Environmental and Nutritional Pathology Flashcards
What is the difference between phase I and phase II reactions?
Phase I:
- Oxidation/ Reduction reactions
- Hydrolysis
- Ex: monooxygenase systems, peroxidase-dependent cooxidation
Phase II:
- Conjugations/ Additions
- Glucuronidation
- Sulfation
- Methylation
What enzyme system converts benzo [a] pyrene (found in tobacco smoke) to an epoxide that covalently binds and damages DNA? What phase reaction is this?
Cytochrome P-450 dependent monooxygenase system
Phase I
Liver
What enzyme system metabolizes Nicotine and other amides? What phase reaction is this?
flavin-containing monooxygenase system
Phase I
Liver
What enzyme system metabolizes naphthylamine to its carcinogenic derivative? (There are two.) What phase reaction?
- Peroxidase- dependent cooxidation
- Phase I
- Catalyzed by prostaglandin-H synthase
- seminal vesicles, kidney, liver
- P-450 followed by glucuronidation
- Phase I and II
- secondary metabolite excreted in urine, carcinogen, causes bladder cancer
What metabolic reaction is used to process inorganic mercury? What is the resulting molecule? What organ systems are affected?
- Biomethylation => methyl mercury
- Organ systems:
- uptake by GI
- crosses BBB (brain damage)
- crosses placenta
How are drugs metabolized by glutathione conjugation excreted?
bile and urine
What carcinogens are present in tobacco and what organs do they affect?
- tar
- aromatic hydrocarbons
- cancer of mouth, larynx, lungs
- N-nitrosonicotine
- cancer of esophagus
- 4-aminobiphenyl and 2-naphthylamine
- bladder cancer
What are the physiological effects of nicotine?
- increased HR and BP
- increased coronary artery blood flow
- Increased cardiac outbut (increased O2 demand)
- Mobilization of FFA
What are the most common diseases associated with smoking?
- Lung Cancer
- emphysema/ COPD
- MI
- Systemic atherosclerosis
What receptors does ethanol act on?
- GABA
- N-methyl-aspartate
- Opioid receptors
How is ethanol metabolized?
- enzyme: alcohol dehydrogenase in gastric mucosa
- end product: acetaldehyde
What are the effects of ethanol on the liver?
- Steatosis
- Peripheral fat catabolism
- Lipid synthesis
- Hepatitis
- Fever, hepatomegaly, and jaundice
- Mallory bodies (fat and hyalin accumulation)
- Cirrhosis
- Path: Necrosis and fibrosis
- Symptoms: muscle wasting, ascites, GI bleed
What does the presence of Mallory bodies in the liver signal?
Acute Alcoholic Hepatitis
(fat and hyaline accumulation)
What are the effects of ethanol on the CNS?
- Cause:
- thiamine (Vit B1) deficiency
- Path:
- Neuronal degeneration
- Cerebellar atrophy
- Syndromes:
- Wernike and Korsakoff syndromes
- Symptoms:
- Ataxia
- Ophthalmoplegia
- Nystagmus
- Amnesia
What are the effects of ethanol on the CV system?
- Cardiomyopathy
- HTN
- From increased release of catecholamines
What are the effects of ethanol on the GI tract?
- Cause
- impaired absorption of nutrients
- Result:
- Gastritis
- Pancreatitis
What are the effects of ethanol on skeletal muscle?
- Rhabdomyolysis from a breakdown of myoglobin
What are the effects of ethanol on the reproductive system?
- Testicular atrophy
- Decreased fertility
- Spontaneous abortion
What types of cancer are caused by ethanol?
- Oral cavity
- Pharynx
- Esophagus
- Breast
- Liver
- esp. in combination with HBV/ HCV
What are the symptoms of Fetal Alcohol Syndrome?
- Growth and mental retardation
- microcephaly
- facial dysmorphology
- malformation of brain, heart, GU tract
- atrial septal defects
What are the metabolites of Methanol? What are the side effects of ingestion?
- Metabolites:
- Formaldehyde
- Formic Acid
- SE
- Metabolic acidosis
- Vomiting
- Blurred vision
- Respiratory distress
What is the treatment for Methanol poisoning?
Ethanol
(competes with alcohol dehydrogenase)
What are the metabolites of Ethylene Glycol? What are the side effects of ingestion?
