Pathology - part 1 Flashcards
acute inflammation
Vascular events: 1) vasoconsctriction of arterioles (neurogenic reflex for seconds), 2) arteriole dilation (histamine, NO, etc) 3) ↑ permeability of venules (histamine) -4) edema - 5) d. blood flow neutrophile (PMN): 3-4 segmented nucleus; >5: megaloblastic anemia; B12 or folic acid deficiency rolling (selectin, for weak binding) - adhension (beta2 integrins: CD11a: CD18) integrin表达在neutrophil上，bind to ICAM/VCAM on endothelial cells; ICAM/VCAM activated by IL-1, TNF
2 important platelet disorders: TTP/HUS cause? symptoms? treatement
- TTP (thrombotic thrombocytopenic purpura) 血栓性血小板减少性紫癜 [mortality: 10 - 20% even with plasma exchange!!} deficiency in vWF-cleaving metalloprotease in endothelial cells, ↑ platelet adhension to areas of endothelial injury at arteriole-capillary junctions . platelets are consumed (but NOT DIC) pentad: fever, thrombocytopenia, renal failure, microangiopathic hemolytic anemia with schistocytes (裂红细胞）， CNS deficits 血小板减少性紫癜、微血管病性溶血、中枢神经系统症状、发热以及肾脏损害，并称之为TTP五联征 2. HUS (hemolytic uremic syndrome): primarily in children < 10, caused by endothelial damage at arteriole - cap junction dues to E. coli toxin clinic sym: similar to TTP, but less CNS findings, bloody diarrhea in 75% cases treatment for TTP and HUS: plasma exchange transfusion; corticosteroids
mallory bodies
damaged (ubiquinated) cytokeratin intermediate filaments in hepatocytes note: Ub labels damaged intermediate
alkalosis vs. acidosis对血K+影响？
Alkalosis: H+ moves outside of cells, K+ move in → hypokalemia acidosis: H+ moves inside of cells, K+ move out → hyperkalemia
hypertrophic cardiomyopathy
most common cause of sudden death in young people, autosomal dominant mutation in heavy chain of b-myosin and in the troponins 病理： asymmetric hypertrophy of septum, anterior MV leaflet drawn against septum (obstruct blood flow). Aberrant conduction system causes sudden death
allergic transfusion reaction: cause, clinic, Rx?
IgE-mediated Type I HSR (hypersensitivity reaction) IgE triggers mast cells release of preformed mediators: histamine, serotonin, etc urticaria + pruritis, fever, tachycardia, wheezing, potential anaphylactic shock Rx: antihistamine
ataxia-telangiectasia
AR, ATM (DNA repair mutation) thymic hypoplasia, cerebellar ataxia, telangiectasias of eyes and skin, risk of lymphoma and leukemia, ↑ of serum α-fetoprotein
anemic infarcts vs. hemorrhagic infarcts
anemic infarcts: (pale or white color): happen in solid organs with single blood supply (spleen, kidney, heart) hemorrhagic infarcts: (red color): happen in solid organs with dual blood supply or collateral circulation (lung, intestines)
aspirin overdose
symp: NS: [tinnitus 耳鸣， vertigo (眩晕）， change in mental status (confusion, seizures)], hyperthermia (damage mito membrane, uncouple oxidative phosphorylation and ATP synthase), fulminant hepatitis (爆发性肝炎，除了aspirin还有acetaminophen 扑热息痛也会引起） respiratory alkalosis occur initially (12-24 hrs) due to direct stimulation of the respiratory center, then shift to metabolic acidosis with ↑ anion gap
anemia associated with chronic alcoholism?
sideroblastic anemia [铁幼粒细胞贫血； 此病也可能由VB6 deficiency, Lead poisoning引起】 defect in heme synthesis in mitochondria! BM aspirate shows “ringed sideroblasts” (drak blue iron granules around the nucleus of developing normablasts-iron trapped in mito.)
Brunton’s agammaglobulinemia
XR; mutated Tyr kinase: pre-B cells fail to mature opsonization defect: neutrophils have membrane receptors for opsonin (调理素，包括IgG, C3b fragment of complement, etc). Binding enhances neutrophil recognition and attachment to bact. sinopulmonary infections. Maternal Ab protects up to 6 months, then ↓ immunoglobins
Budd–Chiari syndrome
caused by occlusion of the hepatic veins. congestion. It presents with the classical triad of abdominal pain, ascites and hepatomegaly
Calcium function in coagulation?
bind γ-carboxylated VitK-dependent factors (VII, XI, X, II)
cancer引起endocarditis的机制？
paraneoplastic syn: sterile vegetations on the MV: procoagulant effect of circulating mucin （粘蛋白）from mucin-producing tumors of the colon and pancreas embolization can be a complication
catalase-positive organisms
can produce H2O2, but H2O2 is degraded by catalase, so the bact. are not killed by the MPO system
chronic granulomatous desease (CGD) vs. MPO deficiency (myeloperoxidase)
CGD: absent NAPDH oxidase and respiratory burst MPO deficiency: normal respiratory burst, but no MPO to convert (H2O2 + CL-) to HOCL’ (hypochlorous free radicals), which kill bact.
