Overview of the Principlesof
Environmental Medicine Diagnosis and Treatment
Kalpana D. Patel, M.D. FAAP, FAAEM
DABP, DABEM
Environmental Health Center: Buffalo, NY
65 Wehrle Dr. Ph: 716 833-2213
Buffalo, NY 14225 Fax: 716 833-2244
The Basic Principles of Environmental MedicineTotal Body LoadHormesisHomeostasis Biochemical IndividualityAdaptationBipolaritySpreading PhenomenonSwitching PhenomenonDenervation Hypersensitivity
(Important to understand Dx, Rx & Prevention of C-S)
Total Body Burden
Pollutants
Total body load is the total of all pollutants in the air, food and water that the body incorporates
WaterAir
Food
Total Body Load
Quantitative aspect of the stimulus is far more important in triggering reactions than the quality
The Total Load Effectdepends upon
Your State
of health
Food
Chemicals
Inhalants
GeneticsInfections
Emotional
ElectromagneticNutrition
Total Load
Kinetics of pollutants –• Half life• Biotransformation• Toxicity• Virulence
Quantity of the LoadBody’s state of NutritionCapacity of the body’s holistic Makeup to deal with entering stimuli
Portal of Entry & Quantity of the dose are extremely important for Toxic Effects
Toxic Effects of Nonspecific& Specific Total Env. Load depends upon:
The Total Load Effect: * = Modifiable
Your State
of health
Food*
Chemicals *
Inhalants*
Genetics ?Infections*
Emotional*
Electromagnetic*Nutrition*
The Total Load Effect
The cumulative and combined effect of all the patient’s stressors.
That is,
It places a stress on dynamics of homeostasis, modify its function and prime the body for eventual dysfunction when patient exceeds its tolerance
Total Environmental Load
Adverse Effect of Increased Total Body Load
Disturbances in Metabolic changes and biological detoxification systems
Conjugation PathwayDepletion of nutrient Fuels
↑↑ Total Body Load tends to disturb many of the body’s homeostatic mechanisms
Cumulative Total Body Load of Pollutantsinvolve two types of exposure
1. Sudden massive exposure ex: Auto accident, acute pesticide or accidental toxic chemical exposure
2. Ongoing Low Level Toxic exposure to pollutants which built up gradually• Biologic Pollen, dust, dust mites, molds, • chemicals, etc.
• Auto exhaust• Refineries• Natural Gas• Pesticides• Formaldehydes• Chlorine
• Physical Pollutants
Increase in Total Body Load
More tissue damage – Intolerance to an equal amount of chemical
In other words, one becomes intolerant to the dose of chemicals that she was
able to tolerate before
Bioaccumulation of toxic substances in the food chain increase Total Body Load
Humans are at the end of the food chain
Acquire Higher Levels of Pollutants
Pollutants may have high dose inhibition and Low dose stimulation effect or vise-versa
Hormesis:
Homeostasis
AdaptationAcute Survival MechanismAllows an individual to “get use to” an acute toxic exposureBody adjusts to this exposure by adjusting to “New Set Point” with induction & up regulation of enzyme detoxification systemImmune System remains within physiologic range
Adaptation
Adaptation can occur in any or all organs following pollutant exposure
Pollutant load may increase in one or all organs
AdaptationMasking: State of Toxicological Tolerance
Rinkle demonstrated how masking occurs with cyclic food sensitivityRandolph demonstrated masking with chemical sensitivity
Cig Smoke Runny nose Lung Ca- C.O.P.D.- Lung Failure- CVS Disease
Pollutant Pulmonary Function 15 – 20% initiallyBut
By fourth day of exposure returns to Control LevelLoss of Cause & Effect Connection
AdaptationIt Consists of 3 Stages1. Alarm
Cause & Effect is PerceivedMild Stimulus – Pharmacological EffectStrong/Prolonged Pathological Response
Intervention ReversibleNo Intervention Masking (Stage 2)
AdaptationMasking – Toxicological tolerance
Phase I Phase of physiologic adjustment
by• Induction of the Immune
detoxification system• No depletion of Nutrient fuel
2.
Adaptation
Phase II – MaskingEarly MaladaptationDevelopment of Symptoms
metabolic changes outside physiologic parameters precede pathologic tissue changesDepletion of nutrient pool
Adaptation
Stage 3End Organ FailureThis is the phase where fixed named disease occurs
Adaptation - Challenge Tests
Remember - Challenge tests performed on a patient in an adapted state are frequently negative
Therefore deadaptation by reduction (avoidance of a suspected harmful substance 3-4 days) of total body load must take place before causal & effect relationships can be identified by a challenge
Bipolarity
Bipolarity response stimulation & withdrawal to pollutants may occur at any stage of adaptation process
It is a two part response of the:immune systemenzyme detoxmetabolic systems
when exposed to a toxic & nontoxic substance
Bipolarity
Pharmacologic PhaseStimulatory phase is dominantAcute – Limited Exposure Reversible
Pathological Phase:Withdrawal phase is dominantChronic Exposure ResponseIrreversible
It has two phases:
Bipolarity
• Stimulatory Response is Dominant• Upregulation of Enzyme detoxification
system• Upregulation of Immune Systems
Pharmacologic Phase–Stimulatory–Withdrawal Response
Stimulatory Response:
BipolarityWithdrawal Response
•Stimulus is removed acutely
•Slow turn off of Enzyme –detox system 3-4 days
•Slow turn off of Immune System 3-4
Sudden removal of incitants takes 3-4 days to turnoff Sxs
BipolarityPhase I: Pharmacological Response:Withdrawal Response: “Hang Over” Sunday AM after drinking on Sat. Night.
“Hang Over” on Saturday morning at home –withdrawal from the exposure to toxic substances at work place during work weekExperiences withdrawal headaches, muscle ache, shakiness & impaired ability to function through Sat & early Sunday. Sunday afternoon he feels better.
EHC-Buffalo
Bipolarity
As Toxic Pollutant overload is removed by up-regulated detoxification system
System Returns to Pre-Stimulatory level Monday AM Feels fit to work
(not totally well)
If this continues person develops end stage disease
EHC-Buffalo
Bipolarity Withdrawal Response (Cont)
Bipolarity Stimulatory – Withdrawal Response If continued leads to:
Addictive Phenomenon
Results
Pollutant Intake Total Body LoadEx: Coffee addiction & glue sniffing addiction.Withdrawal symptoms might consciously or unconsciously seek re-exposure in order to maintain stimulatory phase and feel “high”eventually it results in addiction
BipolarityPhase 2 Pathological Response
1 Stimulatory response is very transientStimulus is intactUpreg enzyme Induction - It results in:
Increase Energy ATPGlucose, Protein, Lipid, MetabolismAntipollutant Enzymes S.O.D., Catalase,
GPxUpreg. Immune System
BipolarityDepressive Response is Predominant
Stimulus is intact - continuos daily exposure to toxic sub total load
↓↓ Enzyme induction↓↓ Immune induction↓↓ of Nutrient Fuels
Over Period of Minutes, Months, Yrs. Defense breaks down from overuse
Tissue Destruction - Scar Formation
END STAGE DISEASE
Phase 2 Pathological Response:
Bipolarity
Phase II: Pathological Depressive Response Occurs only in Stage III of adaptation
Mal adaptation - End organ Failure
Spreading Phenomenon
Secondary Response to Pollutant ExposureInvolves either new incitant or new target organs
Spreading PhenomenonTotal Body Toxic Load exceeds, increased sensitivity to increasing numbers of incitants biological inhalants, toxic chemicals and food at increasingly smaller doses.
