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Antibodies are immunoglobulin proteins secreted by B-lymphocytes after stimulation by a specific antigen. The antibody formed binds to the specific antigen in order to mark the antigen for destruction.The type of antigenic exposure occurring in the body determines if the antibody is a naturally occurring or immune antibody.Naturally occurring antibodies can be formed after exposure to environmental agents that are similar to red cell antigens, such as bacteria, dust or pollen. Sensitization through previous transfusions, pregnancy or injections is not necessary. These antibodies are usually IgM and react best at room temperature or lower. Most of these antibodies are not clinically significant with the exception of ABO antibodies. Examples of naturally occurring antibodies include anti-A, anti-B, anti-Cw, anti-M, and antibodies in the Lewis and P system.

Malignant cells that have broken away from tumors located in other areas of the body may be seen in spinal fluid. All of the cells in this field are tumor cells. The cells in this slide are characterized by an open, loose chromatin pattern, nucleoli and vacuoles. Notice that the vacuoles are present in both the nucleus and the cytoplasm. Vacuoles in the nucleus are an unusual finding even in tumor cells. Tumor cells are often found in clumps and may have more than one nucleus due to their erratic mitotic patterns. Malignant cells sometimes have an irregular nuclear shape. Bizarre granules may be found in malignant cells but are absent in mesothelial cells.

When the body breaks down fat for energy, three intermediate products are formed. These products, collectively referred to as ketones, are acetone, acetoacetic acid, and beta-hydroxybutyric acid. Normally, the body gets the energy it needs from carbohydrates in the diet. However, stored fat is broken down and ketones are produced and appear in the urine if the diet does not contain enough carbohydrate to supply the body with glucose for energy or if the body cannot use glucose properly.

Ketone bodies are usually absent in urine. The presence of ketones in the urine probably indicates that the body is using fats rather than carbohydrates for energy. High levels of ketones may be present in the urine of individuals with uncontrolled diabetes because the body's ability to metabolize carbohydrates is defective. Detecting the presence of ketones in the urine is a valuable aid to managing and monitoring individuals with diabetes mellitus. Ketonuria is an indication that the insulin dose needs to be increased. Electrolyte imbalance and dehydration occur when ketones accumulate in the blood. If these conditions are not corrected by adjusting the dose of insulin, the patient may develop ketoacidosis and ultimately diabetic coma. Low levels of ketones may be detected during conditions of physiological stress such as fasting, rapid weight loss, frequent strenuous exercise or prolonged vomiting. The presence of ketones in these situations is due to either inadequate intake of carbohydrates or increased loss of carbohydrates.

Ketonuria can also be found in conditions associated with a decreased intake of carbohydrates (starvation), digestive disturbances, dietary imbalance (high fat/low carbohydrate diet), eclampsia, prolonged vomiting and diarrhea, glycogen storage diseases, vigorous exercise, fever, and following administration of anesthesia. Ketone bodies are mildly toxic to the body, tending to interfere with the excretion of uric acid, produce mild depression of the central nervous system, and cause acidosis.

A 63 year old man was seen in the emergency room with the complaints of sudden onset of fever, chills, and abdominal pain, accompanied by mild diarrhea. The blood pressure was 140/84, the pulse rate 82/minute, and the body temperature 39.8C. A blood sample was drawn for a complete blood count, and a blood culture.A second blood culture was drawn from the opposite arm, with 10 ml of blood being placed into each an aerobic and an anaerobic bottle, following customary practice.The complete blood count revealed a hemoglobin of 15.8 mg/dl, a hematocrit of 45%, and a white blood count of 4.2/L. The neutrophils were 39%, lymphocytes 45%, monocytes 10%, eosinophils 4% and basophils 2%. The platelet count was 255/L. The patient was admitted to the hospital for further work-up and empiric antibiotic therapy.Within 24 hours after admission, the body temperature had decreased to 38.2C, although the mild diarrhea persisted.A stool toxin test for Clostridium difficile was negative and neither enteric pathogens nor Campylobacter species were recovered in stool culture after 24 hours incubation. Fecal neutrophils were not seen on direct examination. The anaerobic blood culture became positive 36 hours after inoculation.

Ladhani S. Joannou CL. Lochrie DP. Evans RW. Poston SM.: Clinical, microbial, and biochemical aspects of the exfoliative toxins causing staphylococcal scalded-skin syndrome. Clinical Microbiology Reviews. 12:224-242, 1999The exfoliative (epidermolytic) toxins of Staphylococcus aureus are the causative agents of the staphylococcal scalded-skin syndrome (SSSS), a blistering skin disorder that predominantly affects children. Clinical features of SSSS vary along a spectrum, ranging from a few localized blisters to generalized exfoliation covering almost the entire body.The toxins act specifically at the zona granulosa of the epidermis to produce the characteristic exfoliation, although the mechanism by which this is achieved is still poorly understood.Despite the availability of antibiotics, SSSS carries a significant mortality rate, particularly among neonates with secondary complications of epidermal loss and among adults with underlying diseases.

