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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.

Autoimmune diseases are a group of disorders where the body's immune system malfunctions and attacks its own tissues. One aspect of these diseases is the formation of antibodies that are directed to self-antigens (autoantibodies). Autoimmune diseases can be divided into two general groups: Organ specific, where the autoantibodies attack a specific organ, and Non-organ specific (or systemic), where the autoantibodies attack multiple organ systems. An example of an organ specific autoimmune disease is Hashimoto thyroiditis where autoantibodies damage the thyroid gland. An example of a systemic autoimmune disease is systemic lupus erythematosus (SLE) where the autoantibodies may attack any organ in the body.

Many skin excisions are submitted in an elliptical shape. This is because it creates wounds that lie parallel to the skin tension lines, so the wounds tend to heal with less scaring. Frequently, elliptical skin specimens will have sutures to indicate how the specimen was oriented on the body. Embed these skin shapes so that the cut surface of the tip (broadest surface of the triangle) is down in the block face. This results in successive sections that progress towards the tip and become smaller over multiple sections. This orientation allows the residual tumor, if present, to be traced out to the tiniest point of the tip. The body, or mid sections, of the specimen will be placed on the cut surface to be serially sectioned at an angle perpendicular to the epidermis.

Under normal circumstances, fluids collected from any enclosed body space such as a cerebrospinal fluid (CSF), pleural, peritoneal, pericardial or synovial fluids, should be sterile. When an infection occurs within a body cavity, the fluid that is collected from that site for diagnostic purposes will potentially have infectious organisms present on the cytospin. There can be several types of organisms demonstrated on the Wright stained preparation.Bacteria and fungus are the most common but it is possible to demonstrate the presence of protozoan parasites as well.Spirochetes and acid fast bacilli (AFB) such as mycobacteria will not stain with Wright stain so they will not be detected even if they are present.Since bronchial alveolar lavages, or BALs, are collected through an open airway it is normal to observe respiratory flora, however yeast and hyphae are never normal in a BAL.It is standard practice before reporting the presence of bacteria in a fluid to correlate/confirm the findings with the microbiology lab.

There are a wide variety of solid tumors that can metastasize and spread into body fluids. As with cytospins positive for leukemia or lymphoma, any smear with tumor or suspected tumor should be sent for pathology or hematologist review.Body fluids tend to be a good growth medium for metastatic tumors. These tumor cells tend to be present in sheets and clumps. Frequently there will be reactive changes with increased mesothelial cells and macrophages associated with metastatic tumors as well.Tumor cells, in general, typically appear large with fine/open chromatin patterns, dismorphic or dysplastic nuclei and prominent nucleoli. They will have varying amounts of basophilic cytoplasm depending on the tissue of origin.

Carr JH, Rodak BF. Body Fluids. In: Clinical Hematology Atlas, 3rd ed. St. Louis, Missouri: Saunders Elsevier; 2009: 231-253.Galagan KA, Blomberg D, Cornbleet PJ, Glassy EF. Color Atlas of Body Fluids: An Illustrated Field Guide Based on Proficiency Testing. Northfield, IL: College of American Pathologists; 2006.Kjeldsberg CR, Knight JA. Body fluids: laboratory examination of amniotic, cerebrospinal, seminal, serous & synovial fluids. Chicago, Illinois: ASCP Press; 1993.McKenzie SB, Williams JL. Morphologic Analysis of Body Fluids in the Hematology Laboratory. In: Clinical Laboratory Hematology, 2nd ed. Upper Sadle River, New Jersey: Pearson Education, Inc.; 2010: 583-611.

Fungal infections can also be identified in the cytospin preparations from various body fluids. The next series of photos shows the peritoneal fluid from an immunosuppressed patient in renal failure requiring peritoneal dialysis.Note the cluster of yeast cells in the center of the photo. This was eventually identified as Candida albicans.

Reactive mesothelial cells can be found when there is an infection or an inflammatory response present in a body cavity. This condition can be due to the presence of a bacterial, viral or fungal infection. It can also be the result of trauma or the presence of metastatic tumor.Reactive mesothelial cells tend to come in clusters and clumps and have a more washed out cytoplasm in body fluids. Notice in the image on the right, how indistinct the cytoplasmic borders are in this clump compared to normal mesothelial cells. The wide separation of the nuclei and the well defined nucleoli help to identify these as reactive mesothelial cells. However if there is any doubt, the smear should be sent for hematology or pathology review.Note: It is not uncommon for macrophages to be mixed into a reactive mesothelial clump.

