Lecture 99: Circulatory Disorders and Hepatic Infiltrations

what is passive congestion characterized by?

reduced hepatic outflow due to cardiac dysfunciton

what is passive congestion caused by?

right-sided heart failure which produces elevated pressure in the caudal vena cava that extends to the hepatic vein and its tributaries

what does high pressure in hepatic veins lead to?

centrilobular congestion of sinusoids

what are common causes of right sided heart failure resulting in hepatic congestion?

1. valvular endocardiosis of the tricuspid valve (old dogs)

2. canine heartworm

what is the pathway that leads to passive congestion?

1. congestion

2. hypoxia

3. centrilobular degeneration

4. atrophy and loss of hepatocytes

besides congestion, what else can chronic hypoxic injury lead to?

steatosis (fatty degeneration)

what do the combined changes in passive congestion lead to?

enhanced lobular pattern (nutmeg liver)

how does passive congestion appear grossly?

lobes of liver are enlarged with rounded edges

what does the image show?

passive congestion

what does the image show?

enhanced lobular pattern from passive congestion

MCQ: a seven year old male lab presents with right-sided congestive heart failure and is diagnosed with chronic canine heartworm disease. What lesion would be expected in the liver of this dog?

chronic passive congestion

what is congenital portosystemic shunt?

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

in which circulatory disorder will animals appear stunted?

congenital portosystemic shunt

what signs will animals with congenital portosystemic shunt develop?

signs of hepatic encephalopathy due to hyperammonemia

how does the liver appear grossly in animals affected by congenital portal systemic shunt?

liver is small with single anomalous vessels connecting portal circulation with systemic circulation

how does the liver appear histologically in animals affected by congenital portal systemic shunt?

1. lobular atrophy 

2. portal miniaturization with small or absent portal veins

3. reduplication of arterioles

what does the image show?

Congenital portal systemic shunt

what are the types of PSS?

1. intrahepatic shunts

2. extrahepatic shunts

what causes intrahepatic shunts?

failure of closure of the ductus venosus (fetal vessel)

what animal is intrahepatic shunts common in?

large breed dogs

what are the causes of extrahepatic shunts?

1. portal vein to caudal vena cava anastomosis

2. portal vein to azygos vein anastomosis

what animal are extrahepatic shunts common in?

small breed dogs and cats

what does the image show?

congenital intrahepatic portosystemic shunts

what can result in dogs from congenital PSS?

ammonimum biurate crystalluria

what does the image show?

urinary bladder with ammonium biurate crystals

what else can congenital portal vein hypoplasia be called?

hepatic microvascular dysplasia

what animals does congenital portal vein hypoplasia occur in?

dogs and sometimes cats

what breeds does congenital portal vein hypoplasia appear in?

1. yorkshire terrier

2. maltese 

3. cairn terriers

4. tibetan spaniels

5. shih-tzus

6. havanese

what does congenital portal vein hypoplasia result in?

diminished hepatic perfusion and portal hypertension

what signs do animals affected by congenital portal vein hypoplasia typically have?

1. microhepatica

2. ascites

what test is conducted to differentiate PSS from congenital portal vein hypoplasia?

radiology

what are the causes of portal hypertension?

1. thrombosis

2. occulusion within portal vein or hepatic outflow

3. intrahepatic causes

what are intrahepatic cause of portal hypertension?

1. fibrosis

2. nodular regeneration

3. lobular remodeling

4. veno-occlusive disease

5. microvascular disease

6. sinusoidal amyloidosis

what can persistent portal hypertension lead to?

1. ascites

2. development of acquired portosystemic shunts

what does the image show?

acquired portosystemic shunts from portal hypertension

what are examples of hepatocellular infiltrations?

1. amyloid

2. copper

3. iron

4. bile pigments

5. lysosomal storage disease

6. glycogen

7. lipids

what are the main mechanisms of abnormal intracellular accumulations?

1. inadequate removal and degradation

2. excessive production of an endogenous substance

3. deposition of an abnormal exogenous material

what are the four pathways in abnormal cellular infiltrations?

1. defect in metabolism

2. defect in protein folding or transport

3. lack of an enzyme resulting in failure to degrade a substance

4. ingestion or inhalation of indigestible materials (respiratory not hepatic)

amyloidosis

extracellular deposition of abnormal proteinaceous substance in tissues

what type of disorder is amyloidosis?

protein misfolding disorder

what two forms of protein can result from amyloidosis?

