Pathology (3rd Year)

What is the largest organ in the body?

Liver

Where does 70-80% of the liver's blood supply come from?

Portal vein

The portal vein makes up 70-80% of the liver's blood supply, what vessel supplies the remaining 20-30%?

Hepatic artery

Bile is secreted from hepatocytes and travels through the hepatic ducts. What duct does the hepatic ducts unify with at the bile ducts?

Cystic duct of gallbladder

Bile entered the duodenum at the level of the ______________

major duodenal papilla

Blood flows towards the ____________, whereas bile flows towards the ______________

central veins, portal triad

Which zone in the liver parenchyma is most prone to both hypoxic and toxic injury due to cytochrome P450 metabolites?

Zone 3 (centrilobular)

Which hepatic zone has the highest concentration of cytochrome P450?

Zone 3 (centrilobular)

What are the functions of the liver?

Bile production and excretion, bilirubin, carbohydrate, lipid, xenobiotic, and ammonia metabolism, protein synthesis, immunity

Necrosis of zone 3 associated with hypoxia

Centrilobular necrosis

What are the causes of centrilobular necrosis?

Anemia, cardiac dysfunction, toxins, some viral infections (adenovirus 1)

Zone 2 necrosis that can spread to centrilobular areas

Midzonal necrosis

What causes midzonal necrosis?

Some toxins

Uncommon necrosis of zone 1.

Periportal necrosis

What causes periportal necrosis?

Direct acting hepatotoxins that do not require metabolism

Necrosis of zone 1 that indicates ischemic injury

Paracentral necrosis

What causes paracentral necrosis?

Infarcts, thrombosed vessels, DIC

Paracentral necrosis can occur with _____________

anemia

Necrosis of the entire hepatic lobule

Massive necrosis

What can cause massive necrosis in the liver?

Amanita mushroom, blue-green algae, aflatoxin, sago palm, xylitol, vitamin E/selenium deficiency in pigs

What can cause individual cell necrosis?

Immune mediated disease (chronic interface hepatitis), certain toxins, certain infections

Why is the centrilobular region more prone to hepatocelluar injury?

Hypoxia may occur due to distance from portal vein, increased concentration of P450 enzymes which generates a toxic metabolite

What is the mechanisms of hepatocellular lipidosis/steatosis?

Lipid accumulation in response to injury; Too much lipid/triglycerides going in, too much lipid being synthesize and stored, not enough lipid going out

What are some potential causes of hepatic lipidosis?

Excessive dietary intake, starvation, late pregnancy, lactation, hypoxia, mitochondrial damage

Type of fibrosis that occurs in response to massive necrosis or infarcts

Postnecrotic scarring

Type of fibrosis often in response to ongoing hepatic injury, such as, individual cell necrosis, chronic toxicity

Portal fibrosis

Type of fibrosis that occurs in chronic passive venous congestion

Centrilobular fibrosis

What are some potential causes of centrilobular fibrosis?

Right heart failure, chronic hypoxia injury, certain toxins

Fibrosis that occurs with chronic extra hepatic biliary obstruction

Biliary/peribiliary fibrosis

What are some causes of biliary fibrosis?

Chronic biliary tract infections, GB mucocele, neoplasia in biliary tract

Diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules

Cirrhosis

What are the features of cirrhosis?

Bridging fibrosis, formation of regenerative nodules

Most domestic species do not develop cirrhosis with chronic hepatic injury, what is the exception?

Dogs with chronic hepatitis

Both fibrosis and cirrhosis can lead to __________

Acquired portosystemic shunting

Which region of the hepatic lobule has the least amount of oxygen?

Centrilobular

Which pattern of hepatic necrosis would you associate with anemia?

Centrilobular necrosis

What are the sequela of hepatic dysfunction?

Cholestasis, icterus, hemorrhage, ascites and edema, hepatic encephalopathy, hepatocutaneous syndrome, hepatorenal syndrome, photosensitization

What type of cholestasis occurs due impaired uptake, metabolism, secretion, or transport of bile components

Hepatocellular cholestasis

What type of cholestasis occurs due to bile flow obstruction of major bile ducts or gall bladder?

Obstructive cholestasis

Icterus/jaundice occurs due to excess ____________ in plasma

bile pigments (bilirubin)

What type of icterus occurs due to hemolytic anemia causing a large release of bilirubin accumulating in the liver and overwhelming the system > Unconjugated bilirubinemia

Pre-hepatic

What type of icterus occurs do to hepatic dysfunction and an inability to adequately conjugate bilirubin?

