Lungs, Gas Exchange and Respiration Flashcards
Are the lungs symmettrical?
No, left and right hiliums are not symmetrical due to cardiac notch in left (only one oblique fissure)
What are the lobes of the lungs?
Superior, middle and inferior
What are the roles of the oral and nasal cavity in the lung structure?
Moisturise air coming in, important to prevent damage to lungs as alveoli are single celled and will deteriorate if they get dry
Once oxygen has entered the blood via the lungs what happens?
Taken up by haemoglobin in red blood cells going through the alveolus, so the RBCs become fully oxygenated
Where are RBCs oxygenated?
In capillaries adjacent to the alveolus (CO2 out, O2 in)
What are the features of a RBC?
Biconcave disc = larger surface area
2.5 micrometres thick
7.5 micrometres wide
Haemoglobin
What does a haemoglobin molecule consist of?
4 units, each one has an iron/porphyrin complex
How many oxygen molecules can each haemoglobin molecule carry?
4
What is cooperativity?
When O2 binds to an oxygen carrying area, the other free areas become bigger allowing more O2 molecules to attach more easily. Altering protein structure, so affinity for O2 binding site increases as more O2 bind enabling O2 to attach to Hb until all 4 sites are full. This is COOPERATIVITY
Why is cooperativity important?
Allows us even in low O2 state, (emphysema, damaged lungs, COPD etc) to still fully oxygenate haemoglobin, so there is redundancy in system allowing us to cope in these circumstances.
How many lobes does the right lung have? Is this different to the left?
Right has superior, middle and inferior lobes while left has superior and inferior lobes
Why is the right bronchus more prone to having objects going down it?
Right bronchus is wider and more vertically orientated than the left
if a patient is choking on something, which lung is most likely to be affected?
Right lung, because right bronchus is wider, shorter and steeper, so will find object in right inferior lobe
What are the two types of pneumocytes and what makes them different from each other?
Type 1 and type 2 pneumocytes, type 1 are structural cells for gaseous exchange while type 2 reduce surface tension by secreting surfactant, prevent alveolar collapse and increase compliance (lungs inflate more easily)
What are the two zones in the tracheobroncial tree?
Conducting zone (areas of lung that conduct gas) and Respiratory zone (where gas exchange occurs)
What anatomical structures are in the conducting zone?
Trachea, bronchi, terminal bronchioles
What anatomical structures are in the respiratory zone?
Respiratory bronchioles, alevolar ducts, alveolar sacs
Describe the passage of blood through the alveoli and what gases are exchanged in this process
Blood enters through pulmonary arterioles (O2 depleted blood from cells where O2 has been utilised) and exits through pulmonary venule
Between them is capillary network covering alveolus surface, facilitates O2 and CO2 exchange- CO2 leaves blood and goes to alveoli for excretion, O2 leaves alveoli and into blood to be transported to heart and rest of body
How would an infection disrupt good gas exchange?
By blocking O2 in lungs, eg via mucus. This could affect O2 delivery into body and CO2 excretion. Unable to get inhaled gas down into alveoli for gas exchange, blockages of alveoli preventing adequate ventilation
How would a blood clot affect gas exchange?
A blood clot in a pulmonary vessel could prevent blood flowing through lungs, so while O2 is arriving at alveoli, without blood coming through arterioles or venules then the gas cannot get into the circulation, so inadequate perfusion
What are the two ways that gas exchange can be affected?
Inadeuqate ventilation (oxygen content of blood) Inadequate perfusion (blood flow)
What does the oxygen content of blood depend on?
O2 carried by Hb (majority)
O2 in solution (minority)
What are the key cells in the lungs?
Type 1 and type 2 pneumocytes
TYPE 1: structural cells for gas exchange (squamous epithelial)
TYPE 2: reduce surface tension, prevent alveolar collapse and increase lung compliance (cuboidal)
What is the role of Type 2 pneumocytes?
Reduce alveolar surface tension by secreting pulmonary surfactant, this prevents alveolar collapse. Also increase lung compliance (inflate more easily)
What is the difference between parietal and visceral pleura?
