ILA Flashcards
Key facts about DNA transcription
Transcription – 1st stage protein synthesis
First step of gene expression, where the DNA sequence is copied to make an RNA molecule.
Performed by RNA polymerases.
Occurs in the nucleus.
Describe the process of preparing the DNA for transcription
*DNA helicase breaks the hydrogen bonds in the DNA double helix, unwinding it
* RNA polymerase binds to the TATA promoter region of the gene
Describe the actual process of DNA transcription
Single stranded binding proteins stop DNA strands reannealing
The RNA polymerase then adds complementary mRNA nucleotides to this template strand, building an RNA chain. (C-G, but A-U (not T as in DNA)). Moves in a 3’to 5’ direction. This transcript now contains the same information as the non-template (coding) strand of DNA.
Describe the process of ending transcription
Sequences called terminators or stop codons signal the transcript to be released from the RNA polymerase. → mRNA strand produced with a poly-A tail (end – stops DNA degrading) & a 5’ cap (beginning)
Describe the modification of pre-mRNA
The molecule formed is called pre-mRNA, as it forms exons and introns. Introns are removed in a post-transcriptional modification phase = Splicing → carried out in nucleus by slicosomes & mRNA leaves nucleus via nuclear pore
Key facts about translation
Second step of gene expression, where proteins are synthesised.
Occurs in the cytoplasm – mRNA binds to ribosome
Key facts about tRNA and ribosomes
- tRNAs connect mRNAs to the amino acids they code for
- At the end of each tRNA there’s an anticodon, which can bind to specific mRNA codons.
- Each ribosome has a small and a large part. These join together over the mRNA. The ribosome provides sites for the tRNA to bind. Ribosomes also act as enzymes and catalyse the reaction
Describe the process of translation
A ribosome binds to the start codon on the mRNA. mRNA moves in a 3’ to 5’ direction. tRNA molecules bind to the ribosome via codon-anticodon interactions. A peptide bond forms between the two amino acids attached to the tRNA.
* The ribosome moves along the mRNA one codon at a time, until it reaches a stop codon. This is the end of the process. Post-translational modification may then occur.
What is the role of mRNA?
synthesized in the nucleus using nucleotide triphosphates and RNA polymerase II - Attaches to ribosomes during translation to allow correct tRNA to bind to form polypeptide chain.
What is the role of tRNA?
Binds to specific amino acids at complementary mRNA codon to hold the amino acids in place to form the polypeptide chain.
What is a transcriptome?
The sum total of all the mRNA molecules
What is single nucleotide polymorphism (SNP)?
- DNA sequence variation when a single nucleotide (ATCG) differs/is substituted * Most common type of genetic change & occur normally → SNPs can occur once in every 1000 nucleotides → 4-5 million in persons genome
What are some of the consequences of SNP?
Can result in a different codon which generates a different protein and thus disease – but most don’t (often introns) E.g. sickle cell anaemia or cystic fibrosis
* If present in recognition sequence of restriction enzyme or affect recognition / promoter/termination sequences they can change the length of proteins or produce different length DNA fragments
* Can act as biological markers to locate genes associated with disease
What causes sickle cell anaemia?
Haemoglobin S (Hb S) = sickle cell haemoglobin. It’s caused by a SNP of adenine to thymine ((GAG codon changes to GTG) on 17th nucleotide.
In sickle cell anaemia, both genes that code for haemoglobin are abnormal (Hb SS). In sickle cell trait, only one chromosome carries the abnormal allele (Hb AS).
Mutation occurs in the HBB gene (codes for beta subunit) & in sickle cell disease only one of the beta-globin subunits is replaced by Hb S.
What changes are made to haemoglobin with sickle cell disease?
Haemoglobin has two subunits ( 2 alpha & 2 beta subunits) . The alpha subunit is normal in people with sickle cell disease. The beta subunit has the amino acid valine at position 6 instead of the normal glutamic acid = different primary structure
Why does the haemoglobin form differently in people with sickle cell disease?
