Page 65 - Textbook of Pathology, 6th Edition

found in programmed cell death of nematode worm virulent bacteria resulting in massive tissue necrosis. Thus, 49
Caenorabditis elegans. BCL-2 gene family is located in the outer the end-result of necrotising inflammation and gangrene is
mitochondrial membrane and includes both activators and the same but the way the two are produced, is different. The
inhibitors of apoptosis. Thus, it may regulate the apoptotic examples of necrotising inflammation are: gangrenous
process by binding to some related proteins (e.g. to BAX and appendicitis, gangrenous stomatitis (noma, cancrum oris).
BAD) for promoting apoptosis, or to BCL-XL for inhibiting There are 2 main forms of gangrene—dry and wet, and a
apoptosis. The net effect on the mitochondrial membrane is variant form of wet gangrene called gas gangrene. In all types CHAPTER 3
thus based on the pro-apoptotic and anti-apoptotic actions of gangrene, necrosis undergoes liquefaction by the action
of BCL-2 gene family. of putrefactive bacteria.
Besides BCL-2, the apoptotic pathway is partly also
governed by p53 molecule which promotes apoptosis. Dry Gangrene
iv) Cell death. The above mechanisms lead to proteolytic This form of gangrene begins in the distal part of a limb due
actions on nucleus, chromatin clumping, cytoskeletal to ischaemia. The typical example is the dry gangrene in the
damage, disruption of endoplasmic reticulum, mitochondrial toes and feet of an old patient due to arteriosclerosis. Other
damage, and disturbed cell membrane. causes of dry gangrene foot include thromboangiitis
obliterans (Buerger’s disease), Raynaud’s disease, trauma,
3. Phagocytosis. The dead apoptotic cells develop ergot poisoning. It is usually initiated in one of the toes which
membrane changes which promote their phagocytosis. is farthest from the blood supply, containing so little blood
Phosphatidylserine and thrombospondin molecules which that even the invading bacteria find it hard to grow in the
are normally present on the inside of the cell membrane, necrosed tissue. The gangrene spreads slowly upwards until Cell Injury and Cellular Adaptations
appear on the outer surface of the cells in apoptosis, which it reaches a point where the blood supply is adequate to keep
facilitate their identification by adjacent phagocytes and the tissue viable. A line of separation is formed at this point
promotes phagocytosis. The phagocytosis is unaccompanied between the gangrenous part and the viable part.
by any other inflammatory cells.
The mechanism of apoptosis is schematically represented MORPHOLOGIC FEATURES. Grossly, the affected part
in Fig. 3.31. is dry, shrunken and dark black, resembling the foot of a
mummy. It is black due to liberation of haemoglobin from
GANGRENE haemolysed red blood cells which is acted upon by
hydrogen disulfide (H S) produced by bacteria resulting
2
Gangrene is a form of necrosis of tissue with superadded in formation of black iron sulfide. The line of separation
putrefaction. The type of necrosis is usually coagulative due usually brings about complete separation with eventual
to ischaemia (e.g. in gangrene of the bowel, gangrene of limb). falling off of the gangrenous tissue if it is not removed
On the other hand, gangrenous or necrotising inflammation is surgically (Fig. 3.32).
characterised by primarily inflammation provoked by

Figure 3.31 Molecular mechanism of apoptosis.