X. Regulation of respiration and changes of partial pressures of respiratory gases

1  Terms

alveolo-capillary membrane a barrier through which gasses are exchanged between the lungs and the blood. It is composed of respiratory epithelium (type I. pneumocytes) basement membrane and capillary endothelium .
anatomical dead space a space in upper and lower respiratory tract where diffusion does not occur (the wall is composed of cartilage and it is too thick). The volume of dead space may be increased by a straw, gas mask and snorkel.
anoxia Ø  the absence of oxygen in tissues
apnea Ø  a suspension of breathing
asphyxia a condition, when partial pressure of oxygen is decreased and partial pressure of carbon dioxide is increased in blood and tissues due to suffocation (during delivery,strangulation)
Biot’s breathing an abnormal pattern of breathing due to damage to medulla oblongata
bradypnea Ø  an abnormally slow breathing rate
gas diffusion the exchange of oxygen and carbon dioxide between alveoli of the lungs and blood and between blood and tissues (down the concentration gradient)
dyspnea Ø  pocit nedostatku vzduchu, dušnost

a feeling of insufficient supply of oxygen

eupnea Ø  normal breathing
Alveolar dead space a sum of volumes of alveoli that are not perfused enough and diffusion does not occur (even though anatomical conditions are favourable)
global respiratory insufficiency

(type II. respiratory failure

respiratory insufficiency, caused by inadequate alveolar ventilation leading to decrease of partial pressure of oxygen and increased partial pressure of carbon dioxide (hypoxemia with hypercapnia)
hyperpnea Ø  increased depth of breathing
hyperventilation increased depth of breathing or increased rate of breathing leading to decreased partial pressure of carbon dioxide in arterial blood (paCO2)  and change of blood pH (respiratory alkalosis)
hypopnea Ø  decreased depth of breathing
hypoventilation shallow and insufficient breathing (ventilation) leading to build up of carbon dioxide in blood (hypercapnia) with respiratory acidosis and lack of oxygen (hypoxemia)
hypoxemia Ø  decreased partial pressure of oxygen in blood
hypoxia Ø  decreased partial pressure of oxygen in tissues
Cheyne – Stokes breathing an abnormal pattern of breathing with fluctuating rhythm: progressive decrease in the depth of breathing followed by apnoea and then increased depth of breathing


deep and fast breathing (hyperventilation) caused by metabolic acidosis that reduces carbon dioxide in the blood and compensates acidosis
dead space a space in respiratory tract where diffusion does not occur. There is anatomical and alveolar dead space.
ortopnea a shortness of breath when lying that requires patient to sit, support the arms and use auxiliary breathing muscles
paCO2 Ø  partial pressure of carbon dioxide in arterial blood, it corresponds to the amount of CO2 that is disolved in arterial blood (N: 5,3 ± 0,5 kPa @ 40 mmHg = 40 mmHg)
paO2 Ø  partial pressure of oxygen in arterial blood (corresponds to the amount of oxygen dissolved in the arterial blood capable to diffuse across the capillary wall(N: 12,4 ± 3,1 kPa @100 mmHg = 100 mm Hg)
pAO2 Ø  partial pressure of oxygen in alveoli (pO2 in alveoli is higher than in arteries, depends on pACO2  and pO2  in inhaled air)
partial respiratory insufficiency

(type I respiratory failure)

respiratory failure defined by low partial pressure of oxygen in arterial blood (hypoxemia), without hypercapnia
partial pressure it is a hypothetical pressure of an individual gas in a mixture of gasses (it correspond to the volume of a particular gas in a mixture)
lung perfusion Ø  blood flow through lungs
polypnea Ø   increased depth of breathing, rapid breathing
respiration Ø  an exchange of gases with the environment by inhaling and exhaling
respiratory centres centres that regulate breathing – a group of nuclei in reticular formation of medulla oblongata and pons. They are involuntary.
respiratory insufficiency respiratory failure caused by inability to sustain sufficient gas exchange. There are two types partial (hypoxic, type I.) and global (hypercapnic,type II.)
tachypnea Ø  increased rate of breathing
ventilation Ø  the movement of gases between external and internal environment

