Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease...

Disease, and Other Clinical Natural Kinds

Barry Smith

Gradualist Approaches to Health and DiseaseBerlin, March 23, 2012

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Natural Kind

2/

Synonyms: universal, type

= entities of the sorts which are referred to by general terms of natural science

Instances, particulars, individuals

= entities of the sorts which can be observed in experiments of natural science

Old biology data

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MKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDV

New biology data

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How to do biology across the genome?MKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVMKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVMKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVMKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDV

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how to link the kinds of phenomena represented here

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or here

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or here

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MKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPIPSKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESATSELMANHSVQTGRNIYGVDSFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVVAGEAASSNHHQKISRVTRKRPREPKSTNDILVAGQKLFGSSFEFRDLHQLRLCYEIYMADTPSVAVQAPPGYGKTELFHLPLIALASKGDVEYVSFLFVPYTVLLANCMIRLGRRGCLNVAPVRNFIEEGYDGVTDLYVGIYDDLASTNFTDRIAAWENIVECTFRTNNVKLGYLIVDEFHNFETEVYRQSQFGGITNLDFDAFEKAIFLSGTAPEAVADAALQRIGLTGLAKKSMDINELKRSEDLSRGLSSYPTRMFNLIKEKSEVPLGHVHKIRKKVESQPEEALKLLLALFESEPESKAIVVASTTNEVEELACSWRKYFRVVWIHGKLGAAEKVSRTKEFVTDGSMQVLIGTKLVTEGIDIKQLMMVIMLDNRLNIIELIQGVGRLRDGGLCYLLSRKNSWAARNRKGELPPKEGCITEQVREFYGLESKKGKKGQHVGCCGSRTDLSADTVELIERMDRLAEKQATASMSIVALPSSFQESNSSDRYRKYCSSDEDSNTCIHGSANASTNASTNAITTASTNVRTNATTNASTNATTNASTNASTNATTNASTNATTNSSTNATTTASTNVRTSATTTASINVRTSATTTESTNSSTNATTTESTNSSTNATTTESTNSNTSATTTASINVRTSATTTESTNSSTSATTTASINVRTSATTTKSINSSTNATTTESTNSNTNATTTESTNSSTNATTTESTNSSTNATTTESTNSNTSAATTESTNSNTSATTTESTNASAKEDANKDGNAEDNRFHPVTDINKESYKRKGSQMVLLERKKLKAQFPNTSENMNVLQFLGFRSDEIKHLFLYGIDIYFCPEGVFTQYGLCKGCQKMFELCVCWAGQKVSYRRIAWEALAVERMLRNDEEYKEYLEDIEPYHGDPVGYLKYFSVKRREIYSQIQRNYAWYLAITRRRETISVLDSTRGKQGSQVFRMSGRQIKELYFKVWSNLRESKTEVLQYFLNWDEKKCQEEWEAKDDTVVVEALEKGGVFQRLRSMTSAGLQGPQYVKLQFSRHHRQLRSRYELSLGMHLRDQIALGVTPSKVPHWTAFLSMLIGLFYNKTFRQKLEYLLEQISEVWLLPHWLDLANVEVLAADDTRVPLYMLMVAVHKELDSDDVPDGRFDILLCRDSSREVGELIGLFYNKTFRQKLEYLLEQISEVWLLPHWLDLANVEVLAADDTRVPLYMLMVAVHKELDSDDVPDGRFDILLCRDSSREVGELIGLFYNKTFRQKLEYLLEQISEVWLLPHWLDLANVEVLAADDTRVPLYMLMVAVHKELDSDDVPDGRFDILLCRDSSREVGE

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to this?

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or this?

answer: through annotation of data with terms from a controlled vocabulary or ‘ontology’

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sphingolipid transporter activity

Holliday junction helicase complex

this allows integration of databases

MouseEcotope GlyProt

DiabetInGene

GluChem

Holliday junction helicase complex

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and supports logical reasoning over data

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‘Ontology’ in PubMed

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GO, in particular, is tremendously successful

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$100 million invested in literature and data curation using GO

over 11 million annotations relating gene products described in the UniProt, Ensembl and other databases to GO termsexperimental results reported in 52,000 scientific journal articles manually annoted by expert biologists using GO

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1. rooted in basic experimental biology

2. links people to data and to literature

3. links data to data

• across species (human, mouse, yeast, fly ...)

