What are some acute complications of diabetes?
- Insulin-induced hypoglycemia
- Diabetic ketoacidosis
- Hyperosmolar hyperglycemic nonketotic state (HONK)
- Lactic acidosis
What are some hypoglycemic reactions?
Neurogenic (responses of S/PS systems):
- Heart Pounding
Neuroglycopenic (responses of central NS):
- Difficulty thinking/confused
- Tired/drowsy, faint, dizzy
- Difficulty speaking
- Blurred vision
What are counterregulatory responses (substances) to hypoglycemia?
- Glucagon* (fastest)
- Growth hormone (slowest)
*(Normally low insulin levels correspond to higher glucagon, which would seem to be protective about hypoglycemia in diabetes... but for some reason, not the case. No surge; it's an acute response)
What is Diabetic Ketoacidosis?
Uncontrolled diabetes leading to:
- Osmotic diuresis
- Volume depletion
2. Ketogenesis: anion-gap acidosis
3. Other metabolic changes
Difference between volume depletion and dehydration?
- Volume depletion: loss of isotonic fluid
- Gauged pretty much only clinically: blood pressure, urine production, orthostatic hypotension, mental status, skin turgor...
- Dehydration: loss of water; hypertonic serum
- Measured by serum sodium or serum osmolarity
Describe the liver and adipocyte collaborate to produce ketoacidosis?
- Insulin fails to restrain storage of fatty acids in adipocyte
- FAs released and go to liver
- Liver has high oxidation and ketone production (faster than ability to esterify fatty acids)
Depends on 2 things:
- Complete lack of insulin
- Excess of glucagon
What 2 things are necessary for the regulation of ketogenesis?
1. Insulin deficiency
- Activates lipolysis (fat cells)
- Increased plasma FFA concentration
- Increased liver fatty acids
- Accelerated ketogenesis
2. Glucagon excess
- Increased hepatic carnitine content with decreased malonyl CoA content (removes inhibition from --)
- Activation of CPT-1
- Accelerated ketogenesis
T/F: Massive excess of glucagon, cortisol, GH, and catecholamines (due to increased stress) can also push pt into DKA despite normal (not low) insulin levels
False- really never happens
- If someone comes in with DKA, suspect sudden drop in insulin rather than acute rise in other factors
What are etiologies of DKA?
86% of DKA episodes have an identifiable precipitating factor:
- Treatment errors
How do trauma, stroke, and pregnancy contribute to DKA?
Stress levels (?)
Do people with Type I or Type II DM get DKA more commonly?
- Type I are morel likely to get DKA in black and white populations
- Type II more commonly get DKA in Hispanic and Asian
What is the cause of hyperglycemia in DKA?
Insulin deficiency leading to:
- Increased hepatic glucose production
- Decreased peripheral glucose utilization
What are the effects of hyperglycemia in DKA?
- H20 from ICF to ECF
- Osmotic diuresis ECF volume
Renal loss of water > electrolytes
- Volume depletion
- Some degree of dehydration
What causes metabolic acidosis in DKA?
- Excess acetoacetic acid and β-OH butyric acid production (ketones)
- Diminished renal excretion of H+
What are effects of metabolic acidosis in DKA?
Buffer of protons and bicarb increases CO2 and H2O production, but ultimate correction of H excess depends on:
- Oxidation of AAA + βOHB - Renal excretion of H+
- Exchange of H+ for Na+
- Ammonia -> ammonium
- Loss of electrolytes in urine
What causes water and electrolyte imbalance in DKA?
- Osmotic diuresis
- Increased aldosterone
- ICF – ECF shift (K+3PO4)
What are the effects of water and electrolyte imbalance in DKA?
10% body weight lost as fluid
- 50% extracellular
- 50% intracellular
Significant loss of extra- and intracellular electrolytes
What are symptoms of DKA? Signs?
