The Cafe Of The Crash Dieter Flashcards
What are Lipoproteins?
The lipid components of lipoproteins are not soluble in water; however, because of their detergent-like (amphipathic) properties, apolipoproteins and other amphipathic molecules (such as phospholipids) can surround the lipids, creating the lipoprotein particle that is itself water-soluble, and can thus be carried through water-based circulation (i.e. blood, lymph).
Five major classes of Lipoprotein
Chylomicrons (CM) Very low density lipoprotein (VLDL) Intermediate density lipoprotein (IDL) Low density lipoprotein (LDL) High density lipoprotein (HDL)
Why is HDL considered ‘protective’?
HDL particles are secreted by the intestine and the liver
• They adsorb cholesterol from cells in the vascular endothelium and recycle it back to the liver as LDL
• Therefore HDL is considered to be protective
The liver produces both the bile acids and … involved in the creation of … for lipid absorption from the gut
The liver produces both the bile acids and cholesterol involved in the creation of micelles for lipid absorption from the gut
NORMAL SERUM LIPID CONCENTRATIONS AND THERAPEUTIC THRESHOLDS - what is normal?
- The normal range for a variable in a particular population is chosen to include values between the 2.5 and 97.5 percentiles, on the assumption that 19 out of 20 of the population are normal
- The implication must also be that those people in the normal range are healthy.
- In the case of cholesterol, which is linked to CHD, the healthy range must be that of a society in which CHD is uncommon.
An optimal serum cholesterol level is
An optimal serum cholesterol level is < 5.0 mmol/L in individuals without cardiovascular disease
Relationship between serum Cholesterol
and CHD risk
The upper limit of normality for fasting serum triglycerides is … mmol/L
The upper limit of normality for fasting serum triglycerides is 1.7 mmol/L
The lower limit of normality for serum HDL-C is … mmol/L in men and 1.2 mmol/L in women
The lower limit of normality for serum HDL-C is 0.9 mmol/L in men and 1.2 mmol/L in women
The lower limit of normality for serum HDL-C is 0.9 mmol/L in men and … mmol/L in women
The lower limit of normality for serum HDL-C is 0.9 mmol/L in men and 1.2 mmol/L in women
The lower limit of normality for serum HDL-C is 0.9 mmol/L in … and 1.2 mmol/L in …
The lower limit of normality for serum HDL-C is 0.9 mmol/L in men and 1.2 mmol/L in women
Primary Dyslipidaemias
Exclude secondary causes of dyslipidaemia first
• Often a family history of early cardiovascular disease
• May be monogenic, or polygenic
• May still respond to lifestyle modification
• May be due to mutations of proteins associated with lipid metabolism
Autosomal dominant disorder of lipid metabolism
– One mutant gene is enough!
• Affects up to 1 in 270 in the UK population • Features:
– Raised blood cholesterol (specifically low density lipoprotein cholesterol)
– Tendon and skin xanthomata (deposits of cholesterol)
What is this condition?
Familial Hypercholesterolaemia (FH)
Familial Hypercholesterolaemia (FH) - what is it?
Autosomal dominant disorder of lipid metabolism
– One mutant gene is enough!
• Affects up to 1 in 270 in the UK population • Features:
– Raised blood cholesterol (specifically low density lipoprotein cholesterol)
– Tendon and skin xanthomata (deposits of cholesterol)
What are the physical signs of familial hypercholesterolemia (HeFH), which result from cholesterol deposited within in specific sites?
Familial hypercholesterolaemia is an autosomal … condition
Familial hypercholesterolaemia is an autosomal dominant condition
The Difficulties of Diagnosing FH?
The Difficulties of Diagnosing FH: Overlapping levels of Cholesterol, particularly if LDL is not measured
Several Genetic Mutations are implicated in FH.
FH is a genetically heterogeneous
• Mutations have been found in at least three genes, which co- segregate with the disease:
APOB
• the protein that binds to the LDL
receptor 9 mutations described
– PCSK9
• a protein involved in receptor degradation 6 mutations described
– LDLR
• Over 1000 mutations spread throughout gene described
Secondary Dyslipidaemias - types?
Hypertriglyceridaemia , Hypercholesterolaemia
Hypertriglyceridaemia - caused by … (6)
- Obesity • Diabetes mellitus • XS alcohol • Renal failure • Gout • Drug treatment (thiazides, beta blockers, retinoic acid derivatives, oestrogen therapy)
Hypercholesterolaemia - caused by what? (5)
- Hypothyroidism • Nephrotic syndrome • High saturated fat diet • Cholestatic liver disease • Anorexia nervosa
Traditional definition of obesity
BMI = weight (kg) / height (squared) (m squared) Healthy = 18.5 - 24.9 Overweight = 25.9 - 29.9 Obese class I = 30.0 - 34.9 Obese class II = 35.0 - 39.9 Obese class III = >40.0
Intra-abdominal (visceral) fat
High visceral fat increases … risk
High visceral fat increases cardiovascular risk
What is the Metabolic Syndrome?
Clinical identification of the metabolic syndrome according to IDF criteria
Waist circumference
– Men (Europid) > 94 cm (> 90 in S Asians) – Women (Europid) > 80 cm (> 80 in S Asians) Plus any two of:
• Fasting Serum Triglycerides 1.7 mmol/L or treatment
• Serum HDL-cholesterol
– Men < 1.03 mmol/L
– Women < 1.29 mmol/L
• Blood pressure > 130/85 mm Hg or treatment
• Fasting glucose > 5.6 mmol/L or diagnosis of DM
Visceral obesity/ectopic fat - what effects does it have on the body?
Metabolic syndrome overview
Metabolic syndrome is common and becoming more common
• Central obesity and insulin resistance are important features
• Its definition is gender, age and ethnicity dependent
• Its features are associated with a very high risk of diabetes mellitus and CHD
• Weight reduction and exercise are key aspects of its management
CHD: A multi-factorial disease
Q Risk 2 Score
Drug Treatment Options for the dyslipidaemias
