Pathology of Diabetes Mellitis and its Complications Flashcards Preview

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Flashcards in Pathology of Diabetes Mellitis and its Complications Deck (67)
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1
Q

What is the normal strucutre of the pancreas?

A

Normal pancreas – lobules of glandular tissue surrounded by fat

2
Q

What is normal insulin secretion in the pancreas done by?

A
3
Q

2/3 of islet cells are what?

A

2/3 of islet cells = B cells

4
Q

what do B cells secrete?

A

insulin

5
Q

What stimulates the release of insulin and where is it secreted into?

A

Intake of food – converted to glucose = stimulates insulin

Insulin - secreted into blood in capillaries

6
Q

does insulin act on just one tissue type?

A

no

e.g. muscle, fat

7
Q

what happens when insulin binds to its receptors on adipocytes?

A

Insulin binds its receptor and drives glucose into adipocytes (= fat cells)

8
Q

hwat is the basic glucose and insulin pathway?

A
9
Q

what is the aetiology of type I diabetes mellitus?

A

not entirely known

10
Q

What are genes found so far that may be the aetiology of type I diabetes mellitus and their effect

A

Molecules that help T cells recognise self from non-self = Human Leukocyte Antigen (HLA) molecules

And in type 1 diabetes they cannot distinguish own cells from other cells = autoimmune attack on pancreatic B cells

Autoimmune attack on islet cells – lymphocyte infiltration of islets (insulitis) – destruction of B cells

11
Q

what does destruction of islets cause?

A

decreased insulin

12
Q

It is thought that environemtnal tirggers may play a part in causing type 1 diabetes

What are some environmental tirggers that may be involved in causing type 1 diabetes?

A

Chemicals

Bacteria in gut altered in infancy - People with different bacteria in their gut when their 6 months old may have an increased chance of having type 1 diabetes

Viral infection - Molecules on viral surface mimic molecules on outside of B cells

13
Q

Genes + Environment ——– > Destruction of _____

A

B cells

14
Q

Destruction of B cells _______ insulin and _________ Glc

A

decreased

increased

15
Q

what is the aetiology of type II diabetes mellitus?

A

Not entirely known

Combination of:

  • 1) reduced tissue sensitivity to insulin (insulin resistance) and
  • 2) inability to secrete very high levels of insulin

Another way of putting it = a failure of the B cells to meet an increased demand for insulin in the body

16
Q

What environment is the aetiology of type II diabetes mellitus?

A

Expanded upper body visceral fat mass (pot belly)

central adiposity = accumulation of fat in the lower torso around the abdominal area

Expanded upper body fat mass is due to increased intake of food + lack of exercise (genes relatively unimportant)

17
Q

What does expanded upper body visceral fat mass (pot belly) result in?

A

Expanded upper body visceral fat mass (pot belly) results in increased free fatty acids in blood (Note - patient is not yet diabetic)

because ‘overweight’ adipocytes are probably ‘stressed’ and release fatty acids

18
Q

Expanded upper body visceral fat mass leads to increased free fatty acids which leads to what?

A

decreased insulin receptor sensitivity

19
Q

Expanded upper body visceral fat mass leads to increased free fatty acids which leads to decreased insulin receptor sensitivity

why?

A

not clear why the fatty acids interfere with the insulin receptor pathway

20
Q

What happens now someone has insulin receptors that do not work very efficiently due to the central adiposity?

A

Some glucose (Glc) gets into cells but some does not

Not working very well so one glucose gets in and one doesn’t and then more insulin in blood as there is excess glucose and you need more insulin to make that glucose go into cells

Now need more insulin to get same amount of glucose into cells so the pancreas needs to secrete more insulin to move glucose into cells

21
Q

So pancreas needs to secrete more insulin to move glucose into cells in person with _____ ______

A

central adiposity

22
Q

Decreased insulin receptor sensitivity in central adiposity – why?

A

not clear why the fatty acids interfere with the insulin receptor pathway

23
Q

Expanded upper body visceral fat mass leads to decreased insulin receptor sensitivity which then causes _________________________

A

decreased removal of glucose from blood

24
Q

Decreased removal of glucose from blood
leads to raised glucose, and insulin levels then have to markedly ___________ to make glucose go back to ___________

A

increase

normal levels

This is what is happening in people with central adiposity so they have high insulin but not yet diabetic as they have enough intact cells to be able to produce more insulin

25
Q

central adiposity leads to what?

A

hyperinsulinaemia

if you were to measure the levels in someone with central adiposity who is not diabetic they would have increased insulin levels due to having to secreate more in order to compensate for the increased glucose in the blood

26
Q

expanded upper body visceral fat mass leads to peripheral insulin resistance

So need _______ insulin to cope with _______ tissue sensitivity to insulin

No diabetes will occur if can _______ insulin substantially

A

increased

decreased

increased

27
Q

If peripheral insulin resistance is present how do we keep glucose levels normal?

A

Need pancreas that produces more and more insulin

28
Q

Which genes control insulin secretion in pancreas?

A

Many different genes

Some of these genes control whether you can secrete very large amounts of insulin or not

29
Q

What may a persons insulin secretion genes in the pancreas look like if they have type 2 diabetes?