The substitution of glutamate for valine is a nonconservative replacement → different biochemical properties, in this case glutamate is a negatively charged amino acid whereas valine is a hydrophobic branched chain aliphatic amino acid.
When hemoglobin is in its deoxygenated, the additional valine residues bind to a hydrophobic area on other S-hemoglobin molecules, forming a chain of hemoglobin that in turn pulls the red blood cell into its signature sickle shape, therefore it now has a different quaternary structure.
Why does the altered haemoglobin cause the RBC to be a sickle cell?
Abnormal haemoglobin molecules clump together into linear chains (polymerisation) which reduces the haemoglobin’s affinity for oxygen
NB this is Temperature dependent
What are the functional changes to the RBC in sickle cell ?
- Cells don’t live as long
- Lower affinity for oxygen
- Gets stuck in blood vessels
- Overall, leads to reduced delivery of O2 to muscles
Describe the different levels of protein structure
Primary= chain if amino acids – covalent bonds
Secondary = alpha helix, beta pleated sheets – H+ bonds
Tertiary= 3D structure of a single chain of amino acids
- Van der Waals bonds
- H+ bonds
- Electrostatic
- Ionic
- Disulphide bridges
Quartenary = overall 3D structure of a polypeptide
Can sickled cells return to their original shape?
Deoxygenated Hb S molecules are insoluble and polymerise. The flexibility of cells is decreased, and cells become rigid and take up the characteristic sickle appearance.
This process is initially reversible, but with repeated sickling, cells will eventually lose their membrane flexibility. They then become irreversibly sickled
What are some of the complications of sickle cell disease?
Complications can include infections, delayed growth, and these episodes of pain which are sometimes called pain crises.
Pain crises typically occur in the bone.
Sickle cell patients are at increased risk of stroke but this is far less common than in the bone.
What is a positive of sickle cell disease?
Because people with one copy of the “faulty” gene are resistant to malaria, it is beneficial in areas with a high risk of malaria - Africa, the Mediterranean, the Middle East, India, South America or the Caribbean - so people who are from or have ancestors from these areas are more likely to carry the “faulty” gene. This means they are also more likely to have two copies of it, and so suffer from sickle cell disease
What are the symptoms of sickle cell anaemia?
In cold weather, our blood vessels narrow to retain heat (vasoconstriction). Sickle-shaped red blood cells can become stuck in small blood vessels due to their abnormal shape. This can lead to the blood vessel becoming blocked, and can also mean that oxygen may not reach certain tissues, and can lead to tissue death. This can cause a pain episode or crisis to start suddenly, usually in the lower back, arms, legs, chest and belly. When blood returns to the affected area, it can also cause inflammation and pain. If lots of these crises occur, it could cause long term damage to the tissues.
What are some of the treatments of sickle cell anaemia?
- Hydroxyurea used as treatment because it stimulates the bone marrow to make foetal haemoglobin (foetal Hb) → foetal Hb has a better ability for carrying the oxygen around the blood
- This is why newborn babies don’t present with sickle cell → HbF prevents sickle cell but stops being produced after a year
- Embolising drugs
- Can give a plasma exchange to reduce the number of sickle cells
Describe the distribution of water and sodium
2/3 body’s water (60%) in intracellular fluid compartment (all fluid in cells, enclosed by plasma membrane)
* 1/3 body’s water in extracellular fluid compartment → further divided into plasma (fluid part of blood) & interstitial (fluid surrounding cells)
* 70% body’s sodium is ‘exchangeable
* 30% in bone crystal
* ECF – 50% total body sodium
* ICF – 5% total body sodium
NB 60% of body weight = water
Define osmolality
Concentration of solution expressed as solute particles per kg
Define osmolarity
Concentration of solution expressed as solute particles per L
Define oncotic pressure/colloid osmotic pressure
Pressure exerted by plasma protein on capillary wall (e.g. albumin displacing water molecules in plasma)
- opposing effect = hydrostatic blood pressure & interstitial colloidal oncotic pressure & determine balance of total extracellular water
Define osmosis
Process by which molecules within a solvent pass through a semi permeable membrane (high conc. To low conc.)
