The Sequence of Early Events

Abstract

A. Introduction When living tissues are injured, a characteristic series of changes follows in the small vessels and related tissues within the damaged area. The reaction in the first few hours is more or less independent of the nature of the noxious agent, the response being very similar after widely diverse types of injury. The sequence and interrelation of the complex dynamic changes that occur in the first few hours after injury can be appreciated fully only by examination ofliving transparent tissues. The changes seen in living preparations are the basic frame of reference with which information ac-quired by all other techniques-histological, ultrastructural, biochemical or pharma-cological-must be compared in order to determine its relevance to the morphology and mechanisms of the tissue response to injury. More than 100 years ago, ADDISON, WALLER, COHN HElM and others described in detail the essential features of the early stages of inflammation as seen in living transparent tissues, and subsequent studies using more sophisticated techniques have added little to their findings. The reactive changes that occur in the first few hours after sublethal injury involve, in varying degree, three processes: 1. Changes in the calibre of and flow in small blood vessels. 2. Increased vascular permeability, which leads to the formation of protein-rich exudate and to local oedema. There is a consequential increase in the volume and protein content of the lymph that drains from the injured area. 3. Escape of leucocytes from circulating blood into extravascular tissues. Eryth-rocytes may accompany the emigrating white blood cells. In milder injuries only a few red cells escape but after more severe stimuli there may be gross haemorrhage into the damaged tissues. Once this initial reaction to injury has developed, subsequent changes within the area of damaged tissue depend upon the severity, nature and duration of action of the injurious agent. If this is of brief duration or is rapidly and successfully overcome by the defence mechanisms of the host, the inflammatory changes will either resolve completely or subside leaving a variable amount of scar tissue within the injured area. However, many irritant stimuli are of much longer duration and tissue injury may continue beyond the period necessary for full development of the initial stages of the inflammatory reaction. In these circumstances the later changes within the injured area depend upon the nature of the noxious agent. Some types of persistent stimulus lead to massive continued polymorph migration and to suppuration (i.e. pus formation) within the damaged area; with other types oflong-acting stimulus the initial stages of inflammation are succeeded by a chronic granulomatous reaction. In the first part of the present chapter current knowledge of each of the three processes which together make up the early stages of the inflammatory reaction will be reviewed. This will be followed by an account of the phenomena involved in resolution of an area of inflammation and in pus formation. Granulomatous inflam-mation and the formation of scar tissue will be dealt with in Chapters 3 and 6 respectively.