Respiratory system: Mechanism Flashcards
Lung volumes and capacities:
Restrictive lung disease
difficulties with filling lung with air
“hugging bear disease”
Obstructive lung disease
Difficulties with exhaling air
(like hand in front of mouth)
Dead space (different types + volumes)
Physiological dead space: air that does not participate in gas exchange
Split into
- anatomical dead space = air conducting system, normally 150ml
- alveolar dead space= alveoli wihout blood supply –> normally 0ml
Boyles Law
Gas can be compressed (volume is determined by pressure)
Chest wall- Lung relationship
Are attached to each other via Pleura
Normally: chest would be bigger, lung would be smaller but form equilibrium in middle
–> this allows minimal changes around neutral pressure to have bigger effects on lung volume
The three compartment model
Three compartments with different pressures:
- Atmospheric (Patm)
- Interpleural pressure (P Ip/Pi) )
- Inraalvelolar pressure (Palv)
Three Pressure Gradients can be calculated:
- Transpulmonary pressure (PTp= PPi - PAlv)
- Transthoracic pressure (PTT= Ppl- Patm)
- Transrespiratory system pressure (PRS=PAtm - PAlv)
—> most importatn: drives inspiration+ expiration
Pulmonary function test: Protocol for Volume time curve
Protocol
- Patient wears noseclip
- Patient inhales to TLC
- Patient wraps lips around mouthpiece
- Patient exhales as hard and fast as possible
- Exhalation continues until RV is reached or six seconds have passed
- Visually inspect performance and volume time curve and repeat if necessary. Look out for:
- a)Slow starts
- b)Early stops
- c)Intramanouevervariabiltiy
Explain volume-time curves, important measurements and effect of obstructive /restrictive lung disease on it
FVC= forced vital capacity
FEV1 = Forced expiration volume after one minute
–> Measures airway resistance and FVC
Peak flow
Measures peak flow (l/min)
Measures Airway resistance (how fast can be exhaled?)
The peak flow meter can measure it.
–> Normal ranges for sex, age, and height
Compare alveolar vs pulmonary ventilation
Pulmonary ventilation:
gas that is taken into the lungs in one breath
Alveolar ventilation:
air that reaches the alveoli (Tidal volume - dead space)
Classification of Lung disease
Control of airway function (Neurological pathway, hormonal way)
Parasympathetic innervation: contraction via Vagus nerve
Vasodilation (more blood supply to tissue)
Sympathetic: Dilation (via doral route ganglion and adrenaline)
BUT also NO synthesis (only species, causing relaxation)
Changes in Cells in Ashmah
- overresponsiveness to stimuli causes airway obstruction
- Airway inflammation –> remodeling
- More mucus production (Hypertrophy/Hyperplasia of mucous glands)
- Airway constriction (SM hypertrophy/Hyperplasia)
- New vessels formation
–> positive feedback: inföammatory agents feedbak on rest
Daltons Law
the pressure of gas mixture = sum of the pressure of all partial pressures of the gases in it
P(gas mixture) = ∑P(gas 1) + P(Gas 2) ………P(<strong>Gasn</strong><strong>)</strong>
Ficks law
diffusion of a gas across a membrane is determined by
- a concentration gradient (p1-P2)
- and surface area(A)
- the thickness of the surface(T)
- and diffusion capacity of gas (D)
“V Gas”= 𝑨/𝑻∙𝑫∙[𝑷_𝟏−𝑷_𝟐]
Hernry’s law
solubility
is determined by Pressure (P) of gas and individual solubility
𝑪_( 𝑫 𝑮𝒂𝒔)=𝒂_( 𝑮𝒂𝒔) ∙ 𝑷_( 𝑮𝒂𝒔)
Boyle’s law
At constant temperature, the volume of a gas is inversely proportional to the pressure of a gas
P_(Gas)∝ 1/V_(Gas)
Charle’s law
At constant pressure, the volume of a gas is proportional to the temperature of a gas
𝑽_( 𝑮𝒂𝒔)∝ 𝑻_( 𝑮𝒂𝒔)
Differentiate between different form of Haemoglobin
1.“Normal” Haemoglobin (HbA) : Two alpha, two beta chains
When 4 O2 bind–> 5th binding site for 2,3-DPG appears (Allosteric –> effect on another binding site than ligand, regulatory function) –> when binding this “pushes” oxygen out
2. HbA2: two alpha, two delta chains
found in thalassemia
2. Fetal Haemoglbin (HBF): Two alpha, two gamma chains
– steals o2 from maternal haemoglobin –< higher affinity
3. Meta Haemoglobin (MetHb):
does not bind oxygen (F3+ already in middle) –< can convert into HbA (constant changing between two forms) by MetHb reductase
Cooperative binding
First O2 in haemoglobin in difficult to bind, following get easier
Myoglobin
haemoglobin in muscle –> stores 02 and extracts it from blood –> higher affinity for O2
When does a Sidewards shifts in the Oxygen dissociation curve occur?