Define hydrostatic pressure
force exerted by a fluid against a wall, causes movement of fluid between compartments
Describe the response to low blood volume
Blood volume drops (dehydration or blood loss) –> hydrostatic pressure becomes less than oncotic pressure → fluid from IF moves into blood to restore volume via osmosis –> gradient change between IF and ICF –> fluid from ICF moves into IF to restore the balance → cells shrink
What is albumin?
Protein made by your liver found in the blood
Low albumin (Hypoalbuminaemic)
Decreased oncotic pressure
Less water moves from interstitial space into plasma
Causes excess accumulation of fluid in interstitial space
What causes hypoalbuminaemia?
- Liver failure- makes albumin so less made
- Heart failure- they don’t know
- Kidney damage- more into urine
- Protein losing enteropathy- GI conditions
- Malnutrition- Not eating enough protein
Inflammation throughout the body- e.g by surgery, sepsis and mechanical ventilation
Key routes of water loss in the body
- Urine
- Faeces – lack of water = constipation, water loss = diarrhoea
- Sweat
- Breath – via evaporation from respiratory tract
- Vomiting
What are the two types of water loss?
Two types of water loss – sensible (can be perceived and measured e.g. urine) and insensible (not perceived and can’t be measured e.g. sweat, lungs. Faeces, through breathing + evaporation during surgery → estimated 40-60 cc)
What do osmoreceptors in the hypothalamus do?
- Osmoreceptors in hypothalamus detect when water potential in blood is low (detect changes in osmotic pressure)
- Water diffusion into osmoreceptor cells changes when osmolarity of blood changes (cells expand when plasma is more dilute)
- Loss of water (high plasma osmolarity) reduces their volume, triggering stimulation of nerve cells in hypothalamus
- Triggers ADH to release from posterior pituitary
- NB also signals biological sensation of thirst
Describe the role of the posterior pituitary and arginine vasopressin
- Posterior pituitary stimulated by hypothalamus
- Action potentials travel down & cause ADH release into bloodstream (acts to reduce plasma osmolarity back to normal)
- This acts on kidneys causing insertion of aquaporin channels into membrane, increasing fluid retention
Describe the process of water conservation by reabsorption in the nephron
- Urine is diluted as it moves through the loop of Henle
- It is concentrated again in the distal tubules and collecting ducts
- The descending loop is impermeable to sodium chloride and permeable to water * The ascending loop is permeable to sodium chloride and impermeable to water * Once dilute urine enters the distal tubules, water is reabsorbed without sodium chloride → concentrated urine
- Water reabsorption driven by concentration gradient created as sodium is pumped into interstitial space, creating osmotic gradient
- ADH acts upon collecting duct & DCT, increasing number of aquaporins
How does vasopressin work?
ADH binds to receptors on the collecting duct membrane, causing intracellular production of cAMP which activates protein kinase, which phosphorylates proteins that increase the rate of fusion of vesicles containing aquaporins with the membrane.
Describe the mechanism of thirst
- Thirst is stimulated by an increase in plasma osmolarity & a decrease in extracellular fluid volume
- Also induced via angiotensin II (RAAS system)
Describe sodium homeostasis- RAAS
- When renal blood flow is reduced, juxtaglomerular cells convert prorenin to renin (in kidneys)
- Plasma renin then converts angiotensinogen to angiotensin I
- This is converted to angiotensin II by ACE
What does angiotensin II do?
Angiotensin II increases blood pressure via vasoconstriction and simulates secretion of aldosterone from the adrenal cortex
What does aldosterone do?
Aldosterone causes renal tubules to increase the reabsorption of sodium and water into the blood (and excretion of potassium) + increased expression of ATPase pumps in nephron, increasing water resorption through sodium co transport
* This increases the volume of ECF and increases blood pressure
How does ADH work?
NB ADH increases water reabsorption by increasing the nephron’s permeability to water, while aldosterone works by increasing the reabsorption of both sodium and water
What is the link between Na+ balance and BP?
