Pathology of Anemia 2

Question 1

What are thalassemias?

Answer 1

group of genetic disorders characterized by the lack or decreased synthesis of either alpha or beta globin chains of hemoglobin a
a thalassemia-alpha globin chain synthesis is reduced
b thalassemia-b globin chain synthesis is absent (b0) or deficient (b+)

Question 2

Alpha thalassemia?

Answer 2

deletions 
two genes on chromosome 16
4 degrees 
silent: 
-a/aa
alpha thalassemia trait: 
--/aa(asian) , -a/-a (black)
HbH disease:
--/-a
Hydrops fetalis:
--/--

Question 3

B-thalassemias

Answer 3

mutations

one gene on chromosome 11

Question 4

How does B-thalassemia lead to anemia? hemolytic anemia?

Answer 4

Anemia:
reduced synthesis of B-globin leading to inadequate HgbA formation

Hemolytic:
relatively excess alpha globulins
-form insoluble aggregates which damage cell membranes-reduce cell membrane plasticity and allow RBCs to be susceptible to phagocytosis

Question 5

Thalassemia major vs minor?

Answer 5

major: severe disease, reliance on transfusions
minor: asymptomatic, mild or absent anemia, some RBC abnormalities

Question 6

What is B thalassemias major?

Answer 6

• marrow space is expanded causing skeletal deformities
• hepatosplenomegaly from extramedullary hematopoiesis causes abdominal distention
• multiple transfusions necessary, leading to excessive deposition of iron (death may result from cardiac failure)

Question 7

What is B-thalassemia minor?

Answer 7

• minor microcytic hypochromic anemia (must be distinguished from an iron deficiency)
• hemoglobin electrophoresis and iron studies are used to make diagnosis
• HgbA(a2b2)-reduced
• HgbA2 (a2g2)-increased

Mediterranean patients

Question 8

What do you see on a blood smear of a patient with B-thalassemia?

Answer 8

target cells

-decrease in hemoglobin in cytoplasm(basketball)-bleb in the membrane in the center

Question 9

What is paroxysmal nocturnal hemoglobinuria?

Answer 9

the only acquired defect in the red cell membrane

1. stem cell disorder that results from a mutation in the phosphatidylinositol glycan A gene (PIGA)
2. deficiency of GPI anchor
3. lack of expression of GPI linked proteins
   such as
   -CD55 (DAF)
   -CD59(MIRL)
   -C8 binding protein
   –>involved in inactivating the complement pathway

Question 10

What are classical findings in PNH?

Answer 10

1. patient has classic intravascular hemolysis
2. paroxysmal and nocturnal in only 25% of cases
3. infections and venous thrombosis
4. occasional evolution to aplastic anemia or acute leukemia

Question 11

Some intrinsic abnormalities of RBC caused hemolysis, such as hereditary spherocytosis, G6PD deficiency, sick cell anemia, thalassemia, and PNH, what are some extrinsic abnormalities that can lead to hemolysis of the RBC?

Answer 11

1. antibody mediated
2. mechanical trauma
3. infections
4. chemical injury

Question 12

What are some examples of mechanical trauma that cause hemolysis?

Answer 12

1. prosthetic cardiac valves
2. narrowing of small vessels and fibrin deposition (microangiopathic hemolytic anemia)
   - TTP, HUS, DIC
   - ->presence of schistocytes in peripheral blood

Question 13

What causes iron deficiency anemia?

Answer 13

1. malabsorption of iron
   - low dietary intake not often the cause of deficiency in the us
2. may not meet demand during pregnancy or infancy
3. most common cause of iron deficiency is western world is blood loss!

Question 14

What is the order of depletion in iron deficiency anemia?

Answer 14

1. stored iron first depleted
   - serum ferritin declines, bone marrow iron depleted
2. circulation iron then decreases
   - measured serum iron low
3. increased total iron binding capacity (TIBC)
4. hemoglobin eventually decreases
5. RBCs become small with reduced hemoglobin concentration

Question 15

What are signs of iron deficiency anemia?

Answer 15

1. nails may develop ridges and become spoon shaped
2. tongue may become smooth
3. intestinal malabsorption may develop
4. esophageal webs may appear (rare today)

Question 16

What does iron deficiency anemia look like on a blood smear?

Answer 16

central pallor is almost entire cell

Question 17

What leads to megaloblastic anemias?

Answer 17

Disturbances of proliferation and maturation of erythroblasts due to defective DNA synthesis

Two Principle types

1. B12 deficiency
2. folate deficiency

Question 18

megaloblasts

Answer 18

enlarged red cell precursors

Question 19

macrocytes

Answer 19

enlarged red blood cells

Question 20

What is the ratio of cytoplasm to nuclei like in megaloblastic anemias?

Answer 20

nuclei are immature and cytoplasm is fully mature: nuclear cytoplasmic asynchrony

Question 21

What leads to vitamin b12 megaloblastic anemia?

Answer 21

1. inadequate diet-takes a long time
2. increased requirements
3. impaired absorption

Question 22

What leads vitamin B12 impaired absorption?

Answer 22

1. IF deficiency
2. pancreatitis
3. gastrectomy
4. ileal resection, regional enteritis
5. parasites (fish tapeworm)

Question 23

What is pernicious anemia?

Answer 23

B12 deficiency secondary to atrophic gastritis with failure of production of intrinsic factor

Question 24

How does B12 affect THF and DNA synthesis?

Answer 24

transfer of methyl group to B12 so THF can do its DNA job without B12 impaired DNA synthesis

Question 25

How does B12 affect homocysteine and methionine?

Answer 25

B12 transfers methyl group to homocysteine to make methionine without B12 homocysteine builds up

Question 26

How does B12 affect succinyl Coenzyme A?

Answer 26

For methylmalonyl coA to make succinyl coA there needs to be B12 -without it there is an increase in methylmalonate and that is associated with CNS symptoms

Question 27

What are clinical findings of a b12 deficiency?

Answer 27

1. alimentary tract: atrophic glossitis, chronic gastritis 2. blood and bone marrow: megaloblastic anemia, leukopenia with hypersegmented granulocytes, mild to moderate thrombocytopenia 3. CNS findings: involvement of posterolateral spinal tracts, leading to sensory and motor abnormalities - subacute combined degeneration-->spastic paraparesis, sensory ataxia, lower limb paresthesias

Question 28

How does someone get a folate deficiency?

Answer 28

- inadequate intake or impaired absorption | - reserves are modest-still does not appear for months unless demand increased

Question 29

Is there CNS abnormalities in folate deficiency? Can you reverse the problems seen in folate deficiency, what about B12 deficiency?

Answer 29

no

Question 30

Can you reverse the problems seen in folate deficiency, what about B12 deficiency?

Answer 30

yes but there is no reversal of CNS abnormalities with B12 deficiency

Question 31

What is anemia of chronic disease?

Answer 31

associated with: 1. chronic infections 2. chronic immune disorders 3. malignancies -caused by high levels of plasma **hepcidin that blocks the transfer of iron from macrophages to erythroid precursors like iron deficiency but high ferritin decreased total iron binding capacity increased bone marrow iron stores

Question 32

What is aplastic anemia?

Answer 32

failure or suppression of stem cells leads to hypocellular marrow Peripheral blood findings: - anemia - granulocytopenia - thrombocytopenia *PANCYTOPENIA Frequently idiopathic but may result from: 1. whole body irradiation 2. myelotoxic drugs/chemicals 3. viral infections Bone marrow is typically hypocellular with increased fat and small foci of lymphocytes and plasma cells Clinically: symptoms may develop insidiously and reflect effects of anemia, neutropenia, and thrombocytopenia -must be distinguished from other syndromes causing pancytopenia -prognosis unpredictable

Question 33

What is aplastic anemia likely secondary to?

Answer 33

1. defect or deficiency of hematopoietic stem cells 2. defect in bone marrow stroma 3. suppression of marrow stem cells by T cell mediated immune mechanisms