HYPOXIA We will be adding the information on the physiology of respiration, with a description of situations that commonly occur in our lives - especially during holidays - alpine hiking, flying, diving. First, a few clinical notice: Periodic breathing •It is not regular, rhythmic, but respiration occurs in periods ("a moment to breathe, take a moment to not breathe„) • •CHEYNE-STOKES The only one that can be physiological is that it occurs in young children in their sleep •BIOT‘S Always pathological, in CNS diseases - meningitis, encephalitis, injuries •„gasping“Most often in newborns with a disorder of cardiorespiratory reconstruction after birth, the baby "catches" the breath; one breath and nothing for a long time •KUSSMAUL type of hyperventilation with the olfactory sensation of acetone It has a spindle shape The picture shows the different types of breathing: Eupnoea - resting, physiological breathing Sigh - a significant increase in chest volume and tidal volume, used to open collapsed alveoli, short-term increases blood oxygenation. Apneusis - is a special type of breathing, the position of inspiration is interrupted by momentary expirations; was described in animal experiments in lesions over the medula oblongata Vagal breathing – slowly- decrease frequency, with prolongation of inspirium Hypoxia, hypoxemia •Hypoxia is a general name for a lack of oxygen in the body or individual tissues. •Hypoxemia is lack of oxygen in arterial blood. •Complete lack of oxygen is known as anoxia. The most common types of hypoxia: 1.Hypoxic - physiological: stay at higher altitudes, pathological: hypoventilation during lung or neuromuscular diseases 2.Transport (anemic) - reduced transport capacity of blood for oxygen (anemia, blood loss, CO poisoning) 3.Ischemic (stagnation) - restricted blood flow to tissue (heart failure, shock states, obstruction of an artery) 4.Histotoxic - cells are unable to utilize oxygen (cyanide poisoning - damage to the respiratory chain) Hypercapnia • Hypercapnia - increase of concentration of carbon dioxide in the blood or in tissues that is caused by retention of CO2 in the body • possible causes: total alveolar hypoventilation (decreased respiration or extension of dead space) • mild hypercapnia (5 -7 kPa) causes stimulation of the respiratory center (therapeutic use: pneumoxid = mixture of oxygen + 2-5% CO2) • hypercapnia around 10 kPa - CO2 narcosis - respiratory depression (preceded by headache, confusion, disorientation, a feeling of breathlessness) •hypercapnia over 12 kPa - significant respiratory depression - coma and death. Do not forget - Experiment with a mild hyperkapnia – see Textbook Physiology and neuroscience practicals…….estimation of sensitivity of respiratory centre to hyperkapnia. Spiroergometry – combination of ergometry and analysis of breathing gases during work load on bicycle This slide shows influence of breathing during exercise: Change in ventilation immediately after the start of muscle work = a combination of chemical and other non-chemical influences. Nervous regulation is probably decisive, chemical stimuli specify the setting of lung ventilation. Minute ventilation increases in direct proportion to oxygen consumption - pO2, pCO2 and pH values do not change significantly. The respiratory center is activated from the motor areas of the cerebral cortex (efferent corticospinal pathways to the motoneurons of the anterior horns of the spinal cord and at the same time by collaterals to the brainstem) . The lifelong learning process modulates these changes so that the amount of ventilation corresponds as closely as possible to the body's metabolic requirements Irritation of proprioceptors in working muscles, tendons and joint capsule (afferent pathways to the spinal cord, ascending pathways with collaterals activate respiratory centers) •Change in ventilation immediately after the start of muscle work • = a combination of chemical and other non-chemical influences. •Nervous regulation is probably decisive, chemical stimuli specify the setting of lung ventilation. Minute ventilation increases in direct proportion to oxygen consumption - pO2, pCO2 and pH values in blood do not change significantly. • The respiratory center is activated from the motor areas of the cerebral cortex (efferent corticospinal pathways to the