i.e. minute toxic exposure of any substance may be sufficient to trigger a response of one system or more than one system
Spreading Phenomenon
Asthma Triggered by
Food
Perfume Phenol
Formaldehyde
Person who developed asthma from TCE. Exposure initially when spreading phenomenon also experience tachycardia, cardiac arrhythmia, sinusitis from the solvent exposure
Exposure TCC and Other Incitants
Cardiac Arrhythmia
Asthma Sinusitis
Ex. Person may be initially damaged by acute exposure to solvents - Asthma
Spreading Phenomenon
Failure of detoxification mechanismOxidation - ReductionConjugation
Depletion of Nutrient fuels of Enzyme, Coenzyme
Nutrient FuelsAA, FA, Vit.Bs, Mg, Zn
Damaged Blood Brain Barrier Mucosal System Cell Membranes
Mechanism
Switch Phenomenon (Savage - 1800’s)
Change of Pollutant - Stimulated Response from One End-Organ to another
This occurs over a longer period of time or suddenly
• Mental Pts - when Mentally worse get better from asthma sinusitis
• Asthma Flare Up - Mentally Better
Switch Phenomenon
Transient Brain Dysfunction
Arthalgia - Diarrhea
Cardiac Arrhythmia
Target organ responses
Switch to many different organs during24hours
Switch PhenomenonIt Can Occur from
UnsuspectedUnrecognized
Pesticide Spray May CauseHeadache - NeurologistJt Pains - Rheumatologist gets symptomatic Rx
When Cause & Effect Connection is missedTotal Body Load remains elevated
) Exposure
Switch PhenomenonSwitch Phenomenon with cluster of symptoms signals a big problem
Pt needs an astute physician cognizant of this phenomenon during initial evaluation to identify cause & effect connection who helps to curtail a life long progression of illness
Biochemical Individuality
Focus on variability of molecular biology in HumansThis Model believed that many diseasesresult from disordered body chemistry either genetic or acquiredCorrection of these imbalances is essential to achieve individual optimal health
First described by Roger Williams
Biochemical IndividualityIndividual’s ability to defendhimself against the effects ofpollutant exposure is determined by his total load and nutritional state at the time of exposureDaily fluctuations of these factors in opposite direction makes him susceptible to chemicals
Immune, Detox Enzyme Parameters
Intensity of reaction to toxic exposures
Susceptibility to chemical exposures
Variation in these parameters determine an individual’s ability to process the noxious substance he encounters:
There is a variation in the:
Example: Group of individuals exposed to same pollutant:
One develops Arthritis One SinusitisOne diarrhea
One Cystitis One AsthmaOne Unaffected
Biochemical Individuality
Toxic Chemicals may cause depletion of:
Biochemical Individuality
♦ Vitamins
♦ Minerals
♦ Amino Acids
♦ Lipids
Enzyme Defect
Results In
Nutritional Depleted Individual(Non genetically regulated)
↑↑ Total Toxic Load
Biochemical Individuality response of each individual is dependent on three factors:
Genetic SusceptibilityState of a fetus’ nutritional healthToxic body burden during gestation
Biochemical Individuality
Genetic Susceptibility Plays a great role in predisposing an individual to disease
Genetic defect of some type is found virtually in every person There are > 2000 metabolic defects described in the literature. Appears to be a “time bomb”awaiting to explodeIn absence of certain genes body is not able to respond appropriately to pollutant exposure & defend it from their effects. It results in stress on homeodynamics and eventually dysfunction if It continues in excess
Biochemical Individuality
Genetic expression guides the general response
But
Env pollutants trigger env.receptor system
&Homeodynamic response of the matrix.
Thus Environmental load influences the GRS genetic expression
Biochemical Individuality
State of Nutrition and Total Toxic Load exposure in Utero plays a great role in augmenting
Acquired non genetic susceptibility from Environmental Toxic Exposures cause damage to:
SpermOvumFetuses
Non Genetic Susceptibility
Bio concentration of toxic chemicals in newborns may accompany or result in Enzyme defect, nutritional depletion Fetus’s inability to clear pollutants
effectively results in ↑↑Total body toxic load and potential for damage to developing cells and organsNewborns may have malfunctioning immune and enzyme detox system & ↑↑ Total body load↑↑ susceptibility to infection & inability to eat/failure to thrive
Non Genetic Susceptibility
Env. Total Toxic Load - Body
the total number of pollutants an individual absorbs from
The air he breathesThe food he eatsThe water he drinks & cleans with
Dietary Habits - Nutritional State
Individual’s total toxic load varies daily depending on:
Law Of Nerve DamageDennervation Super sensitivity
THE COMPLETE OR PARTIAL DAMAGE OF A NERVE RESULTS IN AN INCREASED SENSITIVITYTO THE REMAINDER OF THE NERVE OR ORGAN AS SENSITIVE AS TO THE SENSORY/MOTOR END PLATE ex,RSD
Dennervationsupersensitivity
Altered function in peripheral nerve without altered structure
In other words in Neuropathic pain there is only Functional Disturbance without Pathological changes & tissue damage
There is loss of electrical charge in endothelium, becomes sensitive to innocent substances like histamine results in leakage of fluid -> trophic edema
Blood vessel contracts->VasospasmMuscle contracts->shortened muscle
sometimes pain is so severe in absence of any pathology it is mistaken as pschosomatic.
Dennervation HypersensitivityThis occurs when nerves malfunction following:
minor irritation from sequestration of chemicalsspondylosis (degeneration of spine which can be the result of normal wear & tear)
Nerves & Nerve endings become extremely sensitive to innocent harmless substances, chemical substancesex. Hist/sero, A. choline, epi, Norepi & biological
inhalants, foods, ambient doses of chemicals Cause signals which are exaggerated and misperceived as harmful. This results in hypersensitivity/supersensitivity