307 exam 2

Macrocytic anemias are classified as?

megaloblastic and nonmegaloblastic

A deficiency of either B12 or folate causes impaired what?

thymidine nucleotide synthesis

impaired DNA synthesis and very large erythroid cells in the bone marrow is associated with which anemia?

megaloblastic

This tetrapyrrole (“cobalamin”) has a single cobalt atom in the middle and changes form & function based on what it is attached to

vitamin B12

it’s job is to transfer methyl groups and circulates as 5-methyl-THF

folate or folic acid

What testing can help diagnose for vitamin B12 deficiency?

methylmalonyl acid (MM acid)

methylmalonyl coA requires what to turn into succinyl coA?

vitamin B12 and MM CoA mutase

If vitamin B12 is absent, what accumulates and turns into MM acid?

MM CoA

If vitamin B12 is absent, what accumulates and turns into the folate trap?

5-methyl-THF & homocysteine

How is vitamin B12 and folic acid connected?

folic acid transfers a methyl group to homocysteine, then vitamin B12 allows homocysteine to be generated to methionine

what are megaloblastic characteristics?

oval macrocytes, hypersegmented neutrophils, and pancytopenia

what are CBC characteristics for megaloblastic anemia?

low HGB, high MCV, high MCH, normal MCHC, high RDW, pancytopenia

If DNA function is impaired from vitamin B12/folate deficiency, is RNA function also impaired?

No, RNA contains uracil instead of thymine so cytoplasmic development progresses normally

in megaloblastic anemia, the erythroid precursors are larger than normal, so?

their nuclei appear immature compared to the cytoplasm

clinical symptoms for vitamin B12/folate deficiency include fatigue, shortness of breath, weakness, AND …?

glossitis & loss of epithelium along GI tract leading to gastritis, nausea, and/or constipation

neurologic symptoms for this deficiency include:

• memory loss

• personality changes and psychosis

• numbness and tingling

• loss of balance

vitamin B12

clinical symptoms for this deficiency include:

• increased risk of cardiovascular disease

• depression

• peripheral neuropathy and psychosis

• deficiency during pregnancy can lead to malformation of the fetal nervous system, causing neural tube defects (NTDs)

folate

this is not heat-lebile and not available from veggies, legumes, or fruit

vitamin B12

lack of intrinsic factor can lead to pernicious anemia with impaired absorption of?

vitamin B12

______ _______ is produced in the stomach wall and is critical for vitamin B12 absorption because the enterocyte has a receptor for the cobalamin + ______ _______ complex

intrinsic factor

this is heat-lebile and available from veggies, legumes, and some fruit

folic acid

celiac disease or inflammatory bowel disease impairs folate absorption from foods because?

folate must be hydrolyzed in the gut

screening tests for megaloblastic anemia include:

CBC, PBF, serum bilirubin, LDH

a CBC for megaloblastic anemia looks like:

pancytopenia, decreased HGB & HCT & Retics, increased MCV & MCH, normal MCHC

You find the following in a PBS:

• oval macrocytes

• hypersegmented neutrophils

• tear drops, schistocytes, spherocytes, targets

• HJ bodies, basophilic stippling

• nRBCs

• macrocytic, normochromic, anisocytosis

megaloblastic anemia

what would you find in a BM examination for megaloblastic anemia?

megaloblasts

increased serum/plasma homocysteine could indicate?

folate or vitamin B12 deficiency

serum gastrin can be markedly elevated in?

pernicious anemia

nonmegaloblastic anemias usually have increased MCV but milder than megaloblastic

True

macrocytic nonmegaloblastic traits appear in this patient without anemia present

• increased HGB

• burr cells, fragments, spherocytes, polychromasia

• nRBC

newborn

this anemia is characterized by round macrocytes & target cells and is secondary to abnormalities in liver function

anemia of liver disease

what is the most common cause of liver disease anemia?

anemia of alcoholism

nonmegaloblastic anemia of alcoholism is characterized by:

round macrocytes and acanthocytes

this disease’s mechanism can be caused by:

• antibodies

• loss of parietal cells of stomach

• gastrectomy

pernicious anemia

what is the best diagnostic test for pernicious anemia?

detection of antibodies against IF, then serum gastrin level

during hemolysis, BM tries to compensate by?

polychromasia, nRBC, and reticulocytosis

hemolytic anemias are considered what MCV and MCHC?

normocytic / normochromic

an example of acute hemolytic anemia is?

paroxysmal cold hemoglobinura (PCH)

an example of chronic hemolytic anemia where the BM compensates is?

G6PD deficiency

an example of inherited hemolytic anemia is?

thalassemia

an example of acquired hemolytic anemia is?

malaria

an example of intrinsic hemolytic anemia is?

hereditary spherocytosis

intravascular hemolytic anemias occur by?

fragmentation

extravascular hemolytic anemias occur by?

macrophage-mediated hemolysis

1% of RBCs are removed daily through this process and 80% of normal hemolytic processes is (extra/intravascular)?

macrophage-mediated extravascular hemolysis

In the splenic macrophage, HGB is broken down into?

polypeptides & heme

In the splenic macrophage, heme is broken down into?

protoporphyrin 9 & iron

In the splenic macrophage, protoporphyrin 9 is broken down into?

bilirubin

When old/damaged RBCs are broken down in splenic macrophages, what is/are recycled?

polypeptides & iron

Approximately 10 – 20% of normal RBC destruction is via?

fragmentation

haptoglobin–hemopexin–methemalbumin system is?

mechanisms to salvage free hemoglobin iron and prevent oxidation reactions

The following are lab findings for?

• unconjugated hyperbilirubinemia

• increased urinary and fecal urobilinogen

excessive extravascular hemolysis

The following are lab findings for?

• hemoglobinuria

• hemoglobinemia

• hemosiderinuria

• methemalbuminemia

• low/undetectable levels of haptoglobin/hemopexin

excessive intravascular hemolysis

symptoms in severe anemia include:

All of the above

??? for anemia include:

• CBC

• retic %

• PBS

routine screenings

??? for anemia include:

• lactate dehydrogenase

• glycosylated hemoglobin

special diagnostic tests

This intrinsic hemolytic anemia is caused by a mutation in the vertical membrane interactions of the RBC membrane. MCHC is increased and DAT is negative. some patients clinical present with gallstones.

hereditary spherocytosis

additional lab tests for this instrinsic hemolytic anemia include:

• increased osmotic fragility

• decreased eosin-5’-maleimide binding

• corrected autohemolysis test

hereditary spherocytosis