Pathology of the Liver and Biliary Tract 1 Normal Liver; Hepatic Injury, Response, and Failure

Transcription

1 Pathology of the Liver and Biliary Tract 1 Normal Liver; Hepatic Injury, Response, and Failure Shannon Martinson, August

2 WELCOME! Dr Boute is the coordinator Course content on Moodle / pathologists websites Textbook for the course? Buy at bookstore or from your friends Available at the library! Download a chapter at a time for free Labs enter through the PM lab Safety gear Wear boots Grey labcoats (available in pm) Bring gloves

3 OUTLINE Normal anatomy & function Hepatobiliary injury and responses Manifestations of hepatic failure Developmental anomalies and miscellaneous lesions Circulatory disturbances Metabolic & nutritional disturbances Infectious diseases of the liver (hepatitis) Toxin-induced liver diseases Diseases of uncertain cause Proliferative lesions of the liver Diseases of the gallbladder and bile ducts

4 Largest visceral organ Size Carnivores 3-4% body weight Omnivores 2% body weight Herbivores 1% body weight 25% cardiac output 2/3 via portal vein 1/3 via hepatic artery Functions: multiple Injurious agents: myriads Clinical signs: variable INTRODUCTION - GENERAL CONSIDERATIONS

5 INTRODUCTION - NORMAL ANATOMY Hepatic lobule The traditional structural unit is the hepatic lobule: Hexagonal structure 1-2 mm wide Central vein at the centre Portal triads at the periphery Bile ducts (BD) Branches of portal vein (PV) Hepatic artery (HA) Nerves and lymphatics Limiting plate

6 INTRODUCTION - NORMAL ANATOMY Portal triad Hepatic artery Bile duct Portal vein

7 INTRODUCTION - NORMAL ANATOMY Robbins and Cotran Pathologic Basis of Disease (2010), 8 th ed., Elsevier Portal triad Hepatic acinus Limiting plate

8 Pathologic Basis of Veterinary Disease (2006), 4 th ed., Mosby-Elsevier, chapter 8 INTRODUCTION - NORMAL ANATOMY Acinus = the functional unit Hepatic acinus centroacinar intermediate periacinar

9 Pathologic Basis of Veterinary Disease (Elsevier 2017), 6 th ed., chapter 8 INTRODUCTION - NORMAL ANATOMY Acinus = the functional unit Hepatic acinus Periportal hepatocytes are the most resistant to hypoxia and toxic insult Centrilobular hepatocytes are the most vulnerable

10 INTRODUCTION - NORMAL ANATOMY Hepatic sinusoids Robbins and Cotran Pathologic Basis of Disease (2010), 8 th ed., Elsevier, Inc. chaper 18 Hepatocytes are arranged in cords separated by sinusoids Pathologic Basis of Veterinary Disease (2012), 5 th ed., Mosby-Elsevier, chapter 8

11 INTRODUCTION - NORMAL FUNCTION Bilirubin metabolism Bile acid metabolism Carbohydrate metabolism Lipid metabolism Xenobiotic metabolism Protein Synthesis Immune function

12 HEPATOBILIARY INJURY AND RESPONSES Clinical Signs of Liver Disease Similar regardless of the cause Occur : If functional reserve and regenerative capacity are overwhelmed If there is impaired bile flow Often see icterus, ascites, hepatomegaly Liver lesions Location and type are important Histopathology is essential for diagnosis Methods of evaluating the liver include Imaging Serum biochemistry FNA (US guided) Liver biopsy (US guided or exploratory) Necropsy

13 HEPATOBILIARY INJURY AND RESPONSES Portals of entry of injurious agents 1. Hematogenous 2. Retrograde through biliary & pancreatic ducts 3. Direct extension through liver capsule 3 2 1

14 HEPATOBILIARY INJURY AND RESPONSES Patterns of Hepatocellular Degeneration and Necrosis Zonal Random Single cell necrosis Multifocal necrosis Centrilobular Midzonal Periportal Bridging Massive

15 HEPATOBILIARY INJURY AND RESPONSES Patterns of Hepatocellular Degeneration and Necrosis Random Single cell necrosis Multifocal necrosis Often due to infectious disease process

16 HEPATOBILIARY INJURY AND RESPONSES Patterns of Hepatocellular Degeneration and Necrosis Zonal Centrilobular Midzonal Periportal Bridging Massive Often due to metabolic or toxic injury