- Na+ balance determines ECF volume, blood volume and blood pressure - Increase in Na+ in ECF → increase in ECF volume, increase in blood plasma volume → increased BP
- Decrease in Na+ in ECF → ECF decrease → blood volume decrease –> blood pressure decreases
What is the mechanism of sodium loss in the body?
Extra sodium is lost from the body by reducing the activity of the renin angiotensin system that leads to increased sodium loss from the body → Sodium is lost through kidneys, sweat and faeces
Normal homeostatic fluid
Excess fluid causes a decrease in the ECF osmolality (lower concentration of particles in the fluid). This is detected by osmoreceptors and causes 3 things to occur:
* It causes water to move into the ICF
* It stops the stimulation of the thirst centre in the hypothalamus
* It inhibits ADH in the posterior pituitary. This will result in an increased urine volume.
What are the potential dangers of excess water consumption?
Too much water in the bloodstream can cause hyponatremia.
Hyponatremia Is where the large amount of water = low concentration of sodium in the blood plasma = cells in the body to swell up. I
f these cells are in the brain it can cause an increase in intracranial pressure which can interrupt the brain’s blood flow and cause seizures, unconsciousness or coma. Excess fluid accumulation in the brain = cerebral oedema (can affect the brain stem and CNS dysfunction.)
What are the symptoms of excess water consumption?
Symptoms can include: Headache, Nausea, Vomiting.
Severe cases can produce more serious symptoms, such as:
o Increased blood pressure.
o Confusion.
o Double vision.
o Drowsiness.
o Difficulty breathing.
o Muscle weakness and cramping.
o Inability to identify sensory information
Normal response to dehydration
During dehydration, a loss of water from ECF will increase the ECF osmolality.
Describe the 3 ways that the hypothalamus acts in response to increased ECF osmolality
- Move water from the ICF to ECF
- Stimulate thirst centre of hypothalamus to increase water intake
- The hypothalamus of a dehydrated person sends signals via the sympathetic nervous system to the salivary glands in the mouth. The signals result in a decrease in watery output (and an increase in stickier, thicker mucus output). These changes in secretions result in a “dry mouth” and trigger thirst..
- Release ADH (Antidiuretic hormone) from the posterior pituitary gland which causes
Water distribution in the body?
Total body water for a healthy 70kg man = 42L, made up of:
* Intracellular 28 L
* Interstitial 11 L
* intravascular 3 L
Equation for estimated osmolality
Estimated plasma osmolality = 2[Na] + 2[K] + urea + glucose mmol/L (this was in the lecture Water and sodium concentration)
What happens if plasma osmolality increases?
If plasma osmolality increases → sensed by hypothalamus → more ADH released → concentration of ADH increases → fluid retention intravascularly.
Where are all of the hormones involved in water regulation produced?
- ADH made in hypothalamus, stored in the posterior pituitary, then acts on the kidneys
- Aldosterone is produced and secreted from the adrenal cortex
- Renin is produced and secreted in the juxtaglomerular cells of the kidney
Equation for cardiac output
Cardiac output = stroke volume x heart rate
What is cardiac output?
Cardiac output = volume of blood heart pumps around the circulatory system in one minute
What is stroke volume?
Stroke volume is a measure of the blood that is pumped out of the ventricles with every contraction
What is the equation for stroke volume?
SV = EDV – EDS
What is the average CO?
Average CO is 5L/min
What are the factors affecting heart rate?
Autonomic innervation (autonomic control of HR via parasympathetic NS - involves the vagus nerve) , hormones, fitness levels & age
What are the factors affecting stroke volume?
contractility (force of heart contraction, performed by myocytes), preload (myocardial distension prior to shortening Preload is, in simplest terms, the stretching of ventricles), afterload (force against which ventricle must act in order to eject blood Afterload is a fancy word for the pressure required for the left ventricle to force blood out of the body to exert during systole), heart size, fitness, gender & contraction duration
Factors affecting blood pressure
(smaller ones) vasopressin, aldosterone, ANP, haemorrhage, sweating, stressors, hydration, weight, muscular activity, posture
- Blood viscosity
- Volume of circulating blood
- Elasticity of blood vessels
- Peripheral vascular resistance
- Cardiac output
How does blood viscosity affect blood pressure?
