Breathing, Circulation and Blood Flashcards
What is the cardiovascular system?
The cardiovascular system is sometimes called the blood-vascular, or simply the circulatory, system.
It consists of the heart, which is a muscular pumping device, and a closed system of vessels called arteries, veins, and capillaries.
What are the functions of the cardiovascular system?
- Circulates OXYGEN and removes Carbon Dioxide.
- Provides cells with NUTRIENTS.
- Removes the waste products of metabolism to the excretory organs for disposal.
- Protects the body against disease and infection.
- Clotting stops bleeding after injury.
- Transports HORMONES to target cells and organs.
- Helps regulate body temperature.
How would desrcibe the pumping system?
Double pump system
1. Pulmonary circulation
2. Systemic circulation
Note - Systemic system is smaller and operates at a lower pressure, while the pulmonary circulation is larger and operates at a higher pressure.
In terms of fluid in the body, what proportion is located intracellularly and extracellularly?
Intracellular fluid - 2/3 - ~24L
Extracellular - 1/3 - ~9L
Intravascular (forms part of the extravacular fluid) - 25% ~3L
What is Poiseuille’s Law and what can it tell us about blood vessel diameter?
Equation for flow (Q) through a rigid tube (radius r, length L) due to a
pressure gradient (Pin-Pout)
As we can see from the equation - the flow rate Q is directly proportional to the radius of the blood vessel - Q ∝ r^4
Also… viscosity will have a (smaller) effect - inversely proportional - Q ∝ 1/n
Can we see differences in blood vessel diameter in the cardiovascular system?
Yes, vessel internal diameters vary over a 3000-4000 fold range - which has implications for flow rate
Wider diameter - increased flow rate - visa-versa
Explain what these two graphs are trying to show.
Shows the patterns in vessel diameter and cross-sectional area
Arteries and Veins - largest diameter - increase flow rate to and from the heart
Capillaries high levels of branching – resulting in increased cross –sectional area
Outline the changes in blood pressure and velocity in the different types of blood vessels.
Highest pressure in the arteries - heart action
Substantial drop in pressure in the capillary bed
Pressure lowest in venous vessels - venae cavae
Velocity - vessels with the greatest radius have the highest velocity
What is an important thing to keep in mind when thinking about blood pressure across the systemic circulation?
Two pressures - systolic and diastolic
Pressure highlights pulsatile nature of blood flow
Pressure differneces dampens as you move away from the aorta
Explain what this diagram is showing.
Shows composition of the elements of in the vascular wall
Arteries – elastic tissue, smooth muscles and increased wall thickness
Capillary wall - minimal elements – allows diffusion
Veins - Lower less of elastic tissue and reduced wall thickness
What is pulsatile contraction and why is it important?
Refers to the recoil/elastic action of the artery walls that propels blood forward when the heart is not beating (diastolic) - allows for continuous flow
Outline the importance of smooth muscle in arteries.
Muscular tone plays a roles in regulating the circulation & regional flow - allows for the precise control of fluid in tissue beds
Walls of smaller arteries, arterioles have more muscular (less elastin) than aorta
Vascular smooth muscle ~ always has basal vascular tone
Systemic and Local regulators are used to alter tone
- at systemic level – altering blood pressure – ‘resistance vessels’
- at local level – modulate local blood flow (arterioles, pre-capilliary and sphincter)
Release of vasodilators and vasocontrictors
Examples of key vasodilators and vasocontrictors that act on smooth muscle?
Vasoconstrict –> alpha1-adrenergic receptor (sympathetic nerves), AngII, Endothelin and other circulating mediators
Vasodilate –> Beta2-AR receptor (parasympathetic nerves), Histamine, NO (nitric oxide) and prostaglandins PGE2 and prostacyclin
Adrenaline signals via alpha1 and Beta2 receptors
Note there are also local paracrine effects
- Stretch itself – myogenic response
- Local chemicals especially - decreased interstitial pO2, increased pCO2, decreased pH –> vasodilate (opposite to pulmonary)
- [K+], lactate, ATP/ADP/adenosine
What are the different layers that make up arteries?
