Breathing Flashcards
(109 cards)
1
Q
What is respiration?
A
Includes two processes:
External respiration, the absorption of O2 and removal of CO2 from the body as a whole;
Internal respiration, the utilization of O2 and production of CO2 by cells and the gaseous exchanges betweenthe cells and their fluid medium
2
Q
How is breathing controlled spontaneously?
A
In the brain, the medulla controls spontaneous breathing, it is where respiratory pacemaker lies.
Central Chemoreceptors detect CO2 concentration;
Peripheral Chemoreceptors detect CO2 concentration and blood pH;
Both chemoreceptors feedback to brain stem respiratory centres, so increased CO2 and acid during exercise causes more breathing.
We can override this to an extent but respiratory pacemaker is a fail safe - you’ll eventually pass out and return to spontaneous breathing if you hold your breath.
3
Q
Why do we need gas exchange?
A
To get oxygen to tissues and CO2 away from it.
4
Q
What enables pulmonary gas exchange in the lungs?
A
Adequate ventilation (air going into lungs) and perfusion (adequate blood entering lungs that can be oxygenated).
Mainly due to diffusion of gas across the alveolar-capillary membrane. Thin walled alveoli and thin walled capillaries in contact allow for this.
5
Q
How do we carry oxygen in the blood?
A
We have haemoglobin in the blood - a tetramer with 2 alpha and 2 beta subunits, each of which has a Haem group (a porphyria with a central Ferrous atom).
The Oxygen binds to the Ferrous atom when they come into contact, initially loosely.
Once one Oxygen has bound, easier for it to bind to the other haem groups on the other subunits as the initial combination alters the shape of the haemoglobin, making it more efficient in binding to oxygen.
6
Q
What is the Oxygen-Haemoglobin dissociation curve?
A
Compares haemoglobin-oxygen saturation at different concentrations of oxygen. Steep curve - only 1 of 4 of the possible O bound at very low concentrations but sharply increases after 1 has bound to all possible bound.
7
Q
What does a right shift in the oxygen haemoglobin dissociation curve mean?
A
The haemoglobin has less affinity for oxygen so gives it up more readily.
8
Q
What causes haemoglobin to have a lower affinity for oxygen?
What does it do to the haemoglobin oxygen dissociation curve?
A
Increase in CO2
Increase in [H+] (pH)
Increase in temperature
Increase in 2,3-DPG (metabolite)
These all happen in muscles during exercise.
This shifts the oxygen-dissociation curve to the right.
9
Q
How is carbon dioxide carried in the blood?
A
Main way is by CO2 dissociating with water to form H2CO3 which further dissociates into H+ and HCO3- to be carried in blood.
Dissolves back into CO2 and goes down concentration gradient into lungs and expelled into alveolar space.
A small amount will also be bound to haemoglobin and a small amount bound to amino acids in body system but most dissolved.
10
Q
Why do we need oxygen?
A
Essential for aerobic respiration (glycolysis to get ATP).
11
Q
What is required for adequate oxygen?
A
A supply of oxygen, working lungs, working heart, haemoglobin.
12
Q
What happens at higher altitude to partial pressure of oxygen?
A
Lower partial pressure.
Should be about 21 kPa at sea level.
13
Q
How do we quantify oxygen carriage?
A
Non-invasive: haemoglobin saturation (oxygenated haemoglobin is red and uses absorption spectroscopy so as long as Hb is normal, accurate)
Invasive: arterial blood gas (more complicated but if Hb is abnormal good as detects overall oxygen levels and CO2 levels in blood as well as saturation, also pH, bicarbonate, electrolytes and other form of haemoglobin)
14
Q
Not enough oxygen getting into the lungs is a way that respiration can go wrong.
What are some reasons this can happen?
A
High altitude or low Oxygen environments like industrial accidents.
Diseases that obstruct flow of air (and so oxygen) to alveolus which cause not enough gas getting across airway, something in way of gas exchange (acute inflammation/pus/water), chronic alveolar thickening (pulmonary fibrosis);
Asthma causes an inflamed airway so not enough gas can get across airway,
Cystic Fibrosis causes mucus build up and inflammation in airway,
COPD increased mucus and destruction of alveoli and connecting tissue so collapse of conducting airways,
Pneumonia causes inflammation (narrowing airways), damage in the small airways and alveoli (fluid in alveoli). This means not enough oxygen gets into the blood, causing ventilation to perfusion (V/Q) mismatch - treat by increasing oxygen provision.
