1 / 1, 3, 4 - 11. , 2. ( CO)3. 4. 5. pH 6. ' . Steatosis (fatty change) -ccl4- . (anoxia) - ". - . - " . - , , . . : . : , , . -er . . : - . - . - . - . - .steatohepatitis -fatty liver disease () .CCl4-induced liver cell injury -> fatty liver of CCl4 poisoningcarbon tetrachloride (CCl4)P450 CCl4 - CCl3 . -SER -autooxidation . lipid peroxides - lipid peroxides . , SER -RER. . -fatty liver of CCl4 poisoning. . " -SER . .atherosclerosis ( ) . (foam cells). (atheromas). 11. .xanthomas - . ( ) , . - cholesterol needles xantomasinflammation and necrosis- ( , , ). . myelin figures . .cholesterosis -lamina propria Niemann-Pick disease, type C .proteinuria , -proximal tubule. ( ). , -proteinuria . -ER , , Russell bodies.alpha1-antitrypsin deficiency -ER CF ' familial hypercholesterolemia -LDL unfolded protein response .proteinopaphies = protein-aggregation diseasemercuric chloride poisoning... -sulfhydryl ATP . , , : ' . -cytochrome oxidase , oxidative phosphorilationAcetaminophen (Tylenol) - . " " P450 . - GSH. GSH , - . GSH , 3-5 . fatty change of the liver - - .fatty change of the liver - fatty change of the liver - fatty infiltration - - coagulative necrosis, .1. 2. -ghost 3. blebing 4. 5. , Dense bodies 6. 7. -RER.8. -ER . 9. 10. 3 : Pyknosis - karyorrhexis - kariolysis - - liquefractive necrosis -clostridium , , . PMN PMN , fat necrosis " , " Saponification. : ( ) - caseus necrosis - , , '. fibrinoid necrosis , ( )1- 2- 3- , 4- 5- 6- 7- (body builders), , 1. - 2. - 3. - 4. - 5. - " 1- - 2- () 3- A - ' 4- / - () () " . - displasia o - - o D- , , - , , . " 2 - 1 (anthracosis) , , " - . melazema " " ACTH. ACTH -MSH neurofibromatosis , Nevus () . .Lentigo () . = . . , , . .Viteligo , .- , , " . Albinism - . () . - . - ( C) . . - . . : , .. - . . - . . - , , . , () (). " ". . - - " , ( ) , . . BBB . - . kernicterus 1. :. (hepatitis). . . 2. :. '. 3. :. dubin Johnson. - Primery billiary cirrhosis . . dubin Johnson , . .Primery billiary cirrhosis , , . . . . -1. 2. inflammation3. " 5 - + ( 5) ATP7B 2 , . - Mallory bodies - - - " - - . . - - . - . calating agent ( ) - rheumatic fever / ( ) . . H&E . , , . Psammoma bodies- , . . " . apatite. : initiation -propagation ) PTH- ) : , , turnover . ) D: , sacroidosis, ) - .) ) milk-alkali syndrome- (, ) , . , , ( ) (nephrocalcinosis) EDS *: , .*: * : , (EDS ), (EDS ), (EDS ).EDS type 1 " . ??? 1 -3 -2, 4 -5 . 5 ??? , EDS like syndrome - EDS - 6 ( ) , .Hypotonia, joint laxity, congenital scoliosis, ocular fragility EDS - 4 III - Thin skin, arterial or uterine rupture, bruising, small joint hyperextensibility EDS arthrochalasia I I ISevere joint hypermobility, skin changes mild, scoliosis, bruising EDS dermatosparaxis 1 1 I ISevere skin fragility, cutis laxa, bruising Marfan's Syndrome (500 , missense) FBN1 15q21 - -1. -. . , , : : . . . - . . " " ". : (ectopia lentis) : : -35-40% . . - MPS , , ( ) . , ( ), -. , , : , , - . - - . (), "" -cornea, . . hurler -MPS 1 H -1- 6-24 , , . " 6-10 , - MPS 2 -cornea x-linked - hexsoze aminidase A = GM2 Gangliosidosis = - 15 -> -hexose aminidase A n-actyl galactose amine GMA - . , . myelin bodies (). , , , (cherry red spot) . - 2-3.exose aminidase activator deficiency = tay sacks like disease hexose aminidase - (Niemann-Pick) A missense . . m90 , . . -EM . zebra bodies. , , , , ' . , . : -gyri -sulci . ' . , . Cherry red spot . 