Chong Zhou

Factors and processes causing accelerated decomposition in human cadavers - An overview.

Artefactually enhanced putrefactive and autolytic changes may be misinterpreted as indicating a prolonged postmortem interval and throw doubt on the veracity of witness statements. Review of files from Forensic Science SA and the literature revealed a number of external and internal factors that may be responsible for accelerating these processes. Exogenous factors included exposure to elevated environmental temperatures, both outdoors and indoors, exacerbated by increased humidity or fires. Situations indoor involved exposure to central heating, hot water, saunas and electric blankets. Deaths within motor vehicles were also characterized by enhanced decomposition. Failure to quickly or adequately refrigerate bodies may also lead to early decomposition. Endogenous factors included fever, infections, illicit and prescription drugs, obesity and insulin-dependent diabetes mellitus. When these factors or conditions are identified at autopsy less significance should, therefore, be attached to changes of decomposition as markers of time since death.

Armanni-Ebstein lesions: a need for clarification.

Armanni–Ebstein lesions were first described by Luciano Armanni, a pathologist at the University of Naples, during autopsy studies undertaken in 1872, as a unique vacuolar nephropathy associated with poorly controlled diabetes that involves selective renal epithelial cell glycogen accumulation. However, within the last two decades, a broader range of vacuolar changes, including lipid deposition, have also been termed Armanni–Ebstein (AE) lesions, creating some confusion on possible etiology. We would suggest that the term AE phenomenon would be best reserved for the original clear cell change associated with glycogen deposition, and that this should be clearly distinguished from subnuclear lipid vacuolization (“basal vacuolization”). Although there is obvious inter‐relation between these two types of vacuoles, they appear morphologically and biochemically distinct from each other. More precise classification may assist in clarifying the causal processes and possible diagnostic significance of different types of renal epithelial vacuolization at autopsy.

Basal Renal Tubular Epithelial Cell Vacuolization and Alcoholic Ketoacidosis

Abstract:  Subnuclear renal tubular epithelial cell vacuolization is a marker for diabetic ketoacidosis. Whether it is because of hyperglycemia or of ketoacidosis is unclear. To examine the effect of ketoacidosis on renal cells in isolation, five cases of lethal alcoholic ketoacidosis without hyperglycemia were examined (vitreous humor β‐hydroxybutyrate: 6.42–8.75 mM, mean 7.66 mM; and glucose: 0.1–4.2 mM, mean 1.46 mM). Microscopic examination of the kidneys revealed basal vacuoles in three cases (60%). Seven control cases with acute alcohol toxicity without ketoacidosis (blood alcohol: 0.18–0.43%, mean 0.31%; and β‐hydroxybutyrate: 0.12–0.42 mM, mean 0.21 mM) did not have these changes. In this study, basal epithelial vacuolization was found only in cases with significant ketoacidosis. Although the numbers are small, the finding of basal renal tubular epithelial vacuolization in normoglycemic cases with elevated β‐hydroxybutyrate levels provide further evidence that disordered lipid metabolism may be involved in the pathogenesis of this phenomenon.

How Useful is Basal Renal Tubular Epithelial Cell Vacuolization as a Marker for Significant Hyperglycemia at Autopsy

Abstract:  Basal vacuolization of renal tubular epithelial cells (so‐called Armanni–Ebstein phenomenon) has been attributed to hyperglycemia causing accumulation of cytoplasmic glycogen. Review of 34 autopsy cases with significant hyperglycemia (vitreous glucose ≥15 mmol/L/270 mg/dL) was undertaken to determine whether there was any significant association between the degree of hyperglycemia and the severity of this morphological change (graded as 0, 1+, 2+, and 3+). No association was demonstrated. Review of the subgroup of 14 cases with terminal hyperglycemia without ketoacidosis was then undertaken to assess the effect of hyperglycemia in isolation on renal tubular epithelial cells. Vitreous glucose levels in these 14 cases ranged from 17 to 49.7 mmol/L (306–894.6 mg/dL) with a mean of 26.25 mmol/L (472.5 mg/dL) and β‐hydroxybutyrate levels ranged from 0.02 to 2.55 mmol/L (0.36–45.9 mg/dL) with a mean 0.79 mmol/L (14.22 mg/dL). Not one of the latter cases displayed basal vacuolization. No relationship between basal vacuolization of renal tubular epithelial cells at autopsy and terminal hyperglycemia could, therefore, be demonstrated.

Early diagnosis of Armanni–Ebstein phenomenon at autopsy

Case reportA 41-year-old woman with a past history of insulin-dependent diabetes mellitus, intravenous drug use andasthma was found collapsed and unresponsive at her homeaddress. Her history also included previous hospitaladmissions with diabetic ketoacidosis. She was conveyedby ambulance to hospital, where she was found to beunconscious, hypotensive and acidotic with a markedlyelevated blood glucose level. Resuscitative efforts wereunsuccessful.At autopsy, the most significant finding was of markedpallor of both renal cortices on cut section (Fig. 1). Otherfindings included pulmonary edema with evidence ofrecent attempts at resuscitation.