- Metabolites
- Glyceraldehyde
- Oxalic acid
- SE
- Vomiting
- Seizure
- Renal tubular necrosis
- accumulation of oxalate crystals
What is the treatment for ethylene glycol poisoning?
Ethanol
(competes for aldehyde dehydrogenase)
What are the symptoms of Heroin overdose?
Opioid receptor binding
- Convulsions
- Cardiorespiratory arrest
What infections are associated with IV drug use?
- HIV
- Hepatitis
- HBV, HCV, HDV
- Endocarditis
- S. aureus
- Lung infection
- M. tuberculosis
What drug can cause perforation of the nasal septum?
Cocaine
What are the effects of cocaine on the CV system?
- Increased catecholamines
- arrhythmias
- infarction
- hemorrhage
- Enhanced platelet activation
- atherosclerosis
What is the effect of amphetamine on the CV system?
ischemic myocardial necrosis
What are the symptoms of amphetamine overdose?
- Delirium
- Convulsions
- Arrhythmias
What are the effects of Ecstasy use?
- Panic disorder
- Hyperthermia
- DIC
- Rhabdomyolysis
- Renal failure
- Liver failure
What are the acute effects of Cannabinoids?
- Impaired memory
- Incoordination
- Euphoria
What are the beneficial effects of THC?
- Decreases intraocular pressure in glaucoma
- Relieves nausea from chemo
- Relieves chronic pain
What are the adverse effects of anabolic-androgenic steroids in men?
- Testicular atrophy
- Gynecomastia
- excess androgens converted to estradiol
- HTN
- Edema
- Sleep disorders
What are the adverse effects of anabolic-androgenic steroids in women?
- Decreased breast size
- HTN
- Edema
- Sleep disorders
What are the CV effects of anabolic-androgenic steroids?
- HTN
- Cardiac hypertrophy
- Sudden death from cardiac arrest
What risks are associated with use of oral contraceptives?
- Cervical cancer
- in women with HPV
- Venous thrombosis and Pulmonary Embolism
- in women deficient in proteins S and C or antithrombin
Which drugs cause erythema multiforme, Stevens Johnson syndrome, and toxic epidermal necrolysis?
- Sulfonamides
- AEDs
- NSAIDs
What is the difference between erythema multiforme, Stevens Johnson syndrome, and toxic epidermal necrolysis?
- erythema multiforme
- rash localized to skin
- Target “bull’s eye” lesions
- Stevens Johnson syndrome
- rash on skin and mucous membranes
- up to 10% epidermal loss
- toxic epidermal necrolysis
- epidermal loss >30%
- viscera involvement
What is the most serious respiratory reaction associated with NSAIDs? What causes it?
Asthma
- Cause:
- inhibition of COX stimulates lipoxygenase pathway
- Leukotriene overproduction
What are the effects of aspirin overdose?
- Acute
- Tinnitis
- Tachypnea
- Severe
- Delirium
- Seizures
- Pulmonary edema
What are the symptoms of Acetaminophen toxicity?
- Hepatotoxicity
- elevated aminotransferases and billirubin
- Liver failure
What is the primary target of outdoor air pollutants?
the lungs
What size particulates penetrate the lung and cause symptoms?
10 um or less
What are they symptoms of asbestosis? Where are abestos commonly found?
- Signs and Symptoms
- cough
- exertional dyspnea
- Asbestos bodies: fibers coated with iron containing proteins
- Abestos is common in insulation of old buildings
What are the symptoms of pneumoconiosis? What is the cause?
- aka Black lung disease
- Signs and symptoms:
- Cough
- Exertional dyspnea
- anthracosis and fibrosis
- Cause:
- inhaled organic or mineral dust
- coal workers
What are the signs and symptoms of silicosis?
- Signs and symptoms:
- Cough
- Exertional dyspnea
- Pulm infiltrates
What are the signs and symptoms of beryllium disease?
- Signs and symptoms:
- Cough
- Exertional dyspnea
- Pulm infiltrates
What is the predominant symptoms associated with inhalation of petroleum products?
headache
What is the most toxic aromatic hydrocarbon? What are the side effects resulting from exposure?
- Benzene
- SE
- aplastic anemia
- acute leukemia
What are the effects of exposure to benzo[a]pyrene?
- Short term
- anemia
- immunosuppression
- Long term
- lung, bladder, skin cancers
Exposure to what chemical causes increased risk for angiosarcoma of the liver?
