MLAB 2401: Clinical Chemistry
Keri Brophy-Martinez
Cardiovascular Conditions and
Assessment
Functions of the Heart
• Pumps blood to the organs of the body
• Delivers oxygen and nutrients where they are
needed
• Removes waste products from tissues
Symptoms of Heart Disease
Pathologic Conditions of the Heart
• Congenital Cardiovascular Defects
– Abnormality arises from abnormal formation of
heart or its major blood vessels
– Present at birth
• All defects develop before the 10th week of pregnancy
– Origin unknown but appear to be based on
genetic disposition and environmental influences
Congenital Cardiovascular Defects
• Symptoms
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Cyanosis
Pulmonary hypertension
Embolism
Clubbed fingers
Reduced growth
Syncope
• Examples
– Tetralogy of Fallot
– Ventricular septal defects “hole in the heart”
Pathologic Conditions of the Heart
• Heart Failure or Congestive Heart Failure
– Any structural or functional cardiac disorder that impairs
the ability of the ventricle to fill with or eject blood
– Result
• Excess fluid accumulates in the lungs producing edema
• Reduced output of blood to systemic circulation
• Retention of fluid by the kidneys
Heart Failure or Congestive Heart
Failure
• Examples
– Left ventricular dysfunction
– Coronary artery disease
– Cardiac arrhythmias
• See it:
http://www.youtube.com/watch?v=3cW8__wFXDA
Pathologic Conditions of the Heart
• Acute Coronary Syndromes
– Term used to describe a series of events
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Angina
Reversible tissue injury
Unstable angina
Myocardial infarction
Extensive tissue necrosis
Acute Coronary Syndromes
• Clinical Symptoms
– Chest pain
– Referred pain
– Nausea
– Vomiting
– Dyspnea
– Diaphoresis
– Light headedness
Acute Coronary Syndromes
• Causes
– Atherosclerosis
• Inflammatory disorder
• Plaques deposit in
artery walls
• Leads to ischemia
Stages of Atherosclerosis
1. Initial vascular injury caused by:
1. Hypertension, hyperlipidemia, hyperhomocysteinemia
2. Increased permeability to lipids especially LDL/VLDL
1. Results in inflammation
3. Monocytes & Leukocytes arrive to help!
4. Macrophages scavenge LDL/cholesterol-rich lipoproteins- become foam cells
5. Foam cells promote lesion progression
6. T and B lymphocytes are recruited by the plaque
7. Interactions between T/B lymphs and foam cells recruits smooth muscle cells into
the lumen
8. Smooth muscle cells secrete collagen, elastin, and proteoglycans to fix the plaque
to the vessel wall
Presentation of Coronary Heart Disease
Hypertension
• Persistent systolic BP of at least 140 mm HG
and/or diastolic BP of at least 90 mm Hg
• Prevalence increases with age
• Contributing factors
– Obesity
– Physical inactivity
– Unhealthy nutrition
Hypertensive Heart Disease
• Term used to describe heart disease caused by
direct or indirect effects of increased BP
• Peripheral resistance determining factor in BP
– Increases workload of left ventricle resulting in
hypertrophy and dilation of mitral valve. This valve
is affected and blood is regurgitated to the left
atrium
Infective Heart Disease
• Heart disease caused by infectious agents
• Examples
– Rheumatic Heart Disease
• Complication of rheumatic fever due to autoimmune response.
• Causative organism is Group A streptococcus
• Usually affects young adults and children
– Infective Endocarditits
• Infection of endocardial surface of the heart
• Causative organism Group D streptococcus, but others also
– Pericarditis
• Inflammation of the pericardium
• Causative agents include bacteria, fungi, viral, autoimmune, others
Diagnosing Heart Disease
• Myocardial Infarction
– Diagnosis based on clinical symptoms, EKG
changes and the rise/fall of biochemical markers
– Samples collected at onset, 6-9 hours and 12-24
hours if previous samples were negative
– Preferred biomarkers are Troponin I and T.
• Specific and sensitive for myocardial necrosis
• Current guidelines suggest the use of 2 markers for
diagnosis
Current Cardiac Panel
– Myoglobin
• Released from damaged cardiac/skeletal muscle
– Cardiac troponins
• See upcoming slide
– CK
– CK-MB
– BNP
• Discussed later
Time Course Of Enzyme Activity in MI’s
• Historically CK, CK-MB, AST, LD/LDH
isoenzymes used
Enzyme
Onset of
Elevation
(Hr)
Peak
activity
(Hr)
Duration
of
Elevation
CK
4-8
12-24
3-4
CK-MB
4-6
12-24
2-3
AST
8-12
24
5
LD
12-24
72
10
LDH
isoenzymes
12-24
5
Time Course Of Enzyme Activity in MI’s
• Troponin
– Rises 4-10 hours after
onset
– Peak at 12-48 hours
– Elevated for 4-10 days
• Myoglobin
– Released 1-4 hours after
onset
• CK-MB
– Rises within 4-6 hours after
onset
– Peaks at 12-24 hours
– Normal at 2-3 days
Troponin
• Consists of three proteins that bind to thin filament(actin) of
cardiac and skeletal muscle
– Troponin T (TnT)
– Troponin I (TnI)
– Troponin C (TnC)
• Function to bind Ca+ and regulate muscle contraction
• Absent in the serum of healthy people
What’s So Special About Troponin?
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Specific for cardiac tissue
High diagnostic specificity and sensitivity
Early detection following MI
Remain elevated for several days
Undetected in healthy people
Few interfering substances in detection
Markers of Inflammation
• High Sensitivity C-Reactive Protein (hsCRP)
– Acute phase protein
– Produced in the liver in response to injury,
infection and inflammation
– Increases in CRP correlate with the risk of
coronary artery disease
Markers of Congestive Heart Failure
• Natriuretic peptide
– Hormones that include atrial natriuretic peptide
(ANP), B-type natriuretic peptide(BNP), C-type and Dtype
– Assist in regulation of cardiovascular homeostasis
– BNP
• Released on ventricular stretch or stress to myocytes in the
absence of necrosis
• Increased BNP indicates expanded fluid volume such as that
seen in renal failure and CHF
Vascular Inflammation
Plaque Destabilization
Plaque Rupture
Acute Phase Reactant (CRP)
Ischemia
Necrosis (Troponin)
Myocardial Dysfunction (BNP, NT-proBNP)
References
• Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry:
Techniques, principles, Correlations. Baltimore: Wolters
Kluwer Lippincott Williams & Wilkins.
• http://medicinembbs.blogspot.com/2010/12/congestiveheart-failure.html
• http://www.resverlogix.com/product_development/cardiovas
cular_disease/atherosclerosis.html
• http://www.youtube.com/watch?v=upb37rbS1dE
• http://www.youtube.com/watch?v=3cW8__wFXDA
• http://smabiology.blogspot.com/2009_04_01_archive.html
• Sunheimer, R., & Graves, L. (2010). Clinical Laboratory
Chemistry. Upper Saddle River: Pearson .