Right shift (increased pressure required to get same saturation)
- increase in temperature
- acidosis
- hypercapnia
- increase 2,3, DPG
Left shift (less pressure required for same saturation
- decreased temperature
- alkalosis
- hypocapnia
- decreased 2,3, DPG
Up and downwards shifts in oxygen dissociation curves
Down: Anaemia: 100% saturated but not enough Hb available
UP: Too much Haemoglobin (e.g. doping, altitude), greater capacity of Hb to bind O2
Oxygen dissociation cuve
–> shows oxygen saturation of Hb (at normal Hb levels proportional to Oxygen in the blood)
Big range in Systemic circulation: (low partial pressure of O2) Oxygen can match tissue demand
Only small range in Pulmonary (high partial pressure of O2) circulation –> allows 02 to get saturated
Transport of Co2 in Blood
1. Solution with blood
–> non-enzymatic, low rate (H20+Co2= H2Co3)
2. In Erythrocyte
- In solution with water –> enzymatic via carbonic anhydrase (increases rate by 5000 times)
- –> Dissociation into H2Co3= HCo3- –> HCo3- get exchanged via AE1 transporters with Cl- and leaves Erythrocyte
3. In Erythrocyte: bound to haemoglobin
- binds to amin Ends of globin chains –> Carbamino haemoglobin
- H+ binds to h+ acceptors like Histidine on globin chain
CO2 dissociation curve
Co2 dissociation curve
Linear for used ranges –> Changes in partial pressure of CO2 and concentration are less significant for Co2
Also different for different saturations fo Hb –> when 100% O2 bound no Co2 bound
Alkaalemia and Acidaemia
Alkalaemia to proton concentration –> higher or lower than normal
Acidosis and alkalosis
conditions that influence pH –> they cause alkalaemia or acidaemia
Basic ranges for PO2
>10 kPa normal
8-10 = mild hypoxaemia
6-8= moderare hypoxaemia
<6 kPa= severe hypoxameia
How is an alkalosis compensated?
Compare respiratory compensation for pH to renal
Alkalosis needs acidosis to compensate (and another way around)
Respiratory: fast compensation
renal: slow (reuptake of H+/HCO3-)
Base exess (explenation and normal ranges)
Is calculated:
Difference between measured HCO3- and expected HCO3- based on PCO2
Normal ranges: -2 - 2 mmol/l
Normal ranges for PH, Po2, PCO2, HCO3-
pH= 7.35 to 7.45
pCO2 = 4.7 to 6.4 kPa (35 - 48 mm Hg)
PO2= >10 kPa (>80 mmHg)
HCO3-= 22-26 mEq/L
How to access/describe blood gases
- pH
- PCo2
- BE
- PO2
- Acid-base status
- Oxygenation
Example: Uncompensated respiratory alkalosis with severe hypoxaemia
Pressure-volume loops
(Name A-E)
A: Normal tidal breathing
B: Inhalation to Total Lung Capacity
C: Exhalation as hard as possible
D: Exhalation slows down
E: Immediate inhalation to TLC
–> produces a respiratory flow envelope (all values will lie within this values, anatomical restriction)
How does PVL changes in Obstructive Lung disease?
How do Pressure-Volume loops change in restrictive disease?
Differentiate between Hypoxia, Hypoxaemia and Ischaemia
Hypoxia= low PO2 in that environment
Hypoxaemia = low PO2 in blood
Ischaemia= lack of O2 in tissues
Summarise the oxygen cascade
decreasing oxygen tension from air to tissues /respiration cells
Two great points of loss of PO2:
- Mixing a fiar in lungs /upper airway
- In respiration tissues
How much arrives in tissues/vessels is dependant on Ficks law
What are the Challenges of high altitude?
Hypoxia (low Patm)
Thermal stress (cold)
Increased solar radiation
Hydration (dry air)
Dangerous(wind, hypoxia-induced confusion etc.)
