernous haemangioma?

A

Benign neoplasm of liver

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54
Q

What are the 4 gross features of a cavernous haemangioma?

A

1) Subcapsular
2) Discrete
3) Red-blue
4) Soft

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55
Q

What is 1 histological feature of cavernous haemangioma?

A

Large vascular channels separated by thin fibrous connective tissue

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56
Q

What are 3 complications of cavernous haemangiomas?

A

Rupture →
1) Intraperitoneal bleeding
2) Thrombosis
3) DIVC

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57
Q

What is a hepatocellular adenoma?

A

Benign tumour arising from hepatocytes

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58
Q

What are the risk factors hepatocellular adenoma?

A

1) Oral contraceptives
2) Anabolic steroids

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59
Q

How do px with hepatocellular adenomas present?

A

Incidental abdo pain (rapid growth of haemorrhage)

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60
Q

What are the 3 gross features of a hepatocellular adenoma?

A

1) Pale
2) Soft
3) Non-cirrhotic background
±haemorrhage

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61
Q

What are 2 histological features of a hepatocellular adenoma?

A

1) 2-3 cell thick hepatocytes cords
2) ± steatosis and haemorrhage

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62
Q

What is hepatocellular carcinoma?

A

1 malignant neoplasm of liver

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63
Q

What are 4 major etiological associations pf HCC?

A

1) Viral infections (HBV, HCV)
2) Toxins (Aflatoxin: from aspergillus, alcohol)
3) Metabolic diseases (hereditary haemochromatosis, Wilson disease (WD) and alpha1-antitrypsin deficiency (AATD))
4) Non-alcoholic fatty liver disease (NAFLD) w metabolic syndrome

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64
Q

What are the 2 most common mutational events in Hepatocarcinogenesis?

A

1) ß catenin activation (40%) → genetic instability
2) p53 inactivation (esp for aflatoxin)

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65
Q

How does chronic liver disease predispose a px to hepatocarcinogenesis?

A

IL-6/JAK/STAT pathway → hepatocyte proliferation (HNF4a transcription factor)

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66
Q

True or false: cirrhosis is a prerequisite for hepatocarcinogenesis.

A

False
- progression to cirrhosis and hepatocarcinogenesis can be parallel

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67
Q

What are 3 clinical presentations of HCC?

A

1) Asymptomatic
2) Ill-defined upper abdo pain, malaise, fatigue, WL
3) Hepatomegaly, abdominal mass, fullness
4) Rare: jaundice, fever, variceal bleeding

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68
Q

What are 2 Ix for suspected HCC?

A

1) Serum α-fetoprotein
2) Radio imaging w contrast

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69
Q

What are the 3 areas of spread in HCC?

A

1) Intrahepatic (vascular) → satellite lesions
2) Portal/hepatic vein
3) Lymph nodes

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70
Q

What are 3 gross findings of HCC?

A

1) Unifocal (large) mass
2) Multifocal (variable) nodules
3) Diffuse and infiltrative
4) Pale or variegated

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71
Q

What are 5 histological features of HCC?

A

1) Well to poorly differentiated
2) Growth patterns: (i) trabecular-sinusoidal (ii) pseudoacinar (iii) compact
3) Polygonal cells w eosinophilic cytoplasm and central, round, distinct nucleolus
4) Pleomorphism
5) Bile production

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72
Q

What is the prognosis for HCC and what are the factors?

A

Factors:
1) Stage/grade
2) No./size of nodules
3) Vascular spread
4) ±cirrhosis

Poor 5 yr survival (most <2 years)
Death by:
- cachexia
- variceal bleeding
- liver failure/hepatic coma
- rupture → haemorrhage

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73
Q

What are 4 treatment options for HCC?

A

1) Surgical resection
2) Liver transplantation
3) Immunotherapy
4) Locoregional ablation
(transarterial chemoembolisation, transarterial Y90 radioembolisation, radiofrequency ablation)

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74
Q

What are 2 ways screening and surveillance is done for HCC?

A

1) US + serum α-fetoprotein
2) CT + MRI w Contrast

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75
Q

What is the most common liver tumour in early childhood?

A

Hepatoblastoma

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76
Q

What are the 2 main histological variants of hepatoblastoma?

A

1) Epithelial type:
- polygonal fetal/smaller embryonic cells
- vaguely recapitulating liver development

2) Mixed epithelial and mesenchymal type:
- Primitive mesenchyme, osteoid, cartilage, striated muscle

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77
Q

What is the hepatoblastoma associated syndrome for FAP?

A

Beckwith Wiedemann syndrome

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78
Q

What are 2 treatment options for hepatoblastoma?

A

1) Surgical resection
2) Chemotherapy

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79
Q

What is the 2nd most common primary malignant tumour of the liver?

A

Cholangiocarcinoma

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80
Q

What are 4 risk factors that predispose to cholangiocarcinoma?

A

1) Liver fluke infestation
2) Primary sclerosing cholangitis
3) Hepatolithiasis
4) Fibropolycystic liver disease
5) HBV, HCV, NAFLD
6) Premalignant lesions: BilIN, Intraductal papillary biliary neoplasia, Mucinous cystic neoplasms

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81
Q

How does the location of cholangiocarcinoma affect presentation?

