Anemias Flashcards
Iron deficiency affects which stage of heme synthesis
final step in heme syntheis
ferrocheletase protoporphyrin to heme
What are the labs that would be seenin iron deficiency anemia Iron: TIBC: Ferritin: Erythrocyte protoporhyrin: RDW:
Iron: DEC TIBC: INC Ferritin: DEC Erythrocyte protoporhyrin: INC RDW: INC
In which populations are the cis and trans alpha thalessemia traits more prevalent
Cis: asian populations
trans: african populations
What is seen with 3 deletions of the alpha thal gene
Hemoglobin H disease
excess B globin forms B4
Moderate to severe microcytic hypochromic anemia
What is seen with 4 deletions of the alpha thal gene
Hemoglobin Barts
Excess y globin forms y4
Hydrops fetalis; incompatible with life
In which population is B thalaseemia mor prevalent and what causes it
Point mutations in splice sites and promoter sequences
Prevalent in mediterranean populations
What is the presentation of B thal minor
Usually asymptomatic
Inc HbA2 on electrophoresis (>3.5%)
What can be seen with B thal major
anisopoikilocytosis requiring blood transfuioions
marrow expansion leading to crew cut xray and chipmunckf faceis
hempatosplenomegaly
inc reisk of parvo aplastic crisis
What occurs with HbS/Bthal hetero
mild to moderate sickle cell disease
What effect does lead have on read blood cells (enzymes, byproducts, etc)
inhhibits ferrocheletase and ALA dehydratase (DEC heme synth, INC RBC protoporphyrin)
ALso inhibits rRNA degradation (RBC retain aggregates and see basophilic stipling)
What is the first line treatment of lead poisoning in adults and in kids
Adults: dimercaprol and EDTA
Kids: Succimer
List 6 symptoms of lead poisoning
Lead lines on gingivae/metaphyses of long bones Encephalopathy Erythrocyte basophilic stippling Abdominal colic Anemia Drops- wrist and foot drops
What causes sydneroblastic anemia (genetic)
x linked defect in ALA synthase gene
What causes syderoblastic anemia (acquired/reversible)
acquiered: myelodysplastic syndrome Reversible: Alcohol Lead B6 deficiency Copper deficiency Isoniazid Chloramphenicol
What are the lab findings of sideroblastic anemia
Iron:
TIBC:
Ferritin:
Iron: INC
TIBC: normal/DEC
Ferritin:INC
How do you treat Sideroblastic anemia
Pyridoxine B6 (cofactor for ALA synthase)
What levels are inc in folate deficiency
INC homocysteine
Normal Mehtylmalonic acid
What levels are inc in Cobalamin deficiency
INC homocysteine
INC methylmalonic acid
How does B12 deficiency cause neurologic issues
B12 is involved itn the fatty acid pathways and myelin synthesis
(can also causse reversible dementia)
How is B12 deficiency diagnosed
Schilling test
4 stage test to determin if cause is dietary deficiency or malabsorption
What causes Orotic aciduria
Inability to convert orotic acid to UMP
Auto recessive defect in UMP SYNTHASE
How does Orotic aciduria present in children
failure to thrive, developmental delay, and megalobalastic anemia refractory to folate and B12
NO HYPERAMMONEMIA
How can you differentia orotic aciduria due to UMP synthase and due to ornithine transcarbamylase deficiency
UMP synthase: No hyperammonemia
Ornithine transcarbamylase: Hyperammonemia
How do you treat orotic aciduria
uridine monphosphate or uridine triacetate to bypass mutated enzyme
What is the difference between megaloblastic and nonmegaloblastic anemia
Nonmegaloblastic: no hypersegemented neutrophils DNA synthesis is unimpaired
Megaloblastic: opposite ^
What is the cause of diamond blackfan anemia
intrinsic defect in erythroid progenitor cells
What is the presentation of diamond blackfan anemia
Inc % HbF (but DEC total Hb)
Rapid onset anemia in 1st year of life
Short stature, craniofacial abnormalities, upper extremity malformations (TRIPHALANGEAL THUMBS)
Errors/deficiencies in porphobilinogen deaminase would result in what condition
Acute intermittent porphyria
What are 5 symtptoms of acute imntermittent porphyria
Painful abdomen Portwine colored urine Polyneuropathy Psychological disturbances Preciptated by drugs (p450 inducers), alcohol starvation
How would you treat AIP
hemin and glucose
they inhibit ALA synthase
