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

EnzymesInvolved in Glycogen Metabolism

g.-synthase - brancher phophorylase kinase - debrancher g-6-phosphatase -glucosidase

Storage DiseasesDef.:

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“

 

E defect - gl-6 - phosphatase

Organ damage - liver, kidney

Glycogenosis I – von Gierke

 

E -defect - alfa1, 4 - glycosidase Organ damage - heart

Glycogenosis II – Pompe

Glycogen Storage Diseases -1.

Disease 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)

Lethal Liver (+systemic)

Glycogen Storage Diseases -2.

Disease 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

phosphorylaseMild 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

CalcificationDef.:

depositions of Ca (mostly phosphate

salts) in tissues or organs Classification:

dystrophic

metastatic

  

Matrix vesicles - osteoblasts- nidus calcification

Non collagen proteins - osteopontin,

osteonektin, osteokalcin, Gla protein, sialoprotein

Alkalic phosphatase Phospholipids Collagen I Hydroxyapatite

Calcification - physiology

 

Calcification dystrophic metastatic

Calcinosis localized generalized

Chondrocalcinosis - pseudogout

Pathology Conditions with Calcium Deposits

Basophilic

Von Kossa - Ag impregnation

Alizarine red +

Tetracyclin fluorescence

Polarized light birefringence

Calcification - Microscopy

Calcification

Dystrophic Serum Ca level: normal

Tissues/Organs status

dystrophic changes

(necrosis, scar…, low

metab. turnover)

MetastaticSerum Ca level:

Tissues/Organs status

normal, local alcalisation

(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

Activaton of proteases

Cytoskeletal disassembly

Membrane damage

Phosphorylation of protein

andchromatin

phragmentation

Necrosis or degeneration

of tissue

Release of enzymes

Breakdown of organic

phophatesAlteration of pH

Increased deposition of calcium

Dystrophic Calcification

Calcification

Dystrophic Serum Ca level: normal

Tissues/Organs status

dystrophic changes

(necrosis, scar…, low

metab. turnover)

MetastaticSerum Ca level:

Tissues/Organs status

normal, local alcalisation

(acid secretion - urine,

stomach juice, sweat…)

Ca phophate Ca3(PO4)2

Ca diphosphate (Ca2P2O7)

Hydroxyapatite (Ca5 (PO4)3.OH

Ca Salts in the Calcified Foci

 

Calcification dystrophic metastatic

Calcinosis localized generalized

Chondrocalcinosis - pseudogout

Pathology Conditions with Calcium Deposits

Frequent necrotic tissue connective tissue vessels kalkospherites intracellular calcifiction of lysosoms

Less frequent tendon, cartilage, elastics, bas. membranes

Dystrophic Calcification

 

Forms - localised generalised

Localisation – connective tissue,

muscles

Calcinosis

 

pyrophophate and hydroxyapatite deposits

localisation – synovial membrane, cortilage, bone

Chondrocalcinosiscrystal deposit disease (pseudogout)

Calcium pyrophosphate deposition disease(Chondrocalcinosis, pseudogout)

Clinic: may simulate different diseasesArthroscopy - chalky white depositsTophaceus deposits with crystalline aggregatesCrystals stain with von Kossa techniqueForeign body type multinucleated giant cell reactionDeposits are in synovium, cartilage, bone