Significant ketoacidosis at autopsy: a single-centre systematic review

AimTo examine the value of vitreous beta-hydroxybutyrate and serum acetone in the investigation of sudden unexpected death.MethodsCoroners’ autopsy reports from a provincial UK city, with a population of approximately 900 000, over a 24-month period with significant ketoacidosis were studied. Demographic features, medical history, anatomical and histological findings, and biochemical parameters, including renal function, vitreous glucose, serum and vitreous alcohol, were analysed.ResultsForty-two cases (28 males and 14 females) were identified; 55% had a history of alcohol and/or substance misuse, and mental health problems, particularly depression and anxiety, and 16% were diabetic. In all, 50% of subjects had alcoholic ketoacidosis (AKA), 19% had diabetic ketoacidosis (DKA) and 12% had a history of both diabetes and alcohol abuse. In 19% of cases, an exact cause of ketoacidosis was established. In AKA, the subjects typically had low vitreous glucose and low or undetected blood alcohol levels. All of the subjects with raised vitreous glucose levels had DKA.ConclusionKetoacidosis is relatively common and should be considered as a cause of sudden death, especially in alcoholic patients and patients with diabetes with no clear cause of death at autopsy.

The Importance of BHB Testing on the Post-Mortem Diagnosis of Ketoacidosis

Although beta-hydroxybutyrate (BHB) analysis has proved its importance in forensic pathology, its effects on cause-of-death diagnostics are unaddressed. Therefore, this study aims at evaluating the effects of BHB analysis on the number of deaths by DKA (diabetes ketoacidosis), AKA (alcoholic ketoacidosis), HHS (hyperosmolar hyperglycaemic state), hypothermia, diabetes, alcoholism, and acidosis NOS (not otherwise specified). All 2900 deaths from 2013 through 2019 in which BHB was analysed at the National Board of Forensic Medicine, and 1069 DKA, AKA, HHS, hypothermia, diabetes, alcoholism, and acidosis cases without BHB analysis were included. The prevalence of BHB-positive cases for each cause of death, and trends and proportions of different BHB concentrations, were investigated. The number of BHB analyses/year increased from 13 to 1417. AKA increased from three to 66 and acidosis from one to 20. The deaths from alcoholism, DKA, and hypothermia remained stable. It is unclear why death from alcoholism remained stable while AKA increased. The increase in unspecific acidosis deaths raises the question why a more specific diagnosis had not been used. In conclusion, BHB analysis is instrumental in detecting AKA and acidosis. The scientific basis for the diagnosis of DKA and hypothermia improved, but the number of cases did not change.

Starvation Ketosis and the Kidney

<b><i>Background:</i></b> The remarkable ability of the body to adapt to long-term starvation has been critical for survival of primitive man. An appreciation of these processes can provide the clinician better insight into many clinical conditions characterized by ketoacidosis. <b><i>Summary:</i></b> The body adapts to long-term fasting by conserving nitrogen, as the brain increasingly utilizes keto acids, sparing the need for glucose. This shift in fuel utilization decreases the need for mobilization of amino acids from the muscle for purposes of gluconeogenesis. Loss of urinary nitrogen is initially in the form of urea when hepatic gluconeogenesis is dominant and later as ammonia reflecting increased glutamine uptake by the kidney. The carbon skeleton of glutamine is utilized for glucose production and regeneration of consumed HCO₃⁻. The replacement of urea with NH₄⁺ provides the osmoles needed for urine flow and waste product excretion. Over time, the urinary loss of nitrogen is minimized as kidney uptake of filtered ketone bodies becomes more complete. Adjustments in urine Na⁺ serve to minimize kidney K⁺ wasting and, along with changes in urine pH, minimize the likelihood of uric acid precipitation. There is a sexual dimorphism in response to starvation. <b><i>Key Message:</i></b> Ketoacidosis is a major feature of common clinical conditions to include diabetic ketoacidosis, alcoholic ketoacidosis, salicylate intoxication, SGLT2 inhibitor therapy, and calorie sufficient but carbohydrate-restricted diets. Familiarity with the pathophysiology and metabolic consequences of ketogenesis is critical, given the potential for the clinician to encounter one of these conditions.