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Heart Information and Courses from MediaLab, Inc.

These are the MediaLab courses that cover Heart and links to relevant pages within the course.

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Laboratories Individuals

Antibody Detection and Identification
Case Study One- Immune Alloantibody

A 42 year old male received 6 units of RBCs during an open heart surgery 6 months ago. His antibody screen was negative at that time. He has returned for a follow up surgery and his antibody screen is now positive with both screen cells at the AHG phase.Reactions are occurring at AHG phase which indicates a possible clinically significant antibody, Jka showing dosage. Refer to Case Study 1 panel below to see reactions of antibody panel.IS = Immediate Spin; AHG = Antihuman Globulin Phase; CC = Check Cells; AC = Auto Control; ND= Not doneCase study 1 conclusion:Patient's previous transfusion 6 months ago exposed him to the Jka antigen, causing the formation of this antibody which is known for showing dosage.

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CLIA Chemistry / Urinalysis Review
Match the tissues on the left with the corresponding LDH isoenzyme peak on the right.View Page
The following LDH Isoenzyme pattern would be seen in:View Page
The following LDH Isoenzyme pattern would be seen in:View Page
The following LDH Isoenzyme pattern would be seen in:View Page
Label the scan:View Page

CLIA General Laboratory Review
An increase in CEA levels is most closely associated with which of the following organs:View Page

CLIA Hematology / Hemostasis Review
What best describes the cells seen in this illustration:View Page

Current Topics in Clinical Microbiology
Illustrated in this photograph is a quadrant plate containing brain heart infusion agar plate supplemented with 6 ug/ml of vancomycin. The right upper quadrant was inoculated with the test strain of Enterococcus faecium. The presence of growth in the inoculated quadrant indicates resistance to vancomycin.View Page

Emerging Cardiovascular Risk Markers
Introduction

We are all aware of the clinical laboratory's role in assessing overall health and we are also aware that measuring a patient's serum lipids will provide some insight into their cardiovascular health. The traditional measurements of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides are the 'classic' cardiovascular risk markers.Laboratorians, and even the general public are now well-aware that LDL-C ('bad' cholesterol) concentrations should be low while HDL-C ('good' cholesterol) concentrations should be high. Triglycerides should be kept in check as well. Optimal levels are shown in the table below. So what is the risk if these values are not within optimal ranges?Cardiovascular risk can be simply defined as increasing the odds of having a pathology which affects blood flow and/or the heart. The most common cardiovascular pathology is atherosclerosis. Other cardiovascular pathologies whose odds increase as serum lipids and other cardiovascular markers become suboptimal are myocardial infarction (heart attack), stroke, congestive heart disease and coronary artery disease. Other diseases such as diabetes and the metabolic syndrome are also strongly associated with the classic cardiovascular risk markers LDL-C, HDL-C and triglycerides.

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Risk Markers

We have listed the 'classic' cardiovascular risk markers as LDL-C, HDL-C and triglycerides. But there are many more cardiovascular risk markers as well as cardiovascular risk factors. A cardiovascular risk factor is a condition (not a laboratory analyte) that is associated with an increased risk of developing cardiovascular disease. Examples include: Age Gender (males are at increased risk) Heredity Hypertension Cigarette Smoking Obesity Diabetes StressThere are also negative risk factors, factors which decrease a person's risk of cardiovascular disease. Examples include: Optimal HDL-C concentration Exercise Estrogen Moderate alcohol intakeThis course will not focus on cardiovascular risk factors. Instead we will focus on newer, emerging cardiovascular risk markers. There are well over twenty well-studied cardiovascular risk markers; in this course we will focus on some of the more established markers and the ones which are becoming more commonly measured in the clinical laboratory. These include apolipoprotein A1/apolipoprotein B100, Lp(a), oxidized LDL, LpPLA2, hsCRP and lipoprotein particle size and concentration.It is important to remember that the association between a cardiovascular risk marker and actually having or developing cardiovascular disease is a statistical one. The fact that a patient has a particular risk marker which is abnormal simply increases the probability of developing cardiovascular disease, it does not mean that he or she is certain to develop cardiovascular disease. Conversely, if an individual does not have a particular cardiovascular risk marker present it does not guarantee protection against cardiovascular disease. We must always remember that some percentage of individuals who have heart attacks or strokes will not have abnormal risk markers present.

