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ED Primary Exam > Week 19 Pathology - Liver/Biliary > Flashcards

Week 19 Pathology - Liver/Biliary Flashcards

1
Q

What percentage loss of liver function before failure occurs?

A

90%

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2
Q

What are the most common causes of liver failure/disease?

A

Acute: viral hepatitis, drugs/toxins –> acute fulminant necrosis

Chronic: most common route to failure, either chronic viral infection, alcoholic or NAFLD steatohepatitis –> cirrhosis

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3
Q

What is the mechanism by which hepatic encephalopathy occurs?

A

Porto-systemic shunt means that ammonia and other toxic metabolites bypass the liver not metabolised to the same extent –> direct toxicity effect on cerebral cortex.

More chronically, derangement of neurotransmitter production causes neuronal dysfunction, fluctuating episodes usually secondary to reversible insults (metabolic, drugs, increased protein load in gut)

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4
Q

What are clinical symptoms/signs of hepatic encephalopathy?

A

Behavioural changes
Confusion/stupor
Flap
Hyper-reflexia
Coma

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5
Q

What is the functional unit of the liver?

A

Lobule

Hexagonal unit, with portal triad on each corner, and central vein in middle. Sinusoids connect the triads to central vein. Bile flows central to peripheral, venous and arterial blood from triads to central vein.

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6
Q

What is cirrhosis?

A

Replacement of normal architecture of liver with fibrous/collagenous tissue

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7
Q

What are the characteristic histological findings of cirrhosis?

A

Bridging Fibrous septa
Parenchymal nodules

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8
Q

What is the ‘Space of Disse’?

A

Space between sinusoidal epithelial cells and hepatocytes

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9
Q

What cell is responsible for the deposition of proteins/collagen in the space of disse?

A

Perisinusoidal stellate cells (usual role is Vit A storage, but become activate into myofibroblast in cirrhosis)

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10
Q

What is the pathophysiology of cirrhosis/liver inflammation?

A

Inflammation/hypoperfusion in liver lobules (from different causes) results in parenchymal atrophy and stellate cell regeneration.

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11
Q

How does cirrhosis lead to ascites?

A

Due to remodelling and destruction of vascular architecture, significantly increased resistance to blood flow through portal system, increased hydrostatic pressure and transudative effect with leakage of fluid into peritoneal cavity

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12
Q

What are kuppfer cells?

A

Resident macrophages of the liver responsible for mopping up GI bacteria/toxins and preventing entry to systemic circulation

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13
Q

List some causes of pre-hepatic, intra-hepatic and post hepatic portal hypertension?

A

Pre = portal vein thrombosis, massive splenomegaly
Intra = cirrhosis
Post = right heart failure, hepatic vein outflow obstruction, constrictive pericarditis

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14
Q

How does the RAAS system exacerbate ascites?

A

Renal retention of sodium and water occurs as under-perfusion of kidneys, despite portal HTN causing leakage of volume into peritoneum –> viscous cycle

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15
Q

What are the sites of collateral circulation in portal HTN?

A

Anterior abdomen - caput medusae
Rectum - haemorrhoids
Lower 1/3 oesophagus - varices

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16
Q

What is hepatorenal syndrome?

A

In setting of severe liver disease, development of renal failure without primary abnormalities of the kidneys (i.e. retina ability to concentrate urine) –> unknown mechanism, but splanchnic vasodilation and systemic vasoconstriction

Clinically presents with reduced urine output, rising urea and creatinine, hyperosmolar urine without protein

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17
Q

What is portopulmonary HTN?

A

Pulmonary arterial hypertension associated with liver disease/portal HTN. Due to pulmonary vasoconstriction and vascular remodelling –> cor pulmonale.

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18
Q

What is hepatopulmonary syndrome?

A

Abnormal intrapulmonary vascular dilation and increased pulmonary blood flow –> increased shunting and V/Q mismatch. Unclear pathophysiology.

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19
Q

What are the common histological feature of alcoholic and NAFL disease?

A
  1. Steatosis –> fatty change/deposition in centrilobular hepatocytes
  2. Hepatitis –> hepatocyte ballooning, swelling and necrosis, neutrophil infiltrations permeate lobule
  3. Fibrosis –> collagen desposition in space of disse
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20
Q

What is the threshold of EtOH consumption for development of ALD?

A

60g/day, 10-15 years

  • 90% develop steatosis
  • 10-35% steatohepatitis
  • 2-20% cirrhosis
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21
Q

What is the rate of HCC in patients with cirrhosis?

A

10-20%

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22
Q

What is the pathogenesis of steatosis in ALD?

A

Shunting of substrates towards lipid biosynthesis, impaired lipoprotein synthesis and secretion, and increased peripheral catabolism of fat –> increased fat deposition in the hepatocytes

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23
Q

What mechanisms perpetuate hepatocyte injury in ALD?

