HBP Pathology Flashcards
Anatomy of the Liver: location, structure, vascular supply, portosystemic anastomoses and clinical significance
Location: right 5th intercostal space to just below the costal margin at the mid clavicular line
Structure: 2 lobes, 8 segments, covered by Glisson’s capsule (contains pain fibres)
Vascular supply: portal vein deO2 (66%), hepatic artery O2 (33%)
Portosystemic anastomoses (clinically significant consequences in portal hypertension)
- oesophageal vein (systemic) – left gastric vein (portal) –> oesophageal varices and bleeding
- inf/middle rectal vein – superior rectal vein –> haemorrhoids (controversial)
- superficial epigastric vein – paraumbilical vein –> caput medusae
Basic histology of the liver: model, 6 features
Lobular model (hexagonal) - centrilobular region (terminal hepatic venule/ central vein) --> least O2 therefore more susceptible to metabolic stress and toxins
- periportal region (portal triad) –> most O2, more susceptible to blood borne infections
- trabeculae –> arrangement of hepatocytes between central vein and portal tracts; in “plates” 1-2 cells thick
- sinusoids between plates where blood traverses to exit at central vein
- bile canaliculi –> 1-2 micrometer channels formed by grooves in membrane of adjacent hepatocytes; drains into periportal bile ductules then terminal bile ducts
- kupffer cell and stellate cell
Functions of the liver (6)
Nutrient metabolism, protein synthesis, drug/ hormone/ toxin metabolism, excretion (bile), storage, immunity (increase acute phase reactants e.g. CRP, SAA, Hepcidin)
Bilirubin metabolism
Haemoglobin –> globin + haem
Haem –> iron + bilirubin
Unconjugated Bilirubin carried by albumin to liver
Bilirubin conjugated and excreted in bile into gut
Gut bacteria convert bilirubin to urobilinogen
Urobilinogen then either
- further converted to stercobilin and ejected in stool
or
- enter portal vein via enterohepatic circulation to return to liver or to go to kidneys to be excreted in urine
Liver biopsy: indications (5), routes (3), complications (3)
Indications:
- Diagnosis
- liver mass with inconclusive imaging (30-60% cases), abnormal LFT with unknown aetiology, pyrexia of unknown origin, multiple possible parenchymal liver diseases (exclude common conditions)
- Prognosis
- staging and grading of known liver disease - Management
- treatment plans based on histological analysis; distinguish between primary and metastatic CA
Route:
- percutaneous (risk of tumour seeding, bleeding, injury to adjacent organs)
- transjugular (IJV-SVC-IVC) – safer
- open wedge (laparoscopy)
Complications:
- bleeding
- puncture of adjacent organs
- tumour seeding along needle track
Hepatocyte Injury: general changes, regeneration, scar formation
Potentially reversible changes e.g. fat and bilirubin accumulation
Irreversible = cells die by apoptosis or necrosis –> widespread death leads to confluent necrosis
Regeneration of hepatocytes is mainly by mitotic replication of hepatocytes adjacent to those that died; stem cell-proliferation and differentiation in long standing CLD
Scar formation by perisinusoidal stellate cells activation
Stigmata of Chronic Liver Disease: general, impaired liver functions, complications
General:
- malaise, fatigue, RUQ pain, hepatomegaly, weight loss
Impaired liver function:
- protein synthesis –> leukonychia + ascites; bruising
- biliary excretion –> jaundice + pruritus
- waste metabolism –> hepatic flap, fetor hepaticus
- estrogen metabolism –> gynaecomastia, spider naevi, palmar erythema, testicular atrophy
Complications:
- liver failure –> encephalopathy, hepatorenal syndrome
- portal hypertension –> formation of portosystemic shunts: haematemesis, varices, splenomegaly (congestive, platelets sequestered in expanded red pulp), caput medusae, ascites
Jaundice: cause, classifications (2)
Hyperbilirubinaemia (normally first presenting as yellow sclera)
Pre-hepatic, hepatic and post-hepatic
Unconjugated vs Conjugated
Unconjugated Hyperbilirubinaemia: presentation (2), causes (2), Gilbert’s syndrome cause/ prevalence/ bilirubin levels
Normal coloured urine and stool
Clinically detectable jaundice at >35 micro mol/L
Pre-hepatic:
- increased production of bilirubin
e. g. Haemolytic Anemia, Ineffective erythropoiesis, resorption of internal bleeding
Hepatic:
- decreased uptake and conjugation of bilirubin
e. g. Gilbert’s syndrome*, physiological jaundice of newborn, drugs such as rifampicin
