Pathology of the Liver and Biliary Tract 2 Developmental...

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Pathology of the Liver and Biliary Tract – 2 Developmental, Circulatory and Metabolic Disorders Shannon Martinson, August 2017 http://people.upei.ca/smartinson/

Transcript of Pathology of the Liver and Biliary Tract 2 Developmental...

Page 1: Pathology of the Liver and Biliary Tract 2 Developmental ...people.upei.ca/smartinson/VPM_2210_LIVER_LECT_2_SAM_2017.pdfDevelopmental, Circulatory and Metabolic Disorders Shannon Martinson,

Pathology of the Liver and Biliary Tract – 2 Developmental, Circulatory and Metabolic Disorders

Shannon Martinson, August 2017 http://people.upei.ca/smartinson/

Page 2: Pathology of the Liver and Biliary Tract 2 Developmental ...people.upei.ca/smartinson/VPM_2210_LIVER_LECT_2_SAM_2017.pdfDevelopmental, Circulatory and Metabolic Disorders Shannon Martinson,

• Congenital cysts most likely originate from capsule or the embryonic bile ducts (ductal plate malformations)

DEVELOPMENTAL ANOMOLIES

Congenital Cysts

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• Differentiate from parasitic cysts

DEVELOPMENTAL ANOMOLIES

Congenital Cysts

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• Polycystic liver disease can be incidental or significant!

DEVELOPMENTAL ANOMOLIES

Congenital Cysts

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• Hepatic Displacements

• Ventral hernia

• Diaphragmatic hernia

MISCELLANEOUS CHANGES

Rupture and Displacements

• Rupture • Trauma • Enlarged liver is predisposed • Rapidly fatal (blood loss)

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Focal areas of lipidosis near mesenteric attachments

• Cattle and horses

MISCELLANEOUS CHANGES

Tension Lipidosis

Capsular Fibrosis

Common in horses

• Resolution of peritonitis

• Parasitic migration?

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Grouped according to whether blood flow into, through, or from the liver is impaired

CIRCULATORY DISTURBANCES

Impairment of blood flow from the liver

Impairment of blood flow through the liver

Impairment of blood flow to the liver

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Impaired blood flow into the liver

• Impairment of blood flow through the portal vein (>hepatic artery) before it enters the liver

• Possible sequelae:

• Portal hypertension (prehepatic)

• Liver infarcts

CIRCULATORY DISTURBANCES

Impairment of blood flow to the liver

• Congenital malformation → portal vein hypoplasia

• Histologic diagnosis – US is often normal

• Small and toy breed dogs: Yorkies

• Secondary histologic findings: arteriolar hyperplasia, lobular atrophy

• Clinical findings are similar to PSS

• +/- portal hypertension and ascites

Portal Vein Hypoplasia

(Microvascular dysplasia)

http://www.askjpc.org/wsco/wsc/images/2012/122402-1.jpg

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CIRCULATORY DISTURBANCES

Impaired blood flow through the liver

Impairment of blood flow through the liver

• Due to increased resistance of blood flow within the sinusoids

• Cirrhosis*

• Amyloidosis

• Intrahepatic arteriovenous shunts

• Sequela:

• Portal hypertension (intrahepatic)

• Acquired PS shunts

Cirrhosis, cat

Pathology of Domestic Animals, 6th Ed. 2015, G Maxie

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• Conditions that lead to ↑ resistance to venous outflow in the hepatic vein or vena cava

• Passive congestion*

• Right heart failure*

• Venal caval thrombosis

• Thrombosis of the hepatic vein

• Veno-occlusive disease

• Sequela:

• Portal hypertension (posthepatic)

CIRCULATORY DISTURBANCES

Impaired blood flow from the liver

Impairment of blood flow from the liver

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Pathologic Basis of Veterinary Disease (2006), 4th ed., Mosby-Elsevier, ch 8

