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
What is Fournier’s gangrene?
Infection and ischemia can combine
to cause massive necrosis in the
perineum
What 4 things are included in metabolic syndrome?
DM, HTN, dyslipidemia, abdominal obesity
Epidemiology of metabolic syndrome
The prevalence is highest in native Americans, followed by Hispanics, African Americans
and European Americans.It increases with age.
What drugs are associated with metabolic syndrome?
atypical antipyschotic medications like clozapine
Metabolic syndrome is a pro- ______ state. What mediators are usually elevated?
pro-inflammatory and pro-thrombotic; IL-6, CRP, PAI-1
Modifiable risk factors of metabolic syndrome?
4/5 of the ones for atherosclerosis- SHODY ( not smoking, HTN, obesity, DM, Dyslipidemia)
A person with metabolic syndrome who started smoking is at risk for ____.
atherosclerotic CV disease
Metabolic syndrome responds to ____ and _____.
Diet and exercise
What specific diets have additional benefits with metabolic syndrome?
- Mediterreanean diet 2. DASH, 3, Low glycemic index
For what 4 reasons may metabolic syndrome not really be a syndrome?
No unifying pathophys has been found, features vary so much, the 4 components are only additive factors for heart disease, Dx does not alter tx
Onset of diabetic neuropathy is determined by ___ and ____.
duration and severity of hyperglycemia
What are the 2 major forms of diabetic neuropathy?
peripheral- all eventually get it but 50% subclinical
Autonomic: not universal and commonly asymptomatic
Pathogenesis of diabetic neuropathy
(1) Activation of polylol pathway
(2) Increased oxidative stress
(3) Injury to Schwann cells
(4) Demyelination of nerves
(5) Accumulation of sorbitol & fructose
(6) Activation of protein kinase C
(7) Accumulation of advanced
glycation end-products (AGEs)
What is the earliest histo-pathologic change in diabetic neuropathy?
segmental demyelination
Describe pathology of peripheral neuropathy and how it is manifested
Distal SYMMETRIC polyneuropathy (length-dependent dying back of axons, primarily sensory).
Manifested by loss of vibratory sensation and proprioception, then impaired pain, light tough and temparature sensation ascending from the feet. Can have pain early on or weakness.
Manifestations of autonomic neuropathy
Manifested by resting tachycardia, exercise intolerance, gastrointestinal dysmotility especially gastroparesis), impotence, orthostatic hypotension, silent myocardial ischemia & infarction, increased mortality (30% over 5 years)
What does diabetes do to aging?
As suggested by the role of AGE in the pathogenesis of diabetic neuropathy, the excess glucose in diabetes sticks to everything and causes it to age faster.A massively experienced elderly diabetologist taught an intern decades ago that each year of insulin-dependent diabetes adds a year to the physiologic age.
Diabetic retinopathy is a type of _____
microangiopathy
What are the 2 forms of diabetic retinopathy?
background + proliferative
Describe background retinopathy
capillary thickening, microaneurysms,venous dilations, edema, hemorrhages,soft exudates (“cotton wool spots”, = microinfarcts) and hard exudates(precipitates of plasma proteins + lipids)
Describe proliferative diabetic retinopathy
neovascularization and fibrosis
What are the 3 types of diabetic nephropathy?
glomerular, papillary, tubulo-interstitial
What are the 2 kinds of glomerular diabetic nephropathy?
Diffuse and nodular (Kimmerlstiel wilson)
What are the 2 kinds of papillary diabetic nephropathy?
pyelonephritis, papillary necrosis
What are the 2 kinds of tubulo-interstitial diabetic nephropathy?
Tubular BM thickening, interstitial fibrosis
Describe diffuse type diabetic glomerulopathy
earlier, less severe = the most common type
Identical glomerulopathy occurs with hypertension and aging
Consists of capillary basement membrane thickening and increased mesangial matrix
(begins in stalk of glomerular tuft)
Describe nodular type diabetic glomerulopathy?
later, usually only after >10 years of diabetes
Much more characteristic of diabetes, superimposed on diffuse glomerulopathy
Features Kimmelstiel Wilson nodules and hyaline sclerosis of afferent and efferent arterioles
What are Kimmelstiel Wilson nodules?
Ovoid or spherical, hyaline, sometimes laminated deposits of mucopolysaccharides, lipids and fibrillary proteins within mesangium in periphery of glomerular tuft, unclear if are
product of expanded lysed mesangial matrix or massively thickened basement membrane,
Eventually squeeze capillaries shut
Describe exudative fibrin lesions
crescentic deposits of condensed leaked plasma proteins overlying peripheral capillaries between endothelial cell and basement membrane or between basement membrane and epithelial cell
(also occur in non-diabetic disease)
Describe exudative capsular drops.
deposits of partly plasma proteins and partly basement membrane in parietal layer of Bowman’s capsule, protruding into urinoferous
space
(do not occur in non-diabetic
glomerulopathies)
Nodular glomerulosclerosis correlates with _____.
renal failure eventually requiring dialysis
Do exudative lesions correlate with renal failure?
No
End stage nodular glomerulopathy histology
Gross: diffuse fine granularity of cortical surface
(nephrosclerosis)Microscopic: globally sclerotic glomeruli, dilated tubules resembling thyroid
follicles, interstitial fibrosis
What is the most common immediate cause of death due to diabetes?
Atherosclerotic CV disease (70%)
What is the second most common immediate cause of death due to diabetes?
Renal failure 10%
What is the third most common cause of immediated death due to diabetes?
infection 5%
Long term conditions of diabetes tend to appear ____ years after the onset of sustained hyperglycemia.
15-20
_______ can delay the onset and decrease the severity of microvascular complications, retinopathy, neuropathy, and nephropathy
Tight control of blood glucose
The major disadvantage of tight control of blood glucose is ______.
episodes of hypoglycemia.