A bone marrow biopsy is obtained by a similar technique but rather than aspirating liquid marrow, a core of bone is allowed to enter the biopsy needle and is then removed within the needle. The image* illustrates the body site where the bone marrow is normally obtained.The core can be rolled between two slides to make touch preparatons (touch preps), which are then stained and reviewed. The bony core is fixed and sent to pathology, where it will be decalcified and prepared for sectioning and staining.Reference: Bone marrow biopsy. National Cancer Institute. Available at: http://www.cancer.gov/Common/PopUps/popDefinition.aspx?id=46506&version=Patient&language=English. Accessed July 3, 2011.

The human heart is a muscular organ that is formed into four chambers with an interconnecting vascular system. Venous blood from the body enters the right atrium, is pumped into the right ventricle and from there is pumped to the lungs for reoxygenation. Oxygenated blood from the lungs accumulates in the left atrium and is pumped into the left ventricle and out to the body. Myocytes (muscle cells) require large amounts of energy and oxygen to accomplish this. The capacity of the heart to pump adequately is regulated by the volume of blood, systemic blood pressure, and the force of contraction achieved in the left ventricular wall.

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, 1999 The 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.

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, include 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.

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.

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 does 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.

In addition to the puncture device, additional equipment may be required when performing a successful dermal puncture.Plastic microcollection devices: Plastic microcollection devices are small plastic tubes designed to collect capillary blood from a dermal puncture wound. Each small collection tube is color-coded in the same manner as blood collection tubes used for venipuncture. The color of the cap of each container tube corresponds to the type of additive inside the tube, most often an anticoagulant. The additive coats the inside of the tube. Examples of microcollection devices are shown below. Heel warmer: It is best practice to warm the heel of an infant with a warming device known as a heel warmer. The heel warmer, when activated, is designed to warm its contents to a standardized temperature. This temperature will be hot enough to effectively warm the heel and facilitate blood flow to the area without causing heat injury to the patient. It is unacceptable to warm a cloth using a microwave. There may be "hot spots" on the cloth that could potentially burn the patient. Keep in mind, what may feel warm to you, the phlebotomist, may feel hot to your patient!Plastic or Mylar-wrapped capillary tube: In some facilities blood from a capillary puncture is collected directly into a capillary tube. These tubes are very delicate and must be used with great caution. As soon as the tube is two thirds to three-fourths filled, one end is sealed to prevent blood from leaking out.Glass microscope slides: In some facilities, the person collecting the capillary specimen may also be required to prepare a blood smear for laboratory examination. A drop of blood is placed directly on a glass slide and spread to create an area for cell examination. If you are required to prepare blood smears, remember that the slide is considered infectious until fixed or stained. It is also important to remember that glass is a sharps hazard. If not used correctly, the glass may cause injury to both the patient and the phlebotomist. Be as cautious with a glass slide containing blood as you are with a contaminated needle. Dispose of glass slides that will not be used for testing in approved sharps containers.Alcohol and gauze pads: Alcohol is the disinfectant of choice for dermal puncture. The alcohol must be allowed to air dry, which will prevent hemolysis of the specimen and discomfort for the patient. A piece of clean or sterile gauze is used to wipe away the first drop of blood. Gauze is also used to apply pressure to the wound after the specimen collection is complete to stop the wound from bleeding.Iodine or other approved cleaning agents may be used as an alternative to alcohol.Bandage: It may be necessary to apply a bandage to the puncture wound on a finger or heel if the site continues to bleed. However, it is NOT recommended to bandage the finger of a child who is 2-years-old or younger since the bandage may become a choking hazard if the child puts that finger in his/her mouth.Personal protective equipment (PPE): All healthcare professionals that may come in contact with blood and/or body fluids while performing a laboratory procedure are required to wear intact gloves. It is against safety guidelines to alter gloves in any way that may compromise the integrity of the gloves. Eye protection, such as safety goggles, is recommended if there is the possibility of a splash of blood while collecting a capillary blood specimen. In many facilities, special gowns are required in some patient areas such as special-care nurseries. Always follow the policies of your facility in regard to PPE.