• across granularities (molecule, cell, organ, organism, population)

4. links medicine to biological science

5. promotes cumulation of scientific knowledge in algorithmically tractable form

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Benefits of the GO

National Center for Biomedical Ontology (NIH Roadmap Center)

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− Stanford Biomedical Informatics Research− The Mayo Clinic− University at Buffalo Department of

Philosophy

http://bioportal.bioontology.org

http://bioportal.bioontology.org/

GO supports only three types of annotation

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what cellular component?

what molecular function?

what biological process?

no diseases in GO

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RELATION TO TIME

GRANULARITY

CONTINUANT OCCURRENT

INDEPENDENT DEPENDENT

ORGAN ANDORGANISM

Organism(NCBI

Taxonomy)

Anatomical Entity(FMA, CARO)

OrganFunction

(FMP, CPRO) Phenotypic

Quality(PaTO)

Biological Process

(GO)CELL AND CELLULAR

COMPONENT

Cell(CL)

Cellular Compone

nt(FMA, GO)

Cellular Function

(GO)

MOLECULEMolecule

(ChEBI, SO,RnaO, PrO)

Molecular Function(GO)

Molecular Process

(GO)

OBO Foundry (first version, 2006)Yellow = Gene Ontology

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http://obofoundry.org

http://obofoundry.org/

Current OBO Foundry Ontologies

• Biological process (GO)• Cellular component (GO)• Chemical entities of biological interest• Molecular function (GO)• Phenotypic quality• PRotein Ontology (PRO)• Xenopus Anatomy and Development• Zebrafish Anatomy and Development

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Foundry ontologies under review

Cell Ontology (CL)Foundational Model of Anatomy (FMA)Infectious Disease Ontology (IDO)

Staph. aureus Ontology (IDO Sa)

Malaria Ontology (IDO MAL)

Influenza Ontology (IDO Flu)

HIV Ontology (IDO HIV)

Ontology for Biomedical Investigations (OBI)Ontology for General Medical Sciences (OGMS)Plant Ontology (PO)

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Ontologies under construction

Allergy OntologyEnvironment Ontology (EnvO) Immunology Ontology (IDO)Mental Functioning Ontology (MFO)

Emotion Ontology (MFO-EM)Pain Ontology

Mental Disease Ontology (MDO)Neurological Disease Ontology (ND)Vaccine Ontology (VO)

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FMA has 83281 types and 3 million relations representing canonical adult human anatomy= the anatomy generated by the coordinated expression of the organism’s own structural genes.

Canonical ≠ statistically normal

32 teethtwo arms two legs

one nosetwo nostrilstwo kidneys, …

Foundational Model of Anatomy Ontology

Foundational Model of Anatomy (FMA)

Pleural Cavity

Pleural Cavity

Interlobar recess

Interlobar recess

Mesothelium of Pleura

Mesothelium of Pleura

Pleura(Wall of Sac)

Pleura(Wall of Sac)

VisceralPleura

VisceralPleura

Pleural SacPleural Sac

Parietal Pleura

Parietal Pleura

Anatomical SpaceAnatomical Space

OrganCavityOrganCavity

Serous SacCavity

Serous SacCavity

AnatomicalStructure

AnatomicalStructure

OrganOrgan

Serous SacSerous Sac

MediastinalPleura

MediastinalPleura

TissueTissue

Organ PartOrgan Part

Organ Subdivision

Organ Subdivision

Organ Component

Organ Component

Organ CavitySubdivision

Organ CavitySubdivision

Serous SacCavity

Subdivision

Serous SacCavity

Subdivision

part

_of

is_a

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An ontology

is a controlled structured vocabulary

that includes a backbone taxonomy (nodes connected by the is_a [subtype] relation)

together with further logically defined relations such as part_of, regulated_by

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Basic Formal Ontology (BFO)

A simple top-level ontology to support information integration in scientific research

Serves as starting point for OBO Foundry ontologies

Domain ontologies built by downward population

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Basic Formal Ontology

http://www.ifomis.org/bfo/

Continuant Occurrent

IndependentContinuant

DependentContinuant

Organism

Life

Temperature

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http://www.ifomis.org/bfo/

Example: The Cell Ontology

Continuant


DependentContinuant

..... .....