Thicker the blood = reduced fluidity = travels slower = increased force
How does the volume of circulating blood affect blood pressure?
Increased volume in the circulatory system = larger volume in a specific capacity = causes partial expansion (via elasticity of the vessels)
How does the elasticity of blood vessels impact blood pressure?
Capacity of the heart vessels to resume normal shape after stretching, stiffening of any vessels or the heart due to reduced elasticity, as heart has to pump blood all the way around the body, increased resistance (no assistance by elastic vessels) = increased blood pressure
What is the impact of peripheral vascular resistance on blood pressure?
Greater compliance leads to regulated ability to deal with more blood (surges via ventricular contraction) , stiffening of vessels leads to reduced compliance, hence more turbulence reduced blood flow = increased BP
What is the impact of cardiac output on blood pressure?
Any factor affecting SV or HR with have stimulating affect to blood pressure, increased SV/HR = increased BP
Why do patients with heart failure feel exhausted?
Heart overworking so exhaustion caused by further work of the heart or lack of function of the heart to supply enough blood to tissues of the body.
Why do patients with heart failure feel short of breath?
Cardiac failure increases BP and put increased strain on the heart, usually requiring more contraction in order to pump required volume of blood around the heart, requiring more aerobic and anaerobic respiration. More ventilation required to supply more oxygen to blood and remove more waste products from blood.
Why do patients with heart failure have swollen ankles?
Oedema caused by cardiac failure and increased blood pressure prevents the correct circulation of blood back to the heart = the blood plasma filtered out of the blood enters the tissue fluid and is unable to re-enter due to reduced blood flow = accumulation of tissue fluid (oedema in the legs/ ankles)
Describe the frank-starling law
Frank-starling law → greater the stretch on the myocardium before systole (pre-load), the stronger the ventricular contraction
- stroke volume of heart increases in response to increased volume of blood in ventricles before contractions (end diastolic volume)
Increased force because actin & myosin filaments are brought to more optimal degree of overlap for force generation
What is end diastolic volume?
End diastolic volume = normal ventricle filling leads to ventricle volume 110-120ml
What are the signs and symptoms of heart failure?
- potentially affect Ca2+ uptake, so less Ca released during heartbeat so contraction is not as strong – reduced contraction effectiveness
- shortness of breath + increased exhaustion: lack of oxygen to respiring tissues - ankle swelling: increased venous capillary pressure, decreased plasma oncotic pressure – build up of fluid in lower limbs
- low mood: reduced quality of life, hospitalisation & mortality risk
Why does the heart contract harder when there is a higher volume of blood?
In skeletal muscle, the normal point for contraction is the optimal length, but in cardiac muscle, the optimal length is reached only when the fibres are stretched, so the heart will contract harder when the fibres are stretched by increased volume of blood.
What is diastolic heart failure?
In diastolic heart failure - ventricle has reduced compliance, so it can’t fill properly and there’s a lower end-diastolic volume.
What happens in diastolic heart failure?
This results in a reduced stroke volume by the Frank-Starling mechanism, so a lower blood pressure. This pressure is detected, leading to increased HR (increased sympathetic and reduced parasympathetic) and fluid retention (renin-angiotensin-aldosterone system). This increased fluid leads to the consequences of heart failure: larger volume means greater resistance, so the heart has to work harder in order to continue to pump the blood.
What is the first step in the cardiac cycle?
Cycle initiates when SAN node fires
—> causes the atria to depolarize.
This is represented by the P wave
on the ECG. (DIASTOLE)
What is the second step of the cardiac cycle?
