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

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. 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)

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

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

Glycogen easily lost in long lasting water based fixative solutions 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 - osteoblasts- nidus calcification Non collagen proteins - osteopontin, 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 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…)

Dystrophic Calcification

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…)

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 Localisation – connective tissue, muscles   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