Vinyl chloride
What are the effects of vinyl chloride exposure? What is the metabolite that causes these effects?
- Metabolite
- chloroacetaldehyde
- Effects
- destabilizes DNA (carcinogen)
- Angiosarcoma of the liver
What are the effects of Elemental mercury exposure?
- hemoptysis
- chest pain
What are the effects of oxidized elemental mercury exposure?
- CNS manifestations
- Nephrotic syndrome
What are the effects of inorganic mercury exposure?
Occurs from ingestion
- GI symptoms
- Renal (nephrotic syndrome)
What are the effects of methylmercury exposure?
from eating fish
- sensorimotor syptoms
- parasthesias
- paralysis
- vision or hearing loss
Who is most susceptible to lead poisoning? Why?
Children and infants
Taken up by developing bones and teeth
What are the effects of lead toxicity?
What are the effects of lead toxicity?
- Blood
- Microcytic hypochromic anemia
- CNS
- inhibits nerve transmission and brain development
- Other
- Renal damage
- Interferes with vit D metabolism
Why does lead poisoning cause microcytic hypochroic anemia?
it inhibits incorporation of iron into heme
What are the effects of Cobalt toxicity?
- Peripheral neuropathy
- Renal tubular necrosis with proteinuria
- Lung fibrosis
Chromium exposure is associated with an increased risk of what type of cancer?
Lung cancer
What are the effects of Nickel toxicity?
- Contact dermatitis
- increased risk of lung cancer
What are the effects of organochlorine exposure?
low toxicity for humans
High exposure causes immunosuppression
What are the effects of organophosphates?
AChE inhibitors (anti-muscarinic actions)
Abnormal nerve transmission
What are the effects of carbamate exposure?
- AChE inhibitor
- teratogen
What are the effects of exposure to botanicals?
- paresthesias
- pulmonary irritation
- contact dermatitis
(insecticide)
What are the effects of herbicide exposure?
cancer
What are the effects of fungicide exposure?
reproductive toxicity
What are the effects of ergot alkaloid exposure?
- Gangrenous form of ergotism
- Convulsive ergotism
What are the effects of aflatoxin exposure?
- Target: liver
- hepatitis
- hepatocellular carcinoma
What is the cause of scombroid fish poisoning? What reaction results?
- Cause
- improperly stored fish (above 20C for a few hours)
- Reaction
- resembles IgE-mediated rxn
- flushing, rash, tachycardia
- resembles IgE-mediated rxn
What is the cause of Ciguatera fish poisoning? What symptoms result?
- Cause:
- ciguatoxin
- comsumption of contaminated reef fish
- Carribean
- Symptoms
- Acute gastroenteritis
- Neuro
- paresthesia
- blurred vision
- hot/cold temp reversal
- CV
- arrhythmia
- heart block
What is the cause of Paralytic shellfish poisoning? What symptoms result?
- Cause:
- saxitoxins
- Symptoms:
- Neurologic
- face and neck numbness
- incoordination
- difficulty breathing
- Paralysis
- Respiratory failure
- Neurologic
What is the cause of Amnesic shellfish poisoning? What symptoms result?
- Cause
- domoic acid
- contaminated mussels
- Symptoms
- GI symptoms
- Confusion
- memory loss
- disorientation
What is the cause of Neurotoxic shellfish poisoning? What symptoms result?
- Cause
- brevetoxin (neurotoxin)
- hemolysin
- Symptoms (ingestion)
- gastroenteritis
- face and neck numbness
- incoordination
- Symptoms (inhalation)
- reversible respiratory syndrome
- rhinorrhea
- cough
- bronchoconstriction
- reversible respiratory syndrome
What are the characteristics of ionizing radiation?
- Characteristics
- short wavelength
- high frequency
- ionize biologic molecules
What are two types of particulate radiation and what are their properties?
- alpha particles
- strong ionizing power
- large (don’t penetrate well)
- beta particles
- weak ionizers
- greater penetration (small)
What is a unit of charge produced by x-rays or gamma rays that ionize a specific volume of air?
roentgen
What is the dose of radiation that will produce absorption of 100 ergs of energy per gram tissue?
rad (radiation absorbed dose)
What is the dose of radiation that causes a biologic effect equivalent to 1 rad of x rays or gamma rays?
rem (roentgen equivalent in man)
What is the dose of radiation that produces the absorption of 1 joule of energy/kg of tissue?