Gilbert’s syndrome is UGT1A1 mutation causing defective glucuronosyltransferase activity
- common
- mild defect, usually bilirubin <100, rarely clinical jaundice
(vs. Crigler-Najjar with more severe jaundice - type I has absent enzyme, very rare, bilirubin >340, early manifestation, kernicterus; type II bilirubin 100-340, rare, moderately decreased enzyme)
Conjugated Hyperbilirubinaemia: presentation (2), causes
Tea-coloured urine, pale stool
Clinically detectable jaundice at >45 micro mol/L
Hepatic:
- intrahepatic cholestasis (if there is insufficient compensatory drainage)
e. g. inherited hepatocellular injury (hepatitis), intrahepatic bile duct disease (PBC), drugs such as OCP/anabolic steroid/ augmentin
Post-hepatic:
- extra hepatic cholestasis
e. g. intraluminal gallstone, mural cholangiocarcinoma or PSC, extraluminal CA pancreas or lymphoma
Portal hypertension: causes (3 classes), pathogenesis of cirrhosis causing portal HT (2)
Pre-hepatic:
- portal vein thrombosis/ congenital stenosis/ compression by mass
Hepatic:
- cirrhosis
- non cirrhotic schistosomiasis, diffuse granulomatous disease
Post-hepatic:
- heart – right HF or TR (c.f. nutmeg liver)
- IVC thrombosis
- Budd Chiari syndrome (obstruction of >2 hepatic veins)
Portal HT secondary to cirrhosis
- Increased vascular resistance: mechanical obstruction by portal, perisinusoidal and perivenular fibrosis and increased endothelin with decreased NO from sinusoid endothelial cells = vasoconstriction
- Increased blood flow: anastomosis of hepatic arteries and portal veins through fibrous septa and increased splanchnic arteriolar vasodilation by increased NO production in gut (decreased clearance of gut bacteria material by liver)
Liver congestion: pathophysiology, histology (3), clinical presentations (3)
Heart failure increases CVP which is transmitted backwards to IVC and hepatic veins –> dilation of hepatic sinusoids and central veins
Nutmeg appearance (alternating dark sinusoids and pale parenchyma) Centrilobular zone necrosis (red/brown) with atrophy and fatty change, surrounded by uncongested periportal zone (tan-coloured)
Clinical:
- hepatomegaly
- RUQ tenderness
- CCF signs
Ascites: pathophysiology (3), potential treatment
Excessive fluid accumulation in peritoneal cavity
Caused by
- increased hydrostatic pressure in portal HT increasing the venous pressure at peritoneal capillary beds
- decrease in osmotic pressure due to hypoalbuminaemia
- decrease in ECV due ascites and splanchnic vasodilation (decreased CO) leads to activation of RAAS (and ADH) –> increase water retention –> further increase portal HT (and causes dilutional hypoNa)
(liver also unable to metabolise aldosterone)
Aldosterone antagonist (spironolactone) can break vicious cycle
Hepatorenal syndrome: definition, pathophysiology
Pre-renal renal failure due to excessive vasoconstriction of afferent arterioles (decrease renal perfusion pressure and GFR)
Portal HT causes splanchnic arteriolar vasodilation –> decrease ECV –> strong RAAS and SNS activity –> intense renal vasoconstriction overwhelming renal vasodilator system
Hepatic encephalopathy: cause, pathophysiology (2), precipitating factors (1), presentations (5)
Hyperammonaemia
Pathophysiology:
- decrease functional hepatocytes for urea cycle
- portosystemic shunt of ammonia to systemic circulation – physiological, pathological (I.e. portal HT), iatrogenic (trans jugular intrahepatic portosystemic shunt TIPS for portal HT)
Precipitated by variceal bleeding (resorption of internal bleed –> Hb degradation –> protein)
Clinically presents as:
- behavioural abnormalities, insomnia –> confusion/ stupor –> coma, death
- develop over days/wks/mths with fluctuating neurological signs (rigidity, hyperreflexia, asterixis)
Liver failure: definition of acute liver failure, fulminant liver failure, clinical course, histology, biochemical levels, acute-on-chronic examples
Acute liver failure is the presence of encephalopathy within 6 months of disease diagnosis
- usually due to paracetamol overdose, Hep B/E
Fulminant liver failure = encephalopathy within 2 weeks of jaundice onset
Nausea, vomiting, jaundice, fatigue followed by encephalopathy, coagulation defects, portal HT (although more of a chronic feature) and ascites
AST very high, swelling and oedematous liver initially then shrink dramatically and AST decrease
- massive hepatic necrosis with small and shrunken liver; large zones of destruction with loss of architecture microscopically (very pink)
