Cardio Flashcards
(116 cards)
1
Q
Why is CV important
A
Diffusion can only do short distances when it comes to transporting oxygen
Thus, in order to achieve a rapid transport of nutrients and oxygen to tissue and removal of waste we need the CV system
2
Q
problems with coronary circulation
A
- Coronary blood flow occurs during diastole
- Coronary arteries are end arteries, ie if there is blockage there is not good anastomoses resulting in ischaemia and necrosis
3
Q
How does the heart adapt to the coronary problems
A
- Structural adaptability:
Myocardial capillary density is very high in comparison to skeletal cells - Functional adaptability:
- Even at rest the heart has high blood flow and extracts a large portion of O2 due to high metabolic demand
- during exercise metabolic demand increased and thus metabolic hyperaemia increases blood flow to the heart (increased blood flow)
- auto-regulations which is maintaining steady blood flow despite fluctuations in BP
4
Q
What is cardiac output
A
The volume of blood ejected by 1 ventricle in 1 min
5
Q
What is stroke volume
A
The volume of blood ejected from the ventricles in systole
6
Q
Equation for cardiac output
A
Stroke vol x HR
= cardiac output
7
Q
How is the blood divided in the body?
A
8
Q
What is the issue with cardiac output not being evenly distributed between tissues?
A
The heart only receives 4% of the cardiac output but in turn due to density of capillaries it had maximised how much O2 it receives (10%) the medical significance if there is a blockage:
- coronary blood has little spare O2
- cardiac pain due to lack of O2 can be triggered by modest fall in coronary blood flow
9
Q
What controls HR?
A
- HR is controlled by sympathetic and parasympathetic nerves which innervate the SA and AV nodes
- resting HR is 50-100 BPM
- increased sympathetic activity > tachycardia
- increased parasympathetic activity > Bradycardia
10
Q
What factors control stroke volume?
A
Preload
Contractility
They control contractility of the heart, any increase in those factors causes increased SV
After load if increased causes decreased SV
11
Q
What is preload?
A
The amount of stretch of the ventricular fibres just before contractions at the end of diastole
Measured by end diastolic preload
12
Q
Starling Law
A
The greater the preload the greater the stroke volume.
Frank Starling mechanism (the law of the heart)
13
Q
What are the exceptions to measuring preload with end diastolic pressure
A
Examples
In hypertension the heart is stiff- so a minor increase in blood in the ventricle causes a massive rise
In dilated ventricular disease- a large increase in volume does not cause for a stretch in fibres and thus only minimally increasing end diastolic pressure
14
Q
How is end diastolic pressure determined?
A
Central venous pressure > right ventricular pressure > right ventricular end diastolic pressure
15
Q
What factors influence central ventricular pressure
A
- Volume of blood in circulation
- Distribution of blood between central and peripheral veins, which is influenced by gravity, sympathetic nerves, respiratory, skeletal muscle and heart pumping
16
Q
Example: why do guards faint?
A
Standing up: gravity
Standing still; calf muscle not operating
Warm clothing: blood vessels dilated
> less blood returning to the heart > pre load reduced > central venous pressure lower than usual > RVEDP is lower > RV stroke vol is reduced > less filling of the left ventricle > left ventricular stroke vol is reduced > cardiac output reduced> BP reduced > less blood to the brain > loss of consciousness
17
Q
What are the implications of starling’s law?
A
As the RV is connected to the LV by the pulmonary circulation, high CVP determines SV for both SV and LV.
This ensures balanced output from the RV and LV
If there is no balance between the two, the blood might end up in the lungs/ pulmonary circulation
18
Q
What is contractility and what controls it?
A
It is a change in the force of contraction that is caused by neurohumoral factors
It is independent of fibre lengthy
Intrinsic: pressure of opposing ejection (reduces energy of contractility) and filling pressure (starling’s law)
Extrinsic: sympathetic nerves, drugs and hormones (adrenaline, noradrenaline)
19
Q
What is afterload?
A
Refers to the amount of resistance the heart must pump against when ejecting blood
It is influenced by aortic/ pulmonary pressure in diastole
Afterload for the LV = aortic diastolic pressure
Hypertension and stenosis affects afterload
20
Q
Demands on CVS from exercise
A
- Increased cardiac output to increase o2 supply and removal of CO2
- Increase blood flow to active muscle
- Stabilise BP
- Regulate core temp
21
Q
How does CO increase during exercise?
