UNF PathoPharm Hematology

RBC Indicies/Reference Ranges

MCV = Mean corpuscular volume (80-95) MCH = Mean corpuscular hemoglobin (27-31) MCHC = Mean copruscular hemoglobin concentration * RDW (Red Cell Distance Width) = an index of size variation. 11.5-14.5%

Polycythemia risk

Thromboembolic phenomena

Plasma

approx. 92% water, 8% dissolved substances

Splenomegaly

enlarged spleen; may or may not be pathologic

hemoglobin (Hgb) counts

females: 12-16 males: 14-18

hematocrit (Hct)

females: 37-47% males: 42-52%

red blood cell counts

females: 4.2-5.4 million males: 4.7-6.1 million

Lymphocytosis

high lymphocyte count most commonly seen in acute viral infections

Lymphocytopenia

lymphocyte deficiency caused by either abnormalities in their production or destruction by radiation, drugs, etc. (major problem in AIDS)

Hemoglobin electrophoresis

measures different kinds of hemoglobin present

TIBC (total iron binding capacity)

measures the ability of the body to take in iron + iron is low = high TIBC +iron is high = low TIBC

Folate

measures the amount of folate in the blood

Serum Fe

measures the amount of iron in the blood + females: 60-160 + males: 80-180

Serum Ferritin

measures the amount of iron stored in the entire body

Hemoglobin/hematocrit lab

measures the quantity of hemoglobin present in the blood

Red Cell Indices/Morphology

measures the size and shape of cells

Fibrinogen

most abundant clotting factor

B12

necessary for RBC development

Hypersplenism

pathologic condition in which the normal functions of the spleen become overactive

serum

plasma that has been allowed to clot in lab to remove fibrinogen & other clotting factors that may interfere with some diagnostic tests

Retraction

platelets contract and pull the fibrin strands closer together, sealing the site of injury

hypoxemia

reduced oxygen levels in the blood

Globulins

responsible for serum electrophoresis

Relative polycythemia

results from dehydration

hemoglobin levels - children

values are age dependent + Age 1-1.9 = 11/33 + Age 2-4.9 = 11.2/34 + Age 5-7.9 = 11.4/34.5 + Age 8-11.9 = 11.6/35

Basophil

+ <1% of leukocytes + Structurally similar to mast cells + Cytoplasmic granules contain vasoactive amines (e.g., histamine) & an anticoagulant (heparin)

leukemia - 4 types

+ AML: Acute Myelogenous + CML: Chronic Myelogenous + ALL: Acute Lymphocytic + CLL: Chronic Lymphocytic

Burkitt Lymphoma

+ B cell tumor accounting for 30% of children's lymphomas worldwide + fast-growing tumor of the jaw and facial bones

Multiple Myeloma (MM)

+ B-cell cancer where malignant plasma cells proliferate & infiltrate bone marrow and become tumors throughout the skeletal system

Pediatrics

+ Blood cell counts increase above adult levels at birth & then decrease gradually throughout childhood + After birth O2 from lungs saturates arterial blood & more O2 is delivered to tissues + Infants: RBC lifespan is 60-80 days; children's is the same as adult's + At birth, lymphocyte count is high and rises during 1st year, but declines after

Aging

+ Blood composition changes little with age + Erythrocytes replenish slower after bleeding + Lymphocyte function decreases with age causing changes in cellular immunity & some decrease in T cell function + No changes in platelet numbers or structure + iron deficiency is often responsible for low hemoglobin levels

Mononuclear Phagocyte System

+ Cells that originate in bone marrow & settle in tissues as mature macrophages + Ingest & destroy unwanted materials (i.e., foreign protein particles, microorganisms, debris from dead or injured cells, defective or injured erythrocytes, & dead neutrophils) + The main line of defense against bacteria in the bloodstream + Cleanses the blood of old, injured, or dead erythrocytes, leukocytes, platelets, coagulation products, antigen-antibody complexes, & macromolecules

Hematologic System

+ Cellular components of blood & lymphoid organs + Blood that flows through vessels throughout the human body provide our tissues & organs with oxygen & nutrients needed for them to survive + Blood also cleans discarded waste from tissues, transports WBCs & other ingredients necessary for protecting the body from injury & infection

lymph nodes

+ Clustered around lymphatic veins + Large number of lymphocytes, monocytes, macrophages develop or function within lymph nodes + As lymph filters through lymph nodes clustered in inguinal, axillary, cervical regions of body, it is cleansed of foreign particles & microorganisms by monocytes & macrophages + Microorganisms in lymph stimulate resident lymphocytes to develop into antibody-producing plasma cells + During infection, rate of proliferation of lymphocytes within nodes is so great the nodes enlarge & become tender