Multiorgan failure eventually
Acute on Chronic liver failure:
- established cirrhosis and extensive vascular shunting/ borderline vascular supply –> liver vulnerable to insults
e.g. Hep D superimposed on Hep B
Ascending bacterial chlangitis in PSC
Primary or metastatic CA
Resistance to medical therapy for viral hepatitis
Definition of Cirrhosis** and classification
**Definition: disrupted architecture of liver with diffuse, regenerative nodules that are separated by bridging fibrous septa
- dynamic and bidirectional (potentially reversible with regression of fibrosis with cure of CLD)
(fibrous septa formed by activation of stellate cells when underlying reticulin collapses in severe injury)
Classified into macro-nodular (e.g. viral hepatitis) and micro-nodular (e.g. AFLD, haemochromatosis) with 3mm as limit – not clinically useful
Cirrhosis: scoring of severity, aetiology (5), complications, lab results (4)
Child-Pugh Score for severity
- Albumin, Bilirubin, Clotting profile (INR), Distended abdomen (ascites), Encephalopathy
- 1-3 points for each category
- Class A (5-6) 95% survival, B (7-9) 75% survival, C (10-15) 50% survival
Aetiologies:
- Infection (viral hep - HBV most common, HCV, non-viral)
- Metabolic (AFLD, NAFLD, Haemochromatosis, Wilsons, alpha-1 antitrypsin deficiency)
- Immune mediated (autoimmune hepatitis, PBC, PSC)
- Drug induced (methotrexate, paracetamol, aspirin)
- Cryptogenic, Idiopathic
Complications (refer to details in other flashcard)
- HCC
- Portal HT
- Synthetic dysfunction
Lab results:
- low platelet, increase PT
- increase ammonia, decrease urea (except after GI bleed)
- reversed A:G ratio – hypoalbuminaemia, increased IgA
- LFT mild to moderate elevation
Infectious Liver Diseases: types (4), duration, clinical presentation, possible disease course
Acute hepatitis
- <6 months
- fever, jaundice, RUQ pain, deranged LFT, malaise
- remit or progress to chronic hepatitis
Chronic hepatitis
- > 6 months
- asymptomatic or deranged LFT
- remit, static, flare-up (acute-on-chronic) or progress to chronic
Fulminant hepatitis
- severe acute hepatitis leading to liver failure within 8 weeks
- high mortality (25-90%)
- usually caused by drugs (isoniazid, rifampicin) + toxins (50%), viral (12%; higher risk in HBV/HDV co-infection or HEV during pregnancy)
Non-viral hepatitis
- bacteria –> pyogenic liver abscess e.g. E.coli, Klebsiella, MTB
- parasites –> amoeba, echinococcus, clonorchis sinensis
Viral hepatitis: causes, presentations, details for each virus (transmission, incubation, risk of fulminant hepatitis, progression to chronic hepatitis or HCC, serology test)
Causative agents: HBV and HCV
(HIV, CMV, EBV in immunocompromised)
Presentation:
- asymptomatic, acute, chronic or fulminant hepatitis
HAV – faecal oral route of transmission, 2-6 weeks incubation, <2% fulminant hepatitis, no progression to chronic hepatitis and no risk of HCC, Anti-HAV IgM serology
HBV – parenteral route of transmission, 4-26 weeks incubation, <1% fulminant hepatitis, 5-10% chronic hepatitis (90% in neonatal), risk of HCC, HBsAg/ Anti-HBc IgM serology, 2% carrier in HK (10% in IVDA)
HCV – parenteral route, 2-26 weeks, <1% fulminant, 80% chronic hepatitis, risk of HCC, Anti-HCV IgM, 0.1% carriers in HK (45% in IVDA)
HDV – parenteral route, 4-7 weeks, 4% fulminant in co-infection; 10% fulminant in superinfection, 5% chronic hepatitis in co-infection; 80% chronic hepatitis in superinfection, risk of HCC same as HBV, Anti-HDV IgM serology
HEV – faecal oral route, 2-8 weeks incubation, 2% fulminant; 15-20% in pregnancy, no chronic hepatitis, no risk of HCC, Anti-HEV IgM serology
Pathology of viral hepatitis: acute (5), chronic (6), grading and staging
Acute viral hepatitis:
- LOBULAR (among hepatocytes) necroinflammatory activity –> cellular damage, spotty necrosis, apoptosis, confluent bridging necrosis if severe
- lobular lymphocyte infiltrate (found in all types of acute hepatitis except for bacterial abscess)
Chronic viral hepatitis:
- PORTAL BASED necroinflammatory activity
- PORTAL BASED fibrosis (Sirius red stain, Trichrome stain)
- Interface hepatitis
- Ground glass hepatocytes (HBsAg cytoplasmic inclusion) – finely granular pink on H&E, can also be seen on orcein stain or IHC cytoplasmic stain
- Sanded nuclei (HBcAg) - IHC nuclear stain
- Mild steatosis and large lymphoid aggregates (HCV)
Grading and Staging (not malignancy!)