The last type of collection is the observed collection. In this type of collection both the donor and “observer” enter the collection stall. Observed collections afford less privacy in order to guard against the donor using items which are designed specifically to beat the testing process. Under the Department of Health and Human Services mandatory guidelines for Federal workplace drug testing the observer must directly watch the urine go from the donor’s body into the collection container. The use of mirrors or video cameras is not permitted.The observed collection is expanded under the Department of Transportation’s 49 CFR § 40. After entering the stall the observer requests the donor to: Raise shirt, blouse, dress / skirt as appropriate, above the waist, just above the navel, Lower clothing and underwear to mid-thigh, and, Then turn around to show the observer that the donor dies not have a prosthetic device. After the observer has determined that the donor does not have a prosthetic device, the donor is permitted to return clothing to proper position. The observer must personally watch the urine go from the donor’s body into the collection container. The use of mirrors or video cameras is not permitted.

Serum and plasma are the most common clinical specimens used for electrophoresis applications. Urine and cerebrospinal fluids (CSF) are also suitable. Other body fluids such as pleural fluid and pericardial fluid are analyzed less frequently. Some specimens require pretreatment before electrophoresis. Low concentrations of proteins normally in urine and CSF are concentrated in order to have enough proteins for detectable separations. Some body fluids require removal of pigments, salts, and other compounds that interfere with electrophoresis or the detection of separated solutes. In molecular diagnostic testing of DNA and RNA, the nucleic acids must first be isolated from the specimen and then purified before separation with electrophoresis.

With a pH 8.0-9.0 used for protein electrophoresis, proteins take on a negative charge, that is a negative ion cloud forms. As the negative ion cloud migrates to the anode, the proteins are pulled to the anode. Several gels used routinely for protein electrophoresis attract positive ions from the buffer and form a positive ion cloud. This ion cloud moves in the opposite direction to the cathode. This phenomenon is called electroendosmosis or endosmosis.The tension created by these oppositely moving ion clouds can affect the movement of sample macromolecules. The migration of some proteins can be slowed, some proteins can become immobile, and other proteins are pushed toward the cathode. Many protein electrophoresis methods take advantage of this tension and use it to achieve better separation of protein bands. The gamma globulin band in serum, urine, and other body fluids will separate more sharply by being pushed to the cathode and will appear behind the point of sample application.

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.

Many lipophilic substances, including fat-soluble vitamins, cholesterol, and triglycerides are essential for life. The body needs to be able to absorb and transport these substances. However, lipophilic substances are not water-soluble, and, since blood is aqueous, this presents a challenge. The body addresses this need by using 'carriers' which can bind or sequester lipophilic molecules to aqueous 'vehicles' and thus transport them through the aqueous environment of the blood. Small lipid-soluble hormone molecules like estrogen, testosterone or cortisone are carried through the blood by binding to carrier proteins. Cholesterol and triglycerides are carried through the body in small spherical particles which trap the lipophilic molecules in their centers. These particles have an outer shell that is polar on the surface so that the particles are soluble in the blood but they have a lipophilic core which can hold fat-soluble molecules.

By measuring ApoB we can quantify the amount of all atherogenic or potentially atherogenic lipoproteins that carry this apolipoprotein. Although lipoprotein particles other than LDL can carry ApoB, LDL accounts for the vast majority of ApoB; therefore, it is a good index of LDL particle number. Furthermore, the other particles that can have ApoB (such as IDL and Lp(a)) are also atherogenic and so it is not problematic if they are counted along with LDL, since they also contribute to cardiovascular risk. What about ApoA1? HDL-C is known as 'good cholesterol'. The role for HDL in the body is to sequester excess cholesterol and bring it back to the liver. Since HDL can remove cholesterol and transport it back to the liver for excretion or re-utilization it is indeed good. HDL is a negative cardiovascular risk factor; as its concentration goes up, a person's cardiovascular risk decreases. A person with low cardiovascular risk would have low ApoB levels and high ApoA1 levels. If we measure both ApoB and ApoA1 and express them as a ratio of ApoB/ApoA1 we get a powerful cardiovascular risk marker. The ratio should be approximately 0.3-0.9. Patients with a higher ratio have elevated ApoB (LDL) and/or low ApoA1 (HDL) and are thus at increased risk. By combining these two markers in a ratio, we get synergy and enhanced predictive power.

Under normal conditions, Howell-Jolly bodies are thought to be remnants of nuclear fragments due to incomplete expulsion of the nucleus. In pathological conditions, they are aggregates of chromosomes which have separated from the mitotic spindle during abnormal mitosis. Single or multiple Howell-Jolly bodies may be found in a red cell. A single HJ body in a red cell may be seen in megaloblastic anemia, hemolytic anemia such as sickle cell anemia and after splenectomy. Megaloblastic anemia or abnormal erythropoiesis is usually present when multiple Howell-Jolly bodies are observed in a single cell.

In section A of the image, the arrow points to an RBC with basophilic stippling.In section B, the arrows point to erythrocytes containing Pappenheimer bodies.The arrows are pointing to Howell-Jolly bodies in section C.By contrast, in section D the arrow is pointing to a platelet that is sitting on top of an RBC. This may be mistaken for an inclusion. One of the distinguishing characteristics that can alert you to the fact that it is not an inclusion is the halo around the platelet.

