Hematology/Oncology Flashcards
Lifespan of erythrocyte
120 days
Anisocytosis
Varying sizes
Poikilocytosis
Varying shapes
Erythrocytosis
Polycythemia = ↑ Hematocrit
Reticulocyte
Immature erythrocyte marker of erythroid proliferation
Platelet
Derived from…
What do they contain
Storage
Derived from Megakaryocytes
Dense granules (ADP, Ca) and α granules (vWF, fibrinogen)
1/3 stored in spleen
Results of Thrombocytopenia or Platelet Dysfunction
Petechiae
vWF receptor
GpIb
Fibrinogen receptor
GpIIb/IIIa
Leukocyte
Subtypes
Normal range
Granulocytes (Neutrophils, Eosinophils, Basophils)
Mononuclear cells (Monocytes, Lymphocytes)
4000-10000
WBC differential
"Neutrophils Like Making Everything Better" Neutrophils (60%) Lymphocytes (30%) Monocytes (7%) Eosinophils (2%) Basophils (<1%)
Neutrophil Increased in what state? Function Histo Granules
Bacterial infection
Phagocytic
Multilobed nucleus
Small numerous specific granules (ALP, Collagenase, Lysozyme, Lactoferrin)
Larger less numerous Azurophilic granules are lysosomes (Acid phosphatase, Peroxidase, β-glucuronidase)
Hypersegmented polys
Histo
Seen in
5 or more lobes
VitB12/Folate Deficiency
Increased Band Cells
What are they?
What do they reflect?
Immature Neutrophils
Increased myeloid proliferation (bacterial infection or CML)
Monocyte
Where do they exist?
What does it differentiate into?
Histo
In blood
Macrophages in tissue
Large, kidney shaped nucleus with extensive frosted glass cyto
Macrophage Function Lifespan What activates them? Marker
Phagocytosis, APC via MHCII
Long life in tissues
Activated by γ-Interferon
CD14
Eosinophil
Function
Histo
What does it produce?
Defends again helminthic infections. Phagocytic for Ag-Ab complex
Bilobate nucleus. Large eosinophilic granules
Produce Histaminase and Arylsulfatase to limit reaction following mast cell degranulation
Causes of eosinophilia
“NAACP”
Neoplastic, Asthma, Allergy, Collagen vascular disease, Parasites
Basophil
Function
Histo with function
Mediates allergic reactions
Basophilic granules with heparin (anticoagulant), Histamine (vasodilator), and Leukotrienes (LTD4)
Mast Cells Function Histo Physiology Molecules it releases What type of reaction is it involved with? Inhibition?
Allergic reactions in local tissue
Resemble basophils
Can bind Fc portion of IgE to membrane. IgE cross-links upon Ag binding –> degranulation
Releases Histamine, Heparin, Eosinophil chemotactic factors
Type I hypersensitivity reaction
Cromolyn prevents degranulation
Dendritic cells Function Role Re Immune systems Expresses... In skin they are called
Phagocytic APC
Link between innate and adaptive immune systems
MHCII and Fc receptor
Langerhans cells in skin
Lymphocyte
Mediates what kind of immunity
Subtypes
Histo
Adaptive immunity
B and T cells
Densely stained nucleus with small amount of cytoplasm
B Lymphocyte What kind of immune response? Where does it arise from? Where does it mature? Where does it migrate to? What does it differentiate into? Function MHC Markers
Humoral response
Bone marrow
Bone marrow
Migrates to peripheral lymphoid tissues (follicles of lymph nodes, white pulp of spleen, unencapsulated lymphoid tissue)
When encounters Ag, differentiates into Ab producing plasma cell and memory cells
APC via MHCII
CD19 and CD20
Plasma Cell
Function
Histo
Pathology
Ab production
Off center nucleus, clock face chromatin, RER, well developed Golgi
Multiple Myeloma
T Lymphocyte What kind of immune response? Where does it arise from? Where does it mature? What does it differentiate into? Surface marker Percentage of circulating lymphocytes
Cellular immune response Bone marrow Thymus Tc cells (CD8), Th (CD4), Treg (CD28) CD3 80%
Blood group A
A Ag and B Ab
Blood group B
B Ag and A Ab
Blood group AB
A and B Ag. No Abs
Universal Recipient of RBCs
Universal Donor of Plasma
Blood group O
No Ag. A and B Abs
Universal donor of RBCs
Universal Recipient of Plasma
Rh factor
Ag on RBC surface
Erythroblastosis Fetalis
PathoPhys
Treatment
Rh- mother exposed to fetal Rh+ blood. Mother makes anti-Rh IgG that crosses placenta and causes hemolytic disease in the next fetus
Rho (D) immune globulin for mother at first delivery to prevent initial sensitization of Rh- mother to Rh Ag
Blood groups Re crossing placenta
anti A and anti B IgM does not cross placenta
anti Rh IgG does cross the placenta
Intrinsic Coagulation Pathway
Collagen, Basement membrane, Activated platelets, or HMWK –> XII –> XI –> IX
IX + VIII –> X
XII –> Kallikrein
Extrinsic Coagulation Pathway
Thromboplastin (tissue factor) –> VII –> X
Common Coagulation Pathway
X + V –> II (thrombin) –> Fibrin
XIII (fibrin stabilizing factor) helps stabilize fibrin mesh
Thrombin also activates V, VIII, XIII
Kinin Cascade
Kallikrein thurs HMWK into Bradykinin
Bradykinin ↑ Vasodilation, Permeability, and Pain
Fibrinolytic System
XII –> Kallikrein –> Plasmin –> Fibrin mesh degradation
Plasmin also activates C3
Which reactions of the coagulation cascade require Ca and Phospholipids
XIa –> IX
VII –> VIIa
VIIa and (IXa + VIIIa) activation of X
Xa + Va activation of II
Hemophilia A
Deficiency in VIII
Hemophilia B
Deficiency of IX
VitK Pathway
Oxidized VitK –> [epoxide reductase] –> Reduced VitK
Reduced VitK is a cofactor for the maturation of II, VII, IX, X, C, and S
Warfarin
MoA
Inhibits Epoxide Reductase
Why are neonates given VitK?
