General Pathology

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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
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Glycogen

• linear and branched polymer
• cca 60 000 ?- D-glucose molecules
• monoparticles (beta) - muscle
• complex particles (alpha) - hepatocyte

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EnzymesInvolved in Glycogen Metabolism

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

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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

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Glycogenosis I von Gierke
  E defect - gl-6 - phosphatase Organ damage -
liver, kidney
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Glycogenosis II Pompe
  E -defect - alfa1, 4 - glycosidase
Organ damage - heart
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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)
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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 phosphorylase Mild Liver
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Clear Intracellular Vacuoles adjunct
techniques

• accumulations of water neg.
• lipides SUDAN, OIL RED
• polysaccharides PAS, A-PAS

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Glycogen

• water soluble
• easily lost
• in long lasting
• water based fixative solutions

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Calcification

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

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Calcification - physiology

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

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Pathology Conditions with Calcium Deposits

•  
• Calcification
• dystrophic
• metastatic
• Calcinosis
• localized
• generalized
• Chondrocalcinosis - pseudogout

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Calcification - Microscopy

• Basophilic
• Von Kossa - Ag impregnation
• Alizarine red
• Tetracyclin fluorescence
• Polarized light birefringence

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Calcification

• Dystrophic
• 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)

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Dystrophic Calcification
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Calcification

• Dystrophic
• 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)

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Ca Salts in the Calcified Foci

• Ca phophate Ca3(PO4)2
• Ca diphosphate (Ca2P2O7)
• Hydroxyapatite (Ca5 (PO4)3.OH

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Pathology Conditions with Calcium Deposits

•  
• Calcification
• dystrophic
• metastatic
• Calcinosis
• localized
• generalized
• Chondrocalcinosis - pseudogout

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Dystrophic Calcification

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

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Calcinosis
  Forms - localised
generalised Localisation connective
tissue, muscles
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Chondrocalcinosis crystal deposit disease
(pseudogout)
  pyrophophate and hydroxyapatite
deposits localisation synovial membrane,
cortilage, bone
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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