Renal Tubular Epithelial Vacuoles— A Marker for Both Hyperlipidemia and Ketoacidosis at Autopsy

Review of 15 cases of nephrotic syndrome found that eight had significant hyperlipidemia with serum cholesterol levels ranging between 10.59 and 18.60 mmol/L (mean 12.88) and serum triglyceride levels between 2.30 and 9.92 mmol/L (mean 4.58); all of these cases displayed basal lipid vacuolization. Seven of the 15 study cases had normal–mild hyperlipidemia with serum cholesterol levels ranging between 4.71 and 7.54 mmol/L (mean 6.02) and serum triglyceride levels between 0.65 and 4.1 mmol/L (mean 1.57). Six of the seven cases had basal lipid vacuoles (86%). Of these, five cases were hyperlipidemic and one case had borderline hyperlipidemia with a serum cholesterol level of 4.71 mmol/L. Although hyperlipidemia was associated with renal tubular epithelial vacuolization, the vacuoles appeared morphologically different to those found in ketoacidosis. This study has shown that while hyperlipidemia in isolation may result in basal lipid vacuolization within renal tubular epithelial cells, the phenotype differs from that observed in ketoacidosis.

Septic Ketoacidosis—A Potentially Lethal Entity with Renal Tubular Epithelial Vacuolization

Fatal ketoacidosis due to diabetes mellitus, alcoholism, and starvation may produce characteristic basal vacuolization of renal tubular epithelial cells (RTEC). Septic ketoacidosis has recently been recognized clinically as a distinct condition in which septicemia can lead to elevation of ketones and various anions unrelated to diabetes mellitus, alcoholism, or caloric deprivation. We report four lethal cases with significantly elevated vitreous ketones secondary to sepsis and/or severe localized infection in individuals with no history of diabetes mellitus, alcoholism, or starvation. Three of four cases exhibited typical basal vacuolization of RTEC. We suggest that septic ketoacidosis is an appropriate cause of death in the forensic setting where sepsis or severe localized infection is found with significant ketoacidosis (β‐hydroxybutyrate > 5 mmol/L)—in the absence of diabetes mellitus, alcoholism, starvation, or other states associated with accelerated ketogenesis. The finding of basal vacuolization of RTEC in such cases provides morphological support for the underlying metabolic derangement.

Renal cortical pallor--a useful macroscopic marker for metabolic derangements at autopsy.

Renal cortical pallor was studied as a potential marker at autopsy of diabetic ketoacidosis in 23 cases, hyperglycemic nonketotic coma in eight cases, and alcoholic ketoacidosis in five cases (vitreous humor glucose level ≥11.1 mM; β‐hydroxybutyrate level ≥5 mM). Renal cortical pallor was noted on macroscopic examination in 10 of 23 cases of lethal diabetic ketoacidosis (43.5%), three of eight cases of fatal hyperglycemic nonketotic coma (37.5%), and in two of five cases of alcoholic ketoacidosis (40%). Histologic examination revealed basal vacuolization of renal tubular epithelial cells in 12 cases, Armanni–Ebstein lesions in 10, and osmotic nephrosis in three. Although renal cortical pallor did not appear to be a particularly sensitive marker for hyperglycemia or ketoacidosis, and did not correlate with the severity of these parameters, it may still represent a useful macroscopic marker for underlying metabolic conditions at autopsy and should therefore prompt measurement of vitreous humor glucose and β‐hydroxybutyrate levels.

Basal Vacuolization in Renal Tubular Epithelial Cells at Autopsy and Their Relation to Ketoacidosis

Basal vacuolization of renal tubular epithelial cells is a useful postmortem marker for ketoacidosis. To investigate its incidence and relationship to the severity of ketoacidosis, 158 autopsy cases with elevated β‐hydroxybutyrate (>1 mmol/L) over a 7‐year‐period were retrospectively reviewed. Sixty‐eight cases (43%) exhibited basal vacuolizations (vitreous β‐hydroxybutyrate: 1.16–29.35 mmol/L, mean 10.28 mmol/L), and 90 cases (57%) did not (vitreous β‐hydroxybutyrate: 1.03–13.7 mmol/L, mean 2.84 mmol/L). Quantitative analysis revealed on average a fourfold elevation in β‐hydroxybutyrate in cases with basal vacuolizations compared to those without; 10.3% of cases with β‐hydroxybutyrate concentrations between 1.01 and 2.00 mmol/L had basal vacuolizations, and this incidence increased to 33.3% with concentrations between 4.01 and 6.00 mmol/L. A marked increase in incidence to >70% was observed with concentrations >6.00 mmol/L, and basal vacuoles were invariably present (100%) with concentrations >14.01 mmol/L. This study demonstrates that basal vacuolizations are a sensitive marker for significant ketoacidosis and reaffirms its use as an indicator for likely cases of fatal ketoacidosis at autopsy.

Armanni–Ebstein Lesions in Terminal Hyperglycemia

Armanni–Ebstein lesions (AEL) occur in deaths related to uncontrolled diabetes mellitus. To investigate the relationship between AEL and terminal hyperglycemia, we retrospectively reviewed 71 cases with vitreous glucose levels ≥11.1 mmol/L; 27 (38%) cases had AEL (vitreous glucose 14.0–77.3 mmol/L); and 44 cases (62%) did not (vitreous glucose 11.1–91.9 mmol/L). There was no significant difference (p = 0.271) in vitreous glucose levels between the cases with AEL (mean 39.2, SD 16.7 mmol/L) and those without (mean 34.2, SD 19.8 mmol/L). Similarly, there was no difference in the degree of dehydration, renal failure, or osmolality. However, there was a significantly higher level of β‐hydroxybutyrate among the cases with AEL compared to those without (p = 0.007), suggesting that ketoacidosis may facilitate the development of AEL. Given the possible synergistic role of β‐hydroxybutyrate, the correlation between AEL and terminal hyperglycemia in animal studies may not be applicable to humans. AEL may also possibly occur with sublethal elevations in glucose.