Lipids and Cardiovascular Diseases Flashcards
1
Q
Types of lipid
A
- fatty acids (saturated or unsaturated)
- glycerides
- complex lipids
- nonglycerides (sphingolipids, steroids)
2
Q
Steroid class of lipids
A
- Cholesterol
- Cell membranes, female sex hormones, vitamin D, bile salt precursor and adrenocortical hormones
- Linkage to CVD
- Bile Salts
- Important in lipid digestion
3
Q
Lipoproteins
A
- complex lipid
- Molecular complexes found in blood plasma
- contain: neutral lipid core of cholesterol esters and/or TAG
- Surrounded by layer of: phospholipid, cholesterol, protein
4
Q
Major classes of lipoproteins
A
- Chylomicrons: very large and very low density, transport intestine - adipose
- VLDL: made in liver, transport lipids to tissues
- LDL: carry cholesterol to tissues
- HDL: good cholesterol, made in liver, scavenge excess cholesterol esters
5
Q
Global atlas of CVD
A
- CVDs account for >17 million deaths globally each year
- correlates to 30% of all deaths worldwide
- mortality from CVD reveals 80% occur in low-income and middle-income countries,
- figure is expected to grow to 23.6 million by 2030
- Ischaemic heart disease alone; 7 million deaths in 2010, 35% increase since 1990.2
- Coronary heart disease (CHD) is largest contributor to CVD
6
Q
Obesity driven Lipid based abnormalities
A
- Imbalance in food intake, life style and genetic factors lead to Obesity
- Obesity aggravates: dyslipidaemia, hypertension and insulin resistance
7
Q
Healthy total cholesterol level
A
- below 200 mg/dL (5.2 mmol/L)
8
Q
Healthy LDL cholesterol
A
- below 130 mg/dL (3.4 mmol/L)
9
Q
Healthy HDL cholesterol
A
- above 40 mg/dL (1 mmol/L) in men
- above 50 mg/dL (1.3 mmol/L) in women
10
Q
Laboratory analysis
A
- Fasting lipid profile: Total cholesterol, HDL, and triglycerides are measured
- LDL level can be measured directly using assays or estimated using Friedewald formula
- [LDL-chol] = [Total chol] - [HDL-chol] - ([TG]/2.2) where all concentrations are given in mmol/L
- if calculated using all concentrations in mg/dL then the equation is [LDL-chol] = [Total chol] - [HDL-chol] - ([TG]/5)
11
Q
Structure of lipoproteins
A
- free cholesterol
- peripheral apoprotein (A, C or E)
- phospholipid
- cholesterol ester
- triglyceride
- integral apoprotein
12
Q
Apolipoprotein B (apo B)
A
- proteincomponent of lipoproteins, complexes that transport lipids throughout the bloodstream
- two forms of apo B: apo B-100 (made by liver) and apo B-48 (made in intestines)
- provide structural support to lipoproteins and shield the water-repellent (hydrophobic) lipids at their centre
13
Q
Role of ApoB
A
- Apo B-48: integral part of the structure of chylomicrons, large lipoproteins responsible for initial transport of dietary lipids from intestines to liver
- In the liver, body repackages lipids and combines them with apo B-100 to form triglyceride-rich VLDL
14
Q
Formation of LDL ApoB
A
- In bloodstream, lipoprotein lipase (LPL) removes triglycerides from VLDL to create IDL and then, LDL
- Lab tests for apo B typically measure only apo B-100 but are often reported as simply apo B
- Apo B-100 concentrations tend to mirror the concentration of LDL-C
15
Q
Glucocorticoid suppressive
Hypo-aldosteronism
A
- autosomal dominant
- mutation causes fusing of regulatory sequence of steroid 11b hydroxylase with aldosterone synthesis
16
Q
Liddle Syndrome
A
- autosomal dominant
- activating mutant in distal convoluted tubules sodium transporter
17
Q
Gordon Syndrome
A
- autosomal recessive
- mutation leads to increased distal renal tubule chloride reabsorption
18
Q
Steroid 11β-hydroxylase deficiency
A
- autosomal recessive
- leads to plasma 11-deoxycortisol and 11-deoxycorticosterone increase
19
Q
Steroid 17α- hydroxylase deficiency
A
- autosomal recessive
- leads to plasma 11-deoxycortisol and 11-corticosterone increase
20
Q
Xanthelasmas
A
- type of xanthoma; raised, yellowish macules that typically appear around the medial canthus, can extend to the eyelids or skin immediately below the eye
- occur in patients with FH, familial defective apoB100, or
