Flashcards in Hematology Deck (110)
Leukemia vs. Lymphoma
Leukemia: malignancy in the marrow
Lymphoma: malignancy outside of the marrow, usually WBCs in a secondary lymph organ
Acute vs. Chronic Leukemia
Acute involves immature cells, more rapid
Chronic involves more mature cells
Measured components of CBC (8)
WBC, RBC, Hemoglobin, Hematocrit, Platelet Count, Mean Corpuscular Volume, Differential, Mean Platelet Volume
Calculated Components (6)
Hematocrit, Mean Corpuscular Volume, Mean Corpuscular Hemoglobin, Mean Corpuscular Hemoglobin Concentration, Red Cell Distribution Width, Absolute Leukocyte Counts
Transcription Factor most common in innate immunity
Cytokine vs. Chemokine
Cytokine: general small protein signaling molecule
Chemokine: cytokine that promotes chemotaxis
Purpose of innate immune system
Start inflammation quickly, Rubor/Calor/Tumor/Dolar
Signals adaptive immune system through dendritic cells
Count: counting on slide, 0.4-1.7% of total cells
Absolute: Percentage x RBCs. >50,000/uL is elevated
Index: fold increase beyond baseline, countx(pt/normHgb)x1/stress factor, 1-2 is normal
Anemia General Symptoms and Signs
Symptoms: SOB, Tachy, dizziness, fatigue, claudication, angina, pallor
Signs: tachycardia, tachypnea, dyspnea, pallor
65% Hemoglobin, 6% myoglobin, 25% ferritin/hemosiderin,
Iron from food made soluble in gastric pH
Gastroferrin binds elemental or heme-bound iron
Ferric iron is transported into cells through DMT1 transporter and DCYTB converts ferric (3+) iron to ferrous (2+) iron.
Either bound to ferritin in cell or exported via ferroportin and converted to ferric through hephaestin
Hepicidin inhibits ferroportin. AAs and VitC improve absorption. Erythropoiesis improves absorption.
Transferrin binds 2 moles ferric iron and delivers to bone marrow. Interacts w/ transferrin R, clathrin-mediated pinocytosis.
pH in endosome causes iron dissociation and it enters cytoplasm through DMT1.
Development of Iron Deficiency
See reduced Hemoglobin, RBC production, cell rigidity.
Causes: failure to absorb or inability to keep up w/ production demands.
1. Iron depletion in ferritin stores, absorption increases, functions are normal
2. Serum iron reduced, iron binding affinity increases, iron loading is impaired, normal RBC production.
3. Low serum iron, increased transferrin, reduced erythropoiesis,
Signs: microcytosis, hypochromia, increased protoporphyrin
Symptoms of Iron Deficiency
Pallor, Fatigue, Loss of Exercise Tolerance, Irritability,
Effects of Iron Deficiency
Heart, Liver, Endocrine disorders
Treatments of iron deficiency
Hemoglobin only binds __ Iron
P50 Oxygen in body
pH and oxygen affinity
decreases as pH decreases
[CO2] and oxygen affinity
decreases as CO2 increases
Temperature and oxygen affinity
decreases as temperature increases
Binds between beta chains, stabilizes T conformation.
Affinity decreases as enzyme increases
Myoglobin vs. Hemoglobin oxygen dissociation curves
Myoglobin is monomer, no cooperativity, hyperbolic dissociation curve hyperbolic w/ high affinity at low concentration.
Poor O2 transporter b/c dissociation only occurs at very low O2 but effective in very low O2 environment of cell.
Hemoglobin 4-14 weeks
Z2E2 and A2E2
Hemoglobin 18 weeks - Birth
1-5 Years onward
A2B2 and little A2D2 (2%)
Increased affinity, red appearance, high RBC count
Increases CO2 affinity, similar to smokers
mild anemia, reticulocytosis, splenomegaly
Hemoglobin binding ferric iron, usually 1%
Caused by NADPH metHgb reductase deficiency or increased free radical exposure.
Genetically: cytochrome b5 reductase deficiency
CO affinity for Hgb
250x higher, smokers 10-15% (normal 3%). Negative cooperativity
How does a pulse oximeter work?
DeoxyHgb absorbs 660nm; OxyHgb absorbs 940nm. Only pulsatile flow measured. CO heme absorbs 940, MetHgb absorbs both
Where does hepatopoiesis occur?
