Chapter 9: Environmental and Nutritional Diseases Flashcards
1
Q
What is the leading causes of death in developed countries?
What is the leading cause of death in developing countries?
What are the 3 preventable leading cause of death in kids <5yo?
A
ischemic heart disease and cerebral vascular disease
Infectiious disease
pneumnia, diarrhea, malaria
2
Q
Generally, what trends have we observed in diseases that are increasing?
A
Cardiovascular disease
Cancer
HIV/AIDs and TB
3
Q
Generally, what trends have we observed in diseases that are decreasing?
A
Neonatal conditions
Diarrhea
Lower respiratory infections
4
Q
What are the 3 categories of emerging infectious diseases?
A
newly evolved strains (drug resistant TB)
strains that “jumped” to human population (HIV)
pathogens with increased incidence (dengue in southern US due to warming)
5
Q
What are some negative impacts on human health suffered from climate change?
A
Air pollution/heatwaves –> Cardiovascular, cerebrovascular and respiratory dzs
Floods/disruption of clean water supplies –> Gastroenteritis, cholera & foodborne/waterborne infectious dzs
Disrupted crop production –> malnutrition
Increased temps, extreme weather –> Malaria, dengue fever (vector borne infectious disease(
6
Q
What are xenobiotics?
How do they enter and how are they metabolized in the body?
A
exogenous chemicals absorbed into the body
most are lipophilic and able to penetrate into the basement membrane
either metabolized to inactive (detoxification) or activated to form toxic metabolites (needs to be repaired so they don’t cause damage)
7
Q
What is the role of cytochrome P450?
A
detoxifies xenobiotics or convert them to active compounds, activity decreased by malnutrition
both tyeps of rxn produce ROS (like CCl3- from CCl4 metabolism)
8
Q
How are humans exposed to pollutants?
A
air, water, soil > skin, lungs and GI tract > bloodstream
9
Q
What population is most vulnerable to air pollution?
A
people with preexisting pulmonary or cardiac diseases
10
Q
Pollutant:
Ozone
Populations at risk?
A
Healthy children
Healthy adults
Atheletes
Outdoor workers
Asthmatics
11
Q
Pollutant:
Ozone
Effects on healthy adults/chilrden?
A
Decreased lung function
Increased airway reactivity
Lung inflammation
12
Q
Pollutant:
Ozone
Effects on Athletes, outdoor workers, asthmatics?
A
Decreased exercise capacity
Increased hospitalizations
13
Q
Pollutant:
Sulfur Dioxide
Populations at risk?
A
Healthy adults
Individuals with chronic lung disease
Asthmatics
14
Q
Pollutant:
Sulfur Dioxide
Effect on healthy adults?
A
Increased respiratory symptoms
15
Q
Pollutant:
Sulfur Dioxide
Effect on Individuals with chronic lung disease?
A
Increased mortality
16
Q
Pollutant:
Sulfur Dioxide
Effect on Asthmatics?
A
Increased hospitalization
Decreased lung function
17
Q
How is ozone toxic?
A
ozone gets damaged by CFCs, resulting in free radicals > injure respiratory epithelium and type 1 alveolar cells > release of inflammatory mediators. usually leads to mild symtpoms but more dangerous for patients with asthma or emphysema
18
Q
Why is sulfur dioxide toxic?
A
combines with ozone and particulate matter = withce’s brew (often made by industrial plants)
sulfuric acid & sulfuric trioxide causees burning sensation in nose & throat, SOB and asthma attacks
19
Q
Why is particulate matter (soot) so dangerous to inhale?
A
*THEY ENTER THE ALVEOLI –> which causes the release of inflammatory mediators
Induces pulmonary inflammation and secondary CV effects
Fine or Ultrafine particles less than 10microm in diameter are the most harmful since they are so small and can travel further into the alveoli
20
Q
What is the major hallmark for carbon monoxide poisoning?
A
Cherry red color of the skin and mucous membranes
21
Q
Describe carbon monoxide’s characteristics as a gas
A
Nonirritating
Colorless
Tasteless
Odorless
22
Q
What are some notable situations where a person is suceptible to chronic CO poisoning?
A
Working in tunnels
Underground garages
Highway toll booths
23
Q
What are some notable situations where a person is suceptible to acute CO poisoning?
A
In small, closed garage w/ running car (can produce sufficient CO to cause death in 5 minutes)
Mine fires
24
Q
How does CO poisoning ultimatley kill?