T. Intima – endothelium Internal elastic lamina
T. Media – muscular, and elastic fibres (External elastic lamina)
T. Externa – adventitia – supportive
connective tissue layer, protects vessel
What are two distinguishing features of veins when compared to arteries?
- Veins have valves to prevent backflow
- Vein appear partially collapsed whereas arteries do not in a histological section -
What is the relationship between volume/flow rate and pressure in the aorta and vena cava?
Aorta - Increases in aortic pressure result in a directly proportional increase in flow -
Note - change in gradient around (less steep at higher pressures) meaning that a change in pressure will driver a smaller change in volume
Vena Cava - Logarithmic relationship between pressure and volume change - indicating that a small change in pressure results in a significantly greater increase in volume
General terms, which of the two circulations will have the greatest volume of blood moving through it? Also how does the volume between the heart and pulmonary circulation differ?
The systemic circulation carries the greatest circulatory volume - ~84%
Whereas the pulmonary circulation has around 8.8% of the total blood volume
This is quite similar to the amount present in the heart - ~ 7.2%
What is the prinicipal function of capillaries? What are the different types?
Thin cell wall - allows for the movement of fluids/nutrients/gases between the blood and the surrounding tissue
Various levels of adaptation depending on the tissues requirements
1. Continious - Nervous tissue, muscles, skin, fat, etc.
2. Fenesterated - Kindeys, endocrine glands and small intestine
3. Sinusoid - mainly found in the liver
What forces determine whether molcules diffuse in or out of capillaries?
Depends on the balance between osmotic pressure retaining fluid and hydrostatic pressure drive fluid out - known as starling forces
- Arterial end –> hydrostatic pressure is greater than the osmotic - drives outward movement - hydrostatic pressure
- Venous end –> osmotic pressure exceeds the hydrostatic pressure - net flow inwards - ontonic pressure
Equation - flow determined by the permeability times the hydrostatic gradient minus the oncotic gradiet
How can we get oedema and what are the different causes?
High hydrostatic pressure - high levels of fluid moving into the interstitium - oedema
This can happen when…
1. There is heart failure
2. Venous obstruction
3. Incompetence in valves in veins
Anything that drives up venous pressure can lead to this
Low oncotic pressure - less force pushing fluids into the circulation
This can happen when…
1. There is protein loss - nephrotic syndrome or protein losing enteropathy
2. Protein synthesis drops - hepatic disease or failure, malnutrition, acute illness
- Reduced oncotic pressure typically due to hypoalbuminemia - albumin is a main driver of oncotic pressure
Note - Oedema can also occur when…
1. There is capillary dysfunction
2. Lymphatic dysfunction
How does oedema present itself in patients?
Interstitial fluid moves with gravity
1. Ankle Oedema - Swelling of ankles, standing –> increasingly when standing/sitting
2. Sacral oedema – when in bed, overnight – easier to miss
Pulmonary oedema also possible - serious consequences for gas exchanges
Gets worse when lying flat – orthopnoea, paroxysmal nocturnal dyspnoea (PND)
What are some different aspects of the circulatory system that will be touched upon later in the course?
- Kidney - excretion, autoregulation
- Gut - Liver (2 blood supplies)
- CNS - autoregulation, blood brain barrier (BBB)
- Fetal circulation + change at birth
Identify/Name all the different parts of that make up the heart.
Outline, generally, what happens during diastole and systole.
Diastole - filling phase – ventricles fill with blood - contraction of atria pushes blood into the ventricles - marks the end of diastole
Systole - ejection phase - ventricles contract, closing AV valves (preventing backflow into atria) and opens the semi-lunar valves when the pressure exceeds the arterial pressure – valves open –> blood flows out of the heart
When ventricualr pressure drops below aoritc pressure the semi-lunar valves close and we repeat the pumping cycle.
What are the different elements of the cardiac conduction system?
