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Pathobiology > Inhalant, Chemical, and Drug Toxicity > Flashcards

Inhalant, Chemical, and Drug Toxicity Flashcards

1
Q

Why is ozone bad near the ground?

A

It produces free-radical injury and secondary inflammation

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2
Q

Other than ozone, what organic compounds are pollutants in the air?

A

Sulfur and nitrogen oxides

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3
Q

What sized particulates or “soot” are most likely to cause problems?

A

Small particles inhaled into the alveoli

-> are able to get through small airways, activate inflammatory response

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4
Q

What are the major indoor air pollutants? Include one radioactive gas.

A

Smoke (from tobacco or wood)
Allergens (mold, dust mites)
Radon - radioactive gas
Formaldehyde - from cigarette smoke, also carcinogenic

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5
Q

How does nicotine exert its stimulant effects?

A

Stimulates the release of catecholamines -> also increases blood pressure and pulse rate

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6
Q

Give an example of a mucosal irritant in tobacco smoke

A

Nitrogen oxide (also a part of outdoor pollution)

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7
Q

What are the two types of chemical carcinogens in tobacco smoke?

A

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

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8
Q

What are the two primary features of COPD?

A

Chronic bronchitis and emphysema

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9
Q

What types of carcinoma does cigarette smoking predispose you to?

A

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

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10
Q

What two conditions of cardiovascular disease does smoking predispose you to and why?

A
  1. Atherosclerosis - toxins injure the endothelium
  2. Myocardial infarction - oxygen supply decreased by atherosclerosis + increased oxygen demand from catecholamine stimulation (nicotine = stimulant)
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11
Q

What pregnancy-related complications occur as a result of tobacco use?

A

Miscarriages + intrauterine growth retardation / premature birth

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12
Q

What two systems are turned online to metabolism ethanol in overdose scenarios? What is their end product?

A
  1. MEOS - CYP2E1 primarily
  2. Catalase - in peroxisomes

Both form acetylaldehyde which will later be turned to acetate by aldehyde dehydrogenase

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13
Q

Alcohol causes fatty change in the liver acutely, kk? What is one upper GI manifestation which can occur acutely and why?

A

Mallory-Weiss tears in lower esophagus
Think of mallory mager marrying a troll
-> due to vomiting from alcohol intoxication

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14
Q

What nutritional deficiencies is chronic alcoholism most commonly associated with?

A

Protein-energy malnutrition, as well as thiamine and folate deficiencies

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15
Q

What liver damage is chronic alcoholism associated with?

A

Possibility of alcoholic hepatitis -> rapid necrosis
Cirrhosis -> portal hypertension and hepatic failure
Cirrhosis also increases your risk of hepatocellular carcinoma

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16
Q

What GI tract manifestations does chronic alcoholism produce?

A

Gastritis, acute and chronic pancreatitis, peptic ulcer disease, and esophageal varices (can cause severe GI bleed)

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17
Q

What cardiovascular changes are likely in chronic alcoholism?

A

Atherosclerosis, hypertension, and dilated cardiomyopathy

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18
Q

What does alcohol cause liver damage?

A

Direct effects on cell membranes, oxygen-derived free radical damage, and direct damage from acetaldehyde

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19
Q

What are the central and peripheral manifestations of chronic alcoholism on the nervous system?

A

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

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20
Q

What cancers does alcoholism predispose you to?

A

Upper aerodigestive tract (as in tobacco smoking)
Esophagus
Liver

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21
Q

What characterizes fetal alcohol syndrome?

A

Microcephaly, impaired cognition, facial defects, growth retardation, behavioral abnormalities

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22
Q

Why is lead poisoning really unfortunate in terms of its effects?

A

It is developmentally toxic at its lowest levels, and toxicity is more frequent in children due to increased absorption and decreased BBB function

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23
Q

What is the most common manifestation of lead poisoning, and what is its mechanism?

A

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

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24
Q

How can a history of lead toxicity be dangerous to pregnant mothers?

A

Lead which incorporates into bones may be resorbed and carried across the placenta

25
Q

What two primary enzymes are inhibited by lead? By what mechanism? What buildups does this cause in urine?

A
  1. ALA dehydratase - aminolevulinic acid accumulates
  2. Ferrochelatase - protoporphyrin 9 builds up in urine (final step to put iron in heme)

Disrupts the sulfhydryl groups of enzymes

26
Q

How do RBCs appear in the bone marrow as a result of lead toxicity?

A

Ringed sideroblasts

  • > iron cannot be put into heme (ferrochelatase inhibition)
  • > erythrocyte precursors with ironladen mitochondria on prussian-blue stain.
27
Q

How do RBCs appear in peripheral blood as a result of lead toxicity

A

Microcytic, hypochromic anemia with basophilic stippling (aggregates of ribosomal RNA caused by 5’ nucleotidase inhibition, RNA stays in the cell)

28
Q

What part of the nervous system is most prominently affected in children by lead poisoning? Mechanism and manifestations?

A

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
29
Q

What part of the nervous system is most commonly affected in adults via lead poisoning and how does this manifest?