Gray (Gy)
1 Gy = 100 rads = 1 J/kg
What is the dose of radiation that causes a biologic effect equivalent to 1 gray (Gy)?
sievert (Sv)
1 Sv= 100 rem
What is the average whole body lethal dose (LD50) of radiation?
3.5-5.5 Gy (w/i 3-6 weeks)
What is the dose of radiation that leads to 100% death in 2-3 weeks?
5.5-7.5 Gy
What cells are most susceptible to radiation?
Rapidly dividing cells
Cells in G2 and M phases
What are the chronic effects of radiation injury?
- Fibrosis
- Carcinogenesis
What form of acute radiation syndrome is associated with doses < 0.5 Gy?
Subclinical
- Symptoms
- mild nausea and vomiting
- slight depression of lymphocytes (still normal)
- <1500
What form of acute radiation syndrome is associated with doses 0.5 - 3.5 Gy?
Hematopoietic
- Symptoms
- intermittant nausea/ vomiting
- Petechiae
- hemorrhage
- lymphocytes <1000
- May require BM transplant
What form of acute radiation syndrome is associated with doses 3.5 - 10 Gy?
GI
- Symptoms:
- Vomiting and diarrhea
- hemorrhage and infection
- lymphocytes <500
- thrombocytopenia
- Shock and death result
What form of acute radiation syndrome is associated with doses < 10 Gy?
Cerebrovascular
- Symptoms
- GI
- Neuro
- confusion
- convulsions
- Lymphocytes absent
- Rapid death results
What are the risks of radiation to fetus less than 9 weeks old?
malformations
(critical stages of organogenesis)
What are the risks of radiation to fetus more than 9 weeks old?
CNS abnormalities
Reproductive abnormalities
What are the risks of radiation postnatally?
retarded bone growth
CNS developmental delays
What disease results from fibrosis of the kidneys from radiation damage?
HTN
What can result from radiation exposure of the eye?
cataracts
What can result from radiation exposure of the spinal cord?
Transverse myelitis
- demyelination leading to paraplegia
What results from intense UVA and UVB exposure?
- Mast cell degranulation and release of cytokines
- erythema
- Increased pigmentation
- injury to Langerhans cells and keratinocytes
- Damage to collagen and elastin
- Premature aging
What is the UV response pathway?
- Activation of proto-oncogenes associated with cell proliferation
- Result: Cancer
- no DNA damage
How much blood must be lost for shock to occur?
1/3 of blood volume
Full-thickness Burns
- Extent of damage to skin
- Treatment
- Total destruction of epidermis and dermis
- loss of dermal appendages that would have provided cells for epithelial regeneration
- Treatment:
- skin grafting
What is the main concern when more than 20% of the body surface has been burned?
Hypovolemic shock
What is the main concern when over 40% of the body surface has been burned?
Hypermetabolic state
- Increased heat loss
- Need parenteral nutrition
What is the difference between hyperthermia and heat stroke?
- Hyperthermia
- core temp above 37.5C
- Loss of electrolytes causes heat cramps and exhaustion
- Heat stroke
- core temp above 40.5C (105F)
- Peripheral vasodilation and pooling of blood
- Arrhythmias and rhabdomyolysis may occur
Lichtenberg figures are pathognomonic for what?
Lightning strike injuries
(feathering skin injury)
Caisson disease of the bone is caused by what?
Decompression disease
- Focal area of necrosis from embolic occlusion of the vascular supply
What are the symptoms of decompression disease?
aka Caisson disease
- muscle and joint pain
- respiratory difficulties
- CNS problems (vision, headache)
Patient presents with a 60% reduction in normal body weight with a significant loss of muscle mass and body fat. Serum albumin levels are near normal. What is the disease? What is the cause?
Marasmus
- Severe reduction in caloric intake
Patient presents with growth retardation, skin lesions (hypo and hyperpigmentation), edema, enlarged fatty liver, and hypoalbuminemia. What is the disease? What is the cause?
Kwashiorkor
- Caloric intake normal but proteins are absent from diet
- utilize visceral protein stores (ex: liver)
What are the major clinical findings in anorexia?
endocrine abnormalities
- decreased GnRH
- Amenorrhea
- decreased TH
- Cold intolerance
- bradycardia
What are the functions of Vit A?