A
Kills by inducing CNS depression and widespread ischemic changes
25
What anatomic structures are affected by **CO poisoning?**
Basal ganglia
Lenticular nuclei
26
What would you expect to see on a patient who dies rapidly of CO poisoning?
How about a patient who dies but survived longer?
no morphologic changes
edematous, pnctate hemorrhages and hypoxia induced neuronal changes
27
If your patient recovers from **CO poisoning,** what would you expect to be lasting effects?
Memory, vision, hearing and speech impairment
28
With 60-70% CO saturation of Hb, what happens?
If Hb is saturated 20-30% with CO, what happens?
Unconsciousness \<5 minutes
systemic hypoxia
29
What is unique about a **CO poisoned** brain vs a normal brain?
CO posioned brain has increased detail in anatomical structures
petechial hemorrhages seen 24-48 hours after exposure
30
How does a CO poisoned brain appear under the microscope?
appearance of dead red neurons
31
Which CNS cell types are particularly vulnerable to CO poisioning?
Neurons (especially Sommer's in hippocampus and Purkinje's in the cerebellum)
Oligodendrocytes
Astrocytes
Endothelium
32
What are examples of **indoor air pollution?**
- Wood smoke
- Bioaerosols (pet dander, fungi, molds)
- Radon (from uranium)
- Formaldehyde
- Sick building syndrome (fungal mold develop from poor ventilation)
33
**Lead**
What are it's effects on the human body?
Hematologic
Skeletal
Neurologic
GI
Renal
TOXICITIES!!!!
34
Where is **lead** frequently found by children?
Flaking lead paint and soil
35
Where are common places for adults to encounter **lead** during _occupational exposure?_
Battery manufacturing
Pigments
Car radiators
Tin cans
36
Where does **lead** primarily deposit in the human body?
How long does it stay there?
Bone & Developing teeth
20-30 years!
37
Low levels of **lead** in the body lead to in children?
Subtle deficits in...
- Intellect
- Behavioral problems
- Hyperactivity
- Poor organizatinoal skills in kids
- Brain damage
38
Low levels of **lead** causes what symptoms in adults?
CNS disturbances
**Wrist drop**
**Foot drop**
39
What is a hallmark finding in the bones to indicate lead poisoning?
"Lead lines"
40
What are the major morpholigcal features you will see in a patient with lead posioning?
**Hypochromic microcytic anemia**
Basophilic stippling
Ring sideroblasts (red cell precursors with iron laden mT due to inhibitioin of ferrochelatase)
41
What is **"lead colic"?**
Extremely severe and poorly localized abdominal pain caused by **lead poisoning**
42
What effect does lead poisoning have on the kidney?
proximal tubule damage leading to fibrosis and renal failure
43
What is this showing?
Lead lines
44
What is this showing?
Lead lines
45
What is this?
**_Ringed Sideroblast_**
Associated with _sideroblastic anemia_ due to excess **IRON** in mitochondria
46
Classification of anemia
What are the lab values for:
MCV
MCH
That would allow a microcytic anemia diagnosis?
[average RBC size] MCV \<80 fL
[hemoglobin amount per RBC] MCH \<27 pg
47
Histologically speaking...
How big should a RBC be?
A RBC should be about the same size as the nucleus of a normal lymphocyte
48
What is this?
Microcytic/hypochromic anemia
49
What is this?
Basophilic stippling
50
What are **three major metals** that are enviornmental pollutants?
Mercury
Arsenic
Cadmium
51
What disease is related to **mercury poisoining?**
***_Minamata disease:_***
Cerebral palsy, deafness, blindness, mental retardation and major CNS defects in children exposed in utero (brain atrophy worse in kids than adults)
52
How is mercury toxic?
What is the major protective substance against mercury in the body?
- binds to sulfhydryl groups and damage the developing CNS and kidney (lipid soluble so it accumulates easily there)
- Glutathione
53
What disease is related to **cadmium poisoning?**
"***_Itai-Itai"_*** (ouch-ouch)
Oseoporosis and osteomalacia w/ renal disease, increased risk for lung cancer
54
What are visual indicators that someone has had **arsenic poisoning?**
Hyperpigmentation
Hyperkeratosis
(increased risk of lung, bladder and skin cancer)
"MEES lines" in the nails
55
What are examples of **organic solvents?**
Chloroform
Carbon Tetrachloride
56
What happens if you get exposed to large quantities of arsenic?
