T1DM Pathophysiology Flashcards
Outline the natural history of the development of T1DM
- Long pre-clinical period of immune-mediated destruction of beta cells. Insulin secretion is sufficient despite death of beta cells.
- Onset of hyperglycemia when 80-90% of beta cells are destroyed
- Occasionally, there is a “honeymoon phase” period of transient remission before established disease develops and insulin replacement is necessary
- End result: pancreatic beta cell failure with absolute deficiency of insulin secretion
Identify the autoimmune markers that can be used to identify people with type 1 diabetes
- GAD-65 autoantibodies (positive in 70-80% at time of diagnosis)
- Islet cell autoantibodies (ICA or anti-iA-2)
- Insulin antibodies
List the common presenting symptoms of a person with newly diagnosed type 1 diabetes
- more common in T1DM
- Central: Polydipsia, polyphagia, *lethargy, *stupor
- Systemic: *Weight loss
- Respiratory: *Kussmaul breathing
- Eyes: Blurred vision
- Breath: Smell of acetone
- Gastric: *Nausea, *vomiting, *abd pain
- Urinary: polyuria, glycosuria
Identify the causes of hyperglycemia in a person with type 1 diabetes
- A result of the lack of insulin
- Peripheral cells cannot take up glucose, liver continues to break down glycogen to produce more glucose
- Muscle breaks down and aa turned into glucose in the liver
- Adipose tissue breaks down and glycerol is turned into glucose in the liver and FFA are turned into ketones
- All the extra glucose production is added to dietary glucose sources and none is able to enter cells due to lack of insulin
List the commonly occurring ketones in a metabolic acidosis due to a severe insulin deficiency
- Acetone
- Acetoacetate
- Beta-hydroxybutyrate
Define ketoacidosis
When ketone accumulation in the blood is great enough to decrease the pH of the blood below 7.35
Define the renal threshold for glucose
180 mg/dL
What happens when blood glucose exceeds the renal threshold?
- Kidneys are no longer able to reabsorb all the filtered glucose; filtered glucose remains in the tubule and leaves the body in urine
- Glucose is osmotically active and water follows it, increasing the volume of water lost in urine.
What are the results of a severe insulin deficiency on the muscle, adipose tissue, and liver
This is covered in the NC for T2DM
What is the cause of polydipsia in the person with severe insulin deficiency
- Osmotic diuresis occurs due to increased glucose (water follows glucose)
- Hypothalamus receptors monitor osmolality, determine hyperosmolality, reacts by increasing thirst drive. ADH is released to increase water reabsorption
What is the cause of polyphagia in the person with severe insulin deficiency
- Lack of insulin → diminished uptake of glucose into peripheral tissues, body thinks it’s starving
- Increased stimulus to eat despite possible weight loss
How are ketones are produced
- In the liver
- Beta oxidation of FFA released from adipose tissue
Describe how ketones can be determined in the urine and in the serum
- If urine dipstick is positive for ketones, serum ketones are tested
- Urine ketones: nitroprusside test
- Serum ketones: nitroprusside test or direct assay of beta-hydroxybutyrate
- Direct assay of beta-hydroybutyrate levels is preferred, particularly for monitoring response to therapy.
Describe the role of bicarbonate in buffering metabolic acidosis secondary to ketones
- A small amount of ketones are used by tissues as fuel but production exceeds demand and ketones accumulate
- Bicarbonate buffer system is easily overwhelmed by the ketones and the serum pH falls.
Describe the role of the respiratory system in buffering metabolic acidosis secondary to ketones
- Acetone can be eliminated by the lungs during expiration (source of rotten fruit breath odor)
- Decrease in blood pH (increase in CO2)stimulates increased respirations in an attempt to reduce acidosis (Kussmaul respirations)
Describe the role of the renal in buffering metabolic acidosis secondary to ketones
takes too long to kick in, not much effect on DKA
What is the effect of DKA on serum sodium
- Hyponatremic
* Osmotic changes pull water out of cells, reducing plasma Na concentration
What is the effect of DKA on serum potassium
- DKA causes a potassium deficit, average 300-600 mEq.
- Factors that cause hypokalemia:
• Urinary losses
• Glucose osmotic diuresis
• Excretion of potassium ketoacid anion salts
Presentations of potassium when in DKA
- Hyperkalemic: shift of K out of cells but hasn’t been peed out yet
- Eukalemic: shift of K out of the cells but have peed enough out that the serum concentration appears normal. Person has lost sig amts of K
- Hypokalemic: shift of K out of the cell and have peed it out, this is worst case scenario
What is the effect of DKA on serum phosphate
- Hypophosphatemia
- Causes
• Decreased intake
• Acidosis-related shift into ECF
• Phosphaturia dt osmotic diuresis - Same as potassium, might present early with hyperphosphatemia or euphosphatemia
What is the effect of DKA on serum creatinine
- Acute elevations in serum Cr (and BUN)
* Reflects reduction in glomerular filtration dt hypovolemia
What is the effect of DKA on plasma osmolality
- Increased dt elevations in glucose
* Plasma osmolality = sodium + glucose + BUN (not full equation)
What is the effect of DKA on WBC count
Generally slightly elevated 12,000-13,000 (4,000-11,000 nl)
What is the effect of DKA on lipids
elevated TG
Given a blood glucose and a serum Na, determine the corrected sodium value
- Serum Na concentration will fall approx. 1.6 mEq/L (2) for every 100 mg/100mL increase in glucose concentration
Ex: If blood sugar is 550 and measured serum Na is 130
• 550-100 = 450, the amount of sugar above normal
• 450/100 = 4.5, conversion based on ratio
• (4.5)(2) = 9, amount serum Na is under reported
• 130 + 9 = actual serum sodium level
Normal range for serum sodium
135 to 145 mEq/L
How does blurry vision develop in a person with significant hyperglycemia due to severe insulin deficiency?
- Glucose accumulates in the lens of the eye
- Due to osmosis, water is attracted to the glucose
- Lens swells and is less able to accommodate
Explain the anion gap metabolic acidosis findings in DKA
- Serum anion gap = Na – (Cl + bicarb) or cations - anions, nl 3 to 10 mEq/L
- In DKA often greater than 20 mEq/L
- Serum bicarb in DKA is moderately to markedly reduced, reducing the anion side of the equation
- Caused by the accumulation of beta-hydroxybutyrate and acetoacetic acids