6 . . , , , lymphadenopathy . . . . - . - (Niemann-Pick) B organomegaly ( ) -CNS. ". - -> -hexose aminidase B = Gaucher Disease ( ) ( Gaucher Cells), -CNS. . . , . , . , , lymphadenopathy " . Chitotrionsidase, " , . Gaucher chronic non-neuronopathic form (type I) . . - , , , , . , , pancytopenia - thrombocytopenia, Gaucher Acute neuronopathic (type 2) . ' , , . - CNS .Gaucher type 3 I II von gierke = 1 -6- : ( ) () : , , , (hyperuricemia), goat , . : ' = 5 ( ) : - , . -50% . . . 2 = - ( ) ( ) , ( ). - , , - . 4 = ' , , , . (alkaptonuria) . , . , , - , . . ochronosis - ( -) , - . - , , . 1 = - NF-1 , down-regulation p21 ( - tumor suppressors)1. : (, ) . - . , . : , -: , , : - , . " -. .2. : -, " . 1. () 2. , 3. () lisch. 4. : , , , ( ) 5. , ( ), ( ), ( " ), , ( ). 6. . 7. . 8. - 1 : 3000. 2 = , NF-2, tumor suppressor. , , , - ( ). . , ( ) -, , . -, (), ( ) ( -, " ). -, lisch. 1, 1 -40 50 .CF . . , " .Familial Hypercholesterolemia (FH) -LDL 19 -LDL -FH 50% - -LDL . -LDL " . , LDL, -> + -> (MI) , . ?? -LDL . HMG CoA Reductase " -LDL. gene therapy.Class 1 , Class 2, -ER 'Class 3 , LDLClass 4 , LDL, .Class 5 -LDL , -LDL. .Metachromatic leukodystrophy Arylsulfatase A Sulfatide 6 - + - -ECM. . (" - ): 1- - ( )2- - - kwashiorkor.3- - ( )4- - :1- 2- 3- Sodium and water retention- , * - , , * - * : 1. 2. : 3. 4. 5. - filariasis6. Anasarca . -pitting edema, .acsitis subcutaneous edema . , dependent . . . " . . acute respiratory distress syndrome. . . ( - " ). . , .* 2-3 . * ( , ) * " 1. - 2. - -encephalitis, hypertensive crises 1. 2. - . . . , , . . " ( ) , . .= passive hyperemia congestion = ( ) , , , , . . - - , , ( ) = chronic passive congestion of the liver , , . ( ) , . , " . nutmeg liver. cardiac cirrhosis acute hepatic congestion . ( ) fatty change. , , , , . = chronic pulmonary congestion , ( ) , , () . . , " (heart failure cells). . splenomegalia- 2 -3 , , , , , (" ). long standing congestion = chronic passive congestion (stasis) -> -> -> congestion -> severe long standing hepatic congestion " , ( )Hemorrhage () : , , atherosclerosis chronic congestion (= hematoma = ). . : hemorrhagic (hypovolemic) shock ( ). ( ) ( )petechiaeo o (thrombocytopenia)o ( uremia) o (1-2 ") , . " '. ( -) ( -) ( -)Purpurao -petechiaeo : (vasculitis) (amyloidosis) ( 3 "). " '. ( -) ( -) ( -)ecchymoses , " - ( 1-2 ") . " '. ( -) ( -) ( -)hemothorax, hemopericardium, hemoperitoneum, hemarthrosis ( ) 8 - + + + ( ) :1- - : ( ) (= ) . . - rheumatic fever2- - : . 3- - :1- 2- - 3- Dissaminated Intravadcular Coagulation 4- ( " )5- 6- , : , mural thrombus. ( ). , , " zahn ( . , ( ) , . ). : ( ). : - . . . , " - recanalization. ( ) . , . " " .thrombophlebitis ( ) phlevothrombisis ( ) - , . . . . - systemic thromboembolism - , , . 