Enzymes and Cardiac markers Flashcards
Define what an enzyme does
An enzyme is a biological catalyst to one or more specific biological reactions
Why measure enzymes?
- Identify diseases that occur as a result of abnormalities in enzymes concentration or function e.g. many inherited diseases
- To identify tissue injury
Where are the majority of enzymes found?
Intracellularly
Small amounts of intracellular enzymes are routinely detected in plasma as a result of normal cell turnover
When measuring intracellular enzymes in plasma, what happens when there is tissue injury?
Levels of intracellular enzymes found in the plasma increases
- What are the two types of enzyme in a cell (based on location)?
- Why do enzyme levels increase after tissue injury?
- Some enzymes are present in the cytosol (cytosolic)
- Some enzymes are subcellular
- When tissue is damaged, the cell membrane becomes leaky causing cytosolic enzymes to leak out, causing it to rise in the plasma
If there is damage such as necrosis to cells, then this breaks down sub cellular organelles within the cell, which releases subcellular enzymes, as well as cytosolic enzymes
Why is timing of measuring enzymes important?
Because cytosolic enzymes are released first whne there is acute damage. While sub-cellular enzymes are released after continued damage and necrosis of cells
As well as tissue damage, what also causes enzyme levels to increase?
- Increased synthesis
- Decreased clearance
Describe the distrubution of enzymes in tissues
- Few are highly specific
- Most others more widely distributed across many tissues
Which of these tissues makes ALP?
1: Intestines
2: Bone
3: Liver
4: Placenta
5: All of the above
All of the above
Where can enzymes be measured when being used as a marker for disease?
- in serum to detect injury to a tissue that makes the enzymes (increased levels)
- in the tissue to identify abnormalities in or absence of the enzymes, which may cause disease (usually decreased levels)
- Enzymes are most useful when measured in the context of working clinical diagnosis
What is an iso-enzyme?
Enzymes are usually not specific and are present in many different tissues. Sometimes it is the same enzyme in each tissue, but some enzymes exist in different tissues as iso-enzymes. These individual iso-enzymes are characteristic to particular tissues, they just have a slight different arrangement of atoms in space.
Describe the reasons why ALP increases
- Present in high concentration in liver, bone, intestine and placenta
- Pathological increases most frequently due to liver or bone diseases
- Increased in bone diseases associated with increased osteoblastic activity
- Higher levels in adolesences - due to development of bone
A 39 year old woman with BMI of 43, presented with elevated alkaline phosphatase and RUQ pain. Your laboratory does not offer iso-enzyme testing. What other enzyme can you measure?
GGT - specific to the liver
AST is not specific to the liver - also raised by skeletal muscle
How do you differentiate ALP raised by bone and by liver?
Liver and bone ALP can be differentiated by
- GGT measurement
- Electrophoretic separation
- Bone specific ALP immunoassay now available
What are the causes of a raised ALP?
- Physiological
- Pathological
- Physiological
- Pregnancy (placental ALP) – 3rd trimester
- Childhood- especially during growth spurt
- Pathological
- > 5x Upper limit of normal
- Bone ( Pagets, Osteomalacia)
- Liver ( cholestasis, cirrhosis)
- < 5 x Upper Limit Normal
- Bone ( tumours, fractures, osteomyelitis)
- Liver (infitrative disease,hepatitis)
- ALP IS NOT INCREASED IN OSTEOPOROSIS UNLESS COMPLICATED BY FRACTURES
What is serum amylase used to diagnose?
- Acute pancreatitis
- Secreted by exocrine pancreas
- High serum amylase activity in acute pancreatitis
- Usually > 10 times upper limit of normal
- Remember salivary isoenzyme exists
- Small increases may be seen in other acute abdomen states
Nowadays, we also measure lipase - which is better for Acute pancreatitis
- Why measure Creatine kinase?
- What are the three forms and where are they found?
- Most widely used marker of muscle damag
- Three forms - dimers containing the M (muscle) and B (brain) subunits
- CK-MM- skeletal muscles
- CK-MB (1 & 2) – cardiac muscles
- CK- BB – brain – activity minimal even in severe brain damage
- CK-MM accounts for almost entire normal plasma activity
What is statin related myopathy?
What are the risk factors?
- Statin related myopathy is the spectrum of conditions of myalgia to rhabdomyolysis that are seen in patients that are taking statins
- Polypharmacy ( fibrates – gemfibrosil, cyclosporin, other drugs metabolised by the CYP 3A4 system)
- High dose
- Genetic predisposition
- Previous history of myopathy with another statin
- Also affected by vitamin D deficiency and thyroid issues - both can cause statin intolerance
What are other causes of raised plasma CK activity?
