Environmental and Nutritional Disorders Flashcards
Toxicology Definitions
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Threshold dose
- Expressed as a range
- Where effect first occurs
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Threshold limit values / Permissible exposure level
- Max exposure before harmful effect occurs
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Ceiling effect
- Plateau: if increases in dose, does not change level of response
Metabolic Metabolites
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Metabolism of parent compounds
- To more toxic metabolites (e.g. mercury)
- To less toxic substances
- To conjugation products
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Exposures due to metabolites of lipophilic toxicants include:
- ↑ Bladder CA in dye workers
- ↑ Hepatic angiosarcoma in persons working w/ vinyl chloride
- Remember the concept of bioaccumulation
- Minamoto mercury poisoning
- Fish poisoned w/ mercury, then human eats fish
Smoking
-
Know adverse effects include:
- Cancers
- Heart disease
- Chronic respiratory disease
- Atherosclerosis
- Cerebrovascular disease
- Low birthweight in fetus
Acute Alcohol Intoxication
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BAC between 0.01 and 0.1 percent:
- Feelings of wellbeing and confidence
- Disinhibition
- Urge to speak
- Feelings of tranquility and relaxation
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Mild deficits in coordination
- Unsteady gait
- Difficulties standing upright
- Slightly decreased attention, memory, and judgement
- Reddening of the skin or flushing of the face
- Slightly ↑ HR
-
BAC between 0.15 and 0.3 percent:
- Mood variability
- Pronounced disinhibition
- Slurred speech
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Greater deficits in coordination and psychomotor skills
- ↑ Unsteadiness of gait
- Clumsiness
- Increasingly impaired attention, memory, and judgement
- Reduction in responsiveness, alertness, and reaction time
- Confusion
- Uncontrolled eye movements
- Sleepiness
- Dizziness
- Nausea and vomiting
- Impaired vision and sound localization
- Memory gap
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BAC greater than 0.3 percent:
- Delusions and hallucinations
- Severe difficulty speaking
- Severe dizziness
- Severe deficits in coordination and psychomotor skills
- Potential hypothermia
-
Potential coma
- Usually BAC > 0.4 percent
- LOC
- Lack of defensive reflexes
- Respiratory failure
- Usually BAC > 0.4 percent
Chronic Alcoholism
- Liver: steatosis, alcoholic hepatitis, cirrhosis
- GI: acute gastritis, acute and chronic pancreatitis
- CNS: atrophy of mamillary bodies
- Reproductive: testicular atrophy
- Heart: cardiomyopathy
Fetal Alcohol Syndrome
Alcohol and Cancer
↑ risk of oral cavity, pharyngeal, esophageal, liver cancers
Effects of Other Alcohols
Methanol toxicity: blindness
Ethylene glycol toxicity: obstruction of renal tubules by calcium oxalate crystals
Commonly Abused Drugs
- CNS depressants
- CNS stimulants
- Narcotics
- Hallucinogens
- Combinations of drugs: e.g. alcohol and barbiturates
HRT and Oral Contraceptives
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Exogenous estrogen: possible effects of unopposed estrogen
- Endometrial carcinoma
- Thromboembolism: natural less risk than synthetic
- Cardiovascular disease
-
Oral contraceptives
- Breast carcinoma: probably slight ↑ in women over age 45
- Endometrial cancer: protective effect
- Cervical cancer: ↑ risk related to duration of use and lifestyle
- Ovarian cancer: protective effect
- Thromboembolism: higher risk w/ older women who smoke
- Hepatic adenoma
Acetominophen
- Toxic doses may cause hepatic necrosis
- Concurrent renal and myocardial damage may occur
- Toxicity: Nausea, vomiting, diarrhea and shock, jaundice days later
Aspirin
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Acute overdose
- Respiratory alkalosis followed by metabolic acidosis
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Chronic aspirin toxicity (Salicylism)
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CNS changes
- HA, dizziness, tinnitus, AMS, drowsiness, N/V/D
- Acute erosive gastritis
- Bleeding tendency: petechial hemorrhages
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Analgesic nephropathy
- Renal papillary necrosis
- May be caused by combo of aspirin and phenacetin or its metabolite; also acetaminophen
-
CNS changes
Outdoor Air Pollution
- Acute toxicity: proximal effects
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Subacute/chronic: distal effects
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Subclinical chronic inflammation and fibrosis
- Ongoing toxic effects and hypersensitivity
- Degenerative changes
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Subclinical chronic inflammation and fibrosis
Common Indoor Pollutants
- Carbon monoxide
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Radon
- Emanates from earth into basements of homes
- Inhaled into lungs where decay products emit alpha radiation
- Asbestos: lung CA, mesothelioma
- Fiberglass: skin and lung irritation
- Bioaerosols: dust mites, fungi, molds
Industrial Exposures
Volatile organic compounds:
-
Aliphatic hydrocarbons: dry cleaning
- CCl4 and chloroform: acute CNS depression, liver and kidney toxicity
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Aromatic hydrocarbons
- Benzene inhalation: bone marrow toxicity, aplastic anemia, acute leukemia
- Petroleum products: CNS depression
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Aromatic halogenated hydrocarbons
- Soot: scrotal cancer in chimney sweeps