Accomodation and Acclimatisation in high altitude
Prophylaxis in altitude sickness
- Cllimation = artificial exposure to an environemnt
- Acetoazolamide
–> carbonic acid inhibitor: accelerates renal compensation
Chronic mountain sickness (cause, pathophysiology, symptoms, consequences, treatment)
Causes: unknown
Pathophysiology:
- polycythaemia (high RBC) –> increases viscosity in blood
- blood can only sludge through capillaries –> inadequate O2 delivery
Symptoms
- Cyanosis, fatigue
Consequences:
- ischaemic tissue damage
- heart failure
- death
Treatment
- only known treatment: descending
Acute mountain sickness (cause, patophysiology, symptoms, consequences, treatment)
Cause:
- Maladaptation to high altitude
Patophysiology:
- cerebral oedema
Symptoms:
- nausea, vomiting, impaired decision making, fatigue, insomnia, –>“hangover”
Consequences
- development of high altitude cerebral oedema, high altitude pulmonary oedema
Treatment:
- stop ascent, analgesia, fluid, monitor symptoms, azetazolamide or hyperbaric O2, –> symptoms after 48h lower (renal adaptation)
High altitude pulmonary oedema (pathophysiology and treatment)
Pulmonary arteries constrict due to hypoxia –> increased pulmonary pressure (and thereby increased leakage)
Treatment
descent, hyperbaric O2therapy, nifedipine (calcium antagonist), salmeterol(Sympathomimetics), sildenafil (vasodilation)
High altitude cerebral oedema (pathophysiology and treatment)
vasodilation of vessels in response to hypoxaemia (to increase blood flow) more blood going into the capillaries increases fluid leakage
Treatment: immediate descent, O2therapy, hyperbaric O2therapy, dexamethasone (anti-inflammatory glucocorticoid)
Type 1 Respiratory failure
Hypoxic respiratory failure
- Low PO2 (<8)
- Low or normal PCO2
- –> Diffusion issue (oxygen can’t get into the body but normally Co2 can get out)
Reasons:
- Pneumonia
- Pulmonary oedema
- High altitude
Type 2 Respiratory failure
Type 2: Hypercapnic respiratory failure
“getting gas there problem”
- High CO2 –> more production of CO2 and too little elimination of it
- Most of the time: O2 aswell problematic low but not main problem
Causes:
- Ventilation / Perfusion mismatch
- Pulmonary fibrosis (increase in dead space)
- obesity
- neuromuscular disease, decreased CNS drive
How do PVL change with an Extrathoracic obstruction?
Blunted inspiration
How do PVL change with intrathoracic obstruction?
Blunted expiration
How do PVC change with fixed airway obstruction?
Both: blunted inspration and expiration
How does mechanical realtionship between pleura (pressure) and chest wall changes in lung diesease?
Compliance
the tendency to distort under pressure
Compliance = ►V / ►P
–> A condom is more compliant than a balloon
Elastance
The inverse of compliance
The tendency to go back to the original volume
Elastance = ►P / ►V
Balloon is more elastant than a condom
Surfactant: Role of surfactant in alveoli
Normally: Surface tension of water would lead to collapsing of alveoli
But: Surfactant: phospholipid (bipolar) produced by type 2 pneumocytes
- reduces surface tension –> prevents collapsing
- increases compliance
- Reduces work of breathing
Factors which influence resistance in airway
- Generation
Resistance decreases with airway generation (counter-intuitive as radius decreases BUT so many airways –> sum increases)
- Lung volume
Airways dilate with breathing –> further reduce resistance
Explain the Flow of air in collapsible tubes
Pressures determine if the flow is even possible:
If the pressure in pleura (outside) is bigger than on the inside (airway) e.g. in hard expiration
—> Airways might collapse
–> This is why airway is supported by Cartilage
Changes to ventilation and Blood gases in Sleep
- Ventilation (tidal volume) drops
- very little changes to So2 (because of the plateau phase of ODC)
- BUT. Increased PCO2
Which gas increases in sleep?
Why, how much and which effects can this cause?
CO2
- The mechanism that keeps you breathing
- in healthy people: by 0.5 kPa
- because: sensitivity to Co2 decreases during sleep
–> induces apnoeic threshold
Apnoeic threshold
stage/level of CO2 where you would not breathe during sleep because CO2 levels are too low
When CO2 levels are below this threshold: It can lead to Central sleep apnoea
Central sleep apnoea
Nor effort to breath –> central drive is lost due to low CO2 (below apnoeic threshold)
What can happen to airway during sleep? What does that cause?
