Practical session 15 -Pathology of Liver Practical session -Pathology of Liver (Objectives) By the end of this session, students will be able to: Identify.

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Presentation transcript:

Practical session 15 -Pathology of Liver

Practical session -Pathology of Liver (Objectives) By the end of this session, students will be able to: Identify morphological changes (gross and microscopic) in Hepatitis, Alcoholic liver disease and Hepatocellular carcinoma Suggested reading: Robbin’s Basic Pathology, 8 th Ed. Page , &

Case No 1 A 30-year-old man presented to the local clinic complaining of anorexia, nausea, vomiting, and malaise. He had a history of intravenous drug use. He admitted to drinking alcohol. Physical examination revealed a thin man who looked ill. His BP-110/80 lying down, which decreased to 90/60 upon sitting. His T- 37.5C, and his RR was 20. His eyes were yellow. There was mild right UQ abdominal tenderness. The liver is slightly enlarged 3 cm below the costal. No spleen was palpated. Cardiac, respiratory, and other parts of the examination were normal.

PT = 13 second (11–15 s) Aspartate aminotransferase : 1240 U/L (8–20 U/L) Alanine aminotransferase = 1650 U/L (8–20 U/L) Alkaline phosphatase = 198 U/L (20–70 U/L) Total bilirubin= 12.0 mg/dL (0.1–1.0 mg/dL) Direct bilirubin= 8.0 mg/dL (0.0–0.3 mg/dL) Anti-HAVTotal - positive; IgM fraction - negative HBsAg Anti-HBs Positive Negative Anti-HBcTotal - positive; IgM fraction - positive Anti-HCVNegative Anti-delta virusSent to outside lab Anti-HIVNegative

LIVER BIOPSY: The diagnosis is usually based on the clinical presentation and laboratory results, serologic tests. a cellular infiltrate throughout the hepatic lobule- chronic, inflammatory cellular infiltrate and Kupffer cell hypertrophy and hyperplasia.

Acute hepatitis- MORPHOLOGY cells injury& ballooning Lobular inflammation Acute Hepatitis ; Cholestasis& MQ reaction

Councilman, or acidophilic, bodies

Questions ◆ What is the most likely diagnosis? ◆ What are the possible etiologies of this disorder? ◆ What other tests would be appropriate? ◆ What are the possible complications? ◆ Describe the morphologic features of this condition?

Questions ◆ What is the most likely diagnosis? Acute viral hepatitis (hepatitis B virus) ◆ What are the possible etiologies of this disorder? Hepatitis B virus- acute infection ◆ What other tests would be appropriate? PCR ◆ What are the possible complications? Progress to Chronic hepatitis or Fulminant hepatitis with confluent necrosis ◆ Describe the morphologic features of this condition? >>>>………………………………

Acute hepatitis B virus- morphology Lobular hepatitis: a cellular infiltrate throughout the hepatic lobule Chronic, inflammatory cellular infiltrate. Loss of normal architecture. Ballooning of the cytoplasm in degenerating hepatocyte. Kupffer cell hypertrophy and hyperplasia. Hepatocyte necrosis - individually necrotic or apoptotic hepatocytes= Councilman bodies Regenerating hepatocytes are large, frequently containing multiple nuclei. Cholestasis

Case No 2 Over the past 4 days, a previously healthy, 38-year- old woman has become increasingly obtunded. On physical examination, she has scleral icterus. She is afebrile, and her BP is 110/55 mm Hg. Laboratory findings show a PT of 38 seconds, serum ALT of 1854 U/L, AST of 1621 U/L, albumin of 1.8 g/dL, and total protein of 4.8 g/dL withraised plasma ammonia (> 100 IU/L) “hyperammonemia”? From history what’ the most likely diagnosis? Mention other helpful serological investigations? Describe the expected liver morphologic changes?

Questions From history what’ the most likely diagnosis? Acute fulminant hepatitis with massive hepatic necrosis.

Case 2: Fulminant hepatitis : liver is smaller than normal, due to extensive areas of liver necrosis. The surface is soft with a wrinkled capsular surface.

