Hematopoiesis

Protein molecule that transports respiratory gases

hemoglobin

normal hemoglobin for male and female

male = 14-18

female = 12-16

decreased hemoglobin results in ___________ anemia

hypochromic

what causes hypochromic anemia?

decreased hemoglobin

what protein structure is hemoglobin?

complex quaternary

how many subunits are there in hemoglobin?

4

each subunit of hemoglobin contains?

- one molecule of heme

- each heme contains one iron ion and binds to one O2

How many oxygen molecules can be transported by one hemoglobin molecule?

4

during RBC destruction, what do phagocytic cells in the spleen, liver, bone marrow & lymph nodes do?

they recognize old and defective RBC's and ingest & destroy them in a series of enzymatic reactions

what happens to the amino acids and iron within the globin chains of RBCs during RBC destruction?

they are salvaged and reused

what is most of the heme unit converted to in RBC destruction?

bilirubin (the pigment of bile)

what is the pigment of bile?

bilirubin

how is bilirubin transported?

Bilirubin is insoluble in plasma & attaches to plasma proteins for transport

is bilirubin soluble or insoluble in plasma?

insoluble

what allows for the excretion of bilirubin?

it is conjugated with glucuronide (in the liver) making it water soluble & excretable in the bile, feces or urine

normal bilirubin levels are less than?

less than 1-1.5mg/dl

what level bilirubin would cause jaundice?

> 2-3 mg/dL

where is conjugated bilirubin found? where is unconjugated bilirubin found?

conjugated: liver

unconjugated: bound to albumin

If you centrifuge (spin) whole blood, you will find the red blood cells (erythrocytes) at the bottom of the tube and white blood cells atop them. What does this imply?

that red blood cells have a greater density than white blood cells

if you centrifuge whole blood, what will be on top and what will be on bottom?

white blood cells on top and red blood cells at bottom

If you centrifuge (spin) whole blood you will find the band of white blood cells and platelets (the buffy coat) is much thinner than the packed red blood cells below it. This difference reflects the fact that ________.

white blood cells are fewer in number than red blood cells

What organ in the body regulates erythrocyte production?

kidney

Which blood component primarily contributes to plasma osmotic pressure?

albumin

three typical plasma proteins

albumin

globulins

fibrinogen

Loss of fibrinogen within the plasma would most likely cause what?

loss of blood clotting

With a patient that is administered an injection of erythropoietin (EPO) you would expect to see increased ________.

hematocrit

With a patient who is administered an injection of colony stimulating factor (CSF), you would expect to see increased _____________

WBC

Normally, the amount of plasma in whole blood is ________ than the amount of formed elements; plasma makes up approximately ________ percent of whole blood.

greater; 55

The hematocrit measures ________.

the volume of RBC in a blood sample

what measures the volume of RBCs in a sample?

hematocrit

This component of blood plasma includes molecules that are important for body defense, osmotic balance, and lipid transport.

plasma proteins

The most numerous blood cells are ________.

RBCs

Granulocytes include ________.

neutrophils, eosinophils, basophils

These are the most abundant leukocytes, constituting 50-70% of all white blood cells.

neutrophils

These white blood cells kill parasitic worms and play a complex role in allergic responses and asthma.

eosinophils

This cell is the largest white blood cell. It lacks cytoplasmic granules and has a kidney-shaped nucleus.

monocyte

The final step in coagulation is the formation of ________.

fibrin clot

RBCs outnumber WBCs by how much

1,000 : 500

when would you find red bone marrow in the shafts of adult bones?

if they are anemic (the yellow bone marrow will change back to red bone marrow to make more RBCs)

what is albumin? what does it do?

protein in blood; maintains the proper amount of water in the blood

immunoglobulins

antibodies

fibrinogen

plasma protein that is converted to fibrin in the clotting process

what are the "granules" within phagocytes?

lysosomes

what WBCs are phagocytes?

neutrophils, eosinophils, basophils

are macrophages granulocytes?

no (monocytes are agranulocytes)

•A diminished oxygen-carrying capacity

•Tissue hypoxia

•An abnormally low number of circulating red blood cells or level of hemoglobin, or both

anemia

is anemia a disease?

Anemia is not a disease, but an indication of a disease process or alteration in body function

what happens to red blood cell indices and hemoglobin levels in anemia?

decreased

tissue hypoxia symptoms (as a result of anemia)

pale skin

shortness of breath

arrhythmia

fatigue

dizziness

cold skin

headaches

chest pain

what are some compensatory mechanisms that can occur secondary to anemia?

•Tachycardia and palpitations – body tries to increase cardiac output

•Flow-type systolic murmur due to change in blood viscosity

•Ventricular hypertrophy & heart failure

•Erythropoiesis is accelerated (w/ diffuse bone pain & sternal tenderness)

•Hemolytic anemias – jaundice due to bilirubin

•Aplastic anemia - petechiae and purpura – reduced platelet function

jaundice is present in what type of anemia?

hemolytic anemia

petechiae and purpura are present in what type of anemia? they occur secondary to what?

aplastic anemia

secondary to reduced platelets/platelet function

accelerated erythropoiesis due to anemia can cause what symptoms?

diffuse bone pain and sternal tenderness

which lab results might determine severity & what which might determine the cause of anemia?

severity: RBC count & hemoglobin levels

cause: RBC size, color shape

4 etiologies of anemia

1. Blood loss

2. Hemolytic - destruction

3. Defective production

4. Inadequate production

what is corpuscular hemolytic anemia?

hemolytic anemia caused by intrinsic defects within the red blood cells (RBCs) themselves such as hemoglobinopathies

hemoglobinopathies are examples of what kind of anemia?

corpuscular hemolytic anemia

what is extracorpuscular hemolytic anemia?

hemolytic anemia caused by external factors that lead to red blood cell (RBC) destruction such as drugs, infections, antibodies, or trauma

what kind of anemia would include drugs, infections, antibodies, or trauma resulting in damage to RBCs?

extracorpuscular hemolytic anemia

what would cause inadequate production of RBCs?

bone marrow failure

clinical manifestations & red blood cell counts during blood loss depend on?

