Sys Path Exam 2

Year 2 Semester 1

why is it more likely to have liver disease than liver failure

• only need 30% of the liver to maintain functions, there are no clinical signs often before that

• liver is very regenerative

why can acute clinical signs of liver insufficiency be misleading

they can reflect chronic underlying disease

describe blood supply to the liver

dual: 25% CO

1. hepatic artery: oxygenated, provide oxygen to the organ

2. portal vein: low oxygen from GI tract and spleen

describe why there is low oxygen supply to the liver regarding its blood supply

the oxygenated and low oxygenated blood is mixed causing decreased perfusion and causing oxygen tension

what is the lining of the liver in the sinusoids and what is the significance

fenestrated, giving the hepatocytes direct access to the plasma

1. can take up things easier for filtration

2. can deposit synthesized proteins directly into the blood stream

2 important cells of the liver

1. kupffer cells: macrophages

2. Stellate cells: stem cells, repair and fibrosis and live between hepatocytes and sinusoids

describe the enzyme gradient in liver cells and what does it mean

• metabolic heterogeniety

• centrilobular cells have the greatest enzymes and metabolistic ability (cytochrome P450)

• they are more susceptable to toxic metabolites

in what case are periportal hepatocytes more susceptable to toxins

primary toxins that are immediatly toxic and kill the first thing they contact

Liver fucntions (5)

1. detoxification

2. synthesis of plasma proteins

3. secretion and conduction of bile

4. energy metabolism

5. Maintain water balance

where do endogenous and exogenous toxins in the liver come from

endogenous: metabolites produced by liver

exogenous: GI

give 2 examples of liver detoxification dysfunction

1. Ammonia build up causing hepatic encephalopathy

2. Phyloerythrin build up

explain hepatic encephalopathy mechanism and clinical signs

• ammonia build up which is toxic to astrocytes, neurons, and endothelial cells in CNS blood vessels

• can worsen after a mean due to increased ammonium production

clincial signs

• blindness

• head pressing

• seizures

• dementia

• behavior changes

describe phyloerythrin

• consume chlorophyl which the GI flora turns into phyloerythrin which is a toxic metabolite

• usually excreted in bile

• if there is cholestasis or hepatocellular injury, there is a reduced excretion and build up

• flourecent pigment causes hepatogenous photosensitization in UV radiation = sunburn, ulceration, scaring

• mostly in poorly pigmented areas, melanin offers some protection

• herbivores

what are the two main plasma proteins that the liver produces

1. albumin (exclusively by hepatocytes)

   1. oncotic pressure and carrier protein

2. clotting factors

clinical signs of hypoalbuminemia

• edema (tissues)

• effusion (body cavity)

clincial signs of clotting factor deficiency

coagulopathy

function of bile fluid

1. excrete toxins and detoxified chemicals

2. bile acids entry into small intestine for fat absorbtion and digestion

what is the most sensitive measure of hepatic function

bile acids

what could cause elevated bile acids 3

1. injured/dysfunctional hepatocytes cannot excrete, build up systemically

2. impaired bile flow (decreased conduction)

3. altered portal circulation(shunt)

main concenrs with hyperbilirubinemia

1. bilirubin is milkdly toxic

2. there is something worng causing failure to eliminate toxins excreted in bile

3 groups of causes of hyperbilirubinemia

1. pre-hepatic (hemolytic)

2. hepatic(impaired coagulation and or excretion)

3. post hepatic (obstructive) - inhibition of flow

what is the liver’s role in energy metabolism

body cells cannot store their own energy sources, fats are sent to the liver to be convered into lipoproteins to be used for energy by cells

describe hepatic lipid accumulation

• common

1. increased fat/ energy metabolism

• anorexia, pregnancy, diabetes mellitus causing high energy demands and overwhelming the liver with lipids (can be normal)

2. decreased ability of hepatocytes to secrete lipoproteins

• passive to uptake FA

• conjugation and secretion of lipoproteins is active

• can uptake fat, but sick hepatocytes cannot process it so it accumulates

consequences 4 of hepatic lipid accumulation

1. predisposing liver fracture (fat makes the liver friable)

