FIGURE 4.1

Myocardial infarction. The posterior wall (top) is thinned and there is an area of yellow discoloration representing dead myocardium. A coronary artery (arrow) is seen; this is occluded by complicated atheroma.

FIGURE 4.2

Key targets of cellular injury. Individual agents may disrupt more than one subcellular compartment.

FIGURE 4.3

Overview of changes during the reversible and irreversible phases of cellular injury. Note that the precise point of no return is not fully established but loss of membrane integrity appears to be an important factor.

FIGURE 4.4

Role of reactive oxygen species in cellular injury. Several molecular structures are generated during cellular injury that can damage membranes, proteins and nucleic acids. A number of inherent antioxidant compounds are present within the cell to limit the damage. Cellular injury due to reactive oxygen species occurs when these normal defence mechanisms are overwhelmed. SOD = superoxide dismutase.

FIGURE 4.5

Simple fatty liver. Most of the hepatocytes contain pale droplets; in some cells this is a large single droplet, in others there are smaller droplets. In this case lipid accumulation in hepatocytes has occurred as a consequence of excess alcohol.

FIGURE 4.6

Neurofibrillary tangles in Alzheimer’s disease. Tau protein is seen in an astrocyte (arrow) and in a plaque (arrowhead). (Courtesy of Professor David Ellison.)

FIGURE 4.7

Common forms of necrosis. (A) Renal infarction. A well-defined area of renal parenchyma has undergone necrosis due to an embolus in a renal artery. (Courtesy of Dr Katrina Wood.) (B) Cerebral infarction. (Courtesy of Professor David Ellison.)

FIGURE 4.8

Other forms of necrosis. (A) Fibrinoid necrosis. In this artery there is accumulation of a fibrin-like substance (arrow) in the media. In this case it is part of a generalized systemic vasculitis. (Courtesy of Dr Katrina Wood.) (B) Caseous necrosis. This is granulomatous inflammation with degeneration at the centre of the lesion, a characteristic feature of tuberculosis. (Courtesy of Dr Fiona Black.) (C) Fat necrosis. In this case destruction of the peritoneal fatty tissue has resulted from the release of lipases following pancreatitis.

FIGURE 4.9

(A) Scheme of events in apoptosis. The accompanying electron micrographs in (B), (C) and (D) demonstrate the changes at an ultrastructural level. (B) Cellular shrinkage and blebbing. (C) Nuclear condensation. (D) Phagocytosis within a neighbouring cell whose own nucleus (N) is normal. The
boundaries of the phagosome are arrowed. (Courtesy of Professor Andrew Wiley.)

FIGURE 4.10

Labelling of nuclei in cells undergoing apoptosis (TUNEL method). In this case the injury has been induced in the liver during radiofrequency ablation of a tumour. (Courtesy of Dr Helen Robertson.)

FIGURE 4.11

Role of caspases in apoptosis. Note: the caspase system can be activated via a variety of routes. The common result is DNA fragmentation and disruption of the cytoskeleton. TNF = tumour necrosis factor; ROS = reactive oxygen species.

FIGURE 4.12

Cellulitis. Note: swelling and reddening of the skin. (Courtesy of Dr Clifford Lawrence.)

FIGURE 4.13

Overview of vascular changes in acute inflammation.

FIGURE 4.14

Exchange of fluid by extra-filtration across the wall of small blood vessels. HP and OP represent the difference between the hydrostatic and colloid osmotic pressures (mmHg) of plasma and extravascular space. The solid arrows indicate the net movement of fluid in and out of vessels along their length. The interrupted arrows indicate the direction of forces exerted by HP, OP and tissue pressure (TP). Upper figure, normal tissue: fluid movement across vessel wall approximates to equilibrium. Lower figure, acute inflammation: much more fluid leaves vessels than is returned to them. The values of HP and OP are approximations. In inflammation, HP may be less than indicated because of rise of TP and OP will also be reduced due to escape of plasma protein (via endothelial gaps) into the extravascular space which increases OP in the extravascular fluid (shown as 10 mmHg). The level of TP varies depending upon the nature of the tissue involved. In loose tissue TP will show no increase, whereas in tissues which are tightly tethered or have fibrous capsules TP can rise considerably (hence the question mark in this figure).

FIGURE 4.15

Margination of leucocytes, endothelial adhesion and leucocyte emigration. PECAM = platelet/endothelial cell adhesion molecule; ICAM intercellular adhesion molecule.