- Grade = necroinflammatory activity
- Stage = degree of fibrosis –> stage 1 portal fibrosis, stage 2 periportal fibrosis, stage 3 bridging fibrosis, stage 4 cirrhosis
Alcoholic Fatty Liver Disease: units, pathophysiology (3), manifestations (2) and their definition, presentations, treatment
Standard unit = 10g in Asia (beer 1.8, red wine 1.5)
Prescribed limit for driving = 50mg/dL blood
Male: >2 units per day = significant intake (chronic drinker); >8 units per day = heavy drinker
Female: >1 unit per day = significant intake (chronic drinker); >4 units per day = heavy drinker
Pathophysiology of fatty acid accumulation:
- Ethanol impairs assembly and secretion of lipoproteins
- Increase NADH leads to increased shunting of substrates to lipid biosynthesis
- Acetaldehyde induces lipid per oxidation, disrupts cytoskeleton and membrane to cause hepatitis
- Microsomal ethanol oxidising system has drug interactions
Manifestations:
- Fatty Liver/ Steatosis
- steatosis in >5% hepatocytes
- asymptomatic, hepatomegaly, mildly deranged LFT - Alcoholic Steatohepatitis (10-35% of heavy drinkers)
- steatosis in >5% hepatocytes + ballooning degeneration (hallmark of steatohepatitis) + lobular inflammation
- acute: RUQ pain, fever, jaundice, nausea, vomiting
- chronic: asymptomatic, progress to cirrhosis (8-20%) of which 10-20% HCC
Treatment:
- abstinence from alcohol
Non-alcoholic Fatty Liver Disease: epidemiology, presentation, associations (5), pathophysiology, pathology (6)
27% in HK, MC cause of chronic hepatitis in HK
Asymptomatic, incidental finding (may have hepatomegaly +++)
Associated with metabolic syndrome:
- HT, DM, Hypertriglyceridemia, Low HDL-C (<1.03 mmol/L in male and <1.29 in female), Central obesity (waist circumference >80cm in female, >90 cm in male)
Pathophysiology:
- insulin resistance increases fatty acid mobilisation from adipose tissue to hepatocytes and increases hepatic fatty acid synthesis –> sensitise to toxic effects of infl. cytokines and increase toxic lipid metabolites –> steatohepatitis
Pathology:
- Macroscopically: large, soft, yellow, greasy, distended capsule
- Microscopically (can’t distinguish with ALFD!!!)