15
Q
What is asthma?
A
Asthma causes basement membrane and smooth muscle thickening of the alveoli so not enough gas can get across this narrowed airway since it’s thicker and inflamed.
Treat with bronchodilators.
16
Q
What is cystic fibrosis?
A
Cystic Fibrosis causes mucus build up and inflammation in airway, making it harder for oxygen to get in to alveoli.
We now have drugs that call alter the mutated protein in CF.
17
Q
What is COPD?
A
COPD increased mucus and destruction of alveoli and elastic fibres in the lung so collapse of conducting airways, limiting airflow.
Treat with bronchodilators.
18
Q
What is Pneumonia?
A
Pneumonia causes inflammation (narrowing airways), damage in the small airways and alveoli (fluid in alveoli). This means not enough oxygen gets into the blood, causing ventilation to perfusion (V/Q) mismatch.
Dense shadowing on x-ray since alveoli full of pus and fluid.
Treat by increasing oxygen provision and if bacterial, give antibiotics.
19
Q
What is pulmonary fibrosis?
A
Causes chronic alveolar thickening, preventing adequate gas exchange.
See as shaggy shadowing on x-ray.
20
Q
What is pulmonary oedema?
A
Extra fluid in the lungs because heart isn’t pumping properly, meaning fluid in way of gas exchange at alveoli.
Shadowing on x-ray but outline of lungs normally quite clear.
Treat with diuretics.
21
Q
What is a pulmonary embolism?
A
Blood clots move into lung and block deoxygenated blood getting to area where it’s oxygenated.
Some shadowing and darkness on an x-ray as where blood isn’t getting to the lung, darkness. But normally we use CT scan - darkness on area is clot where tracer is so should be bright (pulmonary artery).
Treat with anti-coagulators.
22
Q
How is oxygen therapy given?
A
Variable performance masks are cheap but the exact inspired O2 concentration is not known.
Fixed function masks have constant, known inspired concentration.
Reservoir mask have high inspired concentration of Oxygen.
Invasive Ventilation is required for severe respiratory failure not responding to oxygen therapy.
Generally treat with oxygen alongside trying to treat cause.
23
Q
What is Invasive Ventilation?
A
Invasive Ventilation is required for severe respiratory failure not responding to oxygen therapy, but it is not a suitable treatment for all patients and is provided in intensive therapy units.
24
Q
What does the circulation do?
A
Allows oxygen and CO2 to go to cells and be taken away, provides cells with nutrients, allows waste products to be taken away, also allows for metabolism, immune system, circulating hormones, body temperature regulation…
25
What are the two circulatory systems?
Pulmonary - smaller, arterial pressure of about 25/10mmHg, only lungs
Systemic - much larger, arterial pressure of about 120/70, all of body
Side note: there is circulation systems involving circulatory fluids like lymph as well as blood.
26
Aside from the heart, what controls circulation?
Brain and kidneys
27
Describe distribution of fluid in the body.
We are 60% water.
1/3 of that is extracellular, 2/3 intracellular.
25% of extracellular fluid is intravascular fluid (plasma), 75% extravascular (interstitial).
So of a 60kg body, 36L fluid, 3L of plasma.
28
What is the haematocrit?
Ratio of blood plasma and blood cells present. Broadly 55% plasma, 45% cells.
[Haematocrit: in men it’s actually 0.4-0.52, in women 0.36-0.47]
29
What is the circulating volume in an average adult?
5 litres (3L plasma, 2.4L blood cells, roughly)
30
What does the lymphatic system so?
Mops up any fluid not taken back up by small veins and return it to the large veins.
31
What is laminar flow?
How does this relate to blood vessels?
In a tube, fluid won’t flow equally across the tube. This is due to friction at the walls, so closer to centre has a greater flow.
