16. DM Flashcards
DM definition
DM is a heterogeneous metabolic disorder, characterized by chronic hyperglycaemia with disturbance of carbohydrate, fat and protein metabolism (WHO)
Literally means sweet siphone(i.e sweet urine)
glut
diagnostic criteria
fasting
pre 100-125
diabetic> 126
hemoglobin
pre 5.7-6.4
diabetic >6.5
2 hr plasma
pre 140-199
diabetic >200
random
diabetic
>200
complications
microangiopathy- hemorgae
retinopathy
hypertension
atheroscelerosis - hyaline arteriolo
nephroscelerosis
peripheral neuropathy and peri. vascular
autonomic neuropathy
Pathogenesis of Complications
Formation of advanced glycation end products (AGE):
Nonenzymatic reaction glucose with amino group of proteins
AGE crosslinked proteins are resistance to proteolytic digestion
Biologic properties of AGE–RAGE complex
-ROS and NF-kB activation
- monocyte emigration
- cytokine and growth factor secretion
-↑ vascular permeability and procoagulant activity
-↑ ECM production and cellular proliferation
AGE bind to plus how
to Y receptors in macrophage endothelial cells vascular smooth muscle
or without receptor to
intimal matrix proteins
BM collagen 4
hyperglycemia increases de novo synthesis of what
DAG then protein kinase c
Activation of protein kinase C downstream effects
VEGF production (induces neovascularization characterizing diabetic retinopathy)
↑activity of endothelin-1 and ↓activity of nitric oxide synthase (NOS) - net constriction
↑TGF- β fibrosis
↑PAI-1 - plasminogen activator inhibitor
↑proinflammatory cytokines by endothelium
Diabetic nephropathy charachters
Microalbuminuria - (>30 mg/day but <300 mg/day)
Diffuse glomerulosclerosis and nodular glomerulosclerosis (Kimmelstiel Wilson disease)
Renal vascular lesions: Renal arteriosclerosis and atherosclerosis
Pyelonephritis including papillary necrosis (necrotizing papillitis) - because susceptible to infection
CKD
diffuse glomeruloscelerosis
increased fibrosis of mesangial matrix
thick basement membrane
nodular glomerylonephritis or kimmsel wilson lesion
nodular deposition in mesangial matrix
benigh nephroscelerosis with surface apearance
hyaline arterioloscelerosis
leathery granulairty surface
renal papillary necrosis cause plus presentation
cause SODA
sickle cell
obstructive pylonephritis
diabetes
analgesics
present with hematuria
Diabetic retinopathy types
Nonproliferative retinopathy
Microaneurysms, retinal hemorrhages, and retinal exudates
Proliferative retinopathy
Neovascularization and fibrosis
Diabetic Neuropathy pathogenesis
AGEs may interfere with normal protein function and activate inflammatory signaling
Injury by ROS and osmotic damage
Ischemic damage of the nerves
Clinicopathologic patterns of diabetic neuropathy 3
Ascending distal symmetric sensorimotor polyneuropathy
Diabetic autonomic neuropathy (20% to 40%)
Asymmetric neuropathy(rare)
Ascending distal symmetric sensorimotor polyneuropathy
Numbness, loss of pain sensation, difficulty with balance,
“positive” symptoms; paresthesias or dysesthesias
Foot and ankle fractures and chronic skin ulcers
Diabetic autonomic neuropathy (20% to 40%)
Postural hypotension, neurogenic bladder and sexual dysfunction
Asymmetric neuropathy(rare) cased ny
May be caused by microvascular disease
E.g mononeuropathy, cranial neuropathy, and radiculoplexus neuropathy
Macroangiopathy list
-Cardiovascular disease is the leading cause of death
-Peripheral vascular disease lead to atrophy of skin and loss of hair of the lower extremities, claudication, nonhealing ulcers, and gangrene (leading cause of nontraumatic amputations)
-Cerebrovascular disease (strock)
Body defense and Diabetes
↑susceptibility to infections of the skin and to tuberculosis, pneumonia, and pyelonephritis
cause of decreased defense
decreased neutrophil function (chemotaxis, adherence to the endothelium, phagocytosis, and microbicidal activity),
impaired cytokine production by macrophages and
Poor blood supply
gyperglycemia block - in neutrophil function and others
adgesion
NET formation
degranulation
opsonization
phagocytosis
doesnt block or increases
macrophage to M2 macrophages
