Brainscape's Knowledge GenomeTM

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


See full index

Disease of Major Organs > Lipid metabolism > Flashcards

Lipid metabolism Flashcards

1
Q

What are lipids?

A 
Any of a class of organic compounds that are fatty acids or their derivatives and are insoluble in water but soluble in organic solvents
- Fatty acids, cholesterol, triglycerides, phospholipids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the circulating lipids?

A

carried by apolipoproteins to be transported to tissue for energy, steroid hormone production and bile acid formation.

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

Function of cholesterol

A

important functions in the cell membrane, bile acid synthesis, steroidogenesis (adrenal and gonadal), vit D precursor

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

How is cholesterol synthesised?

A

Primarily: de novo synthesis from acetate in the liver

- rate limited by HMG CoA reductase

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

Formation of triglycerides

A

Esterification of glycerol with 3 long chain fatty acids - requires transport from sites of synthesis and absorption to sites of utilisation.

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

Structure of phospholipids

A

Fatty acyl group esterified to an alcohol, which are important to cell membranes

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

What makes lipid transport possible?

A

Lipoproteins act as carriers of lipids to transport it in the body.

  • core contains fat and cholesterol
  • outside have apolipoproteins which aid in lipoprotein accessing specific sites for delivery
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What form is cholesterol transported as?

A

Esters since it is the protective form for storage and transportation

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

What are the 5 different lipoprotein classes?

A 
VLDL
IDL
LDL
HDL
Chylomicrons
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What 3 functions does the apolipoprotein have?

A

structural, ligand for receptors and act as a cofactor

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

What is the exogenous pathway of triglyceride metabolism?

A
  • starts with absorption of dietary lipids at enterocyte, cholesterol and triglycerides
  • ApoB48 is synthesied by enterocytes - causes synthesis of chylomicron in ER
  • ApoB48 combine with chylomicron, cholesterol, TG
  • ApoB48 chylomicron obtains more apolipoproteins from HDL.
  • The obtained ApoC-II allow chylomicron interaction with lipoprotein lipase to allow hydrolysis of triglycerides into FFA to enter adipose or muscle
  • ApoC-II lost as chylomicron decreases in size
  • Remnant chylomicron B48B enters the liver where more TG is removed by HL and LPL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

In the exogenous pathway of TG what does the liver do?

A

It can be utilized for the formation of VLDL, bile acids, or secreted back to the intestine via secretion into the bile

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the endogenous lipoprotein pathway?

A
  • VLDL is formed from triglyceride synthesis in the liver either de novo or by the re-esterification of FFAs. TG and cholesterol esters are transferred to ER to the newly synthesised ApoB-100
  • Once released from liver it will obtain ApoC-II from HDL.
  • This allows the interaction with LPL for the hydrolysis of triglycerides into FFA entering the adipose and muscle
  • ApoC-II is lost as the lipoprotein decrease in size
  • Remnant B100 E particle aka IDL is taken up via the liver. As ApoE binds to LDL and LRP receptors
  • Further hydrolysis hy hepatic lipase to form LDL
  • LDL contains cholesterol esters and ApoB100 acting as a ligand for LDL receptors in peripheral tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What occurs as the LDL binds to the LDL receptor

A

The receptor acts to mediate endocytosis of cholesterol rich LDL in the liver and peripheral tissue. Once internalised the receptor will dissociate from the ligand and recycles back to the cell surface. Rapid recycling provides an efficient mechanism of cholesterol delivery to tissues.

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

What lab investigations are available to examine the exo-and endogenous pathways?

A

The receptor acts to mediate endocytosis of cholesterol rich LDL in the liver and peripheral tissue. Once internalised the receptor will dissociate from the ligand and recycles back to the cell surface. Rapid recycling provides an efficient mechanism of cholesterol delivery to tissues.

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

Nascent HDL formation

A

Occurs in the liver and intestine - forming a bilayer of PLs, ApoAI and ApoAII.

  • Free cholesterol is acquired from tissue and lipoprotein remnants. Allowing maturaiton of HDL
  • Cholesterol is esterified by lecithin-cholesterol acyl transferase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What function does the reverse cholesterol transport serve?

A

It acts to redistribute cholesterol from cells which are increasing in cholesterol without a function to catabolise it into e.g. hormones.
- Excess cholesterol will be sent to the liver where it will redistribute it again or remove it using the gallbladder

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe how reverse cholesterol transport works

A
  • Increase in cholesterol causes the cell to increase ABCA-1 expression resulting in enhanced efflux
  • Efflux to HDL
  • cholesterol ester transfer protein mediates the transfer of cholesterol esters to LDL & VLDL
  • Alternatively, once cholesterol transfer into HDL it can interact with the liver directly using hepatic SR-BI receptors (scavenger receptor B1) to induce the uptake of cholesterol.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are some general complications from raised lipoproteins

A

Raised LDL/reduced HDL = atheroma (CHD)

Increased chylomicrons/VLDL = pancreatitis

20
Q

What are secondary dyslipidaemias?

A

Caused by unhealthy lifestyle or acquried medical conditions. Accounts for 30-40% of all dyslipidaemias.

