Liver Pathology

Mind Map by , created almost 6 years ago

Doctorate Pathology (Systems Pathology) Mind Map on Liver Pathology, created by melian.yates on 11/04/2013.

Created by melian.yates almost 6 years ago
Clinical Pathology (301-400) MCQs- Year 4 PMU
Med Student
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Pathology of Joints
Germany 1919-1945
paul giannini
General Pathoanatomy Final MCQs (301-400)- 3rd Year- PMU
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patho. practical slides
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Endocrine Pathology
Pathology of the Alimentary Tract 1 (Oral Cavity & Oesophagus)
Liver Pathology
1 Functions
1.1 Portal Vein
1.1.1 Metabolic processing Dietary carbohydrates Lipids Amino Acids Vitamins
1.1.2 Detoxification, Degredation &/or Biliary Excretion Endogenous wastes Toxic molecules Hormones Xenobiotic compounds Biotransformation of drugs Detoxified chemical wastes Bile salts, Bilirubin, cholesterol, HCO3-, H2O
1.1.3 Blood from Intestinal tract
1.1.4 Processing & Activation of some xenobiotic agents Pro-drugs Ex. Cytochrome p450
1.2 Synthesis of Plasma Proteins
1.2.1 Albumin Globulins Clotting factors Complement proteins Other serum transport/ binding proteins
1.3 Storage
1.3.1 Glycogen Fats Fe Cu Vitamins Ex. Vitamin A (stored in Hepatic stellate cells)
1.4 Processing of Vitamin D
1.4.1 With Kidneys
1.5 Removal of Bacteria & Erythrocytes
1.5.1 Kupffer cells
1.5.2 Removal of Erythrocytes also occurs in the Spleen
2 Clinical Signs of Liver Disease
2.1 Jaundice/ Icterus
2.1.1 Accumulation of bilirubin in the body
2.1.2 Mechanism Pre-Hepatic Excessive breakdown of Erythrocytes Liver is overwhelmed & cannot excrete the bilirubin fast enough Ex. IMHA (Immune mediated Haemolytic Anaemia) Post-Hepatic Physical obstruction of bile outflow Damage, disease, compression or obstruction of the gallbladder or common bile duct Prevents Bile from being excreted into the small intestine (Cholestasis) Ex. Gallstones, compressive tumor Hepatic Liver is diseased & cannot excrete even the normal bilirubin load Ex. Cirrhosis
2.2 Oedema/Ascites/Anasarca
2.2.1 If the liver is unable to synthesize the normal plasma proteins, there will be a reduction in plasma oncotic pressure Ex. Decrease in serum Albumin, Decrease in Oncotic pressure Fluid moves out of circulation => Fluid accumulates in the body cavities & subcutaneous spaces
2.3 Coagulation (Clotting) Disorders
2.3.1 If liver is unable to produce sufficient clotting factors, fibrinolytic proteins, complement proteins & acute phase proteins: => Poor or inappropriate Haemostasis & immune function Risk of Haemorrhage after liver biopsy Paradoxial balance Liver products Pro-coagulation Lack of Anti-clotting factors Anti-coagulation Lack of clotting factors
2.4 Hepatic Encephalopathy
2.4.1 Liver usually converts ammonia into urea (excreted by the kidneys) NH3 produced in intestine by bacteria
2.4.2 Liver disease: Reduced ability to detoxify &/or remove nitrogenous compounds from the body Increased [NH3] & other toxic substances (Mn?) in the blood => Impairs brain function =>Status spongiosus of white matter in CNS Multiple fluid filled spaces of microscopic size in cerebral white matter Toxicity
2.5 Metabolic disease & dysfunction
2.5.1 Liver disease (Reduced ability to): Process dietary components delivered from the portal blood Store Glycogen, fat & vitamins Detoxify endogenous or exogenous toxins Implications for drug selection, administration & dosage
3 Incidental Post-Mortem Changes
3.1 Prone to rapid PM change:
3.1.1 Composition Vascularity Proximity to the intestine
3.2 Softening & increased friability
3.3 Production of gas bubbles (Putrefactive bacterial fermentation)
3.4 Black discoloration (bacterial breakdown of Hb)
3.5 Green discoloration (Bile leakage)
3.5.1 Biliary Imbibition
3.6 Microscopically:
3.6.1 Dissociation of hepatocyte cords Pyknosis of nuclei Lysis of hepatocytes
4 Hepatic Degeneration
4.1 Hydrophobic Degeneration (Cloudy swelling)
