complications of DM Flashcards

1
Q

pathology of hyperglycemia?

A

-hyperglycemia causes excess glucose to be stuck to everything (glycosylation) esp basement membranes. - excess intracellular glucose can go through SORBITOL pathway to fructose which is a never more potent glycosylator than glucose.

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2
Q

what are three mechanisms by which long term complications of DM arise?

A

1) formation of advanced glycation end products (AGEs)
2) activation of Protein kinase C (PKC)
3) disturbance of polyol pathway with glucose converted to sorbitol.

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3
Q

pathology of AGE mechanism

A
  • AGE products are peptides with glucose IRREVERSIBLY stuck on them which cross-links with collagen trapping albumin in basement membrane and LDL in arterial atheromas.
  • It also binds pro-inflammatory cell surface receptors which cause endothelial generation of ROS like superoxide
  • cause pro-coagulant state
  • cause pro-fibrogenic state
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4
Q

pathology of PKC mechanism

A
  • activation of PKC cause production of pro-fibrogenic cytokines such as TGF-beta, which cause BM thickening.
  • pro-angiogenic cytokines sych as VEGF which cause neovascularization in retinopathy
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5
Q

Pathology of polyol pathway mechanism

A
  • disturbance of polyol pathway, with glucose converted to sorbitol (a polyol) by aldose reductase, and then fructose
  • Uses NADPH as cofactor which keeps it from reducing glutathione which is needed to catabolize ROS causing injury by ROS.

-

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6
Q

What is this? Describe and diagnose

A

Type 1 diabetes mellitus is associated with insulitis with T lymphocytes

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7
Q

What is this? Describe and diagnose.

A
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8
Q

What is the pathophysiology of T1DM?

A
  • Destruction of beta cells rendenring these patients dependent on exogenous insuling—> sustained hyperglycemia
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9
Q

What is the pathophysiology of T2DM?

A
  • Insulin resistance*** –> sustained hyperglycemia
  • amyloidosis of islets render some of the patients dependedn on exogenous insulin.
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10
Q

How does hyperglycemia impair innate immunity?

A
  • impairs neutrophil function
  • upregulates CD11b on neutrophils and upregulates ICAM-1, VCAM-1, and E-selectin on endothelial cells, creating an adhesive phenotype keeping neutrophils from leaving blood vessels to sites of infection.
  • hyperglycemia causes unactivated C3 complement to bind to Staph aureus which inhibits the activation of the functionally active forms (c3b/ic3b) on the bacterial surface –> decreased c5a generation –> **decreased phagocytosis. **

**- **consitutive activation of NET formation

  • malfunction of monocytes and natural killer cells –> impairing back-up first responders in the innate immune response to infection
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11
Q

How does hyperglycemia impair bacterial killing?

A
  • via oxidative burst
  • hyperlgycemia saturates the kexokinase pathway which results in formation of sorbitol via aldose reductase
  • hgih sorbitol = decreased NADPH => reduced production of superoxide in phagosomes whichi s needed to kill bacteria.

** too much superoxide/ROS -> diabetic triopathy
and
too little superoxide/ROS = diabetic infections

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12
Q

What is resisitin? where is it produced? what does it do?

A
  • peptide hormone that renders cells resistant to insulin
  • produced by monocytes as well as other cell types and is present at high levels in DM…duh.
  • resistin inhibits neutrophil chemotaxis and oxidative burst via phosphatidyl-inositol-3-kinase pathways
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13
Q

how is NET and hyperglycemia related?

A
  • hyperglycemia causes CONSTITUTIVE ACTIVATION of neutrophil extracellular trap (NET) formation –> decreased response to subsequent pathogens normally mediated by IL-6
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14
Q

what are the most common sites of infections in d/t diabetes impaired neutrophil function?

A

1) skin
2) feet (bone, soft tissue)
3) lungs
4) urinary tract

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15
Q

which pathogens cause the most infections in diabetes-impaired neutrophil function?

A

1) staph aureus
2) pseudomonas aeruginosa
3) candida species
4) zygomycetes (mucor)
5) many other bugs

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16
Q

What is shown here? Describe.
What treatment is needed?