dysbetalipoproteinemia - occasionally occur in patients with normal cholesterol levels
- regress w/cholesterol lowering and may be treated with cholesterol-lowering drugs
21
Q
Dysbetalipoproteinemia
A
- rare familial dyslipidemia characterized by approx. equally elevated serum cholesterol and triglyceride levels due to accumulated remnant lipoproteins in apolipoprotein E2/E2 homozygotes
- associated with increased risk for premature CVD
22
Q
Lipemia retinalis
A
- lipemic blood causes opalescence of retinal arterioles
- can be observed during funduscopic examination
- typically seen only when the triglyceride levels are 22.6 mmol/L (2000 mg/dL) or higher
23
Q
Tendon xanthomas
A
- nodular deposits of cholesterol that accumulate in tissue macrophages in the Achilles and other tendons, including the extensor tendons in the hands, knees, and elbows
- often present in patients with FH or familial defective apoB100 and sometimes in those with dysbetalipoproteinemia
24
Q
Tuberous or tuboeruptive xanthomas
A
- Develop in areas such as the elbows and knees
- range from pea-sized to lemon-sized and can be seen in dysbetalipoproteinemia and FH
- Palmar xanthomas: found in the palmar and digital creases of the hands. Almost pathognomonic for high plasma levels of β-VLDL and dysbetalipoproteinemia.
- caused by accumulation of triglyceride in dermal histiocytes and occur when the plasma triglyceride level is 11.3 to 22.6 mmol/L (1000 to 2000 mg/dL) or higher
- can disappear rapidly with lowering of the plasma triglyceride concentration
25
Q
Thrombosis
A
- healthy human heart
- plaque with fibrous cap
- cap ruptures
- blood clot forms, blocking artery
- dead heart tissue qt blockage site
- coronary thrombosis: formation of a blood clot inside blood vessel of the heart, restrict blood flow within the heart, leading to heart tissue damage, or heart attack
26
Q
Obesity-Induced Changes in Adipose Tissue and Impact on CVD
A
- Functional adipose tissue, found in lean organisms, express anti-inflammatory adipokines that protect against CVD
- excess adipose tissue expansion promotes dysfunction, leading to the expression of proinflammatory adipokines that promote CVD
27
Q
Insulin resistance
A
- adipokine imbalance can affect function of metabolically important tissues and the microvasculature, promoting insulin resistance and indirectly contributing to CVD
28
Q
Wider Impact of elevated Lipid Levels
A
- CVD
- sensory neuropathy
- erectile dysfunction
- renal impairment
- cognition
29
Q
Common Lipid Disorders that Lead to Atherosclerosis
A
- Dyslipidemia: abnormal lipoprotein levels (LDL and HDL) in association with an increased risk of CVD
- Hyperlipidemia: elevated blood lipid levels (total cholesterol, LDL, triglycerides)
- Hypercholesterolemia: elevated total cholesterol> 200 mg/dL
- Hypertriglyceridemia: elevated triglyceride levels
- Hyperlipoproteinemia: elevated levels of a certain lipoprotein
30
Q
Acute Myocardial Infarction (AMI)
A
- If diagnosed quickly and the patient sent to a CCU then appropriate care can be initiated
- trouble its too expensive for everyone who comes in with chest pain, since it could be simply heart-burn
- WHO classification relies on any 2 of the following:-
- Severe chest pain that lasts for more than 30 mins
- characteristic ECG changes
- and finally a characteristic rise and fall in cardiac enzymes, now changes in Cardiac Markers
31
Q
Aspartate Transaminase
A
- Poor clinical specificity
- Ref. range: male <56 IU/L female <45 IU/L
- detect an increase in AST it could be from the heart, liver or skeletal muscle, and although clinical symptoms should help determine the source, we can’t be 100% sure
32
Q
Factors into increased AST
A
- haemolysis: RBC’s have slightly more AST, levels are only raised slightly
- post partum, levels can be increased due to trauma of birth itself
- cholestasis
- liver metastases
- post op
- haemolytic disease
- viral hepatitis
- toxic liver necrosis
- circulatory failure
33
Q
Lactate dehydrogenase
A
- Ref. range: 90-230 IU/L
- Increased LD: viral hepatitis, malignancy, pulmonary embolism, shock
