1. MLAB 2401: Clinical Chemistry Keri Brophy-Martinez
Cardiovascular Conditions and Assessment

2. 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

3. Symptoms of Heart Disease

4. 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

5. Congenital Cardiovascular Defects
Symptoms
Cyanosis
Pulmonary hypertension
Embolism
Clubbed fingers
Reduced growth
Syncope
Examples
Tetralogy of Fallot
Ventricular septal defects “hole in the heart”

6. 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

7. Heart Failure or Congestive Heart Failure
Examples
Left ventricular dysfunction
Coronary artery disease
Cardiac arrhythmias
See it:

8. Pathologic Conditions of the Heart
Acute Coronary Syndromes
Term used to describe a series of events
Angina
Reversible tissue injury
Unstable angina
Myocardial infarction
Extensive tissue necrosis

9. Acute Coronary Syndromes
Clinical Symptoms
Chest pain
Referred pain
Nausea
Vomiting
Dyspnea
Diaphoresis
Light headedness

10. Acute Coronary Syndromes
Causes
Atherosclerosis
Inflammatory disorder
Plaques deposit in artery walls
Leads to ischemia

11. Stages of Atherosclerosis
Initial vascular injury caused by:
Hypertension, hyperlipidemia, hyperhomocysteinemia
Increased permeability to lipids especially LDL/VLDL
Results in inflammation
Monocytes & Leukocytes arrive to help!
Macrophages scavenge LDL/cholesterol-rich lipoproteins- become foam cells
Foam cells promote lesion progression
T and B lymphocytes are recruited by the plaque
Interactions between T/B lymphs and foam cells recruits smooth muscle cells into the lumen
Smooth muscle cells secrete collagen, elastin, and proteoglycans to fix the plaque to the vessel wall

12. Presentation of Coronary Heart Disease

13. 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

14. 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

15. 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

16. 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 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

17. Current Cardiac Panel Myoglobin Cardiac troponins CK CK-MB BNP
Released from damaged cardiac/skeletal muscle
Cardiac troponins
See upcoming slide CK
CK-MB
BNP
Discussed later

18. 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
2-3
AST
8-12 24 5 LD 72 10
LDH isoenzymes

19. Time Course Of Enzyme Activity in MI’s
Troponin
Rises 4-10 hours after onset
Peak at hours
Elevated for 4-10 days
Myoglobin
Released 1-4 hours after onset
CK-MB
Rises within 4-6 hours after onset
Peaks at hours
Normal at 2-3 days

20. 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

21. What’s So Special About Troponin?
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

22. 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

23. Markers of Congestive Heart Failure
Natriuretic peptide
Hormones that include atrial natriuretic peptide (ANP), B-type natriuretic peptide(BNP), C-type and D-type
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

24. Vascular Inflammation Plaque Destabilization
Plaque Rupture
Acute Phase Reactant (CRP)
Ischemia
Necrosis (Troponin)
Myocardial Dysfunction (BNP, NT-proBNP)

25. References
Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins.
Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson .