Hematology - oncology Flashcards
“Starry sky” lymph nodes: which disease? prevalence in which ages? genetic mutation? Viral association lesion常见部位？
Burkitt lymphoma (non-hodgkin lymphoma of mature B cells) occurs in adolescents or young adults genetic mutation: t (8: 14) [c-myc (8) and heavy chain Ig (14), - constitutive overproduction of C-Myc] Viral association - EBV lesion常见部位: in endemic form in Africa: jaw lesions; in sporadic form: pelvis or abdomen
2 direct factor Xa inhibitors? clinical use? 是否需要监测？toxicity?
Apixaban, rivaroxaban bind to directly inhibit Xa clinical use: 和warfarin类似，用于预防：treatment and prophylaxis of DVT and PE (rivaroxaban), stroke prophylaxis in pts. with AF 口服， 一般不需要监测 toxicity：bleeding, [no specific reversal agent available]
5-fluorouracil (5-FU) 是什么药？机制 （target which phase of cell cycle)？用途？toxicity以及如何reverse?
抗肿瘤 机制 : pyramidine analog bioactivated to 5F-dUMP, which covalently complexes with folic acid; this complex inhibit thymidylate synthase ⇒ ↓ dTMP ⇒ ↓ DNA and protein synthesis target which phase of cell cycle： s phase-specific 用途: colon cancer, pancreatic cancer, basal cell carcinoma (topical) toxicity以及如何reverse: 1. 类似MTX有myelosuppression, 但和MTX不一样（不能用leucovorin亚叶酸）reverse: overdose rescued with uridine 2. photosensitivity
ACD (anemia of chronic disease)引起贫血的机理？Lab? 属于哪种贫血？
inflammation ⇒ liver release of hepcidin ↑ ⇒ binds ferroportin on intestinal mucosal cells and macrophages to inhibit iron transport ⇒ ↓ release of iron from macrophage Lab: ↓ iron, ↓ TIBC, ↑ ferritin 一般是nonhemolytic, normocytic, 也可以是microcytic, hypochromic
Acute intermittent porphyria: affect E? accumulated substances? Cx? Rx?
affect E: porphobilinogen deanimase accumulated substances: porphobilinogen, delta-ALA, urine coporphobilinogen Cx: 5 P’s Painful abdomen Port wine-colored urine Polyneuropathy Psychological disturbances Precipitated by drugs, alcohol, starvation Rx: glucose + heme (inhibit ALA synthase)
Abciximab是什么药？机制？用途？toxicity
抗凝，inhibit platelet aggregation by binding to GIIb/IIIa on activated platelets made from McAb Fab fragments 用途: unstable angima, PTCA (经皮穿刺冠状动脉造影） toxicity: bleeding, thrombocytopenia
adult T-cell lymphoma: 发病年龄? specifically affect which populations? virus association? Cx?
发病年龄: adults specifically affect which populations: Japan, West Africa, Carribbean virus association: HTLV-1 (Human T-cell lymphotropic virus type 1), IV drug abuse Cx: lytic bone lesions, hypercalcemia
ALL: age? associated with other disease? Peripheral blood and BM see? Cx? Surface markers? does it respond to therapy? which gene translocation has better prognosis?
age: < 15 associated with other disease - downs Peripheral blood and BM see: ↑↑↑ lymphoblasts Cx- 如果是T cell ALL, 可表现为纵膈mass (infiltrate thymus) Surface markers: CD10+ (if pre-B cell only); TdT+ (pre-T and pre-B both) does it respond to therapy - yes which gene translocation has better prognosis: t (12:21)
AML: age? Peripheral blood smear? risk factors? genetic mutation？ Rx? 常见的一个Cx?
age: median onset of 65 Peripheral blood smear: 1) 非常特征性的Auer rods (奥尔小杆:白血病患者成髓细胞胞浆中小杆状体）， 2) peroxidase+ cytoplasmic inclusions seen mostly in M3 AML; 3) ↑↑↑ circulating myeloblasts risk factors: alkylating chemotherapy, radiation, myeloproliferative disorders, downs genetic mutation: t (15:17) - M3 Rx:所有AML 亚型都respond to AT-RA (VitA), which induces differentiation of myeloblasts 常见的一个Cx: DIC (can be induced by chemotherapy due to release of Auer rods)
Argatroban（阿戈托班）, bivalirudin是什么药？
抗凝血药（derivatives of hirudin 水蛭素）-inhibit thrombin directly used instead of heparin for anti-coagulating pts with HIT
associated patho basophilic stippling?
Basically, ACiD alcohol is LeThal. Basophilic stippling: anemia of chronic disease, alcohol abuse, Lead poisoning, Thalassemias
associated patho: acanthocyte?
liver disease, abetalipoproteinemia (cholesterol dysregulation)
associated patho: teardrop RBC Target cell
teardrop RBC - BM infiltration (RBC sheds a tear because it’s forced out of its home) Target cell: “HALT”, said the hunter to his Target (HbC disease - beta-globin mutation引起的贫血, asplenia, Liver disease, Thalassemia
associated patho: Heinz bodies
oxidation of Hb sulfhydryl group (硫氢基) → denatured Hb precipitation and phagocytic damage to RBC membrane → bite cells crystal violet可以把Heinz bodies染出来 seen in G6PD deficiency, Heizn body-like inclusions seen in a-thalassemia
associated patho: Howell-Jolly bodies
脾脏是个吞噬RBC的器官，嚎叫着（howell)吃Jelly (Jolly) Howell-Jolly bodies: basophilic nuclear remnants found in RBC, normally removed by splenic macrophages seen in functional hyposplenia, or asplenia
basophil function? granules contain? Isolated basophilia indicates?
basophil function - mediate allergic reaction granules contain: 1) heparin (anticoagulant) 2) histamine (vasodilator) 3) leukotrienes Isolated basophilia indicates myeloprolifeative diseases, especially CML
bevacizumab 什么药？mechanism? clinical use? toxicity?
