• airway irritation/inflammation
• exacerbate asthma/bronchitis
  • compromise oxygen exchange
  • predispose to pulmonary infection
• particulates cause pulmonary fibrosis (asbestos, silica, coal)
• carcinogenesis (ex: tobacco smoke)

• tar
• CO
• nicotine
• carcinogens (polyaromatic HC's)
• metals (arsenic, nickel, chromium)

1. coat airways
2. along with cilia toxins in smoke, inh. clearance of mucus and debri

1. binds Hb with much higher affinity than oxygen
2. this compromises O₂ delivery to tissues, leading to hypoxia
3. called cherry red cyanosis (blood is still red, but you are hypoxic)

• stimulate CNS nicotinic R's
• leads to increase in HR and bp

• laryngeal
• esophageal
• pancreas
• bladder

• carbon monoxide
• cyanides
• sewer gas
  • CO
  • cyanides
  • H₂S

auto exhaoust

poor combustion

• sources
  • plant seeds
  • silver polish
  • combustion products in burning buildings
  • pesticides
• mechanism
  1. block cytochrome oxidase
  2. oxygen cannot be removed from RBC's
  3. results in bright red oxygen saturated blood with hypoxia

• vasorestrictive agents
  • ergot alkaloids drugs (treat migraines)

• cause acute generalized hypoxia and death without anatomic lesions
• if survive, often permanent brain damage due to hypoxia

Chemicals that cause local necrosis and their nature and mechanism of action (hint: based on pH)

corrosives

• strong acids
  1. withdrawal water
  2. char the mucosa
• alkalis
  1. liquify tissue penetrating deeply
  2. leads to:
     • hemorrhage
     • ulcerations
     • perforations

• lead
• mercury
  • inorganic
  • organic
• arsenic

• paint
• water from lead pipes
• improper glaze on ceramics
• illicit whiskey
• pesticides
• dust/dirt from renovations
• leaching of external hourse paint

• adult signs
  • peripheral neuropathy
  • gum line
• basophilic stippling of RBC's
• if chronic, lead lines (radiodensitives) in growing metaphyses of long bone
• increased ALA in urine
  • lead inhibit ALA synthase and ferrochelatase
  • no heme syn. leads to anemia
• Pb in blood, urine, hair

• necrosis/sloughing off PCT epithelium w/ acid-fast intranuclear inclusions
• anemia (heme cant be made)
• acute poisoned children
  • cerebral capillaries injured, leading to injuring BBB, so cerebral adema occurs
  • this leads to possible hemorrhages and laminar necrosis in severe cases
  • lose fine moter control and mental retardation
• chronic poisoned children
  • increased CSF leading to brain atrophy
  • decrease cartilage remodeling in bone, leading to Pb lines (radiodensitives) in growing metaphyses of long bones

• main target- kidney leading to nephrosis
  • also hit CNS, leading to neurosis
• sources
  • drugs
  • disinfectants
  • plastic, electrical industry

NOT AS SERIOUS AS ORGANIC!!!!!

• main target: CNS
  • but can effect the kidney
  • especially hurts fetus (cerebral, cerebllar hypoplasia)
• sources
  • predatory fish
  • fungacides
  • ingest fungicide treated grain or animal that ingested grain treated with fungicide

• cerebellar/cerebral neuronal necrosis and atrophy
  • ataxia
  • dysarthria
  • constrict vision
  • memory loss
  • personality change
• nephrotaxic
  • renal failure
  • oliguria

• source- rat poison, insecticides, contaminated (water well industry)
• signs
  • acute- CNS depression, GI hemorrhage
  • chronic- hyperkeratosis and hyperpigmentation of skin leading to:
    • squamous cell carcinoma
    • peripheral neuropathy
    • cancer: liver, lung

• gastritis
• fatty change in liver
• edema of brain
• pancreatitis

• fatty change in liver, kidney, heart
• gastric ulcers
• encephalopathy
• cardiomyopathy
• decrease resistance leading to pneumonia
• hepatic injury
  • cause cirrosis than
  • portal HTN causing
  • acities and esophageal verices
  • leading to hematemesis and liver failure
  • causing vitamin deficiencies
  • leading to hemorrhagic diathesis
• cerebral and testicular atrophy
• FAS
• cancer: mouth, esophagus, stomach
• decreased atheroschlerosis

antifreeze

certain plants

1. metabolizes alcohol DH
2. produces:
   1. glycoaldehyde
   2. glycolate
   3. glycolic acid
   4. glyoxylate
3. metabolites cause:
   1. tissue destruction (mainly from calcium oxalate crystal depostion)
   2. metabolic abnormalities
      • high anion gap metabolic acidosis
      • lactic acidosis
      • hypocalcemia
4. by calcium oxalate crystal deposit on kidney, this will lead to:
   • hypocalcemia
   • hematuria
   • proteinuria
   • increased creatinine aka renal failure
     • crystals block renal tubules leading to uremia
5. deposit on cerebral vessels leading to convulsions

• myelosuppresion
• immunosuppresion
• carcinogenesis
• lesions
  • heart
  • lung
  • liver
  • kidney

gastritis

hemorrhage

• reproductive problems in those exposed in utero
  • includes clear cell carcinoma of vagina

• source- dry cleaning
• ex: chloroform, carbon tetrachloride

1. CCl₄ metabolized to CHCl₃ (preferably in zone 3) via cyc P450 enzymes
   • enhanced by alcohol
   • enhanced by acetomenaphin (would cause same effects as carbon tetrachloride, but over a longer time)
2. Leads to:
   • CNS depression
   • liver necrosis (mainly in zone 3- more enzymes than the other zones)
   • kidney necrosis
   • potential carcinogens

Necrosis initiated within minutes and at its maximal response within 1-2 days.

• examples- benzene, toluene, xylene
• source- solvents

• bone marrow toxicity
• aplastic anemia
• leukemia

• source- byproduct of fuel combustion
• example- benzopyrene

• carcinogenic
  • tobacco and lung cancer
  • chimney soot and scrotal cancer

• ex: vinyl chloride
• source- manufacturers
• effects- carcinogenic (liver angiosarcoma)

1. shock waves of overpressure and underpressure cause alternate rapid compression and decompression
   • tissue disrupted by overcoming their elasticity
   • this leads ot rupture of internal organs and bv's
     • hemorrhage

• loss of oxygen tension
  • obtundation
  • confusion
• increase vascular permeability
  • pulmonary edema

• previously solubilized gas (esp. nitrogen) in blood forms bubles of gas that embolize and block capillaries and arterioles
  • acute aka bends- emboli in lung, brain and muscle
  • chronic aka caisson disease- emboli cause multiple small infarcts in bone