Lab 10- Liver 2 Flashcards
What can impaired protein synthesis cause?
decreased colloid osmotic (oncotic) pressure of the blood, quicker ESR (erythrocyte sedimentation rate) (hypoalbiminaemia), and longer PI (prothrombin time)
Why does the blood pressure decrease with impaired protein synthesis
(due to hypoalbuminaemia),
Why does the PI time increase with impaired protein synthesis
lower fibrinogen level
What can impaired liver function lead to?
hormonal imbalances
lysomal enzymes with severe liver necrosis
catepsin-D, carboxypeptidase) can be elevated in the blood
Parameters to be measured:
TP, albumin, and fibrinogen concentration by spectrophotometric, refractometric methods and fibrinogen by the thrombin time.
When can edema be expected?
if albumin concentration is < 20 g/l, and there is edema formation if albumin concentration is < 11 g/l
how do we measure alpha and beta globulins
electrophoresis
how are coagulation factors measured?
APTT and PR
Why do we need to measure ammonia conc?
1) in carnivores to diagnose severe decrease of liver function (i.e. cirrhosis), portosystemic shunt
2) in ruminants as a consequence of ruminal alkalosis, or decomposition of ruminal fluid severe systemic alkalosis can be developed due to hyperammoniaemia,
3) in case of horse, rabbit pathologic breakdown of ingest in the colon or caecum or in case of liver failure .
Where is ammonia produced and absorbed
produced in the intestines by the bacteria, it is absorbed to the portal vein
How is ammonia detoxified
in the liver
- ornithine cycle
- GLDH untilised alpha keto glutaric acid
After what time period can we take ammonia measurements?
How should we take samples.
animals should starve for 24 hours.
We take blood samples to tubes that contain EDTA or citrate as an anticoagulant.
Samples should be taken by avoiding air - contamination of them
Normal value for ammonia conc
<120 μmol/l in dogs
<175 μmol/l in cats.
Basis of ammonia measurement (standard) method
ammonia with alpha-ketoglutaric acid and NADH+ H+ and GLDH enzyme produces glutamic acid and NAD+
What type of sample do we need for ammonia conc measurement?
plasma sample for standard method
Whole blood sample for portable ammonia checker
Ammonia tolerance test:
- when do we perform this?
when basal NH3-concentration values do not show alteration and the suspect of portosystemic shunt is strong
Ammonia tolerance test:
pretreatment
with neomycin
Causes of increased NH3.concentration in the blood
Impaired liver function - decreased urea prod
Ruminal alkalosis or ammonia toxicosis
Intestinal overgrowth of ammonia producing bacteria
Congenital enzymopathies
mild vs severe liver damage effect on cytoplasmic and mitochondrial enzymes
mild - cytoplasmic increase
severe - mitochondrial ones increase
AST (Aspartate-aminotransferase)
- location
mitochondria
muscles
RBC
AST (Aspartate-aminotransferase)
- function
converts alpha-keto-glutaric acid to L-glutamic acid, and L-aspartate to oxalic acetic acid.
AST (Aspartate-aminotransferase)
- Basis of measurement method
Oxalic-acetate with NADH+H+ and malate-dehidrogenase (this is in the reagent) produces malate and NAD+ .
This NADH+H+ →NAD+ change cause absorbancy reduction. The speed of it is in correlation with AST activity.
AST (Aspartate-aminotransferase)
- cause of increased activity
muscle cells
- exercise, muscle necrosis, inflamation, injury, myocarditis
- Generally LDH and CK enzymes elevated too
Liver cells
- ethonal consumption, hepatopathy,
RBC
- haemolysis
AST (Aspartate-aminotransferase)
- Decreased activity
metronidasol (an antimicrobial drug, which can cause liver function problems), vitamin B6 deficiency,
liver specific enzyme in herbivores
AST
ALT (Alanine-aminotranferase)
- location
liver cells (in carnivores liver specific), red blood cells (false increase) in the cytoplasm
ALT (Alanine-aminotranferase)
- function
converts alpha-keto-glutaric acid to L-glutamic acid, and L-alanine to piruvic acid
ALT (Alanine-aminotranferase)
- determination
produced piruvic acid is converted to lactic acid by lactate dehydrogenase (LDH)
ALT (Alanine-aminotranferase)
- increased activity
liver cell damage (especially in carnivores), chronic active hepatitis (CAH),
cholangiohepatitis (CH)
virus hepatitis (human) (AST/ALT1)
hepatic lipidosis
cirrhosis,
bile duct obstruction,
liver neoplasm (AST/ALT1),
pancreatitis,
septicaemia
neoplasm,
Drugs causing increased ALT
barbiturates, glucocorticoids, salicylates, tetracyclines
- from cell damage
Copper storage disorder
- breeds
Doberman pincher, West highland white and Bedlingtone terrier !