What happens 2-8 weeks post exposure to arsenic?
GI, CV and CNS issues
neuropathy, parasthesia, numbness, pain
57
What toxins lead to heart disease?
What toxins lead to lung cancer?
What toxins lead to COPD?
CO, lead
Radon, arsenic
cadmium
58
What toxins lead to peripheral neuropathies?
What toxins lead to ataxia?
What toxins lead to renal toxicity?
mercury, lead, arsenic
mercury
mercury
59
What toxins lead to infertility and teratogenesis?
What toxins lead to leukemia?
What toxins lead to liver angiosarcoma?
lead and mercury
benzene
vinyl chloride
60
What can prolonged exposure of **chloroform** and **carbon tetrachloride** do to the human body?
CNS depression
Coma
61
ASSOCIATE: Occupational exposure of rubber workers to ...
Benzene and 1,3-butadiene
62
What is the effect of **benzene/1,3-butadiene** on these rubber workers?
Marrow aplasia
HUGE RISK for **acute myeloid leukemia**
63
What do polycyclic hydrocarbons lead to?
lung, bladder and scrotal cancers
exposed from fossil fuel combustion and chimney sweeps
64
What do organochlorines lead to?
examples: PCB, dioxin and DDT that disrupt hormonal balance by targeting steroid activity
PCB and dioxin lead to chloracne: acne, hyperpigmentation, hyperkertaosis in face and behind ears, also liver and CNS problems (what the Ukrainian president got)
65
What do mineral dusts like abestos, silica and beryllium lead to?
pneumonoconioses, abestosis and ferruginous bodies
66
Asbestosis leads to?
Mesothelioma ; black lung
67
What are **furrungious bodies?**
Asbestos fibers coated in iron
68
**Vinyl chloride** leads to?
Angiosarcomas in liver
69
What is bisphenol A?
BPA
Lines almost all food bottles and cans
\*Is a potential endocrine disruptor
70
What is this?
Aplastic anemia
71
Name the disease
Mesothelioma
72
Name the disease
Black lung from abestosis
73
Tobacco accounts for \_\_\_% of lung cancers
90%
74
How do you calculate pack years?
Pack years = average number of cigarette packs smoked/day (x) # years smoking
the higher the pack years athe worse the odds
75
Describe the benefits of cessation of smoking for a smoker
Within 5 years, cessation of smoking improves **mortality** and **decreases risk of death from cardiovascular disease**
Lung cancer mortality drops by _21% w/in 5 years_
76
Even if you quit smoking, the excess risk of smoking persists...
For 30 years
77
How do tobacco agents cause disease?
irritate the tracheobronchial mucosa \> inflammation and mucus production (production)
smoke causes recrutiment of leuks to the lung \> increase elastase \> emphysema
78
Abestos workers and uranium miners are at higher risk for?
Tobacco used with alcohol increases the risk of?
Tobacco smoking with HTN and hypercholesterolemia increases the risk of?
lung cancer
laryngeal and oral cancers (multiplicative)
MI (multiplicative)
79
Cigarette smokers are at an increased risk of:
Emphysema
Bronchitis
ALL forms of cancer
COPD
MI
Atherosclerosis
80
Maternal smoking poses in increased risk of?
Spontaneous abortions
Preterm births
Intrauterine growth redardation
81
What risks does passive smoke expsoure have?
1.3x risk of lung cancer, increased risk of CAD, fatal MI and asthma in children
82
What are the 3 ways alcohol is metabolized to acetaldehyde?
After it gets converted to acetaldehyde, what happens?
Microsomes: by CYP2E1
Cytosol: Alcohol dehydrogenase/ADH
Peroxisomes: Catalse
-ALDH (acetaldehyde dehydrogenase) convert it to acetic acid
83
What happens when you consume high amoutns of alcohol?
competes with CYP2E1 substrates and delays catabolism of the drugs = potentiate the depressant effect of drugs
84
Why do alcoholics get fatty liver?
alcohol metabolism requires NAD+ \> NADH = NAD+ is depleted.
NAD+ is required for FA oxidation so FA accumulates in the liver
85
What conditions are characteristic of alcoholism?
steatosis, cirrhosis, alcoholic cerebellar degeneration, esophageal varices that could rupture and lead to death
86
What are the ACUTE adverse effects of EtOH?
