Blood Disorders Flashcards
What cell types are found in the buffy coat?
White blood cells
Platelets
Hemoglobin
Complex molecule consisting of 4 heme groups and 4 globins
Always 2 alpha chains, adult has beta, fetus has gamma
Purpose is to transport oxygen
Need iron!
Gets broken down to bilirubin
Live in circulation for 120 days
What 4 things are needed for hemoglobin synthesis?
Iron
Vitamin B12
Vitamin B6
Folic acid
How is hemoglobin degraded?
Split into heme and globin
Globin is degraded further into amino acids which are reutilized
Heme is broken into iron and bilirubin (iron reused, bilirubin to liver and turned into bile)
What is anemia?
Reduction of hemoglobin in blood to below normal levels
May be associated with appearance of abnormal hemoglobin, reduced number of RBCs, or structural abnormalities of RBCs
Decreased hematopoiesis, abnormal hematopoiesis, or increased loss/destruction of RBCs
2 causes of decreased hematopoiesis
Bone marrow failure (aplastic anemia or myelophthisic anemia)
Deficiencies of nutrients (low B12 and folic acid, or protein deficiency)
Myelophthistic anemia
Bone marrow stem cells are damaged or replaced by infiltrates of metastatic tumors cells
Cause of abnormal hematopoiesis
Usually a consequence of genetic abnormalities
Ex: sickle cell anemia
4 causes of anemia from increased loss and destruction of RBCs
Bleeding
Intrasplenic sequestration
Immune hemolysis
Infections (malaria)
Aplastic anemia
Idiopathic, secondary
Bone marrow depleted of hematopoetic cells - only fibroblasts, fat cells, and scattered lymphocytes
Causes anemia, leukopenia, and thrombocytopenia
Uncontrollable infections, bleeding tendency, chronic fatigue, sleepiness, weakness
Stem cells disappear from the bone marrow with consequent pancytopenia (lack of all blood cells) in the periphery
Iron deficiency anemia
Most common form of anemia
Hypochromic, microcytic anemia
Etiology: increased loss of iron, inadequate iron intake or absorption, increased iron requirements
Megaloblastic anemia (caused by, morphology, what are the deficiencies from, effects on bone marrow/peripheral blood/neutrophils)
Caused by deficiency of vitamin B12 or folic acid
Opposite morphology from iron deficiency anemia (large red cells)
Lack of B12 from: pernicious anemia, lack of GIF, atrophic gastritis
Lack of folic acid from: inadequate intake in diet or malabsorption caused by intestinal disease
Bone marrow gets hypercellular with numerous megaloblasts
Macrocytic anemia in peripheral blood
Hypersegmentation of neutrophils
Definitions
- Hypochromic
- Microcytic
- Macrocytic
- Pale red cells
- Small red cells
- Large red cells
Hemolytic Anemia
Increased red blood cell destruction (hemolysis)
Intra and extra cellular defects
Compensatory erythroid hyperplasia of bone marrow
Hyperbilirubinemia, jaundice
Intracorpuscular defects for hemolytic anemia
Structural abnormalities
Sickle cell anemia, thalassemia, hereditary spherocytosis
Infection (malaria)
Extracorpuscular defects for hemolytic anemia
Antibodies, infectious agents, mechanical factors
Autoimmune hemolytic anemia, hemolytic disease of the newborn, transfusion reactions, hemolytic anemia caused by cardiac valve prosthesis, DIC
Sickle cell anemia
Substitution of glutamic acid by valine
Synthesis of abnormal beta chain of globin
Multiple infarcts in various organs (neurologic defects, sharp pain in bones, spleen, extremities, retinal infarcts)
Hyperbilirubinemia, jaundice
Long term complications of sickle cell anemia
Delayed intellectual development, neurologic deficits (largely avoided)
Cardiopulmonary insufficiency
Recurrent infections
Thalassemia
Genetic defect in synthesis of hemoglobin A, reduced rate of globin chain synthesis
No abnormal hemoglobin produced
Beta and alpha types depending on what chain has reduced synthesis
Calvarium, hyperbilirubinemia, jaundice
Chronic anemia that slows children’s growth
Impairment of intellectual development
Cardiorespiratory insufficiency
Thalassemia minor/trait vs thalassemia major
Minor: heterozygotes, mild non specific symptoms
Major: homozygotes, severe serious disease
Calvarium
“Crew cut” hair on readiographic study
There is a lot of hematopoiesis happening in the skull which is abnormal
In thalassemia
Definitions:
- Autoantigens
- Alloantigens
- Neoantigens
- Antibodies you make against yourself
- Against someone else’s RBCs
- When 2 things come together. Ex: penicillin gets absorbed into red cell membranes and forms something that causes antibodies to form
