Flashcards in Topics A50-52 Environmental Causes of Disease: Tobacco, Pollution, Alcohol, Radiation Deck (40):
List 6 major outdoor air pollutants, and which one is the most dangerous?
(prob not essential to be able to recite them all)
2. Sulfur Dioxide
3. Nitrogen Dioxide
4. Carbon Monoxide
6. Particulate matter: worst one
What size particles in air pollution are the most dangerous? Why?
Particles < 10 micrometers are the most dangerous because when they are inhaled, they make it to the alveoli, are phagocytosed, and inflammatory rxn / ROS release occurs
Larger particles are caught in the upper respiratory tract with mucous and cilia, can be removed more safely
What is the most common source of INDOOR pollution?
What are some others to be familiar with?
Most common: tobacco smoke
Others: wood smoke, microbes like Legionella, allergens like pet dander, dust mites, fungi, mold
What does "xenobiotic" mean?
How does this differ from "toxin?"
Xenobiotic = exogenous chemicals in the environment that can be absorbed by the body through inhalation, ingestion, or skin contact.
"Toxin" is a vague term - technically anything can be toxic in the right concentration. Xenobiotics may or may not cause harm, depending on concentration and how they are processed by the body.
What are the 2 major biotransformation steps (just a few very important concepts from biochem)
Phase I rxn: make xenobiotic more water soluble. Adds a polar group, usually with CP450 enzyme
Phase II rxn: conjugation to more polar molecule like glucuronic acid.
Goal is to make xenobiotic water soluble for excretion. The process sometimes may actually make the xenobiotic more harmful than it was.
Tobacco is responsible for what percentage of lung cancers?
How many deaths worldwide can be contributed to tobacco every year?
What percentage of smokers survive to age 70?
90% lung cancers
>4 million deaths / year worldwide
Only 50% smokers survive to age 70
Smoking is the most preventable cause of human death
The International Agency for Research on Cancer has 4 categories of substances to say if they are carcinogenic to humans, what are they?
Which one is cigarette smoke in?
1: Definitely carcinogenic (cigarette smoke)
2: 2a probably carcinogenic, 2b possibly carcinogenic
3. Not classifiable if carcinogenic or not
4. Probably not carcinogenic
Of the 4700 chemicals found in cigarette smoke, about how many are known carcinogens? How many are promoters of carcinogenic effects?
~ 60 carcinogens
(promoters drive proliferation without causing mutations themselves. Alone they are not very problematic, but bad when mixed with carcinogens)
Which carcinogen in cigarette smoke is also related to pancreatic cancer?
NNK (nicotine-derived nitrosamine ketone)
It accumulates in the pancreatic juice
Which strong carcinogen in cigarette smoke is actually just from the burning paper?
4 other harmful carbon-based components of cigarette smoke:
-Polycyclic hydrocarbons (PAH) - carcinogenic
-Carbon Monoxide: not carcinogenic, but creates carboxyhemoglobin -> continuous hypoxia. Major risk for fetus during pregnancy.
-Formaldehyde: not carcinogenic directly, but -> constant irritation related to carcinogenesis
Which radioactive compound is inhaled from cigarette smoke?
Polonium-210: has halflife over 400 years, and emits α radiation
Which component of cigarette smoke inhibits mucociliary movement?
Which cancer of the genitourinary tract is most closely related to smoking? Why?
Bladder cancer: nitrosamines and aromatic amines are concentrated in the bladder, have more time to take part in carcinogenesis
(Note smoking cigarettes, cigars, or chewing tobacco etc have relation to oral, laryngeal, esophageal cancers)
What are the 3 major diseases that develop in the lungs as a result of smoking?
1. Chronic bronchitis: smoke irritation causes inflammation and also goblet cell metaplasia that -> more mucous in lungs, good breeding ground for bacteria
2. Emphysema: smoke destroys elastic fibers and alveoli become distended (centriacinar emphysema specifically from smoking)
3. Lung cancer: covered later
What are the two vascular diseases associated with cigarette smoke?
1. Atherosclerosis: high association with MI, dry gangrene. Increased platelet aggregation.
2. Buerger's Disease: necrosis in fingers due to hypersensitivity against materials in cigarette smoke -> proliferation of fibroblasts and thrombus formation inside small peripheral arteries + inflamm of arterial wall (thrombangitis obliterans)
What are the 2 most important enzymes to know for alcohol metabolism?
1. ADH - Alcohol dehydrogenase: most important. Converts ethanol into acetaldehyde intermediate (more toxic than ethanol). Creates NADH from NAD+
2. CYP2E1: a CYP450 isoform that also converts ethanol to acetaldehyde, but only when ADH is overloaded from high ethanol concentration. Other drugs compete to use this enzyme, meaning alcohol has synergistic effects with them. Uses NADPH and creates ROS
(catalase has a minor role for ethanol degradation; aldehyde dehydrogenase performs the final step of converting acetaldehyde to acetic acid)
What are 3 major mechanisms of cell injury from alcohol metabolism?
1. Increase of NADH and decrease of NAD+ means that fatty acid oxidation is impaired, causing fat accumulation in the liver and lactic acidosis
2. Acetaldehyde intermediate is toxic. Many Asian people are deficient in in ALDH -> poor removal of acetaldehyde, causing flushing, tachycardia, and hyperventilation.
3. Metabolism by CYP2E1 -> ROS that cause lipid peroxidation of cell membranes
How much alcohol is the "healthy limit" for men vs women?
Men: 80g pure alcohol (2 liters of 4% alcohol)
Women: 1/4 of that. Only 20g / 0.5 liters
What are the 3 steps of changes in the liver as a result of chronic alcohol consumption?