A deficiency in one or more coagulation factor will also cause abnormalities in hemostasis. The image to the right depicts the coagulation cascade. Notice how one factor acts upon another to eventually form a stabilized fibrin clot, the end product of the coagulation cascade. Having an abnormally low level, or a complete lack, of a coagulation factor can cause the extrinsic, intrinsic, or common pathways to malfunction, resulting in dangerous hemorrhagic issues including spontaneous bleeding. Two of the most common factor deficiencies are factor VIII (hemophilia A) and factor IX (hemophilia B). Hemophilia A comes in two forms: congenital (inherited) or acquired. Congenital hemophilia A represents the condition where an individual is born defecient (to various degrees) of factor VIII. Acquired hemophilia A is a condition in which an individual spontaneously produced an autoantibody to factor VIII, leaving the body unable to use the factor VIII that may be present. Hemophilia B is an inherited condition where the individual has a mutation of the factor IX gene and is unable to produce adequate levels of this coagulation factor.In some cases, patients have multiple factor deficiencies that are secondary to a primary condition such as vitamin K deficiency, disseminated intravascular coagulation (DIC), and liver disease. With vitamin K deficiency, the liver is unable to produce the coagulation factors that are vitamin K-dependent. During liver disease, the liver may be unable to produce coagulation factors effectively. In DIC, the clotting processes are in overdrive and will consume the coagulation factors that are being produced, leading to low levels of circulating coagulation factors.

Diabetes results when insulin concentrations are absent, reduced, or when insulin action is impaired (referred to as insulin resistance). Without cellular uptake of blood glucose for energy, the balance of metabolizing carbohydrates, fats, and proteins for energy is lost. Hyperglycemia and excess use of fats and proteins for energy result. The latter causes excess acetyl-CoA which is converted to ketone bodies or to cholesterol.Polydipsia, polyuria, and unexplained weight loss are symptoms of diabetes. Polydipsia and polyuria occur as the body tries to lower blood glucose concentrations with increased urinary excretion of glucose. Weight loss results from increased utilization of proteins and fats for energy. The image on the right represents impaired metabolism in diabetes. The thicker arrows represent the pathways that are imbalanced. In normal carbohydrate metabolism, the opposing arrows would be of the same size, representing a normal pathway and a balanced metabolism.

Ketoacidosis is always a serious complication for type 1 diabetics. Due to lack of uptake of glucose into cells by insulin, proteins and fats are utilized as energy sources. This results in excess acetyl CoA which is converted to ketone bodies. A serious acidosis results and if untreated or not resolved by the body, coma and death can occur.Most often the acetyl CoA in a type 2 patient is converted to cholesterol and results in hyperlipidemia and heart disease in these patients.The elderly type 2 diabetic is at risk for a hyperosmolar nonketotic coma. The patient becomes dehydrated due to increased urine excretion to lower the blood glucose. If reduced renal or cardiac function is also present, glucose excretion is impaired and blood glucose concentrations can become extremely high. Ketones are not produced in excess, thus the patient remains nonketotic. Insufficient hydration, elevated blood glucose, and decreased renal excretion of waste products result in an increased osmolality and total concentration of all plasma components.

Acetyl CoA is converted to acetone, acetoacetate, and beta-hydroxybutyrate. These are acids and when dissolved in body fluids in excess lower the blood pH. Increased ketones can result in a metabolic acidosis referred to as ketosis, ketoacidosis or diabetic acidosis. Type 1 diabetic patients are especially at risk for ketoacidosis. Urine and serum ketones are measured semiquantitatively and a diabetic in ketosis is monitored for ketones and blood pH.

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. 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 (platelet adhesion). As the platelets stick, they change their shape (platelet activation) and release chemicals which signal other platelets to respond (platelet secretion). As other platelets arrive, they begin sticking to one another, clumping together, forming a plug to fill in the breach (platelet aggregation). 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 (secondary hemostasis).

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. The image on the right shows iron deposits in a liver section that was stained with Prussian blue.Image is courtesy of John Woosley, MD.