Questions ◆ What is the etiology of this condition? ◆ Can you name some causes, other than hepatotropic virus infections, that can cause a similar clinical picture? ◆ Describe the morphologic features of this condition? ◆ What’s the complications of this condition?

Questions ◆ What is the most likely diagnosis? Fulminant hepatitis with massive hepatic necrosis ◆ What are the possible etiologies of this disorder? Acute hepatitis A, acute HBV (+\- HDV), other viruses. ◆ Can you name some causes, other than hepatotropic virus infections, that can cause a similar clinical picture? 1- Toxin- excessive alcohol intake(severe alcoholic hepatitis. 2- Drugs(paracetamol, Aspirin overdose). 3-Hereditary copper accumulation (Wilson's disease) 4- Infection (bacterial….) ◆ What’s the complications of this condition? Renal failure, coagulopathy, cerebral edema, encephalopathy Haemodynamic distrubance, Adrenal insufficiently-hepatorenal syn ◆ Describe themorphologic features of this condition? There is massive necrosis of hepatocytes throughout the lobules in fulminant hepatitis………….

Fulminant Hepatitis morphology FH-indicates that the liver has sustained severe damage (loss of function of 80-90% of liver cells) Location: Entire liver or only random areas may be involved. Severe necrotizing process. Inflammatory response: little inflammatory reaction. Macrophages response: Massive influx of macrophages for phagocytosis Ductular reaction: If pt. survive hepatocytes replication started with ductular reaction

Case No 3 A 34-year-old woman known case of Hepatitis C virus- HCV presented with fatigue for month ago. LFT along with liver biopsy done for follow-up, staging and grading: _____________________________________ 1- describe the morphologic features? 2- mention other differentials for similar changes? 3- What’s the commonest complications of this conditions?

Chronic hepatitis- portal inflammation

Liver biopsy- lower power Portal hepatitis + focal steatosis Cells necrosis+ inflammation + focal steatosis

Chronic Hepatitis: Piecemeal necrosis

Fibrosis with incomplete septa

Answers-HCV I. Describe the morphologic features? 1- Portal hepatitis with acinar extension (chronic inflammatory cells infiltrates). 2- Cells death. 3-Steatosis (focal, diffuse) (mild, moderate, severe) 4- Interphase hepatitis (piecemeal necrosis). 5- Degree of fibrosis II. Mention other differentials for similar changes? Alcohol, DM, Obesity, Malnutrition, AIH, Idiopathic. III. What’s the commonest complications? Cirrhosis, Liver failure, hepatocellular carcinoma.

Case No 4 A 27-year-old man with a history of intravenous drug use has been known to be infected with hepatitis B virus for the past 6 years and not ill. He is seen in the emergency department because he has had nausea, vomiting, and passage of dark-colored urine for the past week. Physical examination shows scleral icterus and mild jaundice. There are recent and healed track marks in the right antecubital fossa. Neurologic examination shows a confused, oriented only to person. Laboratory studies show total protein, 5 g/Dl (decreased); albumin, 2.7 g/dL (decreased) ; ……………

PT = 13 second (11–15 s) Aspartate aminotransferase : 1240 U/L (8–20 U/L) Alanine aminotransferase = 1650 U/L (8–20 U/L) Alkaline phosphatase = 198 U/L (20–70 U/L) Total bilirubin= 12.0 mg/dL (0.1–1.0 mg/dL) Direct bilirubin= 8.0 mg/dL (0.0–0.3 mg/dL) Anti-HAVTotal - positive; IgM fraction - negative HBsAg Anti-HBs Positive Anti-HBcTotal –IgG positive ; IgM fraction - Negative Anti-HCVNegative Anti-delta virusPending?? Anti-HIVNegative

Hepatitis: Areas of necrosis &collapse of lobules: ill-defined areas ( pale yellow& Hemorrhagic)

Liver biopsy: Chronic viral hepatitis (HBV)

Ground-glass appearance- Hepatitis B virus Hepatocytes nuclei Immune-stained positive for HBc - HBV

Immune-stain positive for HBsAg (right) : hepatocytes show diffuse granular cytoplasm=(ground glass )

Questions ◆ What is the most likely diagnosis? ◆ What are the possible etio-pathogenesis of this disorder? ◆ What other tests would be appropriate? ◆ Mention the factor (s) predisposing to the poor prognostic outcome of this condition? ◆ What amount of alcohol consumption is required to develop alcoholic cirrhosis? ◆ What are the possible complications? ◆ Describe the morphologic features of this condition?

