Chapter 2 Inflammation and Repair
2-1: Signs of acute inflammation. The patient has erysipelas of the face due to group A streptococcus. Signs of acute inflammation that are present in the photograph include redness (rubor) and swelling (tumor). The infection is associated with warm skin (calor) and pain (dolor).
(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 37, Fig. 1-106.)
2-3: Acute inflammation. Histologic section of lung in bronchopneumonia showing sheets of neutrophils with multilobed nuclei.
(From Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 182, Fig. 8-8.)
2-4: Oxygen-dependent myeloperoxidase system. A series of biochemical reactions occurs in the phagolysosome, resulting in the production of hypochlorous free radicals (bleach; HOCl•) that destroy bacteria. Fe2+, reduced iron; GSH, reduced glutathione; G6-P, glucose 6-phosphate; GSSG, oxidized glutathione; H2O2, peroxide; MPO, myeloperoxidase; NADP, oxidized form of nicotinamide adenine dinucleotide phosphate; NADPH, reduced nicotinamide adenine dinucleotide phosphate; OH•, hydroxyl free radical; 6PG, 6-phosphogluconate; SOD, superoxide dismutase.
Chronic granulomatous disease (CGD) is an X-linked recessive (XR) disorder (65% of cases) or autosomal recessive disorder (35% of cases). The X-linked type is characterized by deficient NADPH oxidase in the cell membranes of neutrophils and monocytes. The reduced production of O2•¯ results in an absent respiratory burst. Catalase-positive organisms that produce H2O2 (e.g., Staphylococcus aureus) are ingested but not killed, because the catalase degrades H2O2. Myeloperoxidase is present, but HOCl• is not synthesized because of the absence of H2O2. Catalase-negative organisms (e.g., Streptococcus species) are ingested and killed when myeloperoxidase combines H2O2 with Cl− to form HOCl•. Granulomatous inflammation occurs in tissue, because the neutrophils, which can phagocytose bacteria but not kill most of them, are eventually replaced by cells associated with chronic inflammation, mainly lymphocytes and macrophages. Macrophages fuse together to form multinucleated giant cells. Patients have severe infections involving lungs, skin, visceral organs, and bones. The classic screening test for CGD is the nitroblue tetrazolium (NBT) test. In this test, leukocytes are incubated with a colorless NBT dye, which is converted to a blue color if the respiratory burst is intact. This test has been replaced by a more sensitive test involving oxidation of dihydrorhodamine to fluorescent rhodamine. Bone marrow transplantation is the treatment of choice for the XR type of CGD.
Myeloperoxidase (MPO) deficiency, an autosomal recessive disorder, differs from CGD in that both O2•¯ and H2O2 are produced (normal respiratory burst). However, the absence of MPO prevents synthesis of HOCl•.
2-5: Arachidonic acid metabolism. Arachidonic acid is released from membrane phospholipids. It is converted into prostaglandins (PGs), thromboxane A2 (TXA2), and leukotrienes (LTs).See text for further discussion.
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