Anatomical Pathology

Question 1

Describe the pathogenesis of DM complications.

Answer 1

Advanced Glycation End Products (AGEs): High blood sugar levels can lead to the formation of advanced glycation end products (AGEs), which are harmful compounds that can accumulate in tissues and organs and cause damage over time.
A. Sheer stress because of decreased elasticity to connective tissue
Thickened BM of vessels :
i] inc fluid filtration
ii] decreased breakdown
iii] inc protein deposition
iv] inc trapping LDL
* B. Plasma Proteins and AGE : binding to AGE receptors
i] inc growth factors from macrophages and mesangium : proinflammatory
molecules and cytokines
ii] increased synthesis of matrix : atheroma

2. ACTIVATION OF PROTEIN KINASE C
   i] angiogenesis
   ii] inc deposition of E matrix and BM
   * Inflammation and cytokines
3. SORBITOL AND FRUCTOSE :
   i] H20 into cell  damage
   * Ii] dec myoinositol  inc injury Schwann cells and pericytes
4. EXCESS 02 FREE RADICALS

• Atherosclerosis as in non-diabetic patients - but more severe and at an
  earlier age since DM accelerates atherosclerosis.
• Thus patients with DM have an earlier age of onset of
  (i) Coronary atheroma.
  (ii) 1-2x excess mortality in due to CVA
  (iii) Peripheral vascular disease - gangrene of feet and toes. (the “diabetic
  foot”, with ischaemic and neuropathic ulceration and superimoposed.
  infection in the deep tissues (cellulitis) and even bone (osteomyelitis).

Question 2

What is the Pathogenesis of Microvascular lesions of DM?

Answer 2

thickening of capillary basement membranes - a specific complication of diabetes

Question 3

How does microvascular lesions of DM affect the eye?

Answer 3

Eye: diabetic retinopathy : microaneurysms, haemorrhages, exudates
* [can cause blindness].

Question 4

What happens to microvascular in the kidneys?

Answer 4

• Kidney:
  1. Kimmelstiel-Wilson lesions – nodules of increased mesangial matrix
  (glomerulosclerosis),
  2. thickening of the basement membrane with altered charge and thus increased
  permeability  proteinuria.
  [3. pyelonephritis] increased sugar in urine, thickened vessel BM  poor acute
  inflammatory response to bacteruria
  4. renal papillary necrosis : swelling from pyelonephritis, vessel changes in papillae 
  infarction of the papillae

Question 5

What are possible complications that can occur in pregnancy due to DM?

Answer 5

: increase in congenital malformations, large foetus (obstructed labour),
polyhydramnios, neonatal distress syndrome, pregnancy-induced hypertension.

Question 6

Discuss the neuropathy in terms of DM.

Answer 6

Debate as to whether basement membrane thickening with subsequent
capillary closure results in ischaemic demyelination and axonal
degeneration, or whether there is a more direct effect of chronic
hyperglycaemia causing peripheral neuropathy.