Disruption of Membrane, A Brief Literature Review
A community consciousness and brain health essay.
Disruption of Membrane (DOM) is the term used in Integrative Manual Therapy (IMT) to describe any loss of integrity in a membrane. The term describes the range from a tissue or cell wall with a greater permeability than normal to a ruptured membrane wall as in a ruptured appendix or an aneurysm. Membrane walls are meant to keep some things in and other things out. When the membrane integrity is less than ideal, fluids, toxins and other components of the body can be incorrectly placed.
Look at “good bacteria” in the digestive system as an example. If the person has leaky gut syndrome, the membrane walls in the digestive system are less than ideal and the “good bacteria” can move out into general abdominal cavity. This can lead to peritonitis, an inflammatory condition. The “good bacteria” are not inherently good, they are useful when they are in the gut doing their job and contributing to the absorption of nutrients. Out in the abdominal cavity, they are a toxin contributing to a potentially life threatening problem.
In the medical literature there are many examples of tissues that have disruptions of membrane. Leaky gut syndrome, leaky vessel syndrome and blood brain barrier changes are just some of the dysfunctions created by disruptions of membranes.
In the digestive system, a number of toxins can cause problems. Gluten, a protein found in wheat and other grains, can contribute to increased membrane permeability in the digestive system leading to celiac disease. Alcohol increases intestinal permeability leading to leaky gut syndrome. One study showed, that people abstaining from alcohol for less than 4 days almost invariably had higher intestinal permeability than non-drinkers, and in many the increased permeability lasted up to 2 weeks after they stopped drinking. (Bjarnason, 1984). O’Dwyer found that, “A brief exposure to circulating endotoxin increases the permeability of the normal gut” and hypothesized that “during critical illness, prolonged or repeated exposure to systemic endotoxins or associated cytokines may significantly compromise the integrity of the gastrointestinal mucosal barrier.” (O’Dwyer, 1988).
Celiacs disease, neurodenegerative disorders and limited system sclerosis are just some of the diseases related to membrane permeability imbalances. The mucosal barrier in the digestive system is particularly susceptible to problems. One study found that severe attacks of acute pancreatitis are associated with gut barrier dysfunction. (Ammori, 2003).
Eczema and food allergies are also both related to increased intestinal permeability. Jackson suggested that there is an intestinal mucosal defect in eczema which exists whether or not there is coexistent food allergy. This could be the result of abnormal permeability in the more distal small intestine or colon. (Jackson, 1981).
Direct trauma and infection lead to disruptions of membrane but the intestine can also be injured by more systemic trauma. “Intestinal permeability was increased in patients with moderate to major burn injuries shortly after injury.” (Deitch, 1990). The affect of trauma on intestinal permeability may be related to the release of toxins and the inflammatory response to the trauma. “Increased intestinal permeability and the release of toxic intraluminal materials have been implicated in the systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF) observed in patients after severe trauma. These observations demonstrate that the increased intestinal permeability observed after trauma correlates with severity of injury only after 72 to 96 hours and not within the initial 24 hours of injury. A large increase in intestinal permeability is associated with the development of SIRS, multiple organ dysfunction, and an increased incidence of infectious complications.” (Faries, 1998).
Disruptions of the blood vessels in the kidneys also have serious consequences. A loss of blood flow (ischemia) to the kidneys leads to obstructions of the kidney tubules, reduced sodium absorption and a reduction in the kidney’s filtration rate. In diabetic nephrophathy (a kidney dysfunction), the membrane lining of the kidneys or the glomerular basement membrane (GBM) is damaged. Normally it is a “fine meshwork structure consisting of fibrils forming the small pores.” In diabetic nephropathy there is irregular thickening of the membrane. At higher magnification, cavities and tunnel structures, not seen in normal kidneys are observed in the thickened membranes. (Ota, 1995). These cavities and tunnels allows proteins to leave the blood stream and enter the urine, contributing to protein loss and fluid imbalances in the body.
The cardiovascular system is particularly vulnerable to disruptions of membrane and the consequences are severe. Red blood cell osmotic hemolysis or the breakdown of the cell membranes due to pressure leading to anemia. Iron may play a role in disruptions of membrane in blood vessels. Iron reacting with hydrogen and oxygen forms free radicals. “Free radicals react with cell membranes and cell organelles and could lead to the development of atherosclerosis by initiating lipid peroxidation.” (Candore, 2003). Iwata also noted that abnormal fluctuations in blood flow to the legs (intermittent claudication) can induce a generalized increase in vascular permeability, including in intestinal permeability. (Iwata, 2000).