- Reduced muscular tone during sleep lead to
- a decrease in intraluminal pressure (during inspiration)
- Can be amplified by extra-luminal pressure (adipose tissue)
–> Airway blocked during sleep but still want to breath
There is still effort to breath (because of hypoxia)
This is called obstructive sleep apnoea
Effects of sleep on COPD patients
- Different oxygen dissociation curve
- saturation of oxygen changes significantly with only little changes in PO2 changes
- ventilation during sleep might be needed
Effects of heart failure during sleep
- Leads to oedema
- Hyperventilation
- decreased in PCO2 below the apnoeic threshold
- Central sleep apnoea
How is breathing (awake) being controlled?
Which nerves control reflexes in breathing? What do they cause?
V
IX
X
–> all: irritant leading to a defensive mechanism (cough, sneeze)
X (Vagus) also stretch
What controlles breathing?
PCO2
How does the sensitivity of carotic receptors changes with the environment?
Increasing Sensitivity:
- hypoxia ( Low PO2)
- acidosis
Decreased sensitivity:
- Alkalosis
Overall: Saturation of O2 (SO2 is stronger defended than PO”)
Minute ventilation (definition, formula)
Ventilation in one minute
VE = Vt (tidal volume) x f(frequency)
Three types of breathlessness
- Tightness –> restriction due to airway narrowing (inspiration)
- Increased work and effort –> High minute ventilation, high lung volume, against resistance (inspiratory or expiratory)
- Air hunger –> powerful urge to breath –> Mismatch between VE demand and VE achieved
What scale can be used to measure breathlessness?
BORG scale
Subjective but still quite reliable and reproducible
What are the main control centers for Breathing?
1. Medulla
- central, involuntary breathing, controlled breathing via PCO2
- Gets influence by limbic system and peripheral ( carotid chemoreceptors)
2. Behavioral center
- cerebral cortex
1 always dominates 2
Name the main difference between pulmonary and systemic circulation
Pulmonary circulation = low pressure (25/8 mmHg), high capacity circulation (10% of overall blood)
–> Thin walled arteries
What is special about endothelial cells in pulmonary circulation?
Specialiced –> has ACE on suface
–> Angiotensin 1 to Ang2 converstion
+
break down of Bradykinin
Bradykinin effects
Vasodilation
Increases leakiness of endothelial
Explain the filter capacity of the pulmonary circulation
Is a very good filter: has a huge surface area
Can filter: small emboli as well (disseminates in pulmonary microcirculation)
What are the three tasks of the pulmonary circulation?
- Gas transport
- Metabolic actions (ACE)
- Filtration of blood
Shunting: explain the concept of shunting and provide and explain anatomical examples
Ways to bypass respiratory exchange surface (and therefore gas exchange)
- Anatomical
* Bronchial circulation –> leaves via thoracic aorta and returns via pulmonary veins - Fetal circulation
- Ductus arterosus
- Foramen ovale
- Congenital defect
- atrial septal defect (patent foramen ovale)
- ventricular septal defect
Congenital defects are generally okay it left ventricle is still stronger than right ventricle but because right ventricle has to operate under high pressure –> right ventricle gets stronger over time
This can lead to mixed venous blood bypassing pulmonary circulation —> Hypoxaemia
Effects of increased Cardiac output on pulmonary circulation
- increased diameter in arteries (compliant)
- increased perfusion in hypoperfused beds (Apex of lungs)
- This leads to minimal changes in MAP
- Minimal changes in fluid leakage
Effects of increased ventilation on pulmonary circulation
Vascular resistance changes with ventilation
At max expiration: extra-alveolar vessels compressed (too much pressure in the thorax)
At max inspiration: Alveolar so big that they compress capillaries
Pulmonary hypoxic vasoconstriction: explain the importance, advantages and disadvantages of pulmonary hypoxic vasoconstriction in humans in health and disease and how this differs from the systemic response
In Hypoxia:
- Vessels constrict to achieve good ventilation-perfusion matching
–> in areas that are poorly ventilated perfusion would be wast
- Can be pathophysiologic in a hypoxic environment
- In systemic response: vasodilation to ensure more blood flow –> better oxygen supply
When is pulmonary hypoxic vasoconstriction beneficial?
During foetal development
- •Blood follows the path of least resistance
- •High-resistance pulmonary circuit means increased flow through shunts
- •First breath increases alveolar PO2and dilates pulmonary vessels
When is pulmonary hypoxic vasoconstriction very bad?
