Intro to Hematology

hematology

study of blood and blood-forming organs

bone marrow

thymus

spleen

lymph nodes

liver

blood forming organs

bone marrow

makes RBCs, platelets, and 60-70% WBCs

thymus, spleen, lymph nodes

these three make lymphocytes

liver

makes clotting factors and proteins

6 L (7-8% body weight)

total volume of blood in an average adult

45% cells

55% plasma

circulating blood is divided into…

RBCs

WBCs

platelets

what the 45% of cells are made up of

erythrocyte development

maturation process in bone marrow —> peripheral blood

maturation process in bone marrow

normalblast

proniormoblast

polychromatic erythrocyte

orthochromatic erythrocyte

reticulocyte

erythrocytes

contained in peripheral blood

reticulocytes

young erythrocytes that have matured enough to extrude their nucleus but not their cytoplasmic RNA

lack full amount of Hb

appears as polychromatic RBCs (bluish tint) on Wright’s stain

production of RBCs

the number of circulating reticulocytes is a measure of the _______________

if a bone marrow transplant is successful

the number of circulating reticulocytes is used to determine ….

reticulocytes

bone marrow

where hemoglobin synthesis occurs

iron

heme portion of hemoglobin contains…

protein

globin portion of hemoglobin contains…..

heme

globin

2 portions that form the activated form of hemoglobin that is ready to carry oxygen

heme

4 tetrapyrrole rings ending in protoporphyrin with a central iron

porphyrias

disorder of heme synthesis

globin

protein part that contains 4 chains of amino acids as a polypeptide

hemoglobin

composed of 4 protein globin chains, each surrounding a central heme group

RBC formation + destructive process

3 ways:

1. reticulo endothelial system “breakdown system” —> “waste products” in the form of bile pigments excreted in the urine and feces

2. reticulo endothelial system “breakdown system” —> protein storage pool —> back to bone marrow for formation of new red cells

3. reticulo endothelial system “breakdown system” —> iron storage pool —> back to bone marrow for formation of new red cells

erythrocytes - extravascular metabolism

iron is recycled:

• iron absorption happens in the duodenum

• iron bound as ferritin

• iron circulates as transferrin

duodenum

Fe absorption happens in the _______ in erythrocyte extravascular metabolism

ferritin

Fe is bound as _______ in erythrocyte extravascular metabolism

Fe circulates as _____ in erythrocyte extravascular metabolism

erythrocytes - intravascular metabolism

Fe distribution:

• as hemoglobin

• ferritin and hemosiderin

• transferrin

Fe metabolism:

• taken up by RBC precursors

• combined with globin

Fe storage:

• macrophages

hemoglobin

ferritin and hemosiderin

transferrin

Fe distribution in intravascular metabolism

taken up by RBC precursors

combined with globin

Fe metabolism in intravascular metabolism

macrophages

Fe storage in intravascular metabolism

hemoglobin function

carries oxygen to tissues

iron

essential for hemoglobin being able to carry oxygen to tissues

if lacking, anemia develops due to Hb not being formed in sufficient quantities

oxyhemoglobin

reduced Hb (not carrying oxygen) when exposed to oxygen at increased pressure, oxygen is taken up at the iron atom until each molecule of Hb has bound 4 oxygen molecules

Fe2+

ferrous state

Hb bound (reduced oxidation state)

Fe3+

ferric state

no Hb bound

(oxidized)

(methemoglobin)

what happens in your lungs

left shift in oxygen dissociation curve represents —> ?

what happens in your tissues

right shift in oxygen dissociation curve represents —> ?

alpha

beta

gamma

delta

4 types of amino acid chains in hemoglobin

alpha chains

has 141 amino acids

beta chains

has 146 amino acids

hemoglobin A

alpha and beta chains compromise about 95% of adult hemoglobin and are called ?

oxyhemoglobin

when hemoglobin carries oxygen (bright red)

temporary bond with oxygen

when iron is in the ferrous state (Fe2+) (reduced), it forms a ___________ to transport it to tissues

methemoglobin

when iron is in the ferric state (Fe3+) (oxidized), it does not bind oxygen and is called ?

Hb A

Hb A2

Hb F

normal variants of hemoglobin

Hb A

2 alpha + 2 beta chains

Hb A2

2 alpha + 2 delta chains

Hb F

2 alpha + 2 gamma chains

Hb C

Hb S

(both have beta chains)

abnormal variants

Hb C

lysine for glutamic acid 6th position)

