metabolic disorders 4 Flashcards
Describe Familial Hypercholesterolaemia (FH)
FH is an autosomal dominant disease characterized by high levels of total serum cholesterol, particularly in homozygotes (>900 mg/dL). It is associated with high LDL levels and normal HDL levels.
Do individuals with Homozygous FH have a high risk of coronary heart disease (CHD
Yes, individuals with Homozygous FH have a high mortality rate from CHD the age of 30, with an increased risk of myocardial infarction () at 56 years of age.
Define LDLR in the context of FH
LDLR stands for low-density lipoprotein receptor and is the most common defect associated with Familial Hypercholesterolaemia.
How does Hypercholesterolaemia impact the risk of CHD/AMI in individuals without a genetic defect?
Hypercholesterolaemia is a major risk factor for CHD/AMI even in individuals without a genetic defect, emphasizing the importance of cholesterol management.
Describe the reasons why screening for FH is not recommended by the UK National Screening Committee
The lack of evidence on the effectiveness of childhood screening, uncertainty about reducing illness or death from FH, unanswered questions about universal screening, and the general lack of awareness among GPs are key reasons for not recommending screening.
Describe atherosclerosis.
A disease of large/medium arteries characterized by the accumulation of LDL in the vessel wall, leading to the formation of ‘foam cells’ and plaques with a fibrous cap, which can rupture and cause thrombosis.
What is the role of LDL in atherosclerosis?
LDL accumulates in the vessel wall, where it is taken up by macrophages to form ‘foam cells’ and contributes to the formation of plaques.
Define xanthoma.
A condition characterized by the accumulation of cholesterol in tissues, leading to yellowish nodules in areas such as the skin of hands, elbows, knees, and around the cornea of the eye.
How did the discovery of the LDL receptor impact our understanding of familial hypercholesterolemia (FH)?
The discovery of the LDL receptor by Goldstein and Brown in the 1970s revealed that mutations in the LDL receptor were responsible for FH, as cells from patients with FH could not take up LDL, leading to increased plasma LDL/cholesterol levels.
Describe the role of LDLR in cholesterol metabolism.
LDLR is a major regulator of circulating LDL/cholesterol levels, as its loss leads to increased plasma LDL/cholesterol levels due to reduced uptake of LDL by the liver and peripheral tissues.
What are the main types of lipoprotein particles involved in cholesterol and triglyceride transport?
The main types are chylomicrons, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL).
How does LDL contribute to cholesterol transport in the body?
LDL plays a role in cholesterol transport by carrying cholesterol esters to various tissues, where it is taken up by cells through the LDL receptor.
Describe the composition and function of low-density lipoprotein (LDL).
LDL consists of a single apoprotein component, ApoB-100, which acts as the ligand for the LDL receptor and is responsible for transporting cholesterol to tissues by interacting with the LDLR in the liver and peripheral tissues.
Describe the role of LDL in the formation of foam cells in the vessel wall.
LDL leads to an increase in circulating LDL, which further increases levels in the vessel wall and promotes foam cell formation.
What is the major drug therapy for familial hypercholesterolemia?
Statin drugs, specifically HMG-CoA reductase inhibitors, are the major drug therapy for familial hypercholesterolemia.
Define the term ‘reverse cholesterol transport’ in lipoprotein metabolism.
Reverse cholesterol transport refers to the process where HDL transports cholesterol back to the liver from peripheral tissues.
