Major DM Complications Flashcards
1
Q
HHS
A
Hyper-osmolar Hyperglycemic State
- Hyperglycemia (extremely high compared to DKA), severe dehydration, may have low bicarb but not large degree of acidosis, high Osm
- Pathophysiology
- Lack of insulin –> hyperglycemia –> osmotic diuresis –> water loss > Na/K loss –> high Osm
- Also dec GFR due to volume depletion (further inc Osm)
- HHS has less ketosis than DKA b/c hormone-sensitive lipase requires insulin to be shut off; those w/ Type II DM have some insulin which can shut off hormone sensitive lipase; TGs remain in fat cells
CAUSES
- Infection
- Infarction - MI, stroke
- Insulin Omission -new onset - no treatment yet; or stop insulin purposefully
- Indiscretion - drugs/alcohol
- Infants - pregnancy
Tx
- Vol replacement
- Insulin
- Monitor electrolytes every 4 hrs
2
Q
Macroangiopathy (process and tx)
A
- atherosclerosis of medium/large vessels –> MI, stroke, peripheral vascular disease
1- Endothelial injury - from sugar itself and oxidized LDL (+ smoking, hyperlipidemia, HTN)
2- Fatty streak - made worse by oxidized LDL which further damages vessel and attracts monocytes which become macrophages and engulf LDL (foam cells)
3- Fibrous plaque - collagen fibers and smooth muscle cells wall off foam cells; then macrophages burst leaving free cholesterol core
4- Unstable plaque/rupture - inc plasminogen activator inhibitor and dysfunctional endo cells –> faster rate of clot formation after rupture in DM
- TX - smoking cessation, hyperglycemia control, statin, anti-platelet, control HTN
3
Q
Microangiopathy In General
A
- affects retina, kidneys, nerves
- In capillaries, thick BM, endothelial cell damage and loss of pericytes –> weak wall so microaneurysms OR capillary closure so ischemia
- In arteriole/venules, also smooth muscle proliferation - dec lumen
4
Q
3 Underlying Mechanisms of DM Complications
A
1- non enzymatic glycosylation
2- polyol pathway
3- insulin resistance
5
Q
Non-Enzymatic Glycosylation (8 effects of AGEPs)
A
- Glucose attaches to amino groups –> Schiff base adducts on proteins (reversible) BUT inc vascular permeability and inc ECM –> rearranged into Amadori glycosylation products (ex - glycosylated Hb) –> crosslinking and reactions to become adv glycosylation end products (AGEPs - irreversible)
- AGEPs …
1- Bind endothelial cells - permeable and interact w/ platelets forming microthrombi
2- Bind macrophages which inc plasminogen activator inhibitor
3- Induce monocytes to migrate and release cytokines including TGF-beta which inc ECM
4- Enhance proliferation of fibroblasts and smooth muscle cells (atherosclerosis) and ECM
5-React w/ LDL particles where they are oxidized making them toxic to endothelial cells
6- Dec endothelial cells –> more vessel wall exposure –> permeability and clots
7- Modify collagen so it resists degradation –> thicker BM
8- Dec prod of NO and prostacyclin from endo cells - impairs vasodilation and normal clot inhibition
6
Q
Polyol Path (5 effects of sorbitol)
A
- Hyperglycemia –> inc glucose in tissues that do not require insulin (nerve, lens, kidney, vessels) –> hexokinase saturated so glucose shunted to polyol pathway –> aldose reductase convert glucose to sorbitol and eventually fructose
- Sorbitol …
1- Osmotically active - inc osmotic pressure - cellular edema / impaired diffusion, tissue hypoxia and cell damage
2- Inc sorbitol –> dec myoinositol which normally inc diacylglycerol, protein kinase C and Na-K pump activity
3- Damages Schwann cells (dec myelination thus dec conduction)
4 - Damages pericytes in retinal capillaries –> retinal microaneurysms
5 - Damages lens –> swelling and opacity (cataracts)
7
Q
Insulin Resistance
A
Normally insulin binding receptor –> NO and prostacyclin so when insulin resistance there is dec NO and prostacyclin –> vascular smooth muscle growth, vasoconstriction, inc platelet aggregation and accelerated coagulation
