Diabetic Neuropathy Flashcards
two classifications of neuropatheis
focal/multifocal. symmetrical
4 examples of focal/multifocal neuropathies
mononeuropathy, amyotrophy (muscle tissue wasting), radiculopathy, multiple lesions “mononeuritis multiplex”
2 types of symmetrical neuropathies
distal symmetrical polyneuropathy, DSPN, most common. diabetic autonomic neuropathy, DAN.
DSPN: common? distribution?
most common: ~75% of diabetic neuropathy. sock + glove distribution: long nerves.
DSPN: symptoms? (4)
often asymptomatic. slow loss of sensation, parasthesia. neuropathic pain. slowed nerve conduction velocity.
DAN: symptomatic? affects what organs? coexists? mortality?
often asympatomatic. can affect every organ. freq. coexists w/ other neuropathies. sign. increases mortality
cardiovascular autonomic neuropathy: 3 clinical symptoms
resting tachycardia. exercise intolerance. orthostatic hypotension.
CAN: resting tachycardia due to? progression?
due to loss of vagal tone. may slow w/ time due to progression of symp. dysfunction
CAN: exercise intolerance - why? progression?
bc adaptations to increase muscle blood flow don’t occur. severity inversely proportional to max heart rate
CAN: orthostatic hypotension due to?
impaired baroreflex, due to loss of symp efferent function
CAN: high risk of?
high risk of silent myocardial infection: 1/5th patients, decreased survival rate
diagnosis of CAN
w/ 3 standard tests: valsalva, HR response to deep breathing, postural BP testing. CAN = slower compensation to re-establish homeostasis
DAN: GI neuropathy (5)
esophageal dysmotility (acid reflex, regurgitation, dysphagia). gastroparesis diabeticorum (aka reduced gastric emptying). constipation, diarrhea, fecal incontinence.
DAN: genitourinary symptoms?
diabetic cystopathy/neurogenic bladder (enlargement, retention, incontinence, inability to sense fullness). erectile dysfunction
neuropathy pathogenesis: main risk factor?
hyperglycemia: uptake of glucose into nerve tissue is non-insulin dependent, so results in intracellular hyperglycemia in neurons = aberrant metabolic processes
4 hypothesis for neuropathy pathogensis
microvasculature ischemic changes. polyol pathway. advanced glycation end products. oxidative stress.
3 microvascular changes? result?
thickening of capillary BM, endothelial hyeprplasia, increased vasoconstriction = ischemia, hypoxia in local neurons
polyol pathway?
aldose reductase; normally inactivates toxic aldehydes but with hyperglycemia you get increased flux = more sorbitol = less myoinositol which you need for Na/K ATPase
AGE: formation?
precursors formed due to intracellular hyperglycemia - bind to proteins = AGEs
AGE/RAGE actions
intracellular: modify protein function. extracellular: perturb matrix. receptor: bind circulating enzymes, bind RAGE, inflammatory pathway induction
oxidative stress pathway?
high glucose in neurons = increased flux through ETC = high proton gradient = inhibits ETC3 = electrons back up, donated to oxygen = superoxide
ROS: causes?
tissue injury, cell death, DNA damage, function of receptors, enzymes, transport proteins affected, induces gene transcription