1. the rate of hemorrhage

2. internal vs external hemorrhage

compare the clinical presentation of chronic hemorrhage to acute blood loss anemia

chronic: the RBC loss may reach 50% with no signs or symptoms

acute: quick loss of intravascular volume results in cardiovascular collapse and shock

What happens to RBC count, hematocrit, and hemoglobin levels in blood loss anemia and why?

they fall due to hemodilution (fluid movement into the vascular compartment)

What causes hemodilution in blood loss anemia?

the movement of fluid into the vascular compartment to compensate for lost blood volume

How do RBCs appear initially in blood loss anemia?

they are normal in size (normocytic) and color (normochromic)

What stimulates erythropoiesis after blood loss and what lab value does this effect?

hypoxia due to blood loss stimulates erythropoiesis and results in an increase in reticulocytes

What is the bone marrow's response to blood loss anemia?

It increases production of RBCs, leading to a rise in reticulocytes in the blood

Aplastic anemia

failure of blood cell production in the bone marrow

•Premature destruction of erythrocytes

•Retention of iron and other products of hemoglobin destruction

•Increase in erythropoiesis

•Normocytic & normochromic red cells

•Bone marrow hyperactive

•Increased reticulocytes in circulating blood

•S/s of impaired oxygen transport

hemolytic anemia

What is the defining characteristic of hemolytic anemias?

premature destruction of RBCs

What happens to iron and other hemoglobin breakdown products in hemolytic anemia?

they are retained in the body and appear elevated

How does the bone marrow respond to hemolysis? what lab value does this effect?

bone marrow becomes hyperactive and increases erythropoiesis - this results in an increased reticulocyte count

What are the size and color of RBCs in hemolytic anemia?

normocytic and normochromic

What are some general symptoms of impaired oxygen transport in hemolytic anemia? (4)

Fatigue

pallor

shortness of breath

tachycardia

in ______________ hemolysis, RBCs get caught in splenic sinusoids and lyse

(extravascular or intravascular)

extravascular

______________ hemolysis is less common and normally occurs due to mechanical injury, transfusion reaction, or toxicity

(extravascular or intravascular)

intravascular

what are two examples of intrinsic hemolytic anemia and what is the mechanism?

- Sickle cell disease

- Thalassemias

defects of the red cell membrane

what gene is altered in sickle cell anemia and how?

recessive HbS gene

Glutamine is replaced by Valine

where is the HbS gene located?

sixth codon of the beta-chain gene

when does gene HbS become sickled?

when it's deoxygenated

What process occurs inside RBCs with deoxygenated HbS?

Deoxy-Hb aggregates and polymerizes in the cytoplasm. This forms a semisolid gel, which deforms the cell into a sickle shape.

what may return normal shape to the cell in sickle cell anemia?

oxygenation in the lungs

what are two major consequences of sickle cell anemia?

1. chronic hemolytic anemia

2. blood vessel occlusion

what causes the chronic hemolytic anemia present in sickle cell anemia?

there is premature destruction (lysis) of RBCs in the spleen due to deformed membranes

where does lysis of RBCs occur in sickle cell anemia?

spleen

what are some signs and symptoms of sickle cell anemia?

- pain, swelling

- recurrent infection

- stroke or MI

- splenomegaly

Pain, swelling, infections, stroke, MI, and splenomegaly can be seen as a consequence of what disease?

sickle cell disease

what are some external factors that can further precipitate blood vessel occlusion in sickle cell anemia?

cold

stress

physical exertion

infection

hypoxia

dehydration

acidosis

what is Thalassemia?

an inherited condition that results in abnormal hemoglobin synthesis

what type of RBCs are seen in Thalassemias?

hypochromic, microcytic

how can hemolysis occur in Thalassemias?

accumulation of the unaffected chains interferes with normal RBC maturation resulting in membrane changes --- hemolysis & anemia

α-Thalassemia

Alpha chain abnormality

4 Genes (2 pairs) located on chromosome 16

how many genes are present and where does the chromosomal abnormality occur in α-Thalassemia? β-Thalassemia?

α-Thalassemia: 4 Genes (2 pairs) located on chromosome 16

β-Thalassemia: 2 Genes (1 pair) on chromosome 11

what form of α-Thalassemia has a modified hemoglobin with a high affinity for oxygen?

Bart's

what are the four categories of α-Thalassemia?

- Carrier

- Trait (minor)

- Hb-H

- Hb-Barts (hydrops fetalis)

symptomatic, hemolytic, hypochromic, microcytic anemia, splenomegaly - what category of α-Thalassemia?

Hb-H

asymptomatic, mild anemia, no RBC abnormality - what category of α-Thalassemia?

Trait 1 (carrier)

asymptomatic, mild microcytic and hypochromic anemia - what category of α-Thalassemia?

Trait 2 (minor)

β-Thalassemia

•Beta chain abnormality

•2 Genes (1 pair) on chromosome 11

what happens to the excess alpha chains created in β-Thalassemia?

they are denatured in the bone marrow - can be seen as intracellular inclusions called Heinz bodies