Necrosis, Cell (Liquefactive, Coagulative, Caseous, Fat, Fibrinoid, and Gangrenous)


Article Author:
Rotimi Adigun
Hajira Basit


Article Editor:
John Murray


Editors In Chief:
Michael Labanowski


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
6/30/2019 11:44:09 AM

Introduction

Cell Necrosis

Irreversible injury to cells as a result of encounters with noxious stimuli invariably leads to cell death. Such noxious stimuli include infectious agents (bacteria, viruses, fungi, parasites), oxygen deprivation or hypoxia, and extreme environmental conditions such as heat, radiation, or exposure to ultraviolet irradiation. The resulting death is known as necrosis, a term that is usually distinguished from the other major consequence of irreversible injury, known as cell death by apoptosis. Apoptosis is a programmed or organized cell death which could be physiological or pathological. Additional information regarding this form of cell death is outside of the scope of this chapter. Necrosis as a form of cell death is almost always associated with a pathological process.

When cells die by necrosis, they exhibit two major types of microscopes or macroscopic appearance. The first is liquefactive necrosis, also known as colliquative necrosis, is characterized by partial or complete dissolution of dead tissue and transformation into a liquid, viscous mass. The loss of tissue and cellular profile occurs within hours in liquefactive necrosis. In contrast to liquefactive necrosis, coagulative necrosis, the other major pattern, is characterized by the maintenance of normal architecture of necrotic tissue for several days after cell death.

Liquefaction derives from the slimy, liquid-like nature of tissues undergoing liquefactive necrosis. This morphological appearance is attributable in part to the activities of hydrolytic enzymes which causes dissolution of cellular organelles in a cell undergoing necrosis. The enzymes responsible for liquefaction are derived from either bacterial hydrolytic enzymes or lysosomal hydrolytic enzymes.[1][2][3]

Other types of Necrosis

In addition to liquefactive and coagulative necrosis, the other morphological patterns associated with cell death by necrosis are:

  • Caseous Necrosis
  • Fat Necrosis
  • Gangrenous Necrosis
  • Fibrinoid necrosis

The other types of necrosis listed above do not represent distinct pathological entities. Rather, they are descriptive terms that are widely used to describe necrosis occurring in specific clinical scenarios or organ damage.

Coagulative

This is the default pattern of necrosis associated with ischemia or hypoxia in every organ in the body except the brain.[4][5]

  • Gross Appearance: tissue is firm and architecture is maintained for days after cell death.
  • Microscopic: Preserved cell outlines without nuclei.

Liquefactive

The pattern of necrosis seen with infections. Also, the pattern is seen following ischemic injury in the brain. While the reason for liquefactive necrosis following ischemic injury in the brain is poorly understood, the release of digestive enzymes and constituents of neutrophils is the reason for liquefaction in infections.[6][7]

  • Gross Appearance: The tissue is in a  liquid form and sometimes creamy yellow because of pus formation.
  • Microscopic: Inflammatory cells with numerous neutrophils.

Caseous

A unique type of cell death seen with tuberculosis.

  • Gross Appearance: White, soft, cheesy-looking (caseating) material
  • Microscopic: A uniformly eosinophilic center (necrosis) surrounded by a collar of lymphocytes and activated macrophages (giant cells, epithelioid cells). The entire structure formed in response to tuberculosis is known as a granuloma.

Fat Necrosis

Fat necrosis occurs from acute inflammation affecting tissues with numerous adipocytes such as pancreas and breast tissue. Damaged cells release digestive enzymes which break down lipids to generate free fatty acids.

  • Gross Appearance: Whitish deposits as a result of the formation of calcium soaps.
  • Microscopic: Anucleated adipocytes with deposits of calcium (Seen on H&E as areas of bluish stains).

Fibrinoid Necrosis

This is a pattern associated with vascular damage (autoimmunity, immune-complex deposition, infections (viruses, spirochetes, rickettsiae)).

  • Gross Appearance: Usually not grossly discernible.
  • Microscopic: Deposition of fibrin within blood vessels.

Gangrenous Necrosis

Clinical use, to describe ischemic necrosis of the lower limbs.(sometimes upper limbs or digits).

  • Gross Appearance: Black skin with varying degree of putrefaction.
  • Microscopic: Combination of coagulative necrosis, due to ischemia (dry gangrene); and liquefactive necrosis (wet gangrene) if a bacterial infection is superimposed.

These all represents morphological patterns which are visible grossly and microscopically. Fibrinoid necrosis is usually visible only microscopically. We discuss the characteristic gross and microscopic findings in liquefactive necrosis in subsequent paragraphs.

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.

Pearls and Other Issues

 

 

Enhancing Healthcare Team Outcomes

There are several types of necrotic processes that occur following injury or an infection. The final diagnosis of the type of necrosis is made by the pathologist. Sometimes patients may need to be referred to the surgeon or radiologist for aspiration or debridement of the necrotic tissues. Often radical debridement is required in cases of fournier gangrene and the patient and family should be notified about the possibility of a stoma. If time permits, a stoma nurse should visit patients who are about to undergo an abdominal procedure for gangrene or necrosis.


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Necrosis, Cell (Liquefactive, Coagulative, Caseous, Fat, Fibrinoid, and Gangrenous) - References

References

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Chung AG,Frye JB,Zbesko JC,Constantopoulos E,Hayes M,Figueroa AG,Becktel DA,Antony Day W,Konhilas JP,McKay BS,Nguyen TV,Doyle KP, Liquefaction of the Brain following Stroke Shares a Similar Molecular and Morphological Profile with Atherosclerosis and Mediates Secondary Neurodegeneration in an Osteopontin-Dependent Mechanism. eNeuro. 2018 Sep-Oct;     [PubMed]
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