# Metabolic Periparturient Diseases in Small Ruminants: An Update
## 2 Pregnancy Toxemia and Lactational Ketosis
### Etiopathology  
PT is triggered by a deficient energy intake coupled with increased energy demand to support exponential fetal growth. Fetuses' weight reaches 60 to 80% of their live weight at birth during the last weeks of gestation, consuming 30 to 40% of glucose/day [13; 26]. Females with twin or triplet pregnancies require at least 180 to 240% more energy, respectively, than females with singleton pregnancies [26]. PT, as well as LK, can be classified as primary and secondary. Primary ketosis is due to the energy deficit itself. Secondary ketosis develops intercurrently with other diseases (e.g., acidosis, dehydration, hypocalcemia, parasitic infections, or chronic wasting diseases), causing a decrease in feed intake [27; 28]. Following severe undernutrition is normal, and a homehetic adaptation occurs [29]. The problem arises when the disruption of this adaptative mechanism occurs. Under normal conditions, small ruminants consume approximately 5-6% of their live weight of dry matter (DM) per day [30]. From middle (about 1.33 kg DM/day) to late pregnancy, and due to the pressure exerted by the pregnant uterus on the rumen, the ingestion capacity progressively decreases until parturition (about 1.21 kg DM/day). This decrease in DM intake is also associated with the development dynamics of rumen papillae according to the type of feed (amyloidic/cellulolytic) provided. In this way, and also regarding LK, there is an increase in the amount of feed ingested from the kidding or lambing time, reaching peak intake at approximately eight weeks in lactation. The peak intake occurs approximately 2-3 weeks later than the peak of lactation. As a result, approximately 2 to 6 weeks of the antepartum period and in the following 8 weeks after parturition, there is, to a greater or lesser extent, an insufficient energy supply causing hypoglycemia (normal serum levels of 2.2 to 3.3 mmol/L). In ruminants, the energy deficit is compensated through mobilization (triglyceride hydroxylation) of adipose tissue reserves by lipolysis, which is mediated mainly by the hormone glucagon. A loss of body condition score is observed, and the so-called negative energy balance (NEB) is established. When energy input exceeds energy output, generally after the 2 nd month of lactation, excess energy is metabolized by lipogenesis mediated by the insulin hormone, resulting in adipocyte accumulations, mainly subcutaneous. When NEB occurs, circulating non-esterified fatty acids (NEFA) originating from adipocyte lipolysis are transported to the mitochondria of the hepatocyte and are metabolized there into three types of ketones, beta-hydroxybutyrate (BHBA), acetoacetate, and acetone (which are strong acids causing metabolic acidosis) [31]. From the combination of the acyl group of ketones with coenzyme A (limiting factor), acetyl coenzyme A arises, an energy source in various tissues (mitochondria of skeletal muscle, mammary gland, heart, and kidneys [32; 33; 34]. Oxidation of acetyl coenzyme A also produces lactic acid. Hyperketonemia occurs when high levels of circulating NEFA are metabolized in the liver (see the hepatic oxidation theory by [PERSON] et al. [35]. As ruminants have limitations in the export of lipoproteins into the bloodstream at the membrane level [36], hyperketonemia is normally associated with a certain degree of hepatic lipidosis due to diffuse lipid accumulation in hepatocytes, i.e., hepatic steatosis or fatty liver. This lipidosis causes liver dysfunction [37], with a poor prognosis when it reaches 35% of the liver weight [38]. In PT, hepatic steatosis assumes a relevant manifestation with an impact on the evolution of the disease. Ketosis is also classified as type 1 and type 2, similar to type 1/type 2 diabetes mellitus in humans, and also known as thin cow syndrome and fat cow syndrome in cattle, respectively [39]. Ketosis type 1 occurs when the demand for glucose exceeds the capacity for neoglucogenesis.