Circulating Information and Courses from MediaLab, Inc.
These are the MediaLab courses that cover Circulating and links to relevant pages within the course.
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| Pia Arachnoid Mesothelial Cells (continued) A reactive pia arachnoid mesothelial cell as noted by the darker cytoplasm is present in this field. Reactive cells are a common finding in cytospin smears from spinal fluid samples and are sometimes difficult to distinguish from tumor cells. Mesothelial cells are usually interspersed among the other cells, rather than appearing in clumps. They have a single distinct nuclei that may be eccentric.
The macrophages (histiocytes) are seen next to the mesothelial cell. Macrophages are distinguished from circulating monocytes by the irregular appearing cytoplasm. Bacteria, red cells or other debris can often be seen in the cytoplasm of macrophages.
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| Monocytes The arrow in this slide is pointing to a monocyte. The nucleus has an open chromatin pattern which gives it a spongy appearance. There is another monocyte in the lower right corner of the field. The other two cells could be classified as macrophages (histiocytes) because the nucleus is oval or kidney bean-shaped and the cytoplasm is very irregular. After circulating in the blood for one to three days, monocytes enter the tissues. The tissue form of the monocyte is called a macrophage or histiocyte.
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| Which of the following set of conditions would preclude hemolytic disease of the newborn as a result of ABO incompatibility: | View Page |
| Which of the following will give the best overall picture of a patient's iron stores: | View Page |
| Circulating organic iodine is found primarily in the form of: | View Page |
| Which of the following is not a feature of systemic lupus erythematosus (SLE): | View Page |
| Which of the following is not true in terms of platelet characteristics? | View Page |
| Primary Hemostasis – The Vascular System & Platelet Involvement As discussed earlier, a break in the vessel endothelium leads to exposure of collagen and the vessel's subendothelial surface. Ruptured endothelial cells leak ADP and Serotonin, which are the chemical triggers that induce platelet adhesion, the next step in the sequence of hemostatic events. Circulating platelets are drawn to the area by those liberated chemical signals, and begin to physically attach themselves to the rough, damaged surfaces of the breach. As platelets continue to arrive and bind to the exposed collagen and basement membrane, a rudimentary barrier begins to form, as the platelets themselves serve to fill in the breached vessel wall. Platelets possess an inherent “sticky” property which enables them to adhere to one another, and not just to the damaged vessel endothelium. The process by which platelets bind to one another is referred to as platelet aggregation, and is vital because it allows for a platelet plug to be formed. The platelet plug is the structure responsible for plugging the hole in the vessel wall. | View Page |
| Primary Hemostasis – Characteristics of the Platelet Platelets are produced in the bone marrow by highly specialized cells called megakaryocytes. About 70-80% of a person's total platelet count is circulating in the vasculature at any given time. Approximately 20-30% of a person's total platelet count is pooled in the spleen. The average lifespan of a platelet is 9-12 days. | View Page |
| Secondary Hemostasis – The Extrinsic Pathway It should be noted that this pathway is sometimes referred to as the Tissue Factor Pathway.
Once a vessel has been breached, tissue factor is exposed to circulating factor VII, and the two substances bind to form a complex.
The newly formed tissue factor/factor VII complex is thought to be the primary physiological stimulus for blood coagulation.
In other words, more hemostatic activities are initiated by the extrinsic pathway than the intrinsic.
This complex leads to the activation of factor VII (factor VIIa) which is now ready to catalyze the conversion of factor X to factor Xa as part of the common pathway.
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| Summary The bone marrow is structured to provide a suitable environment for developing cells as well as mechanisms for delivering mature cells to the circulating blood. The bone marrow is also capable of increasing production in one or more cell lines when needed. | View Page |
| Sinuses/Blood Vessels Circulating blood enters the bone through the central artery which branches out into small arterioles. These arterioles are interspersed in the cords of hematopoietic tissue. The arterioles drain into venous sinuses (space or cavity). Sinuses have a basement membrane which is lined by endothelial cells within the sinus and surrounded by reticular (e.g. adventitial) cells on other side. Blood from several venous sinuses may combine in a collecting sinus which leads to a central vein. The venous sinuses alternate with hematopoietic cords in a spokelike pattern with the central vein as the core. | View Page |
| A hematology technologist observed the intracellular forms seen in the field of view of a Wright-Giemsa-stained peripheral blood smear shown in this photomicrograph. In consultation, the microbiology technologist advised that the form seen most likely represents: | View Page |
| The half-life of monocytes in the circulating blood is: | View Page |
| Platelet Kinetics Platelets are derived from the cytoplasm of megakaryocytes, giant cells in the bone marrow. At any given time, two thirds of the total platelets are in the circulation and one third are present in the spleen. In persons with enlarged spleens 80-90% of the platelets are in the spleen resulting in a decreased concentration of circulating platelets. In individuals who have had a splenectomy all of the platelets will be in the circulating blood. The life span of the platelet is 8-10 days. | View Page |
| Glossary of Terms A through M. 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. | View Page |
| Segmented Neutrophil Segmented Neutrophil is also be referred to as seg, polymorphonuclear leukocyte, poly and PMN. Segmented neutrophils are the most mature neutrophilic granulocytes present in circulating blood. Their diameter is approximately 9-15 microns, and their N:C ratio is 1:3. | View Page |
| The Process of Phagocytosis 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. | View Page |
| Life Span and function of Eosinophils Eosinophils have a circulating half-life of approximately 18 hours and a tissue life span of at least 6 days.They are capable of locomotion and phagocytosis and can enter inflammatory sites, but do so less readily than neutrophils.In tissues the primary location for eosinophils is in the epithelial barriers to the outside world such as, lungs, skin and GI tract.They are capable of returning to the circulating blood and bone marrow after they enter the tissues. | View Page |
| Unexpected Concentrations 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. | View Page |
| Plasma Plasma and formed elements stay mixed in circulating blood.