- MACROvesicular steatosis –> nucleus displaced (vs microvesicular)
- BALLOONING DEGENERATION with MALLORY DENK bodies –> misfolded and damaged intermediate filament in cytoplasm (deeply eosinophilic)
- LOBULAR necroinflammatory activity (neutrophilic around degenerating hepatocytes)
- PERIVENULAR AND PERISINUSOIDAL fibrosis (distinctive feature of fatty liver, c.f. portal based in chronic viral hep) –> central vein sclerosis – perisinusoidal scarring “chicken wire fence pattern” –> link to portal tract to create central portal fibrous septa –> MICRONODULAR cirrhosis
Drug Induced Liver Injury: onset, presentation, causes, Reye’s syndrome (cause, effect, pathology), Paracetamol overdose (effect, pathology), other possible causes
Variable onset, presentations, pathological features resembling all forms of hepatitis caused by other aetiologies
- direct toxicity, toxic metabolite or immune response e.g. haptens
- intrinsic dose dependent vs idiosyncratic dose independent e.g. isoniazid, rifampicin, halothane
Reye’s syndrome - idiosyncratic
- potentially fatal mitochondrial dysfunction involving mainly liver and brain
- use of aspirin in children (<12 yrs) with viral illness
- pathology: microvesicular steatosis (nucleus not displaced)
Paracetamol Overdose (adult >4gm/day, child >60-90mg/kg/day) - intrinsic
- emergency: potentially causing fulminant hepatitis
- accumulation of NAPQI toxic metabolite due to saturation of conjugation pathways leading to increased CYP450 metabolism and production of NAPQI (which also saturates GSH detox pathway)
- pathology: pan-acinar necrosis (massive hepatic necrosis)
- antidote should be given within 24 hrs
Other causes:
- herbal medicines common, methotrexate (macro vesicular, fibrosis), isoniazid/ rifampicin (massive necrosis), methyldopa (hepatitis), OCP/ Chlorpromazine (cholestasi), allopurinol (granuloma)
Comparison of pathologies : necroinflammatory activity, fibrosis and steatosis
Necroinflammatory activity:
- acute viral hep – lobular with lymphocytes
- chronic viral hep – portal based
- FLD – lobular with neutrophils
Fibrosis:
- chronic viral help – portal based
- FLD – perivenular and perisinusoidal
Steatosis:
- FLD – macrovesicular
- DILI – microvesicular
Normal iron physiology recap
- iron exported to bloodstream by Ferroportin 1 –> binds to plasma transferrin (Tf) –> complex binds with receptor (TfR1) on basolateral surface of hepatocytes –> iron enters cells and receptor deactivated
- lack of iron = increase ferroportin
- excess iron = increase mucosal ferritin (later sloughed off) and increase hepcidin (inhibit ferroportin)
- —– no active mechanism to reduce body Fe load so tightly regulate intestinal absorption
Haemochromatosis: definition, onset, primary causes (3), secondary causes and pathophysiology (3)
Excessive Fe accumulation in organs especially liver and pancreas
Onset usually after >20gm Fe accumulated
Primary (hereditary) or Secondary
Secondary = most common cause of haemochromatosis in HK
- frequent blood transfusion in thalassemia
- ineffective erythropoiesis, haemolysis, inflammatory syndromes, various CLD
Primary
- Ferroportin Haemochromatosis –> mutant ferroportin resistant to hepcidin regulation
- Transferrin receptor-2 haemochromatosis –> TfR2 facilitates transferrin bound Fe uptake after TfR1 downregulated by iron excess
- HFE Haemochromatosis (70% of primary cases) –> inhibit hepcidin and TfR1 mediated-uptake
HFE Haemochromatosis: epidemiology, pathphysiology (3), presentations, lab (3), pathology (2)
70% of primary haemochromatosis
Rare in Chinese, M>F, 40-60 years old
Pathophysiology:
AR mutation of HFE gene (rare in Chinese)
–> inhibit hepcidin expression leading to excessive intestinal absorption by ferroportin
–> inhibit TfR1 mediated uptake leading to excessive deposition of Fe in other organs
Presentation: Deposits anywhere!!
- Cirrhosis
- Cardiomyopathy (and arrhythmia)
- Cancer (HCC) - 200x risk
- DM (pancreatic fibrosis, atrophy)
- Arthropathy
- Bronze pigmentation of skin (increase epidermal melanin)
- Hypogonadism
Lab: - increase transferrin saturation - increase serum ferritin - increase hepatic iron index >1.9 Dx by genetic test
Pathology:
- Siderosis in iron stain (Perls stain); brown granules on H&E - starts at periportal area
- micronodular cirrhosis
Wilson’s disease: epidemiology, pathphysiology (4), presentations (3), lab (4), pathology (4)
Relatively common (1 in 5400) – MC metabolic liver disease in Chinese
Pathophysiology:
AR mutation in ATP7B gene
–> defect Cu excretion into bile
