Heme/onc just a bit Flashcards
Rostocetin
activates vWF to bind GpIb (GpIb is on the platelet) and VwF other side binds to exposed collagen upon endothelial damage
Orotic aciduria
- inability to convert orotic acid to UMP (de nova pyrimidine synthesis pathway)
- defect in UMP synthase
- Autosomal recessive
present:
megloblastic anemia that cannot be curred by folate or B12 with failure to thrive
-no hyperammonemia
-hypersegemented neutorphils, glossitis, orotic acid in urine
treat: give UMP
what are the lab findings in anemia of chronic disease?
- decrease iron and TIBC
- increase ferritin
recall release more hepcidin, so less iron is reasbsorbed and released into the system via the GI, so it builds up in the ferritin
What precipitates sickling in sickle cell?
-low oxygen
-dehydration
-acidosis
deoxygenated HbS sickles
What are some renal consequences of sickle cell?
-renal papillary necrosis (due to low O2 in papilla, also seen in heterozygotes) and microhematuria (medullary infarcts)
Autoimmunie hemolytic anemia:
Warm agglutinin IgG
assoc with SLE, CLL, alpha methyl dopa
coombs positive
Autoimmunie hemolytic anemia:
Cold agglutinin IgM
acute anemia triggered by cold
assoc. CLL, mycoplasma pneumonia infections or infectious mononucleosis
Direct coombs test
detects antibodies that are bound directly to surface RBC
-add an anti-Ig antibody to patients srum, the RBC agglutinate if the RBC already are coated with Ig
Indirect coombs test
detects free floating antibodies in the serum
-take normal RBC and add then to patients serum. Agglutinate if the patients serum has anti RBC surface Ig
corticosteroids cause neutrophilia but eosinopenia and lymphopenia
- decrease the activation of neutrophil adhesion molecules, impairing migration out of the vasculature to sites of inflammation
- corticosteroids sequester eosinophils in lymphnodes and cause apoptosis of lymphocytes
Lead poisoning
- inhibit ferrochelatase (last step in mitochondria) and ALA dehydratase (second step) (cytoplasm)
- protoporphyrin and ALA accumulate
present: GI and kidney disease, children –> mental deterioration
adults: memory loss, demyelination
Lead poisoning clinical
- lead lines on gingivae (burtons)
- encephalopaty and erythrocyte basophilic stippling
- abdominal colic and sideroblastic anemia
- drops - wrist and foot drop
- dimercaporl and EDTA are 1st line treatment
Chelation for lead for kids
succimer
chelation for lead in adults
dimercaprol
EDTA
acute intermittent porpyria
- prophobilinogen deaminase defective
- build up of porphorobilinogen, ALA and coporphobilinogen in the urine
symptoms 5p’s
- painful abdomen
- port wine colored urine
- polyneurapath
- psychological disturbances
- precipitated by drugs, alcohol and starvation
treatment: glucose, heme (inhibit ALA synthase)
porphyria cutanea tarda
- uroporphrinogen decarboxylase is the defect
- uroporphyrn accumulates and causes tea colored urine
- most common!!!
- blistering cutaneous photosensitivity
Bernard-soulier
- defect in GPIb needed for platelet to vWF adhesion
- decreased paltelt count
- increased bleeding time
Glanzmann thrombasthenia
- Defect in GpIIb/IIIa leads to a defect in platelet to fibrin to platelt aggregation
- blood smear shows no platelet clumping
- increased bleeding time
immune thrombocytopenia
autoimmune to GpIIb/IIIa leads to splenic macrophage consumption of platelet/antibody complex.
- may be triggered by viral illness
- decreased platelet survival
- decreased platelet count, increased bleeding time and increase baby megakaryocytes on bone marrow to offset the loss
Thrombotic thrombocytopenic purpura
- inhibition of deficiency of ADAMTS 13 vWF metalloprotease
- so vWF multimers build up
- increases platelet adehesion and platelet aggregation and thrombosis
- decreases platelet survival
- decreased platelets and increase bleeding time
labs: schistocytes and increased LDH - fever, thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms and renal symptoms
treat: exchange transfusion and steroids
prothrombin gene mutation is an activating mutation
-mutation in 3’untranslated region –> increased production of prothrombin and increase plasma levels and venous clots
antithrombin deficiency
has no effect on PT/PTT or thrombin time
- but diminishes the increase in PTT one would normally observe following heparin administration
- recall antithrombin helps inhibit 2,7,9,10,11,12 but mainly 2 and 10
- antithrombin can also be lost in the urine during renal failure or nephrotic syndrome
protein C or S deficiency
- inability to inactivate facors V and VIII
- skin and subcutaenous tissue necrosis after warfarin administration. recall warfarin inhibit vitamin K production of 2,7,9,10 C and S. remember activated C breaks down V and VIII so they are antiplatelet. But if there is no C and S at all, then nothing to cancel coagulation and warfarin is tooo effective
leukomoid reaction
- acute inflammatory response to infection
- increase WBC with increased neutorpils and bands left shift, increase in neutrophil ALP (being release by mature neutrophils for the infection)
but in CML there is a decrease in ALP because there are too much proliferation of mylo and not enough maturation and they are not activated so no release of ALP