They lack enteric bacteria that produce VitK
What does vWF do?
Carries/protects VIII
Anticoagulation cascade
Thrombomodulin on endothelial cells –> Protein C
C + S cleaves and inactivates Va and VIIIa
What does antithrombin do?
Inhibits activated forms of II, VII, IX, X, XI, XII
Function of Heparin
Activates Antithrombin
Factor V Leiden mutation
Classical presentation
Factor V resistant to inhibition by protein C
DVT –> PE
tPA
Thrombolytic that activates plasmin
Platelet Plug Formation Schematic
Injury: vWF binds exposed collagen upon endothelial damage
Adhesion: Platelets bind vWF via Gp1b and release Ca and ADP.
Activation: ADP binding induces GpIIb/ IIIa expression on platelet surface –> aggregation
How does ADP affect coagulation
Released by platelets.
Helps platelets adhere to endothelium and induces platelets to express GpIIb/IIIa at platelet surface
Platelet Aggregation Pathway
Fibrinogen binds GpIIb/IIIa and links platelets
Pro Platelet Aggregation Factors
TXA2 (released by platelets), ↓ blood flow, ↑ platelet aggregation
Anti Platelet Aggregation Factors
PGI2 and NO (released by endothelial cells)
↑ blood flow
↓ platelet aggregation
Ticlopidine
Inhibits ADP induced expression of GpIIb/IIIa
Causes Neutropenia, Oral Ulcers, Fever
Clopidogrel
Inhibits ADP induced expression of GpIIb/IIIa
Abciximab
Inhibits GpIIb/IIIa directly
ESR
What causes it to increase?
↑ ESR
↓ ESR
Acute phase reactants in plasma (Fibrinogen) cause RBC aggregation and ↑ ESR
↑: Infection, Autoimmune, Malignancy, Pregnancy
↓: “CHaMP”
Polycythemia, Sickle Cell Anemia, CHF, Microcytosis, Hypofibrinogenemia
Acanthocyte
Spur cell indicative of Liver disease or Abetalipoproteinemia (cholesterol dysregulation)
Basophilic Stippling
“BASte the ox TAiL”
Thalassemias, Anemia of chronic disease, Lead Poisoning
Bite Cell
G6PD deficiency
Eliptocyte
Hereditary Elliptocytosis
Macro-Ovalocyte
Megaloblastic anemia (w/ hypersegmented polys) and Marrow failure
Ringed Siderblasts
Sideroblastic anemia
Excess Fe in Mito
Schistocyte
Helmet Cell
DIC, TTP/HUS, Traumatic Hemolysis (metal heart valve prosthesis)
Sickle Cell
Sickle Cell Anemia
Spherocyte
Hereditary spherocytosis, Autoimmune hemolysis
Teardrop cell
“RBC sheds a tear because it has been forced out of its home”
Bone marrow infiltration (myelofibrosis)
Target Cell
“HALT said the hunter to his target”
HbC disease, Asplenia, Liver disease, Thalassemia
Heinz Bodies
Process
Associated pathology
Oxidation of sulfhydryl groups leads to denatured Hb precipitation and damage to RBC membrane –> formation of bite cells
G6PD deficiency and α-thalassemia
Howell-Jolly Bodies
What is it?
How are they normally dealt with?
