Inhalant, Chemical, and Drug Toxicity Flashcards
Why is ozone bad near the ground?
It produces free-radical injury and secondary inflammation
Other than ozone, what organic compounds are pollutants in the air?
Sulfur and nitrogen oxides
What sized particulates or “soot” are most likely to cause problems?
Small particles inhaled into the alveoli
-> are able to get through small airways, activate inflammatory response
What are the major indoor air pollutants? Include one radioactive gas.
Smoke (from tobacco or wood)
Allergens (mold, dust mites)
Radon - radioactive gas
Formaldehyde - from cigarette smoke, also carcinogenic
How does nicotine exert its stimulant effects?
Stimulates the release of catecholamines -> also increases blood pressure and pulse rate
Give an example of a mucosal irritant in tobacco smoke
Nitrogen oxide (also a part of outdoor pollution)
What are the two types of chemical carcinogens in tobacco smoke?
Initiators and promoters
Initiators - cause DNA damage in the first place which confers a growth advantage
Promoters - promote the uncontrolled growth of the cell
-> puts you on the path to cancer
What are the two primary features of COPD?
Chronic bronchitis and emphysema
What types of carcinoma does cigarette smoking predispose you to?
Lung, upper digestive tract (lip, mouth, pharynx/larynx), esophagus (all easy)
Harder:
Pancreas
Urinary bladder and kidney -> excretion of products
Uterine cervix -> helps support fullblown cancer in precancer cells
What two conditions of cardiovascular disease does smoking predispose you to and why?
- Atherosclerosis - toxins injure the endothelium
- Myocardial infarction - oxygen supply decreased by atherosclerosis + increased oxygen demand from catecholamine stimulation (nicotine = stimulant)
What pregnancy-related complications occur as a result of tobacco use?
Miscarriages + intrauterine growth retardation / premature birth
What two systems are turned online to metabolism ethanol in overdose scenarios? What is their end product?
- MEOS - CYP2E1 primarily
- Catalase - in peroxisomes
Both form acetylaldehyde which will later be turned to acetate by aldehyde dehydrogenase
Alcohol causes fatty change in the liver acutely, kk? What is one upper GI manifestation which can occur acutely and why?
Mallory-Weiss tears in lower esophagus
Think of mallory mager marrying a troll
-> due to vomiting from alcohol intoxication
What nutritional deficiencies is chronic alcoholism most commonly associated with?
Protein-energy malnutrition, as well as thiamine and folate deficiencies
What liver damage is chronic alcoholism associated with?
Possibility of alcoholic hepatitis -> rapid necrosis
Cirrhosis -> portal hypertension and hepatic failure
Cirrhosis also increases your risk of hepatocellular carcinoma
What GI tract manifestations does chronic alcoholism produce?
Gastritis, acute and chronic pancreatitis, peptic ulcer disease, and esophageal varices (can cause severe GI bleed)
What cardiovascular changes are likely in chronic alcoholism?
Atherosclerosis, hypertension, and dilated cardiomyopathy
What does alcohol cause liver damage?
Direct effects on cell membranes, oxygen-derived free radical damage, and direct damage from acetaldehyde
What are the central and peripheral manifestations of chronic alcoholism on the nervous system?
Central - cerebral and cerebellar atrophy, with progression to Wernicke-Korsakoff syndrome
Peripheral - Neuropathy and loss of reflexes / sensations in lower limbs associated with dry beriberi
What cancers does alcoholism predispose you to?
Upper aerodigestive tract (as in tobacco smoking)
Esophagus
Liver
What characterizes fetal alcohol syndrome?
Microcephaly, impaired cognition, facial defects, growth retardation, behavioral abnormalities
Why is lead poisoning really unfortunate in terms of its effects?
It is developmentally toxic at its lowest levels, and toxicity is more frequent in children due to increased absorption and decreased BBB function
What is the most common manifestation of lead poisoning, and what is its mechanism?
Incorporation of lead into matrix of bone (instead of calcium), leading to radiodense lead lines at the metaphysis and areas of poor density due to decreased calcification rate
How can a history of lead toxicity be dangerous to pregnant mothers?
Lead which incorporates into bones may be resorbed and carried across the placenta
What two primary enzymes are inhibited by lead? By what mechanism? What buildups does this cause in urine?
- ALA dehydratase - aminolevulinic acid accumulates
- Ferrochelatase - protoporphyrin 9 builds up in urine (final step to put iron in heme)
Disrupts the sulfhydryl groups of enzymes
How do RBCs appear in the bone marrow as a result of lead toxicity?
Ringed sideroblasts
- > iron cannot be put into heme (ferrochelatase inhibition)
- > erythrocyte precursors with ironladen mitochondria on prussian-blue stain.
How do RBCs appear in peripheral blood as a result of lead toxicity
Microcytic, hypochromic anemia with basophilic stippling (aggregates of ribosomal RNA caused by 5’ nucleotidase inhibition, RNA stays in the cell)
What part of the nervous system is most prominently affected in children by lead poisoning? Mechanism and manifestations?
