Nichols Diabetes Flashcards
The essence of diabetes is hyperglycemia. The bad thing about hyperglycemia is that it causes excess glucose to stick to everything. ESPECIALLY BASEMENT Membranes
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What’s the bad thing about Sorbitol Pathway?
It eventually turns things into FRUCTOSE which is an even STRONGER glycosylator than glucose is.
KNOW the BIG THREE…mechanisms of long term complications
1) AGEs
- Glucose binds to peptides, this complex interacts with collagen to trap albumin in BM, LDL in arterial atheromas (atherosclerosis), and interactes with AGE receptors (RAGE) to form ROS like superoxide
2) Protein Kinase C:
- Forms profibrogenic TGF-beta (BM thickening)
- forms pro-angiogenic (VEGF) ….retinopathy
Polyol
- glucose—–sorbitol via aldose reductase—–fructose using NADPH. This NADPH was suppusoed to be used to reduce glutathione which you need to break down ROS. But not its used to make fructose, a terrible glycosylator.
Insulinitis with T cells…..what type of D
D1
Amyloidosis of islets
D2
Hyperglycemia impairs immune system? How?
Neutrophil function is impaired.
How does Hyperglycemia disable neutrophil function
Excess glucose causes upregulation of CD11 on neutrophils and upregulation of ICAM, VCAM, and E selectin on endothelial surfaces. All of this leads to sticky vessels and disables the neutrophils from geting to the site of infection.
C3 and hyperglycemia
hyperglycemia causes unactivated complement (C3) to bind to staph. This inhibits the activation of active forms of complement like C5
KNOW..TOO MUCH SUGAR IMPAIRS BACTERIAL KILLING by reducing oxidative burst.
Blame it on the sorbitol. Overactive sorbitol pathway steals NADPH which is needed to make the superoxide in phagosomes.
TEST»»
Too much ROS is a characteristic of the BIG 3, too little ROS (superoxide) is a mechanism of diabetic infection
Resistin
hormone that makes cells resistant to nsulin.
Also inhibits neutrophil chemotaxis
Constitutive activation of Neutrophil extracellular trap formation..
Reduces response to pathogens
ALL this leads to greater rate of infection in:
skin, feet, lungs, urinary tract
Furuncle
Follicle that is infected. Breaks through the BM and into the subcutaneous fat.
Furuncle cause
staph
Carbuncle
Coalescence of furuncles…..cause fever. need to be incised to drain
EXTERNAL OTITIS
Pseudomonas Aeruginosa!!!
Mucormycosis, the rhinocereral form, starts in the nose, spreads into the paranasal sinus, orbit, skull and base of brain
Need amphtericin and surgery
Diabetes predisposes to UTI that can spread into the kidney and cause pyelonephritis
KNOW
Pyelonephritis + Ischemia
renal papillary necrosis
Infection + Ischemia + Neurpathy
Ulceration and gangrene
What is the metabolic syndrome
Diabetes + Hypertension + Dyslipidemia + Abdominal Obesity
Also called teh deadly quartet…..diabetes, high blood pressure, high cholesterol, obesity
Deadly quartet characterized by what
pro-thrombotic, pro-inflammatory
- Associated with high levels of C-reactive protein, IL-6, and Plasminogen activator 1
What medication is associated with the metabolic syndrome
Clozapine
What are the five major risk factors for atherosclerosis
SHODDY S- smoking H- HTN O- obesity D-Diabetes DY- Dyslipidemia
MEtabolic syndrome respondes to diet, some good diets are the mediterranean diet, DASH diet (no salt), low glycemic index
Gotta exercise too
ok
Two forms of diabetic neuropathy
peripheral and autonomic
Autonomic Neuropathy comes later
It is manifested by:
- resting tachycardia
- exercise intolerance
- GI dysmotility
- Impotence
- Orthostatic hypotension
Retinopathy is acually a type of
microangiopathy
2 forms of retinopathy
Background and proliferative
Background retinoipathy
capillary thickening, microaneurysms, venous dilation, hemorrhages.
Prliferative
neovascularization and fibrosis
The three major types of diabetic nephropathy are
Glomerular (diffuse) also called kimmelstiel wilson
Papillary- pyelonephritis and papillary necrosis
Tubulointerstitial- BM thickening and intersitial fibrosis
Nodular type of diabetic glomerulopathy
usually only after more than 10 years of diabetes
much more characteristic of diabetes superimposed on diffuse glomerulopathy
kimmelstiel wilson nodules
ovoid or spherical nodules.. squeeze capillary shut…again, the kidneys have been damaged for a long time.