Churg-strauss syndrome
autoimmune medium and small vessel vasculitis. p-ANCA. 几乎所有病例都以asthma起病，发展到血管炎阶段时常有腹痛（腹部血管被累及）。多数死于eosinophilic myocarditis usually (but not always) manifests in three stages. 1) Allergic stage: marked by airway inflammation: almost all patients experience asthma and/or allergic rhinitis; 2) Eosinophilic stage: abnormally high numbers of eosinophils, which causes tissue damage — most commonly to the lungs and the digestive tract. 3）final stage: vasculitis, which can eventually lead to necrosis and is potentially life-threatening.
clinic findings in VB12 deficiency
3大症状： 1）macrocytic/pernicious anemia; 2) smooth, sore tongue with atrophy of papillae; 3) neurological disease (peripheral neuropathy; dementia, etc) 与folate缺乏鉴别：叶酸缺乏没有神经症状！！！ Pernicious anemia: 1）lack of gastric acid - Ab destruction of parietal cells [chronic atrophic gastritis, ↑ incidence of gastric adenocarcinoma] , 2) Ab: against proton pump; block binding of VB12 to IF 【intrinsic factor]; block binding of VB12-IF complexes to ileal receptors 其中Ab blocking binding of VB12 to IF is most specific for diagnosis
coagulation cascade?
Extrinsic: VII Intrinsinc: XII → XI → IX → VIII common pathway: X → (Xa + V + PF3 + Calcium) 这个complex叫做“prothrombin complex”, convert prothrombin to thrombin thrombin: 1) convert fibrinogen to fibrin monomer (still soluble) + fibrinopeptides A+B 2) activate factor XIII to cross-link fibrin (become insoluble)
coagulation cascade?
Extrinsic: VII Intrinsinc: XII → XI → IX → VIII common pathway: X → (Xa + V + PF3 + Calcium) 这个complex叫做“prothrombin complex”, convert prothrombin to thrombin thrombin: 1) convert fibrinogen to fibrin monomer (still soluble) + fibrinopeptides A+B 2) activate factor XIII to cross-link fibrin (become insoluble) 3) activate VIII:C in intrinsic pathway
coagulation necrosis
凝固性坏死， preserve structural outlines of dead cells mechanisms: 1) denaturatio of E. and proteins (accumulation of lactate or heavy metals such as lead, mercury, UV) 2) inactivation of E prevents dissolution (autolysis) of the cells 镜下特征： 1）indistinct outline of cells within dead tissue 2) absent nuclei or karyolysis ( fading of chromatin, 核溶解） e.g.: MI
coarctation (狭窄）of aorta: 分为infantile vs. adult2型
- infantile coarctation: associated with Turner syn, occurs between the subclavian A (锁骨下A) and ductus arteriosus 2. adult coarctation: constriction of aorta distal to the ligamentum arteriosum; 1) blood flow into the proximally located branch vessels ↑ (i.e., ↑ cerebral blood flow ⇛ ↑ risk of berry aneurysms), ↑ upper extremity BP, dilation of aorta and aortic valve ring (regurgitation) 2) blood flow below the constriction ↓ (i.e., ↓ renal blood flow ⇛ activate the renin -Ang -aldosterone system to ↑ BP ), ↓ BP in the lower extremity, leg claudication (pain in calf or buttocks when walking) 成人主动脉狭窄的特点：disparity between upper and lower extremity BP > 10 mmHg
common variable immunodeficiency
adult immunodeficiency disorder B cells fail to mature into plasma cells Sinupulmonary infections, GI infections, autoimmune disease, ↓ Ig
confirm SLE
主要靠血清检验确诊：serum ANA : anti-ds-DNA and anti-Sm Ab (highly specific, very few false-positive) anti-Ro Ab are positive for 25- 50% cases Note: lupus erythemastosus cells are NOT specific for SLE! (these are neutriphils containing phagocytosed altered DNA) Libman-Sacks endocarditis: associated with SLE, sterile vegetations located over the MV surface
corticosteroids抗炎机理
1）absolute neutrophili leukocytosis, inc. neutrophil > 90% 2) lymphopenia: sequester B and T cells in lymph nodes, signal for apoptosis 3) eosinopenia: sequester eosinophils in lymph nodes
cryoglobulinemia
small vessel vasculitis, involve skin (palpable purpura, Raynaud’s phenominon), GI, kidney associated with HCV
cryoprecipitate, Rx for what?
To acquire cryprecipitate, thawed fresh frozen plasma should be centrifuged and the precipitate should be collected. contains fibrinogen, factor VIII, factor XIII Rx: treat coagulation factor deficiency (DIC, etc)
dermatomyositis 皮肤肌炎/ polymyositis 多肌炎 DM/PM
in women 40-60 year old DM: with skin involvement, Ab-mediated damage PM: no skin involvement, T cell-mediated muscle pain and atrophy, shoulders are affected, “racoon eyes”(purple-red eyelid discoloration), ↑ serum CREATINE KINASE; ANA positive for 30%
difference between plasma and serum?