2. swollen hepatocytes - compressing bile ducts (cholestasis)

3. decreased metabolic abilities

4. increased susceptabily to toxins

what is seen on a blood test for feline hepatic lipidosis

ALP increased mostly because also measure cholestasis (also see increase ALT, ASP), icterus

gross appearance of feline hepatic lipidosis

enlarged, yellow-tan, greasy liver that floats in formalin

treatment for hepatic lipidosis

caloric therapy with percutaeous endoscopic gastrostomy tube

livers role in maintaining liver water balance

1. normal liver = portal blood flow without resistnace

2. liver produces albumin = soruce of intravascular oncotic pressure

describe dysfunction of liver maintaining water balance

• ascities

• usually due to chonic liver disease

• cirrhosis increases resistance of sinusoidal blood increassing portal system pressure

• decreased albumin decreases oncotic pressure

• cause low protein transudate effusion in all vessels in the whole body

how do bacteria access the liver for hepatitis

1. GI (common) by portal blood

2. systemic circulation with hepatic artery (sepsis)

lesions of bacterial hepatitis

• random

• multifocal embolic seeding

• white spots: neucrosis and leukocytes (Neuts)

what is the thick muscle often seen around abscesses

fibrosis

what is a common cause of hepatic abscesses in ruminants

ruminal acidosis- any breaking down of rumen mucous barrier allow microbes to exit and colonize next capillary bed (liver)

besides older ruminants, what other species can get hepatic absesses and from where

calves and lambs from intestins and umbilicus (omphalitis)

significance of bacterial hepatitis

1. ruminants can be subclinical

2. rupture into caudal vena cava can lead to absesses in lungs, pulmonary thromboembolism, eating vessels, sudden death

2 groups of parasites in the liver

1. pass thorugh the liver: nemotodes

2. destination is the liver and bilary tree: flukes/ trematodes, cestodes

explain ascaris suum

• pig roundworm passing through liver

• migrate from GI tract and through liver that heal with fibrosis = milk spotted liver

• cause localized damage and move on

what parasite causes milk spotted liver

Ascaris Suum (porcine)

describe fasciola hepatica: patient, location, mechanism, gross lesions

• parasite with adult desitnation = bile ducts

• common in sheep and cattle

• pass eggs in bile and feces

• intermediated host of aquatic snails and larval forms eaten off plants

• enter duodenum and travel to liver

gross

• pipestem bile ducts due to chronic cholangitis and fibrosis and duct stretching

• migratory tracts in liver: necrosis and fibrosis with some black pigment (hemazoin)

what parasite causes pipestem bile ducts

fasciola hepatica

describe mechanism of bacillary hemoglobinuria (red water disease)

• fasciola hepatica/ liver fluke migration in ruminants cause necrosis and makes anerobic enviornment for Clostridium hemolyticum to germinate spores

• Clostriuium hemolyticum releases exotoxin = acute hepatic necrosis, intravascular hemolysis, hemoglobinuria

describe fungal hepatitis

multisystemic, granulomatous inflammation

3 viruses causing hepatitis

1. infectious canine hepatitis (canine adenovirus 1)

2. alphaherpesvirus

3. theiler’s disease (equine parvoviral hepatitis)

canine adenovirus 1

1. patient

2. pathogenesis

3. gross appearance

1. young dogs <2years

2. oral → lymph tissue → viremia → kupfer cells, hepatocytes, liver endothelium (on 2nd round of replication)

3. 
   