Third degree burns or second degree burns involving more than 20% of body surface area must receive immediate emergency medical attention.

The ability of the body to maintain a state of homeostasis, or physiological equilibrium, is absolutely essential for effective, efficient functionality of all body systems. The mechanisms involved in blood coagulation, also known as hemostasis or blood clotting, serve to illustrate this concept. Hemostasis is the cessation of free blood flow, external to the vascular system, when a vessel wall has been breached. With the maintenance of homeostasis in mind, it is vital that the body be able to rapidly repair vascular damage, arresting blood flow in the process, while simultaneously maintaining blood in a fluid state within the vascular compartment.

In summation, we have covered the following sequence of events which comprise primary hemostasis. The process begins with damage to a vessel wall, as blood flows outside the vasculature. The body responds with vasoconstriction, decreasing blood flow to the affected area. Platelets begin sticking to the damaged vessel walls. As the platelets stick, they release chemicals which signal other platelets to respond. As other platelets arrive, they begin sticking to one another, clumping together, forming a plug to fill in the breach. This plug, while strong, is a temporary fix, and must be reinforced with fibrin strands to effectively fill the breach during the vessel repair process. Construction of the fibrin strands occurs during secondary hemostasis, our next topic to be covered.

The liver is the site of production for the vast majority of our clotting factors. Therefore, impaired liver function could adversely affect these hemostatic proteins. Some early indicators of a potential liver problem include: An increase in factor VIII. It is not produced in the liver and will be present in elevated numbers as the body attempts to compensate. The PT is sensitive to liver function, so an unexpected, prolonged PT should be evaluated. A lack of fibrinogen is often indicative of severe liver disease. It is difficult to treat liver disease, so therapy typically centers around replacing the missing factors by way of administration of fresh frozen plasma.

Molecular based clinical diagnostic test methodologies differ according to the target of interest. For example, patients suspected of having different diseases will require the identification of different targets. These targets might be found in different cells of the body and may therefore require different specimens to provide the answers. Patient A suspected of having Disease 1-requires the identification of a target of missequenced DNA- might require specimen of whole blood Patient B suspected of having Disease 2-requires identification of a target of antibody production-methodology might require specimen of serum Using this specific approach of disease diagnosis based on unique target identification, tests can provide answers that are more rapid sensitive specific

Adverse drug reactions are a leading cause of morbidity and mortality in the United States. Drug metabolism is a process whereby drugs are delivered to the body, distributed, metabolized and then ultimately excreted. As there can be potentially significant differences between patient drug absorption, metabolism and excretion, molecular testing allows a physician to work with a patient's individual phenotype and/or genotype to deliver an optimum pharmaceutical selection and/or dosage.

Because hereditary hemochromatosis (HH) is a disease of iron overload, a review of the basic principles of iron metabolism is helpful in understanding its pathophysiology. Iron is needed by all body cells and is crucial for oxygen transport, oxidative metabolism, and cell growth and proliferation. To serve these functions, iron must be bound to protein. Iron is potentially harmful when ionized or complexed to inorganic compounds. Iron must be present in amounts sufficient to carry out these normal functions, but not in excessive amounts which may be toxic.Two types of iron-containing compounds are normally found in the body: compounds that serve in metabolic or enzymatic functions and storage compounds. Hemoglobin, myoglobin, cytochromes and other proteins are involved in oxygen transport and utilization. Iron in hemoglobin comprises about 67% of total body iron, thus erythrocytes are rich in iron. Approximately 27% of iron is found in storage compounds. Myoglobin, other tissue iron, and transport iron comprise the remaining 6% of total body iron. (2)

Storage forms normally comprise approximately 27% of total body iron. Stored iron provides a source of iron when physiologic demand is high, such as in blood loss, pregnancy, and periods of rapid growth. Storage compounds include ferritin and hemosiderin. Ferritin is a protein-bound, water-soluble, mobilizable storage compound and is the major source of stored iron. Hemosiderin is a water-insoluble form that is less readily available for use. When the amount of total body iron is relatively low, storage iron consists predominately of ferritin. When iron stores are increased, hemosiderin predominates. Unlike ferritin, hemosiderin stains with the Prussian blue stain (Perls reaction) and may be observed in tissues.

Serum iron (SI) is a measure of circulating iron bound to transferrin and is reflective of total body iron. SI is elevated in hereditary hemochromatosis (HH) and acute hepatitis. SI is decreased in iron deficiency anemia and chronic inflammation. SI concentrations exhibit diurnal variation, with the lowest values occurring around midnight. In addition, specimens collected from the same individual at the same time of the day may exhibit day to day variations as high as 40%. SI determinations are also affected by diet, menstrual cycle, pregnancy, ingestion of iron supplements, and oral contraceptive use. SI levels alone are considered insensitive indicators of HH. SI is typically measured on automated analyzers using spectrophotometric methods. Iron in the sample is released from transferrin with an acid reagent, reduced to the ferrous state, and reacted with a chromogen such as bathophenanthroline or ferrozine. The intensity of the color change is proportional to the iron concentration. Interference can arise from the use of a hemolyzed sample and contamination of reagents and water with iron. A typical reference interval for SI is 60 - 150 micrograms/dL. SI is usually ordered along with its companion test, the total iron binding capacity (TIBC), or with transferrin (Tf).(2)

Genetic mutations in HIV are well known and are very likely, considering the presence of two RNA molecules per virus. Either or both RNA molecules can mutate. These mutations potentially lead to drug resistance or encourage the virus to evade the body's immune response. Mutations have created three major groups of HIV - M, N, and O. M is found in 99% of all the HIV cases in the world. N and O are primarily found in West African countries. N, though, infects only a very small number of individuals. The M group has subgroups lettered A to J. Subgroup B predominates in North America.

