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54 Cards in this Set
- Front
- Back
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Glucose flux:
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*Balance between influx and utilization
*Postpandrial- plasma glucose INCREASES *Fasting- plasma glucose DECREASES |
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Hormones that regulate glucose homeostasis: 5
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Insulin
Glucagon Catecholamins Cortisol Growth hormone |
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Euglycemia--
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balance b/t insulin and counter-reg hormones
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Influx- Postpandrial- plasma glucose increases:
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insulin +
counter-reg hormones decrease |
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Insulin:
what is insulin release suppressed by? what does low insulin level facilitate? |
*Major glucose regulatory hormone
-Released after glucose stimulation of β cells *Insulin release is suppressed by; -Reduced glucose stimulation to β cells -Increased catecholamines-α adrenergic effect *Low insulin level facilitates -Counterregulatory hormones increase -Glycogenolysis and lipolysis -Upregulation of hepatic & renal enzymes for gluconeogenesis -Prevents muscle consumption of glucose |
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Glucose homeostasis-- POSTPRANDRIAL:
where does all the glucose go? |
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Glycogen metabolism:
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*Takes place in liver
*Glycogen stores available for use 4 hrs after fasting (end of meal) |
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Fasting- plasma glucose does what? insulin? cxregs?
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*****KNOW THIS YO*****
1) insulin plummets 2) Glycogen gets used w/i 4 hrs 3) Gluconeogenesis from AAs and lipolysis *Keeps glucose level constant 4) Glycogen depleted 5) Ketosis |
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Major Actions of Counterregulatory Hormones:
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G=GLUCAGON
E=EPI GH=GROWTH C=CORTISOL **JUST KNOW EACH PATHWAY HAS SPECIFIC HORMONES TO REGULATE THEM** |
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Glucagon:
key hormone in? is increased by? it increases what? |
*Key hormone affecting recovery from acute hypoglycemia
Less important in SLOWLY developing hypoglycemia *Glucagon increase by -β adrenergic effect -Direct glucose effect on pancreatic α cells -Decrease insulin level *Glucose increase by glucagon -Direct hepatic (no renal) glycogenolysis and facilitation gluconeogenesis |
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Catecholamines:
major role in gluc homeostasis? symptoms? |
*Major backup system right after glucagon
-α and β adrenergic receptor activation leading to variety of effects *Symptoms -Tachycardia -Tremor -Anxiety |
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Catecholamines biochemical effects:
alpha? beta? |
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ACTH/Cortisol and Growth Hormone:
-when are they released? elevated cortisol enhances what? |
*Released in response to neuroglycopenia together with sympathetic nervous system stimulation
*Elevation of plasma cortisol level enhances -Protein catabolism -Gluconeogenesis -Lipolysis |
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Major organ systems involve in glucose metabolism: 3
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Liver
Muscle Adipose tissue |
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Glucose in the liver--
Postpandrial- Fasting- |
Postpandrial- Glucose storage in the form of glycogen.
Fasting- Releases glucose from glycogen into the blood for other organs to be used when glucose levels start to fall. Gluconeogenesis from Alanine. |
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Metabolism of glucose:
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Liver
Muscle Fat |
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Lipolysis:
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Major gluc source via ketones after 10-12 hrs of fasting
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Fasting- Glucose source over time:
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IMPORTANT PICTURE
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Hypoglycemia definition:
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No specific number!
Decreasing glucose concentration resulting in autonomic response Symptomatic hypoglycemia |
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Autonomic response to hypoglycemia, correlated to specific plasma gluc levels:
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Clinical signs of Hypoglycemia:
*Autonomic/adrenergic responses: “warning signs”-- *Neuroglycopenia-- |
*Autonomic/adrenergic responses: “warning signs”
Sweating Weakness, lethargy Tachycardia, tachypnea Tremor Feelings of nervousness ± hunger Feeding problems in the neonate *Neuroglycopenia Lethargy Irritability Headache Confusion Behavior out of character Seizure Coma *May be asymptomatic (rare, if can't communicate) |
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Classification of Hypoglycemia: 7
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*Drugs- insulin, sulfonylurea, alcohol
*Hormonal deficiency- cortisol, growth hormone, glucagon and epinephrine *Critical illness- liver disease *Insulinoma *Factitious *Autoimmune hypoglycemia *Defects in glycogenolysis, gluconeogenesis and lipolysis |
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Understand this.