A

Extrahepatic:
- present earlier w RUQ pain, smaller biliary obstruction, cholangitis

Intrahepatic:
- detected late

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82
Q

What is the prognosis of cholangiocarcinoma?

A

poor
- ~15% survival @ 2 years
- 6mths median survival after surgery for intrahepatic CCA

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83
Q

What are the difference in gross features of a extrahepatic and intrahepatic cholangiocarcinoma?

A

Intrahepatic: mass-forming, periductal/mixed

Extrahepatic: papillary/polyploid, stricture, diffusely-infiltrative adenocarcinoma, lymphovascular adn perineural infiltration

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84
Q

What are 2 vascular malignant primary hepatic tumours?

A

1) Angiosarcoma
2) Epithelioid haemangioendothelioma

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85
Q

What are 3 malignant primary hepatic lymphomas?

A

1) DLBCL
2) MALT lymphoma
3) Hepatosplenic δ-γ T cell lymphoma

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86
Q

True or false: Primary hepatic neoplasms are the most common tumours in the liver

A

False.
- metastases far more common than primary hepatic

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87
Q

Where do secondary hepatic neoplasms usually spread from (3)?

A

1) Breast
2) Colon
3) Lung
4) Pancreas

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88
Q

What are 3 gross features of secondary hepatic neoplasms?

A

1) Hepatomegaly
2) Multiple pale nodules in non-cirrhotic liver
3) Subcapsular umbilication of nodules (from central tumour necrosis)

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89
Q

What is the most common malignancy of the extrahepatic biliary tract?

A

Gallbladder Carcinoma

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90
Q

What are 2 risk factor for gallbladder carcinoma?

A

1) Gallstones
2) Chronic bacterial and parasitic infections

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91
Q

What are the 6 areas of spread for gallbladder carcinoma?

A

Direct:
- Liver
- Stomach
- Duodenum

Metastasis:
- Liver
- Regional lymph node
- Lungs

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92
Q

What 2 gross features of gall bladder carcinoma?

A

1) Diffuse (70%) / infiltrating
2) Polyploid (30%) / exophytic

93
Q

What are 4 congenital anomalies of the pancreas?

A

1) Pancreas divisum (failed fusion of dorsal and ventral pancreatic primordia duct systems)

2) Annular pancreas (ring encircling duodenum)

3) Ectopic pancreas (elsewhere eg. stomach, SI)

4) Agenesis (homozygous mutation of PDX1 gene)

94
Q

What is the most common congenital anomaly of the pancreas?

A

Pancreas divisum
- failed fusion of dorsal and ventral pancreatic primordia duct systems
→ CBD and main pancreatic duct enter duodenum separately
→ predisposition to chronic pancreatitis

95
Q

What are the sequelae of an annular pancreas?

A

Stenosis and obstruction

96
Q

What are the sequelae of an ectopic pancreas?

A

Pain from localised inflammation or mucosal bleeding

97
Q

What are the 3 normal mechanisms protecting the pancreas from self-digestion by secreted enzymes?

A

1) Most digestive enzymes synthesised as zymogens, packaged in secretory granules

2) Intrapancreatic activation of proenzymes are limited to the small bowel (enterokinase→trypsin→proenzymes)

3) Acinar and ductal cells secrete trypsin inhibitors (including serine protease inhibitor SPINK1 → limits intrapancreatic trypsin activity)

98
Q

True or false: Acute pancreatitis is a reversible pancreatic parenchymal injury a/w inflammation.

A

True

99
Q

What are the etiologies of acute pancreatitis?

A

I GET SMASHED
Idiopathic
Gallstones
Ethanol
Trauma
Steroids
Mumps and other infections
Autoimmune (SLE, PAN)
Scorpion toxin
HyperCa, HyperTG, Hypothermia
ERCP (endoscopic retrograde cholangiopancreatography)
Drugs (furosemide, azathioprine)

Others: CF, HOP cancers, pancreas divisum

100
Q

What are the 3 mechanisms/pathways for the pathogenesis of acute pancreatitis?

A

TLDR:
Acinar cell injury → activated enzymes → (i) interstitial inflammation + edema (ii) Proteolysis (iii) fat necrosis (iv) hemorrhage

1) Duct obstruction (eg. stones, chronic alcoholism)
→ interstitial edema → ↓blood flow → Ischemia

2) Acinar cell injury (eg. drugs, trauma, ischemia, viruses)
→ oxidative stress → release + activation of enzymes

3) Defective Intracellular transport
→ proenzymes delivered to lysosome → activation of enzymes

101
Q

How can alcohol consumption lead to pancreatitis?

A

1) Transient ↑ in contraction of sphincter of Oddi
2) Secretion of protein-rich pancreatic fluid → deposition of inspissated proteins plugs and obstruction of small pancreatic ducts
3) Direct toxicity on acinar cells → oxidative stress

102
Q

What is the typical clinical presentation of acute pancreatitis?

A

Constant intense epigastric/central abdo pain
- radiates to upper back or left shoulder
- a/w nausea, vomiting, LOA

103
Q

What are the types of acute pancreatitis in order of severity?

A

Full-blown (SIRS) > Hemorrhagic > Acute necrotising > Acute interstitial

104
Q

How does full-blown acute pancreatitis cause SIRS?

