Week 2 Flashcards
1
Q
What are the three classes of lipids
A
Cholesterol
Triglycerides
Phsopholipids
2
Q
Function of cholesterol
A
Synthesis of bile acids - allowing absorption of fat soluble vitamins.
Precursor for endogenous vit D production
Precursor for steroid hormones
3
Q
5 Examples of steroid hormones
A
Oestrogen
Progesterone
Testosterone
Cortisol
Aldosterone
4
Q
Function of triglycerides
A
used as energy source in tissues
used for energy source in adipose tissues
5
Q
describe the structure of lipoproteins
A
- complex spherical structure
- central core of hydrophobic lipids (triglycerides and cholesterol esters)
- surface layer of polar components (phospholipids, free cholesterol, proteins and the apoplipoproteins)
6
Q
4 types of lipoprotein
A
chylomicron
very low density lipoprotein
low density lipoproteins
high density lipoproteins
7
Q
describe chylomicron
A
synthesised in gut after a meal
main carrier of dietary triglyceride
8
Q
describe VLDLs
A
synthesised in the liver
Main carrier of endogenously produced triglyceride
9
Q
describe LDLs
A
generated from VLDL in the circulation
main carrier of cholesterol
10
Q
describe HDLs
A
return cholesterol from extrahepatic tissues to the liver for excretion
11
Q
Describe the structure of apolipoproteins
A
Amphiphilic compounds
Hydrophobic region interacting with lipid core provides structure
Hydrophilic region interacts with aqueous environment
12
Q
Role of apolipoproteins
A
Guide the formation of lipoproteins
- Act as ligands for lipoprotein receptors
- Serve as activators or inhibitors of enzymes involved in the metabolism of lipoproteins
13
Q
Examples of circulatory CVD
A
Ischaemic heart disease
Myocardial infarction
14
Q
Example of cerebral circulator CVD
A
Stroke
15
Q
Example of peripheral circulatory CVD
A
Peripheral vascular disease
16
Q
Ages for premature onset of CVD
A
Males <55 yo
Females <65 yo
17
Q
Non modifiable risk factors for CVD
A
Sex
Age
Ethnicity
Family History
Comorbidities
18
Q
Modifiable risk factors for CVD
A
Smoking
Hypercholesterolaemia
BP
Diabetes
Body weight
Poor diet
Lack of exercise
19
Q
What individuals are known to be high risk of CVD and so get tested
A
Those already diagnosed
Stage 3+ chronic kidney disease
Diabetics >40 yo or with >20 years of disease
OR evidence of diabetes-related organ damage
Those with familial hypercholesterolaemia
20
Q
how often is assessment of CVD for those not known to be high risk
A
offered every five years in adults >40 years
21
Q
what is the risk calculator used for CVD
A
ASSIGN Risk calculator is validated in scottish population but underestimates risk in
- some ethnic groups
- women with early menopause
- those with atrial fibrillation
22
Q
how is a lipid profile taken
A
Lipid profile provided in lab contains total cholesterol, HDL, LDL, VLDL and triglycerides, but only total C, HDl and TGs are measures - LDL is calculated by:
(total cholesterol) - (HDL) - (0.2*[Trigs])
VLDL can be estimated (in fasting state) as 0.2* Trig concentration
23
Q
Describe the exogenous pathway
A
Dietary fats are packaged into chylomicrons in the small intestine.
The chylomicron then deposits these fats into their target tissues where they are broken down by lipoprotein lipases. The CM remnant is then received by receptors on the liver.
24
Q
Describe the endogenous cycle
A
- free fatty acids and cholesterol packaged into VLDLs in the liver.
- Fat and cholesterol disposed in tissues via lipoprotein lipase in adipose tissue.
- Empty HDLs formed as a byproduct
- IDLs then absorbed by liver
- Hepatic lipase breaks IDLs into LDLs
- LDLs taken up by LDL receptors in peripheral tissues.