2 Introduction

Function of respiratory system

  • the exchange of gases between the body and the environment and maintaining partial pressures of those gases according to the needs of metabolism
  • metabolic function: regulation of acid base balance (ABB), thermoregulation and endocrine function (conversion of angiotensin I to II)
  • speech

The structure of respiratory tract

thorax –  an enclosed cavity with important properties – compliance and elastance

breathing muscles – muscles stimulated by respiratory centres, expand thoracic cavity and cause inspiration (increase the volume of thoracic cavity). The most important breathing muscles are diaphragm and intercostal muscles. Auxiliary breathing muscles are activated during increased physical activity (muscles of the back, neck and shoulder) and also under pathological circumstances (orthopnea).

pleurae – there is visceral and parietal pulmonary pleura with a serous fluid in between. The negative pressure in the pleural cavity helps the lungs to expand and increase its volume.

respiratory tract – upper: nasal and oral cavity, pharynx, larynx, lower: trachea, bronchi, bronchioles. Diseases of respiratory tract cause obstructive lung diseases (bronchoconstriction, hypersecretion of mucous)

respiratory tissue – part of respiratory system where an exchange of gases through alveolocapillary membrane occurs between the alveoli and blood. The area of respiratory tissue is  50-100 m2. If the compliance of the lungs decreases due to edema or interstitial fibrosis restrictive lung diseases develops.   

functional and nutritive blood supply to lungs – functional: vessels responsible for blood perfusion are pulmonary arteries coming from right ventricle and pulmonary veins drain to the left atrium. It is a low pressure circuit. The purpose of the circuit is gas exchange. Nutritive: blood supply from (a.bronchiales) supplies the lung tissue with nutrients and oxygen. Diseases: embolia, pulmonary hypertension, ventilation perfusion ratio disbalance.

Dýchání se skládá z několika dějů:

The act of breathing is composed of a series of individual actions:

  1. ventilace –  výměna plynů mezi organismem (plicními alveoly) a okolím. Probíhá za pomoci tzv. respirační pumpy (hrudní koš, bránice, ostatní inspirační svaly, pleura). Při nádechu (inspiraci) se plíce plní vzduchem, při výdechu (exspiraci) je vzduch z plic vypuzen. Inspirace je aktivní děj: dýchací svaly rozšíří hrudní koš, vlivem adheze parietální a viscerální pleury za přítomnosti pleurální tekutiny se roztáhnou plíce a vznikne v nich podtlak. Vzduch může proudit dýchacími cestami do alveolů. Za fyziologických okolností je klidový výdech (exspirace)  děj pasivní. Jakmile pomine tah svalů, smrští se hrudník i plíce a zvýšením tlaku se obsažený vzduch vydechne do dýchacích cest a ven z organismu.
  2. ventilation – the exchange of gases between the body (alveoli) and external environment. The action is maintained by the activity of respiratory pump (thorax, diaphragm, inspiratory muscles, pleaura). Lungs are filled with air during inspiration (inhalation) and air gets out of the lungs during expiration (exhalation). Inspiration: is an active process, the breathing muscles help the thoracic cavity to expand, negative pressure is formed in pleural cavity due serous fluid that causes the adhesion of a visceral and a parietal pleurae. Air passes through respiratory tract to the alveoli. Under physiological circumstances the expiration is passive process. As soon as the breathing muscles relax, the volume thoracic cavity decreases, the pressure inside the lungs increases and the air is moving out of the body.

Ventilation is dependent on the compliance of the chest wall, negative pressure in the thoracic cavity, the compliance of the lungs, the surface tension of the lungs, the resistance of respiratory tract, the volume of dead space and the activity of breathing muscles. The most commonly used method to measure how well the lungs work is spirometry. Plethysmography may also be used.