This is governed by Poiseuille’s Law (flow through a rigid tube is due to a pressure gradient) and most greatly influenced by the radius, but also by the liquid’s viscosity and the tube length.
Means vessel size will have a dominant effect on the flow through them, more so than viscosity/length.
32
What are resistance vessels?
Arterioles and the smallest arteries.
They have small diameters and many branches.
33
Where is there a bottleneck in the vascular system?
Why is this?
Bottleneck at the arterioles.
This is because as well as having a small radius, they are not very numerous (capillaries and venules have many branches which overcomes their small radii).
The cross-sectional area increases greatly in the capillaries and venules.
34
How does the velocity of blood flow change across the vasculature?
Why is this useful?
Greatest in the arteries, then decreases at the arterioles, slowest in capillaries and then increases again in veins.
This means tissues bathed carefully in the fluid so function of gas exchange can be fulfilled.
35
How does the blood pressure change in the vascular system?
Continuously decreases but pressure drops with greatest gradient across the arterioles.
Pulsitivity of the pressure also decreases as the arteries get smaller until continuous flow at end of arterioles.
36
What function do veins have that compensate for their low pressure?
Valves
37
What tissue type is present in capillaries?
Only endothelium - this allows for greatest diffusion.
38
Which vessels ave a greater proportion of elastic tissue?
Why is this useful?
Larger arteries as they are closest to the heart which is a pump.
This means there is elastic recoil, propelling fluid forward in between cycles (each pump of the heart), dampening down the pulsatile swings very effectively so by the time it reaches the arterioles it’s much weaker and by the time it reaches small arterioles and capillaries, it has gone and there’s a continuous flow.
39
What types of tissues are present in the venous system?
In venules, only epithelium and fibrous tissue.
In veins, have epithelium, elastic, smooth muscle and fibrous tissue but much less than in arteries. This allows for them to be less sprung open than arteries to allow them to absorb changes in blood volume.
40
What types of vessels have muscular tissue?
What is the benefit to this?
Smaller arteries and arterioles.
These have a basal vascular tone which allows them to respond to systemic and local regulators by altering their tone.
Systemic regulators can alter blood pressure, especially in resistance vessels.
Local regulators modulate local blood flow, providing more blood to where there’s a greater need, especially in arterioles and pre-capillary sphincter.
41
What is the structure of arterial walls?
Tunica intima - endothelium and internal elastic lamina (keeps it sprung)
Tunica media - smooth muscle (sometimes elastic lamina beyond that in larger vessels)
Tunica external - loose connective tissue
(This is from deep to superficial)
42
What regulates vascular tone in smooth muscle in vessels?
Adrenaline and noradrenaline which act on alpha-1-adrenergic receptors (vasoconstrictive - increase blood pressure, reducing blood flow) and beta-2-adrenergic receptors (vasodilators - decrease blood pressure, increase blood flow).
Other vasoconstrictors are Angiotensin2, Endothelin, inflammatory mediators…
Other vasodilators are Histamine (like in allergies) which can be released and cause swelling, nitric oxide, prostaglandins…
43
What changes local to a muscular vessel cause vasodilation?
Interstitial pO2 decreasing, pCO2 increasing, pH decreasing.
These have the opposite effect in the pulmonary system.
44
What makes veins more collapsible than arteries?
Why is this important?
Contain less elastin tissue so they’re less sprung and can collapse more easily.
This means veins can respond more to changing volume/pressure.
45
What equation is the filtration and absorption and the capillary bed described by?
The Starling equation:
Fluid movement (Qf)=k[(Pc−Pi)−(πp−πi)]
where Pc, Pi = hydrostatic pressure in capilliary,interstitium; πp, πi = oncotic pressure of plasma, interstitial fluid; k=capillary filtration constant
46
What are capillary walls made of?
Selectively permeable membrane of one layer of endothelial cells (so only have tunica intima) so blood cells can pass through.
Some have specialised holes developed called fenestrations, and complete gaps called sinusoids (only in the liver) that allow lager things to cross. But this is unusual.
47
What is hydrostatic pressure?
The pressure from the blood/vasculature, pushing it out of the vessel.
48
What is oncotic pressure?
The drag of proteins retained within vascular space through osmotic forces to restrict fluid leaving vessels.