A

Peripheral nervous system

  • > demyelinating motor neuropathy
  • > muscle weakness leading to wrist-drop and foot drop
30
Q

What are the GI manifestations of severe lead toxicity?

A

Lead colic - severe abdominal pain

31
Q

What does lead do to the kidneys?

A

Causes tubular injury with intranuclear lead inclusions

-> decreased uric acid excretion (saturnine gout)

32
Q

What does lead do to the mouth?

A

Reacts with bacteria at gum margins -> causes lead lines at gum margins

33
Q

What are all three forms of mercury, where do you get them, and which is most common?

A
  1. Organic mercury - most common, from eating fish / marine animals
  2. Inorganic mercury - from mining of mercury, fossil fuels, etc
  3. Elemental mercury (liquid metal which vaporizes at room temp) - mercury-containing products like dental amalgams and thermometers
34
Q

How does organic mercury get into our marine animals?

A

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

35
Q

Who experiences the most severe manifestations of mercury poisoning?

A

Those children exposed in utero

36
Q

What is the primary system affected by mercury poisoning and what does this cause?

A

Central nervous system
-> impaired hearing / vision, seizures, sensory / motor nerve dysfunction, fine tremor / ataxia, and personality changes

“mad as a hatter”

37
Q

What is the most common source of Arsenic exposure?

A

Via ingestion of contaminated groundwater -> most severe in Bangladesh

  • > can be from agricultural runoff (used in pesticides / herbicides)
  • > mining / industrial processes
38
Q

What happens in acute arsenic poisoning?

A

This is an old very common poison

  • > looks like food poisoning then you die
  • > abdominal pain, blood diarrhea, vomiting, hypovolemic shock, seizures, death
39
Q

What nonmalignant skin changes occur with chronic, low-level arsenic poisoning (as seen in Bangladesh)?

A

Pigmentation abnormalities like raindrop pigmentation or Mees lines in nails

Hyperkeratosis of palms and soles

40
Q

What happens to the nervous system in chronic As poisoning?

A

Sensorimotor peripheral neuropathy which is often painful

41
Q

What are the most common malignancies of arsenic poisoning?

A

Skin and lung cancer

42
Q

Other than batteries and manufacturing, what is one other source of cadmium exposure?

A

Cigarette smoking (inhalation)

Even batteries and stuff leads to cadmium inhalation

43
Q

What is the most common toxicity of Cadmium, and its indirect consequence?

A

Renal tubular dysfunction (kidney damage)

-> leads to osteomalacia from failure to make vitamin D, and resultant osteoporosis

44
Q

What are the respiratory tract manifestations of cadmium inhalation, acutely and chronically?

A

Acutely - chemical pneumonitis - potentially lethal

Chronic - anosmia with obstructive changes, and lung cancer

45
Q

Where does benzene come from?

A

Inhaled as vapor mostly, used in industrial processes and from incomplete combustion of carbon materials (like tobacco)

46
Q

What are the acute and chronic effects of benzene?

A

Acute - CNS effect, mostly sedating / confusing but can lead to LOC and death

Chronic - Increased risk of acute myeloid leukemia**** (AML)

47
Q

What is vinyl chloride associated with increased risk of?

A

Hepatic angiosarcoma (cancer of the liver sinusoid endothelial cells)

Very rare malignancy, only happened in PVC factories

48
Q

What is 2-naphthylamine associated with?

A

Due to toxicity of glucuronidated product -> increased risk of urothelial carcinoma of urinary bladder

49
Q

Why can estrogen as hormone-replacement therapy not be given to POSTMENOPAUSAL women unless they’ve had a hysterectomy?

A

Increased risk of endometrial carcinoma

50
Q

What are the risks of post-menopausal hormone-replacement therapy?

A
  1. Increased thromboembolic complications
  2. Increased breast carcinoma / increased breast density (false positive mammograms)
  3. Coronary artery disease
  4. Gall bladder disease (its a steroid)
51
Q

What do oral contraceptives reduce your risk of in pre-menopausal women?

A

Endometrial and ovarian carcinoma

52
Q

What do oral contraceptives increase your risk of in pre-menopausal women, especially if you’re a smoker?

A
  1. Thromboembolic events
  2. Cardiovascular disease
  3. Even nonsmokers: Liver cell adenoma (benign tumor associated with prolonged use)
53
Q

What is the most common cause of acute liver failure in the US?

A

Hepatocellular necrosis due to acetaminophen toxicity

54
Q

What are the acid-base disturbances of aspirin toxicity, from early to late?

A

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

55
Q

Why is aspirin contraindicated in children?

A

Increases chances of Reye syndrome, a progressive encephalopathy with liver damage most commonly caused by salicylate poisoning

56
Q

What are the CNS defects of aspirin overdose?

A

lethargy, excitability, seizures, coma

57
Q

What does aspirin overdose do to your core body temp?

A

Increases it due to uncoupling of OxPhos, can lead to dehydration

58
Q

What is a hearing manifestation of aspirin OD?

A

Ototoxicity -> tinnitus / hearing loss

Pathobiology (20 decks)

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