- Muscle damage due to any cause
- Myopthy e.g. Duchenne muscular dystrophy (>10xULN)
- Myocardial Infarction (>10xULN)
- Severe exercise (5xULN)
- Physiological – Afro-Caribbean (<5xULN)
A 45 year old woman with long standing history of high alcohol intake, presents to A&E with severe epigastric pain, which radiates to her back and associated with vomiting. Her pain is partially alleviated by sitting forward. What is the most likely working clinical diagnosis?
1: Acute Pancreatitis
2: Renal Colic
3: Intestinal Obstruction
4: Gallstones
5: Myocardial infarction
- Acute pancreatitis
A 45 year old woman with long standing history of high alcohol intake, presents to A&E with severe epigastric pain, which radiates to her back and associated with vomiting. Her pain is partially alleviated by sitting forward. Which enzyme measurement might be helpful with the diagnosis?
Amylase or lipase
An 82 year old women presented with bone pain, history of fractures and bowing of her tibia. Which enzyme measurement might be helpful with the diagnosis?
ALP - suggestive of Paget’s disease
A 64 year old man who smokes and has a family history of cardiovascular disease has recently been started on atorvastatin. Three weeks after commencing the tablet, he complains of generalised muscle pain. What is the working clinical diagnosis?
- Swine Flu
- Statin related myopathy
- Vitamin D deficiency
- Depression
- Statin related myopathy
Can present months after starting a statin
A 64 year old man who smokes and has a family history of cardiovascular disease has recently been started on atorvastatin. Three weeks after commencing the tablet, he complains of generalised muscle pain. What enzyme will help with the diagnosis?
Creatine kinase - measure it all at once, don’t commonly request individual CK subtypes
What are the current markers for myocardial infarction?
When do they peak after an MI?
- Cardiac troponin, CK-MB
- Cardiac troponin peaks and rises the most following an MI, and CK-MB gives a small peak
Myoglobin is also released initially but this isn’t specific to heart muscle.
D - how troponin increases when there is angina/ACS - not full MI
Why is troponin and CK-MB released after an MI and from where?
- Myoglobin is released first as is a cytosolic enzyme and with damage to the heart with MI - ischaemia, the cell membranes become leaky and release myoglobin
- As cells die and become necrosed, as do the subcellular componenets releasing:
- CK-MB which is found in the nucleus and mitochrondria
- Troponin which is found in the contractile apparatus of the heart muscle
When does troponin rise, peak and how long does it last?
Rise 4-6 hours post MI
Peak at 12 -24 hours post MI
Remain elevated for 3 -10 days
Troponin - actin myosin filaments
Timing is cruical - after 24 hours, if you have not detected a troponin rise then there is a high likelihood that this is not an MI
- Sensitivity
- 17% at 0-6 hours
- 92% at 6-12 hours
- 100% at 12 -24 hours
- Specificity
- 95 % at 0 -12 hoursl98% at 12 -24 hours
What is the diagnostic criteria for an acute MI?
Either one of the following
- l1) Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) with at least one of the following:
- (a) ischemic symptoms
- (b) pathologic Q waves on the ECG
- (c) ECG changes indicative of ischemia
- (d) coronary artery intervention
(2) Pathologic findings of an acute MI
What are the different biomarkers in heart failure, and where do they come from?
Natriuretic peptides
- Atrial natriuretic peptide – secreted by the atria
- Brain natriuretic peptide – secreted by the ventricles
BNP can be measured to assess ventricular function
BNP can be used to exclude heart failure in the clinical setting
A 52 year old man presented to his GP with a history of exercise-induced central chest pain which radiated to his left arm and neck a week ago. As the pain lasted for half an hour, and subsided on rest he decided to not to go to his GP until today. He’s currently pain free, and his ECG at the GP surgery was normal. Which biomarker measurement might be helpful with the diagnosis?
Troponin - longer peak of 3-10 days post MI
What is the measurement unit of enzyme activity?
- One International Unit (U) of enzyme activity is defined as the quantity of enzyme that catalyses the reaction of one μmol of substrate per minute
- Activity of an enzyme is dependent on assay conditions such as temperature, pH
- Enzymes are measured by activity not mass
What is the unit of measurement for plamsa enzyme activity?
1: mmol/L
2: mg/L
3: kPa
4: U/L
5: g/dl
- U/L