17 HEPATOBILIARY INJURY AND RESPONSES Patterns of Hepatocellular Degeneration and Necrosis Zonal Centrilobular necrosis* Centrilobular hepatocytes receive the least amount of oxygen and have the greatest MFO function Common causes: Anemia, Right heart failure, hypoxia Pathologic Basis of Veterinary Disease (2012), 5 th ed., Mosby-Elsevier

18 HEPATOBILIARY INJURY AND RESPONSES Patterns of Hepatocellular Degeneration and Necrosis Zonal Midzonal necrosis Periportal necrosis Caused by toxins that don t require activation by metabolism Pathologic Basis of Veterinary Disease (2012), 5 th ed., Mosby-Elsevier

19 HEPATOBILIARY INJURY AND RESPONSES Patterns of Hepatocellular Degeneration and Necrosis Zonal Bridging necrosis (central to central) Massive necrosis Pathologic Basis of Veterinary Disease (2012), 5 th ed., Mosby-Elsevier

20 HEPATOBILIARY INJURY AND RESPONSES Patterns of Hepatic Inflammation Acute hepatitis Chronic hepatitis Cholangitis Cholangiohepatitis

21 HEPATOBILIARY INJURY AND RESPONSES General Responses of Liver to Injury Nature of the response depends on duration and severity of damage Clinical signs don t occur until there is a 75% loss of functional reserve Liver enzymes can be elevated earlier Regeneration of Parenchyma Replacement by Fibrosis Biliary Hyperplasia

22 HEPATOBILIARY INJURY AND RESPONSES General Responses of Liver to Injury 1. Regeneration Very good regenerative ability Hepatocytes and Oval (stem) cell proliferation For optimal regeneration (without scarring) the following are necessary: Intact reticulin framework Good blood supply Patent bile ducts to drain bile Pathologic Basis of Veterinary Disease (2006) 4 th ed., Mosby-Elsevier, chapter 8

23 HEPATOBILIARY INJURY AND RESPONSES General Responses of Liver to Injury 1. Regeneration If chronic / ongoing damage Nodular proliferations with scarring Image: Dr A Lopez Pathologic Basis of Veterinary Disease (2006) 4 th ed., Mosby-Elsevier, ch 8

24 General Responses of Liver to Injury HEPATOBILIARY INJURY AND RESPONSES Images - Pathologic Basis of Veterinary Disease (2006), 4 th ed., Mosby-Elsevier 2. Fibrosis Increased amount of connective tissue within the liver Ito (stellate) cells Significance is dependent upon effects on normal hepatic function, blood and biliary flow

25 HEPATOBILIARY INJURY AND RESPONSES General Responses of Liver to Injury Multifocal Fibrosis 2. Fibrosis Patterns of Fibrosis Focal/multifocal fibrosis Diffuse hepatic fibrosis Biliary fibrosis Diffuse Fibrosis Biliary Fibrosis

26 HEPATOBILIARY INJURY AND RESPONSES General Responses of Liver to Injury Multifocal Fibrosis 2. Fibrosis Patterns of Fibrosis Focal/multifocal fibrosis Diffuse hepatic fibrosis Biliary fibrosis Image: Dr A Lopez Biliary Fibrosis

27 HEPATOBILIARY INJURY AND RESPONSES General Responses of Liver to Injury 3. Biliary hyperplasia Proliferation of new bile ducts within the portal areas Nonspecific Bile drainage obstruction Often seen in chronic hepatotoxicity Pyrrolizidine alkaloids Aflatoxins Can occur quickly in young animals An attempt to regenerate hepatocytes?

28 HEPATOBILIARY INJURY AND RESPONSES End-Stage Liver - Cirrhosis Final irreversible result of hepatic disease Distortion of the architecture Cause cannot be determined Characterized by 3 components*: 1. Nodular regeneration 2. Fibrosis 3. Bile duct hyperplasia

29 HEPATOBILIARY INJURY AND RESPONSES End-Stage Liver - Cirrhosis Final irreversible result of hepatic disease Distortion of the architecture Cause cannot be determined Characterized by 3 components: 1. Nodular regeneration 2. Fibrosis 3. Bile duct hyperplasia Cirrhotic liver, Masson trichrome stain

30 HEPATOBILIARY INJURY AND RESPONSES End-Stage Liver - Cirrhosis Several possible causes: Chronic toxicity Chronic cholangitis Biliary obstruction Right sided heart failure Inherited metabolic disease Chronic hepatitis Idiopathic Cirrhotic liver, Masson trichrome stain

