Life Transitions: Necrosis

LIFE TRANSITIONS: NECROSIS

1.0 Introduction

Death of cells in the animal body may either occur normally or pathologically (caused by disease). There are three distinct modes of cell death, Necrobiosis, Apoptosis, and Necrosis. The first two are considered as a homeostatic (the ability or tendency of an organism or cell to maintain internal equilibrium by adjusting its physiological processes) mechanism of the body in controlling cell population, renewal of cells, and in the process of “improving” organs. Necrosis is the term used for the un-programmed death of tissue. Apoptosis and Necrobiosis are programmed cell-deaths. Necrosis is not reversible. The causes of Necrosis may be internal or external, and there are various types of Necrosis, some of which are:

• Coagulative Necrosis

• Avascular Necrosis

• Ischemic Necrosis

• Osteonecrosis

• Aseptic Necrosis

• Liquefactive Necrosis

• Caseous Necrosis

• Fat Necrosis

• Fibrinoid Necrosis

• Zenker Necrosis

• Gangrenous Necrosis

• Acral Necrosis

• Arteriolonecrosis

• Central Necrosis

2.0 Necrobiosis: Group Culling

Necrobiosis is programmed cell death. It is the death of a part by molecular disintegration and without loss of continuity, as in the processes of degeneration and atrophy. This is, however, a normal series of events in a cell leading it to termination. Notably, cancer cells avoid this process.

Necrobiosis occurs in adults as part of a normal cell renewal. For example:

In Blood:

Red blood cell turnover process starts when the haemoglobin molecules begin to precipitate and new haemoglobin cannot be synthesised. The marrow, to replace the dying red blood cells, produces new red blood cells with new haemoglobin.

In the Intestines:

The cells which are continually produced in the epithelium (the membranous tissue covering the internal organs and other internal surfaces of the body) of the crypts, which is the site of stem cell proliferation, shed 3~5 days later at the tips of the villi (intestinal cover).

In Skin:

Keratin is the primary protein of skin, hair and nails. The process of keratinisation is where the cells become filled with keratin. During this process the nuclei degenerates, and the cell scales off from the skin surface.

2.1 Necrobiosis Lipoidica (NL)

Originally known as Necrobiosis Lipoidica Diabeticorum, NL was found to be characteristic with diabetes patients. NL is a degenerative disease of the connective tissue in the skin. In 1935 NLD was renamed to NL as the first case of NL was reported in a non-diabetic patient. NL is a disorder of collagen degeneration with a granulomatous response (small or granular nodular inflammatory lesions), thickening of blood vessel walls, and fat deposition. The exact cause of NL is unknown. Some theories focus on trauma, inflammatory or metabolic changes. NL is often associated with diabetes mellitus, type 1 being a severe, chronic form of diabetes caused by insufficient production of insulin, and resulting in abnormal metabolism of carbohydrates, fats and proteins. The symptoms consist of oval plaques, usually on the lower legs. It may start as small red spots or raised areas, which develop a shiny, porcelain-like appearance. The plaques often turn a light colour due to extracellular fat (the “lipoidica”). They are often itchy or painful. Typically the spots turn a brownish colour, which fades slowly but is permanent. NL is considered to be a warning sign of diabetes. More than half of people with NL have diabetes. NL does not lead to gangrene.

3.0 Apoptosis: Single Culling

Apoptosis is defined as the ability of a cell to respond to stimuli by initiating pathways that lead to its death by a defined set of reactions. The process involves the disintegration of cells into membrane-bound particles that are then eliminated by phagocytosis (ingestion of micro-organisms) or by shedding. Its initiation is governed by chemical signals a cell receives from its neighbours, it uses specialised cellular machinery to kill itself; a cell suicide mechanism that enable metazoans (multicellular organism, contrary to the unicellular organism protozoan) to control cell number and eliminate cells that threaten the animal’s survival. The way the apoptotic process is executed facilitates the safe disposal of cell corpses and fragments. When this programmed cell death is interrupted, allowing cells to grow unchecked, the result may be a cancerous tumour.

Apoptosis may occur normally in several processes that include the following:

• Embryonic morphogenesis-

The developmental processes by which defined structures within an embryo are generated, such as the deletion of interdigital tissue in developing chicks

• Metamorphosis-

The process of changing body forms, like the deletion of the tail in a tadpole as it matures into a frog. In metamorphosis the differentiation of human fingers in a developing embryo requires the cells between the fingers to initiate apoptosis so that the fingers can separate.

• Mature tissue homeostasis-

The tendency in an organism towards maintenance of physiological stability, as in the remodelling of the uterus after a pregnancy.

• Involution of adult tissue-

Like thymic involution, the regression of the human thymus (the �chest’ behind the breastbone).

• Pathological states-

As