Heme Onc Flashcards
Alpha Thal
Defect in alpha chain that leads to decreased production
- 4 in total, 4 mutated leads to Hb Bartz and fetal hydrops
- 3 mutated leads to B4 tetramers of HbH
- Cis mutations on same chromosome are more common in asians and transmutations are more common in blacks
Beta Thal
- Splicing or promotor error leads to altered expression level
- Minor usually presents with a slight increase in HbA2 (D) and major usually presents with profound anemia and increased fetal hemoglobin
- Can get secondary hemochromatosis and treat with difuimox
Lead Poisoning
- Leads to a sideroblatic anemia with increased Fe deposits in mitochondria
- Inhibits Ferrocheltase
- Basophilic stippling occurs because of dysfunction of An enzyme that degrades ribososmes, basophilic stipplic is ribosomal RNA
- Dementia, belly pain, decreased IQ
- Wrist drop and neurologic signs
- Treat with succimer, EDTA, dimercaperol
Sideroblastic anemia
- X linked is defect in ALA dehydratase which leads to decreased heme synthesis in mitochondria leading to Fe accumulation and sideroblastic anemia
- Can also be seen with B6 deficency as B6 is a necessary cofactor for HLA-D
- Decreased B6 from INH, Alcohol, dietary
- Treatment is B6
- There will be elevated Fe and Ferretin with normal TIBC
Folate Deficency
Caused by diet, MTX, phenytoin
- Megaloblastic with pancytopenia, no neurologic complaints
- Increased homocysteine with normal methylmalonic acid
- Glossitis
B12
Pernicous anemia, D lattum from fish, Crohns, PPI?
- Leads to megaloblastic anemia with neurologic dysfunction
- Elevated homocysteine and methylmalonic acid
- Involves posterior columns, spinocerebellar, and corticospinal
- May also cause dementia
Orotic Aciduri
- Impaired UDP synthase, backs up into urea cycle (Carbamoyl P)
- Doesn’t correct with Folate and B12
- Give uridine to bypass enzyme
Macrocytosis without megaloblastosis
Think of liver or alcoholic
-Can also be due to drugs which cause reticulocytosis: 5-FU, AZT, hydroxyurea
Intravascular
Intrinsic red cell defect and lysis in vasculature, decreased haptoglobin and increased LDH
-PNH and mechanical valve
Extravascular
- Most commonly in spleen, stuctural or functional defect
- UCB emia, increased LDH, Jaundice
Anemia of chronic disease
Mediated by cytokines IL-6 that increases hepcidin from liver which is master regulator
- Also reduces EPO
- Increased ferretin with decreaed Fe and TIBC, sequester in tissues
Aplastic
Viral
- Drugs, Chemo, Radiation
- Fanconi’s syndrome (DNA repair)
Spherocytosis
- Defect in anhyrin or spectrin leads to osmotic fragility (band 3)
- increased MCHC
- Overactive spleen that consumes RBC leadin to elevated UCB
- Aplastic crisis
G6PD
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Pyruvate Kinase
Defect in glycolysis (PEP synthesis) leads to decreased ATP and fragility of red cells
-Hemolytic disease in newborns is common presentation
HbC
Milder than SS
-Add lysine instead of valine
PNH
- GPI to DAF leads to hemolysis comlpement mediated
- Increased risk of venous thromboembolus
- PE or Budd Chiari
- Diagnose with flow
- Is a mutation post zygotic, in HSPC
Sickle Cell
Gluatmine to valine -Sickling at low Oxygen tensions -Splenic sequestration crisis: Massive autoinfarcion of spleen leading to rapid decrease in RBC number -EMH Renal papillaryu necrosis
Warm Hemolytic Anemia
- IgG
- CLL, Lupus, Methyldopa
- Haptens like penicilin
Cold Hemolytic anemia
-CLL, M Pneumonia, Hepatitis, mono
Microangiopathic
HUS, TTP, DIC, SLE, Malignant HTN
OCP changes to Fe profile
-Increase binding globulins leading to decreased increased ferretin
AIP
- Defect in porphobilinogen deaminase, or uroporphyrin synthase
- Leads to increase in uroporphyrin and porphobilinogen
- Psychosis and red urine
- Brought on by drugs (phenobarbitol)
- AD in cytosol
PCT
- Skin hypersensitivity
