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Heme/onc Flashcards

1
Q

why can deoxy blood carry more CO2 for a given PCo2 than oxygenated blood?

A

Deoxyhemoglobin is a better buffer of H+ than oxyhemoglobin

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2
Q

DIC (consumptive coagulopathy) develops when blood is exposed to large amounts of what over a brief period of time?

A

Tissue factor.

Causes massive generation of thrombin –> coagulation. Eg amniotic fluid embolism or abruptio placentae

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3
Q

Hashimoto’s is an autoimmune dz of the thyroid in which thyroid parenchyma is destroyed by lymphocytic infiltrate. This increases risk of what cancer?

A

Non-Hodgkin B cell lymphoma

Sjogren synd and chronic H pylori gastritis also inc risk of NHBCL

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4
Q

Asian diet predipsoses patients to high incidence of gastric adenocarcinoma due to high concentration of what?

A

Food preservatives (nitrosamines, polycyclic hydrocarbons, nitrites)

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5
Q

Fever, microangiopathic anemia, thrombocytopenia, renal insufficiency, and neuro problems caused by what?
Labs?

A

TTP:
Deficiency in a metalloprotease that cleaves ultralarge von Willebrand factor multimers that combine with platelets (ADAMTS-13)
Antibodies recognize ADAMTS-13
Labs: schistocytes, inc LDH

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6
Q

Lack of what cellular organelle in erythrocytes results in inability to synthesize heme?

A

Mitochondria

needed for first and last 3 steps of heme synth

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7
Q

What substance is secreted by hepatic parenchymal cells that controls Fe storage and release by other cells involved in Fe homeostasis?

A

Hepcidin

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8
Q

Precursor B-ALL or T-ALL?

TdT+, CD10+, CD19+

A

precursor B-ALL

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9
Q

Precursor B-ALL or T-ALL?

TdT+, CD2, CD3, CD4, CD5, CD7, CD8, CD1a

A

precursor T-ALL

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10
Q

B or T cell marker? CD5

A

T cell

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11
Q

B or T cell marker? CD19

A

B cell

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12
Q

How does ESRD cause bleeding problems?

A

Build-up of up uremic toxins impairs platelet aggregation and adhesion. Platelet count is normal

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13
Q

Define O2 content of the arterial blood?
What happens to it in methemoglobinemia?
Anemia?

A

Both dissolved O2 and O2 attached to Hb

Decreased in both methemoglobinemia and anemia

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14
Q

Define partial pressure of O2.
What happens to it in methemoglobinemia?
Anemia?

A

Dissolved o2 in the plasma - unrelated to Hb function

Normal in both methemoglobinemia and anemia

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15
Q

How does >1 body blood volume (5-6L) of whole blood transfusions or pRBC cause paresthesias?

A

Citrate (found in stored blood) will be elevated. Citrate chelates Ca and Mg, and may reduce their plasma levels –> paresthesia

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16
Q

Activating mutations of what gene lead to constitutional activation of EGFR pathway, promoting inc cell proliferation and growth?

A

KRAS

Tumors with mutation in KRAS can resist anti-EGFR drugs (eg cetuximab and panitumumab)

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17
Q

Recurrent vaginal Candida infections indicates a patient has what? This patient has risk of developing a malignant B-lymphocyte proliferation associated with what?

A
  1. HIV

2. EBV (latent EBV infection is present in 90% of nl individuals, with reactivation common in the immunosuppressed).

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18
Q

How does carbon tetrachloride cause hepatic necrosis and fatty change of the liver?

A

Free radical injury

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19
Q

Platelet endothelial cell adhesion molecule 1 (PECAM-1) is involved in what part of inflammatory leukocyte accumulation?

A

Transmigration

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20
Q

ICAM-1 and CD18 beta 2 integrins are involved in what part of inflammatory leukocyte accumulation?