Leukocytes

+ Defend the body against organisms that cause infection & also remove debris + Average adult approx. 5000-10,000 leukocytes/mm3 of blood + Classified according to structure & function granulocytes or agranulocytes (structure) phagocytes or immunocytes (function) + arise from stem cells in bone marrow + Bone marrow selectively retains immature granulocytes as reserve pool that can be rapidly mobilized in response to body's needs + Leukocyte production increases in response to: Infection, presence of steroids, decrease of reserves in marrow Also associated with: strenuous exercise, convulsive seizures, heat, intense radiation, increased HRs, pain, n/v, anxiety

Chief functions of blood components

+ Delivery of substances needed for cellular metabolism in tissues + Removal of wastes of cellular metabolism + Defense against invading microorganisms & injury + Maintenance of acid-base balance

Thrombocytosis

+ Excess production of platelets + Primary - due to a bone marrow disorder + Secondary - due to another problem: Cancer Severe infections (esp. TB) Deficiency of iron or vitamins Anemias Toxic response to medications (i.e. chemo, retin-A)

spleen

+ Located in LUQ abdomen, concave, curved around portion of stomach, size of a fist + Largest of the lymphoid organs + Site of fetal hematopoiesis + Phagocytes filter & cleanse blood + Lymphocytes mount immune responses to blood-borne microorganisms + Serves as a blood reservoir - up to 300 mL + Sudden decreases in BP cause SNS to stimulate constriction of sinuses & expel as much as 200 ml of blood into venous circulation + Spleen not necessary for life or adequate hematologic function + Leukocytosis often occurs after splenectomy, so spleen must exert some control over rate of proliferation of leukocytes + After splenectomy iron levels in circulation are decreased, immune function is diminished, & blood contains more structurally defective blood cells than normal

Normocytic

+ MCV 80-100 +Hemolysis +Chronic disease +Renal failure +Hypothyroidism +Early stage of Fe deficiency +Sideroblastic +Mixed (Fe & B12)

Macrocytic

+ MCV > 100 +B12 deficiency +Aplastic anemia +Chronic liver disease +Severe hypothyroidism

Microcytic

+ MCV<80 +Iron deficiency +Anemia of chronic disease +Thalassemia trait +Sideroblastic anemia

Folate deficiency anemia

+ Macrocytic-Normochromic Anemia + folate is essential for DNA and RNA synthesis in the RBC (dietary folate intake requirement is 50-200 mg/day)

Pernicious anemia

+ Macrocytic-Normochromic Anemia + most common type of MNA + vitamin B12 deficiency, which often accompanies gastritis + absence of intrinsic factor (IF), which is necessary for gastric absorption of B12, essential for synthesis of DNA in RB + hemoglobin > 8 nonspecific symptoms mood swings, GI upset, etc. + hemoglobin 7-8 weakness, fatigue, difficulty walking, loss of appetite, weight loss, glossitis (sore, beefy, red tongue)

Sideroblastic anemia

+ Microcytic-Hypochromic + caused by altered heme synthesis in erythroid cells

Iron Deficiency Anemia

+ Microcytic-Hypochromic + most common type of anemia; especially in children due to high need for iron + most commonly caused by pregnancy and blood loss + iron is necessary for hemoglobin production & function + hemoglobin 7-8 pallor, koilonychia (concave nails), glossitis, angular stomatitis (corners of mouth sore and dry), neuromuscular changes, numbness, etc.

Anemia - clinical manifestations

+ Moderate: 7-10 g Hgb/dl + Severe: <7 g Hgb/dl + Exertional dyspnea + light-headedness + vertigo + headache + muscle weakness + general lethargy + severe pallor + smooth tongue + Pale coloration of nailbeds + Muscle weakness + Increased cardiopulmonary rates + Pica-eating of ice, starch or clay + If rapid onset > Hypotension, tachycardia and dyspnea; may lead to a precipitous loss of intravascular volume

Agranulocytes

+ Monocytes, macrophages are phagocytes + Lymphocytes are immunocytes

Erythrocytes

+ Most abundant cells of the blood: approx. 42-48% blood volume + Primarily responsible for tissue oxygenation Mature erythrocyte lacks nucleus & cytoplasmic organelles, limited life span about 120 days + Small disk, biconcave shape, reversibly deformed Flattened, biconcave shape provides surface area/volume ratio optimal for gas diffusion into & out of cell + Reversible deformity enables erythrocyte to assume compact torpedo-like shape, squeeze through microcirculation, & return to normal

Morphologic Classification of Anemia

+ Normocytic - normal size + Microcytic + Macrocytic

aplastic anemia

+ Normocytic-Normochromic + "Empty" bone marrow results in the lack of production of RBCs, WBCs and Platelets + Blood smear shows "pancytopenia" + Causes: Radiation and chemo Toxic exposures Some drugs Autoimmune disorders Unknown