• multifocal hemorrhage and necrosis

• gall bladder edema and hemorrhage

• corneal edema (blue eye)

Alphaherpesvirus

1. patient

2. gross

3. mechanism

4. classic presentation

1. species specific: canid, equine, bovine

2. multifocal tiny white necrotic dots, random distribution

3. cause necrosis to whichever organ they infect (commonly liver)

4. kidney involvement

Theiler’s disease

1. common infection process

2. cause

3. gross

1. animals infected through treatment with equine serum

2. equine parvovirus

3. diffuse hepatic necrosis, dishrag liver, wipe out entire liver structure

what disease causes dishrag liver

theilers disease/ equine serum hepatitis/ equine parvoviral hepatitis

name inflammation of bile duct

cholangitis

name inflammed gallbladder

cholecystitis an

name inflammed bile duct and surrounding liver

cholangiohepatitis

4 causes of cholangitis

1. parasitic

2. bacterial

3. feline traditis

4. ideopathic

name for pattern affecting protal or centralobular areas of liver

enhanced reticular pattern

parasitic cause of cholangitis

• liver flukes

• pipestem bile ducts

• inflammation leads to fibrosis and bilary hyperplasia

• potential secondary bacteremia

bacterial cause of cholangitis

• where does it come from

• what does it look like

• predisposisiton?

• gross

• dfdx

• ascend from duodenum

• suppurlative inflammation

• predisposition of bilary obstruction causing stasis

• white streaks in liver, cannot diagnose from this

• lymphoma, lymphocytic cholangitis (likes portal areas)

what is feline traditis

pancreatitis, cholangitis, and enteritis at major duodenal papilla

what is the ideopathic cause of cholangitis

• name

• description

• pathogen

• progression

• patient

• dfdx

feline lymphocytic cholangitis

• intrahepatic cholestasis

• lymphocytic inflammation with fibrosis causing enhanced reticular pattern between portal regions

• unclear pathogen

• slow progressive

• older cats

• dfdx: lymphoma, bacterial cholangitis

Hepatic Passive congestion

1. cause

2. gross

3. progression

1. cardiac decompensation (congestive heart failure)

• decrease R ventricle output, increasing venous pressure

• edema backup into centralobular areas = hypoxia

• congestion in sinusoids and central veins

2. nutmeg liver, dark red central veins with surrounding fat and necorsis (pale) and fat accumulation in hepatocytes

3. chronic = centrilobular necrosis and fibrosis

2 types of portosystemic shunts

1. congenital→ large and 1

2. aquired → many and small

2 types of congenital PSS

1. extrahepatic: goes around the liver

• Portal caval shunt

• portal azygous shunt

2. intrahepatic: goes through the liver

Congenital PSS

1. results

2. signalment

3. consequences

4. diagnosis

1. GI toxins have direct access to systemic circulation

2. young

3. 
   

• stunted growth (liver makes growth factors)

• increase ammonia and decreased BUN → hepatic encephalopathy

• increased bile acid

• decreased liver size

• urine urate crystals

4. signalment, history, imaging, liver function (bile acids) - liver enzymes can be normal because the problem is not the liver

treatment for congenital PSS

ligate anomalous vessels over time

• cannot do right away or will; get protal hypertension and ascities

• body sends other vessels out

decrease ammonia in diet

aquired PSS

1. pathogenesis

2. gross

3. clinical features

1. fibrosis decreases hepatic flow causing protal hypertension leading body to send vessels out to find least resistant path

2. common, multiple small shunts

3. 
   

• ascities

• increased liver enzymes

• splenic congestions

for congenital and aquired PSS

1. age

2. stature of animal

3. portal pressure

4. ascities

5. surgically fixable?

6. Bile acids

7. BUN

8. ammonia

9. hepatic encephalopathy

10. liver appearance

congenital: young, yes, normal, no, yes, increased, decreased, increased, yes, small

aquired: older, no, increased, yes, no, increased, decreased, increased, yes, cirrhotic

components of liver chirrhosis

fibrosis, inflammation, regenerative nodules

is chirrhosis end stage fibrosis

no

chirrhosis

1. key features

2. potential causes

3. consequences

1. regenerative nodules surrounded by fibrous septa commonly due to systemic pathologic processes causing cell death and inflammation

2. chronic toxins, drugs, chronic canine hepatitis, persistant viral infections

3. liver failure, portal hypertension (scar and compress)

chirrhosis most common species

dog ch

chirrhosis 2 gross types and how they are clinically different

1. micronodular

2. macronodular (dogs) - not neoplasia because liver is small

not clinically different

chronic canine hepatitis

1. predisposition

2. key features

3. signalment

4. dfdx

1. breed: bedlington terrior, doberman, dalmation, spaniels, west highland white terrier

