Tradition of Excellence

Session outline
• Processes of respiration Tradition of Excellence

• Components of respiration
• Pulmonary ventilation
• Gas exchange across alveolar-capillary membrane
• Transport of gases to and from tissues including
• Tissue perfusion and causes of disorders
• The oxygen haemoglobin dissociation curve
• Metabolic energy processed in cell

• Disorders of oxygen delivery including

• Anaemia
• Polycythaemia
Craft, J., Gordon, C., Huether, S.E.,
McCance, K.L. and Brashers, V.L.,
• Compensatory mechanisms 2015. Understanding pathophysiology-
ANZ adaptation. Elsevier Health Sciences,
Sydney
Respiration - Two processes Tradition of Excellence
• External respiration (pulmonary ventilation)
• involves extracting oxygen from the surrounding gas and expiring
carbon dioxide

• Internal /cellular respiration - the process by which

glucose or other small molecules are oxidised to produce
energy
• requires oxygen and generates carbon dioxide

If gas transport is impaired by a respiratory or

cardiovascular disorder, gas exchange at the cellular level
is compromised
The four components of respiration Tradition of Excellence

1. Mechanical movement of gases in and out of lungs

(i.e. pulmonary ventilation)

2. Gas exchange across the alveolar-capillary

membrane

3. Transport of gases to and from tissues

4. Metabolic processes of the cell to produce energy

1. Mechanical movement of gases in
and out of lungs (i.e. pulmonary
ventilation) Tradition of Excellence
1. Mechanical movement of gases in
and out of lungs (i.e. pulmonary
Tradition of Excellence
ventilation)

Silverthorn, 2001

Boyle’s law: The volume of gas varies inversely with the pressure. As the chest increases in
volume just prior to inspiration the pressure drops (in relation to the outside) and gas
rushes in. Equally as the chest decreases in volume during expiration the pressure
increases in the chest and the gas rushes out.
2. Gas exchange across the alveolar-capillary
membrane
Tradition of Excellence

Structure of lung lobe, Silverthorn Structure of alveoli, Silverthorn, 2001

As PaO2 increases in the capillaries, O2 moves into the erythrocytes and attaches to Hb
molecule (diffusion ceases when PaO2 equals alveolar O2 pressure (PAO2))
3. Transport of gases to and
from tissues: tissue perfusion Tradition of Excellence

Flow of blood through the capillaries of the lung tissues

and the body organs and tissues
• Dependent on:
• Volume
• Amount of blood circulating
• Pressure and resistance
• Arteriole and venule vessel radius and length
• Blood viscosity
• Haematocrit (ratio of RBCs to whole blood)
• Cardiac function
• Pumping strength
Examples of potential causes of tissue
Tradition of Excellence
perfusion disorder
• Hypertension
• Arteriosclerosis and atherosclerosis
• Emboli and thrombi
• Varicose veins
• Localised vasoconstriction disorders
• e.g. pulmonary hypertension, Raynaud's disease
• Cardiac (pump) failure/ inadequacy
• Elevated haematocrit (increased blood viscosity)
• Profound hypovolaemia
 3. Transport of gases to and from
tissues: four steps of O2 transport Tradition of Excellence

O2 transport

diffusion of oxygen to
ventilation of lungs
cells

perfusion of systemic
capillaries with diffusion from alveoli
oxygenated blood into capillary blood

N.B. Disease processes may disrupt any of the steps

 3. Transport of gases to and
from tissues: oxygen
Tradition of Excellence

O2 is considerably less soluble than CO2

• most O2 carried attached to haemoglobin (about 97% of total)
• measured using SpO2 (oxygen saturation monitor) or SaO2 (arterial gas analysis)
Remainder (3%) is dissolved in plasma
• PaO2 80-100mmHg
Oxygen delivery (DO2) to tissues in healthy
• Approx. 1000mL/min O2

