Metabolic Syndrome and CVD

Question 1

Define metabolic syndrome

Answer 1

a constellation of interconnected physiological, biochemical, clinical, and metabolic factors that directly increases the risk of cardiovascular disease, type 2 diabetes mellitus, and all cause mortality

Question 2

Describe the diagnostic criteria for metabolic syndrome

Answer 2

Insulin resistance (impaired glucose tolerance or impaired fasting glucose levels) and any 2 of the following:

1) Obesity (BMI over 30)
2) Dyslipidaemia (raised TGs over 150mg/dL and/or reduced HDL under 39 mg/dL)
3) Raised BP
4) Raised blood glucose (impaired glucose tolerane or T2D

Question 3

How much does CVD cost the NHS per year

Answer 3

£6.9 billion

Question 4

Describe the renal effects of MetS

Answer 4

Microalbuminuria, hypofiltration, hyperfiltration, glomerulomegaly, focal segmental glomerulosclerosis, and chronic kidney disease.

Question 5

Describe the hepatic effects of MetS

Answer 5

Increased serum transaminase, nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), hepatic fibrosis, and cirrhosis.

Question 6

Describe the dermatological effects of MetS

Answer 6

Acanthosis nigricans, lichen planus, systemic lupus erythematosus, burn- induced insulin resistance, psoriasis, androgenetic alopecia, skin tags, skin cancer, and acne inversa.

Question 7

Describe the ocular effects of MetS

Answer 7

Nondiabetic retinopathy, age related cataract-nuclear, cortical, posterior subcapsular; central retinal artery occlusion, primary open angle glaucoma, oculomotor nerve palsy, and lower lid entropion.

Question 8

Describe the sleep effects of MetS

Answer 8

Obstructive sleep apnea (OSA).

Question 9

Describe the reproductive effects of MetS

Answer 9

Hypogonadism, polycystic ovarian syndrome (PCOS), and erectile dysfunction.

Question 10

Describe the cancers associated with MetS

Answer 10

Breast, pancreas, and prostrate

Question 11

How much of the variety of insulin action to do being overweight (in a percentage)

Answer 11

25/35%

Question 12

Describe the pathophysiological process of atherosclerosis

Answer 12

1) Increased LDL deposits in the tunica intima and they become oxidised which in turn activates endothelial cells
2) Adhesion of blood leukocytes (monocytes and t-helper cells) to activated endothelium
3) Monocytes and t-helper cells move to tunica intima
4) Monocytes takes in the oxidised LDL and become foam cells
5) Foam cells promote migration of SMC from tunica media to intima and smooth muscle cell (SMC) proliferation
6) Increased SMC proliferation causes increased heightened synthesis of collagen
7) Foam cells die releasing lipid contents (this is the plaque)
8) Thrombosis, plaque ruptures, blood coagulation, thrombus and causes there to be an impeded blood flow

Question 13

Describe the normal regulatory function of endothelial cells

Answer 13

Vasodilation, thrombolysis, platelet disaggregation, antiproliferation and lipolysis

Question 14

Describe the abnormal regulatory function of endothelial

Answer 14

Vasocontriction, thrombosis, adhesion molecules, growth fators and inflammation

Question 15

Discuss the metabolic abnormalities that characterize diabetes and their effect on blood vessels

Answer 15

Three main aspects to it all:
1) Hyperglycaemia
2) Free fatty acids 
3) Insulin resistance
These come together to have a large impact on the structure and function. 

Firstly, there is an increase in oxidative stress, disturbance of intracellular signal transduction (such as PKC activation) and activation of RAGE.

This causes a decreased availability of NO, increased endothelin-1 (causing vasoconstriction), increased transcription factors (inflammation) and increasing production of prothrombotic factors (such as TF and plasminogen activator inhibitor-1)

Question 16

What can obesity cause in arteries, liver and pancreas

Answer 16

Artery: Atherosclerosis
Liver: Liver steatosis
Pancreas: Beta-cell degeneration

Question 17

What diseases in the brain can atherosclerosis

Answer 17

Stroke and dementia

Question 18

Describe the non-amyloidogenic pathway

Answer 18

1) Amyloid precursor protein (APP) is a transmembrane protein with a beta-amyloid segment that, when processed, can aggregate and form amyloid beta plaques (a hallmark of alzheimers)
2) In the non-amyloidogenic pathway APP is first cleaved by an alpha-secretase
3) This results in soluble APP fragment alpha (sAPPalpha) and C83 (still in the membrane)
4) C83 is cleaved by gamma secretase resulting in APP intracellular cytoplasmic domain (AICD) and soluable peptide P3

Question 19

Describe the amyloidogenic pathway

Answer 19

1) In the amyloidogenic pathway beta-secretase cleaves APP
2) This is split into s-APPbeta and C99 (transmembrane segment)
3) C99 is cleaved by gamma-secretase creating AICD and AB segment
4) AB segments that are 42 amino acids long (AB42) aggregate into plaques and induce toxicity