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DIABETIC ACIDOSIS
1. What is the cause of this patient’s very high plasma glucose level?
3. Glucose production and release by the liver in part reflect the balance between glycolysis
(glucose to pyruvate) and gluconeogenesis (pyruvate to glucose). What control points
regulate the rates of bidirectional flow between glucose and pyruvate, and how are they
affected by the relevant hormones?
4. What has replaced bicarbonate in the patient’s plasma, and by what mechanisms?
5. Why is the patient breathing rapidly, and why is the blood pH low?
6. Why is the blood pressure low and the pulse rate high?
7. What levels of free fatty acid and triglycerides might you expect in plasma?
[ANSWER]
1. The primary cause is insulin deficiency resulting from destruction of the beta cells of the
pancreatic islets. Secondarily, loss of insulin leads to disinhibition of glucagon secretion by
the alpha cells of the islets, and thereby causes glucagon excess. The clinical
consequences of insulin deficiency and glucagon excess create a state of "stress," which
additionally stimulates cortisol secretion, growth hormone secretion, and epinephrine and
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norepinephrine release. This complete hormonal setting of insulin deficiency arrayed
against increases of glucagon, cortisol, growth hormone, and catecholamines generates
hyperglycemia.
2. Hepatic glucose production and release are elevated, initially because of exaggerated
glycogen breakdown (low insulin, high glucagon, high epinephrine) and subsequently
because of increased rates of gluconeogenesis (high glucagon, cortisol, catecholamines,
low insulin). The efficiency of glucose uptake by both muscle and adipose tissue is
diminished because of impaired glucose transport and intracellular blocks in glucose
metabolism (low insulin, high cortisol, high epinephrine). The high plasma glucose level is
required to maintain normal rates of intracellular glucose utilization. Finally, as
dehydration occurs, plasma glucose rises still further because of a reduction in glomerular
filtration rate.
6. For 6 weeks, high plasma glucose levels created a filtered load of glucose that exceeded
the tubular maximum for renal tubular glucose reabsorption. The glucose that escaped
reabsorption caused an osmotic diuresis. This, along with the lessened oral intake of water
and the gastrointestinal losses from vomiting, resulted in severe dehydration and
hypovolemia that lowered the blood pressure. In turn, decreased baroreceptor firing
caused a reflex tachycardia.
7. Plasma free fatty acids will be high because of increased lipolysis. Plasma triglycerides will
be high because of increased production of very low density lipoprotein from the increased
free fatty acid load to the liver. This elevation of triglycerides will be aggravated by
decreased clearance of very low density lipoprotein from plasma because of loss of
adipose tissue lipoprotein lipase activity when insulin is deficient.
8. Plasma branch chain amino acids will be high because of increased muscle proteolysis in
the absence of insulin and because of elevated cortisol levels. The high amino acid flow to
the liver sustains accelerated rates of gluconeogenesis.
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9. Plasma aldosterone will be high, stimulated by the renin-angiotensin system, which is
activated by the patient's hypovolemia. Plasma antidiuretic hormones (ADH) will be high,
mostly stimulated by a high plasma osmolality from glucose and secondarily by
hypovolemia.
10. There are three components to the patient's weight loss: (a) extracellular fluid losses from
osmotic diuresis and vomiting; (b) loss of adipose mass because insulin deficiency leads to
increased lipolysis and decreased reesterification of free fatty acids by glycerol phosphate;
and (c) loss of lean body mass because insulin deficiency accelerates proteolysis and
diminishes protein synthesis. In addition, somatomedin levels fall, further decreasing
protein synthesis.
11. High plasma osmolality plus hypovolemia stimulates thirst. Appetite increases in response
to wasting large quantities of calories as glucose in the urine.
12. Urea nitrogen excretion will be elevated, reflecting high rates of amino acid use for
gluconeogenesis instead of for protein synthesis. Ammonia excretion will be elevated as a
means of buffering excess hydrogen ion generated by the presence of strong ketoacids in
the tubular urine. Potassium phosphate and magnesium excretion will be increased
because these intracellular electrolytes are released when glycogen and protein stores
diminish.
13. Restoration of insulin will inhibit lipolysis and reduce production of the strong ketoacids.
This will result in an increase in plasma bicarbonate and pH. Plasma potassium will fall for
several reasons: (a) insulin directly stimulates potassium uptake by cells; (b) as insulin
diminishes ketoacid levels and extracellular fluid acidosis, potassium will move from
extracellular fluid to intracellular fluid in exchange for hydrogen ion released from
intracellular buffers; and (c) as insulin decreases plasma glucose, water will move from
extracellular space to the intracellular space, and potassium will be carried along by
solvent drag. Plasma phosphate will fall because insulin stimulates cellular uptake of
phosphate as glucose transport is increased and phosphorylated glucose intermediates
are formed.
Increased urination
Nausea and vomiting
Stupor
Semi coherence
Skin and mucous membrane dryness
Low blood pressure (84/52), high pulse rate (120beats/min)
Deep and rapid breathing (30 respirations per minute)
Urine contained a glucose concentration of 5% and positive for acetoacetic acid