(Oxygen transport) http://www.youtube.com/watch?v=WXOBJEXxNEo&feature=related

3.09 mins
3. Transport of gases to and from tissues:
Tradition of Excellence
erythrocytes
• Most numerous cells in blood
• Responsible for
• Transporting oxygen to tissues in the form of oxyhaemoglobin
• the ‘haem’ portion has atoms of iron which can bind with a molecule of oxygen
• Removal of carbon dioxide
• Buffering pH
• Have no nucleus or mitochondria
• Cannot carry out oxidative processes
• Cytoplasm consists of electrolytes, proteins and haemoglobin
• Discs but can become torpedo shaped to get through small
capillaries
• Viable for 80-120 days in the circulation
3. Transport of gases to and from
tissues: erythrocytes Tradition of Excellence
• Manufacture of erythrocytes (Erythropoiesis) in
the bone marrow usually keeps pace with
erythrocyte destruction (elderly cells are recycled
in the liver by macrophages)
• Approx. 1% of the circulating erythrocytes are replaced
every 24 hours

• Erythropoiesis is accelerated in response to oxygen

deficiency
• erythropoietin (EPO) is secreted by peritubular capillary
lining cells in the kidney (and a small amount by the
liver)
• EPO stimulates haematopoietic stem cells in the bone
marrow to become erythrocytes
 3. Transport of gases to and from
tissues: disorders of erythrocytes Tradition of Excellence
Anaemia - low level of erythrocytes or/and haemoglobin
Three main classes / causes
• excessive blood loss
• excessive blood cell destruction (haemolysis)
• deficient/ineffective erythrocyte production e.g. iron and vitamin
B12 (or intrinsic factor in stomach mucosa) deficiency
Polycythaemia – overproduction of erythrocytes
• primary process in bone marrow (myeloproliferative syndrome)
• compensation (chronically low oxygen levels when living at high
altitude)
• malignancy (rare)
3. Transport of gases to and from tissues:
Tradition of Excellence
oxyhaemoglobin
In conditions of high PaO2 reduced haemoglobin binds
with oxygen to form oxyhaemoglobin
• HB + O2 ↔ HbO2
• The affinity of haemoglobin increases after O2 combines
with each of the four haem molecules
• In arterial blood when the SaO2 is 98% haemoglobin is
said to be fully saturated
• Unsaturated haemoglobin is deoxyhaemoglobin
• When SaO2 and PaO2 are plotted on a graph a
distinctive S-shaped curve results called the oxygen-
haemoglobin dissociation curve
3. Transport of gases to and from tissues:
Oxygen-haemoglobin dissociation curve Tradition of Excellence

Note that at PaO2 of

60 to 100mmHg Hb
is >90% saturated.
Blood picks up
almost a full load of
oxygen in the lungs

Large amounts of O2 are

released in the tissues
in response to only
small changes in PaO2 .

Silverthorn, 2001
3. Transport of gases to and from
tissues: Oxygen-haemoglobin Tradition of Excellence
dissociation curve
• In healthy conditions haemoglobin has a high affinity
for O2
• Cells must consume a substantial amount of dissolved
oxygen (PaO2) before O2 splits from Hb
• However in states where metabolism is raised O2 splits
from Hb easily
• e.g. increased temperature or metabolic acidosis
3. Transport of gases to and from tissues:
Oxygen-haemoglobin dissociation curve Tradition of Excellence
(pH)
Hb has a high affinity for oxygen
at high pH (low H+ ion conc.)
Hb has a low affinity for oxygen at
low pH (high H+ ion conc.)

Silverthorn, 2001
 3. Transport of gases to and from tissues: Oxygen-
haemoglobin dissociation curve (temperature)
Tradition of Excellence

Hb has a high affinity for

oxygen at low temperatures
(more O2 combines with
Hb)
Hb has a low affinity for oxygen at
high temperatures (less O2
combines with Hb and more is
available to the tissues)

Silverthorn, 2001
 3. Transport of gases to and from tissues: Oxygen-
haemoglobin dissociation curve (PaCO2)
Tradition of Excellence

Hb has a high affinity for oxygen

at low levels of PaCO2 (more O2
combines with Hb)
Hb has a low affinity for oxygen at
high levels of PaCO2 (less O2
combines with Hb)

