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This presentation discusses the cellular mechanisms of Diabetes Mellitus and its correlation with clinical presentation, focusing on the case of a patient with Diabetic Ketoacidosis (DKA). Topics include the regulation of glycolysis by glucagon and insulin, therapeutic measures for treating DKA, and the cellular impact of the condition.
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DIABETES MELLITIUS Cells and Molecules Clinical Application Presented 9/6/02 By M. Grant Ervin MD,MHPE,FACEP
Objectives • Correlate clinical presentation of patient with DKA with occurrences on cellular level • Describe mechanisms by which glucagon and insulin regulate glycolysis • Discuss therapeutic measures used to treat the patient in DKA and the cellular impact
A 45 year old male is brought into the ED c/o increased thirst, dizziness, weakness for the past week. He denies any medical problems, medications, allergies.BP – 100/60, RR-24, HR – 120, Temp.99.9 F
What are the abnormalities? • Thirst • Weakness • Low blood pressure • Fast heart rate • Fast respiratory rate
Simultaneous Diagnostic, Therapeutic, and Rescuscitative Measures Pulse Ox EKG IV line, blood for I-stat, extra tubes to be determined Cardiac monitor, BP monitor Physical Exam significant dry mucus membranes and abnormal vital signs as stated
Carbon monoxide/cyanide exposure Alcohol Touluene Methanol uremia DKA Paraldehyde ingestion Isoniazid/Iron Lactic acidosis Ehtylene glycol salicylates Causes of Elevated Anion Gap Metabolic Acidosis
Cellular Correlations • Elevated glucose levels secondary to decreased insulin, liver has diminished enymatic capacity to remove glucose • Decreased glucokinase activity • Loss of insulin’s action on key enzymes of glycogenesis and the glycolytic pathway • Liver stuck in gluconeogenesis fueled by substrate from body protein degradation
Cellular Correlations (con.) • Muscle fails to take up glucose with decreased insulin • Adipose tissue is stimulated to lipolysis due to low insulin/glucagon ration • Leads to increased blood levels fatty acids • Accelerated ketone body production • Metabolic acidosis • Increase respiratory rate is trying to correct acidosis
Overall metabolism is stuck in every tissue continuing its catabolic state producing more fuel despite increase glucose. Insulin/ glucagon ration is unbalanced
Therapeutic Measures • Fluids • Insulin • Correct electrolyte deficiencies • Look for precipitating causes
Summary • In Insulin Dependent and Non-Insulin Dependent Diabetes the insulin/ glucagon ratio is vital in intracellular glucose control • Therapeutic measures are directly tied to what is occurring on a cellular level