Visceral pleura INNER: nerve supply is pulmonary plexus, senses are stretch only via Vagas nerve, and arterial supply is bronchial arteries
Parietal pleura OUTER: nerve supply is phrenic and intercostal nerves, sensitive to pressure, pain and temeperature, and arterial supply is intercostal arteries
Pleural cavity between both parietal and visceral
Parietal pleura is sensitive to what 3 sensations?
Pain, touch and temperature
What are the 3 fissures of the lungs and what lobes do they separate?
Horizontal fissure (seperates superior and middle lobes on right lung) Oblique fissure (seperates middle and inferior lobes on right lung) Oblique fissure (seperates superior and inferior lobes on left lung)
How does gaseous exchange occur in the lungs?
Oxygen diffuses into the capillaries proximal to the alveolar walls (and CO2 diffuses out)
In carbon dioxide transport, what 4 ways is CO2 carried in?
- CO2 dissolved in plasma
- CO2 combines with water (H2O) in plasma in a SLOW reaction to produce bicarbonate (HCO3-) and H+ (carried in blood)
- CO2 and H2O in RBCs is a FAST reaction via enzyme carbonic anhydrase to produce bicarbonate (HCO3-) and H+
- Some CO2 combines with Hb -> HbCO2
What 3 compounds is CO2 transported as?
70% bicarbonate in the plasma (HCO3 - )
20% carbaminohaemoglobin in RBCs (HbCO2 )
10% carbon dioxide dissolved in plasma (CO2 )
What enzyme rapidly converts CO2 into unstable carbonic acid (H2CO3)?
Carbonic anhydrase (CAH)
How does carbonic anhydrase (CAH) convert CO2 into carbonic acid?
Breaks down into HCO3 - and H+
Haemoglobin binds to H+ to maintain the pH “buffers”
Chloride shift regulates the electric charge within the RBC
Describe the structure of Adult Haemoglobin
4 polypeptide subunits- 2 alpha and 2 beta (quaternary tetramer)
Each subunit contains a haem (iron-based)
How does oxygen interact with Adult Haemolgobin?
1 molecule of O2 attaches to 1 haem molecule
What is the T state?
Deoxyhaemogobin (tense)
What is the R state?
Oxyhaemoglobin (relaxed)
Where is the majority of oxygen in the body and what happens to the rest?
Majority is carried on haemogobin and a smaller percentage (2%) is dissolved in the plasma (can be increased medically to 6-7%)
What gas do tissues produce as part of metabolism?
CO2
Why is too much bicarbonate (HCO3-) in a RBC a bad thing and how is it prevented?
Would destroy the cell, so we need chloride shift to maintain cell homeostasis
What is chloride shift in carbon dioxide transport?
Chloride shift is when the cell removes the bicarobonate and replaces it with Cl- (chloride)
H+ from the FAST reaction (CO2 and H2O –> HCO3- and H+) combines with Hb after O2 released at tissues to form HHb
This buffers the cell internally so it doesn’t get too acidic (also called Hamburger shift)
Why is it important that bicarbonate percentage in plasma is 70%?
Must be present in vast amounts as a buffer to soak up acid to keep blood from being too acidic (eg. septic tissues produce lots of acid)
What happens with oxygen transport in the lungs?
High partial pressure of O2 in lungs drives O2 to attach to HHb, wich dissociates from H+ and H+ moves back across and gets involved in chloride shift to produce more CO2
If someone is getting acidotic from sepsis, what gas must be removed and how will their body react to do this?
Removing CO2 will reduce amount of H+ and therefore reduce acidity of blood. Higher CO2 makes a person breathe faster, so someone acidotic will breathe quickly and deeply to get CO2 low as possible and get rid of H+.
What is the oxygen cascade?
Relates to the drop in O2 partial pressure going from room air to mitochondria in cells.
Summary:
From air to gas in alveoli = relative amount of O2 drops (because we humify air as we breathe in) so lower partial pressure
Gas in alveoli to capillaries, then to arteries = O2 drops again
Arteries to tissues = O2 drops further
Describe the oxygen dissociation curve
Y axis: % saturation of haemoglobin (0-100)
X axis: partial pressure of oxygen (Kpa) (0-14)
curve is sinusoidal, 98% is around normal
Kpa relates to how much Hb is saturated, how many of 4 binding sites are saturated
POSITIVE COOPERATIVITY RELATIONSHIP = SIGMOIDAL SHAPE
What are the 3 main areas of the oxygen dissociation curve? Why is the sinosoidal shape important?
