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)

[@Rashedov]

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