Environmental and Nutritional Disorders Flashcards
What are four disease groups that climate change is expected to increase the incidence of? (and why?)
- Cardiovascular, cerebrovascular and respiratory diseases (exacerbated by heat waves and air pollution)
- Gastroenteritis (contamination of food and water e.g. with flooding)
- Vector-borne infectious diseases (increased temps, crop failures and more extreme weather variation expected to change vector number and distribution)
- Malnutrition (disruption to crop production)
Define xenobiotics
Exogenous chemicals in the environment in air, water, food and soil that may be absorbed into the body through inhalation, ingestion, and skin contact
Briefly describe the cytochrome P-450 enzyme system:
Large family of heme-containing enzymes, each with preferred substrate specificities. Catalyses reactions (in two parts) that either detoxify xenobiotics or, less commonly, convert xenobiotics into active compounds that cause cellular injury.
What are three important outdoor air pollutants, and the main reason for their toxicity?
- Ozone - free radial production
- Sulphur dioxide - converted into sulphuric acid and sulphuric trioxide in the air
- Particulate matter - less than 10um reach alveoli and are phagocytosed leading to inflammation
CO can cause chronic and acute poisoning. How does it lead to death?
Induces insidious CNS depression (widespread ischemic change). Hb has 200-fold greater affinity for CO than O2 (creating a stable carboxyhaemoglobin) 20-30% saturation with CO leads to systemic hypoxia and unconsciousness and death are likely at 60-70% saturation.
What are some pollutants that may accumulate indoors and cause disease?
Smoke, bioaerosols, radon and formaldehyde
Lead poisoning can lead to haematological, skeletal, neurologic, gastrointestinal and renal toxicies.
What makes children more susceptible to these effects than adults?
Children absorb more than 50% of lead from food whereas adults absorb about 15%. They have a more permeable blood-brain barrier and are more actively developing bones and teeth.
What does lead have a high affinity for that leads to interference with two enzymes involved in heme synthesis (delta-aminolevulinic acid dehydratase and ferrochelatase) meaning iron incorporation into heme is impaired?
Sulphydryl groups
What neurologic condition is frequent in adults rather than children with lead poisoning?
Peripheral demyelinating neuropathy
Mercury can enter the food chain in organic form (high levels more likely in carnivorous fish), and people can be exposed to the metallic form from industrial processes. Both of these forms are readily absorbed by the body, where it binds to sulphydryl groups in certain proteins with high affinity. What are some symptoms of mercury toxicity?
- CNS - cerebral palsy, deafness, blindness, ID and major effects if exposed in utero (Minamata disease)
- Renal - acute tubular necrosis and renal failure. Chronic can cause nephrotic syndrome
- GI - ingested can injure gut and cause ulcerations and bloody diarrhoea
Arsenic salts interfere with several aspects of cellular metabolism (including ox-phos). What are some possible consequences of exposure?
- Death
- GI upset
- Neurological effects (usually sensorimotor neuropathy causing paresthesias, numbness and pain)
- Cardiovascular effects including HTN and long QTc with ventricles arrhythmias
- Hyperpigmentation and hyperkeratosis of skin
- Increased cancer risk - particularly lung, bladder and skin
What are three important carcinogens in tobacco smoke?
Polycyclic aromatic hydrocarbons, nitrosamines and aromatic amines
What levels of ethanol cause drowsiness and stupor respectively?
- 200mg/dL
- 300mg/dL
What are four causes of toxicity in alcohol metabolism?
- Acetaldehyde (direct product of alcohol oxidation)
- Increase in NADH/NAD ratio (NAD is reduced by alcohol dehydrogenase). NAD required for fatty acid oxidation and lactate -> pyruvate
- ROS generation
- Provokes release of endotoxin from gram negative bacteria in intestinal flora
In order of increasing blood level what areas of the brain does alcohol depress?
Subcortical structures that modulate cerebral cortical activity -> cortical neurons -> lower medullary centres (including those that regulate respiration)
Paracetamol toxicity begins with nausea, vomiting, diarrhoea and sometimes shock. Severe overdose can lead to liver failure, starting with centrilobular necrosis. What is the cause of paracetamol toxicity?
5% of paracetamol is converted to NAPQI by CYP2E1 (Rest is detoxified by phase II enzymes and excreted). This is normally detoxified by conjugation with GSH. High levels overwhelm this mechanism, depletion of GSH makes hepatocytes susceptible to ROS-induced injury. NAPQI also covalently binds hepatic proteins causing damage to membranes and mitochondrial dysfunction.
(note NAC restores GSH levels)
What is analgesic nephropathy?
Tubulointerstitial nephritis caused by long term combined use of aspirin and paracetamol
What are the affects of 1. acute and 2. chronic injury by aspirin?
- Alkalosis (respiratory) followed by metabolic acidosis which can cause symptoms ranging from nausea to coma
- Headaches, dizziness, tinnitus, hearing impairment, mental confusion, drowsiness (can develop convulsions and coma) N&V&D. GI bleeding and ulceration.
