Cardiovascular and Respiratory

What does the thoracic wall contain

sternum

T1-12

12 pairs of ribs and costal cartilages

Intercostal muscles

Arteries and nerves

what are true ribs

costal cartilage attached to the sternum

what is a false rib

costal cartilages will attach to the cartilage above

What are floating ribs

ribs which do not attach to the sternum

what ribs are true, false and floating

True - 1-7

False 8-10

Floating 11-12

What are the costovertebral joints

head of rib articulates with the superior demi-facet of corresponding vertebra and inferior demi-facet of the vertebra superior to it

what is a costotransverse joint

the tubercle of the first rib articulated with the transverse process of the corresponding vertebra

What nerves supply the diaphragm

phrenic nerve C3-5

What levels are the IVC, oesophagus and aortic hiatus found

IVC - T8

oesophagus - T10

aortic hiatus - T12

what are the external intercostals - functions, muscle fibre direction

found in the intercostal spaces, most active during inspiration and muscle fibres run anteroinferiorly

what are the internal intercostals - action and muscle directions

they are found in the intercostal spaces, they are most active in expiration and muscle fibres run anteroposteriorly

where does the neurovascular bundle lie

between the internal and innermost intercostals

what are some of the accessory muscles of respiration

expiration - abdominal and external/internal obliques

inspiration - sternocleidomastoid, serratus anterior and pecs

what is the nerve supply of the T1-11 neurovascular bundle

anterior rami of T1-11 spinal nerves forms intercostal nerves

what is the nerve supply of the T12 neurovascular bundle

anterior rami of T12 spinal nerves forms subcostal nerves

what order is the neurovascular bundle from superior to inferior

vein

artery

nerve

where does the posterior intercostal artery originate form

aorta

where does the anterior intercostal artery originate from

internal thoracic artery

what does the subclavian artery bifurcate into

musculophrenic and superior epigastric arteries

what are the regions of pleura called

visceral

parietal

costal

diaphragmatic

mediastinal

cervical

Blood pressure values

120/80 is optimal

130/85 is normal

130-139 is higher but not hypertension

85-90 is higher but not hypertension

140-159 - grade 1

160-179 - grade 2

180+ - grade 3

90-99 - grade 1

100-109 - grade 2

110+ - grade 3

What can chronic hypertension lead do

damaged endothelium

impaired endothelial function

decreased blood flow to organs

SMC hypertrophy

increased vessel thickness

increased vessel leakiness

increased thrombosis risk

increased TPR

list the main medications for hypertension

beta blockers

diuretics

ACE inhibitors

angiotensin receptor blockers

calcium channel inhibitors

What is the RAAS system

angiotensinogen is converted to angiotensin I using renin which is produced by the juxtaglomerular apparatus in the kidneys, angiotensin I is converted to angiotensin II by ACE. the angiotensin II can bind to receptors which will activate the aldosterone which is released from the adrenal gland

what affect does angiontensin II have on aldosterone production

promote release of the aldosterone hormone from adrenal gland and also directly target the hypothalamus for secretion, mediate vasoconstriction and increase sodium reabsorption by tubule and this will increase blood volume.

How does an ACE inhibitor work

it will prevent the conversion of angiontensin I to angiotensin II, this means that the angiotensin II mediated release of aldosterone cannot occur. angiotensin II is a vasoconstrictor, the fewer released of this will cause inc in peripheral resistance, it will reduce blood volume and reduce blood pressure due to less aldosterone

what is a side effect of ACE inhibitors

persistent cough due to the breakdown of bradykinin

sudden fall of bp on first dose so should be given gradually

contra-indications of ACEi

pregnancy

reno-vascular disease

what is the mechanism of angiotensin receptor blockers

reduces the effect of angiotensin mediated aldosterone release and mediates vasoconstriction

what is the action of minerocorticoid receptor antagonists

blocks effects of aldosterone

what may minerocorticoid receptor antagonist cause

hyperkalaemia

give an example of a type of minerocorticoid

spironolactone

what is the actions of calcium channel blockers - the two actions

both DHP and non-DHP

DHP when channel is inactive and Non-DHP when channel is active

they will bind to and block the l type calcium channels, decreasing calcium entry this will cause vasodilation and a reduced force of contraction which will decrease heart rate

DHP is better for smooth muscle but non-DHP works on both

Non-DHP causes vasodilation, decreased ionotropy, and decreased HR

what is particularly sensitive to Non-DHP

AVN

what are side effects of calcium channel blockers

headache, dizziness, AV block

what can Non-DHP cause (that DHP does not)