A

Release of toxic enzymes, cytokines, etc. into circulation → systemic inflammatory response (SIRS)

105
Q

How is acute pancreatitis diagnosed?

A

1) ↑ serum amylase (1st 24hr) + Lipase (72-96hrs)
2) Glycosuria (10%)
3) Hypocalcemia (Ca soaps deposit in necrotic fat)
4) Leukocytosis, DIC
5) ± jaundice (only if due to gallstones)

106
Q

What are the 5 histological features of acute pancreatitis?

A

1) Microvascular leak and edema
2) Fat necrosis
3) Acute inflammation
4) Destruction of pancreatic parenchyma
5) Destruction of blood vessels and interstitial hemorrhage

107
Q

In acute pancreatitis,
i) Head of pancreas shows __________
ii) Omental fat shows ____________
iii) Fat necrosis with __________________

A

i) Head of pancreas shows hemorrhage and necrosis
ii) Omental fat shows necrosis with saponification
iii) Fat necrosis with neutrophilic response “chicken broth” peritoneal fluid

108
Q

What are 3 complications of acute pancreatitis?

A

1) Systemic organ failure
- Shock (SIRS)
- Acute respiratory distress syndrome
- Acute renal failure (renal tubular necrosis)
- DIVC

2) Sterile pancreatic “abscess”
- can become infected

3) Pancreatic pseudocyst

109
Q

What is chronic pancreatitis?

A

Prolonged inflammation of pancreas a/w irreversible destruction of exocrine parenchyma, fibrosis and later, destruction of endocrine parenchyma

110
Q

What are 4 etiologies of chronic pancreatitis?

A

1) Long-term alcohol abuse (#1)
2) Long-standing obstruction of pancreatic duct by calculi/neoplasm
3) Autoimmune (IgG4+ plasma cells, mimic pancreatic carcinoma, responds to steroid therapy)
4) Hereditary pancreatitis

111
Q

What differentiates chronic pancreatitis from acute pancreatitis?

A

Chronic inflammatory cells
Fibrogenic factors predominate (activation and proliferation of periacinar myofibroblasts/pancreatic stellate cells) → collagen and fibroblast deposition

112
Q

What are the clinical presentations of chronic pancreatitis?

A

Repeated/persistent epigastric/central abdo pain
- radiates to upper back or left shoulder
- precipitated by alcohol, overeating, opiates, drugs that ↑tone of sphincter of Oddi

or asymptomatic until pancreatic insufficiency (intestinal malabsorption) and DM develop

113
Q

How is chronic pancreatitis diagnosed?

A

Pancreatic calcifications on CT/US

114
Q

What are 4 complications of chronic pancreatitis?

A

1) Pancreatic exocrine insufficiency → chronic malabsorption
2) Endocrine insufficiency → DM
3) Sever chronic pain
4) Pancreatic pseudocysts

115
Q

What are 5 histological features of chronic pancreatitis?

A

1) Variable dilatation of pancreatic ducts w protein plugs/calcified concretion
2) Fibrosis
3) Atrophy, Acini dropout with sparing of islets
4) Pseudocysts
AI: ductocentric inflammation, venulitis, ↑IgG4+ plasma cells

116
Q

What are 3 non-neoplastic pancreatic masses?

A

Solid:
1) Autoimmune pancreatitis

Cystic:
2) Pseudocysts
3) Congenital

117
Q

What are 4 solid neoplastic pancreatic masses?

A

1) Ductal adenocarcinoma
2) Acinar cell carcinoma
3) Pancreatoblastoma
4) Neuroendocrine tumours

118
Q

What are 4 cystic neoplastic pancreatic masses?

A

1) Serous cystadenoma (benign)
2) Mucinous cystic neoplasm (pre-malignant)
3) Intraductal papillary mucinous neoplasm (pre-malignant)
4) Solid pseudopapillary neoplasm (malignant)

119
Q

How are pancreatic masses diagnosed?

A

Endoscopic ultrasound-guided fine needle aspiration cytology

120
Q

Pseudocysts are (localised/diffuse) collections of necrotic and haemorrhagic material rich in ___________ and (have/lack) an epithelial lining.

And have 3 end-results: ________________

A

localised collections of necrotic and haemorrhagic material

rich in pancreatic enzymes

NO epithelial lining.

1) Spontaneously resolves
2) Secondary infection
3) Compress/perforate adjacent structures

121
Q

What are the 3 histological features of congenital cystic non-neoplastic pancreatic masses?

A

1) Unilocular
2) Contain serous fluid
3) Thin fibrous wall lined by single later of variably attenuated uniform cuboidal epithelium

122
Q

In serous cystadenoma,
i) which part of the pancreas in affected
ii) what are the histological features
iii) what are the most commonly associated gene mutation?

A

i) Tail
ii) Multicystic, lined by glycogen-rich cuboidal cells
iii) VHL inactivation

123
Q

In mucinous cystic neoplasm,
i) which part of the pancreas in affected
ii) what are the histological features
iii) what are the most commonly associated gene mutation?

A

i) body/tail (not connected to duct)
ii) columnar mucinous epithelium with “ovarian cortical-type” stroma
iii) KRAS mutation

124
Q

In intraductal papillary mucinous neoplasm,
i) which part of the pancreas in affected
ii) what are the histological features
iii) what are the most commonly associated gene mutation?

