Liver 1, 2 and 3 Flashcards
What are the three common congenital defects of the liver?
Absence/supernumerary lobes
Intrahepatic congenital cysts-
cats, polycystic kidney syndrome- Persian cats
Congenital portosystemic vascular shunts
What is an intrahepatic shunt and what causes it and what species?
What is an extrahepatic shunt and what species?
What doe they cause and how does the liver appear grossly?
What does it show histologically?
Why can it lead to cranial displacement of the stomach?
Intrahepatic shunt is caused by the persistence of the foetal ductus venosus which is the foetal connection between the left umbilical vein and caudal vena cava
-large breed dogs
Extrahepatic shunt- due to direct connections between the portal vein and vena cava
-Small breed dogs and cats
Large amount of blood bypasses the liver- causing a small liver
Histology- small hepatocytes, small/absent portal veins in triads, replications of arterioeles
Microheptatica- liver is small and therefore results in cranial displacement of the stomach
How can a liver be dislocated?
What can cause liver rupture?
What predisposes to liver rupture?
What does liver rupture lead to?
Diaphragmatic hernia
Torsion
Rupture-
RTA/ physical abuse- direct blunt truama
Usually when softer- alterations in parenchyma- (amyloid accumulation, neoplasms)
Ruptured liver- haemoperitoneum
What circulatory disorders can affect the liver?
Passive hyperaemia- acute/chronic congestion
Acquired portosystemic shunts
Teleangiestasis
Peliosis hepatis
What causes acute congestion of the liver?
What causes chronic congestion of the liver?
What condition does chronic lead to?
How does it appear grossly and histologically?
Describe the pathogenesis of chronic liver congestion
Acute congestion- heart failure as the animal died
Chronic- congestive heart failure
Leads to nutmeg liver
Grossly- slightly nodularr and rough, ascites, fibrin
Histological- centrolobular necrosis, fibrosis around central vein
Pathogenesis- congestion > decreased oxygen supply > hypoxia/anoxia > necrosis > fibrosis
What causes acquired portosystemic shunts?
Due to chronic liver disease- extrahepatic shunts form
Hepatic fibrosis and/or cirrhosis-
development of portal hypertension
dilation of non-functional veins between portal vein and vena cava
What is telengiectasis?
What species are more affected?
What is peliosis hepatis?
What causes it and what species mainly affected?
Telangiectasias-
dilation of functional blood vessels
Liver- intense dilation of small groups of sinusoids- pathogenesis unclear
Mainly in cattle and cats
Peliosis hepatis-
Irregular blood-filled cystic spaces in the liver parenchyma
Due to focal necrosis
mainly in cats
Why do hepatocytes easily degenerate?
How do they appear with degeneration?
High metabolic rate- prone to alterations in oxygenation of blood
‘Cloudy swelling’ or hydrophobic degeneration
non-specific change, the influx of Na and water into the cytoplasm
What is atrophy a specific type of?
What is it?
What causes hepatocyte atrophy?
Atrophy is a specfic type of degeneration
Reduction is the size of cells
Due to:
pressure from internal organs
reduced blood supply- shunt
What is hepatic lipidosis?
Describe the different pathogenesis?
What normally happens to fat in the liver?
Steatosis/lipidosis- abnormal accumulation of triglycerides with hepatocytes
Pathogenesis-
- Nutritional
- Excessive release of free fatty acids from adipose tissue
- Hypoxic lipidosis
- Toxic lipidosis
Normal-
free fatty acids from digestion to the liver into hepatocytes, free fatty acids esterified to triglycerides and form lipoproteins in circulation
What clinical scenarios predispose to lipidosis in a horse?
- Enterocolitis
- Feed restriction for treatment of colic
- Obesity
- Pregnancy
- Lactation
What 5 specific conditions can cause hepatic lipidosis?
Hyperlipidaemia-
diabetes Mellitus, pancreatitis, hypothyroidism, hyperadrenocorticism
with high dietary fat intake
Equine hyperlipidaemia, feline idiopathic
Ketosis- with starvation, diabetes mellitus, pregnancy/lactation
increased demand for gluconeogenesis or impaired utilisation of glucose- breakdown of adipose
Hypoglycaemia and fatty liver syndrome in small dog breeds
Hyperadrenocorticism-
glucocorticoids
decrease in lipogenesis
increase in lipolysis of adipose tissue, catabolism of skeletal muscle proteun, gluconeogenesis in liver
Tension related- cattle
What is glycogen?
