(F) L2: Markers for Cardiac Damage and Function (Part 1) Flashcards
- This disease commonly occurs in the general population and affects the majority of people older than 60 years old
- Its commonality is that it refers to blocked arteries therefore inhibiting adequate blood supply to tissues
Cardiovascular Diseases (CVD)
Types of CVD (acc. to location)
Concerns the arteries that supply blood to the heart muscle
Coronary Heart Disease (CHD)
Types of CVD (acc. to location)
Concerns the blood supply to the brain as the point of blockage
Cerebrovascular Disease
Types of CVD (acc. to location)
Concerns the extremities wherein a balloning of the aorta (aneurysm) is possible
Peripheral Artery Disease
Types of CVD (acc. to location)
Refers to the the gradual buildup of plaque in your aorta
Aortic Atherosclerosis Disease
- A chronic process involving damage to the endothelium and buildup of cholesterol-rich lesions (plaques) that occlude the vasculature
- Increases the likelihood of ischemia (lack of blood supply)
Atherosclerosis
In atherosclerosis, when the diameter of the coronary artery decreases by less than how many percent (range), angina/chest pain may start to develop?
< 10-20%
- A medical disorder that damages the lumen of the arteries due to plaque deposits
- Is mainly acquired through lipid accumulation due to a high cholesterol diet and poor exercise
- Can also be acquired through genes (e.g. hyperlipidemia)
Atherosclerosis
- A disease that blocks the artery walls due to aging
- Genetics is the main cause of this disease
Arteriosclerosis
Refers to the cutting-off of blood supply resulting to reduced oxygen in a particular area
Ischemia
Ischemia-induced Diseases
- An activity-related chest pain which occurs with a given amount of activity
- Can be resolved with rest
Stable Angina
Ischemia-induced Diseases
- It occurs unpredictably and does not respond to when you stop a particular activity
Acute Coronary Syndrome (ACS)
What are the 2 classifications of Acute Coronary Syndrome (ACS)?
- Unstable angina
- Severe myocardial infarction (aka heart attack)
TOF: Between unstable anginas and myocardial infarctions, which marker is significantly higher than the other?
Myocardial Infarctions
A manifestation that often radiates to the left shoulder, neck, or arm and typically increases in intensity over a period of minutes and gets worse with either physical or psychological stress
Angina/Chest Pain
Common or Non-Classical Symptoms of Angina?
- Heavy chest pressure
- Squeezing of chest
- Burning feeling
- Difficulty in breathing
Common Symptoms
Common or Non-Classical Symptoms of Angina?
- Stabbing and pulsating chest pains
- Nausea
Non-Classical Symptoms
Symptoms not related to ischemia-induced angina
Due to respiratory movements or coughing
Pleuritic pain
Symptoms not related to ischemia-induced angina
The sole location is in the abdomen
Epigastric pain
Symptoms not related to ischemia-induced angina
Refers to somatoform disorders, panic attacks, and anxiety disorders
Psychiatric disorders
Symptoms not related to ischemia-induced angina
- Sepsis
- Burns
- Acute neurological diseases
- Drug toxicity
- Cancer chemotherapy
- Hyperacidity
Severe Non-Cardiac Conditions
- Commonly known as a heart attack which refers to irreversible ischemic damage
- There is death of cardiac muscle due to ischemia
- Diagnosis includes the use of electrocardiograms (ECGs) and lab measurements of cardiac markers
Myocardial Infarction (MI)
2 types of Myocardial Infarction
Ischemic necrosis involves the full thickness of the ventricular wall with “ST Elevation Myocardial Infarction” (STEMI) on the ECG
Transmural MI
2 types of Myocardial Infarction
Necrosis is limited to the inner 1/3 or 1/2 of the ventricular wall with non-STEMI on the ECG
Subendocardial MI
MI definitions acc. to different organizations
A typical rise and fall of (troponin/CK-MB) with one value (above/below) the 99th percentile of the (upper/lower) reference limits
- Troponin
- Above
- Upper
MI definitions acc. to different organizations
Sudden unexplained cardiac death before samples are obtained or before biomarkers can appear in the (serum/plasma/blood)
Blood
MI definitions acc. to different organizations
For Percutaneous Coronary Intervention (PCI) and Coronary Artery Bypass Graft Surgery (CABG) patients with a normal baseline troponin, a level (less than/greater than) the 99th percentile of the upper reference limit is indicative of periprocedural myocardial necrosis
Greater than
What are the 6 waves present in an ECG?
