Hypoglycemia

Question 1

what blood glucose levels are considered to be hypoglyemia?

specify for each population.

Answer 1

• in adults w/out diabetes: < 50 mg/dL (2.8 mmol/L)
• in people with diabetes: < 70 mg/dL (3.9 mmol/L)
• in newborns: < 40mg/dL (2.2 mmol/L)

Question 2

when do symptoms of hypoglycemia tend to appear?

Answer 2

at blood glucose < 50 mg/dL

Question 3

symptoms of hypoglcyemia?

Answer 3

• sweating / papitations
• irritability / anxiety / confusion
• headache / dullness / fatigue
• extreme cases : –> seizure, brain dysfunction, coma

Question 4

what is whipple’s triad?

Answer 4

the three criteria that must be met for dx of symptomatic hypoglycemia::

1. Symptoms of hypoglycemia
2. Plasma [glucose] < 50 mg/dl
3. Amelioration of symptoms by restoration of normal plasma [glucose]

Question 5

what are the main causes of hypoglycemia?

which one is the m/c?

Answer 5

• drug induced hypoglycemia
  
  • non-titrated insulin dose / insulin without food
  • sulfonlyurea therapy
  • ethanol
• tumors - eat up all the glucose
• counter regulatory hormone defiency- any non-insulin glucose regulator (glucagon, epi, GH, glucocorticoids)
• hepatic disorders
• glycogen storage diseases - defect in debranching enyzme, g. phosphorylase, phosphorylase kinase

Question 6

what are the major causes of drug-induced hypoglycemia?

Answer 6

= m/c cause of hypoglycemia

1. diabetes drug therapy
   
   • insulin - incorrect dose, taking w/out food
   • sulfonyureas, repaglinide
2. ethanol - induces hypoglycemia by inhibiting gluconeogenesis:
   
   • ​in the body, ethanol is oxidized to acetic acid, which eats up 2 NAD+ molecules.
     
     • this depletes NAD+ that can be used to
       
       • convert lactate –> pyruvate
       • convert malate –> OAA (malate asparate shuttle)

Question 7

how does ethanol inhibit gluconeogenesis?

how does this often present clinically?

Answer 7

• ​in the body, ethanol is oxidized to acetic acid, which eat up 2 NAD+ molecules.
  
  • this depletes NAD+ that can be used to
    
    • convert lactate –> pyruvate
    • malate –> OAA (moves OAA to cytosol)
  • thus impairing key gluconeogenic steps & substrate usage
• a classical clinical picture is a pt with:
  
  • hypoglcyemia (< 50 mg/dl)
  • along with:
    
    • high blood alcohol
    • high blood lactate
    • low pH (acidosis)
    • deep breathing (resp compensation)

metabolic acidosis d/t lactic acidosis, which is d/t accmulating lactate from impaired conversion to pyruvate

Question 8

which tumors induce hypoglycemia and how?

Answer 8

• insulinoma - unregulated insulin secretion from pancreas
• all other tumors - utilize great amounts of blood glucose

Question 9

what are “glycogen storage diseases”

Answer 9

a group of inherited disorders defined by

1. deposition of abnormal type/quantity of glycogen
2. failure to mobilize glycogen

Question 10

von Gierke’s disease

• what type of glycogen storage disease?
• presentation?
• tx

Answer 10

• Type I: deficiency of glucose-6-phosphotase - the only enzyme that can release glucose from glycogen for tissue use (mobilization defect)
• presentation:
  
  • SEVERE hypoglycemia
  • lactic acidosis
• tx - dietary

Question 11

Pompe’s storage disease

• what type of glycogen storage disease?
• clinical presentation?
• tx?

Answer 11

• Type III: deficiency of lysosomal a1,4 glucosidase an enzyme that degrades glycogen in lysosomes. large glycogen vacuoles accumulate in cells (deposition defect)
• clinical presentation:
  
  • cardiomegaly / heart failure
  • normal blood glucose
• tx - none

Question 12

Cori’s disease

• what type of glycogen storage disease
• clinical presentation
• treatment\

Answer 12

• type III: deficiency of debranching enzyme resulting in inc [glycogen] + shorter outer branches (mobilization / deposition defect)
• presentation:
  
  • hepatomegaly
  • mild hypoglycemia
• tx - dietary

Question 13

Anderson’s

• what type of glycogen storage disease
• clinical presentation
• tx

Answer 13

• type IV: defect in branching enzyme: normal glycogen [] with long filamtenous structure (deposition defect)
• presentation:
  
  • hepatomegaly, cirrhosis
  • normal blood glucose
  • early death d/t liver failure

Question 14

Tarui’s

• what kind of glycogen storage disease
• what clihnical effects
• tx

Answer 14

• type VII: deficiency of muscle phosphofructokinase. impaired glycolysis leads = accumulating glucose –> glycogen synthesis. increased glycogen [] w/ normal structure
• clinical presentation - exercise intolerance
• tx - avoid strenous exercise

Question 15

Type VIII glycogen storage disease?

• deficiency in what enzyme?
• has what effects?

Answer 15

• deficiency of liver phosphorylase kinase
• increased glycogen [] - normal structure
• liver affected

Question 16

fructosuria?

which enzyme effected?

how does it affected the fructose metabolism path?

clinical presentation?

Answer 16

• deficiency of fructokinase
• fructose accumulates in blood –> appears in urine
• clinical
  
  • fructosuria
  • otherwise asmptomatic

Question 17

hereditary fructose intolerance

which enzyme effected?

how does it affected the fructose metabolism path?

clinical presentation?

Answer 17

• deficiency of aldolase B
• fructose -1- P accumulates
  
  • this uses up all the Pi, reducing Pi pool. this inhibits
    
    • glycogenolysis - glycogen phosphorylase (relies on P)
    • glycolysois - aldolase A (relies on P)
• clinical:
  
  • severe hypoglycemia
  • abdominal pain / vomitting
  • infant death

Question 18

lactase deficiency - clinical presentation & tx

Answer 18

= lactose intoleranec

• diarrhea
• flatulence
• discomfort

tx: avoidance

Question 19

galactosemia

• caused by deficiency of what enzyme?
• effects glucose metabolism how?
• clinical presentation?

Answer 19

non-classical galactosemia

• galactokinase deficiency
• galactose accumulates
• clinical:
  
  • cataracts

classical galactosemia

• transferase deficiency
• galactose + Gal-1-P accmulates
• clinical:
  
  • cataracts
  • growth failure / mental retardation

Question 20

McArdles

• what kind of glycogen storage disease?
• clinical presentation?
• tx?

Answer 20

• type V: deficiency of muscle glycogen phosphorylae
• clinical presentation
  
  • exercise intolerance
  • muscle damage
• tx - avoid strenuous exercise

Question 21

Her’s

• what kind of glycogen storage disease
• clinical presentation
• tx

Answer 21

• type VI: deficiency of liver glycogen phosphorylase. increased glycogen [], normal structure
• clinical presentation
  
  • infrequent/mild hypoglycemia
• tx - avoid fasting

Question 22

which glycogen storage disease cause hypoglycmemia?

Answer 22

• von kierkes (glucose-6-phosphotase deficiency) - SEVERE
• cori’s (debranching enzyme deficiency) - mild
• her’s (liver glycogen phosphorylase deficiency) - mild/intermittent

Question 23

which glycogen storage diseases cause hepatomegaly?

Answer 23

• cori’s (debranching enzyme deficiency)
• anderson’s (branching enzyme deficiency)