What can cause an abnormal accumulation in the liver generally?
What specifically?
What stain can be used for diagnosis?
Glycogen- rapidly available energy store in cytoplasm or hepatocytes
Accumulation with abnormal glucose or glycogen metabolism
Specific-
Diabetes mellitus
Glycogen storage disease
Steroid induced hepatopathy- dogs (exogenous/iatrogenic, cushings)
PAS- periodic acid- Shiff- shows polysaccharides
What is amyloid?
What causes amyloidosis?
What can cause secondary amyloidosis?
Amyloid is a pathological proteinaceous substance normally in between cells-
space of dissé and sinusoids
Usually AA- amyloid associates-
synthesised in hepatocytes derived from serum amyloid A (SAA) precursor
usually systemic- several organs
Secondary- reactive
Immunoglobulin complication of chronic inflammation
What different pigments can be stored abnormally in the liver?
- Bile- jaundice
- Lipofuscin ceroid- older animals
- Melanin- sheep, cattle
- Iron porphyrin
What is haemochromatosis of the liver?
What are the pathological findings?
What stain can be used for diagnosis?
Hepatic haemosiderin accumulation due to increased iron uptake
common in some birds
Pathological findings-
Hepatomegaly
Haemosiderin accumulation in hepatocytes, Kuppffer cells, lymph nodes, pancreas, spleen
Periportal bridging fibrosis and nodulat regeneratoin
Perls prussion blue stain shows iron
What are the two causes of photosensitisation?
What can cause the two types?
Due to defective pigment synthesis-
endogenous pigment accumulation with defect in porphyrin metabolism
photodynamic agents- uroporphyrin, coprophyrin, protoporphryin
Bovine congenital erythropoietin porphyria- reddish-brown pigment deposition in dentin and bone and liver, skin leions develop because uropotphyrins absorb UV-A- reactive O2 speceis
Due to intoxications-
St John wort
Buckwheat
Spring parsely
What type of necrosis usually affects the liver?
How is hepatic necrosis classified?
How do they appear and what can cause them?
Usually coagulative necrosis- not liquefactive
Classified according to the location:
- Focal- aggregates of necrotic hepatocytes ‘random’-
disseminated infections - Zonal necrosis- a particular part of lobule/acinus- in the whole liver
- Massive necrosis- necrosis of the entire lobe
with extensive zonal or circulation, pigs with vit E/selenium, torsion
What are the three types of zonal necrosis?
Which is the most common
Centrolobar/periacinar necrosis-
Most frequent
hepatocytes most at risk of hypoxia, metabolically active (C-P450)
Mid-zonal
rare
Periportal necrosis
unusual, biliary inflammation, portal circulation
peri-portal necrosis- ascending inflammation
What is the name for the disease caused by Vitamin E/Selenium deficiency in pigs?
What does it cause?
Hepatosis dietetica
Associated with
Massive necrosis
Oedema of the gall bladder
Mulberry heart disease
What are the potential outcomes of liver necrosis?
Removal of dead hepatocytes
Resolution by
- Regeneration of hepatocytes
- Replacement of parenchyma by fibrous scar- due to destruction of reticular framework
What does fibrosis pattern depend on?- give examples
Depends on the distribution of injury
Periportal- biliary fibrosis
Centrilobular- periacinar fibrosis
Diffuse- bridging fibrosis
Post-necrotic scarring- massive necrosis
With diffuse necrosis and then bridging fibrosis of the liver, what are the different types?
Central- central- connects central veins with chronic congestion
Porto-portal- follows inflammation which extends to portal venules
Porto-central- after centrolobular necrosis
What is liver cirrhosis?
What are the characteristic features?
Cirrhosis- end-stage liver disease
Characteristic
Degeneration- disruption of entire liver architecture
Regeneration- regenerative nodules of heptocytes
Repair- bridging fibrosis
What are regenerative nodules and how do they appear?