motoneurons of the anterior horns of the spinal cord and at the same time by collaterals to the brainstem) . The lifelong learning process modulates these changes so that the amount of ventilation corresponds as closely as possible to the body's metabolic requirements Irritation of proprioceptors in working muscles, tendons and joint capsule (afferent pathways to the spinal cord, ascending pathways with collaterals activate respiratory centers) • HYPOXIA is oxygen deficiency at the cells or the tissue or the organs or the organism level OXYGEN FALL pO2 in mmHg dry atmospheric air 159 humid atmospheric air 149 ideal alveolar gass 105 end-expirated air 105 Arterial blood 77 Cytoplasma – mitochondria 3-10 Mixed venous blood 40 Venous blood 20 You can see the values (approx. = approximate) of pO2 as they gradually go in individual parts of our organism. S02401-002-f007 pO2 = 1 mmHg = critical level of pO2 for mitochondrial activity Important note: pO2 = 1 mmHg-this is a critical level of pO2 for mitochondrial activity Hypoxia has been divided into following types: 1.Decrease oxidation of blood in the lung 2.Pulmonary disease 3.Venous-arterial shorts in circulation 4.Oxygen transport disorder (blood – tissue) 5.Decrease utilization of oxygen by the tissue 6. This slide indicates that you will also encounter another distribution of hypoxia in the clinic The slide indicates that you will also encounter another distribution of hypoxia in the clinic, eg - see the slide. 1.Decrease oxidation of blood in the lung 2. -hypoxic hypoxia: - -lower oxygen in atmospherical air - -hypoventilation (neuromuscular diseases) 1. Classic hypoxic hypoxia - it's not just a lack of oxygen in the surrounding air (in the experiment described in practical exercises in physiology, we use Krogh's respirometer, when we create this type of hypoxia; or when we climb to higher altitudes). But lack of oxygen can also be caused by hypoventilation - insufficient range of chest movements - whether in neuromuscular diseases, or fractures of the ribs and plaster carapace during treatment; for example, in women wearing a corset (see the movie Pirates of the Caribbean and the scene of Elizabeth falling from a tower into the sea… she has a very laced corset, she complains that she can't breathe,…) 2. Pulmonary disease -hypoventilation : - We breathe superficially when we have - narrowed airways - increase airway resistance (asthma bronchiale attack) or - due to lung fibrosis - decrease pulmonary compliance - We breathe superficially when we have narrowed airways (asthma attack) or lung fibrosis with reduced compliance 3. Venous – arterial shunts from fetal circulation: ductus arteriosus Botali foramen ovale Problems with pO2 can occur in the above cases, especially in newborns after birth. However, the unrecognized imperfect closure of the foramen ovale may persist into adult and manifest as minor microembolizations with clinical signs in adult. Problems with pO2 can occur in the above cases, especially in newborns after birth. However, the unrecognized imperfect closure of the foramen ovale may persist into adult and manifest as minor microembolizations with clinical signs in adult. 4. Oxygen transport disorder (anemic hypoxia, stagnant hypoxia, ischemic hypoxia) -Anemia - -Special type of hemoglobin (hemoglobin S-sickle cell anemia) - -Decrease of temperature - -Cardiovascular diseases - -Local disorder in circulation 5. Decrease utilization of oxygen by the tissue (histotoxic hypoxia) -enzyme blocade of respiratory circle (poisoning) - e.g. Cyanid poisoning – cyanid inhibits cytochromoxidase; treatment: methylen blue or nitrites (methemoglobin + cyanid=cyanmetHg=nontoxic compound) - -lower capacity of cells for utilization of oxygen (deficit of vitamins) hypoxie765.jpg Hypoxia is clearly associated with sympathetic activation, which then has other clinical implications (especially in the cardiovascular system) Hypoxia is clearly associated with sympathetic activation, which then has other clinical implications (especially in the cardiovascular system) EXPERIMENT - should be performed exactly according to the instructions in the scripts: Practical exercises in physiology and neuroscience, 2017; Exercise: Determining the sensitivity of the respiratory center to hypoxia •Note: we are creating an example