The 'big picture'
- Medzhitov R. Origin and physiological roles of inflammation. Nature 2008; 454:428-435
- Ashley NT, Weil ZM, Nelson RJ. Inflammation: mechanisms, costs, and natural variations. Annual Review of Ecology, Evolution and Systematics 2012; 43:385-406
- Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. Journal of Leukocyte Biology 2007; 81:1-5
- Tracey KJ. The inflammatory reflex. Nature 2002; 420:853-859
pathophysiology of inflammation videos
animations of the inflammatory response
The cardinal signs of acute inflammation are depicted in this cartoon. They are redness (rubor), warmth (calor), swelling (tumour), and pain (dolor). Loss of function (functio laesa) is also often included in this list of signs.
The pathophysiological basis and consequences of fever is described in this article.
This image of cellulitis clearly shows the clinical signs of redness and swelling of the left leg compared with the right. If you could examine this leg you would be able to feel that it was warm to the touch, and the patient would be able to tell you that it was painful to touch, and walk.
Other images of acutely inflamed tissues/ structures can be found here:
cells involved in inflammation
The principal cell involved in the acute inflammatory process is the neutrophil , a type of white blood cell.
Interesting articles describing the functions of neutrophils include:
- Nauseef WM, Borregaard N. Neutrophils at work. Nature Immunology 2014; 15:602-611
- Amulic B, Hayes G. Neutrophil extracellular traps. Current Biology 2011; 21:R297-298
- Yang F, Feng C, Zhang X, Lu J, Zhao Y. The diverse biological functions of neutrophils, beyond the defense against infections. Inflammation 2017; 40:311-323
Collections of living and dead neutrophils, dead tissue debris (with or without microorganisms) is called an abscess.
The principal cell involved in the chronic inflammation process is the macrophage (another type of white blood cell).
Interesting articles about the functions of the macrophage include:
- Epelman S, Lavine KJ, Randolph GJ. Origin and functions of tissue macrophages. Immunity 2014; 41:21-35
- Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nature Reviews. Immunology 2005; 5:953-964
Neutrophils and macrophages are phagocytes - they can ingest microbes by an active process called phagocytosis (as depicted in the 'Epic Bob' video).
Myeloid cells - including neutrophils and monocytes/macrophages - can also participate in the inflammatory process by activation of so-called inflammasomes. Interesting articles about inflammasomes include:
- Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annual Review of Immunology 2009; 27:229-265
- Singhal G, Jaehne EJ, Corrigan F, Toben C, Baune BT. Inflammasomes in neuroinflammation and changes in brain function: a focused review. Frontiers in Neuroscience 2014; 8:1-5 (article 315)
- Sharma D, Kanneganti TD. The cell biology of inflammasomes: mechanisms of inflammasome activation and regulation. Journal of Cell Biology 2016; 213:617-629
Innate lymphoid cells and Natural killer cells are also important cellular constituents of the inflammatory process and interesting articles about these cells include:
- Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nature Immunology 2008; 9:503-510
- Mandal A, Viswanathan C. Natural killer cells: In health and disease. Haematology/ Oncology and Stem Cell Therapy 2015; 8:47-55
- Fuchs A. ILC1s in tissue inflammation and infection. Frontiers in Immunology 2016; 22:104
inflammation and the cardiovascular system
Atherosclerosis is an inflammatory process. Interesting articles on atherosclerosis, acute coronary syndromes, and the complications of this disease process include:
- Libby P, Tabas I, Fredman G, Fisher EA. Inflammation and its resolution as determinants of acute coronary syndromes. Circulation Research 2014; 114:1867-1879
- Ridker PM. Targeting inflammatory pathways for the treatment of cardiovascular disease. European Heart Journal 2014; 35:540-543
- Prabhu SD, Frangogiannis NG. The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis. Circulation Research 2016; 119:91-112
Other inflammatory conditions affecting the cardiovascular system include:
- myocarditis (Elamm C, Fairweather D, Cooper LT. Pathogenesis and diagnosis of myocarditis. Heart 2012; 98:835-840), and
- endocarditis (Cahill TJ, Prendergast BD. Infective endocarditis (Seminar). Lancet 2016; 387:882-893)
An interesting article on the possible link between inflammation and venous thrombosis can be found here (Piazza G, Ridker PM. Is venous thromboembolism a chronic inflammatory disease? Clinical Chemistry DOI: 10.1373/clinchem.2014.234088)
inflammation and the lungs
Pneumonia (van der Poll T, Opal SM. Pathogenesis, treatment, and prevention of pneumococcal pneumonia. The Lancet 2009; 374:1543-1556)
Inflammation in the lungs causing acute pneumonitis, and pneumonia, can follow breathing-in oral, or gastric content (and is called aspiration pneumonitis/ pneumonia).
