ACP-L21 & 22 HBP Pathology Revision Notes PDF

38 ACP-L21 & 22 HBP pathology Anatomy and physiology of liver Heaviest visceral organ: 1500 g Location: between right 5th ICS to just below costal margin, at mid-clavicular line Structure: 2 lobes (where portal triad follows), 8 segments (self-sustained unit), covered by Glisson...

38 ACP-L21 & 22 HBP pathology Anatomy and physiology of liver Heaviest visceral organ: 1500 g Location: between right 5th ICS to just below costal margin, at mid-clavicular line Structure: 2 lobes (where portal triad follows), 8 segments (self-sustained unit), covered by Glisson's capsule Vascular supply: portal vein (75%), hepatic artery (25%) Portosystemic anastomosis (6 in total) [HUS1] Location Systemic drainage Portal drainage Consequence if portal hypertension Lower oesophagus Oesophageal vein (azygos) Left gastric vein (portal) Oesophageal varices Anal canal Inferior/middle rectal vein Superior rectal vein Haemorrhoids (controversial) Umbilicus Superficial epigastric vein Para-umbilical vein Caput medusae dilation of veins in the abdomen Histology: hexagonal (theoretical) o Centrilobular region: central vein o Periportal region: portal tract (portal vein, hepatic artery, bile duct) o Trabeculae: 1-2 cells thick Bilirubin metabolism network I (Macrophage) trabeculae in blood stream (lipid-soluble) & water-soluble can be excreted , ① back to bile ② excreted by Kidney intestinaa Curbilincolour (brown colour in feces) Liver biopsy Indications Diagnosis: liver mass with inconclusive imaging result (30-60%) Prognosis: staging of known parenchymal liver disease Management: treatment plans based on histologic analysis Route Percutaneous o Risk: tumour seeding along the need track, bleeding (coagulopathy), puncture of adjacent organs Transjugular: IJV → SVC → IVC; safer Open wedge: laparoscopy  39 Stigmata of chronic liver disease General Malaise, fatigue, anorexia, weight loss RUQ pain, hepatomegaly portal hypertension Impaired liver Impaired protein synthesis Leukonychia, ascites: albumin aka albumin function Bruising: clotting factor Impaired biliary excretion Jaundice, pruritus F, Abile level salt Impaired waste metabolism Fetor hepaticus: defective demethylating process of dimethyl sulphide volatile organic compound (can be exhaled Hepatic flap Casterixis ELE) Mtoxic substance blood g ammonia brain function in e.. Impaired oestrogen metabolism Palmar erythema, spider naevi, testicular atrophy, gynaecomastia Complication Liver failure Hepatic encephalopathy liver inability detoxify harmful substances to Hepatorenal syndrome · portal hypertension renal malfunction (X damage) > - n Portal hypertension Hematemesis from oesophageal varices, caput medusae, haemorrhoid Ascites Splenomegaly Jaundice Hyperbilirubinaemia, first presented as yellow sclera (high affinity to bilirubin) Site Pre-hepatic Hepatic Post-hepatic (obstructive) Type of bilirubin Unconjugated (CB/T bili < 20%) Conjugated^ (CB/ T bili > 50%) Presentations Normal coloured urine & stool Tea-coloured urine, pale stool Clinically detectable jaundice: > 35 umol/L Clinically detectable jaundice: > 45 umol/L (within liver ( Pathophysiology production uptake & conjugation Intrahepatic Extrahepatic cholestasis liver duodenum/s > - bile cholestasis blockage blood over ↑ bilirubin in Examples Haemolytic anaemia Inherited: Gilbert's syndrome* Inherited ⑯Hepatocellular injury: Intraluminal: gallstone of duct bile duct wall Mural: cholangiocarcinoma, CA PSC 11) Sclerosing cholangitis) inflammation& one scarin Ineffective Drug: rifampin, ribavirin hepatitis & erythropoiesis Neonate: physiological Intrahepatic bile duct Extramural: CA pancreas, Resorption of jaundice of new-born disease: PBC tobiliary holangitisa lymphoma > - obstruction internal bleed Drug: OCP, anabolic steroid, chlorpromazine, Augmentin ^ Conjugated bilirubin (CB) or bilirubin may not be increased in intrahepatic cholestasis → check ALP & GGT + liver USG [CPY-L16] *Gilbert's syndrome: UGT1A1 mutation causing defective glucuronosyltransferase (UDP-GT) activity in blood Gilbert Crigler-Najjar type II Crigler-Najjar type I Quoted bilirubin level (µmol/L) 340 Clinical