of hypoxic hypoxia •The Krogh respirometer in this case is filled only with ambient air, CO2 absorber (calcium hydroxide) is present. The volume of the respirometer is 10 l of air, one-fifth of which is oxygen - we have 2 liters of oxygen available. The test person is connected to a Krogh respirometer and the gas analyzer (see the following figure). We measure parameters: pO2, pCO2, movements of the respirometer show the respiratory rate and tidal volume, the computer calculates the minute ventilation. Using a pulse oximeter, we also read the oxygen saturation of hemoglobin from the finger of the hand. In addition, we have a record of the heart rate from the sphygmographic curve on the finger of the hand. The test person is connected to a respirometer and begins to breathe at rest. It takes about 2-5 minutes to achieve the effect of hypoxic hypoxia (depending on the intensity of the subject's metabolism, how fast and how much oxygen he consumes). The effect of hypoxia begins to show an increase in minute ventilation as both parameters - pO2 and saturation - decrease. We end the experiment when the saturation drops below 80%. We also notice responses to changes in heart rate. • Hypoxia setup Results We evaluate the experiment in exactly the same way as in the practical exercise, the task of determining the sensitivity of the respiratory center to hypercapnia. We see a gradually increasing parameter of minute ventilation as an effort by the respiratory center to increase the supply of oxygen to the body. The respiratory center is informed of the situation of decreased pO2 via peripheral chemoreceptors. We have a record of two experimental persons, we can compare the parameter of the sensitivity of the respiratory center to hypoxia with each other, according to the steepness of the curve. Person A (black curve) shows a higher sensitivity of the respiratory center to hypoxia - it has a higher steepness. Hypoxic hypoxia – during a trip to high mountains e.g. with cable car to Mont Blanck Effect of high altitude on arterial oxygen saturation (numbers in parenthese are acclimatized value) Altitude barometric pO2 pCO2 pO2 arterial oxygen pressure in air in alveoli in alveoli saturation (m) (mmHg) (mmHg) (mmHg) (mmHg) (%) 0 760 159 40 (40) 104 (104) 97 (97) 3 048 523 110 36 (23) 67 (77) 90 (92) 6 096 349 73 24 (10) 40 (53) 73 (85) 9 134 249 47 24 (7) 18 (30) 24 (38) 12 192 141 29 15 240 87 18 Classical distribution of barometric air pressure and the amount of pO2 and pCO2 with increasing altitude. Breathing pure oxygen altitude barometric pCO2 pO2 arterial oxygen pressure in alveoli in alveoli saturation (m) (mmHg) (mmHg) (mmHg) (%) 0 760 40 673 100 3 048 523 40 436 100 6 096 349 40 262 100 9 134 349 40 139 99 12 192 141 36 58 84 15 240 87 24 16 15 When climbers use oxygen bombs, their saturation at 6,000 m above sea level changes for the better. When climbers use oxygen bombs, their saturation at 6,000 m above sea level changes for the better. Work capacity at high altitude work capacity (compare with normal condition) (%) Unacclimatized 50 Acclimatized for 2 months 68 Native living at 4 023 m but working at 5 182 m above sea level 87 To evaluate the adaptation to alpine conditions, we can use the parameter of work capacity and its comparison: alpine environment versus work in the lowlands: newcomers, non-acclimatized individuals reach only half of their lowland work capacity, and even after 2 months of acclimatization are maximum 60-70%. However, people living permanently (from birth) in the high mountains have a much higher work capacity - (although it does not reach 100% lowland), but it is around 90%. To evaluate the adaptation to alpine conditions, we can use the parameter of work capacity and its comparison: alpine environment versus work in the lowlands: newcomers, non-acclimatized individuals reach only half of their lowland work capacity, and even after 2 months of acclimatization are maximum 60-70%. However, people living permanently (from birth) in the high mountains have a much higher work capacity - (although it does not reach 100% lowland), but it is around 90%. High altitude hypoxia – mountain sickness – alpine disease clinical signs -- mild step CNS disorientation Sensitivity headache Respiration increase (dyspnea, rapid breathing, hyperventilation) BP