Respiratory Pathophysiology 1 and 2 (Kolbe)

Question 1

What is respiratory failure?

Answer 1

When the lungs fail to adequately oxygenate the arterial blood and/or fail to prevent undue CO2 retention

Practical terms:

• When PaO2 < 8kPa (60mmHg) - hypoxic type I
• When PaCo2 > 6.6kPa (50mmHg) - hypercapnic type II

Question 2

What is the partial pressure of oxygen?

Answer 2

partial pressure of oxygen in arterial blood (PaO2) the portion of total blood gaspressure exerted by oxygen.

Question 3

Define hypercapnia

Answer 3

Alveolar hypoventilation (not minute ventillation)

V(dot)/ Q(dot) mismatch

A condition of abnormally elevated carbon dioxide (CO2) levels in the blood.

Question 4

Describe the relationship between partial pressure of carbon dioxide and alveolar ventilation

Answer 4

Inverse relationship

Question 5

Is minute ventillation same as alveolar ventillation?

Answer 5

No.

VE = V(Alveolar) + V(Dead space)

In pathology, it is possible to have increased minute ventillation but decreased alveolar ventillation because of increased deadspace

Question 6

______ in association with ______ may cause hypercapnia

Answer 6

Hypoventilation in association with metabolic alkalosis may cause hypercapnia

Question 7

What are some causes why PAO2 is different to PO2 in the air?

Answer 7

1. Reduced PiO2 (inspired O₂) – occurs at altitude
2. Hypoventilation
3. V/Q Mismatch
4. R-L Shunt
5. Diffusion

Question 8

Why the is the PO₂ of arterial blood greater than in the tissues

Answer 8

Question 9

HWat is the difference between Partial pressure of oxygen, oxygen content and oxygen saturation?

Answer 9

• Partial Pressure of Oxygen (Pa02) = pressure that is exerted by oxygen when you have a mixture of gases
• Oxygen content (CaO2) = Amount of O2 bound to Hb + amount of O2 dissolved in blood (mL/dL)
• Oxygen saturation = Fraction of oxygen saturated Hb relative to total Hb (saturated & unsaturated)

Question 10

What are the 3 causes of hypoventilation?

Answer 10

Hypoventilation in association with metabolic alkalosis may cause hypercapnia

1) Decreased respiratory drive

2) Neuromuscular competence

• Decreased drive
• Decreased neuromuscular transmission
• Muscle weakness/fatigue (reversible)
  
  • Electrolytic disturbances
  • Malnutrition
  • Abnormal length tension relationship

3) Abnormal load

• Increased resistive load
• Increased lung elastic load
  
  • Chest wall elastic load
  • Minute ventillation load

Question 11

Mr Smith is now 75

At age of 20 years, he contracted poliomyelitis and spent many months in an “iron lung”.He subsequently developed markey kypho-scolosis.

He has put on 25 kg.He now presents iwth worsening shortness of breath, reduced exrcise tolerance and morning headache.

His ABG shows PaCO2 = 7.5kPa (NA 4.5-6.0)

Why is he hypercapnic?

Answer 11

1) Respiratory drive
2) Neuromuscular transmission
3) Load

Hypercapnic because of

1- impairment of Neuromscular transmimssion

• (less anterior horn cells - polio) and

2- increased load/work (kypho-scolosis and 25kg)

• r_educed chest wall compliance b_/c of distortion of kypho-scoliosis& obesbity)

3- reduced drive

• (may be associated with obesity or congenital?)

Question 12

Answer 12

Hypoventilation.

Respiratory drive reduced due to generalised cerebral depression secondary to drug narcotics e.g. heroin

Question 13

• If the lungs were perfect ______ = _____
• This measures the adequacy of gas exchange
• In clinical practise _____ is measured, _____is estimated

Answer 13

• If the lungs were perfect PAO₂ = PaO₂
• This measures the adequacy of gas exchange
• In clinical practise – PaO₂ is measured, P_AO₂ is estimated

Question 14

How do you calculate the PAO2?

Answer 14

• Things that influence P_AO₂ (alveolar partial pressure)
  
  • Patm - Atmospheric pressure
  • Fi0₂ - Fraction of inspired O2
  • PH₂O - Water vapour pressure
  • PACO₂ - Alveolar CO2
  • RQ?P_b = Patm
• PACO2 = can measure with PaCO2 (good at diffusion)
• R = Respiratory quotient/exchange ratio = 0.8
• k=?

Question 15

What are the 2 consequences of working in a mine?

Answer 15

1) Pulmonary fibrosis
2) Malignant mesothelioma

Question 16

Why is he Short of Breath and Hypoxaemic?

Answer 16

Interstitial lung disease.

• X-ray
  
  • shadowing around periphery of lungs, worse on R
• CT
  
  • characteristic fibrosis, distortion of lungs, scarring.