Questions ◆ What is the most likely diagnosis? Chronic viral hepatitis (HBV) with Super-infection by HDV ◆ What are the possible etiology? HBV infection (chronic) with HDV ◆ What other tests would be appropriate? Confirmatory- Recent infection by HDV infection-anti- HDV IgM antibodies ◆ What are the possible complications? Cirrhosis, Liver failure, HCC ◆ Describe the morphologic features of this condition? …………………….

Morphologic features of HBV-HDV: 1- Hepatocytes cells injury- necrosis (some time progress to form Fulminant-confluent necrosis). 2- Ballooning hepatocytes degeneration with eosinophilic "councilman body" 3- Inter-phase reaction\necrosis (piecemeal necrosis) 4- Hepatocytes- ground glass appearance, indicate intra-cytoplasmic accumulation of HBsAg 5- Mixed chronic inflammatory cells infiltrates. 6- Fibrosis- varying degree

Case No 5 A 41-year-old man has a history of drinking 1 to 2 liters of whisky per day for the past 20 years. He has had numerous episodes of nausea and vomiting in the past 5 years. He now experiences a bout of prolonged vomiting, followed by massive hematemesis. On physical examination his vital signs are: T 36.9°C, P 110/min, RR 26/min, and BP 80/40 mm Hg lying down. His heart has a regular rate and rhythm with no murmurs and his lungs are clear to auscultation. There is NO abdominal tenderness OR distension. Bowel sounds are present. His stool is negative for occult blood. 1- LIVER US? 2- LFT? 3- VIRAL MARKER? 4-LIVER BIOPSY

Alcoholic Fatty Liver: Lipid droplets accumulate in hepatocytes (around hepatic venule) microvesicular or macrovesicular macrovesicular steatosis

Alcoholic hepatitis : Mallory's hyaline (Globular red hyaline material within hepatocytes (

Questions ◆ What is the most likely diagnosis? ◆ What are the possible etio-pathogenesis of this disorder? ◆ What other tests would be appropriate? ◆ Mention the factor (s) predisposing to the poor prognostic outcome of this condition? ◆ What amount of alcohol consumption is required to develop alcoholic cirrhosis? ◆ What are the possible complications? ◆ Describe the morphologic features of this condition?

Questions ◆ What is the most likely diagnosis? Chronic alcoholic hepatitis ◆ What are the possible etiologies of this disorder? Excess consumption of alcohol lead to……………………….. ◆ What other tests would be appropriate? VIRAL MARKER (HBV, HCV) - “ELISA+ PCR” Screening for AIH- (ANA, Liver kidney microsome (LKM-1) antibody (IgG): “ELISA+IF” ◆ Mention the factor (s) predisposing to the poor prognostic outcome of this condition? The severity &prognosis depends on the amount, pattern and duration of alcohol consumption. ◆ What are the possible complications? Liver cirrhosis, Hepatic failure, HCC ◆ Describe the morphologic features of this condition? …….

Alcoholic hepatitis- morphology Macroscopic -varying from liver with steatosis to cirrhotic liver The liver is enlarged, yellow, soft, and greasy, due to accumulation of fat in the hepatocytes. Microscopic: Lipid droplets accumulate in hepatocytes (around hepatic venule) microvesicular or macrovesicular. Cells injury Intra-cellular accumulation (hemosidrin)+ cholestasis Mallory bodies Neutrophilic reaction. Fibrosis

Alcoholic Liver Injury: Pathogenesis Daily intake of 80 gm or more of ethanol generates significant risk for severe hepatic injury, and daily ingestion of 160 gm or more for 10 to 20 years is associated more consistently with severe injury. Hepatic steatosis lead to : 1.Excess reduced NADH producton by the two major enzymes : Alcohol dehydrogenase and acetaldehyde dehydrogenase;   triglycerides synthesis 2.Impaired production and secretion of lipoproteins by hepatocytes. 3.Increased catabolism of fat throughout the body Liver cell necrosis Acute Inflammation Stimulates collagen synthesis – fibrosis. Micronodular cirrhosis.