increase HR increase, arrhythmias muscle loss of co-ordination GIT nausea You read many times that there are injuries in the mountains - this is also a logical consequence of hypoxia - poor coordination of movements (you stumble where this would not normally happen to you). Believe that hypoxia affects everyone a little differently - from my own experience I have a funny incident when we went to Mont Blanc as a family… the track there is very fast, because the cable car will take you there in about 45 minutes - up to 4000m above the sea (you will produce amazing acute hypoxia). The male half of the family had perfect euphoria, "nothing was a problem," running across the plateau from place to place, admiring the mountain and the snow; on the contrary, I could hardly move and lift my legs to one step, and coordinating the movement was almost beyond my power; my daughter was in such a headache that she refused to get back on the cable car, so we all walked from the middle of the hill on foot. The following 3 slides describe the clinical signs of alpine disease (high altitude hypoxia). In each of us, they may manifest as multiple symptoms from multiple areas or only as a single symptom from one area… probably most often (most hypoxia suffers from the brain) from the CNS area symptoms (headache, dizziness, etc.) and from the respiratory system (dyspnea, rapid breathing, hyperventilation…). You read many times that there are injuries in the mountains - this is also a logical consequence of hypoxia - poor coordination of movements (you stumble where this would not normally happen to you). Believe that hypoxia affects everyone a little differently - from my own experience I have a funny incident when we went to Mont Blanc as a family… the track there is very fast, because the cable car will take you there in about 45 minutes - up to 4000m above the sea (you will produce amazing acute hypoxia). The male half of the family had perfect euphoria, "nothing was a problem," running across the plateau from place to place, admiring the mountain and the snow; on the contrary, I could hardly move and lift my legs to one step, and coordinating the movement was almost beyond my power; my daughter was in such a headache that she refused to get back on the cable car, so we all walked from the middle of the hill on foot. High altitude hypoxia – middle step CNS dimness of vision, vertigo, anxiosity GIT nausea Sensitivity chest pain Respiration apnoe BP increase HR decrease, irregulary muscle spasmus Gradually deepening symptoms of altitude sickness. High altitude hypoxia – severe step CNS coma GIT nausea, vomiting Sensitivity chest pain Respiration Cheyn-Stokes breathing BP drop HR decrease Muscle muscle weakness Travelling by aircraft The reason for all the problems described in the following pictures is the fact that we have pressure on board the aircraft as if we were at an altitude of 2000 meters above sea level. Travelling by aircraft This results in an increased risk for patients with: - Concentration of hemoglobin above 60 % - Atherosclerosis - severe step - Cardial insuficiency - Respiratory insuficiency - Hypertension - untreated (BP ower 200/100) (On board aicraft is pressure as on 2000 m above see level) Reduced pO2 in the air on board the aircraft affects the values of systolic and diastolic pressure: - lower pO2 - stimulated sympaticus - increase periphery resistence - decrease stroke volume - decrease pulse pressure - decrease perfusion in tissues - redistribution of blood in circulation - increase of position of diaphragma (decrease hemodynamics and respiration) And this creates an increased risk for patients with - cardio – vascular diseases - - tromb – embolic diseases Diving during holidays - recreational Caution: it is not recommended to dive in one morning and fly home in the afternoon Diving uThere is an increase in ambient pressure - hyperbaria (proportional to the depth of immersion); at every 10m depth the pressure increases by 100kPa The body must be able to cope with the unavailability of a normal supply of air to the lungs uWhen breathing, the respiratory muscles must overcome the water pressure on the chest and at the same time develop sufficient lowpressure(vakuum) in the thoracic cavity for the inspiration to take place. uBy strenuous contraction of the