- Uroporphyrin deaminase leads to tea colored urine and skin sens
Hemophilia A/B
defect in intrinsic cascade, factors 8 and 9
- Hemarthroses and increased PTT
- Significant bleeding
- XR
Vitamin K deficency
-Longterm antibiotics or pancreatic/malabsorption
Platelt defects
-Lead to purpura and mucosal bleeding (epistaxis)
Bernard Soulier
GP 1b impaired adhesion, increased BT
-Decreased platelt count
Glanzmans
GP2b3a impaired aggregation, increased BT. Normal platelt count
ITP
Antibody to Gp2b3a leading to consumption of platelts by spleen
- Leads to thrombocytopenia and increased megaK
- Bleeding time
- Commonly young viral
TTP
Defect is ADAMSTS13, which is MMP that cleaves vWF multimers
- Leads to increased vWF multimers that elads to abberant clotting and platelet consumpton
- microangiopathic hemolytic anemia and decreased palteltes
- Neurologic and renal symptoms
vWF defect
AD decrease in vWF number or function
-Leads to increased bleeding time
Dx with risotcetin assay
-Treat with DDVAP to increase release from WP bodies
-vWF also protects factor 8, so depending on severity, can decrease factor 8 levels and increase PTT
-Most common inherited bleeding disorder AD
Factor V lieden
Site on factor 5 can’t be cleaved by protein C
- Activated by thrombomodulin and factor S
- Hypercoagulable
PT
-Noncoding region increases expression leading to hypercoag
ATIII
- Decreased levels will lead to hypercoag
- Blunted PT response to heparin
C/S def
Leads to hypercoag, can have skin necrosis with warfarin administration
Transfusions
-Can induce hyperkalemia due to lysed RBC or hypocalcemia due to citrate
Leukemoid Vs Leukemia
- Leukemoid will have classic left shift and will have luekocyte acid phosphatase
- Leukemia will not have LAP
Hodgkins
- Reed Sternberg cells CD15 and 30
- Involves a single group of nodes
- Constiutional B symptoms
- Greater than 50% arise in the context of EBV
Nonhodgkins
- Multiple nodes throughout body, don’t involve Reed Sternberg cells,
- Commonly effect immunosuppressed
- majoirty are B cells and are monocellular
Reed Sternberg
- Larg bilobed/binucleate cells, positive for CD 15 and 30
- Secrete cytokines and attract a pleimorphic cell mixture
Hodgkins
- Younger and older
- Multiple cell type
- Nodular sclerosing is the most common and has large bands of fibrosus throughout nodes
- Lymphocyte mixed or depleted is a worse prognosis
Follicular Lymphoma
14: 18 translocation
- 14 is Ig and 18 is BCL-2
- LEads to lack of death, large germinal celnter appearing B cells that lack macrophages, can turn into DLBCL
- Most common
DLBCL
- Loss of normal cellular architecture and germinal center morphology
- USually the end of the road for other cancers
- Aggressive and worse prognosis
Burkitts
- t8:14, puts C-Myc onto IgHC gene region
- LEads to massive growth (Jaw/ABdomen) characterized by lots of macrophages and cellular death in starry sky backgound
- Is associated with EBV (Like hodgkins)
Mantle
t11: 14
- Move cyclin D onto promotoer leads to overexpressiona dn increased rate of entry into S phase
Marginal Zone
- Occurs in the context of chronic inflammation
- H Pylori, Sjogrens, Hashimotos
Adult T Cell
Usually has cutaneous involvemtn
-Associated with HTLV-1 and seen most commonly in asians and carribeans
Szesary/Mycosis Fungoides
T cell lymphoma that has extensive skin involvment
- Normally can be treated
- Sezeary when enters blood and mycoces when confined to skin
Multiple Myeloma
- Leukemia of plasma cells that have a characteritic clock faced nuclei with nucleoli (Produce large ammounts of Ig) and have cytoplasmic inclusions of Ig
- Characterized by M spike of monoclonal Ig on SPEP
- Light chains are excreted into the blood in excess and cause AL amyloid throughout body and especially in kidney. Nephrotic syndrome that may progress to renal failure
- Lytic bone lesions lead to hypercalcemia