picture Rarely produce clinical Clinical jaundice more Congenital non-haemolytic jaundice, early manifestation jaundice evident than Gilbert (e.g. neonate), kernicterus, could be lethal UDP-GT activity Mildly decreased Moderately decreased Absent neurological disease by hyperbilirubinemia cause Prevalence Common Rarer Very rare Response to phenobarbital Yes Yes No Portal hypertension Pre-hepatic Portal vein: thrombosis, congenital stenosis, compression by mass lesion Hepatic Cirrhosis* formation of granulomas liver disruptnormalblood in : a o Non-cirrhotic: schistosomiasis, diffuse granulomatous disease Post-hepatic Heart: right HF, TR IVC thrombosis (stasis of blow flow) Hepatic vein thrombosis (Budd-Chiari syndrome) *Portal hypertension secondary to cirrhosis: 1. ↑Vascular resistance: mechanical obstruction + functional vasoconstriction (↑endothelin-1, ↓NO production by hepatic sinusoid endothelial cells) CT SMA IMA (Glarteries). , 2. ↑Portal blood flow: abnormal anastomosis in fibrous septa + splanchnic arteriolar vasodilation by ↑NO production in gut fibrous connective tissue form within after inflammation various organ  40 Ascites Excessive fluid in peritoneal cavity Pathophysiology: Local ① Hydrostatic pressure: portal HT ② osmotic pressure: hypoalbuminaemia – synthetic dysfunction effective circulating volume Systemic ① 2o hyperaldosteronism: ECV → RAAS ② Liver unable to metabolise aldosterone – synthetic dysfunction Hepatorenal syndrome Pre-renal failure: intense renal vasoconstriction due to a loss of renal autoregulation Pathophysiology: strong RAAS & SNS due to ↓ECV overwhelms renal vasodilator system Hepatic encephalopathy Hyperammonaemia due to: oels o ↓Functional hepatocytes for urea cycle toximoitiationcirmation CLD cirrhosis portal hepatic vein > - vein congenital e. g. , o Portosystemic shunt: physiological, pathological (∵portal HT) or iatrogenic (e.g. transjugular intrahepatic portosystemic shunt (TIPS) for portal HT) Precipitated by variceal bleeding: resorption of internal bleeding → Hb degradation → protein 16 perfusion of tissues & organs) · DECF ① ② ③ (pre-renal failure  41 Cirrhosis &ofibrous Diffuse, regenerative nodules separated by bridging fibrous septa surrounding (septal regeneration of hepatocyte due inflammation to o Healing process partly by regenerative nodules and partly by fibrosis (fibrous tissue) tissue It is o Currently believed to be potentially reversible alcoholic fata abnormal acc. Classically classified into macro-nodular (e.g. viral hepatitis) & micro-nodular (e.g. AFLD, hemochromatosis) ↑ iron absorption using 3mm as limit – not clinically useful Child-Pugh score To assess and monitor severity in blood [ L produced by liver congujated by liver Aetiology and complications Instead of a single “end-stage” liver disease, better regarded as a spectrum of advanced liver disease Infection Viral: HBV (MC), HCV Non-viral Hepatocellular carcinoma Ascites Metabolic fatty non-alcoholic liver disease Variceal haemorrhage alcoholic liver disease ALD, NAFLD ↑ Feabsorption Haemochromatosis Hepatorenal syndrome ↑ body Wilson’s disease In acc in CIRRHOSIS Portal hypertension LAAT) α1-antitrypsin deficiency XI- AAT produced by liver caused by inflammation Encephalopathy prevent tissue damage Immune Synthetic dysfunction Coagulopathy PBC 10 biliary cholangitis PSC 1" sclerosing cholangitis Jaundice Drug-induced Hypoalbuminaemia DILI normal liver : area cycle > urea Lab investigations [CPY-L17] ammonia - LF : hyperammonemia Low platelet count, ↑PT ↑ protein load stimulate gastrointestina sing liver ↑Ammonia, ↓urea (except after GIB: Hb returns to gut → “protein meal” → ↑urea, ↑urea:Cr ratio) Trenal function Reversed A:G ratio: low albumin, IgA production (immune defence at GI lumen) remains intact inflammation : LFT: mild to moderate elevation  42 Infectious liver disease Acute hepatitis Duration < 6 mo Presentations: fever, jaundice, RUQ pain Outcome: remit or progress to chronic hepatitis Chronic hepatitis Duration ≥ 6 mo Asymptomatic or deranged LFT Outcome: remit or static or flare-up (acute-on-chronic) or progress to cirrhosis t Fulminant hepatitis Severe acute hepatitis leading