Enzymology, lipid, cardiac biomarkers Flashcards
What are “leakage enzymes” ?
May be in cytosol, organelles, or both
Enzymes escape from the cell as a result of injury to cell membranes or organelles
What are “induced enzymes”?
Usually attached to membranes, rarely due to cell injury
Increased are usually due to increased production
What are the liver leakage enzymes?
ALT
AST
SDH (large animal)
GLDH (large animal)
What are induced enzymes associated with the liver?
ALP and GGT
T/F: serum ALT will be increased more with sublethal damage then it is with necrosis
True
What enzyme is muscle specific, an increase indicates damage to muscular tissue
Creatine kinase (CK)
Asparatate aminotransferase has the highest activity in what organs?
Skeletal and cardiac muscle
Hepatocytes
What is the half life of creatinine kinase (CK)?
Rapidly peaks in 6-12hrs following injury and has a half life of 2-4hrs
Is AST a good indicator of muscle injury?
Can be
Creatinine kinase is muscle specific but has a very short half life. AST stays elevated longer in muscle injury, but is not muscle specific
_________ is a liver specific enzyme in dogs and cats but can be incresed with severe muscle damage
ALT
__________ is released from dead/dying muscle. It is not protein bound in the blood and is excreted in the urine
Myoglobin
Dipstick positive for blood/hemoglobin. How can you distinguish myoglobin from hemoglobin in the urine?
Ammonium sulfate precipitation test
-hemoglobin precipitates, myoglobin does not
Anemia -> hemoglobin
CK increased -> myoglobin
Triglycerides synthesized in the liver are not water soluble and must be attached to proteins in the blood
Very low density lipoprotein (VLDL)
What are the uses of cholesterol?
Produce steroid hormones
Component of cell membranes
Precursor to bile acids
What are the most commonly measured blood lipids?
Triglyceride and cholesterol
A primary hyperlipidemia is due to ?
Inherited disorder
Secondary hyperlipidemia is associated with ??
Endocrine or metabolic disorders
T/F: hyperlipidemia always results in lipemia
False
Hyperlipidemia -> trigyclerides and cholesterol
Lipemia–> chylomicroins or VLDL
What do you see commonly in small equids during starvation or chronic illness secondary to negative energy balance?
Equine hyperlipidemia
What are primary hyperlipidemia ? What breed of dogs is this seen most frequently?
Inherited defect in lipoprotein lipase or apoprotein CII
Miniature schnauzers
What diseases are associated with secondary hyperlipidemia?
Hypothyroidism Diabetes mellitus Hyperadrenocorticism Pancreatitis Hepatic disease Nephrotic syndrome
What is nephrotic syndrome?
Hypercholesterolemia is a common finding in dogs and cats with protein losing glomerulonephropathy
- hypoalbuminemia
- proteinuria
- hypercholesterolemia
- edema or ascities
What can cause a hypolipidemia?
Liver failure - hypocholesterolemia
Maldigestion/malabsorption
Protein losing enteropathy
Starvation
During starvation, ________ can occur due to fat mobilization from adipose tissue exceeding the ability of the liver to oxidase the fat
Ketosis
Lactating dairy cows, anorexic obese cats, and anorexic small equids can have ______________ because of increased hepatic uptake of LCFA plus impaired hepatic synthesis of triglyceride rich lipoproteins
Hepatic lipidosis
What are the two main tests for cardiac function/damage
Myocardial cell injury test - leakage markers
Specific cardiac function proteins - functional markers
Cardiac biomarkers should have what prerequisites?
Quick turn around time
High sensitivity and specificity for cardiac injury
Affordable
Screening test for asymptomatic heart disease
Distinguish cardiac vs non cardiac dyspena
Identify myocardial injury
Troponin complex regulates??
Calcium-mediated interaction of myosin and actin
The tropnonin complex in made up of what 3 proteins ?
Cardiac troponin I
Cardiac troponin T
Cardiac troponin C
What one of the troponin proteins is inhibitory and prevents contraction when calcium is not present and is the most diagnostically useful?
Troponin I
Increasing troponin concentrations suggest?
Worsening condition of the heart
Eg congestive heart failure, pericardial disease, or cardiac injury due to sepsis, doxorubicin toxicity, gastric-dilatation-volvulus, and myocarditis
What is the most useful functional marker for the heart
Natriuretic peptide (hormone regulating salt and water homeostatis and BP control )
Brain natriuretic peptide is produced by the ________
Ventricles
What is increased in production with increased ventricular wall tension hypertrophy, or myocardial dysfunction
Brain natriuretic peptide (BNP)
Cleaved to pro-BNP where the N terminal is cleaved
N-Terminal has a long halflife and what is measured
Under what conditions can plasma NT-proBNP be increased?
Ventricular hypertrophy Tachycardia Hypoxia Expanded fluid volume Reduced renal clearance of the peptide