A

i) Head (connected to duct)
ii) intraductal papillae lined by columnar mucinous epithelium
iii) KRAS, GNAS mutation

125
Q

In solid-pseudopapillary neoplasm,
i) which part of the pancreas in affected
ii) what are the histological features
iii) what are the most commonly associated gene mutation?

A

i) body/tail
ii) well-circumscribed, solid vascular nests w pseudopapillae
iii) CTNNB1 (ß-catenin)

126
Q

True or false: Pancreatic carcinoma is very aggressive and have one of the highest mortality rates

A

True

127
Q

What are 5 risk factors for pancreatic carcinoma?

A

1) Smoking
2) High-fat diet
3) Chronic pancreatitis
4) DM
5) Genetics (BRCA2, CDKN2A)

128
Q

What are 2 precursors of pancreatic carcinoma?

A

1) Premalignant neoplasms (IPMN, MCN)
2) Non-invasive small duct lesions (pancreatic intraepithelial neoplasia)

129
Q

What are 4 genes commonly mutated in pancreatic carcinoma?

A

1) KRAS
2) CDKN2A
3) TP53
4) SMAD4

130
Q

What are 5 clinical presentation of pancreatic carcinoma?

A

1) Asymptomatic
2) Pain
3) Obstructive jaundice (head of pancreas lesions)
4) Systemic symptoms (advanced: LOW, LOA, lethargy)
5) Migratory thrombophlebitis (trosseau’s sign)

131
Q

How is pancreatic carcinoma diagnosed?

A

1) Serum CEA, CA19-9↑
2) Imaging
3) EUS-FNAC/Core biopsy

132
Q

How is pancreatic carcinoma treated?

A

1) Surgical resection
2) Chemoradiotherapy

133
Q

What are the 3 gross features of pancreatic carcinomas?

A

1) Large pale firm mass w infiltrative border
2) Adenocarcinoma w desmoplasia
3) Perineural/lymphatic involvement

134
Q

True or false: All pancreatic neuroendocrine tumours have malignant potential regardless of grade and appearance.

A

True

135
Q

Which pancreatic neuroendocrine tumour is most commonly benign compared to the rest?

A

Insulinomas

136
Q

What are 7 types of pancreatic neuroendocrine tumours and their clinical syndromes?

A

1) Insulinoma (ß-cell) → Whipple triad (hypoglycemia, CNS, relief on glucose)

2) Glucagonoma (α-cell) → mild DM, anemia, necrolytic migratory skin erythema

3) Somatostatinoma (δ-cells) → DM, Cholelithiasis, Steatorrhoea, Hypochlorhydria

4) PP-secreting endocrine tumour → asymptomatic (just mass)

5) VIPoma (D1 cells) → Watery diarrhoea, HypoK+, Achlorhydria

6) Carcinoid (ECF cells) → carcinoid syndrome (flushing, diarrhoea, bronchospasm, heart valve lesions)

7) Gastrinoma (G cells) → Zollinger-Ellison syndrome (diarrhoea, intractable peptic ulceration, hyperchlorhydria)

137
Q

What are the 3 histological features of pancreatic neuroendocrine tumours?

A

1) Solid pale mass ± cystic change
2) Nests, islands, trabeculae of small round cells w “salt and pepper chromatin
3) Highly vascular

138
Q

How are pancreatic neuroendocrine tumours diagnosed?

A

1) IHC stain for neuroendocrine and secretory products
2) Ultrastructural image of neurosecretory granules in cytoplasm

139
Q

What are the 3 major genes/pathways for the pathogenesis of sporadic (90%) pancreatic neuroendocrine tumours?

A

1) MEN1
2) lof mutations in TS genes (eg. PTEN, TSC2), resulting activation of mTOR pathway
3) Inactivating mutations in ATRX and DAXX genes

140
Q

What are 4 example genes for syndromic/familial pancreatic neuroendocrine tumours (10%)?

A

1) MEN1
2) VHL
3) NF1
4) TSC1/2

141
Q

What are 3 tests that are done to assess hepatocyte integrity?

A

Cytosolic hepatocellular enzymes:
1) AST
2) ALT
3) LDH

142
Q

What are 5 tests that are done to assess biliary excretory function?

A

Substances normally secreted in bile:
1) Serum bilirubin: total, unconj, conj
2) Urine bilirubin
3) Serum bile acids

Plasma membrane enzyme (dmg to canaliculi):
1) ALP
2) GGT

143
Q

What are 3 tests that are done to assess hepatocyte synthetic function?

A

Proteins secreted into blood:
1) Serum albumin
2) PT
3) PTT

144
Q

What are 2 tests that are done to assess hepatocyte metabolism?

A

1) Serum ammonia (↑ in disease)
2) Aminopyrine breath test (hepatic demethylation)

145
Q

Why are most liver diseases chronic at the time of clinical presentation (except acute liver failure)?

A

Liver has enormous functional reserve

  • Mild liver damage may be clinically masked
  • Liver injury and healing may occur without clinical detection
  • Liver disease is usually an insidious process
146
Q

What are 3 degenerative but reversible hepatocyte/ parenchymal responses to liver insult?