to liver failure within 8 weeks High mortality Causes: drug/ toxin (50%), viral hepatitis, idiopathic Non-viral hepatitis Bacteria: pyogenic liver abscess [MIC-L31] Parasites: amoeba, Echinococcus, Clonorchis sinensis (Chinese liver fluke) [MIC-L31] Viral hepatitis Causative agents having effect liveron o Hepatotropic virus: HBV, HCV, etc o Other viruses: especially in immunocompromised patients, e.g. HIV, CMV, EBV Clinical presentations: asymptomatic (serological evidence only), acute, chronic, fulminant HAV HBV HCV HDV HEV Nucleic acid RNA DNA RNA RNA (incomplete) RNA (other G1 tract) than Transmission Faecal-oral Parenteral Parenteral Parenteral Faecal-oral Incubation (days) 15-45 40-180 20-120 30-180 14-60 Fulminant 56 >28 Pathology: see NAFLD Manifestations: Fatty liver/ steatosis Alcoholic steatohepatitis (ASH) acc. of fat lin hepatocyte Definition Steatosis ≥ 5% of hepatocytes enlargement of Steatosis ≥5% of hepatocytes + ballooning swelling & due liver cells to acc of fat degeneration + lobular inflammation Manifestation Asymptomatic Acute: fever, RUQ pain, jaundice, n/v Hepatomegaly, mildly deranged LFT Chronic: usually asymptomatic, may progress to alcoholic cirrhosis Treatment: abstinence from alcohol Non-alcoholic fatty liver disease (NAFLD) Epidemiology Prevalence in HK: 27%; MC cause of chronic hepatitis in HK Low in pre-menopausal female: protective effect of oestrogen Associated with metabolic syndrome: o Central obesity ▪ Defined by waist circumference: > 90cm in male, > 80cm in female ▪ Obesity defined by BMI > 25 o Hypertension o Hyperglycaemia o Hypertriglyceridemia o Low HDL-C Pathological features Indistinguishable between ALD and NAFLD Macrovesicular steatosis (nucleus displaced, c.f. nucleus not displaced in microvesicular steatosis) Ballooning degeneration with Mallory-Denk bodies (cell injury with damaged intermediate filament) surroundLobular central vein necroinflammatory surround sinusoids activity (c.f. portal-based in chronic HBV) Perivenular and perisinusoidal fibrosis - distinctive feature of fatty liver (c.f. portal-based in chronic HBV) Perivenular and perisinusoidal fibrosis (in Sirius red stain for fibrotic tissue)  44 Drug-induced liver injury (DILI) Variable onset, presentations, pathological features resembling all forms of hepatitis caused by other aetiologies Reye's syndrome Potentially fatal mitochondrial dysfunction involving mainly liver and brain Use of aspirin in children with viral illness Pathology: microvesicular steatosis in liver (see above) Paracetamol overdose Emergency: potentially causing fulminant hepatitis panlobular Pathology: pan-acinar necrosis Antidote should be given with 24 hours Comparison of pathologies Acute viral hepatitis Chronic viral hepatitis Fatty liver disease DILI Necroinflammatory Lobular with = Portal-based Lobular activity lymphocytes - Fibrosis Portal-based Peri-venular/ -sinusoidal Steatosis Macrovesicular Microvesicular Metabolic liver disease ① Ferroportin haemochromatosis ③ HFE haemochromatosis HFE: high Fe ② TfR2 haemochromatosis TfR2: transferrin receptor 2 Iron physiology and pathophysiology [ACP-L4, CPY-L17] Normal physiology: iron is exported to the bloodstream via Ferroportin 1 → iron binds to transferrin (Tf) → Iron-Tf complex binds with transferrin receptor (TfR1) on the basolateral surface of hepatocytes → iron brought into cell, TfR1 deactivated Lack of iron: ↑ferroportin expression Excess of iron: ↑mucosal ferritin (later sloughed off) + ↑hepcidin (↓ferroportin activity) o No active mechanism to reduce body Fe load o Passive mechanism includes menstruation Haemochromatosis: X haemoglobin production o 2o haemochromatosis: MC cause in HK ∵ frequent transfusion in thalassaemia o Ferroportin haemochromatosis: mutant ferroportin resistant to hepcidin regulation o Transferrin receptor-2 haemochromatosis: TfR2 facilitates transferrin-bound Fe uptake after TfR1 is downregulated by Fe overload o HFE haemochromatosis: table below  45 produced by liver HFE Haemochromatosis* Wilson’s disease 1-antitrypsin deficiency Pathophysiology AR mutation of HFE gene: AR mutation of ATP7B gene AR mutation of protease C282Y, H63D - rarely