PATHOLOGICAL
CALCIFICATION
• Pathological calcification is the abnormal deposition of calcium salts
in tissues. It is categorized into dystrophic calcification and metastatic
calcification based on the underlying cause and site of deposition.
Dystrophic Calcification
•Definition: The deposition of calcium salts in dead or degenerated tissues despite normal serum
calcium and phosphate levels.
•Mechanism:
1.Tissue damage or necrosis leads to the release of phosphate.
2.Calcium binds with phosphate, forming calcium phosphate deposits.
Common Sites:
• Areas of necrosis (caseous necrosis in tuberculosis, fat necrosis, etc.).
• Atherosclerotic plaques.
• Heart valves (especially in rheumatic heart disease).
• Tumors (e.g., psammoma bodies in papillary thyroid carcinoma).
•Dystrophic calcification happens when calcium gets deposited in tissues that are damaged or
dead, even though the levels of calcium in the blood are normal.
•How does it happen?
1.When a part of the body gets injured or some cells die, certain substances, like phosphate, are
released from these damaged cells.
2.Calcium, which is naturally found in the body, combines with phosphate in the damaged area.
3.This forms hard deposits, like tiny pieces of chalk, in the affected tissue
• Steps in the Pathology of Dystrophic Calcification
1.Tissue Damage:
1. Dystrophic calcification occurs in areas of cell injury or death, such as necrosis (cell death
caused by lack of blood supply or trauma).
2. Damaged or dead cells release substances like phosphate into the surrounding area.
2.Formation of Calcium Phosphate Crystals:
1. Calcium from the body's fluids binds to the released phosphate.
2. This results in the formation of calcium phosphate crystals, which are hard and insoluble.
3.Propagation of Calcification:
1. Over time, these crystals grow in size as more calcium and phosphate accumulate.
2. The calcified deposits may appear granular or clumpy under a microscope and are often
blue when stained (basophilic).
COMMON SITES
Necrosis:
•Caseous Necrosis: Found in tuberculosis lesions (e.g., in lungs or lymph nodes).
•Coagulative Necrosis: Seen in ischemic tissue (e.g., heart after a myocardial infarction).
•Fat Necrosis: Occurs in damaged fatty tissues (e.g., in pancreatitis).
Atherosclerosis:
•Calcification in the walls of arteries affected by atherosclerotic plaques.
•It can stiffen arteries and lead to complications like heart attacks or strokes.
Heart Valves:
•Chronic inflammation or damage to heart valves (e.g., due to rheumatic fever or aging) can lead to calcification.
•Commonly seen in the aortic and mitral valves, causing valve stiffness and impaired function (stenosis).
Tumors:
•Calcification can occur in long-standing tumors, especially in cancers like papillary thyroid carcinoma or ovarian
serous cystadenocarcinoma.
•The calcified deposits in tumors are called psammoma bodies (small, round, laminated calcifications).
Infections and Chronic Inflammation:
•Chronic infections like tuberculosis or parasitic diseases (e.g., schistosomiasis) can cause calcification in
affected tissues.
Consequences of Dystrophic
Calcification
1.Mechanical Dysfunction:
1. In heart valves, calcification can cause stiffness, impairing the opening and
closing of the valve, leading to stenosis or regurgitation.
2. In arteries, calcified plaques can restrict blood flow, increasing the risk of
heart attacks or strokes.
2.Tissue Stiffness:
1. In calcified tissues, normal elasticity and function are lost. For instance, in
muscles or skin, calcification can lead to reduced flexibility.
3.Marker of Disease:
1. Dystrophic calcification often indicates chronic injury or a history of disease,
such as chronic infections or ischemia.
• Microscopic Appearance:
• Basophilic, granular deposits in tissues.
• May coalesce into larger clumps.
• Clinical Significance:
• Can impair tissue function, e.g., calcification of heart valves causing stenosis.
Metastatic Calcification
• Metastatic calcification is the abnormal deposition of calcium salts in
normal, healthy tissues caused by hypercalcemia (high levels of
calcium in the blood). Unlike dystrophic calcification, metastatic
calcification occurs when calcium and phosphate levels are elevated,
even in the absence of tissue damage.
