heme Flashcards
major functions of blood
transport (O2, CO2, nutrients, hormones)
immunity (WBCs)
hemostasis (stop bleeding)
homeostasis (provide optimal environment to
maintain steady state (pH, ions, temp, nutrient supply)
main role of RBCs
transportation of oxygen
how long do RBCs survive?
4 months (120 days)
precursor RBC in bone marrow
erythroblast
what are platelets?
essential for blood coagulation
much smaller than leukocytes
represent bits of the cytoplasm of megakaryocytes
largest precursor cells in the bone marrow
short survival, about 10 days
most numerous of the WBCs in an adult
neutrophils
what are bands?
slightly less mature neutrophils that have a non-segmented or band-shaped nucleus - neutrophils which have just been released from the bone marrow
sites of hematopoiesis
yolk sac
liver and spleen
bone marrow
what is a granulocyte?
WBC that is filled with microscopic granules
little sacs containing enzymes that digest microorganisms
innate immune system
role of basophil
secretory cell which mediates the hypersensitivity reaction
what is the largest cell in the peripheral blood?
monocytes
which WBCs are referred to as mononuclear?
monocytes and lymphocytes
what is the flexible inner protein fiber in RBCs?
spectrin
hematopoiesis occurs in the red bone marrow of what?
axial skeleton and girdles
epiphyses of the humerus and femur
Erythropoietin (EPO) release by the kidneys is triggered by:
Hypoxia due to decreased RBCs
Decreased oxygen availability
Increased tissue demand for oxygen
where does the body get iron from?
stores iron in Hb, the liver, spleen, and bone marrow
intracellular iron is stored in protein-iron complexes such as ferritin and hemosiderin
circulating iron is loosely bound to the transport protein transferrin
where does RBC breakdown occur?
spleen - dying RBCs are engulfed by macrohages. heme and globin are seperated and the iron is salvaged for reuse
what is heme degraded into?
Fe recycled ot ferritin or hemosiderin
yellow pigment called bilirubin
what is hematocrit?
portion of total blood volume that is RBC
what is MCV?
mean corpuscular volume - average volume/size of a single RBC
abnormal variation in cell volume
anisocytosis
when will you see target RBCs?
iron deficiency
liver disease
spleen removal
thalassemia
*densely stained central area with a pale surrounding area
what are platelets?
cytoplasmic fragments of megakaryocytes - in adults megakaryocytes are exclusively in the bone marrow
what is thrombopoeitin?
promotes the grown of Meg-CFC
increases the rate of endomitosis
inhibits apoptosis
stimulates magakaryocyte maturation
does thrombopoeitin promote platelet release?
no
what inhibits platelet aggregation?
cyclic AMP
- Cyclic AMP increased by prostoglandins
what do anti-platelet drugs do?
interfere with prostaglandin synthesis
Aspirin, NSAIDS - COX1 inhibitor
Celebrex - COX 2 inhibitor
interfere with cyclic AMP, ADP binding, and inhibition of the GPIIb/IIIa receptor
acquired platelet dysfunction is from what?
liver disease cadiopulmonary bypass uremia dysproteinemia myeloproliferative disorders (bone marrow) alcohol toxicity
inherited platelet dysfunction
giant platelet disorders Wiskott-aldrich syndrome storage pool disorders glanzmann thrombasthenia platelet release disorders
what is thrombocytopenia?
reduced platelet count in peripheral blood
what causes thrombocytopenia?
increased destruction**
decreased production
abnormal pooling or distribution within the body
artifact
what is pseudothrombocytopenia?
conformational change in plt membrane
Immune clumps the platelets
cold dependent clumping
*evaluate with smear
what is ITP?
immune thrombocytopenic purpura
also called idiopathic autoimmune thrombocytopenic purpura
occurs in both children and adults
caused by platelet specific antibodies which bind to the platelets
this mediates adhesion of platelets to the collagen exposed on endothelial cell surfaces
von willebrand factor - acts as a bridge between a specific glycoprotein complex on the surface of platelets and collagen fibrils
vWF is required to bind to and stabilize coagulation factor what?
VIII
what is aggregation?
binding to other platelets via fibrinogen
aggregation is mediated by what?
fibrinogen receptors (GPIIb/IIIa)- undergo conformational change to active state
goal of clotting cascade
form fibrin
this is initiated when contact is made between blood and exposed negatively charged surfaces
intrinsic cascade
this is initiated upon vascular injury which leads to exposure of tissue factor
extrinsic pathway
what pathway does aPTT (activated partial thromboplastin time) evaluate?
intrinsic
what pathways doe PT/INR (prothrombin time) evaluate?
extrinsic
factors determining hemoglobin values
age gender race degree of sexual maturation altitude heredity
what does a high retic count indicate?
bone marrow is trying to compensate for anemia
symptoms of iron deficiency anemia
asymptomatic weakness, fatigue, SOB, pallor, dizziness, irritability, decreased exercise tolerance pica - severe state (ice craving) palor koilonychia tachycardic glossitis
what is sideroblastic anemia?
iron fails to bind to pophyrin ring in the erythroblast to produce heme
iron is retained in the mitochondria of the cell
ringed sideroblasts (normoblast with perinuclear halow of blue-stained material) seen on bone marrow smear with prussian blue staining
what is sideroblastic anemia characterized by
anemia
low retic count
ineffective erythropoiesis with distinctive mophology
treatment of sideroblastic anemia
remove offending agent
trial of pyridoxine to correct nutritional deficience
what are folate and B12 required for?
DNA synthesis and regulation
B12 and folate deficiency anemia results in what?
megaloblastic anemia due to reduced DNA replication
clinical manifestations of folate deficiency
jaundice due to ineffective erythropoiesis
smooth tongue
lab findings for folate and cobalamin deficiency
macrocytosis howell-jolly bodies relatively low retic count mild thrombocytopenia and/or neutropenia hypersegmentation of neutrophils megaloblastic changes in marrow
will magaloblastic anemia of B12 deficiency respond to folic acid in high doses?
yes, but neurologic deficits do NOT respond
what is anemia of chronic disease?
occurs in setting of chronic disease states associated with inflammatory cytokines or impaired marrow production
induce production of hepcidin - blocks iron absorption from gut
causes of anemia of chronic disease
acute and chronic infections inflammatory and autoimmune diseases (T-cell mediated) cancer CKD liver disease MDS (myelodysplastic syndromes) aging
what is aplatic anemia
failure of bone marrow due to injury or abnormal expression of pluripotent hematopoietic stem cell
hallmark: bone marrow shows hypocellularity and hypoplasia of all cell lines
most common cause of non-immune hemolytic anemia
hereditary spherocytosis
manifestations of sickle cell disease
chronic hemolytic anemia pain dactylitis acute chest syndrome chronic organ damage (spleen, brain, kidneys)
most frequent reason for sickle cell hospitalization
vaso-occlusive pain crisis
severe, agonizing pain usually starting in limbs
transfusion indications in sickle cell
acute stroke or TIA acute chest syndrome priapism splenic sequestration pre-operative sympotomatic anemia aplastic crisis abnormal transcranial doppler
what is not indicated for a sickle cell transfusion?
pain crisis
anemia
neonatal factor assays for hemophilia
should be performed on male infants with a family hstory of bleeding problems or prolonged bleeding after circumcision
hemophilia A - can be diagnosed from FVIII levels in CORD BLOOD collected immediately after delivery
hemophilia B- requires blood to be taken after 6 months of age since FIX is vitamin-K dependent and all neonates have low levels of vitamin K and FIX
what should you avoid in patients with severe pain due to bleeding in joints?
aspirin and NSAIDS - can exacerbate bleeding
what is DIC characterized by?
clotting and bleeding
systemic activation of coagulation system results in overactivation of the fibrinolytic system
- clotting due to circulating thrombin
- bleeding due to depletion of clotting factors and excessive fibrinolysis
why do you have platelet dysfunction in coagulopathy of liver failure?
splenomegaly due to portal hypertension - sequesters platelets
ETOH cirrhosis- suppression of thrombopoeisis by toxicity of alcohol or concomitant folate deficiency
where are you clotting factors made?
liver - except VWF
what is the best prognostic indicator in Acute liver failure?
factor V level- helps determine need for urgent transplant in patient presenting with encephalopathy
treatment of coagulopathy in liver failure
not curative, only supportive
novoseven (recombinant human factor VII) - off label use in liver disease but use is restricted due to limited data and excessive cost
what coag factors are dependent on vitamin k?
II, VII, IX, X
what is virchow’s triad?
pathrogenesis of a thrombus
endothelial injury
abnormal bloodflow
hypercoagulability (primary - genetic or secondary - acquired)
what signs/symptoms are indicative of a DVT?
painful, swollen, warm and plethoric extremity with reduced pulse volume
what signs/symptoms are indicative of a PE?
cough, SOB, hemoptysis, tachycardia
hypercoagulable state workup for primary
protein C activity - impaired inactivation of factors V and VIII –>unregulated fibrin production
protein S activity - impaired inactivation of factors V and VIII –>unregulated fibrin production
antithrombin III - major inhibitor of thrombin and fibrin formation
factor V leiden
hypercoagulable state workup for secondary
anticardiolipin antibody
lupus anticoagulant
homocysteine
what is factor V leiden mutation?
activated protein C resistance
point mutation in gene for Factor V renders it unable to be inactivated by protein C
primary HCS screening guidelines
VTE
primary HCS treatment
heparin drip until therapeutic with warfarin
goals: 2-3
primary HCS duration of tratment
first VTE episode: 6-12 months
recurrent VTE: lifelong therapy
who is likely to have antiphospholipid syndrome
often associated with Lupus
recurrent pregnancy loss
what is antiphospholipid syndrome?
autoantibodies directed against phospholipids in cell membranes lining blood vessels
induces endothelial cell damage, predisposing to thrombosis - starts coag cascade with no tissue damage
what should you suspect in patients with prolonged aPTT with no clinical bleeding?
lupus antigoagulant - clinically not a bleeding disorder. just an antibody that prolongs aPTT by binding to phospholipid in the lab assay
what are mixing studies used for?
performed on blood plasma used to distinguish factor deficiences from factor inhibitors
what are the primary lymphoid organs?
thymus and bone marrow
what are the secondary lymphoid organs
spleen
MALT
lymph nodes
tonsils
what is the complication from tumor lysis syndrome (TLS)?
marked increase in uric acid excretion can result in ACUTE RENAL FAILURE
- occurs with rapid release of intracellular potassium and phosphorous into blood stream
diagnostic tests for tumor lysis syndrome
LFT and LDH uric acid renal function test serum electrolytes EKG if hyperkalemic