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Atherosclerosis continued

If a plaque ruptures it will expose sub-endothelial tissue to blood cells and in so doing stimulate the formation of a clot. The clot is the body's attempt to seal off the crack but the clot itself can cause further obstruction to blood flow. This sudden increase in the blockage caused by the raised ruptured plaque and associated clot can transform a mild blockage into a critical one within a matter of hours. If it occurs within the blood vessels of the heart, the decrease in blood flow leads to severe and prolonged chest pain known as unstable angina. Such a patient is at obvious risk for a myocardial infarct should the blockage become any worse.Atherosclerosis typically begins in early adolescence, and is found in most major arteries but since it is asymptomatic during the early half of life we need cardiovascualr risk markers to help assess patient risk. If an at-risk patient is identified early, the hope is that medication, lifestyle changes or medical procedures can be used to avert a serious cardiovascular event. So, although the vast majority of us have some degree of atherosclerosis, risk markers can help identify those among us who are in more imminent danger or who have increased risk of an adverse cardiovascular event.

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Atherosclerosis

Atherosclerosis is a clogging, narrowing and hardening of the body's large and medium-sized blood vessels. Atherosclerosis can lead to hypertension, stroke, myocardial infarction (heart attack), renal problems, etc. Not surprisingly, cardiovascular risk markers tend to reflect a person's degree of atherosclerosis.Atherosclerosis is actually a chronic inflammatory response within the walls of arteries. Small lipoproteins like LDL are able to diffuse through the endothelial wall of blood vessels and accumulate. The inflammatory component of atherosclerosis results from the migration of leukocytes (mainly macrophages) that enter the blood vessel walls. These macrophages seek to remove the deposited LDL as well as intermediate-density lipoproteins (IDL). As macrophages phagocytose these lipoproteins, they become foam cells that get trapped in the endothelial space. This eventually leads to "hardening" or "furring" of the arteries and plaque formation. Arteriosclerosis is a general term describing any hardening (loss of elasticity) of medium or large arteries whereas atherosclerosis is a hardening of an artery specifically due to plaque. The risk to patients with significant atherosclerosis is that eventually a narrowing of the artery (stenosis) can cause a reduction in oxygen delivery to tissues and plaque rupture can lead to an acute coronary event.

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The hs-CRP Test

The traditional CRP test has a typical reference range of < 8 mg/dL. The hs-CRP test, with its increased sensitivity has a reference or optimal range of < 3 mg/dL. As with most risk markers, the results of hs-CRP testing are generally interpreted on a relative scale; the higher the value, the higher the risk of a future cardiovascular event.The American Heart Association and Centers for Disease Control and Prevention has defined risk groups with hs-CRP as follows: Low risk: < 1.0 mg/L Average risk: 1.0 to 3.0 mg/L High risk: > 3.0 mg/L It is important to note that hs-CRP assays are measuring the same protein as traditional CRP assays. Thus, in patients with active inflammation (such as chronic, active arthritis; lupus; infection; etc.) hs-CRP values would be expected to be high and would not necessarily implicate cardiovascular risk. If values greater than 10 mg/L are seen in repeated measurements, a non-cardiovascular cause should be considered. Taking anti-inflammatory drugs (NSAIDs, aspirin, etc.) or the statin-class of cholesterol-lowering drugs may reduce CRP levels in patients. This is not an artifact, but is thought to be an effect of treating the underlying inflammatory process.

