Page 300 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Late Complications of Prolonged Hyperglycemia (Diabetes Mellitus)
The metabolic abnormalities of inadequately lagen in the basement membranes of the blood
treated relative or absolute insulin deficiency vessels. The formation of connective tissue is
(→ p. 286–289) will in the course of years or in part stimulated via transforming growth
decades lead to extensive irreversible changes factor β (TGF-β). Additionally, however, the
in the organism. Hyperglycemia plays a central collagen fibers can be changed by glycosyla-
role in this. tion. Both changes produce thickening of the
Glucose is reduced to sorbitol in cells that basement membranes with reduced perme-
contain the enzyme aldosereductase. This ability and luminal narrowing (microangiopa-
hexahydric alcohol cannot pass across the cell thy; → A7). Changes occur in the retina, also as
membrane, as a result of which its cellular a result of microangiopathies, that ultimately
concentration increases and the cell swells may lead to blindness (retinopathy; → A8). In
(→ A1). Due to an accumulation of sorbitol in the kidney glomerulosclerosis (Kimmelstiel–
the lens of the eye, water is incorporated, im- Wilson) develops, which can result in protein-
pairing lenticular transparency (clouding of uria, reduced glomerular filtration rate due to
the lens [cataract]; → A2). Accumulation of a loss of glomeruli, hypertension, and renal
sorbitol in the Schwann cells and neurons re- failure (→ A9). Because of the high amino acid
Hormones fecting mainly the autonomic nervous system, place in the remaining intact glomeruli, which
concentration in plasma, hyperfiltration takes
duces nerve conduction (polyneuropathy), af-
as a result are also damaged.
reflexes, and sensory functions (→ A3). To
Together with a rise of VLDL in blood
off myoinositol which then, however, will not
9 avoid swelling, the cells compensate by giving (→ p. 288) and the raised clotting tendency of
be available for other functions. the blood (see above), hypertension promotes
Cells that do not take up glucose in suffi- the development of a macroangiopathy (→
cient amounts will shrink as a result of extra- A10) that can further damage the kidneys and
cellular hyperosmolarity (→ A4). The func- cause myocardial infarction, cerebral infarc-
tions of lymphocytes that have shrunk are im- tion, and peripheral vascular disease.
paired (e.g., the formation of superoxides, Lastly, glucose can react with hemoglobin
which are important for immune defense). (HbA) to form HbA 1c , whose increased concen-
Diabetics are thus more prone to infection tration in blood points to a hyperglycemia that
(→ A5), for example, of the skin (boils) or kid- has been present for some time. HbA 1 c has a
ney (pyelonephritis). These infections, in turn, higher oxygen affinity than HbA and thus
increase the demand for insulin, because they releases oxygen in the periphery less readily
lead to an increased release of insulin-antago- (→ A11). The persisting insulin deficiency
nistic hormones (→ p. 286). further leads to a reduction in the erythrocytic
Hyperglycemia promotes the formation of concentration of 2,3-bisphosphoglycerate
sugar-containing plasma proteins such as fi- (BPG), which, as allosteric regulator of hemo-
brinogen, haptoglobin, α 2 -macroglobulin as globin, reduces its oxygen affinity. The BPG de-
well as clotting factors V–VIII (→ A6). In this ficiency also results in an increased oxygen af-
way clotting tendency and blood viscosity finity of HbA.
may be increased and thus the risk of throm- Diabetic mothers have a statistically higher
bosis raised. chance of giving birth to a heavier than normal
By binding of glucose to free amino-groups baby (→ A12). This may be the result of an in-
of proteins and a subsequent, not fully under- creased concentration of amino acids in blood,
stood, irreversible Amadori reaction, advanced producing an increased release of somatotro-
glycation end products (AGEs) are formed. pin.
They also occur in increasing amounts in the
elderly. A protein network can be formed
through the formation of pentosin. AGEs bind
290 to respective receptors of the cell membrane
and can thus promote the deposition of col-
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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