Hepatic

What type of icterus occurs due to an obstruction of the biliary drainage system?

Post-hepatic

Why does hemorrhage occur in hepatic dysfunction?

Clotting factor consumption (acute liver necrosis), reduced synthesis of clotting factors (chronic liver disease)

Why does ascites and edema occur in hepatic dysfunction?

Decreased synthesis of albumin leading to a low Oncotic pressure, altered blood flow through the liver

Why does hepatic encephalopathy occur in liver dysfunction?

Ammonia not converted to urea, ammonia crosses BBB and accumulates in the brain

What kind of dermatitis occurs with hepatic dysfunction?

Superficial Necrolytic dermatitis

What is the pathogenesis of hepatorenal syndrome as sequela to hepatic dysfunction?

Splanchnic vasodilation leading to decreased venous return and CO, Compensatory renal arterial vasoconstriction which decreased GFR

What are the hepatocellular leakage enzymes that elevate due to hepatic necrosis or sublethal injury?

AST, ALT (SDH, LDH, GDH)

What are the induced hepatic enzymes that increase due to activity associated with cholestasis, drugs, or hormones?

ALP, GGT

Breakdown product of hemoglobin and myoglobin. Conjugated in the liver and excreted via bile. Elevates in liver disease

Bilirubin

Secreted in the bile to help solubilize lipids and aid in fat digestion, Brought back to portal circulation and recycled. Elevated in liver disease.

Bile acids

From protein/AA breakdown in GI. Converted to urea in the liver. Will elevate if liver is not functioning properly since it cannot be converted.

Ammonia

Besides, enzymes, bilirubin, bile acids, and ammonia, what are some other biochemical markers of liver disease?

Albumin, glucose, cholesterol, BUN

What type of icterus would you expect in an animal with hemolytic anemia?

Pre-hepatic

Excess of which compound causes hepatic encephalopathy?

Ammonia

What breeds are predisposed to congenital extrahepatic portosystemic shunts?

Mainly small breed dogs, yorkies (can affect cats too)

What breeds are predisposed to congenital intrahepatic shunts? (Porto-azygous shunt, Porto-caval shunt)

Mainly large breed dogs

What are the consequences of congenital portosystemic shunting? (PDA)

Portal blood supply is diverted away from liver, hepatotrophc factors, nutrients, and blood supply do not get to liver, bile acids not recycles, ammonia bypasses liver

What gross features would you find with portosystemic shunting?

Hypoplastic liver, smooth, normal color

What histo features would you find with portosystemic shunting?

Centrilobular atrophy, portal vein hypoplasia, portal arteriolar hyperplasia, closer apposition of portal triads to central veins, smaller hepatocytes

What breeds are predisposed to primary hypoplasia of the portal vein (microvascular dysplasia)?

Yorkies, cairn terriers

T/F: Primary hypoplasia of the portal vein can involve intrahepatic or extrahepatic portal veins

T

Why does primary hypoplasia of the portal vein present very similar to congenital portosystemic shunting?

Decreased portal venous perfusion to liver

Animals with primary hypoplasia of the portal vein will develop portal _________. This disease can occur concurrently with ___________________

hypertension, congenital PSS

Will a dog with congenital PSS or a dog with primary hypoplasia of the portal vein have ascites?

Primary hypoplasia of the portal vein

What are some chemistry features of impaired portal venous blood flow?

Low albumin, TP, BUN, glucose, cholesterol, High bile acids, ammonia. ALP and ALT may be mildly elevated

What are some hematology findings with impaired portal venous blood flow?

Low MCV, microcytic anemia

What are some urinalysis findings with impaired portal venous blood flow?

Ammonium bifurcate crystalluria, bilirubinuria

What are some clinical signs of portal venous blood shunting?

Failure to thrive, depression, lethargy, neuro signs (elevated ammonia, hepatic encephalopathy)

Ductal plate malformations are persistent remodeling of embryonic ductal plate which can give rise to a variety of cystic biliary disease, what is this referred to?

Congenital hepatic fibrocystic disease

Blood pressure in hepatic veins increases relative to portal veins

Passive congestion

What is the general cause of passive congestion in the liver?

Cardiac dysfunction (right sided heart failure)

What causes acute passive congestion in the liver?

Sudden cardiac decompensation, shock

What gross findings would you see with ACUTE passive congestion?

Mildly enlarged dark red liver, bleeds on cut section, enhanced lobular pattern

What Histopathologic findings would you see with ACUTE passive congestion in the liver?

Distention of central vein and sinusoids, progression to hepatic steatosis to atrophy to centrilobular necrosis with hemorrhage

What is the classic cause of CHRONIC passive congestion in the liver?

Chronic heart failure (right sided usually)

What gross findings would you see in an animal with CHRONIC passive congestion in the liver?

Nutmeg liver (red centrilobular areas with pale surrounding areas), rounded margins of central lobes, capsular fibrosis

What histopathologic findings would you see in an animal with CHRONIC passive congestion in the liver?

Centrilobular fibrosis, hemosiderin laden macrophages around fibrotic central vein

What is the pathogenesis of dirofilaria immitis causing hepatic passive congestion?

Adult heartworms living in pulmonary vessels causing endarteritis (inflammation of artery wall lining), right heart failure

High dirofilaria immitis worm burden (>100) results in worms filing right atrium and vena cava

Vena Caval syndrome

What does vena caval syndrome result in?

vena cava obstruction, severe hepatic congestion, acute liver failure, hemolytic anemia

A 1 year old yorkie presents for intermittent seizures and is small for its age. Histopath shows portal vein collapse and lobular atrophy. What biochemistry patterns would you likely see?

Normal ALT, ALP, low BUN, BG, albumin, increased bile acids

A 1 year old yorkie presents for intermittent seizures and is small for its age. Histopath shows portal vein collapse and lobular atrophy. On biochemistry, you see normal ALT, ALP, low BUN, BG, albumin and increased bile acids. What's the most likely cause?

Primary portal vein hypoplasia

An 8 year old Dottie presents for an enlarged spleen and liver masses. What would be your diagnosis? The liver is rough diffusely but there are no nodules.

hepatocellular carcinoma

Granulomatous hepatitis

Chronic passive congestion

Cirrhosis

Chronic passive congestion

Inflammation along the portal interface. Also called chronic activity hepatitis. Primarily seen in dogs.

Chronic interface hepatitis

What are the histologic features of chronic interface hepatitis in dogs?

Inflammation along portal interface, lymphocytes, plasma cells, neutrophils, individual hepatocytes necrosis, fibrosis, biliary hyperplasia (may progress to cirrhosis)

What breeds are predisposed to chronic interface hepatitis?

Bedlington terriers, westies, dobies, Skye terriers, labs, Dalmatians, spaniels

What are some possible etiologies of chronic interface hepatitis in dogs?

Unknown, associated with copper. maybe viruses, toxin/drug reactions, immune-mediated, autoimmune, familial/genetic component

Majority of canine chronic hepatitis in dogs are __________

idiopathic

Chronic interface hepatitis is likely to be associated with _______

copper

What is the role of copper in chronic hepatitis?

Liver is central to copper hemostasis and is regulated via biliary excretion

How can copper accumulate in chronic hepatitis?

Primary metabolic defect in metabolism, secondary to abnormal hepatic function and altered biliary copper excretion, excess dietary intake

Where does copper accumulate in the liver?

Centrilobular areas (with genetic storage disorder or excess dietary intake), periportal areas (impaired hepatic function)

What genetic component is associated with copper and chronic hepatitis?

In bedlington terriers, there is an autosomal recessive mutation in the COMMD1 gene (causes copper-associated hepatopathy with impaired biliary copper excretion and progressive copper accumulation)

Evidence suggests primary accumulation plays a role for chronic hepatitis in the following breeds:

Dobies, westies, labs, Skye terriers, dalmations

Unique form of chronic hepatitis that affects juvenile to young dogs. Has a rapid clinical progression

Lobular dissecting hepatitis

Chronic hepatitis in cats is ___________. Cases have been associated with excessive ________ accumulation. Can lead to __________

uncommon, copper, cirrhosis

Chronic hepatitis in cats with an unknown etiology but suspected to be an immune-mediated disease. Also referred to as lymphocytic cholangiohepatitis

Lymphocytic cholangitis

Lymphocytic cholangitis in cats can be difficult to distinguish from _________

lymphoma