A
Stroke volume increased due to increased preload > due to skeletal muscle pump and peripheral venoconstriction > also due to increased contractility
Heart rate increased because of decreased parasympathetic activity and increased sympathetic activity
22
Q
Explain the mechanism behind hypotension in exercise
A
BP= COx SVR
Decreased vascular resistance in active muscle and skin can cause BP to fall despite increased cardiac output
Compensatory vasoconstriction in inactive tissue > attenuated fall in total peripheral resistance
23
Q
Cardiovascular cycle
Mid to late ventricular diastole
A
1st phase: Ventricular filling
Atrial > ventricular pressure
Arterial pressure > ventricular pressure
AV valves are open
SLV valves closed
EKG P wave
SA node pushes the 20% blood remaining by depolarising the atrium (contractility occurs)
The blood is coming from SVC, IVC, p. Veins
24
Q
Cardiovascular cycle
Isovolumetric contraction systole
A
2nd phase
Atrial < ventricular pressure
Arterial pressure > ventricular pressure
AV valves are closed > shutting down > LUB ‘s1’ sound
SLV valves closed
EKG QRS wave
The myocardial depolarisation causes contractility of the ventricles pushing the blood up
25
Cardiovascular cycle
Mid to late ventricular systole
(Ventricular ejection)
3rd phase
Atrial < ventricular pressure
Arterial pressure < ventricular pressure
AV valves are closed
SLV valves are open
EKG QRS wave
26
Cardiovascular cycle
Isovolumetric relaxation
4th phase
Atrial < ventricular pressure
Arterial pressure > ventricular pressure
AV valves closed
SLV valves closed- DUB (2nd heart sound) ‘S2’
EKG T wave
End systolic volume- blood left at the bottom of the ventricles
27
Arteriosclerosis
“hardening of the arteries”; it is a generic term reflecting arterial wall thickening and loss of elasticity.
28
What are the general patterns of athrogenesis
1. Arteriolosclerosis
- small arteries and arterioles
- downstream ischaemic injury
- thickening of wall, narrowing the lumen
- associated with diabetes and hypertension
- two variants: hyaline and hyperplastic (onion like)
2. Monckeberg medial sclerosis
- calcific deposits
- muscular arteries
- may undergo metaplastic change into bone
- does not cause narrowing of vessel lumen
3. Atherosclerosis
- characterised by intimal lesions called atheroma/ atherosclerotic plaques that protrude into vessel lumen
- atheromatous plaque consist of a raised lesion with core of lipid covered by fibrous cap
- they obstruct blood flow, they can rupture leading to vessel thrombosis
- they also lead to aneurysm formation
29
Complications of atherosclerosis
- Occlusive thrombosis
- Sudden death
- MI
- Stroke
- Acute ischaemia of legs and abdominal organs
- Aortic aneurysm
30
Targets of atherosclerosis
- Large elastic arteries such as aorta, carotid and iliac arteries
- Medium muscular arteries such as coronary and popliteal arteries
- Symptomatic disease often involves arteries supplying- heart, brain, kidneys and lower extremities
31
Risk Factors for atherosclerosis
- Age
- Male
- Genetic abnormalities
- Family history
- Hyperlipidemia
-Hypertension
- Smoking
- Diabetes
- C - reactive protein inflammation
- Hypercholestreolemia
- Obesity
- Endothelial dysfunction
- loss of elastic properties
32
Forms of coronary syndrome
Acute coronary syndrome: unstable angina, MI (STEMI and NSTEMI)
Complications: chronic angina
Due to atherosclerosis (thrombosis, inflammation, lipid disposition)
33
Pathophysiology of coronary artery disease
34
Inflammatory process of atherosclerosis
35
Risk factors for CAD
Modifiable risks:
- smoking
- hypertension
- high cholesterol
- diabetes
Non modifiable risks:
- age
- gender
- family history
- ethnicity especially south Asian and east European
Less clear link but also modifiable:
- obesity
- poor diet
- physical inactivity
36
How to assess CAD
QRISK2 CVD risk calculator
If more than 10% they should receive secondary help
37
Pathophysiology of stable angina
Ischaemia due to fixed vessel narrowing and abnormal vascular tone
Coronary atheroma prevents blood flow from matching the demand as seen in graph
38
Name the factors for oxygen supply and demand
Supply problems: coronary stenosis, anaemia, lung problems
Demand problems: tachycardia, preload (venous return), afterload (BP), muscle mass (e.g hypertrophy or infarcts)and muscle contractility
39
What causes abnormal vascular tone