Two main nodes - SA node and the AV node
SA node is the master node which intiates the contraction of the heart - pacemaker
What differentiates the two atrio-ventricular (AV) valves?
Right side of the heart - receiving systemic circulation - tri-cuspid valve
Left side of the heart - receiving pulmonary circulation - bi-cuspid valve
What are the 4 different steps of the cardiac cycle (make sure to outline the activity of the valves at each stage)?
Explain what is happening in the attached diagram.
Note - Isovolumic contraction and relaxation refers to the activity of the ventricles
What is the definition of stroke volume, heart rate and cardiac output?
Stroke volume - volume ejected per heart beat
Heart rate - number of heart beats per minute
Cardiac output - total volume ejected by the heart in 1 minute = Stroke volume (SV) x Heart rate (HR)
Note that within 1 minute most of the blood circulate around the body - so cardiac output can be said to equal venous return
What is meant by preload?
Preload - refers to the amount of load that comes into the heart
Venous return = preload to the cardiac pump
Tell us how much blood is present in the ventricles at the end of diastole
Hence….
Higher preload means higher stroke volume and thus higher cardiac output - simply put… higher pre-load means that the heart pumps more effectively - more blood moving through the system
What are two factors that effect preload?
Preload affected by…
1. Venous capacitance (sympathetic NS effects) - degree of active constriction of vessels (mainly veins) which affects return of blood to the heart and thus cardiac output
2. Venous filling – rise in plasma volume and extracellular fluid rising - e.g. because of more water retention by the kidneys
What is the Frank-starling mechanism?
Mechanism that describes how a higher pre-load results in a higher cardiac output
Important as it….
1. Ensures that the heart can deal with wide variations in venous return
2. Also for balancing of the outputs of the two sides of the heart
How does it work?
Higher Preload results in higher CO as the stretch of ventricles with a higher preload drives an increase in CO
Other intrinsic mechanisms at play…
Intrinsic rate-induced regulation – allows increased cardiac force to develop at higher heart rate –> largely via changes muscle Ca2+ dynamics + sensitivity - resulting in increased cardiac force
Note - this increase plateaus at a given point - preload too high - beginning of heart failure
What is the equation that relates cardiac output to aterial blood pressure and total peripheral resistance?
CO influenced by resistance
If resistance rise we require higher blood pressure in order to maintain output
Explain how homeostatic mechanisms that help to restore Cardiac output and arterial blood pressure may excerbate heart failure?
Reduction in cardiac function - drives homeostatic mechanisms to restore CO + ABP via neuroendocrine activation – which can exacerbate heart failure
Why?
- Baroreflex - drive venoconstriction - increases preload - increase CO
- Activation of Renin-AngII system - also drives vasocontriction - increases afterload/resistance
- Also an increase in water retention - driving up blood pressure –> increasing preload
Normal adaptations that are present to keep the heart working but if the heart is near failing - this may stress the system as the heart has to work more
Treatment to – block sympathetic NS, block Renin-AngII, and reduce ECF with diuretics may all be useful.
What are the 4 steps that form part of the viscious cycle of heart failure?
Outline what happens with O2 and CO2 in the lungs and tissue? What adaptations ensure maximum O2 is taken up in the lungs and that O2 is delivered to ischaemic tissues?
Uptake of O2 and removal of CO2 in the pulmonary circulation
Release of O2 and uptake of CO2 in the systemic circulation
Uptake of O2 is faciliatate in the lungs as the pulmonary arterioles and small arteries dilate in the presence of high O2 - higher levels of blood level in areas of high oxygenation
Conversely, systemic arterioles/small arteries dilate with decreases in pO2, decreases in pH and increase in CO2 - basically, this increases blood towards ischaemic tissues
In longer term new vessels form in response to same stimuli to meet demand – adaptations
Other local factors (eg NO) and systemic signaling (eg CNS) regulating local/regional perfusion (passage of fluid) – systemic adaptations directing blood flow
Also on a systemic level we have baroreceptors and chemoreceptors which influences the CV system
Highlights the different levels at which the CV system is self-adapting
What are some risk factors for atherosclerosis and coronary heart disease?