AV block

what is an example of an ACE inhibitor

captopril, ramipril

what is an example of a angiotensin receptor blocker

losartan, valsartan

what is an example of a calcium channel blocker

nifedipine, amlodipine

What is the action of diuretics

they will cause less aquaporins to be inserted into the tubule, there will be less reabsorption of sodium and therefore water in distal tube which will cause more excretion which allows the blood volume to reduce to decrease blood pressure

side effects of diuretics

fatigue

dizziness

headache

What is the action of adrenoreceptor blockers

alpha 1 - these will reduce the arterial pressure, the blood vessels will be under less stress and decrease blood pressure

beta 1 - these will act directly on the heart causing a reduced heart rate and stroke volume so cardiac output is lower

beta 1 - this will reduce the renin production in kidneys

what is an example of adrenoreceptor - alpha and beta

propanolol, bisoprolol - beta

prazosin, doxasosin - alpha

what is the side effects of adrenoreceptors - alpha and beta

bronchospasm - this is why they are contraindicated with asthma and COPD (beta)

bradycardia (beta)

tachycardia (alpha)

contraindications of adrenoreceptor blockers

COPD and asthma

what do small changes to radius have a profound change in

flow

Describe the process of atherosclerosis

It starts with endothelial dysfunction and a loss of protective agents such as nitric oxide

initiation of the lesion - LDL particles will diffuse across the membrane to the intima where they will be oxidised and enhance production of adhesion molecules

Monocytes will adhere here and will then become macrophages

the macrophages will then take up the oxidised LDL particles to form large foam like cells which create a fatty streak

PDGF will signal SMCs to move into the intima

SMCs and macrophages will secrete a fibrous network which will create a protective cap

SMCs and macrophages will begin to divide and will then die

SMC can no longer produce collagen due to IFN

Cellular debris will accumulate and form a necrotic lipid rich core

MMPs will break down the collagen matrix which will cause the weakling of the plaque and allows it to rupture

what are the risk factors for atherosclerosis

obesity, genetics, hypertension, hyperlipidaemia, age, gender, smoking, diet, exercise

what initiates atherosclerosis

smoking

shear stress

infection

diabetes

how is atherosclerosis diagnosed - what would be found

angiogram; measures stenosis and not plaque

intravascular ultrasound; measures plaque

CT; calcification of plaque

tunica intima - composition and role

made of endothelial cells

will detect changes to the environment such as bp and stress which allow them to produce signals for constriction or dilation

tunica media - composition and role

made up for smooth muscle cells and elastin

will contact and relax depending on the signals

tunica externa - composition and role

adipose tissue mainly but also fibroblasts (ECM secreting), immune cells, nerve cells

regulated energy metabolism and adipokine secretion

list types of artery

elastic

muscular

arterioles

function of elastic arteries

pressure buffering

what is the role of muscular arteries

blood distribution

what is the role of arterioles

bp regulation

what are haemodynamic and maladaptive causes of vascular remodelling

ageing, pregnancy

HT, atherosclerosis, heart failure

list what can go wrong when endothelial cells become dysfunctional

decreased endothelial relaxation

increased endothelial vasoconstriction

SMC hyperplasia → increased contraction

Calcification → decreased elastin

increased ECM remodelling

proinflammatory cytokines from immune cells

adipokine secretion from adipose tissue

what is the role of adipose tissue

to store fat and synthesise inflammatory cytokines and hormones

what is the role of cholesterol

to maintain membrane permeability and fluidity and also production of steroids and fat soluble vitamins

what is the role of liver in relation to cholesterol

the liver will monitor levels of cholesterol - does this via synthesis, absorption and secretion of bile

what is the composition of a lipoprotein

core - cholesterol ester, triglycerides

coat - phospholipids and free cholesterol

what is an apoprotein

stabilises lipoproteins and is recognised by specific cells

Function of chylomicrons

takes triglycerides from intestines to liver, muscle and adipose tissue

Function of VLDL

carry triglycerides from liver to adipose tissue

Function of LDL

main reservoir or cholesterol

Function of HDL

absorb cholesterol from dying cells and will take cholesterol to the liver

Outline the process of exogenous cholesterol transport

Cholesterol and TGs are combined with apoproteins in the intestinal mucosa to form chylomicrons

Chylomicrons pass into the blood stream using lymphatic system and bind to the capillary endothelium of tissues which express lipoprotein lipase

LPL will catalyse the hydrolysis of TGs to release glycerol and free fatty acids, which are taken to the cells

HDL donates apoE to chylomicrons leanings HDL empty

ApoE is essential for signalling to the liver to recognise and remove chylomicron remnants from the blood

The chylomicron remnants are broken down by the liver

Outline the process of endogenous cholesterol transport

The liver repackages cholesterol and fatty acids to form VLDLs which are rich in TGs and contain ApoB