4.1.1 Hepatocellular swelling Early manifestation of cell injury (Hypoxia, toxins) Hepatocytes unable to maintain normal homeostatsis NRG production decreases => membrane pumps fail => lack of ATP Intracellular accumulation of H2O Swelling of mitochondria & other organelles Cytoplasmic vacuoles may develop if severe
4.1.2 Reversible Hepatocytes not damaged or destroyed
4.2 Fatty Change
4.2.1 Lipid accumulates in cytoplasm of injured hepatocytes
4.2.2 Inability to metabolize/function normally (Hypoxia, toxins) I.e. Conversion of FFA => TAG
4.2.3 Often more severe damage than in hydropic degeneration/cloudy swelling
4.2.4 Reversible (If inciting cause is removed/corrected)
4.2.5 Fatty change (due to hypoxia/toxins) may eventually lead to lipidosis/steatosis when severe &/or chronic
4.2.6 Hepatic Lipidosis/Steatosis Hepatocytes distended by discrete circular lipid vacuoles (displace nucleus to periphery of cell) Due to massive uptake of fatty acids from the bloodstream following excessive mobilisation of adipose tissue reserves => Overloads metabolic capacity of hepatocytes & further inhibits their function
4.2.7 Pale, yellow, friable, "greasy" liver
4.2.8 Causes: Starvation Equine hyperlipaemia Negative NRG balance in cattle Feline hepatic lipidosis Feline hyperlipaema Diabetes mellitus (Glycogen vs. lipid) Hypoxia/toxins => Lipidosis
4.3 Glycogen (Steroid Induced Hepatopathy)
4.3.1 Excessive accumulation of glycogen in the presence of high levels of corticosteroids Exogenous corticosteroids E.g. Dexamethasone (iatrogenic) Endogenous corticosteroids Hyperadrenocorticism Diabetes mellitus Glycgoen &/or fat accumulations
4.3.2 Hepatocytes distended by floccular ("feathery") cytoplasmic vacuoles (do not displace the nucleus)
4.3.3 Ballooning degeneration may occur Irreversible
4.4 Amyloidosis
4.4.1 Primary Can be familial Shar pei dogs Abyssinian, Siamese & other exotic cats
4.4.2 Secondary Chronic inflammation
4.4.3 Gross pathology Liver is enlarged Pale & firm Rounded borders
4.4.4 Histopathology Amyloid is deposited extracellularly around portal tracts & along sinusoids in the space of Disse Can also be deposited in kidneys, pancreas, blood vessels
4.4.5 Special stains Congo red + Green birefringence
4.4.6 Types: AA Type Derived from the inflammatory acute phase protein serum amyloid A AL Type Derived from Ig light chains ABeta type Derived from amyloid precursor protein & islet amyloid polypeptide (IAPP: Hormone produced by Beta cells in pancreatic islets of cats)
5 Hepatic Necrosis
5.1 Mode of action of agent
5.1.1 Directly affects hepatocellular or biliary cells
5.1.2 Secondary to interference with blood supply or biliary tract damage
5.2 Severity & duration of action of agent
5.2.1 Mild &/or short duration => Reversible change
5.2.2 Severe, constant or repeated action => Irreversible change
5.3 Route of Access of Agent
5.3.1 Umbilical vein in foetus/neonate Portal Vein Hepatic Artery (O2) Transcoelemic Infections, neoplasms Biliary system Ascending infections Toxins
5.4 Single-Cell Necrosis
5.4.1 Coagulative necrosis of individual cells & their immediate neighbors
5.4.2 Some forms of viral hepatitis e.g. Herpesvirus
5.5 Focal Necrosis
5.5.1 Usually a microscopic change in hepatocytes/biliary cells randomly distributed without obvious relationship to lobular pattern
5.5.2 Can be of minimal clinical significance
5.5.3 Viral & bacterial agents most common
5.6 Zonal Necrosis
5.6.1 Centrilobular (Periacinar) Necrosis Hepatocytes are vulnerable to Hypoxic damage (Chronic venous congestion; Anaemia) b/c of relatively low gradient of O2 in center of the lobule Also susceptible to toxic insult by toxins requiring hepatic biotransformation
5.6.2 Most common
5.6.3 Periportal Necrosis Commonly seen in toxic damage where the toxin is preformed (closest to the incoming blood supply) Portal vein or Hepatic artery
5.7 Massive Necrosis
5.7.1 Complete necrosis of individual lobules (cells & connective tissue scaffold)
5.7.2 May be isolated or multiple lobules
5.7.3 More Serious insult &/or longer duration insult
5.7.4 Does not neccessarily mean whole organ is affected
5.7.5 Followed by "Post-necrotic lobular collapse" & fibrosis (due to loss of reticulin scaffold
5.7.6 Ex. Hepatosis dietica (Vit. E deficiency - Pigs)
