Environmental disease Flashcards
environmental risks to health
All the external physical, chemical, biological, and work related factors that affect a person’s health, excluding factors in the environment that cannot reasonably be modified
Heavy metals
-They are naturally occuring elements that have a high atomic weight and a density at least 5 times greater than that of water
toxicity of heavy metal factors
depends on:
1. Route of exposure
2. Form of elements, i.e. chemical species (e.g. oxidation state, inorganic vs organic)
3. Individual factors, i.e. nutritional status
Trace elements
-Include heavy metals such as copper, chromium, maganese, nickel, cobalt, iron, and molybdenum
-Required for key enzymes and other physiological functions however have no biological functions and act as systemic toxicants (affect many organs)
Common states of arsenic
As(o)
AS(III)
AS(V)
arsine gas
The organic form occur through biotransformation while environmental pollution occurs through volcanic eruptions, soil erosions and human activity
Chronic arsenic exposure location
27 million individuals in Bangladesh and India
-Have aresenic levels in water >50 when WHO reccomends <10ppb
Historic use of arsenic
-Treat diseases caused by protoza (amoebic dysentery) and syphilis
-Paul Ehrlich and Sahachiro Hata developed Salvarsan in early 1900s for syphilis
-arsenic trioxide is used to treat promyelocytic leukaemia
General effects of arsenic
-it virtually effects all organ systems including the cardiovascular, dermatologic, nervous, hepatobilliary, renal, gastro-intestinal and respiratory systems
-High concentrations of arsenic in drinking water causes clinciopathological conditions including cardiovascular and peripheral vascular disease, developmental anomalies, neurologic and neurobehavioural disorders, diabetes and cancers of the bladder, kidney, skin and liver
Arsenate (pentavalent)
it may replace phosphate in several reactions
-Arsenate has similar structure and properties to phosphate
-In vitro studies show aresente reacts with glucose to form glucose-6-arsenate which inhibits hexokinase which is NB in glycolysis
Arsenite ( Trivalent arsenic)
-Most toxic form compared to arsenate
-Arsenite reacts with thiol and sulfhydryl groups which are major components of multiple proteins and enzymes and therefore cause the dysregulation and inhibition of the proteins and enzymes
-One crucial enzyme affected is pyruvate dehydrogenase which requires lipoic acid dithiol for activation. It is vital in the citric acid cycle and alteration can cause impairment of respiration and ATP formation
Genotoxicity of arsenic
-It inhbits DNA repair, induces chromosomal abberrations, sister chromatid exchanges and micronuclei formation but is not directl mutagenic
-Indirect effect through reactive oxygen species formation which occurs due to antioxidants such as glutathione are sequestered by metal
arsenic-induced carcinogenesis
-Intefere with cell signaling pathways
-induce DNA hypomethylation which causes abberrant gene expression
-inhbits p53 signaling
Lead
Bluish grey metal in earth crust
-it is used in industrial, agriculutral and domestic applications such as batteries and ammunitions
Mechanisms of lead
-Like arsenic, it has a strong affinity for sulfhydryl groups (thiol groups) and electron donor groups that it ends up affecting a wide range of proteins
-Because of its similarity to other divalent cations like Ca and Zn, it interferes with a vast array of cell mechanisms that are regulated and mediated by these cations in virtually every organ system
lead exposure
Lead is not biodegradeble and exhibits environmental persistance
-lead paint was used in households
-Additive for petrol but now discontinued but is still found in soil
–found in tap water due to old pipes
neurological effects of lead
-it undermines normal synaptic processes in developing brains which leads to cognitive and behaviour
-chronic exposure leads to diminished intelligence, lower IQ, impaired neurobehavioural development, speech and language handicaps, growth retaration and anti social behaviour
-In adults, lead leads to peripheral neuropathy, reproductive effects, decreased sperm count and spontaneous abortions, kidney damage, gastrointestinal disease, blood pressure and vitamin D metabolism
Abestos consists of
-made of 6 types of natural fibrous minerals:
chrysolite
amosite
crocidolite
actinolite
tremolite
anthophyllite
Asbestos use
used for thermal and electrical insulating properties and fireproof building material
asbestos effect
-Ab fibres are released into air when ab undergoes damage or deterioration
-inhalation of fibres can cause serious health problems such as mesothelioma and lung cancer
Asbestos in SA
-AB mining was mainly in Limpopo, Northern Cape and Mpumalanga
-71 mines employed 20,000 workers in 1960
-Many communities in prevously mined areas are still at risk
-Mesothelioma in SA is among highest in world
-Christopher Wagner showed a link between asbestos and cancer in 1960
Uncertainty about Ab
-not clear why Ab enetering alveoli during respiration exerts toxicity in pleura
-Not understood how Ab causes mesothelioma since mesothial cells are killed upon Ab exposure
Mechanical interference mechanism
-Previous model that predicted that phagocytosed asbestos fibres mechanically interact with mitotic spindle and cause chromosomal changes leading to carcinogenesis
-However, mesothelial cells were killed 2-10 days of asbestos exposure
Frustrated phagocytosis and continuous inflammation hypothesis
-explains mesothelial transformation
-Alveolar macrophages phagocytose particles such as dust and micro organisms to remove them from alveoli
-Macrophages can encapsulate short fibres less than 5um in lenght
-Longer fibres are imperfectly phagocytosed which results in frustrated phagocytosis where the fibres activate inflammasome and trigger production of inflammatory cytokines
-chronic inflammation has a pleitropic (tumor promoting ) effect which results in malignant transformation
