Hypoglycemia

Chapter 69 Hypoglycemia

Amie Koenig, DVM, BS, DACVIM, DACVECC

• Normoglycemia is maintained by a balance between the glucose-lowering hormone insulin and glucose-elevating hormones glucagon, cortisol, epinephrine, and growth hormone.

• Hypoglycemia occurs via one of several mechanisms: inadequate dietary intake, excessive glucose utilization, dysfunctional glycogenolytic or gluconeogenic pathways or inadequate precursors for these pathways, or endocrine abnormalities.

• The most common causes of hypoglycemia include exogenous insulin overdose, hypoglycemia of puppies and toy breeds, sepsis, insulinoma and other insulin analog-secreting tumors, hypoadrenocorticism, and severe liver disease.

• Neuroglycopenia causes alterations in mentation, seizures, blindness or alterations in vision, somnolence, and weakness or ataxia.

• Adrenergic stimulation in response to declining blood glucose accounts for other common clinical signs of restlessness, anxiety, tachypnea, vomiting or diarrhea, and trembling.

• In hypoglycemic crises, parenteral dextrose administration is the most effective therapy. Food should be offered as soon as possible. Glucagon infusion may be used for cases of intractable hypoglycemia secondary to insulinoma or insulin analog-secreting neoplasms.

INTRODUCTION

Euglycemia is maintained by a balance of glucose production, storage, and release from storage forms. Many disease processes can interfere with normal glucose homeostasis and lead to hypoglycemia. This chapter will review normal glucose homeostatic mechanisms, clinical signs and causes of hypoglycemia, and treatment of a hypoglycemic crisis.

NORMAL GLUCOSE HOMEOSTASIS

Glucose comes from three sources: (1) intestinal absorption of glucose from digestion of carbohydrates; (2) breakdown of the storage form of glucose (glycogen) via glycogenolysis; and (3) production of glucose from precursors lactate, pyruvate, amino acids, and glycerol via gluconeogenesis. Glucose homeostasis is maintained by a balance between the glucose-lowering hormone insulin and glucose-elevating hormones, primarily glucagon, epinephrine, cortisol, and growth hormone.

Insulin is secreted by β-cells of the pancreas in response to the rising concentrations of glucose, amino acids, and gastrointestinal (GI) hormones (gastrin, secretin, cholecystokinin, and gastric inhibitory peptide) present after a meal.¹ Insulin inhibits gluconeogenesis and glycogenolysis, promotes glycogen storage, stimulates glucose uptake and utilization by insulin-sensitive cells, and decreases glucagon secretion. Insulin also promotes triglyceride formation in adipose tissue and the synthesis of protein and glycogen in muscle. Decreased levels of insulin stimulate gluconeogenesis and reduce glucose used by peripheral tissues.

As blood glucose concentrations fall, the counter-regulatory hormones glucagon, epinephrine, cortisol, and growth hormone are released. Both glucagon and epinephrine levels rise within minutes of hypoglycemia and have a transient effect on increasing glucose production; they subsequently support basal rates of glucose production.² Cortisol and growth hormone are released after a few hours, but their effects are also longer lasting.

Glucagon is secreted from pancreatic α-cells. It acts on the liver to stimulate glycogenolysis and, to a lesser extent, gluconeogenesis, thereby increasing hepatic glucose production. This is transient, however, and glucose production quickly declines toward basal rates as increasing levels of insulin counteract the effects of glucagon. Glucagon directly stimulates hepatic glycogenolysis and gluconeogenesis, mobilizes gluconeogenic precursors, and reduces peripheral glucose utilization. Epinephrine limits insulin secretion and increases glucagon secretion. Cortisol increases glucose-facilitating lipolysis and release of amino acids from muscle for gluconeogenesis in the liver. Growth hormone antagonizes effects of insulin by decreasing peripheral glucose utilization and promoting lipolysis.

