Hem/onc Flashcards
Fetal erythropoeisis
yolk sac (3-8 weeks)
Liver (6 weeks - birth)
Spleen (10-28 weeks)
Bone marrow (18 weeks to adult)
Rh hemolytic disease of the newborn
Rh- mother, Rh+ fetus
first pregnancy: mother exposed to fetal blood –> mom form anti D IgG
Subsequent pregnancies: anti D IgG crosses the placenta –> attacks fetal RBC –> hemolysis in fetus
presents as hydrops fetalis, jaundice shortly after birth, kernicterus
ABO hemolytic disease of the newborn
Type O mom; Type A or B fetus
preexisting maternal anti A or anti B IgG Ab cross placenta –> hemolysis in fetus
Presents as mild jaundice in the neonate within 24 hours of birth. CAN OCCUR IN FIRST BORN and less severe
Tx: phototherapy or exchange transfusion
Neutrophils
Acute inflammatory response cells
Numbers increase in bacterial infection
Phagocytic
multilobed nucleus
specific granules contain leukocyte, alkaline phosphatase, collagenase, lysozyme and lactogerrin
Azurophilic granules contain proteases, acid phosphatase, myeloperoxidase and B glucuronidase
Hypersegmented neutrophils
vit B12/ folate deficiency
Left shift with increased band cells
increase myeloid proliferation (bacterial infection, CML)
Neutrophil chemotaxis
C5a, IL8, LTB4, kalikrein, PAF
Erythrocytes
Carry O2 to tissues and CO2 to lungs
Anucleate and lack organelles, biconcave with large surface area to volume taio for rapid gas exchange.
Life span of 120 days
USE GLUCOSE
Thrombocytes
primary hemostasis
small cytoplasmic fragments derived from megakaryocytes
Contains Ca2+, ADP, 5HT, Histamine and a granules
Monocytes
found in blood, differentiate into macrophages in tissues
Large kidney shaped nucleus
Macrophages
phagocytose bacteria, cellular debris and senescent RBCs
Activated by y interferon
Eosinophils
heminth infection
Produce histamine, major basic protein, eosinophil peroxidase, cationic protein, neurotoxin
Basophils
mediate allergic reaction
heparin
Mast cells
mediate local tissue allergic reactions
Can bind IgE to membrane
histamine, heparin, tryptase and eosinophil chemotactic factors
Type 1 hypersensitivity
Dendritic cells
APC
MHC II and Fc receptors
Lymphocytes
B, T and NK cells
Natural killer cells
innate immunity (Intracellular pathogens) perforin and granzymes
B cells
in follicles of LN, white pulp of spleen, unencapsulated lymphoid tissued
HUMORAL IMMUNITY
T cells
mediate CELLULAR IMMUNE RESPONSE
mature in thymus
Plasma cells
produce Ab specific to particular antigen
Bone marrow and do not circulate
Thrombogenesis
Formation of insoluble fibrin mesh
Aspirin irreversible inhibit COX –> inhibit TXA2 synthesis
Clopidogrel inhibit ADP induced expression of gpIIb/IIIa by irreversibly blocking P2Y12 receptor
Abciximab inhibit gpIIb/IIIa directly
Ristocetin activates vWF to bind gpIb. Failure of aggregation with ristocetin assay occurs in vWd and Bernard Soulier syndrome
Vitamin K deficiency
decreased synthesis of Factors 2, 7, 9, 10, protein C and S
Warfarin inhibits vitamin K epoxide reductase. FFP and PCC reverse warfarin actions
Anticoagulation
Antithrombin inhibits thrombin and factors 7a, 9a, 10a, 11a, 12a
Heparin enhances the activity of antithrombin
Acanthosis
Liver Disease, abetalipoproteinemia
Projections of varying sizes at irregular intervals
Echinocytes
Liver disease, ESRD, pyruvate kinase deficiency
Smaller and more uniform projections
Dacrocytes
teardrop cells
Bone marrow infiltration
Mechanically squeezed out of bone marrow
Schistocytes
MAHA, mechanical hemolysis
fragmented RBC
Degmacytes
G6PD deficiency
removal of heinz bodes by splenic macrophages
Elliptocytes
Hereditary elliptocytosis
mutation in genes encoding RBC membrane proteins
Spherocytes
Hereditary spherocytosis, autoimmune hemolytic anemia
small spherical cells without central pallor
Macro ovalocytes
Megaloblastic anemia
Target cells
HbC disease, asplenia, liver disease, thalassemia
Sickle cell
Sickle cell anemia
sickling occurs with low O2 conditions
Iron granules
Sideroblastic anemias
perinuclear mitochondria with excess iron
REQUIRE PRUSSIAN BLUE STAIN
Howell Jolly Bodies
functional hyposplenia, asplenia
Basophilic nuclear remnants
removed by splenic macrophages usually
Basophilic stippling
sideroblastic anemia, thalessemia
Pappenheimer bodies
sideroblastic anemia
basophilic granules
Heinz bodies
G6PD deficiency
denatured and precipitated Hb
Microcytic, hypochromic anemias
Iron deficiency a thalassemia B thalassemia Lead poisoning Sideroblastic anemia
Iron Deficiency Anemia
via chronic bleeding, malnutrition, absorption disorders, , GI surgery or increase demand –> low final step in heme synthesis
Low Fe, high TBC, low ferritin, high free erythrocytic protoporphyrin, high RDW, low RI
Sx: fatigue, pallor, PICA, spoon nails
glossitis, cheilosis, Plummer Vinson
a thalassemia
a globin gene deletion on Chromosome 16 –> low a globin synthesis
More deletion –> more microcytic hypochromic anemia
3 deletions –> B4 (HbH)
4 deletions –> y4- hydrops fetalis
B thalassemia
point mutation in splice sites and promoter sequences on chr 11 –> decrase B globin synthesis
B thalassemia minor
B chain is underproduced
Asymptomatic
Dx via high HbA2 on electrophoresis
B thalassemia major
B chain absent –> severe microcytic hypochromic anemia with target cells
Marrow expansion –> skeletal deformities. Extramedullary hematopoiesis –> hepatosplenomegaly
Increase risk of parvovirus B19 aplastic crisis
HbS/ B thalassemia heterozygote
mild to moderate sickle cell disease
Lead poisoning
Inhibits ferrochelatase and ALA dehydratase –> low heme synthesis and high RBC protophyrin
inhibits rRNA degradation –> RBCs retain aggregates of rRNA
Lead lines gingivae and metaphyses of long bones on Xray, encephalopathy and erythrocyte basophilic stippling, ab colic and sideroblastic anemia, wrist and foot drop
Tx Dimercaprol and EDTA
Sideroblastic anemia
X linked defect in ALA synthase gene, myeloblastic syndrome and alcohol, lead poisoning, drugs
High iron, normal TIBC, high ferritin
ringed sideroblasts in bone marrow.
Tx pyridoxine
Megaloblastic anemias
impaired DNA synthesis –> maturation of nucleus of precursor cells in bone marrow delayed relative to maturation of cytoplasm.
Causes vit B12 deficiency, folate deficiency, meds
Folate Deficiency
malnutrition, malabsorption, drugs, high requirement
Increased homocysteine, normal methylmalonic acid
NO NEURO
Vit B 12 deficiency
pernicious anemia, malabsorption, pancreatic insufficiency, gastrectomy, insufficient intake
High homocysteine, methylmalonic acid
NEURO: reversible dementia
Folate correct anemia but worsens neuro
Orotic aciduria
inability to convert orotic acid to UMP because defect in UMP synthase.
AR
failure to thrive, developmental delay and megaloblastic anemia.
Nonmegaloblastic anemia
macrocytic anemia in which DNA synthesis is normal
Alcoholism and liver disease
NO HYPERSEGMENTED NEUTROPHILS
Diamond Blackfan
Congenital pure red cell aplasia
rapid onset anemia within first year of life due to intrinsic defect in erythroid progenitor cells
short, craniofacial abnormality, UE malformation
Intravascular hemolysis
low haptoglobin
high schistocytes
mechanical hemolysis, paraxysmal nocturnal hemoglobinuria, MAHA
Extravascular hemolysis
macrophages in spleen clear RBCs
spherocytes
no hemoglobinuria, hemosideriuria
can present with urobilinogen in urine
