Anemia

Question 1

What is hematopoiesis?

Answer 1

• formation of blood cellular components
• derived from hematopoietic stem cells
• largely controlled by feedback mechanism (cytokines)

Question 2

What is Erythropoiesis?

Answer 2

• the process which produces red blood cells
• which is the development from erythropoietic stem cell to mature red blood cell
• it is stimulated by decreased O2 in circulation which is detected by the kidneys which then secretes the hormone erythropoietin

Question 3

Erythropoiesis through out life?
Which organs does it happen in?

Answer 3

1. fetal
   - occurs in yolk sac, liver and spleen
   - At ~7 months moves to the BM and hepatic production decreases during the 3rd trimester and ceases soon after birth
2. child
   - active bone marrow is present in all skeleton
3. adult
   - active bone marrow is present in axial skeleton (head and trunk of vertebrae)

Question 4

Erythropoiesis process?

Answer 4

1. pluripotent hematopoietic stem cell
2. proerythroblast
3. erythroblast
   - loses nucleus + some organelles
   > processes above happen in bone marrow
4. reticulocyte
   - spends 3 days in marrow, 1 day in blood
   - loses remaining organelles
5. erythrocyte
   - lifespan aprox. 120 days (90 in an infant)
   > processes above happen in blood

Question 5

Physiology of erythropoiesis?

Answer 5

Erythropoietin > hormone produced in the kidney
- Induces erythroid progenitor cells to differentiate into proerythroblasts
- Brings about expansion of the erythroid marrow and an increase in red cell production

Question 6

Requirements for erythropiesis?

Answer 6

1. Metals: Iron, cobalt, Mn.
2. Vitamins: Vit B12, Folic acid, Vitamin C, Vitamin E Vit B6, Riboflavin.
3. Amino acids
4. Hormones: Erythropoietin, Androgens, Thyroxin

Question 7

Structure of a normal erythrocyte?

Answer 7

Typically, without a nucleus.
Contain the pigment hemoglobin
Shape: Biconcave disks
Size:
~Diameter of 7.8um.
Thickness of 2.5um at the edge and 1um at the center
Volume: 90-95 m
Form: Flexible, deformable, elastic

Question 8

Structure of RBC membrane?

Answer 8

1. outer membrane
   - hydrophilic : glycolipids, glycoprotein, proteins
2. inner layer
   - hydrophilic : proteins
3. central layer
   - hydrophobic : proteins, cholesterol, phospholipids

Question 9

RBC membrane function?

Answer 9

Maintain structure and contain the contents of the red cell- chiefly, hemoglobin.
Maintain cellular functions in transport of salts and nutrients.
Avoid adhesion to self and vascular wall
Deformability, metabolism, senescence
Provides cellular shape

Question 10

What is hemoglobin?

Answer 10

iron containing oxygen transporting metalloprotein

Question 11

2 parts of hemoglobin?

Answer 11

1. Globin
   Consists of 4 polypeptide chains:
   Two alpha chains
   Two beta chains
2. Heme
   Flat ring molecule with 4 pyrrole ring.
   Single Fe2+ ion at centre of each pyrrole ring.
   Without iron ring – Porphyrin Ring.

Question 12

Hemoglobin function?

Answer 12

1. Delivery of oxygen from the lungs to the tissues
2. Transport of CO2 and protons from tissue to lungs for expiration and excretion

Question 13

How does Hb work?

Answer 13

1. One molecule of hb will bind to 4 molecules of O2
2. Cooperative binding of O2 to hb: binding of O2 to one heme increases the binding of O2 to other heme

Question 14

Bohr effect of hemoglobin?

Answer 14

1. Haemoglobin’s lower affinity for oxygen secondary to increases in partial pressure of carbon dioxide and/or decreased blood pH.
2. This lower affinity, in turn, enhances the unloading of oxygen into tissues to meet the oxygen demand of the tissue.
3. It causes shift in the O2 dissociation curve to the right

Question 15

Describe the oxyhemoglobin dissociation curve?

Answer 15

1. right shift
   - increase pCO2, H+, temp, DPG, decrease pH, sulf-Hb, HbSS > decrease O2 affinity so increase O2 unloading
2. left shift
   - decrease pCO2, H+, temp, DPG, increase pH, decrease phosphate, met-Hb, CO-Hb, fetal-Hb > increase O2 affinity sp decrease O2 unloading

Question 16

What is globin switch?

Question 17

Fate of the RBC?

Answer 17

• RBCs normally circulate an average of 120days before being destroyed
• Once the red cell membrane becomes fragile, the cell ruptures

Question 18

Where do RBCs self destruct?

Answer 18

• Many of the red cells self destruct in the spleen
• Squeeze through the red pulp
  > Space between the structural trabeculae are only 3 umeters wide, in comparison with the 8-umeter diameter of the red cell

Question 19

What are the products released when the RBC is destroyed?
What happens to them?

