· Intro
· Endocrine and metabolic effects
· Organ system effects
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Definition |
· Life-threatening acute metabolic complication of type 1 diabetes mellitus |
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Pathophysiology |
· Absolute or near insulin deficiency o Missed doses o Sudden ↑ insulin resistance e.g. acute illness · ↓↓ peripheral glucose uptake · Cells metabolise alternative substrates · Hence ↑[glucose], ↑[ketones], ↑anion gap metabolic acidosis (HAGMA) |
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Hormone profile |
· ↓ insulin · ↑ glucagon, cortisol, catecholamines |
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Metabolic pathways |
· ↑[glucose] o ↓GLUT-4 -> ↓uptake into skeletal muscle and fat o ↓glycolysis o ↑gluconeogenesis from glycerol/lactate/pyruvate/amino acids (liver > kidney) o ↑glycogenolysis, ↓glycogenolysis (liver, skeletal muscle) · ↑[lipids] o ↑Hormone-sensitive lipase activity · ↑[ketones] o ↑ratio acetyl-CoA : oxaloacetate -> ↑ketogenesis |
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Fluid |
· ↑Osmolarity (due to ↑glucose more than ↑ketones) · ↓Blood volume, cellular dehydration (due to osmotic diuresis) · ↑RAAS (early ↓due to ↑NaCl at macula densa, late ↑ due to ↓afferent arteriolar stretch) · ↓ADH early if ↑osmolality (sensitive ±1-3%), ↑ADH late if ↓blood volume (sensitive ±10%), ↓mAP |
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Electrolytes |
· Dilutional ↓[Na+] o ↓1mmol/L for each +1mmol/L ↑[glucose] · ↑[K+] o ↓ insulin-mediated cell uptake, ↑K+/H+ exchange) o Note global K+ depletion due to urinary loss (osmotic diuresis -> ↑ROMK activity) · ↑[Ca2+] o ↑ H+/Ca2+ exchange with bone |
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Acid-base |
· Ketoacids -> HAGMA · Lactic acid -> HAGMA (if ↓blood volume -> ↓tissue pO2 -> ↑anaerobic metabolism) |
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Renal |
· Initial ↑ urine output o Transport maximum of 375mg/min exceeded at BSL >10mmol/L o Hyper-osmolar urine, osmotic diuresis · Later ↓ urine output o Due to ↓blood volume -> mAP <70mmHg -> ↓ GFR o ±ARF, anuria, ATN · ↑Gluconeogenesis |
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Cardiovascular |
· Heart: o Acidosis: ↓ inotropy, arrhythmia, arrest (predominates if pH <7.2) o SNS: ↑ inotropy, ↑ HR (predominates if pH >7.2) · ↓Blood volume -> ↓ preload -> ↓ cardiac output -> ↓ mAP · Vessels: o Acidosis: systemic dilatation, pulmonary constriction o SNS: systemic + pulmonary constriction |
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Respiratory |
· Acidosis: systemic dilatation, pulmonary constriction, right shift OHDC · SNS: systemic + pulmonary constriction |
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Central nervous system |
· Acidosis -> ↑SNS output · Glucose supply preserved by constitutive GLUT1 |