What else is characteristic other than the three main?
What can cause it?
What are the sequelae?
Regen nodules- composed of hepatocytes, lack of lobular organisation, often hydropic degeneration, surrounded by fibrous connective tissues
Further characteristics-
parenchymal injury and fibrosis, balance between regeneration and constrictive scarring, reorganisation of vascular structure
Causes
Majority- idiopathic
Dogs- persistent CAV-1 or leptospira
Rare- parasitic, post-necrotic, pigment, biliary, toxic
Sequalae-
Jaundice- icterus- due to impairedred function
Ascites- portal hypertension
Heptatoencephalic syndrome- failure to remove ammonia
What is jaundice?
High billirubin in the blood causing yellow tinge of all tissues-
sclera, omentum, mesentery, fat, aorta
Seen only grossly and diffusely
What is pre-hepatic jaundice?
What causes pre-hepatic jaundice?
Due to excessive haemolysis of erythrocytes in peripheral blood- unconjugated bilirubin in blood
Causes-
Infections- lepto, EIA, haemolytic strep, anthrax, snake venom
Massive internal haemorrhage- bilirubin from disintegrating erythrocytes
Icterus neonatorum
What causes hepatic jaundice?
Due to severe heptic injury by:
toxic substances, infectious agents
Damaged hepatocytes do not uptake bilirubin or perform conjugation
or
Severe hepatocyte swelling blocks outflow of bile from canaliculi- reabsorbed into the blood
What is post-hepatic jaundice?
What causes it?
Describe haemoglobin breakdown?
What are the components of bile?
Due to obstruction of normal bile-flow- reabsorbed into blood- obstructive
Causes- hepatic jaundice, obstruction (flukes), fibrous tissue (cirrhosis), cholangitis, pressure, closure of excretory duct
Haemoglobin breakdown-
Haem-> biliverdin- >bilirubin-> (in macrophages) bind to albumin, uptake by hepatocytes, conjugation with glucoronic acid-> bilirubin glucuronides then exreted into gall bladder
Bile- water, cholesterol, bile salts, bile pigments from Hb
What is associated with disturbances of liver function?
Jaundice
Hypoalbuminaemia- reduced synthesis and secretion of albumin
Coagulopathy- reduced synthesis of clotting factors
Hyperammoniameia- reduced detoxification by conversion to urea
Portal hypertension- cities
What is hepatic encephalopathy?
What causes it?
What lesions does it lead to?
Seen with hepatic failure it is due to exogenous metabolites in circulation which pass the blood-brain barrier
Hyperammonemia- inhibit the generation of excitatory and inhibitory post-synaptic signals, ammonia alters the transit of amino acids, water, electrolytes across the neuronal membrane
Lesions-
Cerebral oedema
Neuronal necrosis and swelling
Degeneration of astrocytes
What is nodular hyperplasia?
What are regenerative nodules?
Nodular hyperplasia-
Not a neoplasm- common in older dogs, single or multiple
Compression of normal adjacent tissue, containing portal areas (not regenerative)
Regenerative nodules-
not a neoplasm, common in older dogs, multiple or numerous, adjacent tissue usually fibrotic, loss of lobular architecture
Describe the characteristics of hepatocellular adenoma?
Usually single
Sharply delineated
No portal areas/lobular structure
Compression of adjacent tissue
Benign- size main issue
Describe the characteristics of hepatocellular carcinoma
What can cause it?
Compression and invasion of adjacent tissue
Metastasis
Growth pattern-
Trabelular
Acinar
Solid
Viral aetiology- hepatitis B in humans
What neoplasms can affect the bile ducts?
How do they function?
Bile duct adenoma-
often cystic, usually single
sharply delineated, compression may be problematic with size
Bile duct carcinoma-
Commonly spreads along the biliary tract,
metastasis- hepatic serosa, LNs to lungs
Often induce desmoplasia
What can cause liver haemangiosarcomas?
Liver as the primary site
or metastasis
Secondary neoplasms common- portal vein, contact- often lymphomas
What does acute hepatitis cause?
What happens in acute hepatitis due to septicaemia?