Errors/deficiencies in Urophyrinogen decarboxylase would cause what condition
Porphyria cutanea tarda
What is the inheritance of PCT
Autosomal dominant
What is the inheritance of AIP
Autosomal dominant
What condition is associated with PCT
Hepatitis C
What is the most common porphyria
PCT
What changes the change in urine color with PCT
uroporphyrin
What substrates are accumulated in AIP and PCT
AIP: porphobilinogen, ALA
PCT, Uroporphyrin
What enzymes does lead inhibit
Ferrochelatase and ALA dehydratase
How do symptoms of lead intoxication differ from adults to kids
Kids: mental deterioration
Adults: headache, memory loss, demyelination
What inhibits ALA Dehydratase vs Synthase
Dehydratase: lead
Synthase: x linked sideroblastic anemia
What Causes the toxicity behind iron poisoning and how might it happen
Cell death due to PEROXIDATION of membrane lipids
accidental ingestion by kids, tablets may look like candy
What are the symptomsof iron poisoning
N/v
Gastric bleeding
lethargy
scarring leading to GI obstruction
What is the inheritance and pathology behind G6PD deficiency
X linked recessive
Dec reduced glutathioine; rbc more susceptibnle to oxidant stress
What is the pathology and inheritance behind Pyruvate kinase deficiency
Autosomal recessive
Dec ATP leads to rigid RBC and extravascular hemolysis
What substrate does pyruvate kinase deficiency increase and what is the effect
INC 2-3 BPG leading to dec hemoglobin affinity for O2
What is the acquired mutation in Paroxysmal nocturnal hemoglobinuria
acquired mutation in PIGA gene
decreases synthesis of GPI anchor for DAF/CD55 and MIRL/CD59
(decay accelerating factor and membrane inhibitor of reactive lysis)
in what cell is the mutation for paroxysmal nocturnal hemoglobinuria acquired
hematopoietic stem cell
What is there an increased incidence of with paroxysmal nocturnal hemolobinuria
acute leukemias
How is PNH treated
eculizumab (inhibits terminal complement formation)
Test for CD55/59 on flow cytometry to diagnose
What are the characteristics of PNH
Triad of: coombs - hemolytic anemia, pancytopenia, venous thrombosis and possibly red or pink urine
usually upon waking
What type of crisis can be associated with sickle cell
dactylitis, priapism, acute chest syndrome, avascular necrosis, stroke
With regards to the kidney what is sickle cell associated with
Cells sickle in the renal medulla (DUE TO DEC PO2) leading to RENAL PAPILLARY NECROSIS and microhematoruia
What conditions can be associated with the crew cut on xray
sickle cell and thalassemias
Warm autoimmune hemolytic anemia is caused by what antibody
IgG
Cold autoimmune hemolytic anemia is caused by what antibody
IgM
What can cause Warm autoimmune anemia
SLE
CLL
Certain drugs (eg a methyl dopa)
idiopathic
What can cause Cold autoimmune anemia
Mycoplasma pneumoniae CLL Cold Infectious mono idiopathic
What anemia is Coombs - vs +
+: autoimmune hemolytic anemia
-: Paroxysmal nocturnal hemoglobinuria (others as well but yeah)
What is Coritcosterioids effect on:
neutrophils:
Eosinophils
Lymphocytes
Neutrophilia: due to dec activation of adhesion molecules impairing migration out of vasculature
Eosinopenia: beceause they are sequestered in lymph nodes
Lymphopenia: because they cause apoptosis of lympocytes
What is a leukoerythroblastic reaction
left shift of immature RBC; occurs with severe anemia or marrow response
Iron Studies of: Iron deficiency Serum Iron: Transferrin/TIBC: Ferritin: % transferrin saturation (serum iron/TIBC):
Serum Iron: DEC (primary)
Transferrin/TIBC: INC
Ferritin: DEC
% trans Sat : DECDEC
Iron Studies of: Chronic Disease Serum Iron: Transferrin/TIBC: Ferritin: % transferrin saturation (serum iron/TIBC):
Serum Iron: DEC
Transferrin/TIBC: DEC
Ferritin: INC (primary)
% trans Sat : -
Iron Studies of: Hemochromatosis Serum Iron: Transferrin/TIBC: Ferritin: % transferrin saturation (serum iron/TIBC):
Serum Iron: INC (primary)
Transferrin/TIBC: DEC
Ferritin: INC
% trans Sat: INCINC
Iron Studies of: Pregnancy/OCP use Serum Iron: Transferrin/TIBC: Ferritin: % transferrin saturation (serum iron/TIBC):
Serum Iron: -
Transferrin/TIBC: INC (primary)
Ferritin: -
% trans Sat : DE
