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AMYLOIDOSIS
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Amyloidosis
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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
TABLE 296-1 CHEMICAL CLASSIFICATION OF HUMAN AMYLOID
Amyloid
Protein
Precursor
Clinical Syndromes
Involved Tissues
AL
Ig light chain,
κ or λ
• primary
• myeloma associated
kidney, heart,
peripheral nerve,
tongue, bone marrow
(Apo)serum AA
• chronic inflammation
• familial Mediterranean fever
• familial amyloid nephropathy with
urticaria and deafness
• tumors
kidney, liver, spleen
ATTR
Transthyretin
• familial amyloidotic polyneuropathy
• familial amyloidotic cardiomyopathy
• senile systemic (cardiac) amyloid
peripheral nerves
autonomic nerves
heart, kidney
Aβ2M
β2-microglobulin
• dialysis-related amyloid
synovium,
carpal tunnel, tongue
AA
Goldman: Cecil Medicine, 23rd ed.
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 )
Pathobiology
-AA Amyloidosis
 Serum amyloid A
• Acute-phase apoprotein synthesized in the liver
• Transported by high-density lipoprotein, HDL3, in the plasma
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Several years of an underlying inflammatory disease
Degradative proteolytic cleavage↓
Abnormal cleavage of a normal protein ↑
Misfolded conformer ↑
 Chronic elevation of SAA
 Fibril formation
• hepatomegaly
• cholestatic liver fun
ction abnormalities
• liver failure
: uncommon
• the most frequently
affected (80%)
• proteinuria
(~nephrotic range )
• RTA
• renal failure
• 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 myocardi
al deposition
diastolic dysfx
CHF, arrhythmia
sudden death
• preserved systolic fx.
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
 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
<case 1>
 57/M, indigestion, jaundice,
<case 2>
wt.loss for 1month
 PEx : hepatomegaly
 TB 3.7 mg/dl, AST/ALT 45/38 IU,
ALP/GGT 713/278 U/l
 50/M, abd. Pain and diarrhea for
5days, known ESRD on HD(5yrs ago)
 PEx : Hepatomegaly
 AST/ALT 25/33 IU
 Abd sono : hepatomgegaly d/t
infiltrative disease
 Echo : hypertrophic cardiomyopathy
 Liver bx(HD#17)  Congo red stain (+)
 Abd. CT : diffuse enlargement of the
liver without focal lesion, ascites
 Progressive jaundice, AST/ALT↑,
PT↑, ascites
 Hepatic failure with encephalopathy
 Died (HD#59)
 Liver bx : Congo red stain (+)
Table 304-1,2 Indication and contraindication of liver transplantation
Indication
Contraindication (absolute)
Primary or secondary biliary cirrhosis
Uncontrolled extrahepatobiliary infection
Primary sclerosing cholangitis
Active, untreated sepsis
Autoimmune hepatitis
Uncorrectable, life-limiting congenital
anomalies
Chronic hepatitis with cirrhosis
Active substance or alcohol abuse
Cryptogenic cirrhosis
Advanced cardiopulmonary disease
Hepatic vein thrombosis
Extrahepatobiliary malignancy
Fulminant hepatitis
Metastatic malignancy to the liver
Alcoholic cirrhosis
Cholangiocarcinoma
Chronic viral hepatitis
AIDS
Primary hepatocellular malignancies
Life-threatening systemic diseases
Hepatic adenomas
Familial amyloid polyneuropathy
Harrison’s Principles of Internal Medicine, 17th edition
LT 응급도 기준
STATUS 1
•18세 이상의 전격성 간부전증(Fulminant liver
failure)
•7일 이내에 간이식을 받지 않으면 생명연장의 희
망이 없는 상태
•다음 중 한가지 이상에 해당하는 경우
•만성 간질환 없이 간질환의 증상이 나타난 후 8
주이내에 급성 전격성 간부전증이 발생하고 뚜렷
한 간성혼수가 동반된 경우
-flapping tremor, hyperbilirubinemia
-PT > 20초 or INR> 2.5 or hypoglycemia
•간이식후 7일 이내에 이식된 간이 기능을 하지
못하는 경우
•간이식후 7일 이내에 간동맥성 혈전증(hepatic a.
thrombosis)이 있는 경우
•윌슨병(Wilson's disease) 환자에게 급성 간기능
부전이 동반된 경우
STATUS 2A
•만성 간부전증(Chronic liver failure) 환자가 집
중치료실에 입원해야만 하는 상태로 7일 이내에
간이식을 받지 않으면 생명연장의 희망이 없는
경우
•CTP가 10점 이상이면서 다음 중 한가지 이상에
해당
•치료에 반응하지 않는 활동성 정맥류 출혈
(active variceal hemorrhage)로 판명된 경우
- 내시경으로 확인된 식도 또는 위정맥류로 내
시경적 지혈치료에도 불구하고 하루 4unit이상
의 수혈이 필요한 상태로 TIPS 또는 수술적인 치
료가 불가능하거나 실패한 경우
•간신증후군(Hepatorenal syndrome)
-쇼크나 진행되는 세균성 감염, 신독성 물질, 체
액소실에 의한 것이 아니어야 하며, 적극적인 대
증치료에도 불구하고 2일동안 하루 소변량이
500cc이하 이면서 혈청 크레아티닌>2.0mg/㎗
인 경우. 다만, 혈액투석을 시행했을 경우 혈액
투석 시행 전 2일간을 기준으로 한다
•난치성 복수/간-흉수증(ascites / Hepatohydrothorax)
- 복수를 조절하기 위해 시행한 TIPS 치료방법
에 반응하지 않거나 적응증이 되지 않는 환자로
이뇨제나 소금의 절제와 같은 내과적 치료방법
이 실패하여 1주일에 1회 이상 4ℓ이상의 복수 또
는 흉수천자가 필요한 환자
•내과적 치료에 반응하지 않는 stage Ⅲ나 Ⅳ인
뇌질환(encephalopathy)