Path: Environmental Diseases Flashcards
Toxins in cigarette smoke can injure the ____ apparatus for escalating bacteria out of the lungs.
mucociliary
Toxins in cigarette smoke can cause inflammation recruiting phagocytes that can leak their ____.
proteases
Toxins in cigarette smoke can inhibit ____ needed to protect against protease tissue injury.
anti-proteases
Toxins in cigarette smoke can cause ____ production and secretion, yielding a place for bacteria to grow.
mucus
Toxins in cigarette smoke can inhibit ____ and bacterial killing by ____.
phagocytosis; phagocytes
Toxins in cigarette smoke can cause ____ ____, removing mucociliary clearance of bacteria.
squamous metaplasia
Toxins in cigarette smoke can kill ____ ____ cells, removing a barrier to bacterial invasion.
respiratory epithelial
What does pulmonary emphysema looks like on macroscopic examination?
abnormal permanent enlargement of airspaces due to the destruction of the walls between alveoli
How does smoking cause pulmonary emphysema?
- nicotine gets into blood and activates neutrophils, which increase production of neutrophil elastase, causing tissue damage; they also produce ROS
- ROS in tobacco and those produced by neutrophils inactivate anti-proteases which results in increased neutrophil elastase, resulting in tissue damage
True or false: there is no synergistic toxicity between cigarette smoking and alcohol consumption.
False - in fact there is a multiplicative increase in the risk of laryngeal cancer from the interaction between cigarette smoking and alcohol consumption.
What are the characteristic histopathological features of respiratory bronchiolitis?
large number of macrophages, loaded with “dusty” frinely granular brown + black pigment, in the bronchiolar lumen; a few lymphocytes are also seen
____ ____ is characteristic of smoking injury to bronchioles.
Respiratory bronchiolitis
What are the 5 main things that cigarette toxins do when they get into the bloodstream?
- injure endothelial cells, increasing permeability of lipids into arteries
- induce a procoagulant state
- increase heart rate, BP, and myocardial contractility, which increases heart need for blood
- decrease blood O2-carrying capacity
- plays role in causing 1/3 of MIs
True or false: toxins in cigarette smoke cause most of the cardiovascular harm.
False: nicotine causes most of the cardiovascular harm of smoking
True or false: smoking is the second most prevalent preventable cause of human death.
False - it’s the MOST prevalent preventable cause of human death
Which ingredient in tobacco smoke is responsible for tobacco addiction?
nicotine
What are the main potent carcinogens in tobacco smoke?
polycyclic aromatic hydrocarbons, nitrosamines, and aromatic amines
What percentage of lung cancers occur in smokers?
approximately 90%
Does cessation of smoking reduce the risk of lung cancer?
You betcha.
Smokeless tobacco is an important cause of ____ cancers.
Oral cancers
What other lung diseases does tobacco predispose a patient to, in addition to lung cancer?
emphysema, chronic bronchitis, and chronic obstructive disease
Maternal smoking increases the risk of what 3 harms to the fetus?
- abortion
- premature birth
- intrauterine growth retardation
What are the 4 heavy metals most commonly associated with harmful effects in humans? Are they visible as pigments in tissue?
lead, mercury, arsenic, and cadmium; they are not visible as pigments in tissue
What is hemochromatosis?
a genetic disease causing excess iron absorption and injurious accumulation in hepatocytes and other cells
What are smoker’s macrophages?
Macrophages that fill bronchiole and adjacent alveoli and contain finely granular golden brown pigment; they are also iron positive
(according to Stanford)
What are hemophages, again?
hemosiderin-laden macrophages, aka heart failure cells; pigment within is dark brown, in large/chunky/refractile granules
“Cherry red” referring to red discoloration of skin and mucous membranes is a “code word” for what condition?
carbon monoxide poisoning
Carbon monoxide is a ____ ____ that is an important cause of accidental and suicidal death.
systemic asphyxiant
True or False: Carbon monoxide is a nonirritating, colorless, tasteless, odorless gas.