found in → defective Cu excretion inhibitor Pi gene (Pi ZZ) Chinese → into bile & binding with Inflammation inflammatory cells release protease which damage lung & liver Inhibit hepcidin ceruloplasmin → Free Cu Ca carrying protein produced by liver T expression X1-antitrysin Inhibit TfR1-mediated uptake Epidemiology Rare in Chinese, male more Relatively common: 1 in 5400 Very rare in Chinese affected (female alleviated by menstruation) Presentation HaemoChromatosis Can Cause Liver: chronic hepatitis Neonatal: jaundice, acute Deposits Anywhere mimicking AIH autoimmune hepatitis hepatitis ↑ FSH LH (testosteronTo Hypogonadism , Basal ganglia: parkinsonism Adult: chronic hepatitis, Cancer (HCC) - 200x risk Eye: Kayser-Fleischer rings panacinar emphysema [L19] entire alveolar destructed - Cirrhosis (present only in 50%) loss of recoil in lung tissue Cardiomyopathy DM oint pain Arthropathy: bronze associated WithFe pigmentation Lab ↑transferrin saturation (male > ↓serum ceruloplasmin 60%, female > 50%) ↑24-hour urine Cu ↑serum ferritin StoreIron Mutation analysis of ATP7B ↑hepatic iron index > 1.9 (liver gene (gold standard) [CPY- [Fe] in biopsy / patient age) L22] deposition of pigment body iron in Histopathology Siderosis in iron stain ①Copper-associated protein in Intracellular globular of protein in globular shape Micronodular cirrhosis hepatocytes inclusion aggregation thickband of connective tissue < 3 mm ②Glycogenated nuclei in Micronodular fibrosis nodules Vscarring separating periportal hepatocytes fibrous septa (before cirrhosis) 3 Mallory-Denk body Portal-based fibrosis → cirrhosis *Haemochromatosis can be primary (hereditary, e.g. HFE haemochromatosis) or secondary (frequent transfusion, ineffective erythropoiesis, etc)  46 F Immune-mediated/ cholestatic liver disease Cirrhosis without chronic liver failure inflammation AIM system scarring + Primary biliary cholangitis (PBC) Primary sclerosing cholangitis (PSC) thickening + scarring Definition Granulomatous destruction of Obliterative fibrosis of intrahepatic and ↳ inflammation due to chronic chronic inflammation extrahepatic bile ducts> - intrahepatic bile ducts Sex (M:F) 1:9 2:1 Age at onset 40-60 Any, mean age 39 → middle-aged women → young male Seropositivity Anti-mitochondrial antibodies (AMA) Anti-neutrophil cytoplasmic antibodies (ANCA) F Dx 2 out of the following 3: Cholangiogram (ERCP/ MRCP): "beads on string" phosphatase enzyme produced by bile liver bile duct Endoscopic RetrogradegraphyMagnetiResonancea raphy alkaline ↑ALP : accumulation of - Seropositive AMA endoscopy Histological evidence: portal tract granuloma Bo as Crohn's vicerative colitis Disease Associated Sjogren syndrome (70%) inflammatory IBD (70%): UC > CD ↳ dry eye dry month disease , Other sclerosing disorders, e.g. retroperitoneal sclerosing fibrosis Biliary tree disease Gallstone skin ligh age 10 Common among middle-aged obese women: fair, forty, fat, fertile Manifestations: o Asymptomatic (80%) o Biliary colic: dull, constant RUQ pain, precipitated by fatty meal, breathing, radiation to back and inflammation of cholecystoenteric fistula > right shoulder, a/w n/v inflammation of - gallstonetointestine it causing bile duct system (e g bile duct) gallbladder.. o Complications: potentially life-threatening, e.g. cholecystitis, acute cholangitis, gallstone ileus, CA gallbladder, acute pancreatitis Acute cholecystitis (gallstone Calculous type (> 90%): acute obstruction of Hartmann's pouch Acalculous type: after trauma, burns and major surgery Presentations: fever, biliary colic, vomiting, guarding, Murphy's sign Pathology: acute inflammation Chronic cholecystitis Can develop without any history of acute attack Pathogenesis: chronic supersaturation of bile by cholesterol, instead of gallstone Pathology: chronic inflammation Acute cholangitis Acute obstruction of extrahepatic bile duct due to bacterial infection Sepsis/severe systemic infection 2 additional component( + Charcot's triad (high fever, biliary colic, jaundice), Reynold's pentad (+ hypotension, confusion) Recurrent pyogenic cholangitis (RPC) Stone formation in intrahepatic & extrahepatic ducts causing recurrent