0-3 months, 2-7 months, 7-9 months, Childhood, Adult
0-3 months Yolk Sac
2-7 months Liver w/ some spleen
7-9 months Bone Marrow
Childhood Most BM
Adult Axial BM
HSCs and Progeitor Cells
HSCs self renew and become colony stimulating units
Progenitors: limited self renewal, limited to 1-2 lineages w/in set
Precursors: dedicated to 1 lineage
Major Growth Factors
large nucleus, immature cytoplasm (blue), large nucleolus
2-7 days maturation in BM w/ 3-5 days of division.
Reticulocytes 1 day BM and 2-3 days in periphery
120 day lifespan
3-5 days mitotic pool
5-7 day maturation
10 hour lifespan
Things to evaluate w/ marrow biopsy (6)
Myeloid-Erythroid ratio: 3:1
Maturation: heterogenous appearance
Reasonable # of megakaryocytes
Proper iron amount in macrophages (Prussian Blue)
Lesions: no fibrosis, tumors, granulomas, etc.
Normal WBC results
40-60% neutraphils, 1-4% eosinophils, 0.5-1% basophils, 2-8% monocytes, 20-40% lymphocytes
Major Central Lymphoid Organs
Bone Marrow and Thymus
Peripheral Lymphoid Organs
Lymph Nodes, Spleen, Peyer Patches, Tonsils
Blood-Lymph Circulation of Lymphocytes
Extravasate in post-capillary venules at high cuboidal endothelial cells. Either stay in lymph node or enter lymph and return to system circulation via at SVC.
Antigen that elicits an immune response after binding an AB/TLR
High affinity, multiple bound ABs, co-stimulation of other surface molecules important
Anemia of Chronic Disease Causes (4)
Neoplasms and Sepsis
Anemia of Chronic Disease Pathogenesis
TNF from neoplasms/sepsis reduces erythropoiesis, iron stores, and INF-beta which collectively reduce erythropoiesis.
Inflammation/Infection produces IL-1 which reduces erythropoietin and iron metabolism. Also produces INF-gamma which suppresses erythropoiesis.
Renal is lack of erythropoiesis
Lead inhibits protoporphyrin ring synthesis and iron addition to rings
EPO vs. Transfusion treatments for chronic anemia
EPO preferred for absolute deficiencies or EPO loss.
Transfusions indicated when heart damage possible.
B-12 and Folate Deficiencies (basis)
Both important co-factors for hematopoiesis, covert methionine to homocysteine which creates tetrahydrofolate for DNA synthesis. Decreases cause RBCs to decrease in size, arrest in size, and get destroyed.
Meat, Eggs, Milk. It is released in acidic gastric environment and binds Intrinsic Factor from GI cells, absorbed in terminal ileum and released from IF, binds transcobalamin binding protein II that transports it to liver for storage or bone marrow for use.
Folate is in many foods, absorbed in jejunum, hydrolyzed, reduced, and methylated before distribution to tissue or stored in liver. Biliary secretion and enterohepatic circulation provides constant supply for tissue.
Bone Marrow Findings in B12/Folate Deficiency
Erythroid hyperplasia. Megaloblastic changes. Larger nuclei than anticipated based on maturity level.
Peripheral Blood Findings B12/Folate Deficiency
variable anemia, low reticulocyte count, macrocytosis, high bilirubin, and high LDH.
Causes of B12 anemia (3)
Autoimmune destruction of IF producing epithelial cells
Lack of IF synthesis
Malabsorption of B12
B12 deficiency timeline
Slow. High liver stores take long time to deplete w/ long half life for b12. Neruoabnormalities possible.
Causes of Folate Anemia (2)
Inadequate Dietary intake
Malabsorption (enterohepatic circulation disruption, alcohol consumption)
Folate Deficiency Timeline
Much faster than B12. Neuro abnormalities rare.
Diagnosing B12/Folate Deficiency
Both produce elevated plasma homocysteine. B12 also produces high methylmalonic acid levels.
Treatments for B12/Folate
Cobalamin deficiency treated w/ IM or SC daily for 2 weeks with monthly doses for life.
If absorption is not an issue, can be given PO
Folate given orally or parenternally
Hemoglobin tetramers through development
0-4 Months: A2E2 and Z2E2
4-Birth: Fetal A2G2
After birth: A2B2 w/ 2% A2D2
Alpha Thalassemia usually caused by.....
Deletion on Chromosome 16
Beta Thalassemia usually caused by....