  1. perfusion – functional blood supply to the lungs maintained by the capillaries around the alveoli and alveolar septi. The intensity of perfusion depends on the air distribution to the individual areas of the lungs, gravity, position of the body and acceleration (positive or negative – e.g. being on a spaceship). It is very important to maintain constant alveolar ventilation and perfusion. Ventilation perfusion coefficient shows the ventilations- perfusion ratio (V/Q). Functional alveoli are those, that are ventilated as well as perfused. Some reflexes were developed to maintain constant V/Q ratio – decreased partial pressure of oxygen in the alveoli causes vasoconstriction of the arteries, so the blood from poorly ventilated alveoli does not mix with well oxygenated blood and is prevented from coming to the left heart.
  2. diffusion – the exchange of gases between the alveoli and the blood. It depends on the size of the areas where the diffusion occurs (respiratory tissue – the number of functional alveoli, the thickness of the septi), the thickness of the alveolo-capillary membrane, pressure gradient of the gasses, properties of the gasses (CO2 diffuses more easily than oxygen). We measure arterial blood gases ( partial pressure of carbon dioxide and oxygen in the arterial blood) to measure how well does the diffusion work.
  3. internal respiration – the exchange of gases between the blood and the tissues (diffusion)

3 Control of ventilation

There are two ways how respiration is regulated: nervous regulation (respiratory centres in the brain and nervous stimuli) that maintains the automaticity of the respiratory processes and humoral regulation, that adjust the activity of respiration according to the internal need (central and peripheral chemoreceptors control the partial pressures of gases and pH)

Nervová regulace se z hlediska ovladatelnosti vůlí dělí na řízení automatické a volní. Automatické dýchání  je řízeno z dýchacích center v prodloužené míše a pontu, které přímo aktivují inspirační dýchací svaly. Volní dýchání je řízeno mozkovou kůrou. Kontrola účinku dýchacích funkcí je prováděna chemoreceptory, které monitorují parciální tlaky dýchacích plynů, rozpuštěných v arteriální krvi, a pH. Centrální chemoreceptory v prodloužené míše reagují hlavně na parciální tlak oxidu uhličitého (pCO2), periferní chemoreceptory, uložené v oblouku aorty a karotických tělískách, reagují hlavně na parciální tlak kyslíku (pO2) a na pH krve (částečně i na pCO2).

Nervous regulation is automatic and voluntary. The automatic ventilation is regulated by respiratory centres in medulla oblongata and pons that directly stimulate inspiratory breathing muscles. Voluntary respiration is regulated by the cerebral cortex. Chemoreceptors control respiratory function, also monitor partial pressure of gases dissolved in the arterial blood and the blood pH. Central chemoreceptors are located in medulla oblongata and their main stimulus is partial pressure of carbon dioxide (pCO2), peripheral chemoreceptors are located in aortic arch and carotid bodies and are stimulated by partial pressure of oxygen and blood pH.

Pic. 10.1: A diagram of regulaltion of ventilaton:.Respiratory centres send impulses to stimulate inspiration. Negative feedback comes back from mechanoreceptors (inflation and deflation receptors in the lungs), proprioreceptors and J receptors. Ventilation changes partial pressure of gases in the blood. Respiratory centres are informed by negative feeback about the efficiency of partial pressure changed: central chemoreceptors monitor pCO2,  peripheral chemoreceptors monitor pO2,  and pH and partially pCO2.

During eupnea, inspiration lasts 1-2 seconds, passive expiration lasts 2-3 seconds. Respiratory rate is 12-16/min.

3.1  Nervous regulation

The most important regulation centres are localized in medulla oblongata and brainstem. Neurons in the respiratory centres hardly influenced by hypoxia.

Centres in the medulla oblongata:

Centres are group of cells, whose activity regulates ventilation. They are localized in medulla oblongata and can be divided into groups:

  • dorsal respiratory group (around ncl. tr. solitarii) (DRG)
  • ventral respiratory group (VRG)
  • Botzinger complex (BOT) close to retrofacial nucleus. Its projections to DRG and VRG have inhibitory effect.