北伐单抗 mechanism： McAb against VEGF ⇒ inhibit angiogenesis clinical use： solid tumors (colorectal cancer, renal cell carcinoma) toxicity: hemorrhage and impaired wound healing
bleomycin: 是什么药？机制 ？用途？toxicity:
博来霉素，抗肿瘤药 机制: induces free radical formation, to cause breaks in DNA strands (G2) 用途: tesicular cancer, Hodgkin lymphoma toxicity: 1) pulmonary fibrosis!! 2) skin changes, mucositis note: 和别的抗代谢药不一样：minimal myelosuppression
Cilostazol, dipyridamole是什么药？机制？用途？toxicity?
Cilostazol (西洛他唑）, dipyridamole （双嘧达莫; 潘生丁）：抗凝药 机制：PDE III inhibitor: 1) ↑ cAMP in platelets, thus inhibit platelet aggregation; 2) vasodilators 用途: intermittent claudication (PAD的上佳药物）, coronary vasodilation, presentation of stroke or TIAs when combined with aspirin, angina prophylaxis toxicity: 因为扩张血管引起：nausea, headache, facial flushing, hypotension, abdominal pain
cisplatin, carboplatin: 是什么药？机制 ？用途？toxicity以及如果预防？
anti-tumor 机制: cross link DNA 用途: testicular, ovary, bladder, and lung carcinoma toxicity： 1）nephrotoxicity (prevented with amifostine 阿米斯丁， free radical scavenger) and chloride diuresis 2) acoustic nerve damage
CLL/SLL （small lymphocytic lymphoma): age? Peripheral blood smear? Cx? Surface markers? SLL和CLL鉴别？
age: > 60 Peripheral blood smear: “smudge cells” Cx: often无症状，进展很缓慢 Surface markers：CD20+/CD5+ B-cell neoplasm SLL和CLL鉴别: same as CLL except CLL has ↑ peripheral blood lymphocytosis or BM involvement
CML: age? Peripheral blood smear? risk factors? genetic mutation？ E的变化？ Cx? Rx?
age: 45-85, median 64 Peripheral blood smear: ↑ neutrophils, metamyelocytes, basophils genetic mutation: Philadelphia chromosome ( t (9:22), bcr-abl) E的变化: very low LAP (leukocyte alkaline phosphatase) (vs. leukemoid reaction, in which LAP ↑) Cx: 肝脾肿大，may transform to AML or ALL (blast crisis) Rx: imatinib (small-molecule inhibitor of the bcd-abl tyrosine kinase)
CO poisoning对O2 delivered to tissue有什么影响？ 这些指标怎么变化：PaO2? carboxyhemoglobin? methemoglobin?
CO poisoning对O2 delivered to tissue有2大影响： 1. 对Hb有超过O2 250倍的affinity, 占据Heme位点后，O2无法再和heme结合 ⇒ O2 content of blood ↓ (这一点和hypoxia一样） 2. 使Hb-O2 dissociation curve left shift!!! [非常重要的变化，意味着即使氧气好不容易结合上血红蛋白被运送到了组织，也很难被释放出来 - 这是一般hypoxia中没有的变化】 CO中毒时： PaO2： 不变（这是partial pressure of O2 dissolved in the plasma, 是氧气的溶解度，和CO中毒一点关系都没有） carboxyhemoglobin：↑ methemoglobin 高铁血红蛋白：不变（这是由Fe2+被氧化为Fe3+时升高，出现在nitrites, dapsone【麻风病中的抗生素】中毒时）
corticosteroids对neutrophil, eosinophil, lymphocytes的影响？
corticosteroids对neutrophil的影响：cause neutrophilia 中性白细胞增多, 但是这些中性粒到不了感染部位：corticosteroids ↓ activation of neutrophil adhesion molecules, impair their migration out from the vasculature to the site of inflammation corticosteroids对eosinophil的影响: eosinopenia [sequester eosinophils in lymph nodes] corticosteroids对 lymphocytes的影响: lymphopenia [cause apoptosis of lymphocytes
Cytarabine 是什么药？机制 （target which phase of cell cycle)？用途？toxicity
pyrimidine analogs ⇒ inhibit DNA polymerase taget S-phase (和MTX, 5-FU不同的地方是：与叶酸代谢无关） 用途： lymphoma, leukemias toxicity: CYTarabine causes panCYTopenia leukapenia, thrombocytopenia, megaloblastic anemia
dactinomycin: 是什么药？机制 ？用途？toxicity
放线菌素D = actinomycin D 机制: intercalates in DNA 用途: childhood tumors (“children act out”) Wilms tumor, Ewing sarcoma (10 - 20 yrs old, sarcoma in pelvis or long tubular bones); rhabdomyoscarcoma 横纹肌肉瘤 toxicity: myelosuppression
cyclophosphamide, ifosfamide(IFO): 是什么药？机制 ？用途？toxicity (如何预防）？
alkylating agents (anti-tumor) 烷化剂 机制：covalently X-link (inter strand) DNA at guanine N-7; [require liver bioactivation] 用途: solid tumors, leukemia, lymphomas, some brain cancers toxicity (如何预防）： 1) myelosuppresson 2) hemorrhagic cystitis - partially prevented with mesna [美司钠,巯乙磺酸钠: its thiol group binds toxic metabolites]
define: dendritic cells? function? surface marker? what is it called in the skin?
dendritic cells function - highly phagocytic APCs; link innate and adaptive immune systems surface marker: MHC II, Fc receptor what is it called in the skin - Langerhans
DIC: causes? Labs?
causes: “STOP Making New Thrombi” (widespread activation of clotting - deficiency in clotting factors, - a bleeding state S: sepsis (gram-negative) Trauma Obstetric complications (例如羊水栓塞） acute Pancreatis Malignancy Nephrotic syn Transfusion Labs: schistocytes, ↑ D-dimer (fibrin split products), ↓ fibrinogen, ↓ factors V and VIII. ↓ PC, ↑ BT, PT, PTT
define: tumor stage? grade?
tumor stage: how far the tumor spread to the adjacent tissue, lymph nodes, metastasis, grade: differentiation
Down syn pts: 儿童期死因？成人死因？
儿童期死因：acute lymphoblastic (or myelogenous) leukemia 成人死因: AD
doxorubicin: 是什么药？机制 ？用途？toxicity: which drug to prevent the toxicity?
