Hematology

plasma proteins

*albumins*-- 60% of plasma proteins -produced by liver -main contributor to osmotic (colloid) pressure -carrier to shuttle certain molecules through circulation -important blood buffer *globulins*-- 36% of plasma proteins -alpha-1, alpha-2, beta and gamma -acute phase reactants, important in the acute inflammatory process -produced by liver -most are transport proteins that bind to lipids, metal ions and fat-soluble vitamins -gamma-- antibodies released by plasma cells during immune response, contains classes of immuniglobulins (IgA, IgD, IgE, IgG, IgM) *fibrinogen*-- 4% of plasma proteins -produced by liver -forms fibrin threads of blood clots when activated

blood functions

*transportation*: -delivers O2 from lungs and nutrients from digestive tract all over body -transports metabolic waste from cells to elimination sites (lungs and kidneys) -transports hormones from endocrine organs to target organs *regulation*: -maintain body temp by absorbing/distributing heat to body -maintains normal pH in body tissues; many blood proteins and solutes act as buffers; blood is a major reservoir for bicarb -maintains adequate fluid vol in circulatory system; blood proteins prevent excessive loss from bloodstream to tissues *protection*: -prevents blood loss; platelets and plasma proteins initiate clot formation -prevents infections; blood has antibodies, complement proteins and WBCs to help defend body against foreign invaders

Erythropoiesis

- production of RBCs occurs in the bone marrow -this is part of the process of hematopoiesis-- production of all formed elements in the blood -red bone marrow, in adults, is mainly found in bones of the axial skeleton, pelvic girdles and in the proximal epiphysis of the humerus and femur -all formed elements arise from a hematocytoblast (pluripotent hematopoietic stem cell)

anemia

-*decrease in number of RBCs and/or their Hb content* -results from insufficient erythropoiesis (bone marrow not producing enough RBCs efficiently) or incr destruction or loss (hemolysis-- break down of RBCs, self-destruction or hemorrhaging) -classified by: basic etiology (incr loss or destruction or insufficient production) or by morphology of RBCs -etiology: decr production and deficient maturation, incr loss (hemorrhage) or incr destruction (hemolysis) -morphology: look at shape, size and Hb content measured as RBC indices

red cell distribution width (RDW)

-Measure of the variability of the size of RBCs -larger cells than higher RDW--> can indicate macrocytic cells--> can lead to help diagnosis of anemia or nutrient deficiency

blood components

-Plasma, red blood cells, white blood cells, and platelets -55% Plasma, 45%-Formed Elements

Phagocytes: Neutrophils

-also referred to as PMN's (polymorphonuclear neutrophils) or polys -predominant in early inflammatory responses and persist in ongoing bacterial infections -ingest bacteria, dead cells and cellular debris -cells are short lived and become a component of the purulent exudate

control of hemostatic mechanisms

-antithrombin III (AT-III)-- circulating plasma protease inhibitor which inhibits both thrombin formation and activation of factor Xa -tissue factor pathway inhibitor-- circulating protease inhibitor synthesized by endothelial cells -protein C and S-- proteins found on surface of endothelial cells which change the shape of thrombin and cause it to become inactive

Mean Corpuscular Volume (MCV)

-average size of RBC -if low--> possible iron deficiency -gives you volume of corpuscule

hemostasis step 3: coagulation

-begins 15-120 secs after rupture of vessel -ends in formation of fibrin clot -called "coagulation cascade" b/c activation of one factor leads to activation of the next until the final product formed involves 2 pathways: intrinsic or extrinsic -activation of either or both of these pathways leads to activation of final common pathway -final common pathway starts w/ activation of factor X--> conversion of prothrombin to thrombin--> thrombin--> conversion of fibrinogen to fibrin--> fibrin precipitates and forms a fibrin mesh of cross-linked fibrin -feedback control of these process necessary to prevent continual clotting -process starts with thrombin and tissue plasminogen activator (t-PA) stimulating the activation of plasminogen to plasmin -all pathways require Ca++ -vitamin K necessary for production of 4 of the coagulation factors by liver (Factors II, VII, IX and X)

Red Blood Cells

-biconcave shaped cells (this shape helps to incr surface area and improve flexibility) -made up of 97% hemoglobin -have no nucleus or organelles; no mitochondria--> don't use up O2 it's carrying

Mean Cell Hemoglobin Concentration (MCHC)