- Plastics, rubber, polymers
Lead
“PLUMBISM”
Peripheral demyelinating neuropathy
Lead lines in bones/gums
Urinary excretion: damage proximal tubules, interstitial fibrosis
Mental deterioration
Brain damage in children
Intestinal Manifestations: colic, anorexia
Serum: ↑ zinc protoporphyrin
Microcytic, hypochromic, mild hemolytic anemia
“BITES”
Bone accumulation
Inhibition of heme synthesis
Toxic blood level is greater than 10 micrograms/L
Erythrocyte basophilic stippling
Surgical abdomen: lead colic
Cobalt/Tungsten Carbide
Metal workers: asthma, interstitial fibrosis
Cadmium
Acute toxicity: swelling of pneumocytes
Chronic toxicity: kidney
Nickel
Topical exposure: contact dermatitis
Inhalation: carcinogenic
Mercury
Renal toxicity, dementia
Chromium
Carcinogen in industry
Arsenic
Skin, lung, liver cancers
Occupational Exposure
Respiratory Effects
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Nasal cancer
- Isopropyl alcohol, wood dust
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Lung cancer
- Radon, asbestos, nickel, arsenic, chromium, mustard gas
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COPD
- Grain dust, coal dust, cadmium
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Hypersensitivity
- Beryllium
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Irritation
- Ammonia, sulfur oxides, formaldehyde
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Fibrosis
- Silica, asbestos, cobalt
Agricultural Hazards
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Insecticides
- Many linked to neuro- and hepatotoxicity
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Herbicides
- Arsenic compounds: hyperpigmentation, gangrene, anemia, sensory neuropathy, cancer
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Fungicides
- ? Reproductive toxicity
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Rodenticides
- Warfarin: hemorrhage
Natural Toxins
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Mycotoxins
- Ergot alkaloids: gangrene, convulsions, abortion
- Aflatoxins: liver cancer
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Animal toxins
- Venoms
- Cinguatoxin: parasthesias, vomiting, diarrhea
- Tetrodotoxin (puffer fish): neurotoxin, shock
Radiation
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Factors influencing damage to tissue/cells:
- Total dose
- Rate at which dose is delivered
- Rate of cell turnover
- Capacity for cellular repair
- Oxygen effects: free radicals
-
Radiation-induced vascular changes
- Injury → fibrosis and loss of the lumen
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History:
- Areas w/ nuclear disaster, after therapeutic radiation: Papillary thyroid cancer
- Early radiologists: ↑ aplastic anemia, brain tumors
- Fetal exposure: Mental retardation, leukemia, malformations
Ionizing Radiation Damage
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Acute effects after exposure
- Edema, mucosal erosion, atrophy of many tissues
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Delayed effects after exposure
- Fibrosis in lung, heart, GI tract, bladder, ovary, breast
- Malignancies of bone marrow, liver, bladder, thyroid, breast, lymph nodes, brain
Know which organ systems are affected as whole-body dosage of ↑ radiation
Radiation Effects
Mechanical Trauma
-
Injuries are the most common cause of death in US up to age 34
- Violence is an important factor
- Abrasion (scrape)
- Contusion: blunt force; damages small blood vessels, bruise
- Laceration: irregular skin tear, overstretching w/ bridging strands of fibrous tissue or blood vessels
- Incised wound: cut
- Puncture wound
- Gunshot wound: distance, direction
Thermal Burns
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Classification
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Partial thickness
- First degree: epidermis only
- Second degree: epidermis and superficial dermis
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Full thickness
- Third degree: Into deep dermis, will need skin graft
- Fourth degree: Into subcutaneous tissue
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Partial thickness
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Factors for clinical significance
- Depth of burn
- Percentage of body surface involved (rule of 9s)
- Possible presence of internal injuries
- Inhalation of hot/toxic fumes
- Promptness and efficacy of therapy is very important
- Electrolyte management is key
- Infection prevention/control is a critical component of therapy
Barotrauma
- High altitude sickness
- Blast injury
- Air/gas embolism
- Decompression (caisson disease): bends, chokes and staggers from too rapid ascent
Pneumoconiosis
- Simple coal workers pneumoconiosis (CWP)
- Complicated CWP: progressive massive fibrosis
- Silicosis
- Asbestosis
Primary Nutritional Deficiency
Caused by inadequate diet
Can be due to poverty, anorexia nervosa, lack of ionized salt, chronic alcoholism (inadequate diet aspect, remember thiamine)
Secondary Nutritional Deficiency
Malnutrition despite adequate nutrient supply
- Failure of digestion or absorption: e.g. fat soluble
- Failure of utilization: e.g. liver disease so can’t store Vitamin A
- ↑ Requirements: pregnancy, acute, or chronic illness
- ↑ Excretion: sweating
- Drugs: can block uptake or use of nutrients
Malnourishment
Weight is below 80% of normal
Marasmus
Wasting due to too few calories
Weight below 60% of normal
- Growth retardation
- ↓ muscle mass due to catabolism: loss of somatic protein compartment
- Deplete subcutaneous fat: emaciated
- Serum albumin only slightly reduced
- See anemia, immune deficiency, vitamin def.