inspiratory muscles we reach a maximum vacuum of about 11kPa = depth 110cm (in greater depths it is not possible to breathe, it is necessary to use a breathing apparatus that adjusts the pressure of the inhaled air to the ambient water pressure - breathing with normal effort u Diving - risks Diving uShort-term - breath holding, rise in pCO2 above 6.6 kPa - stimulation of the respiratory center, compulsion to inspiration u uBreathing using a snorkel The volume of the anatomical dead space of the respiratory tract increases - the limitation of alveolar ventilation (maximum length 40cm, lumen 2 cm) u uLong-term diving - with a breathing apparatus, the question is the content of the apparatus: pure oxygen (toxicity); compressed air - only to a depth of 30-40m (large proportion of nitrogen), to great depths - a mixture of oxygen and helium uHelium is less soluble in tissues, has a smaller molecule than nitrogen - it is excreted faster from the body u u C:\Documents and Settings\ja2\Dokumenty\DEMONSTRACE\regulace dýchání\zadržení dechu 1001.jpg The picture shows the activity of the respiratory muscles during breath holding during diving Begining End easy phase difficult phase … .in the beginning without problems, in the difficult phase you see that the activity of the respiratory muscles increases (activated through the respiratory center, which registers lack of oxygen and CO2 accumulation; fails to maintain this activity of the respiratory muscles and we inhale (… and drown) The picture shows the activity of the respiratory muscles during breath holding… .in the beginning without problems, in the difficult phase you see that the activity of the respiratory muscles increases (activated through the respiratory center, which registers lack of oxygen and CO2 accumulation; fails to maintain this activity of the respiratory muscles and we inhale (… and drown) C:\Documents and Settings\ja2\Dokumenty\DEMONSTRACE\regulace dýchání\zadržení dechu 2002.jpg Forced to breath brain hypoxia loss of consciousness The danger of hyperventilation before diving This picture shows the danger of hyperventilation before diving (please - do not hyperventilate). We must realize that the beginning of respiration is started mainly by the amount of pCO2 in the body. If we hyperventilate before diving, we think that we will accumulate more oxygen in the body and thus stay under water for a longer time… BUT during hyperventilation, pCO2 is also exhaled and we put down the fuse to start breathing in time (you see a shift between the left arrow during normal breathing, and when it will force us to inhale after hyperventilation.This difference is whether we survive diving or drowning.We prolong the dive time, dive deeper, more inhaled oxygen and can affect the CNS euphorically, and loss of orientation below the surface, we won't know where it's up-where it's down, and our "forced breath" signal will be late and we may not be able to emerge. Toxicity of oxygen Toxicity of oxygen The toxicity seems to be due to the production of the superoxid anion and H2O2 Causes: -Loss of the ability to bind CO2 in the venous blood - CO2 output through the lungs is hampered by the development of toxic pulmonary edema Symptoms due to oxygen toxicity manifest themselves depending on the pressure under which we breathe oxygen and mainly depends on the time of exposure Critical values occur when oxygen is exposed to> 40 kPa (300 mmHg) as a function of time Toxicity of oxygen When exposed around 8 hours, occurs - respiratory passages became irritated - Substernal distress - Nasal congestion - Sore throat - Cough When exposed around 24-48 hours, occurs: - damage of lungs – decrease production of surfactant Symptoms: Pulmonary disorders with O2 exposure under pressure> 70 kPa will manifest within a few days - symptoms: cough, respiratory pain; under pressure of 200 kPa for 3 - 6 hours with symptoms: convulsions, loss of consciousness TOXICITY of OXYGEN Recommendation: 100 % - give discontinuosly Best through the so-called "oxygen glasses" - when they add oxygen to the surrounding air Gregg L. Semenza Nobel Prize in Physiology or Medicine 2019 Were awarded the Nobel Prize in Physiology or Medicine 2019 for delineating the biochemical details of elegant stress respons pathway Complex of proteins „Hypoxia inducibile factor“ - HIF