21
Q

Treatment of dyslipidaemia with example

A

Treat the underlying cause, diseae or drug. E.g. hyperlipidaemia due to hypothyroidism treated with statin can cause myopathy and serious adverse effects, e.g. rhabdomyolysis

22
Q

What tests are necessary for dyslipidaemia?

A

Laboratory testing by differential diagnosis:

  • U&E (Na, K, urea, creatinine, eGFR): Exclude renal failure
  • Liver profile (total protein, albumin, ALP, ALT, GGT): exclude cholestasis
  • TFTs: exclude hypothyroidism
  • HbA1cs: exclude diabetes
  • Urine protein: exclude nephrotic syndrome
23
Q

What criteria is used to class lipid disorders?

A

The fredricksons/WHO classification

- Provides a phenotype based on lipoprotein, cholesterol levels, triglyceride levels and associated clinical disorders.

24
Q

What tests are available to investigate lipid disorders?

A

Total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, risk ratio (TC:HDL). Further testing includes direct LDL, ApoB, lipoprotein A, ApoE genotype, FH genotype.

25
Q

Define severe hypertriglyceridaemia

A

Condition is characterised by serum triglycerides often>10mmol/L

26
Q

Features of severe hypertriglyceridaemia

A

Susceptible to pancreatitis

Physical features include eruptive xanthomata, hepatosplenomegaly due to fat accumulation, lipaemia retinalis

27
Q

Causes of severe hypertriglyceridaemia

A

Primary cause - familial chylomicronaemia, familial dysbetalipoproteinaemia

Secondary - alcohol and diabetes

28
Q

What causes Familial dysbetalipoproteinaemia and what are its characteristics?

A

Caused by mutation to ApoE2 gene

- Characterised by increased circulating chylomicron remnants/IDL and increase in serum cholesterol and TG

29
Q

Risks to Familial dysbetalipoproteinaemia

A

Accelerated atherosclerosis

30
Q

How can cholesterol and ApoB be used to diagnose Familial dysbetalipoproteinaemia?

A

If the patient presents with low ApoB conc and apoB/total cholesterol ratio of <0.15g/mmol then it should raise some suspicion

31
Q

What is familial hypercholesterolaemia?

A

This is a dominant autosomal condition associated with serum cholesterol of up to 15mmol/L
- has a large assoicated morbidity

32
Q

Symptoms of familial hypercholesterolaemia?

A

Corneal arcus

Tendon Xanthanoma

33
Q

How is familial hypercholesterolaemia diagnosed?

A

Using the simon broome diagnostic criteria

34
Q

Match the following (ADULTS)
1. Definite familial hypercholesterolaemia
2. Possible familial hypercholesterolaemia
A. FH is TC>7.5mmol/L
B. LDL-C>4.0mmol/L
C. LDL-C>4.9mmol/L
D. Familial history of MI <50y in 2nd degree or <60y 1st degree relative
E. Tendon xanthoma or evidence in 1st/2nd degree relative
F. FH is TC>6.7mmol/L

A
  1. AorCandE

2. AorCandD

35
Q

What causes familial hypercholesterolaemia?

A 
1000 mutations of the LDL receptor pathway have been recorded as causative.
3 main genes:
- LDLR
- ApoB100
- PCSK-9
36
Q

How is familial hypercholesterolaemia treated ?

A

Medical intervention is using statin, ezetimibe, PCKS9i, aphereiss

37
Q

What is polygenic hypercholesterolaemia?

A

associated with the overproduction of VLDL by liver which is converted to LDL. Phenotype IIa and IIb in criteria.

  • Condition exacerbated by obesity and high fat diets
  • Diagnose by genetic analysis
38
Q

What is familial chylomicronaemia syndrome (fredrickson type I)?

A

An inherited condition disrupting the normal breakdown of fats in the body, causing buildup of fats in the blood.

39
Q

What is familial chylomicronaemia syndrome (fredrickson type I) caused by?

A

180 mutations have been identified.

- Mutations occur in lipoprotein lipase, cofactor deficiency, ApoA5, GPIHBP1, ApoC2 and LMF1

40
Q

Presentations of fredricksons type I?

A

Recurrent episodes of pancreatitis - and eruptive xanthomata, lipaemia retinalis.

41
Q

How is fredricksons type I diagnosed?

A

By raised TC and TG, chylomicronaemia, and an ApoB of <1g/L.

42
Q

How is fredricksons type I treated?

A

Using a low fat diet

43
Q

What is Familial combined hyperlipidaemia – Fredrickson type IIb?

A

Condition associated with increased cholesterol and TG.

- raised VLD and ApoB>1.2g/L

44
Q

Distinct features of fredrickson type IIb for diagnosis?

A
  • Cholesterol 6.5-10mmol/L
  • TG 2.3-6mmol/L
  • Raised VLDL
  • ApoB > 1.2g/L
  • Family history of premature CHD
45
Q

How do you treat fredrickson typeo IIb?

A

Treated using statin, fibrates, together with healthy eating

Disease of Major Organs (14 decks)

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