Pathology of the Hepatobiliary System #2 Flashcards

1
Q

List the functions of the liver.

A
  • Bile synthesis & secretion
  • Bilirubin metabolism
  • Carbohydrate metabolism
  • Lipid metabolism
  • Protein Synthesis
  • Ammonia Metabolism
  • Xenobiotic Metabolism
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2
Q

Describe bilirubin metabolism and elimination

A

Starts in spleen
RBC, when are too old, are phagocytized by MCQs. Hb inside RBC are separated into heme and globin. Globin will eventaully be metabolized into AA. Heme has a center filled with iron. Within this process, the iron is excreted and heme is transformed into perforin Green –> unconjugated bilirubin. After being transformed into uncon bili, this will be bind with albumin b/c this is how the unconjug bili can be transported., Goal of hepatocyte is to form unconjug to conjugate bili. Bili will be able to be excreted through biliary system. Whatever happens in each step causes dysfunction of bilirubin, so this can be icterus or lysis.

In IMHA –> jaundice
Liver disease –> cirrhosis is a general term used to describe end stage liver disease. Lot of fibrosis, regenerative nodules.
Anything obstructing biliary system, e.g. tumor, post-hepatic hyperbilirubinemia.

Hemosidderin contains iron, which is the end product of RBC breakdown/hemorrhage, before iron is excreted.

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3
Q
  1. What process has occurred here?
  2. What is seen clinically?
A
  1. Dysfunction of Bilirubin Metabolism
  2. Yellow discoloration of the skin or mucosal surface. The conjunctiva of the eye or oral mucous membranes.
  • Hyperbilirubinemia = icterus (jaundice)
  • Gross: yellow staining of tissue
    Icterus, Hemolytic Anemia, Dog
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4
Q

What are the 3 types of causes for icterus:

A
  • Prehepatic
  • Hepatic
  • Posthepatic
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5
Q

What does pre-hepatic icterus result in?

A
  • Increased unconjugated bilirubin
  • Hemolysis (immune-mediated, infectious, metabolic,
    trauma, toxin, etc.)
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6
Q

What does hepatic icterus result in?

A
  • Defective uptake or conjugation of conjugated
    and/or unconjugated bilirubin
  • Liver disease or congenital anomalies
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7
Q

What does post-hepatic icterus result in?

A
  • Increased conjugated bilirubin
  • Bile duct obstruction

^listen to all above slides, you were in the bathroom

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8
Q

What can be seen in this image below?

A

Histo: Brown, amorphous, globular pigment (canalicular plugging)

Normally you would not see this pigment, located in the bile caniliculi, which connect to the larger ducts. When you see this you cna be confident that there is bilrubin

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9
Q

How does the liver metabolize carbohydrates?

A
  • Regulation of plasma glucose concentration
  • Glycogenolysis and glycogenesis

May also see hypoglycemia

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10
Q

What causes glycogen accumulation?

A
  • Excess glucocorticoids (“steroid hepatopathy”) – dogs only!
    • Endogenous = aniaml has cushings, so now there is elevated cortisol levels in the blood or exogenous: these animals are on steroids for along time –> glycogen accumulation in liver
  • Glycogen storage diseases
  • congenital disease; glycogen storage in multiple tissues in organs. On histo, see a l,ot of glycogen accumulation –> dysfunction of glucose regulation
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11
Q
A

Diffuse color change, yellow
Normal liver should be a dark brown.
Glucocorticoid-Induced Hepatopathy, Liver, Dog

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12
Q
A

Glucocorticoid-Induced Hepatopathy, Liver, Dog. Note the swollen hepatocytes (arrows)

Pink strings in between vacuoles is where glycogen is stored. This is what we see in steroid hepatopahy

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13
Q

How does the liver regulate lipid metabolism?

A
  1. Start where fat is. The TAG is a triglyceride. In a normal indivudal, when you don’t eat/are fasting you have a low insulin level and sothe insulin inhibits hydrolysis of TAG inito Free fatty acid.
    Free fatty acids can be utilized for energy (beta oxidation) or can be partitioned into VLDL particles (both occurs in liver).
    When you have intake of sugar, this will also trigger another process where DNL –> FA.