Dorsal respiratory group is a pacemaker , it has it own, automatically generated rhythm. It is responsible for the automaticity of breathing, it generates stimuli for inspiratory neurons (I), neurons that are actived right before inspiration. During rest the inspiration is an active process and expiration is passive – expiration is a break of a active inspiration.

Efferent pathways of inspiratory neurons from DRF activate motor neurons of diaphragm and other inspiratory muscles (external intercostal muscles). They also influence other ‘respiratory’ centres.

Ventral respiratory group

It is composed of inspiratory (I) and expiratory (E) neurons. VRG regulates activity of the auxiliary breathing muscles and its activity is influenced by DRG and Botzinger centre. VRG does not have its own pacemaker properties. It is activated by increased inspiratory activity (physical activity) and by active exhalation. VRG and Botzinger complex regulate the diameter of the lumen of upper respiratory tract.

Centres in brainstem and pons:

In pons there are two areas that have an impact on respiratory activity coming from the medulla oblongata. It is the pneumotaxic centre and apneustic centre.

Pneumotaxic centre (PNC) is localized close to medial parabrachial nucleus in the upper part of the pons. Its activity decreases the activity of inspiratory neurons, therefore it shortens the time for inspiration and the start expiration. (expiration then starts earlier than it would do normally). This process increases the rate of ventilation. It is referred to as “phase switching”.

Apneustic centre (APN) is localized in the lower third of ponds. It inhibits the activity of pneumotaxic centre (it does not allow pneumotaxic centre to shorten  inspiration too much – some books say that is had excitatory effect on inspiratory neurons of DRG). Under physiological circumstances, apneustic centre maintains activity of the inspiratory neurons in such a level, that keeps the lungs sufficiently ventilated. It is important to maintain constant tidal volume at rest.

A damage to pneumotaxic centre or vagal nerve (inhibitory innervation of apneustic centre), makes the apneustic centre dominant and ventilation stops during inhalation (apneusis). If both of the pontine centres are damaged, the respiratory centres in medulla are capable to maintain slow rhythmic activity of ventilation – ‘gasping”.

The tracts from brain stem descend in ventrolateral and ventral columns as bulbospinal tract.

Pic.10.2: The localization of respiratory centres: PNC pneumataxic centre, APC apneustic centre, DRG dorsal respiratory group, VRG ventral respiratory group.

The description of the areas in which the respiratory centres are localized may differ according to the source. However it is always a group of neurones which activity increases or decreases during certain phases of respiration.

Factors that impact ventilation rate:

There are several factors that can impact the rhythm. They come from CNS or periphery. The most important factors come from chemoreceptors.

CNS factors

Hypothalamus influences the activity of respiratory centres:

-change of temperature: thermoregulatory centres in hypothalamus have a direct effect on the rate of ventilation (fever)

– change of activity of sympathicus or parasympathicus

– hormone release (TRH, CRH)

Limbic system influences respiratory centres via emotions e.g. fear and anger increase the rate of ventilation.

Cerebral cortex can voluntarily change ventilatory rate

  • voluntary control of ventilation: change of ventilation frequency, volumes, start apnoic or apneustic break. Many descending cerebral tracts bypass respiratory centres and directly stimulate motor neurons of breathing muscles. These tracts are localized in the lateral column – corticospinal tract.

Pathophysiology: a damage to corticospinal tract damages the innervation of breathing muscles and may have an effect on the loss of voluntary control of breathing. The most common cause is intracranial bleeding.

A damage to bulbospinal tract causes Ondine’s curse – the failure of autonomic control of breathing (patient has to consciously think to breath). Affected people suffer from respiratory arrest during sleep. Patient require lifetime mechanical ventilation.