1. amyloid light chain protein (AL)

2. amyloid associated protein (AA)

amyloid light chain protein (AL)

derived from abnormal plasma cells secreting light chain fragments into circulation

amyloid associated protein (AA)

secreted in liver in response to cytokines

which form of protein from amyloidosis is most common?

amyloid associated protein (AA)

what is amyloidosis commonly a result of?

secondary (reactive) amyloidosis due to prolonged systemic inflammation (amyloid AA)

what breeds is amyloidosis seen in?

1. shar-pei dogs

2. abyssian cats

3. siamese cats

how do amyloidosis in the liver appear grossly?

livers are enlarged with rounded edges, friable, and pale

what are severely affected livers from amyloidosis susceptible to?

fracture and hemorrhage

what does the image show?

amyloidosis

where does amyloid deposit?

1. space of disse

2. portal tracts

3. within and around blood vessels

where does amyloid deposition start?

space of disse and extends into the sinusoids

what can severe deposition of amyloid cause?

pressure atrophy and necrosis of hepatocytes

what stain is used for amyloid?

congo red

what does the image show?

amyloidosis

what does accumulation of copper lead to?

production of reactive oxygen species causing oxidative injury to mitochondria

what breeds do we see disorders of copper metabolism?

1. bedlington terriers

2. labrador retrievers

what is canine copper associated hepatopathy the common cause of?

chronic hepatitis in dogs

where does copper accumulate in the liver?

centrilobular regions and within kupffer cells

what does the image show?

canine copper-associated hepatopathy

what animal is copper storage poorly regulated in?

sheep; more prone to copper toxicosis

what can exacerbate copper toxicosis in sheep?

low dietary molybdenum and sulfur

what can trigger copper release in sheep?

stress or illness

what does the image show?

copper accumulation

what does diagnosis of hepatocellular copper accumulation require?

liver biopsy

what stain is used to identify granules of copper?

rhodanine special stain

iron storage disease (hemochomatosis)

abnormally increased amount of iron storage within the liver

when does bile pigment accumulate in the liver?

during cholestatic disease and contributes to hepatoceullular injury

what does the image show?

bile pigment acummulation

what causes lysosomal storage diseases?

missing enzyme that are inherited as autosomal recessive disorders

what does accumulation of lysosomes result in?

abnormally increased amount of iron storage within the liver

MCQ: the bedlington terrier carries a genetic mutation that predisposes this breed to which of the following liver diseases?

copper-associated hepatopathy

what are the two types of canine degenerative vacuolar hepatopathy?

1. glycogen type

2. lipid type

what is glycogen-type VH associated with?

1. stress

2. cushing’s disease

3. genetic storage disease

4. glucocorticoid administration

what is lipid-type VH associated with?

1. hypoxia

2. certain toxins

3. hypothyroidism

4. diabetes

what does the image show?

glycogen type VH

what does the image show?

lipid type VH

what can severe cases of VH result in?

progessive injury leading to end-stage liver

why is liver biopsy pursued in patients suspected of canine degenerative VH?

due to unexplained increase in serum ALP and mildly elevated ALT

why is there increased ALP in patients with canine degenerative VH?

severe swelling of hepatocytes leads to blockage of bile canaliculi and intrahepatic cholestasis

how does the liver appear with hepatocellular glycogen accumulation?

liver is enlarged and pale with enhanced lobules

what does diagnosis fo hepatocellular glycogen accumulation require?

liver biopsy

what does the image show?

canine steroid induced hepatopathy

what does treatment of hepatocellular glycogen accumulation require?

identification of underlying cause

what does the image show?

hepatocellular glycogen accumulation

bovine fatty liver disease

common in dairy cows in late gestation or peak lactation, especially after any period of inappetence or anorexia

when does hepatic lipidosis of ponies, mini horses, and donkeys occur?

occurs in overweight pregnant or lactating mares after a period of stress or anorexia

feline hepatic lipidosis

occurs in obese cats after a period of anorexia;  frequently develop hepatic failure, icterus, and hepatic encephalopathy

what type of hepatocellular accumulation is characterized by discrete vacuoles that push the nucleus to the periphery?

lipid VH

what type of hepatocellular accumulation occurs when the liver is enlarged, yellowish, with an enhanced lobular pattern. Small pieces can float in water if severe

hepatic lipidosis

what kind of hepatocellular accumulation has Indiscrete intracytoplasmic vacuoles. Can be induced by prolonged treatment with steroids in dogs

hepatocellular glycogen accumulation

what kind of hepatocellular accumulation occurs as brown granules after staining with rhodanine special stain. Can cause oxidative injury to hepatocytes

hepatocellular copper accumulation

what kind of hepatocellular accumulation is associated with cholestasis?

bile pigment