Serum does NOT have fibrinogen, prothrombin (III), factor V, factor VIII
DIC
thrombohemorrhagic disorder; produce fibrin thrombi + bleeding Fibrin thrombi contain RBCs with trapped leukocytes and platelets
Kawasaki disease
necrotizing medium-sized vessel vasculitis: in children < 4 yrs persistent fever (>100 C, > 5 d) in acute phase. swelling of hands and feet, oral erythema (strawberry tongue, bright red lips), abnormal ECG, cardiac complications (aneurysms in coronary vessels) are the most important aspect of this disease treatment: IVIG + aspirin
types of microcytic anemia
iron deficiency (most common), ACD (anemia chronic disease), thalassemia, sideroblastic anemia (高铁成红细胞性贫血，least common) 病理：defects in Hb synthesis Hb = heme ( heme = iron + protoporphyrin; defect in iron deficiency, ACD, sideroblastic anemia) + globin (↓ in thalassemia)
DiGeorge Syn
T cell disorder: 3rd and 4th pharyngeal pouches fail to develop, no thymus and parathyroids hypoparathyroidism (tetany); absent thymic shadow on radiograph, PCP; danger of GVH reaction
diseases associated with platelet aggregation: von Willebrand disease Bernard-Soulier Syn Glanzmann thrombasthenia
von Willebrand disease: deficiency in vWF, which binds to exposed subendothelial collagen and facilitate platelet adhension; Bernard-Soulier Syn: AR, ↓expression of GPIb (glycoprotein Ib, on surface of platelet, to bind to vWF) Glanzmann thrombasthenia (血小板机能不全): AR, inactive GPIIb-GPIIIa complex , defective platelet aggregation)
function of plasmin?
1) cleave insoluble fibrin monomers and fibrinogen into fibrin(ogen) degradation products (FDPs) [fragments of insoluble fibrin monomers: “D-dimer”] 2) degrade factor V, VIII, and fibrinogen 被liver合成的α2-Antiplasmin给inactivated
Gross and microscopic findings of acute MI?
1) 0-24 hr: no gross change, coagulation necrosis (no neutrophil infiltration at this time) 2) 1-3 d: pallor; myocyte nuclei and striations disappear; neutrophils lyse dead myocytes 3) 3-7 d: red granulation tissue surrounds area of infarction, macrophages remove necrotic debris 4) 7-10 d: necrotic area is bright yellow; granulation tissue and collagen formation 5) during 2 months: infarcted tissue replaced by white noncontractile scar
GVH reaction
complication in BMT or liver transplation Donor T cells activates host CD4 and CD8+ T cells 临床表现：jaundice (bile duct necrosis); bloody diarrhea (GI mucosa ulceration), dermatitis
immune hemolytic anemia
3种：autoimmune [AIHA, autoimmune hemolytic anemia], drug-induced [penicillin, quinidine, methlydopa]; alloimmune pathogenesis: 1) IgG-mediated (warm type AIHA): extravascular hemolysis, spherocytosis 2) complement-mediated: extra- or intra-vascular 3) IgM-mediated (cold type AIHA) Lab: DAT (direct antihuman globulin test）-most important marker for AIHA
HELLP syn
属于microangiopathic hemolytic anemia H: hemolytic anemia EL: elevated transaminases LP: low platelets associated with preeclampsia
Henoch-Schonlein purpura (HSP)
过敏性紫癜， Type III hypersensitivity (immunocomplex), common in 3-11 yr kids; often related to a recent upper respiratory infection, develop a few weeks after the associated illness resolves systemic vasculitis, palpable purpura (hemorragic, raised, painful to palpation: [note:鉴别于purpura caused by thrombocytopenia or vessel instablity such as scurvy is NOT palpable, because acute inflammation is not involved]) ; also caused hematemesis and bloody diarrhea classic triad for HSP: Purpura, arthritis and abdominal pain IgA and C3 deposition to arterioles, cap. and venules)
hemophilia A, B: cause? sym? treat?
A: XR, deficiency in factor VIII:c (intrinsic pathway); % of VIII:c directly correlates with severity B: XR, deficiency in factor IX Can’t be distinguished clinically ↑ PTT, normal PT (because it’s intrinsic pathway problem) DNA techniques to detect carrier treatment： mild case may respond to desmopressin acetate (抗利尿剂） severe case: infusion of recombinant factor VIII
hereditary angioedema
AD, deficiency in C1 esterase inhibitor (continued activation of C1, ↓ C2 and C4; normal C3 because alternative pathway intact), swelling of face and oropharynx
MHC
Class I: . present on nucleated cells (so not on mature RBCs). . coded by HLA-A, -B, -C . recognized by CD8 T.c and NK Class II: . coded by HLA-DP, DQ, DR genes . presented on APCs . recognized by CD4 T.c
How does INH cause anemia?
Isoniazid （INH 异烟肼， 一线抗结核药）cause VB6 deficiency. VB6 is co-factor of δ-aminolevulinic acid synthase [氨基戊酮酸合成酶】， which is the rate-limiting E for heme synthesis in mito
how to prevent Rh HDN in Rh-negative mothers WITHOUT anti-D? Rx for Rh(-) mothers WITH anti-D?
No anti-D: received anti-D globulin at 28 wks of pregnancy： it does NOT cross placenta, but protects mother from sensitazation to fetal Rh-positive RBCs that may enter her circulation anti-D positive: monitor Ab titer and periodic amniocentesis (bilirubin absorbance at 450 nM- detect by spectrophotometer) Δ OD450: degree of increase in amniotic fluid correlates with severity of hemolysis
acute MI lab and ECG changes?
