Endocrine
Energy Production and Glucose Homeostasis
- Five hormones regulate energy production and glucose homeostasis:
- Insulin
- Glucagon
- Epinephrine
- Cortisol
- Growth hormone
- Focus will be on disorders related to insulin and glucagon.
Insulin
- Anabolic (energy-producing) hormone.
- Secreted by beta islet cells of the pancreas in response to high serum glucose levels.
- Increases glucose uptake into cells, thus lowering serum glucose levels.
- Stimulates:
- Glycogen formation (glycogenesis).
- Protein synthesis.
- Adipose formation.
- Genesis means to create, opposite of lysis (to break down).
Glucagon
- Counterregulatory hormone to insulin (opposite effect).
- Secreted by the pancreas in response to low serum glucose levels.
- Increases serum glucose levels by:
- Stimulating glycogen breakdown (glycogenolysis).
- Increasing production of new glucose molecules (gluconeogenesis).
- Lysis means to break down.
Hypoglycemia
- Too much insulin and not enough glucagon.
- Serum glucose level \le 50 \text{ mg/dL}.
- Can be caused by:
- Developing glycogen stores in neonates/young infants.
- Transient or persistent hyperinsulinism.
- Hypopituitarism.
- Adrenal insufficiency.
- Liver failure.
- Inborn errors of metabolism.
- Symptoms:
- Decreased level of consciousness.
- Seizures and tremors.
- Hypotonia.
- Apnea (especially in neonates/young infants).
- Tachycardia.
- Diaphoresis.
- Anxiety.
Management of Hypoglycemia
- Be suspicious of symptoms.
- Check bedside glucose and monitor for improvement after treatment.
- Mild/moderate hypoglycemia: oral carbohydrate or glucagon.
- Severe hypoglycemia or inability to take oral medications: IV glucose.
- Determine and treat the underlying cause.
Diabetic Ketoacidosis (DKA)
- Diabetes mellitus patients have an underproduction or deficit of insulin.
- Without insulin, glucose cannot enter the cell for energy, leading to cellular energy debt.
- The body increases counterregulatory hormones (glucagon, catecholamines, cortisol, growth hormone) to produce more glucose.
- The body uses fat and muscle proteins as alternative fuel sources, leading to fatty acid oxidation.
- Fatty acid oxidation produces ketones and causes acidosis.
- DKA is a state of:
- Hyperglycemia.
- Ketonuria and ketonemia.
- Metabolic acidosis.
- Dehydration.
- Electrolyte imbalances.
Pathophysiology
- Lactate production from alternate metabolic pathways leads to acidosis.
- Hyperosmolar diuresis leads to dehydration.
- Electrolyte imbalances due to acidosis and electrolyte losses in urine.
Clinical Presentation
- Severe hyperglycemia and ketoacidosis.
- Electrolyte abnormalities (hyperkalemia, hyperphosphatemia, hypernatremia).
- Hyperosmolar state leading to osmotic diuresis and dehydration, potentially progressing to hypovolemic shock.
- Altered mental status and possible signs of elevated intracranial pressure.
- Dehydration signs (tachycardia, hypotension, poor perfusion; hypotension is a late sign).
- Tachypnea with Kussmaul respirations and sweet-smelling acetone breath.
- Abdominal tenderness (especially with nausea/vomiting).
- Possible signs of infection (precipitating event).
Management of DKA
- Airway and breathing management.
- Volume resuscitation.
- Blood sugar control.
- Electrolyte imbalance correction.
- Education for patient and family about diabetes management.
Volume Resuscitation
- Rapid IV access and fluid bolus.
- Isotonic fluid (20 mL/kg bolus).
- Reassess response after each intervention and adjust fluid management.
- Correct 10-20% dehydration over 48 hours, along with maintenance fluids.
Insulin Therapy
- Essential to normalize blood glucose and suppress lipolysis/ketogenesis.
- Avoid insulin bolus to prevent rapid glucose drop (no faster than 50-100 mg/dL per hour).
- Regular insulin IV infusion at 0.05-0.1 unit/kg/hour.
- Add glucose to infusion (5% dextrose at serum glucose ~300 mg/dL, 10% dextrose at ~200 mg/dL).
- Use established insulin and dextrose protocols.
Electrolyte Management
- Patients are often hyperkalemic and hyperphosphatemic initially.
- Electrolyte levels decrease as acidosis resolves, requiring possible replacement.
- Add electrolytes to IV bag as needed rather than giving single replacement doses.
- Frequent electrolyte monitoring is necessary until DKA is corrected.
Cerebral Edema
- Occurs in about 1% of DKA episodes, with significant morbidity and mortality.
- Symptoms can be present initially or occur within the first 48 hours of treatment.
Risk Factors for Cerebral Edema
- First-time DKA (new onset).
- Younger age at diagnosis.
- Increased BUN.
- Decreased CO_2.
- Poor DKA management (insulin bolus, rapid glucose correction, aggressive fluids, bicarbonate administration).
Response to Cerebral Edema Signs
- Respond quickly with typical therapies for increased intracranial pressure.