Diabetic Neuropathy

Question 1

two classifications of neuropatheis

Answer 1

focal/multifocal. symmetrical

Question 2

4 examples of focal/multifocal neuropathies

Answer 2

mononeuropathy, amyotrophy (muscle tissue wasting), radiculopathy, multiple lesions “mononeuritis multiplex”

Question 3

2 types of symmetrical neuropathies

Answer 3

distal symmetrical polyneuropathy, DSPN, most common. diabetic autonomic neuropathy, DAN.

Question 4

DSPN: common? distribution?

Answer 4

most common: ~75% of diabetic neuropathy. sock + glove distribution: long nerves.

Question 5

DSPN: symptoms? (4)

Answer 5

often asymptomatic. slow loss of sensation, parasthesia. neuropathic pain. slowed nerve conduction velocity.

Question 6

DAN: symptomatic? affects what organs? coexists? mortality?

Answer 6

often asympatomatic. can affect every organ. freq. coexists w/ other neuropathies. sign. increases mortality

Question 7

cardiovascular autonomic neuropathy: 3 clinical symptoms

Answer 7

resting tachycardia. exercise intolerance. orthostatic hypotension.

Question 8

CAN: resting tachycardia due to? progression?

Answer 8

due to loss of vagal tone. may slow w/ time due to progression of symp. dysfunction

Question 9

CAN: exercise intolerance - why? progression?

Answer 9

bc adaptations to increase muscle blood flow don’t occur. severity inversely proportional to max heart rate

Question 10

CAN: orthostatic hypotension due to?

Answer 10

impaired baroreflex, due to loss of symp efferent function

Question 11

CAN: high risk of?

Answer 11

high risk of silent myocardial infection: 1/5th patients, decreased survival rate

Question 12

diagnosis of CAN

Answer 12

w/ 3 standard tests: valsalva, HR response to deep breathing, postural BP testing. CAN = slower compensation to re-establish homeostasis

Question 13

DAN: GI neuropathy (5)

Answer 13

esophageal dysmotility (acid reflex, regurgitation, dysphagia). gastroparesis diabeticorum (aka reduced gastric emptying). constipation, diarrhea, fecal incontinence.

Question 14

DAN: genitourinary symptoms?

Answer 14

diabetic cystopathy/neurogenic bladder (enlargement, retention, incontinence, inability to sense fullness). erectile dysfunction

Question 15

neuropathy pathogenesis: main risk factor?

Answer 15

hyperglycemia: uptake of glucose into nerve tissue is non-insulin dependent, so results in intracellular hyperglycemia in neurons = aberrant metabolic processes

Question 16

4 hypothesis for neuropathy pathogensis

Answer 16

microvasculature ischemic changes. polyol pathway. advanced glycation end products. oxidative stress.

Question 17

3 microvascular changes? result?

Answer 17

thickening of capillary BM, endothelial hyeprplasia, increased vasoconstriction = ischemia, hypoxia in local neurons

Question 18

polyol pathway?

Answer 18

aldose reductase; normally inactivates toxic aldehydes but with hyperglycemia you get increased flux = more sorbitol = less myoinositol which you need for Na/K ATPase

Question 19

AGE: formation?

Answer 19

precursors formed due to intracellular hyperglycemia - bind to proteins = AGEs

Question 20

AGE/RAGE actions

Answer 20

intracellular: modify protein function. extracellular: perturb matrix. receptor: bind circulating enzymes, bind RAGE, inflammatory pathway induction

Question 21

oxidative stress pathway?

Answer 21

high glucose in neurons = increased flux through ETC = high proton gradient = inhibits ETC3 = electrons back up, donated to oxygen = superoxide

Question 22

ROS: causes?

Answer 22

tissue injury, cell death, DNA damage, function of receptors, enzymes, transport proteins affected, induces gene transcription