Pathology of Diabetes Flashcards
Islets of Langerhan are found where
endocrine pancreas
2/3 of islet cells in pancreas are
B cells
which cells in pancreas secrete insulin
B cells
insulin is secreted into blood via
capillaries
Insulin binds to what and drives glucose into adipocytes
receptor
When glucose is taken up by cells what happens to glucose in serum
decrease
Molecules that help T cells recognise self from non-self?
HLA Molecules
lymphocyte infiltration of islets (insulitis) leads to
destruction of B cells
What does destruction of B cells do to insulin
Decreases it
What does destruction of B cells and destruction of insulin do to glucose
rises glucose
Aetiology of type 2 diabetes (2)
reduced tissue sensitivity to insulin and inability to secrete very high levels of insulin
What happens in the environment in terms of obesity in diabetes
Expanded upper body visceral fat mass (pot belly)
Expanded upper body visceral fat mass (pot belly) results in
increased free fatty acids in blood (Note - patient is not yet diabetic)
What releases fatty acids in diabetes
Adipocytes
Expanded upper body visceral fat mass leads to increased free fatty acids which leads to
decreased insulin receptor sensitivity
Increased Free fatty acids in blood leads to what regarding insulin
decreased Insulin receptor sensitivity to insulin
In a person with central adiposity what does pancreas need to do to move glucose into cells
Pancreas needs to secrete more insulin
Increased free fatty acids in blood in diabetes leads to
decreased insulin receptor sensitivity to insulin
Expanded upper body visceral fat mass leads to decreased insulin receptor sensitivity which then causes
decreased removal of glucose from blood
Decreased insulin receptor sensitivity to insulin leads to
decreased removal of glucose from blood, rise glucose and insulin
Decreased removal of glucose from blood leads to raised glucose what happens to insulin levels
insulin levels then have to markedly increase to make glucose go back to normal levels
central adiposity leads to
hyperinsulinaemia
Are people diabetic in Central Adiposity
Not yet
Central Adiposity causes what to happen to insulin
Increase
expanded upper body visceral fat mass leads to
peripheral insulin resistance
No diabetes will occur if can do what to insulin
Increase it substantially
If peripheral insulin resistanceis present how do we keep glucose levels normal?
Need pancreas that produces more and more insulin
Which genes control insulin secretion in pancreas?
If gene is a variant it may promote insulin production at
low levels but not high levels
If a patient has many gene variants for low insulin secretion what happens
cannot produce large amounts of insulin
In a normal person what happens to glucose when insulin rises
It decreases
In type 1 diabetes what happens to glucose when insulin decreases
It rises
In central adiposity with normal gene for high end insulin secretion what happens when insulin increases
decrease glucose which is normal
In type 2 diabetes insulin secretion what happens to insulin secretion
does not increase enough to counteract insulin resistance caused by central adiposity
What genes involved in Type 2 Diabetes
Not HLA Genes
Not Adiposity Genes
What unmasks Type 2 Diabetes in genes
A multiple gene defect of pancreatic B cell insulin production which is unmasked by central adiposity
Which part of Type 2 Diabetes pathology is reversible
Central Adiposity
Diabetes decreases life expectancy by
5-10 years
Commonest cause of death in Diabetes
Myocardial Infarction
What does Diabetes accelerate
Atherosclerosis
How is atherosclerosis accelerated (2)
Glucoses attach to low density lipoprotein
Low density lipoprotein is not removed by liver cells leads to lipoprotein and lipid stay in blood leads to Hyperlipidaemia
Hyperlipidaemia can lead to
Atherosclerosis
Microvascular disease in diabetes affects which vessels
arterioles
What surrounds basal lamina
smooth muscle cells
what happens to basal lamina in diabetes
becomes thick
arteriolar disease is also called
hyaline change
what happens in small vessel disease and glycosylation
increased connective tissue around capillaries
Collagen is said to be what
glycosylated
Collagen is related to basal lamina how
It is in normal basal lamina
Normal collagen does not bind
albumin
What happens to albumin in sub endothelial space of arterioles
no accumulation
Glycosylated collagen does bind
Albumin
Glycosylated Collagen leads to what happening to Albumin
accumulation of albumin in sub endothelial space of arterioles
Rigid Cross Linked Protein in Diabetes what happens to it?
It cannot easily be removed
What two things does Glycosylation lead to
Accumulation of trapped plasma proteins +
Accumulation of cross-linked basal lamina proteins
