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Lec 3 Nutritional Anemia Flashcards

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1
Q

What is the pathology that causes megaloblastic anemia?

A

impaired DNA synthesis

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2
Q

What are 3 complications of impaired DNA synthesis?

A
  • megaloblastic anemia
  • malabsorption b/c GI mucosal cells affected
  • increased risk of thrombosis
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3
Q

hyperhomocysteinemia is a risk factor for what?

A

development of thrombosis

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4
Q

What is the ineffective erythropoiesis seen in megaloblastic anemia?

A

asynchrony between maturity of nucleus and that of cytoplasm b/c protein synthesis normal but DNA replication abnormal –> prematurely destroyed in the bone marrow = intramedullary hemolysis

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5
Q

What happens to retic count in medulloblastic anemia?

A

low retic count

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6
Q

What two cellular reactions is B12 a cofactor for?

A
  • methylmalonyl CoA mutation rxn of methylmalonyl CoA –> succinyl CoA
  • homocysteine-methionine methyltransferase rxn of n5-methyl THF + homocysteine –> methionine and THF
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7
Q

What B12, homocysteine, methylmalonic acid levels in B12 deficiency?

A
  • decreased B12
  • increased methylmalonic acid
  • increased homocysteine
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8
Q

Can humans synthesize folate?

A

nope! dependent on dietary intake

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9
Q

Where does absorption of folate occur?

A

primarily in duodenum and jejunum

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10
Q

What is pathogenesis of folate deficiency?

A

folate –> impaired generation of THF + thymidylate –> slowed DNA synthesis

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11
Q

How can you distinguish between B12 and folate deficiency?

A

indistinguishable by CBC, bone marrow, peripheral blood

both have high homocysteine

only B12 deficiency has high methylmalonic acid; only B12 has neurologic symptoms

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12
Q

What is the mech of action methotrexate?

A

inhibits dihydrofolate reductase –> kills cells by diverting metabolically active folates into inert pool of DHF –> causes megaloblastic anemia

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13
Q

What kind of hemolysis in megaloblastic anemia? signs?

A

extravascular hemolysis in spleen –> can cause jaundice and splenomegaly

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14
Q

What is the effect of decreased folate in pregnancy?

A

increased incidence of neural tube defects –> spina bifida

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15
Q

Why do you get neuro symptoms in B12 deficiency?

A

B12 is needed for myelin synthesis

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16
Q

What is the source of vit B12?

A

microorganisms

animal products + dairy

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17
Q

What is the source of folate?

A

veggies, fruits, liver

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18
Q

How much folate do we need per day? normal body stores?

A

need 50 ug/day

body stores 5 mg

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19
Q

What is the most common cause of folate deficiency?

A

dietary insufficiency or increased demand [aka pregnancy]

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20
Q

What are signs/symptoms of megaloblastic anemia?

A
  • sore mouth/tongue = glossitis b/c oral mucosa proliferation impaired
  • if malabsorption –> diarrhea/steatorrhea
  • jaundice/splenomegaly from extravascular hemolysis
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21
Q

What do you see on CBC with megaloblastic anemia?

A
  • high MCV
  • low retic count
  • low Hbg
  • low WBC
  • low RBC
  • low platelets
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22
Q

What are signs of megaloblastic anemia on peripheral smear?

A
  • macrocytic RBCs

- hypersegmentation of neutrophils

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23
Q

What do you see in bone marrow with megaloblastic anemia?

A

megaloblasts = abnormal, large erythroid precurosrs w/ persistent immaturity of nuclei even as cells mature

als have giant white cell precursors

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24
Q

What type of bilirubin do you see in megaloblastic anemia?