True
How long will it take to fall into a coma or die when the average car is running in a small, closed garage?
about 5 min
How does CO kill such that victims don’t really notice they’re being poisoned?
in part, by inducing CNS depression which appears so insidiously that victims are often unaware of their plight
What are the progressive signs of CO poisoning?
- headaches
- nausea
- dizziness
- breathlessness
- collapse
- loss of consciousness
What is the pathophysiology of CO poisoning?
CO binds Hgb better than O2 and thereby block O2 binding, transport, and delivery to tissues
Symptoms of headache and exertional dyspnea appear when ____% of Hgb is bound to CO; symptoms of coma and death appear when ____% of Hgb is bound to CO
20-30%; 60-70%
Chronic poisoning by CO develops because ____ is remarkably stable.
carboxyhemoglobin
Can there be permanent neurologic sequelae from CO poisoning, even after a patient recovers?
Yes, because in the time that they were being poisoned, there could have been widespread ischemic changes in the CNS, which may result in permanent impairment of memory, vision, hearing, and speech
What are possible morphologic changes seen in the brain of CO poisoning with slightly longer survival?
the brain may be slightly edematous, with punctate hemorrhages and hypoxia-induced neuronal changes; these changes are not specific and may stem from systemic hypoxia
What does basophilic stippling consist of and what condition is it associated with?
clumped ribosomes; lead poisoning, as well as megaloblastic anemia due to Vit B12 or folate deficiency
Say that you’re babysitting a little kid who’s an annoying little booger, mostly because he likes to eat things he shouldn’t. But you can deal with him, the parents are paying you a lot and they live in this nice big old house. At one point you walk in the kid’s play room to find him eating the wall paint. Besides being grossed out, you’re also concerned because it’s an old house. What are some manifestations of low concentrations of lead toxicity that you want to look for in Junior now?
- Cognitive impairment, especially memory - he doesn’t remember eating the paint! Uh-oh.
- Behavior problems, especially hyperactivity - but he was like that already…
- Decreased verbal ability - he was still running around but not making lion noises this time.
- Hearing loss - he never paid attention to you when you called his name though…
- Irritability - he threw a fit when you said it was time to stop playing and have lunch
- Lethargy - he usually hates naptime, but this time he went right to sleep
- Myalgia - he woke up complaining that his whole body hurt, but it could be because he slept on the floor without a pillow
- Vomiting - I mean, it could have been the hot dogs you fed him that expired last week.
- Anemia - good thing his parents have a lab in their basement and you could run a blood test. RBC were low.
I think this kid has lead poisoning.
What are the manifestations of lead toxicity in children at higher concentrations?
Colicky abdominal pain, arthralgia, renal insufficiency, constipation, tremor, headache, intellectual disability, seizures, coma and death
What are the manifestations of lead toxicity in adults at lower concentrations?
Short-term memory loss, difficulty concentrating, anxiety, phobias, irritability, depression and hostility
What are the manifestations of lead toxicity in adults at higher concentrations?
Peripheral demyelinating neuropathy (especially motor, especially of hands, then feet), myalgia, arthralgia, diffuse severe abdominal pain (lead colic), constipation, renal insufficiency, anemia, headache, anorexia and decreased libido
Explain the pathophysiology of lead toxicity, based on the electropositive nature of lead and its divalent competition with calcium.
Electropositivity = heme toxicity because it inhibits sulfhydryl-dependent enzymes needed for heme synthesis
Divalent competition with calcium = neurotoxicity because it competes with calcium in mitochondrial respiration and various nerve functions, it also interferes with action of protein kinase C
How can you differentiate the anemia of lead toxicity from iron deficiency?
Both are hypochromic and microcytic, but lead toxicity is associated with basophilic stippling of red cells and high red cell free protoporphyrin (or zinc protoporphyrin)
Do children absorb more ingested lead than adults? What is the main source of exposure of lead for children?