- Excess LDLs reabsorbed by liver.
25
How many fatty acids make up each dietary fat
Triglyceride - 3
Phospholipids - 2
Cholesterol - 1
26
how many lobes does each lung have
right - 3
- superior lobe
- middle lobe
- inferior lobe
left - 2
- superior
- inferior
27
which lung is heavier
right. It is also shorter and wider than the left
28
name the lines separating the lobes of the lungs
oblique fissure - separates the middle and inferior lobe of the right lung. And the superior and inferior lobe of the left lung
horizontal fissure - separates the superior from the middle lobe of the right lung
29
what is the lingula
projection of the superior left lobe
30
what is the hilum of the lung
the 'doorway' area where structures enter and leave the lung
31
general arrangement of the hilum of the right lung
most anterior and inferior - pulmonary veins
superior to the veins - pulmonary artery
central ann posterior - bronchii
32
general arrangement of the hilum of the left lung
most superior - pulmonary artery
most anterior and most inferior - pulmonary veins
central and posterior - bronchii
33
what is the name for the point at which the trachea splits into the two main bronchi
Carina - at level of sternal angle or T5
34
divsions of the right main bronchus
right superior lobar bronchus
right middle lobar bronchus
right lower lobar bronchus
35
divisions of the left main bronchus
left superior lobar bronchus
left inferior lobar bronchus
36
what are the borders of the heart
superior border
right border
diaphragmatic border
apex
left border
37
what is the coronary sulcus
groove that divides the atria from the ventricles
38
what is the anterior interventricular sulcus
the groove that runs between the two ventricles
39
what vessel runs through both anterior sulci of the heart
anterior interventricular artery
40
what is the biggest vein of the heart
the coronary sinus
41
what vessels passes down the posterior interventricular sulcus
the posterior/inferior interventricular artery
42
what are the right coronary artery branches
sino-atrial nodal branch
right marginal branch
posterior inteventricular artery
43
left coronary artery branches
anterior interventricular artery
- diagonal branch
circumflex artery
- left marginal
44
which vessels are most often harvested for a coronary bypass
great saphenous vein - diameter is equal to coronary arteries
radial artery
45
describe the internal thoracic artery
AKA internal mammary
arises from internal subclavian
lies very close to the sternum
optimal position for harvesting
supplies the intercostal arteries
46
where does the trachea begin and divide
level of C6, below the cricoid cartilage of the larynx.
Divides into bronchi at level of T4
47
describe the carina
thick incomplete cartilaginous ring that runs between the two primary bronchi at the bifurcation of the trachea.
Its role is to direct the air into each principal bronchi during respiration
48
describe the differences between the bronchi
right - more vertical, shorter and wider
left - more horizontal, longer and thinner
49
describe the tertiary (segmental bronchi)
they each serve a specific bronchopulmonary segment
right - ten
left - eight
Dont have C shaped cartilage, instead have cartilaginous plates.
Branch into bronchioles
50
Describe bronchioles
composed of fibroelastic membrane and msooth muscle (usually no cartilage)
control the resistance to airflow and the air distribution in the lungs
51
lung tissue blood supply
oxygenated blood via the bronchial arteries that are direct branches of the thoracic aorta.
52
what is surfactant
fluid rich in phospholipids and proteins that decreases the surface tension in the alveoli, preventing them from collapsing
53
What is absolute risk
incidence of a disease in a given population
number of new cases per population over a specified time
x new cases per x population per x years
54
what is relative risk
expresses risk as how mnay times greater or smaller among exposed.