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Hypoglycemia in diabetes: reasons it happens: 5
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*Deficient glucagon response
*Hypoglycemia unawareness *Diabetic gastroparesis *Renal insufficiency *Concurrent Addison's disease |
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Factitious Hypoglycemia:
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*Administration of xs exogenous insulin
-High insulin level, suppressed C peptide -Circulating antibodies to insulin (can be absent) *Sulfonylurea taken in xs -High insulin, high C peptide, Sulfonylurea -Liver dysfunction prolongs effect of Tolbutamide, Glyburide and Glipizide -Renal dysfunction prolongs effect of Chlorpropamide and Glyburide *Mainly in adults; can happen in kids |
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Medications causing hypoglycemia: 5
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10% of hypoglycemia is caused by:
Propranolol Salicylates Sulfonamides ACE inhibitors Pentamidine |
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Insulinoma:
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*Insulin secreting tumors of Islets of Langerhans
*80% benign and single *10% malignant *May be part of MEN1 *Neuroglycopenic symptoms >>adrenergic symptoms *Fasting insulin ≥6μU/ml with glucose ≤45mg/dl *Pretty rare, but you have to exclude it |
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*Insulinoma
*B-OHbutyrate indicates lipolysis |
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Treatment of insulinoma:
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*Tumor resection
*Diazoxide *Octreotide (synthetic somatostatin analog) *Streptozocin -Cytotoxic destruction of malignant β cells |
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Treatment of hyperinsulinemia:
diazoxide-- |
-Stabilizes ATP sensitive K channel and inhibits insulin secretion
-Increased catecholamine release (insulin release suppression) -Inhibits insulin action on periphery -Response within 48 -Efficacious in 1/4 patients -Side effects: Fluid retention, Hypertrichosis, Coarse facial changes |
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Treatment of hyperinsulinemia:
octreotide-- |
*Somatostatin analog
*Antagonist of G protein coupled receptor *Second line treatment, rarely effective alone, used as BRIDGE to surgery *Side effects -Inhibits Pituitary, Adrenal, Thyroid axes -Decreases: -Perfusion of splanchnic circulation -Gallbladder contractility and cholelithiasis |
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Treatment of hyperinsulinemia:
glucagon-- |
-Initial management of hypoglycemic infants
-Continuous infusion -Works via promoting hepatic glycogenolysis -Very effective -BRIDGE TREATMENT |
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Autoimmune hypoglycemia: 2
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*Circulating insulin antibody
-HLA class II alleles -Higher incidence Japan and Korea -Hypoglycemia 3-4 hours after meal -Spontaneous resolution 3-6 months after the diagnosis if offending agent discontinued -Treatment is with frequent small meals and Prednisone *Insulin receptor autoantibody -Women with autoimmune condition -Agonistic vs. antagonistic effect of antibodies on insulin receptor -Treatment with steroids |
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Reactive hypoglycemia:
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*Postgastrectomy/Postgastric bypass
-Hypoglycemia 1-3h postprandialy -Rapid intestinal transit of ingested food -Increase in vagal response and secretion of incretins -β cells diffuse hyperplasia |
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*Effect of incretins
*Postgastrectomy/Postgastric bypass -Hypoglycemia 1-3h postprandialy -Rapid intestinal transit of ingested food -Increase in vagal response and secretion of incretins -β cells diffuse hyperplasia |
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Differential diagnosis of hypoglycemia:
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*SU AND INSULINOMA LOOK THE SAME
*SKIPPED IGF-2 MEDIATED |
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Physiology of Glucose Homeostasis IN KIDS:
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*Glucose is the central role of body’s fuel economy.
*Glucose metabolism accounts for ~50% basal daily energy needs. HIGHER THAN IN ADULTS! *Glucose can be stored in the form of glycogen and fat; GLUCONEOGENESIS NOT AS IMPORTANT IN KIDS. *Glucose is the preferred substrate for brain. |
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Neonatal Glucose Metabolism:
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One of the most important events that marks the transition from fetal to neonatal life is ADAPTATION from environmental that glucose is readily available from maternal blood to an environment where glucose supply is limited and intermittent.
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Physiology of Perinatal Glucose Homeostasis:
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*Fetal glucose derived completely from mother.
*Changes at birth- goal to keep infant’s glucose normal. *Hormonal mechanisms:- increased glucagon, decreased insulin, increased catecholamine and growth hormone secretion. *Glycogenolysis, gluconeogenesis, lipolysis and ketogenesis. |
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Neonatal and Infantile Hypoglycemia:
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*Glucose less than 40 mg/dl (BRAIN DEV IN DANGER!!)
*MUST TREAT!!!! *Symptoms can be subtle to profound. *Cyanotic episodes, apnea, respiratory distress, poor feeding, myoclonic jerks, seizures, somnolence, subnormal temperature and sweating. |
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Categories of neonatal hypoglycemia: 2
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Transient hypoglycemia
Persistent hypoglycemia |
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Transient neonatal hypoglycemia risk factors:
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Risk factors incluse prematurity, SGA (small for gestational age), twins, severe RDS (resp. distress), infant of diabetic mother (including gest. DM).
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Persistent Neonatal Hypoglycemia causes: 7
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*Hyperinsulinism- genetic cause
*Hormone Deficiency -Panhypopituitarism (most common) -Isolated GH deficiency -ACTH, glucagon or epinephrine def. *Limited substrates -Glycogen storage disease (3rd most common) -Defect in gluconeogenesis *Disorders of Fatty Acids Oxidation (2nd most common) *Drug/toxin *Systemic Disorders-sepsis *Genetic disease- Beckwith Wiedemann Synd. (4th most common) |
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Work up for hypoglycemia in kids:
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*Endocrine causes:
-Hypopituitarism -Isolatated growth hormone deficiency -Adrenal insufficiency -Hyperinsulinism *Metabolic causes |
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Helpful clues to make the diagnosis of hypoglycemia in kids:
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*Evidence of midline defect, micropenis.
*Hepatosplenomegaly (glycogen storage disease) *Hyperpigmentation *Specific dysmorphism-BWS *Metabolic acidosis (gluconeogenesis issues) *Inappropriate hypoketonemia *Glucose infusion rate *Family history |
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Know steps to insulin secretion
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Genetic causes of persistent hyperinsulinemic hypoglycemia in kids:
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*Inactivating mutations of ABCC8 (SUR1)gene- 45%
*Inactivating mutations of KCJN11 (Kir6.2) gene- 5% *Activating mutations of GLUD1 (glutamate dehydrogenase)- 5% *Activating mutations of glucokinase- rare |
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*Katp channel
*Muts--> hyperinsulinemic hypoglycemia Lesson learned from congenital hyperinsulinemic hypoglycemia. |
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Treatment- hyperinsulinemic hypoglycemia in kids:
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*Diazoxide-binds to the ABCC8 subunit of the Katp channel, increases the channel's probability of being open, resulting in membrane hyperpolarization and inhibition of insulin release.
*Octreotide-suppress insulin secretion by binding to specific beta-cell receptors. *Surgery |
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Goal of treatment of hypoglycemia:
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Maintain normal glucose, duh
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