Bottom of curve: slow uptake, no partial pressure oxygen and low % saturation of blood
Top area, flattened: around 8Kpa, not a lot of change in Hb saturation because all O2 carrying sites are saturated and cant make much increase (also if damaged lungs, hypoxemic and not much Kpa can still 100% saturate Hb to supply O2 to rest of the body, so body can tolerate damage or high altittude to a degree)
Middle area: sinusoidal shape, IMPORTANT because here there is COOPERATIVITY, less of an increase in Kpa (partial pressure) = more rapid increase in saturation, which reflects cooperativity (binding sites taking up O2 more easily)
What is the purpose of the oxygen dissociation curve?
Relates to the affinity of Hb for oxygen, Hb affinity is continuously dynamic
What is left shift?
LEFT SHIFT: INCREASED AFFINITY Hb has more affinity for O2 (small changes in partial pressure = rapid increases in oxygen saturation) O2 picked up
Increase in pH (Decreased H+)
Decrease in CO2
Decrease in temperature
Decrease in 2,3-Diphosphoglycerate (2,3-DPG)
What is right shift?
RIGHT SHIFT: DECREASED AFFINITY of Hb for oxygen, so less increase in saturation for every increase in partial pressure - O2 delivered to tissues
Decrease in pH (Increase in H+)
Increase in CO2
Increase in temperature
Increase in 2,3-Diphosphoglycerate (2,3-DPG
Why do we want the curve to be right shifted as Hb moves through the body?
So it can give up O2 to oxygenate tissues, as right shift means Hb has a lower affinity for O2 and will actively unload it from the binding sites
Will shift right in working muscles producing lots of H+ so decrease in pH (acidic)
What is 2,3 DPG?
Protein that forms in Hb in hypoxic conditions and decreases affinity of Hb for oxygen = enhances offloading (allows tissues to get adequate oxygen if in a higher altitude, septic tissues etc)
Intermediate product from glycolysis
Why can’t DPG bind to foetal Hb?
Requires Beta subunit (Foetal Hb has gamma)
What is the Haldane effect?
O2 binding to Hb actively promotes CO2 release, directly reduces affinity of Hb for CO2, important in lungs (due to positioning of gases on protein molecule, knock each other off)
What is the Bohr effect?
Increase in CO2 (or decrease in pH), lowers Hb affinity for O2. (more H+ = decreased Hb affinity for O2) enhances unloading of O2 proportional to metabolic active tissues (ie, septic or working muscle tissues, encouraging O2 to be knocked off Hb and then oxygenate these tissues)
Why is carbon monoxide entering the lungs a problem?
CO binds to Hb around 200x more strongly than O2, knocks off O2 and stays attached
Why is carbon monoxide poisoning not evident after checking oxygen saturation?
Pulse oxomiter will probably show 100% saturation as it cannot tell between CO and O2
How to treat carbon monoxide poisoning?
Increase O2 concentration in lung, give patient FiO2 via face mask and in extremity put someone in hyperbaric oxygen therapy HOTB
What is atmospheric pressure at sea level?
101 kPa
What is PO2 in the air?
(21/100) x 101 kPa
= 21.2 kPa
What is the path of the oxygen cascade?
Atmospheric gas 21 PO2 kPa Tracheal gases 20 PO2 kPa Alveolar gas 14 PO2 kPa Arterial blood 13 PO2 kPa Capillary blood 7 PO2 kPa Mitochondria 3 PO2 kPa
concentration of O2 deteriorates as it goes to cellular level
What is the rate of oxygen delivery at rest?
cardiac output X oxygen output
= 51/min X 200ml/l DIVIDED BY 1000ml O2/min
= REST 250ml O2/min
How can we increase oxygen stores in the body?
By adding 100% O2 and displacing other gases, removing nitrogen from lungs (eg, 100% O2 makes lung 450ml –> 3000ml)
Why does PO2 kPa reduce as it goes through the body?
