یرومیت دیعس رتک

د

یلغش یاهیرامیبو راک بط صصختم ناهفصا یعامتجا نیمات نامرد تیریدم دابا سابع سدق هاگنامرد

Route of Exposure

 Inhalation  Ingestion  Percutaneous absorbtion

Liver Disorders Induced by physical agents



Hyperthermia

& cholestasis (Heat stroke): Necrosis 

Ionizing radiation

2-6 Week later (>3000 to 6000 rad): Hepatitis

Aminotransferase

(

Transaminase

)  AST & ALT: most useful indicators of

damage hepatocellular High level:



Viral, alcoholic, or ischemic hepatitis, extrahepatic obstruction,



False positive: erythromycin, aminosalicylic acid, DKA



A serum AST:ALT ratio <1 with trnsaminase level < 300 IU/L may suggestive occupational liver disease

Alkaline Phosphatase (ALP)

 Several forms   Bone, intestine, liver, kidney, placenta, leukocyte In the absence of bone disease or pregnancy, elevated levels of ALP activity reflect impaired biliary tract functon.

Slight & moderate elevation

in parenchimal liver disorders such as hepatitis, cirrhosis

High elevation

   in extrahepatic biliary tract obstruction intrahepatic cholestasis (drug induced or PBC) more sensitive marker than bilirubin in biliary tract obstruction  To diffentiate hepatic origin from nonhepatic origin  5 ’-nucleotidase or g-glutamyl- trasnspeptidase (GGT)  isoenzyme assay; not practical

Morphologic patterns of liver injury

Acute

Cytotoxic Necrosis(Centrizonal)

CCL4,chloroform,TNT,PCB

Steatosis

C CCL4,chloroform,P,DM hydrazine,styrene

Cholestatic

MDA,Rapeseed oil, aflatoxin

Acute Hepatic Injury

 Carbon tetrachloride  Dizziness, headache, visual disturbances, confusion  Nausea, vomiting, abdominal pain, diarrhea  Palpable liver & spleen, jaundice, elevated serum transaminase, prolonged PT  Renal failure  Hypoglycemia, encephalopathy, hemorrhage

Morphologic patterns of liver injury

Sub acute

TNT

Chronic

Cirrhosis

TNT,PCBs,tetrachloroethane,Arsenic

Sclerosis Porphyria

Arsenic, vinyl chloride, thorium Dioxin

Neoplasia Steatosis Granoluma

Arsenic , vinyl chloride DMF , CCL4 Beryllium , copper

Fatty liver (steatosis)

 Steatosis is defined greater than 5% hepatocytes containing fat.  Steatosis occurs in diabetes mellitus, hypertriglyceridemia, obesity  There is multifactorial , thus industrial hepatotoxins interact with underlying metabolic disorders and other causes of non-alcoholic steatohepatitis ( NASH ).

Fatty liver (steatosis)



pathology

:alteration of hepatic fat metabolis  Hepatotoxins can block fat metabolism at accumulation of free fatty acids and triglycerides.

Fatty liver (steatosis)

 . Patients are usually asymptomatic.

  Screening tests (AST, ALT) may not detect steatosis in the absence of inflammation and necrosis.

 . Diagnosis is complicated by confounding etiologies , including alcohol consumption, obesity, diabetes, medications, and their  interactions with suspected toxins.

Fatty liver (steatosis)

 Necrosis, steatosis, and fibrosis can be induced in animals by the chronic administratio of carbon tetrachloride.  Human studies that steatosis can occur in the absence of elevated serum hepatic transaminase levels.

Fatty liver (steatosis)

 individuals with alcohol-induced or metabolically induce significant progression of steatosis to fibrosis histologically, termed ‘

steatocirrhosis’,

often in the absence of an inflammatory response and associated transaminase elevation.

Fatty liver (steatosis)



Diagnosis

 Laboratory tests may not be helpful  because they frequently do not detect steatosis in the absence of inflammation .

 ultrasonography and CT scan can suggest hepaticsteatosis.  The definitive diagnosis a liver biopsy specimen.

Fatty liver (steatosis)

  When significant steatosis is found, should attempt to differentiate occupational from other known causes :

Medications

associated with steatosis (such as phenytoin tetracycline, isoniazid, nitrofurantoin,  Hyperlipidemia, diabetes mellitus,obesity or pregnancy, and substance abuse,.

 Laboratory evaluation fasting blood sugar and triglyceride levels. .

Fatty liver (steatosis)



Management

 The presence of steatosis without other obvious etiologies, with

exposure to hepatotoxic

, is suggest toxic exposure should be minimized, and removal from the workplace .

 Resolution elevation aminotransferas elevels after removal from exposure supports an occupational etiology.