Lab: 3个指标： 1）cardiac troponins (cTnI, cTnT): gold standard for diagnosis of acute MI. appear with 3-6 hr, peak at 24 hrs, disappear with 7- 10 days; 2）CK-MB (creatine kinase isoenzyme MB): appears within 4-8 hr, peak at 24 hr, disappears within 1.5-3 days 3). LDH1-2 flip: normally LDH2 > LDH1; in acute MI, LDH1 is released from cardiac muscle to cause a flip. appears within 10 hr, peak at 2-3 d, disappears within 7 days ECG: inverted T waves, elevated ST segment, Q waves
PE (pulmonary embolism) outcome?
usually have no symptoms, due to the dual blood supply (pulmonary artery + bronchial arteries) PE are the most commonly missed diagnosis in hospitalized patients (arise from deep leg vein thrombosis) If cardiopulmonary comprimise happens: infarction in the lung (typical wedge-shaped infarct)
IgA deficiency
most common congenital immunodeficiency IgA B cells fail to mature into plasma cells. Sinupulmonary infections, anaphylaxis if exposed to blood product with IgA
hypersensitivity reactions:
4 types Type I: IgE-dependent activation of mast cells, which have early and late phase reactions (early phase: release of preformed mediators such as histamine - tissue swelling and bronchoconstriction; late phase: mast cells synthesize and release PG, LTs to enhance the acute reacion) 包括asthma, hay fever, eczema, hives; drug hypersensitivity Type II: Ab-dependent reaction,分为complement-dependent和 -independent 2种：前者包括ABO mismatch, hyperacute transplantation rejection; 后者包括Grave’s dis Type III: circulating Ag-Ab complex Ag2次exposure; (SLE, Rheumatoid arthritis) Type IV: Ab-independent, T-cell mediated (cellular immunity); contact dermatitis, TB granuloma,
WAS: Wiskott-Aldrich syn
XR, combined B-/T- cell disorder, WASp mutation on X-chromsome: WASp activates actin polymerization by binding to the Arp2/3 complex, ↓ antibody production, T cells can’t polarize progressive deletion of B and T cells symptom triad: eczema, thrombocytopenia (low platelet count), sinupulmonary infections (immune deficiency) 典型维阿三联征 associated risk of malignant lymphoma, ↓ IgM, normal IgG, ↑ IgA and IgE treat: BMT/CBMT, avoid Aspirin and NSAID (will interfere with platelet function)
In addition to ABO (glycoprotein on RBC) and Rh systems, 2 more important non-Rh antigens?
1) Duffy (Fy) Ag: binding sites on RBC for Plasmodium Vivax (间日虐）- most Black lack this Ag: protect from malaria 2) I, i Ag: anti-I cold IHA (immune hemolytic anemia): Mycoplasma pneomomiae infection anti-i cold IHA: infectious mononucleosis
iron deficiency的例子和病理？
blood loss, ↑ utilization (pregnancy/lactation, infants), ↓ intake, (PNH = paroxysmal nocturnal hemoglobinuria); [note: Plummer-Vinson syn] 病理：↓ iron, % saturation, ferrintin; ↑ TIBC (total iron binding capacity), RDW peripheral blood smear shows characteristic enlarged central area of pallor in the RBC, indicate ↓ synthesis of Hb [normal RBC: central pallor area is roughly the same as 周边区域】
mechanism for phenytoin/alcohol /oral contraceptives to cause folate deficiency?
folate is presented in veggies and animal proteins as “polyglutamates”; intestinal conjugase converts it to “monoglutamate”, which is reabsorbed in the jejunum. Monoglutamate is converted to “methltetrahydrofolate” (the circulating form of folate) Phenytoin: inhibit intestinal conjugase alcohol and oral contraceptives: inhibit monoglutamate reabsorption
mechanism for varicose veins
incompetence of venous valves; occur after deep vein thrombosis, pregnancy, or genetic predisposition
leukocyte adhension deficiency (LAD)
AR, 分2型： Type 1: deficiency of beta2-integrin (CD11a:CD18) (for neutrophil adhension) Type 2: def selectin (for neutrophil rolling) 表现：delay seperation of umbilical cord (>1m), severe gingivitis 龈炎, poor wound healing, peripheral blood neutrophic leukocytosis (外周血白细胞增多）
SIADH
Syndrome of Inappropriate secretion of AntiDiuretic Hormone, 80% caused by small cell carcinoma of the lung (稀释性低钠血症） Gain of water, TBNa+/↑↑ TBW, net ↓ of POsm/Na+; both ECF and ICF volume expand, normal skin turgor
MCTD (mixed Connective Tissue Disease)
anti-RNP (ribonucleoprotein) Ab: in 100% cases similar to SLE, SS and PM, renal disease is uncommon
marker for effective erythropoiesis?
corrected reticulocyte count ≥ 3% (< 3% = ineffective erythropoiesis) EPO: synthesized in the endothelial cells of peritubular capillaries in the kidney. . stimuli for EPO release: hypoxemia, severe anemia, left-shifted O2 binding curve, high altitude % count of reticulocyte is falsely increased in anemia, so it must be corrected: corrected recitulocyte count = (actual Hct/45）× reticulocyte count [45: is the normal hematocrit 红细胞比容】
markers for folate/VB12 deficiency? indicator for folate deficiency?
hypersegmented neutrophils (> 5 nuclear lobes) in peripheral blood, 显示megaloblastic anemia 鉴别是否为叶酸缺乏：RBC folate ↓ It’s important to distinguish folate from VB12 deficiency, cause pharmacological dose of folate can correct the hematologic findings in both cases, but neurological diseases wtih VB12 deficiency cannot be corrected!!!!
mechanism for Aspirin as anti-coagulation?
irreversibly acetylates/inhibit cyclooxygenase, prevent platelet production of Thromboxane A2 (potent mediator of aggregation)
mechanism for blue fluorescent light /sunlight to treat jaundice in the newborn?