Endothelial dysfunction causing the abnormality which results in:
- Inappropriate vasoconstriction of coronary arteries
- Loss of normal anti-thrombotic properties
40
Symptoms of angina
41
Angina syndromes
42
Differential diagnosis of recurrent chest pain
Cardiac:
- angina
- pericarditis
Gastrointestinal:
- reflux
- peptic ulcer
- oesophageal spasm
- biliary colic
MSK:
- costochondrial syndrome
- cervical radiculitis
43
Diagnosis of angina
- ECG
- Stress tests- exercise ECG, myocardial perfusion imaging, stress echocardiography, stress MRI
- Imaging: CT coronary angiogram, coronary angiogram
44
What does sub-endothelial injury cause on ECG
ST depression
45
What does transmural injury cause on ECG
ST elevation
46
What causes ACS
Most likely due to plaque rupture which exposes thrombogenic extra cellular matrix and lipid core to circulation causing PLT aggregation and thrombus formation
This can be asymptomatic with reabsorption into plaque or occlusive with infarction
47
Types of plaques
Stable- thick fibrous cap, small lipid pool
Vulnerable- thin fibrous cap, large lipid pool
48
How to diagnose and classify ACS
Hx
ECG ST or NST
Cardiac Troponin, non specific but sensitive
49
What is the main difference between stable angina and ACS
Ruptured plaque that has lead to thrombosis
Acute occlusion
Acute severe inefficiency in blood supply
whilst in stable angina the pain is reproducible and is resolved
50
Tx of stable angina
1. Lifestyle changes
2. Revasculrisation with PCI or CABG
3. Drugs: statins, spirit, +/- beta blocker and ace inhibitors, nitrates
51
Anti angina pharmacological Tx
- Beta blockers are first line- aim for HR of 50-60 bpm
- long acting oral nitrates can be added, e.g isosorbide mononitrate
- CCB (diltiazam or amlodipine)
- if angina not controlled on 2 drugs, consider revasculrisation
On presentation patient should be referred for an angio
Headache is a transient side effect that may last around 2 weeks
52
Investigations for angina
- Exercise stress test, but it does not have much impact
- MIBI
- CTCA
- Stress MRI
- Dobutamine stress echo
- coronary angio
53
Indications for PCI
stable angina:
- limiting symptoms despite 2 anti anginals
- 1,2,3 vessel or LMS disease
- Less complex disease (SYNTAX score
54
Indications for coronary artery bypass grafting (CABG)
55
What is the basic structure of the circulatory system
Tunica intima:
- Compromised of flattened epithelial cells- endothelium
- Supported by a basement membrane and a delicate collagenous tissue
- acts as a selective permeable anti thrombotic barrier
- determines when and where the WBC leave the circulation for the interstitial space of tissue
- secretes paracrine factors for vessel dilation/ constriction and growth of adjacent cells
Tunica Media:
- Intermediate muscular layer
Tunica Adventitia:
- Outer supporting tissue
56
What is the structure of blood vessels
Tunica interna/ intima:
- endothelial layer that lines the lumen
- in vessels larger than 1 my, a subendothelial connective tissue basement membrane is present
Tunica Media:
- Smooth muscle and elastic fibre layer, regulated by sympathetic NS
- Controls vasoconstriction/dilation of vessels
Tunica Adventitia/externa:
- Collagen and elastic fibres that protect vessels
- Larger vessels contain vasa vasorum
Large elastic vessles have alternaating elastic laminae in addition to smooth muscle
57
role of vasa vasorum
Intima and internal regions of the media receive O2 and nutrients by diffusion from the blood in the lumen
Whilst the outer layer are too thick, hence arterioles, capillaries and venules that branch profusely in the adventitia and outer media providing metabolites
58
Function of elastic fibre in large vessels
Stretches during systole- storing some of the energy from the impulse
Recoils during diastole propelling blood the rough to the more distal vessels
These two result in maintaining blood flow during diastole and stabilising blood flow
59
Features of large arteries
- large lumen (1-2.5 cm in diameter), allowing for low resistance
- contain elastin in all three tunics
- withstand and control large blood pressure fluctuation
- allow blood to flow fairly continuously through the body
60
muscular arteries features
- They are medium sized (3 mm - 1 cm), the diameter changes in response to organ needs
- Distributing arteries (e.g smaller branches of the aorta like the coronary and renal arteries)
