COMPLICATION OF DIABETES (Pathological aspects).pptx

pathology Robbins

1. COMPLICATION OF DIABETES

2. ACUTE METABOLIC COMPLICATION OF DIABETES Diabetic ketoacidosis is a severe acute metabolic complication of type I diabetes it may occurs in type II diabetes. Most common precipitating factor are, 1. failure to take insulin 2. intercurrent infections 3. illness 4. trauma These factors are associated with release of catacholamine epinephrine which blocks any residual insulin action and stimulates the secretion of glucagon. The insulin deficiency coupled with glucagon excess decreases peripheral utilization of glucose while increasing gluconeogenesis severely exacerbating hyperglycemia (glucose level range between 250 to 600mg/dl). The hyperglycemia causes an osmotic diuresis and dehydration and characteristics of ketoacidosis.

3. Insulin deficiency stimulate lipoprotein lipase with resulted breakdown of adipose stores and increase in level of fatty acids. These fatty acids reach liver and esterified to fattyacyl coenzyme-a produces ketone bodies. The ketone bodies formed exceed the rate at which they can be utilized by peripheral tissue leading to ketonemia and ketonuria .

4. CLINICAL MANIFESTATION OF KETOACIDOSIS. It includes, 1. fatigue 2. nausea and vomiting 3. severe abdominal pain 4.characteristic fruity odor 5. labored breathing ( kussmaul breathing) Persisting of ketotic state eventually lead to coma. Administration of insulin is required for correction of metabolic acidosis.

5. Hyperosmolar hyperosmotic syndrome This condition develop in type II diabetics, due to severe dehydration resulting from sustained osmotic diuresis in patients who do not drink enough water to compensate the urinary losses from chronic hyperglycemia. It occurs in older diabetic who are disabled by stroke, or infection, unable to maintain water intake. In abscense of ketoacidosis and its symptoms delays to seek the medical attention until severe dehydration and impairment of mental status occur. The hyperglycemia is more severe than diabetic ketoacidosis that ranges from 600 to 1200mg/dl.

6. Hypoglycemia It is the most common metabolic acute complication in both type of diabetes. It results due to, 1. missed a meal 2. Excessive physical exertion 3. Excess insulin administration 4. During the phase of dose finding for antidiabetic agents.

7. Signs and symptoms: 1. dizziness 2. confusion 3. sweating 4. palpitation and tachycardia 5. if hypoglycemia persists loss of consciousness. Oral or intravenous glucose intake prevents permanent neurological damage.

8. Chronic complication of diabetes Morbidity associated with long standing diabetes, leading to damage induce in large and medium size muscular arteries (macro vascular disease, micro vascular disease). Macro vascular disease causes accelerated athereosclerosis in diabetes resulting in, Myocardial infarction, stroke and lower extremity ischemia. Micro vascular diseases occur in retina, kidneys and peripheral nerves resulting in diabetic retinopathy, nephropathy and neuropathy.

9. DIABETIC MACRO VASCULAR DISEASE Myocardial, infarction cause by athereosclerosis of coronary arteries is the most common cause of death in diabetes. Gangrene of lower extremities due to advance vascular disease is 100 times more common in diabetics than in general population.

10. DIABETIC MICRO ANGIOPATHY One of the most consistent morphological diabetic feature is diffuse thickening of basement membrane. Diabetic capillaries are more leaky than normal to plasma protein. The micro angiopathy underlies the development of diabetic nephropathy, retinopathy and some forms of neuropathy.

11. DIABETIC NEPHROPATHY Three lesions are encountered, 1. glomerular lesions 2. renal vascular lesions (arteriolosclerosis) 3. pyelonephritis. Basement membrane thickening : It occurs in all cases of diabetic nephropathy. This thickening begins as early as 2 years after the onset of type I diabetes and by 5 years amounts to abut 30% increase.

12. DIFFUSE MESENGIAL SCLEROSIS: It consists of diffuse mesengial matrix. It is associated with over all thickening of GBM. The expansion of mesengial of area can extend to nodular configuration. This expansion can co relate with deteriorating renal function renal function as increasing protienuria . NODULAR GLOMERULO SCLEROSIS: Kimmelstiel-wilson disease. It takes the form of ovoid or spherical nodules of matrix situated in the periphery of glomerulus it is PAS positive, it is surrounded by patent peripheral loops. Not all nodules but all the individual glomeruli show striking diffuse mesengial sclerosis. As the disease advances the nodules enlarge may eventually compress and engulf capillaries obliterating the glomerulo tufts as a results the kidney suffers from ischemia, atrophy and interstitial fibrosis leading to contraction in size of the kidney. The individuals in long term associated renal failure .

