Diabetes mellitus complications Flashcards
Long term complications of diabetes mellitus occur by 3 major mechanisms. What are they?
- AGEs cross link with collagen, trap albumin in BM and LDL in atheromas, bind RAGE–> ROS and pro coag.fibrogenic state
- PKC–> TGFB, VEGF ( neovascularization in retinopathy)
- Polyol disturbance uses up NADPH –> oxidative stress, ROS
TID is associated with ____ of islets. T2D is associated with ______.
insulitis with T cells; amyloidosis of islets
The final common pathway for both T1D and T2D is _____.
sustained hyperglycemia
Hyperglycemia impairs ____ immunity. Which cell specifically?
innate; neutrophils
Hyperglycemia upregulates ______ on neutrophils and ____ on endothelial cells creating an _____ phenotype.
CD11b; ICAM1, VCAM1, E selectin, Adhesive
What does hyperglycemia do to unactivated C3 complement?
causes binding of unactivated C3 complement to Staphylococcus aureus, inhibiting activation to functionally active forms (C3b/iC3b) on the bacterial surface, associated with decreased C5a generation and decreased phagocytosis.
Excessive intracellular glucose impairs bacterial killing by _____. How does this happen?
Oxidative burst; It saturates the hexokinase pathway resulting in formation of sorbitol via aldose reductase. High sorbitoldecreases NADPH, which leads to reduced production of superoxide in phagosomes when and where it is needed for killing bacteria (SO is over produced in all the wrong places)
Too much SO is a major mechanism of ________. But too little SO is a mechanism of ______.
Diabetic triopathy; diabetic infections
What is resistin?
peptide hormone named for its ability to render cells resistant to insulin; it is produced by monocytes (among other cell types) and present at high levels in diabetes
What does resistin do to neutrophils?
inhibits neutrophil chemotaxis and oxidative burst via phosphatidyl- inositol-3-kinase pathways.
What does hyperglycemia do to NET formation?
constitutive activation- reduced response to subsequent pathogens normally mediated by IL-6
What does hyperglycemia do to monocytes and NK cells?
malfunction– impairing the back-up first responders
Diabetes impaired neutrophil function leads to more numerous and more severe infections in :
skin, feet, lungs, urinary tract
Diabetes impaired neutrophil function leads to more numerous and more severe infections with:
- S. aureus
- Pseudomonas
- Canada
- Zygomycetes
- Many other bugs
What is a furuncle and what are predisposing factors?
It is acute necrotizing infection of a hair follicle that breaks through the basement membrane into adjacent subcutaneous fat.Anything that breaks the skin predisposes to developing a furuncle. This includes, especially, shaving.
____ is the most common cause of furuncles. Describe these furuncles and what should be done.
Staph aureus; painful, tender, fluctuant with a central pustule with surrounded erythema and edema–> DRAIN (spontaneous with warm compress or with needle)
_____ is a coalescence of multiple furuncles creating a subcutaneous complex of abscesses.
carbuncle
What kind of symptoms are associated with carbuncles? What should be done? And when are they more common?
Carbuncles can cause systemic symptoms like fever and commonly need incision for drainage. They are much more common in diabetics.
_____ can cause malignant external otitis in diabetics.
Pseudomonas aeruginosa
What is malignant external otitis? How does it present and what should be done?
Pseudomonas aeruginosa can cause malignant
external otitis in diabetics.It usually involves adjacent mastoid, with osteomyelitis of the ear canal and should be suspected when canal skin necrosis appears; the pain is disproportionate; he patient’s temperature exceeds 102.2° F (39° C);facial paralysis, vertigo, or meningeal signs may occur. It usually requires debridment as well as antibiotics.
Describe mucormycosis presentation and tx.
Rhinocerebral form starts in the nose, spreads into paranasal sinuses, orbit, skull base, brain–> amphoterrible and surgery
How does zygomycetes look histologically?
Very distinctive- large empty hyphae with rare, random angle branching and collapse–> twisted ribbon?
Complications of UTI (diabetes predisposed…)
ascend into the kidney–> pyelonephritis
How can pyelonephritis lead to renal papillary necrosis?
pyelonephritis + ischmia related to diabetes
Infection can combine with ___ and ____, all related to diabetes, to cause foot ulcerations and gangrene.
neuropathy,ischemia