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1、Complications of diabetes mellitus,Anca Bacrea,Alexandru Schiopu,Complications of diabetes mellitus,Acute complications:KetoacidosisThe hyperglycemic hyperosmolar nonketotic syndromeHypoglycemiaChronic complications:Disorders of the microcirculationNeuropathiesNephropathiesRetinopathiesMacrovascular
2、 complicationsFoot ulcers,Diabetic ketoacidosis(DKA),It occurs when ketone production by the liver exceeds cellular use and renal excretion.Most commonly occurs in a person with type 1 diabetes,in whom the lack of insulin leads to mobilization of fatty acids from adipose tissue because of the unsupp
3、ressed adipose cell lipase activity that breaks down triglycerides into fatty acids and glycerol.The increase in fatty acid levels leads to ketone production by the liver.Stress increases the release of gluconeogenic hormones and predisposes the person to the development of ketoacidosis.DKA often is
4、 preceded by physical or emotional stress,such as infection,pregnancy,or extreme anxiety.In clinical practice,ketoacidosis also occurs with the omission or inadequate use of insulin.,Diabetic ketoacidosis(DKA),The three major metabolic derangements in DKA are:HyperglycemiaKetosisMetabolic acidosisTh
5、e definitive diagnosis consists of hyperglycemia(blood glucose levels 250 mg/dL),low bicarbonate(15 mEq/L),and low pH(7.3),with ketonemia(positive at 1:2 dilution)and moderate ketonuria.Hyperglycemia leads to osmotic diuresis,dehydration,and a critical loss of electrolytes.Hyperosmolality of extrace
6、llular fluids from hyperglycemia leads to a shift of water and potassium from the intracellular to the extracellular compartment.Extracellular sodium concentration frequently is low or normal despite enteric water losses because of the intracellular-extracellular fluid shift.This dilutional effect i
7、s referred to as pseudohyponatremia.Serum potassium levels may be normal or elevated,despite total potassium depletion resulting from protracted polyuria and vomiting.Metabolic acidosis is caused by the excess ketoacids that require buffering by bicarbonate ions;this leads to a marked decrease in se
8、rum bicarbonate levels.,Manifestations,The person typically has a history of 1 or 2 days of polyuria,polydipsia,nausea,vomiting,and marked fatigue,with eventual stupor that can progress to coma.Abdominal pain and tenderness may be present without abdominal disease.The breath has a characteristic sme
9、ll because of the presence of the volatile ketoacids.Hypotension may be present because of a decrease in blood volume.A number of the signs and symptoms that occur in DKA are related to compensatory mechanisms:The heart rate increases as the body compensates for a decrease in blood volumeThe rate an
10、d depth of respiration increase(i.e.,Kussmauls respiration)as the body attempts to prevent further decreases in pH.,Treatment,The goals in treating DKA are:To improve circulatory volume and tissue perfusionTo decrease serum glucoseTo correct the acidosis and electrolyte imbalancesThese objectives us
11、ually are accomplished through the administration of insulin and intravenous fluid and electrolyte replacement solutions.Identification and treatment of the underlying cause.,The hyperglycemic hyperosmolar nonketotic(HHNK)syndrome,The hyperglycemic hyperosmolar nonketotic syndrome is characterized b
12、y hyperglycemia(blood glucose 600 mg/dL),hyperosmolarity(plasma osmolarity 310 mOsm/L)and dehydration,the absence of ketoacidosis,and depression of the sensorium.It may occur in various conditions including:Type 2 diabetesAcute pancreatitisSevere infectionMyocardial infarctionTreatment with oral or
13、parenteral nutrition solutionsIt is seen most frequently in people with type 2 diabetes.Two factors appear to contribute to the hyperglycemia that precipitates the condition:An increased resistance to the effects of insulinAn excessive carbohydrate intake.,The hyperglycemic hyperosmolar nonketotic(H
14、HNK)syndrome,In hyperosmolar states,the increased serum osmolarity has the effect of pulling water out of body cells,including brain cells.The condition may be complicated by thromboembolic events arising because of the high serum osmolality.The most prominent manifestations are dehydration:Neurolog
15、ic signs and symptoms:Grand mal seizuresHemiparesisAphasiaMuscle fasciculationsHyperthermiaVisual field lossNystagmusVisual hallucinationsExcessive thirstThe onset of HHNK syndrome often is insidious,and because it occurs most frequently in older people,it may be mistaken for a stroke.,Treatment,Jud
16、icious medical observation and care because water moves back into brain cells during treatment,posing a threat of cerebral edema.Extensive potassium losses that also have occurred during the diuretic phase of the disorder require correction.,Hypoglycemia,Hypoglycemia occurs from a relative excess of
17、 insulin in the blood and is characterized by below-normal blood glucose levels.It occurs most commonly in people treated with insulin injections,but prolonged hypoglycemia also can result from some oral hypoglycemic agents(i.e.,beta cell stimulators).Many factors precipitate an insulin reaction in