• Slight enlargement of liver

• Prominent reticular pattern

Acute Passive Congestion

• Hepatomegaly with rounded margins

• Nutmeg appearance

• Centrilobular congestion

• Midzonal fatty change

• Centrilobular fibrosis & hemosiderosis

Chronic Passive Congestion

CIRCULATORY DISTURBANCES

Impaired blood flow from the liver Acute passive congestion

Chronic passive congestion

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Centrilobular fibrosis and siderophages

Pathologic Basis of Veterinary Disease (2006), 4th ed., Mosby-Elsevier, chapter 8

CIRCULATORY DISTURBANCES

Impaired blood flow from the liver Histology – Chronic passive hepatic congestion

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CIRCULATORY DISTURBANCES

Congenital portosystemic shunts

• Allows blood from the portal venous system to bypass the liver and enter systemic circulation • Usually a single large-caliber vessel (unlike acquired shunts → multiple small vessels)

• Decreased vascular flow and trophic substances to the liver → hepatic atrophy • No portal hypertension or ascites (unlike portal vein hypoplasia/microvascular dysplasia) • Toxic substances (ammonia) are not removed from the blood • Ultrasound +/- contrast imaging are crucial for clinical diagnosis!

Other Vascular / Circulatory Disorders

Clinical signs:

• Stunted growth

• Hepatic encephalopathy

Clinical pathology findings:

• Hyperammonemia

• Decreased urea

• Increased bile acids

• Ammonium biurate crystals in urine

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CIRCULATORY DISTURBANCES

Extrahepatic PSS:

• Portocaval or Portoazygous

• Small breed dogs and cats

Intrahepatic PSS

• Patent ductus venosus

• Large breed dogs

• Secondary changes: – Portal regions lack a portal vein and have multiple

arterioles

• Looks identical to primary portal vein hypoplasia

(microvascular dysplasia) on histology

Pathologic Basis of Veterinary Disease (2006), 4th ed., Mosby-Elsevier, ch 8

Congenital portosystemic shunts Other Vascular / Circulatory Disorders

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CIRCULATORY DISTURBANCES

• Focal areas with dilated sinusoids filled with blood

• Gross: Multiple 1 – 5 mm dark red foci

• Histo: Dilated sinusoids and loss of hepatocytes

• Incidental in cattle and cats

Telangiectasia

• Centrilobular degeneration / necrosis

• This zone receives the least O2

Anemia

Other Vascular / Circulatory Disorders

Centrilobular degeneration / necrosis

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Hemorrhagic infarcts secondary to mycotic rumenitis, cow

CIRCULATORY DISTURBANCES

Other Vascular / Circulatory Disorders

• Uncommon

• Dual blood supply

• Thrombosis of hepatic artery

• Torsion of hepatic lobe

• Infarction, shock and death may occur

• Secondary to mycotic rumenitis

• Hepatic vein thrombosis

Infarction

Noah’s arkive

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METABOLIC DISTURBANCES

ACCUMULATIONS OF:

• Fat

• Glycogen

• Amyloid

• Copper

• Pigment

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• Sources of FFA: • Adipose tissue • Chylomicrons from gut • Hepatic production from AA

and glucose (not in ruminants)

• FFA in liver: • Esterified to triglycerides • Used as energy (oxidized) • Production of phospholipids

& cholesterol • Complexed with apoproteins

• Released as lipoproteins

Pathologic Basis of Veterinary Disease (2006), 4th ed., Mosby-Elsevier, chapter 8

METABOLIC DISTURBANCES

Fatty Liver (Hepatic Lipidosis)

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Potential mechanisms of hepatic lipidosis:

• Excess dietary intake of fat / carbohydrates

• Excess mobilization of fat from stores • Due to ↑ demand (lactation, starvation)

• Abnormal hepatic function(↓ oxidation FA)

• ↑ esterification of FA

• ↓ apoprotein synthesis or impaired secretion (hepatoxins / drugs)

METABOLIC DISTURBANCES

Fatty liver occurs when the rate of triglyceride accumulation in liver exceeds rate of degradation or secretion into circulation