determine the absolute risk in each group (exposed and non exposed) and compare
55
principal regulators of lipid metabolism
insulin and noradrenaline
56
how are lipids used for ATP generation transported
Triglycerides (in lipoproteins - chylomicrons and VLDL)
Fatty acids (bound to albumin)
57
describe lipid digestion
Occurs in small intestine
Pancreatic lipase and colipase breakdown triglycerides into 2 fatty acids and a monoglyceride
Process also requires bile salts
- synthesised from cholesterol
- secreted by liver through bile duct
- emulsify fats to micelles (tiny fat droplets)
58
function of lipoproteins
transport triacylglycerols and cholesterol (as cholesteryl esters) in plasma
transport of dietary lipids from intestine to liver (exogenous) by chylomicrons
transport lipids from liver to peripheral tissues by VLDL, IDL and LDL or from peripheral tissues to liver by HDL (endogenous)
59
what enzyme takes triglycerides off chylomicron to leave the remnant
lipoprotein lipase
60
what synthesises HDL
extrahepatic tissues
61
describe the build-up process before beta oxidation
the generation of ATP from fatty acids
fatty acids first added to CoA to form fatty acyl-coA in cytoplasm (this is to make it soluble)
This first stage uses ATP
THEN the fatty acyl-coA can undergo beta oxidation in the mitochondrion to produce more ATP
62
describe carnitine
needed as a carrier molecule to transport fatty acyl-CoA across the inner mitochondrial membrane
derived from lysine and methionine
high levels of carnitine in the muscle
63
describe fatty acid entry into mitochondria
Step 1: Carnitine palmitoyl transferase 1 will swap carnitine and FaCoA into CoA and FACarnitine ACROSS FIRST MEMBRANE BARRIER
Step 2: CPT2 will swap them back ACROSS SECOND MEMBRANE BARRIER
64
what is beta oxidation
Fatty acyl CoA are degraded by oxidation at the beta carbon
Occurs in rounds reducing size of fatty acyl chain by 2 carbons each time
Produces 1 FADH2 and NADH and acetyl CoA (2 carbons) per turn
Ends up with a final acetyl CoA
65
describe fatty acid synthesis
built 2 carbons at a time from acetyl CoA
limit is 16 carbons in humans
key regulatory enzymes: Acetyl CoA carboxylase (first step)
Fatty acid synthase (everything else)
occurs in cytoplasm
requires NADPH
66
describe fatty acid synthase enzyme
multi functional enzyme
Intermediates in fatty acid synthesis are linked to an acyl carrier protein (part of FASynthase)
ACP acts to take developing fatty acid from active site to active site
67
Describe the importance of Malonyl CoA
When synthesizing fatty acids you also make lots of Malonyl CoA.
This inhibits CPT. This means Fatty Acids cannot enter mitochondria.
And so when you are making fatty acids, you switch off fatty acid oxidation. This prevents a futile cycle.
68
Describe regulation of ACC and FAS in the Fed state
Insulin rapidly stimulates ACC
- Fatty acid synthesis increased
-Fatty acid oxidation decreased (as more malonyl CoA)
Insulin stimulates glucose uptake into adipocytes (GLUT 4)
- Excess glucose after meal used for lipid synthesis
Insulin stimulates transcription of FAS gene
69
Describe regulation of ACC and FAS in the fasted state
Lack of insulin inhibits ACC
- Fatty acid synthesis decreased
- Fatty acid oxidation increased (as less malonyl-CoA)
Little glucose uptake by adipocytes as no insulin
70
What substrates are used in the generation of fatty acids by fatty acid synthase
Acetyl CoA, Malonyl CoA, NADPH
71
define thrombosis
inappropriate occlusion of a blood vessel (venous or arterial) by an intravascular blood clot or platelet clumo
72
function of PCSK9 inhibitors
PCSK9 binds to LDL receptors and promotes their intracellular degradation
inhibiting PCSK9 can decreases LDL-C substantially
73
mechanism of aspirin
irreversibly binds to cyclo-oxygenase
inhibits platelet synthesis of thromboxane A2
inhibits platelet adhesion and aggregation
74
function of Clopidogrel
selectively inhibits adenosine diphosphate induced platelet aggregation. This is done by bocking ADP (P2Y12) and so preventing expression of GpIIb/IIIa