A

Tight adhesion and crawling

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21
Q

L selectin (on neutrophils) and E/P-selectin on endothelial cells are involved in what part of inflammatory leukocyte accumulation?

A

Rolling

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22
Q

Which is more aggressive? HER2 or ER receptor positivity in breast cancer?
What drugs are used to treat these?

A

HER2 - assoc with signal transduction
Tx
- HER2: Trastuzumab
- ER: tamoxifen

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23
Q

As PO2 increases on the oxygen dissociation curve, what is released?

A

H+ and CO2 are released from Hb (Haldane effect), and O2 binding to Hb is increased.
This occurs in the lungs where pO2 increases.

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24
Q

Infections or use of sulfa drugs can cause hemolytic anemia if a patient has what problem?

A 
G6PD deficiency (XR) - 
RBC use reduced NADPH to maintain glutathione to protect the cell against oxidative damage. 
RBC are more susceptible to oxidative damage during times of oxidative stress (eg use of sulfa drugs).
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25
Q

What drug targets a platelet surface glycoprotein receptor that binds fibrinogen to support platelet aggregation?

A

Abciximab - blocks GPIIb/IIIa

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26
Q

Melanoma and other tumors exhibit poor adhesion to what part of the ECM?

A

Fibronectin
Adhesion of cells to the ECM involves integrin-mediated binding to fibronectin, collagen and laminin. Differential integrin types affects adhesion

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27
Q

What is a significant adverse effect of ganciclovir therapy, especially with co-admin of zidovudine or TMP-SMX?

A

Neutropenia

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28
Q

What are common precipitating factors of G6PD deficiency anemia?

A
  1. infections
  2. Drugs: DAPSONE, antimalarials, sulfa drugs
  3. DKA
  4. fava beans
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29
Q

HER2 oncogene codes for what type of receptor that has tyrosine kinase activity? What is the function of the protein receptor?

A

Epidermal growth factor.

Accelerates cell proliferation

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30
Q

Patient with chronic pancreatitis can get macrocytic anemia how?

A

Diminished thymidine synthesis (impaired purine/pyrimidine synthesis) through Vit B12 and folate deficiency

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31
Q

Patient with new-onset neuro sx (numbness), anemia w/schistocytes, and thrombocytopenia likely has what?

A

TTP: Impaired cleavage fo vWF (def in ADAMTS13) –> prothrombotic

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32
Q

Patient on low calorie diet, abdominal pain, confusion and resolution with infusion of hemin is due to a deficiency in what enzyme?

A

Dx - acute intermittent porphyria
porphobilinogen deaminase deficiency plus ALA synthase induction (low calorie diet, meds, ETOH)
Note: Enzyme is also known as hydroxymethylbilane synthase or uroporphyrinogen I synthase.

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33
Q

Differentiate tacrolimus from sirolimus

A

Tacrolimus - prevents IL-2 transcription in T cells; inhibit calcineurin
sirolimus - prevents IL-2 signal transduction by inhibiting mTOR

34
Q

In anemia, arterial O2 content is decreased, arterial O2 sat and pO2 are normal, and venous pO2 is dec. Why does venous Po2 dec?

A

Dec o2 carrying capacity –> inc CO –> inc O2 extraction from tissues –> reduced venous o2 tension

35
Q

COPD does what to hematocrit?

A

Increase due to physiologic need to maintain perfusion

This is called a secondary erythrocytosis

36
Q

Accumulation of uroporphyrin in the urine and photosensitivity indicates what?

A

Porphyria cutanea tarda

Deficiency in uroporphyrinogen decarboxylase

37
Q

In melanoma tx, monoclonal antibodies block what cell surface receptor found on T lymphocytes that facilitate destruction of cancer cells?

A

PD-1 (program death)

inhibits cytotoxic T cells when it binds to its ligand PD-L1

38
Q

Key lab findings in polycythemia vera

A

Inc RBC mass, inc plasma volume, low epo

39
Q

Chronic lymphedema is a RF for the development of what cutaneous condition?

