Hepatobiliary III Flashcards
(48 cards)
Chronic hepatitis in dogs:
histological features
Hepatocellular apoptosis or necrosis, variable mononuclear or mixed inflammatory infiltrates, regeneration, and fibrosis.
Drug and toxins as Etiology of Chronic hepatitis in dogs.
Many potential causes. Underlying cause is not often identified. Some underlying conditions are treatable, diagnostics are worthwhile.
Drugs and toxins:
* Variety of drugs and toxins can cause liver injury.
Important to identify any toxin exposure and all medications given to the dog. E.g herbal remedies
* Intoxications are often acute and followed by resolution or death.
* Some can however, lead to CH (chronic hepatitis).
Infectious agents behind chronic hepatitis in dogs.
Viruses have not actually been identified as a cause of CH in dogs.
Bacterial cultures of liver and bile from dogs with CH are usually negative. Not all bacteria chronically infecting the liver and potentially causing CH are easy to grow invitro.
Leptospiral organisms were identified using florescence in situ hybridization (FISH) in 10 dogs with granulomatous hepatitis.
Immune mediated causes behind chronic hepatitis in dogs.
Immune-mediated underlying cause is not identified for about 60% of dogs with primary hepatitis.
Evidence supporting an immune-mediated etiology includes:
1) Female predisposition in Doberman Pinschers, English Springer Spaniels, and other breeds of dog
2) Association with certain major genetic variations in Doberman Pinschers and English Springer Spaniels
3) Positive titers for autoantibodies that target hepatic proteins in Doberman Pinschers and other breeds of dog
4) Positive response to immunomodulatory drugs in some.
Histologically predominant lymphoplasmacytic infiltrate, often with interface hepatitis (destruction of hepatocytes at the limiting plates), is expected.
Presumptive diagnosis made by ruling out other known causes, typical histopathologic findings, and documenting a positive response to immunomodulatory therapy.
Describe Lobular dissecting hepatitis.
Is an uncommon form of chronic hepatitis often seen in younger dogs.
Histologically bands of myofibrocytes and thin strands of extracellular matrix between individual and small groups of hepatocytes.
Progresses quickly to cirrhosis/end-stage liver disease.
Likely represents a pattern of liver injury rather than a distinct disease process.
Describe copper as a common cause of chronic hepatitis in dogs.
Seen in about a third of primary hepatitis cases.
- Liver is the principal recipient of copper absorbed from the GI tract.
- Copper in hepatocytes is bound to proteins, when hepatocyte copper binding proteins are saturated, harmful free copper ions are released that can form radicals capable of causing oxidative liver damage.
Breed predisposition:
Dogs with genetic defects in its biliary excretion and/or due to increased dietary intake of copper.
Bedlington Terrier, Labrador Retriever, Doberman Pinscher, Dalmatian, and West Highland White Terrier etc.
Can develop in other breeds or mixed-breed dogs.
Chronic hepatitis in dogs: Pathogenesis
Chronic inflammation, inflammatory cells move in in excess ->
infiltrate with copper accumulation in centrilobalar zone ->
activation of myofibroblasts, including hepatic stellate cells and portal fibroblasts ->
increase in extracellular matrix deposition relative to its removal with resultant hepatic fibrosis.
Hepatic fibrosis diminishes liver function, as hepatocytes are replaced by fibrous tissue.
Complications of Chronic hepatitis in dogs (2 main and how they occur).
Portal hypertension, Ascites
- Fibrosis leads to increased intrahepatic resistance to blood flow.
- Then Hepatic portal vein hypertension
- Promotes formation of ascites
- Can cause development of aquired PortoSystemic shunts, ammonia dysmetabolism and hepatic encephalopathy.
Dogs often have hypoalbuminemia -> low oncotic pressure, also contributing to ascites formation.
Describe dog Chronic hepatitis Complication Hemostasis in the GI tract.
Liver synthesizes all the coagulant and anticoagulant factors.
Spontaneous bleeding is rare, but can occur in end-stage disease and may contribute to GI bleeding.
Portal vein thrombosis, a potential complication can contribute to portal hypertension.
GI signs are common in CH
Gastroduodenal ulceration has been a purported complication.
Chronic hepatitis in dogs: Signalment and Clinical signs
Can occur in any breed or mixed breed dog
Increased risk for developing in American Cocker Spaniels, Doberman Pinchers, English Cocker Spaniels, English Springer Spaniels, Labrador Retrievers etc.
Median age at diagnosis 7.2 years, range is wide though.
Early in CH, there may not be any clinical signs and the earliest are often nonspecific: Decreased appetite and lethargy.
Liver specific signs tend to occur later in the course of disease: Icterus, ascites, or HE.
Blood test changes in chronic hepatitis in dogs.
Nonspecific hematological changes
Mild to moderate thrombocytopenia
Mild normocytic normochromic non-regenerative anemia.
Increased serum ALT activity (Earliest and most common biochemical change, 71% sensitive for subclinical CH) but Some dogs with CH have normal ALT activities.
Serum ALKP activities commonly increased (35% sensitive for subclinical liver disease). Usually of lower magnitude and occur later in the course of disease than those of ALT.
Serum AST and GGT activities are less consistently increased.
Liver specific Blood test changes in chronic hepatitis in dogs.
TBIL: Many dogs with CH have normal serum bilirubin concentrations. Hyperbilirubinemia typically occurs late in the course of CH and is a negative prognostic factor.
BUN, ALB, CHOL all decrease also late in the course of CH.
Pre- and postprandial serum total bile acids Lack of sensitivity for CH and other liver diseases in the absence of PSS.
Decreased plasma protein C activity,
prolonged coagulation times,
hypofibrinogenemia and
decreased plasma antithrombin activity may be noted.
Dogs with CH may be hypocoagulable, hypercoagulable, or normocoagulable and hyperfibrinolysis is common……
Diagnostic Imaging in diagnosis of chronic hepatitis in dogs.
No diagnostic imaging modality allows a definitive diagnosis!
Abdominal radiographs are Often normal but may reveal microhepatica.
Abdominal ultrasound may show Diffusely hyperechoic liver due to fibrosis and/or glycogen deposition.
With advanced liver disease/cirrhosis nonspecific changes: mixed echogenicity, subjective microhepatica, and/or small nodules.
Absence of changes on US does not rule out CH!
Acquired portosystemic collateral blood vessels (often multiple anomalous vessels caudal to the kidneys) or evidence of portal hypertension (reduced or reversed portal blood flow).
CT angiography also allows the detection of aPSS or portal hypertension.
Cytology in diagnosis of chronic hepatitis in dogs.
Straightforward and of relatively low risk, FNA sample taken through abdominal wall.
BUT Chronic hepatitis cannot be definitively diagnosed cytologically.
Cytologic findings consistent with hepatic fibrosis
Increased spindle cell to hepatocyte ratio and mast cells.
The presence of hepatic copper granules on rhodanine stained cytologic smear is consistent with copper accumulation but Their absence does not rule this out.
Liver biopsy in diagnosis of chronic hepatitis in dogs.
Definitive diagnosis of CH and subsequent treatment planning requires histologic assessment!
Needle, laparoscopic or laparatomy: Each have own advantages and disadvantages.
* Risk of hemorrhage
For Culture, Histology, Copper Quantification do
Sampling of multiple liver lobes.
Histologically: Hepatocellular apoptosis or necrosis, a variable mononuclear or mixed inflammatory infiltrate, regeneration, and fibrosis.
Infectious diseases testing in diagnosis of chronic hepatitis in dogs.
Bile/liver specimen should be submitted for aerobic/anaerobic bacterial culture.
Testing for geographically relevant infectious agents should be performed and If histology reveals granulomatous/pyogranulomatous hepatitis with no apparent etiology.
Fluorescent in situ hybridization for eubacteria can also be helpful.
Chronic hepatitis in dogs: Management with General support. (4)
High-quality diet
Cytoprotective agents
Treating any complications of CH
Copper chelators and immunomodulatory
* For histopathologically confirmed cases!
Copper-Associated chronic hepatitis in dogs: Indications for chelation therapy
When Hepatic copper concentrations exceed 1000 mcg/g dry weight or Considered when between 600 and 1000 mcg/g dry weight. (Depending on the presence, grade, and localization of histologic copper staining.)
In the absence of copper quantification so Histologic assessment grade of copper accumulation.
Copper score of ≥3 out 5 typically supports chelation initiation.
Copper-Associated chronic hepatitis: Chelating Agents: Actions, Options, Side Effects
Removes hepatic copper by making it soluble -> excreted in the urine.
E.g. compound D-penicillamine (most common)
* Not licensed for use in small animals
* Commonly causes GI side-effects
* Give with small amount of food
* Add antiemetics and/or reduce the dose temporarily
* Glomerulonephropathy and dermatological lesions uncommonly in which case discontinue the medication.
E.g. Trientine
* Less experience
* Not recommended in a recent expert consensus statement
E.g. Ammonium tetrathiomolybdate
* Appears to be reasonably well-tolerated
* Further studies are needed before its routine use can be recommended.
Copper-Associated chronic hepatitis: Duration of chelation therapy
Treatment usually takes months, 6-10 months of chelation should be adequate for most dogs. Rarely prolonged therapy can result in copper deficiency.
* Microcytic hypochromic anemia, anorexia, vomiting, and weight loss
Must monitor the dog’s clinical signs and liver enzyme activities, especially ALT. Several months for ALT activity to return to normal. Advisable to treat for at least a month after this.
A second hepatic biopsy procedure with hepatic copper quantification can be considered.
Some dogs require repeated intermittent therapy with D-penicillamine. Bedlington Terriers may need lifelong therapy.
Decision to restart therapy is made based on an increasing ALT activity.
Copper-Associated chronic hepatitis: Diet and supportive care
Copper-restricted diet Such as a commercial liver support diet.
Zinc acetate is suggested, it decreases copper absorption from GI tract. Zinc Concentrations should be measured to avoid toxic concentrations.
Start this diet when D-penicillamine is discontinued!
S-adenosyl methionine and/or vitamin E are Antioxidant agents that can be supplemented as
Accumulation of copper causes oxidative stress.
Immune-mediated chronic hepatitis in dogs tx
Immunomodulatory therapy but only after other Causes such as copper, toxins, drugs and infectious agents have been eliminated first.
Prednisolone
* Liver enzyme activites may improve but often do not return to normal
Cyclosporine
* Median time to remission 2.5 months. Defined as a return of ALT activity to the normal range.
Mycophenolate mofetil (immunosuprresive) and
Azathioprine are also options if prev dont work.
Chronic hepatitis in dogs: Cytoprotective agents (4)
Managing the complication of liver disease: Ascites. (5)
Avoid high sodium diets.
Spironolactone for diuresis (Aldosterone receptor antagonist) Because mechanism of ascites formation in chronic liver disease involves RAAS activation so you wanna reduce RAAS.
Add furosemide If spironaloctone ineffective alone. But can cause Hypokalemia and metabolic acidosis, both of which may precipitate Hepatic encephalopathy,
Closely monitor patient during diuresis therapy!
* General condition, hydration status, abdominal circumference, serum electrolytes, renal values, serum protein concentrations.
Paracentesis when Dyspnea due to cranial displacement of the diaphragm and High intra-abdominal pressures causing inappetence and discomfort.