Associated pathology
Basophilic nuclear remnants found in RBCs
Normally removed from RBCs by splenic macrophages
Functional hyposplenia, asplenia, mothball ingestion (naphthalene)
Microcytic Anemias
“Find Those Small Plump Cells”
Iron Deficiency, ACD, Thalassemia, Pb poisoning, Sideroblastic anemia
Nonhemolytic Normocytic Anemias
ACD, Aplastic, Chronic Kidney Disease
Hemolytic Normocytic Anemias
Intrinsic: “SHEEPS”
Spherocytosis, G6PD or PK deficiency, HbC, Sickle Cell Anemia, Paroxysmal Nocturnal Hemoglobinuria
Extrinsic: Autoimmune, Microangiopathic, Macroangiopathic, Infections
Megaloblastic Macrocytic Anemias
Folate deficiency, B12 deficiency, Orotic Aciduria
NonMegaloblastic Macrocytic Anemias
Liver disease, Alcoholism, Reticulocytosis
Iron Deficiency Anemia What kind of anemia What causes it? PathoPhys Labs Histo How may it manifest
Microcytic, Hypochromatic ↓ Fe due to chronic bleeding, malnutrition, or pregnancy Impaired final step in heme synthesis ↓ Fe and Ferritin, ↑ TIBC Microcytosis (MCV<80) and hypochromia Plummer Vinson Syndrome
α Thalassemia What kind of anemia PathoPhys Epidemiology How # of gene mutations re disease
Microcytic, Hypochromatic
α globin gene mutation
cis deletion in Asians, trans deletions in Africans
4 deletions: No α, excess γ forms γ4 (Hb Barts), Incompatible with life (Hydrops Fetalis)
3 deletions: HbH disease. Very little α, excess β forms β4 (HbH)
1-2 gene deletions: no clinical significance
β Thalassemia
What kind of anemia
PathoPhys
Epidemiology
Microcytic, Hypochromatic
Point mutation in splice sites and promoter sequence –> ↓ β
Mediterranean populations
β Thalassemia minor
PathoPhys
Symptoms
Diagnosis
Heterozygote: β chain underproduced
Asymptomatic
Increased HbA2 on electrophoresis
β Thalassemia major PathoPhys Symptoms Treatment Complications Presentation Hb
Homozygote: β chain absent Severe anemia Blood transfusions (--> hemochromatosis) Marrow expansion (crew cut on skull XR) --> skeletal deformities. Chipmunk facies HbF (α2γ2)
Presentation of HbS/β-Thalassemia Heterozygote
Mild to moderate sickle cell disease depending on amount of β globin production
Lead Poisoning What kind of anemia PathoPhys Presentation Treatment
Microcytic, Hypochromatic
Pb –/ ferrochelatase and ALA dehydratase which leads to ↓ heme synthesis
Pb –/ rRNA degradation causing RBCs to retain rRNA aggregates (Basophilic Stipling)
“LEAD”
Lead lines on Gingivae (Burton’s Lines) and on metaphysis of long bones
Encephalopathy and Erythrocyte basophilic stippling
Abdominal colic and sideroblastic Anemia
Drops (wrist and foot)
Treat with Dimercaprol and EDTA
Succimer in children
Sideroblastic Anemia What kind of anemia PathoPhys What causes it? Histo Labs Treatment
Microcytic, Hypochromatic
Defect in Heme synthesis
X linked defect in δALA synthase, EtOH, Lead, Isoniazid
Ringed sideroblasts (with iron laden mito)
↑ Fe and ferritin, Normal TIBC
Treat with VitB6
Megaloblastic Anemia
Basic Pathology
Consequences
Impaired DNA synthesis –> maturation of nucleus delayed relative to cytoplasm
Ineffective erythropoiesis –> pancytopenia
Folate Deficiency What kind of anemia Etiologies Presentation Histo Labs
Megaloblastic
Malnutrition (alcoholics), malabsorption, antifolates (methotrexate, trimethoprim, phenytoin), ↑ requirement (hemolytic anemia, pregnancy)
Glossitis
Hypersegmented neutrophils
↓ Folate, ↑ Homocysteine, normal Methylmalonic acid
B12 Deficiency What kind of anemia Etiologies Presentation Histo Labs
Megaloblastic
Insufficient intake, Malabsorption, Pernicious anemia, Diphyllobothrium latum (fish tapeworm), PPI
Glossitis, B12 invovled with FA and myelin synthesis leading to Peripheral neuropathy w/ sensorimotor dysfunction, Posterior column (vibration/propioception), Lateral CST (spasticity), and Dementia
Hypersegmented neutrophils
↓ B12, ↑ Homocysteine, ↑ Methylmalonic acid
Orotic Aciduria What kind of anemia? PathoPhys Presentation Histo Labs Treatment
Megaloblastic
Enzyme deficiency impairs conversion of uridine from orotic acid
Children with glossitis and megaloblastic anemia that cannot be cured by folate or B12
Hypersegmented neutrophils
Orotic acid in urine
Uridine monophopshate to bypass mutated enzyme
NonMegaloblastic Macrocytic Anemia
Pathology
What causes it?
Macrocytic anemia in which DNA synthesis is unimpaired
Liver disease, Alcoholism, Retculocytosis, Drugs (5FU, AZT, Hydroxyurea)