Atrial contraction happens shortly
after the P wave starts —> causing
an increase in atrial pressure —>
this forces blood into the ventricles
causing an increase in ventricular
volume (Note: Ventricular volume
does not start at zero as there is
passive movement of blood from
the atria to the ventricles as the AV
valves are open due to the
pressure gradient) —> thus
increases ventricular pressure
(DIASTOLE)
Atrial pressure then drops –> forces the AV valves shut —> produces first heart sound S1 (SYSTOLE)
During the closing of the AV valves, ventricular depolarization is half way through, this is represented by the QRS complex on the ECG —> causes ventricles to contract — > causing a rapid increase in ventricular pressure (Note: the ventricular volume does not change for a while, this is due to the semilunar valves being shut, this is known as isovolumetric contraction) (SYSTOLE)
Ventricular ejection occurs when the ventricular pressure exceeds that of the aorta and pulmonary artery —> causes the semilunar valves to open —> blood is ejected out of the ventricles (known as the rapid ejection phase) (SYSTOLE)
When ventricular repolarization occurs, represented by the T wave on the ECG—> ventricular pressure starts to fall along with ventricular volume (SYSTOLE)
Once ventricular pressure falls below aortic pressure —> the semilunar valves shut — > producing the second heart sound S2 (DIASTOLE)
Ventricles start to relax with all valves closed (known as isovolumetric relaxation) — >ventricular pressure decreases rapidly (Note: the ventricular volume is unchanged as the valves are closed) (DIASTOLE)
At the same time, atria are being filled again —> slowly increases the atrial pressure —> when atrial pressure becomes greater than ventricular pressure —> AV valves open —> allows passive filling of the ventricles which slowly increases ventricular volume (DIASTOLE)
What happens to the subendocardial vessels during ventricular systole?
During contraction of the ventricular myocardium (systole), the subendocardial coronary vessels (the vessels that enter the myocardium) are compressed due to the high ventricular pressures. This compression results in momentary retrograde blood flow (i.e., blood flows backward toward the aorta) which further inhibits perfusion of myocardium during systole.
Do the epicardial coronary vessels close during ventricular systole?
No, the epicardial coronary vessels (the vessels that run along the outer surface of the heart) remain open
When does most of the myocardial perfusion occur?
Most myocardial perfusion occurs during heart relaxation (diastole) when the subendocardial coronary vessels are open and under lower pressure.
Describe the coronary circulation of the heart
Coronary arteries supply oxygenated blood to the heart muscles
- Cardiac veins draining deoxygenated blood → drain into the coronary sinus → then drain into the right atrium.
Describe the left main coronary artery
supplies blood to the left side of the heart (left ventricles and atrium).
Left anterior descending artery branches off the left coronary artery and supplies blood to L. side of the heart. Left marginal descending (MAD).
Circumflex artery branches off left coronary artery and encircles heart muscle. Artery supplies blood to outer side and back of heart.
Describe the right coronary artery
Supplies blood to right ventricle, right atrium, SA and AV nodes regulating the heart rhythm.
Will branch out into right posterior descending artery and acute marginal artery. Also supplies blood to middle/septum of the heart.
Describe the left anterior descending artery (LAD)
Largest coronary artery, running in the anterior ventricular groove & giving rise to the septal branch & diagonal branch
Describe the septal branch of the LAD
Septal branch supplies the anterior two thirds of the septum, including interventricular septum, bundle branches & Purkinje fibres.
Describe the diagonal branch of the LAD
Diagonal branch runs over the anterior section of the left ventricle, terminating at the apex of the heart
Describe occlusion of the LAD
Most common occlusion = plaque from cholesterol (atherosclerosis)
Describe the territory of an LAD occlusion
Anterior 2/3 of interventricular septum, lateral wall of left ventricles and anterolateral papillary muscle
Describe the effects of an LAD occlusion
lock impulse conduction between atria and ventricles
* Left/right heart block
What are the symptoms of an LAD occlusion?
Infarction of conducting system, atheroma production, ST elevation (indicates blockage in coronary artery - ST elevation on ECG), heart block and arrhythmia (impulses can’t travel down left and right ventricle branches simultaneously) or heart failure, prolonged PR (type 1 heart block). Nausea, shortness of breath, pain in head, jaws, arms
Why is an LAD occlusion known as the widow maker?
Due to high mortality rate
Territory of an occlusion of the RCA
RCA supplies SAN and AVN (branches to form RMA & PDA)
Describe the effects of a RCA occlusion
Conduction of nodes affected, contractions become out of rhythm or slower → inefficient blood flow (ischaemia) and potential backflow
What are the symptoms of an RAC occlusion?
