DM Complications (Nichols) Flashcards by Jennifer Watson

Glycosylation favors what structures

basmement membranes

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What does the sorbitol pathway do? Significance with DM (2 things)?

Sorbitol pathway converts glc → sorbitol → fructose

it is inc in DM and fructose, the product is a more potent glycosylator than glc
mediated by aldose reductase, using NADPH
NADPH is needed by glutathione to catabolize/breakdown ROS → more ROS is around → oxidative stress

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What are the 3 major mechanisms for long-term complications of DM?

formation of AGEs
activation of PKC
↑sorbitol pathway

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3 major effects of ↑AGEs that contribute to long term complications of DM

trap LDL in arterial artheromas
bind cell surface receptors (RAGE) → ROS
causes things to age faster: each year of insulin-dept DM adds 1 year to the persons physiologic age

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How does activation of PKC contribute to long term complications of DM

pro-fibrinogenic and angiogenic cytokines released:

TGF-beta → BM thickening
VEGF → neovascularization in retinopathy

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insulitis with T lymphocytes (in islets

T1DM

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_______ increases susceptibly to infections

hyperglycemia

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Ways that hyperglycemia inc susceptibly to infections (2(.5) reasons)?

Microbes “RAN –> away from C3(PO)”
Ros, Adhesion Molecules, Nets –> C3

Upregulates CD11b on neutrophils and ICAM-1, VCAM-1, and E-selectin on endothelial cells → neutrophils cannot get to site of infection
impairs phagocyte killing by oxidative burst bc hexokinase pathway is saturated so more glc enters sorbitol pathway → Decreased NADPH → decreased production of superoxide in phagosomes
constitutive NET formation → decreased response to subsequent pathogens
is specific to S. aureus?? causes binding of UN-activated C3 to S. aureus → C3 cannot become activated (form C3b/iC3b) on bacterial surface → decreased phagocytosis

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Destruction of beta cells by lymphocytes → insulin DEFICIENT

T1DM

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too much superoxide is mech of …

diabetic triopathy

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too little superoxide is a mech of …

diabetic infections

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peptide hormone made in monocytes that

(1) renders cells resistant to insulin
(2) inhibits neutrophil chemotaxis
(3) decreases oxidative burst via phosphatidyl-inostiol-3-kinase pathway

resistin

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amyloidosis of islets

T2DM

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normally mediated by IL-6

constitutive NET formation

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Where in the body are infections in DM most likely?

DM pts get --> Sick w/the FLU
Skin
Feet
Lungs
Urinary tract

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What does resistin do?

(1) renders cells resistant to insulin
(2) inhibits neutrophil chemotaxis
(3) decreases oxidative burst via phosphatidyl-inostiol-3-kinase pathway

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Insulin RESISTANCE is characteristic

T2DM

**but the amyloidosis renders them somewhat deficient too

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What are the most likely organisms for diabetic pts to be infected with?

Sick Patients Cause Messes

S. aureus
Pseudomonas aeruginosa
Candida
Zygomycetes/Mucormycosis

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skin abscess from acute necrotizing infection of hair follicle

furuncle

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how deep is a furuncle?

down to subcut

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most common but to cause furuncles

S. aureus

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Treatment of furuncle

Drained!! warm compress to aid spontaneous drainage or use a needle

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coalescence of multiple furuncles that creates a subcut complex of abscesses

Carbuncle

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other than their size and #of follicles involved, what diff a carbuncle from a furuncle

carbuncles can cause systemic symptoms like fever

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* Facial paralysis, vertigo * Pain is disproportionate * Temp >102.2/39

malignant external otitis + other signs, like necrosis of skin in ear canal or meningeal signs

What is infected in malignant external otitis?

Osteomyelitis of ear canal (and often adjacent mastoid) | necrosis of skin in ear canal

What bug commonly causes malignant external otitis?