HIV transmission, due to occupational exposure, occurs by: Percutaneous injury, such as a needlestick or a cut with a sharp object; Contact of mucous membrane or abraded skin with HIV-infected blood or body fluids. The risk of HIV transmission after a percutaneous exposure to HIV-infected blood is 0.3%.The risk of HIV transmission after a mucous membrane exposure to HIV-infected blood is .09%.The risk of HIV transmission after contact of abraded skin with HIV-infected blood is estimated to be less than .09%.

Gloves must be worn: when there is a reasonable chance of exposure to blood, other infectious body fluids, mucous membranes, or nonintact skin. during vascular access procedures, including phlebotomy. when handling contaminated items or surfaces.Wear only flat rings under gloves as large rings may tear gloves.Replace gloves: Between patient contacts If they are damaged or contaminated Before leaving the work area. Wash hands after removing gloves.Never wash disposable gloves.

The DNA provirus continues to encode new HIV particles within the host cell. During this early stage the injured host cells, such as T-lymphocytes, are able to replace themselves, and the body remains able to launch a defensive response. Eventually, though, the number of viruses becomes overwhelming.

Most likely means of dissemination: Solid, liquid or aerosolPrimary route of entry: Absorption, inhalation, ingestionGeneral signs and symptoms: Vary by type of viral hemorrhagic fever (VHF), but initial signs and symptoms often include marked fever, fatigue, dizziness, muscle aches, loss of strength, and exhaustion. Severe cases of VHF often show signs of bleeding under the skin, in internal organs, or from body orifices like the mouth, eyes, or ears.  Photo courtesy of the CDC archives.

Examining the biopsy allows the structure of the marrow to be viewed as it exists in the body. It provides essential diagnostic information in conditions that disrupt the normal architecture, such as metastatic carcinoma, myelofibrosis, Hodgkin's lymphoma and granuloma. A biopsy may also be used to evaluate cellularity and identify acid-fast bacteria or fungi in less time than is needed for routine culture methods. One disadvantage of the tissue sections prepared from the biopsy sample is that morphologic detail is lost. For this reason, in many cases imprint slides or smears from the aspirated sample are also examined.

It is also important to note that in addition to red cells, ABO antigenic determinants (epitopes) are found in many tissues, body fluids, and other cells including endothelial cells and platelets. Because ABO antigens are so widely expressed, ABO antigens are also a major consideration in solid organ and bone marrow transplants.

Pam is seated at the workbench where she routinely prepares dilutions using an automated pipette. She leans to the right and stretches over her rack of tubes each time she needs to change a pipette tip. Pam is working in an awkward body position because the pipettes are not in a convenient location and the space is not well organized.By changing the location of the pipettes to within her routine work area, she can avoid overstretching to reach the pipettes and avoid contorting her body into an awkward position that could eventually result in an MSD. As shown in the image, regularly used items should be close to the worker to avoid leaning forward and over-extending reach radius. Adjust your work space so that you can reach tools and equipment without unusual bending or twisting; arrange the work area properly within the "work zone".Avoid reaching more than 10 inches (25 cm) in front of the body for frequently used materials or 20 inches (50 cm) for items that are used occasionally.

Take frequent posture breaks; if standing, sit periodically. If sitting, stand about every 20 minutes and walk around. Shoulders and Arms Keep the shoulders relaxed, not shrugged-up or slumped-down. Keep your elbows close to your body Keep work at elbow height and directly in front of you as shown in the image below. Head and Neck Avoid situations that require prolonged or repetitive twisting, forward-bending, or backward-bending of the neck.Hands and Wrists Keep the hand in line with the forearm. Avoid repetitive twisting of the wrists. Avoid working with wrists pressed against hard surfaces or edges as shown in the image below. Feet and Legs Place a foot on a footrest for comfort Provide a toe space to allow work closer to counters and reduce reaching. Use mats on hard floors to reduce fatigue as shown in the image below.Back Stand straight. Avoid situations that require bending forward, backward, leaning side-to-side, or twisting. Use a stool to provide an occasional change in posture. If working seated, use a back rest/support to maintain proper posture. The chair that is shown in the image below offers neck, back, and lumbar support.

