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AMYLOIDOSIS 소화기 내과 R3 박지영
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Amyloidosis Amyloid Cellulose-like deposits Virchow in 1854 Positive birefringence with polarized light Biochemical nature of the protein in the fibril deposits Systemic or localized, acquired or inherited, clinical patterns A subset of a larger class of diseases The aggregation of misfolded proteins and extracellular deposits of the aggregated protein At a distance from the site of synthesis Ultimately compromise function of the target organ
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Amyloid Protein PrecursorClinical SyndromesInvolved Tissues AL Ig light chain, κ or λ primary myeloma associated kidney, heart, peripheral nerve, tongue, bone marrow AA(Apo)serum AA chronic inflammation familial Mediterranean fever familial amyloid nephropathy with urticaria and deafness tumors kidney, liver, spleen ATTRTransthyretin familial amyloidotic polyneuropathy familial amyloidotic cardiomyopathy senile systemic (cardiac) amyloid peripheral nerves autonomic nerves heart, kidney Aβ2MAβ2Mβ 2 -microglobulin dialysis-related amyloid synovium, carpal tunnel, tongue TABLE 296-1 CHEMICAL CLASSIFICATION OF HUMAN AMYLOID Goldman: Cecil Medicine, 23rd ed.
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Etiology and Incidence- AA Amyloidosis Chronic inflammatory states : rheumatoid arthritis, lupus, Crohn's disease Chronic infections : tuberculosis, subacute bacterial endocarditis In the United States and Europe Uncommon, <1% of patients Because of advances in anti-inflammatory and antimicrobial therapies In Finland The most common cause of nephrotic syndrome with RA More common in Turkey and the Middle East (in association with familial Mediterranean fever )
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Pathobiology - AA Amyloidosis Serum amyloid A Acute-phase apoprotein synthesized in the liver Transported by high-density lipoprotein, HDL3, in the plasma Several years of an underlying inflammatory disease Degradative proteolytic cleavage↓ Abnormal cleavage of a normal protein ↑ Misfolded conformer ↑ Chronic elevation of SAA Fibril formation
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the most frequently affected (80%) proteinuria (~nephrotic range ) RTA renal failure hepatomegaly cholestatic liver func tion abnormalities liver failure : uncommon peripheral sensory neuropathy (18%) carpal tunnel syn (25%) autonomic dysfx with gastrointestinal motility disturbances orthostatic hypoTN (16%) cardiac sx (40%) death (75%) arrhythmias CHF ventricular myocardia l deposition diastolic dysfx CHF, arrhythmia sudden death preserved systolic fx.
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Treatment - AA Amyloidosis Treatment of the underlying inflammatory or infectious disease ! Colchicine : in familial Mediterranean fever, esp. renal disease Cytotoxic and immunosuppressive agents Azathioprine, chlorambucil, methotrexate, cyclophosphamide Anti-cytokine therapy : etanercept and infliximab Rheumatoid arthritis (RA), ankylosing spondylitis Eprodisate To interfere with the interaction of AA amyloid protein with glycosaminoglycans in tissues