-comparison of the weight of hemoglobin in a red blood cell to the size of the red blood cell, expressed in percentage or g/dL

plasma protein electrophoresis

-divided into 5 broad sections: albumins, alpha-1, alpha-2, beta and gamma -albumins are most numerous (highest peak) -alpha-1 and 2 and some beta are acute phase reactants -gamma= immunoglobins -IgD and IgE are not in the plasma; IgG is the most abundant

platelets

-formed elements in peripheral blood that are fragments of bone marrow cells-- called megakaryocytes -formed and regulated in thrombopoietin -crucial in homestasis -normal range 150,000-400,000 with considerable variation from day to day and in different states of health

lab parameters for anemias

-hematocrit -hemoglobin -RBC indices: MCV, MCH, MCHC -serum iron, serum ferritin, total iron binding capacity (TIBC), transferrin saturation (serum Fe/TIBC) -serum folate and serum B12 -peripheral smear visualization -red cell count -reticulocyte count

macrocytic/normochromic anemia

-high MCV and normal MCHC -macrocytic= large cell -normochromic= normal Hb density -causes: vit B12 or folic acid deficiency -B12 not essential part of RBC but comes in to aid steps of RBC formation; with a B12 deficiency, expect a low reticulocyte count since B12 aids process of RBC formation but note it isn't necessary for RBC structure

basic principles of antigens and antibodies

-if you have an antigen on red cell surface, you will not have that antibody against that antigen in your plasma -if a person has type A, B or AB antigens on their RBCs, they will not make an antibody versus that antigen -these antigens are common in nature, so, if the person doesn't have the major blood group antigen, they will have an antibody to that antigen in their plasma -in hospitals, will test plasma and blood to ensure your blood won't fight donor blood -if someone has type A blood, expect B antibodies in their plasma and A antigens on their RBCs -don't encounter D in the environment, need to be transfused or exposed by blood to D (if you are Rh - and have never been exposed, don't expect D in their plasma) -person can develop anti-D antigen if they come into contact with blood from a D+ (Rh+) person

Hb-O2 saturation curves

-incr in temp, blood pH, PCO2, H+ or BPG levels in blood decr O2 affinity for O2--> enhancing O2 unloading from blood--> rightward shift of curve--> more O2 in areas of metabolizing tissues -decr in any of these factors incr Hb affinity for O2--> decr O2 unloading

polycythemia

-incr in total RBC mass manifested by greater than normal ranges of RBC counts, hemoglobin and hematocrit -problems encountered w/ this due to incr viscosity of the blood which leads to clots and decr tissue perfusion type: -primary-- due to an acquired or inherited mutation leading to an incr in red cell mass -secondary-- there is a stimulus (usually incr levels of EPO due to hypoxia), this may be due to chronic exposure to high altitudes or any chronic interference w/ O2 delivery high altitudes or any chronic interference w/ O2 delivery to or form the lungs (COPD, emphysema, etc.)

white blood cells (leukocytes)

-leukocytes arise from pluripotential bone marrow stem cells--> go into myeloid/lymphoid stem cell lines -lymphoid= lymphocytes; myeloid= RBCs and WBCs -granulocytes mature in red bone marrow -growth factors and colony-stimulating factors encourage production and maturation of leukocytes -band cells= similar to red cell reticulocytes but are immature WBC's -monocytes become macrophages

microcytic/hypochromic anemia

-low MCV and variable MCHC -microcytic= small cells -hypochromic= low density of Hb -pale RBCs -cells small and not staining darkly -causes: iron deficiency (most common cause) or thalassemia (disruption of gamma globin gene) -cells have decr ability to carry O2

hemoglobin

-made up of protein globin bound to the red heme pigment -globin made in liver; has 4 polypeptide chains (2 alpha and 2 beta) -each heme group has iron molecule in center, 98.5% of O2 is bound to hemoglobin this way -oxyhemoglobin-- when O2 binds to iron of heme group, ruby red color -deoxyhemoglobin-- when O2 detaches from iron in tissues, dark red color -carbaminohemoglobin-- when CO2 bound to globin's AA rather than heme like O2; this occurs mostly when Hb in reduced state; CO2 binds on in tissues and unbinds in lungs to be discarded

Blood Types

-major blood groups: A, B, AB and O -Rh factors are C, D, E; D is the one tested for routine blood typing -blood type designation is by the major type and presence/absence of D (Rh +/-)

phagocytes: eosinophils *seeve's fav*

-mildly phagocytic -think about parasites and allergies functions: -defense against parasites and regulation of vascular mediators -predominant in allergic reactions -produce major basic protein (MBP)-- causes a lot of damage to tissues that it secretes this material into

normocytic/normochromic anemia

-normal RBC indices-- lab test normal -can run other tests to figure out what class this anemia is -most hemorrhage and hemolysis (destruction of RBC) fall into this type of anemia -cells normal size and color -thick acute blood loss (too few RBC or Hb) -look at reticulocyte count as additional lab test

