Ganong's Review of Medical Physiology, 23rd Edition

460 SECTION V Gastrointestinal Physiology
CLINICAL BOX 27–2
Disorders of Iron Uptake
Iron deficiency causes anemia. Conversely, iron overload
causes hemosiderin to accumulate in the tissues, producing
hemosiderosis. Large amounts of hemosiderin can
damage tissues, causing hemochromatosis. This syndrome
is characterized by pigmentation of the skin, pancreatic
damage with diabetes (“bronze diabetes"), cirrhosis of the
liver, a high incidence of hepatic carcinoma, and gonadal
atrophy. Hemochromatosis may be hereditary or acquired.
The most common cause of the hereditary forms is a mutated
HFE gene that is common in the Caucasian population.
It is located on the short arm of chromosome 6 and is
closely linked to the human leukocyte antigen-A (HLA-A)
locus. It is still unknown precisely how mutations in HFE
cause hemochromatosis, but individuals who are homogenous
for HFE mutations absorb excess amounts of iron because
HFE normally inhibits expression of the duodenal
transporters that participate in iron uptake. If the abnormality
is diagnosed before excessive amounts of iron accumulate
in the tissues, life expectancy can be prolonged by
repeated withdrawal of blood. Acquired hemochromatosis
occurs when the iron-regulating system is overwhelmed by
excess iron loads due to chronic destruction of red blood
cells, liver disease, or repeated transfusions in diseases such
as intractable anemia.
The amount of energy liberated per unit of time is the metabolic
rate. Isotonic muscle contractions perform work at a
peak efficiency approximating 50%:
Essentially all of the energy of isometric contractions
appears as heat, because little or no external work (force multiplied
by the distance that the force moves a mass) is done
(see Chapter 5). Energy is stored by forming energy-rich
compounds. The amount of energy storage varies, but in fasting
individuals it is zero or negative. Therefore, in an adult
individual who has not eaten recently and who is not moving
(or growing, reproducing, or lactating), all of the energy output
appears as heat.
CALORIES
Efficiency =
Work done
------------------------------------------------------
Total energy expended
The standard unit of heat energy is the calorie (cal), defined as
the amount of heat energy necessary to raise the temperature
of 1 g of water 1 degree, from 15 °C to 16 °C. This unit is also
called the gram calorie, small calorie, or standard calorie. The
unit commonly used in physiology and medicine is the Calorie
(kilocalorie; kcal), which equals 1000 cal.
CLINICAL BOX 27–3
Obesity
Obesity is the most common and most expensive nutritional
problem in the United States. A convenient and reliable indicator
of body fat is the body mass index (BMI), which is
body weight (in kilograms) divided by the square of height (in
meters). Values above 25 are abnormal. Individuals with values
of 25–30 are overweight, and those with values > 30 are
obese. In the United States, 55% of the population are overweight
and 22% are obese. The incidence of obesity is also increasing
in other countries. Indeed, the Worldwatch Institute
has estimated that although starvation continues to be a
problem in many parts of the world, the number of overweight
people in the world is now as great as the number of
underfed. Obesity is a problem because of its complications.
It is associated with accelerated atherosclerosis and an increased
incidence of gallbladder and other diseases. Its association
with type 2 diabetes is especially striking. As weight
increases, insulin resistance increases and frank diabetes appears.
At least in some cases, glucose tolerance is restored
when weight is lost. In addition, the mortality rates from
many kinds of cancer are increased in obese individuals. The
causes of the high incidence of obesity in the general population
are probably multiple. Studies of twins raised apart show
a definite genetic component. It has been pointed out that
through much of human evolution, famines were common,
and mechanisms that permitted increased energy storage as
fat had survival value. Now, however, food is plentiful in many
countries, and the ability to gain and retain fat has become a
liability. As noted above, the fundamental cause of obesity is
still an excess of energy intake in food over energy expenditure.
If human volunteers are fed a fixed high-calorie diet,
some gain weight more rapidly than others, but the slower
weight gain is due to increased energy expenditure in the
form of small, fidgety movements (nonexercise activity
thermogenesis; NEAT). Body weight generally increases at a
slow but steady rate throughout adult life. Decreased physical
activity is undoubtedly a factor in this increase, but decreased
sensitivity to leptin may also play a role.
CALORIMETRY
The energy released by combustion of foodstuffs outside the
body can be measured directly (direct calorimetry) by oxidizing
the compounds in an apparatus such as a bomb calorimeter,
a metal vessel surrounded by water inside an insulated
container. The food is ignited by an electric spark. The change
in the temperature of the water is a measure of the calories
produced. Similar measurements of the energy released by
combustion of compounds in living animals and humans are
much more complex, but calorimeters have been constructed
that can physically accommodate human beings. The heat