A

1.Metabolism of EtOH to aldehyde uses up a lot of the NAD required for metabolising fats

2.Decreased methionine metabolism = less glutathione, which means more oxidative damage from metabolising EtOH, toxins etc

3.Alcohol metabolism induces production of ROS that can damage cell structures/DNA and cause cell damage

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24
Q

What are the criteria for diagnosis of metabolic disease?

A

HTN
Hyperlipidaemia
Insulin resistance
Obesity

**2 or more

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25
Q

What is the brief outline of bilirubin metabolism?

A

RBCs –> macrophages, Hb split into heme and globin

Haem split into Fe2+ and protoporphyrin –> acted on by enzymes to be converted into biliverdin –> bilirubin.

UC bilirubin bound to albumin in plasma, travels to hepatocytes, metabolised there via UGT-1 to conjugated bilirubin –> able to be excreted in bile/urine.

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26
Q

What changes occurs to bilirubin in faeces?

A

Deconjugated via gut bacteria to urobiliniogens, excretion in faeces or reabsorption in ileum/colon and re-excretion in bile.

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27
Q

What are causes of unconjugated hyperbilirubinaemia?

I.e. too much bilirubin generated, or too little conjugated

A

Haemolytic anaemia
Haemorrhage/GI bleed
Haemoglobinopathies
Liver disease (hepatitis, cirrhosis, drug induced)
Physiological jaundice of the newborn

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28
Q

What are the causes of conjugated hyperbilirubinaemia?

(Impaired intra-extra hepatic blood flow)

A

Inflammatory destruction of intrahepatic bile ducts –> Primary biliary cirrhosis, Primary sclerosing cholangitis

Gallstones

Pancreatic/Gallbladder carcinoma causing obstruction of bile flow

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29
Q

What is the mechanism behind Gilbert’s syndrome?

A

Fluctuating unconjugated hyperbilirubinaemia due to decreased levels of hepatic glucuronosyltransferase

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30
Q

What are common symptoms/signs of cholestasis?

A

Jaundice
Pruritis (deposition of bile salts)
Skin xanthomas

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31
Q

What are the differences in patterns of cell injury in acute vs chronic viral hepatitis?

A

Acute = minimal or absent portal inflammation (i.e. skips the inflammation phase, but cell injury/necrosis occurs

Chronic = dense mononuclear portal infiltrates

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32
Q

What are the two forms of hepatocyte cell injury/death in viral hepatitis?

A

1) Ballooning degeneration, emptying pale cytoplasm, swells and ruptures (necrosis)
2) Apoptosis, cell shrinkage, eosinophilic, fragmented nuclei

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33
Q

What are the rough time frames for incubation of viral hepatitis(es)?

A

Oral transmission (A+E) = 2-8 weeks

BBV (B,C,D) = 4-26 weeks (2-26 for Hep C)

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34
Q

What is the major cause of cellular injury in Hep A virus?

A

T Cell mediated damage/killing.

Virus itself doesn’t appear to be toxic to hepatocytes

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35
Q

What are the various responses to Hep B infection? (in terms of resolution vs chronic infection?)

A
  1. Acute hepatitis with recovery and clearance
  2. Fulminant hepatitis with massive liver necrosis
  3. Non progressive chronic hepatitis
  4. Progressive chronic hepatitis –> cirrhosis
  5. Asymptomatic carrier state
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36
Q

What % of Hep B infections progress to chronic infection?

A

10%

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37
Q

What are the different components of the Hep B virus that relate to serology?

A

Hep B surface antigen
Hep B core antigen
Hep B DNA

38
Q

Outline the interpretation of serology for Hep B infection vs clearance vs immunity?

A

HepBsAg = virus present in blood, infection confirmed the supervillain)

Hep B cAg = viral particles present in blood, marker of infection

HepB eAg = marker of active replication

HepB surface IgG Ab/Anti-HBs = immunity (either vaccine or exposure and clearance)

HepB core antibodies = infection

39
Q

What is the clinical course with Hep B and associated serological findings?

A

HepBsAg appears before onset of symptoms , peaks during overt disease, becomes undetectable in 3-6 months

HbeAg, HBV-DNA, DNA polymerase in serum soon after HbsAg, signify active replication

In chronic infection, HepB C IgM becoming Hep B C IgG = sign of persistent infection/not being cleared

40
Q

What proportion of Hep C progresses to chronic infection?

A

80%

41
Q

What serology is important in establishing presence of infection in Hep C?

A

HCV IgG
HCV RNA PCR

Viral RNA load marker of ongoing infection if remaining static vs decreasing

42
Q

What are other viruses capable of causing hepatitis?

A

EBV
CMV
HSV
Yellow fever

43
Q

What is the pathogenesis for cholecystitis?