18、a person with type 1 diabetes,including:Error in insulin doseFailure to eatIncreased exerciseDecreased insulin need after removal of a stress situationMedication changes and a change in insulin siteAlcohol decreases liver gluconeogenesis,and people with diabetes need to be cautioned about its potent
19、ial for causing hypoglycemia.,Hypoglycemia,Because the brain relies on blood glucose as its main energy source,hypoglycemia produces behaviors related to altered cerebral function:HeadacheDifficulty in problem solvingDisturbed or altered behaviorComaSeizures At the onset of the hypoglycemic episode,
20、activation of the parasympathetic nervous system often causes hunger.The initial parasympathetic response is followed by activation of the sympathetic nervous system;this causes anxiety,tachycardia,sweating,and constriction of the skin vessels(i.e.,the skin is cool and clammy).,Treatment,The most ef
21、fective treatment of an insulin reaction is the immediate ingestion of a concentrated carbohydrate source,such as sugar,honey,candy,or orange juice.Alternative methods for increasing blood glucose may be required when the person having the reaction is unconscious or unable to swallow:Glucagon may be
22、 given intramuscularly or subcutaneously.In situations of severe or life-threatening hypoglycemia,it may be necessary to administer glucose intravenously.,The Somogyi effect,The Somogyi effect describes a cycle of insulin-induced posthypoglycemic episodes.In people with diabetes,insulin-induced hypo
23、glycemia produces a compensatory increase in blood levels of catecholamines,glucagon,cortisol,and growth hormone.These counterregulatory hormones cause blood glucose to become elevated and produce some degree of insulin resistance.The cycle begins when the increase in blood glucose and insulin resis
24、tance is treated with larger insulin doses.The hypoglycemic episode often occurs during the night or at a time when it is not recognized,rendering the diagnosis of the phenomenon more difficult.Measures to prevent this phenomena include a redistribution of dietary carbohydrates and an alteration in
25、insulin dose or time of administration.,The dawn phenomenon,The dawn phenomenon is characterized by increased levels of fasting blood glucose or insulin requirements,or both,between 5 and 9 AM without preceding hypoglycemia.It has been suggested that a change in the normal circadian rhythm for gluco
26、se tolerance,which usually is higher during the later part of the morning,is altered in people with diabetes.Growth hormone has been suggested as a possible factor.When the dawn phenomenon occurs alone,it may produce only mild hyperglycemia,but when it is combined with the Somogyi effect,it may prod
27、uce profound hyperglycemia.,Chronic complications,These disorders occur in the insulin-independent tissues of the body tissues that do not require insulin for glucose entry into the cell.This probably means that intracellular glucose concentrations in many of these tissues approach or equal those in
28、 the blood.Chronic complications can be reduced by intensive diabetic treatment.,Peripheral neuropathies,Two types of pathologic changes have been observed in connection with diabetic peripheral neuropathies.The first is a thickening of the walls of the nutrient vessels that supply the nerve,leading
29、 to the assumption that vessel ischemia plays a major role in the development of these neural changes.The second finding is a segmental demyelinization process that affects the Schwann cell.This demyelinization process is accompanied by a slowing of nerve conduction.The clinical manifestations of th
30、e diabetic peripheral neuropathies vary with the location of the lesion.,Classification of diabetic peripheral neuropathies,Somatic:Polyneuropathies(bilateral sensory)Paresthesias,including numbness and tinglingImpaired pain,temperature,light touch,two-point discrimination,and vibratory sensationDec
31、reased ankle and knee-jerk reflexesMononeuropathiesInvolvement of a mixed nerve trunk that includes loss of sensation,pain,and motor weakness.AmyotrophyAssociated with muscle weakness,wasting,and severe pain of muscles in the pelvic girdle and thigh.,Autonomic:Impaired vasomotor functionPostural hyp
32、otensionImpaired gastrointestinal functionGastric atonyDiarrhea,often postprandial and nocturnalImpaired genitourinary functionParalytic bladderIncomplete voidingImpotenceRetrograde ejaculationCranial nerve involvementExtraocular nerve paralysisImpaired pupillary responsesImpaired special senses,Dia
33、betic nephropathy,Diabetic nephropathy is the leading cause of end-stage renal disease,accounting for 40%of new cases.The term diabetic nephropathy is used to describe the combination of lesions that often occur concurrently in the diabetic kidney.The most common kidney lesions in people with diabet