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49/F, fatigue, nausea, vomiting, weight loss for 6 month AST/ALT 120/39 U/L, ALP/GGT 2680/762 U/L, TB/DB 8.0/6.5 mg/dL Viral marker, autoAb : negative Abdominal sono : normal other than ascites Echo, ERCP : no abnormality HD #15 : confusion, general condition ↓ Progressive metabolic acidosis and hepatorenal syndrome HD #21 : died Post-mortem liver biopsy : amyloid deposition on Congo Red staining Immunohistochemical staining : AA type
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57/M, indigestion, jaundice, wt.loss for 1month PEx : hepatomegaly TB 3.7 mg/dl, AST/ALT 45/38 IU, ALP/GGT 713/278 U/l Abd sono : hepatomgegaly d/t infiltrative disease Echo : hypertrophic cardiomyopathy Liver bx(HD#17) Congo red stain (+) Progressive jaundice, AST/ALT↑, PT↑, ascites Hepatic failure with encephalopathy Died (HD#59) 50/M, abd. Pain and diarrhea for 5days, known ESRD on HD(5yrs ago) PEx : Hepatomegaly AST/ALT 25/33 IU Abd. CT : diffuse enlargement of the liver without focal lesion, ascites Liver bx : Congo red stain (+)
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IndicationContraindication (absolute) Primary or secondary biliary cirrhosisUncontrolled extrahepatobiliary infection Primary sclerosing cholangitisActive, untreated sepsis Autoimmune hepatitis Uncorrectable, life-limiting congenital anomalies Chronic hepatitis with cirrhosisActive substance or alcohol abuse Cryptogenic cirrhosisAdvanced cardiopulmonary disease Hepatic vein thrombosisExtrahepatobiliary malignancy Fulminant hepatitisMetastatic malignancy to the liver Alcoholic cirrhosisCholangiocarcinoma Chronic viral hepatitisAIDS Primary hepatocellular malignanciesLife-threatening systemic diseases Hepatic adenomas Familial amyloid polyneuropathy Table 304-1,2 Indication and contraindication of liver transplantation Harrison’s Principles of Internal Medicine, 17 th edition
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STATUS 1 18 세 이상의 전격성 간부전증 (Fulminant liver failure) 7 일 이내에 간이식을 받지 않으면 생명연장의 희 망이 없는 상태 다음 중 한가지 이상에 해당하는 경우 만성 간질환 없이 간질환의 증상이 나타난 후 8 주 이내에 급성 전격성 간부전증이 발생하고 뚜렷한 간성혼수가 동반된 경우 -flapping tremor, hyperbilirubinemia -PT > 20 초 or INR> 2.5 or hypoglycemia 간이식후 7 일 이내에 이식된 간이 기능을 하지 못 하는 경우 간이식후 7 일 이내에 간동맥성 혈전증 (hepatic a. thrombosis) 이 있는 경우 윌슨병 (Wilson's disease) 환자에게 급성 간기능 부전이 동반된 경우 LT 응급도 기준
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STATUS 2A 만성 간부전증 (Chronic liver failure) 환자가 집중 치료실에 입원해야만 하는 상태로 7 일 이내에 간 이식을 받지 않으면 생명연장의 희망이 없는 경 우 CTP 가 10 점 이상이면서 다음 중 한가지 이상에 해당 치료에 반응하지 않는 활동성 정맥류 출혈 (active variceal hemorrhage) 로 판명된 경우 - 내시경으로 확인된 식도 또는 위정맥류로 내시 경적 지혈치료에도 불구하고 하루 4unit 이상의 수혈이 필요한 상태로 TIPS 또는 수술적인 치료 가 불가능하거나 실패한 경우 간신증후군 (Hepatorenal syndrome) - 쇼크나 진행되는 세균성 감염, 신독성 물질, 체 액소실에 의한 것이 아니어야 하며, 적극적인 대 증치료에도 불구하고 2 일동안 하루 소변량이 500cc 이하 이면서 혈청 크레아티닌 >2.0mg/ ㎗인 경우. 다만, 혈액투석을 시행했을 경우 혈액투석 시행 전 2 일간을 기준으로 한다 난치성 복수 / 간 - 흉수증 (ascites / Hepato- hydrothorax) - 복수를 조절하기 위해 시행한 TIPS 치료방법 에 반응하지 않거나 적응증이 되지 않는 환자로 이뇨제나 소금의 절제와 같은 내과적 치료방법이 실패하여 1 주일에 1 회 이상 4ℓ 이상의 복수 또는 흉수천자가 필요한 환자 내과적 치료에 반응하지 않는 stage Ⅲ나 Ⅳ인 뇌 질환 (encephalopathy)
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