- P
- Q
- R
- S
- T
- U
In an ECG, where can the ST segment be found?
Between the S and T waves
Types of MI
- Spontaneous MI
- MI related to CABG
- MI secondary to ischemic imbalance
- MI resulting in death w/o biomarkers
- MI related to PCI
- MI related to stent thrombosis
Choices: 1, 2, 3, 4A, 4B, and 5
- Type 1 (plaque rupture with thrombus formation)
- Type 5
- Type 2 (can be due to vasospasm, endothelial dysfunction, or supply-demand imbalance)
- Type 3
- Type 4A
- Type 4B
The pathophysiology of atherosclerosis involves a progressive accumulation of lipids, smooth muscle cells, macrophages, and connective tissue within the large and medium-sized arteries causing luminal (narrowing/widening) and (decreased/increased) perfusion
- Narrowing
- Decreased
Refers to a type of atherosclerosis that is acquired wherein there are high levels of LDL and low levels of HDL
Dyslipidemia
As more LDL diffuses and accumulates across damaged endothelium, it will eventually rupture. This is why (blank) is recommended to greatly aid in collagen formation, resulting to better endothelium healing
Vitamin C (a lack of it will result to fat deposits covering the tear instead of collagen)
LDL in the intima will oxidize into lipids that trigger what event causing the recruiting of macrophages into the vessel wall?
Chronic Inflammation
Once macrophages phagocytose the oxidized LDL they become filled with fat, which are called as what?
Foam Cells
Foam cells accumulate in the intima to form what which will be surrounded by connective tissue forming a fibrous cap?
Lipid Core
Note: The fibrous cap is difficult to remove therefore a stent/bypass is done to enlarge the space
Refers to a lipid-filled plaque that can enlarge and eventually impinge on the vessel lumen resulting in atherosclerosis
Atheroma
Note: It continues to increase as long as inflammation persists
A common complication of the formation of a fibrous cap is that it may also form what which will later on rupture resulting to thrombosis, complete vessel occlusion, or a combination
Vascularization
When the heart muscles undergo this event, it will excrete biomarkers which may be in the form of an enzyme or a protein
Necrosis
These are protein molecules released into the bloodstream from damaged heart muscle and have their own characteristic rise and fall patterns
Cardiac biomarkers
This is a non-specific biomarker, therefore, elevated levels do not necessarily indicate cardiac problems
AST/SGOT
What are the 3 non-specific cardiac biomarkers?
- AST/SGOT
- LDH
- Creatinine Phosphokinase (CPK)
What are the 3 initial cardiac markers?
- AST/SGOT
- LD
- CK
Initial Cardiac Marker
- Is not that specific since it can be sourced from cardiac tissue, liver, and skeletal muscle
- Its diagnostic significance is in the evaluation of AMIs, hepatocellular disorders, and skeletal muscle involvement
Aspartate Transaminase (AST/SGOT)
Initial Cardiac Marker
- Although found in other tissues, some isoforms may be specific for cardiac function
- A zinc-containing enzyme that catalyzes the interconversion of lactic and pyruvic acids
Lactate Dehydrogenase (LD)
Lactate Dehydrogenase (LD)
The LD1:LD2 ratio exceeds by approximately how much 24-48 hours past the onset of MI symptoms and will remain elevated for how long?
