section 22.8
Abnormalities of Metabolic Homeostasis
511
F IG U R E 2 2 -2 4
Postabsorptive metabolism of amino acids and the acid-base metabolic
switch. In the early postabsorptive phase, the liver is the primary source of
plasma glucose formed from alanine, delivered from muscle or intestine.
The primary nitrogen product is urea. As starvation progresses, the need
for acid-base balance results in decreased glutamine uptake by the
splanchnic bed and increased uptake by the kidney. In the kidney,
glutamine produces ammonium ion as counterion for /1-hydroxybutyrate
and acetoacetate. The carbon chain of glutamine is used in
gluconeogenesis. If starvation progresses, the need for acid-base balance
results in decreased glutamine uptake by the splanchnic bed and increased
uptake by the kidney. The branched-chain amino acids serve as major
substrates for muscle metabolism. Later in starvation, some of the
branched-chain amino acids, notably valine, are released from muscle and
can be used by the brain as a source of energy.
utilized for renal gluconeogenesis, the activity of which
is quantitatively equivalent to that of liver. The change
in location of glutamine metabolism with long-term star-
vation has been termed the
acid-base metabolic switch.
Figure 22-24 summarizes the organ interrelationships in
amino acid fluxes postprandially and during extended
starvation. Figure 22-25 shows the sources and sites of
glucose production during starvation. In early starvation,
hepatic glycogen becomes depleted as gluconeogenesis
increases. As starvation progresses, gluconeogenesis di-
minishes in the liver but increases in the kidney as
the need for ammonia excretion increases. This switch
is reflected by the nitrogen excretion products. In the
fed state, urea predominates. In fasting, the total ni-
trogen excreted decreases, and as starvation progresses,
G lu c o se production
D a y s of starvation
F IG U R E 2 2 -2 5
Sources of glucose production during starvation. [Reproduced with
permission from F. J. Cahill, Physiology of insulin in man:
D i a b e t e s
20,
783 (1971).]
urea excretion decreases while ammonia excretion in-
creases, coinciding with the increased rate of renal
gluconeogenesis.
22.8 Abnormalities of Metabolic Homeostasis
In this section two major health problems are discussed—
diabetes mellitus and obesity.
Diabetes Mellitus
Diabetes mellitus
is a syndrome consisting of a group
of metabolic diseases all of which are characterized by
hyperglycemia. The development of diabetes comprises
several pathogenic processes involving autoimmune de-
struction of pancreatic
ft
cells with consequent insulin
deficiency and resistance to insulin action. The abnor-
malities of insulin deficiency or its action on target tis-
sues lead to derangements in carbohydrate, lipid, and
protein metabolism. The symptoms of hyperglycemia
consist of polyuria, polydipsia, polyphagia, weight loss,
blurred vision, and susceptibility to infections. The acute
life-threatening complications of diabetes are ketoacido-
sis in the absence of insulin therapy or the nonketotic
hyperosmolar coma (Chapter 39). Long-term complica-
tions of diabetes are development of retinopathy with po-
tential loss of vision, nephropathy with end-stage renal
disease, neuropathy with a potential for foot infections
