eLearning - Cardiac Biomarkers of Myocardial Infaraction Flashcards
What are the ideal characteristics of a biomarker for the detection and management of myocardial infarction?
(1)very specific to cardiac muscle and absent from nonmyocardial tissue (2)released quickly into the peripheral blood after onset of injury and reflect quantitatively the magnitude of necrosis (3)easy to use, quick to measure, cheap to measure, and stable in vitro.”
What are some good biomarkers for an MI?
Of the cardiac biomarkers listed in the table from Hurst’s The Heart, cTn and CK-MB offer the best match to the optimal properties. Their normal biological properties are not related to their use as biomarkers; they are simply released from cells that died from necrosis. cTn and CK-MB are complementary markers, since troponins are able to detect old MI and CK-MB levels can reflect reinfarction.
How does the use of cardiac-specific isoforms of troponin and CK (CK-MB) increase their utility as cardiac biomarkers?
Tissue specificity of a marker makes it far more useful for specific diagnosis. A widely expressed protein that is released upon damage of any tissue would not allow the specific diagnosis of myocardial infarction. For example, myoglobin (as well as non-cardiac specific CK) is released following skeletal muscle injury, which would result in a false positive for MI. Other conditions also cause elevated CK and Mb.
Why is skeletal muscle damage a confounding issue for the use of myoglobin?
myoglobin (as well as non-cardiac specific CK) is released following skeletal muscle injury, which would result in a false positive for MI. Other conditions also cause elevated CK and Mb.
How might different isoforms of a protein be produced by different cells?
Different isoforms of a protein can arise from several mechanisms, the key is that the mechanisms must show tissue specificity (i.e. occurs in one specific tissue). The potential mechanisms include: (1) multiple genes that have tissue-specific expression (2) alternative mRNA splicing that is tissue specific (3) post-translational processing or modification that is tissue specific (4) tissue specific quaternary structures. The cardiac troponins arise from specific genes expressed only in the heart. There are two different CK genes, CK-M and CK-B. The proteins dimerize to create three different isozymes: CKMB, CKMM, CKBB. So it is the relative expression of two genes that determines the tissue specificity of the isozymes. CKMB is found at high levels in cardiac tissue, CKMM in muscle, and CKBB in brain and lung. Additional isoforms of CKMB can be created by cleavage of the Cterminal lysine by carboxypeptidase (no need to discuss in detail).
What type of assay would most likely be used to differentiate between two isoforms that differ by relatively few amino acids
For proteins that have limited amino acid differences, mass spectroscopy is the “gold standard” for their identification. Additionally, if monoclonal antibodies can be raised against unique epitopes of the isoforms, they can be used in ELISA or RIA.
An experimental biomarker for AMI is copeptin. Based on the data in Figure 4 [shown here; taken from European Heart Journal (2014) 35, 552–556] assess the utility of copeptin and explain how it differs biochemically from currently used biomarkers.
Unlike the other biomarkers, copeptin is not released from necrosed cardiomyocytes. Copeptin is the C-terminal domain of the vasopressin prohormone that is cleaved off during processing. Endogenous stress occurring with the onset of AMI results in the rapid release of active vasopressin and thus elevation of copeptin.
It does not work nearly as well as the others
The following is an ECG recording in the frontal plane leads from a 61-year-old man. His chief complaint upon arrival at the Emergency Department was severe chest pain. Compared to a normal ECG recording, what is the significant finding on this man’s ECG recording? Explain the mechanism responsible for this change in his ECG recording.
ST segment elevations are prominent in leads II, III, and aVF. This indicates myocardial ischemia within an area of the ventricles. The decreased flow to this region results in local hyperkalemia as potassium accumulates in extracellular fluid (normally some potassium is removed from the tissue by the blood, and ischemia reduces the removal of potassium). Local hyperkalemia depolarizes resting potential in the ischemic region and is evidenced by a shift in the ST segment from the isoelectric baseline.
How can ST elevation in different leads on an EKG allow you to figure out where an MI occurred?
If blood flow is significantly reduced to an area of the ventricles, myocytes in this region swell. Explain the mechanism responsible for increased size of myocytes in this situation.
Decreased blood flow to a region of the ventricle will reduce oxygen delivery to this tissue and result in decreased ATP generation. The activity of the sodium/potassium pump is dependent on ATP levels, and so pump activity will be reduced in the ischemic zone. The sodium/potassium ATPase extrudes 3 sodium ions from the cell while bringing 2 potassium ions into the cell. Decreased pump activity will cause intracellular solute concentration to rise and so water will move into the cell, causing myocytes to swell.
The mean electrical axis reflects the average direction and magnitude during ventricular depolarization. If a significant number of myocytes are lost from the left ventricle, how would this affect the mean electrical axis? How would the recordings of the QRS complex in lead I and aVF change after loss of functional tissue in the left ventricle?
The mean electrical axis reflects the balance between depolarizing currents (phase 0 voltage-gated sodium current) between the right and left ventricles. A severe myocardial infarction in the left ventricle would decrease the number of functional myocytes in the left ventricle and so decrease the magnitude of the sodium current during depolarization of the left ventricle. As a result, the direction of the mean electrical axis would be shifted towards the right ventricle (greater than +90 degrees). The net QRS complex would be positive in lead aVF (as in normal conditions) but the net QRS complex would be negative in lead I (normally net positive) as shown in the above diagram for right axis deviation.
What is the most common cause of Right axis deviation?
Right ventricular hypertrophy
What are the most common causes of left axis deviation?
Left ventricular hypertrophy or inferior MI
What could lead to extreme right axis deviation?
Right ventricular hypertrophy and loss of tissue in the lead ventricle