- The media is composed primarily of SMC with elastin limited to the internal and external elastic lamina
- Tunica media larger in proportion to the lumen, thus “muscular”
Although arterial wall thickness diminishes with decreasing vessel size, the ratio of wall thickness to lumen diameter actually increases for these vessels
61
Compare elastic arteries to muscular arteries
62
Structure of small arteries and arterioles
- They distribute blood by vasoconstriction and dilation
The layers:
Tunica intima:
- endothelium
- thin subendothelial connective tissue
- internal elastic lamina in small arteries
Tunica media:
- 3-8 layers of circularly arranged smooth muscle in small arteries and 1-2 layers in arterioles
- collagen fibres, elastic fibres and ground substance present
Tunica adventitia:
- thin layer of connective tissue that blends with surrounding CT
Small arteries 2mm or less in D and arterioles (20-100 um)
lie within the interstitial connective tissue of organs
The media is essentially all SMCs
63
What vessel is the principle control point for regulation of physiologic resistance to blood flow
Arterioles
In arterioles, the pressure and velocity of blood flow are both sharply reduced
Steady flow not pulsatile, controlled by smooth muscle contraction/ relaxation hence a change in the lumen size
resistance to fluid flow in a tube is inversely proportional to the fourth power of the diameter
64
Features of capillaries
- the smallest
- 8-10 micrometer in diameter
- big enough for single file erythrocytes
- composed of a single layer of endothelial cells surrounded by basement membrane
- function: O2 and nutrient delivery to tissue, CO2 and N2 waste removal
65
Types of capillaries
- Continuous capillaries: muscle, lungs, CNS
- Fenestrated capillaries: endocrine, site of metabolic and fluid absorption e.g gallbladder, kidney and GI
- discontinues capillaries (sinusoidal capillaries): liver, spleen and bone marrow
66
Features of continuous capillaries
- Abundant in the skin and muscles
They have:
- Endothelial cells that provide an uninterrupted lining
- Adjacent cells that are held together with tight junctions
- Intercellular clefts of un-joined membranes - allow the passage of fluids
Continuous capillaries of the brain:
– Have tight junctions completely around the endothelium
– Constitute the blood-brain barrier
67
Fenestrated capillaries features
- Found wherever active capillary absorption or filtrate formation occurs (e.g., small intestines, endocrine glands, and kidneys)
Characterized by:
– An endothelium riddled with pores (fenestrations)
– Greater permeability to solutes and fluids than other capillaries
68
Features of sinusoids capillaries
• Highly modified, leaky, fenestrated capillaries with large lumens
• Found in the liver, bone marrow, lymphoid tissue, and in some endocrine organs
Features:
- The endothelial cells form a discontinuous layer and separated from one another by wide spaces
- The cytoplasm of the endothelial cells shows multiple fenestrations without diaphragms
- The basal lamina is discontinuous
- Allow large molecules (proteins and blood cells) to pass between the blood and surrounding tissues
69
Compare the types of capillaries
70
Types of arteries
- Elastic
Conducting, pressure reservoir, maintain diastolic flow
- Muscular
Distribution, regular rate of flow
- Arterioles
Resistance, regulate flow of blood into capillaries
- Capillaries
Exchange
71
Veins features and classification
They collect blood from all tissue back to the heart
- venules
- medium sized veins
- large veins
72
Venules features
- Endothelial layer backed by a basal lamina which may contain paricytes
- some may be supported by a thin layer of smooth muscles
- They collect blood from capillary networks and merge them to form veins
- A characteristic feature of all venules is the large diameter of the lumen compared to the overall thickness of the wall
- Venules converge into larger collecting venules which have more contractile cells. With greater size the venules become surrounded by recognizable tunica media with two or three smooth muscle layers and are called Muscular venules
73
postcapillary venules
- diameter from 15 to 20um
- participate in the exchanges between the blood and the tissues and, are the primary site at which white blood cells leave the circulation at sites of infection or tissue damage
74
Types of common cardiomyopathies