GLDH (glutamate-dehydrogenase)
- locatiom
liver specific, small amount is found in nerves and muscles in mitochondria only !
Liver specific in ruminants, horses and dogs.
GLDH (glutamate-dehydrogenase)
- function
binds NH3 to form glutamic acid.
GLDH (glutamate-dehydrogenase)
- determination
GLDH (glutamate-dehydrogenase)
- causes of increased activity
severe liver cell necrosis that leads to mitochondrial membrane damage.
BILE DUCT OBSTRUCTION ENZYMES
ALKP
GGT
ALKP (AP-Alkaline-phosphatase)
- location
every cell really
- hepatic and bone ALKP appears in blood
ALKP (AP-Alkaline-phosphatase)
- what causes ALKP increase in urine
Tubular Cell damage
ALKP (AP-Alkaline-phosphatase)
- isoenzymes
liver one - heat stabile
bone one - heat labile
ALKP (AP-Alkaline-phosphatase)
- optimum pH
- function
- 10
- phosphotransferases and not phosphatases. Generally phosphate-esters are translocated to one alcohol or phenol hydroxyl groups to another by ALKP.
ALKP (AP-Alkaline-phosphatase)
- determination
yellow colour detected by spectrophotometrically
ALKP (AP-Alkaline-phosphatase)
- causes of increased activity
bone
- young dogs, pregnant animals, bone tumours
Paraneoplastic processes
Liver
- cholestasis, bile acids, acute hepatic, necrosis, bilary obstruction
SIAP synthesis
- hyperadenocorticism
- Chronic stress
ALKP (AP-Alkaline-phosphatase)
- causes of decreased activity
severe cirrhosis
ALKP (AP-Alkaline-phosphatase)
- what causes ALKP increase in urine
Tubular Cell damage
GGT (gamma glutamyl-transferase)
- location
produced by different organs
- endothelial cells of bile ducts concentrates it
GGT (gamma glutamyl-transferase)
- specific to
horses (and cats)
GGT (gamma glutamyl-transferase)
- function
L-alpha-aminoacids can be attached to reduced glutathione and transported through the membrane by GGT (GGT is bound to glutathione).
GGT (gamma glutamyl-transferase)
- determination
yellow
GGT (gamma glutamyl-transferase)
- increased activity
biliary stasis (cholestasis),
cholangiohepatitis
cirrhosis,
neoplasm (hepatic, pancreatic),
hepatic lipidosis,
barbiturates,
ethanol specifically exaggerates the GGT excertion (human)
GGT (gamma glutamyl-transferase)
- Decreased activity
cirrhosis,
More liver specific enzymes in large animals
OCT (ornityl-carbamyl-tranferase,
Ar (arginase),
SDH (sorbite dehydrogenase).
What is SDH specific in?
swine, cattle, horse
OCT specific in?
Dogs
AR specific in?
Equine
What do we measure in
- dogs
ALT, (AST, GLDH), ALKP, GGT
What do we measure in
- cat
ALT, (AST, GLDH), GGT, (ALKP in acute processes)
What do we measure in
- ru
AST, GLDH, (GGT)
What do we measure in
- eq
AST, GGT, (Arg)
What do we measure in
- swine
AST, GGT, ALKP, OCT, SDH
What does decreased total cholesterol conc cause
decreased esterification ability
decreased apolipoprotein synthesis
What does increased FFA conc cause
decreased FFA utilisation
What does lipid accumulation in the liver cause?
decreased ability to perform beta-oxidation (decreased lipid breakdown)
decreased synthesis of lipid-transporting apolipoprotein molecules
