Lec 3 Nutritional Anemia Flashcards
What is the pathology that causes megaloblastic anemia?
impaired DNA synthesis
What are 3 complications of impaired DNA synthesis?
- megaloblastic anemia
- malabsorption b/c GI mucosal cells affected
- increased risk of thrombosis
hyperhomocysteinemia is a risk factor for what?
development of thrombosis
What is the ineffective erythropoiesis seen in megaloblastic anemia?
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
What happens to retic count in medulloblastic anemia?
low retic count
What two cellular reactions is B12 a cofactor for?
- methylmalonyl CoA mutation rxn of methylmalonyl CoA –> succinyl CoA
- homocysteine-methionine methyltransferase rxn of n5-methyl THF + homocysteine –> methionine and THF
What B12, homocysteine, methylmalonic acid levels in B12 deficiency?
- decreased B12
- increased methylmalonic acid
- increased homocysteine
Can humans synthesize folate?
nope! dependent on dietary intake
Where does absorption of folate occur?
primarily in duodenum and jejunum
What is pathogenesis of folate deficiency?
folate –> impaired generation of THF + thymidylate –> slowed DNA synthesis
How can you distinguish between B12 and folate deficiency?
indistinguishable by CBC, bone marrow, peripheral blood
both have high homocysteine
only B12 deficiency has high methylmalonic acid; only B12 has neurologic symptoms
What is the mech of action methotrexate?
inhibits dihydrofolate reductase –> kills cells by diverting metabolically active folates into inert pool of DHF –> causes megaloblastic anemia
What kind of hemolysis in megaloblastic anemia? signs?
extravascular hemolysis in spleen –> can cause jaundice and splenomegaly
What is the effect of decreased folate in pregnancy?
increased incidence of neural tube defects –> spina bifida
Why do you get neuro symptoms in B12 deficiency?
B12 is needed for myelin synthesis
What is the source of vit B12?
microorganisms
animal products + dairy
What is the source of folate?
veggies, fruits, liver
How much folate do we need per day? normal body stores?
need 50 ug/day
body stores 5 mg
What is the most common cause of folate deficiency?
dietary insufficiency or increased demand [aka pregnancy]
What are signs/symptoms of megaloblastic anemia?
- sore mouth/tongue = glossitis b/c oral mucosa proliferation impaired
- if malabsorption –> diarrhea/steatorrhea
- jaundice/splenomegaly from extravascular hemolysis
What do you see on CBC with megaloblastic anemia?
- high MCV
- low retic count
- low Hbg
- low WBC
- low RBC
- low platelets
What are signs of megaloblastic anemia on peripheral smear?
- macrocytic RBCs
- hypersegmentation of neutrophils
What do you see in bone marrow with megaloblastic anemia?
megaloblasts = abnormal, large erythroid precurosrs w/ persistent immaturity of nuclei even as cells mature
als have giant white cell precursors
What type of bilirubin do you see in megaloblastic anemia?
high indirect bilirubin
What level of LDH in megaloblastic anemia?
high LDH = sign of hemolysis
What is treatment for B12/folate deficiency?
make diagnosis and give whichever is missing
What is schilling test?
- give radioactive B12 orally –> measure amount excreted in urine
decreased urinary excretion indicated absorption impaired
What are some GI diseases that cause folate malabsorption?
celiac
crohns
What are two drugs that could cause folate deficiency?
- methotrexate
- trimethoprim sulfamethoxazole
What are functions of iron normally?
- needed for oxidative metabolism [krebs cycle]
- cellular growth + proliferation
- O2 transport
- heme formation
How much iron is stored in the body?
3.5 g in men; 2.5 g in women
Where is iron absorbed?
absorbed in duodenum; inorganic iron must first be reduced from Fe3 –> Fe2 by ferric reductase before absorption
What percent of ingested iron is normally absorbed?
10%
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
What is effect of hepcidin on iron absorption?
leads to decreased absorption of iron
What are 3 things that stimulate hepcidin synthesis?
- iron intake
- inflammation
- infection
What are 4 things that suppress hepcidin synthesis?
- anemia
- hypoxemia
- erythropiesis
- iron deficiency
What is most common cause of low iron?
bleeding; particularly chronic GI blood loss
What is iron’s carrier protein in the blood? How much of it is normally saturated with iron?
transferrin
30% normally saturated with iron
What happens to transferrin sat with iron deficiency?
transferin sat increases
What happens to amount of transferrin receptor in iron deficiency?
transferrin receptor synthesis increases b/c erythroid precursors want more transferrin-iron complex!
What does total iron binding capacity of blood measure?
concentration of transferrin
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
What does amount of cellular ferritin in blood tell you?
correlates to body iron stores
What happens to plasma ferritin in iron deficiency?
plasma ferritin decreases
What things cause an increase in ferritin?
inflammation, infection, malignancy
ferritin = acute phase reactant
What are clinical signs of iron deficiency?
anemia, pica [chew on things], cheilosis [dry edges of lips], pallor, glossitis, koilonychia [spoon nails]
What is major cause of iron deficiency in developing countries?
GI blood loss from hookworm infection
What is pathogenesis of iron deficiency causing anemia?
lack of iron incorporation into heme –> deficient heme synthesis –> poor cell growth
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
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
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
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
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
What are symptoms of hereditary hemochromatosis?
cirrhosis, cardiac arrhythmias, HF 2ndary to restrictive cardiopyopathy, DM, arthralgias, bronze skin
What do you see in blood of hereditary hemochromatosis?
serum Fe, transferrin sat, and ferritin will all be abnormally elevated
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
What are some acquired causes of sideroblastic anemia?
alcohol
isoniazid
toxins [lead]
all antagonists of pyridoxal phosphate = coenzyme of heme synthesis
What is the mutation in inherited form of sideroblastic anemia?
defect in ALA synthase which is required for heme synthesis
What do you see on CBC in sideroblastic anemia?
low MCV
low retic
What do you see in bone marrow with sideroblastic anemia?
hypercellular BM with erythroid hyperplasia
ringed sideroblasts
What do you see in labs with sideroblastic anemia?
- high serum Fe
- high transferrin saturation
- high ferritin
- nomral TIBC
What is treatment for sideroblastic anemia?
pyridoxine [vit B6] b/c its a cofactor the ALA-synthase
What are some common causes of anemia of inflammation?
- chronic infection
- chronic inflammatory disease [IBD, SLE, sarcoidosis, etc]
- cancer
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
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
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