Peripheral factors

Receptors in the lungs

  • inflation receptors are mechanoreceptors (overstimulation causes Hering Breuer inflation reflex – prevents over-inflation of the lungs and alveoli). Hering Breuer inflation reflex determines the breathing rate and depths in newborns and determines the tidal volume.
  • deflation receptors (regulates the extend of expiration – Hering Breuer deflation reflex – shortens the exhalation when the lung is empty)
  • J receptors (juxtacapillary – free nerve ending innervated by fibres from vagal nerve)  – in the alveolar septi, close to pulmonary capillaries. They are activated during lung edema, embolism of the lungs, chronic and restrictive diseases (decreased lung compliance). Its increased activity changes the breathing pattern to ‘restrictive” type – increased ventilation frequency and decreased tidal volume.

Receptors in respiratory tract:

laryngeal and tracheal receptors: localized in the mucosa of larynx and trachea. They are activated by mechanical and chemical stimuli – they stimulate the cough reflex that clears up the upper respiratory tract

– irritation receptors in the lower respiratory tract – they are localized in the epithelium in a trachea all the way to respiratory bronchioli. The are stimulated by mechanical and chemical stimuli especially histamine. Stimulation of these receptors leads to bronchoconstriction, hypersecretion of mucous and cough, which increases the resistance in respiratory tract.

Other receptors:

-proprioceptors – brainstem receives information from peripheral proprioreceptors (muscle spindles, fibrous capsules in joins and Golgi tendon organs. Increased physical activity (stimuli from breathing muscles or limb) stimulates these receptors which stimulate the brain stem to increase respiratory activity.

3.2  Chemical regulation of respiration

        Chemical regulation of respiration is based on negative feedback control, that regulates the respiratory centres according to chemical consequences of breathing (partial pressures of gases). There are central and peripheral chemoreceptors. Peripheral chemoreceptors are activated later but they reacts in terms of seconds.

3.2.1 Central chemoreceptors

(- are indirectly activated by partial pressure of carbon dioxide in arteries paCO2)

        they are used to control of partial pressure of carbon dioxide in the arteries (PaCO2)

        – they are localized on the ventral part of medulla oblongata

        -they are directly connected with dorsal respiratory group and regulate the rhythm of DRG

        Central chemoreceptors are localized directly in cerebrospinal fluid (CSF), that is separated from blood plasma by hematoencephalic barrier (HEB). The composition of CSF is almost identical to blood plasma, however it has less protein therefore its buffer capacity to buffer hydrogen ions is lower.

  Ions cannot move freely across the HEB, however lipophilic CO2 can. In the CSF, CO2 binds to water and dissociates to hydrogen ion and bicarbonate (carboanhydrase). Hydrogen ion binds to chemoreceptors in medulla oblongata and it has an impact on ventilation. This happens 60-90s after pCO2  was changed in blood plasma, after 5 minutes it balances out. However if there is increased protein concentration in CSF due to inflammation or bleeding, the function of central chemoreceptors is disrupted because the hydrogen ions bind to proteins instead of receptors, which leads to ventilation disorders.


        During long term pCO2 increase (1-2 days), there is increased movement of H+  and  HCO3 across the HEB : H+  is transferred from CSF to blood plasma (according to concentration gradient, as there is lower H+  concentration in blood plasma, because H+  in CSF was buffered by proteins and bicarbonate present in CSF). HCO3 is transferred to CSF and buffers the newly formed H+  . Central chemoreceptors are not in use, they have adapted. Respiratory acidosis that aroused from increased pCO2, stimulates compensatory reaction by the kidneys that decreases the effect of hypercapnia on central chemoreceptors.

1. Akutně

Pic.10.3: Central chemoreceptors respond to a change of pCO2, despite the receptors responding to H+. Carbon dioxide is a lipophilic substance without a charge. It crossed the HEB and in CSF it is transformed to carbonic acid by carboanhydrase. Then the acid dissociates to hydrogen ion and bicarbonate. There are less buffers in CSF, therefore free hydrogen ions can bind to central chemoreceptors and according to the concentration of hydrogen ion they affect ventilation.