Hemostasis Step 1: Vascular Spasm

-occurs within seconds of injury -stimulated by direct injury to smooth muscle of vessel, release of endothelial and platelet chemicals and reflexes stimulated by pain receptors

hemostasis step 4: fibrinolysis

-plasma starts to digest fibrin -results in limitation of clotting process -prevents blood clots from growing and becoming deadly -tissue plasminogen activator (t-PA) and urokinase convert plasminogen to plasmin--> trigger fibrinolysis

phagocytosis

-process by which a cell ingests and disposes of foreign material -production of adhesion molecules -margination-- adherence of leukocytes to endothelial cells -diapedesis-- emigration of cells through endothelial junctions; cells go through by putting out "little feet"

Phagocytes: Monocytes/Macrophages

-produced in bone marrow -enter circulation and migrate to the inflammatory site where they develop into macrophages -ingest dead polys and clean up area -macrophages typically arrive 3-7 days after neutrophils -macrophage activation results in incr cell size, plasma membrane area, glucose metabolism and convert monocytes to macrophages

haptoglobin

-protein produced in liver, finds and attaches to free Hb in blood -when large # of RBCs are destroyed, concentration will temporarily decr as rapid consumption of haptoglobin exceeds production liver -released Hb captured by haptoglobin--> phagocytized -it is an acute phase reactant that complexes with free heme when there is rapid *hemolysis* -when haptoglobin complexes with free heme it is no longer measurable as haptoglobin and plasma level of haptoglobin decr (test haptoglobin levels to test for hemolysis) -rapid hemolysis leads to incr bilirubin which may lead to "jaundice"

hemostasis step 2: platelet phase

-results in formation of platelet plug -platelets come in contact with vascular wall collagen they enlarge, extrude multiple chemical factors, including ADP and thromboxane A2, both of which adhere to collagen in tissues and to a protein on the endothelial surface (called Willebrand factor) -glycoproteins= glycoproteins IIa and IIIa -glycoproteins receptors for vonWillebrand Factor (vWF) and fibrinogen which are important in platelet activation, aggregation and endothelial adherence -glycoproteins are targets for anti-platelet drugs called "GPIIb/IIIa inhibitors" -activated platelets aggregate--> additional platelet activation form "platelet plug", temporarily closes vessel wall -ADP, serotonin and thombroxanes secreted from platelets; all of these enhance vasoconstriction and platelet aggregation and incr the size of platelet plug -platelet plug becomes more stable due to the attachment of fibrin crossed linked fibers which result from the coagulation process

reticulocytes

-slightly immature RBCs that still have some cytoplasmic RNA -normally present in peripheral blood representing ~1-2% of total # of RBC's 1) If patient anemia and reticulocyte count elevated, indicative of anemia and incr loss or destruction -MCV, MCHC and MCH= normal --> normocytic/normochromic anemia--> bone marrow trying to compensate for loss -EPO stimulates incr reticulocytes in blood (hypoxia= main stimulus), red bone marrow is the target organ for EPO 2) if patient anemic and reticulocyte count normal or decr--> anemia of decr production -ineffective erythropoiesis--> issue with bone marrow, not able to react to low RBC count

iron cycle

-total body iron bound to heme or stored bound to ferritin or hemosiderin in mononuclear phagocytes and hepatic parenchymal cells -transferrin= protein-Fe complex -ferritin= protein-Fe complex which is stored in a variety of organs including spleen and red bone marrow

Blood compatibility

-transfuse type specific blood; type A should receive type A blood -since most transfusions are packed RBCs (not whole blood b/c antibodies in plasma), other compatible types may be given if necessary after compatibility tests -can give blood that is compatible with other types (O-) - O- may be a problem if a person has other antigens present--> always do cross-match -compatibility is determined by the antibodies the recipient has in their plasma; antibodies of recipient are going to interact with donor's red cells

hypovolemia

-volume depletion (caused by hypotension, lethargy, muscle cramps, syncope, shock) -kidney effects: decr CO--> decr glomerular filtration rate (GFR) which may cause renal damage and renal failure if persistent -if you decr CO b/c of low blood vol, you can cause very significant damage to the kidneys -renin is secreted which gives rise to angiotensin II, however this won't happen for a couple days

