Transcript Disease, and Other Clinical - Buffalo Ontology Site

Disease, and Other Clinical
Natural Kinds
Barry Smith
Gradualist Approaches to Health and Disease
Berlin, March 23, 2012
1
Natural Kind
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
2/
Old biology data
3/
New biology data
MKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSF
YEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVMVGKNVKKFLTFV
EDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLF
YLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIV
RSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDT
ERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNF
GAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRL
RKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVA
QETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTD
YNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFN
HDPWMDVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYAT
FRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYES
ATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQ
WLGLESDYHCSFSSTRNAEDVDISRIVLYSYMFLNTAKGCLVEYA
TFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYE
4
SATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWI
How to do biology across the genome?
MKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVIS
VMVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLER
CHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERL
KRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVC
KLRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGIS
LLAFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWM
DVVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSR
FETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVM
KVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISV
MVGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERC
HEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLK
RDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCK
LRSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLL
AFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMD
VVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRF
ETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVMK
VSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVM
VGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCH
EIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKR
DLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNFGAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKL
RSPNTPRRLRKTLDAVKALLVSSCACTARDLDIFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLL
AFAGPQRNVYVDDTTRRIQLYTDYNKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMD
VVGFEDPNQVTNRDISRIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRF
ETDLYESATSELMANHSVQTGRNIYGVDFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVMK
VSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRKRSFEKVVISVM
VGKNVKKFLTFVEDEPDFQGGPISKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSLFYLNRGYYNELSFRVLERCH5
EIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLLHVDELSIFSAYQASLPGEKKVDTERLKR
how to link the kinds of
phenomena represented here
6/
or here
7
or here
8
MKVSDRRKFEKANFDEFESALNNKNDLVHCPSITLFESIPTEVRSFYEDEKSGLIKVVKFRTGAMDRK
RSFEKVVISVMVGKNVKKFLTFVEDEPDFQGGPIPSKYLIPKKINLMVYTLFQVHTLKFNRKDYDTLSL
FYLNRGYYNELSFRVLERCHEIASARPNDSSTMRTFTDFVSGAPIVRSLQKSTIRKYGYNLAPYMFLLL
HVDELSIFSAYQASLPGEKKVDTERLKRDLCPRKPIEIKYFSQICNDMMNKKDRLGDILHIILRACALNF
