A hypothesis on the pathogenesis of rheumatoid and other non-specific synovitides. IV A. The possible intermediate role of local hypoxia and metabolic alterations

Med Hypotheses. 1984 Mar;13(3):257-302. doi: 10.1016/0306-9877(84)90162-2.


According to the original hypothesis, synovial tissue (ST) oedema and synovial fluid (SF) volume increase contribute to local hypoxia and metabolic alterations and to inflammation (A 1). Studies on biochemical mechanisms (A 2) in synovitides show that the SF volume correlates to SF hypoxia that correlates to lactate increase, acidosis and to some decrease in glucose. Normal ST produces lactate by glycolytic and pentose phosphate pathway activity, both, as well as the normally low oxygen utilization, being increased in synovitides . In ST very little carbohydrate seems to pass directly into the citric acid cycle and oxidation of fat may be involved, but it is not known if the fat is carried to ST by the blood or if it is synthetized locally (B). ST oedema and effusions may be most important as causes of local hypoxia (C). Acidosis alters physico-chemical properties of proteins, possibly changing their chemotactic and antigenic qualities, etc. Hypoxia and fuel supply might be related to fibroblast, macrophage and neutrophil reactions, and, in view of the high metabolic demands of villi, they may contribute to, e.g., ST necroses, and to erosions (D). I shall summarize some essentials of my present views on the pathogenesis (E 1 a) and causes in single cases (E 3 b) of synovitis, and comment on two other new hypotheses on rheumatoid arthritis (E 2) and on therapeutic (E 4) and other implications of this concept (E).

MeSH terms

  • Acidosis / metabolism
  • Animals
  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / metabolism
  • Cartilage, Articular / metabolism
  • Citric Acid Cycle
  • Fatty Acids / metabolism
  • Gluconeogenesis
  • Glycolysis
  • Humans
  • Hypoxia / metabolism*
  • Lipolysis
  • Oxidative Phosphorylation
  • Pentosephosphates / metabolism
  • Rheumatic Diseases / etiology*
  • Rheumatic Diseases / metabolism
  • Synovial Fluid / metabolism
  • Synovial Membrane / metabolism
  • Synovitis / etiology*
  • Synovitis / metabolism


  • Fatty Acids
  • Pentosephosphates