PATHOLOGICAL CALCIFICATION PATHOLOGICAL CALCIFICATION

Definition:-

Abnormal deposition of calcium salts together with smaller amount of Mg++ ,Fe++ & other minerals in tissues other than osteoid or enamel

• Dystrophic calcificationDystrophic calcification

• Metastatic calcificationMetastatic calcification

Pathologic calcificationPathologic calcification

• Dystrophic calcification

refers to local deposition of calcium salts in necrotic or degenerate tissues, whatever the type of necrosis, in spite of normal serum Ca++

Pathologic CalcificationPathologic Calcification

Dystrophic CalcificationDystrophic Calcification

- Area of tissue necrosis- Area of tissue necrosis

- Aging or damage heart valve- Aging or damage heart valve

- Atherosclerosis- Atherosclerosis

- Single necrotic cell- Single necrotic cell

“ “psammoma body”psammoma body”

Aortic valve , gross , (calcified aortic stenosis).

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Metastatic calcification reflects deranged calcium metabolism in contrast to dystrophic calcification and is associated with increase serum calcium level & systemic deposition of Ca++salts in interstitial tissue of gastric mucosa, kidney,lungs,systemic arteries& pulmonary veins.

• Increased secretion of parathyroid hormone Increased secretion of parathyroid hormone • Destruction of bone tissue 2ndry to primary tumor of Destruction of bone tissue 2ndry to primary tumor of bone marrow ( multiple myeloma, leukemia), or diffuse bone marrow ( multiple myeloma, leukemia), or diffuse skeletal metastasis.skeletal metastasis.• Vitamin D-related intoxicationVitamin D-related intoxication• Renal failureRenal failure•Excessive intake of calcium & absorbable antacids as Excessive intake of calcium & absorbable antacids as milk or calcium carbonate.milk or calcium carbonate.

Metastatic calcificationMetastatic calcificationHypercalcimiaHypercalcimia

This is dystrophic calcification in the wall of the stomach. At the far left is an artery with calcification in its wall

“Metastatic calcification" in the lung of a patient with a very high serum calcium level (hypercalcemia).

PIGMENTSPIGMENTSEX-ogenous--- (tattoo, Anthracosis)

END-ogenous--- they all look the same, (e.g., hemosiderin, melanin, lipofucsin, bile), in that hey are all golden yellowish brown on “routine” Hematoxylin & Eosin (H&E) stains

Accumulation of PigmentsAccumulation of Pigments

• Exogenous pigments Carbon ( anthracosis) Coal dust ( pneumoconiosis) Lung: pick up by alveolar macrophages

regional lymph nods

blackening the tissues of the lungs (anthracosis)

TATTOO, MICROSCOPICTATTOO, MICROSCOPIC

ANTHRACOSISANTHRACOSIS

Pulmonary anathracosis (deposition of carbon particles)

Carbon- laden macrophages (black exogenous pigment)

• Endogenous pigment

:Lipofuscin – aging pigment(fucus=brown)

lipid, phospholipid-protein complex (lipid peroxidation) ,brown-yellow pigment accumulated as the atrophic and dying cells undergo autophagocytosis. Harmless,Sign of free radical injury & lipid perioxidation, seen in aging patients severe malnutrition & cancer cachexia.

Accumulation of PigmentsAccumulation of Pigments

Lipofuscin granules in a cardiac myocyte as shown by A, light microscope (deposits indicated by arrows) , and B,Electron microscopy (perinuclear ,intralysosomal location).

Lipofuscin (wear & tear) pigments in cardiac myocytes

MelaninMelanin

• Melanin – melas= black

• In melanocytes formed by oxidation of tyrosine to dihydroxyphenylalanine by tyyrosinase enzyme

Nevus ( melanin pigmentation)

:Hemosiderin – aggregates of ferritin micelles (iron + apoferritin = ferritin) Hemosiderosis:- Excess of hemosiderin granules in mononuclear phagocytes without organ dysfunction Causes:- Local (bruise) Systemic as Hemolytic anemia, Increased absorption of dietary iron Repeated blood transfusion

Hemochromatosis:- Excess of hemosiderin granules in mononuclear phagocystic system & paranchymal cells causing organ dysfunction ( liver fibrosis, DM, heart failure).

Hemosiderin granules in liver cells A, H&E section showing golden-brown,finely granular pigment. B, Prussian blue reaction, specific for iron.

Alveolar (hemosiderin-laden) macrophages in patient with heart failure (heart failure cells)

Heart failure cells (hemosiderin-laden macrophages ),Prussian blue reaction

Jaundice

Yellowish discoloration of skin & sclera due to deposition of bilirubin pigment.

Bile pluges in liver of patient with obstructive jaundice

HemosiderinHemosiderin

The brown coarsely granular material in macrophages in this alveolus is hemosiderin

These renal tubules contain large amounts of hemosiderin, as demonstrated by the Prussian blue iron stain

• Fig 1-20

Ageing:Ageing:

“Progressive time related loss of structural and functional

capacity of cells leading to death”

• Senescence, Senility, Senile changes.

• Ageing of a person is intimately related to cellular ageing.

Factors affecting Ageing:Factors affecting Ageing:

• Genetic – Clock genes, (fibroblasts)

• Diet – malnutrition, obesity etc.

• Social conditions -

• Diseases – Atherosclerosis, diabetes etc.

• Werner’s syndrome.

Cellular mechanisms of Cellular mechanisms of ageingageing

• Cross linking proteins & DNA.

• Accumulation of toxic by-products.

• Ageing genes.• Loss of repair

mechanism.• Free radicle injury• Telomerase shortening.

Telomerase in ageing:Telomerase in ageing:

GermCells

SomaticCells

Ageing Ageing ––changes:changes:

• Gradual atrophy of tissues and organs.

• Dementia

• Loss of skin elasticity

• Greying and Loss of hair

• BV damage – atherosclerosis/bruising.

• Loss of Lens elasticity opacity vision

• Lipofuscin pigment deposition – Brown atrophy in vital organs.

Pathology Pathology of elderlyof elderly

Factors affecting ageing:Factors affecting ageing:

• Stress• Infections• Diseases• Malnutrition• Accidents

• Diminished stress response.

• Diminished immune response.

• Good health.

Conclusions:Conclusions:

• Cellular Injury - Various causes• Reversible Injury Adaptations

– Hypertrophy, Hyperplasia, Atrophy– Accumulations - Hydropic, hyaline, fat..

• Irreversible Injury - Necrosis– Coagulative, Liquifactive, Caseous

• Ageing - Causes, Changes, Factors

THE END