Polycythemia (difference between primary and secondary)
Increased numbers of RBCs
Primary (polycythemia vera): clonal proliferation of hematopoietic stem cells resulting in an uncontrolled production of RBCs and an increased total red blood cell mass - erythropoietin INdependent
Secondary: increased RBC volume because of erythroid bone marrow hyperplasia caused by erythropoietin - caused by hypoxia
Symptoms of Polycythemia
Hypertension Dark red or flushed face Headaches, visual problems, neurologic symptoms Splenomegaly Hypercellular bone marrow
4 leukocytic disorders
Leukopenia
Leukocytosis
Leukemia
Lymphoma
Leukopenia
Reduction in WBC count
Neutropenia due to bacterial infections or drugs
Lymphopenia due to bacterial, viral, fungal, or parasitic infections
Leukocytosis
Increased number of WBCs in peripheral blood
Neutrophilia from bacterial infection
Eosinophilia: allergies, some skin diseases, or parasitic infections
Lymphocytosis: viral infections, chronic infections, some autoimmune disorders
Splenomegaly, lymphadenopathy
Leukemia
Malignant disease involving WBCs or their precursors in bone marrow, peripheral blood (acute and chronic)
Can be myeloid or lymphoid
Bone marrow overrun with leukemia cells
Increased number of immature blood cells in peripheral blood
Complications: anemia, recurrent infections, uncontrollable bleeding
Doesn’t make red/white cells or platelets normally
Lymphomas
Lymphoid cell malignant diseases predominantly involving lymph nodes
Non-Hodgkins or Hodgkins
Plasma cell myeloma
Malignant disease of plasma cells
Non-Hodgkin’s vs Hodgkin’s lymphoma
NH: B, T, or NK cells
H: B cell only
Translocations:
- 8,14
- 9,22
- 15, 17
- Burkitt’s lymphoma
- Chronic myelogenous leukemia (Philadelphia chromosome)
- Acute promyelocytic leukemia
Acute lymphoblastic leukemia
Most common form of leukemia in children
Almost always B cell origin
Massive infiltration of bone marrow, peripheral blood with immature lymphoid cells
Symptoms: recurrent infections, weakness, bleeding into skin and major internal organs
Treatment: chemo - remission possible in nearly all patients
Acute Myelogenous Leukemia
Most common form of acute leukemia in adults
Clonal proliferation of myeloid precursors in bone marrow
20% abnormal cells, or cytogenetic abnormalities
Without treatment, most patients die within 6 months after symptom onset
Chronic Myelogenous Leukemia
Bone marrow, peripheral blood overrun with neutrophils and their precursors
3 phases: chronic, accelerated, blast crisis
Treatment: tyrosine kinase inhibitors
Philadelphia chromosome, with BCR-ABL gene rearrangment t(9;22)
Chronic lymphocytic leukemia
Malignant disease involving lymphocytes (almost all B cells)
Most patients over 50
Should be suspected if lymphocytes greater than 5000/mL
Median survival: 7-9 years from diagnosis
Non-Hodgkin’s Lymphomas
No benign lymphomas
Most have B-cell phenotype
All age groups affected (more common in adults than children)
Can spill over into blood; present as leukemia
Involve lymph nodes, bone marrow, spleen, thymus, but can be of extranodal origin
Follicular lymphoma
Most common form of lymphoma in US
Mostly older people
Slow growing
Presents with long-standing enlargement of lymph nodes, mild constitutional symptoms
Median survival: 7-9 years after diagnosis
Diffuse Large-Cell Lymphomas
Most common aggressive form of NHL
Tissue in filtrated by large lymphoid cells with irregular nuclear outlines, prominent nucleoli
Complete remission induced in 75% of patients with chemotherapy
Is it easier to treat fast or slow growing cancers? Why?
Fast growing
If they grow more rapidly they are more sensitive to the chemos
Burkitt’s Lymphoma
Highly malignant tumor composed of small B-cells
Extranodal masses: more prominent than enlarged lymph nodes
Endemic and sporadic variant
Most children and young adults can be cured
Hodgkin’s Lymphoma
Bimodal age distribution curve: peaks at 25 and 55 years
Five types
Reed-Sternberg cells present
Clinically: enlarged lymph nodes, rarely extranodal involvement or leukemic spread
5 types of HL
Nodular sclerosing Lymphocyte rich Mixed cellularity Lymphocyte depleted Lymphocyte predominant (non classical)
Classical vs Nonclassical HL
Reed-Sternberg cells present in classical only
Reed-Sternberg cells
Bilobed or multilobed nucleus, prominent nucleoli surrounded by clear halo
Plasma Cell Myeloma
Malignant disease of plasma cells Most patients older than 45 Proliferate in bone marrow Punched out holes in calvaria vertebrae Hypercalcemia, renal failure, anemia, leukopenia