- No edema or hepatomegaly
Kwashiorkor
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Loss of visceral protein compartment
- More severe than marasmus
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Weight is 60-80% of normal
- Masked by fluid retention
- Relative sparing of subcutaneous fat and muscle mass
- Skin lesions
- Flaky paint sign: affects squamous epithelium resulting in alternating zones of hyperpigmentation, desquamation and hypopigmentation
- Hair changes: flag sign
- Also, apathy, listlessness, loss of appetite, enlarged fatty liver, immunosuppression
Secondary Protein–Energy Malnutrition
Complication in patients w/ advanced cancer, AIDS (also called cachexia or wasting syndrome)
Anorexia Nervosa
Severe protein energy malnutrition w/ additional endocrine system manifestations
Includes amenorrhea, skin changes, ↓ body hair, ↓ bone density, ↑ susceptibility to cardiac arrhythmia
Fat Soluble Vitamins
Vitamins A, D, E, K
Patients w/ biliary tract and pancreatic dysfunction and intestinal malabsorption syndromes (e.g. cystic fibrosis) are predisposed to deficiency of fat-soluble vitamins
Vitamin A
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Vitamin A Deficiency
- Eye changes
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Defects in cell differentiation
- Epithelial metaplasia
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Vitamin A Toxicity
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Acute
- HA, vomiting, stupor, papilledema (pseudotumor cerebri)
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Chronic toxicity
- Weight loss, nausea, vomiting, dry lips, joint pain
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Acute
Vitamin D
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Deficiency causes derangement of plasma levels of phosphorous and calcium, w/ resultant mineralization
- See excess of mineralized matrix (osteoid material and cartilage)
- Children: rickets
- Altered endochondral bone growth
- Prominent head deformity in infant, lumbar lordosis, bowed legs in children w/ rachitic rosary and pigeon breast deformity
- Adults: osteomalacia
Vitamin E
- Important antioxidant
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Deficiency
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Spinocerebellar degeneration due to degeneration of axons in posterior columns of spinal cord
- ↓ DTRs, ataxia, dysarthria, loss of position and vibration sense, loss of pain sense, myopathy
- Hemolytic anemia: RBCs more susceptible to oxidative stress
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Spinocerebellar degeneration due to degeneration of axons in posterior columns of spinal cord
Vitamin K
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Deficiency is rare due to endogenous production by gut flora
- Seen in newborns (no gut flora, fat malabsorption, diffuse liver disease, suppression of nl intestinal flora due to use of abx)
- Blood clotting abnormality due to deficiency of clotting factors II, VII, IX, X and proteins C and S
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Infants: hemorrhagic disease of the newborn
- Intracranial bleed
- Adults: ecchymosis, gingival bleed, hematoma, hematuria, melena
Vitamin B1
(Thiamine)
Deficiency seen in areas w/ polished rice diet and in chronic alcoholism
- Dry Beriberi: demyelinating peripheral polyneuropathy
- Wet Beriberi: w/ pulmonary edema, =/- mural thrombi secondary to hypokinetic walls
- Wernicke Korsakoff syndrome: nystagmus, ataxia, mental confusion, disorientation, confabulation, see atrophy of mamillary bodies
Vitamin B2
(Riboflavin)
Deficiency: cheilosis, glossitis, dermatitis, corneal vascularization
Vitamin B3
(Niacin)
Deficiency: Pellagra
Dermatitis, diarrhea, dementia
Vitamin B6
(Pyridoxine)
Deficiency: Seborrheic dermatitis, cheilosis, peripheral neuropathy, glossitis
Vitamin C
Deficiency (scurvy)
- Hemorrhages: skin, gingival mucosa, subperiosteal hematomas, intracranial hemorrhages (due to loss of collagen in vessel walls)
- Perifollicular, hyperkeratotic papular rash which may be ringed by hemorrhages
- Abnormal wound healing and localization of focal infections
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In growing child: bone abnormalities
- Can fracture due to inadequate osteoid at epiphyseal plate
Folate
Deficiency: Megaloblastic anemia, neural tube defects in fetus
Vitamin B12
(Cobalamin)
Deficiency: Megaloblastic anemia and degeneration of posterolateral spinal cord tracts