2. chronic inflammation, fibrosis with potential chirrhosis, necrosis

3. middle age to old dog

4. copper toxicity (share some same breeds : doberman, belington terrier)

chronic canine hepatitis

1. definitive diagnosis

2. prognosis

3. treatment

1. histopath with copper stain and potential copper quantification of fresh liver

2. depends on severity, if loset lobular archetecture wit fibrosis then poor, if mild, can delay progression with anti inflammatory and hepatoprotectant medications

3. no specific treatment

3 reasons why the liver is a common target of hepatotoxins

1. anatomically: Gi toxins first come to liver

2. metabolic: compounds covered into toxic metabolites

3. toxins concentrate in bile for excretion and conjugated

describe the 2 types of hepatotoxins

1. predictable: cause lesions in exposed animals, dose dependent and reproducible

2. idiosyncratic/unpredictable: some animals affected at low dose, some not affected at high dose representing animals ability to metabolize → often drugs safe ofr majority of individuals

4 factors affecting hepatotoxin toxicity

1. competition for detox pathway (treat antifreeze with alcohol to saturate enzymes)

2. drug bind in plasma (albumin) but only unbound molecules can enter hepatocytes

3. decreased drug metabolism due to other drug causing first drug to stick around longer

4. genetic: defects in individual or species biochem pathways

name 5 types of hepatotoxin distribution

1. periprotal

• uncommon, toxins directly toxic

2. centrilobular

• common, drugs coverted into toxic metabolite

• appears likel hypoxic injury

3. midzonal

• rare

4. massive: panloabular

• not diffuse

• could affect 1 region, most often also diffuse affecting all parts of all lobes

5. random

• not usually toxic, usually infections

types of acute toxicity

1. cytotoxic

• hepatocellular injury

• most common centrilobular

• pallar from necrosis and lipidosis

• severe destruction of endothelium = hemorrhage

2. failure of bile excretion

• subtle

• secondary necrosis from bile toxic affects

3. both - often

what does acute toxicity look like in the liver grossly

enlarged with rounded margins

what are pigs more susceptable with toxins to in the liver

hemorrhage

what is the combination that is usually found in chronic liver toxicity

• chronic lymphohistocytic inflammation

• lipidosis

• fibrosis

• nodular regeneration

• cholestasis (choke bile flow)

what is seen histologically with chronic liver toxicity

collagen and fibros tissue seperating hepatocytes → this never goes away, bad sign

what is seen grossly with liver chronic toxicity

small and firm liver (microhepatica)

cyanobacteria

1. name

2. toxin

3. patient/is common?

4. lesion

5. chronic or acute liver toxicity

1. microcystis aeruginosa

2. microcystin LR

3. common, canine and ruminant

4. centrilobular to massive hepatic necrosis

5. acute

aflatoxins

1. agent

2. patient

3. resistance

4. pathogenesis

5. chronic or acute

1. fungi: aspergillus sp or peicillium species growing in stored crops with high moisture

2. dogs, cats, pigs, birds, salves, younger animals more than older

3. adult sheep and cattle are resistant

4. bind to adenine → adduct DNA formation → DNA mutates and is damaged → inhibit replication and risk of tumor formation

5. could be either

difference between acute and chronic aflatoxin hepatic toxciity

acute

• young, sensitive species

• large dose

• lesion: centrilobular to massive necrosis

chronic

• resistant animals

• low dose for a long period

• lesion: fibrosis, cholestasis, bilary proliferation, megalocytosis (large nuclei due to DNA damage), carginagenic

dfdx for chronic aflatoxins

pyrrolizidine alkaloids

pyrrolizidine alkaloids haptic toxicity

1. agent

2. susceptable patients

3. pathogenesis

4. gross

5. histo

6. dfdx

7. acute or chronic

1. non palatable plant toxin, eaten when there are poor forage options

2. pigs > cattle and hores> sheep

3. metabolize reactive pyrroles that are bioactivated and inhibit mitosis

4. small, firm, fibrotic liver

5. megacytosis, bilary proliferation, fibrosis

6. alfotoxins

7. chronic

copper hepatic toxicity

1. patient

2. potnetial contributing factors

3. pathogenesis

4. lesion

5. acute or chronic

1. sheep, bedington terrior

2. 
   