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)

Mucopolysaccharides also known as mucins are a group of glycoconjugates consisting of polysaccharides linked to proteins. Mucins are gel-like secretions from various epithelial cells and tissues in the body including the: tissues of the GI Tract Mast cells Cornea Cartilage Arterial walls Skin Heart valves Ovarian follicles

Connective tissue offers structural and metabolic support structure for organs and tissue. It is the most abundant tissue type in the body and can be found throughout. Cells and extracellular material called connective tissue matrix make up connective tissue. Fibroblasts, mast cells, macrophages, adipose cells, blood leukocytes, and plasma cells can all be found to some degree in connective tissue. In addition to cells, the matrix has 3 different fibers present:Reticular fibers - Support soft organs and the network around nerve fibers, fats cells, lymph nodes, and muscle fibers.Collagenous fibers - Found in ligaments, tendons, cartilage, and bone.Elastic fibers - Allow tissue to expand and are typically located in skin and blood vessel walls.

Reticular fibers support body organs like the liver, spleen, and kidney. The Gordon and Sweet's silver staining method is used to demonstrate abnormal reticular fiber patterns that may indicate cirrhosis or necrosis of the liver. This is why reticular stains are often requested on liver biopsies. Abnormal reticular fiber patterns may also indicate the presence of certain tumor types in the liver, spleen, or kidney.

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.

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 accommodate 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 seat back 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 (ABN), 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.

Over twenty adipokines have been identified. Some adipokines are secreted solely by adipocytes; several are secreted by adipocytes and other body cells. Their role is very widespread as they integrate with various body organs and tissues: skeletal muscle, adrenal cortex, brain and sympathetic nervous system. Adipokines function in: Energy balance Immune reactions Insulin sensitivity Angiogenesis Blood pressure maintenance Lipid metabolism Hemostasis

The role of leptin in obesity and insulin resistance is sometimes confusing. Some authors refer to leptin as a hormone, not an adipokine. Leptin is synthesized and released from adipose cells in response to adipose tissue changes. It reduces intracellular lipid levels in many types of body cells and thus improves insulin sensitivity. It is an appetite suppressant and inhibitor of fatty liver formation.Leptin is referred to as a "starvation signal" and the leptin gene, is sometimes referred to as "the obesity gene". These names refer to leptin's important function as a messenger in energy metabolism. Leptin signals the hypothalamus when there are increases in fat stores. The hypothalamus then restores metabolic balance by decreasing appetite, stimulating physical activity, and burning of excess calories. During fasting, leptin levels decrease rapidly and hypothalamus signaling results in an increase in cortisol and a decrease in thyroid, sex, and growth hormones. These actions work together to restore energy balance. Leptin is usually increased in obesity, however, similar to increased insulin in obesity, leptin resistance develops. In obesity, appetite suppression does not take place and metabolic rates are lowered. Secreted leptin is not able to stimulate energy balance and healthy caloric intake.

Insulin is a pancreatic hormone that plays a vital role in carbohydrate and lipid metabolism. Insulin regulates glucose concentrations by: Promoting glycolysis - the uptake of glucose by cells for energy Stimulating glycogenesis - the conversion of excess blood glucose to glycogen storage in the liver Inhibiting glycogenolysis - the conversion of glycogen back to glucose Inhibiting gluconeogenesis - the formation of glucose from noncarbohydrates Insulin increases lipid synthesis in the liver and fat cells and inhibits lipolysis, the release of non-esterified fatty acids (NEFAs) from triglycerides in fat and muscle cells. Insulin also promotes protein synthesis.If insulin resistance occurs, carbohydrate and lipid metabolism are impaired. Insulin resistance ordinarily results in increased insulin levels as the body senses a need for more insulin action. The impaired insulin action results in elevated plasma glucose levels. The increase in lipolysis increases blood concentrations of NEFAs and causes abnormal blood lipid levels.

According to the American Heart Association, the risk factors for metabolic syndrome include:Abdominal obesity (excessive fat tissue in and around the abdomen) Atherogenic dyslipidemia (blood fat disorders – high triglycerides, low HDL cholesterol and high LDL cholesterol – that foster plaque buildups in artery walls) Elevated blood pressure Insulin resistance or glucose intolerance (the body can't properly use insulin or blood sugar) Prothrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor–1 in the blood) Proinflammatory state (e.g., elevated high sensitivity C-reactive protein in the blood) Reference: Metabolic syndrome.The American Heart Association website. Available at:http://www.heart.org/HEARTORG/Conditions/More/MetabolicSyndrome/Metabolic-Syndrome_UCM_002080_SubHomePage.jsp#. Accessed December 5, 2011.