Central nervous system (poorer BBB)
- > mechanism: substitution for calcium channels during nerve conduction
- > learning disability, ADD, behavior problems / coordination problems, decreased IQ / hearing
- > neuronal necrosis and demyelination
What part of the nervous system is most commonly affected in adults via lead poisoning and how does this manifest?
Peripheral nervous system
- > demyelinating motor neuropathy
- > muscle weakness leading to wrist-drop and foot drop
What are the GI manifestations of severe lead toxicity?
Lead colic - severe abdominal pain
What does lead do to the kidneys?
Causes tubular injury with intranuclear lead inclusions
-> decreased uric acid excretion (saturnine gout)
What does lead do to the mouth?
Reacts with bacteria at gum margins -> causes lead lines at gum margins
What are all three forms of mercury, where do you get them, and which is most common?
- Organic mercury - most common, from eating fish / marine animals
- Inorganic mercury - from mining of mercury, fossil fuels, etc
- Elemental mercury (liquid metal which vaporizes at room temp) - mercury-containing products like dental amalgams and thermometers
How does organic mercury get into our marine animals?
Inorganic / elemental mercury from atmosphere / soil get into bodies of water, contaminating them
Methylmercury is made by bacteria from this, and this concentrates up the food chain into our fish
Who experiences the most severe manifestations of mercury poisoning?
Those children exposed in utero
What is the primary system affected by mercury poisoning and what does this cause?
Central nervous system
-> impaired hearing / vision, seizures, sensory / motor nerve dysfunction, fine tremor / ataxia, and personality changes
“mad as a hatter”
What is the most common source of Arsenic exposure?
Via ingestion of contaminated groundwater -> most severe in Bangladesh
- > can be from agricultural runoff (used in pesticides / herbicides)
- > mining / industrial processes
What happens in acute arsenic poisoning?
This is an old very common poison
- > looks like food poisoning then you die
- > abdominal pain, blood diarrhea, vomiting, hypovolemic shock, seizures, death
What nonmalignant skin changes occur with chronic, low-level arsenic poisoning (as seen in Bangladesh)?
Pigmentation abnormalities like raindrop pigmentation or Mees lines in nails
Hyperkeratosis of palms and soles
What happens to the nervous system in chronic As poisoning?
Sensorimotor peripheral neuropathy which is often painful
What are the most common malignancies of arsenic poisoning?
Skin and lung cancer
Other than batteries and manufacturing, what is one other source of cadmium exposure?
Cigarette smoking (inhalation)
Even batteries and stuff leads to cadmium inhalation
What is the most common toxicity of Cadmium, and its indirect consequence?
Renal tubular dysfunction (kidney damage)
-> leads to osteomalacia from failure to make vitamin D, and resultant osteoporosis
What are the respiratory tract manifestations of cadmium inhalation, acutely and chronically?
Acutely - chemical pneumonitis - potentially lethal
Chronic - anosmia with obstructive changes, and lung cancer
Where does benzene come from?
Inhaled as vapor mostly, used in industrial processes and from incomplete combustion of carbon materials (like tobacco)
What are the acute and chronic effects of benzene?
Acute - CNS effect, mostly sedating / confusing but can lead to LOC and death
Chronic - Increased risk of acute myeloid leukemia**** (AML)
What is vinyl chloride associated with increased risk of?
Hepatic angiosarcoma (cancer of the liver sinusoid endothelial cells)
Very rare malignancy, only happened in PVC factories
What is 2-naphthylamine associated with?
Due to toxicity of glucuronidated product -> increased risk of urothelial carcinoma of urinary bladder
Why can estrogen as hormone-replacement therapy not be given to POSTMENOPAUSAL women unless they’ve had a hysterectomy?
Increased risk of endometrial carcinoma
What are the risks of post-menopausal hormone-replacement therapy?
- Increased thromboembolic complications
- Increased breast carcinoma / increased breast density (false positive mammograms)
- Coronary artery disease
- Gall bladder disease (its a steroid)
What do oral contraceptives reduce your risk of in pre-menopausal women?
Endometrial and ovarian carcinoma
What do oral contraceptives increase your risk of in pre-menopausal women, especially if you’re a smoker?
- Thromboembolic events
- Cardiovascular disease
- Even nonsmokers: Liver cell adenoma (benign tumor associated with prolonged use)
What is the most common cause of acute liver failure in the US?
Hepatocellular necrosis due to acetaminophen toxicity
What are the acid-base disturbances of aspirin toxicity, from early to late?
Early - respiratory alkalosis due to direct stimulation of respiratory center, with compensatory loss of bicarbonate in kidney
Late - metabolic acidosis due to uncoupling of OxPhos leading to lactate buildup, and lack of buffering of acid due to renal excretion of bicarbonate
Why is aspirin contraindicated in children?
Increases chances of Reye syndrome, a progressive encephalopathy with liver damage most commonly caused by salicylate poisoning
What are the CNS defects of aspirin overdose?
lethargy, excitability, seizures, coma
What does aspirin overdose do to your core body temp?
Increases it due to uncoupling of OxPhos, can lead to dehydration
What is a hearing manifestation of aspirin OD?
Ototoxicity -> tinnitus / hearing loss
