Hematopoietic and Lymphoid System Flashcards
Anemias of increased RBC destruction:
-4 types
- hereditary spherocytosis
- Sickle Cell Anemia
- G6PD Deficiency
- Thalassemia
*Anything that deforms cells basically
hereditary spherocytosis
- causes
- how to remember
spherocytosis = “sphere shaped” RBCs
Causes:
- Intrinsic
- 75% Autosomal Dominant
- 25% Autosomal recessive
hereditary spherocytosis
-pathophysiology
- Mutation makes hard for RBCs to keep doughnut shape
- RBCs are less stable, so lose membrane fragments and adopt simpler sphere shape
- Sphere shape not as flexible so RBCs get stuck in spleen and lysed more often
hereditary spherocytosis
-Clinical
- Jaundice*
- Hemosiderosis*
- Pigment Stones*
- Splenomegally
*Due to increased hemoglobin degradation
Sickle Cell Anemia
-What is it?
Doughnut is also the optimal shape for malaria
As a defensive mechanism, RBCs adopt another shape: sickle shape
(HbS for Sickle Shaped)
Sickle Cell Anemia
-Pathophysiology
- HbS polymerize and stick together when deoxygenated
- Sickling initially reversible
- Repeated sickling leads to membrane damage and irreversible sickling
- Stick in spleen more easily and are destroyed
Sickle Cell Anemia
-Clinical
- Chronic hemolytic anemia
- increased number of immature RBCs*
- Hyperbilirubinemia*
- Prone to infection
- Splenomegally as adult
- VASO-OCCLUSIVE PAIN CRISES:
- ->hypoxic injury to bone marrow
- ->increased stroke risk
G6PD Deficiency
- What is normal function?
- How to remember
G6PD: normal function is to recycle reduced glutathione “G for Glutathione”
-Reduced Glutathione is needed to protect cells from oxidative stress
“G6PD…Glutathione…Stress…Bites…Beans”
G6PD Deficiency
-Pathophysiology
-Without G6PD not enough reduced glutathione and oxidative stress “bites” membranes of cells creating “bite cells” (think called schistocytes)
G6PD Deficiency
-Symptoms may occur after ingesting:
- FAVA beans
- MOTH balls
- Antimalarials
- Sulfonamides
Thalassemia
-What is it?
-Deficient globin synthesis of the a- or B-globin chains
Thalassemia
-Pathogenesis
Target cells:
- cells with unbalanced ratios of globin chains
- these cells are more likely to be lysed
Thalassemia
-Clinical
- Bone marrow has to work harder to churn out cells
- Iron overload leading to severe hemosideris
- NEW BONE FORMATION DUE TO MARROW HYPERPLASIA RESULTS IN DISTINCTIVE “CREW CUT” APPEARANCE OF THE SKULL IN X-RAY
Anemias of diminished erythropoiesis
-Two kinds
- Iron Deficiency Anemia
2. Pernicious Anemia
Iron Deficiency Anemia
-Causes
- Chronic blood loss
- dietary deficiency
- inadequate iron absorption (celiac disease, decreased stomach acid production)
- Increased iron demands (Pregnancy, Lactation, Infancy*)
*Pregnant women and infants have higher demands in general hehe
Iron Deficiency Anemia
- Histopathology
- Clinical
Histopathology:
- Anisocytosis (cigar-shaped cells)
- microcytic-hyperchromic anemia
Clinical: everything related to iron is low
-low bone marrow iron stores
-low serum iron
-low serum ferritin levels
EXCEPT: total iron binding capacity is increased
Pernicious Anemia
- What is it
- How to remember
- Causes
-Anemia caused by impaired DNA synthesis and maturation of RBC precursors in Bone Marrow
“No other anemias start with P. P looks like B and F”
Causes:
- B12 deficiency* (not enough Intrinsic Factor)
- Inadequate Folate (malnutrition, alcoholism, pregnancy)
*Autoimmune attack of gastric mucosa atrophies the fundic glands
Polycythemia
- What is it?
- Two classification
- Two types (which i suppose can apply to each class)
Polycythemia is an abnormally high RBC count with increased hemoglobin level
Classifications are Primary and Secondary
Types:
- Absolute: actual increase in RBC mass
- Relative: increased hemoconcentration due to a decreased plasma volume
Primary Polycythemia
Primary Polycythemia:
- More RBCs without an increase in EPO
- Eg Polycythemia Vera (“True” Polycythemia:)
- -> EPO independent RBC proliferation cuz of mutations in EPO receptors
Secondary Polycythemia
What?
Caused by?