Pic 10.4: Adaptation of central chemoreceptors. During chronic increase of pCO2 , H+  a  HCO3 cross the HEB and H+  is transferred from liquor to blood plasma (according to concentration gradient, as there is lower H+  concentration in blood plasma, because H+  in CSF was buffered by proteins and bicarbonate present in CSF).HCO3 is transferred to liquor and buffers the newly formed H+  .Central chemoreceptors are not activated by hydrogen ions, they have adapted.

3.2.2 Peripheral chemoreceptors

– they are  the main receptors that control hypoxemia (decreased partial pressure of oxygen in blood). The cells have potassium channels on their membrane that are sensitive to paO2 – the conductivity decreases proportionally to the hypoxemia level. The polarity of the cell  changes and it becomes activated.

– they monitor blood pH and stimulate compensatory hyperventilation during metabolic acidosis and hypoventilation during metabolic alkalosis

-they respond to potassium concentration changes (the activity of potassium channels dependent on paO2 is affected by the concentration of potassium)

Peripheral chemoreceptors are located in aortic a carotid bodies. (The aortic body is less important than carotid bodies). They are composed of tissue that has the richest supply of arterial blood (blood flow is 2000ml/100g/min – the perfusion of brain is 54 ml/100g/min, kidneys 420 ml/100g/min. The oxygen consumption in the carotid bodies is 9ml/100g/min is a lot higher than elsewhere)

The aortic body is innervated by the vagus nerve and the carotid bodies by the glossopharyngeal nerve.

Peripheral chemoreceptors respond to dissolved oxygen in the blood plasma. When the partial pressure of oxygen is normal, they are not activated.  When the arterial pO2 is bellow 100mmHg  and over 60 mmHg they get activated. Stimulation of peripheral chemoreceptors directly leads to inspiration. These chemoreceptors monitor the partial pressure of oxygen (not the amount). They respond to hypexemia – decreased partial pressure of oxygen in the blood (in high altitudes, lung diseases) but they do not respond to a change of saturation of hemoglobin (lack of hemoglobin, defected hemoglobin, carbaminohemoglobin). During cyanide poisoning, the peripheral receptors are fully activated as the cells of the receptors are unable to obtain oxygen (as the oxidative phosphorylation is blocked) .

4 The relationship between partial pressure of gases and ventilation

        Respiration is affected by the partial pressure of oxygen (not by the volume of oxygen – that depends on the amount of saturated hemoglobin). Long term monitoring of paO2 during various activities confirmed that paO2 rarely fluctuated beyond 5mmHg. (paCO2 fluctuates only by 1-2 mmHg).  During apnoea increased paCO2 stimulates central chemoreceptors to stimulate inspiration.

4.1 Respiratory response to acute hypercapnia

Breathing air mixed with more than 1% of CO2 significantly increases respiratory rate (frequency and depth). Respiratory response slowly increases up till 5% of CO2 in the inhaled air.  If the CO2  raises above 5% respiratory rate increases rapidly. (Intracellular fluid is capable of ‘hiding’ up till 5% of CO2 in HCO3 ) If the CO2 raises above 20%, the respiratory centres are no longer stimulated, CNS activity decreases and CO2 narcosis arises.

4.2  Respiratory response to acute hypoxia when paCO2  is normal

A response to acute hypoxia (with normal  paCO2 ) is relatively small and varies. If the paO2  is above 60mmHg, ventilation stays unchanged. However ventilation greatly increases when paO2  drops below 60mmHg. This stimulated peripheral chemoreceptors.

The sensitivity of the receptors depends on genetics and external environment. Individuals with less sensitive receptors are more likely to develop acute altitude sickness, however in chronic altitude sickness the sensitivity of chemoreceptors is increased due to long term stay in high altitude with low partial pressure of oxygen and peripheral chemoreceptors undergo hypertrophy.