Evaluate your work station including leg room, reach radius, accessibility of commonly used materials, and height of the work surface. Adequate space should be available to accomodate equipment and allow for full range of motion. ChairPersonnel who sit for long periods of time should adjust chairs so that feet are flat on the floor or on a footrest. Chairs should have some primary features that can be easily adjusted including controls to raise and lower chair, seat pan adjustment, lumbar support, and backrest tilt or angle. Adjust the seatback slightly forward if necessary to avoid leaning forward unsupported or jutting your head forward. Reach radius Regularly used items should be close to the worker to avoid leaning forward and over-extending reach radius. Adjust your work space so that you can reach tools and equipment without unusual bending or twisting.Avoid reaching or bending - arrange the work area properly within the "work zone". Avoid reaching more than 10 - 15 inches in front of the body for frequently used materials or 20 inches for items that are used occasionally.Avoid reaching above shoulder height, below waist level, or behind the body to minimize shoulder strain.Avoid repetitive work that requires full arm extension (i.e., the elbow held straight and the arm extended).The image illustrates a workstation that is used by a technologist who performs microscopic work for the majority of the workday. The workstation is designed to prevent musculoskeletal disorders and fatigue.

Specialists in microbiology perform testing to diagnose and stop the spread of infectious organisms, including bacteria, viruses, and parasites. Specialists should be able to isolate and identify a wide variety of these organisms. Testing procedures include direction examination and antigen detection methods. Specialists in serology and immunology measure antibodies to infectious organisms. Specialists should be familiar with all serology techniques (except those specific to immunohematology). This specialty includes all lab procedures performed in the specialty of histocompatibility. Specialists in hematology must be able to identify and evaluate cells in blood and bone marrow and identify disorders of these cell. Specialists should be familiar with routine and special tests to determine the number, morphology, and function of cells in body fluid.

Specialists in radioassay use radionuclides to determine the chemical makeup of body fluids such as blood and urine. Specialists in blood gas analysis evaluate lung and breathing function by levels of oxygen, carbon dioxide, pH, and hemoglobin with automated tests. Specialists in histology examine cellular and tissue samples using fixation, dehydration, embedding, microtomy, frozen sectioning, staining, and other similar techniques. Histology specialists licensed as technicians can perform specimen processing, embedding, cutting, staining, and frozen sectioning only under the general supervision of a director, supervisor, or technologist. Specialists in cytology process and interpret samples relating cytopathological disease. Non-gynecological cytology preparations can be screen by a specialist in cytology but final review and interpretation must be done by a physician.

Sentinel Events are sentinels--they function as guards or watchkeepers. They indicate serious situations that require immediate attention: Patient deathParalysisComaPermanent loss of functionAny procedure on the wrong patient, the wrong side of the body, or the wrong organ Hemolytic transfusion reaction involving major blood group incompatibility

The Centers for Medicare and Medicaid Services (CMS), the US agency that administers the Medicare program, defines "medical necessity" as services or items reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member. Medicare will not pay for any tests that CMS determines as unnecessary for diagnosis or treatment of disease.A laboratory may not submit a claim to Medicare or other government payers for any test it suspects is not medically necessary unless: The patient has signed an Advanced Beneficiary Notice, or A patient has requested the lab to submit such a claim for a determination by Medicare. Medicare does not pay for screening tests or tests that are ordered in the absence of signs or symptoms. Billing department employees are responsible for following all policies and procedures related to the submission of claims to reduce erroneous billings.

Monocytes are phagocytes which remove injured and dead cells, cell fragments, microorganisms and insoluble particles from the blood and body tissues.Monocytes also secrete substances that affect the function of other cells, especially lymphocytes.They are produced in the bone marrow, and when mature are released into the peripheral blood. Although they do serve a phagocytic role in the blood, their main site of action is the body tissues.The half-life for monocytes in the peripheral blood is approximately 8 hours. Monocytes migrate into the tissues, often to sites of inflammation, where they serve their primary purpose.Here they transform into fixed or free macrophages, and continue their function as avid phagocytes.When activated, macrophages may enlarge and have enhanced metabolism.

The first group is composed of erythrocytes or red blood cells (RBC's). The main function of the erythrocytes is the transport of oxygen from the lungs to the body tissues. Most of the cells in this Wright's stained peripheral blood smear are red cells. On is shown at the arrowhead.

