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