A cerebral aneurysm or disruption of membrane of a blood vessel in the brain leads to bleeding and a secondary loss of blood flow to certain parts of the brain, a disruption of the blood-brain barrier and swelling leading to spasms in major blood vessels in the brain. “It is increasingly apparent that oxygen radical-induced, iron-catalyzed lipid peroxidation (LP) within the subarachnoid blood and vascular wall plays a key role in the occurrence of these secondary events.” (Hall, 1996).
Sometimes the technology used to find disruptions of membrane can contribute to the problem. Ultrasound has been shown to transiently disrupt cell membranes and the effects are thought to be mediated by cavitation. (Cochran, 2001). Ultrasonography is used for “recognition of interosseous membrane disruption associated with radial head injury.” ( Jaakkola, 2001).
Toxins though are one of the main causes of disruptions of membrane. Bacteria like E coli disrupt the structure and barrier function in the membrane of the intestine, particularly the epithelial tight junction and leads to the disruption of normal gut function. (Muza-Moons, 2003). Copper toxicity can also lead to disruption of plasma membrane integrity. “Cellular and plasma membrane fatty acid compositions can dramatically alter microbial sensitivity to copper.” (Avery, 1996).
Membrane dysfunctions of the blood brain barrier are implicated in several neurodegenerative disorders. P-glycoprotein, a membrane protein encoded by the MDR1 gene, is present in endothelial cells of the blood-brain barrier. A gene mutation in the P-glycoprotein MDR1 gene predisposes the individual to Parkinson’s by allowing the damaging effects of pesticides and possibly other toxic xenobiotics transported by P-glycoprotein. (Drozdrik, 2003). Membrane proteins are altered in neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, Lou Gehrig’s and Huntington’s disease. Novel preventative and therapeutic approaches for neurodegenerative disorders are emerging from basic research on the molecular and cellular actions of metals and membrane-associated oxidative stress (MAOS) in neural cells. (Mattson, 2004).
Irritation by bile salts from the liver and gallbladder may contribute to dysfunctions like gall stones and heart burn. Bile has a lot of water phobic bile salts, but is normally not toxic to the gallbladder and digestive system in part because bile is also high in lecithin. “Lecithin may play a key role in preventing bile salt injury of biliary and gastrointestinal epithelia.” (Narain, 1998).
There are a number of ways cells and tissues can response to disruptions of membrane and also prevent them from happening in the first place. “Survival requires that the cell rapidly repair or reseal the disruption.” (McNeil, 2003). There are also protective mechanisms. “Tissue and cell level architecture prevent disruptions from occurring, either by shielding cells from damaging levels of force, or when this is not possible, by promoting safe force transmission through the plasma membrane via protein-based cables and linkages. Prevention of disruption can also be a dynamic cell or tissue level adaptation triggered when a damaging level of mechanical stress is imposed. Disease results from failure of either the preventive or resealing mechanisms.” (McNeil, 2003).
Once a tissue has been damaged, Integrative Manual Therapists use the Disruption of Membrane (DOM) technique with the intention to aid in the body’s repair and adaptation mechanisms. Nutritional support is also recommended.
References
1. Akeson, S. P. and H. C. Mel (1982). “Osmotic hemolysis and fragility. A new model based on membrane disruption, and a potential clinical test.” Biochim Biophys Acta 718(2): 201–11.
2. Ammori, B. J., P. Fitzgerald, et al. (2003). “The early increase in intestinal permeability and systemic endotoxin exposure in patients with severe acute pancreatitis is not associated with systemic bacterial translocation: molecular investigation of microbial DNA in the blood.” Pancreas 26(1): 18–22.
3. Ashworth, S. L. and B. A. Molitoris (1999). “Pathophysiology and functional significance of apical membrane disruption during ischemia.” Curr Opin Nephrol Hypertens 8(4): 449–58.
4. Avery, S. V., N. G. Howlett, et al. (1996). “Copper toxicity towards Saccharomyces cerevisiae: dependence on plasma membrane fatty acid composition.” Appl Environ Microbiol 62(11): 3960–6.
5. Bjarnason, I. and T. J. Peters (1984). “In vitro determination of small intestinal permeability: demonstration of a persistent defect in patients with coeliac disease.” Gut 25(2): 145–50.