49
What is the pressure balance at the arteriole end of the capillary bed?
Larger hydrostatic pressure (roughly 35mmHg), smaller osmotic pressure (25 mmHg) so net outflow of about 10mmHg out of capillary into tissue.
50
What is the pressure balance at the venule side of the capillary bed?
Larger osmotic pressure (roughly 25mmHg), smaller hydrostatic pressure (15 mmHg) so net inflow of about 10mmHg out of tissue into capillary.
51
What is oedema?
What causes it?
Where do we see this clinically?
Detectable interstitial fluid that’s in excess of normal.
Hydrostatic causes - heart failure (not enough arterial pressure), venous obstruction, incompetent valves
Oncotic causes - loosing proteins cause fluid to leave circulation easier (diseases like nephrotic, protein loosing enteropathy), less protein synthesis
Increased capillary permeability - often in infection (oedema often coincides with inflammation)
Lymphatic dysfunction - lymphatic contribution is less
See this clinically as;
Peripheral oedema - ankle swelling/sacral/back, goes with gravity
Pulmonary oedema - in pulmonary system it goes into interstitial spaces, can hear crackles in the lungs; can be worse when lie flat (paroxysmal nocturnal oedema - PND)
52
What controls the filling of blood in the heart?
The valves - they close once pressure is equal on both sides.
53
What is diastolic?
What is systole?
Diastole is the relaxed state of the heart.
Systole is the contacting state of the heart. Usually refers to ventricular systole but there is an atrial systole too.
54
What are the heart valves?
What do they do?
Antroventricular (R - tricuspid, L - mitral) and semilunar (R - pulmonary, L - aortic)
They prevent backflow of blood during contraction.
55
Describe the blood vessels connected to the heart.
2 vena cavas (inferior and superior) going into the right atrium. Blood travels from right atrium to ventricle (past tricuspid valve) and out through the pulmonary artery which takes it to the lungs (past pulmonary valve).
4 pulmonary veins collect the blood from the lungs to the left atrium. Blood travels into the ventricle (past mitral valve) and out through the aorta (past aortic valve).
56
Where is the pacemaker of the heart?
What does it do?
The sinoatrial node.
From here signal goes to A-V node (then into A-V bundle) at the septum and spreads around the tissue via purkinje fibres.
57
What do the tendons/cords attached to A-V valves do?
Anchored in papillary muscles on ventricular surface.
Slight contraction in these muscles combine with the tensile strength of the tendon means when ventricles contract, billowing part of the valves stay in place, shutting it perfectly.
58
What is the cardiac cycle?
1) Atrial fills and ventricle fills rapidly as antroventricular valves open (diastole)
2) Passive slower ventricular filling as pressure is slightly higher than before (diastole)
3) Atrial systole pushing further blood into ventricles
3.5) Antrovenrticular vales shut - first heart sound
4) Ventricular systole and semilunar valves open, blood pushed into arteries
4.5) Semilunar valves shut - second heart sound
Cycle repeats.
Pulse happens between first and second heart sounds at step 4.
59
What is stroke volume?
What is a typical value?
The amount of blood ejected per beat of the heart. About 70ml at rest in a healthy adult.
60
What is heart rate?
What is an average vale?
How many times the heart beats per minute. About 70bpm in a healthy adult.
61
What is the cardiac output?
How is it calculated?
It’s the amount of blood ejected by the heart per minute. About 5L/min in a healthy adult.
Heart rate x stroke volume
(CO=HRxSV)
Arterial blood pressure / total peripheral resistance
(CO=ABP/TPR)
Cardiac output has to be the same as venous return in a steady state.
62
What is venous return?
The amount of blood entering ventricles in diastole; the preload to the heart. Should be the same as the cardiac output.
63
What happens if preload to the heart increases?
What has an effect on preload?
Stroke volume will increase so cardiac output increases (sometimes heart rate increases too).
It is affected by the circulating volume, venous capacitance (contraction of veins by sympathetic/autonomic nervous system).
64
What happens to preload in heart failure?
Heart can’t meet increased demand if preload increases (which it often will) so there is an increased back pressure (venous pressure), the blood dams back leading to higher pressure at end of capillary beds.