Utilisation of O2 and other gases being added to gases already there
What affects oxygen affinity?
pCO2, pH, temp and DPG
CADET turn right so INCREASED: CO2 Acidity DPG Exercise Temp
= right shift
What is tissue hypoxia?
Deficiency of oxygen at cellular level due to increased demand, reduced supply or abnormal cell utilisation
What factors reduce oxygen delivery?
Cardiac output
Abnormal Hb
Oxygen saturation
What are NADH and FADH2?
Coenzymes that act as electron carriers for aerobic respiration
NADH = 3 ATP
FADH2 = 2 ATP
What is the process of glycolysis?
In cytosol
Glucose –> 2x pyruvate
Costs 2 ATP
Produces 4 ATP + 2 NADH
Net gain 2 ATP
What is the process of the Krebs cycle?
Pyruvate goes to mitochondrial matrix
Pyruvate is DECARBOXYLATED –> Acetyl CoA (1x NADH, 1x CO2) citrate
citrate DECARBOXYLATION 2x –> 2 oxogluterate
2 oxogluterate –> Succinyl CoA
AT THIS POINT (2x NADH produced, 2x CO2 released)
S CoA –> oxaloacetate
(1x ATP, 1x NADH, 1x FADH2)
FOR ONE PYRUVATE, SO 2X FOR ONE GLUCOSE
What type of phosphorylation occurs in Krebs cycle?
Substrate level phosphorylation occurs (some ATP made, FADH2 produced)
What is the process of the ETC?
NADH and FADH2 enter the mitochondrial crista
Oxidation of NADH and FADH2 –> electrons being free to power the protein complexes
Electrons move down the electron transport chain
Energy is used to pump protons (chemiosmosis)
Chemiosmosis = ATP generated in the final protein complex – ATP Synthase
Oxygen is the final electron acceptor in complex IV
28-34 ATP made
Occurs in inner mitochondrial membrane
What occurs in anaerobic respiration?
Occurs during strenuous exercise
Pyruvate –> lactic acid using NADH
Lactic acid is transported to the liver (Cori Cycle)
Why is anaerobic respiration not a good process?
Requires large amounts of glucose
Lactic acid accumulates → muscle soreness
Why is lactic acid monitored in critically ill patients?
Lactic acid is monitored in critically ill patients to determine whether sufficient respiration is occurring
How does carbon monoxide disrupt respiration?
Carbon monoxide binds to the oxygen-binding sites on haemoglobin much tighter than oxygen can (~200x greater affinity) = Less oxygen available to act as the final electron acceptor in the E.T.C
Carbon monoxide disrupts the electron transport chain for aerobic respiration = Irreversibly binds to and inhibits Complex IV (same as cyanide!)
Overall carbon monoxide poisoning results in lactic acidosis (a type of metabolic acidosis)
Respiratory rate increases in an attempt to increase the pH of blood (less acidic)
What is the difference between hypoxic type 1 and 2 respiratory failure?
Type 1: hypoxia without hypercapnia (low PaO2 < 8kPa)
Type 2: hypoxia with hypercapnia (low PaO2 and high PaCO2)
What are the signs of carbon monoxide poisoning?
Raised COHb (normal < 2% and smokers <10%) Cherry-red lips Peripheral cyanosis Increased pulse (tachycardic) Increased breathing (tachypnoea)
What are the symptoms of carbon monoxide poisoning?
Headache
Vomiting
Confusion
Drowsiness
What investigations should be carried out if you suspect carbon monoxide poisoning?
Blood tests: ABG, FBC, U&E, CRP Radiology: Chest X-ray Spirometry (rule out COPD) Microbiology (rule out sepsis) Stool samples
Management for CO poisoning
Remove the source of carbon monoxide –> Give 100% O2 until COHb < 10%
Metabolic acidosis usually responds to correction of hypoxia
Hyperbaric oxygen chamber is also advantageous (COHb >20%)
Monitor patient’s ECG – QT interval is useful when monitoring acute poisoning
FOR SEVERE CASES (COHb > 30%)
Anticipate cerebral oedema
Give mannitol IV (reduces intracranial pressure)
Anticipate fits, coma and cardiac arrest
