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Diabetic ketoacidosis (mechanism of disease)

This is a mechanism of disease map for diabetic ketoacidosis, covering the etiologies of DKA, the diabetes pathophysiology, and some of the DKA-specific manifestations. ADDITIONAL TAGS: Inflammation / cell damage Signs / symptoms Labs / tests / imaging results Diabetic ketoacidosis Core concepts Social determinants of health / risk factors Drugs / pharmacology Microbial pathogenesis Osmolarity / fluid status Hormone communication Homeostasis / regulation Biochemistry Diabetes pathophysiology Insulin deficit; glucagon excess Adipose catabolism (lipolysis → release of glycerol + fatty acids) Muscle catabolism (protein breakdown + release of amino acids) ↑ hepatic fatty acid oxidation ↑ ketone body production Ketosis: ↑ urine and serum ketones Amino acids and glycerol carbons are used for gluconeogenesis Polyphagia Weight loss Hyperglycemia (moderate, 250 mg/dL) ↑ glucose filtering at nephron Kidney unable to reabsorb filtered glucose Glycosuria Osmotic diuresis Polyuria Dehydration, volume depletion ↓ circulating volume → ↓ renal blood flow → ↓ glucose to nephron Polydipsia Hyperosmolarity in blood and tissues Stimulation of osmoreceptors in hypothalamus Undiagnosed, untreated diabetes Drugs (steroids, cocaine, alcohol) Insulin pump failure Forgotten injection Poor adherence Cannot afford Stress (trauma, surgery, infections [pneumonia, UTI], MI, burns, heatstroke) Insufficient insulin ↑ insulin demand Etiology ↑ hepatic glucose output, ↓ peripheral tissue glucose uptake ↑ anion gap ketoacidosis Resp compensation to produce more bicarb Production of protons (H+) Depletion of plasma bicarb Shift of K from intra- to extracellular fluid Hyperkalemia Hyperpnea; long, deep breaths (Kussmaul respirations) Abdominal pain, nausea, and/or vomiting Ileus, gastric stasis, electrolyte imbalance, peritoneal irritation, and/or gastric mucosal damage Altered mental status Cerebral hypoperfusion Acid alters neural function Osmotic shifts, cerebral ischemia, BBB destruction Cerebral edema DKA manifestations Anuria, oliguria Fruity odor on breath (from acetone)