GAGPRGGAGDEEDRSITNEEPIIPSVDEHGLKVCKLRSPNTPRRLRKTLDAVKALLVSSCACTARDLD
IFDDNNGVAMWKWIKILYHEVAQETTLKDSYRITLVPSSDGISLLAFAGPQRNVYVDDTTRRIQLYTDY
NKNGSSEPRLKTLDGLTSDYVFYFVTVLRQMQICALGNSYDAFNHDPWMDVVGFEDPNQVTNRDIS
RIVLYSYMFLNTAKGCLVEYATFRQYMRELPKNAPQKLNFREMRQGLIALGRHCVGSRFETDLYESA
TSELMANHSVQTGRNIYGVDSFSLTSVSGTTATLLQERASERWIQWLGLESDYHCSFSSTRNAEDVV
AGEAASSNHHQKISRVTRKRPREPKSTNDILVAGQKLFGSSFEFRDLHQLRLCYEIYMADTPSVAVQA
PPGYGKTELFHLPLIALASKGDVEYVSFLFVPYTVLLANCMIRLGRRGCLNVAPVRNFIEEGYDGVTDL
YVGIYDDLASTNFTDRIAAWENIVECTFRTNNVKLGYLIVDEFHNFETEVYRQSQFGGITNLDFDAFEK
AIFLSGTAPEAVADAALQRIGLTGLAKKSMDINELKRSEDLSRGLSSYPTRMFNLIKEKSEVPLGHVHKI
RKKVESQPEEALKLLLALFESEPESKAIVVASTTNEVEELACSWRKYFRVVWIHGKLGAAEKVSRTKE
FVTDGSMQVLIGTKLVTEGIDIKQLMMVIMLDNRLNIIELIQGVGRLRDGGLCYLLSRKNSWAARNRKG
ELPPKEGCITEQVREFYGLESKKGKKGQHVGCCGSRTDLSADTVELIERMDRLAEKQATASMSIVAL
PSSFQESNSSDRYRKYCSSDEDSNTCIHGSANASTNASTNAITTASTNVRTNATTNASTNATTNASTN
ASTNATTNASTNATTNSSTNATTTASTNVRTSATTTASINVRTSATTTESTNSSTNATTTESTNSSTNA
TTTESTNSNTSATTTASINVRTSATTTESTNSSTSATTTASINVRTSATTTKSINSSTNATTTESTNSNT
NATTTESTNSSTNATTTESTNSSTNATTTESTNSNTSAATTESTNSNTSATTTESTNASAKEDANKDG
NAEDNRFHPVTDINKESYKRKGSQMVLLERKKLKAQFPNTSENMNVLQFLGFRSDEIKHLFLYGIDIYF
CPEGVFTQYGLCKGCQKMFELCVCWAGQKVSYRRIAWEALAVERMLRNDEEYKEYLEDIEPYHGDP
VGYLKYFSVKRREIYSQIQRNYAWYLAITRRRETISVLDSTRGKQGSQVFRMSGRQIKELYFKVWSNL
RESKTEVLQYFLNWDEKKCQEEWEAKDDTVVVEALEKGGVFQRLRSMTSAGLQGPQYVKLQFSRH
HRQLRSRYELSLGMHLRDQIALGVTPSKVPHWTAFLSMLIGLFYNKTFRQKLEYLLEQISEVWLLPHW
LDLANVEVLAADDTRVPLYMLMVAVHKELDSDDVPDGRFDILLCRDSSREVGELIGLFYNKTFRQKLE
9
YLLEQISEVWLLPHWLDLANVEVLAADDTRVPLYMLMVAVHKELDSDDVPDGRFDILLCRDSSREVG
ELIGLFYNKTFRQKLEYLLEQISEVWLLPHWLDLANVEVLAADDTRVPLYMLMVAVHKELDSDDVPDG
to this?
or this?
10
answer: through annotation of data with terms
from a controlled vocabulary or ‘ontology’
sphingolipid transporter activity
Holliday junction helicase complex
11
this allows integration of databases
GlyProt
MouseEcotope
Holliday junction
helicase complex
DiabetInGene
GluChem
13
and supports logical reasoning over data
15
‘Ontology’ in PubMed
16/24
GO, in particular, is tremendously successful
17
$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 terms
experimental results reported in 52,000
scientific journal articles manually
annoted by expert biologists using GO
18
Benefits of the GO
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
19
National Center for Biomedical Ontology
(NIH Roadmap Center)
− Stanford Biomedical Informatics Research
− The Mayo Clinic
− University at Buffalo Department of Philosophy
http://bioportal.bioontology.org
24
25
26
GO supports only three types of annotation
what cellular component?
what molecular function?
what biological process?
no diseases in GO
27
28
RELATION
TO TIME
CONTINUANT
INDEPENDENT
OCCURRENT
DEPENDENT
GRANULARITY
ORGAN AND
ORGANISM
Organism
(NCBI
Taxonomy)
CELL AND
CELLULAR
COMPONENT
Cell
(CL)
MOLECULE
Anatomical
Organ
Entity
Function
(FMA,
(FMP, CPRO) Phenotypic
CARO)
Quality
(PaTO)
Cellular
Cellular
Component Function
(FMA, GO)
(GO)
Molecule
(ChEBI, SO,
RnaO, PrO)
Molecular Function
(GO)
Biological
Process
(GO)
Molecular Process
(GO)
OBO Foundry (first version, 2006)
Yellow = Gene Ontology
29
http://obofoundry.org
30
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
31
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)
32
Ontologies under construction
Allergy Ontology
Environment 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)
33
Foundational Model of Anatomy Ontology