Chronic obstructive lung disease
- •Reduced alveolar ventilation and air trapping
- •Increased resistance in pulmonary circuit
- •Pulmonary hypertension(Cor pulmonale)
- •Right ventricular hypertrophy
- •Congestive heart failure
Pulmonary fluid balance: What factors influence pulmonary fluid balance? What might be the problem with changes?
- Hydrostatic pressure –> pushing force
- Oncotic pressure –> pulling force
(rest neglectable)
If lymphatic drainage fails or too high hydrostatic pressure –> pulmonary edema
How can pulmonary hypertension cause heart problems?
Pulmonary hypertension e.g. in COPD –> vasoconstriction due to hypoxia
–> Increased resistance
leads to cor pulmonale –> hypertrophy of right ventricle
–> Might lead to Congestive heart failure
What is an allosteric protein?
Why is haemoglobin an allosteric protein?
A protein that changes its affinity when other molecules bind to it
–> 2,3 DPG can bind to haemoglobin that helps to kick off O2 when 4 O2 already bound
What is the definition of hypoxia?
It is a low PO2 environment
Define hyoxaemia
Low PaO2 in the blood
Define Ischaemia
Inadequate tissue perfusion of oxygen
What happens to PaO2 with age?
It will decline because of poorer lung function
What is Acclimation?
Like acclimatisation but stimulated by an artificial environment (e.g. hypobaric chamber or breathing hypoxic gas)
What medical prevention could you prescribe when someone is planning to spend some time in high altitude?
Acetazolamide
- Carbonic anhydrase inhibitor
- accelerates renal acclimatisation to high altitude (hypoxia induced hyperventilation) (inhibts HCO3- reabsorbtion)
What makes the pulmonary circulation a good filter?
What can it filter?
It is a good filter because it has a huge surface area!
It can e.g. filter small emboli (dissolved at end of vessels)
What are the 3 functions of the pulmonary circulation?
- Gas exchange
- Metabolism of vasoactive substances (ACE)
- Filtration of blood (emboli)
Which ion movements are involved in the hypoxia-induced vasoconstriction in pulmonary circulation?
Where is perfustion of the lung greatest?
Where is ventilation in the lung greatest?
Apex: Alveoli large, less compliant + gravity less
–> Both less perfustion and ventilation
Base: ventilation (small alveoli, more compliant) + perfustion (gravity) bigger
When is pulmonary vascular resistance highest?
It is highest at its extreme volume (Residual volume and Total lung capacity) because of pressure changes
What is the most common cause of Hypoxaemia in lung disease?
Ventilation/Perfusion mismatch
If pulmonary blood flow isn’t reaching the ventilated alveoli, gas exchange can’t occur. Many lung diseases are associated with global V/Q mismatch
Which weeks of gestation involve the embryonic phase of lung development?
What happens in this phase?
Embryonic phase: 0-7 Weeks
- lung buds and main bronchi develop
- (inkl. vascular supply)
In which weeks of gestation does the Pseudoglandular phase of lung development occur?
What happens during this phase?
Pseudoglandular phase: 5-17 Weeks (2nd)
- Around seven weeks: tertiary (segmental) bronchi form
- By the end of 17th week: most structures have formed
- Vessels: surround lung but gas-blood barrier not yet formed –> not viable yet
During which weeks of gestation do the Canalicular period occur in lung development?
What happens during this phase?
It is the third phase (16-25w)
- Tissue differentiation occurs (muscle, cartilage etc, alveoli)
- Respiratory bronchioles form (after week 24)
- 24-26 weeks: surfactant is secreted
- Blood-Gas barrier starts to form
During which weeks of gestation does the Saccular (terminal sac) period in lung development occur?
Saccular period: 24 Weeks - Parturation
- number of terminal sacs develop
- Immature alveoli form from week 32
When does the alveolar phase in lung development occur?
What happens during this phase?
Late Fetal time to childhood
- Further development of alveoli
- Increase in lung size over first 3 years (increased number of alveoli and respiratory bronchioles)
- –> More than 90% of alveoli are formed after birth!
Which mechanisms lead to change from umbilical circulation to pulmonary circulation at birth
- First breath: expansion of lung
- Triggers production of vasodilatory agent + inhibition of vasoconstrictive agents
- O2 relaxed muscle
- Leading to reduced resistance –> increased blood flow to lungs
