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General Pathology
Cellular and Organ Pathology
Disorders of Glycogen Degradation.
Pathology of Calcification.
Jaroslava Dušková
Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague
Glycogen
linear
and branched polymer
cca 60 000 - D-glucose
molecules
– monoparticles (beta) - muscle
– complex particles (alpha) hepatocyte
Enzymes
Involved in Glycogen Metabolism
 g.-synthase
- brancher
 phophorylase kinase - debrancher
 g-6-phosphatase
 -glucosidase
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
„thesaurismoses“
Glycogenosis I – von Gierke
E defect - gl-6 - phosphatase
Organ damage - liver, kidney
Glycogenosis II – Pompe
E -defect - alfa1, 4 - glycosidase
Organ damage - heart
Glycogen Storage Diseases -1.
Disease
E- def
Severity of Tissues
Disease
Involved
von
Gierke
Glucose-6
Severe
phosphatase
Liver,kidney,
gut
Pompe
 1,4
Lethal
glucosidase
Heart
(+systemic)
Cori
Amylo-1,6
Lethal
Glucosidase
(debrancher)
Liver
(+systemic)
Glycogen Storage Diseases -2.
Disease
E- def
Andersen Amylo-1,4-1,6
Severity
of
Disease
Lethal
Tissues
Involved
transglucosidase
(brancher)
Liver
(+systemic)
Mc Ardle
Muscle
phosphorylase
Mild
Skeletal
muscle
Hers
Liver
phosphorylase
Mild
Liver
Clear Intracellular Vacuoles
& adjunct techniques



accumulations of water neg.
lipides SUDAN, OIL RED
polysaccharides PAS, A-PAS
Glycogen
water soluble
easily lost
in long lasting
water based fixative solutions
Calcification
Def.:
depositions of Ca (mostly phosphate
salts) in tissues or organs
Classification:
dystrophic
metastatic
Calcification - physiology

Matrix vesicles -

Non collagen proteins - osteopontin,
osteoblasts- nidus calcification
osteonektin, osteokalcin, Gla protein, sialoprotein




Alkalic phosphatase
Phospholipids
Collagen I
Hydroxyapatite
Pathology Conditions
with Calcium Deposits
Calcification
 dystrophic
 metastatic
Calcinosis
 localized
 generalized
Chondrocalcinosis - pseudogout
Calcification - Microscopy

Basophilic

Von Kossa - Ag impregnation
 Alizarine
red +

Tetracyclin fluorescence

Polarized light birefringence
Calcification
Dystrophic
Metastatic
Serum Ca level: normal
Serum Ca level:
Tissues/Organs status
Tissues/Organs status
dystrophic changes
normal, local alcalisation
(necrosis, scar…, low
metab. turnover)
(acid secretion - urine,
stomach juice, sweat…)
Ca in mitochondria
and GER
in cytoplasm
bound to proteins
Released
after cell damage
Activaton
of protein kinases
Activaton
of phospholipid
degradation
and loss
Phosphorylation
of protein
and
chromatin
phragmentation
Membrane
damage
Activaton
of proteases
Cytoskeletal
disassembly
Dystrophic Calcification
Necrosis or
degeneration
of tissue
Release
of enzymes
Breakdown
of organic
Alteration of pH
phophates
Increased
deposition
of calcium
Calcification
Dystrophic
Metastatic
Serum Ca level: normal
Serum Ca level:
Tissues/Organs status
Tissues/Organs status
dystrophic changes
normal, local alcalisation
(necrosis, scar…, low
metab. turnover)
(acid secretion - urine,
stomach juice, sweat…)
Ca Salts in the Calcified Foci
Ca phophate
Ca3(PO4)2
Ca diphosphate (Ca2P2O7)
Hydroxyapatite (Ca5 (PO4)3.OH
Pathology Conditions
with Calcium Deposits
Calcification
 dystrophic
 metastatic
Calcinosis
 localized
 generalized
Chondrocalcinosis - pseudogout
Dystrophic Calcification
Frequent





necrotic tissue
connective tissue
vessels
kalkospherites
intracellular calcifiction of lysosoms
Less frequent
tendon, cartilage, elastics, bas. membranes
Calcinosis
Forms - localised
generalised
Localisation – connective
tissue, muscles
Chondrocalcinosis
crystal deposit disease (pseudogout)
pyrophophate and hydroxyapatite
deposits
localisation – synovial membrane,
cortilage, bone
Calcium pyrophosphate deposition disease
(Chondrocalcinosis, pseudogout)
Clinic: may simulate
different diseases
Arthroscopy - chalky
white deposits
Tophaceus deposits with
crystalline aggregates
Crystals stain with von
Kossa technique
Foreign body type
multinucleated giant cell
reaction
Deposits are in
synovium, cartilage,
bone