BLD 324 Exam 3

What is the definition of Anemia?

Decrease in the oxygen-carrying capacity of blood.

What are the generic signs of anemia?

Pallor of skin and mucous membranes
Fatigue and dyspnea
neurologic symptoms (e.g. headache)
cardiac symptoms (e.g. palpitations)
if severe/prolonged - heart failure and death :(

What is the laboratory definition of anemia?

Decreased hemoglobin

What causes anemia in pregnant women?

Increase plasma volume while red cell mass is unchanged

What causes red blood cell production?

Production increases when Erythropoietin increases and it increases when kidneys detects hypoxia.

What causes increase of EPO?

Increases when kidneys detect hypoxia

What is the definition of Polycythemia?

Increased blood cells

What is the definition of Erythrocytosis?

Increased red cells

What is Absolute Erythrocytosis?

Increased red blood cell mass (truly an increase in red blood cell numbers in the vasculature)

What is PRIMARY Absolute Erythrocytosis?

-No underlying hypoxia and no increase in EPO, but RBCs increase dramatically
-Seen in polycythemia (rubra) vera
-leukemia
-NO INCREASE IN EPO

What is SECONDARY Absolute Erythrocytosis

-Increased red clood cell mass due to increased EPO
-Primary events are those that increase EPO
-Cause hypoxia
-INCREASE IN EPO

What are primary events that increase EPO?

-cigarette smoking
-living at high altitude
-increased HbF in newborns
-abnormal hemoglobins that don't carry oxygen well
-lung and cardiac diseases that impair oxygenation of blood

What is Relative Erythrocytosis?

-The red cells are unchanged in number, but the plasma component of blood changes
(Decrease in plasma volume creates false impression of erythrocytosis e.g elevated Hct)
-Lab results can be misleading

What laboratory testing is performed to distinguish relative and absolute polycythemia?

red cell mass measurement and measure plasma volume

What is the expected response to anemia?

Accelerated reticulocytosis
Requires: increase in reticulocytes and must be over 3% to adequately compensate for anemia

Microcytic ref range

Normocytic ref range

80-100 fL

Macrocytic ref range

>100 fL

What does cell color reflect?

Hemoglobin concentration in cells

Hypochromic ref range

Normochromic ref range

>32

Four major pathophysiological classifications

-Whole blood loss from the vascular system
-Increased destruction of red blood cells
-Mechanically by fragmentation - membrane rupture

What is the effect of fragmented red blood cells in the peripheral blood (shistocytes or schzocytes) on MCV and RDW?

MCV decreases; RDW increases

True or False. there is morphologic evidence in peripheral blood if the macrophage is fully successful in phagocytizing the red cell

False

What happens if the macrophage is partly successful in phagocytizing the red cell?

A sperocyte forms

What binds free heme in the plasma?

Hemopexin

What binds free hemoglobin?

Haptoglobin

What causes the anemia of pregnancy?

increase in plasma volume

What is the cause of Primary Absolute Erythrocytosis?

Increased EPO sensitivity

On Day 1 what distinguishes intravascular vs extravascular?

Plasma hemoglobin

What are pathophysiologic category of anemia?

Whole blood loss, Increased destruction, Decreased production

Where is conjugated bilirubin produced?

In the liver

Fragmentation Hemolysis (intravascular)
THINK OF GRAPH

Decrease in serum haptoglobin as mega increase in plasma hemoglobin ( serum haptoglobin returns to normal when plasma hemoglobin decreases)

Macrophage-mediated Hemolysis (extravascular)
THINK OF GRAPH

No plasma hemoglobin
No urinary hemoglobin
Normal serum haptoglobin

Why does plasma volume in pregnant women increase?

They retain water in blood cells

Intravascular Hemolytic Anemia

decreased haptoglobin (binds Hb to try and save it), increased LDH and bilirubin
-INCREASED RETICS

Macrophage mediated hemolytic anemia

-SPHEROCYTES

RDW in Hemolytic anemia

Elevated

Types of Anemias

-Sickle cell, chronic inflammation, sideroblastic, iron deficiency, intravascular hemolytic, extravascular hemolytic

Sickle Cell Anemia

-Normochromic, normocytic
-Defect in base pair : GAG - GTG
-Deoxygenated molecule is less soluble and it polymerizes (crystallization)
-Crystallization of hemoglobin leads to sickle shape
-Hemoglobinopathies
-RDW Increased
-Howell Jolly bodies and siderocytes
-thrombocytosis and leukocytosis
-Increased SI and total bilirubin
-Decreased haptoglobin
-Increased LD
-Increased Stool and Urine Urobilinogen

Chronic Inflammation Anemia

Microcytic, Hypochromic
Serum Iron Decreased
FEP decreased due to decreased Iron

Sideroblastic Anemia

Microcytic, Hypochromic

Iron Deficiency Anemia

Microcytic, Hypochromic
LOW MCV HIGH RDW
RDW elevated
Ferritin Decreased
Total Serum Iron Decreased
Total iron Binding Capacity Increased
Percent Saturation Decreased
Protoporphyrin IX Increased
Zinc Protoporphyrin Increased
Serum transferrin receptor Increased
Stainable iron in bone marrow Decreased

Intravascular Anemia

Normocytic, Normochromic

Extravascular Anemia

Normocytic, Normochromic

What is a cause of Sideroblastic Anemia?