Fibrous tissue laid down in alveolar walls, can progress to d_istort and damage lungs._

• Interstitial lung disease ( affects loose CT, not airway, air space or blood vessel).
• Collagen thickened in airway wall (space between alveoli and capiillary) & a_round small BVs._
  
  • ​Alveolar- capillary block

Question 17

Why does the hypoxemia worsenw hen he walks across the room?

Answer 17

O2 stat 92% at rest, fall to 86% walking across room.

• Muscles use more O2
• Transit time of RBC in the capillaries is reduced
  
  • Collagen / fibrous tissue is laid down around small airways but also laid down in space between alveolus and capillary = alveolar-capillary block.
  • ** With exercise, cardiac output increases to allow for i_ncreased oxygen intake_ and delivery to tissue.
  • With increased CO, the transit time of RBC in the pulmonary capillary goes down.
    
    • ​The small reduction in transit time will not affect healthy individuals, however in a diseased individual (thickening of alveolar wall) it excerbates this issue.
  • So even if hypoxemia is OK and rest, it is unmasked on exercise.
  • Thickened wall + Less time = Worsening of hypoxemia
• Diffusion is impaired.

Question 18

Decribe DLCO

Answer 18

Diffusing capacity of CO

Lung Function Lab – DLCO

Use of CO

• Diffusion (and not perfusion limited)
• Soluble
• Avidly binds to Hb, therefore zero back pressure

Diffusion Depends on

• gas
• diffusion distance/thickness
• surface area
• (Hb)
• Capillary volume

Question 19

What are 3 processes that give you Abnormal Diffusion?

Answer 19

1. Alveolar capillary block -
   
   • Interstitial/diffuse lung disease
2. Loss of diffusing surface area (alveolar surface area) –
   
   • Emphysema
     
     • primarily causes shortness of breath due to over-inflation of the alveoli (air sacs in the lung).
3. Capillary volume/Haemoglobin –
   
   • Group of diseases that affect pulmonary vasculature (pulmonary hypertension, anemia, pulmonary embolism)

Diffusion Depends on

• gas
• diffusion distance/thickness
• surface area
• (Hb)
• Capillary volume

Question 20

What is the normal A-a gradient

Answer 20

A – a Gradient

= 20 – PaCO2/0.8 – PaO2

= 1-2kPa

. Young healthy person A-a grad <1 kPa. Gets wider, more V/Q mismatch as get older.

Question 21

How do you make the distinction between pure hypoventillation (or hyperventillation) and intrinsic lung disease?

Answer 21

A-a gradient

. Young healthy person A-a grad <1 kPa. Gets wider, more V/Q mismatch as get older.

A – a Gradient = 20 – PaCO2/0.8 – PaO2 = 1-2kPa

Question 22

What are 3 other features of this “classical” pattern of abnormality?

Answer 22

1) Restricted lung volumes
2) Hypocapnic/resp alkalosis
3) Pattern of resp/work of breathing.

Question 23

Define COPD

Answer 23

• Definition:
  
  • A disease state characterised by airflow limitation that is not fully reversible (differs from asthma which is reversible).
  • The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases
• Cause: Cigarette smoking is the primary cause of COPD in “developed” countries

Question 24

What are 3 symptoms/consequences of COPD that cause ventillation issues

Answer 24

1. Chronic mucus hyper- secretion
2. Emphysema (destruction of alveolar walls with major agent being proteases from neutrophils)
3. Small airway inflammation (and obstruction)

Question 25

Describe the pattern of pulmonary decline over time of cigarette smoking

Answer 25

• Fall in FEV1 over time
• All on the decline after 25years
• Some are more susceptible to cigarette smoking than others
• Some are relatively more resistant
• If you stop smoking, although you don’t get an increase in LF, your rate goes back to the same as a non smoker

Question 26

Describe the why a person with COPD may show compensatory hyperventillation

What are the consequences of this compensatory hyperventillation?

Answer 26

In a normal patient, you have mostly compartment 2 (V/Q=1). As you smoke, you get more of compartment 1 and 3, but compartment 1 is just dead space and does not contribute to the arterial blood gases. We are only interested in compartments with V/Q between 1 and 0.

Compartment 2 (I): Normal content of O2 and CO2. Compartment 3 (II): mixed venous blood you have decreased content of O2 and increased content of CO2. If you mix them together you get an increased content CO2 and decreased O2.

Hypercapnic vs Hypoxic drive

• In response to hypercapnia (high CO2), the patient will increase ventilation rate and alveolar ventilation (deeper and faster).

The respiratory centre is also _very sensitive to H+ ion_s in the CSF as a result from the acidosis from hypercapnia.

• Patients will only respond to a l_ow O2 (hypoxemia)_ when you are significantly hypoxic (<80% saturation).
• Hyperventilation will normalise CO2.
• Oxygen content will not be normalized because you can only effectively hyperventilate the “normal” compartment 2 but still you cannot get more oxygen through the abnormal compartment 3.

Question 27

When someone undergoes compensatory hyperventillation, ___ content becomes normalised but ____ remains reduced.

Explain why this occurs.

Answer 27

CO2 content becomes normalised, but O2 remains reduced.