6 Response of Liver to Inflammation
6.1 Hypertrophy of Hepatocytes
6.1.1 Increase in size of surviving Hepatocytes: Increased amount of cytoplasm
6.2 Regenerative Hyperplasia
6.2.1 Nodular regeneration of existing mature hepatocytes in response to liver injury Ability to regenerate varies w/ species & age
6.2.2 Hyperplasia may be diffuse, but often occurs as: Microscopic nodules (Micronodular Hyperplasia) Macroscopic nodules (Macronodular hyperplasia)
6.3 Nodular Hyperplasia
6.3.1 Common incidental finding in older dogs
6.3.2 Discrete, unencapsulated nodules of hepatocytes which retain good architecture of hepatic lobules & hepatocyte cords Might be slightly vaculated
6.3.3 No evidence of concurrent hepatic disease
6.3.4 Not inflammatory Needs to be differentiated from macronodular regeneration & neoplasia
6.4 Oval Cell Proliferation
6.4.1 Regeneration of new hepatocytes & bile ducts by proliferation of bipotential stem cells ("Oval cells") located in the terminal bile ductules (canals of Hering) Oval cells = source of Hepatic Fibrosis Often just see proliferation of bile duct type cells i.e. more differentiated cells => biliary hyperplasia
6.5 Hepatic Atrophy
6.5.1 Atrophy of the whole liver, individual lobes or parts of lobes
6.5.2 Pressure on liver parenchyma, e.g. External or internal space occupying lesions
6.5.3 Anoxia/Hypoxia (Insidious O2 deprivation)
6.5.4 Impairment of bile flow: Chronic biliary disease Fasciola hepatica infestation (Cattle & Sheep) Cholestasis (Dogs & Cats)
6.6 Fibrosis
6.6.1 Localized or generalized deposition of extracellular connective tissue matrix (fibrous/scar tissue) as a healing response to hepatic injury
6.6.2 Centrilobular fibrosis Prolonged hypoxia, cell death & fibrosis of centrilobular zones Chronic venous congestion (Cardiac failure)
6.6.3 Biliary Fibrosis Chronic periportal inflammation, cholangitis/cholangiohepatitis &/or biliary obstruction Usually fibrosis in portal areas
6.6.4 Post-necrotic scarring Following a single episode of widespread (massive) hepatocellular necrosis Parenchyma & connective tissue scaffold (reticulin) are damaged Post-necrotic collapse Affected area cannot regenerate & is replaced by fibrous tissue
6.6.5 Diffuse Hepatic Fibrosis On-going (Chronic) hepatocyte necrosis => Overwhelms the regenerative capacity Chronic toxic injury => Phenobarbital, copper-associated, chronic inflammation Widespread fibrous tissue deposition Deposition of connective tissue in space of Disse =>Loss of fenestrations in sinusoidal endothelium (capillarisation) => Reduced permeability => Impaired blood-hepatocyte exchange
6.7 Cirrhosis
6.7.1 Diffuse, irreversible, end-stage hepatic disease
6.7.2 Combination of: Hepatocyte destruction Nodular regeneration Biliary hyperplasia Bridging fibrosis (across portal areas) Portal-centrilobular vascular anastomoses
6.7.3 Mostly seen in Dogs Hepatic insufficiency Liver failure Cause cannot always be established
6.7.4 Pathology: Hypoproteinaemia:Ascites Icterus: Hyperbilirubinaemia Coagulopathy Hepatic encephalopathy: NH3 retention 2ndary photosensitisation: Herbivores (Phylloerythrin not excreted due to cholestasis)
7 Hepatic Mechanical Conditions (Trauma)
7.1 Displacement
7.1.1 Aquired displacement of Liver
7.1.2 RTA Dogs, Cats Liver lobe torsion
7.2 Rupture
7.2.1 Compression trauma
7.2.2 RTA (Dogs & Cats) Abuse (Ex. kicks: Dogs & Cats) Overlying (Piglets crushed by Sow) "High rise syndrome" (Dogs & Cats)
8 Developmental Conditions
8.1 Congenital Cysts
8.1.1 Biliary cysts Isolated or clusters Formed from bile ductules Concurrent polycystic kidney disease Pigs, Calves,Lambs, Kittens, Dogs
8.2 Congenital vascular anomalies
8.2.1 Portosystemic Shunts Anomalous development of portal vein Extrahepatic: Prior to liver Intrahepatic: Within liver Persistent ductus venosus Porto-caval; Porto-azygous Sxs (Dogs, Cats): Failure to gain weight, illthrift Hepatic encephalopathy Hypoplasia of liver & portal vein Histopath: Absence of portal venules (portal circulation diverted elsewhere) Proliferation of Hepatic arterioles
8.2.2 Primary portal vein hypoplasia Microvascular dysplasia
