Fibrosis

Fibrosis
Synonyms	Fibrotic disease, pathological scarring
Pronounce
Field	Pathology, Rheumatology, Pulmonology, Hepatology, Cardiology
Symptoms	Organ dysfunction, stiffness, pain, shortness of breath, fatigue, swelling, tissue thickening
Complications	Organ failure, chronic inflammation, tissue damage, mobility impairment
Onset	Progressive over time; triggered by chronic injury, inflammation, or disease
Duration	Chronic and often irreversible
Types	Pulmonary fibrosis, liver fibrosis, cardiac fibrosis, renal fibrosis, systemic fibrosis
Causes	Chronic inflammation, persistent injury, autoimmunity, environmental toxins, infections, genetic predisposition
Risks	Chronic infections, autoimmune diseases, radiation exposure, environmental pollutants, metabolic disorders
Diagnosis	Histopathology, biopsy, imaging studies (MRI, CT, ultrasound), blood tests (fibrosis markers)
Differential diagnosis	Scar formation, tumor growth, normal wound healing, edema
Prevention	Controlling chronic inflammation, reducing exposure to toxins, early treatment of infections and autoimmune diseases
Treatment	Anti-fibrotic medications, immunosuppressive therapy, physiotherapy, surgical intervention in severe cases
Medication	Pirfenidone, Nintedanib, corticosteroids, immunosuppressants, antifibrotic agents
Prognosis	Variable; progressive fibrosis may lead to severe organ dysfunction or failure
Frequency	Common in chronic diseases such as liver disease, lung disease, and autoimmune disorders
Deaths	Can be fatal if fibrosis leads to irreversible organ failure

Cardiac amyloidosis very high mag movat

Cirrhosis at high magnification

Bridging fibrosis in rat liver exposed to toxins

Fibrotic scarring in myocardial infarction

Fibrosis is a pathological process characterized by the excessive accumulation of connective tissue in response to chronic injury, inflammation, or persistent disease. It involves the overproduction of extracellular matrix components such as collagen, which can disrupt normal tissue function, leading to organ stiffness, dysfunction, and eventual failure. While fibrosis shares similarities with the normal wound healing process, it becomes problematic when it is excessive or persistent, impairing the function of affected organs.

Pathophysiology

Fibrosis results from the excessive activation of fibroblasts and myofibroblasts, which are responsible for producing collagen and other matrix proteins. These cells are activated by inflammatory cytokines, growth factors, and immune mediators, particularly:

• Transforming Growth Factor-beta (TGF-β) – A key regulator of fibrosis, promoting fibroblast activation and extracellular matrix deposition.
• Connective Tissue Growth Factor (CTGF) – Involved in fibroblast proliferation and tissue remodeling.
• Platelet-Derived Growth Factor (PDGF) – Stimulates fibroblast migration and proliferation.
• Interleukin-10 (IL-10) – Regulates immune responses and contributes to chronic inflammation and tissue remodeling.

The persistence of these signals leads to excessive deposition of connective tissue, resulting in structural changes that impair normal organ function. If unchecked, fibrosis can cause irreversible damage and loss of function in affected tissues.

Causes

Fibrosis develops as a response to various stimuli, including:

• Chronic inflammation – Persistent immune activation due to autoimmune diseases or infections.
• Repeated tissue injury – Damage from toxins, radiation, or mechanical stress.
• Genetic predisposition – Some inherited conditions promote excessive fibrotic responses.
• Infections – Chronic infections like hepatitis C, tuberculosis, or schistosomiasis.
• Metabolic disorders – Conditions such as non-alcoholic fatty liver disease and diabetes mellitus.
• Environmental factors – Exposure to pollutants, smoke, or radiation.

Affected Organs and Conditions

Fibrosis can develop in virtually any organ system, with varying clinical consequences.

Pulmonary Fibrosis

Fibrotic changes in the lungs lead to decreased elasticity, impaired gas exchange, and progressive respiratory failure.

