Bacterial meningitis pathophysiology: Difference between revisions
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Latest revision as of 20:34, 29 July 2020
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Bacterial meningitis Microchapters |
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Diagnosis |
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Treatment |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]
Overview
Pathogenensis of bacterial meningitis may include the transmission, colonization, invasion and seeding of meninges. It is a complex process involving interaction between bacterial pathogenic elements and host immune response. There may be genetic predisposition to develop infection. The sequence of events that may ensue after bacterial invasion of meninges include injury to the blood brain or blood CSF barrier, disruption of intercellular tight junctions, vasogenic edema, loss of cerebral autoregulation, increased intra cranial pressure, and development of Signs and symptoms due to raised IC pressure. The inflammatory molecules which may play a role in this pathogenic process includes interleukins IL1, IL6, TNF and matrix metalloproteinases.[1][2][3][4][5][6][7][8][9]
Pathophysiology
Pathogenesis of bacterial meningitis is a complex process which may occur due to imbalance between the host immune response and virulence factors of pathogen causing infection. Following steps may explain the underlying process in a comprehensive way: [1][2][3][4][5][6][7][8][9][10]
Transmission
- H. influenza type b and N. meningitides may be transmitted by close contact or prolong contact with patient suffering from meningitis[10]
- It may also spread by exchanging throat and respiratory secretions (coughing and kissing)
- Listeria monocytogenes may spread by eating contaminated food.
- Most people are carriers and do not develop the disease.
Colonization and evasion of host immune response
- Colonization of pathogenic organism involves evasion of host immune response mechanism.
- IgA protease produced by bacterial pathogen cleave mucosal IgA antibodies which prevent the bacteria from attachment to the mucosal surface.[1][2]
- Once host immune response is evaded, bacteria attach themselves to the mucosa via fimbriae or pilli which facilitate colonization process.
Invasion and seeding
- Once colonized, the invasion of bacteria occurs via special adhesion proteins called adhesins.[1]
- Adhesins may help bacteria to cross epithelial barrier intracellularly or intercellularly.
- Bacteria seeds transcellularly to enter the intravascular space.
- Surface encapsulation may play important role in entry of bacterial pathogen across epithelium into blood stream
- Blood stream entry of bacterial pathogen may result in activation of complement pathway and inflammatory process[3]
- Bacterial capsule helps evasion of complement system and ultimate entry into the CNS through blood brain barrier[3]
- Individual genetic susceptibility and immune response determine the severity of infection
Meningeal infalmmation
- Meningeal inflammation follows bacterial invasion into the blood.[11]
- Bacterial entry into brain may occur through highly vascularized areas such as leptomeningeal blood vessels or choroid plexus.
- Intracranial entry of bacterial pathogen through tight junctions of blood CSF or blood CNS barrier may occur through special interaction of adhesins and proteins on the surface of choroid epithelial cells[12]
Role of inflammatory molecules in the pathogeneis of bacterial meningitis
Inflammatory molecules and bacterial components which may play a role in the pathogenesis of bacterial meningitis may include following:[13][14]
- Subcapsular bacterial surface components-teichoic acid and peptidoglycans[14]
- Bacterial lysins-pneumolysins in strept pneumoniae
- Bacterial lipoligosaccharide or lipopolysaccharide-N.meningitides and S.pneumoniae
- In situ production of inflammatory cytokines such as IL-1, IL-6, TNF, and matrix metalloproteinases[13][14]
Sequence of microscopic changes caused by inflammatory molecules
- Once inflammation sets in due to combination of bacterial components and host inflammatory cytokines, the sequence of events that causes signs and symptoms may be as follows:[7][15]
- Injury to the blood brain or blood CSF barrier
- Disruption of intercellular tight junctions
- Vasogenic edema
- Loss of cerebral autoregulation[15]
- Increased intracranial pressure
- Signs and symptoms of raised IC pressure
Inflammatory mediators causing complications of meningitis
- Inflammatory mediators and molecules such as nitric oxide, reactive oxygen species and amino acids
- Neuronal damage, neuronal apoptosis, and brain ischemia may result in complications such as infarction, hydrocephalus and brain abscess
Associated conditons
Following conditions may increase the susceptibility to develop bacterial meningitis:
- Trauma to skull
- HIV
- Diabetes mellitus
- Organ transplant
- Immunosuppresion
Role of Genetics
- Genetic polymorphism in the individuals may determine the susceptibility to develop bacterial meningitis, the severity of infection and the ability to recover.[4]
- Single nucleotide polymorphism in the complement system may determine the increased or decreased susceptibility to develop bacterial meningitis in these patients[5][6]
Gross pathology
Gross pathological findings of bacterial meningitis may include:[10]
- Clouded appearance of meninges
- Presence of exudate
- Obliteration of sulci
- Pus
- Petechiae
- Cerebral hemorrhages
Microscopic pathology
Microscopic pathological findings in bacterial meningitis may include the following:[10]
- Neutrophilic exudate seen in meninges
- Prominent dilated blood vessels
- Edema and focal inflammation
References
- ↑ 1.0 1.1 1.2 1.3 Stephens DS, Farley MM (1991). "Pathogenic events during infection of the human nasopharynx with Neisseria meningitidis and Haemophilus influenzae". Rev Infect Dis. 13 (1): 22–33. PMID 1901998.