Non-realizableDependentContinuant(quality)

Realizable DependentContinuant(function, role, disposition)

TYPES

INSTANCES

depends_on

Continuant


thing

DependentContinuant

quality

.... .....

example: temperature dependson bearer

TYPES

INSTANCES

DependentContinuant

QualityRealizable Dependent

Continuant

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Disposition Function Role

of banana, to ripen

of heart, to pump blood

of employee, to work for pay

process of realization depends_on realizable

Continuant Occurrent


bearer

Realizable DependentContinuant

disposition

.... ..... .......47

Process of realization

Four distinct classificatory tasks

1. of people (patients, carriers, …)

2. of diseases (cases, instances, problems, …)

3. of courses of disease (symptoms, treatments…)

4. of representations (records, observations, data, diagnoses…)

ICD confuses 1. & 2.

Most standard terminologies confuse 2. and 4

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Four distinct BFO categories

1. person (patient, carrier, …) – independent continuant

2. disease (case, instance, problem, …) – specifically dependent continuant

3. course of disease (symptom, treatment…)– occurrent

4. representation (record, datum, diagnosis…)– generically dependent continuant

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Four distinct BFO categories

1. people (patients, carriers, …) – independent continuants

2. disease (case, instance, problem, condition …) – disposition

3. course of disease (symptom, episode, outbreak …)– realization of dispositions

4. representations (records, data, diagnoses…)– generically dependent continuants

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Big Picture (Ontology for General Medical Science)

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Elucidation of Primitive Terms

‘extended organism’ = the organism and all the material entities located within it

‘bodily feature’ = either a physical part of the extended organism, a bodily quality, or a bodily process.

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Elucidation of Primitive Terms

clinically abnormal - some bodily feature that (1) is not part of the life plan for an organism of the

relevant type (unlike loss of milk teeth, aging or pregnancy),

(2) is causally linked to an elevated risk either of pain or other feelings of illness, or of death or dysfunction, and

(3) is such that the elevated risk exceeds a certain threshold level.*

*Compare: baldness

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DisorderA material entity (fiat object part) which is clinically abnormal and part of an extended organism

Compare:

Downtown Santa Barbara

Mount Everest

Peter Hucklenbroich’s pate

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Definitions - Foundational Terms

Pathological Process =def. – A bodily process that is clinically abnormal.

Disease =def. – A disposition (i) to undergo pathological processes that (ii) exists in an organism because of one or more disorders in that organism.

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61http://code.google.com/p/ogms/

http://code.google.com/p/ogms/

Big Picture (Ontology for General Medical Science)

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63http://code.google.com/p/ogms/

http://code.google.com/p/ogms/

Disease Course=Def. The sum of processes through which a given disease instance is realized.

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independentcontinuant

dependentcontinuant

disposition

diseaseorganism

John John’s disease

occurrent

process

course of disease

course of John’s disease

TY

PES

INS

TA

NC

ES

coronary heart disease

John’s coronary heart disease

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CHD in phase of asymptomatic

(‘silent’) infarction

CHD in phase of early lesions

and small fibrous plaques

stable angina

CHD in phase of surface

disruption of plaque

unstable angina

instantiates at t1

instantiates at t2

instantiates at t3

instantiates at t4

instantiates at t5

in nature, no sharp boundaries here

human

John

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embryo fetus adultneonate infant child

instantiates at t1

instantiates at t2

instantiates at t3

instantiates at t4

instantiates at t5

instantiates at t6


A disease is a disposition

etiological process

produces

disorder

bears

disposition

realized_in

pathological process

produces

abnormal bodily features

recognized_as

signs & symptomsinterpretive process

produces

diagnosis

used_in71

Cirrhosis - environmental exposure Etiological process - phenobarbitol-

induced hepatic cell death produces

Disorder - necrotic liver bears

Disposition (disease) - cirrhosis realized_in

Pathological process - abnormal tissue repair with cell proliferation and fibrosis that exceed a certain threshold; hypoxia-induced cell death produces