6. Bjarnason, I., T. J. Peters, et al. (1984). “The leaky gut of alcoholism: possible route of entry for toxic compounds.” Lancet 1(8370): 179–82.
7. Bkaily, G. (1994). Membrane Physiology, Kluwer Academic Publishers.
8. Cameron, I. L., L. A. Cox, et al. (1991). “Maintenance and mobility of hemoglobin and water within the human erythrocyte after detergent disruption of the plasma membrane.” J Cell Physiol 149(3): 365–74.
9. Candore, G., C. R. Balistreri, et al. (2003). “Association between HFE mutations and acute myocardial infarction: a study in patients from Northern and Southern Italy.” Blood Cells Mol Dis 31(1): 57–62.
10. Catanoso, M., R. Lo Gullo, et al. (2001). “Gastro-intestinal permeability is increased in patients with limited systemic sclerosis.” Scand J Rheumatol 30(2): 77–81.
11. Cochran, S. A. and M. R. Prausnitz (2001). “Sonoluminescence as an indicator of cell membrane disruption by acoustic cavitation.” Ultrasound Med Biol 27(6): 841–50.
12. Deitch, E. A. (1990). “Intestinal permeability is increased in burn patients shortly after injury.” Surgery 107(4): 411–6.
13. Drissche, T. V. (1996). Membrane and circadian rhythm, Springer.
14. Drozdzik, M., M. Bialecka, et al. (2003). “Polymorphism in the P-glycoprotein drug transporter MDR1 gene: a possible link between environmental and genetic factors in Parkinson’s disease.” Pharmacogenetics 13(5): 259–63.
15. Faries, P. L., R. J. Simon, et al. (1998). “Intestinal permeability correlates with severity of injury in trauma patients.” J Trauma 44(6): 1031–5; discussion 1035–6.
16. Garcon, G., P. Shirali, et al. (2000). “Polycyclic aromatic hydrocarbon coated onto Fe(2)O(3) particles: assessment of cellular membrane damage and antioxidant system disruption in human epithelial lung cells (L132) in culture.” Toxicol Lett 117(1–2): 25–35.
17. Hall, E. D. (1996). “Efficacy and mechanisms of action of the cytoprotective lipid peroxidation inhibitor tirilazad mesylate in subarachnoid haemorrhage.” Eur J Anaesthesiol 13(3): 279–89.
18. Iwata, H., M. Matsushita, et al. (2000). “Intestinal permeability is increased in patients with intermittent claudication.” J Vasc Surg 31(5): 1003–7.
19. Jaakkola, J. I., D. H. Riggans, et al. (2001). “Ultrasonography for the evaluation of forearm interosseous membrane disruption in a cadaver model.” J Hand Surg [Am] 26(6): 1053–7.
20. Jackson, P. G., M. H. Lessof, et al. (1981). “Intestinal permeability in patients with eczema and food allergy.” Lancet 1(8233): 1285–6.
21. Mattson, M. P. (2004). “Metal-catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders.” Ann N Y Acad Sci 1012: 37–50.
22. McNeil, P. L. and R. A. Steinhardt (2003). “Plasma membrane disruption: repair, prevention, adaptation.” Annu Rev Cell Dev Biol 19: 697–731.
23. Muza-Moons, M. M., A. Koutsouris, et al. (2003). “Disruption of cell polarity by enteropathogenic Escherichia coli enables basolateral membrane proteins to migrate apically and to potentiate physiological consequences.” Infect Immun 71(12): 7069–78.
24. Narain, P. K., E. J. DeMaria, et al. (1998). “Lecithin protects against plasma membrane disruption by bile salts.” J Surg Res 78(2): 131–6.
25. O’Dwyer, S. T., H. R. Michie, et al. (1988). “A single dose of endotoxin increases intestinal permeability in healthy humans.” Arch Surg 123(12): 1459–64.
26. Ota, K., Z. Ota, et al. (1995). “The ultrastructural disruption of the glomerular basement membrane in diabetic nephropathy revealed by “tissue negative staining method”.” J Diabetes Complications 9(4): 285–7.
27. Winkle, L. J. V. (1999). Biomembrane Transport. San Diego, California, Academic Press A division of Harcourt Brace and Company.
Originally published at http://kimberlyburnham.blogspot.com on January 31, 2005.
