# Examination of Postmortem \(\beta\)-Hydrobutyrate Increase in Forensic Autopsy Cases
## 1 Introduction  
Metabolic acidosis is defined as the imbalanced condition of increased hydrogen ions and reduced bicarbonate ions in the body [1]. It has two categories, acute and chronic. According to one review, acute metabolic acidosis could result in an increased mortality rate [2]. Three pathologies are well known in the developmental mechanisms of metabolic acidosis: acid excretion decrease in the kidney, loss of bicarbonate ions, and an increase in acid generation. Usually, nonvolatile metabolic acids from daily meals are excreted in the urine from the kidney. However, in cases with decreased renal function or type 1 and 4 renal tubular acidosis, acid excretion from the kidney decreases, and it results in metabolic acidosis [1]. Loss of bicarbonate ions could happen in conditions such as severe diarrhea or type 2 renal tubular acidosis. The stool osmolality of people who have diarrhea could almost be equal to the serum osmolality. As the diarrbed stool contains electrolytes, this results in the loss of bicarbonate ions [3]. In type 2 renal tubular acidosis, the reabsorption of bicarbonate ions was decreased, which caused metabolic ketoacidosis [4]. The increase in acid generation simply means that elevated acid levels cause metabolic ketoacidosis. Although there are several causes that promote the acid generation, the above review reported that the increase in acid generation, especially lactic acidosis and ketoacidosis, accounts for up to 70% of severe metabolic acidosis [2]. Lactic acidosis is usually caused by hypoperfusion of tissues, such as sepsis, or toxin-induced such as methanol poisoning [5].  
Ketoacidosis is one of the most common disease states in the field of forensic science. Ketoacidosis is known as metabolic acidosis caused by the accumulation of ketone bodies. There are several causes that could trigger ketoacidosis, such as diabetes, alcohol, or specific intoxication [6; 7; 8]. Diabetic ketoacidosis is the most common cause. There are multiple case reports that show death as the result of diabetic ketoacidosis [9; 10; 11]. Patients with type 1 diabetes are often associated with diabetic ketoacidosis. Even patients with type 2 diabetes could suffer from it. This can include severe stress, infection, and trauma [12]. Usually, serum glucose levels are maintained primarily by two hormones, glucagon, and insulin. As mechanisms of diabetic ketoacidosis, the deficiency and/or tolerance of insulin, and glucagon excess are considered [13; 14]. Chronic alcoholism patients with malnutrition are at risk of suffering from alcoholic ketoacidosis. When they cannot drink alcohol due to nausea or vomiting caused by alcoholism, the catecholamine levels elevate, which results in an increase in lipolysis [15]. Therefore, fatty acid oxidation results in ketone body production.  
Measuring ketone bodies, such as acetone, acetoacetate, and \(\beta\)-hydroxybutyrate (BHB), is necessary to diagnose diabetic or alcoholic ketoacidosis as a cause of death [16; 17; 18]. In addition to ketone bodies in the blood, other fluids, such as vitreous or pericardial fluid, have been investigated [19; 20; 21]. Samples other than blood could also be alternative tools for diagnosing ketoacidosis. BHB measurement is the most important test to establish the diagnosis of postmortem ketoacidosis [22; 23]. This is because that BHB should be stable even after death for a period of 24-72 h [24]. However, patients with increased BHB values, which were unlikely to be caused by ketoacidosis or pathologies that increase BHB, such as hypothermia, can occasionally be found [25]. Although reports indicate that BHB values do not increase after death, one study demonstrated increased postmortem BHB levels [26]. Thus, a long postmortem interval (PMI) was often suspected in these patients. The current study aimed to determine the relationship between the PMI and BHB levels in autopsies.