Why do tissues need oxygen

Within the mitochondrial inner membrane, oxygen acts as the terminal electron acceptor at the end of the electron transport chain whereby oxidative phosphorylation results in the synthesis of adenosine triphosphate ATP , the coenzyme that supplies energy to all active metabolic processes.

This article will discuss the key physiological concepts underpinning the movement of oxygen within the human body and also highlight some clinical applications that serve as examples of these concepts. With respect to human physiology, oxygen transport can be divided into that occurring through convection and that occurring by diffusion.

In this context, convection describes the movement of oxygen within the circulation, occurring through bulk transport. This is an active process requiring energy, in this case derived from the pumping of the heart. On the other hand, diffusion describes the passive movement of oxygen down a concentration gradient, for example, from the microcirculation into the tissues and ultimately the mitochondria.

Deoxygenated venous blood becomes oxygenated in the pulmonary capillaries after diffusion down a concentration gradient across the alveolar capillary membrane see Section 2: diffusive oxygen transport. The physiology of control of ventilation and the determinants of alveolar oxygen partial pressure, ventilation—perfusion matching, and diffusion within the alveolar—capillary unit are dealt with elsewhere.

Oxygen is carried in the blood bound to haemoglobin and dissolved in plasma and intracellular fluid. Haemoglobin, an allosteric protein, consists of four protein globin chains, to each of which is attached a haem moiety, an iron-porphyrin compound.

Two pairs of globin chains exist within each haemoglobin molecule. Mutations in the amino acid sequences in the globin chains give increase to both pathological [e. Once oxygen has diffused across the alveolar membrane, it binds reversibly to haemoglobin within the pulmonary capillaries in a cooperative manner forming oxyhaemoglobin.

Up to four molecules of oxygen can be carried simultaneously by one haemoglobin molecule. When a molecule of oxygen binds to haem, the shape of the globin chain is altered, leading an overall change in the quaternary structure of haemoglobin. Subsequent oxygen molecules are then bound with greater affinity. This relationship is best described by the sigmoid-shaped oxyhaemoglobin dissociation curve ODC, Fig. The standard human ODC at pH 7. Drawn from equations described by Roughton and Severinghaus 8 , 9 subsequently validated.

Haemoglobin exists in two forms: taut T , which has a low affinity for oxygen; and relaxed R , which has a high affinity for oxygen. The taut form predominates in the tissues a high carbon dioxide, low pH environment promoting oxygen release, whereas the relaxed form binds oxygen more avidly in areas of high pH, low carbon dioxide tension, and high partial pressures of oxygen such as in the alveoli. This relationship between haemoglobin, oxygen binding, carbon dioxide tension, and pH is known as the Bohr effect.

Carbon dioxide is returned to the lungs from the tissues dissolved in the plasma, either directly or as bicarbonate, and through the formation of carbaminohaemoglobin species within the erythrocyte. Deoxygenated blood has a greater ability to transport carbon dioxide when compared with oxygenated blood, and this is known as the Haldane effect.

In combination therefore, the Bohr and Haldane effects promote oxygen binding and carbon dioxide release in the pulmonary capillaries, with the reverse occurring in the tissues.

Haemoglobin has a maximum theoretical oxygen-carrying capacity of 1. However, due in part to the existence of abnormal forms of haemoglobin such as methaemoglobin and carboxyhaemoglobin, which reduce the oxygen-carrying capacity of haemoglobin, empirically this value seems to be closer to 1. It is a marker of haemoglobin's affinity for oxygen and is used to compare changes in the position of the curve. The ODC position changes in the face of various chemical and physiological factors, and also with different haemoglobin species.

The various factors and their effects on the curve are described in Table 1 , and also the effects of a change in position of the curve on oxygen loading and unloading. Factors that affect the standard human oxygen dissociation curve. Adapted from Thomas and Lumb 6 and Leach and Treacher Of clinical relevance:. Increased 2,3-DPG production is seen in anaemia, which may minimize tissue hypoxia by right-shifting the ODC and increasing tissue oxygen release. Inorganic phosphate is a substrate for the production of 2,3-DPG and thus capillary haemoglobin oxygen release may be impaired if hypophosphataemia is not corrected.

Causes of hypophosphataemia can be divided into: decreased intestinal absorption e. In critical care, hypophosphataemia is often seen in sepsis, after operation, in refeeding syndrome, in diabetic ketoacidosis due to increased urinary phosphate excretion , and during renal replacement therapy. Hypophosphataemia is also noted after an acute liver injury caused by, for example, paracetamol overdose and after hepatic resection. First of all, the word delivery implies that all the oxygen so described is delivered to, and utilized by, metabolizing cells.