A
  • zygomycetes- large empty hyphae with rare, random angle branching and collapse looking like twisted ribbon
  • biopsy, good pathologist, prompt diagnosis, amphotercin and maybe surgery needed
17
Q

Describe what you see. What is this?

A

Papillary tip with inflammatory cells (blue) infiltration.

  • pyelonephritis caused by UTI infection ascending into kidney (risk factor for those with diabetes)
18
Q

Describe what you see.

A

where the arrows are pointing, you can see renal papillary necrosis which is prevalent in diabtes bc pyelonephritis + ischemia (both related to dm) can cause renal papillary necrosis.

19
Q

what is metabolic syndrome?

A

1) DM
2) HTN

3) Dyslipidemia
4) abdominal (male pattern) obesity

** all of these things speed pts toward death d/t heart disease.

20
Q

what is elevated in metabolic syndrome?

A

since it is a pro-inflammatory and pro-thrombotic state, CRP, IL-6, and plasminogen activator inhibitor-1 are all elevated

21
Q

what drug(s) are associated with metabolic syndrome?

A

atypical antipsychotic medications especially clozapine

22
Q

Tx for metabolic syndrome?

A

1) diet leading to weight loss. esp mediterranean diet, dash diet, diet of foods with lower glycemic index
2) regular exercise- min of 30 min brisk walking a day. May be more beneficial beyond weight loss by removing abdominal fat esp in women.

23
Q

What is the pathogenesis of diabetic neuropathy?

A

1) activation of polyol pathway
2) increase oxidative stress
3) injury to schwann cells (PNS)
4) demyelination of nerves
5) accumulation of sorbitola nd fructose
6) activation of PKC
7) accumulation of AGEs

24
Q

what is this showing?

A

this is eariliest histopathoogic change showing segmental demyelination using a luxol fast blue stain. it stains myelin blue.

  • this nerve lost about 75% of its myelin.
25
Q

What is this showing? who gets this and why? what other disease/process show the same thing(s)?

A

this is showing diffuse mesangial thickening (purrrrple stuff) and capillary basement membrane thickening.
- diabetic patients with diabetic glomerulopathy gets this. This is the diffuse type which is the most common. It is less severe and earlier.

  • identical glomerulopathy occurs with HTN and aging
26
Q

what is this showing? where do you see this?

A
  • this is showing hyaline sclerosis of (afferent and efferent) arterioles and small nodular lesion (orange-red)
  • seen in nodular type diabetic glomerulopathy. This is seen later in patients with >10yrs of dm and is more characteristic of dm than diffuse glomerulopathy.
  • Kimmelstiel wilson nodules (red) that you seen on the pictures on this page with small capsular drop showin in arrow. Capsular drops are deposits of partly plasma proteins and parly BM in parietal layer of bowman’s capsule protruding into urinoferous space. ***CAPSULAR DROPS DO NOT OCCUR IN NON-DIABETIC GLOMERULOPATHIES
  • KW nodules are ovoid/spherical, hyaline deposits of mucopolysaccharides, lipds, and fibrillary proteins in the mesangium in the periphery of glomerular tuft. We are ot sure if KW are products of expanded lysed mesangial matrix or thickened BM. These eventually squeeze capillaries shut!
27
Q

What is this showing?

A
  • the red stuff is fibrin caps which are crescentic deposits of condensed leaked plasma proteins overlying peripheral capillaries between endothelial cells and BM or btwn bm and epithelial cells

** this can also occur in non-diabetic disease

28
Q

what is this? describe gross and micro

A

this is end-stage nephropathy. It looks like htn nephropathy

  • gross: diffuse fine granularity of cortical surface (nephrosclerosis)
  • micro: globally sclerotic glomeruli, dilated tubules resembling thyroid follicles, interstitial fibrosis.
29
Q

what are the three most common immediate cuase of death d/t diabetes? name from most common to not

A

1) atherosclerotic cardiovascular disease- 70%
2) renal failure-10%
3) infection-5%

30
Q
A