What are the different types of heart diesease?
What is vasculitis?
Inflammation of vascular segments
Different types include…
1. Large vessel vasculitis
2. Medium vessel vasculitis
3. Immune complex small vessel vasculitis
4. ANCA- associated small vessel vasculitis
What are the different organs/systems we need to thinking about when talking about breathing/respiration?
- Lungs - gas exchange
- Heart - engine - pumping of blood
- Blood - transport of gases
- Brain - control center
What region in the brain controls our breathing rate?
Breathing controlled by breathing pacemaker in medulla – located in the brain stem - back-up breathing mechanism as this regulation occurs without conscious awareness
Known as the respiratory pacemaker
What are the three main variables that dictate/influence our breathing rate?
Partial pressure of CO2 - detected by central chemoreceptors
Partial pressure of O2 and Blood pH - detected by peripheral chemoreceptors (located in the carotid artery)
Note the body is most sensitive to changes in pH/CO2 changes in the blood rather than oxygen levels
Describe the O2 dissociation curve and the factors that cause it to shift.
Oxygen haemoglobin dissociation curve highlights the cooperative binding nature of Hb - sigmoidal shape
At high O2, low H+/high pH, low CO2, low temperature, low 2,3 DPG –> left shift in the O2 dissociation curve –> favours uptake of O2 at lower pO2
At low O2, high H+/low pH, high CO2, high temperature, high 2,3 DPG –> right shift in the O2 dissociation curve –> favours release of O2 at higher O2 concentrations
How is CO2 transported to the lungs?
Some CO2 also dissolves in the plasma
But most of it diffuses into red blood cells and gets converted into carbonic acid (H2CO3) by carbonic anhydrase, which then dissociates releasing an H+ and HCO3-
Following this we get what is called the Chloride shift - HCO3- is transproted out of the RBC in exchange for a Cl- ion.
Reverse process happens in the lungs in order to release CO2
What is normally measured in an arterial blood gases measurmenet?
- PaO2
- PaCO2
- Hydrogen ion/pH
- Bicarbonate
- Some analysers may also measure electrolytes and Hb
Other forms of haemoglobin:
Carboxyhaemoglobin – CO poisoning
Levels of gases remain constant between people in the population - utilization of gases is what differs
Note
PA= partial pressure in alveolus
Pa= partial pressure in arterial circulation
What happens during asthma? Why does this limit the amount of oxygen into the lungs?
Airway inflammation - constriction of airway (eosinophils and other immune debris also accumulate) – prevents adequate air flow
Inflammation, constriction of airways, mucus production –> all lead to airway obstruction
What happens in cystic fibrosis? Why does this limit the amount of oxygen into the lungs?
Cystic fibrosis – progressive lung obstruction
Abnormal Cl- channel – resulting in excessive mucus accumulation in the airways
New drugs targeting this underlying protein transporter
Median survival has increased to the mid 50’s
What happens in chronic obstructive pulmonary disease? Why does this limit the amount of oxygen into the lungs?
COPD - smoking related – airway inflammation (vasoconstriction) and increased mucous production, as well as destruction of alveoli (break down of connective tissue) - reducing the movement of air
Driven by a inflammatory in response to inhaled irritants
Explain how pneumonia can block adequete gas exchange?
Pneumonia – classic cause - build up of fluid in alveoli – impacts gas exchange
Causes a V(ventilation)/Q(perfusion) mismatch - treatment by increasing oxygen supply to prevent V/Q mismatch
Explain how pulmonary fibrosis can block adequete gas exchange?
Interstitial lung disease - Pulmonary fibrosis involves gradual exchange of normal lung parenchyma (tissue) with fibrotic tissue.
The replacement of normal lung with scar tissue causes irreversible decrease in oxygen diffusion capacity
Causes - autoimmune, viral infections, bacterial infection and idiopathic
What is one main reason why not enough blood is reaching the lungs, resulting in breathlessness?