leukaemia, haemolysed samples, AMI
34
Q
Creatine kinase
A
- very important for energy storage and production, muscle and brain have very high levels
- catalyses reversible transfer of phosphate between ATP and creatine to produce creatine phosphate and ADP
- Ref. Range: males 40-165 IU/L, females 40-150 IU/L
35
Q
Factors into increased CK
A
- Haemolysed sample
- IM injections
- hypothyroidism
- neonates
- post -partum
- muscular dystropy
- surgery/trauma
- AMI
36
Q
Measuring CK-MB
A
- Immuno assay
- Immobilising through binding only the M subunit
- Eliminate CK containing B subunit
- Differential binding of the antibody with the B subunit
this enables binding only with the B subunit of CK enzyme - results in only measuring the cardiac specific CK-MB isoform
37
Q
Relative index of CK-MB and AMI protocol
A
- Relative Index = CK-MB Mass / Total CK x100
- If total CK is high and CK-MB is <5% of total = not cardiac
- If total CK is high and CK-MB is >15% = cardiac
38
Q
New markers for AMI
A
- Myoglobin (small, released at 30mins)
- CK-MB isoforms (lysine – not hydrolysed)
- Troponins
39
Q
Tropomyosin
A
- 2 strands of a thin protein which are wrapped around each other like a helix to give them strength
- Along the chains are globular proteins called actin
40
Q
Troponin
A
- along the thin tropomyosin filaments is a cluster of 3 proteins
- first is troponin-I or inhibitor complex
- This is pulled out of the way by troponin-C in the presence of calcium (this is increased when a nerve impulse to contract is received)
- With inhibitor out of the way the T protein (which is the 3rd in the complex) can interact with the other muscle protein fibres
41
Q
Myosin
A
- Each bundle is made up of a long protein strand with a sticky head
- There are hundreds or thousands of these in each myosin bundle
- troponin-T can interact with these stick heads and forms a complex
42
Q
Troponin and myosin interaction
A
- signal to contract is received, the calcium levels go up and allows the troponin-T to alter its structure
- causes it to stretch and interact with another myosin head further along the filament
- ATP used in this process is sufficient to pull the troponin back to its original position and also pulls the mysoin fibre with it
43
Q
Troponins as cardiac markers
A
- Troponin-C: same in all muscle types, not specific
- cTnT: levels rise within 3-4 hrs, peak at 10-12 hrs, 10-14 days to return to normal, Some renal interference
- cTnI: considered more cardiac specific, levels rise within 3-6 hour, peak at 14-20 hours, return to normal after 5-6 days
44
Q
Diet (management of CVD risk)
A
- Professional advice to compose suitable diet
- Aims: weight reduction, reducing blood pressure, appropriate lipid and glycaemic control
- Increase intake of fruit and veg, wholegrain cereals and bread, lean meat and fish (omega-3 oils)
- Replace saturated fats (animal fats) with complex carbs, monosaturated and polyunsaturated fats (vegetable and seafood)
45
Q
Increase physical exercise (management of CVD risk)
A
- Should be encouraged in ALL age groups and all patients
- Healthy individuals: 30-45 minutes, 4-5 times a week at 60-75% of average maximum heart rate
- High risk/establish CVD patients: exercise regime based on comprehensive clinical assessment and judgement
46
Q
Blood pressure (management of CVD risk)
A
- Risk of CVD increases as BP rises from normal
- Decision to treat depends on assessment of total cardiovascular risk, evidence of target organ damage as well as actual BP
47
Q
Behavioural risk factors (management of CVD risk)
A
- Diet, smoking, sedentary lifestyle
- Very difficult to alter; socioeconomic factors, stressful lifestyles, lack of social support, negative emotions
48
Q
Expert consultations (management of CVD risk)
A
- Ensure patients understand relationships between behaviour, health and disease
- Gain commitments to behavioural change
- Involve patients in identifying and selecting risk factors to change
- Design of lifestyle modification plans; Diet, exercise
- Monitor progress through follow ups
- Involve appropriate healthcare staff wherever possible