In dzed, insulin resistance which leads to less ibnhibition, so more TAG being transported so more lipids need ot be metabolized in the liver. Liver is confused and tries ot figure out how to use this energy. When you eat a lot of sugar, in disease person there is an increase in denovo lipogenesis.

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14
Q
A
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15
Q

What are the causes of hepatic lipidosis?

A

Causes: HE KNIT
* High-fat or cholesterol diet
* Negative energy balance (e.g. secondary to anorexia, pregnancy = more energy needed for fetus etc.)
* Toxin
* Ketosis
* Endocrine disorders (e.g. diabetes mellitus, hypothyroidism)
* Idiopathic (e.g. seen in miniatures horses)

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16
Q
A

Hepatic lipidosis secondary to diabetes mellitus, Ca

Diffuse pallor of liver

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17
Q
A

Hepatic lipidosis due to pregnancy toxemia in a sheep

18
Q

What condition is pictured below?

A

Hepatomegaly, steatosis associated with equine hyperlipemia in a donkey
Entire liver is yellow

Hepatic lipidosis in two species for unknown reason = donkey and miniature horses

19
Q
A

Lipid vacuoles in the liver, Donkey

20
Q

How does the liver perform protein synthesis?

  • The liver is responsible for synthesis of approximately _____% of body proteins.
    • Including _______, _______ proteins, _____-proteins, _________ factors, ________ proteins, some ________ phase proteins etc.
  • Hepatic failure can lead to ?
    —> Examples:?
A
  • The liver is responsible for synthesis of approximately 15% of body proteins.
    • Including albumin, transport proteins, lipoproteins, clotting factors, fibrinolysis proteins, some acute phase proteins etc.
  • Hepatic failure can lead to hypoproteinemia, metabolic disease, bleeding tendencies
    —> Examples:
  • Coagulopathy
  • Hepatocutaneous syndrome (a type of superficial necrolytic dermatitis)
  • Ascites
21
Q

What can be seen below?

A

Hemorrhage, Anticoagulant (Warfarin-Containing) Rodenticide Toxicosis, Skin and Subcutis, Medial Aspect of the Right Hind Leg, Dog

Vitamin K antagonists:
* Found in prescription medications
(warfarin/Coumadin), anticoagulant
rodenticides (e.g., warfarin,
brodifacoum), moldy sweet clover
(dicumarol)

22
Q

What is the pathogenesis of Rodenticide toxicosis?

A
  • Inhibit vitamin K epoxide- reductase
    –> ↓ active reduced vitamin K
    –> ↓ production of vitamin K-
    dependent coagulation factors (II, VII, IX, and X)
    –> hemorrhage
23
Q

Superficial Necrolytic Dermatitis is NOT interchangeable with?

A

hepatocutaneous syndrome

24
Q
  1. In which species does Superfiical Necrolytic Dermatitis occur? At what age?
  2. What can be seen clinically?
  3. What other conditions is this disease associated with?
  4. Describe the pathogenesis of this disease.
A
  1. Small breed geriatric dog
  2. Hyperkeratosis of the paw pad, bilaterally symmetrical erythema, scaling, crusting, erosions, and ulcers
    * Distal limbs, perioral and periocular areas
  3. Associated with:
    - Liver disease (hepatocutaneous syndrome)
    - Glucagonomas
    - Diabetes mellitus
    - Hypoaminoacidemia or hyperglucagonemia
  4. Pathogenesis unknown
25
Q

What can be seen in the image below?

A

Superficial Necrolytic Dermatitis

Liver will have heterogenicity and multifocal nodules

26
Q

What condition do you think this small, geriatric dog is suffering from?

