1. Disorders of Glycogen Degradation. Pathology of Calcification.
General Pathology
Cellular and Organ Pathology
Disorders of Glycogen Degradation.
Pathology of Calcification.
Jaroslava Dušková
Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague

2. Glycogen linear and branched polymer cca 60 000 - D-glucose molecules
monoparticles (beta) - muscle
complex particles (alpha) hepatocyte

3. Enzymes Involved in Glycogen Metabolism
g.-synthase - brancher
phophorylase kinase - debrancher
g-6-phosphatase
-glucosidase

4. 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“

5. Glycogenosis I – von Gierke
E defect - gl-6 - phosphatase
Organ damage - liver, kidney

6. Glycogenosis II – Pompe
E -defect - alfa1, 4 - glycosidase
Organ damage - heart

7. Glycogen Storage Diseases -1.
E- def
Severity of Disease
Tissues Involved
von Gierke
Glucose-6
phosphatase
Severe
Liver,kidney, gut
Pompe
 1,4 glucosidase
Lethal
Heart (+systemic)
Cori
Amylo-1,6 Glucosidase (debrancher)
Liver (+systemic)

8. Glycogen Storage Diseases -2.
E- def
Severity of Disease
Tissues Involved
Andersen
Amylo-1,4-1,6 transglucosidase (brancher)
Lethal
Liver (+systemic)
Mc Ardle
Muscle phosphorylase
Mild
Skeletal muscle
Hers
Liver
phosphorylase

9. Clear Intracellular Vacuoles & adjunct techniques
accumulations of water neg.
lipides SUDAN, OIL RED
polysaccharides PAS, A-PAS

10. Glycogen easily lost in long lasting water based fixative solutions
water soluble
easily lost
in long lasting
water based fixative solutions

11. Calcification
Def.:
depositions of Ca (mostly phosphate salts) in tissues or organs
Classification:
dystrophic
metastatic

12. Calcification - physiology
Matrix vesicles - osteoblasts- nidus calcification
Non collagen proteins - osteopontin, osteonektin, osteokalcin, Gla protein, sialoprotein
Alkalic phosphatase
Phospholipids
Collagen I
Hydroxyapatite

13. Pathology Conditions with Calcium Deposits
Calcification
dystrophic
metastatic
Calcinosis
localized
generalized
Chondrocalcinosis - pseudogout

14. Calcification - Microscopy
Basophilic
Von Kossa - Ag impregnation
Alizarine red +
Tetracyclin fluorescence
Polarized light birefringence

15. Calcification Dystrophic Metastatic Serum Ca level: normal
Tissues/Organs status
dystrophic changes
(necrosis, scar…, low metab. turnover)
Metastatic
Serum Ca level:
Tissues/Organs status
normal, local alcalisation
(acid secretion - urine, stomach juice, sweat…)

17. Dystrophic Calcification

18. Calcification Dystrophic Metastatic Serum Ca level: normal
Tissues/Organs status
dystrophic changes
(necrosis, scar…, low metab. turnover)
Metastatic
Serum Ca level:
Tissues/Organs status
normal, local alcalisation
(acid secretion - urine, stomach juice, sweat…)

19. Ca Salts in the Calcified Foci
Ca phophate Ca3(PO4)2
Ca diphosphate (Ca2P2O7)
Hydroxyapatite (Ca5 (PO4)3.OH

20. Pathology Conditions with Calcium Deposits
Calcification
dystrophic
metastatic
Calcinosis
localized
generalized
Chondrocalcinosis - pseudogout

21. Dystrophic Calcification
Frequent
necrotic tissue
connective tissue
vessels
kalkospherites
intracellular calcifiction of lysosoms
Less frequent
tendon, cartilage, elastics, bas. membranes

22. Calcinosis Forms - localised Localisation – connective tissue, muscles
Forms - localised
generalised
Localisation – connective tissue, muscles

23. Chondrocalcinosis crystal deposit disease (pseudogout)
pyrophophate and hydroxyapatite deposits
localisation – synovial membrane, cortilage, bone

24. 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