Hyperlipidaemia and therapeutic approaches Flashcards

1
Q

hyperlipidaemia

A

is the term used to denote raised serum levels of one or more of total cholesterol (Tchol), low density lipoprotein cholesterol (LDL-C), Triglycerides (TGs) or both Tchol and TG (combined Hyperlipidaemia)

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2
Q

dislipidaemia

A

is a wider term that also includes low levels of high density lipoprotein cholesterol (HDL-C)

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3
Q

chylomicrons

A

transport TGs/cholesterol from intestine indirectly (via lymph) to the blood.

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4
Q

Veyr ow density lipoproteins VLDL

A

(liver synthesised) have a high TG content. The capillary enzyme lipoprotein lipase converts the VLDLs TGs to free fatty acids, used for either energy [in muscle or liver] or storage [in adipose tissue].

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5
Q

low density lipoproteins LDL

A

contain a high cholesterol content.

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6
Q

high density lipoproteins HDL

A

absorb and transport peripherally-mobilised cholesterol from cell breakdown to the liver (protective).

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7
Q

what does the body use lipids for

A
Energy storage
Intracellular signalling 
Extracellular mediators/signalling
(lipoprotein)
Base for steroid hormone synthesis
Vitamin D synthesis
Cell membranes
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8
Q

excess carbs converted to what

A

triglycerides and transported to fat cells

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9
Q

main site of sytnhteis of cholesterol

A

liver

higher TAG( triglycerides) lower cholesterol

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10
Q

choylomicorns sourced where

A

intestines

Dietary Lipids inc chol and FFA emulsified by bile acids & transported within chylomicrons to the liver
Then circulated as chol and triglycerides to disuse inVLDL
Endothelial lipoprotein lipase (LPL) liberate FFA in adipose and muscle for storage or metabolism
Resulting LDL return to hepatocytes via LDL receptors or taken up by LDL receptors in extrahepatic tissue where they are oxidised and contribute to atherogenesis
HDL pool derived from chylomicrons from action of LPL and reverse cholesterol pathways return HDL to liver vis HDL receptors

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11
Q

Hypercholesterolemia

A

Elevated LDL-C

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12
Q

Dyslipidemia

A

Includes elevated triglycerides and low HDL-C

serum total cholesterol, LDL-C, triglycerides, apolipoprotein B, or lipoprotein(a) concentration >90th percentile

HDL-C or apolipoprotein A-I concentrations <10th percentile

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13
Q

why is dyslipidemia important

A

Promotes atherosclerosis-cholesterol plaques
Ischemic heart disease
Cerebrovascular disease
Peripheral vascular disease

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14
Q

LDL-C normal range

A

1.8-2.6 -3.3

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15
Q

total cholesterol desirable range

A

under 5.2 optimal under 4.4

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16
Q

triglycerides desirable range

A

1.1-1.7

17
Q

HDL-C range

A

under 1

18
Q

how do we diagnose high cholesterol

A

rings around eyes

Xanthomas are lesions on the skin containing cholesterol and fats. They are often associated with inherited disorders of lipid metabolism (inherited problems with the way that fats are broken down and used). Xanthomas are raised, waxy-appearing, frequently yellowish-colored skin lesions.

19
Q

primary - eugenics as single gene

Secondary causes of dyslipidemia

A
Diet
Obesity
Diabetes (T1 and T2)
Hypothyroidism
Alcohol dependency
CKD
Nephrotic syndrome
Drugs (glucocorticoids, anti-retrovirals, oral oestrogens, atypical antipsychotics)
Cushings
20
Q

How do we treat hyperlipidemia?

A

lifestyle - reduce total and saturated fats , weigh loss, exercise , plant sterols
this all lowers LDL-C and increases HDL-C

also use statins

21
Q

what are statins

A

HMG-CoA reductase inhibitors (3-hydroxy-3-methylglutaryl coenzyme A)
Important enzyme in cholesterol synthesis

↑ LDL receptors →↑LDL Clearance
Ultimately eliminated in bile (significant re-uptake)

Dose and preparation dependent LDL-C reductions of 20-50%

22
Q

PCSK9 inhibitors

A

Proprotein convertase subtilisin/kexin type 9 binds LDL receptors for degradation in hepatic cell lysosomes

Key determinant of LDL-c concentration

Blocking PCSK9 with a monoclonal antibody allows the LDL receptor to be recycled back to the cell membrane surface to continue LDL uptake from blood

Examples Evolocumab, Alirocumab (specialist rx only)

23
Q

Ezetimibe

A

add on to statin therapy

24
Q

Colestyramine and Colesevelam

A

Bile acid sequestrants

Modest reductions in cholesterol 10-24%

GI side effects limit use (nausea, cramps, bloating, diarrhoea, constipation)

Ineffective in FH

25
Q

fibrates

A

PPARα agonist
Increased FFA uptake by liver
Increased HDL-C

Still in use, though not commonly

26
Q

nicotinic acid

A

B vitamin
Effective
Poor SE profile (flushing due to prostaglandin induction, ) limited use
Rarely used

27
Q

what can you eat to protect

A

omega 3

28
Q

what Is hyperlipidemia?

different types

causes plaques

A

Hyperlipidemia means your blood has too many lipids (or fats), such as cholesterol and triglycerides

29
Q

Hyperlipidaemia is/are most characteristically caused by

A

corticosteroids

30
Q

Familial hypertriglyceridaemia
eruptive xanthomas
Familial hypercholesterolaemia
tendon xanthoma

A

Characteristic xanthomata seen in hyperlipidaemia:

Palmar xanthoma
remnant hyperlipidaemia
may less commonly be seen in familial hypercholesterolaemia

Eruptive xanthoma are due to high triglyceride levels and present as multiple red/yellow vesicles on the extensor surfaces (e.g. elbows, knees)

Causes of eruptive xanthoma
familial hypertriglyceridaemia
lipoprotein lipase deficiency

Tendon xanthoma, tuberous xanthoma, xanthelasma
familial hypercholesterolaemia
remnant hyperlipidaemia

Xanthelasma

Xanthelasma are yellowish papules and plaques caused by localized accumulation of lipid deposits commonly seen on the eyelid. They are also seen in patients without lipid abnormalities.

Management of xanthelasma, options include:
surgical excision
topical trichloroacetic acid
laser therapy
electrodesiccation