Hb S

valine for glutamic acid 6th position

Hemoglobin S (sickle cell)

beta chain containing Val amino acid

normal hemoglobin

beta chain containing Glu amino acid

carboxyhemoglobin

Hb + CO

found in smokers and people exposed to CO

methemoglobin

formed when Fe2+ —> Fe3+

unable to bind with oxygen

normally present in trace amounts (increased amounts occur form ingestion of certain drugs and chemicals)

sulfhemoglobin

Hb + sulfur

once formed, compound is extremely stable and lasts the life of the RBC (120 days)—> results from the ingestion of oxidizing drugs

cyanmethemoglobin method

most accurate method used in hematology instrumentation

mixes cyanide solution (Drabkin’s reagent) with blood sample —> forms very stable, colored compound (cyanmethemoglobin)

oxidized blood is read in spectrophotometer

cyanmethemoglobin

cyanide solution (Drabkin’s reagent) + blood sample

very stable, colored compound

cyanmethemoglobin

Hb + cyanide

cyanmethemoglobin

RBCs are lysed —> ferrous ion (Fe2+) of the released Hb is oxidized to the ferric state (Fe3+) —> forms methemoglobin

methemoglobin reacts with K+ cyanide —> forms ? (read by spectrophotometer at 540 nm)

hemoglobin in sample

concentration of cyanmethemoglobin = concentration of ?

spun hematocrit (packed cell volume)

measurement of the percentage of RBCs in a sample of whole blood

blood sample in EDTA/purple top tube

specimen for hematocrit

capillary tubes

centrifuge

reading device

equipment for manual microhematocrit

3 x RBC value = Hb value

3 x Hb value = Hct value

QC check in healthy patients is the rule of 3….

40-54%

normal hematocrit in adult male

37-47%

normal hematocrit in adult female

RBC indices

RBC measurements that aid in the classification of anemia

RBC indices

calculated using the RBC count, Hb concentration, and Hct measurement

Hct x 10 / RBC

mean corpuscular (cell) volume equation (in fL)

80 - 96 fL

normal MCV value

microcytic (<80 fL)

macrocytic (>96 fL)

terms used to describe abnormal MCV

Hb x 10 / RBC

mean corpuscular (cell) hemoglobin equation (in pg)

27 - 33 pg

normal MCH value

hypochromic (<27 pg)

term used to describe abnormal MCH

red cell distribution width

measurement of the degree of anisocytosis present, or the degree of variability in RBC size, in a blood specimen

SD of MCV / mean MCV x 100

red cell distribution width (RDW) equation (in %)

11-15%

normal value of RDW

anemia

condition in which there is a decrease in the oxygen-carrying capacity of blood and the amount of oxygen that is delivered to the tissues

not specific disease

not always due to a blood disorder

anemia

alterations in RBC morphology are associated with many diseases, including ?

type of anemia present

cause

? and ? must be determined for effective treatment for anemia

symptoms/complaints

all patients with anemia have similar ______/________ regardless of the cause

Hb concentration

severity of anemia depends on ?

fatigue/shortness of breath

faintness

dizziness

heart palpitations

headache

common symptoms of anemia

patient history

physical

CBC

blood smears

used for diagnosis of anemia

RBC appearance (morphology)

physiological cause (etiologic or pathogenic classification)

two factors of anemia classification

normochromic - normocytic

macrocytic

hypochromic - microcytic

three types of anemia classification

blood loss

impaired production

hemolytic anemia

3 etiologic classification of anemia

blood loss anemia

types:

• acute

• chronic

examples:

• trauma

• colon cancer

impaired production anemia

types:

• aplastic anemia

• Fe deficiency anemia

• sideroblastic anemia

• anemia of chronic disease

• megaloblastic anemia

examples:

• radiation exposure

• excessive menstrual bleeding faculty Fe utilization

• cancer

• pernicious anemia

hemolytic anemia

types:

• inherited defects

• acquired disorders

• hemolytic-hemoglobin disorders

examples:

• hereditary spherocytosis

• hemolytic disease of the newborn

• sickle cell, thalassemia

nromochromic-normocytic anemias

number of RBCs produced in the BM are normal, but the number of RBCs circulating is decreased

normal-appearing RBCs on the blood smear and normal RBC indices

overhydration

hypoplastic BM

CA neoplasm

malignancy

hemolytic diseases (chronic kidney or liver disease)

causes of normochromic-normocytic anemias

macrocytic anemias

represented by the megaloblastic anemias that result from a Vitamin B12 or folic acid deficiency

nutritional or form a malabsorption problem (pernicious anemia)

malabsorption leads to an inability to absorb Vitamin B12 —> leads to a nuclear maturation defect and megaloblastic anemia

megaloblastic changes in WBC show open chromatin patterns and larger hyper-segmented neutrophils

RBCs are enlarged with MCV 120-140 fL

malabsorption

leads to an inability to absorb vitamin B12 in macrocytic anemias —> nuclear maturation defect and megaloblastic anemia

megaloblastic changes in WBC (macrocytic anemia)

show open chromatin patterns and larger hyper-segmented neutrophils

macrocytic anemias

can be severe

RBC count is decreased more than the Hb, due the RBCs that are large and almost filled with Hb

megaloblastic anemias —> commonly seen in alcoholics

other malabsorption disorders —> celiac

changes in cells are not limited ot the RBCs → large hyper-segmented neutrophils (lymphocytes are not affected)

hypochromic - microcytic anemias

most common type

Fe deficiency —> results from decreased Fe intake, increased Fe loss, errors in metabolism (sideroblastic anemia), and increased Fe requirements in infancy, pregnancy, and lactation

cause must be determined before treatment