Answer 19

when RBC is destroyed in the spleen hemoglobin is released which in turn breaks down into
1. iron + apoferritin > ferritin > stored and reused
2. globin > protein pool > stored and reused
3. porphyrin > bilirubin > excreted

Question 20

What is anemia?

Answer 20

Reduction in red blood cell mass or blood hemoglobin concentration”
- Hemoglobin level too low to meet cellular oxygen demands.

Question 21

Physiology of anemia?

Answer 21

1. Decreased production
2. Increased destruction
3. Loss
   - In the normal functioning Bone marrow, anemia results in erythroid hyperplasia which can increase RBC production

Question 22

Epidemiology of anemia?

Answer 22

• Most common hematological disorder in childhood
• Iron deficiency- the most common cause of anemia in pediatric age worldwide
• Prevalence of anemia among children 6-59months in Malawi is 55%

Question 23

Epidemiology of anemia is influenced by?

Answer 23

age, race, Tanner stage, altitude, genetics

Question 24

Normal Hgb concentration parameters?

Answer 24

• starts high at birth (mean 18.5)
• declines to its nadir at 2 months (mean 11.5, Lower limit of normal 9.0)
• rises again to adult values around age 12 (mean 14 female, 14.5 male).

Question 25

Compare Hgb between men and women?

Answer 25

Women run about 1 g/dL less than men.

Question 26

MCV normal parameters?

Answer 26

- starts high at birth (mean 108) - declines to its nadir at 6-24 months (mean 78, lower limit of normal 70) - and rises again to mean 85 around age 12, and to adult values around age 18 (mean 90, lower limit of normal 80

Question 27

Physiologic adaptation to anemia?

Answer 27

1. increased heart rate 2. increased stroke volume 3. vasodilation 4. Decreased oxygen affinity (right shift in oxygen dissociation curve) leading to enhanced 02 delivery to tissues 5. Elevated 2,3‐BPG (2,3‐DPG) 6. Bohr effect (↓pH, ↑temp.)

Question 28

Anemia history?

Answer 28

Age of onset Duration Birth Weight and Gestational age Milk intake Solid diet Feeding problems Symptoms attributable to anemia Symptoms of hemolysis History of blood loss or bruising Blood transfusions indicate severity or chronicity Any other symptoms: symptoms of chronic GI, liver or kidney disease Family history Drugs and toxins

Question 29

Anemia examination?

Answer 29

Dysmorphic features – Bone marrow failure syndrome Jaundice -Hemolysis Tongue (atrophy of papillae) –severe Iron deficiency Purpura or bleeding -Thrombocytopenia Koilonychia –severe Iron deficiency Cardiac examination –Heart Failure Lymphadenopathy –leukemia, lymphoma Splenomegaly –Hemolysis, leukemia, lymphoma

Question 30

Anemia investigations?

Answer 30

FBC (Hb, Hematocrit, MCV, MCH, MCHC, Platelets, RDW) Peripheral Blood Film (microcytic, normocytic, macrocytic) Reticulocyte count: High (hemolysis), Low (hypoplastic) ESR,CRP (chronic disease) Serum Ferritin, Serum Iron (Iron deficiency, chronic inflammation) Hemoglobin Electrophoresis (Hemoglobinopathies) Bone Marrow Examination (hypoplasia, leukemia)

Question 31

RBC size morphology?

Answer 31

Normocyte normal size (MCV = 75 105 fl) Microcyte small cells (MCV < 75 fl) Macrocye large cells ( MCV > 105 fl)

Question 32

RBC shape morphology?

Answer 32

Anisocytosis variation in size Poikilocytosis variation in shapes Spherocyte small round cell

Question 33

What is microcytic anemia?

Question 34

What is normocytic anemia?

Question 35

What is macrocytic anemia?

Question 36

How is anemia classified?

Answer 36

1. absolute anemia - decrease in red cell volume 2. relative anemia - increase in plasma volume

Question 37

Classification of absolute anemia?

Answer 37

1. decreased red cell production 2. increased red cell destruction 3. blood loss and blood redistribution

Question 38

What is non severe anemia?

Answer 38

Young children (aged<6years)- Hb <9.3g/dl

Question 39

What is severe anemia?

Answer 39

All children Hb<4g/dl

Question 40

Management of non-severe anemia?

Answer 40

Begin treatment, unless the child has severe acute malnutrition TREAT UNDERLYING CAUSE

Question 41

Management of severe anemia?

Answer 41

Give blood transfusion as soon as possible All children Hb<4g/dl Less severely anemic children (EVF 13-18%, Hb 4-6g/dl) with the following clinical features: Shock Impaired consciousness Heart failure Deep, labored breathing Very high malarial parasitemia (>10% of red cell with parasites)

Question 42

Indications for RBC transfusion?

Question 43

Dos for RBC transfusion?

Question 44

Blood transfusion complications?