• high copper diet

• low diet zine and or molybdenum (compete with copper for absorption)

• hepatic injury - decrease meabolism

3. hepatocytes store copper, if they become overwhelmeed or injured they can release copper into plasma → injure RBCs/ hemolysis→ decrease O2 → hepatocellular injury → release more copper → more intravascular hemolysis

4. icterus (pre and post hepatic), hemoglobinuria, swollen, pale liver

2 most common non neoplstic disruptions of growth in liver

1. nodular hyperplasia

2. nodular regeneration

hepatic nodular hyperplasia

1. common?

2. patient

3. significance

4. gross

5. hsito

1. common

2. pig and dog, age assocaited

3. incidental

4. well demarcated nodules, appear like liver or slightly pale (lipids)

5. normal liver components and archetecture, include bile ducts

hepatic nodular regeneration

1. patient

2. mechanism

3. appearance

4. lesion

1. macro in dogs mostly

2. only with liver damage

3. multifocal

4. several nodules from areas of collapse and fibrosis

hepatocellular adenoma

1. type of disturbance of growth

2. patient/ common?

3. significance

4. gross

5. histo

1. neoplasia, benign

2. dog, common

3. incidental, slow growing but can outgrow blood supply and become necrotic, rupture and cause bleeding out

4. solitary, well demarcated, pale like adjacent liver

5. high mitotic rate, low atypia, no bile ducts

what disease is caused by hepadonovirus in woodchucks

hepatocellular carcinoma

hepatocellular carcinoma

1. type of disturbance of growth

2. patients

3. progression

4. common sign in blood work

5. gross

6. histo

1. neoplastic, malignant, aggressive

2. dogs and rodents

3. rare to mets, cause necrosis → rupture → bleeding out (more often than adenoma)

4. increased liver enzymes

5. solitary, poorly demarcated, pale, mottled pale and red (necrosis and hemorrhage), appears as multiple masses but is 1 mass increased

6. mitosis, cellular atypia, increased necrosis

what hepatic disturbance of growth is found in dogs and rodents and looks like many masses but is 1

hepatocellular carcinoma

biliary carcinoma

1. other name

2. patient

3. progression

4. gross

5. clinical signs

6. histo

7. dfdx

1. cholangiocellular carcinoma

2. cats

3. readily mets, often spread to lung by diagnosis

4. firm, white tan, umbilicated - lose tissue with necrosis and fibrosis contractions down in the center

5. Gi signs like IBD

6. necrotic cells lose nuclear staining, increased fibrous CT between cells

7. metastatic pancreatic carcinoma or GI adenocarcinoma

hepatic lymphoma

1. patient

2. what does it mean if in the liver

3. gross

4. dfdx

1. dogs and cats

2. often multicentric, liver is a common secondary site

3. pale, diffuse hepatomegaly, multifocal nodules (uncommon), lobular appearance with preference to portal areas (unknown why)

4. toxins, right heart failure (hypoxia), cholagitis

metastatic neoplasia to liver

• common?

• species

• gross

• common

• dogs (30% maligant ends up in liver)

  • flat plaques or masses growing down between hepatocytes

levels of respiraotry system

trachea → bronchioles → alveolus

what does gas normally need to cross in alveoli

1. alveolar epithelium

2. fused basement membrane

3. capillary endothelium

what gas does impaired diffusion impact first

O2 because CO2 is more diffusable

describe types of pneumocytes in alveolar epithelium

type 1

• squamous, little repair, no organelles, no regeneration

type 2

• cuboidal (not good for diffusion)

• regenerative, replace damaged Type 1 (proliferate as needed)

• produce surfactant to prevent alveoli from being stuck shut