80% , 2/3 , -1/4 . , () valvular vegetation, paradoxal emboli. . . (75%) (10%), , , . , . ' . - pulmonary thromboembolism - -95% , - , (saddle embolus) ( ) ( ). , (-60% " ) ( ) ( - end artery) ( ) paradoxal emboli : , , (achypnea, dyspnea, tachycardia), (, , progression to delirium ), . A diffuse petechial rash in nondependent areas , , ( ) , ' , , , , - . , , . , , " . , . , : = infract - -99% : , " . , : ( " ) : (, ) " , " () .: - " . . : . , " - ( ), . ( ), (hemorrhagic). " ( ) ( -) (hemorrhagic)1- ( )2- () 3- ( ), 4- 5- , , (' ). . , . . ( anemic)1- end arterial circulation (, )2- . . . , . . (?) , = shock - , , , , .1. nonprogressive phase - - , " . .2. progressive phase - , , , , pH : , , -DIC. , . 3. irreversible phase - . ( NO). , . . " , . , , , , . -ischemic encephalopathy - , contraction band necrosis - (acute tubular necrosis)- , . , (second phase dominant by renal insufficiency), . - ' - (hemorrhagic enteropathy) - central hemorrhagic necrosis1. nonprogressive phase- 2. progressive phase- , .3. irreversible phase- = cardiogenic shock - " (), , ( ) (' ) ; ; ; , , . 75% = hypovolemic shock - " , . ; ; ; , , . - 80%-90% " = septic shock (= ) - (bacilli) , LPS . LPS " , TNF, IL-1, IL-6 . LPS : - ( )- - , - DIC , , -DIC , , ' . -LPS , " . . - (shock lung). 75% - " IgE - , " , .toxic shock syndrometoxic shock syndrome toxins -1 () " T . : , , . 7 + 9 - - 2 .* - , ( , ) (, , )* - * - * - glomerular nephritis* - . ( ) (': , frosebites, , ). (, , ) (hypersensitivity) , , PMN , - -PMN, , . .Serous inflammation - . Fibrinous inflammationFibrinous pericarditis/pleauritis . . ' . , .Supurative/purulent inflamation pyogenic (PUS) , . .- ulcer ( ), helicobacter pylori, , . - :1- (, )2- , ( ).3- 1- active inflammation- . . : , ( ) ( )2- 3- - LAD1 2, LFA-1 -Mac-1. LAD2 LEWIS X, E-Selectin, Fucosyl transferase -LAD1, .Chediak-Higashi Syndrome . ( ), , . " Blood Smears. T . Chronic Granulomatous Disease NADPH Oxidase. : X-Linked (gp91phox) -2 (p47phox -p67phox). -C3 , . Erythematosus C2 C4 Systemic Lupus Erythematosus C2 C4 NeisseriaParoxysmal Nocturnal Hemoglobinuria - -IP , DAF CD59 . Hereditary Angioneurotic Edema C1INH C1 C4 C2. C2: -C2 Kinin . , C1NH kallikrein 12 , , , " .cachexia anorexia ()a1-antitrypsin deficiency -> , antiprotease a1-antitrypsin -> -ECM. (gout)uric acid - ", -. uric acid silicosis particulate silicaatherosclerosis " () TuberculosisMycobacterium tuberculosisNoncaseating tubercle (granuloma prototype): a focus of epithelioid cells, rimmed by fibroblasts, lymphocytes, histiocytes, occasional Langhans giant cell; caseating tubercle: central amorphous granular debris, loss of all cellular detail; acid-fast bacilliLeprosyMycobacterium lepraeAcid-fast bacilli in macrophages; non-caseating granulomasSyphilisTreponema pallidumGumma: microscopic to grossly visible lesion, enclosing wall of histiocytes; plasma cell infiltrate; central cells are necrotic without loss of cellular outlineCat-scratch diseaseGram-negative bacillusRounded or stellate granuloma containing central granular debris and recognizable neutrophils; giant cells uncommonlymphangitislymphadenitis -hyperplasia (follicles) -hyperplasia . reactive, lymphadenitis.bacteremia ( ) 11 - = Atherosclerosis4 :1. 2. 3. 4. . : , , , , , , , A, , . (, , iliac, coronary, " ?? cerebral?? -femoral ??). : LDL . " T helper , , . core -fibrus cap -fibrofatty plaque () . . , , ( ), , , ( ) , , , , .mockeberg medial calcific sclerosis arteriolosclerosis , , pulmonary hypertension - . = ANEURYSM ( , ) " . . 