Hepatobiliary Flashcards
(53 cards)
1
Q
What does an increase in AST indicate?
A
Liver or Muscle damage. Must do CK to determine if muscle is involved
2
Q
What does an increase in Alk Phos and GGT indicate?
A
Cholestasis
3
Q
What are some specific signs of hepatic disease?
A
- Hepatomegaly
- Microhepatica
- Icterus
- Ascities
- Hepatoencephalopathy
4
Q
What are the 2 categories of Hepatic Enzymes?
A
Hepatocellular Leakage Enzymes (indicates hepatocellular damage) Induced Enzymes
5
Q
What are the Hepatocellular Leakage Enzymes?
A
- Alanine Aminiotransferase (ALT)
- Aspartate Aminotransferase (AST)
- Sorbitol Dehydrogenase (SDH)
- Glutamate Dehydrogenase (GLDH)
- Ornithine Carbamyltransferase (OCT)
6
Q
Where is the highest activities of ALT found?
A
In hepatocytes and striated (Skeletal and Cardiac) Muscle Cells
7
Q
Whats the difference between Horses and Dogs & Cats when talking ALT?
A
In Horses ALT is generally from Muscle In Dogs & Cats its from Liver.
8
Q
If we lose 75% of the functional mass of our liver what Biochem changes would we see? (Decreased Functional Hepatic Mass)
A
Decrease in :-
- Glucose
- Urea
- Albumin
- Cholesterol
9
Q
What is the halflife of ALT in a dog?
What is the half life of ALT in a Cat?
A
Dog 60 Hours (2-3days)
Less than 24hours in a Cat
10
Q
What is the half life of Alk Phos in a dog?
A
About 3 days
11
Q
If our Urea is slightly high and our Creatinine is normal what would we need to do next?
A
Do a SG to determine if the azotemia is pre-renal or primary renal.
Concentrated SG = Pre-renal
12
Q
What are some non-specific clinical signs of Hepatic disease?
A
- Depression
- Weight Loss
- Anorexia
- Vomiting
- Abdominal Pain
- PU/PD
13
Q
What are some tests we can do to test for liver disease
A
- CBC
- Serum Biochemistry
- Tests of Liver function
- Urine Sample
- Liver Biopsy
- Abdominal imaging
14
Q
What is this cell?
A
Leptocyte
15
Q
What is the name of this RBC
A
Schistocyte
16
Q
If a Serum biochem results showed a Hyperbilirubinaemia what would your differentials be?
A
- Hyperbilirubinaemia
- Haemolytic Disease
- Decreased hepatic functional mass
- Cholestasis
17
Q
In Dogs and Cats what is ALT considered to be specific for?
A
Hepatic Injury
It will also increase with SEVERE muscle injury
18
Q
After initial liver damage when does serum ALT activity :-
- First increase seen?
- Peaks?
- Returns to the reference range?
A
- 12hours after injury
- 1-2days
- 2-3weeks
19
Q
- What is an increase in AST (Aspartate Aminotransferase) indicate?
- How do you differentiate between the locations that AST has come from?
A
- Acute or Chronic liver injury
- Muscle damage in all domestic species
- Run a CK concurrently to differentiate between AST from muscle and liver.
20
Q
What is the half life of AST in the :-
Dog
Horse
A
- Dog = 12 hours
- Horse = 6-7days
21
Q
Which test will indicate Liver/Biliary damage?
A
- Hepatocellular leakage
- ALT
- AST
- SDH
- GLDH
- OCT
- Induced enzymes
- ALP - Alkaline Phosphatase (AlkPhos)
- GGT - Gamma Glytamyl transferase (GGT)
22
Q
How do you differentiate between acute and an ongoing disease process of the liver?
A
Doing AST/ALT testing a few days apart
23
Q
What tests would you do to measure hepatic synthetic capability?
A
- Albumin
- Urea
- Cholesterol
- Glucose
- Clotting Times
24
Q
What of the liver leakage enzymes do we check in Horses, Sheep, goats and cows for detecting hepatocellular damage?
A
SDH - Sorbitol Dehydrogenase
25
What are the Liver Induced enzymes?
Alkaline Phosphatase (ALP)(Alk Phos)
Gamma Glytamyl Transferase (GGT)
26
What does an increase in ALP activity indicate?
Cholestasis
PS. Only increases of ALP are of significance decreases are not
27
Outline Bilirubin metabolism and excreation
* Extravascular or intravascular hemolysis of RBC, Haemoglobin broken into Haem and Globin -
* **Unconjugated bilirubin + albumin** heads to the Liver wher it becomes **CONJUGATED BILIRUBIN**
* Through the billiary system into the small intestine where bacterial proteases convert it into **Urolibinogen**
* 10% of this Urolibinogen is reabsorbed and taken up via the portal vein. The remaining 90% is eliminated in fecaes
* The Urobilinogen that is now in the blood is then filtered out in the kidney and excreted in urine.
