Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

3 - Pathology > Diabetes Mellitus > Flashcards

Diabetes Mellitus Flashcards

1
Q

What is the function of insulin?

A

Increase glucose uptake by certain cells (via insulin dependent GLUT 4)
Cells = striated muscle and fat cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What type of hormone is insulin?

A

Anabolic hormone - promotes synthesis and decreases degradation of glycogen, lipid and protein in target tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What mitogenic functions does insulin have on target cells?

A

DNA synthesis and stimulation of growth and differentiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the two hallmark metabolic defects in Type 2 diabetes?

A

Insulin resistance - decreased response of target tissues to insulin
Beta cell dysfunction - inadequate insulin secretion in the face of insulin resistance and hyperglycaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What occurs with insulin resistance before frank diabetes?

A

B-cell hyperfunction and hyperinsulinemia - this mechanism is exhausted and hyperglycaemia ensures.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What plays a major role in insulin resistance?

A

Obesity
Risk for diabetes increases as BMI increases
Central obesity is more linked with insulin resistance than gluteal obesity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What 3 components of obesity contributes to insulin resistance?

A

Free fatty acids
Adipokines
Inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

State the function of FFAs in obesity and insulin resistance.

A

Excess intracellular FFAs in obese individuals overwhelm oxidative pathways
Generation of toxic intermediates that inhibit intracellular insulin signaling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe why adipokines are a factor in obesity related insulin resistance.

A

Adipose tissue secretes pro and anti-hyperglycaemic cytokines.
Leptin and adiponectin are anti-hyperglycaemic cytokines that increase insulin sensitivity.
Adiponectin levels are decreased in obesity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How is inflammation involved in obesity related insulin resistance?

A

Excess FFAs in macrophages stimulates secretion of pro-inflammatory cytokines IL-1B which stimulates secretion of other cytokines that impede insulin signaling in target tissues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What causes beta cell dysfunction in diabetes type 2?

A

Excess FFAs that compromise B cell function and insulin release = lipotoxicity
Impact of chronic hyperglycaemia - glucotoxicity
Reduced levels of hormones secreted by gut cells (incretins). These normally promote insulin release following food intake (e.g. GIP)
Amyloid deposition within pancreatic islets
Genetic factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

List the long term complications of diabetes.

A 
Macrovascular disease (macroangiopathy) - retinopathy, nephropathy, neuropathy 
Microvascular disease (mircoangiopathy) - retinopathy, nephropathy, neuropathy 
Susceptibility to infections - skin infections, TB, pneumonia, pyelonephritis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Why are diabetic patients susceptible to infections?

A

Impaired leukocytic functions and vascular compromise

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Name the mechanisms implicated in changes seen in tissues (mainly in blood vessels = angiopathy).

A

Formation of advanced glycation end products (AGEs)
Activation of Protein Kinase C (PKC)
Disturbance in Polyol Pathways

** All due to increased glucose delivery to various intracellular metabolic pathways, generating harmful substrates.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Where do the effects of intracellular hyperglycaemia occur?

A

In tissues where glucose transport is insulin independent

E.g. nerves, kidneys, blood vessels, eyes, brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How are AGEs formed?

Advanced Glycation End Products

A

Formed by binding of glucose derivatives to the amino groups of intra and extracellular proteins
Rate of formation is proportional to the degree of hyperglycaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe how AGEs lead to the crosslinking of ECM proteins.

A

Crosslinking of collagen type I in large vessels - decreases their elasticity predisposing to endothelial injury.
Crosslinking of collagen type IV in vascular basement membrane leads to:
- Protein synthesis and deposition exceeding degradation = BM thickening
- Decreased endothelial activation = vascular leakage and extravasation of fluid

Glycated ECM proteins trap other proteins

  • In large vessels, LDL is trapped = enhanced atherosclerosis
  • In capillaries, albumin binds to BM = further BM thickening
18
Q

Describe AGE-RAGE interactions.

A

AGEs bind to a specific receptor (RAGE) expressed on inflammatory, endothelial and vascular smooth muscle cells.

19
Q

Describe the effect of AGE-RAGE signaling in blood vessels.

A

Inhibition of neutrophil functions
Release of pro-inflammatory cytokines and growth factors
- Transforming growth factor B implicated in BM thickening
- Vascular Endothelial Growth Factor (VEGF) leading to angiogenesis implicated in neovascularization in the retina
Production of reactive oxygen species by endothelial cells
- Increased procoagulant activity of endothelial cells
- Vascular smooth muscle cell proliferation and synthesis of ECM

20
Q

Describe the effect of hyperglycaemia on PKC.

A

Intracellular hyperglycaemia stimulates synthesis of diacyl glycerol (DAG) which activates PKC.

21
Q

List the effects PKC activation has.

A

Production of VEGF = angiogenesis (neovascularization in retina)
Increased production of Endothelin-1 = vasoconstriction
Decreased production of the vasodilator NO
Production of Transforming Growth Factor B (TGF-B) = fibroblastic proliferation and ECM/BM deposition
Production of pro-inflammatory cytokines and procoagulant plasminogen activator inhibitor-1 (PAI-1) by vascular endothelium

22
Q

Explain the disturbances in Polyol Pathways.