13. Renal atherosclerosis and arterosclerosis : Hyaline arterosclerosis effects not only afferent but also efferent arteriole. Such efferent arteriosclerosis is not encountered in individuals who don’t have diabetes. Pyelonephritis: It is acute or chronic inflammation of kidney. It begins in interstitial tissue and then spread to tubules. Both diseases are more common in diabetes than in general population and has more severe involvement. One special pattern of acute pyelonephritis is necrotizing papillitis more prevelant in diabetics than non diabetics.

14. DIABETIC OCCULAR MANEFESTATION Thickening of he basement membrane of epithelium of pars plicata of the ciliary body is reliable histological marker of diabetes mellitus. The ritinal vasculopathy is classified into non proliferative and proliferative retinopathy. Non proliferative diabetic retinopathy: The basement of ritinal blood vessel is thickened Micro aneurysm are an important manefestation of the diabetic microangiopathy . The ritinal micro vasculation in diabetics may be exceptionally leaky giving rise to macular edema a common cause visual loss in these patients.

15. Proliferative diabetic retinopathy: it is defined by appearance of new vessels sprouting on the surface of optic nerve head or surface of retina. Retinal neovascularization is termed when newly form vessels breech the internal membrane of the retina. The following condition may occur 1. Posterior vitreous detachment may occur with massive hemorrhage 2. Tractional retinal detachment which may tear the retina. 3. Neo vascular glucoma , renal neo vascularization involving the iris surface may lead to adhesion between iris and anterior synechiae occluding major pathway for aqueous outflow contributing elevation of intra occular pressure.

16. CLINICAL MANIFESTATION Both types of diabetes are responsible for overwhelming majority of morbidity and mortality. MACRO VASCULAR COMPLICATION: As myocardial infarction, renal vascular insufficiency and cerebro vascular accident are the most common causes of mortality in long standing diabetes. Hypertension is found in approximately 75% individuals with type II diabetes, leads to atherosclerosis. Another cardiovascular risk factor is frequently seen in diabetics is dyslipidemia which includes increased triglycerides and lipoproteins and decreased levels of protective lipoproteins HDL. Finally diabetics has elevated levels of PAI-1 which is an inhibitor of fibrinolysis and act as procoagulant in the formation of atherosclerotic plaque.

17. Diabetic nephropathy: It is a leading cause of ESRD. 30 to 40 % of all diabetics develops clinical evidence of nephropathy but smaller fraction of patient with type II diabetes progress to ESRD stages. The earliest manifestation of diabetic nephropathy is appearance of low amounts of albumin in the urine (>30mg/day but <300mg/day) is microalbuminuria . It is a marker for greatly increase cardiovascular mortality and morbidly.

18. All patients with micro albuminuria should be screen for macro vascular disease and aggressive intervention should be undertaken to reduce cardiovascular risk factor. 80% of type I diabetes and 20 to 40 % of type II diabetes will develop overt nephropathy with macro albuminuria (>300mg/day) over 10 to 15 years usually accompanied by hypertension. By 20 years more than 75% of type I diabetics and 20% of type II diabetics with overt nephropathy will develop ESRD. Visual impairment: Total blindness is sometime one of the most feared consequences sequence of long standing diabetes. 60 to 80% of patients develop diabetic nephropathy approximately 15 to 20 years after diagnosis. The fundamental lesion to retinopathy is revascularization. Current treatment for this condition includes administration of anti angiogenic agents. Diabetics also have propensity for glaucoma and cataract formation.

19. Diabetic neuropathy: The most frequent pattern of involvement is symmetric polyuropathy of the lower extremity that effects both motor and sensory sensation. Over time upper extremity may be involved as well thus ‘’glove and stocking pattern of polyneuropathy “ Other forms includes autonomic neuropathy produces disturbances in bowel and bladder function some times erectile dysfunction. diabetic mono neuropathy may manifest a sudden foot drops wrist drop.

20. DIABETES AND INFECTION: Diabetics are plagued by enhanced susceptibility of infection of skin to tuberculosis, pneumonia and pyelonephritis. Such infections are the cause of deaths in 5% diabetics. In individuals with diabetic neuropathy a trivial infection in a toe may be the first event in long succession of complication (gangrene, bacteremia, pneumonia) may ultimately leading to death. the basis of enhanced susceptibility includes decreased neutrophils function impaired cytokine production by macrophages and vascular compromise reduces delivery of circulating cells and molecules required for host defense. All patients will ultimately require some form of therapeutic intervention to maintain the glycemic control.