causes of anemia

1) hemorrhagic anemia -acute hemorrhagic anemia--> blood loss rapid -chronic hemorrhagic anemia--> slight but persistent blood loss (ulcer, hemorrhoids) 2) not enough RBC produced -lack of essential raw materials (iron) to complete and failure of red marrow to produce enough RBCs -if reticulocytes decr or at a normal level it is an anemia of decr production 3) too many RBC destroyed -if patient anemic w/ elevated reticulocytes--> anemia of incr loss/descruction -hemolytic anemia--> erythrocytes rupture prematurely -Hb abnormalities, transfusion of mismatched blood or from certain infections

hypoxia steps

1) hypoxia due to decr RBC count or decr hemoglobin or decr availability of O2 2) kidney releases EPO 3) EPO stimulates red bone marrow 4) enhanced EPO incr RBC count 5) O2 carrying ability of blood rises 6) return to homeostasis of normal blood O2 levels

fate and destruction of RBC

1) low O2 levels in blood stimulate kidneys to produce EPO 2) EPO levels rise in blood 3) EPO and necessary raw material in blood promote erythropoiesis in red marrow 4) new erythrocytes enter blood stream (func for about 100-120 days) 5) aged and damaged RBC engulfed by macrophages of spleen, liver and bone marrow; and Hb broken down 6) raw materials are made available in blood for erythrocyte synthesis

erythropoiesis steps

1. hemocytoblast senses EPO--> transforms into a proerythroblast (committed cell) 2. proerythroblast--> early erythroblasts, which produce a large number of ribosomes 3. early erythroblast--> late erythroblast--> normoblast, now Hb is being made and iron accumulates -color of cell changes from blue to pink as Hb begins to accumulate and masks the blue stained ribosomes 4. normoblasts accumulates Hb and ejects most of it's organelles--> cell begins to collapse into a bi-concave shape 5. once normoblasts changes shape--> reticulocyte -this is an immature erythrocyte that is released when demand for RBCs is high -normal levels of reticulocytes in blood is ~1-2%, if levels higher--> indicating demand for RBCs was great; reticulocyte count provides a rough index of rate of RBC formation 6. Reticulocytes released into blood stream and become mature erythrocytes within 2 days as ribosomes are broken down by intracellular enzymes -entire process of a hematocytoblast--> erythrocyte takes ~15 days

Plasma composition

90% water, 8% Proteins 2% minerals. -electrolytes-- help maintain plasma osmotic pressure and normal blood pH -proteins-- most plasma proteins made in liver; antibodies are proteins made by B-lymphocytes; contribute to osmotic pressure and maintain H2O balance in blood and tissues -non-protein nitrogenous substances-- by-products of cellular metabolism such as urea, uric acid, creatinine and ammonium salts -nutrients-- materials absorbed from digestive tract and transported for use throughout body (ex: glucose, amino acids, fatty acids, cholesterol, vitamins, etc.) -respiratory gases-- O2 and CO2 -hormones-- steroid and thyroid hormones carried by plasma proteins

hypoxia

Low oxygen saturation of the body, not enough oxygen in the blood -respiratory effects: incr respiratory rate, SOB -cardiovascular effects: incr HR and force of contraction -CNS effects: fatigue, dizziness, syncope -skin effects: slow wound healing, atrophic skin changes, loss of elasticity -GI effects: ulceration, infection b/c of atrophy

Red cell indices

MCV, MCH, MCHC, RDW

bilirubin

an orange-yellow pigment formed in the liver by the breakdown of hemoglobin and excreted in bile -binds to albumin for transport -most of it leaves body has stercobilin (brown pigment)

mean corpuscular hemoglobin (MCH)

average mass of hemoglobin per RBC

2 major stem cell lines

myeloid and lymphoid -myeloid: neutrophils, basophils, eosinophils and monocytes (myeloid also known as granulocytes) -lymphoid: T lymphocytes, B lymphocytes

hemostasis

process of blood clotting

Formed elements of blood

red blood cells, white blood cells, platelets -RBC make up ~45% of whole blood but 99.9% of formed elements -buffy coat= platelets and WBC's -all formed elements produced in red bone marrow

regulation and requirements of erythropoiesis

regulation: -numbers of circulating red cells in healthy indv remain constant -juxtaglomerular cells of kidney produce EPO--> causes incr in red cell production and release from bone marrow normal destruction: -aged red cels sequestered and destroyed by macrophages (primarily in spleen) -globin chains broken down into amino acids and heme reduced to bilirubin--> liver and secreted into bile hormonal controls: -EPO comes from kidney -stimulates formation of erythrocytes -target organ= bone marrow -once normal O2 delivery to kidney is achieved EPO secretion is turned down