These are released into the blood stream and circulate until they bind to capillary endothelium which is expressing LPL

LPL will hydrolyse the Tgs into glycerol and free fatty acids

VLDL is not free and will become IDL

This will produce HDL as a byproduct

The liver absorbs IDL from the blood, IDLs are then broken fown by hepatic lipase into LDL

LDL is released back into the bloodstream

It can then be absorbed by tissues but anything in excess will be reabsorbed by the liver using LDL receptors

What is familial hypercholesterolaemia

A mutation in the LDL receptors which causing excessive cholesterol in the bloodstream, can present with xanthemos, xanthalasmas, argus senilis

What is the mechanism of action of statins

They will inhibit the rate limiting step of cholesterol biosynthesis

they will be inhibitors of HMG CoA reductase, this will lower hepatic cholesterol and increase LDL receptors on surface

What is an example of statins

simvastatin

atherosclerosis treatments

meds

lifestyle management

stents

angioplasty

thrombectomy

What are the layers of the blood vessel

tunica intima, tunica media, tunica adventitia

what is the composition and role of tunica intima

senses a change in blood pressure, it will relay signals for contraction and relaxation

it is composed of endothelial cells

what is the composition ad role of the tunica media

made of vascular smooth muscles and ECM

this will cause contraction due to the muscle

what is the composition and role of adventitia

contains immune cells and fibroblasts, it responds to stress from surrounding tissue and injury

what does perivascular adipose tissue contain and its role

adipocytes, fibroblasts, immune cells, vessels and nerves

it has a role in regulating energy metabolism and adipokine secretion

what types of things are likely to cause vascular remodelling

ageing, pregnancy, HT, atherosclerosis, heath failure

what are the drives of vascular remodelling

aldosterone, proinflammatory cytokines, oxidative stress, shear stress

what do dysfunctional endothelial cells release

nitric oxide, prostacyclin, tpa - vasodilators

Et1, MCP1, PDGF, ang II - vasoconstrictors

What are the types of vascular remodelling

hypertrophy, eutrophy, hypotrophy

inward, compensated, outward

what type of remodelling will large arteries undergo and what will this cause

outward or compensated hypertrophy

this will cause elastin breakdown and hypertrophy = decreased compliance = afterload increased due to the heart having to work harder and has a stiffness

what type of remodelling will small resistance arteries undergo and what till this cause

inward hypertrophic or inward eutrophic

disruption to the distribution of collagen and nutrients which can cause end organ damage

what type of remodelling will small coronary arteries undergo and what is the consequence of this

inward eutrophic remodelling

less able to increase blood flow via vasodilation

what are the key characteristics of endothelial cells

quiescent with low levels of proliferation, low expression of leukocyte recruiting molecules, sense shear stress and mechanical stress

what happens when there is endothelial dysfunction

Downregulation of eNOS expression and NO bioavailability

Promotes leukocyte infiltration and the secretion of proinflammatory molecules eg monocytes

response to proinflammatory mediators in inc expression of adhesion molecules

become pro-constrictive, pro-inflammatory, pro-thrombic

What will activate VSMC

signalling molecules from endothelial cells and decrease of nitric oxide

What will SMC proliferation lead to

Leads to an increase wal thickness

changes ot a proinflammatory secretory phenotype

some acquire fibroblasts and some become macrophages

some express osteogenic cells which will become calcified

vessels will become stiffer

Hypertension and vascular injury

activated in response to proinflammatory signal and Ang II to become contractile myofibroblasts, excessive production of EC will cause fibrosis and result in an increased wall stiffness, they will proliferate and migrate in the vessel wall, secrete proinflammatory molecules which activate ECs, SMCs, leukocytes and macrophages

How can lipids be transported in the body

as triglycerides in lipoproteins or free fatty acids in albumin

How are lipids stored in tissues

as triglycerides

How are triglycerides synthesised

from carbohydrates and some amino acids and are regulated by insulin and noradrenaline

How are lipids digested

In the small intestine using pancreatic lipase or colipase

this will break down TGs into fatty acids and monoacylglycerides

what are bile salts

they are used to emulsify fats

they are produced from cholesterol and secreted by the liver through the bile duct

How are lipids digested

Firstly by bile salts and then digested by colipase and lipase into fatty acids and monoacylglycerides

Lipid absorption

Triacylglycerides packaged with cholesterol, apoplipoproteins to form chylomicrons which are then excreted into lymphatic system

what is chylomicron synthesis, LPL activity and storage like in a fed state

high, LPL activities is also high and storage of FFA and TG in adipose is high