阿霉素, 羟基柔红霉素 【抗肿瘤药】 机制: 1) intercalates in DNA ⇒breaks in DNA ⇒ ↓ replication (for G2 phase) 2) generate free radicals 用途: solid tumors, leukemias, lymphomas toxicity: 1) cardiotoxicity - dilated cardiomyopathy - prevented by Dexrazoxane 右旋丙亚胺(主要用于保护阿霉素引起的心脏毒性) 2) myelosuppression 3) alopecia 脱发 4）toxic to tissues following extravasation 外渗
Dx: neutrophils with bilobed nuclei (2 nuclear masses connected with a thin filament of chromatin)?
Pelger-Huet anomaly, or Pseudo Pelger-Huet anomaly Pseudo Pelger-Huet anomaly: typically seen after chemotherapy 真性的话是良性genetic disorder (AD)
eptifibatide是什么药？机制？用途？toxicity
依替巴肽 和abciximab，tirofiban 一类, inhibit platelet aggregation by binding to GIIb/IIIa on activated platelets 用途: unstable angima, PTCA (经皮穿刺冠状动脉造影） toxicity: bleeding, thrombocytopenia
etoposide是什么药？机制？用途？toxicity
VP-16, 依托泊苷,鬼臼毒素(抗肿瘤药) 机制: inhibit topoisomerase II (target cell cycle S and G2 phases) 用途？toxicity
etoposide, teniposide 是什么药？机制 ？用途？toxicity以及如果预防？
VP-16, 鬼臼毒素 替尼泊苷; 鬼臼噻吩苷 机制: Etoposide inhibits DNA topoisomerase II - ↑ DNA degradation 用途: 1. solide tumors (particularly testicular and small cell lung cancer) 2. leukemias, lymphoma toxicity： 1. myelosuppression 2. GI irratation 3. alopecia
G6PD deficiency是什么遗传？病因？lab? Cx?
[Stress makes me eat bites of fava beans with Heinz ketchup] X-linked recessive (XR) MC RBC酶缺陷 defect in G6PD ⇒ ↓ glutathione ⇒ ↑ RBC susceptibility to oxidative stress 病因: 增加oxidative stress的因素：Fava beans!!， sulfa drugs, antimalaries, infections Cx: oxidative stress后几天出现back pain, hemoglobinuria Lab: blood smear shows RBCs with Heize bodies and bite cells
Glanzmann thrombasthenia 血小板机能不全 发病机理？能被哪个抗凝药物模拟？
deficiency in GpIIb/IIIa Cx: childhood muccotaneous bleeding Dx: peripheral smear shows no platelet clumping = abciximan (inhibit GpIIb/IIIa directly)
Hairy cell leukemia: B or T cells? age? Peripheral blood smear? Dx? 骨穿症状？ Rx?
mature B-cell tumor age: elderly Peripheral blood smear: hair-like projections Dx: 不再用FLOW, 改用TRAP诊断 (tartrate-resistant acid phosphatase + ) 骨穿症状: marrow fibrosis, dry tap on aspiration Rx: Cladribine (2-CDA) 克拉屈滨,2-氯脱氧腺苷, an adenosine analog to inhibit ADA (adenosine deaminase)
heme synthesis中得限速酶？associated disease?
ALA synthase (delta-aminolevulinic acid) associated disease: sideroblastic anemia (X-linked)
Hemophilia A/B: deficiency of which factor? coagulation pathway? vWF carries/protects?
Hemophilia A: deficiency of factor VIII Hemophilia B: deficiency of factor IX vWF carries/protects VIII
heparin抗凝的原理？
heparin enhances the activity of antithrombin antithrombin inhibits activated forms of factors II, VII, IX, X, XI, XII
heprain: mechanism? Difference with LMWH? half life? Clinical use? Monitor? Diff with LMWH? Complications - what is the most severe one, how it’s developed? Antidote for Heparin（how it works)? 如果发生HIT又要抗凝，用什么药？
heprain: cofactor for antithrombin; ↓ thrombin, ↓ factor Xa LMWH: ↓ factor Xa (缺少长链肝素的5肽，无法bind住antithrombin-thrombin complex) half life - short, so used as “immediate anticoagulation” in PE, acute coronary syn, MI, DVT; do not cross placenta - used in pregnancy Monitor: PPT LWMH (enoxaparin, delteparin): act on Xa, better bioavailability, can be used sc, 2-4 times long half-life; 不用monitor Complications - HIT; bleeding, osteoporosis, drug-drug interactions what is the most severe one, how it’s developed: HIT (development of IgG Ab against heparin bound to platelet factor 4; Ab-heparin-PF4 complex activates platelets ⇒ thrombosis and thrombocytopenia Antidote （how it works): protamine sulfate (negatively charged heparin binds to positively charged protamine) 如果发生HIT又要抗凝，用什么药：argatroban （derivatives of hirudin 水蛭素）-inhibit thrombin directly
Hereditary spherocytosis [HS, 遗传性球形红细胞增多症] 会引起aplastic crisis, 这是什么原因？ lab? Rx?
Hereditary spherocytosis会引起aplastic crisis - parvovirus B19 细小病毒 infection lab: 诊断: osmotic fragility test +; screen: eosin-5-maleimide binding test 【 Flow cytometric analysis of eosin-5-maleimide (EMA)-labeled red blood cells (RBCs) has been used as a screening test】 Rx：splenectomy
HUS (hemolytic uremic sym 溶血性尿毒症）： 好发人群？cause? Cx? lab?