Posthemorrhagic

+ Normocytic-Normochromic + results from sudden blood loss

Hemolytic

+ Normocytic-Normochromic may be caused by renal failure or inherited

Hemoglobin (Hb)

+ O2-carrying protein of erythrocyte + Hb-packed blood cells take up O2 in lungs & exchange it for CO2 in tissues + Gives blood it's ruby-red color + 4 hemes, 2 globins

Polycythemia - treatment

+ Remove blood cells + Reduce marrow activity (hydroxyurea) + Prevent clotting - Aspirin, clopidogrel, Anti-coagulants

Thrombopoietin (TPO)

+ a hormone growth factor produced by liver, is main regulator of circulating platelet mass & induces platelet production in bone marrow + when circulating platelet levels are normal, TPO is adsorbed onto platelet surface of platelet cells & prevented from accessing bone marrow & initiating further platelet production + When platelet levels are low free TPO can enter bone marrow & induce platelet production

Anemia of chronic disease

+ a hypoproliferative anemia associated with infectious, inflammatory or neoplastic disorders that lasts > 1-2 months + Late in the process the anemia is microcytic hypochromic with a low RDW (red cell distribution width)

Transferrin

+ a protein that holds on to iron + Increased in IDA + Decreased in Iron Storage Disorders

red bone marrow

+ active + produces RBCs, WBCs, platelets (skull, vertebrae, ribs, sternum, shoulders, pelvis)

Platelets

+ aka Thrombocytes + Average adult approx. 150,000-400,000 platelets/mm3 of blood + Are not true cells + Essential for blood coagulation & control of bleeding + No nucleus, no DNA, incapable of mitotic division + Contain cytoplasmic granules capable of releasing pro-inflammatory biochemical mediators when stimulated by injury to a blood vessel + An additional 1/3 of body's available platelets are in reserve pool in spleen ( in case of emergency) + Circulates for about 10 days, ages, is removed by macrophages mostly in the spleen

Lysis

+ aka fibrinolysis + plasmin, an enzyme that degrades fibrin, is released to dissolve clots

Absolute Primary Polycythemia

+ aka polycythemia vera + rare + Overproduction of red cells by bone marrow with normal erythropoietin levels

Eosinophil

+ approx. 2%-4% of adult leukocyte count + Ingest Ag-Ab complexes + Induced by IgE-mediated hypersensitivity reactions + Granules contain a variety of enzymes (e.g., histaminase) that help to control inflammatory processes

Lymphocytes

+ approx. 20-40% of total leukocyte count + Primary cells of immune response + Transiently circulate in blood & eventually reside in lymphoid tissues as mature T cells, B cells, or plasma cells

Albumins

+ approx. 60% + maintain oncotic pressure + loss of albumin results in excessive fluid movement into tissues leading to decreased blood volume

Relative Thrombocytopenia

+ body consumes platelets + no longer in circulation; aggregated in clumps

Absolute Thrombocytopenia

+ body is not producing platelets + may result from leukemia, radiation, liver disease, etc. + Heparin-induced: most common cause of drug-induced thrombocytopenia

Heme

+ can carry 1 molecule of O2 + 4 hemes can carry 4 O2 molecules + Saturated = If all 4 O2-binding sites are occupied by O2 + CO directly competes with O2 for binding to ferrous ion with an affinity that is about 200-fold > O2; thus, even a small amount of CO can dramatically decrease ability of Hb to bind & transport O2

Hemostasis

+ cessation of bleeding + 3 components: 1. Platelets: adhere to collagen on the injured endothelial vessel wall and aggregate (platelet plug), forming a meshwork of platelets and fibrin 2. Blood proteins (clotting factors): released in response to injury, causing platelet plug formation; strands of fibrin form a blood clot (meshwork of protein strands that stabilizes the platelet plug) around it (2 Pathways: Intrinsic & Extrinsic both lead to the common pathway & activation of factor X, which produces clot formation) 3. Vasculature: endothelial cells and subendothelial matrix

anemia - why?

+ decreased RBC production + increased RBC destruction + loss of red blood cells

Erythropoiesis

+ development of RBCs that occurs in red bone marrow + proerythroblast to erythroblast to reticulocyte

Myeoloproliferative Red Cell Disorder

+ dysfunction resulting from an overproduction of RBCs + known as polycythemia + 2 types: relative and absolute

Lymphadenopathy

+ enlarged lymph nodes due to proliferation of lymphocytes and monocytes or invasion by malignant cells + Common causes: inflammatory condition, immunologic disorders, lipid storage disease, or neoplastic disease

Anemia

+ functional inability of the blood to supply the tissue with adequate oxygen for proper metabolic function + characterized by a low red cell count, a low hemoglobin or a combination of the two