Chest pain, if complete block then heart muscle dies and MI results, pain radiating in arms, shoulders, jaw, neck or back, shortness of breath, weakness and fatigue
How to reduce risk of future heart problems?
- Cut down alcohol intake
- Stop smoking
- More active
- Vaccinations (won’t help directly but are at risk for other diseases so helps with that)
What does sympathetic innervation do to the peripheral blood vessels?
Sympathetic stimulation of peripheral blood vessels causes vasoconstriction → increases blood pressure. Peripheral blood vessels aren’t innervated by parasympathetic.
What is EDV and how does it give us ESV?
Total amount of blood in ventricle just before systole. This is given as 120 in the question.
In contraction, blood leaves (stroke volume). Average stroke volume is around 70. So 50ml left, this gives us the ESV.
Describe the impact of mitral valve stenosis
Mitral valve stenosis → stiffer and requires more pressure to overcome this → left atrium therefore has to contract with more force to generate more pressure to overcome the valve stenosis → atrium contracts with more force so we see an increase in left atrium pressure.
What us the ductus arteriosus?
Ductus arteriosus → ligamentum arteriosum (between pulmonary artery to the aorta)
What is included in the upper airways?
Nose, nasal cavity, pharynx, larynx
What is included in the lower airways?
Trachea, bronchi, bronchioles, alveoli
Where in the respiratory system is there greatest resistance?
resistance increases as airway diameter is reduced BUT greatest resistance is in trachea and larger bronchi → branching of airways means there are many more of the smaller bronchioles airways in parallel, reducing the resistance
Differences between the main bronchi
Right main bronchus has a larger diameter and is aligned more vertically then the left.
Describe the lobar bronchi
two on left and 3 on right, supply each of the main lobes of the lungs.
Describe the segmental bronchi
Supply individual bronchopulmonary segments of the lungs.
What is the pathway of air from the conducting bronchioles to the alveolar sacs?
Conducting bronchioles → Terminal bronchioles → Respiratory bronchioles → Alveolar ducts → Alveolar sacs
Spaces conducting dead space
Anatomical = 150ml
Alveolar = 25ml
SO physiological = 175ml
Describe flow resistance in the lungs
Greatest flow resistance =
segmental bronchi (These are
medium sized )
* If diameter is doubled,
resistance decreases by 1/16
* If diameter is halved,
resistance increases 16-fold
What is the equation for Poiseuille’s law?
R = 8µl / πr*4
How is ventilation?
Nerves fire to the pontine respiratory group
* Apneustic centre has a positive firing - respiratory intensity
* Pneumotaxic centre has a negative firing - time dependent inhibition * Signal to dorsal respiratory group, then stimulate the external intercostals and diaphragm
* The dorsal respiratory group signals to the ventral respiratory group, stimulates internal intercostals and accessory respiratory muscles
* Homeostatic control – inputs to nucleus accumbens, nucleus tractus solitaius * Inputs from CN IX and X
What are central chemoreceptors?
Located on the ventral lateral surface of medulla oblongata & detect changes in pH of spinal fluid. They can be desensitized over time from chronic hypoxia. They detect H+ from CO2 diffusing across the blood-brain barrier.
What are peripheral chemoreceptors?
Include aortic body (detects changes in blood oxygen & CO2 but NOT pH) and carotid body (detects all three). They don’t desensitize & have less impact on ventilation compared to central chemoreceptors.
What is the main drive to breathe?
CO2 is main driver to breathe as chemoreceptors respond to small changes in CO2 levels but only large O2 changes
Describe how CO2 levels cause us to breathe
- Increase in CO2 levels → decrease in blood pH due to production of H+ ions from carbonic acid when CO2 combines with H2O.
- In response, the respiratory centre (in medulla) sends nervous impulses to the external intercostal muscles & diaphragm to increase breathing rate & lung volume during inhalation.
What is the impact of O2 conc. levels on breathing?