31 MANIFESTATIONS OF LIVER FAILURE Liver Failure Liver failure is a clinical syndrome that occurs when there is inadequate liver function It indicates massive reduction of the amount of liver cells or a loss of function Greater than 2/3 loss Result of either acute or chronic liver damage Consequences of hepatic failure differ somewhat among domestic species. They include: 1. Hepatic encephalopathy 2. Disturbances of bile flow & icterus 3. Metabolic disturbances 4. Vascular and hemodynamic alterations 5. Cutaneous lesions 6. Impaired immune functions

32 MANIFESTATIONS OF LIVER FAILURE Hepatic Encephalopathy Signs are variable and nonspecific: Depression, aimless wandering, head pressing, behavioural changes Central blindness Mania, convulsions Many possible underlying causes: Acute liver disease: Horses and ruminants Portosystemic shunts Dogs and cats Chronic liver disease Any species video vet.uga.edu

33 MANIFESTATIONS OF LIVER FAILURE Hepatic Encephalopathy Pathogenesis Blood accumulation of neurotoxic substances bypassing the liver and reaching the brain Clinical signs are more severe after feeding Neurotoxic substances Main substance is ammonia Other factors: +/- Imbalance of inhibitory & excitatory amino acid neurotransmitters +/- Increased brain concentration of benzodiazepines

34 MANIFESTATIONS OF LIVER FAILURE Disturbances of Bile Flow Hyperbilirubinemia Cholestasis Icterus (Jaundice) Elevation of bilirubin in the blood >2 mg/dl leads to icterus Abnormal accumulation of bile within the liver (intrahepatic), extrahepatic bile ducts or within the gall bladder Yellow discolouration of tissues and body fluids due to hyperbilirubinemia

35 MANIFESTATIONS OF LIVER FAILURE Disturbances of Bile Flow Pre-hepatic Icterus Overproduction of bilirubin Intravascular hemolysis in particular Hepatic Icterus Decreased uptake, conjugation or secretion of bilirubin Due to hepatocellular injury Post-hepatic Icterus Reduced outflow of bile within the canaliculi, extrahepatic bile ducts or gallbladder Due to a blockage within the duct system

36 MANIFESTATIONS OF LIVER FAILURE Robbins and Cotran Pathologic Basis of Disease (2010), 8 th ed., Elsevier, Inc. ch 18 Disturbances of Bile Flow Diagnosis of icterus and cholestasis: Gross Generalized yellowish discoloration Yellowish/greenish brown liver Histo Bile in canaliculi & hepatocytes Clinical chemistry blood levels of Bilirubin Cholesterol Bile acids

37 MANIFESTATIONS OF LIVER FAILURE Metabolic Disturbances Hemorrhagic diathesis synthesis of clotting factors clearance of products of clotting (FDP) platelet function absorption of vitamin K (2, 7, 9, 10) Disseminated intravascular coagulation (DIC) Intravascular hemolysis Mainly in horses Hypoalbuminemia Production Loss in ascites or GIT due to portal hypertension

38 MANIFESTATIONS OF LIVER FAILURE Vascular and Hemodynamic Alterations Acquired PSS Portal hypertension Due to impedence of blood flow from portal vein to heart often from hepatic fibrosis Acquired portosystemic shunts Due to portal hypertension Multiple vascular channels open between portal vein and systemic circulation Allows blood to bypass the liver Ascites (dogs and cats) Due to: Portal hypertension colloid osmotic pressure Retention of sodium and water (hyperaldosteronism)

39 MANIFESTATIONS OF LIVER FAILURE Cutaneous Lesions Photosensitization Injury to skin resulting from activation of photodynamic pigments by UV light ( nm) Hepatogenous photosensitization (2⁰) Normally chlorophyll is broken down in the rumen phylloerythrin conjugated and excreted into bile Phylloerythrin is photodynamic With hepatic disease or biliary obstruction, phylloerythrin builds up in the blood Oxidative damage Hair loss, erythema and necrosis Icterus

40 MANIFESTATIONS OF LIVER FAILURE Cutaneous Lesions Hepatocutaneous Syndrome Rare disease in dogs Crusting, erosions & scaling at mucocutaneous junctions and footpads Pathologic Basis of Veterinary Disease (2006),4 th ed., Mosby-Elsevier, ch 8

41 MANIFESTATIONS OF LIVER FAILURE Cutaneous Lesions Hepatocutaneous Syndrome Honeycomb pattern (US) Hyperechoic network (areas of parenchymal collapse) Hypoechoic zones (regenerative nodules) Nodular liver parenchyma Diffuse vacuolar change Regenerative nodules

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