A

1) Ballooning degeneration (cellular swelling)
2) Steatosis
3) Cholestasis (accumulation of bilirubin)

147
Q

What are 2 irreversible hepatocyte/ parenchymal responses to liver insult?

A

1) Necrosis (coagulative)
- ischaemic injury
- cell swelling & rupture → macrophages

2) Apoptosis
- activation of caspases cascade → cell shrinkage and eosinophilia (acidophil bodies)
- spotty → confluent necrosis (zonal → bridging → submassive → massive)

148
Q

What are 2 regenerative hepatocyte/parenchymal responses to liver insult?

A

1) Primary: hepatocyte mitosis
2) Extensive: activation of primary stem cell niche (canals of hering)

  • hepatocyte reach replicative senescence → stem cell activation (ductular rxn)
149
Q

Describe the process of hepatic scar formation and cirrhosis?

A

Zones of parenchymal loss:
→ Collapse of underlying reticulin
→ Hepatic stellate cells activated → highly fibrogenic myofibroblasts (via cytokines and chemokines from inflammatory cells, endothelial cells, hepatocytes, bile duct epithelial cells)

Or:
- Portal fibroblasts, ductular rxn (epithelial-mesenchymal transition)

Eventually:
Portal / periportal fibrosis → portal-central and portal-portal bridging fibrosis / septa → cirrhosis

150
Q

Can liver cirrhosis be reversed?

A

Yes? kinda?
- reversal of fibrosis via cirrhosis regression

151
Q

What are 5 consequences of liver failure?

A

1) Coagulopathy (↓ coag. factors)

2) Hepatic encephalopathy (impaired NH3 metabolism)

3) Cholestasis (impaired bile secretion)

4) Portal HTN (cirrhosis → ascites, congestive splenomegaly, portosystemic venous shunts)

5) Hepatorenal, hepatopulmonary syndrome

152
Q

What are 3 causes of acute liver failure?

A

1) Drugs / toxins (faster time course e.g. within hours to days)

2) Acute Hepatitis A/B/E

3) Autoimmune hepatitis

153
Q

What is the macroscopic and 5 microscopic features of acute liver failure?

A

Macro:
- Small shrunken liver with wrinkled liver capsule

Micro:
1) Massive hepatic necrosis
2) Diffuse injury w/o obv cell death (diffuse microvesicular steatosis)
3) Hepatocyte loss
4) RBC extravasation
5) Florid ductular rxn

154
Q

True or false: Cirrhosis is the precursor to chronic liver failure.

A

False.
- Not all end-stage chronic liver disease is cirrhotic e.g. PBC/PSC

  • Not all cirrhosis leads to chronic liver failure
    (eg. Child-Pugh clinical classification of cirrhosis: Class A (well compensated), B (partially compensated), C (decompensated))
155
Q

What are 4 causes of chronic liver failure?

A

1) Chronic Hep B and C
2) NAFLD
3) Alcoholic liver disease
4) Cryptogenic/Idiopathic

156
Q

What is cirrhosis?

A

Diffuse transformation of the liver into regenerative parenchymal nodules surrounded by fibrous bands (scarring) and accompanied by disturbed vascular architecture (due to variable degrees of vascular (often portosystemic) shunting)

157
Q

What 2 factors influence whether there would be scarring or regression in liver injury?

A

Persistent disease
→ Synthesis via hepatic stellate cell myofibroblastic activity

Vs

Disease inhibition/elimination
→ Degradation via matrix metalloproteinases
→ degrade collagen and elastin fibres

158
Q

What are 6 clinical features of cirrhosis?

A

40% asymptomatic until advanced

1) Non-specific manifestations (anorexia, WL, weakness)
2) Liver failure
3) Hepatocellular carcinoma

Terminal events:
4) Hepatic encephalopathy
5) Bleeding from esophageal varices
6) Bacterial infections/sepsis

159
Q

What are 4 main stigmata of chronic liver disease?

A

1) Cholestasis
→ jaundice → pruritis → scleral icterus

2) Hyperoestrogenemia
- Palmar erythema
- Spider angioma
- Hypogonadism
- Gynaecomastia

3) Coagulopathy
→ easy bruising

4) Portal HTN
- Ascites
- Portosystemic venous shunts (eg. caput medusae, haemorrhoids)
- splenomegaly
- hepatic encephalopathy → asterixis

160
Q

What are 2 pathways for the pathogenesis of portal hypertension?

A

1) ↑ R to portal flow @ sinusoids
- vasoconstriction (smooth muscle + myofibroblasts)
- disrupted blood flow (scarring/parenchymal nodule formation)
- sinusoidal remodelling → intrahepatic shunts + arterial-portal anastamosis

2) ↑ portal venous flow due to hyperdynamic circulation
- arterial vasodilation (splanchnic circulation)

161
Q

What are 7 causative organisms for viral hepatitis?

A

Hepatotropic: A-E (5)
Non-hepatotropic: EBV, CMV

162
Q

What are 4 effects of portal HTN?

A

1) Ascites (↑P in peritoneal capillaries + RAAS)
2) Hepatorenal syndrome (splanchnic vasodilation → RAAS → renal vasoconstriction)
3) Hepatic encephalopathy + collateral channels (Portosystemic shunting of blood)
4) Splenomegaly → pancytopenia

163
Q

What is ascites?

