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.     

Hyperosmolarity Induces Armanni‐Ebstein‐like Renal Tubular Epithelial Swelling and Cytoplasmic Vacuolization

Armanni–Ebstein lesions have been considered pathognomonic for diabetes mellitus and appear as markedly swollen renal tubular epithelial cells with cytoplasmic clearing and glycogen accumulation. However, the extent to which hyperosmolarity contributes to the Armanni–Ebstein phenotype is unclear. Ten sheep were injected intravenously with 20% mannitol at 11 mOsm/kg, and subsequent histological evaluation of the kidneys showed variable degrees of osmotic nephrosis and cytoplasmic clearing of renal tubular epithelial cells similar to that seen with Armanni–Ebstein lesions. However, although morphological changes similar to Armanni–Ebstein lesions could be produced, no intracytoplasmic glycogen was demonstrated with periodic Acid–Schiff (PAS) stain. This suggests that while hyperosmolarity may contribute to the development of an Armanni–Ebstein phenotype, glycogen accumulation may result from the more complex metabolic effects of glucose on renal tubular epithelial cells. Thus, when Armanni/Ebstein‐like vacuolizations are seen at autopsy, a confirmatory PAS stain is recommended because of the potential effect of hyperosmolar states.     

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.     

Letter to the Editor

I was surprised to read in Joseph Savirimuthu's article on theGoogle Print Library project (Volume     

Letter to the Editor

Geneva, 2^nd April 2008 Professor Geoff Gilbert Editor-in-Chief International Journal of Refugee Law Dear Professor Gilbert, May I refer to the article on ‘Redundant or Essential?How politics shaped the Outcome of the 1967 Protocol’by Dr. Sara Davies in the     

A Letter to the Editor

Respected Comrade Editor:

Permit me to relate to you an everyday scene in the life of a lawyer.     

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.     

Letter From the Editor

American Journal of Criminal Justice -     

Letter from the Editor

American Journal of Criminal Justice -