好发人群：children < 10-yr cause： EHEC O157:H7 - secret Shiga-like toxin (ingest undercooked beef, drink unpasteurized milk or contaminated water, person-to-person contact) Cx: 血性腹泻 + 肾衰 （oliguria, ↑ BUN+creatinine ) + 严重腹痛 + CNS syn (somnolence, lethargy) Lab: peripheral blood smear shows fragmented RBCs (UW还以conjuctival pallor的方式考过贫血) 看这个病的名字就知道临床表现：溶血+尿毒症！
hydroxyurea: 机制 ？用途？toxicity？
机制: inhibits ribonucleotide reductase - ↓ DNA Synthesis (S-phase specific) 用途: 1. melonoma 2. CML 3. sickle cell anemia (↑ HbF) toxicity： 1. BM suppression 2. GI upset
Langerhans cell histocytosis (组织细胞增多症） cause? Cx? Cell markers? Dx?
cause: proliferative disorder of dendritic (langerhans) cells from the monocyte lineage; cells are immature and can’t stimulate primary T cells via antigen presentation Cx: child, lytic bone lesions, skin rash or recurrent otitis media, with a mass in the mastoid bone颞骨乳突 Cell markers: S-100 (mesodermal origin)+ /CD1a + Dx: EM 见特征性Birbeck granules (tennis rackets)
irinotecan, topotecan: 是什么药？机制 ？用途？toxicity？
anti-tumor 机制: inhibits DNA topoisomerase I - prevent DNA unwinding and replication 用途: 1. irinotecan: colon cancer 2. topotecan: ovary and small cell lung cancer toxicity： 1. severe myelosuppression 2. diarrhea
Imatinib (Gleevec): mechanism? clinical use? toxicity?
伊马替尼 mechanism: 1) Tyr kinase inhibitor of bcr-abl (Philadelphia chromosome fusion gene in CML) 2) Tyr kinase inhibitor of c-kit (common in GI stromal tumors) clinical use: CML, GI stromal tumors toxicity: fluid retention
Lead poisoning: Lead inhibits which enzymes? 后果？ children/adults 最常见的exposure是什么？ Cx? Lab? Dx?
Lead 1) inhibits ferrochelatase (亚铁螯合酶） and ALA dehydratase ⇒ ↓ heme synthesis, ↑ RBC protoporphyrin 2) inhibits RNA degradation ⇒ RBCs retain aggregates of rRNA (basophilic stippling 噬碱性点彩） Cx: LEAD Lead Lines on gingival, on metaphases of long bones on X-ray Encephalopathy and Erythrocyte basophilic stippling Abdominal colic and sideroblastic Anemia Drops - wrist and foot drop children - exposure to lead paint ⇒ mental deterioration adults - environmental exposure (battery/radiator/aummunition 弹药）factory ⇒ headache, memory loss, demyelination Lab: ↑ blood protoporphyrin, delta-ALA Dx: 1st line: Dimercaprol 二硫基丙醇, EDTA; succimer二硫琥珀酸在kids中用做螯合剂（it sucks to be a kid who eats lead)
leukemoid reaction 的lab? 如何与CML鉴别？
leukemoid reaction： acute inflammatory response to infection lab：↑ WBC count with ↑ neutrophils and its precursors (band cells left shift) ; ↑ leukocyte ALP 如何与CML鉴别: CML also ↑ WBC count with left shift; but ↓ leukocyte ALP !!!
Macrocytic anemias除了巨细胞性贫血外的病因？
diseases that DNA synthesis is impaired： liver disease, alcoholism, drugs: 5-FU, zidovudine (AZT), hydroxyurea
Mantle cell lymphoma: mutation? 发病年龄? B cell marker?
t (11:14) translocation of Cyclin D1 (11) and heavy-chain Ig (14) in older males, CD5+
mast cells: bind to Fc of which Ig? cross-linking cause? involved in which type of hypersensitivity? mechanism for cromolyn sodium in asthma prophylaxis?
bind to Fc of IgE IgE cross-linking cause release of histamine, heparin, eosinophil chemotactic factors involved in type I of hypersensitivity mechanism for cromolyn sodium in asthma prophylaxis - prevent mast cell degranulation
MC porphyria? affected E? accumulated substances? Cx?
MC porphyria - porphyria cutanea tarda 迟发型皮肤卟啉症 affected E - uroporphyrinogen decarboxylase accumulated substances- uroporphyrin (tea-colored urine) Cx - blistering cutaneous photosensitivity
methotrexate (MTX) 是什么药？机制 （target which phase of cell cycle)？用途？toxicity以及如何reverse?
甲氨喋呤 机制- folic acid analog that inhibits dihydrofolate reductase ⇒ ↓ dTMP ⇒ ↓ DNA (both purines and thymidine) and protein synthesis S-phase specific 用途: 2大临床应用：肿瘤及非肿瘤 1. cancers: leukemias, lymphomas, choriocarcinoma (绒毛膜癌), sarcomas 2. non-neoplastic: abortion, ectopic pregnancy (drug of choice in < 6 wk宫外孕） autoimmune类（RA-治疗风湿性关节炎一线药物，UW考到在RA病人中引起肝脏毒性； psoriasis - UW考到治疗牛皮癣的机制是target rapid proliferating epithelial cells in the skin, IBD) toxicity: 1. 骨髓毒性 myelosuppression: reversible with Leucovorin 亚叶酸, “folinic acid” [甲氨蝶岭解毒药,抗贫血药] 2. 肝脏毒性：macrovesicular fatty change; 长期服用MTX (例如RA)可见cirrosis 3. mucositis 粘膜炎 4. teratogenic
direct vs. indirect Coombs test?
direct: 往病人RBC中加入anti-Ig Ab (Coombs reagent). 如果病人RBC表面coated with Ig, 就会凝聚。 Indirect: 取病人serum加入正常RBC. 如果病人血清中含有anti-RBC surface Ig, RBC就凝集。
monocytes - macrophages : 各自存在什么地方？ macrophages activated by which cytokine? function as APC via? surface marker?
monocytes - circulating in the blood macrophages : in tissues macrophages activated by which cytokine? -INFg function as APC via MHC II surface marker CD14
Multiple Myeloma (MM): 病理特征细胞？ associated with? (x-ray, 电泳，urine, RBC) Cx? 鉴别：1）Waldenstrom macroglobulinemia; 2) MGUS (monoclonal gammopathy of undetermined significance)
病理特征细胞: numerous plasma cells with “clock face” or “fried egg” appurtenance: large eccentric nuclei, intracytoplasmic inclusions containing Ig [produce large amounts of IgG (55%) or IgA (25%)] associated with: 1. ↑ susceptibility to infection 2. AL (primary amyloidosis) 3. X-ray: punched-out lytic none lesions 4. Serum protein electrophoresis: M spike (和下面2个病鉴别） 5. urine: Ig light chain (Bence Jones protein) 6. RBC: rouleaux formation on smear Cx: CRAB is yuMMy!! hyperCalcemia (溶骨） Renal insufficiency Anemia Bone lytic lesions/Back pain Multiple Myeloma： Monoclonal, M protein spike M spike还见于以下2个病，需要鉴别： 1. Waldenstrom macroglobulinemia； 1) M spike = IgM (not IgG or A in MM) 2) no lytic bone lesions) 2) MGUS (monoclonal gammopathy of undetermined significance): asymtomatic precursor of MM M spike
mycosis fungoides/Sezary syn 蕈样霉菌病/塞泽瑞(氏)综合征 是一种什么疾病？ 发病年龄? Cx? cell surface marker?