• Idiopathic pulmonary fibrosis (IPF) – Progressive and often fatal lung disease.
• Cystic fibrosis – A genetic disorder leading to excessive mucus production and lung damage.
• Radiation-induced pulmonary fibrosis – Scarring following radiation therapy.
• Sarcoidosis-associated fibrosis – Fibrotic lung disease secondary to chronic inflammation.

Hepatic Fibrosis

Liver fibrosis results from chronic liver damage and can progress to cirrhosis, leading to hepatic failure.

• Chronic hepatitis (B & C)
• Alcoholic liver disease
• Non-alcoholic fatty liver disease (NAFLD)
• Biliary fibrosis – Due to bile duct obstruction.

Cardiac Fibrosis

Heart fibrosis affects the myocardial tissue, reducing cardiac function and increasing the risk of arrhythmias and heart failure.

• Post-myocardial infarction fibrosis – Scarring after a heart attack.
• Hypertensive heart disease – Fibrosis due to chronic pressure overload.
• Endomyocardial fibrosis – A rare condition leading to restrictive cardiomyopathy.

Renal Fibrosis

Chronic kidney disease (CKD) is often associated with renal fibrosis, leading to the loss of functional nephrons.

• Diabetic nephropathy
• Hypertensive nephropathy
• Chronic glomerulonephritis

Neurological Fibrosis

• Glial scarring – Reactive fibrosis in response to brain or spinal cord injury.
• Multiple sclerosis – May involve fibrotic changes in chronic disease progression.

Dermatologic Fibrosis

• Keloids and hypertrophic scars – Overactive wound healing leading to excessive collagen deposition.
• Scleroderma – Systemic fibrosis affecting skin and internal organs.

Diagnosis

Fibrosis is diagnosed using a combination of clinical assessment, imaging, and tissue biopsy:

• Histopathology – Biopsy of affected tissue to examine collagen deposition.
• Imaging techniques:
• Magnetic resonance imaging (MRI) – Identifies tissue stiffness and structural changes.
• Computed tomography (CT) – Used for pulmonary and hepatic fibrosis.
• Ultrasound elastography – Measures liver stiffness in hepatic fibrosis.
• Blood biomarkers – Markers such as hyaluronic acid, collagen peptides, and TGF-β can indicate fibrotic activity.

Treatment

Fibrosis is difficult to reverse, but treatment focuses on controlling the underlying cause, reducing inflammation, and slowing disease progression.

Pharmacological Treatment

• Anti-fibrotic agents:
• Pirfenidone – Used in pulmonary fibrosis to slow collagen deposition.
• Nintedanib – A tyrosine kinase inhibitor that slows fibrosis progression.
• Corticosteroids and immunosuppressants – Reduce inflammatory responses in autoimmune-related fibrosis.
• Angiotensin receptor blockers (ARBs) – Help slow cardiac and renal fibrosis.

Lifestyle and Supportive Therapy

• Smoking cessation – Essential in pulmonary fibrosis.
• Nutritional support – Important for patients with liver or kidney fibrosis.
• Oxygen therapy – Helps manage advanced lung fibrosis.
• Physiotherapy and rehabilitation – Maintain mobility and function in fibrotic conditions affecting muscles and joints.

Surgical and Advanced Interventions

• Lung transplantation – Considered in severe cases of pulmonary fibrosis.
• Liver transplantation – The only definitive treatment for end-stage cirrhosis.
• Cardiac interventions – May include pacemakers or surgical correction in severe heart fibrosis.

Prognosis

The prognosis of fibrosis varies widely depending on the organ involved, severity, and response to treatment:

• Mild fibrosis may be reversible if the underlying cause is effectively managed.
• Moderate to severe fibrosis can lead to progressive organ dysfunction.
• End-stage fibrosis (e.g., cirrhosis, pulmonary fibrosis) may require transplantation.

See Also

• Fibroblast
• Scarring
• Chronic inflammation
• Extracellular matrix
• Wound healing

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