75
function of ticagrelor
reversible and non-competitive ADP receptor antagonist
76
function of Prasugrel
irreversible inhibitor of P2Y12 receptor
77
what are the three acute coronary syndromes
unstable angina
Non-STEMI
STEMI
78
presenting symptoms of MI
chest pain
- crushing
-radiates to arm, neck, jaw
- nausea and vomiting
- sweaty
no chest pain = diabetics elderly
atypical symptoms - upper GI symptoms
Ango animi
79
clinical signs of MI
clutching chest
sweating
tachypnoea
tachycardia/bradycardia
hypertensive/hypotensive
murmurs
third heart sound
80
describe stable angina
one or more coronary arteries have significant structural stenosis due to atherosclerosis
blood flow is sufficient at rest, but O2 demand not met upon exertion
attacks resolve within 5-10 mins ish
ATP and PCr are depleted which can cause impaired contraction and relaxation
81
describe unstable angina
attacks are unpredictable, occur at rest, more painful, often last over 30 mins
caused by coronary artery occlusion due to platelet adhesion to ruptured atherosclerotic plaque
exacerbated by release of vasoconstricting factors from platelet aggregation and by endothelial damage
82
describe variant angina
attacks unpredictable, intensely painful and occur at rest or when sleeping
caused by transient coronary artery occlusion due to vasospasm (often in vicinity of plaques)
likely caused by endothelial dysfunction/hypersensitivity as a consequence of oxidative stress
83
explain why dilation of coronary arteries is not a treatment for angina
Can be dangerous in stable and unstable angina due to coronary steal, where dilation of vessels diverts more blood to already well perfused areas
in vessels where dilation cannot occur, less blood is delivered due to fall in input pressure
84
factors affecting MVO2
increase in heart rate, inotropy or afterload = larger effect to increase MVO2
increase in stroke volume = smaller increase in MVO2
85
describe how dilation of arteries reduces myocardial oxygen demand
decrease afterload
which decreases TPR
which decreases myocardial work
which decreases myocardial O2 demand
86
describe how dilation of veins reduces myocardial oxygen demand
decrease pre-load
which decreases venous return
which decreases stretch of myocardium
which decreases sarcomere length = less crossbridge formation
decreasing the force of contraction
which decreased myocardial work and hence myocardial O2 demand
87
describe long-active nitrovasodilators
ISDN and ISMN
Taken orally
Slower in onset, prolonged duration
Used for sustained prophylaxis
88
describe regular nitrovasodilators
GTN
not orally active
taken as sub-lingual tablet or spray
rapid onset, short lived
used for rapid relief and prophylaxis in stable angina
89
mechanism of sGC
Nitric oxide activates sGC
(cytoplasmic enzyme)
receptor on sGC contains a ferrous haem moiety (like O2 binding site on haemoglobin)
NO binds to haem receptor -> enzyme activation -> converts GTP to cGMP -> increase cGMP -> vasodilation
90
side effects of nitrovasodilators
headache due to dilation of cerebral arteries
flushing
postural hypotension
91
describe how beta-blockers reduce myocardial O2 demand
competitive reversible antagonists of adrenaline and noradrenaline at cardiac Beta1 adrenoceptors
decrease HR and force => decrease myocardial work => decrease MVO2
92
side effects of beta-blockers
intolerance to exercise
impaired LV function and severe bradycardia
Sleep disturbances and nightmares
93
when are beta-blockers NOT used
Asthma
COPD
peripheral vascular disease
Variant angina since may worsen vasospasm due to blockade of Beta2-adrenoceptors (vasodilating) but not the alpha1-mediated (vasoconstricting) effects of sympathetic stimulation
94
describe how Ca2+ channel blockers can reduce myocardial oxygen demand
reduced calcium entry results in coronary and peripheral arterial vasodilation
decreases force of contraction and HR => myocardial work => decrease O2 demand
95
describe Ivabradine
second line treatment for stable angina
Blocks inwards sodium pacemaker current in SA node
