diabetes are prone to many infections.like malignant otitis externa,pyelonephritis,cholecystitis,acute necrotising fascitis..its multi factorial. The main effect f hyperglycemia and additional immune disturbance in type I diabetics do play role. The impairment of wide range of functions in neutrophils and macrocytes (Macrophages) including chemotaxis and adherence phagocytosis and intracellular killing of microorganisms is brought by hyperglycemia. In diabetes the movement of phagocytic cells may be generally impaired.[The W.H.O. has included diabetes in its classification of secondary immunodeficiency diseases].
The development of secondary immunodeficiency seems to be determined by alterations involving at generally including polymorphonuclear granulocytes and/or lymphocytic subsets activity.
Polymorph nuclear granulocytes represent the host’s first defense barrier against bacterial agents. Alternation in chemo taxis, phagocytosis, immunoglobulin production and complement functions do occur in diabetic patients. Polymorph nuclear granulocytes, cells from diabetics have a reduced chemo taxis especially when the diabetes is poorly controlled. There are two stages of phagocytosis adhesion and ingestion of microorganisms into intracytoplasmic vacuoles. An increase in sialidase enzyme secretion together with a corresponding reduction in cell membrane sialic acid may play part along with defective lactin receptors losing their capacity to recognize target and fail to initiate phagocytosis. The critical step of intracellular killing is mediated by the intracellular release of toxic free radicals, super oxides and hydrogen peroxide. This respiratory burst which is impaired in diabetics correlates with intracellular killing. This whole process is dependent on nicotinamide adenine dinucleotide phosphate (NADPH).
The NADPH is normally generated by the metabolism of glucose through the hexose monophosphate shunt and in diabetes more glucose enters the phatogocytes and is metabolized by the polyol Pathway. Aldose reductase, the rate limiting enzyme of this process requires NADPH and this is consumed when flux through polyol pathway increase. This competition for NADPH is thought to account for the reductions in the respiratory burst and in intracellular killing.
The metabolic disturbances associated with diabetes are probably important in impairing the function of polymorphonuclear cells. Once phagosome and lysosome fusion has taken place. Killing is carried out by lysosomal enzymes. A decrease in the killing capacity of polymorph nuclear granulocytes associated with high blood sugar may come to normalization within 48 hours after correction of blood sugar levels.
Several immunoglobulin levels IgG and IgA have been reported to be reduced in diabetics as compared to normal. As well as a significant reduction in the quantity and functional activity of complement components may occur in diabetic patients. Above all these local factors like underlying susceptibility to infection, vascular disease, nerve damage and increase in blood sugar may aggravate the process. This may call upon decrease circulation, hypoxia and reduction in absorption of antibiotics and proliferation of bacteria.
In type I or IDDM, genetics predisposition to infections also plays part. Along with all above factors which are abnormalities of aspects of phagocyte functions – mobilization and chemo taxis, adherence phagocytosis and intracellular killing with bactericidal activities, micro vascular circulations abnormality may result in decreased tissue perfusion. Hyperglycemia per say reduces oxidative killing capacity because of increased glucose Metabolism through polyol pathway depleting NADPH which is necessary for generation of super oxide free radicals.
In type I or IDDM, there is alteration in some lymphocyte subpopulations, a reduction in ‘T’ lymphocytes and under specifically in the number of CD4 phenotype. (‘C’ helper ‘T’ Lymphocytes) and reduction in CD4/CD8 ration serum immunoglobulin levels IgG and IgA have been reported to be reduced in diabetics compared to normal. As well as significant reduction in the quantity and functional activity of complements may occur in Diabetic patients. An underlying susceptibility of target tissues due to hyperglycemia, vascular disease and nerve damage is proved with the relative tissue hypoxia may cause proneness to infections. A reduction in antibiotic absorption due to microangiopathy may lead to persistence of infections. A reduction in antibiotic absorption due to microangiopathy may lead to persistence of infection. About 25% of IDDM subjects have this.
Polymorph nuclear granulocytes represent the host’s first defense barrier against bacterial agents. Alternation in chemo taxis, phagocytosis, immunoglobulin production and complement functions do occur in diabetic patients. Polymorph nuclear granulocytes, cells from diabetics have a reduced chemo taxis especially when the diabetes is poorly controlled. There are two stages of phagocytosis adhesion and ingestion of microorganisms into intracytoplasmic vacuoles. An increase in sialidase enzyme secretion together with a corresponding reduction in cell membrane sialic acid may play part along with defective lactin receptors losing their capacity to recognize target and fail to initiate phagocytosis. The critical step of intracellular killing is mediated by the intracellular release of toxic free radicals, super oxides and hydrogen peroxide. This respiratory burst which is impaired in diabetics correlates with intracellular killing. This whole process is dependent on nicotinamide adenine dinucleotide phosphate (NADPH).
The NADPH is normally generated by the metabolism of glucose through the hexose monophosphate shunt and in diabetes more glucose enters the phatogocytes and is metabolized by the polyol Pathway. Aldose reductase, the rate limiting enzyme of this process requires NADPH and this is consumed when flux through polyol pathway increase. This competition for NADPH is thought to account for the reductions in the respiratory burst and in intracellular killing.
The metabolic disturbances associated with diabetes are probably important in impairing the function of polymorphonuclear cells. Once phagosome and lysosome fusion has taken place. Killing is carried out by lysosomal enzymes. A decrease in the killing capacity of polymorph nuclear granulocytes associated with high blood sugar may come to normalization within 48 hours after correction of blood sugar levels.
Several immunoglobulin levels IgG and IgA have been reported to be reduced in diabetics as compared to normal. As well as a significant reduction in the quantity and functional activity of complement components may occur in diabetic patients. Above all these local factors like underlying susceptibility to infection, vascular disease, nerve damage and increase in blood sugar may aggravate the process. This may call upon decrease circulation, hypoxia and reduction in absorption of antibiotics and proliferation of bacteria.
In type I or IDDM, genetics predisposition to infections also plays part. Along with all above factors which are abnormalities of aspects of phagocyte functions – mobilization and chemo taxis, adherence phagocytosis and intracellular killing with bactericidal activities, micro vascular circulations abnormality may result in decreased tissue perfusion. Hyperglycemia per say reduces oxidative killing capacity because of increased glucose Metabolism through polyol pathway depleting NADPH which is necessary for generation of super oxide free radicals.
In type I or IDDM, there is alteration in some lymphocyte subpopulations, a reduction in ‘T’ lymphocytes and under specifically in the number of CD4 phenotype. (‘C’ helper ‘T’ Lymphocytes) and reduction in CD4/CD8 ration serum immunoglobulin levels IgG and IgA have been reported to be reduced in diabetics compared to normal. As well as significant reduction in the quantity and functional activity of complements may occur in Diabetic patients. An underlying susceptibility of target tissues due to hyperglycemia, vascular disease and nerve damage is proved with the relative tissue hypoxia may cause proneness to infections. A reduction in antibiotic absorption due to microangiopathy may lead to persistence of infections. A reduction in antibiotic absorption due to microangiopathy may lead to persistence of infection. About 25% of IDDM subjects have this.
Posts
0 comments:
Post a Comment
Your feedback, suggestions are most welcome!!!