Silverthorn, 2001
3. Transport of gases to and from tissues:
Oxygen-haemoglobin dissociation curve Tradition of Excellence

• Causes of left shift include

• alkalosis (high pH, low H+ ion conc.)
• decreased temperature
• decreased PaCO2 (alkalosis)
• conditions in which O2 demands are low

• Clinical significance
3. Transport of gases to and from tissues:
Oxygen-haemoglobin dissociation curve Tradition of Excellence

• Causes of right shift include

• acidosis
• Increased body temperature
• increased PaCO2
• increased 2,3 diphosphoglycerate (e.g. chronic hypoxia,
high altitude or anaemia)

• Clinical significance
3. Transport of gases to and from tissues:
carbon dioxide Tradition of Excellence

• CO2 is 20 times more soluble than O2

• Transported in three ways

• 7% dissolved in plasma
• approx 5% dissolved in arterial blood plasma
• approx 10% dissolved in venous blood plasma

• 70% dissolves to become bicarbonate ions in plasma (facilitated by

carbonic anhydrase in red cells first)

• 23% combines with Hb = carb/amino/haemoglobin

3. Transport of gases to and from tissues:
carbon dioxide
Tradition of Excellence

http://www.jcu.edu/biology/RESP1.HTM
3. Transport of gases to and from
tissues: summary Tradition of Excellence

Silverthorn, 2001
Arterial blood gas values Tradition of Excellence

pH 7.35-7.45
PaCO2 35-45 mmHg
PaO2 80-100 mmHg
SaO2 98%
HCO3 22-26 mmol/L
BE -2 to +2
3. Transport of gases to and from tissues:
venous blood oxygen saturation (practice Tradition of Excellence

tip)
• The oxygen saturation (SvO2) of blood returning to the
heart will be approximately 75%
• The body consumes approximately 25% of the
available oxygen
• venous “v” (mixed) sample SvO2
• Should be sampled after all blood returning to the heart is
fully mixed i.e. directly from the right ventricle or from the
pulmonary artery
4. Metabolic processes of the cell to produce energy:
revision (addressed previously) Tradition of Excellence

• Oxygen is required for energy processes and the

complete oxidation of glucose in the mitochondria:

Glucose (C6H12O6) + Oxygen (6O2)  Energy store (38ATP)

+ water (6H2O) + 6CO2

• Without an adequate oxygen supply oxidation is only

partial producing only 2 ATP molecules and pyruvic acid
• Prolonged anaerobic respiration leads to metabolic acidosis
 4. Metabolic processes of the cell to
produce energy: compensation
Tradition of Excellence
• Alterations to cellular respiration affect blood PaO2,
PaCO2, pH and HCO3- levels

• Respiratory acidosis (decreased pH & increased CO2)

• e.g. Hypoventilation, pneumonia etc
• Compensation: increased respiratory rate and increased retention of
HCO3- by renal tubules

• Respiratory alkalosis (increased pH & decreased CO2)

• e.g. hyperventilation (early stages of asthma)
• Compensation: decreased respiratory rate and increased excretion of
HCO3- by renal tubules
4. Metabolic processes of the cell to
produce energy: compensation Tradition of Excellence

• Compensatory mechanisms will attempt to maintain a

20:1 ratio of HCO3- to CO2 to normalise pH

• Renal tubules adjust HCO3- (but takes 1-4 days)

• Pulmonary ventilation ↓ or ↑ to decrease or increase CO2

(occurs within minutes)
Take home summary
• Internal respiration = cellular processes to generate Tradition of Excellence
energy
• External respiration = pulmonary ventilation
• There are four components of respiration
• Mechanical movement of gases from the outside
(atmosphere) to the inside (lungs) (and out)
• Gas exchange in the lungs
• Transport of gases
• O2 mostly attached to haemoglobin
• Oxygen-haemoglobin dissociation curve = relationship between partial
pressure of O (PaO2) and oxygen bound to haemoglobin (SaO2)
• CO2 mostly dissolved in plasma as bicarbonate
• Dependent on tissue perfusion and affected by disorders
• Metabolic processes in the cell