Erythropoietin

+ hormone that stimulates RBC production + Produced in kidney + Production & release stimulated by hypoxia (feedback system)

Monocytes

+ immature macrophages + Formed & released by bone marrow into bloodstream + Migrate into a variety of tissues (e.g., liver, spleen, lymph nodes, peritoneum, GI tract) & fully mature into tissue macrophages + Other monocytes may mature into macrophages & migrate out of vessels in response to infection or inflammation

yellow bone marrow

+ inactive + produces fat, cartilage, bone + The large quantities of fat in inactive marrow make it yellow + Under certain conditions, yellow bone marrow can be converted to red marrow by the actions of erythropoietin

Non-Hodgkin Lymphomas

+ lack RS cells and may arise from B cells, T cells, or NK cells + example- lymphoblastic lymphoma

Reticulocyte

+ last immature form of erythrocyte + Normal retic count is 1% of total RBC count + Therefore, retic count is useful clinical index of erythropoietic activity & indicates whether new red cells are being produced

disorders of white blood cells

+ leukemia + leukopenia

Destruction of RBCs

+ macrophages in the spleen remove and sequester them + porphyrin from the hemoglobin is transported to the liver and excreted in the bile

Absolute Secondary Polycythemia

+ more common + Overproduction of red cells in response to chronic hypoxemia (COPD), decreased barometric pressure (high altitude) or excessive erythropoietin production

secondary leukopenia

+ more common + Result of external factors: Chemotherapy Radiation Exposure Toxic Occupational Exposures Pharmacologic exposures

Neutrophil

+ most numerous, approx. 55% of adult leukocyte + Chief phagocytes of early inflammation + Die in 1 or 2 days + Dead neutrophils release digestive enzymes from their cytoplasmic granules that dissolve cellular debris & prepare the site for healing

Anemia - treatment

+ must be evaluated to their cause before either supportive or replacement treatment is begun, such as blood transfusions + More that one cause of anemia can coexist

Malignant Lymphomas

+ neoplasm that develops from the proliferation of malignant lymphocytes in the lymphatic system + initially identified by palpable, tender lymph nodes

Granulocytes

+ neutrophils, basophils, eosinophils + are all phagocytes + Granules contain: enzymes capable of killing microorganisms & catabolizing debris ingested during phagocytosis and biochemical mediators with inflammatory & immune functions

leukemis - clinical manifestations

+ pallor, fever, bleeding, fatigue, petechiae, and purpura + Blast cell: hallmark of acute leukemia

Thrombocytopenia

+ platelet deficiency + below 150,000, but is not considered significant until it drops below 100,000 + spontaneous bleeding without trauma occurs at levels below 10,000

Hematopoiesis

+ process of creating new blood cells + Typical human requires approx. 100 billion new blood cells/day + Occurring in liver & spleen of fetus & and only in bone marrow after birth (medullary hematopoiesis) Extramedullary hematopoiesis = blood cell production in tissues other than bone marrow; usually a sign of disease (occurs in pernicious anemia, sickle cell anemia, thalassemia, hemolytic disease of the newborn, certain leukemias) + Bone marrow hematopoietic stem cells have the capacity to differentiate into any of the hematologic cell populations but can no longer differentiate into other cell types + hematopoietic stem cells are self-renewing

Hodgkin lymphoma (HL)

+ progression from one group of lymph nodes to another, accompanied by Reed-Sternberg (RS) cells (necessary for diagnosis of HL), which are malignant lymph cells + Clinical manifestations: often asymptomatic mass; about 1/3 experience some systemic symptoms, such as pruritus (itchy skin), night sweats, fatigue, etc.

primary leukopenia

+ relatively rare + Bone marrow does not produce leukocytes + Best treatment: usually bone marrow transplant

Natural killer (NK) cells

+ resemble lymphocytes + kill some types of tumor cells & some virus-infected cells without prior exposure + Develop in bone marrow & circulate in blood

disorders of platelets

+ thrombocytopenia + thrombocytosis

leukemia

+ uncontrolled proliferation of malignant WBCs + other blood components such as RBCs and platelets may be "crowded out."

Thrombocytopenia - clinical manifestations

+ venous thrombosis, which may result in DVT or pulmonary emboli + arterial thrombosis may also occur in lower extremities + CVAs or MIs may occur

Hypersplenism - diagnostic criteria

1.) anemia, leukopenia, thrombocytopenia, or a combination of theses 2.) cellular bone marrow 3.) splenomegaly 4.) improvement after splenectomy

platelet counts

150,000 - 400,000

WBC counts

5000 - 10,000

Whole blood components

55% plasma + 7% proteins + 92% water + 1% other solutes 45% formed elements + 140-340K platelets + 5-16k leukocytes + 402-6.2 million erythrocytes

blood volume - adult

6 quarts (5.5 L)