A

Accumulation of excess fluid in the peritoneal cavity
(500 ml = clinically detectable)

164
Q

What are 4 causes of ascites?

A

1) Cirrhosis
2) Chronic heart failure
3) Hypoalbuminemia
4) Malignancies
5) Peritonitis

Can seep through trans-diaphragmatic lymphatics 
hydrothorax (R>L)

165
Q

How is the etiology of ascites determined?

A

Ascitic tap:
- Few mesothelial cells, mononuclear inflammatory cells → Normal

  • ↑ Neutrophils → infection
  • Malignant cells → disseminated intra-abdominal cancer
166
Q

What is hepatic encephalopathy?

A

Brain dysfunction caused by liver insufficiency and/or porto-systemic shunting manifesting as a wide spectrum of neurological or psychiatric abnormalities ranging from subclinical alterations to coma

(Shunting of ammonia from GIT into general circulation → BBB)

167
Q

How does portal hypertension lead to peripheral cytopenias?

A

↑venous P → congestive splenomegaly

Retention of a large number of leukocytes, erythrocytes
and platelets in the spleen
facilitates capture, phagocytosis or destruction of blood cells by phagocytes
→ peripheral cytopenia

168
Q

The main sequelae of liver failure are:
A___________________
B___________________
C___________________
D___________________
E___________________

A

Ammonia – encephalopathy
Bile retention – cholestasis
Coagulopathy
Distension – ascites
Esophageal varices

169
Q

What is acute on chronic liver failure?

A

1) An unrelated acute injury supervenes on a well-compensated late-stage chronic disease, or

2) The chronic disease itself has a flare of activity that leads directly to liver failure

170
Q

What are 2 hepatic and 2 systemic causes of acute on chronic liver failure?

A

Hepatic:
1) Chronic hep B + Hep D superinfection
2) Ascending cholangitis in px with primary sclerosing cholangitis
3) Development of malignancy e.g. HCC or metastases

Systemic:
1) Sepsis and hypotension
2) Acute cardiac failure
3) Superimposed drug or toxic injury

171
Q

What is a differential for viral hepatitis?

A

1) Autoimmune hepatitis
2) Drug/toxin-induced hepatitis

172
Q

What are 3 sequelae of acute viral hepatitis?

A

1) Asymptomatic
2) Symptomatic w recovery
- incubation → symptomatic pre-icteric → symptomatic icteric → convalescence
3) Acute liver failure with submassive/massive hepatic necrosis
4) Chronic hepatitis ±cirrhosis

173
Q

Which viruses can cause both asymptomatic and symptomatic acute viral hepatitis?

A

All hepatotropic
Hepatitis A, B, C, D, E

174
Q

Which viruses can cause acute liver failure w submassive/massive hepatic necrosis in viral hepatitis?

A

HAV, HBV, HDV
(HEV in pregnancy)

175
Q

Which viruses can cause chronic viral hepatitis?

A

HCV
(some HBV)

HAV and HEV do not unless
immunocompromised

176
Q

Hepatitis A is a (self-limiting/progressive) disease, spread by ________________________.
It causes _________________________.

A

Hep A:
- self-limiting disease
- spread by fecal-oral
- causes: mild symptoms, acute liver failure (uncommon), transient viraemia (aft 2-6 weeks)

Does not cause chronic hepatitis or carrier state

177
Q

After an infection, a px has immunity against HAV for _____________.

A

Life
(IgG anti-HAV persists for years → lifelong immunity)

178
Q

What form of hepatitis can result from a hep A infection?

A

Acute hepatic failure (uncommon)

179
Q

What form of hepatitis can result from a hep B infection?

A

1) Acute hepatitis
2) Acute hepatic failure
3) Chronic hepatitis

180
Q

True or false:
Hep B often causes direct hepatocyte injury via interruption of protein synthesis.

A

False.
HBV generally does not cause direct hepatocyte injury; injury is caused by CD8+ cytotoxic T cells attacking infected cells

181
Q

What are 3 modes of Hep B transmission?

A

1) Vertical
2) Horizontal
3) Sexual/IVdrugs

182
Q

True or false.
Hep B is a risk factor for HCC even w/o cirrhosis and thus vaccination is very important and effective in preventing infection.

A

True.
Vaccination induces protective anti-HBs response in 95% of infants, children and adolescent

183
Q

What are 3 modes of transmission for Hep C?

A

1) IVDA
2) Sex
3) Needle-stick injury
4) vertical

183
Q

Which hepatotropic viruses have a carrier state?

A

Only Hep B
- HBsAg+, HBeAg- but anti-HBe+, low/undetectable HBV DNA

  • AST/ALT normal, liver biopsy no significant inflammation
  • Probably not a stable state – re-activation may occur e.g. co-infection, immune
    changes
184
Q

After an infection, a px has immunity against HBV for _____________.

A

never.
HCV is inherently genomically unstable → Elevated titers of anti-HCV IgG occurring after an active infection do not confer effective immunity; circulating HCV RNA often persists (90%)

185
Q

How is HCV infection (i) diagnosed (ii) prevented (iii) cured?

A

i) HCV RNA testing

ii) No vaccine (just limit transmission

iii) Direct-acting antivirals

186
Q

What are 2 sequelae and 1 association of HCV infection?