8
Q
Diabetic Retina Findings
A
- Microaneurysms - thick BM and loss of pericytes weakens wall
- Hemorrhages - shape dep on layer
- Dot-Blot = middle layers; spherical shape
- Flame = superficial nerve fiber layer; tracks along fibers
- Pre-retinal = on surface b/n retina and vitreous
- Hard Exudates - thick BM, lose charge so lose filtration barrier/ inc permeability of capillaries which lets lipoproteins into interstitium; non-absorbable so they accumulate into yellow solid circumscribed lumps
- Soft Exudates - areas of infarction in nerve fiber layer due to ischemia; diffuse (“cotton wool spots”)
- Retinal Ischemia - leads to retinal edema, neovascularization and cotton wool spots
9
Q
Pathogenesis and Tx of Retina Ischemia
A
- Leaky capillary –> fluid leaks into deep retina layers –> inc diffusion barrier for oxygen –> dec oxygen supply
- Retina comp by forming new vessels but these are superficial so prone to tear
- Can also get accompanying fibrosis –> scars and traction retinal detachment
- Can treat w/ laser photocoagulation to prevent development of new vessels
10
Q
3 Stages of Diabetic Retinopathy
A
- 1- BDR (background diabetic retinopathy) - microaneurysms, dot blot, hard exudates
- 2- Pre-Proliferative DR - soft exudates, retinal edema
- 3- Proliferative DR - neovascularization and fibrous tissue proliferation
11
Q
Claudication
A
- pain in muscle group brought on by exercise and quickly relieved w/ rest
- Predictable and reproducible
- Can progress: occurs w/ less exercise –> pain at rest (critical limb ischemia)
- Once it progresses … Commonly in toes/metatarsals, worse at night (wake pt), aggravated by elevating legs, relieved in dependent position, may also have ischemic ulceration or gangrene which can become infected
12
Q
How do you assess for peripheral vascular disease?
A
- Hx - claudication? pain at rest? hx amputation, risk factors (smoking, diabetes, hyperlipidemia, HTN)
- PE - pulses, cap refill, atrophic shiny skin w/ hair loss, dusky red flush of ischemia skin, foot hygiene/toe nails, sensory exam w/ 5.07 monofilament, check for ischemic ulcers on distal foot and bony prominences
- ABI - ankle brachial indices; meas both brachial and ankle pulses w/ arteriography then divide higher ankle / higher brachial
- Normal ~1 (.9-1.1)
-
- Normal ~1 (.9-1.1)
13
Q
Tx of Peripheral Vascular Disease
A
- Alleviate pain
- exercise (only during)
- smoking cessation
- pentoxifylline = methylxanthine derivative that improves RBC deformity, dec blood viscosity and dec hyper-coag
- cilostazol - inhibits cAMP PDE - vasodilation and platelet inhibition
- Revascularization - reserved for limb threatening ischemia, unresponsive to meds
- Anti-platelet therapy
14
Q
Distal Symmetrical Polyneuropathy (+ tx)
A
- Most common, mainly sensory in stocking and glove distribution (distal –> proximal); may have pain, numbness, hypersensitivity
- Loss of vibratory sense in feet
- Loss of ankle reflexes
- Can progress to motor loss if severe
- Loss of protective sensation to noxious stimuli –> ulcers/infection (so use 5.07 monofilament not superficial cotton to test)
- Tx - glycemic control, treat pain (no opiates), orthotics, smoking cessation
- TCAs - amitryptline for central pain threshold
- Gabapentin, pregabalin, duloxitene
- Capsaicin - binds local TRPV1 (normally activated by heat and pain) –> prolonged activation depletes pre-synaptic substance P so cannot report pain for prolonged time
15
Q
Focal Cranial Neuropathies
A
- III - down and out eye, diabetic opthalmoplegia, pupil function, can resolve, due to ischemic event in vaso nervorum
- VI - lat rectus palsy, bl vision w/ lateral gaze
- IV - sup oblique paralysis so inability to look down and in when walking down steps
