Cell Liquefactive Necrosis

Etiology

Patterns of necrosis (liquefactive or coagulative) are determined by the cause of cell death, organ affected, and duration of cell death.

Liquefactive necrosis is a pattern of cell death caused by several etiological factors. 

The major causes of liquefactive necrosis are:

In all solid organs of the body:

• Infectious agents (bacteria, fungi, viruses, parasites)

In the brain

• Infectious agents
• Hypoxia/Ischemia (the occurrence of liquefaction as a pattern of necrosis in response to hypoxic injury in the brain is an exception to observed findings in the rest of the body. Tissues in all other mammalian body systems usually undergo cell death by coagulative necrosis in response to hypoxia. The reason for this difference is poorly understood).

Pathophysiology

Liquefactive Necrosis

Three major factors contribute to liquefactive necrosis:

1. Enzymatic digestion of cellular debris in dead or dying tissues.
2. Enzymatic digestion of surrounding tissues.
3. Denaturation of cellular proteins.

Because infectious agents are rich in digestive enzymes and likely to elicit an inflammatory response, they can bring about the process of cellular digestion rapidly. This manifests as liquefactive necrosis. Cellular dissolution and digestion are brought about by several enzymes some from the infecting organism and some from the lysosome of the dying cells.

Enzymes involved in liquefaction includes:

• Proteases (Collagenases, elastases),
• DNases
• Lysosomal enzymes

Coagulative Necrosis

A major difference between liquefactive and coagulative necrosis is the fact that in liquefactive necrosis, the enzyme system of the necrotic tissue is intact and can commence the process of cellular digestion almost immediately via autolysis. In addition to self-digestion (autolysis), heterolysis occurs as a result of a release of enzymes and inflammatory cells from the invading organism.

In coagulative necrosis, cellular digestion is principally dependent on heterolysis since a hypoxic injury would have damaged the enzymes of the cell undergoing ischemic necrosis. This partly explains the late onset of digestion and removal of dead tissues in this type of necrosis.

Caseous Necrosis

This pattern is almost unique to tuberculosis. Certain fungi can also exhibit caseous necrosis. In tuberculosis, the organism is partially resistant to digestion and phagocytosis by tissue macrophages, and this leads to activation of the macrophages to form giant cells and epithelioid cells. This sets off several steps which lead to recruitment of more macrophages and inflammatory cells and production of cytokines and slow degradation of the mycobacteria. Mycolic acid and other lipid constituent of the mycobacteria cell wall confers a characteristic "cheese-like" appearance on the tubercle of tuberculosis hence the descriptive term,"caseous."

Fat Necrosis

The release of lipases and amylases from the pancreatic cells is the major trigger for fat necrosis in the pancreas. This processed is usually triggered by several factors leading to inflammation of the pancreas, otherwise known as pancreatitis. Causes of acute pancreatitis include alcohol, gall bladder stones, poisoning, and insect bites. Since fat necrosis in the pancreas is triggered by an inadvertent release of enzymes, this process is also referred to as enzymatic fat necrosis. Breast tissues can also give rise to fat necrosis. The trigger for this is usually trauma.

Fibrinoid Necrosis

This is a pattern which not grossly discernible but can be seen microscopically. Fibrinoid necrosis is a pattern of cell death characterized by endothelial damage and exudation of plasma proteins (especially fibrin).

Gangrenous Necrosis

See description in the introduction above. Not a true pathological type, rather, it is a clinical term describing coagulative necrosis (dry gangrene) or sometimes liquefactive necrosis (wet gangrene) affecting the extremities.

History and Physical

Clinical Examples of  Necrosis

Infections

• Abscesses (brain, lungs, liver, skin)
• Lung infections
• Skin Infections
• Wet Gangrene
• Fournier's gangrene
• Brain abscess

Hypoxic Injury

Cerebrovascular accident (Stroke) (liquefactive necrosis)

Acute Tubular Necrosis (Kidneys) (coagulative necrosis)

Acute Myocardial infarction (coagulative necrosis)

Evaluation

Appropriate history and physical examination findings would guide diagnosis and management including which evaluation studies to order.

Liquefactive necrosis closely mirrors acute inflammation and response to an infectious process. The only exemption is in the brain where liquefaction may occur in response to ischemia.

Evaluation and management are geared toward effective clinical management which could be medical with either antibiotics or surgical management.

Hypoxic injury is the cause of coagulative necrosis. Re-establishment of blood flow or oxygen supply is reperfusion. This is important for management. Hence, for this pattern of tissue damage, studies such as Doppler ultrasound are useful to determine blood flow.

Useful evaluation includes:

• Physical examination, including monitoring vital signs
• Laboratory investigations such (complete blood count, blood culture, urine culture, urinalysis)
• Imaging studies such as x-Rays
• Venous Doppler Scan
• CT
• Blood electrolytes

Treatment / Management

Management of Infectious Processes

Antibiotics are the mainstay of managing infectious processes.[8][9][10]

The choice of antibiotic would be guided by clinical findings and antibiotic susceptibility.

Surgical management is also often indicated and includes:

• Drainage of abscesses
• Wound debridement
• Amputation

Management of Ischemic Processes/Stroke  

• Myocardial infarction is the prototype example of coagulative necrosis which requires urgent management. Early removal of the obstructive lesions in the coronary arteries is a very important step in the management of myocardial infarction. This is usually achieved medically or by an invasive procedure.

• Stroke management is a multi-disciplinary, multi-specialist effort which should take into consideration several factors including, the extent of residual damage, risk of reoccurrence and the rehabilitative needs of the patient.

Management of Caseous Necrosis

This requires standard management for tuberculosis, including the use of combination antibiotics and close laboratory and clinical monitoring.

Management of Gangrenous Necrosis

This is a serious medical and surgical situation which requires antibiotics and sometimes necessitates the removal of dead tissues (debridement). In severe, life-threatening cases, an amputation may be required.

Differential Diagnosis

• Complex regional pain syndrome

• Inflammatory synovitis

• Osteoarthritis

• Osteomyelitis

• Soft tissue trauma (e.g., Labral tear)