A

Cutaneous angiosarcoma (Stewart-Treves syndrome) - infiltration of dermis with slit-like abnormal vascular spaces. Poor prognosis

40
Q

Describe leukemoid reaction

A

Leukemoid - response to underlying condition. alk phos normal or increased. Smear shows Dohle bodies (basophilic peripheral granules in neutrophils)
Mature neutrophil precursors present (less likely to be a leukemia)
Note: decreased alk phos = CML

41
Q

How can you differentiate absolute from relative erythrocytosis (ie inc Hct level)

A

Relative - normal RBC mass

Absolute - increased RBC mass

42
Q

What can be used to treat multiple myeloma?

A

Proteasome inhibitors (eg bortezomib, a boronic acid-containing dipeptide) - blocking proteasomes results in accum of toxic itnracellular proteins and inc in pro-apoptotic proteins –> induce apoptosis of malignant plasma cells

43
Q

Key growth factors that promote angiogenesis in neoplastic and granulation tissue?

A

VEGF
Fibroblast growth factor
Note: proinflam cytokines (IL-1, IFN-y) can indirectly promote angiogenesis through inc VEGF expression

44
Q

Reticulocytes contain bluish cytoplasm why?

A

This immature RBC lacks a cell nucleus, but retains a basophilic, reticular network of residual RIBOSOMAL RNA

45
Q

Erythroid precursors in liver and spleen is indicative of what? This is frequently seen in what conditions?

A 
Extramedullary hematopoiesis (also seen in skull - spike)
Chronic hemolytic anemia like B-thal causes this
46
Q

Patients with familial retinoblastoma also have increased risk of what cancer?

A

Osteosarcomas

47
Q

Paraneoplastic cerebellar degeneration is what type of reaction?

A

Autoimmune - immune reaction against tumor cells that cross-react with normal cells, causing dysfunction and/or damage to healthy organs and tissues

48
Q

Increased osmotic fragility of RBC is diagnostic of what? Increased risk of what?

A

Hereditary spherocytosis due to dec surface area to volume ratio
Pigmented gallstones - inc bilirubin form lysed RBCs precipitates as calcium bilirubinate
aplastic crises from parvovirus b19
Note: MCHC is INCREASED d/t mild dehydration of RBC

49
Q

Clinical features suggestive of a malignant cause of back pain include what?

A

Occurrence at night
not relieved with rest or analgesics
Advanced age
systemic sx

50
Q

What syndrome is caused by an AD mutation in TP53? What cancers are most common?

A

Li-Fraumeni syndrome

Leukemia, sarcoma, tumors of breast, brain, adrenal cortex

51
Q

Pro-carcinogens are metabolized by what in the human body? This process also converts these pro-carcinogens into carcinogens capable of causing what?

A

Cytochrome P450 monooxygenase

Mutations in human DNA

52
Q

What are the 4 chronic myeloproliferative disorders?

Most often have a mutation in what?

A
  1. CML
  2. Essential thrombocytosis
  3. Polycythemia vera
  4. primary myelofibrosis
    3-4 have mutation in JAK2 (cytoplasmic tyrosine kinase) that results in persistent activation of STAT
53
Q

Sickle cell disease does what to the spleen

A

Repeated splenic infarcts (Vascular occlusion) –> fibrosis and atrophy (autosplenectomy)
Inc risk of infection with encapsulated organisms
Note: caused by a point mutation on the 6th codon of the BETA globin chains, resulting in substitution of GLUTAMATE residue w/ a VALINE residue leading physicochemical properties of Hb which will polymerize under hypoxic conditions.

54
Q 
Which of these are oncogenes vs tumor suppressors?
APC
BRCA1
KRAS
TP53
Rb
A

All are tumor suppressors except KRAS (proto-oncogene - gets activated in tumors). Others include BRAF, HER1/2, MYC

BRCA1 - DNA repair
APC - inactivated in FAP
TP53 - inhibits prolif of cells w/genetic probs
Rb - inhibit G1 to S
Others: VHL, WT1, NF1
55
Q

What increases in serum after Vit B12 replacement therapy is initiated in indiv with pernicious anemia?

