Starvation prolonged

The primary fate of acetyl CoA under normal metabolic conditions is degradation in the citric acid cycle to yield C02. When the body is stressed by prolonged starvation, however, acetyl CoA is converted into compounds called ketone bodies, which can be used by the brain as a temporary fuel. Fill in the missing information indicated by the four question marks in the following biochemical pathway for the synthesis of ketone bodies from acetyl CoA ... 

In the liver, it forms ketone bodies (acetone, ace-toacetate, and 3-hydroxybutyrate) that are important fuels in prolonged starvation. 

Free fatty adds in plasma are a major source of energy, particularly under marathon conditions and in prolonged starvation. 

Many tissues (muscle, liver, renal cortex) prefer fat for an energy supply, at least in the resting state. The exception is red blood cells and brain. These tissues depend heavily on glycolysis for energy. Red cells cannot survive without glucose (no mitochondria), but during prolonged starvation, brain can adapt to utilize fat metabolites produced by the liver (ketone bodies). 

Appropriate management of AN also requires the early detection and treatment of any comorbid psychiatric disorders. The most common comorbid conditions associated with AN are major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and substance use disorders. At the time of presentation, over 50% of AN patients also fulfill criteria for MDD however, accurate diagnosis of depression in these patients is complicated by the fact that prolonged starvation often produces a mood disturbance and neurovegetative symptoms identical to MDD. If MDD appears to be comorbid with AN at the time of presentation, there is debate as to whether it is more prudent to withhold treatment of the depression until weight restoration has been initiated. If the depression persists despite refeeding, then treatment of the depression is likely warranted. 

Figure 3.18 Oxidation of glucose and ketone bodies by the brain. Glucose is the sole fuel used by the brain, except in prolonged starvation in adults or relatively short-term starvation in children. In both cases, ketone bodies plus glucose are used.

The extract from Colin Blakemore s book provides a vivid account of the behavionral consequences of a low blood glucose level. This is because the brain uses glucose as the only fuel, except in prolonged starvation. Problems also arise if the blood glucose level increases well above the normal. An increase of only about twofold above the... 

In this book it is suggested that one possible cause of death in prolonged starvation is severe hypoglycaemia. This may be due to a lack of amino acid precursors since almost all the body protein has been broken down. Alternatively, the fat store in the body has been totally depleted, so that the plasma fatty acid level will be close to zero. Consequently, there will be no fatty acid oxidation in the liver and therefore little or no ATP generation to support gluconeogenesis. Post-mortem studies on individuals who have died of starvation show that the fat stores are totally depleted. This topic is discussed further in Chapter 16. 

It is unlikely that the rate of ATP generation in the hver under normal conditions will be decreased to such an extent that ATP/ADP concentration will be seriously affected. However, some extreme physiological conditions, such as intense and prolonged physical activity, prolonged starvation and haemorrhagic shock may result in reduced perfusion of the liver and lack of oxygen that could result in a marked decrease in the rate of ATP generation. The effect... 

Two conditions in which the rate of ketone body formation is increased are hypoglycaemia and prolonged starvation in adults or short-term starvation in children. What is the mechanism for increasing the rate Although there are several fates for fatty acids in the liver, triacylglycerol, phospholipid and cholesterol formation and oxidation via the Krebs cycle, the dominant pathway is ketone body formation (Figure 7.20). Three factor regulate the rate of ketone body formation (i) hormone sensitive lipase activ-... 

Ketone bodies are oxidised by most aerobic tissues including skeletal muscle, heart, kidney, lung, intestine and brain. Since the last two cannot oxidise fatty acids, their ability to oxidise ketone bodies is very important, because they provide another fuel in addition to, or as an alternative to, glucose. Hence, they can be used to replace some of the glucose to maintain the blood glucose concentration (e.g. in prolonged starvation or hypoglycaemia). 

In the 1970s the physiological importance of ketone bodies was revived, quite dramatically, when George Cahill and his colleagues demonstrated that ketone bodies could be used by the human brain during prolonged starvation and, furthermore, contributed significantly to ATP... 

Protein represents the second largest store of chemical energy in the body, but it is not used for generating ATP except in some diseases and in some extreme conditions (e.g. prolonged starvation, very sustained exercise). The largest deposit of protein in the body is in skeletal muscle (about 40% of body weight). The synthesis of proteins requires amino acids whereas degradation of proteins pro-... 

In the fed state, the only fuel used by the brain is glucose, derived from the blood. In prolonged starvation or chronic hypoglycaemia, ketone bodies are nsed which rednce the rate of utilisation of glucose by the brain bnt, even so, glucose still provides about 50% of the energy. Consequently, under all conditions, maintenance of the blood glucose concentration is essential for the function of the brain the mechanisms that are responsible for this are discnssed in Chapters 6, 12 and 16. 

The most obvious cause of undemutrition is prolonged starvation, which is most dramatic in parts of the world where war, drought or other disasters have brought about failed harvests or mass migration. 

The use of prolonged starvation for treatment of obesity has posed a fascinating problem that man is capable of fasting for periods of time beyond which he would have used all his carbohydrate resources and all his protein for gluconeogenesis in order to provide adequate calories as glucose for the central nervous system. 

Very few scientihc studies have been carried out on humans during prolonged starvation. One of the first concerned a single individual and later studies confirmed that the responses observed in this classical experiment were not atypical. Tragically, the Second World War provided the opportunity to study the effects of starvation on much larger populations, for example in the Western Netherlands, the Warsaw Ghetto and German and Japanese... 

On the basis of the resnlts with the obese, starvation can be divided arbitrarily into five phases the postabsorptive period, early starvation, intermediate starvation, prolonged starvation and, finally, the premortal period. Although these are characterised by different metabolic patterns, the transition from one period to another is gradnal. Some of the changes in the postabsorptive period and early starvation are described elsewhere in this book bnt they are bronght together in this chapter for completeness. 

There is no clear-cut division between intermediate and prolonged starvation but after about three weeks the following will apply ... 

The rise in blood ketone bodies continues during intermediate and prolonged starvation. After about 20 days the concentration reaches a plateau at about 8 mmol/L, mostly hydroxybutyrate (Figure 16.10). 

Figure 16.11 Pattern of fuel utilisation during prolonged starvation. The major metabolic change during this period is that the rates of ketone body formation and their utilisation by the brain increases, indicated by the increased thickness of lines and arrows. Since less glucose is required by the brain, gluconeogenesis from amino acids is reduced so that protein degradation in muscle is decreased. Note thin line compared to that in Figure 16.9.

Figure 16.12 Role of ketone bodies leading to a reduction in the high rate of protein degradation in prolonged starvation.

A dehciency of amino acids resnlts in decreased production of albnmin in the liver, lowering its concentration in the plasma and hence the colloid osmotic pressure. Consequently, fluid is lost from the blood and its viscosity increased, so that the heart has to work harder to pnmp the same quantity of blood and eventually it may not be able to cope, especially as cardiac muscle is lost in prolonged starvation (Table 16.6). Death will then resnlt from cardiac failure. 

Figure 16.14 Effect of thyroidectomy on survival of rats during starvation. Thyroidectomy protects rats from starvation that is, the number or rats surviving prolonged starvation is much larger when the thyroid gland is removed (Goldberg et al. 1978).

In prolonged starvation more ammonia than urea is excreted in order to batter the urine from the acidic ketone bodies that are present in the urine. 

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