Starlings forces mean the drop of pressure across capillary beds is less, so more fluid tends to exit the capillary beds and not return, leading to oedema.
65
What is the Frank-Starling mechanism?
As preload increases, heart has an intrinsic ability to respond by increase cardiac output/stroke volume. However it eventually reached capacity, and once the heart is pushed beyond capacity it can’t cope and starts to fail so cardiac output falls.
66
What is intrinsic rate-induced regulation?
Intrinsic mechanism affecting preload, weaker than Frank-Starling, meaning a heart going at a faster rate can generate a greater force.
It allows increased cardiac force to develop at higher heart rate, when preload increases, allowing a higher cardiac output to be generated.
It is largely via changes muscle Ca2+ dynamics and sensitivity.
67
How is the heart regulated extrinsically by the autonomic nervous system?
Autonomic nervous system can anticipate the need for exercise, making feel anxious, heart rate faster, breathing rate faster so more ready to exercise.
Parasympathetic nervous system (through Vagus nerve) has autonomic input to slow the heart rate.
Sympathetic nervous system, related to adrenaline has autonomic input to increase the heart rate.
68
What happens to the intrinsic heart rate when you get a heart transplant?
What does this show?
Average heart rate is faster (100bpm instead of 60-70bpm in normal).
Show at rest, bigger vagal parasympathetic tone at rest to keep it lower (lowers to more normal 60-70bmp) but coordinated autonomic response by sympathetic nervous system can happen very quickly, getting a rapid rise in heart rate.
69
What reflexes affect the heart (extrinsic)?
Baroreceptor reflex - responds to reduction in cardiac output, so if blood pressure drops, autonomic response is to vasoconstrict to increase return of blood into the circulation, directly stimulating heart rate increase as preload rises.
Other weaker reflexes;
Chemoreceptors - blood is deoxygenated so sensors in arterial system and brain pick up the higher acid CO2 levels, causing brainstem to increase CO and respiratory rate.
Bainbridge reflex - volume sensors pick up drop if blood volume in venous tree, increased sympathetic response.
Respiratory effects - deep breath causes pressure in lung cavities to go below atmospheric level, effecting blood flow within chest and heart
70
What circulating factors affect the heart (extrinsic)?
Adrenal Medulla releases adrenaline.
Atrial Natriuretic Peptide, made in atria of the heart affects CO slightly, as well as kidney function.
Other hormones can affect CO also.
These all coordinate so if loose a lot of blood (like in car accident), autonomic NS, intrinsic and extrinsic mechanisms all increase chance of survival.
71
What is the relationship between blood pressure and cardiac output?
What is the other factor of this relationship?
Generally, as CO increases, blood pressure increases.
Resistance of the vasculature (total peripheral resistance) also plays a part as the relationship is CO=ABP/TPR.
This means if the surface area of vessels is greater like vasoconstricted (causing increase in resistance), you need a greater blood pressure to get the same cardiac output.
If someone gets circulatory shock, very dilated blood vessels, blood pressure may get dangerously low.
72
What is afterload?
The pressure the heart is working against when ejecting blood out during systole. Valves close when pressure is equal on either side.
Determined by the peripheral resistance due to aggregated tone/damage to resistance arterioles. This affects CO and ABP - for same CO, if afterload increases then blood pressure must increase.
73
What happens in heart failure?
Maladaptation which actually reduces cardiac function.
74
What are some ways maladaptation happens when cardiac function is reduced?
Neuroendocrine system activates;
The Baroreflex - sympathetic NS causes vasoconstriction which increases preload (not helpful)
The Active Renin-Angiotensin System - releases ang2 which causes vasoconstriction leading to increased afterload as well as it being a stimulator itself and releasing aldosterone which causes increased Na and water absorption in the kidneys, which increases preload.
75
What are some treatments for heart failure?
Block sympathetic NS with beta blockers, Renin-AngII with ACE inhibitors, diuretics to reduce Na and water retention.
76
What do pulmonary arterioles and small arteries do when there is an increase in Oxygen concentration?
Why is this useful?
Thy vasodilate when pO2 increases.