The panel of drugs selected for testing must take into consideration a number of factors: The laboratory performing the testing The number of drugs that can practically be tested Infection control requirements Drugs that are available in formularies Susceptibility patterns exhibited locally Consideration of the body site of the infection and whether the drug is an appropriate therapy

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. All of the cells in this Wright's stained peripheral blood smear are red blood cells. The image to the right shows the normal morphology of red blood cells.

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.

Erythrocytes are produced in the bone marrow and released into the peripheral blood where they may remain for approximately 120 days before senescence. Their main function is the transport of the respiratory gases (oxygen and carbon dioxide) between the lungs and body tissues.Each erythrocyte can be thought of as an "envelope" containing hemoglobin. Each hemoglobin molecule contains iron which has a high affinity for oxygen. As a result, when an erythrocyte passes through one of the capillaries of the lungs, it picks up oxygen. The oxygen is transported through the blood to the tissues where it is released. Carbon dioxide from the tissues then diffuses into the RBC where it undergoes chemical changes. About 70% of the altered carbon dioxide diffuses into the plasma, 25% binds to the hemoglobin molecule, and 5% goes into simple solution within the red cell. In each of these three ways carbon dioxide is transported from the body tissues back to the lungs, where it is released.

N:C Ratio - Nuclear: cytoplasmic Ratio - The ratio of nuclear volume to cytoplasmic volume within any one cell.Neoplasm - Any new and abnormal growth, such as a tumor.Neutrophilic Granules - Specific granules present in the cytoplasm of neutrophils. These granules resemble pencil stippling and stain a lilac color due to their affinity for both basic and acid dyes.Phagocyte - Any cell that ingests microorganisms or other cells and foreign particles.Phagocytosis - The ingestion and destruction of microorganisms or other foreign particles.Plasma - The fluid portion of blood in which the various blood cells are suspended.PF3 (platelet Factor 3) - A lipoprotein component of the platelet membrane; functions as a surface catalyst during blood coagulation.Pseudopod - A temporary protrusion of the cytoplasm of a cell.Refractile - Capable of refracting or changing the direction of light.Senescence - The process or condition of growing old.Serotonin - A constituent of blood platelets and other cells and organs; induces constriction of the blood vessels.Specific Granules - Granules found in cells of the more mature stages of the granulocytic series. They have distinct staining reactions which differ with each type of granulocyte.T-cell - Thymus derived lymphocyte which mediates cellular immunity.Thrombocyte (Platelet) - A circular or oval disk found in the blood; concerned with hemostasis.Thymus - A ductless gland-like body situated in the anterior mediastinal cavity; reaches its maximum development during the early years of childhood.Vacuole - Any small space or cavity formed in the cytotoplasm of a cell.

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 health care worker, you come into contact with materials that may contain bloodborne pathogens. These are infectious organisms, usually viruses, that live in human blood and body fluids.The bloodborne pathogens that are of greatest concern to health care workers 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 laboratory professionals, 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 workday.

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

Patients infected with HBV or other bloodborne organisms can appear healthy, so you can't tell whose blood is infectious.So treat all:bloodbody fluidssecretions (except sweat)excretionsnon-intact skinmucous membranes as if they were infectious.

HBV is spread in society most often:Through shared needles used to inject drugsThrough sexual contactFrom mother to child before or during birth

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 when touching contaminated surfaces.

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

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, and 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

HIV is spread in the community and healthcare workers just like HBV.Sexual contactDrug users sharing infected needlesAn infant's exposure to its mother's body fluids

Put contaminated wastes which do not have the potential to puncture in a red or orange leakproof biohazard labeled bag.If the external surface of this bag is contaminated, place it within a secondary leakproof bag.Always hold full waste bags away from your body to prevent an injury by a protruding sharp.

Even after taking all the proper precautions there is still a small chance of an exposure incident.Exposure incident: Blood or another potentially infectious body fluid coming into direct contact with mucous membranes or nonintact skin.Parenteral exposure: Needle stick or being cut by a contaminated sharp.

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.

Sections twelve through fifteen contain ecological information, disposal considerations, transport information, and regulatory information. Section sixteen contains any other information that was not already covered.