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References

Atherosclerosis. U.S. Department of Health & Human Services National Institutes of Health. Available at http://www.nhlbi.nih.gov/health/dci/Diseases/Atherosclerosis/Atherosclerosis_WhatIs.htmlAccessed June 23, 2009.Daniels LB, Barrett-Connor E, Sarno M, Laughlin GA,Bettencourt R, Wolfert RL. Lipoprotein-associated phospholipase A2 (Lp-PLA2) independently predicts incident coronary heart disease (CHD) in an apparently healthy older population: The Rancho Bernardo study. J Am Coll Cardiol. 2008;51:913-919.Executive Summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001; 285:2486-2497. Frostegard, J, Wu R, Lemne C, Thulin T, Witztum JL and de Faire U. Circulating oxidized low-density lipoprotein is increased in hypertension, Clin Sci 2003; 105, 615.Garza CA, Montoir VM, McConnell JP, et al. Association between lipoprotein-associated phospholipase A2 and cardiovascular disease: a systematic review. Mayo Clin Proc. 2007;82(2):159-165.Interpretive Handbook, (MC0440rev0407) Mayo Clinic, Rochester MN;2007. Maksimowicz-McKinnon K, Bhatt DL, Calabrese LH: Recent advances in vascular inflammation: C-reactive protein and other inflammatory biomarkers. Curr Opin Rheumatol. 2004;16:18-24.Mora S, Szklo M, Otvos JD, et al. LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the multi-ethnic study of atherosclerosis. Atherosclerosis. 2007;192:211-217.NACB Laboratory Medicine Practice Guidelines. Emerging biomarkers of cardiovascular disease and stroke. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines. 2006.PLACtest animation, diaDexus. http://www.plactest.com/laboratorians/action.php Accessed June 23, 2009.Rifai N, Warnick GR. Lipids, lipoproteins, apolipoproteins, and other cardiovascular risk factors. In: Burtis CA, Ashwood ER. Bruns DE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th ed. St. Louis, MO: Elsevier Saunders: 2006; chap. 26.Ridker PM, Rifai N, Rose L, et al. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002;347:1557-1565.Sniderman AD. Differential response of cholesterol and particle measures of atherogenic lipoproteins to LDL-lowering therapy: Implications for clinical practice. J Clin Lipidol 2008;2:36-42.Tsimikas, S, Brilakis ES, Miller ER, et al. Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease, N Engl J Med: 2005;353:46.Tsimikas S, Bergmark C, Beyer RW, et al. Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes. J Am Coll Cardiol. 2003; 41: 360.Tsimikas, S, Lau HK, Han KR, et al. Percutaneous coronary intervention results in acute increases in oxidized phospholipids and lipoprotein(a): Short-term and long-term immunologic responses to oxidized low-density lipoprotein. Circulation. 2004;109, 3164.Tsimikas S, Witztum JL, Miller ER, Sasiela WJ, et al. High-dose atorvastatin reduces total plasma levels of oxidized phospholipids and immune complexes present on apolipoprotein B-100 in patients with acute coronary syndromes in the MIRACL trial, Circulation: 2004;110, 1406. Walldius G, Jungner I, Holme I, et al. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet. 2001;358:2026-2033.Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937-952.

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Size and Number

Although lipoproteins of a particular class are generally within a given size range, there are many biochemical processes that interact with lipoproteins to alter their size, density, and lipid composition. When low-density lipoprotein (LDL) becomes smaller and denser, it is more likely to interact with the arterial wall, leading to deposition of cholesterol and initiating or worsening atherosclerosis. Research has shown that high numbers of smaller, denser LDL are more atherogenic than larger, lighter LDL particles. Small, dense LDL particles are associated with more than a three-fold increase in the risk of coronary heart disease.

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First Aid
CPR

In the event of catastrophic heart failure, Cardio-Pulmonary Resuscitation (CPR) can save lives.However, improperly performed CPR can result in further harm, including internal bleeding.Do not attempt CPR unless you are qualified to do so.Local community centers often provide CPR certification classes that will prepare you to properly administer CPR.

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Fundamentals of Hemostasis
Anticoagulation Therapy

Anticoagulant therapy is employed in a number of clinical situations Some of these clinical situations include: After an episode of thrombosis, such as deep venous thrombosis (DVT) in the veins of the legs, to prevent reoccurrence. Prophylactically after some surgeries, especially those involving vascular repair such as coronary bypass surgery to prevent clots from blocking newly formed vasculature. In heart valve and chamber disorders where there is an increased risk of thrombosis occurring.