-Lead poisioning

What anemia are associated with anisocytosis?

iron deficiency anemia

What is the best test for iron deficiency anemia?

Hemoglobin content of reticulocytes

Is Ferritin a good test for iron deficiency?

No. It is sometimes unreliable

Percent Saturation

SI/ TIBC x 100%

What decreases first in development of iron deficiency anemia

Ferritin

Least likely to be seen in iron deficiency anemia

Macrocytosis

What does Ret-He assay measure?

Ret-He assay measures iron available for hematopoiesis

Increase Lymphocytes

Viral

Increase Neutrophils

Bacterial

Increase Eosinophils

allergies and parasites

How does Fe2+ enter cells?

Tf and TFR

Where does pain from sickle cell disease come from?

Due to blockage of blood vessels

What does sideroblastic anemia lead poisioning inhibit?

Inhibition of Ferrochelatase

Cause of sideroblastic anemia

Failure to incorporate iron into protoporphyrin IX

What cells do not have ferroportin?

Erythroblasts

What distinguishes the anemia of chronic inflammation from other anemias?

Relative Retic count

Hemoglobinopathies

Hereditary qualitative and quantitative defects in globin chain production
-Sickle cell

Qualitative hemoglobinopathies

normocytic anemias of increased destruction

Sickle cell disease

Homozygous
Most severe
Almost all erythrocytes are sickled
Thrombosis -> organ damage
autosplenectomy

Sickle cell trait

Heterozygous condition
one HbA allele and one HbS allele
some normal hemoglobin.

Papenheimer bodies

Iron fragments

Screening for HbS

-Cells are lysed by saponin (soap)
- Released Hb is deoxygenated by sodium dithionite
RESULTS:
HbA stays clear
HbS crystallizes and forms cloudy solution
- Confirm with electrophoresis

Neutrophils

Develop from the HSC (hematopoietic stem cell) by way of the CMP and the GMP (granulocyte monocyte progenitor)
-Circulating and Marginated cells: equilibrium of neutrophils in the vessels (total # of WBCs in the vessels is unchanged but there are more of them circulating)
-Respond to chemical agents released during inflammation
-Move up concentration gradient
-Exit the blood vessel via diapedesis
-Receptor for Antibody and Complement

life span of a neutrophil

7 hours in tissues
4 hours in bloodstream

Electrical impedance

# of pulses
size of cells and complexity of granules

Monocytes

Tuberculosis

What are the FEP levels in Chronic Inflammation

FEP increased due to Decreased iron availability

Viral

leukocytosis, absolute lymphocytosis, atypical lymphocytes

MCHC of spherocytes

Increased MCHC because they have less membrane
Same HGB, smaller size

Sickle Cell Disease

S + A2

Neutrophil Extracellular Traps

Forms a web that traps and digests bacteria with digestive enzymes from release DNA

Important contents of neutrophil granules

-myeloperoxidase
-lactoferrin
-lysozyme
-collagenase

Eosinophils

CMP->GMP->EOP
Downregulate basophils
1-8 hours in blood, longer in tissues
High conc. in skin, GI tract, and respiratory tract

Eosinophil granules contain:

major basic protein
eosinophil cationic protein

Basophils

CMP->GMP-> unknown lol
Have an Fc receptor for IgE
Mediate hypersensitivity reactions
Life span: similar to eosinophils

Basophil granules contain

-compounds that recruit eosinophils
-Histamine
-Platelet and Endothelial cell activators (vaso active compounds)

Myeloblast

Promyelocyte

Myelocyte

Metamyelocyte

Band neutrophil

Neutrophil (PMN)

WBC in Adults vs Children

Healthy children have higher absolute numbers of lymphocytes than adults

How many lobes are in hypersegmentation of neutrophils

more than 5 lobes
Seen in megaloblastic anemia

How many lobes are in hyposegmentation of neutrophils

less than or equal to 2 lobes
genetic - inherited
Pelger-Huet anomaly

Pelgeroid are seen when?

with infections and following chemotherapy

Toxic Triad

-Toxic granulation of neutrophils
-Dohle bodies in neutrophils
-Vaculoization of neutrophils

Toxic granulation of neutrophils

Dark granules in cytoplasm

Dohle bodies in neutrophils

Areas of visible RNA in cytoplasm
Pale blue/gray round, oval, or rod shaped structures in cytoplasm

Vacuolization of neutrophils

Foamy areas, bubbles, or open areas in the cytoplasm
Visible phagolysosomes
Associated with bacterial infections

Neutrophilia

Increase in neutrophils of any and all stages
Associated with inflammation but especially bacterial infections
Stimulated by G-CSF

Lymphocytosis

Increase in lymphocytes

Left Shift

Early release of neutrophilic cells
INCREASE bands
INCrease metamyelocytes
Increase myelocytes

Monocytosis

Increase monocytes
TB