Antibody - A modified type of serum globulin synthesized by lymphoid tissue in response to antigenic stimulus. By virtue of specific combining sites each antibody reacts with only one antigen. Anucleate - Having no nucleus. Azurophilic granules - The well-defined large reddish granules (lysosomes) which may be present in large lymphocytes. They are called "azurophilic granules" because they stain blue with the azure stains which were originally used. Basophilic granules - Specific granules present in the cytoplasm of basophils. These granules are large and stain purple-black due to their strong affinity for basic stain. B-cell - Bone marrow derived lymphocytes which produce humoral antibodies. Biconcave - Having two concave surfaces. Cellular Immunity - The capacity of a small proportion of lymphoid population to exhibit response to a specific antigen. Chromomere - The centrally located granular portion of the platelet. Clone - A population of cells descended from a single cell. Delayed Hypersensitivity - (part of cellular immunity) that develops slowly over a period of 24-72 hours after an antigenic stimulus. It consists of an accumulation of cells around small vessels and/or nerves. Example: Tuberculin skin test reaction. Digestive Enzyme - A substance that catalyzes or accelerates the process of digestion. Eosinophilic Granules - Specific granules present in the cytoplasm of eosinophils. These granules are large, refractile spheres which stain reddish-orange due to their strong affinity for acid stain. Erythrocyte (red blood cell, RBC) - One of the elements found in peripheral blood. Normally the mature form is a non-nucleated, circular, biconcave disk adapted to transport respiratory gases. Fixed Macrophage - A phagocyte that is non-motile. Free Macrophage - An ameboid phagocyte present at the site of inflammation. Graft Rejection - A transplanted tissue that is rejected by the body's antibodies. Graft vs. Host Reaction - A complication that occurs when an implanted piece of tissue, which contains antibodies, rejects the host's tissue. Granulocyte - A leukocyte which contains granules in its cytoplasm, i.e., neutrophilic, eosinophilic, or basophilic granules. Half-life - is the length of time it takes for half of the cells circulating at a given time to leave the blood for the tissues. Hemocyte - Any blood cell or formed element of the blood. Hemostasis - A mechanism of the vascular system to arrest an escape of blood. It involves an interaction between blood vessels, platelets, and coagulation. Heparin - A mucopolysaccharide acid which, when present in sufficient amounts, functions as an anticoagulant by inhibiting thrombin. Histamine - A powerful dilator of capillaries and a stimulator of gastric secretions. Humoral Immunity - Acquired immunity produced after response to an antigenic stimulus in which B cells produce circulating antibodies. Hyalomere - the clear, blue non-granular zone surrounding the chromomere of a platelet. Immune Response - The interaction of a cell and an antigen that results in a proliferation of the cell and a capacity to produce antibodies. Isotonic Fluid - A fluid whose elements have an equal osmotic pressure. Leukocyte (white blood cell, WBC) - One of the formed elements of the blood; involved primarily with the body's defense. Lysosome - A microscopic body within cell cytoplasm; contains various enzymes, mainly hydrolytic, which are released upon injury to the cell. Megakaryocyte - A giant cell of the bone marrow from which platelets are derived. Mononuclear - A cell having a single nucleus.

Neutrophils have a relatively short life span.They are produced in the bone marrow, and when they reach the band or segmented stages are released into the peripheral blood.They remain there for approximately ten hours before randomly entering body tissues.Neutrophils in the blood stream can be divided into circulating granulocyte pool(CGP) and marginating granulocytic pool (MGP).The white blood cell count reflects the cells in the circulating pool.The cells in the marginating pool move quickly into the circulating pool when needed.During an infection the neutrophil concentration of the peripheral blood can increase almost immediately due to the shift of these cells from the marginating pool and release from the bone marrow storage pool, if needed.Neutrophils then migrate to areas of tissue damage or infection.Neutrophils do not reenter the blood stream from the tissues, thus end their life in the tissues either as a result of phagocytosis or senescence.

As a healthcare worker, you come into contact with materials that may contain bloodborne pathogens. These are infectious organisms, usually viruses, which live in human blood and body fluids.The most important ones are: Hepatitis B Virus (HBV) Human Immunodeficiency Virus (HIV) Hepatitis C Virus (HCV)

There are three exposure categories :Category I are those employees who on a day-to-day basis will come in contact with blood or body fluids as part of their normal job. This includes medical technologists, pathologists and operating room nurses.Category II are those employees who may come in contact with blood or body fluid during the course of their normal job. This includes housekeepers, transporters, and some technicians such as EKG techs.Category III are those persons who would not normally ever come in contact with blood or body fluids and generally includes secretaries, administrators and gardeners.Persons may move from one category to another during the course of a work-day.

You can avoid exposure to Hepatitis B by taking the appropriate precautions, such as: Receiving the immunization against Hepatitis B. Following standard precautions. Maintain proper work practices. Using proper techniques when handling materials which may be contaminated with blood or other potentially infected body fluids.

Patients with Hepatitis B and other bloodborne infections can appear healthy, so you can't tell whose blood is infectious.So treat all: blood body fluids secretions (except sweat) excretions non-intact skin mucous membranes as if they were infectious.That's what the term Standard Precautions means.

HBV is spread in the community through: Sexual contact. Drug abusers sharing contaminated needles. An infant's exposure to its mother's body fluids.

It is important to always dispose of contaminated wastes properly!Examples of contaminated wastes: Microbiology waste and pathology waste All body fluids, such as pleural fluid Contaminated sharps and blood specimens

When there is a reasonable chance of exposure to blood, other infectious body fluids, mucous membranes, or nonintact skin. During vascular access procedures, including phlebotomy. When handling contaminated items or surfaces.

This is the most important section of all. It provides information on how the chemical could affect you. Is it a carcinogen? How can it enter your body? What are the signs and symptoms of overexposure to the chemical? What first aid procedures should be used in case of an accident?

The degree of electricity-induced injury is dependent on: The amount of electrical energy that is delivered The resistance that is encountered The type of current The current pathway The duration of contact

A ground is a conducting connection between an electrical circuit or equipment and the earth, or between an electrical circuit and some conducting body that serves in place of the earth.The purpose of a ground is to prevent the buildup of voltages that may result in a hazardous situation for the connected equipment and/or for the person operating the equipment.All electrical equipment in the laboratory that is not clearly marked as "double-insulated" must be grounded by using a three-pronged power cord.