10 + 12 - = scurvy C C - .Marfan syndrome fibrillin, , , , ( - - ), ( - hyperflexion), wound dehiscence ( ) - , (ulceration) - ( ) .hypertrophic scar . . , .keloid . -.exuberant granulation = proud flesh . " .aggressive fibromatosis = desmoid . ( ) . " . , . (contracture) -wound contraction. . . - ....marfan syndrom - (aortic dissection) .von willebrand disease Bernard soulier syndrome Glanzmann thrombasthenia 506 5 " C (G to A transition) -3' - - 3 Heparin-induced thrombocytopenia syndrome + + -Antiphospholipid antibody syndrome (Lupus anticoagulant syndrome) 13 - 16 - HPV (human papiloma virus) 16,18 - . 31,33,35,51 - . -DNA -DNA tumor suppressors (RB, P53) - , . : , , - 'EBV (epshtein barr virus) B CD21 B. B EBV (DNA DNA ) . -B ( ). -B . LMP-1 ' (" " CD40 -B - T-Helper, -B). CD40 , LMP-1 NFkB JAK/STAT B. B ( , B , ') -'.Burkitt Lymphoma 80%, Burkitt Lymphoma, 8 -14, , MYC.Nasopharyngeal Carcinoma 100% ' DNA EBV. , (Caspid), IgA .HBV -DNA . HBV :1. " , , HBV . , , , Dietary aflatoxins.2. HBV -HBx protein . (IGF-2 -IGF-1). HBx p53, HCV (Hepatitis C virus) HHV (capushi sarcoma) HTLV1 (Human T-Cell leukemia virus type 1) T CD4 . T ( ) -> T -> B -> - -> MALToma -> -> , MALToma () CML (chronic myeloid leukemia)Ab1 ( ) bcr " 9:22 gleevec DNA well differentiated adenocarcinoma , , moderately differentiated adenocarcinoma , poorly differentiated carcinoma , , , , familial adenematous polyposis (FAP) APC ( adenomatous polyp ) -100% 18 - ( 6)Systemic Lupus Erythematosus (SLE) : , ANA, ( DNA ) : , , , : - . ( ). 2-antiphospholipid antibody syndrome1. : mallar rush-, 2. Urticaria, bullae, maculopapular lesions, ulcerations. - epiderma-dermal junction 3. 4. 5. - non erosive synovitis with little deformity. 6. - (=) 7. - .8. - , , 9. - , , , 10. DNA , , 11. ANA ............... 1:2,500 antiphospholipid antibody syndrome ( ), Chronic discoid lupus erythematosus - . ANA DNA . - Subacute cutaneus lupus Erythematosus Drug induced lupus erythematosus... ( -ANA). " CNS . Sjogren syndrome RNP , , , , , , , . . . - Sica syndrome () , , , ' . rheumatic fever Sica syndrome 19 - - , , , . , . , . , , ( ), Carpal Tunnel - Peripheral Neuropathy. "congo red"- , - - AL - multiple myeloma AL - amyloid light chain. - ( Bence Jones), " - Multiple Myeloma, AL. , , , . ' (Reactive Systemic Amyloidosis) - : , (Osteomyelitis), (Bronchiectasis), (Ulcerative Colitis), (), , ' - Renal Cell Carcinoma, , AA - Amyloid Associated - SAA Protein. " . , , , , . . '. - AB (amyloid beta microglobulinr) 2 FMF - Familial Mediterranean Fever AA -SAA . . HeredofamilialTTR (transtyretine) , . - Peripheral Neuropathy , , . (Hemodialysis Associated Amyloidosis) - -2 Microglobulin , . . , Medullary Carcinomas ( - " ) 2. . , , , . , , AL.Senile cardiac amiloidosis (AL). - , TTR .Infiltrative (Restrictive) CardiomyopathyCerebral Amyloid Angiopathy (CAA) (CAA 4 ApoE) ( , - 2 ApoE). - -Amyloid - A4 , (). ( , -)HCHWA-D - -Precursor (-PP), 21 , . 