This increases gas exchange efficiency. It is the opposite in the systemic circulation.
77
What are some damages in the microcirculation that can cause limitations in oxygen delivery?
Not enough red cells (vasculature not wide enough to let them through)
Clots in peripheral channels
To much fluid (distance oxygen needs to travel is greater)
Each patient is different.
78
What is atherosclerosis?
What does it cause?
Narrowing of blood vessels.
It can cause heart failure, MIs, strokes, coronary heart disease, peripheral vascular disease, arrhythmias, abdominal aortic aneurysms, sudden cardiac death…
79
What are the contents of blood?
45% RBCs (biconcave disc, 120 day lifespan)
1% WBCs (neutrophils, lymphocytes, monocytes, basofils, esofils, has nucleus and lots of granules which do cytotoxic killing)
1% platelets (help blood clot)
45% plasma (clotting factors, antibodies, electrolytes, proteins, albumin)
80
What does the spleen do?
Removes red blood cells after their 120 day lifespan and they aren’t working quite as well.
81
What is the structure of redd blood cells?
Why is this important for their function?
Flexible, biconcave disc, contains haemoglobin, no nucleus or mitochondria.
Allows them to pass through tiny capillaries so they can transport oxygen to and CO2 away from tissue.
Haemoglobin allows them to carry oxygen more efficiently.
They have proteins on the surface of the membrane which determines blood groups.
82
RBCs have no nucleus or mitochondria. How do these cells get energy?
What do they need energy for?
Relies on glycolysis for energy.
It needs energy to be able to hold it’s shape;
- Maintain glycolysis to provide ongoing energy for cell functions
- Maintain iron in the Hb in it’s reduced (Fe2+) state, so oxygen can bind to it
- Protect metabolic enzymes, Hb and membrane proteins from damage
- Preserve membrane sructure
83
What is haemoglobin?
A tetramer, mostly alpha haemoglobin (HbA), with 2 alpha and 2 beta globin in chains (95% in adults). Each of these globin chains have a haem group that allow oxygen to stick to it, increasing oxygen carrying capacity of blood by 70x.
Babies have more foetal haemoglobin (HbF) which is 2 alpha and 2 gamma chains, then make switch to HbA in early days.
Haemoglobin alpha2 (HbA2) has 2 alpha and 2 delta chains (normally about 3%).
Some diseases (like thalassaemia) have more of non-HbA variants.
Each haemoglobin has haem (iron bound to porphyrin ring temporarily and reversibly) and globin (protein chains that bind haem).
84
What is thalassaemia?
A haemoglobinopathy where the genetic makeup of alpha and beta globin chains is altered and so they don’t carry as much oxygen, may have more HbA2, RBC lifespan is shorter and cell isn’t as stable.
This makes the patient chronically anaemic.
85
What is sickle cell disease?
Change in structure of haemoglobin so cells hold a different shape.
Inheritance abnormal beta globin chain (both copies of the mutated gene) mean red cells that change shape or “sickle” when they deoxygenate.
Consequences to this include increased breakdown of red cells, the red cells getting stuck in vessels…
86
What is the Bohr affect?
Haemoglobin is less likely to bind oxygen when:
- Increase CO2 (brain, muscles working harder…)
- Increase temperature
- Decreased pH
- Increased 2,3-DPG (regulated in lots of states like give more O to foetus during pregnancy and situations like low O2 conc like high altitude)
87
Where are RBCs made?
From 7 months gestation on, in bone marrow (mainly vertebrae, pelvis, sternum, ribs, (long bones until early adulthood)).
At 3 to 6 weeks gestation, they’re made in blood islands in the yolk sac.
At 6 weeks to 7 months gestation, made in liver and spleen.
88
How are RBCs made?
What is the process of red blood cell production called?
Made from pluripotent stem cells (mainly the Megakaryocte Erythroid Progenitor (MEP) which can make red cells or platelets).
This goes through series of changes, condensing and eventually pushing out the nucleus to form a reticulocyte (premature red cell found in peripheral blood, especially when bleeding/loosing blood), which becomes a RBC.
This process is called erythropoiesis.
We make 2 million RBCs every second.
89
What influences red cell production?