- Steatosis (fatty liver)
- CNS effects (depressant)
gastritis
ulceration
\*reversible if etoh is stopped
87
What are the CHRONIC adverse effects of EtOH?
**Liver:** steatosis, alcoholic hepatitis, cirrhosis, portal hypertension, hepatocellular carcinoma
**Thiamine deficiency:** peripheral neuropathies, Wernicke-Korsakoff syndrome
**Fetal alcohol syndrome:** microcephaly, facial anomalies and growth anomalies
**Alcoholic cardioomyopathy**= dilated congestive cardiomyopathy
**Cancer:** especially breast, esophagus and laryngeal (due to acetaldehyde)
**Malnutrition** - VITAMIN B!!!
88
Child presents with microcephaly, epicanthal folds, flat face, low nasal bridge, smooth philtrum and underdeveloped jaw. What is the most likely dx?
Fetal alcohol syndrome
89
Thiamine deficiency secondary to alcohol use results in what neuro issues?
1. Wernicke encephalopathy: psychotic symptoms and opthalmoplegia (eye muscle paralysis), also hemorrhage and nerosis in the mammillary bodies
2. Untreated WE \>\>\> Korsakoff's: irreversible + confabulation
3. cerebellar dysfunction: ataxic gait nystagmus, atrophy of anterior vermis
90
Discoloration of the skin in this image is caused by?
Adverse drug reaction to **_Antibiotic = Minocycline_**
## Footnote
**_iron and melanin pigments seen under microscope_**
91
What are the pathological effects of these drugs?
Anticoagulants
Anabolic steroids
Bleeding (Warfarin inhibits Vit K and dabigatran inhibits thrombin)
gonadal changes, psych issues, increased risk of MI
92
What are the pathologic effects of oral contraceptives?
increased risk of cervical cancer, DVT and PE
2x increase in CAD in \<35 yo who smoke
hepatic adenoma - rare, benign (usually older patient with prolonged OC use)
93
What are you at an increased risk of aquiring with **acetaminophen?**
Liver failure
**Centrilobar necrosis**
94
How is APAP metabolized?
95% of the time: Phase II enzymes detoxify it \> urine excretion
5% of the time: CYP2E1 turns it to NAPQ = 2 outcomes:
1. ) conjugation with GSH (glutathione) = excretion
2. ) lipid peroxidation and protein adducts = liver failure and necrosis
95
What is a typical presentation of APAP overdose commonly seen in teens attempting suicide?
Initial effect: none
Some tme later: liver failure (reversed if treated at hospital, 30% mortality rate for those untreated)
96
What are you at increased risk of aquiring w/ **aspirin?**
salicylate poisoning of CNS (nausea, coma); chronic effects (salicylism (HA, dizz, tinnitus, bleeding,
Analgesic nephropathy
97
What are the profound risks with **opiate** intake?
Respiratory depression
Arrhythmia
Cardiac arrest
"Foamy mouth"
Pulmonary edema
Infections (endocarditis in R heart valves from bacterial penetration from injecting opiate)
98
What are the risks associated with methamphetamine use?
violent behavior, confusion, psychotic sx, hallucinations
99
What are the risks associated with Marijuana use?
increase HR, angina in pts with COD, cognitive and motor impairments, carcinogen exposure
100
What are the major complications associated with **cocaine** use?
Tachycardia
HTN
Peripheral vasoconstriction
101
What risks are associated with huffing/glue sniffing?
What are the risks associated with bath salts?
MRI brain damage ranging from mild - severe dementia
agitation, psychosis, MI and suicide
102
What are the cardiovascular, obstetrical and cerebral effects of cocaine?
CV: coronary artery vasoconstriction + platelet aggregation + thrombus = myocardial ischemia
legal arrythmias that can occur even in low doses
OB: decreased blood flow to placenta leading to fetal hypoxia & spontaneous abortion
Cerebral: hyperpyrexia and seizures
103
What is the rule of nines?
Percentage of body surface covered in burns
104
What factors contribute to the extent of burn damage?
How are burns usually managed?
depth of the burn, % of body surface burned, internal injuries (inhalation, heat that can "cook" organs)
Tx: fluid and electrolytes, infection control
105
Describe the differences b/w **burn classifications**
1st degree= superficial, only epidermis (red)
2nd degree = epidermis and dermis = blisters
3rd degree = full thickness, extend into the subq tissue , can not hurt due to nerve damage
106
What are the major complications associated with thermal injuries?