UCB in the skin absorb light energy from blue fluorescent light or sunlight: photoisomerization converts UCB to nontoxic water-soluble dipyrrole (lumirubin) ➜ excreted in bile or urine
mechanism for Lead (Pb) poisoning to cause anemia
Pb inhibits 3 E in heme synthesis: 1) Ferrochelatase (heme synthase): Iron can’t bind with protoporphyrin; 2) ALA (δ-aminolevulinic acid) dehydrase 3) ribonuclease: ribosome can’t be degraded and then persist in RBC ⇒ 特征性外周血涂片：”coarse basophilic stippling”: blue dots by Giemsa staining 需要和reticulocytes里的thread (RNA filaments)鉴别 Pb中毒的临床症状：abdominal colic+diarrhea; encephalopathy in children (ALA damages neurons), cerebral edema； peripheral neuropathy in adults (footdrop) deposits in epiphyses (骺）- radiography shows ↑ density in epiphyses; nephratoxic damage [Fanconi’s syn] screen and 诊断：↑ whole blood and urine Pb
出现ANCA(antineutrophil cytoplasmic Ab)的病有哪些？
Wegener’s granulomatosis (WG; c-ANCA), Churg–Strauss syndrome, microscopic polyangiitis (p-ANCA)
Tetralogy of Fallot
VSD, infundibular or valvular pulmonary stenosis (key to cyanosis vs. acyanosis) + RVH + overriding aorta degree of pulmonary stenosis correlates with presence or absence of cyanosis
medically significant A-a (Alveolar-arterial) gradient?
≥ 30 mmHg 计算公式：PAO2 = % O2 （713）- arterial PCO2/0.8 ↑ A-a gradient: hypoxemia due to pulmonary cause (acute respiratory distress syn, etc); could ↑ with age normal A-a gradient: hypoxemia of extrapulmonary origin
AIDS
RNA retrovirus, can NOT enter intact skin or mucosa (virus in blood, semen, milk) HIV: gp120 (envelop protein) attached to CD4 T cells, cytotoxic to CD4 T cells, lose cell-mediated immunity reservior cells: follicular dendritic cells in lymph nodes (viral replication occurs here) screen test: Anti-gp120 detected in ELISA; confirm test: Western blotting
Microscopic polyangiitis
autoimmune, p-ANCA, 多发性血管炎累及很多器官的小动脉。理论上已有很多p-ANCA在循环系统里，被一些因素触发： drugs (penicilin), infections (streptococci), immune disorders (SLE) skin affected: palpable purpura, glomerulonephritis
most common cause for acute MI? CHF?
acute MI: ventricular fibrillation CHF: ventricular aneurysm
most common cause for IE (infective endocarditis)? and in drug abuse?
Streptococcus viridans （草绿色链球菌）：most common overall cause of IE in drug abuse: staphylococcus aureus is the most common pathogen producing IE in IV drug abuse 病理：沿着MV或tricuspid valve有large, irregular vegetations, they can embolize distant organ sites → abscesses and infarctions
most common cause for VB12 deficiency?
pernicious anemia 恶性贫血，autoimmune destruction of parietal cells (胃壁细胞） UW Q: if a patient is put on folic acid ⇒ megaloblastic amenia (VB9 or cobalamin-deficiency): high-dose folic acid can improve anemia, but cannot reverse neurological symptoms (ie, foot numbness, etc)
most common CNS fungal infection in AIDS most common malignancy in AIDS most common cause for blindness in AIDS
cryptococcosis 隐球菌病 Kaposi’s sarcoma; Burkitt’s lymphoma (EBV), primary CNS lymphoma (EBV) CMV
most common complement deficiency?
C2 deficiency; associated with septicemia (Streptococcus pneumoniae), lupus-like syn in children
drug-induced lupus
procainamdie (普鲁卡因胺) hydralazine 肼酞嗪(降压药) distinguish from SLE: 1) antihistone Ab (vs. antinuclear Ab, ANA) 2) low incidence of renal and CNS involvement 3) sym disappear when drug is discontinued
most severe manifestation of Rh HDN (hemolytic disease of newborn)？ Mechanism?
