**1. Introduction**

220 From Preconception to Postpartum

Winje B, Saastad E, Gunnes N, Tveit J, Stray-Pedersen B, Flenady V & Frøen J. (2011).

doi: 10.1111/j.1471-0528.2011.02993.x. [Epub ahead of print]

Analysis of 'count-to-ten' fetal movement charts: a prospective cohort study. *BJOG*.

If exhaustion or muscle fatigue is discussed in a general conversation, usually people will refer lactate accumulation as a primary cause. Lactate accumulates in blood and tissues during exercise, particularly when oxygen is lacking. The concentration is highest at or just following exhaustion. Lactate has historically been considered as a dead-end waste product of anaerobic metabolism due to hypoxia and the primary cause of fatigue (Berzelius 1808; Araki 1891; Hartree & Hill 1921; Hill 1922). Lactate has also been considered as a key factor in acidosis-induced tissue damage; however the role of lactate in metabolism has changed during the last decade (Brooks 1986; Brooks 2002; Brooks 2002) Lactate is no longer considered as a harmful end-product, but mainly one of the central players in cellular and whole body metabolism. tissues

The breakdown of glycogen during anaerobic conditions leads to intracellular accumulation lactic acid. Lactic acid is a strong monocarboxylic acid (Pka 3, 86) and it dissociates easily at physiological pH into lactate and hydrogen ions (H+). The lactate itself has been considered to have little effect on muscle contractions. However, increased production of H+ and reduced pH with acidosis has classically been considered as the cause of muscle fatigue. The role of reduced pH as an important cause of fatigue has been challenged (Karlsson et al. 1975). Present day knowledge is that anaerobic metabolism with the production of lactic acid might also lead to increased production of other factors, like phosphate (Allen et al. 2002; Westerblad & Allen 2002; Westerblad et al. 2002) which is likely to have a more prominent role in muscle fatigue.

One important finding, which has influenced the hypotheses for this thesis, is that the myometrium is a lactate producer (Taggart & Wray 1993; Taggart et al. 1996; Taggart et al. 1997; Taggart & Wray 1998; Wray et al. 2003; Quenby et al. 2004), and the level will increase when there is a lack of oxygen.

The essential function of amniotic fluid (AF) is to cushion the fetus. The fluid gives the fetus space to grow, and allows it to undergo a `physical´ development. The AF function is also to protect the fetus from trauma and to maintain temperature. It also has a minimal nutritive function.

Lactate Level in Amniotic Fluid, a New Diagnostic Tool 223

membranes. Ion pumps require ATP to function. Regeneration of sufficient amount of ATP can no longer be sustained if anaerobic metabolism continues. In this catabolic situation, the basic cellular functions start to fail. Three different cellular energy statuses are described (Nordstrom & Arulkumaran 1998). The first one is aerobic when there is sufficient amount of oxygen and a lot of energy is produced in the form of ATP. This is an efficient way of energy production. The two others are dependent on the level of oxygen supply, and if the situation is compensated or not. Lack of oxygen forces the cell into an anaerobic metabolism with production of lactate and H+. Energy is produced but to a limited amount. If the demand of energy is still sufficient, the cellular energy status is compensated. This can continue as long as energy demand and production is in balance. If the situation is progressing, regeneration of ATP can no longer be keep up with demands and the cellular

In a normal state, the buffering systems of the organism have the capacity to maintain pH within a physiological range. It is important for the organism to maintain stability in pH, i.e. H+ concentrations. A fluctuation of H+ is dangerous for the cell. If the concentration of H+ rises it may disturb cellular function and affect the activity of

There are different buffering systems within the organism. The two most important systems are the bicarbonate and the protein buffering systems. These two systems main functions are to neutralize H+ which has been produced through anaerobic metabolism. The role of the bicarbonate buffer is to establish equilibrium between CO2, H2CO3, bicarbonate (HCO3) and hydrogen ions (H+), via the equation shown below (Siggaard-

CO2 + H2O H2CO3 H+ + HCO3- In this reaction CO2 is passing through and at the end is converted to bicarbonate, which leaves the red blood cells by means of an exchange of chlorides. The equation goes from left to right and back again several times until a steady state condition is established. At steady

Knowledge about lactate is a rapidly changing field, and our understanding of the role of lactate metabolism has changed dramatically from the classical views held in the 19th century. The lactic acid era began in 1808 when Berzelius at the Karolinska Institute in Stockholm, discovered elevated concentrations of lactate in `the muscles of hunted stags´ (Berzelius 1808). Araki showed in 1891 that lactic acid concentration in exhausted animal muscles was proportional to the amount of exercise and was associated to O2 availability (Araki 1891). Some 100 years after Berzelius, Fletcher and Hopkins showed that lactic acid appeared in response to muscle contraction in human muscle (Fletcher & Hopkins 1907).They also showed that accumulated lactate disappeared when oxygen became available. Later on the `lactic-acid-cycle´ was described, and showed two distinct pathways in metabolism, the aerobic and the anaerobic. The coming period was called `the revolution in muscle physiology´. From the 1930's to the early

state total cellular CO2 production equals CO2 elimination.

energy status will be decompensated

**2.2 Buffering systems** 

cellular enzymes.

Andersen 1971).

**3. Lactate** 
