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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
What drug targets a platelet surface glycoprotein receptor that binds fibrinogen to support platelet aggregation?
Abciximab - blocks GPIIb/IIIa
26
Melanoma and other tumors exhibit poor adhesion to what part of the ECM?
Fibronectin Adhesion of cells to the ECM involves integrin-mediated binding to fibronectin, collagen and laminin. Differential integrin types affects adhesion
27
What is a significant adverse effect of ganciclovir therapy, especially with co-admin of zidovudine or TMP-SMX?
Neutropenia
28
What are common precipitating factors of G6PD deficiency anemia?
1. infections 2. Drugs: DAPSONE, antimalarials, sulfa drugs 3. DKA 4. fava beans
29
HER2 oncogene codes for what type of receptor that has tyrosine kinase activity? What is the function of the protein receptor?
Epidermal growth factor. | Accelerates cell proliferation
30
Patient with chronic pancreatitis can get macrocytic anemia how?
Diminished thymidine synthesis (impaired purine/pyrimidine synthesis) through Vit B12 and folate deficiency
31
Patient with new-onset neuro sx (numbness), anemia w/schistocytes, and thrombocytopenia likely has what?
TTP: Impaired cleavage fo vWF (def in ADAMTS13) --> prothrombotic
32
Patient on low calorie diet, abdominal pain, confusion and resolution with infusion of hemin is due to a deficiency in what enzyme?
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.
33
Differentiate tacrolimus from sirolimus
Tacrolimus - prevents IL-2 transcription in T cells; inhibit calcineurin sirolimus - prevents IL-2 signal transduction by inhibiting mTOR
34
In anemia, arterial O2 content is decreased, arterial O2 sat and pO2 are normal, and venous pO2 is dec. Why does venous Po2 dec?
Dec o2 carrying capacity --> inc CO --> inc O2 extraction from tissues --> reduced venous o2 tension
35
COPD does what to hematocrit?
Increase due to physiologic need to maintain perfusion | This is called a secondary erythrocytosis
36
Accumulation of uroporphyrin in the urine and photosensitivity indicates what?
Porphyria cutanea tarda | Deficiency in uroporphyrinogen decarboxylase
37
In melanoma tx, monoclonal antibodies block what cell surface receptor found on T lymphocytes that facilitate destruction of cancer cells?
PD-1 (program death) | inhibits cytotoxic T cells when it binds to its ligand PD-L1
38
Key lab findings in polycythemia vera
Inc RBC mass, inc plasma volume, low epo
39
Chronic lymphedema is a RF for the development of what cutaneous condition?
Cutaneous angiosarcoma (Stewart-Treves syndrome) - infiltration of dermis with slit-like abnormal vascular spaces. Poor prognosis
40
Describe leukemoid reaction
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
How can you differentiate absolute from relative erythrocytosis (ie inc Hct level)
Relative - normal RBC mass | Absolute - increased RBC mass
42
What can be used to treat multiple myeloma?
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
Key growth factors that promote angiogenesis in neoplastic and granulation tissue?
VEGF Fibroblast growth factor Note: proinflam cytokines (IL-1, IFN-y) can indirectly promote angiogenesis through inc VEGF expression
44
Reticulocytes contain bluish cytoplasm why?
This immature RBC lacks a cell nucleus, but retains a basophilic, reticular network of residual RIBOSOMAL RNA
45
Erythroid precursors in liver and spleen is indicative of what? This is frequently seen in what conditions?
``` Extramedullary hematopoiesis (also seen in skull - spike) Chronic hemolytic anemia like B-thal causes this ```
46
Patients with familial retinoblastoma also have increased risk of what cancer?
Osteosarcomas
47
Paraneoplastic cerebellar degeneration is what type of reaction?
Autoimmune - immune reaction against tumor cells that cross-react with normal cells, causing dysfunction and/or damage to healthy organs and tissues
48
Increased osmotic fragility of RBC is diagnostic of what? Increased risk of what?
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
Clinical features suggestive of a malignant cause of back pain include what?
Occurrence at night not relieved with rest or analgesics Advanced age systemic sx
50
What syndrome is caused by an AD mutation in TP53? What cancers are most common?
Li-Fraumeni syndrome | Leukemia, sarcoma, tumors of breast, brain, adrenal cortex
51
Pro-carcinogens are metabolized by what in the human body? This process also converts these pro-carcinogens into carcinogens capable of causing what?