neoplasms of mature T cells 发病年龄: adults Cx: cutaneous patches/plaques, potential to spread to lymph nodes and visera 【most common form of cutaneous T-cell lymphoma. It generally affects the skin, but may progress internally over time. 】 cell surface marker: circulating malignant cells CD4+, indolent (无痛的）
myelofibrosis: define mutation? BM改变？
fibrotic obliteration of BM 30~50% have JAK2 mutation Teardrop RBCs and immature forms of the myeloid line “BM is crying because it’s fibrosed”
Neutrophil: function? major chemotaxic factor for neutrophils? 形态？异常形态？ 2种granules各含什么酶？ ↑ band cells意味着什么？
function: acute inflammatory response cell, ↑ in bacterial infection 1) chemotaxis; 2) phagocytosis major chemotaxic factor for neutrophils: IL-8 released by macrophage 形态 - multilobed nucleus 异常形态- hypersegmented polys ( > 5 lobes), seen in VB12 / folate deficiency 2种granules各含什么酶: 1) small, more numerous granules: ALP, collagenase, lysozyme, lactoferrin 2) large, less numerous azurophilic 嗜苯胺蓝颗粒 granules: = lysosomes, contain proteinases, acid phosphatase, myeloperoxidase, beta-glucuronidase ↑ band cells (immature neutrophil) 意味着什么- reflects ↑ myeloid proliferation = bacterial infection, CML
nitrite poisoning机制？表现？ 这些指标怎么变化：PaO2? O2 content of the arterial blood? O2 carrying capacity of the arterial blood? bound fraction of O2 in the arterial blood (= % saturation)? Rx?
机制： nitrites oxidize the heme iron from Fe2+ (ferrous state) to Fe3+ (ferric), 形成methemoglobin 高铁血红蛋白， which CANNOT bind to O2, and LEFT SHIFT the Hb-O2 dissociation curve (这两点和CO poisoning一样） 表现： 1. cyanosis that cannot be corrected by O2 supplementation, 2. functional anemia (weakness, dyspnea, headaches, etc) PaO2 - normal O2 content of the arterial blood: ↓ O2 carrying capacity of the arterial blood ↓ bound fraction of O2 in the arterial blood (= % saturation) ↓ Rx: methylene blue
nitrosoureas: 亚硝尿类 包括哪些？是什么药？机制 ？用途？toxicity？
carmustine 卡莫斯丁 lomustine 罗莫斯丁 (环己亚硝脲) semustine 司莫司汀 (甲环亚硝脲) streptozocin 链佐星，琏唑霉素 抗肿瘤药，require bioactivation 机制: cross link DNA, cross BBB 用途: brain tumors, including GBM toxicity: CNS toxicity (convulsions, dizziness, ataxia)
O2-Hb dissociation curve什么情况left shift? right shift?
left shift: 氧气难以从血红蛋白释放出来 ↓ H+ (= pH上升，血液偏碱性） ↓ 2，3DPG ↓ temperature (低温会稳定O2和Hb结合的化学键，让O2难以释放） right shift：氧气容易从血红蛋白释放出来 ↑H+ (= pH上升，血液偏碱性） ↑ 2，3DPG ↑ temperature (高温时身体需氧）
paroxysmal nocturnal hemoglobinuria (PNH) 病因？lab? Cx? Rx?
病因: ↑ complement-mediated RBC lysis; aquired mutation in HSCs; ↑ incidence of acute leukamias lab: CD55/59 (-) RBCs on Flow Cx: triad (Coombs(-) hemolytic anemia, pancytopenia, VT [stem cell deficiency, 全血受累】 Rx： eculizumab 【mAb against complement. 第一个FDA批准治疗PNH的药，2011年第一个批准治疗aHUS (atypical hemolytic uremic sun]
platelet: life span? contain which granules? receptors for each factors?
life span - 8-10 days contain which granules: 1. dense granules (ADP, calcium) 2. alpha granules (vWF, fibrinogen) receptor for vWF: GpIb receptor for fibrinogen: GbIIb/IIIa
polycythemia vera： mutation? Lab? Cx? if 1°, EPO的变化？ If 2°, caused by ?
真性RBC增多症 mutation：JAK2 (mutation implicated in myeloproliferative disorders other than CML) Lab: hematocrit > 55%, ↑ RBC, WBC and platelets Cx: 最常见的presentation是intense itching after hot shower; 严重的（但是也很经典的）症状是erythromelalgia 红斑性肢痛症; due to episodic blood clots in vessels of the extremities if 1°, EPO ↓ If 2°, caused by : natural or artificial ↑ EPO
prednisone, predisolone用于抗癌的机制？ clinical use?