- ↑ 2.0 2.1 2.2 Plaut AG (1983). "The IgA1 proteases of pathogenic bacteria". Annu Rev Microbiol. 37: 603–22. doi:10.1146/annurev.mi.37.100183.003131. PMID 6416146.
- ↑ 3.0 3.1 3.2 3.3 Joiner KA (1988). "Complement evasion by bacteria and parasites". Annu Rev Microbiol. 42: 201–30. doi:10.1146/annurev.mi.42.100188.001221. PMID 3059994.
- ↑ 4.0 4.1 4.2 Brouwer MC, de Gans J, Heckenberg SG, Zwinderman AH, van der Poll T, van de Beek D (2009). "Host genetic susceptibility to pneumococcal and meningococcal disease: a systematic review and meta-analysis". Lancet Infect Dis. 9 (1): 31–44. doi:10.1016/S1473-3099(08)70261-5. PMID 19036641.
- ↑ 5.0 5.1 5.2 Brouwer MC, Read RC, van de Beek D (2010). "Host genetics and outcome in meningococcal disease: a systematic review and meta-analysis". Lancet Infect Dis. 10 (4): 262–74. doi:10.1016/S1473-3099(10)70045-1. PMID 20334849.
- ↑ 6.0 6.1 6.2 Adriani KS, Brouwer MC, Geldhoff M, Baas F, Zwinderman AH, Paul Morgan B; et al. (2013). "Common polymorphisms in the complement system and susceptiblity to bacterial meningitis". J Infect. 66 (3): 255–62. doi:10.1016/j.jinf.2012.10.008. PMID 23068452.
- ↑ 7.0 7.1 7.2 Quagliarello V, Scheld WM (1992). "Bacterial meningitis: pathogenesis, pathophysiology, and progress". N Engl J Med. 327 (12): 864–72. doi:10.1056/NEJM199209173271208. PMID 1508247.
- ↑ 8.0 8.1 Hoffman O, Weber RJ (2009). "Pathophysiology and treatment of bacterial meningitis". Ther Adv Neurol Disord. 2 (6): 1–7. doi:10.1177/1756285609337975. PMC 3002609. PMID 21180625.
- ↑ 9.0 9.1 Kim KS (2003). "Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury". Nat Rev Neurosci. 4 (5): 376–85. doi:10.1038/nrn1103. PMID 12728265.
- ↑ 10.0 10.1 10.2 10.3 https://www.cdc.gov/meningitis/bacterial.html Accessed on 10th Jan, 2017
- ↑ Kasper, Dennis (2015). Harrison's principles of internal medicine. New York: McGraw Hill Education. ISBN 978-0071802154.
- ↑ Brown EJ, Joiner KA, Gaither TA, Hammer CH, Frank MM (1983). "The interaction of C3b bound to pneumococci with factor H (beta 1H globulin), factor I (C3b/C4b inactivator), and properdin factor B of the human complement system". J Immunol. 131 (1): 409–15. PMID 6223077.
- ↑ 13.0 13.1 Moser R, Schleiffenbaum B, Groscurth P, Fehr J (1989). "Interleukin 1 and tumor necrosis factor stimulate human vascular endothelial cells to promote transendothelial neutrophil passage". J Clin Invest. 83 (2): 444–55. doi:10.1172/JCI113903. PMC 303700. PMID 2643630.
- ↑ 14.0 14.1 14.2 Quagliarello VJ, Wispelwey B, Long WJ, Scheld WM (1991). "Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor". J Clin Invest. 87 (4): 1360–6. doi:10.1172/JCI115140. PMC 295174. PMID 2010549.
- ↑ 15.0 15.1 Tureen JH, Dworkin RJ, Kennedy SL, Sachdeva M, Sande MA (1990). "Loss of cerebrovascular autoregulation in experimental meningitis in rabbits". J Clin Invest. 85 (2): 577–81. doi:10.1172/JCI114475. PMC 296461. PMID 2105342.