- Anemia and pancytopenia due to overdrowding of marrow space
- Increase susceptibility to infection, and is most common cause of death
- Elevated Ig secretion also puts a lot of positive charge and protein into the blodd that breaks the zeta potential between RBC and leads to roleaux formation
- Hyperviscosity also common
Waldenstroms
- M spike of IgM, lack of lytic lesions and other signs
- Increaed hyperviscosity syndrome
MGUS
-ELevated M spike that is IgG or IgA that does not have other findings consistent with MM
Leukemia
- INcrease in wWBC in the blood
- Major problem is a loss of normal marrow function leading to anemia and immunodeficency
- THere will also be hyperviscosity and decrease platelets that can lead to hemorrhage
- Acute is greater than 20 percent blasts
- THere will be no increase in LAP which is how you distingush from leukemoud reactin
- Also look for a monoclonal appearance of Differential
ALL
- Leukemia of immature B and T cells, B cells is most common
- Can be identigied with tdt positivity and CALLA
- Commonly seen in downs syndrome
- T ALL may present as a mediastinal mass in teenagers due to involvment of thymus
- If cells enter CNS and testes treatment becomes more difficult becase drugs can’t cross BBB
SLL/CLL
- Mature naive lymphocytes that are enter blood or nodes
- SLL has more nodal involvment while CLL has more blood involvment
- SLL may progress to DLBCL
- CLL is noticed by the appearance of smudge cells on a smear
- Increase risk of warm and cold agglutanins due to naive mature cells
- hypogammaglobulinemia and increased risk of infection
- Seen very comonly in older patients, and is indolent unless transformes to other kinds.
Hairy Cell
- TRAP positive mature B lymphocytes
- HAve characteristic cytoplasmic extensions
- Treat with clarbarapine, which is an adenosine analog that leads to toxic accumulation and cell death
- Can get a dry tap on marrow aspirate and will see increased EMH and HSM
AML
- Acute leukemia with an increased number of blasts, greater than 20 percent
- Many subtypes and distinguished with presence of auer rods which are crystalized MPO, if these cells are ruptured can activate compliment cascade and leads to DIC
- M3 or APL is famous, has 15,17 translocation involving the ATRA receptor. Immautre cells that if treated with ATRA will mature and can be cured
- Can be a consequence of myelodysplastic syndromes
- Monocytes commonly infiltrate gums
CML
- Characterized by 9:22 translocation of BCR to ABL
- Treated with imatinib inhibitor of ABL
- Type of myelodysplasia, distinguish from a leukemoid reaction using LAP and also with the presence of basophils and other types of cells
- Immunodeficecny is the biggest risk
- Also can transform to AML
Langerhans Cell histiocytosis
- Langerhans cell tumor,
- involves skin and characteristic bierbeck granules
- S-100 positive (neural crest marker) also CD1a positive
- also can have lytic bone lesions
Myelodysplasia
- Characterized by JAK-2 mutations
- Increase in all cells and the disease is named for the most prominent one
Polycythemia Vera
- Myelodysplasia of RBC leads to increase in hematocrit
- OFten presents as pruritis folling shower, increased mast cell activation
- Hyperviscosity syndromes with blurry visiona dn headache, can also get budd chiari
- JAK 2 mutation is characteristic, needs phlebtemy
THrombocytosis
- Seen commonly in downs patients
- Is myelodysplasia of thrombocytes (MEgaK)
- Generaly has JAK-2 mutation
- Rarely transforms to malognancy becaue thrombocytes are anucleate
Myelofibrosis
- Burnout of marrow, fibrosis leads to teardrop cells
- See increased levels of EMH and HSM
PV causes
- Loss of volume leads to concentration of RBC
- PHysiologic adaptations to low oxygen (heart failure, lung diease, shunts)
- EPO producing tumors: RCC, HCC, VHL, Hydronephrosis and renal disease, wilms
