Week 13 Lesson 99: Liver circulatory and infiltrative diseases

Name a circulatory disorder characterized by reduced hepatic outflow due to cardiac dysfunction

Passive congestion

What is passive congestion caused by?

Right-sided heart failure

Right-sided heart failure produces elevated pressure in which major vessel that extends to the hepatic vein and its tributaries?

The caudal vena cava

High pressure in the hepatic vein leads to what specific type of congestion?

Centrilobular congestion of sinusoids

Name a common cause of right-sided heart failure resulting in hepatic congestion in old dogs

Valvular endocardiosis of the tricuspid valve

Name a common cause of right-sided heart failure resulting in hepatic congestion involving parasites

Canine heartworm (Dirofilarial immitis)

Passive congestion leads to centrilobular degeneration, atrophy and loss of hepatocytes due to what initial process?

Congestion leading to hypoxia

What condition results from chronic hypoxic injury during passive congestion?

Steatosis (fatty degeneration)

The combined changes of congestion, hypoxia, and steatosis result in what characteristic pattern?

An enhanced lobular pattern (nutmeg liver)

What is the gross appearance of the liver lobes during passive congestion?

They are enlarged with rounded edges

What is a Congenital portosystemic shunt (PSS)?

An abnormal vascular structure that allows portal blood to bypass the liver and drain directly into the systemic circulation

Affected animals with PSS are often described as what?

Stunted

Animals with PSS frequently develop signs of hepatic encephalopathy due to the buildup of what?

Hyperammonemia

Name a neurological sign associated with PSS and hepatic encephalopathy

Ataxia, Seizures, Blindness, or Head pressing

Grossly, how does the liver appear in congenital portal systemic shunt?

Small (microhepatica)

Name a histological feature of PSS

Lobular atrophy, portal miniaturization with small or absent portal veins, or reduplication of arterioles

Intrahepatic shunts are commonly formed due to the failure of closure of which fetal vessel?

The ductus venosus

In what size dog breeds are intrahepatic shunts most common?

Large breed dogs

Extrahepatic shunts may involve the portal vein anastomosing with the caudal vena cava or what other vein?

The azygos vein

In what size dogs and species are extrahepatic shunts most common?

Small breed dogs and cats

What type of crystals can result in the urinary bladder of dogs with PSS due to abnormal ammonia metabolism?

Ammonium biurate crystalluria

What is another name for Congenital portal vein hypoplasia?

Hepatic Microvascular Dysplasia

Congenital portal vein hypoplasia is a congenital vascular anomaly primarily found in which species?

Dogs and occasionally cats

Name a small breed dog suspected of having inherited congenital portal vein hypoplasia

Yorkshire terriers, Maltese dogs, Cairn terriers, Tibetan spaniels, shih-tzus, or Havanese

Congenital portal vein hypoplasia is characterized by what specific characteristic of the portal veins?

Abnormally small portal veins

Congenital portal vein hypoplasia results in diminished hepatic perfusion and what other major condition?

Portal hypertension

Affected animals with congenital portal vein hypoplasia typically present with what two major gross findings?

Microhepatica and ascites

What diagnostic tool is recommended to differentiate between PSS and Congenital portal vein hypoplasia?

Radiology

Name an intrahepatic cause of portal hypertension

Fibrosis, Nodular regeneration, Lobular remodeling, Veno-occlusive disease, Microvascular dysplasia, or Sinusoidal amyloidosis

What two conditions can persistent portal hypertension lead to?

Ascites and development of acquired portosystemic shunts

What is characteristic of acquired portosystemic shunts in a dog?

Multiple tortuous blood vessels

Which circulatory disorder is associated with ammonium biurate crystaluria?

PSS

Which circulatory disorder causes the liver to resemble a nutmeg?

Passive Congestion

Which circulatory disorder is associated with acquired portosystemic shunts?

Portal hepatic hypertension

Which two circulatory disorders are associated with microhepatica (small liver)?

PSS and Portal hepatic hypoplasia (Congenital portal vein hypoplasia)

Name a hepatocellular infiltration listed in the sources

Amyloid, Copper, Iron, Bile pigments, Lysosomal storage diseases, Glycogen, or Lipid

Name the infiltration pathway exemplified by hepatic lipidosis

Defect in metabolism

Name the infiltration pathway exemplified by amyloidosis

Defect in protein folding or transport

What is amyloidosis?

Extracellular deposition of abnormal proteinaceous substance in tissues

Name the two forms of protein that amyloid consists of

Amyloid light chain protein (AL) and Amyloid associated protein (AA)

Where is Amyloid light chain protein (AL) derived from?

Abnormal plasma cells secreting light chain fragments into circulation

Where is Amyloid associated protein (AA) secreted from?

The liver, in response to cytokines from inflammation

Hepatic amyloidosis is commonly a result of secondary (reactive) amyloidosis due to what?

Prolonged systemic inflammation (amyloid AA)

Name a cat breed reported to have inherited or familial amyloidosis

Abyssinian cats or Siamese cats

Grossly, how do livers affected by amyloidosis appear?

Enlarged with rounded edges, friable, and pale

Severe cases of hepatic amyloidosis can lead to what condition?

Hepatic failure

What special stain is used to identify amyloid?

Congo red

Accumulation of copper leads to the production of what damaging molecules?

Reactive oxygen species

Copper accumulation causes oxidative injury to mitochondria and cellular membranes, resulting in subsequent necrosis in what specific zone?

Centrilobular necrosis

Disorders of copper metabolism have been commonly described in which two specific dog breeds?

Bedlington terriers and Labrador retrievers

What is the disorder caused by copper accumulation in dogs?