1. Hypertrophic cardiomyopathy where it causes thickening of the ventricular wall, affecting diastole but systole is preserved
2. Dilated cardiomyopathy, the heart muscle stretches and weakens starting in the left side and then the right. This affects systole
75
Types of uncommon cardiomyopathies
1. Arrhythmogenic right ventricular cardiomyopathy- fat and scar tissue replace muscle in the R ventricle
2. Restrictive cardiomyopathy- the ventricles become very stiff affecting diastole
76
Hypertrophic cardiomyopathy
unexplained LV hypertrophy: excluding causes such as:
- AS, hypertension need to be excluded as they also cause strain on the heart
- Substance deposits also need to be excluded such as the case with amyloidosis
Septum thickening
Genetic disease, autosomal dominant
Most common cause of death in athletes/ young people, but can present at any age
Myocytes are normally arranged in parallel, but in this case they are disorderly, hypertrophied, and separated by areas of interstitial fibrosis which leads to stiffness in diastole and causes V arrhythmias
The most common type is where part of the septum is stiff and affects the left ventricle outflow tract during systole (either at rest or exercise) > systolic murmur (louder if preload is decreased, such as standing up opposite to aortic stenosis)
during ejection, the mitral valve leaflet is dragged towards the septum occluding blood flow, causing jerky carotid pulse
>>> mitral regurg > reducing cardiac output > reducing blood flow back to the left atrium where pressure then rises feeding back to the pulmonary circulation which then causes breathlessness
77
Structure of the cardiac muscle
78
What is the mutation in cardiac hypertrophic cardiomyopathy
Mutation in the genes encoding sarcomeric protein, resulting in impaired contractile performance of the sarcomere
This puts stress on the myocytes and in response the ventricles hypertrophy
79
Clinical signs of HCM
1. Due to the disorganisation of the myocytes, this can lead to V arrhythmias causing syncope and potentially sudden death
2. High pressure due to LVH causes SoB as this feeds back to the pulmonary circulation and L atrium
3. High O2 demand due to LVH, causing O2 demand/ supply imbalance which in turn causes chest pain
4. LV outflow obstruction causes mitral regurgitation which in turn increases O2 demand > SOB
5. Failure to increase cardiac output with exertion due to LV outflow obstruction causes syncope
80
Risk factors from hypertension
MI, HF, CKD, stroke (intracranial haemorrhage more commonly), peripheral arterial disease, aortic dissection, aortic aneurysms, LV hypertrophy, vascular dementia, hypertensive retinopathy premature death and cognitive decline
81
What influences BP?
82
What reading is considered clinical high blood pressure?
140/90 mmHg, to confirm diagnosis use ambulatory BP monitoring
83
Risk assessment of hypertension
Framingham risk score- overestimates risk in UK population
QRisk2- most reliable in the UK
84
Stages of hypertension
- Stage I: offer lifestyle advice, pt education and monitoring; if less than 40 refer to specialist; if organ damage present of Qrisk > 10% then use drugs
- From stage II onwards offer drugs at any age
- With patients > 80- approach like < 40 ie refer to specialists and investigate presence of end organ failure; target 150mmHg or less- drugs not 1st line
85
Modifiable risk factors in hypertension
obesity, poor diet and physical activity and stress
Every kg drop is associated with 1-2 mmHg drop in SBP
salt daily intake rec 6 g
reduce alcohol intake
smoking no clear association
86
Factors in QRisk2
age
sex
ethnicity
post code
smoking
diabetes
angina/ MI in 1st degree relative < 60
CKD
AF
on blood pressure Tx
RA
cholesterol
systolic BP
BMI
87
2ndry causes of hypertension
Renal disease (most common)
Obesity
Pregnancy induced or pre eclampsia
Endocrine (hyperaldosteronism- Conn's syndrome)
Drugs
88
How to test for end organ damage with hypertension
- Urine albumin creatinine ratio for proteinuria and dispstick for microscopic haematuria to assess for kidney damage
- Bloods for HbA1c, renal function and lipids
- Fundus exam for hypertensive retinopathy
- ECG for LVH and other cardiac abnormalities
89
Management of BP
NICE
Step 1: Aged under 55 or type 2 diabetic of any age or family origin, use A. Aged over 55 or Black African use C.
Step 2: A + C. Alternatively, A + D or C + D.