Degeneration/necrosis of hepatocytes
Leukocyte infiltration in periportal connective tissue and/or within sinusoids
Septicaemia-
increased numbers of leukocytes in sinusoids
activation of kupffer cells
What happens with chronic hepatitis?
What species and breed is affected by chronic active hepatitis?
What does it cause and what is the end stage?
Chronic hepatitis-
predominantly periportal infiltration by lymphocytes and plasma cells
progressive periportal fibrosis- bridging fibrosis
hepatocyte apoptosis/necrosis and some evidence of regeneratoin
Chronic active hepatitis-
Dogs- dobermans
Activity- determined by the quantity of inflammation and extent of hepatocellular death
Cause- unknown- lepto?
End stage- cirrhosis
What is cholangitis/cholangiohepatitis?
What is feline cholangitis associated with?
What are the clinical findings?
What are the three characteristic lesions?
Cholangitis- inflammation originating from the biliary tree
Feline cholangitis-
often associate with inflammatory bowel disease and chronic pancreatitis
clinical findings- ascites, jaundice, polyphagia, weight loss
Three characteristic lesions
suppurative cholangitis
Lymphocytic and plasmacytic periportal infiltration, bile duct hyperplasia and periportal fibrosis
Biliary cirrhosis
What 6 viruses cause viral hepatitis?
Infectious canine hepatitis- CAV-1
Equine herpesvirus infeciton- EHV-1
Canine herpesvirus infection- CaHV-1
Rabbit haemorrhagic disease- calicivirus
Feline systemic calicivirus infection
Feline infectious peritonitis- FCov
Viral hepatitis occurs in the course of systemic infection- viraemia
What causes infectious canine hepatitis?
Describe the pathogenesis?
What happens to the liver with high titre and low titre?
How does it appear histologically?
Agent- canine adenovirus type 1
Pathogenesis-
Oronasal infection- tonsils, regional lymph nodes, lymphatics, thoracic duct to the blood- viraemia
To the liver (hepatocytes and kupffer cells), eye (corneal epithelium), kidney (glomerular epithelium) and blood vessels
High titre- acute necrotising hepatitis
Low titre- chronic hepatitis, fibrosis, persistent infection
In animals which survive the acute phase of the disease- full liver regeneration can occur
Dog- necrotic hepatocytes, intranuclear bodies
What herpes virus can cause viral hepatitis?
Describe the pathogenesis?
How does it grossly appear?
How does it histologically appear?
Equine herpesvirus 1- rarely 4
Pathogenesis-
Transplacental infection- to the uterus
Uterus endothelial cells, perivasculitis, thrombi to placental detachment leading to late abortion >7mo
Foetus- multifocal necrosis in liver, lung, thymus, spleen, brain, adrenal glands
Gross- disseminated, multifocal necrosis
Histology- inflammation and intranucelar bodys
How does the canine herpes virus transmit and affect adults, neonates and foetuses?
Adult- venereal, respiratory
Localised infection and replication
Persistence in respiratory and genital tracts- latency
Stress, immunosuppression, and pregnancy leads to latent infection and replication
Neonate-
Ingestion, inhalation
> 2 weeks leads to same as adult
<1 week- epithelial cell replication, mucosal invasion
Can lead to latent infection or leukocyte associated anaemia
Foetus- in utero
Leukocyte associated viaemia
Lymphoid hyperplasia
Generalised infection- diffuse necrotising vasculitis, multifocal haemorrhagic necrosis of many organs
Recovery- residual CNS signs
Neonatal- illness, death
Pre-natal- abortion, still birth
What agent causes rabbit haemorrhagic disease?
What causes feline infectious peritonitis?
What is the pathogenesis?
Rabit haemorrhagic disease- calicivirus
Pathogenesis- faeco-oral transmission
acute disease with massive necrosis of hepatocytes, DIC
FIP- feline coronavirus
Pathogenesis
Oral infectoin- infection of enterocyres
to monocyte-associated viraemia
granulomatous (peri)phlebitis/serositis/heptatitis
What are the routes of entry for liver abscesses or granulomas?