Hypoglycemia results when glucose utilization exceeds glucose entry into circulation. General mechanisms of hypoglycemia include: (1) inadequate dietary intake, (2) excessive glucose utilization, (3) dysfunctional glycogenolytic or gluconeogenic pathways or inadequate precursors for these pathways, and (4) endocrine abnormalities. On its own accord, inadequate dietary intake is unlikely to cause hypoglycemia, because gluconeogenic and glycolytic pathways dominate during periods of fast. In most animals, a concurrent defect in one of the other mechanisms is required.

CLINICAL SIGNS AND CONSEQUENCES OF HYPOGLYCEMIA

Glucose is an obligate energy source for the brain. The brain has limited ability to use other substrates, can store minimal amounts of glycogen, and cannot manufacture glucose; therefore the brain relies on a constant stream of glucose for its energy needs.³ Glucose enters the brain by facilitated diffusion. Adequate arterial glucose concentration is essential to maintaining a diffusion gradient. Because brain cells rely so heavily on glucose for energy, neuroglycopenia, or hypoglycemia of the central nervous system (CNS), results primarily in neurologic signs. The degree, rate of decline, and duration of hypoglycemia all contribute to type and severity of symptoms.

Neuroglycopenic signs occur as a direct result of CNS hypoglycemia. These include altered mentation or dullness, sleepiness, weakness or recumbency, ataxia, blindness or altered vision, and seizures.^2,4 Prolonged neuroglycopenia can lead to permanent brain injury and neurologic signs, especially blindness, that persist beyond resolution of the hypoglycemia. Neurogenic signs result from activation of the adrenergic system in response to the hypoglycemia. Humans describe being hungry, a tingling sensation, tremors or shakiness, a pounding heart, and anxiety or nervousness.² Similar signs noted in hypoglycemic dogs and cats include anxiety manifest as pacing, vocalizing or restlessness, and shaking or trembling.⁴ Vomiting, anorexia, panting or tachypnea, diarrhea, and urination have been noted in hypoglycemic dogs and cats. Bradycardia and circulatory collapse have also been documented.⁵ Signs may be episodic. Some animals, especially those with prolonged hypoglycemia, demonstrate no associated signs.⁴ This hypoglycemia unawareness may occur in patients whose brains are induced by chronic or recurrent hypoglycemia to upregulate cerebral glucose uptake, thereby decreasing the perception of peripheral hypoglycemia by the brain.³

DIAGNOSIS OF HYPOGLYCEMIA

By definition, hypoglycemia is diagnosed by a blood glucose level of 60 mg/dl or less, although clinical signs often do not develop until the level is less than 50 mg/dl. Whipple’s triad provides guidelines for identifying hypoglycemia: clinical signs consistent with hypoglycemia, a low blood glucose level, and abatement of signs with correction of the hypoglycemia.²

Hand-held glucometers tend to underestimate serum glucose.⁶ Low glucose values obtained on a hand-held glucometer should be confirmed via other methods. Falsely low glucose values, or pseudohypoglycemia, can be obtained if the serum is not separated from the red blood cells within 30 minutes of collection, because the red blood cells continue to consume glucose for glycolysis.⁷ If centrifugation and serum separation must be delayed longer than 30 minutes, collection in a sodium fluoride tube will arrest glycolysis.

Once hypoglycemia is identified, additional diagnostic modalities may be indicated to identify its etiology. Complete blood cell count, serum chemistry analysis, urinalysis, chest and abdominal radiographs, abdominal ultrasonography, insulin levels, and other endocrine testing may be indicated.

CAUSES OF HYPOGLYCEMIA

Many causes of hypoglycemia (Box 69-1) fall into the categories of excess insulin or insulin analog, inadequate glucose production, and excess cellular glucose consumption.

Tags: Small Animal Critical Care Medicine

Sep 10, 2016 | Posted by admin in SMALL ANIMAL | Comments Off

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