Heme Flashcards
RBC source of energy?
glucose: (90% used in glycolysis, 10% used in HMP shunt)
vWF receptor on platelet
GpIb
fibrinogen receptor on platelet
GpIIb/IIIa
causes of eosinophilia
NAACP: Neoplasia Asthma Allergies Connective tissue diseases Parasites
what activates macrophages?
gamma-interferon
how do macrophages function as APC cell?
-MHC II
how do eosinophils protect against helminths?
major basic protein
how do eosinophils limit reaction following mast cell degranulation
histaminase
arylsulfatase
in what conditions are basophils elevated?
myleoproliferative diseases / CML
what are in basophilic granules?
1) heparin
2) histamine
3) leukotrienes
when are mast cells deployed?
1) type I hypersensitivity
how are mast cells reversed / inhibited?
cromolyn sodium prevents mast cell degranulation –> used for asthma prophylaxis
treatment to prevent erythroblastosis fetalis
-administer Rho(D) iG for mother during pregnancy –> prevent sensitization of Rh- mother to Rh antigen
what enzyme doe swarfarin inhibit?
epoxide reductase –> less reduced vitamin K –> less cofactor available to mature II, VII, IX, X, C, S
what is the role of vWF
carries / protects VIII
how does tPA work?
tpa: breaks down plasminogen to plasmin.
plasmin leads to fibrinolysis:
1) cleavage of fibrin mesh
2) destruction of coagulation factors
what are principal targets of antithrombin?
thrombin / factor XA
what are steps in primary hemostasis / platelet plug formation?
1) injury
2) adhesion
3) activation
4) aggregation
what happens with injury in primary hemostasis?
1) vWF binds to exposed collagen due to endothelial damage
describe adhesion of 1* hemostasis
platelets bind vWF via Gp1b –> release of ADP / Ca2+ (coag cascade)
describe activation of 1* hemostasis
ADP binding to receptor –> GpIIb/IIIa expression at platelet surface
aggregation of 1* hemostasis
fibrinogen binds GpIIb/IIIa receptors and links platelets
what are pro-aggregation factors:
- TXA2 from platelets
- dec. blood flow
- incr. platelet aggregation
what are anti-aggregation factors
- PGI2 / NO from endothelial cells
- incr. blood flow
- dec. platelet aggregation
how is ristocetin used?
ristocetin activates vWF to bind GpIB –> diagnoses vWF disease where no aggregation occurs following administration
ticlopidine / clopidogrel
inhibit ADP-induced expression of GpIIB / IIIa
abxicimab
inhibits GpIIb/IIIA directly
what does increased ESR mean?
acute-phase reactants in plasma (like fibrinogen) cause RBC aggregation –> faster sedimentation rate
significance of schistocyte / helmet cell
traumatic hemolysis / DIC / TTP ? HUS
ringed sideroblast
excess Fe in mitochondria = pathologic
target cell
HbC disease, Asplenia, Liver disease, Thalassemia
heinz bodies
oxidation of hemoglobin sulfhydral groups –> denatured hemoglobin precipitation / phagocytic damage to rBC membrane
heinz body significance
G6PD deficiency / alpha-thalassemia
howell-jolly bodies
basophilic nuclear remnants in RBCs –> seen in functional hyposplenia / asplenia
symptoms of 1-2 allele deletion of a-thalassemia?
none –> not clinically significant anemia
4-allele deletion for a-thalassemia
no-alpha globin, excess gamma-globin –> forms Hb Barts (gamma4).
-hydrops fetalis –> incompatible w/ life
beta-thalessemia molecular problem?
point-mutation in splice site / promoter –> dec. beta-globin synthesis
beta-thalassemia minor heterozygote
- b chain underproduced
- asymptomatic
- diagnosis confirmed by greater than 3.5% of HbA2 on electrophoresis
beta-thalassemia major
-beta chain is absent –> severe anemia
-extramedullary hematopoesis:
+hepatosplenomegaly
+skeletal deformaties
why do infants present with b-thal major after 6 months?
HbF is protective
lead poisoning presentation?