Microscopic images of aspiration pneumonia can be found here and here. An interesting article on this topic can be found here (DiBardino DM, Wunderink RG. Aspiration pneumonia: a review of modern trends. Journal of Critical Care 2015; 30:40-48).
Viral pneumonia is discussed here (Yoo J-K, Kim TS, Hufford MM. Viral infection of the lung: host response and sequelae. Journal of Allergy and Clinical Immunology 2013; 132:1263-1276) and here (van der Sluijs KF, van der Poll T, Lutter R, Juffermans NP, Schultz MJ. Bench-to-bedside review: Bacterial pneumonia with influenza - pathogenesis and clinical implications. Critical Care 2010; 14:219).
inflammation, metabolic disorders and cancer
An interesting article on the possible links between inflammation and metabolic disroders can be found here (Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006; 444:860-867).
Associations between inflammation and cancer are discussed in an article which can be found here (Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008; 454:436-444).
sepsis - clinical definitions
Articles discussing new clinical definitions of sepsis include:
- Consensus definitions for sepsis and septic shock
- Sepsis gets an upgrade
- Sepsis definitions and problems
- Batman, the sofa, and the latest sepsis guidelines
- What is qSOFA?
- New guidelines don't fix what isn't broken
You might also find the following article interesting: Alverdy J, Krezalek MA. Collapse of the microbiome, emergence of the pathobiome, and the immunopathology of sepsis. Critical Care Medicine 2017; 45:337-347. The authors are critical of the term 'sepsis' (and advocate a new term, nonresolving organ dysfunction syndrome - nRODs) as well as emphasise emerging research findings relating to the role of the microbiome (and pathobiome) in critical illness.
Sepsis awareness videos and NHS National Early Warning Score
- Life in the Fast Lane - sepsis pathophysiology
- Cohen J. The immunopathogenesis of sepsis. Nature 2002; 420:885-891
- Annane D, Bellissant E, Cavaillon J-M. Septic shock. The Lancet 2005; 365:63-78
- Stearns-Kurosawa DJ, Osuchowski MF, Valentine C, Kurosawa S, Remick DG. The pathogenesis of sepsis. Annual Review of Pathology: Mechanisms of Disease 2011; 6:19-48
- Bhan C, Dipankar P, Chakraborty P, Srangi PP. Role of cellular events in the pathophysiology of sepsis. Inflammation Research 2016; 65:853-868
- Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. BMJ 2016; 353:i1585
- Sepsis syndromes in adults
acute respiratory distress syndrome (ARDS)
Articles to read:
- Definitions (Life in the Fast Lane)
- Rubenfeld GD and the ARDS Definition Task Force. Acute Respiratory Distress Syndrome - The Berlin Definition. Journal of the American Medical Association (JAMA) 2012; 307:2526-2533
- Ware LB, Matthay MA. Medical Progress: The Acute Respiratory Distress Syndrome. The New England Journal of Medicine 2000; 342:1334-1349
- Matthay MA, Ware LB, Zimmerman GA. The acute respiratory distress syndrome. Journal of Clinical Investigation 2012; 122:2731-274
the role of the gut in driving critical illness/ organ failure?