prednisone, predisolone are the most MC glucocorticoids used in cancer therapy, 常是化疗联用药物。 用于抗癌的机制: tigger apoptosis; even work on nondividng cells!! clinical use: 1. CLL 2. non-Hodgkin lymphoma toxicity: 1. cushing-like symptoms: weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis 2. HTN, peptic ulcers, 3. hyperglycemia 4. psychosis
purine analog类抗代谢药：3大代表？ 机制: activated by which E? target which phase of cell cycle？用途？ toxicity? 在和allopurinol联用时会出现什么问题？
- azathioprine 硫唑嘌呤 2. 6-mercaptopurine (6-MP) 3. 6-thioguanine (6-TG) 机制: ↓ de novo purine synthesis; activated by HGPRT 用途: 1. prevent organ rejection, RA 2. SLE (azathioprine) 3. leukemia, IBD (6-MP, 6-TG) toxicity: 1. BM, liver, GI 毒性 2. azathioprine and 6-MP are metabolized by xanthine oxidase, thus both have ↑ toxicity with allopurinol （which inhibits their metabolism)
rasburicase 什么药？用途？
拉布立酶 recombinant urate oxidase (present in mammals but not in humans) prevent and treat hyperuricemia and the resulting renal manifestations of tumor lysis syn
Reed-Sternberg cells: marker for which disease? surface CD markers? MC type, 在男女两性中分布比例？ 决定预后的因素？
distinct tumor giant cells in Hodgkin lymphoma (owl eyes) CD15+/CD30+ B cell origin (2 owl eyes * 15 = 30) necessary but not sufficient for a Dx of Hodgkin disease MC type: nodular sclerosing form 在男女两性中分布比例: equally affected 决定预后的因素: lymphocyte-rich form has best prognosis; lymphocyte mixed or depleted forms have poor prognosis
Retinoblastoma: Cx包括一个特征reflex? if familial, MC secondary malignancies:
特征reflex: white pupillary reflex (leukocoria 白瞳〔症〕，瞳孔泛白) if familial, MC secondary malignancies: osteosarcoma
Reye Sym Cx? Lab? microscope finding?
use of aspirin in 5-14 yr old children with viral infection (aspirin should be avoided for children < 16, 除非是Kawasaki disease) multiple organ damage, especially brain and liver rash, vomiting, and liver damage Lab: 1) hepatic failure: ↑ ALT, AST, ammonia, bilirubin, PT and PPT microscope: microvesicular steatosis (肝脏细胞中脂肪小粒） 2）encephalopathy: ↑ ammonia from liver failure causes cerebral edema
ristocetin作用机理？
activate vWF to bind to GpIb (促进凝血）
rituximab： 什么药？mechanism? clinical use? toxicity?
利妥昔单抗 mechanism: McAb against CD20 (surface marker for most B cell neoplasms) clinical use: 1. non-Hodgkin lymphoma 2. 和MTX联用治疗RA 3. ITP toxicity: ↑ risk for progressive multifocal leukoencephalopathy
sickle cell anemia: 病因？lab? 成人中最凶险的一个并发症？Dx? Rx?
病因：HbS point mutation ⇒ b chain position 6: glutamic acid → Val mutation lab： crescent-shaped RBC, “crew out” on skull X-ray (BM expansion, 和thalassemias颅骨表现一样） 成人中最凶险的一个并发症: acute chest sun ( vaso-occlusive crisis of the pulmonary vasculature commonly seen in patients with sickle cell anemia. This condition commonly manifests with pulmonary infiltrate on a chest x-ray) Dx: Hb electrophoresis Rx: HU (to ↑ HbF) and BMT
sideroblastic anemia有哪些病因？ lab? Dx?
病因: defect in heme synthesis 1). genetic： X-linked, defect in delta-ALA synthase gene 2) aquired: myelodysplastic syndrome 3) reversible: MC is Alcohol, VB6 deficiency, copper deficiency, isoniazid Lab: 1) BM 见ringed sideroblasts, with iron-laden mitochondria 2) ↑ iron, ↑ ferritin, normal TIBC Dx: pyridoxine (B6, a co-factor for delta-ALA synthase)
t (14:18)导致什么基因表达上升？导致哪两种疾病？ 各种发病年龄？
translocation of heavy-chain Ig (14) : bcl-2 (18), 导致overproduction of Bcl-2 (which inhibits apoptosis) 出现于1）diffuse large B-cell lymphoma; 2) Follicular lymphoma 1. diffuse large B-cell lymphoma: usually older adults (MC type of non-Hodgkin lymphoma in adults), 20% in children 2。 Follicular lymphoma adults, bcl-2 inhibits apoptosis; presents with painless “waxing and waning” lymphadenopathy
tamoxifen, raloxifene在cancer中用途？两者不同？ toxicity?
SERMs (selective ER modulators): antagonists in breast, agonists in the bone!!! clinical use: 1. tamoxifen: breast cancer treatment and prevention 2. raloxifene: 不能用于乳腺癌治疗，但可以用于预防；also used to prevent osteoporosis toxicity: 1. tamoxifen: ↑ risk for endometrial cancer (partial agonist in endometrium); hot flashes 2. raloxifene: no risk for endometrial cancer (antagonist in endometrium)
taxols: 是什么药？代表？机制 ？用途？toxicity？
紫杉酚, anti-tumor (microtubule inhibitor) 代表: paclitaxel 紫杉醇 机制：hyper stabilize polymerized microtubules in M phase ⇒ mitotic spindle CANNOT break down (M-phase specific) “It is taxing to stay polymerized” 用途: ovarian and breast carcinomas 【女性喜欢用植物制品】 toxicity: myelosuppression, alopecia 脱发，hypersensitivity
Thalassemia: 属于哪种贫血？ alpha-: gene defect? prevalence? findings: 4 alleles deletion? 3? 1-2? beta- : gene defect? prevalence? findings for minor? Major?
Thalassemia: 属于microcytic, hypochromic 贫血 a-: gene defect - a-globin gene deletion ⇒ ↓ a-globin synthesis prevalence: cis deletion in asian, trans deletion in African populations findings: 4 alleles deletion: no a-globin, not compatible with life, cause hydrous fetalis - 形成的globin Ɣ4 (“Hb brats”) 3 alleles deletion: HbH disease, very little a-globin, excess b-globin forms b4 (HbH) 1-2 alleles deletion: no clinically significant anemia b- : gene defect: point mutation in splice sites and promotor sequences ⇒ ↓ b-globin synthesis prevalence in Mediterrean population, 分为minor vs. major minor: heterozygote, b chain ↓, 通常无症状， Dx by ↑ HbA2 > 3.5% on electrophoresis Major: hemozygote, b chain is absent!! ⇒ severe anemia, require transfusion, can gain 2° hemochromatosis Marrow expansion⇒ skeletal deformities (“crew cut” on skull X-ray， “chipmunk” facies 髓外造血，肝脾肿大， ↑ risk of parvovirus B19-induced aplastic crisis ↑ HbF (a2Ɣ2). HbF is protective in infants, 在6个月后才开始起病 HbS/thalassemia heterozygote: mild to moderate sickle cell disease
Ticlopidine, clopidogrel抗凝的原理？用于哪些情况？ Ticlopidine有一个严重的副作用？如何监测？
inhibit ADP-induced expression of GpIIb/IIIa， so to inhibit platelet aggregation used in percutaneous coronary intervention, unstable angina, non-Q wave MI ； 一般和aspirin联用， aspirin和clopidogrel是2个一线药。如果对它们过敏，可以用ticlopidine, 但是这个药在1%病人中引起严重的副作用：neutropenia, 表现为fever and mouth ulcer. 因此头3个月内biweekly whole blood count
tirofiban是什么药？机制？用途？toxicity
替罗非班 和abciximab，eptifibatide 一类, inhibit platelet aggregation by binding to GIIb/IIIa on activated platelets 用途: unstable angima, PTCA (经皮穿刺冠状动脉造影） toxicity: bleeding, thrombocytopenia
Trastuzumab (Herceptin): mechanism? clinical use? toxicity?