- Monitored by peripheral chemoreceptors → low arterial O2 level stimulates chemoreceptors, increasing number of action potentials sent to centre in medulla * Leads to an increase in ventilation, meaning more oxygen reaches the alveoli, minimising decrease in alveolar and arterial O2 levels
Which chemoreceptors detect CO2 change?
CO2 change is detected in both types of chemoreceptors, with the stimulus being t increased H+ concentration in extracellular fluid & arterial blood →increased stimulation of centre in the medulla oblongata & increase in ventilation.
What are the two stimulation centres in the medulla and what do they stimulate?
- Ventral respiratory group (VRG) → stimulates both inspiratory and expiratory movements
- Dorsal respiratory group (DRG) → primarily stimulates inspiration
Describe the pleura of the lungs
2 membranes – visceral and parietal pleura
Space in between is the intrapleural cavity
Describe inspiration
- The respiratory muscles expand the cavity which creates a negative pressure in the pleural cavity
- Pulls the visceral pleura which pulls on the lungs and decreases the pressure * Air rushes in to the lungs to equalise the pressure = inspiration (increase in transpulmonary pressure greater than elastic recoil of lungs – lungs expand, alveolar pressure reduced below zero)
- diaphragm contracts - dome moves downward into abdomen, enlarging the thorax.
- external intercostal muscles simultaneously contract, leading to an upward and outward movement of the ribs
Why does airflow cease at the end of inspiration?
End of inspiration - pressure in alveoli = atmospheric pressure again because of the additional air within them, so air flow ceases.
Describe expiration
- diaphragm and external intercostal muscles relax. The diaphragm and chest wall are no longer actively pulled out by their muscles, so begin to recoil inwards, due to their elastic properties.
- intrathoracic pressure increases (decreasing transpulmonary pressure, less than elastic recoil of lungs, so they passively recoil) and this forces the air out * As they become smaller, the alveoli are temporarily compressed, so their volume decreases and their pressure becomes greater than atmospheric pressure, causing flow of air out of the lungs.
What is the definition of and equation for flow?
Flow = (Palv – Patm)/R, where Palv is alveolar pressure, Patm is atmospheric pressure and R is a constant. When Palv is less than Patm, the driving force for air flow is negative, indicating that air flow is inward: inspiration. During expiration, the opposite is true.
What is the definition of and equation for Boyle’s law?
Boyle’s law: P1V1 = P2V2: at a constant temperature, an increase in the volume of a gas will cause a decrease in pressure
What is the definition of and equation for transpulmonary pressure?
The difference in pressure between the inside and outside of the lungs. Ptp = Palv - Pip. Because the lungs must always have some air in them, this is always positive relative to atmospheric pressure.
What is the definition of Pip
Pressure of the intrapleural fluid surrounding the lungs. This is negative, because the elasticity of the lungs and the chest wall mean they tend towards collapsing and enlarging respectively, so they more apart from each other. This reduces the pressure of the intrapleural fluid.
What is active expiration?
This can occur under certain circumstances, e.g. exercise. The internal intercostal muscles contract, depressing ribs 1-11, causing a decrease in thoracic volume. Additionally, contraction of the rectus abdominis increases intra-abdominal pressure, forcing the relaxed diaphragm up into the thorax
Describe respiratory failure
A syndrome in which the respiratory system fails in one or both of its gas exchange functions: oxygenation and carbon dioxide elimination
What is hypoxemia?
A drop in the oxygen carried in blood
What is hypercapnia?
A rise in arterial carbon dioxide levels
What are the thresholds for hypercapnia and hypoxemia?
Hypercapnia (PaCO2 >6.0kPa) and Hypoxemia (PaO2 <8kPa)
What is type 1 respiratory failure?
Gas exchange failure (e.g. v/q mismatch, hypoxaemia, high altitude, pneumonia)
What is type 2 respiratory failure?
pump failure (COPD, ventilation failure due to hypercapnia/hypoxaemia)
Define type 1 respiratory failure
low level of oxygen in the blood (hypoxemia) with either a normal or low level of carbon dioxide (PaCO2).