FIGURE 4.16

(A) Phagocytosis and killing of microorganisms. The microorganism is opsonized with antibody or complement. (B) The opsonized particle becomes attached to neutrophil membrane receptors for the opsonin. (C) Engulfment. (D) The opsonized microorganism is internalized into a phagocytic vacuole (phagosome). (E) Fusion of the lysosomes (primary granules) with the phagosome allows the discharge of lysosomal enzymes into the phagolysosome and triggers the respiratory burst which results in bacterial killing. (F) Lysosomal enzymes degrade the dead microorganism (G).

FIGURE 4.17

Electron micrograph of phagocytosis and killing of Staphylococcus aureus by a neutrophil: 1, 2 and 3 are the different stages of engulfment of the microorganisms, leading to their presence in a phagolysosome (4).

FIGURE 4.18

Pathways of intracellular killing of microorganisms.

FIGURE 4.19

(A) A dental abscess. (B) Photomicrograph of abscess cavity with accumulation of neutrophils and fibrin. (Courtesy of Dr Max Robinson.)

FIGURE 4.20

Chronic inflammation in a joint from a patient with rheumatoid arthritis. The inflammatory infiltrate includes lymphocytes and plasma cells with few neutrophils. (Courtesy of Dr Petra Dildey.)

FIGURE 4.21

A well-formed sarcoid granuloma. It is composed of epithelioid and giant cells with surrounding lymphocytes. The giant cell at the lower border contains an asteroid body (most often seen in sarcoidosis).

FIGURE 4.22

Mechanisms of pyrexia. PGE = prostaglandin E.

FIGURE 4.23

Formation of arachidonic metabolites. HPETE = cyclic hydroperodixes.

FIGURE 4.24

Outline of complement activation pathways.

FIGURE 4.25

Hageman-factor-dependent pathways. Activation of Hageman factor (coagulation factor XII) by contact with collagen results in the acquisition of protease activity which is able enzymatically to activate the coagulation system, the fibrinolytic system and the kallikrein–kinin system. Kallikrein, an enzyme which converts kininogen to kinin, also amplifies the system by activating for Hageman factor. Kininases I and II inactivate kinins rapidly.

FIGURE 4.26

Sequelae of acute inflammation.

FIGURE 4.27

Principal steps in biosynthesis of interstitial collagens: (A) 1, Synthesis of pro-α chains in rough endoplasmic reticulum; 2, aggregation of three pro-α chains; 3, hydroxylation of lysine and proline residues; 4, secretion of procollagen molecule; 5, cleavage of propeptides; 6, alignment of collagen molecules to form fibrils; 7, aggregation of fibrils to form collagen fibre, seen here in longitudinal section and showing regular crossbanding (B). N = nucleus; ER = endoplasmic reticulum.

FIGURE 4.28

Comparison of autocrine, paracrine and endocrine signalling.

FIGURE 4.29

Granulation tissue. Note parallel rows of capillaries surrounded by oedema and inflammatory cells, many of which are neutrophils.

FIGURE 4.30

Role of hepatic stellate cells in liver injury. Quiescent stellate cells contain abundant cytoplasmic lipid (vitamin A). In response to a number of cytokines, reactive oxygen species (ROS), proteins from dead hepatocytes and acetaldehyde, the cells proliferate, lose cytoplasmic fat and begin to resemble myofibroblasts. There is increased production of matrix proteins together with a reduction in activity of metalloproteinases which degrade the matrix. The net result is accumulation of collagen and other matrix proteins.

FIGURE 4.31

Outline of stages involved in healing of skin wounds, and comparison of primary and secondary intention.

FIGURE 4.32

Keloid scar after ear piercing. (Courtesy of Dr Clifford Lawrence.)

FIGURE 4.33

Fracture healing. This segment of rib was excised from a woman aged 22 years, who complained of a painful swelling in the chest wall, of a few weeks’ duration. The preoperative diagnosis was of a tumour of bone. (A) The gross specimen shows an irregular fracture line involving both cortices and the medullary canal. The fracture is bridged by periosteal callus, which is particularly marked on the superior surface. (B) Histological examination shows that the periosteal callus consists of arcades of reactive bone and a mass of cartilage overlaying the fracture line. There is also callus within the medullary canal. At this relatively early stage of fracture healing, the fracture gap remains unrepaired.