Point mutation on Chromosome 11
Clinical Signs of Thalassemia
Low Hgb, Low MCV, Low MCHC,
Alpha Thalassemia Trait
Silent: 1/4 deleted genes, no anemia, normal MCV
Trait: 2/4 deleted, no/mild anemia, normal/low MCV
NO transfusions needed
3/4 alpha genes deleted, mod/severe anemia, low MCV, transfusions sometimes needed
4/4 alpha genes deleted, incompatible with life
Thalassemia Smear Findings
microcytosis, target cells, polychromastia, normal RDW
Clinical manifestations of thalassemia
High bilirubin, AST, LDH from hemolysis, splenomegaly, expanded bone marrow, increased iron absorption, delayed growth, pulmonary HTN
Iron Valence States
Ferric 3+ and Ferrous 2+
Iron in Aquesous Solution Considerations
Forms insoluble salts unless protein bound
Where are Iron salts more soluble?
How is body Iron balance controlled?
Absorption, no mechanism for excretion
How do you lose body iron?
exfoliation of skin/musosa, menstruation
Hemoglobin: 30-60; 60-90; 45-75; 10-10
Pneumonic for pO2 and % binding
Lifespans and daily production (RBCs, platelets, Neutrophils)
RBCs: 120 days; 175 bil/day
Platelets: 7-10 days; 200bil/day
Neutrophils: 7 hours; 70 bil/day
Beta globin gene PM: 26 glu-lys. Unstable. Low MCHC
Hydroxyurea in Beta Thalassemia
Induces production of gamma chains, increases HbF
HbD Punjab Mutation
HbO Arab Mutation
Sickle Cell HbSS RBC Lifespan
Complications of chronic hemolytic anemia (4)
Aplastic Crises (Parvovirus B19)
Effects of Vascular Occlusion in hemolytic anemia (8)
Spleen: sequestration and auto-infarction
CNS: large vessel occlusion stroke when young hemorrhagic stroke when older from damage
Lung: occlusion and damage, pulmonary HTN
Kidney: dehydration 2' to damage, glomerulus damage
Retina: detachment and blindness from hemorrhage
Avascular necrosis in joints
Sickle Cell Pain Crisis
Vaso-occlusion and temporary ischemia causing pain in the extremities, abdomen, chest
Complications w/ pain crises (vaso-occlusion) (5)
Acute Chest Syndrome (deoxygenation, pulmonary edema)
Multi-organ failure syndrome
Priapsim (sustained painful erections 2' to trapped RBCs)
Bone Infarction: necrotic injury
Treatments of Sickle Cell (3)
Bone Marrow Transplant: Curative
Hydroxyurea: fetal hemoglobin production
Transfusion Therapy: for severe acute circumstances
Hereditary Spherocytosis Cause
Defect in spectrin ankyrin, or band 3 that weakens cytoskeleton and destabilizes lipid bilayer. Decreased deformability leads to entrapment in spleen and extravascular hemolysis via macrophages.
G-6-PD deficiency inheritance
Loss of G-6-PD creates inability to restore reduced GSH, increased oxidative damage to spectrin, reduced deformity, splenic trapping, macrophage hemolysis
Warm AB Autoimmune Hemolytic Anemia
IgG bind RBCs in warm areas of body, poor complement activation, Fc Receptor mediated macrophage hemolysis in spleen
Cold AB Autoimmune Hemolytic Anemia
IgG/IgM bind RBCs in cold ares of body, activate complement for intravascular hemolysis
Direct DAT/Coombs test
Tests for IgG/C3d/C4d on patient's RBCs by adding ABs against these components and testing agglutination
Checks if patient's serum has IgG/complement that binds normal RBCs
Spleen Immunity Function
Creation of IgM, especially for encapsulated organisms
Complications of Splenectomy
Bacterial sepsis from S pneumoniae
Co-treatments w/ splenectomy
H influenza b, S pneumoniae vaccinations, and meningococcus vaccinations. Prophylactic ABX daily through childhood. See physician immediately w/ F
IgG Half Life
C1 Esterase Inhibitor
Suppresses basal complement activation from minimal concentration AG activation. Makes C1 unable to activate C4 and lead to cascade.
T Helper 1
Release lymphokines to attract macrophages
T Helper 17
Similar to TH1s but more powerful
T Helper 2
Stimulate macrophages to wall-off pathogens and start healing process
Follicular Helper T
After activation, move to B cell region of lymph node to promote B cell activation and class switching
Regulatory T Cell
Suppress activation/function of T helpers to stop immune response
Type I Immunopathology
Too much IgE, hypersensitivty
Type II Immunopathology
Antibodies that react to self or collateral damage to self from AG binding cells
Type III Immunopathology
Antibodies to soluble antigens, cause local damage through complement activation
Type IV Immunopathology
T-cell mediated damage to self (hepatitis, TB)
How many constant heavy chain segments in each type of AB?
3 for IgG, IgD, IgA
4 for IgM and IgE