A

Repeated bouts of hepatic damage occur
1) Persistent infection and
chronic hepatitis (80-90%)
2) cirrhosis (20%)

a/w: metabolic syndrome (esp. HCV genotype 3) – insulin resistance and NAFLD

187
Q

How does acute and chronic disease of HCV infections differ?

A

Acute:
Jaundice, symptoms, serum marker, serum transminases all high and present

Chronic:
Intermittent symptoms
- persistent/fluctuating elevations of AST/ALT (wax and wane)

188
Q

What are 2 sequelae of HDV infections?

A

1) Co-infection → acute hepatitis (self-limited w clearance of both HBV and HDV)

2) Superinfection →
severe acute hepatitis in a previous unrecognised HBV carrier or exacerbation of preexisting chronic Hep B infection

Chronic HDV infection occurs in almost all patients → cirrhosis ± HCC

189
Q

How is HDV transmitted?

A

Blood-borne
- IVDA
- blood transfusions

190
Q

Can HDV alone cause disease?

A

No, require co/super-infection w HBV

191
Q

True or false:
Vaccination for HBV prevents HDV infection

A

True

192
Q

What is the most reliable indicator of recent HDV exposure?

A

IgM anti-HDV antibody

193
Q

HEV infections are usually self-limiting with which 2 exceptions?

A

1) High mortality rate in pregnant women (~20%)

2) Chronic infection only in immunosuppressed patients (HIV / transplant)

194
Q

How HEV transmitted?

A

Fecal-oral
(Zoonotic disease with animal reservoirs: monkeys, cats, pigs, dogs)

195
Q

In a HEV infection, _______________ can be detected by PCR in stool and serum.

IgM replaced by______ anti-HEV (will persist for a few years) when symptoms
start resolving in 2-4 weeks.

A

HEV RNA and virions can be detected by PCR in stool and serum

IgM replaced by IgG anti-HEV (will persist for a few years) when symptoms
start resolving in 2-4 weeks

196
Q

True or false:
Acute and chronic hepatitis can be differentiated histologically by the inflammatory cell infiltrate.

A

False.
It is the time course and pattern of injury that distinguishes acute vs chronic
hepatitis, not the inflammatory cell infiltrate (both are mononuclear, mainly T cells)

197
Q

Lobular hepatitis is seen in which form of hepatitis?

A

Acute viral (<1 mth)

198
Q

Portal hepatitis is seen in which form of hepatitis?

A

Chronic viral (Symptomatic, biochemical or serologic evidence > 6 months)

199
Q

What are 3 histological features of lobular hepatitis in acute viral hepatitis?

A

1) Lobular disarray
- Hepatocyte swelling
- Apoptosis, spotty to confluent necrosis
- Kupffer cell hypertrophy

2) Lymphoplasmacytic infiltrate

3) ± Cholestasis

4) ± portal inflammation

200
Q

What are 3 histological features of portal hepatitis in chronic viral hepatitis?

A

1) Lymphoplasmacytic portal
infiltration

2) Portal and periportal (interface)
hepatitis to bridging hepatic necrosis

3) ± lobular hepatitis in active disease

4) Fibrosis to cirrhosis; regression may
occur

201
Q

“Ground-glass” hepatocytes are seen in which hepatitis infection?

A

Chronic Hep B

202
Q

Lymphoid follicles and fatty change are seen in which hepatitis infection?

A

Chronic Hep C

203
Q

How is hepatitis (i) graded and (ii) staged?

A

Grading: extent of injury and inflammation (Metavir grading)

Staging: progression of fibrosis (Ishak stage)

204
Q

What are 2 non-hepatotropic viruses that implicate the liver?

A

1) CMV
2) HSV
3) EBV
4) Adenovirus

  • Systemic infections with multi-organ
    involvement
  • Immunocompetent versus
    immunocompromised patients
  • Opportunistic infections
205
Q

Bacterial, parasitic and helminthic infections of the liver can cause:

Localised disease:
1) __________ (bacterial or amoebic)
2) ___________(Echinococcus)

A

1) Abscess (bacterial or amoebic)

2) Hydatid cyst (Echinococcus)

206
Q

Bacterial, parasitic and helminthic infections of the liver can cause:

Diffuse disease:
1) Mild hepatic inflammation and varying hepatocellular cholestasis

2) ____________________ – fungal, mycobacterial, parasitic (__________ – ‘pipe stem fibrosis’)

3) ____________________ - liver flukes → high rate of ___________________

A

1) Mild hepatic inflammation and
varying hepatocellular
cholestasis

2) Granulomatous disseminated disease – fungal, mycobacterial, parasitic (Schistosoma – ‘pipe stem fibrosis’)

3) Dilated intrahepatic ducts - liver flukes → high rate of cholangiocarcinoma

207
Q

What is the characteristic finding of miliary TB affecting the liver?

A

Granulomas

208
Q

What are 2 histological features of amoebic liver abscess?

A

1) Abscess contents have lack of inflammatory cells due to process of liquefactive necrosis

2) Trophozoites of Entamoeba histolytica (protozoa)

209
Q

How is autoimmune hepatitis diagnosed (3) ?