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.
32 teeth
two arms
two legs
one nose
two nostrils
two kidneys, …
Canonical ≠ statistically normal
34
Anatomical
Structure
Anatomical Space
Organ Cavity
Subdivision
Organ
Cavity
Organ
Serous Sac
Cavity
Subdivision
Serous Sac
Cavity
Serous Sac
Organ
Component
Organ
Subdivision
Pleural Sac
Pleural
Cavity
Parietal
Pleura
Interlobar
recess
Organ Part
Mediastinal
Pleura
Tissue
Pleura(Wall
of Sac)
Visceral
Pleura
Mesothelium
of Pleura
35
Foundational Model of Anatomy (FMA)
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
36
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
38
Basic Formal Ontology
Continuant
Occurrent
Life
Independent
Continuant
Dependent
Continuant
Organism
Temperature
http://www.ifomis.org/bfo/
39
Example: The Cell Ontology
Continuant
Independent
Continuant
Non-realizable
Dependent
Continuant
(quality)
Dependent
Continuant
TYPES
Realizable
Dependent
Continuant
(function, role,
disposition)
..... .....
INSTANCES
depends_on
Continuant
Independent
Continuant
Dependent
Continuant
thing
quality
.... .....
TYPES
example:
temperature depends
on bearer
INSTANCES
Dependent
Continuant
Quality
Disposition
of banana,
to ripen
Realizable Dependent
Continuant
Function
of heart,
to pump blood
Role
of employee,
to work for pay
46
process of realization depends_on
realizable
Continuant
Independent
Continuant
bearer
Realizable
Dependent
Continuant
disposition
Occurrent
Process of
realization
.... ..... .......
47
Four distinct classificatory tasks
1.
2.
3.
4.
of people (patients, carriers, …)
of diseases (cases, instances, problems, …)
of courses of disease (symptoms, treatments…)
of representations (records, observations, data,
diagnoses…)
ICD confuses 1. & 2.
Most standard terminologies confuse 2. and 4
51
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
52
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
53
Big Picture (Ontology for General Medical Science)
55
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.
56
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
57
Disorder
A 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
58
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.
60
http://code.google.com/p/ogms/
61
Big Picture (Ontology for General Medical Science)
62
http://code.google.com/p/ogms/
63
Disease Course
=Def. The sum of processes through which a
given disease instance is realized.
65
organism
John
occurrent
disposition
process
disease
course of
disease
John’s
disease
course of
John’s disease
TYPES
dependent
continuant
INSTANCES
independent
continuant
coronary heart
disease
in nature, no sharp
boundaries here
CHD in phase
of early lesions
and small
fibrous plaques
instantiates
at t1
CHD in phase of
asymptomatic
(‘silent’) infarction
instantiates
at t2
CHD in phase
of surface
disruption of
plaque
instantiates
at t3
unstable
angina
instantiates
at t4
stable
angina
instantiates
at t5
John’s coronary heart disease
67
human
in nature, no sharp
boundaries here
embryo
instantiates
at t1
fetus
instantiates
at t2
neonate
instantiates
at t3
infant
instantiates
at t4
child
instantiates
at t5
adult
instantiates
at t6
John
68
A disease is a disposition
produces
etiological process
bears
disorder
realized_in
disposition
pathological process
produces
diagnosis
interpretive process
produces
signs & symptoms
used_in
abnormal bodily features
recognized_as
71
Cirrhosis - environmental exposure