Portal vein
Umbilical arteries
Hepatic arteries
Ascending infection via the bile duct systeem
Parasitic migration
Direct extension of infection from adjacent tissue
Name the 6 bacteria that can cause liver abscessed and granulomas?
Enteric bacteria
Francisella tularensis
Nocardia asteroides
Actinobacillus spp
Mycobacterium
Fusobacterium necrophorum
What agent causes necrobacillosis?
What conditions does it cause in ruminants’ livers and why?
Fusobacterium necrophorum-
filamentous, gram-negative, anaerobe, commensal in GI
Ruminants- rumenitis-liver abscess syndrome
Carbohydrate-rich diet- ruminal acidosis:
defects in ruminal mucosa, access of bacteria to blood vessels, portal vein
multifocal necrosis, abscess formation
What agent causes tularemia?
What are the reservoirs for the agent?
What is the pathogenesis?
What does it cause grossly?
Agent- Francisella tularensis- zoonosis
Pleomorphic- gram-negative, non-spore-forming bacillus
Ticks are reservoirs and vectors
Pathogenesis-
inoculation site- skin lesions, tick bite, prey animals (intestine)
localised infection and regional lymphadenitis- bacteraemia, dissemination
Gross pathology-
ulceration of lymph nodes or Peyer’s patches with enteric infection
necrotising lymphadenitis, hepatitis, splenitis
What kind of bacteria is leptospirosis?
What species can it infect?
Describe the pathogenesis and gross lesions on the liver
Motile, filamentous, spiral-shaped
Dogs, cats, horses, ruminants- zoonosis
Pathogenesis- penetration of mucous membranes, abraded skin- replication in blood to the kidneys, liver, spleen, brain, eyes, genital tract
Dogs- dysfunction due to cell damage by toxins, development of chronic active hepatitis, mottled from haemorrhage and necrosis- mottled haemorrhage
Kidneys- tubular necrosis
DIC, uveitis, abortion
Jaundice- due to intravascular haemolysis and/or bile stasis
haemolysis leads to anaemia, centrilobular necrosis in the liver secondary to ischaemia
Liver lesions- loss of tight junctions between hepatocytes, induction of mitosis
Silver impregnation- warthin-starry stain shows leptospira
What agent causes Tyzzer’s disease?
What animals are more commonly affected?
What is the pathogenesis?
Agent- clostridium piliforme-
motile, spore-forming, gram-negative, obligate intracellular, commensal in GI
Young or immunocompromised animals
Pathogenesis-
Contact with rodent faeces- proliferation in intestinal epithelial cells
Immunosuppression- spread to the liver- necrosis
What can cause parasitic hepatitis?
Protoxoan- toxoplasmosis, coccidiosis, leishmanias
Metazoan infections- trematodes, cestodes, nematodes
Where are toxoplasmosis tachyzoites found?
Where does Eimeria stiedia (coccidiosis) replicate in hare/rabbit?
How do animals get infected with leishmaniasis?
What does it cause and infect?
Toxoplasmosis tachyzoites in hepatocytes
Coccidiosis- eimeria stiedai- proliferation of bile duct epithelium
Leishmaniasis- infection via biting insects, generalised chronic infection
infection of macrophages- rupture of cells
What is acute fascioliasis?
What are the potential outcomes?
What is chronic fascioliasis?
What lesions occur?
What are the possible consequences?
Acute fascioliasis-
due to larval migration- haemorrhage and necrosis with eosinophils and granulomatous inflammation
Consequences- hepatic dysfunction, anaemia- healing, black disease or chronic
Chronic fascioliasis-
Mature fluked in bile ducts
Lesions- chronic hyperplastic cholangitis, peribilliary fibrosis +/- calcification
Possible consequences- anaemia, hypoproteinaemia, chronic debilitation, death
What metazoan/cestodes cause parasitic hepatitis?
Hepatophilic-
cystic echinococcosis- echinococcus granulosus
Alveolar echinococcosis- E. multilocularis
Cysticerus cellulosae- C. bovis
Serophillic-
C. tenuicollis, C. pisiformis
Why do nematodes cause parasitic hepatitis?
What causes milk spot liver in pigs?
How does it appear histologically?
Traumatic lesions due to migrating larvae
Ascaris sum- milk spot liver