–> defective incorporation of Cu into apoceruloplasmin leading to increase in free Cu
–> free Cu accumulates in liver –> released from injured hepatocytes and deposited
Presentation:
- Chronic hepatitis (due to ROS)
- Parkinsonism (deposits in basal ganglia)
- Kayser-Fleischer rings (green-brown deposits in eye; 50% cases)
Lab:
- decrease serum ceruloplasmin
- increase 24 hr urine Cu (very specific)
- mutational analysis of ATB7B is gold standard for Dx
- increase hepatic Cu content (>250 microgram/gm) - very sensitive
Pathology:
- copper associated protein in hepatocytes (orcein stain; rhodamine stain for Cu)
- Glycogenated nuclei in periportal hepatocytes
- Mallory Denk bodies with mixed/mild steatosis
- Portal based fibrosis in advanced cases –> cirrhosis
Alpha-1 antitrypsin deficiency: epidemiology, pathphysiology (2), presentations (4), pathology (3)
Very rare in chinese
AR mutation of protease inhibitor Pi gene (Pi ZZ)
–> A1AT retention in hepatocytes
Presents as neonatal jaundice and acute hepatitis
In adults: chronic hepatitis, HCC/ cirrhosis, panacinar emphysema (unopposed action of neutrophil derived protease in smoking)
Pathology:
- intracellular globular inclusion
- strongly PAS +ve
- micronodular fibrosis (periportal)
Immune-mediated/ Cholestatic Liver Disease: presentation, lab results, pathology of cholestasis (2), PBC + PSC definition/ prevalence/ age of onset/ presentation/ serology/ diagnosis/ associated conditions/ pathology
Cirrhosis without chronic liver failure
Cholestasis: jaundice, pruritus, intestinal fat and vitamin malabsorption
Increase in ALP and GGT
Pathology of Cholestasis:
- accumulation of bile pigments in parenchyma and within hepatocytes –> feathery degeneration
- dilated canaliculi (rupture results in Kupffer cells phagocytosing extravasated bile)
Primary Biliary Cholangitis
- granulomatous destruction of INTRAHEPATIC small and medium bile ducts
- F>M (9:1)
- 40-60 yrs old
- insidious pruritus and fatigue
- anti-mitochondrial Ab (AMA)
- Dx (2 out of 3) –> increase ALP, seropositive AMA, histological evidence
- associated with Sjogren’s syndrome (70%), thyroid disease (20%)
Pathology of PBC:
- non-suppurative lymphoplasmacytic destructive cholangitis
- destruction of interlobular ducts
Primary Sclerosing Cholangitis
- obliterative fibrosis of INTRAHEPATIC AND EXTRAHEPATIC bile ducts
- M>F (2:1)
- any age, usually young
- intermittent jaundice, pruritus, weight loss
- anti-neutrophil cytoplasmic Ab (ANCA)
- Dx –> cholangiogram showing “beads on string” bile duct
- associated with IBD (70%) – UC>CD; autoimmune pancreatitis (25%)
- complicated by acute bacterial cholangitis and cholangiocarcinoma
Pathology of PSC:
- “onion skin fibrosis” around smaller ducts
Biliary Tree Disease: Gallstones - prevalence, epidemiology, manifestations (5), complications (5)
- 10-15% adults in developed countries
- Fair, Forty, Fat, Fertile Women
- cholesterol stones, pigment stones (calcium + mucin) and mixed stones
- Manifestations
- -> 80% asymptomatic
- -> Biliary colic: dull constant RUQ pain precipitated by fatty meal, breathing, radiation to back and right shoulder, nausea/vomiting
- -> complications: cholecystitis, acute cholangitis, gallstone ileus, CA gallbladder, acute pancreatitis
Biliary Tree Disease: Cholecystitis - acute and chronic pathogenesis, presentations (5), pathology (5), complications (3)
Acute Cholecystitis
- calculous type >90% –> acute obstruction of Hartmann’s pouch leading to gallbladder distension and secondary bacterial infection
- acalculous type after trauma, burns, major surgery
- presentations: ACUTE fever, biliary colic, vomiting, guarding, Murphy’s sign (no jaundice)
- pathology: acute inflammation with ULCERATION of mucosa and dense neutrophils (TRANSMURAL); oedematous muscle, bleeding
- complications: empyema, perforation and septic shock –> death
Chronic Cholecystitis
- can develop without history of acute attack
- pathogenesis: chronic supersaturation of bile by cholesterol leading to repeated biliary colic
- pathology: chronic inflammation (lymphoplasmacytic); repeated focal mucosal injury/erosion and regeneration (ROKITANSKY-ASCHOFF SINUS); fibrosis and muscular hyperplasia increase thickness of wall
Biliary Tree Disease: Cholangitis - acute cholangitis cause/ presentation (5)/ pathology (3); recurrent pyogenic cholangitis pathogenesis/ prevalence
Acute cholangitis
- acute obstruction of extrahepatic bile duct with superimposed bacterial infection
- Charcot’s triad (fever, jaundice, RUQ pain) or Reynold’s pentad (+ hypotension, confusion – septic shock in 4-6 hrs!)
