# Metabolic Periparturient Diseases in Small Ruminants: An Update
## 2 Pregnancy Toxemia and Lactational Ketosis
### Diagnosis and Biomarkers
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Biomarker** & **Cutoff** & **Se (\%)** & **Sp (\%)** \\ \hline Glucose (mg/dL) & - & - & - \\ (subclinical) & \textless{}40.3 & 63.6 & 83.3 \\ \hline Fructosamine (mmol/L) & \textless{}0.6 & 89.3 & 72.2 \\ (subclinical) & \textless{}1.0 & 90.0 & 75.3 \\ \hline NEFA (mmol/L) & \textgreater{}0.7 & 86.4 & 70.6 \\ (subclinical) & \textgreater{}0.4 & 70.0 & 90.0 \\ \hline Triglycerides (mg/dL) & \textgreater{}29.9 & 73.9 & 64.7 \\ (subclinical) & \textgreater{}20.5 & 72.7 & 83.3 \\ \hline Cholesterol (mg/dL) & \textgreater{}71.0 & 73.9 & 70.6 \\ \hline Albumin (g/dL) & \textless{}2.7 & 73.9 & 64.7 \\ \hline AST (U/L) & \textgreater{}123.8 & 82.6 & 62.5 \\ \hline GGT (U/L) & \textgreater{}76.3 & 81.0 & 66.7 \\ (subclinical) & \textgreater{}47.7 & 66.7 & 75.0 \\ \hline LDH (U/L) & \textgreater{}760.3 & 81.0 & 66.7 \\ (subclinical) & \textgreater{}645.4 & 60.0 & 64.6 \\ \hline CK (U/L) & \textgreater{}222.2 & 76.2 & 64.7 \\ \hline Calcium (mg/dL) & \textless{}7.1 & 68.2 & 64.7 \\ \hline Potassium (mEq/L) & \textless{}3.6 & 66.6 & 58.8 \\ \hline MDA (nmol MDA/mL) & \textgreater{}29.3 & 78.2 & 64.7 \\ (subclinical) & \textgreater{}21.9 & 77.8 & 61.2 \\ \hline SOD (U/g Hb) & \textless{}287.3 & 78.3 & 64.7 \\ \hline CAT (U/g Hb) & \textless{}97.9 & 65.2 & 64.7 \\ \hline \hline \end{tabular} Non-sentiferied acids (NEFA), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), creatine kinase (CK), superoxide dismutase (SOD), catalase (CAT), malondialdehydedehyde (MDA), superoxide dismutase (SOD) and catalase (CAT).  
\end{table} 
Table 1: Thresholds of metabolic and oxidative biomarkers for clinical (and subclinical) pregnancy toxemia in ewes [47]. diffuse hepatic damage impairing albumin synthesis as well as increased production of liver enzymes, mainly aspartate transaminase, gamma-glutamyl transferase, and lactate dehydrogenase, indicators of hepatocyte damage. The increase in creatine kinase has been justified by low protein intake (similar to potassium) and skeletal and myocardial muscle damage (e.g., recumbency) during the evolution of the disease [53; 59]. Calcium is intrinsically connected mainly to tissue reaction [60], and its deficit (ionized) form reduces the production of endogenous glucose in hyperketonemic ewes [61]. Moreover, [PERSON] et al. [52] observed a positive correlation between insulinemia and plasmatic levels of total calcium (r = 0.51) or its ionizable fraction (Ca\({}^{++}\)) (r = 0.52) in goats. Hypoinsulinemia is reported in both ewe [62] and does [59] and is probably related to the adverse effect of NEFA on \(\beta\)-pancreatic cells or cortisol regulation. In fact, negative correlations between insulinemia and NEFA (r= \(-\)0.70) or cortisol (r= \(-\)0.52) were observed in goats [52]. These findings highlight the complex relationships between different metabolites that should be deeply elucidated, including with IR, such as previously mentioned. Regarding oxidative stress, both normal NEB and PT induce reactive oxygen species (ROS) during late pregnancy, such as malondialdehydedehyde (MDA), through lipid peroxidation [63]. MDA, a highly reactive compound causing mutations and cell damage, is a useful general indicator of oxidative status, and as its plasmatic levels increase, it can also serve as a predictor of diagnosis and prognosis. Inversely, the superoxide dismutase enzyme catalyzes ROS to hydrogen peroxide, and the catalase enzyme helps to regulate this peroxidation process [47]. Due to the ROS effect on myocardial muscle, higher plasmatic levels of troponin I, a specific marker of cardiac myocyte damage, were observed in survivors PT ewes (0.7 \(\pm\) 0.4 ng/mL) or non-survivors PT ewes (1.0 \(\pm\) 0.5 ng/mL) than in healthy ewes (0.3 \(\pm\) 0.0 ng/mL; \(p\) < 0.001) [62].