Step 3: A + C + D
Step 4: A + C + D + fourth agent (see below)
Step 4 depends on the serum potassium level:
Less than or equal to 4.5 mmol/L consider a potassium-sparing diuretic, such as spironolactone
More than 4.5 mmol/L consider an alpha blocker (e.g., doxazosin) or a beta blocker (e.g., atenolol)
A – ACE inhibitor (e.g., ramipril)
B – Beta blocker (e.g., bisoprolol)
C – Calcium channel blocker (e.g., amlodipine)
D – Thiazide-like diuretic (e.g., indapamide)
ARB – Angiotensin II receptor blocker (e.g., candesartan)
90
BP targets
Under 80 years
< 140/ < 90
Over 80 years
< 150/ < 90
91
Hypertensive crisis
Accelerated/ malignant hypertension > 180/120 with retinal haemorrhages or papilloedema
Patients needs to be referred on the same day and get a fundoscopy exam
additional assessments for: AKI, HF or ACS
Intravenous options:
Sodium nitroprusside
Labetalol
Glyceryl trinitrate
Nicardipine
Do not lower BP in elderly too quickly > risk of ischaemia
92
Hypotension reading
< 90/60 mmHg
93
define pulse pressure and mean arterial blood pressure
PP: difference between systolic and diastolic pressure
MABP: the average arterial pressure exerted over the course of a cardiac cycle (DP + 1/3 PP). It is a closer figure to diastolic BP as diastole lasts twice as systole
94
How does the aorta keep a more constant/ higher pressure than the LV
Due to elastic recoil in the aorta
- Aorta wall is thick and contains elastic tissue
- This allows for increased blood pressure, expansion during ventricular contraction and energy storing once the valves are open
- Once the valves shut, the stored energy is then used to maintain said pressure in the aorta and thus maintaining the flow of blood through the peripheral circulation whilst the ventricles are refilling
-
95
What are the drivers of MABP
MABP= cardiac output (HR x stroke vol) x total peripheral resistance
so any increase in those in those leads to an increase in MABP
MABP is maintained by:
short term- neuronal
long term- hormonal
MABP is determined by:
1. Blood volume influenced by fluid retention/ intake >> linear
2. effectiveness of the heart (CO) which also includes HR and SV >> linear
3. resistance of the system to the blood flow > vasoconstriction/ dilation of arterioles >> linear
4. distribution of blood in terms of venous system > nonlinear
96
Baroreceptor reflex x BP in the context of MABP
they are myelinated and unmyelinated sensory fibres in the elastic layers of aortic arch ( terminal endings of vagus nerve) and carotid sinus (terminal endings of glossopharyngeal nerve). Some are also present in the atria
The exposed nerve endings fire more when there is higher pressure and vice versa
Feedback info to the medullary cardiovascular control system > NTS
if MABP decreased the receptors decrease their input and this activates the sympathetic NS and deactivates the PNS in order to increase MABP (through controlling SV, HR and TPR)
97
Baroreceptors route in the medulla
Afferent nerves > medulla > NTS > cardio inhibitory area (nucleolus ambiguous and dorsal motor nucleus) > preganglionic vagal parasympathetic neurons > reduce HR and SV
NTS > ventrolateral medulla > bulbospinal fibres > intermediolateral column of spinal cord > preganglionic sympathetic neurons > increase SV and HR
98
How does the nervous system affect TPR and in turn MABP
SNS and PNS regulate TPR by changing the arteriole diameter in the peripheral circulation
SNS releases noradrenaline which interacts with alpha-1 receptors on smooth muscle to cause vasoconstriction and as such increase TPR and MABP
and vice versa
PNS activation leads to more Ach release which acts on muscarinic receptors > SA node > lower HR > less CO
99
Role of baroreceptors in the atria
Monitor venous return, if the walls are stretched means increased venous return and when they fire it leads to increased HR which levels out MABP
known as the bainbridge effect
a sustained increased in the blood volume reflex causes a decrease in the sympathetic vasoconstriction activity in the kidney > increasing renal blood flow > diuresis to reduce blood volume
100
Natriuretic peptides effect on BP
Atrial and brain natriuretic peptides are released in response to myocardial stretch
ANP > atrial
BNP > ventricular
NPs > NP receptors> increase in water and salt excretion > decrease in central sympathetic output > reduce blood volume and pressure
101
The RAAS system x BP
decrease in MABP > decrease in circulating volume
when detected