A

90% gallstone relating biliary obstruction –> exposure of mucosa to detergent action of bile salts, along with distension and compromised blood flow due to increased intraluminal pressure

44
Q

What is the cause of acalculous cholecystitis?

A

Sepsis
Severe burns
Severe trauma

Typically occurs in critical illness, hypoperfusion syndrome to gallbladder

45
Q

What are the 2 major types of gallstones?

A

Cholesterol stones
Pigment stones

46
Q

What are risk factors for formation of cholesterol stones?

A

Dyslipidaemia
Female
Obesity
European/western

47
Q

What is the pathogenesis of cholesterol stone formation?

A

Concentrations of cholesterol in bile exceed solubilising capacity of bile , precipitates out of solution. Most radiolucent, some have CaCO3- to be radioopaque.

48
Q

What are risk factors for pigmented stones?

A

Chronic haemolytic (sickle, spherocytosis) –>elevated levels of unconjugated bilirubin in biliary tree

49
Q

What is cholangitis?

A

Acute inflammation of bile duct wall, usually resulting from bacterial infection

50
Q

What are common causes of cholangitis?

A

Choledocholithiasis
Biliary tree instrumentation
Pancreatitis
Strictures

51
Q

What does ascending cholangitis refer to?

A

Bacteria within biliary tree infecting intrahepatic biliary ducts

52
Q

What organisms are commonly responsible for ascending cholangitis?

A

E. coli
Klebsiella
Enterococci
Clostridium
Bacteroides

53
Q

What proportion of acute pancreatitis is causes by alcohol and gallstones?

A

80%

54
Q

What are the causes of pancreatitis more exhaustively? (IGETSMASHED)

A

Idiopathic/ischaemia
Gallstones
Ethanol
Trauma

Steroids
Mumps
Autoimmune
Scorpion
Hypercalcaemia, hypertriglyceridaemia
ERCP
Drugs (thiazides, chemotherapy, OCP, anticonvulsants)

55
Q

What is the pathogenesis of pancreatitis?

A

Autodigestion of pancreatic substance by inappropriately activated pancreatic enzymes.

56
Q

What 3 pathways can lead to inappropriate activation of trypsin?`

A
  1. Pancreatic duct obstruction: increased intraductal pressure causes accumulation of enzyme rich interstitial fluid (lipase secreted in active form)
  2. Primary acinar cell injury (ischaemic, traumatic, infection)
  3. Defective intracellular transport of of proenzymes within acinar cells (i.e. proenzymes and lysosomal hydrolyses packaged together and leading to activation of enzymes) –> EtOH
57
Q

What are morphological changes/features of acute pancreatitis?

A
  • Microvascular leakage causing oedema
  • Fat necrosis from lipases
  • Acute inflammatory reaction
  • Proteolytic destruction of pancreatic parenchyma
  • Destruction of blood vessels leading to interstitial haemorrhage
58
Q

What are severe complications of pancreatitis?

A

DIC
ARDS
Diffuse fat necrosis
Shock
ATN

59
Q

What are the characteristics of chronic pancreatitis?

A

Long standing inflammation, fibrosis and destruction of exocrine pancreas –> major difference being irreversible impairment of pancreatic function compared with acute pancreatitis

Profibrogenic cytokines lead to remodelling and deposition of collagen –> fibrosis of pancreas

60
Q

What is the clinical presentation of chronic pancreatitis?

A

Malabsoprtion
Diabetes
Recurrent abdominal pain

61
Q

How do oesophageal varices form in portal HTN?

A

Portal HTN makes it harder for returning intestinal venous blood to get back to the IVC, inducing formation of collateral channels via porto-systemic shunts (of which distal oesophagus and stomach are one)

62
Q

What is peptic ulcer disease?

A

Defect in gastric/duodenal mucosa extending to muscular mucosa

63
Q

What location is most common for the formation of PUD?

A

Gastric antrum
Duodenum

64
Q

What is the underlying pathophysiology of PUD?

A

Imbalance in mucosal defences between forces causing chronic gastritis

65
Q

What are common causes of gastric hyperacidity?

A

H. pylori infection
Parietal cell hyperplasia

66
Q

What are common cofactors in development of PUD?

A

NSAID use
Smoking
Steroids
Alcohol

67
Q

What are the major complications of PUD?

A

Perforation
Haemorrhage/GI bleed
IDA

68
Q

What cell type is associated with intestinal metaplasia?

What complication is associated?

A

Change from stratified squamous epithelia to pseudo stratified columnar epithelia (Barrett’s Oesophagus)

Risk of gastric adenocarcinoma

69
Q

What are the 4 categories of diarrhoea?