Fatty Liver (Hepatic Lipidosis)

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• Rounded margins (hepatomegaly)

• Soft – friable greasy texture

• Enhanced reticular pattern or diffuse yellow to orange discolouration

• May float in fluid

Gross

METABOLIC DISTURBANCES

Mink

Cat

UNAM-FMVZ

Fatty Liver (Hepatic Lipidosis)

Dog

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Fatty liver – Oil-red-O stain

METABOLIC DISTURBANCES

Histology

• Macrovesicular lipidosis • Single large distinct clear vacuole in the heptocellular

cytoplasm – displaces the nucleus to the periphery

• Microvesicular lipidosis • Multiple small distinct clear vacuoles within the

hepatocellular cytoplasm

Image: Dr L Ross

Fatty Liver (Hepatic Lipidosis)

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METABOLIC DISTURBANCES

Liver rupture, dog

• Depends on:

• Cause

• Severity

• Duration

• Reversible in mild cases

• May cause:

• Hepatocellular necrosis

• Fat embolism

• Liver rupture →hemoabdomen

• Increased susceptibility to toxic damage

Significance of Hepatic Lipidosis

Fatty Liver (Hepatic Lipidosis)

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• Dietary excess

• Fasting in obese animals

• Cobalt /Vitamin E deficiency

Dietary Cause

• Decreased oxidation of fatty acids

• Decreased formation/secretion of lipoproteins

Toxic / Anoxic Injury

Causes/syndromes of lipidosis

http://www.askjpc.org/wsco/wsc/images/2011/110303-2.jpg

Aflatoxicosis,dog

METABOLIC DISTURBANCES

Fatty Liver (Hepatic Lipidosis)

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METABOLIC DISTURBANCES

Causes/syndromes of lipidosis

• Excess fat metabolism due ↑ energy demand

• Pregnant ewes (= pregnancy toxemia)

• Lactating dairy cow

Ketosis*

• Obese animals

• Anorexia

• Retained placenta, metritis, milk fever, abomasal displacement

Bovine fatty liver syndrome*

© Cornell Veterinary Medicine

Noahs arkive

Cow

Ewe

Fatty Liver (Hepatic Lipidosis)

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METABOLIC DISTURBANCES

Causes/syndromes of lipidosis

• Idiopathic

• Obesity + anorexia

• Progresses to liver failure with icterus and hepatic encephalopathy

Feline fatty liver syndrome*

• Obesity, pregnancy, lactation

• Ponies, mini horses, donkeys

• Hyperlipemia, hepatic encephalopathy, liver rupture, DIC

Equine hepatic lipidosis

• Diabetes

• Hypothyroidism

Endocrine disorders

Cat

Mini horse

Cornell Veterinary Medicine

Fatty Liver (Hepatic Lipidosis)

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• Glycogen is normal in hepatocytes

• Excess storage of glycogen occurs with:

– Diabetes mellitus

– Hyperadrenocorticism*

• “Steroid hepatopathy”

– Cushing’s Disease

– Iatrogenic

– Prolonged stress

– Glycogen storage diseases

METABOLIC DISTURBANCES

Glycogen Accumulation

Glucocorticoid-induced hepatopathy, liver, dog

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Pathologic Basis of Veterinary Disease (2006), 4th ed., Mosby-Elsevier, ch 8

PAS

• Steroids induce glycogen synthetase promotes hepatic storage

• Enlarged, pale liver due to swollen hepatocytes (midzonal areas)

• PAS stain distinguishes it from fat

METABOLIC DISTURBANCES

Glycogen Accumulation

Often have ↑ Alkaline Phosphatase (ALP)

Page 28: Pathology of the Liver and Biliary Tract 2 Developmental ...people.upei.ca/smartinson/VPM_2210_LIVER_LECT_2_SAM_2017.pdfDevelopmental, Circulatory and Metabolic Disorders Shannon Martinson,