A

Reticulocytes inc dramatically after initiation

Hb and erythrocytes inc more gradually

56
Q

Enoxaparin MOA?

A

LMWH
Binds and activates Antithrombin III –> binds factor Xa
Note: does not act on thrombin

57
Q

Thrombin time measures what? What drug has no effect on thrombin time?

A

Meds that directly or indirectly inhibit thrombin

Direct factor Xa inhibitors (eg apixaban, rivaroxaban)

58
Q

What substances is involved in the invasion of cancer cells into the basement membrane?

A

Metalloproteinases

Note: they are also involved in tissue remodeling and embryogenesis.

59
Q

Aplastic anemia causes pancytopenia as the bone marrow is replaced by fat cells and marrow stroma. Absence of what on physical exam is characteristic?

A

Splenomegaly

60
Q

Vascular endothelium secretes what substance to INHIBIT platelet aggregation? PROMOTE?

A
  1. Prostacyclin
  2. Thromboxane A2
    Prostacyclin exists in dynamic balance with TXA2 to maintain capillary patency and normal blood flow.
61
Q

Activating mutation of RET proto-oncogene is assoc with what?

A

Medullary thyroid cancers
Note: Bcl-2 is assoc with follicular lymphoma
RAS gene mutations are found in follicular thyroid cancer and some follicular adenomas

62
Q

What reaction causes inc DHF reductase and DNA polymerase?

A

Activated cyclin-dependent kinase 4 –> hyperphosphorylation of Rb protein (inactive) –> allows cells to transitino unchecked from G1 to S phase
Note: inc activity of DHF reductase and DNA polymerase indicate cell is S phase of cell cycle

63
Q

CO poisoning does what to:
Carboxyhemoglobin
PaO2
Methemoglobin?

A

Carboxyhemoglobin (level of CO bound hb) - increase
PaO2 - normal (doesn’t affect amt of o2 dissolved in plasma, but does dec O2 content of blood)
Methemoglobin - normal (CO doesn’t form Fe3+)

64
Q

High-o2 affinity Hb have reduced ability to release o2 in peripheral tissues (L shift). How does the body compensate?

A

Renal hypoxia –> inc EPO synthesis –> compensatory erythrocytosis

65
Q

Polycythemia vera is a myeloproliferative disorder characterized by uncontrolled erythrocyte production. The mutation in JAK2 is what type of tyrosine kinase?

A

Non-receptor (cytoplasmic) tyrosine kinase

Note: intrinsic (receptor) tyrosine kinases include insulin, insulin-like GF, and epidermal GF

66
Q

Increased myeloid precursors on peripheral blood smear indicate what?

A

CML
eg inc blast cells (almost always indicate hematologic malig) - myeloblast
Differentiate from leukemoid with alk phos.
CML has dec alk phos. Leukemoid rxn has nl or inc alk phos

67
Q

Hereditary hemochromatosis is caused by a MISSENSE mutation in the HFE gene, resulting in what?

A

Excessive intestinal iron absorption and organ damage (cirrhosis, DM, cardiomyopathy, arthropathy) d/t Fe accum w/in parenchymal tissues.
Inc risk of liver cirrhosis and HCC

68
Q

Pancytopenia, dry tap on bone marrow aspirate, splenomegaly indicates what?
What does the peripheral blood smear show?

A

Hairy cell leukemia - see lymphocytes with cytoplasmic projections

69
Q

Erythropoiesis-stimulating agents can substantially improve anemia symptoms and avoids the need for blood transfusions in CKD and dialysis. What are some risks assoc with these agents?