Abnormal bodily features recognized_as

Symptoms - fatigue, anorexia Signs - jaundice, splenomegaly

Symptoms & Signs used_in

Interpretive process produces

Hypothesis - rule out cirrhosis suggests

Laboratory tests produces

Test results - elevated liver enzymes in serum used_in


Result - diagnosis that patient X has a disorder that bears the disease cirrhosis

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Influenza - infectious Etiological process - infection of

airway epithelial cells with influenza virus produces

Disorder - viable cells with influenza virus bears

Disposition (disease) - flu realized_in

Pathological process - acute inflammation produces


Symptoms - weakness, dizziness Signs - fever



Hypothesis - rule out influenza suggests


Test results - elevated serum antibody titers used_in


Result - diagnosis that patient X has a disorder that bears the disease flu

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Huntington’s Disease - genetic Etiological process - inheritance of

>39 CAG repeats in the HTT gene produces

Disorder - chromosome 4 with abnormal mHTT bears

Disposition (disease) - Huntington’s disease realized_in

Pathological process - accumulation of mHTT protein fragments, abnormal transcription regulation, neuronal cell death in striatum produces


Symptoms - anxiety, depression Signs - difficulties in speaking and

swallowing



Hypothesis - rule out Huntington’s suggests


Test results - molecular detection of the HTT gene with >39CAG repeats used_in


Result - diagnosis that patient X has a disorder that bears the disease Huntington’s disease

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Dispositions and Predispositions

Some dispositions are predispositions to other dispositions.

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HNPCC - genetic pre-disposition

Etiological process - inheritance of a mutant mismatch repair gene produces

Disorder - chromosome 3 with abnormal hMLH1 bears

Disposition (disease) - Lynch syndrome realized_in

Pathological process - abnormal repair of DNA mismatches produces

Disorder - mutations in proto-oncogenes and tumor suppressor genes with microsatellite repeats (e.g. TGF-beta R2) bears

Disposition (disease) - non-polyposis colon cancer realized in

Symptoms (including pain)

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Arterial AneurysmDisposition – atherosclerosis

realized inPathological process – fatty material collects within the walls of arteries

producesDisorder – artery with weakened wall

bearsDisposition – of artery to become distended

realized_inPathological process – process of distending

producesDisorder – arterial aneurysm

bearsDisposition – of artery to rupture

realized inPathological process – (catastrophic event) of rupturing

producesDisorder – ruptured artery, arterial system with dangerously low blood pressure

bearsDisposition – circulatory failure

realized inPathological process – exsanguination, failure of homeostasis

producesDeath

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Systemic arterial hypertension Etiological process – abnormal

reabsorption of NaCl by the kidney produces

Disorder – abnormally large scattered molecular aggregate of salt in the blood bears

Disposition (disease) - hypertension realized_in

Pathological process – exertion of abnormal pressure against arterial wall produces


Symptoms - Signs – elevated blood pressure



Hypothesis - rule out hypertension suggests


Test results - used_in


Result - diagnosis that patient X has a disorder that bears the disease hypertension

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Type 2 Diabetes Mellitus Etiological process –

produces Disorder – abnormal pancreatic beta

cells and abnormal muscle/fat cells bears

Disposition (disease) – diabetes mellitus realized_in

Pathological processes – diminished insulin production , diminished muscle/fat uptake of glucose produces


Symptoms – polydipsia, polyuria, polyphagia, blurred vision

Signs – elevated blood glucose and hemoglobin A1c



Hypothesis - rule out diabetes mellitus suggests

Laboratory tests – fasting serum blood glucose, oral glucose challenge test, and/or blood hemoglobin A1c produces

Test results - used_in


Result - diagnosis that patient X has a disorder that bears the disease type 2 diabetes mellitus

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Type 1 hypersensitivity to penicillin Etiological process – sensitizing of mast

cells and basophils during exposure to penicillin-class substance produces

Disorder – mast cells and basophils with epitope-specific IgE bound to Fc epsilon receptor I bears