A

1) Autoantibodies
2) Elevated IgG
3) Liver histology

Likely: Portal lymphoplasmacytic infiltrate + interface/lobular
hepatitis, OR Lobular hepatitis + lymphoplasmacytic infiltrates,
interface hepatitis or portal fibrosis, in the absence of features suggestive of other liver disease

Possible: As above, but if there are also other histologic features suggestive of other liver disease

Unlikely: Non-classic histologic features + features of other liver disease

210
Q

How does autoimmune hepatitis present?

A

1) acutely (40%) / fulminant
presentation within 8 wks of onset, followed rapidly by scarring (40% of survivors will progress to cirrhosis)

2) Indolent, detected incidentally or only when cirrhotic

Female (78%)&raquo_space; male

211
Q

What is the difference between Type I and II autoimmune hepatitis?

A

Type I: Middle-aged to older; ANA, SMA

Type II: Young; anti-LKM1

212
Q

What are 3 mechanisms of drug/toxin-induced liver injury?

A

1) Direct toxicity

2) Hepatic conversion of xenobiotic to an active toxin

3) Immune-mediated mechanisms (e.g. drug acts as a hapten)

213
Q

What should be in the differential diagnosis of any form of liver disease?

A

Drug/toxin-Induced Liver Injury (DILI)

214
Q

How is Drug/toxin-Induced Liver Injury (DILI) diagnosed?

A

Diagnosis is on the basis of
1. A temporal association of liver damage with drug/toxin exposure (may be immediate or weeks-months)
2. Recovery (usually) upon removal of inciting agent
3. Exclusion of other potential causes

215
Q

What are 4 factors that affect the development and severity of ALD?

A

1) Dosage and duration: ≥ 80g/day ethanol (~6 beers) generates significant risk for severe hepatic injury; 10-20 years

2) Gender: females more susceptible

3) Ethnic and genetic differences e.g. in detoxifying enzymes

4) Comorbid conditions e.g. concomitant liver pathologies like viral hepatitis

216
Q

What are 5 mechanisms contributing to the pathogenesis of ALD?

A

1) Shunting
- ↑NADH → shunt ↑lipid synthesis + ↓lipoprotein export + ↑peripheral fat catabolism

2) Dysfunction of mitochondrial and cellular membranes
- acetaldehyde induces lipid peroxidation and acetaldehyde protein adduct formation

3) Hypoxia and oxidative stress
- CYP450 → ↑ROS
- impaired hepatic methionine metabolism → ↓glutathione levels

4) ↑ inflammation
- bacterial endotoxins from gut

5) ↓ Hepatic sinusoidal perfusion
- endothelin release → vasoconstriction + stellate cell contraction

217
Q

What are 4 histopathological features of ALD?

A

1) Centrilobular steatosis (reversible with abstention)
2) Hepatocyte swelling (ballooning degeneration) and necrosis
3) Mallory-Denk bodies
4) Neutrophilic reaction
5) Pericellular/perisinusoidal fibrosis (“Chicken-wire fence” pattern)
6) Cirrhosis (micronodular)

218
Q

What are the expected biochemical findings in a px with ALD?

A

1) AST»ALT (2:1 ratio)
2) Bil, ALP ↑
3) ↑Neutrophils

219
Q

What is NAFLD?

A

Spectrum of disorders that have in common the presence of hepatic steatosis in individuals who do not consume alcohol or do so in very small
quantities (< 20g/wk)

220
Q

What is the pathogenesis of NAFLD?

A

2-hit model:
1) Insulin resistance → dysfunctional lipid metabolism and ↑inflammatory cytokines

2) Oxidative injury → liver cell necrosis as fat laden cells are highly sensitive to
lipid peroxidation products

221
Q

NAFLD is most commonly a/w ___________ and increases the risk of ________

A

NAFLD is most commonly a/w metabolic syndrome and increases the risk of HCC

222
Q

How is MAFLD diagnosed?

A

1) Detection of liver steatosis (via liver histology, non-invasive biomarkers or imaging)

2) at least 1/3 criteria of:
- overweight/obesity
- T2DM
- clinical evidence of metabolic dysfunction e.g. increased waist circumference, abnormal lipid or glycaemic profile

223
Q

In which type of liver disease is cryptogenic cirrhosis seen?

A

Advanced fibrosis “burned out” NAFLD

224
Q

What is Haemochromatosis

A

Caused by excessive iron absorption, deposited in parenchymal organs e.g. liver, pancreas, heart, joints, endocrine organs, skin

225
Q

What is Wilson’s disease?

A

Autosomal recessive disorder caused by ATP7B gene mutation (chr 13)

→ impaired copper excretion into bile and failure to incorporate copper into caeruloplasmin for secretion into blood.

→ Toxic levels of copper thus accumulate
in many tissues and organs

226
Q

What is A1-antitrypsin deficiency?

A

Autosomal recessive disorder of protein folding resulting in impaired secretion and very low serum α1AT (important in inhibition of proteases, particularly those released from neutrophils)

227
Q

What is passive liver congestion?

A

Diffuse venous congestion within the liver that results from right-sided heart failure
→ Dilatation and congestion of
centrilobular sinusoids

→ Centrilobular hepatocytes atrophy with time

228
Q

What is centrilobular hemorrhagic necrosis?

A

combination of both passive congestion
and hepatic hypoperfusion e.g. left
heart failure
→ “nutmeg liver”

GIT (14 decks)

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