Causes of Hypercalcemia Leading to Metastatic
Calcification:
1.Increased Parathyroid Hormone (PTH):
1. Primary Hyperparathyroidism:
1. Overactive parathyroid glands (due to adenoma or hyperplasia) cause increased calcium
release from bones.
2. Secondary Hyperparathyroidism:
1. Seen in chronic kidney disease, where phosphate retention leads to increased PTH levels.
2.Bone Destruction:
1. Osteolytic Metastases: Cancer (e.g., breast cancer, multiple myeloma)
invades bones and releases calcium into the bloodstream.
2. Paget’s Disease: A condition that increases bone turnover, leading to calcium
release.
•Vitamin D Disorders:
•Vitamin D Intoxication: Excess vitamin D increases calcium absorption from the gut.
•Sarcoidosis: Granulomas in this disease can produce active vitamin D, increasing calcium levels.
•Renal Failure (Chronic Kidney Disease):
•Reduced phosphate excretion leads to secondary hyperparathyroidism, causing calcium release from bones.
•This is a common cause of metastatic calcification.
•Other Causes:
•Milk-alkali syndrome (excessive intake of calcium and absorbable alkali).
•Hyperthyroidism (increased bone turnover).
•Prolonged immobilization (bone resorption due to inactivity).
Pathogenesis
1.Hypercalcemia Causes:
1. Elevated blood calcium levels can occur due to various conditions (explained below).
2. High calcium levels increase the deposition of calcium salts in tissues, especially those exposed
to alkaline environments, where calcium phosphate is more likely to precipitate.
2.Sites of Deposition:
1. Metastatic calcification typically occurs in tissues with a high alkaline environment, such as the
lungs, kidneys, and stomach.
2. The alkaline pH promotes the precipitation of calcium and phosphate into insoluble salts.
3.Tissue Changes:
1. Early deposits are microscopic and appear as fine, basophilic granules (bluish under the
microscope).
2. Over time, these deposits grow into larger clumps, impairing the tissue's function.
Microscopic Features:
• Early Stage:
• Fine granules or small clumps of calcium appear basophilic (blue/purple)
under H&E staining.
• Seen in the interstitial spaces or along the basement membranes of tissues.
• Advanced Stage:
• Calcium deposits can grow larger, forming plaques or solid masses.
• These can impair the tissue's structure and function.
Common Tissues Affected by Metastatic
Calcification:
1. Lungs:
1. Deposits in alveolar walls can lead to reduced elasticity and gas exchange.
2. Clinically, this may cause difficulty breathing.
2. Kidneys (Nephrocalcinosis):
1. Calcium deposits in renal tubules or interstitium impair kidney filtration.
2. This can progress to chronic kidney disease or renal failure.
3. Stomach:
1. Calcium deposits in the gastric mucosa can affect acid secretion.
2. Often asymptomatic but may contribute to chronic irritation.
4. Blood Vessels:
1. Vascular calcification stiffens blood vessel walls, increasing blood pressure and the risk of cardiovascular
events.
5. Heart:
1. Calcification in the heart (e.g., myocardium or valves) can impair contractility or conduction, causing
arrhythmias.
Clinical Consequences of Metastatic
Calcification
1.Organ Dysfunction:
1. The affected tissues lose their flexibility and ability to function normally. For
example:
1. Lungs: Breathing difficulties.
2. Kidneys: Reduced ability to filter waste.
3. Heart: Arrhythmias or mechanical failure.
2.Increased Risk of Vascular Disease:
1. Calcification in blood vessels contributes to hypertension, atherosclerosis, and
increased risk of stroke or heart attack.
3.Pain or Irritation:
1. Calcified areas, especially in the skin or muscles, may cause discomfort or visible
lumps.
Comparison Between Dystrophic and Metastatic
Calcification:
Feature Dystrophic Calcification Metastatic Calcification
Calcium Levels in Blood Normal Elevated (Hypercalcemia)
Site of Calcification Damaged or dead tissues Normal tissues
Systemic disturbance in calcium
Pathological Trigger Tissue necrosis or injury
metabolism
Atherosclerotic plaques, valve Lungs, kidneys, stomach, blood
Examples
stenosis, tumors vessels, heart