Case No 6 A 57-year-old man presents with fatigue for several months. He does not take any medications and denies using illegal drugs. He underwent a blood transfusion with several units in 1982 after an automobile accident. Physical examination reveals generalized jaundice, a firm nodular liver edge just below the right costal margin, and a mildly protuberant abdomen with a fluid wave.

Laboratory study Patient’s Value Reference Range RR Alanine aminotransferase (ALT): 80 U/L (8–20 U/L) Alkaline phosphatase: 60 U/L (20–70 U/L) Aspartate aminotransferase(AST): 50U/L (8–20 U/L) Albumin: 2.0 g/dl (3.5–5.5g/dL) Bilirubin, serum, total: 5 mg/dL (0.1–1.0 mg/dL) Bilirubin, serum, direct: 4.2 mg/dL (0.0–0.3 mg/dL) Prothrombin time (PT): 28 s (11–15 s) Partial thromboplastin time (PTT): 50 s (28–40 s)

Questions ◆ What is the most likely diagnosis? ◆ What are the possible etiologies of this disorder? ◆ What other tests would be appropriate? ◆ What are the possible complications? ◆ Describe the morphologic features of this condition?

Mixed mcaro-and micro- cirrhotic nodules Post-hepatitis cirrhosis

Answers ◆ What is the most likely diagnosis? Chronic hepatitis/with transition to cirrhosis. ◆ What are the possible etiologies of this disorder? Most commonly caused by: Progressive Alcohol hepatitis chronic viral infection (HCV, HBV)or; chronic toxin exposure (alcohol), (Drugs), ect.. ◆ What other tests would be appropriate? 1-Hepatitis virus serologies: ICT-rapid, ELISA, PCR. 2- Liver biopsy ◆ What are the possible complications? 1. Hepatic failure, 2.gastrointestinal bleeding, 3. HCC.

Morphology of cirrhosis Nodules and fibrosis (defining features) Fragmentation of the specimen Abnormal structure (reticulin) Clonal variation in hepatocyte size Evidence of hyperplasia Large-cell and small-cell change (dysplasia)

Case No 7 A 56-year-old man from China, has experienced fatigue and a 10-kg weight loss over the past 3 months. Physical examination yields no remarkable findings. Laboratory test results revealed increase level of AFP (650 nanograms per milliliter (ng/mL)) and positive for HBsAg& Anti HBs. Negative for HBc Ag, Anti HBc, anti- HCV and anti- HAV. Abdominal CT scan shows a 10-cm solid mass in the nodular liver.

Questions ◆ What is the most likely diagnosis? ◆ What are the possible etiologies of this disorder? ◆ Which of the following mechanisms is most likely responsible for the development of this lesion? ◆ What other tests would be appropriate? ◆ What are the possible complications? ◆ Describe the morphologic features of this condition?

Liver tumour - GROSS Neoplasm is large and bulky and has a greenish cast because it contains bile. To the right of the main mass are smaller satellite nodules.

Liver: Large whitish mass with satellite extension to adjacent tissue

B. well-differentiated tumor cells are arranged in nests\acinar with bile pigmentation

Section of liver nodule: malignant cells in Branching trabeculae

HCC-Fibrolamellar carcinoma A specimen showing a demarcated hard, Scirrhous nodule B, nests& cords of malignant polygonal hepatocytes separated by dense bundles of collagen

Questions ◆ What is the most likely diagnosis? 1-Hepatocellular carcinoma, 2- Fibrolamellar type ◆ What are the possible etiologies of this disorder? 1- chronic viral hepatitis HBV ◆ Which of the following mechanisms is most likely responsible for the development of this lesion? repeated cycles of liver cell death and regeneration. This repeated cycling increases the risk of accumulating mutations during several rounds of cell division. ◆ What other tests would be appropriate? AFP level ◆ What are the possible complications? ………………………………….. ◆ Describe the morphologic features of this condition? …………………………………