delays time to reach threshold for AP firing
decreases HR but not force => decrease O2 demand
96
describe Nicorandil
Nitrate like action and opens K+ channels
dilates coronary arteries
Venodilation => preload => decreases MVO2
dilates peripheral arterioles => decreases afterload => decreases MVO2
97
side effects of nicorandil
serious GI ulcers
98
what is represented by the P wave
atrial depolarisation
99
what is represented by the PQ segment
delay ate the atrioventricular node
100
what is represented by the Q mark
conduction through bundle branches and conduction through purkinje fibres
101
what is represented by the QRS complex
ventricular depolarisation
102
what is represented by the ST segment
plateau phase of repolarization
103
what si represented by the T wave
final rapid ventricular repolarisation
104
what do unipolar leads measure
potential variation at a single point
105
what do bipolar leads measure
measure the potential difference between two points
106
define attributable risk
incidence of cases among those exposed that are due to the exposure/risk factor
= incidence of disease in exposed - incidence of disease in un-exposed
107
define attributable risk percentage
percentage of cases among those exposed that are due to the exposure / risk factor
= AR x 100 / incidence of disease in exposed
108
define population attributable risk (PAR)
Incidence of cases among whole population (exposed and not exposed) that are due to the exposure
= AR x prevalence of exposure
109
define population attributable risk percent (PAR%)
Proportion of cases in the whole population (exposed and not exposed) that are due to the exposure
= PAR x 100 / incidence of disease in population
110
what are platelets
cell fragments with no nucleus, produced from megakaryocytes in bone marrow
111
what is normal platelet count
150,000 - 350,000 per ml of blood
112
what occurs after vessel injury
immediate transient vasoconstriction to reduce blood loss
due to loss of vasodilatory signals from endothelial cells and direct exposure of SMCs to vasoactive substances
113
what initiates platelet adhesion
surface integrin receptors adhering to vWF on the exposed subendothelial collagen
Tisi tethers platelets to promote contact sites for subsequent activation
114
describe platelet activation
inititaied by binding of GPVI receptors directly to collagen
Platelets change shape, pseudopodia, and make thromboxane A2 (TXA2) via cyclooxygenase
promotes vasoconstriction and platelet aggregation alongside 5-HT and ADP from granules
115
describe platelet plug formation
activated platelets expose another cell surface integrin GPIIb/IIIa
Plasma fibrinogen sticks to GPIIb/IIIa forming cross-links with adjacent platelets causing them to aggregate
this rapidly creates a soft and fragile platelet plus = primary haemostasis
116
describe the coagulation cascade
series of reactions catalysed by plasma proteins called coagulation factors
when activated by protealytic cleavage, these activate and trigger the conversion of other factors
Ca2+ is required for activation of multiple factors
End-product is generation of thrombin
117
describe secondary haemostasis
| (final common pathway)
thrombin converts fibrinogen to fibrin
fibrin polymerises and is cross-linked to factor XIIIa (activated by thrombin) to form a tough network of fibres
fibrin strands enmesh the platelet aggregate to consolidate the haemostatic plus = secondary haemostasis
118
describe what suppresses platelet activation
they remain in resting state until needed
endothelial cells provide antithrombotic boundary layers
continual release of prostacyclin and nitric oxide inhibits platelet aggregation and promotes vasodilation
NO also inhibits adhesion
Membrane-bound E-NTPDase1 limits the prothrombotic signals of ADP by converting to adenosine
119
describe endothelial regulation of coagulation
heparin-like molecules expressed on endothelial surface bind circulating antithrombin III
greatly increases the activity of ATIII to inhibit multiple coagulation factors, including thrombin.