Respiratory response to acute hypoxia is the usual cause of drowning, if a person hyperventilates before diving. pCO2, is exhaled in order to stay longer in the water (increased pCO2, is a stimulus to inhale). The level pO2, drops so low, that it stimulates the person to inhale instantly and the person does not have time to swim back to the surface.

4.3 Ventilatory response to combined acute changes of paO2 and paCO2

Hypoxemia and hypercapnia are called asphyxia or type 2. respiratory failure (global, hypercapnic). If the ventilation does not work properly due to diffusion disorder or disturbed ventilation perfusion ratio, that partial pressure of carbon dioxide in the alveoli increases (because it cannot be exhales) that causes decrease of pO2, that leads to:

  • if paCO2 constantly increases, the treshold for paO2 also increases and hypoxic respiratory response develops
  • if the paO2 constantly increases with increasing paCO2 , the response to hypercapnia is greater

The response of respiratory centres to individual stimuli is greater than the sum of them.

Hypoxemia and hypocapnia is most commonly caused by pulmonary embolism or asthma attack:

  • pulmonary embolism activates sympathicus (due to pain) that causes hyperventilation, which decreases paCO2  without pO2  decrease
  • acute hypoxemia (pO2  below 60 mmHg) activates peripheral chemoreceptors that leads to hyperventilation which lowers CO2  (exhalation) which in turn inhibits the respiratory centres , so the response is less vigorous than we would expect.
  • if the paO2  drops below 50 mmHg, hypoxic stimulus the effect of hypocapnia and respiratory response increases without limits

4.4 Respiratory response to acute acidosis

Respiratory response to respiratory acidosis is not possible because respiratory acidosis arises as a consequence of respiratory disorder.

A response to metabolic acidosis (caused by decreased excretion of hydrogen ions by the kidneys, increased production of ketone bodies, increased concentration of nonvolatile acids (lactic acid)) the rate of ventilation is increased, stimulated by peripheral chemoreceptors due to low pH (increased hydrogen ion concentration).

4.5 Respiratory response to chronic hypoxia with hypercapnia

A patient having problems with ventilation firstly develops hypoxia: hypoventilation in the alveoli causes accumulation of CO2 , its partial pressure is increasing ,therefore the partial pressure of oxygen decreases so the overall atmospheric pressure is constant. CO2 diffuses across the membranes more easily than oxygen, therefore paCO2  remains constant, however partial pressure of oxygen in the arteries decreases. Type I. respiratory failure develops – hypoxemia with normal partial pressure of CO2  (also called partial respiratory insufficiency or hypoxic). If the disorder proceeds, the partial pressure of CO2 in the alveoli rises as does it pa CO2 (arterial partial pressure) – type II. respiratory failure – hypoxemia with hypercapnia.

Respiratory regulation of a patient suffering from respiratory failure is very different from a healthy individual:

-chronic hypoxia leads to hypertrophy of carotid bodies and their increased sensitivity to small changes of  pa O2

– chronic hypercapnia causes adaptation of central chemoreceptors to continually increased pa CO2 and their activity is decreased

Lately a research has shown, that the impact of receptors in this situation is not as important. Using 100% oxygen causes vasodilatation in lung vessels (even around hypoventilated alveoli) that leads to disturbed ventilation perfusion ratio (dead space is increased). Also the affinity of hemoglobin to carbon dioxide is decreased. (Halden effect) . Overall patient gets worse.

In patients with type 2. respiratory failure; hypoxemia with hypercapnia, the main regulatory mechanism is peripheral chemoreceptors. If these patients receive 100% oxygen, their peripheral receptors fail to work, while the central chemoreceptors are inactive due to adaptation – apnoea arrises. Therefore we use 5% carbon dioxide, that activates peripheral receptors by pH change and sudden change of paCO2 .