acute cholangitis, biliary obstruction, stricture Endemic in HK HBP tumours Benign hepatic tumour Epidemiology (M:F) Manifestations Risk factors Hepatocellular adenoma (HCA) 1:15 Acute abdomen: rupture OCP → haemoperitoneum oral contraceptive pills Focal nodular hyperplasia (FNH) 1:15 Asymptomatic OCP Haemangioma 1:5 Asymptomatic mass of blood vessels MC 1o liver tumour No Tx required  47 Malignant HBP tumour EPIDEMIOLOGY RISK FACTORS PRESENTATIONS PATHOLOGY HEPATOCELLULAR 4th in incidence Cirrhosis (of any cause) Local: RUQ mass/pain, blood Architecturally: hepatocellular in differentiation in bilirubin network structure thickened trabeculae rods/tubular in CARCINOMA (HCC) 3rd in mortality Hepatitis B, C obstructive jaundice carcinogenic compound type of mold different form of snape nucleus darker normal (histo) than M:F 3:1 Aflatoxin B1 (from Aspergillus Systemic: cachexia, malaise, Cytologically: pleomorphism, hyperchromasia, - flavus) anorexia nuclear enlargement, increased n/c ratio, frequent Alcohol Complication: massive intra- mitosis NAFLD abdominal bleed due to tumour Grading: defined by histopathology (extent of differentiation) - rupture, liver failure, metastasis Staging: most important prognostic factor - Tumour marker: AFP (also TNM staging: perform best in patients with > - ① ② elevated in hepatoblastoma, yolk surgical resection ( BCLC system: include status of underlying liver disease (Child-Pugh score), performance status (PS) Metastasis: MC to lung HEPATOBLASTOMA MC liver tumour in ① MC epithelial component +/- Cepithelial cells) paediatrics Q Mesenchymal from mesoderm Mostly before 5 yo ⑤ Teratoid components (differentiated cell of an organ) demand of RBC response ↑ Extramedullary haematopoiesis adaptive w M:F 2:1 RBC form outside the bone marrow = METASTASIS MC liver tumour To differentiate from primary HCC: Primary sites: lung Gross: non-cirrhotic favours metastasis (although (MC), breast, colon HCC can arise from non-cirrhotic liver) 7histo Look like-a sie Histology: differentiation of primary Ca, e.g. : glandular differentiation in lung ADC Immunohistochemistry from epithelial cells of bile due CHOLANGIOCARCINOMA Chronic biliary diseases: PSC, Extrahepatic (90%) Architecturally: glandular differentiation metabolic disorder w RPC Intrahepatic (10%) Cytologically: pleomorphism, hyperchromasia, acc of iron in the body Hereditary haemochromatosis Peripheral (to hilum): nuclear enlargement, increased n/c ratio, frequent Thorium dioxide (obsolete clinically silent mitosis contrast medium, also cause Central/Klatskin: early fast angiosarcoma)radiographicimagin biliary obstruction PANCREATIC CARCINOMA M:F ~ 1:1 Smoker, drinker Local: epigastric pain, obstructive Gross: mimic chronic pancreatitis pathologically & High mortality Nutrition: obesity, high fat jaundice, acute pancreatitis radiologically MC at pancreas head diet, low fibre intake Functional: DM (often 1st Histology: Chronic pancreatitis manifestation) Architecturally: glandular differentiation DM Systemic: cachexia, malaise, Cytologically: pleomorphism, hyperchromasia, anorexia nuclear enlargement, increased n/c ratio, frequent Complication: metastasis mitosis PANCREATIC NET 2nd MC NET, after SB neuroendocrine Tumor (small bowel)? ) e g.. Langerhans cell  48 Pancreatic disease Acute pancreatitis Chronic pancreatitis Epidemiology (M:F) 3:1 Causes Gallstone (48%) Alcoholism Idiopathic (34%) Alcoholism (9%) Manifestations Epigastric pain with radiation to back Epigastric pain with radiation to back n/v, fever Pancreatic insufficiency: DM, Severe retroperitoneal bleeding: malabsorption bluish discolouration and the umbilicus Cullen's sign the flanks Grey Turner's sign bruising on ↑↑Amylase > 1000 (damaged & inflamed acinar cells) Complication Acute: disseminated retroperitoneal bleed, shock, Pancreatic insufficiency respiratory distress syndrome intravascular coagulation (small Vessels acute coagulation) ARDS, DIC, death (15%) CA pancreas Chronic: pancreatic abscess, pseudocyst fibrous capsule fluid-filled sac W. Pathology Acute inflammation Chronic inflammation Neutrophilic aggregate: abscess Saponification: fat necrosis fat(oil > soap -