Liver > angiotensinogen > angiotensin I > ACE > angiotensin II > hypothalamus leading to thirst and AVP
Angiotensin II> adrenal gland > aldosterone > increases salt and water absorption
when MABP is high > increase in circulating vol
renin also helps angiotensinogen > angiotensin I
102
explain vasovagal syncope and fight or flight responses
Stress can cause cortical override of autonomic control
vasovagal syncope is a response to emotional stress leading to fainting through bradycardia hypotension and apnoea
done with the overstimulation of PNS and under-stimulation of SNS causing sudden fall in MABP and perfusion to the brain
fight or flight
originates entirely in the CNS via increased input in SNS causing generalised increase in muscle tone and sensory attention
Also causes the release of noradrenaline and Ach to redistribute blood flow to appropriate tissue and increases cardiac output and MABP
103
104
Plaque formation in peripheral arterial disease (in the view of cholesterol)
Damaged endothelial cells provide sites for fat accumulation
Fatty streaks signal for recruitment of immune cells
Macrophages eat cholesterol and turn into foam cells in plaque
Smooth muscle grow into said plaques generating fibrous cap
Plaque reduces blood flow
necrosis at the core can cause plaque rupture due to favours cap thinning and thrombus formation blocking the arteries
105
What type of lipid is cholesterol? What are its functions?
Steroid lipid
- Body synthesises cholesterol ~ 80 mg and we get it from diet ~ 300 mg/ day
- Precursor for steroid hormones progesterone and cortisone and also bile salts
- Regulates cell membrane fluidity for cell movement, endocytosis etc
- in cell membrane, it breaks the hydrophobic bonds allowing movement
106
Solubility and transport of cholesterol
Has hydrophobic head hence insoluble in water
Therefore, it needs to be transported correctly otherwise it would precipitate in blood vessel and form plaques
They are transported via lipoproteins- they have lipid and protein parts; they hydrophilic part points out and the the hydrophobic part points inwards
The lipid part is responsible for packaging cholesterol and the apo protein part is made of several different domains that target receptors indicating where the particle goes
Depending on what type of lipoprotein cholesterol is attached to it determines whether it is low or high density
High lipid low apoprotein is low density
Low lipid high apoprotein is high density
107
Rank cholesterol types’ densities
Low to high
Chylomicrons
VLDL
IDL
LDL
HDL
108
Major sources of cholesterol in diet
Eggs, fatty food, kidney, liver and prawns
109
How are bile salts made
Liver uses excess cholesterol to make bile salts which are then used to assist absorption of insoluble cholesterol from the intestine
110
Cholesterol cycle
Cholesterol complexed with bile salts is taken into the intestinal epithelium > esterified and packaged into lipoprotein particles for transport in the blood in chylomicrons form
Chylomicrons are used up by muscle and adipose tissue for energy
Or they are sent to the liver > VLDL which is also used by muscle and adipose then repackaged into IDL and LDL
LDL is the most used form
Excess cholesterol is packaged as HDL > picked up from tissue to liver to bile salts to intestine
111
Explain BAD and GOOD cholesterol
HDL is anti- atherogenic which is good
HDL is used as a measure of cholesterol headed to liver for execration via bile salts
The rest are pro- atherogenic
LDL is the measure of cholesterol headed to tissue
112
LDL and HDL levels
LDL 70-130 mg/ dL low numbers better
HDL 40-60 mg/ dL high numbers better
Total cholesterol < 200
Triglycerides 10-150
HDL does not effect risk of heart disease, whilst LDL does
Cholesterol in cell is not bad as it is being used, whilst in blood is dangerous
113
Genetics of familial hypercholesterolemia
Single gene
Autosomal dominant transmission
Heterozygote incidence 1:500 > premature CVD ages 30-40
Homozygte incidence 1:1M
Severe CVD in childhood
114
Complications of homozygou familial hypercholestrolemia
Xanthoma
atherosclerosis of the coronary arteries
115
Mechanism of familial hypercholestrolemia
Cells’ LDL receptors are defective hence they can not take up LDL leaving it in the blood causing high plasma levels
NP-X-Y > NP-X-C
116
Mechanism of statins
Statin inhibit the enzyme HMG CoA reductase which catalyses the rate limiting step in cholesterol synthesis in the cells