- vision (night vision)
- rhodopsin in rods
- differentiation of mucous- secreting epithelium
- retinoic acid
What are the consequences of Vit A deficiency?
Night blindness and below
What are the functions of Vit D?
- maintain Ca and P levels
- intestinal absorption
- Mineralization of bone
What are the consequences of Vit D deficiency?
Rickets/ Osteomalacia
normal Ca lvls, decreased P lvls
What is the function of Vit E?
- Antioxidant
- Terminates lipid peroxidation
What are the consequences of Vit E deficiency?
- Degeneration of posterior columns of spinal cord
- loss of reflexes
- ataxia
- weakness
- Loss of cells in dorsal root ganglia
- loss of pain sensation
What is the function of Vit K?
- production of clotting factors
- VII, IX, X, prothrombin
- activation of proteins C and S (anti- coag)
- Inhibit osteoclasts
- promote bone calcification
How does Vit K deficiency occur?
- fat malabsorption syndrome
- loss of gut bacteria
- synthesize Vit K
- broad spectrum antibiotic use
- neonates don’t have bacteria
- Liver disease
What is the most important function of Thiamine (Vit B1)?
Maintains neural membrane integrity
If niacin (B3) is deficient in the diet, what else must be deficient in order to manifest symptoms?
Tryptophan deficiency
(converted to niacin)
What is the function of Pantothenic acid (Vit B5)?
Coenzyme A
Patient presents with symmetric toe, foot, and wrist drop, muscle weakness, and hyporeflexia. What is the disease? In what vitamin is he deficient?
Dry beriberi (polyneuropathy)
Vit B1 (thiamine)
Patient presents with absent reflexes, ataxia, muscle weakness, and loss of pain sensation. In what vitamin is he deficient?
Vit E
Patient presents with bowed legs and a history of increased fractures. Labs show normal blood levels of Ca but decreased levels of P. In what vitamin is he deficient?
Vit D
Patient presents with impaired vision in reduced light, keratomalacia from a dry conjunctiva, and a history of increased infections. Kidney stones are also present. In what vitamin is he deficient?
Vitamin A
Patient presents with peripheral edema and mural thrombi. What is the disease? In what vitamin is he deficient?
Wet beriberi (CV syndrome)
Vit B1 (thiamine)
Patient presents with cracks and fissues at the angles of the mough, a magenta tongue, corneal ulcerations and a scaling dermatitis of the face. In what vitamin is he deficient?
Vit B2 (Riboflavin)
Cheilosis
Glossitis
Keratitis
Patient presents with ophthalmoplegia, nystagmus, confusion, and amnesia. What disease is this? In what vitamin is he deficient?
Wernicke Korsakoff syndrome
Vit B1 (Thiamine)
Patient presents with dermatitis, diarrhea, and dementia. What is the disease? In which vitamin is he deficient?
Pellagra
Niacin (Vit B3)
Patient complains of burning feet from distal paresthesia. In which vitamin is he deficient?
Pantothenic acid (Vit B5)
Patient presents with increased numbers of purpura, bleeding gums, and bowed legs. What is the disease? In what vitamin is he deficient?
Scurvy
Vit C
Abnormal collagen production
Deficiency in which vitamins results in megaloblastic anemia?
Folate
Vit B12
Patient presents with hemorrhagic dermatitis around the mouth and eyes and on the arms. In what mineral is he deficient?
Zinc
function: component of DNA and RNA polymerase
What is the function of selenium? What are the symptoms of deficiency?`
- Function:
- protects against oxidative damage
- part of glutathione peroxidase and superoxide dismutase
- Symptoms:
- myalgia
- cardiomyopathy
Deficiency of which vitamin results in hypochromic microcytic anemia?
Iron
Deficiency of which vitamin results in hyperglycemia?
Chromium
What is the function of leptin?
triggers catabolic circuits
reduce food intake and stimulate energy expenditure
What is the function of adiponectin?
Stimulates FA oxidation
Decreases glucose production (insulin sensitivity)
A cancer patient presents with extreme weight loss, fatigue, muscle atrophy, anemia, and anorexia. What is the disease? What agents induce this change?
Cachexia
- Inciting agents:
- PIF (proteolysis inducing factor)
- LMF (Lipid mobilizing factor)
- TNF