ECs express tissue factor pathway inhibitor (TFPI)
120
describe the fibrinolytic system
ECs continually produce serine protease tissue plasminogen activator
t-PA cleaves plasminogen to form plasmin
this degrades cross-linked fibrin into fibrin degradation products
121
what is hemophilia A
deficiency of factor VIII
122
what is Haeomphilia B
deficiency of factor IX
123
pattern of inheritance of haemophilia
sex-linked recessive
males more often affected
female carriers can also have mild bleeding problems
124
describe von willebrand disease
deficiency of von willebrand factor which stabilises factor VIII and bind platelets to collagen => defective platelet adhesion
males and females affected equally
125
describe haemophilia C
deficiency of factor XI
autosomal recessive (both parents must carry mutation)
126
describe the function of calcium chelators
e.g. citrate and EDTA
Ca2+ is required for activation of multiple factors, V, IX, X, XIa, XIII and prothrombin
Chelating Ca2+ makes it unavailable to participate in coagulation cascade
127
describe heparin
A naturally occurring sulfated glycosaminoglycan (ie, a negatively charged linear polysaccharide)
Heparin binds to antithrombin to inhibit multiple coagulation factors
128
What are the two in vitro anti-coagulants
Calcium chelators and heparin
128
What is the mechanism of action of unfractionated heparin
Binds to and greatly enhances the action of antithrombin III which circulates in plasma
The heparin-antithrombin III complex bind sto and inhibits clotting factors IIa, IXa, Xa, XIa, XIIa
IMMEDIATE clotting inhibition
129
describe the disadvantages and benefits of low molecular weight heparins
any heparin chain can inhibit factor Xa by binding to antithrombin
But to inactivate thrombin, the heparin must be long enough to bind both antithrombin and thrombin
Unfractionated heparin is long enough, but the LMWH are not
benefits: short strands have longer duration and more predictable action
130
side effects of heparin
haemorrhage
allergic reactions
- heparin induced thrombocytopenia
hyperkalemia (due to inhibition of aldosterone secretion)
131
what is used in reversal of heparin in haemorrhage
protamine
132
describe warfarin
ORAL anticoagulant
liver requires vitamin K to complete synthesis of prothrombin and factors VII, IX and X
Warfarin blocks vitamin K epoxide reductase (which reduces Vit K to its active form)
This prevents carboxylation of glutamic acid
133
side effects of warfarin
haemorrhage
crosses placenta and blood brain barrier
134
what is used to reverse side effects of warfarin
transfuse with plasma or recombinant coagulation factors
Oral vitamin K - but reversal is slow
135
how does warfarin have a narrow therapeuric index
Higher INR = risk of haemorrhage
Lower INR = risk of thrombosis
136
describe direct oral anticoagulants
alternative to Warfarin
As effective as preventing strokes
No need to monitor INR
4 in UK
- Dabigatran exilate = direct thrombin inhibitor
- Apixaban, edoxaban, rivaroxaban = direct inhibitors of factor Xa
137
describe reversal of DOACs
Idarucizumab = non competitive binding specifically to dabigatran and its metabolites
Andexanet alfa is a specific reversal agent for apixaban, rivaroxaban, edoxaban
truncated form of Xa, acts as decoy to prevent interaction with real Xa
138
describe dipyridamole
inhibits cyclic nucleotide phosphodiesterases, enzymes which break down intracellular cAMP and cGMP
increasing these potentiates effects of prostacyclin and NO
=> inhibition of platelet activation
139
mechanism of aspirin
irreversibly inhibits cyclooxygenase via acetylation of the terminal serion530 residue
prevents synthesis of platelet thromboxane A2
140
mechanism of clopidogrel
blocks platelet ADP (P2Y12) receptors, preventing GPIIb/IIIa (the one fibrinogen attaches to to form platelet plug) receptor exposure
141
mechanism of abciximab
monoclonal antibody to GPIIb/IIIa
142
two main fibrinolytics
tissue plasminogen activator
streptokinase
143