O2: In the normal compartment you are already on the flat part of the oxygen dissociation curve. Hyperventilation will increase P_A02 but that will lead to little/no change in oxygen

CO2: Hyperventilation reduces P_ACO2 and content of CO2 significantly (different shape of the curve

Question 28

Describe the difference between Hypercapnic vs Hypoxic drive

Answer 28

Hypercapnic drive

• In response to hypercapnia (high CO2), the patient will increase ventilation rate and _alveolar ventilation (_deeper and faster).
• The respiratory centre is also v_ery sensitive to H+ ion_s in the CSF as a result from the acidosis from hypercapnia. Patients will only respond to a low O2 (hypoxemia) when you are significantly hypoxic (<80% saturation).
• Hyperventilation will normalise CO2. O_xygen content will not be normalized_ because you can only effectively hyperventilate the “normal” compartment 2 but still you cannot get more oxygen through the abnormal compartment 3.
• PaO2 is reduced, PaCO2 is normal, normal pH but this is through hyperventilation and metabolic compensation.
• H2O + CO2 à ß H+ + HCO3-
• Patient continues to smoke and her V/Q gets worse. She becomes hypercapnic and hypoxic. She hyperventilates to reduce CO2 but her O2 remains low. She continues to do this until she can no longer maintain this level of hyperventilation.
• She will then let her CO2 climb and reset chemoreceptors to a higher level of CO2. BUT body does not like acidosis so H+ is excreted by the kidneys.
• Chronic hypercapnia seen in a raised blood bicarbonate (compensated chronic respiratory acidosis)

Hypoxic drive

• Now you have an elevated CO2 so respiratory centre is no longer particularly responsive to CO2.
• Now dependent on hypoxic drive to keep her ventilated
• If you give her supplementary oxygen you turn off her drive and stop ventilation

Question 29

What will the arterial blood gases show?

Answer 29

pH: low

PaCo2: high

PaO2: high (patient must be on gas)

HCO3: High

CHRONIC RESPIRATORY ACIDOSIS WITH RENAL COMPENSATION - BUT NORMOXIA?

NORMOXIA -Patient must be on gas!

• A-a gradient of someone breathing room air and sea level = 20 - PaCO2/0.8 - PaO2
• A-a gradient has to be greater than zero (otherwise oxygen moving from blood to alveolus) Therefore, PaCO2/0.8 - PaO2 < 20.
• If it is greater than 20 then they are not acting at sea level. Patient value is over 20 so you can see that she is breathing oxygen.

Question 30

PaCo2/0.8 - PaO2 is above 20.

What does this indicate?

Answer 30

NORMOXIA -Patient must be on gas!

A-a gradient of someone breathing room air and sea level = 20 - PaCO2/0.8 - PaO2

A-a gradient has to be greater than zero (otherwise oxygen moving from blood to alveolus) Therefore, PaCO2/0.8 - PaO2 < 20.

If it is greater than 20 then they are not acting at sea level. Patient value is over 20 so you can see that she is breathing oxygen.

Question 31

What are the dangers of administering high amounts of O2?

What are the dangers of increased PaCo2 (although pH is normalised by renal and other mechanisms?)????

Answer 31

Danger of administered high (as opposed to low) inspired O2 (hypoxic drive abolished, depression of ventilation increase in PaCO2 and development of acidosis (respiratory and metabolic - hypoxic lactic acidosis) with depressant effects.

• Even if O2 is discontinued, may get profoundly hypoxic and take time to u_nload large accumulation of CO2_ in tissues due to large body stores of this gas.
• Role of worsened V/Q mismatch.

Danger of monitoring only O2 saturation

Question 33

Describe the 2 types of shunts

Answer 33

Shunt in the lung bypass alveoli due to either

1. Arterio-venous malformations (abnormal BVs in the lung that does not go near the alveoli) or
2. _Shunt at cardiac level (_from right side of heart to left side). R–> L shunt in some congenital heart disease (note that VSD still would have L–> R shunt)

Question 34

What does the “high colour” suggest?

Answer 34

Blue = cyanosed

Red = red complexion due to erythropoietin (hypoxemia causes a lot of epo production from kidney) -> excessive Hb/RBC à polycythaemia

Question 35

What does the pan systolic murmur suggest?

Answer 35

They are usually due to regurgitation in cases such as mitral regurgitation, tricuspid regurgitation, or ventricular septal defect

Question 36

How do you differentiate between shunts and VS mismatch?

Answer 36

• Administer 100% oxygen (>700mmHg) and measure PaO2
• In V/Q mismatch, the _PaO2 rises to >600mmH_g with 100% O2 despite the mismatch due to
  
  • Absorption atelectasis
  • Relaxation of hypoxic vasoconstriction
• A shunt will not reach >600mmHg. You must measure the blood gas not just 02 saturation
  
  • Shunt will show 100% saturation still but it is a low PaO2. Saturation does not tell you about PaO2, PaCO2 or the pH.

Question 37

____kPa = ___mmHg

Answer 37

1kPa = 7.5mmHg