5 Disorders of respiratory regulation

Sleep, a trauma, encephalitis, certain drugs and toxins change the respiratory regulation. It is always ventilation disorder (perfusion and diffusion are regulated by different mechanisms)

Some irregularities of breathing during sleep are considered physiological. We call them disorders if they are intense enough to cause waking up or affect tissue oxygenation.  Physiologically, falling asleep and nonREM sleep decreases the sensitivity of central chemoreceptors, so there is increased partial pressure of carbon dioxide in arterial blool. (Transfer from being awake to being asleep causes decreased basal metabolism and decreased oxygen demand. Tidal volume decreases as we are falling asleep, also laying changes the mechanics of breathing. Tone of the postural muscles changes according to REM/non REM phases which might lead to changes of ventilation perfusion ratio.

Biot’s breathing is an abnormal type of breathing with deep inspirations followed by periods of apnea of various lengths. It is usually caused by damage to nervous tracts, bleeding or compression of cerebellum and pons. It also develops in dying patients as a part of multiple organ failure. (MOF)

Apneustic breathing is characterized by pause (2-3s) at inspiration followed by insufficient exhale due to damage to lower part of the pons (apneustic centre).

Apnoea – a suspension to external breathing for more than 10s and the flow of air is lower than 80%. It arises due to sedatives or narcotics, damage to nerves innervating breathing muscles, damage to neuromuscular plate (curare, myasthenia gravis etc). It usually occurs during sleep. Central type of apnoea – failure to the CNS (respiratory centres in brain stem) – chest movement  is missing and no air is coming out of the mouth. Peripheral (obstructive) type of apnoea is caused by atrophy of the muscles in the upper respiratory tract or its obstruction. Chest movement is increased and the muscles are trying to overcome the obstruction.The consequences are the same – chronic increased sympathetic activity due to hypoxia that reoccurs during sleep (hypertension, disorders of saccharide and lipid metabolism, increased risk of AMI) and pulmonary hypertension due to vasoconstriction of pulmonary capillaries as a response to hypoxia..

Cheyne – Stokes breathing is a rhythmic type of breathing characterized by progressive decrease of the depth of inspiration all the way to apnoea followed by progressive increase. It is caused by decreased sensitivity of respiratory centres to pCO2. If the pCO2 is normal, breathing is getting less deep and results in apnoea. The pCO2 increases during apnoea which stimulates deeper breathing. This type of breathing arises due to hypoxia or ischemia of medulla oblongata (due to heart failure).

Kussmaul breathing is a consequence of metabolic acidosis, most commonly ketoacidosis (ketoacidotic coma in type II. diabetic patients, or starving patients). Increased hydrogen ion concentration activates peripheral chemoreceptors leading to hyperventilation in order to exhale excess CO2.  

CO2 poisoning: small increase of CO2 concentration in the inhaled air causes hyperventilation via stimulating central chemoreceptors. When pCO2 in the inhaled air reaches 20 %, breathing stops.

Opiates (activate μ-2 receptors in medulla oblongata) decrease sensitivity of central chemoreceptors to CO2.

Benzodiazepines activate inhibitory GABA system in the brain stem and therefore decrease the activity of respiratory centres. However their effect is increased with opiates.

Hypothyreosis (light form) decreases the effect of peripheral chemoreceptors on respiratory centres. Heavy form decreases effect of both peripheral and central receptors.

Metabolic alkalosis decreases the activity of respiratory centres, that increases pCO2 and compensates alkalosis.

Pickwick syndrome is characterized by morbid obesity, alveolar hypoventilation, hypersomnolence, dyspnoea, hypoxemia and pulmonary hypertension. It is caused as a combination of decreased activity of respiratory centres, decreases sensitivity of central chemoreceptors and hypoventilation caused by obese chest and weak breathing muscles. Patient presents of obstructive sleep apnoea – relaxed muscles of nasopharynx narrow the lumen of upper respiratory tract, patient ‘snores’, may experience a complete closure of respiratory pathway. Patient cannot sleep, does not get rested during the night and is tired during the day. Recurring hypoventilation decreases partial pressure of oxygen in the alveoli which leads to vasoconstriction of pulmonary vessels leading to pulmonary hypertension and cor pulmonale.