A Brief Overview of Necrosis

Necrosis

I

 first learned about necrosis in my cell injury lectures during our Pathogenesis unit. Cell injury is so wildly vast and complex with necrosis making up just one part of it! Today, I’ll be giving you a broad overview of necrosis… let’s talk about cell death!

Before we discuss necrosis, what is CELL INJURY?

Cell injury is a pathological process where the cell can no longer maintain homeostasis and respond to functional demands. It can be either reversible or irreversible, the latter being lethal and resulting in cell death; this is what we call necrosis.

What is necrosis?

Necrosis is irreversible cell death.

It differs from reversible cell death in that membranes are damaged, including membranes surrounding organelles. The damaged plasma membrane triggers an influx of Ca²⁺ into the cell and mitochondria. This disturbs ATP production, causes cytoskeletal changes, and activates phospholipases which further exacerbates damage to cell membranes.

Having an intact membrane and enough ATP are absolutely crucial to the survival of a cell. If you were to differentiate irreversible from reversible cell death, it would probably be the interplay between excessive Ca²⁺, membrane damage, and a reduction in ATP which is the underlying cause of irreparable cell damage.

What causes necrosis?

It can be caused by a myriad of things from bacterial and fungal infections to obstructions in vessels restricting blood flow. Sure, these things can all cause cell injury but in order for the injury to progress to a necrotic level, it needs to have passed the sub-lethal stages (reversible). Cells will try to adapt to the injury but when their adaptive capacity is not enough, they’ll reached the point of no return – irreversible cell death… necrosis.

So if you wanted to get to the bottom of the fundamental cause of necrosis, it would be just as explained before. A reduction in ATP interrupting membrane functions which then causes Ca²⁺ to flood into the cells and the mitochondria, damaging the cells to the point of no return.

Necrosis, oncosis, or apoptosis?

Let’s clear up some confusion…

Strictly speaking, necrosis should be an umbrella term overarching both apoptosis and oncosis. Apoptosis refers to the ‘neat’ programmed cell death whereas oncosis is the ‘messy’ cell death. However, when you hear necrosis today, it’s usually just referring to oncosis, with apoptosis being referred to on its own. In this article, we’ve been discussing oncosis, but like most people, we’ve been calling it necrosis.

What does necrosis look like?

In reversible cell injury, there’s general swelling and the nuclear chromatin condenses but the nucleus stays intact. In necrosis, however, the nucleolus is lost and the nucleus degrades in one of three ways:

              Pyknosis – nucleus shrinks

              Karyorrhexis – nucleus fragments

              Karyolysis – nucleus lyses

Furthermore, you’ll see:

•  All membranes damaged!
•  Clumped chromatin
•  Mitochondrial swelling
•  No ribosomes
•  Lysed endoplasmic reticulum
•  Lysosome autolysis
•  Cytoplasm swollen, more eosinophilic
•  Myelin figures (rolled-up phospholipid entities from defective cell membrane)

             

And macroscopically…

             

•  Surrounded by inflammation
•  Tissue swollen and paler
•  Malacia (softened tissue)

What are the 6 types of necrosis?

Coagulative

The cellular detail is gone but the general tissue architecture is maintained. It basically looks like the eosinophilic version of the original cells. Mostly from ischaemia (shortage of blood supply).

Liquefactive

Cellular detail and tissue architecture are gone. Malacia is evident (softened tissue). Mostly from bacterial infections.

Caseous

Overlapping between coagulative and liquefactive. Characterised by cheesy, soft, and pasty tissue. Cheese anyone?

Fat

Lipases are present in adipose tissue and free fatty acids precipitate as calcium soaps in a process called saponification. Evident as yellowish-white nodules.

Gangrenous

Ischaemic (restricted blood supply) necrosis where a dry gangrene is coagulative (tissue architecture still there) and a wet gangrene is liquefactive (tissue architecture lost).

Fibrinoid
Where there's fibrin-like deposits.

What is ischaemia?

Ischaemia is the shortage of blood supply to tissues. The lack of blood flow and oxygen results in an infarct. Infarcts are lesions of necrotic tissue that have died due to the inadequate blood supply. They can appear white or red depending on the affected tissue. We know that an infarct is irreversible because the tissue is necrotic – there is no returning!

So that’s a bite-sized overview on necrosis (maybe more than a bite? haha). Be sure to check out the mind-map below and head to the Vocab page for any terminology you might be unsure of!

See you in my next article Xx

Source:
Higgins, D 2019, AVBS2001 Introduction to Veterinary Pathogenesis, lecture: Cell Injury/Degeneration, lecture PowerPoint slides, The University of Sydney