21 - - :1. - , ( , ).2. polyol pathway- ( )* : : . : -BM . . . : -BM , , , , , , , (background retinopathy), , , . . . -polyol .: : -BM , : nodular glomerulosclerosis. diffuse glomerulosclerosis. . - -. . . Pyelonephritis. . . : - (), , , , (parethesia). , , , , , , , : , , , background retinopathy, : , : .Acanthosis Nigricans - , . . ( 5%) (HbA1c) -4 (120 )Type 1 Diabetes- insulin depended diabetes mellitus (IDDM) - 2 : 1. - ' , ' 2. - ' ' . . , Type 2 Diabetes- non insulin depended diabetes mellitus (NIDM) , , ' . 5-20 , . . (polyuria), (polydypsia) (polyphagia) . , / , ( spina bifida, ", ). . . , , . 24 - - preformed Ab . . , . HLA . : . (IgG) . -EM , . , , . : PMN, . -CD4 -CD8. -HLA " . T, , . : , endothelialitis, -BM, . . ( ) . : , . : IL1, FGF, PDGF . . : , , , , - glomerular sclerosis, , . .PTLD (post transplant lymphoproliferative disorder) B " - EBV . EBV . . , , . , . : . EBV -EBV . -EBV .Acute tubular necrosis . , , .Acute interstitional nephritis , , .stripped fibrosis .fine isometric vacolation , , IgM 25 - 9PEM (Protein Energy Malnutrition)- 25% [ = - 80% ].Marasmus" . (Cachexia), , , -CNS ( ). Kwashiorkor" : , ( ). - , ( ), ( ), , ( , , ), , , (, " ), (" , ). , . (1-3 )PEM = Cachexia , , -. PEM : GnRH ( -), , , , ( , -arrythmias). , . . A: . Xerophthalmia bitot spots ( . , ). Keratomalacia ( ) : : : , . . A " ( ). , . - Brain pseudotumor ( ) : , - papilledema ( ). : , , , ( ). (Rickets - osteomalacia ) D . , P-450 , . - PTH . - epiphyseal plates, , , - . - unmineralized osteoid. - H&E, . . , . , . . E . , , : , , . . CNS. , . K , , . . , , . ( ) K . .(Dry beri beri) polyneuropathy -B1 () - -25% " , , , , .(Wet beri beri) cardiovascular syndrome -B1 () - -25% , C.O . , .Wernicke-Korsakoff syndrome -B1 () - , -mamillary bodies.Wernicke encephalopathy : ophthalmoplegia ( ), nystagmus ( ), ataxia ( , ), .Korsakoff psychosis : retrograde amnesia, . B2 () - 1. , (cheilosis\cheilitis)2. Glossitis ( ) .3. Superficial interstitial keratitis - , opacities () .4. Dermatitis ( ) .5. .pellagra - 3D:1. Dermatitis - -, , " . , 2. Diarrhea - , .3. Dementia () - . B6 - Pyridoxine ( ), , , cheilosis, peripheral neuropathy, glossitis.Scurvy = () C ( Ascorbic acid) . , , . .1. : subperiosteal hematomas . .2. : . ( -rickets). " , , . .3. . B12 (Folate) , - DNA B12 MI (Ischemic Heart Disease) , - " , VasoSpasm, -" " TPA - -Infraction , " - - () (Stable Angina) - ST-Depression . " . ' (Prinzmetal's Angina) . ST-Elevations ST-Depressions - (Unstable Angina) ST-Depression ", ST-Elevation. . Stable Angina, -Stable Angina (Sudden Cardial Death)" , " - MI - Myocardial Infarction* - (Occlusive Intracoronary Thrombus)- * (VasoSpasm) , .* - -Left Sided Mural Thrombosis, Vegetative Endocarditis Paradoxic Emboli Foramen Ovale Staining Defect Basic Fuchsin DyeCoagulation Necrosis Cross Striations, Contraction Bands, Edema, Hemmorage , .Continuing Coagulation Necrosis, -Marginal Contraction Bands. . -. - . MI . :*- * *Congestive Heart Faliure * * ( ).*Mural Thrombosis * , (Tamponade).* -Papillary Muscle, - * Trans-Mural Infract Sub-EndoCardial Infract - 1/3-1/2 . Trans-Mural MI (Ischemic Cardiomyopathy) (Severe Coronary Atherosclerosis), -Major Branches , . , (Decreased Complience), , . , () " . " (Hyperplasia) , ( 2-3 ) . , , -Cardiac Faliure - .

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