Acute and chronic complications of DM Flashcards
1
Q
Complications of DM
A
- Acute: ketoacidosis (DKA), hyperosmolar state
- Sx hyperglycemia: polyuria, thirst, blurred vision
- Chronic: neuropathy, retinopathy, nephropathy, atherosclerosis
2
Q
DKA 1
A
- Diagnostic features: hyperglycemia, excess ketones (acetoacetate, B-hydroxybutyrate), metabolic acidosis
- Can often be seen w/ associated features: dehydration, electrolyte abnormalities, severe metabolic stress (infection, MI, trauma)
- Pathophysiology: absolute insulin deficiency (only seen in T1) leads to reduced glc utilization and increased glc production by liver
- Correction of hyperglycemia requires both hydration and insulin (hydration most important so kidneys can excrete excess glc)
3
Q
DKA 2
A
- FFAs are released from adipose tissue during times of low/absent insulin (stress hormones exacerbate this), and the large amount of FFAs go to liver to be converted to ketones
- Ketone production exceeds utilization and ketones build up in the blood
- To Rx DKA give fluids and insulin (amount of insulin required depends on the amount of endogenous insulin)
- DKA causes a gap metabolic acidosis, and response to Rx is monitored by following the reduction in the gap
- DKA requires insulin for Rx
4
Q
Electrolyte abnormalities
A
- During states of hyperglycemia K is lost in the urine
- Metabolic acidosis shifts K out of cells, and thus serum K levels look normal even though total K is low
- As DKA Rx corrects pH the K moves back into cells and the serum K falls rapidly
- Always give someone in DKA K to prevent this, unless they are ESRD
- Phosphate behaves the same way that K does during DKA, thus you must also give PO4 along w/ K to pts in DKA to avoid hypophosphatemia
- Creatinine tests will be falsely elevated in DKA, so using creatinine as a renal function test should be done after correction of DKA
5
Q
Dehydration
A
- Results from osmotic diuresis, reduced fluid intake, and vomiting
- Worsens DKA by reducing blood flow to kidney and thus limiting glc and ketoacid excretion
- Hydration is critical to correcting hyperglycemia
6
Q
Non-ketotic hyperosmolar state 1
A
- Features that differentiate it from DKA: more extreme hyperglycemia (>600), slower progression than DKA, no ketoacidosis, elevated serum osmolality (>320), variable mental status
- Usually seen in T2, who have some residual insulin release- enough to suppress lipolysis
- Hyperglycemia occurs from the same ways that is does in DKA: low insulin, elevated hepatic glc production, reduced glc utilization, ESP dehydration and impaired renal function
- Elevated serum osm is a sign of dehydration, the most important cause of hyperglycemia
7
Q
Non-ketotic hyperosmolar state 2
A
- Pts that are dehydrated will have very high serum Na and glc
- Idiogenic osmoles (osmotically active particles created by the brain in times of dehydration) clear slowly once Rx of fluids is stated
- If serum ism is corrected too rapidly the brain becomes hypertonic relative to the ECF and the cells will swell causing cerebral edema
- To prevent this correct the dehydration slowly (1/2 water deficit in first 24 hrs)
- Fluid Rx is most important for non-ketotic hyperosmolar states, +/- K and PO4 replacement as they may be lost as well (like in DKA)
8
Q
Developing chronic complications of DM
A
- Some pts do not develop chronic complications despite not controlling diabetes
- Some pts do develop chronic complications even w/ controlling diabetes
- This is because there are genetic factors that are involved, leading some individuals to be more susceptible to chronic complications, and other are less susceptible
9
Q
Mechanisms of chronic complications 1
A
- Glycation of proteins: non-enzymatic glycation of proteins leads to cross-linking of the proteins
- Extent of the glycation depends on the glc concentration and duration of exposure
- Glycation and cross-linking (AGE formation) alters the structure/function of proteins, and can stimulate matrix production of vascular SmM and renal glomerular mesangial cells
- Only Rx for AGE is controlling glc levels
- Aldose reductase pathway: when glc is in excess it is metabolized to sorbitol via a pathway that uses aldose reductase (therapeutic target)
10
Q
Mechanisms of chronic complications 2
A
- Sorbitol pulls water into cells causing swelling and cell damage, this is the cause of diabetic cataracts
- High sorbitol levels cause the depletion of myoinositol, a precursor to signaling molecules
- Depletion of myoinositol leads to deducted activation of PKC, Na/K ATPase activity, and ultimately neuropathy
- PKC activation: endothelial cells, vascular SmM cells, and mesangial cells do not express aldose reductase, thus do not have reduced PKC activity
- Instead these cells have increased PKC activity (directly due to high glc levels)
- PKC in these cells stimulates synthesis of collagen and fibronectin in BMs and matrix
- Thus it leads to atherosclerosis and nephropathy
11
Q
Mechanisms of chronic complications 3
A
- Abnormal microvascular hemodynamics: early in diabetes increased blood flow occurs in capillary beds in renal glomeruli and retina, increasing intracapillary pressure
- This can damage the capillaries leading to nephropathy and retinopathy, but the increased flow can be revered by improved glc control and drugs that inhibit ATII
- Oxidative stress: metabolism of excess glc produces increased quantities of ROS which can lead to proliferation of vascular SmM (atherosclerosis), inhibition of endothelial growth (atherosclerosis), inhibition of NO production (atherosclerosis and HTN), promotion of AGE (many complications)
12
Q
Diabetic nephropathy
A
- Pathogenesis: hyperglycemia is first associated w/ increased GFR, due to increased afferent arteriolar flow (no change in efferent flow)
- Some pts have microalbuminura (indicates abnormal BM and high risk for renal failure)
- High glomerular pressures and glycation lead to mesangial cell proliferation and matrix production which leads to a fall in GFR (kimmelstiel-wilson nodules)
- Once GFR begins to fall there is proteinuria (nephrotic range) and HTN
- Rx is w/ ACEI, glc and HTN control
13
Q
Diabetic retinopathy 1
A
- Initial changes (background retinopathy) are deep in retina: loss of pericytes supporting the capillaries, capillary dilations (micro aneurysms), intraretinal bleeding (dot blot hemorrhages), lipid deposits (hard exudates), capillary loss-> retinal ischemia
- Later there are more severe complications: cotton-wool spots (soft exudates = infarcts), bleeding (boat and flame hemorrhages)
- Proliferative retinopathy: blood vessels growing out of the anterior retina into vitreous humor
- Pathophysiology of background retinopathy: disrupted blood-retinal barrier leads to increased blood flow, BM glycation
14
Q
Diabetic retinopathy 2
A
- Damage to capillaries within the retina leads to intra-retinal bleeding, protein/lipid deposits and ischemia
- These do not cause vision problems unless they occur near the macula (macula edema- use VEGF inhibitors)
- Proliferative retinopathy: elaborating VEGF leads to abnormal vessel and fibrous tissue growth, causes vision loss
- Either vessels bleeds and obstruct light, or fibrous tissue contracts and pulls retina off blood supply (retinal detachment)
- VEGF Rx for macula edema, lasers for both background and proliferative
15
Q
Diabetic neuropathy
A
- Affects smaller nerves over larger ones, and affects longer nerves over shorter ones
- Distal numbness, tingling, pain (feet>hands)
- Also autonomic complications: postural hypotension, importence, constipation, gastroparesis
- Pathophysiology: myoinositol depletion due to increase aldose reductase pathway flux leads to impaired Na/K ATPase activity and altered membrane potentials/conduction