Laboratory specimens that are unlikely to cause disease and do not meet the criteria for category A or B substances are not subject to Division 6.2 regulations. Specimens for which the hazardous materials regulation (HMR) does not apply include human or animal samples (including, but not limited to, secreta, excreta, blood and its components, tissue and tissue fluids, and body parts) being transported for routine testing not related to the diagnosis of an infectious disease. This includes specimens that are being sent for: drug or alcohol testing cholesterol testing blood glucose level testing prostate specific antibody (PSA) testing testing to monitor kidney or liver function pregnancy testing tests for diagnosis of non-infectious diseases such as cancer biopsies

In order to discuss TDM and PGx we need to also introduce the concept of pharmacokinetics. Pharmacokinetics is the study of drug disposition in the body: how and when drugs enter the circulation, how long they remain in the blood, and how they are eliminated. TDM is the clinical assessment of a drug's pharmacokinetic properties. Physicians and pharmacists need to establish that a drug is present at an effective concentration but not at a toxic concentration. The next few pages will describe some of the factors that determine a drug's disposition in the body. These factors ultimately decide the need for therapeutic drug monitoring.

In addition to protein availability, other factors may affect drug absorption and distribution in the body as a whole or at specific sites within the body. The following table highlights some of these other factors. Factor Discussion Regional blood flow Reduced area blood flow can be seen in diabetics and enhanced blood flow can be seen in tumors. Lipid solubility of the drug The more lipophilic a drug is, the more likely it will enter the central nervous system. The integrity of the GI tract In a diseased gut, an orally-administered drug may not be absorbed as expected. Age Drug kinetics and dispositions change throughout life. In general, metabolism of drugs is reduced in the elderly. Genetics Mutations or deletions in drug metabolizing enzymes can greatly affect a drug's disposition.

TDM provides a quantitative measure of the circulating concentration of a drug. The physician determines if the dosage of the drug needs to be adjusted based on this information.If a drug concentration is determined to be outside the therapeutic range, it may be for one of the reasons listed in the table below. Reason Discussion Noncompliance Patients may (intentionally or unintentionally) not take the drug. TDM can thus help monitor compliance. Dosing errors The dose may have been erroneous or inappropriate given the patient's condition. Malabsorption The TDM result will reveal if the drug cannot be absorbed well through the gut and an alternative route of administration will be needed. Drug interactions Many drugs interfere with the absorption or metabolism of other drugs. These interactions will be revealed by TDM. Kidney or liver disease Any pathology that affects elimination will cause an elevation in a drug level that will be unmasked by TDM. Altered protein binding Changes in serum proteins can lead to big changes in the amount of free drug in serum. Variations in the genetics of drug-metabolizing enzymes can also affect drug concentrations in the body. This is the field of pharmacogenomics that will be discussed later in the course.

The amount of time it takes for a drug's concentration in the body to decrease by 50% is called the drug's half-life (t1/2).The longer a drug's half-life, the slower it is removed from the body. Most drugs are eliminated from the body in 1 to 3 days, but some drugs with longer half-lives can still be detected in the body weeks after the initial dose. The figure below illustrates a typical kinetic pattern for an oral drug.

Treat all blood & body fluids as if they were infectious.Always wear gloves during vascular access procedures.

Bloodborne pathogens are infectious micro-organisms which live in the bloodstream.You can be exposed to bloodborne pathogens if you are injured with a contaminated needle.You can also be exposed if your mucous membranes, including eyes, mouth, or the inside of your nose come into contact with contaminated body fluids.

Potentially infectious body fluids include: Blood, Semen, Vaginal Secretion, Peritoneal, pericardial and pleural fluids, and Saliva Sweat and tears are not generally considered infectious. It is important to remember that bloodborne pathogens are not transmitted by casual contact, like a handshake.

The function of the integumentary system is to: Protect the underlying tissues from the external environment. Help regulate body temperature. Conserve moisture.

Red blood cells contain hemoglobin, which carries oxygen from the lungs to the tissues of the body. Hemoglobin gives blood its red color. Red blood cells are shown in the photomicrograph of a stained blood smear to the right.

Epithelial cells in large numbers within sputum smears means that the specimen is predominantly oral saliva, rather than true sputum from the lung. Epithelial cells in urine smears indicate that the sample has been contaminated by organisms found on the vulva or distal urethra. Bacteria found near or on epithelial cells are usually normal contaminating bacterial flora.White blood cells indicate inflammation and possible infection. The direct smear examination should focus within and around these cells.Red blood cells in a direct smear are not usually significant.Yeast may be present as normal flora in upper respiratory tract or genital tract. They may be significant if they predominate, or if budding yeast forms are seen.Hyphae are more likely to indicate the presence of fungal infection, but this determination requires correlation with clinical findings.Bacteria found in spinal fluid, blood, tissue and specimens from other sterile sites are always significant.Body fluids which are normally sterile must be examined carefully. If only one organism per oil immersion field is identified, then there are about 105 organisms per mL present in the sample! Bacteria observed in specimens from the throat, genital tract and other areas containing normal flora suggest infection only if their composition and type varies significantly from the norm.