A

1) Secretory (isotonic stool, persists during fasting)
2) Osmotic (occurring i.e. due to lactase deficiency, unabsorbed luminal solutes ,improves with fasting)
3) Malabsorptive (inadequate nutrient absorption, i.e. steatorrhoea)
4) Exudative (inflammatory disease, purulent, bloody stools, persist during fasting)

70
Q

What is the causative organism for cholera, and how does it cause diarrhoea?

A

Vibrio cholera, gram -ve flagellated bacterium

Preformed enterotoxin activates adenylyl cyclase which leads to increased intracellular cAMP and opening of CFTR chloride channels –> releasing chloride ions into bowel lumen, and impairing sodium and bicarbonate absorption –> SECRETORY DIARRHOEA

71
Q

What are the 4 virulence factors associated with C. jejuni?

A
  1. Motility
  2. Adherence
  3. Toxin production
  4. Invasion
72
Q

What is shigella classified as?

A

Gram -ve, non motile, facoltative anaerobe

73
Q

What diarrhoea syndrome does shigella cause? What is the pathophysiology?

A

Dysentery - resistent to acid of stomach, divides intracellularly, and escapes to invade colonic epithelia via lamina propria

74
Q

What classification exists for different types of E. coli?

A

Enterotoxigenic:
- traveller’s diarrhoea, heat labile and heat stable toxin, increases intracellular cGMP, watery diarrhoea

Enterohaemorrhagic:
- gives rise to HUS, produces Shiga toxin, causes bloody stool

Enteroinvasive:
- resembles shigella, doesn’t produce toxin, causes bloody diarrhoea

Enteroaggregative:
- Produce labile toxin, can cause less severe but more protracted diarrhoea

75
Q

What is the cause of pseudomembranous colitis?

A

C. difficile - Gram +ve bacillus

76
Q

What is the pathophysiology of pseudomembranous colitis?

A

Toxins release by c. difficile cause disruption of epithelia, loss of tight junctions, apoptosis.

Pseudomembrane composed of layer of inflammatory cells + debris at site of mucosal injury

77
Q

What are features of rotavirus?

A

Encapsulated virus, infects mature enterocytes in small intestine - causing repopulation with immature secretory cells –> net loss of absorptive capacity and and osmotic diarrhoea from incompletely absorbed nutrients

78
Q

What are the defining patterns of mucosal injury that differentiate ulcerative colitis and Crohn’s disease?

A

UC = limited to colon and rectum, extending only to mucosa and submucosa

Crohn’s = any area of GIT, frequently transmural

79
Q

What are the macroscopic differences between Crohn’s and UC?

A

Ulcers: deep and narrow for Crohn’s, broad and shallow for UC

Inflammation: transmural Crohn’s, mucosa/submucosa UC

Skip lesions, Crohn’s

Fistulas Crohn’s, not UC

80
Q

What are the microscopic differences in Crohn’s vs UC?

A

Marked lymphoid reaction in Crohn’s, less so UC

Granulomas Crohn’s, not in UC

81
Q

What effect does Crohn’s have on fat/vitamin absorption?

A

Can be impaired, Fe2+ absorption too in terminal ileal disease

82
Q

Which form of IBD does toxic megacolon occur in?

A

Ulcerative colitis

83
Q

What are complications of Crohn’s disease?

A

IDA
Short gut syndrome
Malabsorption/malnutrition
Strictures
Fistulas
Perforation

84
Q

What are extra-intestinal features of Crohn’s disease?

A

Uveitis
Migratory polyarthritis
Erythema nodosum
Clubbing of fingers
Primary sclerosing cholangitis

85
Q

What part of the bowel is always involved in UC?

A

Rectum, then extends proximally

86
Q

Why is screening colonoscopies important for UC/Crohn’s?

A

Risk of colonic epithelial dysplasia and adenocarcinoma

87
Q

What are some causes of acute Ischaemic bowel?

A

Severe atherosclerosis and plaque rupture
Aortic aneurysm
Septic or arterial emboli

88
Q

What are some subacute causes of watershed/not territorial bowel ischaemia?

A

Cardiac failure/shock
Vasoconstrictive drugs
Vasculitides

89
Q

What can cause gut ischaemia involving increased venous pressure?

A

Cirrhosis/portal HTN
Mesenteric vein thrombosis

90
Q

What are the two distinct phases involved in bowel ischaemic injury?

A

1) initial hypoxic insult, where epithelial cells remain pretty resistant to transient hypoxia

2) Reperfusion injury: restoration of blood supply, and associated free radical production and neutrophil infiltration and inflammatory cytokine release

91
Q

What are the watershed zones of intestinal anatomy?

A

Splenic flexure (where superior and inferior mestenteric circulation terminate)

Rectosigmoid colon (termination of inferior mesenteric pudendal and iliac arterial supply)

92
Q
A

ED Primary Exam (46 decks)

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