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Hereditary Hemochromatosis
Altered Iron Absorption

Hereditary hemochromatosis (HH) is a genetic disorder characterized by iron overload as a result of increased iron absorption. As iron absorption increases, the amount of iron bound to transferrin and transported in the plasma subsequently increases.With no available mechanism for excreting excess absorbed iron, normal iron storage sites become overloaded, resulting in ferritin levels that far exceed normal. As a result, iron is deposited in the parenchymal cells of the liver, pancreas, pituitary, heart, synovium, and other tissues with high concentrations of transferrin receptors. Iron in excess of normal cellular ferritin stores contributes to the generation of free radicals and reactive oxygen intermediates that cause cell damage to organs and tissues. This process results in the clinical condition known as iron overload, a hallmark feature of HH.

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Introduction to Bone Marrow
Collection Sites

The sites used to obtain bone marrow samples are:illiac crest (posterior, anterior)sternumspinal processestibia - (infants and newborns)The illiac crest is the most common site for bone marrow collection. Sternal aspiration can have serious or even fatal consequences if the needle penetrates the heart.

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Laws and Rules of the Florida Board of Clinical Laboratory Personnel
Description of Specialties (2)

Specialists in immunohematology perform all testing prior to blood transfusions and work to prevent transfusion infections. They also investigate any post-transfusion reactions. This specialty includes all lab procedures performed in the specialty of histocompatibility. Specialists in clinical chemistry analyze body fluids such as blood, urine, and spinal fluid to determine the chemical makeup, including the amount of carbohydrates, proteins, enzymes, and trace elements. The special covers urine microscopics and chemical evaluation of the liver, kidneys, lungs, heart, and other vital organ systems. This specialty also covers all testing performed in the specialties of radioassay and blood gas analysis. Specialists in blood banking can perform all immunohematology testing as well as testing from the specialties of clinical chemistry, hematology and serology/immunology that relates to donor blood. Clinical laboratory personnel who are licensed in the specialties of immunohematology, clinical chemistry, hematology, and serology / immunology may perform all tests in the blood banking specialty.

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Mycology: Yeasts and Dimorphic Pathogens
This image illustrates a lactophenol blue mount of a mold recovered after 7 days incubation of brain heart infusion broth. The large macroconidia suggests the mold form of Histoplasma capsulatum. However, there is the possibility that this mold represents its saprophytic counterpart, which is:View Page
This image illustrates a lactophenol blue mount prepared from a mold recovered after 7 days incubation on brain heart infusion broth. The individual microconidia, each borne by a delicate conidiophore, suggests the mold form of Blastomyces dermatitidis. However, there is the possibility that this mold represents its saprophytic counterpart, which is called:View Page
The ingredient added to culture media to enhance the recovery of the dimorphic fungi by preventing the overgrowth of more rapidly growing, saprophytic molds is:View Page

Pharmacology in the Clinical Lab: Therapeutic Drug Monitoring and Pharmacogenomics
TDM for Theophylline

Theophylline is used as a bronchodilator for treatment of moderate to severe asthma and chronic obstructive pulmonary disease (COPD). TDM is needed for theophylline because the kinetics of the drug are highly variable. It has a narrow therapeutic window, and overdose can result in elevated heart rate, arrhythmia, and CNS excitability. Clearance of the drug is increased in children, smokers, persons with cystic fibrosis, and persons with hyperthyroidism. Elimination is slowed in congestive heart failure and in the elderly.

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TDM for Cardiac Medications

Inotropics (drugs used to increase the pumping ability of the heart) and antiarrhythmics may need TDM. The cardiac glycoside inotropics digoxin and digitoxin have narrow therapeutic windows. Overdose can cause vomiting, diarrhea, confusion, visual disturbances, and cardiac arryhthmias. Examples of cardiac medications that are monitored by TDM include: Digoxin Digitoxin Procainamide N-Acetylprocainamide (NAPA) -the metabolite of procainamide Quinidine

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Phlebotomy
Cardiovascular system : structure & function

The cardiovascular system consists of the Heart, and Blood Vessels. Its main function is circulate oxygenated blood from the lungs to various organs, and return blood depleted of oxygen to the lungs, where it is reoxygenated. Illustration this screen from LifeArt Collection 2000, with permission. © Lippincott Williams & Wilkins.

