Page 298 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Acute Effects of Insulin Deficiency (Diabetes Mellitus)
Insulin acts to create energy reserves. It pro- guises the negative K + balance. Administration
motes the uptake of amino acids and glucose, of insulin then causes a life-threatening hypo-
especially in the muscle and fat cells. In hepat- kalemia (→ p.124). Dehydration leads to hypo-
ic, muscle, and fat cells (among others) insulin volemia with corresponding impairment of the
stimulates protein synthesis and inhibitis pro- circulation. The resulting release of aldoste-
+
tein breakdown; in the liver and muscles it rone increases the K deficiency, while the re-
promotes glycogen synthesis, inhibits its lease of epinephrine and glucocorticoids ex-
breakdown, stimulates glycolysis, and inhibits acerbates the catabolism. The reduced renal
gluconeogenesis from amino acids. Also in the blood flow diminishes the renal excretion of
liver, insulin promotes the formation of tri- glucose and thus encourages the hyperglyce-
glycerides and lipoproteins as well as the he- mia.
patic release of VLDL. At the same time it stim- The cells further lose phosphate (P i ) and
ulates lipoprotein lipase and thus accelerates magnesium that are also excreted by the kid-
the splitting of triglycerides into lipoproteins ney. If there is an insulin deficiency, proteins
in blood (especially chylomicrons). The free are broken down to amino acids in muscles
fatty acids and glycerol are then taken up by and other tissues. This breakdown of muscles
Hormones Insulin stimulates lipogenesis and inhibits li- lead to muscular weakness. Prevailing lipolysis
the fat cells and stored again as triglycerides.
will, together with electrolyte abnormalities,
polysis in the fat cells. Lastly, it promotes cell
leads to release of fatty acids into blood (hy-
+
acetic acid and β-hydroxybutyric acid from
Na , and cardiac contractility. Part of insulin ac-
9 growth, increases renal tubular absorption of perlipidacidemia). The liver produces aceto-
tion is mediated by cell swelling (especially the fatty acids. Accumulation of these acids
antiproteolysis) and intracellular alkalosis leads to acidosis, which forces the patient to
(stimulation of glycolysis, increased cardiac breathe deeply (Kussmaul breathing; → A3).
contractility). Insulin achieves this effect by Some of the acids are broken down to acetone
+
+
activating the Na /H exchanger (cell swelling (ketone bodies). In addition, triglycerides are
–
+
+
and alkalinization), the Na -K -2 Cl cotrans- formed in the liver from fatty acids and incor-
+
+
porter (cell swelling), and Na -K -ATPase. porated into VLDL. As the insulin deficiency
+
This results in K uptake by the cell and hypo- delays the breakdown of lipoproteins, the hy-
kalemia. As glucose is coupled to phosphate in perlipidemia is further aggravated. Some of
the cell, insulin also reduces plasma phosphate the triglycerides remain in the liver and a fatty
concentration. It further stimulates the cellu- liver will develop.
2+
lar uptake of Mg . Insulin also paracrinally in- The breakdown of proteins and fat as well as
hibits the release of glucagon and thus dimin- polyuria will result in weight loss. The abnor-
ishes its stimulating action on glycogenolysis, mal metabolism, electrolyte disorders and the
gluconeogenesis, lipolysis, and ketogenesis. changes in cell volume brought about by
In acute insulin deficiency the absence of its changed osmolarities can impair neuronal
effect on glucose metabolism results in hyper- function and cause hyperosmolar or ketoaci-
glycemia (→ A1). The extracellular accumula- dotic coma.
tion of glucose leads to hyperosmolarity. The The main effects of relative insulin deficien-
transport maximum of glucose is exceeded in cy are hyperglycemia and hyperosmolarity,
the kidney so that glucose is excreted in the while in absolute insulin deficiency the conse-
urine (→ A2). This results in an osmotic diure- quences of increased proteolysis and lipolysis
+
sis with renal loss of water (polyuria), Na , and (ketoacidosis) are added to these effects.
+
K , dehydration, and thirst. Despite the renal
+
loss of K , there is no hypokalemia because
+
the cells give up K as a result of reduced activ-
+
+
+
–
+
ity of Na -K -2 Cl cotransport and of Na -K -
288 ATPase. The extracellular K + concentration,
which is therefore more likely to be high, dis-
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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