曲妥单抗，群司珠单抗 mechanism： McAb against HER-2 (c-erbB2, a tyr kinase receptor). inhibit HER2-initiated cellular signaling and Ab-dependent cytotoxicity ⇒ help kill cancer cells over expressing HER2 (2 = tras2zumab) clinical use: HER-2 + breast or gastric cancer toxicity: cardiotoxicity (HEARTceptin damages the HEART)
vemurafenib （Zelboraf）： 什么药？mechanism? clinical use?
vemurafenib= V600E Mutation of bRAF Enzyme inhibitor mechanism: B-Raf enzyme inhibitor developed Genentech for the treatment of late-stage melanoma. The name “vemurafenib” comes from V600E mutated BRAF inhibition. clinical use： metastatic melanoma
vinca alkaloids: 包括哪些？是什么药？机制 ？用途？toxicity？
长春花属抗肿瘤药 2大代表药物：vincristine 长春新碱，Vinblastine 长春花碱 机制：bind to beta-tubulin to inhibit its polymerization into microtubulin ⇒ inhibit formation of mitotic spindle (M-phase specific) 用途: solid tumors, leukemias, lymphomas toxicity: Vincristine: 中枢+外周神经毒性 (areflexia, peripheral neuritis), paralytic ileus Vinblastine: blast BM (suppression)
VitK在凝血中的作用？ Wafarin抗凝的原理？用于什么疾病？为什么有delay作用？监测？？ 为什么新生儿要给VK? VitK deficiency会有哪些factor decrease?
oxidized VK 在epoxide reductase作用下变成reduced VitK, which acts as a cofactor for precursors for II, VII, IX，X, C, S to become mature (VitK deficiency这些factor都降低） Wafarin inhibits epoxide reductase/ vitK-dependent carboxylation of glutamic acid residues of clotting factors 。 用于VTE, VitK-dependent factors have long half-life, so wafarin has a few days’ delay for its onset of therapuetic window. monitored by PT (president went to War), standerized by INR Neonates lack enteric bacteria, which produces VitK
vWF disease: defects? Genetics? Cx/lab? Dx? Rx?
defects: 1. defect in platelet plug formation: ↓ vWF ⟹ defect in platelet-to-vWF adhesion 2. defect in intrinsic coagulation pathway: because vWF carry/protect factor VIII: ↓ vWF ⟹ normal or ↑ PTT, depending on severity Genetics: AD, MC inherited bleeding disorder Cx/lab: mild bleeding, PC/PT正常，↑ BT, normal or ↑ PTT Dx: “ristocetin cofactor assay (vWF : RCo assay): ↓ agglutination is diagnostic Rx: DDAVP (Desmopressin: 1-desamino-8-D-arginine vasopressin), a synthetic derivative of the antidiuretic hormone, vasopressin. 这个药已经使用25年，被extensively studied; Mechanism of DDAVP: release vWF stored in endothelium
Wafarin (coumadin): mechanism? 代谢？ clinical use? 监测？ toxicity的表现？治疗？
mechanism：inhibit the 1) synthesis and 2) gamma-carbooxylation of VK-dependent clotting factors (II, VII, IX, X) and Protein C, S [extrinsic pathway] site of action: liver!! 代谢: cytochrome P450 pathway [drug-drug interaction多不胜数！】 clinical use：慢性病和预防（与肝素相反：acute) STEMI (ST Segment Elevation Myocardial Infarction), venous thromboembolism prophylaxis, prevention of stroke in AF [not in pregnancy since it crosses placenta! 和肝素相反】 监测：PT/INR toxicity的表现: bleeding, skin/tissue necrosis, teratogenic, drug-drug interaction 治疗: 1) for reversal of warfarin overdose: give VitK 2) for rapid reversal of severe warfarin overdose: fresh frozen plasma
warm vs. cold agglutinin?
autoimmune hemolytic anemia中的概念： Warm agglutinin = IgG (warm weather is great) Cold agglutinin = IgM (cold ice-cream is yummy) 很多热/冷凝集引起的溶血都是原发性
↑ ESR 在哪些情况出现？ decrease?
↑ ESR: 1) infection 2) autoimmune (SLE, RA, temporal arteritis) 3) malignant neoplasms 4) GI disease (ulcerative colitis) 5) pregnancy decreased ESR: 1) polycythemia 2) sickle cell anemia 3) CHF 4) microcytosis 5) hypofibrinogenemia
临床上唯一一个重要的non-enveloped, ss-DNA virus是什么？引起哪些疾病？
parvovirus 细小病毒组 B19: 1. erythema infectious (the fifth disease) 传染性红斑, 第五病 - “slapped face” rash on face 2. aplastic crisis in sickle cell disease 3. hydrops fetalis
各条chromosome上有什么重要基因？ 8？ 9? 11？ 14？ 18？ 22? 导致疾病： t (8:14) t(14:18) t (11:14） t (15:17) t (9:22)
各条chromosome上有什么重要基因？ 8 - c-myc 9: bcr 11: cyclin D1 14: heavy chain Ig 18: bcl-2 22: abl t (8:14): Burkitt lymphoma (↑ C-myc) t(14:18): diffuse large B-cell lymphoma; follicular lymphoma (↑ Bcl-2) t (11:14）：Mantle cell lymphoma (↑ Cyclin D1) t (15:17): M3 type of AML (which responds to VitA) t (9:22): Philadelphia chromosome (CML) Bcr-abl hybrid
巨细胞贫血3大病因？ 各自表现？lab? Dx?
