Download Calcification - Dr. Terezia Laszlo

Calcification
Dr. Terezia Laszlo
Calcification
• Pathologic calcification is the abnormal
tissue deposition of calcium salts,
• It is a common process occurring in a
variety of pathologic conditions.
Calcification
• Pathologic calcification:
– Dystrophic calcification
– Metastatic calcification
• Dystrophic calcification
– May occur at any serum calcium level
– Usually occurs in previously injured tissue
• Metastatic calcification
– Occurs at high serum calcium levels
– in normal tissue, during periods of
hypercalcemia
Dystrophic Calcification
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Location:
intracellular
extracellular
Both
calcification of injured cells
• in areas of necrosis,
– coagulative, caseous or liquefactive type,
– and in foci of enzymatic necrosis of fat
• in the atheromas of advanced atherosclerosis
• in aging or damaged heart valves
• Heterotopic bone may be formed in the focus
of calcification
• single necrotic cells may constitute seed
crystals that become encrusted by the mineral
deposits
– psammoma bodies
Dystrophic calcification,
Pathogenesis
• the final common pathway is the formation of
crystalline calcium phosphate mineral in the
form of an apatite similar to the hydroxyapatite of
bone
phases:
1. initiation (or nucleation) and
2. propagation
• both can occur
• intracellularly and extracellularly.
Dystrophic calcification
Initiation
of intracellular calcification occurs in the
mitochondria of dead or dying cells that
accumulate calcium.
of extracellular dystrophic calcification
• include phospholipids found in membranebound vesicles about 200 nm in diameter
• known as matrix vesicles
Dystrophic calcification
• calcium is concentrated in these vesicles by a process of
membrane-facilitated calcification, which has several
steps:
• (1) calcium ion binds to the phospholipids present in
the vesicle membrane,
• (2) phosphatases associated with the membrane
generate phosphate groups, which bind to the calcium,
• (3) the cycle of calcium and phosphate binding is
repeated, raising the local concentrations and producing
a deposit near the membrane,
• (4) a structural change occurs in the arrangement of
calcium and phosphate groups, generating a
microcrystal, which can then propagate and perforate
the membrane
Dystrophic calcification
Propagation
• depends on
– the concentration of Ca2+ and PO4 and
– the presence of inhibitors and other proteins
in the extracellular space, such as the
connective tissue matrix proteins.
Dystrophic calcification
• Although dystrophic calcification may be
simply a telltale sign of previous cell injury,
it is often a cause of organ dysfunction.
• calcific valvular disease and
• atherosclerosis
Morphology
• Whatever the site of deposition, the calcium salts appear
macroscopically as fine, white granules or clumps,
often felt as gritty deposits.
• Sometimes a tuberculous lymph node is virtually
converted to stone.
Calcium salts
• stain dark blue on H&E.
• Von Kossa (Silver nitrate solution +Calcium-phosphateform Silver- Phosphate under UV light - black silver
precipit)
Examples for Dystrophic calcification:
• Certain tumors contain "psammoma bodies", little
spherules of basement membrane that calcify
– thyroid cancer, ovarian cancer, meningioma
• Calcium help mammographers recognize breast cancer
– Calcified „Comedo” necrosis
• Advanced atherosclerotic plaques undergo
calcification.
• Malformed or damaged cardiac valves tend to calcify:
– congenitally bicuspid aortic valves
– aortic valve stenosis
- post endocarditis
- ATS
• Caseous granulomas (tuberculosis)
• Scars (surgical, myocardial)
• Little spherical calcifications associated with giant
cells in granulomas are called "Schaumann
bodies" in Sarcoidosis
• Uterine smooth muscle tumors may calcify
Myoma petrificata utery
• If a fetus dies and calcifies, it may be retained for
years as a "lithopedion" ("stone child").
• Precipitation of calcium stearate in pancreatitisassociated fat necrosis.
• Celiac plexus calcification (causes pain
syndromes)
• Low Plasma Calcium: stimulates PTH
release, and PTH acts to resorb Ca2+ from
the pool in bone and to enhance renal reabsorption of Ca2+
• High Plasma Calcium: stimulates CT
secretion which lowers plasma calcium by
inhibiting bone resorption
• Parathyroid Hormone:
• functions to raise plasma calcium
– bone resorption
– renal calcium reabsorption
• stimulates the metabolism of Vitamin D to
its active hormonal form, 1,25(OH)2 / D3
Vitamin D:
Functions
• promotes calcium absorption from the gut
• promotes calcium reabsorption from the
kidney
• promotes calcium mobilization from bone
via resorption
• enhances phosphate absorption by the
intestine
Metastatic calcification
when apparently normal tissue undergoes calcification because of
hypercalcemia / altered Ca2+ metabolism
There are four principal causes of hypercalcemia:
• (1) increased secretion of parathyroid hormone (PTH) with
subsequent bone resorption,
– parathyroid tumors,
• (2) destruction of bone tissue,
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primary tumors of bone marrow (e.g., multiple myeloma, leukemia)
metastasis (e.g., breast cancer),
accelerated bone turnover (e.g., Paget disease)
immobilization;
• (3) vitamin D-related disorders, including vitamin D intoxication,
sarcoidosis (in which macrophages activate a vitamin D precursor)
• (4) renal failure, which causes retention of phosphate, leading to
secondary hyperparathyroidism.
Clinical Correlate(s):
Hyperparathyroidism• Excessive PTH usually due to a Parathyroid
Adenoma, breaks the feedback loops
• Symptoms– renal stones,
– bone pain (due to increased bone resorption)
– Metastatic calcification
Hypoparathyroidism• Lack of PTH (usually due to removal of the
parathyroid gland along w/ the thyroid)
• Symptoms: - hypocalcemia/convulsion
Metastatic calcification
sites: many sites can be affected,
especially
gastric and intestinal mucosa,
walls of blood vessels,
Basal lamina of lung, kidney, etc
Metastatic calcification
• affects the interstitial tissues of the gastric mucosa, kidneys, lungs,
systemic arteries, and pulmonary veins.
• Although quite different in location, all of these tissues lose acid and
therefore have an internal alkaline compartment that predisposes
them to metastatic calcification.
• noncrystalline amorphous deposits or
• hydroxyapatite crystals.
• Usually, the mineral salts cause no clinical dysfunction, but, on
occasion, massive involvement of the lungs produces remarkable xray films and respiratory deficits.
• Massive deposits in the kidney (nephrocalcinosis) may in time cause
renal damage