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 The US Department of Transportation (DOT) has no "Exempt Specimen" classification and there are no DOT guidelines for packaging non-regulated specimens.* According to the DOT, in the U.S., if a package is marked as "Exempt Human/Animal Specimen" the understanding is that it contains no infectious substance. However, both IATA and the US Postal Service (USPS) have these requirements for packaging exempt specimens: Packaging IssueIATAUSPSType of packaging requiredTriple packagingTriple packagingOuter containerOne dimension must be a minimum of 100 mm X 100 mm (approximately 4 x 4 inches) Must be able to survive a drop test of 4 feet One dimension must be a minimum of 100 mm X 100 mm (approximately 4 x 4 inches) Must be able to survive a drop test of 4 feet Quantity limits: outer containerNone NoneQuantity limits: Primary receptacleNone500 mLQuantity limits: secondary packagingNone500 mL* Non-regulated specimens may become regulated because of preservatives, such as 10% formaldehyde (class 9) or 25% formaldehyde (class 8); or 25% ethanol (class 3).

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.

VirusMost Likely Means of Dissemination Primary Route of EntryGeneral Signs and SymptomsLaboratory TestingSmallpox: Image courtesy of CDCAs an aerosol Inhalation High fever with extreme lethargySevere headache, backache, and abdominal painRash that starts as red bumps but quickly develops into small, itchy blisters Consult local APHL prior to sample collectionShell vial and DFA Monoclonal IFAMolecular tests Viral Hemorrhagic Fevers (Ebola, Marburg, Lassa, and Argentine): SolidLiquidAerosol AbsorptionInhalationIngestion Vary by type of viral hemorrhagic fever (VHF), but initial signs and symptoms often include: Marked feverFatigueDizzinessMuscle aches, loss of strength, and exhaustionSevere cases of VHF often show signs of bleeding under the skin, within internal organs, or from body orifices like the mouth, eyes, or ears Enzyme-linked immunosorbent assay (ELISA)Polymerase chain reaction (PCR)Viral culture

When evaluating Gram stains of clinical samples, keep in mind the source of material from which the smear was made. Bacteria found in cerebrospinal fluid (CSF), blood, tissue and specimens from other sterile sites are always significant. Gram stains of body fluids that are normally sterile must be examined carefully. For every one organism per oil immersion field, there are about 105 organisms per mL present in the sample! Examining stained smears of CSF sediment may assist the clinician in establishing a presumptive diagnosis. The Gram stain result and the results of other special stains could also guide in the selection of culture media. If bacteria are observed in a CSF specimen, it is important to determine and report whether the bacteria are inside or outside of white blood cells (intracellular or extracellular). The quantity of organisms seen and the amount and type of host cells are also important to report. 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.

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 onsite collection is not possible:The specimen should be kept between 20 -37°C (room temperature to body temperature) 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.The man should record the time of semen production.The report should note that the sample was collected at a location outside the laboratory.

Therapeutic drug monitoring helps to ensure that a dosing regimen is appropriate for a given patient. The blood plasma concentration of the drug is measured to determine the correct dose that will achieve a therapeutic level of the drug without overdosing into a toxic range. When a drug enters the body, it reaches a peak concentration that starts to fall as the drug is eliminated.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. The longer a drug's half-life, the slower it is removed from the body. Most drugs are eliminated from the body in one to three days, but some drugs with longer half-lives can still be detected in the body weeks after the initial dose.The figure on the right illustrates a typical concentration pattern for a drug that is given orally (ingested).

While pediatric phlebotomy can be challenging, these guidelines can contribute to success.Communication: Always be honest with the child. Never lie to a child and say that it won't hurt. If asked by the child if it will hurt, you could explain that it may feel like an insect bite or it may sting, but if he/she holds really still, it will be over very soon.Correct hold of child: Ask the parent or guardian to assist. If you have determined that the child's parent is willing and able to assist throughout the procedure, have the child sit on the parent's lap . The parent can gently "hug" the child in a way to limit the child's movement and stabilize the arm that will be used for venipuncture. Alternately, the child can lie on a bed or exam table. If the parent does not choose to help, ask for assistance from a coworker. Correct hold of the child's arm: A health care professional familiar with the procedure should assist by holding the arm that will be used for the blood collection. The holder should face the child and gently position the child's arm so that the arm is straight and palm facing up. Next, the holder should place one hand underneath the child's elbow grasping lightly yet firmly to stabilize the elbow. With the other hand, the holder should hold the child's hand firmly. This hold will help prevent movement of the arm, even if the child is moving his/her body. This hold also allows the phlebotomist easy access to the venipuncture site during the procedure. Distractions: At times, the phlebotomist may employ a technique to distract the child during the procedure. For example, to help the child keep still, tell the child that the only thing he/she can move is his/her eyelashes. This places the child's focus on moving only their eyelashes and before you know it, the procedure is done!