8.2.3 Intrahepatic arteriovenous fistulae B/w Hepatic artery & portal vein
8.3 Hepatic Displacement
8.3.1 Congenital pericardial diaphragmatic hernia Proplapse of one or more liver lobes into thorax (pericardial sec) Persian cats Opening in diaphragm to pericardial sac
8.4 Biliary atresia
8.4.1 Absence of bile ducts & ductules
8.5 Absence of gallbladder
9 Acquired Disturbances of Hepatic Circulation
9.1 Telangiectasis
9.1.1 Dilation (ectasia) of groups of sinusoids Filled w/ blood Incidental finding Cattle, Cats
9.2 Vascular Obstruction
9.2.1 Portal Vein Total rapid obstruction: Death as a result of hypovolemic shock (sequestration of blood in splanchnic bed) Medical Emergency Partial or slowly progressive occlusion: Atrophy of lobes of liver, depending on development of accessory portal circulation When accessory circulation is inadequate, portal hypotension develops => Congestion & ascites Aquired porto-systemic vascular shunting Collateral blood vessels bypass the normal route of blood flow through the liver Secondary to Portal Hypertension Severe hepatic disease (fibrosis/cirrhosis) Occlusion of the hepatic vein or portal vein Arteriovenous fistulae Primary portal vein hypoplasia Dogs & Cats Caval obstruction/chronic venous congestion of HEART FAILURE does NOT result in acquired shunts (No pressure gradient, caudal venacava & hepatic circulation are equally affected)
10 Hepatitis
10.1 Acute Hepatitis
10.1.1 Usually associated w/ hepatocellular necrosis Suppurative necrotizing hepatitis (Bacterial infections) Salmonellosis Eosinophilic hepatitis (Parasitic infections) Larval forms migrate through liver => Hepatitis
10.2 Chronic Hepatitis
10.2.1 Chronic inflammatory stimulus
10.2.2 Fibrovascular hyperplasia (Granulation tissue) Nodular regeneration Fibrosis Cellular inflammatory infiltrates Lymphocytes & plasma cells (portal areas) Eosinophils (Portal areas) Granulomatous inflammation
10.2.3 Copper-associated hepatopathy (Dogs) Chronic copper toxicity (Sheep) Ragwort toxicity (Due to pyrrolizidine alkaloids) (Horses, Cattle, Sheep) Alfatoxins (aspergillus flavus) on stored grain (Pigs, Sheep) Ascaris suum (pigs) Milk spot liver
10.2.4 Chronic venous congestion w/ hepatocyte fatty degeneration & necrosis
10.3 Cholangiohepatitis
10.3.1 Inflammation of the biliary tree & hepatocellular parenchyma Inflammation starts in the bile ducts & extends into parenchyma
10.3.2 Chronic fascioliasis in ruminants Bacterial cholangiohepatitis from ascending infections from the intestine to the bile ducts Cats: Chronic Cholangiohepatitis In association w/ chronic pancreatitis &/or enteritis => Triaditis (possibly due to common entry of bile & pancreatic ducts into the small intestine)
11 Biliary Disease
11.1 Cholangitis
11.1.1 Affects intra &/or extra Hepatic bile ducts
11.1.2 Usually an ascending infection
11.1.3 Chronic lymphocytic cholangitis (Cats) Excessive aggregation of lymphocytes in portal tracts, bile duct proliferation & portal fibrosis Possibly immune mediated
11.2 Cholecystitis
11.2.1 Inflammation of the gallbladder
11.2.2 Acute or Chronic
11.2.3 Ascending infection: Salmonella enterica
11.3 Cystic mucinous hyperplasia
11.3.1 Hyperplasia of the gallbladder & lining epithelium
11.3.2 Abundant production of mucous Severe distension (mucocoele) Obstruction (RARE)
11.4 Stenosis of the bile duct
11.4.1 External compression Fibrosis, Inflammation, Tumors
11.5 Cholelithiasis
11.5.1 Gall stones (Choleliths) Usually form in gallbladder Mixture: Bilirubin, Ca carbonate, glycoprotein
11.5.2 Dogs, Cats
11.5.3 Cattle (Incidental finding)
11.5.4 Complete obstruction => Extrahepatic cholestasis => Jaundice
11.5.5 Leakage of bile into portal areas => inflammation & fibrosis
12 Hepatic Neoplasia
12.1 Hepatocellular carcinomas are more common than hepatocellular adenomas
12.2 Cholangiocarcinomas & Cholangioadenomas - Tumors of the gallbladder (Uncommon)
12.3 Vascular tumors - Haemangiosarcoma
12.4 Metastatic neoplasia (To Liver)
12.4.1 Ex. Pancreatic carcinoma, intestinal adenocarcinoma, splenic haemangiosarcoma
12.5 Multicentric neoplasia
12.5.1 Lymphoma or leukaemia