A

HTN

thromboembolic events

70
Q

What is assoc w/painless waxing and waning lymphadenopathy

A

Follicular lymphoma (MC indolent NHL in adults)
B cell origin
t(14;18) assoc w/bcl-2 oncogene

71
Q

Compare hemoglobin to myoglobin

What happens to the O2 dissoc curve if only monomeric beta-hemoglobin subunits are present?

A

Hemoglobin - tetramer. O2-dissoc curve is sigmoidal bc of heme-heme interaction.
Myoglobin - monomeric protein found in blood after mm injury. No heme-heme interactons, so o2-dissoc curve is hyperbolic
Indiv subunits of hb are structurally analogous to myoglobin, so if separated, o2-dissoc curve will be hyperbolic

72
Q

Newborn with profound anemia, jaundice, positive Coombs test, nucleated erythrocytes, and extramedullary hematopoiesis

A

Hemolytic disease of the newborn
Maternal sensitization to Rh ag during prior preg w/Rh(D)+ fetus –> subsequent Rh(D)+ preg, maternal anti-Rh(D) IgG ab cross placenta and cause severe autoimmune hemolytic anemia in the fetus and life-threatening hydrops fetalis

73
Q

Infant with spontaneous bursts of non-rhythmic conjugate eye movements in various directions and also suffers from hypotonia and myoclonus with an abdominal mass is suggestive of what?

A

Neuroblastoma
Opsoconus-myoclonus is a paraneoplastic syndrome assoc with this. Assoc with inc # of N-myc gene copies. MC extracranial neoplasm in kids

74
Q

Dysfunction of what cell proteins allows for neoplastic cells in breast cancer to metastasize and advance through the adjacent basement membrane?

A

E-cadherin

75
Q

What is the most likely cause of pancytopenia in a patient with alcoholic cirrhosis and portal hypertension?

A

Hypersplenism - spleen becomes increasingly active and then rapidly removes the blood cells. It can result from any splenomegaly. It is most common with splenomegaly secondary to portal hypertension and haematological disorders

76
Q

What is the homing phenomenon?

A

preferential spread of a cell to a particular area
Eg. prostate and breast cancers often disseminate first to the bone, and lung cancer often seeds new tumours in the adrenal glands. This homing phenomenon may be related to tumour cell recognition of specific “exit sites” from the circulation or to awareness of a particularly favourable—or forbidding—“soil” of another tissue.

77
Q

Tumor invading the pericardium is likely to affect what nerve?

A

phrenic nerve - innervates the pericardium
Lung cancer, the most frequent source of neoplastic pericardial disease
Breast cancer is the second most common cause of malignant pericardial effusions

78
Q

Lymphocytes with cytoplasmic projections and positivity for acid phosphatase even in the presence of tartrate indicates what?

A

Hairy cell leukemia

79
Q

MOA of Li-Fraumeni syndrome?

A

Impaired regulation of apoptosis
Li Fraumeni is associated with mutation of p53 (tumor suppressor gene). p53 inhibits a defect cell from going from G 1 to S phase by inducing apoptosis of this cell or by activating repair enzymes. If there is a mutation of the P53 gene, apoptosis of the defected cell won’t occur, this cell will replicate and might undergo mutations and lead to cancer.

80
Q

What inflam response is most likely to be abnormal in a patient with prolonged PTT and no history of bleeding problems

A

Kallikrein formation

XIIa converts prekalli->kallikrein

81
Q

Beta thalassemia mutations lead to what problem in B-globin production?

A

Disruption of splicing by creating a new 3’ splice site (Beta thal mutations are usually promoter or splice site mutations)

82
Q

What is the molecular basis for sickling in patients with sickle cell?

A 
Gain of stabilizing hydrophobic interactions in the deoxygenated form of hemoglobin S
glutamic acid(hydrophillic ) is replaced by hydrophobic valine (which increases the number of hydrophobic aminoacids ...which inturn increases hydrophobic interactions ) ..and these hydrophobic interactions stabilize the polymerized sickle hemoglobin....

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