A

Superficial necrolytic dermatitis is characterized by hyperkeratosis of the paw pad

27
Q
A

Any disease that causes hepatic injury, such as hepatitis –> decreased protein production → hypoproteinemia
→ decreased plasma colloid osmotic pressure → ascites

Ascites/peritoneal
effusion secondary to
hepatitis in a do

28
Q

The liver metabolizes amino acids → Conversion of ammonia to _____ in the liver → ____ excreted in the urine

A

Metabolism of amino acids → Conversion of ammonia to urea in the liver → Urea excreted in the urine

29
Q

Liver failure → build up of ________ in blood → _________ neurotransmission in the CNS → Hepatic ________

Look at urine under microscope, may find crystals that are indicative of elevated _________.

A

Liver failure → build up of ammonia in blood → abnormal neurotransmission in the CNS → encephalopathy

Hepatic encephalopathy came from this. If the liver is messed up, you have bad metabolism of ammonia.

Look at urine under microscope, may find crystals that are indicative of elevated ammonia.

30
Q

Xenobiotic Metabolism
* Foreign substances (xenobiotics)
* The enzyme, __________ ____, of the smooth endoplasmic reticulum (microsomes) of hepatocytes serve as the major site of metabolism of these substances in preparation for excretion in ____ or ____.

Usually see in ________ injury b/c this is where there is more cytochrome p450 enzymes

A

Xenobiotic Metabolism
* Foreign substances (xenobiotics)
* The enzyme, cytochrome P450, of the smooth endoplasmic reticulum (microsomes) of
hepatocytes serve as the major site of metabolism of these substances in preparation for excretion in bile or urine.

Usually see in centrilobular injury b/c this is where there is more cytochrome p450 enzymes

31
Q

Toxicant-Induced Liver Disease
* Refer to Lecture 5
* Variable appearance; Most common pattern of acute liver toxicity is ?
* Example: ___________

A

centrilobular necrosis, photosensitization

32
Q

What is Type 1 Photosensitization Dermatitis?

A

Primary
* Ingestion of exogenous agents (plants, drugs)

33
Q

What is Type 2 Photosensitization Dermatitis?

A

Endogenous
* Congenital erythropoietic porphyria - disturbance in porphyrin pigment metabolism

34
Q

What is Type 3 Photosensitization Dermatitis?

A

Hepatogenous photosensitization
* Main causes: plant toxins (Lantana camara, Senecio spp.) and mycotoxin

35
Q
A

Hepatogenous Photosensitization
* Sun-exposed (face, ears) and lightly pigmented regions
* Intensively pruritic
* Erythema progressing to crusting,
erosion, ulcers
* Impaired capacity of the liver to
excrete phytoporphyrins → increase
in blood levels → dermatitis

36
Q

Immune Response
* Synthesis and release of _______ ______ proteins
* E.g. ?
* Enriched with _______ immune cells
* ________ cells (macrophages in the liver)
* __________ cells
* _________ ______ lymphocytes
* ______ ______ ___ lymphocytes

A
  • Synthesis and release of acute phase proteins
  • E.g. C-reactive protein, amyloid A (AA) protein, α1-antitrypsin,
    complement factors
  • Enriched with innate immune cells
  • Kupffer cells (macrophages in the liver)
  • Dendritic cells
  • Natural killer lymphocytes
  • Natural killer T lymphocytes
37
Q

What can be seen here?

A

the kupffer cells are located closely to the hepatic plate. They don’t look like a normal macrophage, but are lining the sinuosoid.

38
Q

Whenever there is chronic inflammation in an animal, what happens to the Kupffer cells?

A

Produce IL-1,6 which will activate hepatocytes –> serum amyloid associated protein (SAA) –> deposition of amyloid in space of
Disse → compresses adjacent hepatocytes → causes atrophy
* Interferes with sinusoidal transfer of blood & nutrients
* Predispose liver to rupture

What causes hepatic amyloidoises? 2 general causes
1. Primary - inhertied seen in certain breeds
2. More common = secondary = result of any type of inflammation. so if you have chronic degernatve joint disease, esp in non-human primates, if you have johnne’s dz you can see amyloidosis here.

39
Q
A

Hepatic Amyloidosis, Liver, Duck
What could cause this? Bumble foot (staph aureus)

40
Q
A

Hepatic Amyloidosis, Liver, Dog.

Congo red used to stain amyloid
see birefringence