Metabolism
Hemoglobin
Supplementary Bilirubin Liver Pathology Slides
For your interest onlyYou will not be required to learn this material for the exam
Globin Hm Bilirubin Liver Bile to Intestine 4
Jaundice (Yellow)
Pre-Hepatic Hepatic Post-Hepatic
Pre-Hepatic Jaundice
Excess bilirubin production
Due to a lot of RBCs undergoing hemolysis
Hepatic (Hepatocellular) Jaundice
Viral hepatitis Alcoholic liver disease Drug-Induced liver disease Cirrhosis
Post-Hepatic Jaundice
Obstructive
Gall stones Cancer of pancreas Cancer of bile ducts
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Acute Viral Hepatitis
Caused by Viruses
A B C (D E)
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Features of Hepatitis
Feature
Viremia Transmission Incubation (days)
Features of Hepatitis
Feature
Chronicity Cancer Risk? Carrier ? Vaccine ?
Hep A
Brief Fecal/Oral 15-45
Hep B
Long Parent/Sex 40 180
Hep C
Long Parent/Sex 15 - 150
Hep A
No No No Yes
Hep B
4% Yes (10%) Yes Yes
Hep C
85 % Yes (2-5%) Yes No
Risk of Fulminant Hepatitis
< 1%
1%
< 1%
Hepatitis A
Sources
Sewage Contaminated food Shellfish
Hepatitis A
Symptoms after short incubation Clinical
Vomiting Anorexia Jaundice Recovery within days
Prevalent in children in underdeveloped countries
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Hepatitis B
Infection after exposure to blood, blood products (including unsterile needles), sexual activity Components generate at least three antigens
HBsAg (Surface Antigen) HBcAg (Core Antigen) HBeAg (e Antigen)
Hepatitis B Clinical
40 180 days after infection Three phases
Preicteric Icteric (jaundice present) Convalescent
Pre-Icteric Phase
Weakness Nausea & vomiting RUQ tenderness
Icteric Phase
Worsening of symptoms Dark urine Jaundice (2 months after exposure)
Post-Icteric Phase
90 % recover completely 10 % develop chronic hepatitis
75% subclinical (asymptomatic carriers) 25% chronic active hepatitis
Progresses to cirrhosis (fatal) A few develop hepatocarcinoma
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HBV and HCV have similarities
HCV Outcome
15% get over it spontaneously 85% develop chronic hepatitis Less than 1% develop fulminating hepatitis (this is fatal but is also very rare)
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Of the 85% that have chronic hepatitis:
80% have asymptomatic chronic hepatitis
May have slightly elevated AST or ALT as only sign Otherwise, feel healthy and are not prone to any specific disorder.
Treatment
HAV and HBV: vaccine HCV no vaccine, but interferon alpha-2b monotherapy leads to 50-70% normalization of AST and ALT. Additional medications may be administered. Canada does the HCV evaluation and treatment in several centres across the nation. Closest one to St. Catharines is Hamilton. There is no charge for evaluation or treatment.
20% develop cirrhosis of which
50% remain chronic 50% develop terminal cirrhosis
2-4% develop hepatocellular carcinoma as a result of unstable environment or deregulation of oncogenes.
Pathology
Reversible hepatocellular changes
Granularity or vacuolization of cells Bile stasis
Pathology
Inflammatory Infiltrates
Macrophages invade Kupffer cells proliferate
Irreversible changes
Death of cells (necrosis)
Karyolysis Councilman bodies
Regeneration of hepatocytes
Many liver cells regenerate completely
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Cirrhosis
Chronic liver disease characterized loss by of normal liver structure & function Irreversible Incurable Morphology: fibrosis & Nodules
Direction of fluid flow
In cirrhosis, the scar matrix (cirrhosis) blocks the lymphatic spaces causing the fluid (lymph) to leak through the wall of the liver and into the abdominal cavity. Lymphatic space up to one third of fluid in blood is returned to the heart by way of the lymphatic system. Note the decreased size of the sinusoid in cirrhosis.
Hepatic sinusoid a branch from the The Liver cells filter all toxins. The hepatic portal vein Kupffer cell phagocytizes bacteria.
Pathogenesis of Cirrhosis
Portal cirrhosis
Liver cell necrosis Ingrowth of fibrous tissue
Etiology of Cirrhosis
Alcohol 65% of Cases Hepatitis virus Hereditary diseases Autoimmune diseases Drugs Biliary obstruction Cryptogenic (hidden cause 30%)
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Biliary cirrhosis (post-hepatic)
Diseases of biliary tree Associated with bile stasis extravasation of bile destruction of liver cells replacement by fibrous strands
Pathology of Cirrhosis
Size: may be larger, Nodular (large or small) Colour usually smaller
Pathology of Cirrhosis
Histology
Normal architecture lost Nodules separated by dense connective tissue
Alcoholic usually yellow (fat) Post-hepatic usually brown
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Complications of Cirrhosis
Fibrosis & nodularity impede blood flow Portal hypertension
Ascites Splenomegaly Porto-systemic anastomoses
Ascites
Accumulation of fluid in peritoneum Portal hypertension & hypoproteinemia
Venous pressure Hydrostatic edema Oncotic pressure
Splenomegaly
Common in cirrhosis Enlarges 3 6 times Will sequester & destroy blood cells anemia or leukopenia
Porto-Systemic Anastomoses
Shunting of portal blood into connections to systemic circulation
Lower esophagus Hemorrhoids Periumbilical plexus
May lead to metabolic consequences coma
Esophageal Varices
Connections lead to venous dilatation called varices Large veins just under mucosa May bleed torrentially
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If the portal system is blocked and portal hypertension occurs, these are the signs
Causes of Portal Hypertension
1. Suprahepatic: Heart failure or pericarditis 2. Intrahepatic: Hepatitis or alcoholic cirrhosis 3. Infrahepatic: Portal vein thrombosis due to stasis of blood secondary to a number of causes.
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Esophageal Varices
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Signs of hepatic cirrhosis
Primary Biliary Cirrhosis
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Carcinoma
Malignant tumor composed of neoplastic liver cells Adults M:F = 5:1 Most originate in cirrhotic livers
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Pathology
3 Forms
Diffuse infiltrative lesion Solitary mass in one lobe Multiple nodules
Yellow, brown, or green Often similar to normal liver cells Synthesize AFP (-Fetoprotein)
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Clinical
Nonspecific signs
Weight loss Anorexia Nausea
Metastatic Cancer
Metastases to the liver more common than primary tumours
GI Tract Lungs Breast
Tumour growth
RUQ tenderness Compression of adjacent organs Portal hypertension
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Clinical Features of Metastases
Hepatic enlargement Jaundice Ascites Splenomegaly
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End of Supplementary Lecture 12a
You are not responsible for the material in this supplementary lecture. It will not be on an exam.
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