# Metabolic Periparturient Diseases in Small Ruminants: An Update
## 2 Pregnancy Toxemia and Lactational Ketosis
### Diagnosis and Biomarkers  
In PT, the main clinical signs that serve as a diagnosis in life are the reduction in physical activity levels with apathy and anorexia in late gestation, showing odontoprises, nervous symptoms (hypoglycemic encephalopathy), and blindness [24; 45]. Progressively, and over a period of three to seven days, affected animals present ataxia and sternal recumbency (mainly in pregnancy toxemia), progressing to coma and death [46] (Figure 1). Dehydration and ketoacidosis develop concomitantly. This evolution is mainly due to the diffuse hepatic steatosis. The degree of fat infiltration in the liver can be achieved through histological evaluation at necropsy [27; 45], or even in live animals by a liver biopsy. Similar symptoms can occur in LK, with a decrease in milk production (hypogaloxia), but the evolution of the disease is less abrupt and intense unless concomitant severe fatty liver occurs. Biochemistry plays a crucial role in the diagnosis and prognosis of ketosis, with emphasis on PT. Several metabolites and enzymes can serve as biomarkers for both purposes (Table 1). Biochemical biomarkers are useful tools, but due to the great variation of values, additional research is needed to establish accurate indicators for early diagnosis and prognosis of different statuses of these diseases. Regarding the metabolic profiles, the measurement of serum BHBA levels, with thresholds between 0.8 and 1.7 mmol/L for subclinical ketosis and clinical form between 2.5 and 3 mmol/L, has been accepted to confirm the diagnosis of both diseases in ewes and does [19; 24; 47; 48; 49; 50; 51]. Nonetheless, the clinical approach of individuals requires the determination of more biomarkers to evaluate the status of different body organs and systems. Although hypoglycemia is common in cases of PT, up to 40% of cases present normal serum levels of glucose, and >20% have hyperglycemia due to cases of insulin resistance in peripheral tissues [45]. However, different proportions of glycemia (hypo, normo, and  
Figure 1: Diagram of diagnosis and therapeutic procedures of pregnancy toxemia in small ruminants. Non-esterified acids (NEFA), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), aspartate transaminase (AST), calcium (Ca), and magnesium (Mg). hyperglycemia) in the ambulatory veterinary clinic have been reported [52; 53]. The normal range (normoglycemia) of serum glucose levels varies between 50 to 80 mg/dL in small ruminants [54]. The variation of serum glucose levels seems primarily related to ketosis type I or II, i.e., involving the mechanism of insulin resistance in peripheral tissues. Some composite indices, such as surrogate indices, have been applied to dairy cows [55] and goats [56] to estimate insulin sensitivity/resistance from glucose, NEFA, BHBA, and insulin. But like in human medicine (e.g., [57]), cut-offs are required to predict its occurrence and the level of intervention (e.g., the dose of insulin to be administered). Further confirmation of cerebrospinal fluid glucose concentrations can be more accurate than blood glucose concentrations, which can serve as a diagnostic value together with the measurement of BHBA. NEFA serum concentration may also be increased above 0.4 mmol/L due to hepatic lipidosis. Mean serum levels of 0.6 \(\pm\) 0.1 and 1.0 \(\pm\) 0.2 (mmol/L) were reported in ewes affected by subclinical and clinical PT, respectively [47]. In does presenting clinical PT, Serum NEFA reached a mean of 1.7 \(\pm\) 0.7 mmol/L [58] Regarding the lipid metabolism, plasmatic levels of triglycerides and cholesterol show a similar profile to NEFA. Fructosamine, an irreversible conjugation between the glucose and amino group of protein, can serve as an indicator of blood glucose levels during the last two weeks and as a consequence of timeline diagnosis of subclinical forms of ketosis. Its low levels can be used as PT (see Table 1) or non-survival (<0.2 mmol/L) predictor [47]. Nonetheless, some care is necessary in interpreting cases of norm or hyperglycemia. Fatty liver is causing