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Circulation: venous portion

Deoxygenated (venous) blood flows from tiny capillary blood vessels within the tissues via progressively larger veins to the right side of the heart.Blood is routinely drawn from veins, but may also be drawn from arteries, or capillaries. Illustration this screen from LifeArt Collection 2000, with permission. © Lippincott Williams & Wilkins.

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Circulation: arterial portion

Blood is then pumped from the right side of the heart to the lungs, where it takes up oxygen. Oxygenated blood is then pumped through the left side of the heart via arteries to tiny blood vessels called capillaries.Illustration this screen from LifeArt Collection 2000, with permission. © Lippincott Williams & Wilkins.

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Red Cell Disorders: Peripheral Blood Clues to Nonneoplastic Conditions
Cardiac hemolysis (Waring Blender Effect)

Two photographs of a peripheral blood smear are submitted for review . The smears are from a 9-month-old baby with a heart valve replacement. In the upper photograph is a nucleated RBC and platelets are decreased. Nucleated red cells and occasional giant platelets indicate an active marrow response. In the process of forcing blood cells through the heart valve, erythrocytes are damaged, schistocytes are formed, and platelets are destroyed leading to thrombocytopenia. In the lower field are schistocytes, acanthocytes, echinocytes (burr cells), spherocytes, and the absence of platelets. The presence of burr cells could represent an artifact of smear preparation, but with the history of valve replacement, the red cell changes are likely the result of red cell damage as the cells circulate through the new valve. This situation is described as Waring Blender Effect because of damage to blood cells passing through the new valve, looking as if they had suffered the onslaught of a blender. Target cells and mild hypochromia may reflect iron deficiency through the loss of iron from destruction of RBC's. Iron loss through red cell destruction may be reflected in some hypochromia.

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Routine Venipuncture
Tourniquets, Alcohol, and Gauze

A tourniquet is used by the phlebotomist to assess and determine the location of a suitable vein for venipuncture. Single-use, latex-free tourniquets are preferred but reusable tourniquets are acceptable. However, if the reusable tourniquet becomes contaminated with blood or body fluid, it must be discarded immediately to avoid the spread of harmful contaminants to other patients. Follow the guidelines established by your facility for cleaning reusable tourniquets.Proper application of a tourniquet will partially impede venous blood flow back toward the heart and cause the blood to temporarily pool in the vein so the vein is more prominent and the blood is more easily obtained. The tourniquet is applied three to four inches above the needle insertion point and should remain in place no longer than one minute to prevent hemoconcentration. If the tourniquet is used during preliminary vein selection, it is best to release the tourniquet after assessing the vein and while you are assembling your supplies. Reapply the tourniquet just before starting the venipuncture; it should then be released soon after the needle has been inserted into the vein and the blood flows into the first tube. If collecting multiple tubes, the tourniquet may remain in place until blood enters the last tube.

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The Urine Microscopic: Microscopic Analysis of Urine Sediment
Formation and Significance of Casts

Casts are cylindrical bodies formed either in the distal convoluted tubules or the collecting ducts of the kidney. Since the walls of the tubule act as a mold for cast formation, the width of the tubule determines the width of the cast. Thus, narrow casts are formed in the distal tubules while broad casts are formed in the collecting ducts. The matrix of all casts is thought to be Tamm-Horsfall protein, a glycoprotein secreted by the distal loop of Henle and the distal tubule. This protein entraps cells and granular material of tubular origin. Very few casts are seen in the urine of a person without renal disease, except for hyaline casts, which may be transiently present after strenuous exercise, and during fever, diuretic therapy, and congestive heart failure. A significant number of urinary casts usually indicates the presence of renal disease.

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Hyaline Casts

Hyaline casts are the type most commonly seen in the urine sediment. A few hyaline casts may occasionally be found in normal urine, and hyaline casts may be seen after strenuous exercise, during fever, diuretic therapy. Pathologically, hyaline casts may be seen with congestive heart failure, and may be seen together with other types of casts in a variety of renal diseases. Hyaline casts have a refractive index similar to the urine in which they are suspended. For this reason, hyaline casts will appear almost invisible under brightfield microscopy, but are easily of seen by phase-contrast microscopy.

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