Microcytic and Macrocytic Anemias Flashcards
Where is iron absorbed normally?
duodenum through the intestinal wall and then is bound by transferrin
Where is iron commonly stored?
bone marrow and macrophages in the liver and spleen
How is iron absorbed?
Iron is reduced as it enters the GI tract and is absorbed into intestinal cells via DMT-1 transporters.
daily absorption ~1mg (also ~1mg lost in urine daily)
What are the major fates of reduced iron inside intestinal cells?
can be transformed in ferritin or it can be transported out of the cell via ferroportin where it is then re-oxidized
What does hepcidin do?
decrease iron transport into blood from GI tract or from storage in bone marrow/macrophages
produces a functional iron deficiency
Signs of iron deficiency?
angular cheilosis- cracking at corners of the mouth
koilonychia (spooning of finger nails)- nails are concave, rigid, and brittle.
glossits- loss of papillae on tongue
craving for ice (pika)
How do iron deficient red cells appear? Would transferrin be increased?
in a peripheral blood smear, the red cells appear hypochromic and microcytic with enlarged central pallor areas and some may appear as target cells (long and slender)
increased transferrin with 5% saturation would be seen
What color does iron stain?
blue via prussian blue. Thus, in bone marrow iron deficient people will show no blue
T or F. Inflammation increases the amount of hepcidin circulating in the body
T. This is a defense mechanism geared toward limiting the amount of iron available to bacteria in the blood
What is hemochromatosis?
too much iron is deposited into tissue (skin-brawnzing of skin, liver- cirrhosis, heart- heart failure, joints- arthritis, endocrine organs- diabetes hypopituitarism)
What is hemochromatosis most commonly caused by? Common where?
defect in HFE gene. Most common in Northern Europe (there, 5 out of 1000 people are homozygous for mutation of the HFE gene)
MOI of genetic hemochromatosis?
AR
What is the most common mutation of genetic hemochromatosis?
C282Y mutation (90%) and is diagnostic
penetrance is variable however
What does mutated HFE cause?
decreased hepcidin levels
How is hemochromatosis treated?
phlebotomy regularly (once a week for a couple weeks, then once every 2 weeks, etc.) to make patient iron deficient, which will hopefully cause iron release from tissues
want ferritin less than 50 ng/ml
What is sideroblastic anemia? Causes?
defect in prophyrin ring enzymes that causes iron to accumulate into mitochondria in red cells that can be seen with prussian blue stain
Causes:
- defect in ala synthase
- myelodysplasia
- lead poisoning
- tuberculosis therapy (isoniazid)
Describe the development of hemoglobin in detail.
hemoglobin synthesis in developing red cells begins as iron enters the cell with transferrin and is combined with protoporphyrin, synthesized largely from glycine and succinyl-CoA in mitochondria, to form heme. One molecules of heme attaches to one of the globin polypeptide chains to from a unit of hemoglobin (1 of 4). Transferrin enter the cell by receptor-mediated endocytosis and then iron is release by a fall in pH, and the apotransferrin and receptor are recycled to plasma and membrane, respectively. Hypochromic anemias arise from lack of iron or failure of heme synthesis.
Basophilic stippling is common in what?
lead intoxication. Caused by precipitates of undegraded ribonucleic acid (RNA), the result of inhibition by lead of pyrimidine 5’-nucleotidase, one of the enzymes responsible for RNA degradation
What are some causes of macrocytosis? 11 things
- b12 and folate deficiency (most common)
- alcohol toxicity
- hypothyroidism
- myelodysplasia
- aplastic anemia
- liver disease
- hypoxia
- raised reticulocyte counts
- myeloma
- cytotoxic drugs
- pregnancy
Why do b12 and folate deficiency result in macrocytic anemias?
Because they result in megaloblastic anemias, in which the maturation of nucleus is delayed because of defects in DNA synthesis
Why are folate and b12 important?
diertary folate that circulates as methyl-THF must be transformed into THF using vitamin B12 (as homocysteine is converted to methionine- important in nerve development) in order to be used for pyrimidine synthesis
Almost all of the B12 we use comes from diet. How is cycled through the body?
Haptocorrin binds B12 in the mouth and then is degraded in more acidic environments (jejunem), where IF binds and transports B12 into blood in the ileum
What is pernicious anemia?
autoimmune disorder that leads to atrophic gastritis/ gastric cancer that binds IF
What tests can be used to diagnose pernicious anemia?
parietal cell antibodies (sensitive- found in 90% of patients, but not specific- i.e. can have these antibodies without this disease)
intrinsic factor antibodies- found in about 50% of PA but VERY specific (if you have these, you have the disease)
Pernicious anemia is common in which patients?
usually over 60 y/o, but black women under 50 have increased incident
Symptoms of B12 deficiency?
glossitis that is more beefy and painful, particularly with got and acidic foods than the glossitis that occurs with iron deficiency
neurologic disorder- balance problems (not true in folate deficiency)
What are the early neurologic symptoms of B12 deficiency?
paresthesia of hands and feet
somnolence and dementia
decreased vibratory and proprioception
loss of position sense
What are the late neurologic symptoms of B12 deficiency?
spastic paralysis from demyelination of dorsal and lateral columns. Not reversible
combined system disease
How do B12 or folate deficient red cells look?
large and oval shaped, as opposed to round
will also see hypersegmented neutrophils (5-6 segments)
How are pernicious anemia patients treated?
parenteral (IM) B12 (1000 micrograms of B12 daily for 1 week, then weekly for 4 weeks, then monthly for life)
If you give very lose doses of B12 you can overcome the IF deficiency, so oral B12 2000 micrograms daily can work even if IF is absent
**However, if you give folate/folic acid without B12 the symptoms (neurologic/balance in particular) will be worsened!!
What test is most helpful in diagnosing iron deficiency?
ferritin. Iron deficiency is the ONLY thing that causes ferritin?
What red cell morphology is most suggestive of autoimmune hemolysis?
microspherocyte
What test best defines inadequate marrow function in anemia patients?
reticulocyte count
Would hepcidin be high or low in pregnancy related anemia?
Low
How would you differentiate between chronic disease anemia and iron deficiency anemia?
iron deficiency anemia - low serum iron and elevated iron binding capacity (ie. low saturation) and low ferritin
chronic disease anemia- both are lower (saturation is slightly lower than normal) and ferritin normal