28
What can Hyperbilirubinaemia be caused by?
* Increased destruction of RBC (Pre-Hepatic) - Unconjugated
* Hepatocellular dysfunction (Hepatic) - Mixed
* Cholestasis (Post-hepatic) - Conjugated
29
What would we see in a horse that is inappetent or decreased feed intake?
The horse could be jaundice and have an increase of plasma biliruben due to the decrease in hepatic up-take and conjugation of biliruben by the liver.
It rapidly resolves following the resolution of the anorexia or an infusion of glucose.
30
Bile Acids
Where are Bile acids synthesised?
WHat is their function?
how are the secreted?
* Bile Acids are Synthesised in the liver from cholestrol
* The Function of Bile Acids are to solubilise lipids and aid in fat digestion.
* Conjugated and secreted into the Bile
31
* How do we test for Bile Acids?
* What can an Increased Bile Acids result be cause by?
* Measure of bile acids in paired (Fastin and 2hr post-prandial samples
* Increased Bile Acid Causes
* Porto-systemic Shunt
* Liver Failure
* Cholestasis
* Inappropriate contraction of the gall bladder
* SIBO (Small Instestine Bacterial Overgrowth)
32
What is the upper limit of fasting Bile Acid concentration for Dogs and Cats?
Dogs \> 30
Cats \>25
33
How is ammonia produced an metabolised within the body?
* Produced inthe GIT by breakdown of Amino Acids and urea by microflora
* Transported to liver via portal circulation
* Converted to Urea via urea cycle in the liver
* Excreated in Urine
34
Why would we see Ammonium bi-urate crystals in urine?
* Normal finding in Dalmations
* Often seen when there is increased blood ammonia levels
35
If we suspect liver insufficency what would you test for to see?
You would see a decrease in :-
Urea
Ammonia
Glucose
Albumin
Clotting Times
36
What cells make up the liver?
* Hepatocytes
* Endothelial Cells
* Kupffer Cells
* Biliary Epithelial cells
* Hepatic Stellate cells
37
What are the normal liver functions?
* Bilirubin/Bile acid metabolism
* Excretion and conduction of bile
* Carbohydrate and lipid metabolism
* gluconegenesis/glycolysis and ketogenesis
* Xenobiotic metabolism
* Especially via cytochrome p450 enzyme system
* Protein synthesis
* Albumin, clotting factors, acute phase proteins
* Also principal site of ammonia metabolism
* Immune Function
38
What is Bile for?
How is it conducted and excreted?
* Important for digestion of fats (Bile acids) and for elimiation of wastes (eg. Bilirubin)
* Excreted into canaliculi --\> intralobular bile ducts (Canals of hering --\> interlobular bile ducts --\> hepatic ducts --\> gallbladder (when present) via cystic duct --?\> common bile duct --\> duodenum
39
What are some consequences of liver dysfunction?
* Disturbances of bilirubin excretion/secretion
* Cholestasis --\> icterus/jaundice, hyperbilirubinuria
* Inadequate conversion of ammonia to urea
* Increased ammonia, decreased urea, hepatic encephalopathy
* Defects in protein synthesis
* Hypoalbuminaemia, decreased clotting factors (coagulopathy)
* Abnormal carbohydrate and fat metabolism
* usually hypoglycemia
* May see decreased cholesterol, hepatic lipidosis
* Aquired portosystemic shunting
* hepatic encephalopathy
* Portal Hypertension
* Ascites
* Abnormal metabolism of chlorophyll
* Secondary (type III) photosensitisation (Herbivours)
* Failure of Kupffer cell activity
* Can lead to increased bacteria entering circulation
* Altered metabolism of drugs and chemicals
40
What is the functional reserve of the liver?
70-75%
41
What are some clinical signs of hepatic disease?
* Lethargy/malaise/ill thrift/depression
* Abdominal distension (Ascites, hepatomegaly)
* CNS signs (hepatic encephalopathy)
* Inappetance/anorexia
* Vomitins and/diarrhoea
* Jaundice and dark urine
* Abdominal Pain
* Weight Loss
* secondary Haemostatic disorders
* Photosensitisation
* Drug intolerance
42
What is Jaundice?
What are the 3 subcategories of causes of Jaundice?
