Pigmenty - Univerzita Karlova v Praze
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Transcript Pigmenty - Univerzita Karlova v Praze
Dementia
Def.
decrease of individual
intelectual abilities under the
formerly reached niveau
Dementia
Clinical features
Disturbances of
memory
(mnestic)
cognitive functions (gnostic)
adaptative behaviour (practice)
Dementia
Beginning
mostly inapparent
Course
reversible
stationary
progredient
Dementia
causes (1)
MALNUTRITION
THERAPY
INTOXICATION VASCULAR
INFECTION
EXPANSION
METABOLIC AFFECTIVE
DISORDERS
DISORDERS
PROGRESSIVE DEGENERATIVE
DISEASES
Dementia
causes (2)
THERAPY
polypragmasia
INTOXICATION
Mn, Cu, Pb,
CO, CS2, Hg, etanol…..
INFECTION
viral, bacterial
protozoan, mycotic
(HIV, PME, Whipple disease, Lues,
toxoplasmosis, cryptococcosis, prion dis.)
Prionoses
- morphology
neuronal loss
spongiosis
gliosis
ATROPHY
Dementia -
causes (3)
METABOLIC DISORDERS
chron. liver or kidney failure,
thesaurismoses
hepatolenticular degeneration
MALNUTRITION
avitaminosis B1
Wernicke-Korsakoff encephalopathy
with dementia
Storage Diseases
Def.:
inborn errors of metabolism (mostly
single gene abnormality) leading to an
enzyme defect with subsequent
accumulation of the substrate (&
lack of the product) in tissues or
organs
Lipid Storage Diseases -1.
Disease
E- def
Accum.
Lipid
Tay-Sachs Hexos
GM2
aminidase A ganglioside
Gaucher
Gluco
Glucosidase cerebrosid
Tissues
Involved
Brain,
retina
Liver, spleen,
bone marrow,
brain
NiemannPick
Sphingo
myelinase
Sphingo
myelin
Brain, liver
spleen
Lipid Storage Diseases – 2.
Disease
E- def
Metachro
matic
Leuco
dystrophy
Fabry´s
Arylsulfat
ase A
Krabbe´s
-galactosid
ase
Galactosyl
ceramidase
Accum.
Lipid
Sulfatid
Tissues
Involved
Brain, kidney,
liver, peripheral
nerves
Ceramid
trihexosid
Skin, kidney
Galactol
Brain
cerebroside
Mucopolysaccharidoses
Disease,
E- def
inheritance
course
Hurler
-liduronidase
AR, severe
Hunter
X, rec.
moderate
Sanfilippo
liduronosulf
ate
sulfatase
Many types
Accum.
Mucopoly
saccharide
Heparan
sulfate,
dermatan
sulfate
Heparan
sulfate,
dermatan
sulfate
Heparan
sulfate
Tissues
Involved
Skin, cornea,
bone heart,
Brain, liver
spleen
Skin, bone,
heart, ear,
retina
Brain, skin
Dementia
– causes (4)
VASCULAR
hypertensive encephalopathy,
MID
EXPANSION
subdural hematoma, hygroma,
neoplasia, hydrocephalus
AFFECTIVE DISORDERS
depression
Dementia -
causes (5)
PROGRESSIVE DEGENERATIVE
DISEASES
dementia – the only one symptome:
m. Alzheimer, m. Pick
dementia – combined with neurology
symptomes:
m. Parkinson, m. Huntington, ALS, PP
M. Alzheimeri - incidence
65 yrs
80 yrs
5%
population
20%
M. Alzheimeri
Extracellular
-amyloid
plaques
dystrophic dendrites
axons
activated microglia
reactive astrocytes
diffuse plaques - A42
mature plaques - A42
and
A40
M. Alzheimeri
Intracellular
neurofibrillary
deposits
hyperphosphorylated
proteins (pair helical
filaments)
glycosaminoglycans
admixture (heparin)
M. Alzheimeri- genetic factors
Chromo
-some
Gene defekt
Age
of onset
A phenotype
50s
Production of total A 42
peptides
60and
older
Density of Aplaques
and vascular deposits
21
APP mutations
19
apo E4
polymorphism
14
presenilin 1
mutations
40s and
50s
Production of A 42
peptides
1
presenilin 2
mutations
50s
Production of A 42
peptides
M. Alzheimeri - diagnosis
age matched
neuritic plaques
quantity
Khachaturyan, Mirra et al.
Dementia -
causes (5)
PROGRESSIVE DEGENERATIVE
DISEASES
dementia – the only one symptome:
m. Alzheimer, m. Pick
dementia – combined with neurology
symptomes:
m. Parkinson, m. Huntington, ALS, PP
Dementia -
causes (5)
PROGRESSIVE DEGENERATIVE
DISEASES
dementia – the only one symptome:
m. Alzheimer, m. Pick
dementia – combined with neurology
symptomes:
m. Parkinson, m. Huntington, ALS, PP
Paralysis agitans
– m. Parkinsoni (1817)
Clinical features
Start 40–60 years
Early stage
dysesthesias
discrete
tremor
hypertonia–hypokinesis syndrome
tremor
rigidity
loss of automatic movements
prognosis: quoad vitam good,
quoad sanationem (L-DOPA, transpl., nicotine)
Paralysis agitans
– m. Parkinsoni (1817)
Morphology
macroscopy
depigmentation of
substantia nigra mesencephali
microscopy
Lewy bodies ,
loss of pigmented neurons
Chorea chronica
progressiva Huntington
Autosomally dominant (!)
4th chromosome
Manifestation 25 – 45 years
(juvenile form prior to 20 years of age)
Duration 15 years
Chorea chronica
progressiva Huntington
Clinical features
contravolitional uncontrolled
dance–like motions
schizophrenic and depressive
personality features
death from intercurrent infection
Chorea chronica
progressiva Huntington
Morphology
macroscopy striatum atrophy
(ncl. caudatus + putamen)
microscopy loss of small GABA
neurons (norm. 80% of
population)
Sclerosis cerebrospinalis
multiplex disseminata MS
Def.
chronic autoimmune
disease with myelin breakdown
Sclerosis cerebrospinalis
multiplex disseminata MS
Clinical features
Disorders of
Course
sight
sensation
motorics
cont. progressive
saw-like
Sclerosis cerebrospinalis
multiplex disseminata MS
Morphological features
– myelinic plaques
acute
chronic
Sclerosis cerebrospinalis
multiplex disseminata MS
Pathogenesis
genetic predisposition
viruses
MS – viral influence (morbilli,
herpes,…)
Pathogenesis
interaction macroorganism x virus
limited production of Ig (only 10-20%
produced viruses are virulent)
virus mutation & immunosuppression
(age, pregnancy, stress, other disease)
MS – viral influence
(2)
Pathogenesis
infection of endothelia – microangiitis
hematoencephalic barier disorder
serum and CSF
CD4,
CD8
(mirror image to AIDS)