Sickle cells, also referred to as drepanocytes, are formed as a result of the presence of hemoglobin S in the red cell. As the red cell ages, it becomes rigid as it passes through the low oxygen tension atmosphere of the small capillaries in the body. In the absence of oxygen, hemoglobin S polymerizes into rods, causing the sickle cell shape. The shape of sickle cells can vary from cigar-shaped, as shown in the upper image, to the more severe sickled-form, shown in the bottom image.

The antecubital area of the arm is usually the first choice for routine venipuncture. This area contains the three vessels primarily used by the phlebotomist to obtain venous blood specimens: the median cubital, the cephalic and the basilic veins.Although the veins located in the antecubital area should be considered first for vein selection, there are alternate sites available for venipuncture. These include the top of the hand, the side of the wrist, and the forearm. These sites should only be considered after determining that the veins of the antecubital area cannot be accessed or cannot be used. Vein Location Reason for Choice Placement Direction Median Cubital Mid antecubital fossa Vertical to diagonal Musculature assists in stabilizing vein; very often largest; ease of access Cephalic Thumb side of antecubital fossa Vertical Ease of access; few nerves and tendons in area Basilic Body side of antecubital fossa Vertical to diagonal More difficult to access; proximity of artery, nerves and tendons. Use this vein only as the final alternative.

Other aspects of specimen collection that must be considered are the temperature of the specimen and the time needed to transport it to the laboratory.Ideally, the specimen should be collected in a room at the testing site.If on-site collection is not possible, the specimen should be kept at body temperature (37°C) from the time of collection until it arrives at the laboratory. This can be facilitated by holding the container close to the body, for example by carrying it in an inside pocket.Semen should arrive at the laboratory as soon as possible after collection, preferably within one hour.Lubricants should not be used for collection unless absolutely necessary as most lubricants are toxic to sperm. If lubricant must be used then non-toxic forms such as KY jelly or cooking oil should be the only options.

Under phase contrast the oval body of the sperm appears bright whereas the tail is dark.

The natural history of TB infection is usually followed by an immune response and latency after exposure. In about 5-10% of cases, the latent period progresses to an active infection.The organism that causes TB infection is Mycobacterium tuberculosis. This organism is pictured in the photograph to the right as observed when stained with acridine orange stain. Infection occurs when a susceptible person inhales droplet nuclei containing Mycobacterium tuberculosis and the organism reaches the alveoli of the lungs.About 2-12 weeks after infection, the immune system limits multiplication of additional bacteria and the immunological test becomes positive.Latent tuberculosis infection (LTBI) is the stage when the viable organism remains in the body, and the patient has no symptoms and is non-infectious.Most infected persons do not experience clinical illness and are noninfectious. About 5-10% of persons infected with Mycobacterium tuberculosis who are not treated will develop TB during their lifetime. The risk for progression is highest during the first several years after infection.TB infects the lungs most often; however, it can infect almost any organ in the body, including bones and joints.

Many variations in morphology may be seen when examining Wright's stained peripheral blood smears. One method of classifying these variations in white cell morphology is based on the way the body responds to a stimulus, deficiency, or the presence of an inherited defect. This classification falls into three groups:Pathological: Cells may show abnormalities in appearance and/or function. The body is responding abnormally to a stimulus or inherited defect, resulting in physiological impairment in the patient. Nonpathological: Cells may show variation in morphology but their function is normal. Their presence does not cause physiological impairment. Reactive: Cells show variation in morphology but are functioning normally in response to a specific stimulus, such as a virus or bacteria. There is a disease process in progress to which the cells are responding. Although the morphology has varied from normal and their presence is significant, the body is responding normally to a stimulus.

There are a number of conditions in which hypersegmented neutrophils may be seen, such as megaloblastic anemias that include folic acid deficiency and pernicious anemia. Individuals who are receiving chemotherapy or have long-term chronic infections may also have hypersegmented neutrophils.The cells seen in these conditions would be classified as pathological since the body is responding abnormally as a result of either a deficiency of a component needed for DNA production or because of the toxic effect that chemotherapy drugs have on DNA.

Vacuoles, toxic granulation and degranulation are classified as reactive since the body is responding normally in an effort to rid itself of infection caused by bacteria. Morphological changes related to aging are also classified as reactive.

Another example of a May-Hegglin-type body. This smear was from a case of pseudo May-Hegglin caused by drugs. Bizarre appearing platelets can also be seen in cases of pseudo May-Hegglin.

Dohle bodies are seen in a number of conditions, including infections, burns, measles, leukemia and chemotherapy. Dohle bodies are classified as pathological in the sense that they are only present when the body is responding to an unusually severe stress or stimulus. This severe stress may cause the cytoplasm of some cells to mature improperly. Their presence does not aid in the diagnosis of the disorders in which they are found, but they are frequently seen along with toxic granulation and/or vacuoles often present in infections and burns. Recognition is important because their appearance is similar to May-Hegglin bodies, which appear in a rare hereditary disorder called May-Hegglin anomaly.