Lead lines on gingivae
Encephalopathy / Erythrocyte basophilic stippling
Abdominal colic / sideroblastic Anemia
Drops: wrist / foot drop; dimercaprol
lead poisoning enzymes
inhibition of ferrchelatase / ALA DEHYDRATASE–> dec. heme sythesis / incr. RBC protoporphyrin
why is there basophilic stippling in lead poisoning?
inhibition of rRNA degradation –> retain aggregates of RBCs
sideroblastic anemia deficiency?
delta-ALA SYNTHASE
iron deficiency labs
dec. iron, incr. TIBC, dec. ferritin
sideroblastic anemia labs
incr. iron, normal TIBC, inc. ferritin
how do you differentiate folate def. from b12 def?
both:
-dec. folate, incr. homocystine
folate def:
-normal methylmalonic acid / no neurological deficits
b12 def:
-incr. methylmalonic acid, neuro problems
neurologic symptoms of B12 deficiency:
- peripheral neuropathy w/ sensorimotor dysfunction
- dorsal columns 9vibration / proprioception)
- lateral corticospinal (spasticity_
- dementia
orotic acid uria enzyme defect + treatment
UMP synthase deficiency
bypass enzyme w/ URIDINE MONOPHOSPHATE
orotic aciduria presentation:
megalblastic anemia in children, unresponsive to folate / B12. no hyperammonemia
how does ornithine transcarbamylase deficiency present?
incr. orotic acid w/ hyperammonemia
findings for intravascular hemolysis
- dec. haptoglobin
- incr. LDH, schistocytes, and reticulocytes
- incr. urobilinogen in urine
features of extravascular hemolysis
-incr. LDH + incr. unconjugated bilirubin –> jaudince / hereditary spherocytosis
labs for hereditary spherocytosis
osmotic fragility test
- eosin-5-maleimide binding test for screening
- normal to dec. MCV
treatment for hereditary spherocytosis (E hemolysis)
splenectomy
GCPD deficiency (I/E)
defect in G6PD –> dec. glutathione –> incr. RBC susceptibility to oxidant stress
G6PD precipitants
sulfa drugs, antimalarials, infections, fava beans
pyruvate kinase deficiency (E)
defect in pyruvate kinase –> dec. ATP –> rigid RBCs
Hemolytic anemia IN A NEWBORN
what is association w/ paroxysmal nocturnal hemoglobinuria (I)?
acquired mutation in hematopoetic stem cell disease –> loss of protective factor from complement-mediated RBC lysis
-increased incidence of acute leukemia
findings for paroxysmal nocturnal hemoglobinuria
-triad:
negative coombs hemolytic anemia
-pancytopenia
-venous thrombosis
labs: CD55/59.
treatment of paroxysmal nocturnal hemoglobinuria
eculizumab
treatment of sickle cell anemia
hydroxuria (incr. HbF) + bone marrow transplant
warm agglutinin
IgG –> chronic anemia seen in SLE, CLL, a-methyldopa + other drugs
what is the diff. b/w direc vs indirect coombs test?
direct coombs: anti-Ig antibody added to patient’s blood, will agglutinate if RBCs coated w/ Ig
indirect coombs = normal RBCs added to patient’s serum. RBCs agglutinate when anti-Ig antibodies are added
cold agglutinin
IgM
diff. b/w microangiopathic vs. macroangiopathic anemia
micropathic is through narrowed vessels; macroangiopathic = mechanical destruction
whats the difference b/w ferrtin + transferrin?
1) transferrin transports Fe in blood
2) ferritin = storage protein for Fe in body
porphyria
hereditary / acquierd defects in heme synthesis –> accumulation of heme precursors –> symptoms
lead poisoning enzymes deficiency
ferrochelatase + ALA dehydratase
lead poisoning accumulated substrate
protoporphyrin / delta-ALA
acute intermittent porphyeria enzyme deficiency
prophobilinogen deaminase
acute intermittent porphyria accumulated substrate
porphobilinogen, delta-ALA, coporphobilinogen in urine
symptoms of acute intermittent porphyria (5)
1) Painful abdomen
2) Port-wine-colored urine
3) Polyneuropathy
4) Psyche
5) Precipitated by drugs, alcohol, starvation
treatment of AIP
1) glucose / heme –> inhibit ALA synthase
porphyria cutanea tarda enzyme deficiency
uroporphyrinogen decarboxylase
accumulated substrate in porphyria cutanea tarda
uroporphyrin –> tea-colored urine
symptoms of porphyria cutanea tarda
blistering cutaneous photosensitivity –> most common porphyria