Hydrops fetalis (胎儿水肿） 1) ↑ erythropoiesis in liver ➜ hepatic dysfunction ➜ albumin ↓ ⇒ plasma oncotic pressure ↓ ➜ ascites/edema; 2) severe anemia ➜ high output cardiac failure ➜ biventricular HF ➜ ascites/edema 3) ↑ risk for bilirubin encephalopathy (kernicterus) 核黄疸 Rx: exchange transfusion
myocarditis病因？pathology? clinic findings?
etiology: 1) 微生物感染： 最常见的是Coxsackievirus, 如果是central/south American: 考虑是克氏锥虫（Trypanosoma cruzi)引起的Chagas disease (查加斯病，南美锥虫病） 2). 非感染的病因，包括SLE, acute rheumatic fever, diphtheria toxin pathology: lymphocytic infiltrate is highly predictive of Coxsackievirus clinic findings: fever, chest pain, CHF; ↑ CK-MB and troponins [note: coxsackievirus is the most common cause of myocarditis and pericarditis】
neutrophilic leukocytosis vs. neutropenia
中性粒细胞增多 vs. (嗜)中性白细胞减少(症) Catecholamine, corticosteroids, lithium inhibit activation of adhension molecules ; ↑ peripheral blood neutrophil count endotoxin: ↓ activation of adhension molecule to ↓ neutrophil count
PaO2, SaO2 change in anemia? MetHb?
PaO2, SaO2 are normal in anemia Normal PaO2, d. SaO2 in MetHb MetHb treatment: methylene blue (activate metHb reductase), ascorbic acid (reduce ferric iron to ferrous iron)
paroxysmal nocturnal hemoglobinuria PNH (Marchiafava-Micheli syndrome)
阵发性夜间血红蛋白尿 (马-米二氏综合征) acquired stem cell deficiency in complement system: defect in molecule anchoring DAF (decay accelerating factor), which normall degrades C3 and C5 convertases on HSC membranes complement-induced intravascular hemolytic anemia, lysis of platelets and neutrophils 诊断： -screen: sucrose hemolysis test (糖水test, sucrose enhances complement destruction of RBC) -confirm: acidified serum test (Ham test): acidified serum activates the alternative pathway, causing hemolysis
ESR (erythrocyte sedimantation rate)
↑ in acute/chronic inflam ↑ fibrinogen, anemia [note: abnormally shaped RBCs such as sickle cells do NOT produce rouleaux]
pericarditis pericardial effusion （心包积液）
most common cause: coxsachievirus pericardial effusion: pulsus paradoxus (奇脉， drop in systolic BP greater than 10 mmHg during inspiration), neck vein distention during inspiration (Kussmaul’s sign, indicate limited RV filling)
Which vasculities are granulomatous? Which ones are necrotizing?
large vessel炎症：Takayasu’s disease, Giant cell (temporal) arteritis necrotizing: 3个累及中、小动脉的病：Kawasaki, Polyarteritis nodosa, Wegener’s
platelet functions?
- fill gaps between endothelial cells: prevent RBC leakage into interstitium 2. form hemostatic plug in small vessel injury 3. PDGF: stimulate vascular smooth muscle hyperplasia
platelet storage proteins?
in dense bodies: ADP (aggregating agent), Calcium (binding agent for VK-dependent factors) α-granules: vWF, fibrinogen [note: platelet receptors: GpIb: receptor for vWF; GpIIb/IIIa: receptor for fibrinogen
Plummer - Vinson syn
caused by chronic iron deficiency, common in postmenopausal women. triad: dysphagia (but only for solids, not for liquids), esophageal web, iron deficiency other symptoms include glossitis, achlorhydria (no HCL in the stomach)
primary leukocytes in acute. vs. chronic inflammation
acute: neutrophil； IgM prodominate chronic: monocytes, macrophages; IgG predominate
PT, PTT?
PT: prothrombin time - evaluate extrinsic coagulation system (VII - X - V - II -I) PTT: partial thrombinplastin time - evaluate intrinsic system (XII - XI - IX - VIII - X - V - II -I) 测这2个数值的意义在于监测wafarin and heparin的使用。when used together, both PT and PTT ↑ PT monitors wafarin better, PTT monitors heparin better
reperfusion damage
1) superoxide (O2-) 2) ↑ cytosolic Ca2+ ↑ of cytosolic Ca2+ cause : 1) activation of E (phospholipase - i. permeability of membrane; proteases - damage the cytoskeleton; endonucleases - DNA fragmentation) 2) re-enter into mito: increase permeability - release cyto C - apoptosis
Rh antigen system
3 gene loci encoding: D (no d: desigated as d), C, c, E, e Autosomal co-dominance Rh+ = D+ (> 85% population)
mitral stenosis
病因：recurrent attacks of rheumatic fever\ MV can’t open in diastole: 听诊出现opening snap followed by diastolic rumble; left atrial hypertrophy + dilation, pulmonary venous hypertension, AF (房颤）很常见。因为LA在整个心脏中位于最后方，compress esophagus ⇒ dysphagia for solids
rheumatic fever
5-15 yr of age; develop 1-5 wks after group A streptococcal pharyngitis type II hypersensitivity: Ab cross-react with human tissues; [cell-mediated immunity also involved] 症状：1）mitral valve: mitral regurgitation in acute attack, mitral stenosis in chronic disease; [verrucoid-appearing vegetations 疣样赘生物 develop along the line of closure of the valve] 2)可累及心脏各层： fibrinous pericarditis, myocarditis, endocarditis 3). most common initial presentation: migratory polyarthritis 诊断：↑ ASO titers (anti-streptolysin O), positive throat culture, ↑ anti-DNase B
S4 gallop S3 heart sound
