Pathology of Diabetes Mellitus Flashcards
What does a normal pancreas look like?
Lobules of glandular tissue surrounded by fat
What histological slide is this? How can you tell? And what is the arrow pointing at?
Pancreas slide
Can tell by the light pink area the arrow is pointing at
It is the islets of langerhands - the endocrine part of pancreas, the rest of the pancreas is exocrine
What are 2/3s of the islet cells made up of?
B-cells
What do B cells do?
Secrete insulin
Where in this picture are the B cells?
Within the endocrine part/islet area - the small pink circles
What is the white areas within the ednocrine pancreas are?
Capillaries for insulin to be secreted to
Is aetiology of type 1 DM known?
No
What do the genes that are found so far (that lead to type 1 DM) do?
Responsible for Human leukocyte antigen (HLA) molecules that help T cells recognise self from non self
What is the pathology behind type 1?
Autoimmune attack on B-cells
What does this slide show? What is arrow pointing at?
An autoimmune attack on iselt cells
Arrow points to a lympoid cell
What is insulitis?
Lymphoid infiltration of islets
Whats arrow pointing at?
A scarred islet
Some hypothosised enviromental triggers of type 1?
Chemicals
Viral infection - molecules on infection mimic moleculs on outside of B-cells
Aetiology of type 2?
Combination of:
Insulin sensitivity
Inability to secrete high levels of insulin
What is the enviromental factors for type 2?
Expanded upper body fat mass due to increase intake of food and lack of diet
What happens if patient has expanded upper body fat mass? Is the patient diabetic at this point?
Adipocytes placed under stress and release FFA’s into blood (patient not yet diabetic)
When FFA’s are released into blood - what chain of events does this start?
FFAs interfere with insulin receptor sensitivity decreasing it
More insulin needed to get same amount of glucose into cells so pancreas makes more (a patient with central adiposity)
So what does central adiposity cause in regards to insulin?
Causes hyperinsulinaemia
If patient has hyperinsulinaemia, are they diabetic?
Not if the can increase insulin substantially (or increase insulin sensitvity via exercise and diet change)
What type of insulin resistance does central adiposity cause?
Peripheral insulin resistance
Since to stop diabetes if insulin receptor sensitivity is low you need more insulin secreted, what gives certain people an dvantage to do this?
Different genes can control if you can secrete a lot of insulin or not
Explain the gene stuff?
If a patients genes that cause poor B-cell production are abnormal they can make lots of insulin
But if a patient has lots of genes that cause low insulin secretion they cannot make large amounts
Can a slim person ever get type 2 diabetes?
Yes, if they have a very high number of genes that result in an inability to even modestly raise insulin
So what genes are NOT involved in this and what genes are?
NOT - HLA genes, adiposity genes
ARE - Genes involving inadequte “high level” insulin secretion by b cells
Whats the commenst cause of death for diabetics?
MI
What does the MI result from?
Poor glycemic control
What vessels fall under macrocascular catagory? What does hyperglycemia do to these vessels?
Arteries - accelerates atheroscerosis
What one is a healthy artery and what one isnt? What is wrong with the unhealthy one…
Right has atherosclerosis with an occlusive thrombosis
How does hyperglyceaemia actually accelerate atheroclerosis?
- Glucose attaches to low densitiy lipoprotein (LDL)
- LDL can’t then bind onto liver receptors
- LDL is therefore not removed by the liver
- Lipoprotein and lipids stay in blood = hyperlipidaemia = atherosclerosis
What vessels are affected in microvascular disease? What picture is abnormal and why?
Arterioles
Right - arteriole is constricted
What cells line arterioles?
Endothelial cells
What do endothelial cells make to sit on?
Basal lamina (collagens)
What is between the basal lamina and endothelial cells?
Potential space
What happens in DM with this potenital space?
Molecules flux into the subendothelial space but find it hard to flux back to blood
What lies around basal lamina?
Smooth muscle cells
What do these trapped molecules cause?
They build up and cause occlusion by thickening the basal lamina
What type of molecules get caught in the subendothelial space?
Plasma proteins - albumin
CT - collagens
What is arteriolar disease also called?
Hyaline change
Where does hyaline change affect most?
Kidney
Eyes
Arterioles supplying nerves
Peripher tissues - feet
State some morbidity risks from hyaline change.
Amputation x40
End stage renal disease x25
Blindness x20
What vessles are affected in small vessel disease?
Capillaries
What pathology effects the capillaries? Give and example
Increased CT arround capillaries - e.g is glomerulus in kidney
How does small vessel disease occur?
- Glucose is added to proteins such as collagen via glycosylation
- Collagen is normal in basal lamina, and albumin can sometimes enter into the subendothelial space
- Albumin and collagen do not normally bind but when collagen has glucose on it these proteins cross link = thickening and occlusion
Is vessel disease reversible?
Not once it is established