A

If gene is a variant it may promote insulin production at low levels but not high levels

Implicated genes are for poor B cell ‘high end’ insulin secretion

So if you have only a few genes abnormal you will be able to secrete lots of insulin but if you have many gene variants for lower insulin secretion then you cannot produce large amounts of insulin

this is bad in a person with increasing central adiposity meaning they will have peripheral insulin resistance and therefore require more insulin to keep the level of glucose at normal levels

30
Q

A

A

normal glucose

31
Q

B

A

Type 1 diabetes

32
Q

C

A

Normal glucose

33
Q

D

A

type 2 diabetes

34
Q

So in type II diabetes insulin secretion does not _________ enough to counteract insulin _________ caused by ___________________

A

So in type II diabetes insulin secretion does not increase enough to counteract insulin resistance caused by central adiposity

35
Q

Can a slim person get type 2 diabetes?

A

Yes

Slim person who puts on a small amount of weight may get type II diabetes if they have very high dosage of genes resulting in inability to even modestly raise insulin

36
Q

what are the genes involved that cause type 2 diabetes?

A

Multiple genes involved in causing inadequate ‘high level’ insulin secretion by B cells

Not HLA genes

Not adiposity genes

A multiple gene defect of pancreatic B cell insulin production which is unmasked by central adiposity

37
Q

What part of type 2 diabetes is reversible

A

not genes

central adiposity is reversible and by loosing this it will decrease the need for lots of insulin to be needed

38
Q

What is the annual mortality of diabetes

A

Annual mortality is 5.4% - double the rate of non-diabetics

39
Q

How does DM affect life expectancy?

A

Life expectancy is decreased by 5-10 years

40
Q

what is the commonest cause of death due to DM

A

Myocardial infarction is the commonest cause of death

41
Q

Do the long term complications only happen in DM due to certain causes? and what are they caused by?

A

Occur regardless of the cause of the DM

Result from prolonged poor glycaemic control

42
Q

Main complication of DM is damage to vessels but what ones?

A
  • Large vessel disease - Arteries
  • Small vessel disease - Arterioles and Capillaries
43
Q

What are large vessel (‘macrovascular’) complications of DM?

A

DM accelerates atherosclerosis

Doesn’t cause it, it just accelerates it

44
Q

DM accelerates atherosclerosis and what does this put someone more at this of and by how many times?

A
  • Coronary heart disease 2-20x
  • Myocardial infarction 2-5x
  • Atherothrombotic stroke 2-3x
45
Q

How is atherosclerosis accelerated?

A

many mechanisms

46
Q

How is atherosclerosis accelerated?
Name one eg of a mechanism

A

Glucoses attach to low density lipoprotein

Glucose molecules stop low density lipoprotein from binding its receptor (on liver cells) tightly

Low density lipoprotein is not removed by liver cells = lipoprotein and lipid stay in blood = Hyperlipidaemia

Hyperlipidaemia = Atherosclerosis

47
Q

Small vessel (‘microvascular’) disease - Arterioles

In the photo which is normal and which is not

A

left is normal

right is abnormal

48
Q

What is this showing the structure of?

(lumen is the space in the middle)

A

arteriole

Endothelial cell lines lumen, so the arteriole lining = several endothelial cells

49
Q

Endothelial cells that line the arterile make what to sit on?

A

basal lamina (collagens) to ‘sit on’

50
Q

Between basal lamina and endothelial cell is what?

A

a potential space

51
Q

What happens in the space between the basal lamina and endothelial cell

A

Molecules flux into and out from this subendothelial ‘space’

52
Q

what is found around the basal lamina in an arteriole

A

smooth muscle cells

53
Q

What happens in arterioles in DM?

A

molecules flux into subendothelial space but find it hard to flux back to blood

Which leads to a build up of ‘trapped’ molecules under endothelial cell

54
Q

In DM, what also happens to the basal lamina in arterioles?

A

Basal lamina also becomes thickened

55
Q

histology image showing ateriole in DM

A
56
Q

Arteriolar disease is also called ___________

A

hyaline change

57
Q

arterilar disease is a process that occurs throughout the ____

A

body

58
Q

Narrow arteriole = poor blood flow = __________

A

ischaemia

59
Q

where is arteriolar disease very damaging?

A

Very damaging in kidney, peripheral tissues (foot), eyes and in arterioles supplying nerves

60
Q

what is the relative risk of morbidity is arteriolar disease?

A
  • Amputation 40x
  • End stage renal disease 25x
  • Blindness 20x
61
Q

how does small vessel disease affect capillaries?

A

Increased connective tissue around capillaries – eg. Glomerulus in kidney

62
Q

how many ways can small vessel disease happen?

A

2

Collagen is glycosylated

Proteins are cross-linked

63
Q

Explain how collagen is glycosylated causes small vessel disease?

A

Collagen is in normal basal lamina

Albumin can sometimes get into subendothelial space and normal collagen does not bind albumin

albumin fluxes out of space - no accumulation of albumin in subendothelial space of arterioles

But glycosylated collagen does bind albumin leading to accumulation of albumin in subendothelial space of arterioles

Albumin is trapped in subendothelial space

64
Q

what does this image show?

A

Accumulation of albumin in subendothelial space of arterioles

65
Q

How does cross linking proteins cause small vessel disease?

A

Many normal basal lamina proteins do not crosslink and can be removed easily

But glycosylated proteins bind their neighbouring proteins

Rigid, cross-linked protein cannot easily be removed

Persistence of proteins in arteriole walls even if return to normoglycaemia

66
Q

Glycosylation leads to what things?

A

Accumulation of trapped plasma proteins

+

Accumulation of cross-linked basal lamina proteins

Arteriole with hyaline change, less compliant, doesn’t open as easy and doesn’t squeeze as easy

67
Q

Large and small vessel disease in DM is:

Typically __________ when established

Occurs in setting of _________, ____ diabetic control

A

irreversible

prolonged, poor

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