Erythropoietin production increases in response to anaemia/hypoxia to increase RBC production. >90% made in kidneys, some made in liver - if kidneys aren’t working properly, this won’t be made so become anaemic and breathless.
Iron, B12 and Folate availability; important in DNA replication to make RBCs and haem.
Some inherited disorders affected the globin chain production (like thalassaemia).
90
What can go wrong in red cell production in the bone marrow?
Broad range of disorders, often with the reduced production of the other blood cell types.
There are inherited (like Fanconi anaemia) and acquired causes, including cancer (leukaemia and haematology malignancies but also lymphomas, bone cancer and other cancer like breast cancer which invades the space taking up room so not enough bone marrow is there), myeloid dysplasia (malignancy causing bone marrow to change shape and not work as well) and immune mediated-conditions (aplastic anaemia).
91
What can go wrong in red cell production due to globin production?
Inherited loss of one of more globin genes (most commonly beta) leads to reduced or absent globin production, collectively known as thalassemias.
These cause chronic anaemia, often patients end up on transfusion programs.
92
What can go wrong in red cell production due to lack of components?
Lack of components required red cells and haem production:
B12 and folate are required for DNA synthesis and red cell proliferation.
Iron required for haem synthesis to allow for oxygen transport (4g of Fe in body, 3G in red cells at one time, it is absorbed by diet and then recycled - decreased iron > decreased haemoglobin > small pale red cells with decreased O2 carrying capacity).
Decreased iron availability is from decreased absorption and/or increased loss (like bleeding - periods, pregnancy, most common is GI bleeding).
Lack of these components limits red cell and/or haem production, all gained from dietary source.
93
What can go wrong in red cell production due to stimuli?
Lack of stimulus/impaired kidney function leads to a loss of appropriate Erythropoietin (EPO) production in response to hypoxia. The EPO drives bone marrow to make blood cells.
Can now give injections of exogenous EPO to help maintain their haemoglobin.
94
What are some intrinsic issues that can arise in red cells?
Red cell membrane defects (membraneopathies) - cause different red cell shapes, increased red cell breakdown, more common is hereditary spherocytosis (rare, inherited disorder)
Red cell enzyme production problems can increase red cell breakdown - like glucose 6 phosphate dehydrogenase (G6PD) deficiency which means can’t react to oxidative stress so red cell are broken down in that situation).
This is the most common enzyme deficiency globally, triggered by stress, some foods (fava beans), medications which increase oxidative stress, G6PD cannot be increased to compensate so red cells break down.
95
What is haemolysis?
Red cell breakdown/destruction.
There are lots of ways this can happen due to red cell extrinsic factors, like immune mediated haemolysis. This is the inappropriate targeting of red cells by the immune system, antibodies target proteins on the red cell surface and labels red cells for destruction by other specialised immune cells.
96
What is anaemia?
What are the most common causes?
Most common causes are bleeding and iron deficiency.
It is caused by the decrease of RBC production/increase of RBC loss, reduced Hb carriage and reduced O2 transport.
97
What are the symptoms of anaemia?
Most common is breathlessness, fatigue.
Red flags are fainting as not perfusing the brain and chest pain because can lead to a heart attack.
Other symptoms are yellow eyes, jaundice, dizziness, low blood pressure, heart palpitations/rapid heart rate, enlarged spleen, stool colour changes, muscular weakness, cold/pale skin. (A lot of these relate to specific causes.)
98
Why do we become breathless in response to anaemia?
It is due to compensatory mechanisms involving:
Increased cardiac output - to increase blood circulation and oxygen delivery
Detection of hypoxia by specialised receptors in tissue - acts centrally in cerebellum making us feel breathless
All as part of wider effort to increase gas exchange and oxygen carriage to tissue
99
What are treatments for anaemia?
Diagnose and treat the cause (why are they loosing blood - bowl cancer?).
Replace what is lacking for RBC production/function - iron supplement for iron deficiency, B12/folate, erythropoietin, transfusion, transplant (bone marrow - haematological cancers, allergenic bone marrow - sickle cell, thalassaemia).
Improve O2 transport to tissues (blood transfusion).
