7 - Hematolymphoid Pathology Flashcards
Describe normal hematopoiesis and lymphopoiesis
Hematopoiesis: synthesis of blood cells, different cell lines each undergo differentiation into committed cells
Lymphopoiesis: synthesis of lymphoid cells. B cells mature in BM, T cells in thymus
What are the main components of peripheral blood? What are some important components of each layer?
Plasma (55%)
- albumin
- immunoglobulins
- clotting factors
Buffy coat (<1%)
- leukocytes
- platelets
Erythrocytes (45%)
- RBC
- serum
Describe the structure of Hb
- consists of 4 globin chains
- each chain has a heme mlc that contains iron
- in most adults, chain is 2 alpha 2 beta
What are the two main types of bleeding in the “increased loss” cause of anemia?
Acute bleeding = trauma
Chronic bleeding = GI bleeding
Describe the inherited (3) and acquired (1) diseases related to destruction of abnormal blood cells
Inherited:
- membranopathy (hereditary spherocytosis)
- enzymopathy (G6PD deficiency)
- abnormal Hb (sickle cell disease)
Acquired:
- PNH (paroxysmal nocturnal hemoglobinuria)
What are the 4 causes of destruction of NORMAL RBC?
- immune hemolytic anemia
- repetitive trauma
- infections (malaria)
- chemical/toxic injury (lead poisoning)
What are three categories of decreased RBC production and name the type of anemia associated with each
- Nutritional deficiencies
- iron deficiency anemia
- Megaloblastic anemia (B12/folic acid def) - Bone Marrow Failure
- Aplastic anemia - Inherited genetic defects
- Thalassemia
What are the 4 signs and 6 symtpoms of anemia?
Signs:
1. pale skin
2. pale mucosa
3. spoon nails, brittle nails
4. tachycardia (heart rate >100 bpm)
Symptoms:
1. fatigue
2. Weakness, exercise intolerance
3. Shortness of breath
4. drowsiness
5. chest pain
6. Unusual cravings (pica, ice)
Where is iron absorbed? How is it stored?
Absorbed in small intestine
Stored in ferritin, which aggregates into brown granules called hemosiderin
4 causes of iron def anemia?
- decreased intake
- decreased absorption
- increased loss
- increased requirements
3 lab results/diagnosis techniques of iron def anemia?
- blood smear
- Hb and low hematocrit
- serum iron and low ferritin
Treatment of iron def anemia?
iron replacement
What is aplastic anemia?
Loss of multipotent stem cells resulting in pancytopenia
Primary and secondary causes of aplastic anemia?
Primary = idiopathic
Secondary = related to BM suppression (chemicals, radiation, viral infection, inheritance)
2 lab results of aplastic anemia?
- CBC -> pancytopenia
- BM biopsy -> decrease in blood forming cells
2 causes of megaloblastic anemia?
- Vit B12 or folic acid deficiency
- Pernicious anemia, Crohn’s diseaese, gastric resection
2 lab results of megaloblastic anemia?
- blood smear -> oval macrocytes, large hyper-segmented neutrophils
- BM biopsy -> hypercellular with megaloblasts
3 pathogenesis of megaloblastic anemia?
- deficiencies delay normal maturation of RBC
- RBC precursors don’t mature but instead transform into megaloblasts
- Megaloblasts destroyed in BM/spleen
Treatment of megaloblastic anemia?
Give patients B12 intravenously or folic acid orally
Is thalassemia a quantitative or qualitiative defect in Hb? What about Sickle Cell Disease?
Thalassemia = quantity
Sickle Cell = quality
For α-thalassemia, what is defective? Describe the differences btwn 1 gene mutation up to 4 gene mutations.
Defect in synthesis of α chain
1 gene defect = asymptomatic
2 gene defect = mild anemia
3 gene defect = moderate to severe
4 gene defect = hydrops fetalis, intrauterine death
For β-thalassemia, what is defective? Describe the difference btwn thalassemia major and minor
Defective synthesis of β chain
Thalassemia minor (heterozygous) = mild, nonspecific symptoms
Thalassemia major (homozygous) = severe, serious disease
Why is it bad to have too many alpha globin chains? Too many beta globin chains?
Alpha = too many alpha chains results in α-globin aggregates (intravascular hemolysis)
Beta = not good for oxygen delivery
What is sickle cell disease caused by? What two things does it normally result into?
Defective β globin chain caused by point mutation (substitution of glutamic acid by valine)
Chronic hemolytic anemia & small vessel occlusion
What is the difference btwn
Sickle Cell ANEMIA vs TRAIT?
Anemia = homozygous for defective gene
Trait = heterozygous for defective gene
Describe HbS levels that lead to asymptomatic, mild-moderate, and severe disease in relation to Sickle Cell Anemia
HbS < 40% = asymptomatic
HbS 40% - 80% = mild to moderate disease
HbS 80% = severe disease
How much percent of HbS is present in people with sickle cell trait? What symptoms do they experience?
≤ 40% of Hb is HbS
Trick question: they are asymptomatic!
What is the main cause of hereditary spherocytosis? What kind of inheritance pattern is this disease?
Defect in structural proteins in RBC (e.g. ankyrin, band 3)
Autosomal Dominant
Three clinical findings of hereditary spherocytosis?
- anemia
- splenomegaly (mega spleen)
- jaundice
What causes immune hemolytic anemia? What are three examples?
Destruction of normal RBCs by antibodies
Incompatible blood transfusions, HDFN, autoimmune hemolytic anemia
Primary and secondary (3) causes of autoimmune hemolytic anemia?
Primary = idiopathic
Secondary = drugs, lymphoproliferative disease, SLE
What is polycythemia? What’s another name for it?
