Microvascular Complications Flashcards
Mechanism for hyperglycemia induced tissue damage
hyperglycemia –> repeated acute changes in cellular metabolism + cumulative long-term changes in stable macromolecules –> tissue damage + accelerating factors (e.g. hypertension)
Molecular pathways implicated in pathogenesis of diabetic tissue damage (4)
polyol pathway, advanced glycosylation end products (AGE), pKC activation, hexosamine pathway
Molecular pathways implicated in pathogenesis of diabetic tissue damage - polyol
decreased NADPH due to altered function of aldose reductase –> decreased glutathione –> oxidative stress
Molecular pathways implicated in pathogenesis of diabetic tissue damage - advanced glycosylation end-products (AGE)
modification of intra/extracellular proteins resulting in increased cytokines and growth factors
Molecular pathways implicated in pathogenesis of diabetic tissue damage - PKC
decreased endothelial nitric acid synthase, increased endothelin1,tgfbeta,pai1,vegf,nfkb –> vasoconstriction, coagulation, angiogenesis, inflammation
Molecular pathways implicated in pathogenesis of diabetic tissue damage - hexosamine pathway
diversion from glycolysis –> increased nacetyl glucosamine –> altered gene expression of cytokines
Diabetic retinopathy
most common cause of blindness in US –> most t1d affected at 20 years, 50-80% of t2d at 20 years
T/F diabetic retinopathy tends to onset after diagnosis of t2d
F –> before diagnosis of t2d and after diagnosis of t1d
Pathophysiology of diabetic retinopathy
dysregulated retinal blood flow, oxidative stress and inflammation, edema, microthrombosis, growth factors leading to proliferation, genetic, hypertension, dyslipidemia, medications
Two categories of retinopathy
non proliferative (mild/moderate/severe) + proliferative (early/high-risk/severe)
Macular edema
can occur at any stage of retinopathy –> “clinically significant macular edema”
Clinical findings of mild retinopathy
microaneurysms, dot hemorrhages, hard exudate (lipid leakage within macrophages)
Clinical findings of moderate/severe retinopathy
soft exudate (cotton wool spots - nerve fiber layer infarct), venous beading, intraretinal microvascular abnormalities (tortuous capillaries, occluded vessels)
dot hemmorhage
mild retinopathy
cotton wool spot
moderate/severe retinopathy
Defining feature of proliferative retinopathy vs non-proliferative retinopathy
neovascularization –> new vessels are fragile and can hemorrhage (also has preretinal and vitreous hemorrhage, fibrosis, ischemia)
Prevention of retinopathy
glycemic control, antihypertensive therapy (maybe lipid lowering, antiplatelet, and carbonic anhydrase inhibitors)
Glycemic control is highly effective in prevention/slowing of retinopathy in t1d
prevention –> less pronounce in slowing
Tx of NPDR/CSME
NPDR with CSME (non prolif + clinically sig macular edema) = focal laser photocagulation
Tx of high risk/severe PDR
panretinal photocoagulation, intravitreal glucocorticoids, VEGF inhibitor
Indications for vitrectomy
non clearing vitreous hemorrhage, traction retinal detachment involving fovea, non responsive pdr
Diabetic nephropathy
most common cause of kidney failure in US, independent risk factor for cv and overall mortality
Pathologic changes of nephropathy
glomerular disease (mesangial expansion, glomerular basement thickening, glomerular sclerosis) + albuminuria (micro or protein/macro)
Prevention of nephropathy
glycemic control, bp control, tx of dyslipidemia, measurement of spot urin microalbum/creatinine ratio
Tx of nephropathy
ace inhibitor/angiotensin ii receptor blocker (improves or normalizes), hypertensive agents, dietary restriction, weight loss
T/F ace inhibitors and angiotensin ii receptor blockers can prevent onset of microalbuminuria
F
Mx of action of ACE inhibitors and ARB
dilation of efferent arteriole –> reduction of glomerular pressure –> decreased urinary protein
Diabetic neuropathy
most common microvascular complication –> polyneuropathy is most common
Peripheral neuropathy
most common diabetic neuropathy –> distal, symmetric (stocking glove distribution) sensory loss > motor loss, worse at night
Clinical findings of polyneuropathy
sensory loss, loss of ankle reflexes/ vibration loss> pain/temp loss
diff dx of polyneuropathy
alcohol, b12, uremia, hypothyroidism
Tx of painful neuropathy
anticonvulsants, tca’s, snris, topical agents, opioids, antioxidants, tens
CV autonomic neuropathy
resting tachycardia/loss of ps tone, exercise intolerance, postural hypertension, silent MI
GI autonomic neuropathy
esophageal enteropathy (GERD, LES relaxation), gastroparesis, diabetic enteropathy, gallbladder atony and enlargement
Gastroparesis
delayed gastric emptying/symptoms = early satiety, vomiting, nausea, worsening of glycemic control, asymptomatic
Tx of gastroparesis
glycemic control, eating less fat and non-digestible fiber, prokinetic agents
Genitourinary autonomic neuropathy
urinary retension (utis and overflow incontinence), ED, retrograde ejaculation, female sexual dysfunction
Peripheral autonomic neuropathy/sudomotor neuropathy
impaired perspiration, peripheral edema, callus formation/ulcers, contributor to neuroarthropathy
T/F neuropathy in diabetes can affect single nerves
T –> cranial nerves (e.g. bells palsy), peripheral nerves (e.g. carpal tunnel), or mononeuritis multiplex (multiple nerves)
Diabetic amyotrophy
an example of radiculopathy with motor neuropathy of l2-l4- -> acute, asymmetric pain followed by weakness of butt and proximal leg
Truncal polyradiculopathy
sever abdominal pain in band like pattern T4-T12
Tx of NPDR without CSME
risk factor management