(2 answers)
Note: This results to a flipped pattern also seen in hemolytic anemia and renal infarction
- Ratio exceeds by 0.75
- Remains elevated for 2 weeks
Initial Cardiac Marker
- The MB isoform of this provides the greatest specificity and is therefore the first choice as a biomarker compared to AST or LD
- A very sensitive indicator of AMI and Duchenne disorder
- A demonstration of levels greater than 6% of the total value of this marker is considered the most specific
Creatine Kinase (CK-MB)
Rise and Fall Patterns of Initial AMI Biomarkers
What is the cardiac marker?
Elevation post-MI: 4-8 hours
Peak: 12-18 hours
Return to baseline (normalized): 48-72 hours
CK-MB
Rise and Fall Patterns of Initial AMI Biomarkers
What is the cardiac marker?
Elevation post-MI: 6-8 hours
Peak: 24 hours
Return to baseline (normalized): 5 days
AST/SGOT
Rise and Fall Patterns of Initial AMI Biomarkers
What is the cardiac marker?
Elevation post-MI: 12-24 hours
Peak: 48-72 hours
Return to baseline (normalized): 10-14 days (remains elevated)
LDH
These are important for the diagnosis of the severity and presence of MI in a patient
The rise and fall patterns
If a patient compains of having chest pains that started a week ago, what is the best biomarker to use in this situation?
LDH (elevation lasts 10-14 days after the suspected MI)
CK-MB Determination
- An immunometric assay using monoclonal lab technology
- Proteins are measured as antigens
- This is determined by a two-antibody “sandwich” assay
CK-MB Mass Assay
CK-MB Determination
- This is equal to CK-MB mass assay divided by CK total activity
CK Relative Index/Relative Percent
CK-MB Determination
In determining CK-MB (mass) per CK (activity), total CK activity is determined by what method wherein phosphocreatinine combined with ADP results in ATP?
Enzyme Assay
CK-MB Determination (CK Relative Index/Percent Index)
Values (exceeding/subceeding) the reference limit for absolute quantity (5ng/mL) and relative index (2%) is suggestive of MI
Exceeding
- These are seen in all types of muscles wherein each source has different make ups of amino acids
- It is a complex of three proteins that regulate the calcium-dependent interactions of myosin heads with actin filaments during striated muscle contraction
- They are considered as the most important marker of cardiac injury (AMI) as they are derived from the heart muscle
Cardiac Troponins
Note: First 2 bullets refer to Troponins in general
Cardiac Troponins
This binds the troponin complex to tropomyosin
Troponin T (TnT)
Cardiac Troponins
This inhibits the binding of actin and myosin
Troponin I (TnI)
Cardiac Troponins
This binds to calcium to reverse the inhibitory activity of TnI
Troponin C (TnC)
Cardiac Troponins
There is little to no difference in troponin C between what 2 types of muscle?
Skeletal and Cardiac
Note: TnI and TnT are different hence these 2 are more commonly used as markers than TnC
Cardiac Troponins
TnT and TnI are measured in what specimen by immunoassay?
Serum
Cardiac Troponins
Reference values of TnI and TnT
- TnI - 0 to 0.04 ng/mL (0 to 40 ng/L)
- TnT - 0 to 0.01 ng/mL (0 to 10 ng/L)
Cardiac Troponins
Troponin I and T can also be measured qualitatively using what principle similar to that of a pregnancy test kit?
Antibody-Antigen Binding
Note: (+) for double bands means that cardiac troponins are present
Troponin T or I?
- Tropomyosin-binding unit
- Assesses early and late MI
- Monitors the effectiveness of thrombolytic therapy in MI patients
- Elevated in renal disease and muscle dystrophy as well
- A sensitive marker for unstable angina
- Uses plasma for qualitative detection
Troponin T
Troponin T or I?
- An inhibitory sub-unit or actin-binding sub-unit
- The gold standard for AMI
- Only found in the myocardium (greater specificity)
- A very sensitive indicator for minor cardiac necrosis
Troponin I
Troponin T or I?
Elevation: 3-4 hours
Peak: 10-14 days
Decline: 7 days
Troponin T
Troponin T or I?
Elevation: 3-6 hours
Peak: 12-18 hours
Decline: 5-10 days
Troponin I