Symptoms of the Influenza A 2009 H1N1 virus are similar to what is currently recognized as typical flu-related symptoms. The most common symptoms for the H1N1 virus include: fever (greater than 100.0° F or 37.8 ° C) sore throat fatigue cough runny / stuffy nose chills diarrhea nausea / vomiting headaches body aches (muscle & joint pain) More severe symptoms may be present.

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

Histology involves studying the structure of body tissues. Because structure is closely related to function, different tissue types are distinguishable from one another by examination of their individual components. Knowledge of the normal histology of the multitude of tissue types within the body is necessary for the recognition and understanding of disease.The tissue on which a diagnosis is made can be taken from a patient in the operating room, a doctor's office, or from an autopsy. Autopsy is an important part of pathology which seeks to establish the cause of sudden or unexpected death, to examine disease progression, and to assist police during the investigation of criminal cases. However, most anatomic pathologists deal with tissue from living patients and a large part of this is the detection and diagnosis of cancer. A tissue diagnosis is essential before a clinician can start treatment involving major surgery, radiation, or drugs.

Adverse complications of transfusions can be classified into several categories: Immune-mediated transfusion reactions are those that trigger a response from the patient's immune system. Many transfusion reactions are mediated by the recipient's immune system. These reactions occur as a result of antigen-antibody interactions. Antibodies involved include those with specificity towards antigens on red cells, white cells, or platelets. In general, the immune responses occur in three stages: the immune system detects foreign material (antigen) the immune system processes the antigen the immune system mounts a response to remove the antigen from the body Non-immune mediated hemolytic transfusion reactions are caused by the physical or chemical destruction of transfused RBCs, bacterial contamination, circulatory overload, or citrate toxicity. Acute reactions are those that occur during or within 24 hours after the transfusion. There is usually a rapid onset of symptoms and these reactions may be fatal. Delayed reactions occur weeks or months after the transfusion of blood or blood components.

Patients can experience a transfusion reaction caused by a range of physical or chemical factors. These factors can either affect the blood component or result from a transfusion event. These reactions include physical red cell damage, depletion or dilution of coagulation factors and platelets, hypothermia, citrate toxicity, hypokalemia or hyperkalemia, and air embolism. Membrane damage and lysis can occur to red blood cells (RBCs) because of hypotonic or hypertonic solutions, heat damage from blood warmers, and mechanical damage caused by blood pumps. Platelets and coagulation factors may become depleted or diluted from a massive transfusion. Hypothermia, a core body temperature of less than 35oC, can occur from transfusions of large volumes of cold products. Hyperkalemia is caused by the intracellular loss of potassium from the red cells during storage. Hypokalemia may result from transfusion of potassium depleted cells such as washed RBCs. Signs and symptoms of physically or chemically induced reactions are non-specific. Some of the more common signs include: Chills Numbness Nausea Vomiting Cardiac arrhythmias Altered respirations Additional laboratory tests to investigate a reaction are electrolytes, blood pH, glucose, urinalysis, complete blood count (CBC), prothrombin time (PT) and activated partial thromboplastin time (aPTT). Treatment involves correcting the underlying cause of the symptoms. For example, a patient with hypothermia may be given a heat blanket. Attention to proper transfusion practices will help prevent these types of reactions.

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.Infection occurs when a susceptible person inhales droplet nuclei containing Mycobacterium tuberculosis and the organism reaches the alveoli of the lungs. The minimal infectious inoculum may be as low as one viable organism.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; the individual has no symptoms and is noninfectious.Most persons infected with M. tuberculosis do not experience clinical illness and are noninfectious. About 5-10% of persons who are infected and are not treated will develop active TB during their lifetime. The risk for progression is highest during the first several years after infection.Most often, M. tuberculosis infects the lungs. However, it can infect almost any organ in the body, including bones and joints. Tuberculosis meningitis is a TB infection that occurs outside the lungs with devastating consequences, most often in young children and patients with AIDS.

Many variations in morphology may be seen when examining Wright 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 (including 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.

Döhle bodies are seen in a number of conditions, including:infections burns measles leukemia chemotherapyDöhle bodies are only present when the body is responding to 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 in cases of infection or burns.