Infectious Agents

HAV HBV & HCV Cytomegalovirus Coxiella burnetti Nursery & kindergarten staff Sewer workers HCWs with blood and body fluid contact Pediatric health care workers Animal care workers, farm workers, slaughterhouse workers Leptospira icterohaemorrhagiae Sewer workers, farm workers

HAV

        HCWs (Emergency rooms, surgery, laundry, children ’s psychiatry, dentists) Transmission: fecal-oral, Blood (rare) Incubation period: average 28-30 days Abrupt onset with fever, malaise, anorexia, nausea, abdominal discomfort, and jaundice Greatest infectivity:2w before the onset of jaundice or liver enzymes Not chronic carrier Dx: IgM anti HAV Ab IgG confer enduring protection

HAV Prevention

 a single IM dose of 0.02 ml/kg gamma globulin before exposure (80-90%)  Routine Ig administration is not recommended for person exposed to a fellow worker with hepatitis A  Close contacts should be given Ig  Vaccine handlers : Travel or work in country with intermediate or high endemicity, lab workers with exposure to live virus, animal  Employee with Hep A should be restricted from work until symptoms subside or 1 W after the onset of jundice

HBV

        A major cause of acute & chronic hepatitis, cirrhosis, hepatocellular carcinoma HCWs with blood or body fluid contact Transmission: Blood or body fluid, not fecal-oral Forms of illness:Acute,Inapparent sporadic episodes,Chronic carrier Incubation period: 45-60 days malaise, anorexia, nausea, abdominal pain, jaundice, skin rash, arthralgia, arthritis Chronic state : presence of HBsAg-positive serum on at least two occasions at least 6 months apart Risk of infection following percutaneous inj (HBeAg+&HBsAg+):22-31%

HBV Prevention

 Individuals at risk for blood borne pathogen exposure should be vaccinated  A three dose series: 95% protection  Not immune: >45y, obesity, smoking  Second three dose: 30-50% protection  Nonresponders to vaccination with HbsAg-negative: Ig  Employee whit Hep B & Liver dis should be advised to avoid exposure to other potentially hepatotoxic agents such as ethanol or workplace solvent

Acute Hepatic Injury

 Anesthetic gases  Bromobenzene  Carbon tetrabromide  Carbon tetrachloride  Chlorinated naphthalenes  Chloroform  Dichlorohydrin  Dimethylformamide  Phosphorus  2-Nitropropane  Tetrachloroethane  Trichloroethylene  Trinitrotoluene

HCV

           Chronic: 70% Transmission: Blood, IV drugs, (sexual, maternal ?) Risk of infection following occupational percutaneous exp:1.8(0-7)% 80% anicteric & asymptomatic Incubation period: 6-8 w FHF is rare CAH & cirrhosis: 60% Major agent in the etiology of hepatocellular carcinoma Dx: measurement of HCV RNA by PCR Following percutaneous or mucosal occupational exposure, baseline and follow-up HCV antibody measurements should be performed (6 w, 3 & 6 m) Not vaccine is currently available

Medical Surveillance

  

Biochemical tests

     AST, ALT ALP LDH Bilirubin Urine bilirubin

Tests of synthetic liver function

    Alb PT Alpha fetoprotein Ferritin

Clearance tests

      Sulfobromophthalein Indocyanine green Antipyrine test Aminopyrine breath test Serum bile acid Urinary D-glucaric acid

  SGGT  More sensitive indicator but not specific LDH  Myocardium, skeletal muscle, brain, kidney, RBC  Liver specific enzymes   Alb  Little value in differential diagnosis Alpha fetoprotein  70% positive in hepatocellular carcinoma  Not utility in the occupational setting

Clinical Management of OCCUPATIONAL Liver Disease

 Occupational & medical Hx   Exposure to hepatotoxins PMH of liver dis,medication  Review of symptoms(CNS Toxicity due to solvent exposure)   Travel to areas with endemic parasitic or viral disease Steroid use,glue sniffing,recreational solvent use     Previous blood transfusion, tattoos, needle sticks, IV drug … Use of protective work practices MSDS Ask about other emploees

Clinical Management of OCCUPATIONAL Liver Disease

 Physical Examination 

Acute liver disease

RUQ tenderness Hepatosplenomegaly Jaundice  Chronic liver disease Spider angioma Palmar erythema Testicular atrophy Ascites Gynecomastia

Clinical Management of OCCUPATIONAL Liver Disease

 Elevated serum transaminase level  R/O nonoccupational causes  Workplace  Remove for 3-4 weeks  Repeat

Heavy metal toxicity.



Arsenic

;Insecticide, Paris green Sensory > motor neuropathy, red hands, burning feet,

hyperhidrosis Lead

neuropathy, painful joints; children: cerebral edema, Paint, gas, batteries Adults: encephalopathy, low IQ 

Mercury

Industrial, polluted fish Severe arm and leg pain, dementia with primarily motor neuropathy 

Thallium

Stocking-glove sensorimotorneuropathy, with alopecia Insecticide, rat poison

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