Necrosis - Pathophysiology, Morphology, and Treatment

What Is Necrosis?

Necrosis is the death of cells in the body due to irreversible injury caused by stimuli like injuries and infections caused by bacteria, viruses, fungi, parasites, and diseases. Lack of oxygen and blood flow to an organ also results in necrosis. Environmental conditions like heat, radiation, and exposure to ultraviolet rays also cause necrosis. Cell death in necrosis is always a pathological process. Once the tissue dies, it can only be removed and can never be returned to normal condition. The process of necrosis cannot be controlled, and it causes swelling of the cell organelles, rupture of the plasma membrane, and cell lysis, resulting in leakage of cellular content into the external surroundings.

What Is the Pathophysiology of Necrosis?

• Liquefactive Necrosis - The main reason for liquefactive necrosis is the digestion of cellular debris and surrounding tissue by enzymes. Infections from bacteria, viruses, fungi, and parasites cause inflammatory reactions. The digestive enzymes cause the degradation and digestion of healthy cells. Lysosomes contribute to cellular dissolution. Proteases, DNAases, and lysosomal enzymes cause cellular liquefaction. In liquefactive necrosis, cellular digestion begins immediately, and the cell digestion process is through autolysis and heterolysis.

• Coagulative Necrosis - Hypoxia damages the enzymes of cells that undergo ischemic necrosis; hence, digestion of the cells is by enzymes and inflammatory cells released by an outside agent (heterolysis). This explains the late onset of the cellular degradation process in coagulative necrosis. Autolysis or self-digestion is impossible in coagulative necrosis as the enzymatic component of the cell gets destroyed due to a lack of oxygen.

• Caseous Necrosis - The necrosis pattern is seen in tuberculosis. In tuberculosis, epithelioid cells and giant cells form due to macrophage activation since the bacteria is moderately resistant to the phagocytic process carried out by tissue macrophages. Once the giant cells are formed, more macrophage and inflammatory cells invade the infected site resulting in increased cytokine production and the slow disintegration of the mycobacterium. The lipid substances on the cell wall give a cheese-like appearance and are called caseous necrosis.

• Fat Necrosis - Fat necrosis occurs due to the death of adipose tissue due to any injury or trauma. It is a slow process, and as the necrosis progresses, changes in the skin texture of the fat tissues are noticeable. The enzymes that contribute to fat necrosis are lipases and amylases. Pancreatitis (pancreas inflammation) is caused by alcohol, gallbladder stone, and poisoning. Fat necrosis can also be seen in the breast tissue due to trauma.

• Fibrinoid Necrosis - Endothelial cell damage occurs, resulting in the secretion of plasma proteins, mainly fibrin. Fibrinoid necrosis does not have a detectable macroscopic or gross appearance.

• Gangrenous Necrosis - It is not a true pathological necrosis; instead, it can be used to describe coagulative necrosis if it is dry gangrene or liquefactive necrosis if it is wet gangrene.

What Is the Morphology (Microscopic and Macroscopic Appearances) Of Necrosis?

Coagulative Necrosis - The main reason for coagulative necrosis is ischemia or hypoxia. Coagulative necrosis is seen in the necrotic process of all organs due to hypoxia (decreased oxygen supply) or ischemia (decreased blood flow) except the brain. The cell structure is preserved.

1. Macroscopic Features - Tissue appears firm, and tissue structure is maintained for longer.

2. Microscopic Features - Cells appear without a nucleus (anucleate cells), appearing eosinophilic, and the cellular structure is intact.

Liquefactive Necrosis - Liquefactive necrosis is mainly seen in infections. However, it is also the necrotic pattern in brain injury due to ischemia. The cellular structure is lost, and the tissue becomes a liquid mass due to digestion by hydrolytic enzymes.

1. Macroscopic Features - Pus formation is observed in the affected tissue. The affected tissue changes into liquid form. They appear creamy yellow due to pus formed in the tissue.

2. Microscopic Features - Inflammatory cells (mast cells, lymphocytes, eosinophils, etc.) with abundant neutrophils are seen in the affected tissue.

Caseous Necrosis - It is a type of cell death where the tissue or the cells appear like cheese and hence the name caseous.

1. Macroscopic Features- The affected area is white and has a cheese-like appearance, also known as caseating material. Granuloma formation is seen.

2. Microscopic Features - The cells have a necrotic center which is eosinophilic in appearance. The macrophages are activated at the site of infection and turn into giant cells and epithelioid cells. The lymphocytes and the activated macrophages encircle the eosinophilic necrotic center.

Fat Necrosis - Fat necrosis is mainly seen in organs with surplus fat cells or adipocytes, like the pancreas and breast tissue. Enzymes released due to cellular degradation cause lipids to break into fatty acids. The fat cells mix with calcium and give a chalky white appearance, also known as saponification.

1. Macroscopic Features - Appears as white deposits due saponification process.

2. Microscopic Features - Fat cells without a nucleus are seen. Deposits of calcium are seen in the tissue and stains blue in H&E (hematoxylin and eosin) staining.

Fibrinoid Necrosis - Fibrinoid necrosis is seen in blood vessels. The immune complexes are deposited along the walls of the blood vessels leading to fibrin leakage. The affected tissue stains pink in H&E (hematoxylin and eosin) staining.

1. Macroscopic Features - Macroscopic features are not commonly seen as it affects mainly the blood vessels.

2. Microscopic Feature - Fibrin deposition in the blood vessels is observed.

Gangrenous Necrosis - It is mainly used to describe the necrosis in the lower extremities caused due to ischemia (decreased blood supply). It is rarely seen in the upper extremities and the fingers.

1. Macroscopic Features - The skin shows signs of decomposition and degradation and appears black.

2. Microscopic Features - Microscopic features of coagulative and liquefactive (if pus formation is present) necrosis are seen.

What Is the Treatment of Necrosis?

• Antibiotic Management - Antibiotic treatment is given to treat the infections and post-surgery.

• Surgical Management - Surgical treatment is often indicated in necrosis and involves abscess drainage, wound debridement, and in the worst scenario, amputation of the affected area.

• Management of Ischemia and Stroke - Coagulative necrosis due to ischemia seen in myocardial infarction needs emergency medical intervention. Obstruction is removed from the coronary arteries for proper blood supply. Stroke management needs a multi-disciplinary approach. Factors like the risk of occurrence and rehabilitation period are considered before starting the treatment.

• Management of Caseous Necrosis - A treatment plan for tuberculosis is followed. Combination of antibiotics is prescribed, and regular clinical and laboratory monitoring is done.

• Management of Gangrenous Necrosis - Surgical debridement and antibiotic therapy are the treatment of choice.

Conclusion

The necrotic process occurs due to an infection or injury. Knowledge about the various types of necrosis helps to identify the cause of necrosis and thus execution of the treatment plan accordingly. Sometimes a surgeon or a specialized doctor is required to perform the debridement or aspiration of the necrotic tissues. In addition, necrosis is often the result of an inflammatory response, and hence research on the response of anti-inflammatory drugs to necrosis should be done extensively.