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