Too much EPO for a variety of reasons Reasons: 1. Compensation -Lung Disease -High altitude -cyanotic heart disease 2. Paraneoplastic syndromes -Tumors (eg Renal Cell Carcinoma) can secrete EPO 3. Genetic Disorders -chuVash (mutated VHL) -Prolyl hydroxylase mutations
Polycythemia
-Clinical (applies to all types of polycythemia)
- Viscous Blood
- cardiac function and blood flow impaired as a result
- Skin Dark Red
Leukopenia
- What is it
- Types of Causes
WBC deficiency
Causes:
- Decreased Production
- Ineffective Production
- Increased Destruction
Leukopenia
-Things that lead to Decreased WBC Production
- Irradiation
- Drugs
- Viral infections
Leukopenia
-Things that lead to ineffective production
megaloblastic anemia
Leukopenia
-Things that lead to increased destruction
- autoimmune related
2. idiopathic infections
Leukopenia
- Bone Marrow Responses
- Clinical
Bone Marrow Responses:
- Marrow hypercellularity
- response to excessive destruction (more cells cuz pumping out more WBC progenitors - Marrow Hypocellularity
- Drugs suppress or are toxic to WBC/RBC production so there are less RBC/WBC progenitor cells
Clinical:
-Vulnerable to infections (duh)
Types of Leukemia
- Acute Promyelocytic Leukemia (APML)
- Chronic Myelogenous Leukemia (CML)
- Acute Lymphoblastic Leukemia (ALL)
All leukemias have to do with the bone marrow, contrasting to lymphomas which originate in lymph nodes
acute promyelocytic leukemia (APML)
- mutation
- Tx
mutations in genes encoding TFs required for normal myeloid cell differentiation
mutation:
-In the fusion protein PML/RARA (a TRANS-cription gene)
-This blocks differentiation at the ProMyelocytic* stage, increasing cell survival
Tx:
-TRANS-cription gene so Tx with all-TRANS retinoic acid
*aPMl so remember blocks differentiation at the ProMyelocytic stage
Chronic Myelogenous Leukemia (CML)
-how to remember
myelogenous. ..myeloproliferative disorder…hyperproliferation…hyperproliferation of neoplastic myeloid progenitors
* Unlike APML, CML has the ability to differentiate terminally
chronic myelogenous leukemia (CML)
- Causes
- What is required to Dx
Causes:
- philadelphia chromosome and or demonstration of BCR/ABL fusion gene*
- This leads to activation of mutations in tyrosine kinase GF receptors causing increased growth and survival
*philadelphia chromosome and or demonstration of BCR/ABL fusion gene (caused by philadelphia translocation) required to diagnose
Acute Lymphoblastic Leukemia (ALL)
ALL: second L for Lymphoblasts
-specifically immature B lymphoblasts
Immature=childhood
-this is the most common childhood leukemia (what Steve Davis had)
Mature B Cell Lymphomas
- Diffuse Large B-Cell Lymphoma (Large BCL)
- Burkitt Lymphoma
- Hodgkin Lymphoma
- Multiple Myeloma
Diffuse Large B-Cell Lymphoma (Large BCL)
how to remember:
- who it affects
- histopathology
- Gene rearrangements
Large=Older
-most common lymphoma in adults
Histopathology:
Large-large cells-LARGE NUCLEOLI
Gene rearrangements:
BCL-Gene rearrangements of BCL2 and BCL6
Burkitt Lymphoma how to remember: -Who does it affect -What causes it -What gene causes it?
who does it affect?:
-Burkitt-kitt-kid:most common childhood malignancy in central africa
what causes it?
-Ebstein Barr Virus
(burkitt has two t’s, Barr has two r’s
What gene causes it?
- Burkitt-kit-tik which rhymes with mic
- caused by the MYC oncogene
Hodgkin Lymphoma
- What is it?
- Who does it affect?
What is it?
-Clonal neoplasms of B lymphocytes
Affects who?
-Burkitt was for kids, Large BCL for adults, Hodgkin is the intermediate (10-30 year olds)
Hodgkin Lymphoma
- Cause
- Dx
- how to remember these
Cause
-arises from a single node or chain of nodes: staging is important as a result
Dx:
-Reed-Sternberg cells: large atypical mononuclear/multinuclear tumor cells
“Sternberg…Staging”
Multiple Myeloma
-What (use definition to remember pathophysiology_
malignant disorders of terminally Differentiated B lymphocytes
-uncurable (untreated: 6 mo survival, chemo: 3 yr survival)
terminally Differentiated b lymphocytes
- Destructive lesions*
- Diffuse Demineralization*
- Dysregulation of D cyclin
- what happens to bone marrow cuz of dysregulated d cyclin
terminally differentiated B lymphocytes
-secrete abnormal ab called Bence-jones protein which Block up or destroy lining of kidneys