Cytochrome P450 monooxygenase | Mutations in human DNA
52
What are the 4 chronic myeloproliferative disorders? | Most often have a mutation in what?
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
Sickle cell disease does what to the spleen
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
``` Which of these are oncogenes vs tumor suppressors? APC BRCA1 KRAS TP53 Rb ```
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
What increases in serum after Vit B12 replacement therapy is initiated in indiv with pernicious anemia?
Reticulocytes inc dramatically after initiation | Hb and erythrocytes inc more gradually
56
Enoxaparin MOA?
LMWH Binds and activates Antithrombin III --> binds factor Xa Note: does not act on thrombin
57
Thrombin time measures what? What drug has no effect on thrombin time?
Meds that directly or indirectly inhibit thrombin | Direct factor Xa inhibitors (eg apixaban, rivaroxaban)
58
What substances is involved in the invasion of cancer cells into the basement membrane?
Metalloproteinases | Note: they are also involved in tissue remodeling and embryogenesis.
59
Aplastic anemia causes pancytopenia as the bone marrow is replaced by fat cells and marrow stroma. Absence of what on physical exam is characteristic?
Splenomegaly
60
Vascular endothelium secretes what substance to INHIBIT platelet aggregation? PROMOTE?
1. Prostacyclin 2. Thromboxane A2 Prostacyclin exists in dynamic balance with TXA2 to maintain capillary patency and normal blood flow.
61
Activating mutation of RET proto-oncogene is assoc with what?
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
What reaction causes inc DHF reductase and DNA polymerase?
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
CO poisoning does what to: Carboxyhemoglobin PaO2 Methemoglobin?
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
High-o2 affinity Hb have reduced ability to release o2 in peripheral tissues (L shift). How does the body compensate?
Renal hypoxia --> inc EPO synthesis --> compensatory erythrocytosis
65
Polycythemia vera is a myeloproliferative disorder characterized by uncontrolled erythrocyte production. The mutation in JAK2 is what type of tyrosine kinase?
Non-receptor (cytoplasmic) tyrosine kinase | Note: intrinsic (receptor) tyrosine kinases include insulin, insulin-like GF, and epidermal GF
66
Increased myeloid precursors on peripheral blood smear indicate what?
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
Hereditary hemochromatosis is caused by a MISSENSE mutation in the HFE gene, resulting in what?
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
Pancytopenia, dry tap on bone marrow aspirate, splenomegaly indicates what? What does the peripheral blood smear show?
Hairy cell leukemia - see lymphocytes with cytoplasmic projections
69
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?
HTN | thromboembolic events
70
What is assoc w/painless waxing and waning lymphadenopathy
Follicular lymphoma (MC indolent NHL in adults) B cell origin t(14;18) assoc w/bcl-2 oncogene
71
Compare hemoglobin to myoglobin | What happens to the O2 dissoc curve if only monomeric beta-hemoglobin subunits are present?
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
Newborn with profound anemia, jaundice, positive Coombs test, nucleated erythrocytes, and extramedullary hematopoiesis
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
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?
Neuroblastoma Opsoconus-myoclonus is a paraneoplastic syndrome assoc with this. Assoc with inc # of N-myc gene copies. MC extracranial neoplasm in kids
74
Dysfunction of what cell proteins allows for neoplastic cells in breast cancer to metastasize and advance through the adjacent basement membrane?
E-cadherin
75
What is the most likely cause of pancytopenia in a patient with alcoholic cirrhosis and portal hypertension?
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
What is the homing phenomenon?
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
Tumor invading the pericardium is likely to affect what nerve?
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
Lymphocytes with cytoplasmic projections and positivity for acid phosphatase even in the presence of tartrate indicates what?
Hairy cell leukemia
79
MOA of Li-Fraumeni syndrome?
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
What inflam response is most likely to be abnormal in a patient with prolonged PTT and no history of bleeding problems
Kallikrein formation | XIIa converts prekalli->kallikrein
81
Beta thalassemia mutations lead to what problem in B-globin production?
Disruption of splicing by creating a new 3' splice site (Beta thal mutations are usually promoter or splice site mutations)
82
What is the molecular basis for sickling in patients with sickle cell?
``` 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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