S4: The late stage of diastole is marked by atrial contraction, or kick, where the final 20% of the atrial output is delivered to the ventricles. If the ventricle is stiff and non-compliant, as in ventricular hypertrophy due to long-standing hypertension, the pressure wave generated as the atria contract produces an S4. It is heard best with the bell of the stethoscope at the apex. left side S3: occurs in early diastole, caused by blood entering a volume-overloaded left ventricle; 1st cardiac sign of LVF. intensity of the heart sound ↑ with expiration right-sided S3 heart sound: due to the volume overload, ↑ with inspiration
Serum protein electrophoresis
5 peaks from + to - : Albumin, alpha1, alpha2, beta, gamma (包括IgG, IgA, IgM; very low IgD and IgE) Acute inflammation: slight d. of albumin, ↑ IgM (but the configuration of gamma peak isn’t changed!) Note: IgM ↑ as the marker for acute infl Chronic infl: polyclonal gammopathy - sign for慢性炎症； further ↓ in albumin
shock: types, changes in CO, LVEDP(左心室舒张末压）， PVR (peripheral vascular resistance)? 血循环由3个因素决定： 心输出量，血容量，外周阻力
shock: reduced perfusion of tissue → impaired oxygenation 1. hypovolemic: cause by blood loss, ↓ CO, ↓ LVEDP, ↑ PVR (因为in response to decreased CO, catecholamines and Ang II are released ➞ vasoconstriction) 2. cardiogenic shock: mostly caused by acute MI ↓ CO, ↑LVEDP (blood can’t be pumped out from LV and gets accumualted), ↑ PVR (same as hypovolemic) 3. septic shock: E. coli 1) endotoxin damage endothelial cells ➞ release of vasodilatiors (NO, PGI2) 2) endotoxin activates alternative complement pathway: C3a, C5a➞ mast cells release histamine (vasodilator) 3) IL1, TNF activate neutrophil adhension molecules ➞ neutrophil adhere to pulmonary cap. initially CO↑ (因为外周血管舒张）， ↓LVEDP, ↓ PVR
Leukoerythroblastic reaction
Immature BM cells enter the peripheral blood 外周血见nucleated RBC, tear drop RBCs If see this in women > 50: usually due to metastic breast cancer
sickle cell anemia
AR, missense point mutation: Val - Glutamic acid at 6th position of β-globin chain HbAS (heterogenous): no anemia; HbSS: intrisic defect, extravascular hemolysis HbF at birth prevents sickling for 5-6 months peripheral blood: sickle cells, target cell [excess RBC membrane, sign of hemoglobinopathy or alcohol excess]; Howell-Jolly boides [RBC containing a single dark, round inclusion represent nuclear remnants， sign of splenic dysfunction]
small, medium- and large size vessel vasculitis: 特征和代表疾病
small vessel vasculitis: palpable purpura (Henoch-schonlein purpura 过敏性紫癜） medium-sized vessel vasculitis: muscular artery vasculitis, thrombosis + aneurysm formation (Kawasaki disease, polyarteritis nodosa 结节性多动脉炎） large vessel vasculitis: elastic artery vasculitis presents with loss of pulse or stroke （1. Takayasu’s arteritis: 高安大动脉炎，“无脉病”，多发于年轻亚洲女性， granulomatous large vessel vasculitis involving aortic arch vessels; absent upper extremity pulse, stroke, visual defects 2. giant cell (temporal) arteritis
HLA-associated diseases: HLA-B27 HLA-DR2 HLA-DR3
HLA-B27: ankylosing spondylitis 强直性脊柱炎 HLA-DR2： mutiple sclerosis HLA-DR3: type 1 DM
systolic vs. diastolic dysfunction
systolic dysfunction: ↓ ventricular contraction; low EF (< 40%; normal: 55 - 80%) diastolic dysfunction: ↑ resistance to fill the ventricle, normal to high EF (stiff ventricle), S4 gallop due to ↑ resistance to filling in late diastole. left atrial pressure ↑
systemic sclerosis (sclerodema)
excess collagen deposition (e.g., tightening of muscles around mouth) Raynaud’s phenomenon: most common initial sign for SS; Lab: serum ANA (70-90% cases), anti-topoisomerase Ab (15-40%) CREST syndrome: = limited sclerosis [anti-centromere Ab > 90%] C = calcification, centromere Ab R = Raynaud’s phenomenon E = esophageal dysmotility S = sclerodactyly 指(趾)硬皮病 T = telangiectasis
Thalassemia (thal; α-, β-)
autosomal recessive, α-thal: in southeast Asia, black Americans. caused by gene deletions trait: ↓ HbA, HbA2, HbF [note: normal Hb electrophoresis because the relative proportions of the normal Hbs remain the same], ↑ RBC count if 3-gene deletion (Hb controlled by 4 gene): 4 β chains; severe hemolytic anemia; electrophoresis detects HbH if 4-gene deletion: 4 γ chains: detects Hb Bart β-Thal: mild: DNA splicing defect [↓ HbA = 2α/2β, ↑ RBC count, HbA2 = 2α/2ζ, HbF = 2α/2γ]; severe - stop codon (nonsense mutation) [no HbA, ↑ HbA2, HbF
Thromboangiitis obliterans
闭塞性血栓血管炎（Buerger’s disease) 手脚中小血管炎，和smoke有强烈相关性。多发于25-50岁吸烟男性。The main symptom is pain in the affected areas, at rest and while walking (food claudication), Raynauld’s phenomenon, ulceration, gangrene
Transplantation rejection
- hyperacute rejection (minutes, irreversible）： type II hypersensitive reaction 2. Acute (days to weeks, most common type), type IV (T-cell) and type II (IgG, IgM) hypersensitivity, reversible with immunosuppresent 3. chronic: months - years, irreversible
PK (pyruvate kinase) deficiency
PK: converts PEP (phosphoenolpyruvate) to pyruvate PK deficiency: AR, intrisic defect, extravascular hemolysis, chronic lack of ATP causes membrane damage hemolytic anemia with jaundice beginning at birth (生理性黄疸出生后3天才开始）， ↑ 2,3-BPG to right shift OBC (cause ↑ release of O2, offset the clinic effects of anemia); RBC → echinocytes (棘红细胞）
VB12 and folate in DNA synthesis?