1. **Shock**: if burn \>20% of body surface, fluid shifts to interstitium leading to generalized and pulmonary edema
also hypermetabolic state from excess heat loss and need nutritional support
2. **Sepsis**: burns colonized by Pseudomonas aeruginosa, MRSA, candida
3. **Respiratory insufficiency**: noxious gas inhalation + heat affects airway within 24-48 hours
4. **Hypertrophic scars**: from excessive collagen deposition
107
What are some defining features of fire damage?
soot in airway + thermal injury of airway from heat
pugilistic stance of burnt body (muscle contractures due to heat), also firm internal organs from "cooking"
108
What is **malignant hyperthermia?**
"Heat-stroke-like" from lack of sweating
Rise in core body temp and muscle contractions
In response to **ANESTHETICS (if patient has RYR1 gene)**
109
What are the effects of hypothermia?
\<90F tempt, LOC, brady, Afib
110
How does electrical injury present?
a. burns
b. vfib or cardiorespiratory failure
c. lightning injury (presents with lichtenberg figures that are transient)
111
What is a curie?
What is a Gray?
What is a Sievert?
unit for radiation emitted
unit for energy absorbed
Eq dose = absorbed dose (gray) x biologic effectiveness of radiation
112
What are the end effects of ionizing radiation molecularly?
cell death, teratogenesis and carcinogenesis
113
What is the morphology of ionizing radiation damage?
swelling, giant cells with pleomorphic (\>1) nuclei,
enodthelial proliferation, hyalinazation and intimal thickening (leading to narrowing of vessel lumen), interstitial collagen (leading to scarring & contractions)
\*looks similar to malignant cells
114
What cancers are at risk of developing from radiation exposure?
What are "second cancers"?
leukemias, thyroid, breast, lung, also birth defects
OTHER cancers develop in indivuduals who received radiation therapy for an initial cancer (AML, myelodysplastic syndrome)
115
How is the brain affected by ionizing radiation?
Brain is affect at high doses and injured in less time compared to other tissues
116
What is primary and secondary dietary insufficiency?
Primary: missing from diet
Secondary: malabsorption, excess loss or increase need
117
What is protein energy malnutrition?
causes death in infants and nursing home patients
symptoms: SubQ fat depletion, wasting of quads and deltoids, ankle or sacral edema
- increased risk fo infection, sepsis, imparied wound healing and death after surgery in bedridden patients
118
Marasmus vs Kwashiorkor vs Cachexia
Marasmus: normal serum albumin, muscle proteins and fat used as fuel leading to really thin extremities
Kwashiokor: hypoabuminemia leading to edema, fatty liver, normal extremities
Cachexia: complication of AIDS or cancer, extreme weight loss and muscle wasting
119
What induces cachexia?
TNF and tumor binds to receptor on muscle cells, activates NF-KB
leads to ubiquitinylation and proteolysis of myofibrils
120
Anorexia nervosa vs. Bulimia
What are both diseases susceptible to?
Anorexia: self induced starvation, amenorrhea, decrease thyroid hormone, decrease bone density (eventual osteoporosis)
Bulimia: binge/purge, leading to hypokalemia \> arrythmia, pulmonary aspiration of gastric contents, esophageal and gastric rupture
arrythmia and death due to hypokalemia
121
What does obesity increase the risk of?
Type 2 DM, dyslipidemia, CVD, HTN, cancer
122
How do you measure risks from obesity?
BMI \>25 (overweight) and BMI \> 30 (obese)
Central obesity - trunk/abdominal accumulation of fat (higher risk for disease)
123
What are the consequences of obesity?
Metabolic syndrome
CAD
non-alcoholic fatty liver dz
cholelithiasis
osteoarthritis
124
What is hypoventilation/pickwickian syndrome?
hypersomnolence from increased intra-abdominal pressure when sleeping leading to sleep apnea, polycythemia and cor pulmonale (right sided heart failure)
125
How does obesity increase cancer risk?
insulin resistance = hyperinsulinemia leading to IGF-1 production, which is a mitogen
obesity = increase estrogen
proinflammatory state associated with obesity also carcinogenic
126
What cancers are these correlated to?
Aflatoxin
Nitrosamines and Nitrosamides
animal fat and low fiber
total dietary fat
hepatocellular carcinoma
gastric carcinoma
colon cancer
breast cancer
127
What are some examples of anticarcinogens?
Vit C, E, B-carotenes and selenium