Specific drugs, immunosuppressants, cancer treatments and emerging gene therapies.
100
What are some causes of breathlessness?
Lungs:
Airway Diseases (Asthma, COPD...)
Interstitial Lung Disease (Idiopathic Pulmonary Fibrosis...)
Pulmonary Embolism (blot clot)
Heart:
Ischaemic Heart Disease (Myocardial Infarction...)
Heart Failure (Chronic Left Ventricular Impairment...)
Arrhythmia (Atrial Fibrillation...)
Blood:
Blood Loss (Fe deficiency...)
Chronic Anaemia (B12/Folate deficiency...)
Haemoglobinopathies (Sick Cell Disease...)
Head:
Psychological Causes (Hyperventilation Syndrome...)
Neurodegenerative Diseases (Motor Neurone Disease...)
101
How do you treat breathlessness?
Treat the cause - find cause using history taking (what, so what - diagnoses, what now - tests).
Presenting complaint (symptoms), history of presenting complaint (context), past medical history, drug History, family history, social history, systemic questions
Onset, duration, pattern, severity (quantify), triggers, relievers, current versus Baseline, associated features.
102
What causes instantaneous breathlessness?
Pulmonary Embolism - pleuritic chest pain, haemoptysis, limb swelling, pre-syncope/syncope, PE risk factors
Pneumothorax - pleuritic chest pain, pre-syncope/syncope, trauma, airways disease
Pulmonary Oedema - ischaemic chest pain, orthopnoea, pink/frothy sputum, ankle oedema, cardiac risk factors
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What are some reasons breathlessness comes on over minutes to hours?
Acute Bleeding - bleeding source, post operative, syncope
Metabolic Acidosis - diabetic ketoacidosis, acute kidney injury, lactic acidosis
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What are some reasons breathlessness comes on over hours to days?
Pneumonia - cough, sputum, pleuritic chest pain, fever
COPD Exacerbation - wheeze, cough, sputum, smoking
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What are some reasons breathlessness comes on over weeks to months?
Tuberculosis - cough, sputum, haemoptysis, fevers, night sweats, weight loss
Lung Cancer - haemoptysis, chest pain, hoarse voice, night sweats, weight loss, smoking
Pulmonary Fibrosis - cough, joint symptoms, occupational risk, medications
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How do we quantify breathlessness?
MMRC Dyspnea Scale:
0 - I only get breathless with strenuous exercise.
1 - I get short of breath when hurrying on level ground or walking up a slight hill.
2 - On level ground, I walk slower than people of the same age as me because of breathlessness or have to stop for breath when walking at my own pace.
3 - I stop for breath after walking about 100 yards or after a few minutes on level ground.
4 - I am too breathless to leave the house or I am breathless when dressing.
Or on a good day, on the flat, how far can you walk until you have to stop? Quantify distance to get a shared mental model.
Then ask why do you stop?
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What other symptoms can help determine cause of breathlessness?
Lungs: cough, sputum, wheeze, pleuritic chest pain (pain on inhale), haemoptysis (cough blood), fevers, weight loss
Heart: ischaemic chest pain (heaviness exertional), palpitations, orthopnoea, paroxysmal noctural dyspnoea, ankle swelling
Blood: bleeding – any site, jaundice, malnutrition/alcohol excess, night sweats/weight loss
Head: anxiety, recent acute/chronic stressors, peripheral tingling (pin+needles), muscular weakness, swallowing/speech difficulties
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What are some reasons breathlessness comes on over seconds to minutes?
Psychogenic - paroxysms, peripheral tingling, chest pains, emotional triggers
Anaphylaxis - generalised swelling, rash, known allergens
Aspiration - dysphagia, intoxication, oesophageal reflux, neurological disorder
Asthma - wheeze, cough, atopy, family history
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What are some reasons breathlessness comes on over days to weeks?
Pleural Effusion - chest pain, weight loss, night sweats, asbestos exposure, systemic disease (cardiac/renal/hepatic)
Left Heart Failure - ischaemic chest pain, orthopnoea, pink/frothy sputum, ankle oedema, cardiac risk factors
Bronchiectasis - purulent sputum, cough, haemoptysis, fevers