A

high indirect bilirubin

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25
What level of LDH in megaloblastic anemia?
high LDH = sign of hemolysis
26
What is treatment for B12/folate deficiency?
make diagnosis and give whichever is missing
27
What is schilling test?
- give radioactive B12 orally --> measure amount excreted in urine decreased urinary excretion indicated absorption impaired
28
What are some GI diseases that cause folate malabsorption?
celiac | crohns
29
What are two drugs that could cause folate deficiency?
- methotrexate | - trimethoprim sulfamethoxazole
30
What are functions of iron normally?
- needed for oxidative metabolism [krebs cycle] - cellular growth + proliferation - O2 transport - heme formation
31
How much iron is stored in the body?
3.5 g in men; 2.5 g in women
32
Where is iron absorbed?
absorbed in duodenum; inorganic iron must first be reduced from Fe3 --> Fe2 by ferric reductase before absorption
33
What percent of ingested iron is normally absorbed?
10%
34
What is hepcidin?
synthesized in liver; negative regulator of iron transport --> binds and internalizes ferroportin so Fe can't be released from intracellular stores --> less Fe avaialable for Hb synthesis
35
What is effect of hepcidin on iron absorption?
leads to decreased absorption of iron
36
What are 3 things that stimulate hepcidin synthesis?
- iron intake - inflammation - infection
37
What are 4 things that suppress hepcidin synthesis?
- anemia - hypoxemia - erythropiesis - iron deficiency
38
What is most common cause of low iron?
bleeding; particularly chronic GI blood loss
39
What is iron's carrier protein in the blood? How much of it is normally saturated with iron?
transferrin | 30% normally saturated with iron
40
What happens to transferrin sat with iron deficiency?
transferin sat increases
41
What happens to amount of transferrin receptor in iron deficiency?
transferrin receptor synthesis increases b/c erythroid precursors want more transferrin-iron complex!
42
What does total iron binding capacity of blood measure?
concentration of transferrin
43
What happens to transferrin level in iron deficiency?
iron deficiecny --> less iron binding to transferrin gene and inhibiting transcription --> increased production of transferrin --> TIBC increases
44
What does amount of cellular ferritin in blood tell you?
correlates to body iron stores
45
What happens to plasma ferritin in iron deficiency?
plasma ferritin decreases
46
What things cause an increase in ferritin?
inflammation, infection, malignancy ferritin = acute phase reactant
47
What are clinical signs of iron deficiency?
anemia, pica [chew on things], cheilosis [dry edges of lips], pallor, glossitis, koilonychia [spoon nails]
48
What is major cause of iron deficiency in developing countries?
GI blood loss from hookworm infection
49
What is pathogenesis of iron deficiency causing anemia?
lack of iron incorporation into heme --> deficient heme synthesis --> poor cell growth
50
What do you see on peripheral blood smear in iron deficiency anemia?
microcytic hypochromic RBCs increased RDW = RBC distribution width FEP = free erythrocyte protoporphyrin target cells low RBC, normal white count
51
What do you see on CBC in iron deficiency anemia?
- decreased Hb and hematocrit - decreased MCV and MCH - low retic count - increased RDW - decreased iron - increased TIBC - decreased ferritin - decreased transferrin sat - increased serum transferrin receptor
52
Why do you get high platelets in iron deficiency anemia?
b/c thrombopietin similar struct to EPO --> when EPO rises can also stimulate platelet production
53
What type of anemia can you see increased iron?
chronic hemolytic anemia --> b/c you are breaking down RBCs you will have increased iron OR secondary yo chronic blood transfusions in severe anemia
54
What is potential cause of idiopathic hereditary hemochromatosis?
autosomal recessive from genetic defect HFE gene on chr 6 --> iron overload through GI absorption and hepcidin deficiency
55
What are symptoms of hereditary hemochromatosis?
cirrhosis, cardiac arrhythmias, HF 2ndary to restrictive cardiopyopathy, DM, arthralgias, bronze skin
56
What do you see in blood of hereditary hemochromatosis?
serum Fe, transferrin sat, and ferritin will all be abnormally elevated
57
What are sideroblastic anemias?
disorder due to impaired incorporation of iron into heme molecule --> Fe accumulates within the mitochondria fo red cell precursors in the bone marrow --> prematurely destroyed in BM --> ineffective erythropoiesis
58
What are some acquired causes of sideroblastic anemia?
alcohol isoniazid toxins [lead] all antagonists of pyridoxal phosphate = coenzyme of heme synthesis
59
What is the mutation in inherited form of sideroblastic anemia?
defect in ALA synthase which is required for heme synthesis
60
What do you see on CBC in sideroblastic anemia?
low MCV | low retic
61
What do you see in bone marrow with sideroblastic anemia?
hypercellular BM with erythroid hyperplasia | ringed sideroblasts
62
What do you see in labs with sideroblastic anemia?
- high serum Fe - high transferrin saturation - high ferritin - nomral TIBC
63
What is treatment for sideroblastic anemia?
pyridoxine [vit B6] b/c its a cofactor the ALA-synthase
64
What are some common causes of anemia of inflammation?
- chronic infection - chronic inflammatory disease [IBD, SLE, sarcoidosis, etc] - cancer
65
What is the pathogenesis of anemia of inflammation?
- cytokines of inflmmation --> inhibit EPO --> decreased RBC production increased synthesis of hepcidin --> decreased transport of Fe; impaired Fe absorption
66
What do you see on peripheral smear in anemia of inflammation?
RBCS normocytic/normochromic OR can be microcytic/hypochromic b/c of functional iron deficiency
67
What do you see in labs in anemia of inflammation?
- low retic count - low serum Fe - decreased transferrin [TIBC] - normal or increased serum ferritin - decreased transferrin sat - normal soluble transferrin receptor levels

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