Yes; the main source of exposure for children is lead-containing paint in older housing
The major source of exposure to mercury is contaminated ____.
fish
What is Minamata disease and what causes it?
it is a fetal disease characterized by cerebral palsy, deafness, and blindness caused by exposure to high levels of mercury in utero
What cellular processes does arsenic interfere with?
mitochondrial oxidative phosphorylation and the function of a variety of proteins; has toxic effects in GI tract, CNS, and CV system
Long-term exposure to arsenic can cause ____ ____ and ____.
skin lesions and carcinoma
Cadmium from nickel-cadmium batteries and chemical fertilizers can contaminate soil. Excess cadmium causes what two organ-level diseases?
obstructive lung disease and kidney damage
Acute alcohol abuse can cause drowsiness starting at what blood concentration?
200mg/dL
Alcohol is metabolized to aldehyde in the liver by what 3 enzymes?
- alcohol dehydrogenase
- cytochrome P-450 system
- catalase (minor importance)
What is the fate of acetaldehyde?
it gets converted to acetate in the mitochondria and utilized in the respiratory chain
How does alcohol oxidation by alcohol dehydrogenase lead to metabolic acidosis?
the oxidation reaction depletes NAD, leading to accumulation of fat in the liver and metabolic acidosis
What are the 3 main effects of chronic alcoholism?
- fatty liver
- alcoholic hepatitis
- cirrhosis
Chronic alcoholism is a major risk factor for cancers of ____, ____, and ____. The risk is greatly increased by concurrent ____.
the oral cavity, larynx, and esophagus; smoking (or use of smokeless tobacco)
How can chronic alcoholics tolerate blood alcohol levels of up to 700mg/dL?
they have accelerated ethanol metabolism caused by a 5- to 10-fold induction of liver CYPs
What is normal liver color traditionally called?
red-brown
What is a condition that may result in the liver appearing tan-yellow?
steatosis
In steatosis of the liver, what is the histological appearance of hepatocytes?
distended with clear cytoplasm actually due to lipid dissolved out in processing
In addition to alcohol, what other conditions can cause steatosis?
obesity, uncontrolled diabetes
How does alcohol cause hepatic steatosis?
- shunting of substrates away from catabolism and toward lipid biosynthesis because of the generation of excess reduced nicotinamide-adenine dinucleotide resulting from metabolism of ethanol by alcohol dehydrogenase and acetaldehyde dehydrogenase
- impaired assembly and secretion of lipoproteins
- increased peripheral catabolism of fat
By what physiologic mechanisms does alcohol cause hepatitis?
acetaldehyde, alcohol directly, reactive oxygen species, cytokine-mediated inflammation, and TNF
In hepatitis, acetaldehyde (a major metabolite of ethanol) induces ____ ____ and acetaldehyde-protein adduct formation, which may disrupt ____ and ____ function.
lipid peroxidation; cytoskeleton and membrane
In hepatitis, alcohol directly affects ____ organization (as illustrated by Mallory-Denk bodies), ____ function, and membrane fluidity.
cytoskeleton; mitochrondrial function
In hepatitis, TNF is considered to be the main effector of injury; what 3 other cytokines may contribute?
IL-1, IL-6 and IL-8
What are Mallory-Denk bodies composed of?
tangled skeins of deranged cytoskeletal cytokeratin intermediate filaments
What is the name for abnormal nodular liver architecture?
cirrhosis
Define cirrhosis.
distinctive form of fibrosis of the liver with regenerative nodules of hepatocytes, not properly connected to the hepatic arterial supply, portal venous circulation, or biliary systems, and surrounded by fibrous tissue
How many alcoholics have cirrhosis, and how long does it take to get?
about 15%; takes about 15 years of chronic alcoholism to get cirrhosis
How can you differentiate cirrhosis due to alcoholism from cirrhosis due to non-alcoholic fatty liver disease (NAFLD)?