- Folate deficiency 2. Vit B12 (cobalamin) deficiency 3. orotic aciduria 1. Folate deficiency: Cause: malnutrition (alcoholism), malabsorption, anti-folate (抗叶酸代表药物：methotrexate甲氨喋呤，trimethoprim TMP 三甲氨苄啶-二氢叶酸类似物，phenytoin), ↑ requirement (pregnancy, hemolytic anemia) Cx/lab: - hypersegmented neutrophils, glossitis, ↑ homocysteine (这3点和VB12缺乏一样） - ↓ folate, normal methylmalonic acid (甲基丙二酸），NO neurological symptoms (这3点和VB12缺乏鉴别！） 2. Vit B12 (cobalamin) deficiency： Cause: insufficient intake (完全吃素）, malabsorption (Crohn disease), pernicious anemia, proton pump inhibitors, fish tapeworm (阔节裂头虫） Cx/lab: - hypersegmented neutrophils, glossitis, ↑ homocysteine (这3点和folate缺乏一样） - ↓ B12, ↑methylmalonic acid (甲基丙二酸）, neurological symptoms (这3点和folate缺乏鉴别！） 神经症状是由myelin合成需要B12引起，累及中枢和外周： 1）peripheral neuropathy: sensorimotor dysfunction 2) dorsal column (vibration/proprioception) 感觉通路 3) lateral corticospinal (spasticity) LMN 运动通路 4) dementia 3. orotic aciduria: defect in UMP synthase ⇒ failure to convert orotic acid to UMP (de novo pyrimidine synthesis); AR Cx: children 表现为巨细胞贫血 (hypersegmented neutrophils, glossitis)，但是无法由folate 或者B12纠正; ↑ orotic acid 需要和ornithine transcarbamylase deficiency鉴别：后者除了↑ orotic acid, 还合并hyperammonemia Rx: UMP to bypass the mutated synthase
病人present hypercoagulability, 考虑inherited 疾病？ 尤其是给warfarin置换后出现skin and subcutaneous tissue necrosis< 考虑什么疾病？
FA cover 4大hereditary thrombosis sym: 1. Factor V leiden (mutated factor V resistant to degradation by protein C; MCC of inherited hyper coagulability in whites) 2. prothrombin gene mutation (mutation in 3’-UTR: ↑ prothrombin- ↑ plasma levels and venous clots 3. antithrombin deficiency (如果是遗传的：ho no effect on PT, PTT or thrombin time, but diminish the ↑ in PTT by heparin; 也可以是获得性：renal failure/nephrotic syn, antithrombin lost in urine - ↑ factors II and X 4. protein C or S deficiency (↓ inactivation of factors V and VIII， ↑ risk of thrombotic skin necrosis with hemorrhage following administration of warfarin) “Protein C Cancels Coagulation)
病人大量输全血后手足发麻是什么引起的？
> 5-6 L within 24 hrs: citrate in the whole blood or packed RBC is a chelator for Calcium - 输血引起的低钙血症
血细胞分类， WBC从多到少排序？
- RBC 2. WBC: 1) 有颗粒（粒系 - granulocytes）：neutrophil, basophil, eosinophil 2）无颗粒（髓系 -mononuclear cells）：lymphocytes (B cells, T cells, NK), monocytes (mature into macrophage) 3) 血小板 WBC从多到少排序： Neutrophils Like Making Everything Better
贫血分类
按体积分（MCV） 1. microcytic (MCV < 80 fL) 小细胞贫血：【死了铁，SLATI] Sideroblastic anemia (高铁成红细胞性贫血, copper deficiency can cause it) Lead poisoning ACD (anemia of chronic disease, late stage) Thalassemias Iron deficiency (late stage) 2. Normocytic (MCV = 80 - 100 fL) 又分为non-hemolytic (reticulocyte count正常或↓）和hemolytic (reticulocyte count ↑）: non-hemolytic : AACID ACD (early stage) Aplastic anemia Chronic kidney disease Iron Deficiency (early) hemolytic: 外源性溶血（autoimmune, infection), 和内源性溶血（RBC membrane or E. deficiency, Sickle cell, etc) 3. macrocytic (MCV > 100 fL) 1) megaloblastic: Folate/VB12 deficiency, orotic aciduria 乳清酸尿症 2) non-megaloblastic: liver disease, alcoholism, reticulocytosis
补体系统是怎么激活？bind to which portion of immunoglobinlin?
The classical complement cascade begins when C1 binds to 2 IgG or 2 IgM (IgM is more potent activator, 因为是五聚体） C1 binds to the Fc region of heavy chain, NEAR the hinge!!
鉴别Hodgkin vs. Non-Hodgkin lymphoma: 1. 累及nodes? extranodal? 有无contiguous spread? 2. 病理特征细胞？ 3. 年龄分布？ 4. virus association? 5. syms?
Hodgkin: 1. 累及nodes: localized, single groups of nodes extranodal? - rare 有contiguous spread, stage is the strongest predictor of prognosis [prognosis is much better than non-Hodgkin’s] 2. 病理特征细胞 - RS (Reed-Sternberg cells, owl eyes, CD15+ CD30+) 3. 年龄分布: bimodal (young adult and > 55; more common in men except for nodular sclerosing type) 4. virus association - 50% with EBV 5. syms: constitutional “B” signs/sym: low grade fever, night sweats, weight loss [B symptoms refer to systemic symptoms of fever, night sweats, and weight loss which can be associated with both Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. The presence or absence of B symptoms has prognostic significance and is reflected in the staging of these lymphomas.] Non-Hodgkin lymphoma: 1. 累及nodes: multiple, peripheral nodes extranodal: common 无contiguous spread 2. 病理特征细胞: majority involves B cells 3. 年龄分布: 20-40 4. virus association: may associate with HIV and immunosuprression 5. syms: fewer constitutional signs/sym
