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 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 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

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 Cardiac troponins CK CK-MB BNP 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 2-3 AST 8-12 24 5 LD 72 10 LDH isoenzymes

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 .