- pathology: ductular reactions and inflammation; periductular neutrophils in bile duct; periportal fibrosis and cirrhosis if untreated
Suppurative cholangitis = purulent bile fills and distends bile ducts
Recurrent Pyogenic Cholangitis
- stone formation in intrahepatic and extrahepatic ducts causing recurrent acute cholangitis, biliary obstruction and stricture
- endemic in HK
- associated with liver fluke (clonorchis sinensis)
- primarily affects left lobe
HBP Tumours: Benign (3) - prevalence, manifestation, risk factors, treatment?
Hepatocellular Adenoma
- 1:15 M:F
- acute abdomen with rupture –> haemoperitoneum
- risk factors: OCP
Focal Nodular Hyperplasia
- 1:15 M:F
- asymptomatic
- risk factors: OCP
Haemangioma
- 1:5 M:F
- MC primary liver tumour
- asymptomatic
- no treatment required
Hepatocellular Carcinoma: epidemiology, risk factors, presentations, complications (3), tumour marker, pathology, grading and staging (2)
4th in incidence, 3rd in mortality
- M:F 3:1
- risk factors: cirrhosis, hepatitis B/C, Aflatoxin B1 (from aspergillus flavus; 200x risk if with HBV), alcohol, NAFLD
Presentations:
- RUQ mass/pain, obstructive jaundice, other stigmata of CLD
- cachexia, malaise, anorexia
Complications:
- massive intra-abdominal bleed due to tumour rupture
- liver failure
- metastasis (most commonly to lung)
Tumour marker:
- AFP (recall also elevated in hepatoblastoma, yolk sac tumour, multiple pregnancies) for prognosis and monitoring
Pathology:
- Architecturally –> hepatocellular differentiation in thickened trabeculae (>2 cells thick)
- Cytologically –> pleomorphism, high N:C ratio, prominent nucleoli/ nuclear enlargement, hyperchromasia, frequent mitosis
Grading: 3-tier, defined by histopathology
Staging: most important prognostic factor
- TNM in patients with surgical resection and liver transplantation (but <20% HK patients are surgical candidates and transplantation uncommon in HK) – otherwise limited use as can’t evaluate vascular invasion without excisional liver specimen and doesn’t consider underlying liver disease which affects management
- BCLC – includes status of underlying liver disease (Child Pugh) and performance status as well as tumour burden
Diagnosis: radiological (contrast enhancement during arterial phase and washout during venous phase) –> if inconclusive then pathological
Hepatoblastoma
MC liver tumour in paediatrics
Mostly <5 years old
M:F 2:1
Pathology:
- epithelial component +/-
- mesenchymal (osteoid) or teratoid (cartilage, skeletal muscles) components
- extra medullary haematopoiesis
Metastasis: prevalence, primary sites, differentiation from HCC (3)
MC liver tumour (in western)
Primary sites: lung, breast, colon
Pathology:
- differentiate from primary HCC by
- -> gross
- - non-cirrhotic liver favours metastasis
- - metastasis usually multiple lesions
- - HCC cells may produce bile and have greenish colour - -> histology – differentiation of cells e.g. lung adenoma with glandular differentiation
- -> cytology – cytoplasmic mucin and columnar tumour cells in adenoCA
- -> IHC – HCC (HepPar-1, Arginase-1) vs pulmonary adenoCA (TTF-1, Napsin-A)
Also differentiate based on history and other clinical signs
Cholangiocarcinoma: risk factors (4), presentations (3), pathology (3)
AdenoCA
- risk factors: cirrhosis, chronic biliary diseases e.g. PSC, RPC (and liver fluke infestation), hereditary haemochromatosis, congenital biliary anomalies
Presentations;
- extrahepatic (90%)
- intrahepatic (10%)
- peripheral (to hilum) = clinically silent
- central/klatskin (around hilum) = early biliary obstruction
Pathology:
- grossly - whitish and firm
- architecturally: glandular differentiation in desmoplastic stroma with irregular angulated and complex glands
- cytologically: main malignant characteristics
Pancreatic Carcinoma: prevalence, mortality, common site, risk factors (5), pathogenesis (2), presentations (5), complications (2), pathology (4)
1:1 M:F
High mortality (3-5 months survival without treatment)
Most common at pancreatic head
Risk factors: smoker (2-3x), drinker, obesity, high fat intake, chronic pancreatitis (10x), DM (1-2x)
Pathogenesis:
- KRAS, TP53 mutations
- precursor lesion: pancreatic intraepithelial neoplasias
Presentations:
- epigastric/back pain, obstructive jaundice, acute pancreatitis
- functional –> DM (often 1st manifestation), steatorrhea, malabsorption
- systemic: cachexia, malaise, anorexia
Complications:
- metastasis (lung, bone, liver)
- IVC invasion
- stasis due to pain/surgery can increase risk of DVT and PE –> RHF and cardiogenic shock –> hypoxia/death
- tumour can also cause emboli
Pathology:
- gross –> mimics chronic pancreatitis pathologically and radiologically; may be haemorrhagic/ invasion to surrounding organs e.g. IVC
- histology –> GLANDULAR differentiation (moderate to poor) with cytoplasmic MUCIN, malignant cytology; perineural and lymphovascular invasion;
Pancreatic NET: features of carcinoids (3), prevalence of pancreatic NET, metastatic potential, presentations (2)
Carcinoid: carcinoma-like features with more indolent course
- in general, 75% NET arise from digestive system, 25% from lung –> but different diagnostic terminologies used
- Digestive: Grade 1-3 and NEC
- Pulmonary: Typical or Atypical Carcinoid, Small cell or Large cell NEC
Pancreatic NET:
- 2nd MC NET after small bowel NET (16% of Digestive NET)
- High metastatic potential (42%)
Presentations
- functional e.g. insulinoma –> fasting hypoglycaemia and neuroglycopenic
- carcinoid syndrome –> abnormal 5HT manifests after liver metastasis; flushing, diarrhoea, tachycardia, dyspnea, wheezing
Acute Pancreatitis: epidemiology, causes (3), pathogenesis (3), manifestations (3), lab, complications (6), pathology (4)
3:1 M:F (both acute and chronic)
- auto-digestion due to inappropriately activated enzymes (premature trypsin)
- causes: GALLSTONES (48%), idiopathic (34%), alcoholism (9%)
(less common causes: trauma, infection e.g. mumps, coxsackie, drugs e.g. steroid, azathioprine, oestrogen, metabolic e.g. hyperCA, hypertriglyceridemia)
Pathogenesis:
- pancreatic duct obstruction –> fat necrosis –> inflammation and edema –> ischaemia and injury
- primary acinar cell injury due to virus, drugs, direct trauma, ischaemia
- defective intracellular transport of proenzymes in acinar cells –> activation and lysosomal rupture
Manifestations;
- epigastric pain with radiation to the back
- nausea and vomiting, fever
- if severe necrotising/haemorrhagic pancreatitis (digestive enzymes leaked from pancreas leading to vascular injury and haemorrhage): retroperitoneal bleed presents as Cullen’s sign and Grey Turner’s sign (subcutaneous greenish discolouration in periumbilical and flank regions as haemorrhagic fluid tracks along gastrohepatic and falciform ligament or through defect in transversalis fascia to lateral abdominal wall muscle)
Lab: amylase >1000
Complications:
- retroperitoneal bleed and shock (with acute renal failure)
- ARDS
- DIC
- Death (15%)
- Chronic –> pseudocyst, pancreatic abscess
Pathology:
- acute inflammation (edema with microvascular leakage)
- neutrophilic aggregate: abscess in severe cases – purulent exudate grossly
- saponification: leakage of lipase causing fat necrosis (white chalky-nodules)
- proteolytic destruction of parenchyma and interstitial haemorrhage in severe cases – swollen, haemorrhage and necrotic pancreas grossly
Chronic pancreatitis: epidemiology, causes (2), pathogenesis (3), manifestations (4), complications (2), pathology (3)
3:1 M:F
- caused by ALCOHOLISM
(other causes: chronic pancreatic duct obstruction, autoimmune, cystic fibrosis…)
Pathogenesis
- contraction of sphincter of Oddi
- direct toxicity of alcohol and increase of O2 stress
- protein plugs
Manifestations:
- epigastric pain with radiation to the back
- pancreatic insufficiency (exocrine and endocrine) –> DM, malabsorption
- weight loss
Complications:
- pancreatic insufficiency
- CA pancreas (10x risk)
Pathology:
- grossly mimics pancreatic CA –> need biopsy
- chronic inflammation
- parenchymal atrophy and fibrosis/ loss of acinar
- dilation of ducts