VB12 removes methyl- from methyl-FH4 (methyl-VB12 transfer the methyl to homocysteine to Met). [folate deficiency is the most common cause of ↑ serum homocysteine in US: damage endothelium → thrombosis] FH4 is required for thymidylate synthase [inhibited by 5-FU] to convert dUMP to dTMP for DNA synthesis. FH4 is converted to FH2 and need to be converted back by dihydrofolate reductase
Job’s syn
AR: T Helper Cells (Th Cells) fail to make Gamma Interferon causing Neutrophils to be inable to respond to Chemotaxis [caused by Staphylococcus aureus] BUZZWORDS: “Cold” Skin Abscesses; Defective PMN Chemotaxis; IgE > 2000 Presentation: FATED, Coarse Faciesm (leonine face) cold, noninflammed Staphylococcus Abscesses retained primary Teeth (Keep Baby Teeth) Increase Serum IgE Derm problems like chronic Unusual Eczema Recurrent Colds Diagnosis: Inc IgE
VitK function?
synthesized by colon bacteria (newborns have to receive VitK injection的原因，还没有肠道细菌生成VitK) as precursor activated in the liver by epoxide (环氧化物）reductase; activated VitK γ-carboxylates factors VII, XI, X, II, protein C and S
vWD? Rx
AD (1:100!) combined platelet and coagulation factor disorder ↑ PTT, BT (normal PTT or BT does NOT rule out the diagnosis), ↓ VIII:c Rx: Desmopressin acetate, OCP (oral contraceptives): ↑ release of vWF to stabilize VIII:c
Wafarin抗凝机制？
inhibit epoxide reductase (thus inhibits activation of VitK), prevent further γ-carboxylation of VitK-dependent coagulation factors Why give patients Wafarin + heparin? Because previously γ-carboxylated factors are still present (prothrombin has longest half-life, take 3-4 days to fully disappear). Heparin: immediately anticoagulates the patient by enhancing ATIII （antithrombin III)
venous vs. arterial thrombi; drug for each type?
Venous thrombi: caused by stasis or hypercoagulable state, in deep vein in the lower extremity below the knee. prevented by heparin and Warfarin Arterial thrombi: caused by turbulent flow or endothelial cell injury, or hypercoagulable state. happens in elastic and muscular arteries, majority overlies with atherosclerotic plaques. prevented by aspirin
Wegener’s granulomatosis
autoimmune, necrotizing small and medium-sized vessel inflammation for respiratory tract and kidney (could be fatal and require long-term immunosupression) childhood - middle age; c-ANCA Ab, saddle nose (/鼻腔里坏死性肉芽肿导致鼻隔膜变形）
What should you hear for mitral valve regurgitation?
Blood entering the left atrium during systole (mitral valve can’t close) produces a PANSYSTOLIC mumer; intensity ↑ with expiration. best heard at apex
hyperglycemia对血浆渗透压和血纳的影响？
↑ POsm, ↓ serum Na+ (dilutional) 稀释性低血纳 例子：diabetic ketoacidosis (DKA), volume depletion (1) dry mucous membrane 2) ↓ skin turgor 3)tilting test: ↓ in BP, ↑ pulse when sitting up from a supine position
↓ PaO2 (hypoxemia) + ↑ A-a gradient can be caused by?
extrapulmonary causes: 1) depression of the respiratory center in the medulla: brain injury, barbiturate overdose 2) upper airway obstruction: epiglottitis due to H. influenzae, virus, etc; mucosal edema narrows the trachea 3) chest bellows (muscles of respiration) dysfunction: paralyzed diaphragm, ALS with degeneration of anterior horn cells
↓ PaO2 + ↑ A-a gradient can be caused by?
ventilation/perfusion/diffusion defects, right-to-left cardiac shunts ventilation defects: airway collapse (ie. respiratory distress syn) perfusion defect: pulmonary embolus diffusion defect: interstitial fibrosis, pulmonary edema R-V shunt: tetralogy of Fallot
most important metabolite of nicotine?
cotinine screening test in blood or urine
吸气，呼气对心音的影响？
expiration: ↑ intensity for left-sided heart mummers and abnormal heart sound inspiration： ↑ for right-sided heart murmers