When centrifuged (or spun down), blood is separated into plasma, and formed elements including red blood cells. The plasma separator tube shown here has a barrier to maintain separation of plasma and cellular elements during centrifugation and storage.
The red cell layer also includes a relatively small amount of platelets and white blood cells, not visible in the photo on the right.
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| Whole blood: components Circulating whole blood is a mixture of:
Plasma (which contains fluid, proteins, and lipids), and
Formed elements, consisting of red cells, white cells, and platelets.
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| Heinz body formation Heinz bodies are 1-3 um particles of denatured hemoglobin settling eccentrically, usually close to the red cell membrane. They are found in erythrocytes in unstable hemoglobin disorders, acute drug induced hemolysis, and following splenectomy. Their formation may be exaggerated by in-vitro incubation of a fresh blood sample with phenylhydrazine. Heinz bodies, as pictured here, are identified using a supra-vital stain, such as new methylene blue or cresyl violet. Bite cells, visible with Wright-Giemsa staining, are visual reminders that the spleen is functional and has pitted the aberrant chunk of hemoglobin from the circulating erythrocyte. | View Page |
| The arrangement of erythrocytes on this peripheral blood smear may be seen in each of the following conditions except: | View Page |
| A blood smear represented by the photograph was submitted for hematologic review. Based on the erythrocyte morphology and the accompanying histogram, which of the following choices is the most likely situation or condition? | View Page |
| Hereditary ovalocytosis and elliptocytosis Ovalocytes are rod shaped erythrocytes with nearly parallel lateral walls. If the long axis of an erythrocyte is no more than twice as long as the short axis, the cell is an ovalocyte. If the long axis is more than twice as long as the short axis, the cell is an elliptocyte. Hemoglobin tends to collect at each end of these cells. The ends of the cells are rounded and never pointed, to be differentated from sickle cells. Ovalocytes present in greater than 25% of red cells on the blood smear are characteristic of hereditary ovalocytosis. The oval shape is attributed to a defect in horizontal red cell membrane protein interactions. Lesser numbers of circulating ovalocytes may be present in various anemias including megaloblastic, sideroblastic, iron deficiency, and in thalassemias. A rare ovalocyte (less than 1%) may be found on almost any peripheral blood smear. Resistance to malarial infection may be a beneficial attribute of hereditary ovalocytosis. | View Page |
| Normoblasts Many of the distorted erythrocytes displayed on the previous page are also present on this one. We see anisocytosis, poikilocytosis, fragmented forms, target cells, and a few Howell-Jolly bodies. Note also circulating nucleated red blood cells (normoblasts). The presence of these normoblasts may represent a premature release from a hyperplastic marrow or, more likely, are due to a lessening of the normal inhibition of erythroid release from the marrow as a result of splenectomy, permitting their earlier entry into the circulation. | View Page |
| Another Example of Macrocytosis Another example of macrocytes is seen in this slide. This patient had pernicious anemia, which results from an inability to absorb the vitamin B12 needed for DNA synthesis. Since many cells are destroyed in the bone marrow, decreased numbers of red cells are present in the circulating blood causing low hemoglobin(anemia).
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| Acanthocytes Acanthocytes have 3-12 thorn-like projections irregularly spaced around the cell. Since these cells have lost their discoid shape, they are frequently smaller than normal and have little or no central pallor. Acanthocytes have an excess of cholesterol and an increased surface area. Large numbers of these cells on a smear can be of diagnostic significance. The largest percentage, 50-100% of circulating red cells, can be seen in the rare abetalipoproteinemia (hereditary acanthocytosis). Acanthocytes are easily seen as horned cells in the smear shown on the right.
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| Schistocytes Schistocytes are red cell fragments which are formed when fibrin strands come in contact with circulating red cells. The strands cut a small piece from the original cell. This is the same mechanism which causes the formation of keratocytes. A schistocyte can be seen in the center of this field. | View Page |
| Match the letter representing the cell type with the condition in which increased numbers of the cell may be found in the peripheral smear. | View Page |
| Assuming that other circulating neutrophils are similar to the band neutrophil in the photograph(see inclusion at arrow tip), which of the following conditions is most likely? | View Page |
| The neutrophil on the peripheral blood smear in this photograph is a mast cell. | View Page |
| Erythrophagocytosis Illustrated in the photograph is a phagocyte devouring several erythrocytes.This uncommon phenomenon occurs in the bone marrow and in the spleen as part of the process of erythrocyte destruction. Erythrophagocytosis is found in histological sections of the spleen in cases of hemolytic anemia.This phenomenon appears also in splenic sections in lupus erythematosis, and in rheumatoid arthritis.Our example is from a patient with a myeloproliferative disorder and is a rare example of a circulating erythrophagocytic cell in the peripheral blood. | View Page |
| Approximately 10% of the circulating white cells were similar to the one seen in the photograph. The patient was 42 years old and visited his physician because of recent bruising. Note the absence of platelets on the smear. Possible associated conditions include: | View Page |