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SBCP Pathology > Endo: Diabetes > Flashcards

Endo: Diabetes Flashcards

1
Q

How many of world’s population have diabetes mellitus?

A

3%

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2
Q

Genetic defects causing B-cell dysfunction in Type 1 DM

A

Chr 2
Chr 7
Chr 12
Mitochondrial DNA

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3
Q

What type of pancreatic tissue is involved in its exocrine function?

A

Pancreatic acinar tissue

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4
Q

What type of pancreatic tissue is involved in its endocrine function?

A

Islets of Langerhans which produce glucagon, insulin and pancreatic polypeptide hormes

Therefore any condition destroying this tissue can cause secondary diabetes

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5
Q

Causes of secondary diabetes (7)

A

Chronic pancreatitis
Haemachromotosis

Endocrine issues (eg adrenal, pituitary tumours)

PREGNANCY
Drugs (eg corticosteroids)

ID (eg congenital rubella, CMV)

Other genetic disorders eg Down’s

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6
Q

Histology of chronic pancreatitis?

A

Loss of pancreas tissue, replaced by fibrous tissue

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7
Q

How many people over age of 55 have DM?

A

50%

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8
Q

Which auto-antibodies occur in DM type 1 and not DM type 2?

A

Auto-islet cell antibodies (HLA-D)

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9
Q

Which type of DM is HLA-D linked?

A

Type 1

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10
Q

What is the concordance in twins of both DM types?

A

50% in type 1

90-100% in type 2

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11
Q

Pathology of type 1 DM?

A

AUTOIMMUNE immunopathological mechanism

Severe insulin deficiency and inflammation or insulitis of islet cells early in the disease

These develop marked atrophy and fibrosis with beta cell depletion

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12
Q

Histopathology of DM type 2

A

Insulin resistance with no inflammation of islets

Focal atrophy and amyloid deposits

Only mild beta cell depletion

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13
Q

How is insulin produced in the islet cells?

A

Increased levels of gluscose in blood are transported across cell boundary by GLUT-2 transporter

Results in production of preproinsulin and proinsulin, then insulin

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14
Q

Where is insulin stored?

A

In granules within islet cell

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15
Q

How does insulin affect a cell?

A

Attaches to insulin receptor on membrane

Leads to increased production of glucose transport units

More glucose uptake

Also, increased protein, DNA synthesis

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16
Q

Genetic factors contributing to type 1 DM? (5)

A 
Northern europeans
1st degree relative (6%)
Identical twin (50%
HLA-D antibody
HLA-DR3 or DR4
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17
Q

Components of autoimmune islet cell destruction in DM1

A

Pre-clinical phase of islet destruction and insulitis, with presence of CD8 and CD9 macrophages

Increase in class 1 MHC and aberrant expression of class 2 MHS

Islet cell autoantibodies

Other autoimmune diseases

18
Q

What percentage of DM type 1 patients have other autoimmune disease?

A

10-20% such as SLE or RA

19
Q

Which viruses have been associated with triggering type 1 DM? (4)

A

?mumps
Measles
Rubella
Coxsackie B

20
Q

Pathology of DM type 2?

A

Genetic predisposition and obesity.

Genetic defects lead to deranged insulin secretion

With obesity, the peripheral tissues develop insulin resistance and are unable to adequately use glucose present in blood

Leads to hyperglycaemia

21
Q

Why is DM type 2 irreversible?

A

Beta cells become exhausted

In the early stages, before exhaustion, the condition is irreversible

22
Q

What is the normal secretion pattern of insulin?

A

Puslatile and oscillating

23
Q

How many type 2 DM pts are obese?

A

80%

24
Q

What is non enzymatic glycosylation?

A

When products of glucose become linked with proteins (eg Hb in HbA1c)

or linked to collagen components (eg advanced glycosylation end products)

25
Q

Pathogenesis of complications of Diabetes, why does high blood sugar cause damage?

A

Non enzymatic glycosylation (formation of HbA1c or AGE)

Intracellular hyperglycaemia with disturbances of polyol pathways and excess sorbitol and fructose in cells

26
Q

Examples of complications in DM?

A

Macrovascular: MI, Hypertension, atherosclerosis, CHD, PAD, arrythmias, cardiomyopathies

Microvascular: Microangiopathy, cerebral infarcts, haemorrhage, retinopathy, cataracts, glaucoma, gangrene, nepthrosclerosis, glomerulosclerosis, pyelonephritis

Nervous system: peripheral neuropathy and autonomic neuropathy

27
Q

Eye complications in DM? (5)

A 
Retinopathy
Maculopathy
Cataracts
Glaucoma
Blindness/visual impairment
28
Q

What is insulinitis?

A

Leukocytes present within the islets

29
Q

How does diabetes affect large vessels eg aorta?

A 
Atherosclerosis
Narrowing of vessels
Ulceration
Calcification
Loss of elasticity
Occluding of branches
30
Q

Gender incidence of MIs in diabetic subgroup?

A

Male=female (in non diabetic group females have lower incidence if they are pre menopausal)

31
Q

Why do vascular complications occur in diabetes?

A

Partly due to raised blood lipids

Low level of protective HDLs

Increase in thromboxane A2, which increases platelet stickiness, and leads to thrombosis

Hyaline arteriolosclerosis

32
Q

How does diabetes affect the renal arteries?

A

Narrows the renal arteries, causing renal ischaemia and hypertension

33
Q

How does diabetes affect basement membrane?

A

Diffuse thickening of basement membrane due to deposition of GLYCOGENATED COLLAGEN proteins

34
Q

What is mesangial matrix?

A

Increases due to increased collagen deposition

Involved in diffuse glomerulosclerosis at the centre of the glomerulus

Narrows the capillary loops

Magenta staining

35
Q

Histology: Increase of menagial matrix in glomerulus with nodular distribution

A

Kimmelstiel-Wilson lesion, typical of diabetic glomerulosclerosis

Results in decrease in glomerular blood flow and renal failure

36
Q

What is hyaline arteriosclerosis?

A

Replacement of blood vessel media layer muscle with hyaline

37
Q

How does hyaline arteriosclerosis affect the kidneys?

A

Narrows the afferent and efferent arterioles

38
Q

What is papillary necrosis?

A

A rare condition seen in diabetics

Associated with some painkillers

Due to inflammation of the kidney and ischaemia causing necrosis of the papilla

Dead papilla passes into ureter and can cause obstruction

39
Q

Why does nerve damage occur in diabetes?

A

Microangiopathy causes loss of blood flow to nerves and they are damaged

40
Q

Skin complications in diabetes

A

Recurrent infections

*Necrobiosis lipoidica diabeticorum

Granuloma annulare

41
Q

Pregnancy complications with diabetes

A

Pre-eclampsia
Large immature babies
Neonatal HYPOglycaemia

SBCP Pathology (24 decks)

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