Disposition (disease) – type I hypersensitivity realized_in

Pathological process – type I hypersensitivity reaction produces


Symptoms – pruritis, shortness of breath Signs – rash, urticaria, anaphylaxis



Hypothesis - suggests

Laboratory tests – produces

Test results – occasionally, skin testing used_in


Result - diagnosis that patient X has a disorder that bears the disease type 1 hypersensitivity to penicillin

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Early Onset Alzheimer’s Disease

Disorder – mutations in APP, PSEN1 and PSEN2bears

Disposition – impaired APP processingrealized in

Pathological process – accumulation of intra- and extracellular protein in the brainproduces

Disorder – amyloid plaque and neurofibrillary tanglesbearsDisposition – of neurons to dierealized in Pathological process – neuronal loss

producesDisorder – cognitive brain regions damaged and reduced in size

bearsDisposition (disease) – Alzheimer’s dementia

realized inSymptoms – episodic memory loss and other cognitive domain impairment

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Arterial Aneurysm• Disposition – atherosclerosis

– realized in• Pathological process – fatty material collects within the walls of arteries

– produces• Disorder – artery with weakened wall

– bears• Disposition – of artery to become distended

– realized_in• Pathological process – process of distending

– produces• Disorder – arterial aneurysm

– bears• Disposition – of artery to rupture

– realized in• Pathological process – (catastrophic event) of rupturing

– produces• Disorder – ruptured artery, arterial system with dangerously low blood pressure

– bears• Disposition – circulatory failure

– realized in• Pathological process – exsanguination, failure of homeostasis

– produces• Death

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Hemorrhagic stroke• Disorder – cerebral arterial aneurysm

– bears• Disposition – of weakened artery to rupture

– realized in• Pathological process – rupturing of weakened blood vessel

– produces• Disorder – Intraparenchymal cerebral hemorrhage

– bears• Disposition (disease) – to increased intra-cranial pressure

– realized in• Pathological process – increasing intra-cranial pressure, compression of brain

structures– produces

• Disorder – Cerebral ischemia, Cerebral neuronal death– bears

• Disposition (disease) – stroke– realized in

• Symptoms – weakness/paralysis, loss of sensation, etc

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Only something like the disposition theory enables us to explain why a fracture is not a disease

PETER HUCKLENBROICH−Radius fracture loco classico “ is a disease”

Advantages of the Disposition Theory

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PETER HUCKLENBROICH

A disease entity is a set of possible alternative courses

x has disease entity D ≡ (x has course D1) or (x has course D2) or … or (x has course Dn)

Only something like the disposition theory can allow us to determine what does and what does not belong to this list.

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Think of all the different temporal extents of the disease courses association with any given disease

• for those who die in an accident 5 seconds after catching the disease

• for those who have no treatment

• for those who have truly excellent treatment

• …

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Think of all the different combination cases:

of diseases with other diseases of diseases with complicationsof diseases at different stages of lifeof diseases with different environments

in igloosin Ost-Thüringenin sub-Saharan Africain space-ships…

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Think of all the different types of patient:

smokernon-smokerbanana-leaf-smokerAm-Sonntag-bei-Mutti-EsserAspirin-vor-dem-Schlafen-Gehen-NehmerAuf-dem-Schiessplatz-Ohrstöpsel-TrägerAuf-Weihnachtsmarkt-Lebkuchenherz-KäuferAuto-in-Waschstrasse-Abschliesser

human

John

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embryo fetus adultneonate infant child

instantiates at t1

instantiates at t2

instantiates at t3

instantiates at t4

instantiates at t5

instantiates at t6


portion of water

this portion of H20

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portion of ice

portion of liquid water

portion of gas

instantiates at t1

instantiates at t2

instantiates at t3

Phrase transitions

temperature

John’s temperature

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37ºC 37.1ºC 37.5ºC37.2ºC 37.3ºC 37.4ºC

instantiates at t1

instantiates at t2

instantiates at t3

instantiates at t4

instantiates at t5

instantiates at t6



Disease, and Other Clinical Natural Kinds Barry Smith Gradualist Approaches to Health and Disease...

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