34、es are those that affect the glomeruli.Various glomerular changes may occur,including capillary basement membrane thickening,diffuse glomerular sclerosis,and nodular glomerulosclerosis.Among the suggested risk factors for diabetic nephropathy are:Genetic and familial predispositionElevated blood pre
35、ssurePoor glycemic controlSmokingHyperlipidemiaMicroalbuminuria,Pathogenesis,Three major histologic changes occur in the glomeruli of persons with diabetic nephropathy.First,mesangial expansion is directly induced by hyperglycemia,perhaps via increased matrix production or glycosylation of matrix pr
36、oteins.Second,GBM thickening occurs.Third,glomerular sclerosis is caused by intraglomerular hypertension(induced by renal vasodilatation or from ischemic injury induced by hyaline narrowing of the vessels supplying the glomeruli).The exact cause of diabetic nephropathy is unknown,but various postula
37、ted mechanisms are:Hyperglycemia(causing hyperfiltration and renal injury)Advanced glycosylation productsActivation of cytokines,Pathogenesis,Hyperglycemia increases the expression of transforming growth factor-beta(TGF-beta)in the glomeruli and of matrix proteins specifically stimulated by this cyt
38、okine.TGF-beta may contribute to the cellular hypertrophy and enhanced collagen synthesis observed in persons with diabetic nephropathy.In addition to the renal hemodynamic alterations,patients with overt diabetic nephropathy(dipstick-positive proteinuria and decreasing GFR)generally develop systemi
39、c hypertension.Hypertension is an adverse factor in all progressive renal diseases and seems especially so in diabetic nephropathy.The deleterious effects of hypertension are likely directed at the vasculature and microvasculature.Familial or perhaps even genetic factors also play a role.Certain eth
40、nic groups,particularly African Americans,persons of Hispanic origin,and American Indians,may be particularly disposed to renal disease as a complication of diabetes.,Pathogenesis,Retinopathies,Although people with diabetes are at increased risk for the development of cataracts and glaucoma,retinopa
41、thy is the most common pattern of eye disease.Diabetic retinopathy is characterized by abnormal retinal vascular permeability,microaneurysm formation,neovascularization and associated hemorrhage,scarring,and retinal detachment.Among the suggested risk factors associated with diabetic retinopathy are
42、 poor glycemic control,elevated blood pressure,and hyperlipidemia.Because of the risk of retinopathy,it is important that people with diabetes have regular dilated eye examinations.Some people develop a condition called macular edema.It occurs when the damaged blood vessels leak fluid and lipids ont
43、o the macula,the part of the retina that lets us see detail.The fluid makes the macula swell,which blurs vision.,Pathogenesis,Diabetic retinopathy is the result of microvascular retinal changes.Hyperglycemia-induced thickening of the basement membrane lead to incompetence of the vascular walls.These
44、 damages change the formation of the blood-retinal barrier and also make the retinal blood vessels become more permeable.The lack of oxygen in the retina causes fragile,new,blood vessels to grow along the retina and in the clear,gel-like vitreous humour that fills the inside of the eye.Without timel
45、y treatment,these new blood vessels can bleed,cloud vision,and destroy the retina.Fibrovascular proliferation can also cause tractional retinal detachment.The new blood vessels can also grow into the angle of the anterior chamber of the eye and cause neovascular glaucoma.,Pathogenesis,Diabetic retin
46、al vascular leakage,capillary nonperfusion,and endothelial cell damage are temporary and spatially associated with retinal leukocyte stasis in early experimental diabetes.Retinal leukostasis increases within days of developing diabetes and correlates with the increased expression of retinal intercel
47、lular adhesion molecule-1(ICAM-1).Several interacting and mutually perpetuating biochemical pathways or systems,such as the polyol pathway,nonenzymatic glycation,oxidative stress,protein kinase and the reninangiotensin system,may be activated as a result of sustained hyperglycemia in diabetes.These
48、abnormally activated pathways may in turn influence several vasoactive factors and cytokines,such as vascular endothelial growth factor,interleukin-6,which are important in mediating the functional and structural changes of diabetic retinopathy.,Macrovascular complications,Diabetes mellitus is a maj
49、or risk factor for coronary artery disease,cerebrovascular disease,and peripheral vascular disease.Multiple risk factors for vascular disease,including obesity,hypertension,hyperglycemia,hyperlipidemia,altered platelet function,and elevated fibrinogen levels,frequently are found in people with diabe
50、tes.In people with type 2 diabetes,macrovascular disease may be present at the time of diagnosis.In type 1 diabetes,the attained age and the duration of diabetes appear to correlate with the degree of macrovascular disease.,Diabetic foot ulcers,Foot problems are common among people with diabetes and