Increase number of RBC
AKA erythrocytosis
Relative cause of polycythemia?
Hemoconcentration (dehydration) is increase in blood cell concentration due to decreased volume of water or plasma
Absolute causes of polycythemia?
Primary (low EPO): polycythemia rubra vera
- uncontrolled production of RBC due to myeloproliferative disorder
Secondary (high EPO)
- living at high altitude
- chronic lung disease
Symptoms and treatment of polycythemia?
Symptoms: increaed blood viscosity, tends to clot
Treatment: phlebotomy (blood letting)
What is leukopenia characterized by? What are the two main types mentioned in the lecture?
Decreased WBC
Neutropenia and lymphopenia
Similarities and differences btwn neutropenia and lymphopenia?
Similarities:
Causes include ineffective synthesis (e.g. aplastic anemia, drugs) and accelerated removal/destruction (e.g. SLE)
Differences:
Neutropenia = decreased neutrophils
Lymphopenia = decreased lymphocytes
What is leukocytosis? Is it typically benign or malignant?
Increased number of WBC
Typically benign, often associated with splenomegaly and lymphadenopathy.
Can lead to hematolymphoid malignancy if persists
Three examples of leukocytosis and their causes?
Neutrophilic: bacterial infections
Eosinophilic: parasites, allergens, drugs
Lymphocytosis: viral infections, chronic infections (TB)
Two main malignant diseases of leukocytes?
Leukemia and lymphoma
Compare and contrast the two main types of acute leukemia. Describe: demographic, type of blast cell involved, treatments
ALL (20%)
- most common type in children
- BM + blood infiltrated with lymphoid blast cells
- Treatment: chemotherapy
AML (40%)
- most common type in adults
- BM + blood infiltrated with myeloblasts
- Treatment: chemotherapy, radiotherapy, BM transplant
Compare and contrast the two main types of chronic leukemia. Describe: demographic, BM infiltrate type, characterizations, and treatments
CML (15%)
- usually affects adults
- BM infiltrated by myeloid cells
- characterized by Philadelphia chromosomes [t(9;22)]. Three phases: chronic, accelerated, blast crisis
- treatment: Gleevec (tyrosine kinase inhibitor)
CLL
- usually affects elderly
- VM infiltrated by lymphoid cells
- involvement of lymph nodes/spleen (small lymphocytic lymphoma SLL)
- Treatment: not chemotherapy
What are three common clinical presentations of both types of lymphoma?
- Lymphadenopathy
- Constitutional symptoms (fever, weight loss, night sweats)
- Infiltration of organs
What are the five main types of HL?
Classical HL (90%):
1. Nodular Sclerosis HL (70%)
2. Mixed Cellularity HL (20%)
3. Lymphocyte-rich HL (5%)
4. Lymphocyte-depleted HL (5%)
- Nodular lymphocyte predominant HL (10%)
Common characteristic and treatment of HL?
Reed Sternberg malignant B cell
Chemotherapy
What are the two main types of B-cell NHL?
Indolent
- Follicular lymphoma (FL)
- Small Lymphocytic lymphoma (SLL)
Aggressive:
- Burkitt Lymphoma (BL)
- Diffuse Large B Cell Lymphoma (DLBCL)
Compare and contrast FL, DLBCL, and BL in terms of commonality, demographic, grade, and architecture/appearance
FL:
- most common type
- elderly
- low grade
- follicular architecture
DLBCL
- most common aggressive lymphoma
- high grade
- diffuse architecture
BL
- Rare
- affects children and young adults
- highly malignant
- Starry sky appearance
What is multiple myeloma? At what age is it most prominent?
Malignant transformation of plasma cells (plasmacytoma)
Middle age
4 Steps in Multiple Myeloma Pathogenesis?
- single plasma cell malignantly transforms
- clones itself
- clones secrete monoclonal IgG
- Monoclonal IgG causes spike in Serum Protein ElectroPhoresis (SPEP)
4 Clinical features of multiple myeloma? (Hint: CRAB)
Calcemia (hypercalcemia)
Renal failure
Anemia
Bone lesion
3 Diagnosis of multiple myeloma?
biopsy, imaging, Serum Protein ElectroPhoresis (SPEP)
What are three examples of vascular bleeding disorder causes?
- Mechanical trauma
- Vessel wall fragility (old age, scurvy, CT disorders)
- Immune damage (vasculitis)
What are three example of quantitative (thrombocytopenia) platelet bleeding disorders?
- Decreased production - aplastic anemia
- Increased destruction - autoimmune disorders (SLE)
- Increased utilization - disseminated intravascular coagulation (DIC)
What are two congenital and two acquired qualitative platelet bleeding disorders?
Congenital:
- defective platelet adhesion (Bernard-Souiler syndrome)
- defective platelet aggregation (Glanzmann thrombasthenia)
Acquired:
- NSAIDs
- aspirin
What are the two main types of bleeding disorders?
Vascular and platelet
What are the two main types of clotting factor disorders?
Congenital and acquired
Two main congenital clotting factor disorders? What factors are affected? Which pathway is affected?
Hemophilia A (factor 8)
Hemophilia B (factor 9)
Intrinsic pathway
2 clinical features of congenital clotting factor disorder? 3 treatments?
Clinical features:
- spontaneous hemorrhage
- internal hemorrhage
Treatment:
- factor replacement
- blood transfusions
- gene therapy
What are the three acquired clotting factor disorders?
- inadequate production (liver disease)
- Increased consumption (DIC)
- Anticoagulants (heparin, warfarin)
What is hemosiderin
When ferritin turns into small brown aggregates when storing iron