Articles to read:
- Swank GM, Deitch EA. The role of the gut in multiple organ failure: bacterial translocation and permeability changes. World Journal of Surgery 1996; 20:411-417
- Mittal R, Coopersmith CM. Redefining the gut as the motor of critical illness. Trends in Molecular Medicine 2014; 20:214-223
- Delibegovic S. Pathophysiological changes in peritonitis. Medicinski Arhiv (MEDARH) 2007; 61:109-113
the community of self, iatrogenesis, and new ways of looking at sepsis
Articles to read:
- Marshall JC. Critical illness is an iatrogenic disorder. Critical Care Medicine 2010; 38:S582-S589
- Seely AJE, Christou NV. Multiple organ dysfunction syndrome: exploring the paradigm of complex nonlinear systems. Critical Care Medicine 2000; 28:2193-2200 (and editorial)
- Buchman TG. The community of the self. Nature 2002; 420:246-251
- Mongardon N, Dyson A, Singer M. Is MOF an outcome parameter or a transient, adaptive state in critical illness? Current Opinion in Critical Care. 2009; 15:431-436
- Fever - friend or foe? (Life in the Fast Lane)
inflammation and trauma
Articles to read (pathophysiology of trauma):
- Keel M, Trentz O. Pathophysiology of polytrauma. Injury 2005; 36:691-70
- Lenz A, Franklin GA, Cheadle WG. Systemic inflammation after trauma. Injury 2007; 38:1336-1345
- Dewar D, Moore FA, Moore EE, Balogh Z. Postinjury multiple organ failure. Injury 2009; 40:912-918
- Tsukamoto T, Chanthaphavong RS, Pape H-C. Current theories on the pathophysiology of multiple organ failure after trauma. Injury 2010; 41:21-26
- Zhang Q, Raoof M, Chen Y et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 2010; 464:104-107
- Xiao W, Mindrinos MN, Seok J et al. A genomic storm in critically injured humans. The Journal of Experimental Medicine 2011; 208:2581-259
- Stoecklein VM, Osuka A, Lederer JA. Trauma equals danger - damage control by the immune system. Journal of Leukocyte Biology 2012; 92:539-551
- Lord JM, Midwinter MJ, Chen TF, et al. The systemic immune response to trauma: an overview of pathophysiology and treatment. Lancet 2014; 384 (9952): 1455-1465
- Hazeldine J, Naumann DN, Toman E. et al. Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury. PLoS Medicine 2017; 14:e1002338
- Carrera CP, Manson J, Shepherd JM. et al. Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: a prospective cohort study. PLoS Medicine 2017; 14:e1002352
Brain injury and inflammation:
- Anthony DC, Couch Y. The systemic response to CNS injury. Experimental Neurology 2014; 258:105-111
- Schwarzmaier SM, Plesnila N. Contributions of the immune system to the pathophysiology of traumatic brain injury - evidence by intravital microscopy. Frontiers in Cellular Neuroscience 2014; 8:1-7 (article 358)
- Catania A, Lonati C, Sordi A, Gatti S. Detrimental consequences of brain injury on peripheral cells. Brain, Behaviour, and Immunity 2009; 23:877-884
- Rathbone ATL, Tharmaradinam S, Jiang S, Rathbone MP, Kumbhare DA. A review of the neuro- and systemic inflammatory responses in post concussion symptoms: Introduction of the "post-inflammatory brain syndrome" PIBS. Brain, Behavior, and Immunity 2015; 46:1-16
Thermal injury (burns) and inflammation:
- Evers LH, Bhavsar D, Mailander P. The biology of burn injury. Experimental Dermatology 2010; 19:777-783
- An G, Faeder J, Vodovotz Y. Translational Systems Biology: Introduction of an engineering approach to the pathophysiology of the burn patient. Journal of Burn Care & Research 2008; 29:277-285
oral health and systemic inflammation
Articles to read:
- Kumar PS. Oral microbiota and systemic disease. Anaerobe 2013; 24:90-93
- Cullinan MP, Seymour GJ. Periodontal disease and systemic illness: will the evidence ever be enough? Periodontology 2000 2013; 62:271-286
- Li X, Kolltveit KM, Tronstad L, Olsen I. Systemic diseases caused by oral infection. Clinical Microbiology Reviews 2000; 13:547-558
- Gurav AN. Alzheimer's disease and periodontitis - an elusive link. Revista da Associacao Medica Brasileira 2014; 60:173-180