History
Hepatocellular carcinoma is the cause of death in ____% of cases of alcoholic liver disease.
3-6%
What 3 abnormalities are seen in fetal alcohol syndrome?
- specific dysmorphic facial features
- growth retardation
- CNS abnormalities, including impaired self-regulation, cognition, and adaptive functioning
True or false: drug injury can be caused by either therapeutic or non-therapeutic agents.
True
Menopausal hormone therapy increases the risk of ____ and ____ cancers as well as ____.
endometrial and breast cancers as well as thromboembolism
Oral contraceptives have a protective effect against ____ and ____ cancers but increase the risk of ____ and ____ adenomas.
endometrial and ovarian cancers; thromboembolism and hepatic adenomas
Aspirin blocks the production of ____, which may produce gastric ulceration and bleeding.
thromboxane A2
Overdoses of acetaminophen can be treated at its early stages (within 12 hours) by administration of ____, which restores ____ levels.
N-acetylcysteine; GSH
True or false: alcohol and acetaminophen have antagonistic liver toxicity.
False - they have SYNERGISTIC liver toxicity
How can cocaine induce myocardial ischemia?
by causing coronary artery vasoconstriction and by enhancing platelet aggregation and thrombus formation
Cigarette smoking potentiates cocaine-induced coronary ____.
vasopasm
With chronic use, what impairments may result with respect to cognition, respiration, and the hypothalamic-pituitary-adrenal axis?
- cognition - loss of ability to judge time, speed, and distance
- respiration - laryngitis, pharyngitis, bronchitis, coughing, and hoarseness
- hypothalamic-pituitary-adrenal axis - changes in appetite, food intake, and energy balance, as well as fertility and sexual behavior
Ionizing radiation can cause damage to what? (3 big general structures)
cells, DNA, vessels
Ionizing radiation damage to cells can be caused by what?
generating free radicals from water or molecular oxygen
Ionizing radiation damage to DNA means that why type of cells are very sensitive to radiation injury?
rapidly dividing cells, such as germ cells, bone marrow cells, and GI tract cells
Ionizing radiation may cause vascular damage and sclerosis, resulting in ____ ____ of parenchymal cells and their replacement by ____ tissue.
ischemic necrosis; fibrous
At extremely high doses of radiant energy, markers of cell death, such as _________, appear quickly.
nuclear pyknosis and lysis
Cells surviving radiation damage show what kinds of changes in chromosomes?
structural changes, such as ds DNA breaks, deletions, translocations, and fragmentation; mitotic spindles become disorderly, polyploidy and aneuyploidy may be seen
Cells surviving radiation damage show what kinds of changes in the nucleus?
nuclear swelling and condensation, clumping of chromatin, disruption of the nuclear membrane; additionally, giant cells with pleomorphic nuclei or more than one nucleus may appear and persist for years after exposure
Cells surviving radiation damage show what kinds of changes in the cell/cytoplasm?
cytoplasmic swelling, mitochondrial distortion, degeneration of the ER; plasma membrane breaks and focal deficits may be seen
Why is it hard for pathologists to evaluate irradiated tissues for the possible persistence of tumor cells?
Because the following are characterisitcs that can be shared by both radiation-nijured cells and cancer cells: histologic constellation of cellular pleomorphism, giant-cell formation, conformational changes in nuclei, and abnormal mitotic figures
____ changes and interstitial ____ are also prominent in irradiated tissues
Vascular; fibrosis
Describe the variety of degenerative changes that vessels undergo as a result of radiation therapy.
- immediate post-irradiation: dilation
- with time or higher doses: endothelial cell swelling, vacuolation, necrosis, dissolution of small vessel walls; vessels may rupture or thrombose
- later: endothelial cell proliferation, collagenous hyalinization, thickening of the intima; results in marked narrowing/obliteration of the vascular lumens