Not Enough Blood: Pulmonary Embolism
Can cause right heart failure - strains heart
What are the different components that make up blood?
Breakdown the sturcture of haemoglobin
Important role - haemoglobin increase oxygen carrying capacity of blood 70-fold
Haemoglobin = haem + globin
Haem = iron bound to porphyrin ring –> iron reversibly binds to O2
Globin = protein chains that bind haem
Each hemoglobin A (HbA) (~95% in adults) molecule is made of…
1. 2 alpha globin chains
2. 2 beta globin chains
What does the oxygen-haemoglobin dissociation curve show? What is the Bohr effect?
Important concept: oxygen-haemoglobin dissociation curve - plots the % of haemoglobin saturated with oxygen vs. oxygen tension (pO2)
Bohr Effect - the effect of CO2 of this curve
Lung alveoli
pCO2 in lung is lower than tissue + higher local pH + lower temperature + lower 2,3-DPG–> increases haemoglobin’s affinity for oxygen/left hand shift–> favouring the generation of oxyhaemogobin and delivery of oxygen away from the lungs
Body tissues
pCO2 in lung is highter than tissue + lower local pH + higher temperature + higher 2,3-DPG –> decreases haemoglobin’s affinity for oxygen/right hand shift –> favoring dissociation of oxygen from oxyhaemoglobin, releasing oxygen to tissues
Note - temperature is a regulator of Hb-O2 affinity (higher metabolic rate in tissues resulting in the release of thermal energy) + 2,3-diphosphoglycerate also decrease Hb affinity by binding to the Hb favouring O2 release
Provide an overview of how RBCs are created
Process of erythropoiesis (aka red blood cell production) begins from haemoapoetic stem cells in the bone marrow
Sequential maturation steps; increase haemoglobin in the cytoplasm and then ultimate ejection of the nucleus
Need to make ~2 million red blood cells / second
Fetus – liver – factory for RBCs
Non-fetus - bone marrow factory for RBCs
Outline the metabolism of iron and why its deficiency results in anemia?
Iron is taken in via the diet and use to produce haemoglobin and myoglobin
Iron can also be stored in the liver and recycled from old RBCs
But Iron is also lost from the body from muscosal cells, desquamation, menstruation and other blood loss - hence, it needs to be taken in via the diet
Low iron –> reduce haem synthesis –> less Hb –> small, pale red cells with decreased O2 carrying capacity - fewer and less capable cells
What are two disorders that negatively impact RBCs ability to function properly - Cell Intrinsic?
RBC defects
Rare set of disorders
- Cell membrane defects (right picture) - problem caused by defective membrane anchoring proteins – EG hereditary spherocytosis (rare & hereditary) – sphere shaped RBC – less flexible, more vulnerable to osmotic stress (increased levels of breakdown) - reduced RBC count and release of waste products
- Red blood cell enzyme production problems (left picture)
Increases oxidative stress – G6PD deficient – most common enzyme deficiency globally - increases levels of oxidative stress - oxidative destruction of RBCs – resulting in shorter lifespan = fewer RBCs
What is one disorder that negatively impact RBCs ability to function properly - haemoglobin variant?
Sickle cell
Inheritance abnormal beta globin chain (both copies)
Red cells that change shape or “sickle” when in their deoxygenated state
Lots of important consequences to this but includes increased breakdown + likely to obstruct/block blood vessels –> reducetion in O2 delivery
Heterozygous - sickle cell trait
Homozygous - sickle cell disease
What are the clinical consequences of anemia?
↓ RBC production / RBC lose
↓ Reduced Hb carriage
↓ O2 transport
Breathlessness response to anaemia - why?
Complex mechanism involving:
1. Increased cardiac output; to increase blood circulation and oxygen delivery - ventilation increases to match V/Q mismatch
2. Detection of hypoxia by specialised receptors in tissue, acts centrally
Severe anemia – fainting, chest pain, angina and heart attack