Etiological process - phenobarbitolinduced 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
Interpretive process
 produces
Result - diagnosis that patient X has a
disorder that bears the disease
cirrhosis
72
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
Abnormal bodily features
 recognized_as
Symptoms - weakness, dizziness
Signs - fever







Symptoms & Signs
 used_in
Interpretive process
 produces
Hypothesis - rule out influenza
 suggests
Laboratory tests
 produces
Test results - elevated serum antibody titers
 used_in
Interpretive process
 produces
Result - diagnosis that patient X has a
disorder that bears the disease flu
73
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
Abnormal bodily features
 recognized_as
Symptoms - anxiety, depression
Signs - difficulties in speaking and
swallowing







Symptoms & Signs
 used_in
Interpretive process
 produces
Hypothesis - rule out Huntington’s
 suggests
Laboratory tests
 produces
Test results - molecular detection of
the HTT gene with >39CAG repeats
 used_in
Interpretive process
 produces
Result - diagnosis that patient X has a
disorder that bears the disease
Huntington’s disease
74
Dispositions and Predispositions
Some dispositions are predispositions to
other dispositions.
75
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)
76
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
77
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
Abnormal bodily features
 recognized_as
Symptoms Signs – elevated blood pressure







Symptoms & Signs
 used_in
Interpretive process
 produces
Hypothesis - rule out hypertension
 suggests
Laboratory tests
 produces
Test results  used_in
Interpretive process
 produces
Result - diagnosis that patient X has a
disorder that bears the disease hypertension
82
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
Abnormal bodily features
 recognized_as
Symptoms – polydipsia, polyuria,
polyphagia, blurred vision
Signs – elevated blood glucose and
hemoglobin A1c







Symptoms & Signs
 used_in
Interpretive process
 produces
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
Interpretive process
 produces
Result - diagnosis that patient X has a
disorder that bears the disease type 2
diabetes mellitus
83
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
Abnormal bodily features
 recognized_as
Symptoms – pruritis, shortness of breath
Signs – rash, urticaria, anaphylaxis







Symptoms & Signs
 used_in
Interpretive process
 produces
Hypothesis  suggests
Laboratory tests –
 produces
Test results – occasionally, skin testing
 used_in
Interpretive process
 produces
Result - diagnosis that patient X has a
disorder that bears the disease type 1
hypersensitivity to penicillin
84
Early Onset Alzheimer’s Disease
Disorder – mutations in APP, PSEN1 and PSEN2
bears
Disposition – impaired APP processing
realized in
Pathological process – accumulation of intra- and extracellular protein in the
brain
produces
Disorder – amyloid plaque and neurofibrillary tangles
bears
Disposition – of neurons to die
realized in
Pathological process – neuronal loss
produces
Disorder – cognitive brain regions damaged and reduced in size
bears
Disposition (disease) – Alzheimer’s dementia
realized in
Symptoms – episodic memory loss and other cognitive domain impairment
85
Arterial Aneurysm
•
•
Disposition – atherosclerosis
–
realized in
Pathological process – fatty material collects within the walls of arteries
–
•
•
•
•
•
•
•
•
•
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
produces
Death
86
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
87
Advantages of the Disposition Theory
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”
88
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.
89
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
• …
90
Think of all the different combination cases:
of diseases with other diseases
of diseases with complications
of diseases at different stages of life
of diseases with different environments
in igloos
in Ost-Thüringen
in sub-Saharan Africa
in space-ships
…
91
Think of all the different types of patient:
smoker
non-smoker
banana-leaf-smoker
Am-Sonntag-bei-Mutti-Esser
Aspirin-vor-dem-Schlafen-Gehen-Nehmer
Auf-dem-Schiessplatz-Ohrstöpsel-Träger
Auf-Weihnachtsmarkt-Lebkuchenherz-Käufer
Auto-in-Waschstrasse-Abschliesser
92
93
human
in nature, no sharp
boundaries here
embryo
instantiates
at t1
fetus
instantiates
at t2
neonate
instantiates
at t3
infant
instantiates
at t4
child
instantiates
at t5
adult
instantiates
at t6
John
94
portion of
water
portion of
ice
instantiates
at t1
portion of
liquid water
instantiates
at t2
Phrase
transitions
portion of
gas
instantiates
at t3
this portion of H20
95
temperature
in nature, no sharp
boundaries here
37ºC
instantiates
at t1
37.1ºC
instantiates
at t2
37.2ºC
instantiates
at t3
37.3ºC
instantiates
at t4
37.4ºC
instantiates
at t5
37.5ºC
instantiates
at t6
John’s temperature
96