Secondly, the word delivery implies an active external process responsible for ensuring arrival of oxygen at the cell. Notwithstanding these comments, we will continue with oxygen delivery within the context of this article in order to remain consistent with common custom and usage.

Global oxygen delivery describes the amount of oxygen delivered to the tissues in each minute and is a product of the cardiac output and arterial oxygen content. It is important to note that this is clearly an overall measure of oxygen delivery and does not describe regional differences—oxygen flux to each tissue bed is not constant throughout the body, rather the microcirculation responds to altering tissue metabolic demands by varying the regional and local blood flow.

As can be seen from the above equation, alterations in cardiac output, arterial oxygen saturation, and haemoglobin concentration will affect oxygen delivery. Under these circumstances, cells have a relative or absolute failure of the capacity to utilize oxygen and increasing D O 2 will have little effect in correcting the hypoxia.

Any cause of microcirculatory dysfunction will affect oxygen delivery, 16 for example, sepsis where nitric oxide production is increased leading to disorders of autoregulation matching of supply with demand within the tissues along with the decreased vascular tone that manifests clinically as hypotension. Manipulation of global oxygen delivery to improve patient outcome has been the focus of goal-directed haemodynamic therapy GDT since its inception in the s.

Given that continuing evidence supports equivalent outcome with low blood transfusion triggers in many clinical contexts haemoglobin concentrations 7. The rate of oxygen consumption depends on cellular metabolic demand and can be manipulated. For example, the use of therapeutic hypothermia to reduce cerebral metabolic demand post-cardiac arrest in order to improve neurological outcome is well documented.

Factors that affect oxygen consumption. Adapted from McLellan and Walsh If D O 2 continues to decrease further below the D O 2 crit, or if V O 2 increases for a given D O 2 crit, tissue hypoxia ensues with resultant anaerobic respiration and lactate production secondary to an imbalance between ATP supply and demand producing a type A hyperlactataemia.

It is also important to highlight that even if global oxygen consumption appears to be supply independent, it does not rule out pathological oxygen supply dependency at a regional or local level, which may only manifest clinically at a later stage.

Figure 2 illustrates the theoretical biphasic relationship between oxygen consumption and oxygen delivery. Points B and E depict D O 2 crit in health and critical illness, respectively.

O 2 ER is known to increase during exercise, peaking at maximal exercise at 0. This is because although D O 2 increases, it does not match the increase in V O 2 required by exercise. In critical illness, however, especially sepsis, V O 2 may continue to increase, even with increasing D O 2 demonstrated by the line EF , and D O 2 crit may be greater than in health. The gradient of slope DE is reduced in critical illness as the tissues are less able to extract oxygen.

A graph depicting the relationship between V O 2 and D O 2. Within the lung, oxygen diffuses from the alveoli into the pulmonary capillaries, driven by the gradient between the partial pressure of oxygen in the alveolar space and that in the deoxygenated pulmonary capillary blood.

In the tissues, oxygen diffuses down a gradient between oxygenated blood in the systemic capillaries and the oxygen-consuming cells. Diffusion can be described by either a phenomenological approach using Fick's laws or an atomistic approach applying the principle known as the random walk of the diffusing particles another example of which is Brownian motion.

Thus, although the global oxygen delivery oxygen flux may be manipulated through changes in cardiac output and oxygen content, at a tissue level diffusion distance and partial pressure gradients will have the greatest effect in altering the diffusive oxygen flux. This is shown in Figure 3.

A diagram illustrating the importance of diffusion distance from capillary to cell and local oxygen tension in determining diffusive oxygen flow rate. Whole-body oxygen transport and utilization can be estimated using two principle approaches: It is worth noting that expired gas analysis, although less invasive, is more direct in its measurement of cellular oxygen consumption.

The humans breathe approximately liters of oxygen per day, and that oxygen helps the tissues in the human body function properly. The body needs approximately Humans need oxygen to provide nutrients to all of the cells in their bodies. If tissues and cells go without oxygen, then they begin to die quickly. For example, brain cells can only go without oxygen for three minutes before they begin to die. The body also needs energy in order to function properly.

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Current paradigms in cellular oxygen sensing. Other Insights:. Benefits of supplementation with Melcalin Vita. The benefits of a synergistic action of red vine, diosmin, hesperidin and vitamin C. Melcalin Flow. Alga Chlorella Pyrenoidosa.