Pseudomonas aeruginosa

Need incision for drainage malignant external otitis

carbuncle

Large empty hyphae that looks like a twisted ribbon on microscope

Murcomycosis/zygomycosis

has rhinocerebral form

Murcomycosis/zygomycosis

Common consequence of UTI that is untreated in diabetic pt

UTI → pyelonephritis + ischemia related to diabetes → ***renal papillary necrosis***

pattern of progression for rhinocerebral of Murcomycosis/zygomycosis

starts in the nose → paranasal sinuses → orbit → skull base → brain

necrosis of skin in ear canal = you should suspect

malignant external otitis

Why are foot ulcerations and gangrene more common in diabetic pts?

infection + ischemia + neuropathy

Fournier's gangrene

massive necrosis in perinuem

Metabolic syndrome =

DM + HTN + Dyslipidemia + Abdominal obesity

Metabolic syndrome "speeds pts toward death from ______"

heart disease

Rank races in order of highest to lowest prevalence of metabolic syndrome

Native Americans > Hispanics > African Americans > European Americans

Pts with metabolic syndrome are in a _______ states. Evident by what labs?

pro-thrombotic and pro-inflammatory elevated CRP, IL-6, and PAI-1

Metabolic syndrome is assc with the use of what drugs?

clozapine and atypical anti-phycotics

5 major risk factors for artherlosclerosis

SHODDY: smoking, HTN, obesity, DM, dyslipidemia

T or F: metabolic syndrome responde to diet and exercise

T: - Mediterranean, DASH diet, diet of foods with a lower glycemic index - Exercise might be most beneficial when it removes abdominal fat

What determines the onset of diabetic neuropathy

duration and severity of hyperglycemia

What are the 2 forms of diabetic neuropathy

peripheral and autonomic

Pathogenesis of diabetic neuropathy

hyperglycemia … → increased sorbitol pathway → inc oxidative stress → injury to schwann cells → DEMYELINATION → accumulation of sorbitol and fructose → activation of PKC → Nerve damage → accumulation of AGEs → nerve damage

earliest histo change seen with diabetic neuropathy

segmental demyelination

Peripherial diabetic neuropathy presents as (proximal, distal) (symmetric, asymmetric) (mono, poly neuropathy)

distal, symmetric, poly

Describe the presentation of diabetic neuropathy

ascends from feet can have pain (early) or weakness PRIMARILY SENSORY LOSS -vibratory sensation, proprioception, impaired pain, temp, and touch perception

Describe the presentation of autonomic neuropathy

* Resting tachycardia, exercise intolerance * GI dysmotility (constipation or diarrhea) * Impotence * Orthostatic hypotension OH, Tits Get Increased (but he cant get hard if he has autonomic neuropathy)

Type of microangiopathy

diabetic retinopathy

2 forms of diabetic retinopathy and how are they distinct/defining characteristic

background: cotton wool spots from micro infarcts, also see edema, hemorrhages, microaneurysms, and capillary thickening proliferative: neovascularization and fibrosis

2 types of diabetic glomerulopathy

diffuse = global (early and less severe) | nodular (later and severe)

3 patterns of diabetic nephropathy

glomerular papillary tubulo-interstitial

Identical to the glomerulopathy seen with HTN and aging

diffuse diabetic glomerulopathy

Eventually requires dialysis

nodular diabetic glomerulopathy

What are Kinnelstiel Wilson nodules? Where are they deposited?

Oval/spherical depostis of mucopolysaccharides, lipids, and fibrillary proteins within the MESANGIUM

What are the 2 types of exudative lesions? how are they differentated?

both made of plasma protiens!!!! fibrin caps: crescentric deposits between epithelial cell and BM capsular drops: round deposits in the parietal layer of Bowman’s capsule

crescentric deposits of condensed leaked plasma proteins

fibrin caps

Oval/spherical depostis of mucopolysaccharides, lipids, and fibrillary proteins within the MESANGIUM

Kinnelstiel Wilson nodules

diffuse fine granularity of cortical surface

end stage diabetic nephropathy | = HTN nephropathy

Capillary BM thickening and increased mesangial matrix

diffuse diabetic glomerulopathy

deposits of plasma protein and BM (in the parietal layer of Bowman’s capsule)

capsular drops

does the presence of fibrin caps and capsular drops correlate to the development of renal failur

globally sclerotic glomeruli

end stage diabetic nephropathy

ranks the most common cause of death in DM pts

atherosclerosis > renal failure > infection

when do the long-term consequences of DM appear?

15-20 yrs after onset of sustained hyperglycemia

What can delay the onset and decrease the severity of these complications?

tight control of blood glc