1. Fatty degeneration / fatty change: from NADH/NAD imbalance, plus acetaldehyde blocks enzyme that makes VLDL. Can see vacuoles, nucleus pushed to periphery.
2. Alcoholic hepatitis: necrosis sites surrounded by PMNs and see horseshoe-shaped Mallory bodies. May get jaundice
3. Cirrhosis: whole liver is diffusely replaced with pseudolobules with connective tissue. Liver is firm and nodular, interferes with blood flow and functions. Portal HTN and hepatocellular carcinoma may result. Largely irreversible.
What are Mallory Bodies (or Mallory-Denk bodies)
Ubiquinated cytokeratin intermediate filaments in hepatocytes, seen in alcoholic liver disease. Appear eosinophilic.
What disease develops in alcoholics as a result of thiamine deficiency?
Wernicke-Korsakoff Syndrome: vision changes, ataxia, confusion, and impaired memory. May be permanent brain damage.
What are the changes to the heart as a result of alcoholism?
Alcoholic Cardiomyopathy: all chambers are dilated, whole heart becomes globular-shaped. Clinically, has biventricular insufficiency due to both sides being dilated. Thrombi frequently seen
May be "cor borvinum" - heart like an ox. Heart weighs over 1 kg
What changes in the pancreas as a result of alcoholism?
Histo: "Dilated duct" is characteristic. Contains protein plaques due to altered pancreatic juice becoming thicker, functions like plaque
May develop either acute or chronic fibrotizing pancreatitis.
Maldigestion occurs from loss of acini, massively decreased enzymes.
What is the most severe consequence to the brain as a result of alcoholism?
Atrophy: brain may weigh 900g instead of 1300. Sulci are deep, gyri are thin.
What are some of the characteristics of fetal alcohol syndrome?
Mental and growth retardation, microcephaly
Facial abnormalities: epicanthal folds, flat midface, smooth filtrum, thin upper lip
4 categories of injury caused by physical agents:
(1 of them is in the title for this topic)
1. Mechanical trauma
2. Thermal injury
3. Electrical injury
4. Ionizing radiation injury
What are some different types of soft tissue injuries?
-Abrasion: scraping or rubbing of superficial layer
-Contusion: bruising, damage to superficial vessels
-Laceration: tearing/stretching via an object more blunt than incision. Bridging vessels are intact
-Incision: sharp instrument cuts bridging vessels
-Puncture wound: instrument penetrates the tissue
What are 4 important hemorrhages that result from trauma to the head?
1. Epidural hematoma: skull fracture, middle meningeal artery rupture. Lose consciousness, lucid interval, lose consciousness again and die.
2. Subdural hematoma: slow progression, bridging veins torn from rapid movement of skull (fall, car crash, etc.)
3. Subarachnoid: often ruptured aneurysms. Rapid onset, "thunderclap" headache. Vomiting, lose consciousness
What factors do the extent of mechanical trauma depend on?
-Shape of the colliding object
-Energy put into the impact
-Which tissue/organ is injured
How do you rank the different degrees of burns?
Partial thickness: 1 and 2
-1st degree: only epidermis
-2nd degree: epidermis + superficial dermis. May have blisters.
Full thickness: 3 and 4
-3rd degree: extends through entire dermis. Stiff, white to brown. Painless at site of burn.
-4th degree: goes even deeper, appears black (eschar).
What are 3 major risks to life from burns / fires?
1. Hypovolemic shock: fluids move to interstitial area and much fluid is lost
2. Infection due to lost protection of skin (Pseudomonas especially)
3. Inhalation injury: life-threatening pulmonary edema often develops within 24-48 hours of exposure after being in burning building
What are the 3 types of hyperthermia?
1. Heat cramps: caused by electrolyte loss from sweating, usually occurs during exercise. Muscles cramp.
2. Heat exhaustion: most common type. Person collapses from hypovolemia due to sweating. Usually after fainting and rest, they recover fine
3. Heat stroke: life-threatening, uncompensated rise in core body temperature. High temperature with high humidity means sweating is ineffective and even stops. Have generalized peripheral vasodilation, arrhythmias, maybe DIC.
At around what hypothermic body temperature does loss of consciousness occur, along with what other serious symptoms of hypothermia?
Around or below 32C / 90F.
Als see bradycardia, atrial fibrillation.
What are the 2 mechanisms of injury for electrical injury?
1. Burns: require longer exposure to electrical source
2. Normal electrical impulses are disrupted: major risk is ventricular fibrillation, but can also paralyze respiratory muscles
What are the 3 forms of ionizing radiation?
1. X and γ rays: high frequency EM radiation. These are "indirectly" ionizing because they react with H2O first to make ROS. (α/β radiation is directly ionizing)
2. α particles: 2 protons and 2 neutrons, steal electrons to stabilize themselves. Most harmful one but it's easily blocked, has short range. Dangerous to ingest.
3. β particles: either high-energy electron or positron emission. Positrons can cause γ rays to be released.
Grays: energy absorbed by target tissue. Joules/kg
Sieverts: "equivalent dose" - basically the energy absorbed multiplied by the relative biologic "effectiveness" of the radiation
Which tissues are most susceptible to mutagenic/carcinogenic effects of radiation?
Cells that divide rapidly:
Most sensitive is bone marrow. Most frequent ionizing radiation problems are acute or chronic myeloid leukemias
Next most affected are breast, lung, salivary glands
(Skin, bone, GI tract are not affected much)
What is the most important intracellular target of ionizing radiation? What are some ways that it can be damaged?
Can cause base damage, single and double-stranded breaks, and cross-links between DNA and proteins. Double-stranded break is most dangerous