); [EMAIL_ADDRESS] (I-A.C.) Institute of Forensic Medicine, 700455 Iasi, Romania 1  
[PERSON]  
1 Faculty of Medicine, \"[PERSON]\" University of Medicine and Pharmacy, 700115 Iasi, Romania; [EMAIL_ADDRESS] (D.B.I. ); [EMAIL_ADDRESS] (R.O.C. ); [EMAIL_ADDRESS] (D.B.I. ); [EMAIL_ADDRESS] (R.O.C. ); [EMAIL_ADDRESS] (D.E. ); [EMAIL_ADDRESS] (M.D. ); [EMAIL_ADDRESS] (A.D.T. ); [EMAIL_ADDRESS](A.K. ); [PERSON] (I-A.C.) Institute of Forensic Medicine, 700455 Iasi, Romania 1
be easily noticed in cases of decompensated diabetes (diabetic ketoacidosis-DKA), starvation/malnutrition, chronic alcoholism (alcoholic ketoacidosis), infections, trauma, hypothermia, or certain intoxations [2; 3]. Serum levels of circulating ketone bodies vary in a not metabolically ill individual depending on the rate of basal metabolism, hepatic glycogen stores and mobilization of amino acids of muscle proteins [3]. Normal serum level of total ketone bodies is generally considered \(<\)0.5 mM (\(<\)500 \(\upmu\)mol/L); hyperketonemia being defined by values \(>\)1 mM (\(>\)1000 \(\upmu\)mol/L), and the state of ketoacidosis is characterized by values exceeding 2.5-3 mM [3]. For each form of ketone bodies, plasma values in a healthy adult vary according to the type and time since food intake, most studies considering the following serum normal values: AcAc \(<\) 56 \(\upmu\)mol/L, BHB \(<\) 86 \(\upmu\)mol/L, Ac \(<\) 5 \(\upmu\)mol/L [4; 5]. [PERSON] et al. and [PERSON] et al. state that in the absence of prolonged periods of food deprivation, normal serum of BHB levels range from 0 to 160 \(\upmu\)mol/L and AcAc from 0 to 70 \(\upmu\)mol/L [6; 7]. Analyzing these data and considering that in an acidic environment, AcAc is rapidly converted to Ac, which is rapidly eliminated by respiration, it can be deduced that BHB is the main serum exponent of total ketone bodies [3; 5; 6]. Diabetic ketoacidosis develops because of insulin deficiency or insulin resistance, with increased production of free fatty acids, decreased utilization in tissues and accelerated transformation into ketone bodies in hepatocyte mitochondria. During starvation, the glucagon/insulin ratio is \(>\)1 and fatty acids are mobilized from triglycerides in adipose tissue and converted to ketone bodies [8]. Disease and trauma can also be associated with rapid protein and lipid depletion, with potential significant metabolic imbalances and endogenous production of ketone bodies. Alcoholic ketoacidosis (AKA) can occur because of glycogen and insulin depletion, reduced extracellular fluid volume, increased NADH/NAD+ ratio secondary to ethanol metabolization, but can also be associated with hypoglycemia because of starvation and lipolysis [9; 10]. Increased ketone body values have been identified in hypothermia, a phenomenon explained by increased levels of glucagon, cortisol, and growth hormones with catabolic action on fatty acids [11; 12]. The first thanatochemical studies to prove ketoacidosis post-mortem involved simple qualitative and/or semi-quantitative determination of total ketone bodies and qualitative and/or quantitative determination of acetone, respectively. Over time, ketoacidosis detection has undergone a series of improvements both in a clinical and forensic setting [13; 14; 15]. Currently, postmortem assessment of endogenous ketoacidosis is primarily focused on the determination of BHB, the biochemical marker that most accurately reflects the level of ketone bodies relative to that present immediately prior to death [16; 17], as BHB is the most stable ketone body that can be identified in a state of ketoacidosis. The other two ketone bodies, AcAc and Ac, are unreliable due to their unstable nature. AcAc is converted to Ac under acidic conditions and Ac is eliminated by respiration. The postmortem diagnosis of endogenous ketoacidosis can only be performed by BHB determination, as it belongs to the category of sudden deaths without an obvious macro/microscopic morphological substrate.