Pathology of Diabetes Mellitus Flashcards
What does a normal pancreas look like?
Lobules of glandular tissue surrounded by fat
How much of islet cells are beta cells?
2/3rds
What do beta cells secrete?
Insulin
What is involved in the glucose metabolism pathway?
Increased glucose so increased insulin
Which increases glucose uptake into cells and decreases glucose in serum
What genes can cause diabetes mellitus type I?
Human Leukocyte Antigen (HLA) molecules - help cells recognises self from non self
So cannot distinguish own cells from other so autoimmune attack on beta cells
What does autoimmune attack on islet cells cause?
Lymphocyte infiltration of islets - destruction of beta cells
Decreases insulin production so increases glucose in blood
Does environment cause diabetes mellitus type I?
Environmental triggers plus genes can lead to the destruction of beta cells
Describe the aetiology of type II diabetes mellitus
Combination of reduced tissue sensitivity to insulin and inability to secrete very high levels of insulin
So failure of beta cells to meet increased demand for insulin in body
What is the environmental cause of type Ii diabetes mellitus?
Expanded upper body visceral fat mass - increased adipocytes due to increased intake of food and lack of exercise
What does expanded upper body visceral fat mass result in?
Increased free fatty acids in blood as adipocytes under stress
This leads to decreased insulin receptor sensitivity
What does decreased insulin receptor sensitivity lead to?
Decreased removal of glucose form blood
So pancreas needs to secrete more insulin to move glucose into cells for person with central adiposity
What does central adiposity lead to?
Hyperinsulinemia
How does the body cope with peripheral insulin resistance?
Need pancreas to produce more and more insulin
Not diabetic if increase in insulin is substantial
What genes are involved in type II diabetes mellitus?
Implicated genes are for poor beta cell ‘high end’ insulin secretion
So if only a few abnormal - lots of insulin can still be produced
If variants for lower insulin production then can’t produce large amounts
What are the 2 factors causing type II diabetes mellitus?
Insulin secretion genetically can only be increased so far in a person who’s weight gain has slowed down for their insulin receptors
What is an exception in type II diabetes mellitus?
Slim person gains small amount of weight but have very high dosage of genes resulting in inability to even modestly raise insulin
What part of type II diabetes mellitus is reversible?
Adipose fat
What are some long term complications of DM?
Annual mortality is 5.4% so double non-diabetics
Life expectancy decreased by 5-10yrs
MI is commonest cause of death
result from prolonged poor glycaemia control
What is the main complication of DM?
Large vessel disease - arteries
Small vessel disease - arterioles and capillaries
What does DM accelerate in large vessels?
Atherosclerosis
Coronary heart disease, MI and stroke increased risk
How is atherosclerosis acclerated?
Glc attaches to low density lipoprotein so stop lipoprotein from binding to receptor on liver cells tightly - lipoprotein stays in blood - hyperlipidaemia then atherosclerosis
What sits on endothelial lining?
Makes basal lamina for collagen to sit on
What happens to small vessels in diabetes mellitus?
Molecules flux into subendothelial space but find it hard to flux back to blood - build up of trapped molecules
Basal lamina also becomes thicker
What builds up between subendothelial space?
Accumulation of plasma proteins and connective tissue
What is hyaline change?
Arteriolar disease
Process occurs throughout body
Narrow arteriole so poor blood flow so ischaemia
Very damaging in kidney, peripheral tissues, eyes and nerve supply
What is the risk of hyaline change?
Amputation
End stage renal disease
Blindness
What small vessel disease happens in capillaries?
Increased connective tissue around capillaries
What is a nodule of connective tissue called?
Kimmelsteil Wilson lesion
Explain glycosylated collagen and small vessels
Collagen in in normal basal lamina and normal collagen does not bind to albumin
Glycosylated collagen does bind to albumin so accumulation in subendothelial space
Explain cross linked proteins and small vessels
Normal basal lamina proteins do not crosslink and can be easily removed
Glycosylated proteins bind to neighbouring proteins - rigid crosslink which cant be easily removed - persistence
What does glycosylation cause?
Accumulation of trapped plasma proteins
Accumulation of cross linked basal lamina proteins
When does large and small vessel disease in DM occur?
Typically irreversible when established
Occurs in setting of prolonged poor diabetic control
