Staging the development of pathological liver changes in metabolic dysfunction in cows: from initial compensation to decompensation

Abstract

Ketosis (acetonemia) is one of the widespread metabolic diseases in cows causing significant economic damage due to reduced productivity and premature culling of animals. Fatty liver disease which develops as a result of energy imbalance and impaired utilization of fatty acids is a key link in the pathogenesis. Despite the sufficient study of the problem, the relationship between the fractions of ketone bodies and specific stages of morphological changes in the liver parenchyma remains understudied. The research goal was to analyze the relationship between the concentration of ketone bodies in peripheral blood and morphological changes in liver tissue in cows with ketosis. Histological and biochemical studies revealed the stages of decompensation of liver function in ketosis. At the initial (functional) stage with the preserved structure of the organ, the peak values of the total number of ketone bodies were recorded up to 3.8 mmol L and beta-hydroxybutyrate (BHB) up to 2.95 mmol L with a coefficient of BHB/AcAs of 3.3-4.4. During the transition to structural changes (centrolobular dystrophy), large-drop liposis is observed in the center of the lobules. At the stage of total dystrophy, multiple destruction of hepatocyte nuclei and proliferation of connective tissue occur. At the same time, the total number of ketone bodies level and the BHB/AcAs ratio naturally decrease to 2.02 mmol L and 1.3, respectively, and the concentration of acetoacetic acid (AcAc) reaches its maximum of 1.15 mmol L. A metabolic paradox was revealed: increase of glucose and alkali reserve levels to a physiological level at deep organ destruction. The severity of ketosis and the stage of fatty liver disease are inversely related to the level of ketonemia. Decrease of the total number of ketone bodies against the background of a critical increase of acetoacetic acid is an unfavorable prognostic sign indicative of the loss of metabolic activity by the parenchyma of the organ and the onset of decompensation.