- Abdominal pains
- Mental changes (lethargy to near-coma)
- “Fruity” breath (due to acetone)
- Kussmaul’s respirations (rapid, deep breaths)
- pH of less than 7.2 (sharp inflection point)
- Signs of volume depletion (tachycardia, orthostatic hypotension)
- Signs related to precipitating factors (infection, MI, trauma, etc.)
What are lab tests that may be done for the diagnosis of DKA?
- Elevated blood glucose
- pH < 7.35
- Low HCO3-
- High anion gap
- Positive serum ketones!
How to calculate corrected serum sodium concentration? Why do you want this?
- Corresponds to initial state of sodium depletion/volume depletion (?)
How to calculate anion gap?
What is normal?
Why do you want this?
AG = Na - (Cl + HCO3)
Normal value = 8-12 (+/-2)
- This can tell you if something else is going on (simple or complex acid-base disorder)
What is the treatment for DKA?
- Mainly isotonic fluid!!
- Reverses ketosis and acidosis
- HyperK due to lack of insulin, but overall body is actually K-depleted (will be seen when volume corrected)
- very rapidly; don't stop insulin when glucose is approaching normal, just add glucose drip (takes longer to correct ketogenesis and acidosis)
- Normalization is marked by disappearance of ketones or normalization of pH
- Treat precipitating cause(s)
What is "HONK"
- Hyperosmolar hyperglycemic nonketotic state
- Extreme hyperglycemia
- Poorly treated/undetected diabetes
- Renal insufficiency
- Age/mental obtundation -> decreased oral fluids
- Absence of ketosis:
- Insulin is not totally deficient
- Severe dehydration and volume depletion
- Coexisting chronic illnesses
- High mortality
What is the critical calculation that should be done if you suspect HONK? Why?
- How to calculate
- Normal values
- HONK values
- Grade of consciousness of patient is quite related to serum osmolality
- Mortality is in turn related to the grade of consciousness
Calculation: 2Na + glucose/18 + BUN/2.8
- Normal is 290-300 mOsm
- HONK is >> 300 mOsm
What is the treatment for HHNS/HONK?
Mainly want to correct fluid-volume situation (first!)
- Isotonic and hypotonic fluids
- Correct volume status first (normal saline); although even normal saline may be somewhat hypotonic compared to their blood
- Correct serum osmolality (hypernatremia and dehydration) next; do so very carefully to avoid bad brain effects
- Electrolyte replacement
In what settings does lactic acidosis occur?
- With hypoxemia/shock ("Type A")
- Without hypoxemia/shock ("Type B")
What diabetic conditions may contribute someone to developing lactic acidosis?
- Hypotension (acute GI hemmorrhage, sepsis, pancreatitis
- Less organ perfusion -> hypoxia -> anaerobic respiration -> lactic acid
- Arterial oxygen desaturation
- (same mechanism as above)
- Decreased cardiac output
- Regional hypoperfusion
- Drugs (Metformin)
What is the upper limit of normal of lactic acid?
1 mmol (after intense exercise... normally much lower)
What is the most concerning ASE of Metformin?
What part of respiration is diverted/altered that increases lactic acid?
- Normally, at the end of glycolysis, pyruvate goes into the citric acid cycle
- If oxygen depleted, converted instead to lactate (this allows regenration of NAD and some slight energy production with continued glycolysis)
What is the treatment for lactic acidosis?
1. Correct hypoxia (most important)
- Give oxygen
- Fix problem (e.g. ischemic liver)
2. Remove toxins
3. Bicarbonate (cautiously!!)
What is the risk of giving bicarbonate in lactic acidosis?
- Heart not pumping well; less O2 delivery to tissues, which are depending on lactic acid production in respiration
- Increase amount of CO2 to breath out in lungs and help compensate in acidosis (removes H+ and HCO3- substrtes)
- CO2 builds up in cells due to excess production, causing a drop in pH and resultant decrease in contraction/function
- Could make heart function even worse by giving more bicarb (more CO2)