Anemia2 Flashcards
ANEMIA OF ABNORMAL NUCLEAR DEVELOPMENT 5
CONGENITAL DYSERYTHROPOIETIC ANEMIAS MEGALOBLASTIC ANEMIAS PERNICIOUS ANEMIA FOLATE DEFICIENCY ANEMIA CONGENITAL DYSERYTHROPOIETIC ANEMIAS
ANEMIA OF ABNORMAL IRON METABOLISM
IRON DEFICIENCY ANEMIA
ANEMIA OF CHRONIC DISEASES
SIDEROBLASTIC ANEMIAS
LEAD INTOXICATION
are a group of disorders in which cell maturation in the bone marrow is abnormal as a result of abnormal development of the nuclei.
anemias of abnormal nuclear development
MEGALOBLASTIC ANEMIA
Less common causes include:
Defects of DNA synthesis
Drug induced disorders of DNA synthesis
anemias of abnormal nuclear development are characteristically classified as 4
MACROCYTIC, NORMO to HYPERCHROMIC,
abnormal leukocytes (hypersegmented neutrophils),
erythrocytes (macrovalocytes), and
platelets (giant platelets)
abnormalities in erythrocytic cell precursors but are INHERITED and NOT ASSOCIATED with leukocyte and platelet disorders.
CONGENITAL DYSERYTHROPOIETIC ANEMIAS
Have a corrin ring (a ring composed of 4 pyrrole rings similar to hemoglobin) that contains cobalt
VITAMIN B12 CYANOCOBALAMIN
Coenzyme forms of B12
– represents 75% of cobalamin in the plasma
– represents 75% of cobalamin in the liver , rbcs, and the kidneys
Adenosylcobalamin
Methylcobalamin
Represents a family of compounds derived from folic acid (pteroylglutamic acid)
FOLATE
Participates in carbon transfers and is required in three reactions that lead to DNA synthesis : 2 for purine and 1 for pyrimidine synthesis
FOLATE
Folate is necessary for efficient _ synthesis and production of _.
thymidilate
DNA
is the most important transcobalamin is a b-globulin synthesized in the liver and transports B12 to the liver, tissues and some in the bone marrow; it is needed in the transport of B12 across membranes
TC II
are present in gastric fluid, plasma, amniotic fluid, milk, saliva, and granulocytes; called R (rapid) proteins or R-binders , since they migrate faster than intrinsic factor on zone electrophoresis
TC I and III
binds most of the B12 in plasma and this is not transported in the marrow; believed to be secreted by granulocytes
TCI
Deficiency in TC II causes _; TC I and III deficiencies are apparently harmless
megaloblastic anemias
Derived from green leafy vegetables, liver, kidney, and whole grain cereals, , yeast, and fruits(especially oranges)
FOLIC ACID
Folate uptake in rbcs require _ as a cofactor!
Vit B12
_ and _ are integral components in DNA synthesis
Vitamin B12 and Folate
MEGALOBLASTIC ANEMIAS
PATHOPHYSIOLOGY:
Vitamin B12 deficiency
“mehylfolate trap” hypothesis
When B12 is deficient, _ cannot be converted to methionine and folate
homocysteine
. THE __ PROVIDES A SENSITIVE TEST FOR B12 DEFICIENCY THAT IS NOT AFFECTED BY FOLIC ACID DEFICIENCY.
methylmalonic acid MMA LEVEL
MEGALOBLASTIC ANEMIA PERIPHERAL BLOOD FINDINGS
```
anemia
MCV
MCH
MCHC
WBC
+
RDW
~~~
Mild to moderate anemia
MCV increased
MCH is increased
MCHC is normal
WBC count is normal but declines
(+) Macroovalocytesn with little or no central pallor
Anisocytosis common [increased random distribution width (RDW)]
is associated with Vitamin B12 deficiency that results from an acquired atrophy of the stomach lining
Pernicious anemia or PA
Vitamin B12 deficiency is associated with _; Folate deficiencies DO NOT exhibit these findings.
NEUROLOGIC DEFICIENCIES
OTHER CAUSES OF ACQUIRED VITAMIN B12 DEFICIENCY 7
- Dietary deficiency
- Castle’s Intrinsic Factor Deficiency
- Intrinsic Factor Molecular Defect
- Small Bowel Bacterial Overgrowth
- Fish Tapeworm disease (Diphyllobothriasis)
- Ileal Disease
- Drugs ( neomycin and ethanol)
A rare hereditary disorder that causes B12 malabsorption
Affects homozygous children in the first 2 years of life
Autosomal recessive inheritance
Vitamin cannot be absorbed with or without IF
Gastric secretion is normal
HEREDITARY VITAMIN B12 DEFICIENCY
IMMERSLUND SYNDROME
Usually same with Vit B12 deficiency
No neurologic findings
Other causes:
Dietary deficiency Alcoholic cirrhosis Pregnancy Infant malnutrition Folate antagonists
(pyrimethamine [antimalarial] and
methotrexate [chemotherapeutic drug])
FOLATE DEFICIENCY ANEMIA
affects the ENTIRE small intestine and causes both B12 and folate deficiency; appears to be caused by infectious agents and responds to folate therapy and antibiotics
TROPICAL SPRUE
Usually affects the PROXIMAL small intestine
Two forms:
– seen in childhood
– seen in adults
GLUTEN SENSITIVE ENTEROPATHY–
Celiac Disease
Non-tropical Sprue
– a rare hereditary autosomal recessive disorder of pyrimidine metabolism resulting in abnormal DNA synthesis, excessive urinary excretion of orotic acid, and megaloblastic anemia
OROTIC ACIDURIA
– Is a rare X-linked disorder of purine metabolism caused by the lack of the enzyme xanthine-guanine phosphoribosyl transferase.
