DM Complications (Nichols) Flashcards
Glycosylation favors what structures
basmement membranes
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
What are the 3 major mechanisms for long-term complications of DM?
- formation of AGEs
- activation of PKC
- ↑sorbitol pathway
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
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
insulitis with T lymphocytes (in islets
T1DM
_______ increases susceptibly to infections
hyperglycemia
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
Destruction of beta cells by lymphocytes → insulin DEFICIENT
T1DM
too much superoxide is mech of …
diabetic triopathy
too little superoxide is a mech of …
diabetic infections
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
amyloidosis of islets
T2DM
normally mediated by IL-6
constitutive NET formation
Where in the body are infections in DM most likely?
DM pts get --> Sick w/the FLU Skin Feet Lungs Urinary tract
What does resistin do?
(1) renders cells resistant to insulin
(2) inhibits neutrophil chemotaxis
(3) decreases oxidative burst via phosphatidyl-inostiol-3-kinase pathway
Insulin RESISTANCE is characteristic
T2DM
**but the amyloidosis renders them somewhat deficient too
What are the most likely organisms for diabetic pts to be infected with?
Sick Patients Cause Messes
S. aureus
Pseudomonas aeruginosa
Candida
Zygomycetes/Mucormycosis
skin abscess from acute necrotizing infection of hair follicle
furuncle
how deep is a furuncle?
down to subcut
most common but to cause furuncles
S. aureus
Treatment of furuncle
Drained!! warm compress to aid spontaneous drainage or use a needle
coalescence of multiple furuncles that creates a subcut complex of abscesses
Carbuncle
other than their size and #of follicles involved, what diff a carbuncle from a furuncle
carbuncles can cause systemic symptoms like fever
- 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
no
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
