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Diarrhea is the most common cause of death in calves, and remains a major health challenge. Although there are many studies on the related pathogens, the understanding of the clinicopathological changes is limited. This study aimed to identify the pathogens and observe the clinicopathological changes in electrolytes and acute phase proteins (APPs) associated with diarrhea. Blood samples and fecal samples were collected from 141 calves for the determination of APPs, electrolyte and acid-base status and identification of enteropathogens, respectively. Single or co-infections with enteropathogens, including virus (bovine viral diarrhea virus, coronavirus, and rotavirus), Eimeria, Cryptosporidium, and Escherichia coli K99 were detected in both non-diarrheic and diarrheic calves. Levels of APPs such as serum amyloid A, haptoglobin and fibrinogen were comparable between diarrheic and nondiarrheic calves. Hypoglycemia, high blood urea, electrolytes and acid-base imbalance (hyponatremia, hypochloremia, and decreased bicarbonate), and strong ion difference (SID) acidosis showed a significant association in diarrheic calves (p < 0.01). Particularly, significant hyponatremia, bicarbonate loss, SID acidosis, hypoglycemia, and elevated blood urea nitrogen were found in rotavirusinfected calves. Monitoring the clinicopathological parameters of APPs and electrolyte levels could be vital in the clinical management of diarrheic calves.