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
There are two major pathways for lipid metabolism (… and …)
There are two major pathways for lipid metabolism (endogenous and exogenous)
… are complexes of apoproteins and other lipids that allow the transport of lipids
Lipoproteins are complexes of apoproteins and other lipids that allow the transport of lipids
The dyslipidaemias may be … or …
The dyslipidaemias may be primary or secondary
Why are dyslipidaemias important?
They are important because they can increase the risk of cardiovascular disease
…. hypercholesterolaemia is associated with early CVD if untreated
Familial hypercholesterolaemia is associated with early CVD if untreated
Metabolic syndrome is characterised by …. resistance, …, central obesity and …
Metabolic syndrome is characterised by insulin resistance, hypertension, central obesity and dyslipidaemia
Metabolic syndrome is characterised by insulin …, hypertension, … obesity and …
Metabolic syndrome is characterised by insulin resistance, hypertension, central obesity and dyslipidaemia
…. are effective at reducing LDL-Cholesterol and CVD risk
Statins are effective at reducing LDL-Cholesterol and CVD risk
Appetite-inducing hormone
ghrelin
appetite-suppressing hormones (3)
insulin, leptin, PYY
Long term appetite regulators?
leptin and insulin
Short-Term Appetite Regulators?
ghrelin, PYY, CCK
what stimulates PYY release?
food presence in SI
also CCK and bile
When is CCK released?
When chyme enters the small intestines
Where is GLP-1 secreted from?
L cells of the small intestine
along with PYY and GIP
Action of GLP-1
enhances insulin secretion in a glucose dependent manner, decreasing blood sugar
When is ghrelin released?
when the stomach is empty
Where is PYY produced?
L cells in small intestine
PYY
Where is PYY produced?
AGRP
A small protein secreted by the arcuate nucleus that initiates eating and blocks melanocortin receptors
drugs causing weight loss (4)
SGLT2 inhibitors, metformin, CNS stimulants, orlistat
6 drugs causing weight gain
antipsychotics antidepressants z drugs steroids insulin pregabalin
how does obesity affect gut hormones?
causes dysregulation, impaired secretion, ghrelin doesn’t reduce after a meal, leptin resistance
Who qualifies for weight loss surgery?
BMI over 40
BMI over 35 but severe related co-morbidity
adjustable gastric banding
adjustable gastric banding
a restrictive procedure in which the opening from the esophagus to the stomach is reduced by a hollow gastric band
Sleeve Gastrectomy (SG)
surgical removal of large portion of stomach
gastric bypass surgery
limits food intake by reducing the capacity of the stomach
Roux-en-Y gastric bypass
surgery which decreases path of food through intestine so reduced absorption of nutrients
What does CCK do?
Gallbladder contraction, bile release
CCK secretion
from the I cells of the duodenal and jejunal mucosa
triggered by acid
Ghrelin is secreted by
.. cells in stomach
Ghrelin is secreted by
A cells in stomach
GIP is secreted by
. cells (duodenum, jejunum)
GIP is secreted by K cells (duodenum, jejunum)
Apo B-48
Found only in chylomicrons
Apo E
mediates chylomicron remnant uptake
where is hepatic lipase found?
liver and adrenal glands
Where is lipoprotein lipase found?
adipose tissue and skeletal muscle
what does liver do in exogenous lipid pathway? (3)
makes bile acid and cholesterol
involved in micelle creation
takes up chylomicron remnants
3 treatment options for dyslipidaemia
statins
cholesterol absorption inhibitors
PCSK inhibitors
QRISK3 score
3 treatment options for dyslipidaemia
statins - mechanism of action?
Inhibit HMG-CoA reductase, which is used by the liver to produce cholesterol
Lower the rate of cholesterol production