* Hepatic injury frequesntly manifests as increased bilirubin in the blood (hyperbilirubinaemia)
* High concentrations leads to yellow staining of the tissue by bilirubin = jaundice (Icterus)
* Pre-hepatic
* Hepatic
* Post-hepatic
43
Of the 3 categories of Jaundice give an example of each and give the mechanism
* Pre-Hepatic
* Due to increased RBC destruction (Haemolysis)
* IMHA, Infectious (rickettsia) Metabolic
* Increased unconjugated (at first)
* Hepatic
* Due to liver disease
* Any disease compromising the livers ability to uptake conjagate, and/or secrete bilirubin
* Usually severe, difuse hepatic disease eg cirrhosis, widespread acute HC degeneration/necrosis
* Increased unconjugated and conjugated bilirubin
* Post-Hepatic Jaundice
* Due to bile duct obstruction eg pancreatitis, choleliths
* Increased conjugated bilirubin
44
What are the main portals of entry by which pathogens gain access to the liver?
* Haematogenous
* Biliary
* Direct Penetration
45
What are the 3 patterns of acute degeneration/necrosis of the liver?
1. Random hepatocellular degeneration/necrosis
* Typically an infectious agent eg bacteria, viruses (herpes), protozoa
2. Zonal hepatocellular degeneration/necrosis
3. Massive Necrosis (and submassive)
46
What are the 5 zonal patterns of hepatocellular degeneratoin/necrosis?
1. Centrilobular degeneration/necrosis (periacinar)
2. Paracentral degeneration/necrosis
* Affects apex of acinus (wedge shaped around central vein)
3. Midzonal degeneration/necrosis
4. Periportal degeneration/necrosis
5. Bridging degeneration/necrosis
47
What would the likely cause of Acute Hepatitis be?
* Usually infectious and part of systemic infection
* Viral : Herpesvirus, Canine infectious hepatitis (CAV-1), FIP
* Bacterial : Salmonellosis
* Parasitic : Toxoplasma godii
* Fungi : Zygomycetes
* Often multifocal random
* Inflammation
* Neutrophils dominate, fibrin, +/- lymphocytes if viral, can lead to abscessation
* Hepatocellular necrosis
48
What are some examples of Acute Hepatic Disease
* Herpesvirus
* Canine infectious hepatitis (Canine adenovirus 1 CAV-1)
* Campylobacteriosis
* Hepatosis dietecia
49
What are the livers responce to injury?
* Regeneration
* Mild to moderate single incident sublethal injury may result in full regeneration and full restoration of function
* Fibrosis
* Repeated bouts of low-level sublethal injury injury or severe, single incident injury can initiate hepatic fibrosis and nodular hepatocellular regneratio - this can lead to progressively worsening fibrosis which eventually bridges across the lobule/between lobules and may progress to cirrhosis
* Biliary hyperplasia
* Non-specific responce to a variety of insults, particularly prominent with biliary obstruction
50
Define Cirrhosis
* A diffuse process characterised by fibrosis and conversion of the normal liver architecture into structurally abnormal lobules
51
List the clinical signs for:-
Acute liver failure
Chronic Liver Failure
* **Acute Liver Failure**
* Early CS
* Dullness, depression, neurologic manifestation (hepatic encephalopathy)
* Vomiting, abdominal pain
* Weakenss (Hypoglycaemia)
* PU/PD, bilirubinuria
* Secondary haemostatic disorders +/- DIC
* Bilirubinaemia/bilirubinuria
* Late CS
* Icterus
* Hepatic encephalopathy
* Chronic Liver failure
* Hypoalbuminaemia
* Portal hypertension --\> ascites
* Acquired portosystemic shunts
* Cutaneous lesions - hepatocutaneous syndrome in dogs and photosensitisation in herbivores
* Imparement of immune function --\> endotoxaemia/systemic infection
52
What is Cholestasis?
What are the 2 types of Cholestasis?
* Suppression of bile production/bile flow
* **Intrahepatic** (Most common)
* decreased ability of Hepatocytes to metabolise/excrete bile (injury/congenital)
* HC swelling --\> compresses and blocks canaliculi
* Inflammation +/- necrosis of bile ductules
* **Extrahepatic**
* ****Due to blockage of extrahepatic bile ducts
* Intraluminal choleliths/parasites
* Extraluminal pressure (adjecent neoplasia, inflammation eg pancreatitis)
53
What are the 3 stages of Chronic Copper Toxicosis:Sheep?
* Slow hepatic copper accumulation within lysosomes due to :
* Excess dietary intake, low molybdenum/ sulfur pastures or pre-sensitisation due to pasture containing hepatotoxic phytotoxins
* Hepatocellular damage
* Haemolytic Crisis
* Stressful event triggers sudden release of coppor into blood --\> triggers acute, severe intravascular haemolysis --\> anaemia --\> extensive centrilobular hepatocellular necrosis due to tissue hypoxia
