MLAB 2401: Clinical ChemistryKeri 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– 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• 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 Atherosclerosis1. Initial vascular injury caused by:

1. Hypertension, hyperlipidemia, hyperhomocysteinemia2. Increased permeability to lipids especially LDL/VLDL

1. Results in inflammation3. Monocytes & Leukocytes arrive to help!4. Macrophages scavenge LDL/cholesterol-rich lipoproteins- become foam cells5. Foam cells promote lesion progression6. T and B lymphocytes are recruited by the plaque7. Interactions between T/B lymphs and foam cells recruits smooth muscle cells into

the lumen8. 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?

• 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 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

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/congestive-heart-failure.html

• http://www.resverlogix.com/product_development/cardiovascular_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 .