Canine copper-associated hepatopathy

Canine copper-associated hepatopathy is a common cause of what chronic liver disease in dogs?

Chronic hepatitis

In Bedlington terriers, mutation in which gene is associated with copper-associated hepatopathy?

COMMD1 gene

Where does copper accumulate in the liver?

In centrilobular regions and within Kupffer cells

What is the eventual end-stage liver condition resulting from ongoing oxidative injury due to copper accumulation?

Cirrhosis (end-stage liver)

Why are sheep more susceptible to copper toxicosis?

Copper storage is poorly regulated in sheep

Low dietary levels of what two substances exacerbate copper toxicosis in sheep?

Molybdenum and sulfur

Rapid release of copper into the blood (often triggered by stress or illness) can result in what acute systemic condition?

Hemolysis

What special stain is used to identify and quantify granules of copper in a liver biopsy?

Rhodanine

What is Iron Storage Disease also known as?

Hemochromatosis

Name a species, besides dogs, reported to have inherited Iron Storage Disease (hemochromatosis)

Mynah birds, toucans, Salers cattle, or horses

What substance accumulates in the liver during cholestatic disease, contributing to hepatocellular injury?

Bile pigment

Lysosomal Storage Diseases (LSDs) are a large group of rare inherited disorders resulting from defects in what cellular function?

Lysosomal function

The accumulation of substances within lysosomes results in what visible change to hepatocytes?

Cytoplasmic swelling and vacuolization

Affected animals with Lysosomal Storage Diseases are usually characterized as being of what age?

Young

What is the type of vacuolar hepatopathy associated with stress, Cushing’s disease, or glucocorticoid administration in dogs?

Glycogen-type VH

What is the type of vacuolar hepatopathy associated with Hypothyroidism and Diabetes mellitus?

Lipid-type VH

Severe cases of Canine degenerative vacuolar hepatopathy (VH) can lead to what end-stage liver condition?

Cirrhosis

In Canine degenerative vacuolar hepatopathy, why is ALP elevated in the serum?

Due to severe swelling of hepatocytes which can lead to blockage of bile canaliculi and intrahepatic cholestasis

What major condition is associated with Feline hepatic lipidosis?

Obese cats after a period of anorexia

What severe conditions do cats with Feline hepatic lipidosis frequently develop?

Hepatic failure, icterus, and hepatic encephalopathy

When does bovine fatty liver disease typically occur in dairy cows?

In late gestation or peak lactation

Grossly, how is a liver affected by hepatic lipidosis described in texture and color?

Diffusely swollen, yellowish, and greasy texture

What happens to small pieces of liver affected by severe hepatic lipidosis when placed in water or formalin?

They float

Histologically, what is the appearance of vacuoles in hepatocytes during hepatic lipidosis?

Well demarcated intracytoplasmic vacuoles

Which hepatocellular accumulation is characterized by discrete vacuoles that push the nucleus to the periphery?

Lipid/Hepatic lipidosis

Which hepatocellular accumulation is characterized by indiscrete intracytoplasmic vacuoles and can be induced by prolonged treatment with steroids in dogs?

Glycogen

Which hepatocellular accumulation occurs as brown granules after staining with rhodanine special stain?

Copper

Which hepatocellular accumulation is associated with cholestasis and contributes to hepatocellular injury?

Bile pigments

What defect involves the lack of an enzyme resulting in failure to degrade a substrate?

Inherited enzyme deficiencies (resulting in storage diseases)

What anatomical location does passive congestion cause high pressure to be observed?

Hepatic vein and its tributaries

Hepatic encephalopathy in PSS is directly caused by the accumulation of which substance?

Hyperammonemia

Besides pressure atrophy, what can severe amyloid deposition in the space of Disse lead to?

Necrosis of hepatocytes

What specific area of the hepatic lobule is primarily affected by congestion and hypoxia in passive congestion?

Centrilobular region (Zone 3)

The histological features of Congenital portal vein hypoplasia are often indistinguishable from which other circulatory disorder?

Congenital portosystemic shunt (PSS)

What is the specific mutation associated with copper-associated hepatopathy in Bedlington terriers?

Mutation in the COMMD1 gene

What gross description indicates a friable liver that is susceptible to fracture and hemorrhage?

Livers severely affected by Amyloidosis

What clinical sign in dogs with PSS causes them to sway as if intoxicated?

Ataxia

What is the general mechanism of hepatocellular injury caused by bile pigment accumulation?

Cholestatic disease

What histological change characterizes the results of accumulated substances in lysosomes in Lysosomal Storage Diseases?

Cytoplasmic swelling and vacuolization

The ductus venosus is a crucial fetal vessel whose failure of closure leads to which specific shunt type?

Intrahepatic shunts

Hepatic lipidosis in ponies, miniature horses, and donkeys occurs after what type of event in pregnant or lactating mares?

A period of stress or anorexia

What specific type of protein is derived from abnormal plasma cells secreting light chain fragments?

Amyloid light chain protein (AL)

What is the gross description of the liver associated with hepatocellular glycogen accumulation?

Enlarged, pale with enhanced lobules

What is often pursued in patients with unexplained increase in serum ALP and mildly elevated ALT associated with vacuolar hepatopathy?

Liver biopsy

Steatosis is also known by what term?

Fatty degeneration

Why is radiology recommended for Congenital portal vein hypoplasia?

To differentiate it from PSS

What specific part of the circulatory system does portal hypertension relate to?

Blood flow pressures

What specific chronic liver condition does Canine copper-associated hepatopathy cause?

Chronic hepatitis

What condition causes the development of acquired portosystemic shunts?

Persistent portal hypertension