LESCH-NYHAN SYNDROME
Characterized by refractory anemia that varies in severity, and abnormalities in rbc bone marrow precursors, including nuclear abnormalities, multinuclearity and other bizarre changes
WBC AND Platelets ARE NOT AFFECTED
CONGENITAL DYSERYTHROPOIETIC ANEMIAS
Causes neonatal jaundice but patients have a normal lifespan; Bone marrow shows binucleated cells; Autosomal recessive
Type I CDA
– Referred to as hereditary erythroblast multinuclearity; Most common of the three; positive HEMPAS antigen which makes these cells resistant to the sugar water test to screen PNH; Autosomal recessive
Type II CDA
– characterized by pronounced multinuclearity (up to 12 nuclei per cell) – called gigantoblasts; Autosomal dominant
Type III cda
___ are negative to acidified serum test; only _ is positive to this test!
CDA Type I and III
Type II
ANEMIA OF ABNORMAL IRON METABOLISM
Three general etiologic mechanisms appear to be involved:
Deficiency in raw material
Defective release in of stored iron from macrophages
Defective utilization of iron within the erythroblasts
(iron deficiency anemia)
(anemia of chronic disorders)
(sideroblastic anemia and anemia of lead intoxication)
– reflects the body tissue iron stores and thus a good indicator of iron storage status; first laboratory test to become abnormal; decreased ONLY IN IRON DEFICIENCY ANEMIA
Reference range:
Men:_
Women:_
SERUM FERRITIN
15-200ug/L
12-150ug/L
CHEMICAL LABORATORY TESTS USEFUL IN DIFFERENTIATING DISORDERS OF IRON DEFICIENCY
- -FREE ERYTHROCYTE PROTOPORPHYRIN
- -TOTAL IRON BINDING CAPACITY (TIBC)
- -TRANSFERRIN SATURATION
- -SERUM IRON
PICA
IRON DEFICIENCY ANEMIA
IRON DEFICIENCY ANEMIA 6
cracks in the corners of the mouth
(soreness of the tongue)
(flattening and spooning of the nails)
Physical Findings:
Angular stomatitis Glossitis Gastritis Koilonychia Splenomegaly – rare Neuropathies – not present
Decreased Hgb, Hct and RBC]
Decreased Indices
Microcytic, hypochromic
Elevated RDW
Variable platelet count
WBC and Reticulocyte count normal
IRON DEFICIENCY ANEMIA
(+) marrow sideroblasts
Are a diverse group identified by a common feature of abnormal iron kinetics that produces excess accumulation of iron, which is deposited in the mitochondria of normoblasts
SIDEROBLASTIC ANEMIAS
Three types of Sideroblasts:
Type I – iron in the form of ferritin aggregates and at least _aggregates can be identified in approximately 50% of normoblasts
Type II – contains _ aggregates
Type III – __; shows larger granules situated in a ring or collar around the nucleus of a normoblast; are representatives of iron-laden mitochondria
4
6
pathologic ringed sideroblast
For a diagnosis of Sideroblastic anemia, at least _ of normoblasts must be __ ringed sideroblasts.
15%
Type III
CLASSIFICATION AND CAUSES OF SIDEROBLASTIC ANEMIA
HEREDITARY (rare)
ACQUIRED (common)
Primary (idiopathic)
Secondary
HEREDITARY (rare)
–ALA synthase deficiency
ACQUIRED (common) Primary (idiopathic) --Acute myeloid leukemia --Myelodysplastic syndromes --Myeloma
- -Alcoholism
- -Lead poisoning
- -Chloramphenicol
- Drugs used in the treatment of tuberculosis
Lead poisoning causes increased levels of _ and normal _ _.
THIS CONFORMATION DISTINGUISH LEAD POISONING FROM ACUTE INTERMITTENT PORPHYRIA in which BOTH d-ALA and PBG are elevated.
d-ALA
porphobilinogen levels
Injury to red cell membrane, possibly by inhibiting ATPase
Defects in a and b globin chain synthesis
LEAD INTOXICATION
LEAD INTOX
Free erythrocyte protoporphyrin is _ in erythrocytes to A MUCH GREATER EXTENT than in iron deficiency.
Urinary ALA is _ and PBG is __. Urinary coproporphyrins are also __
increased
elevated
normal
increased