A

Excess intracellular glucose in tissues that do no require insulin is metabolized to sorbitol (a polyol) and fructose.
This reaction uses up NADPH.
NADPH is also required to generate reduced glutathione (GSH); a major cellular antioxidant mechanism.
Decreased NADPH and GSH makes cells more susceptible to oxidative stress and damage.
= seen in inulin-independent tissues like nerves and eye lenses (sorbitol accumulation in eye lenses leads to cataract)

23
Q

List some examples of diabetic macrovascular disease.

A

Accelerated atherosclerosis = MI, Peripheral vascular disease and gangrene of lower limbs, retinal arteries are also affected
Hyaline atherosclerosis

24
Q

What is hyaline atherosclerosis?

A

Arterioles show a homogenously pink, markedly thickened wall due to plasma protein leakage and ECM deposition leading to narrowing of their lumens
Not specific to diabetes, also caused by HTN

25
Q

What is a normal glomerulus?

A

A vascular structure formed of a network of capillaries that arise from the afferent arteriole then drain into the efferent arteriole.
Lie within bowman capsule

26
Q

Describe what the glomerular capillary wall consists of.

A

A thin layer of fenestrated endothelial cells
A glomerular basement membrane
Podocytes; with their foot processes adherent to the outside of BM
Mesangial cells that support the glomerular tuft. These lie between the capillaries; scattered in basement membrane-like material called mesangial matrix or mesangium.

27
Q

What is the function of the glomerular capillary wall?

A

Filtration barrier with selective permeability

Depends on size and charge of filtering molecules

28
Q

What is the main barrier of the glomerular capillary wall that protects against albumin filtration?

A

Intact podocytes

29
Q

What is the second cause of death from diabetes?

A

Renal failure (ESKD)

30
Q

What is the first clinical change in diabetic nephropathy?

A

Microalbuminuria (endothelial and podocyte dysfunction cause increased permeability of glomerular capillary wall)
This progresses to overt proteinuria and Nephrotic Syndrome.

31
Q

What are the characteristics of diabetic microangiopathy (which underlies Glomerular lesions)?

A

GBM thickening
Diffuse mesangial sclerosis (diffuse increase in mesangial matrix)
Nodular glomerulosclerosis (Kimmelstiel-Wilson lesion - nodular, ball-like increase in mesangium, more specific to Diabetes)

32
Q

List other renal changes/complications of diabetic neuropathy.

A

Atherosclerosis of renal arteries
Arteriolosclerosis of afferent and efferent renal arterioles
= macroangiopathy (both of above)
Infection: pyelonephritis (of renal pelvis and parenchyma) and papillary necrosis
Thickening of tubular basement membrane

33
Q

What is nephrosclerosis?

A

Result of progressive glomerular sclerosis and vascular thickening and narrowing, there is ischaemia, tubular atrophy and interstitial fibrosis (increase in fibrous tissue between glomeruli and tubules).
Loss of renal parenchyma and fibrosis = decrease in size of kidney and gives the surface a pale granular appearance.

34
Q

What is papillary necrosis and in which patients does it commonly occur?

A

Seen mostly in diabetics
Occurs as complication of acute pyelonephritis
Occlusion of the arterial supply to the renal medulla occurs due to the combined effect of diabetic vasculopathy and interstitial edema due to inflammation; which further compresses their lumens
Necrotic material is sloughed into the pelvis

Papillae receive the last part of renal perfusion and are a relatively ischaemic zone.

35
Q

List the characteristics of early non-proliferative diabetic retinopathy.

A

Thickening of BM of retinal BV with change in blood flow
Microaneurysms (Hall mark)
Haemorrhages (dot, blot, splinter)
Macular edema (increase in vascular permeability)
Exudates: Hard lipid exudates (yellow), soft exudates or cotton wool spots which are actually areas of retinal ischemia and infarction

36
Q

What is proliferative diabetic retinopathy?

A

VEGF production leads to angiogenesis (neovascularization)

May lead to massive intraocular haemorrhage and retinal detachment

37
Q

What is diabetic neuropathy?

A

Distal (glove and stocking area) symmetric polyneuropathy presenting with sensory symptoms like numbness, parasthesia or dysesthesia (abnormal sense of touch, feeling of pins and needles) and loss of pain sensation

38
Q

What can autonomic neuropathy lead to?

A

Postural hypotension
Disturbances in bladder function (improper bladder emptying = STIs)
Disturbances in bowel function (diarrhoea or constipation)
Erectile dysfunction

39
Q

What is the pathogenesis behind diabetic neuropathy?

A

Nerve oxidative stress and damage due to disturbances in polyol pathways
Ischaemic damage to the nerves by endoneurial vascular thickening

40
Q

What is the morphology of diabetic neuropathy?

A

Axonal degeneration
Demyelination
Thickening of endoneurial arterioles

3 - Pathology (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions