Compiled By: Palak Brahmbhatt

Laws of Thermodynamics and its relation to energy balance and work within biologic systems Potential Energy And Kinetic Energy Energy-Releasing and Energy-Conserving Processes Interconversions of Energy Forms of Energy Biologic work in Humans

The capacity to extract energy from food macronutrients and transfer it at a high rate to the contractile elements of skeletal muscle largely determines ones capacity for swimming, running, or skiing long distance. All forms of biologic work require power generated from the direct transfer of chemical energy.

Extracting energy from the stored nutrients and transferring it to the contractile proteins of skeletal muscle greatly influences exercise performance. We can not define energy in concrete terms of size, shape, or mass. Rather the term Energy suggests a dynamic state related to change; thus the presence of energy emerges when a change occurs. Within this context, energy relates to the performance of work- as work increases so does energy transfer, thus producing a change.

It describes one of the most important principles related to biologic work. The basic tenet states that energy cannot be created or destroyed but, instead, transforms from one form to another without being depleted. This law describes the immutable principle of the conservation of energy that applied to both living and nonliving systems. In the body, chemical energy stored within the bonds of macronutrients does not immediately dissipate as heat during energy metabolism; instead a large portion remains as chemical energy, which the musculoskeletal system then changes in to mechanical energy.

Potential and kinetic energy together constitutes the total energy of a system. Releasing potential energy transforms in to kinetic energy of motion. In some cases, bound energy of one substance directly transfers to other substance to increase their potential energy. This type provide necessary energy for bodys chemical work of biosynthesis. BIOSYNTHESIS is a process, where specific building block atoms of carbon, hydrogen, oxygen, and nitrogen become activated and join other atoms and molecules to synthesize important biologic compounds and tissues. Other synthesized compounds such as adenosine triphosphate (ATP) and phosphocreatine (PCr) serve the cells energy requirements.

Exergonic energy reactions results In a transfer of energy to the surroundings. Such reactions represent Downhill process. Endergonic energy results in the storage conservation or increase in the free energy. This reaction represents Uphill process. In some instances Exergonic process link or couple with Endergonic reaction to transfer some energy to Endergonic process. In the body, such coupled reactions conserved in a unstable form of a large portion of chemical energy stored within the macronutrients.

Energy transfer in cells follow the same principle in the Waterfall-Waterwheel.

Carbohydrate, lipids, proteins, macronutrient have potential energy

Formation of product substances progressively reduces the nutrient molecules, original potential energy which corresponds increase in the kinetic energy

Enzyme regulated transfer systems conserve a portion of the chemical energy in new compounds for use in biologic work

Leaving cell act as a transducer and had a capacity to extract and use chemical energy stored within a compound atomic structure

Also bond atoms and molecules together, raising the level of potential energy

Transfer of potential energy in any spontaneous research always proceed in a direction that decreases capacity to perform work. The tendency of potential energy to degrade to kinetic energy of motion which a lower capacity of work called second law of thermodynamics. E.g. Flash light battery, electrochemical energy stored within its cells slowly dissipates, even if the battery remains unused. The energy from sunlight also continually degrades to heat energy when light strikes and becomes absorbed by a surface.

Food and other chemicals represent excellent stores of potential energy, yet this energy continually decreases as the compounds decompose through normal oxidative processes. Energy, like water, always runs downhill, so potential energy decreases. Ultimately, all of the potential energy in a system degrades to the unusable form of kinetic or heat energy.

Because the total energy in an isolated system remains constant, a decrease in one form of energy is matched by an equivalent increase in other form. During energy conversions, a loss of potential energy from one source often produces a temporary increase in the potential energy of another source. In this way, nature harnesses vast quantities of potential energy for useful purposes. But even under such favorable conditions, the net flow of energy in the biologic world moves toward entropy, which ultimately results in the loss of potential energy.

Entropy reflects the continual process of energy change. All chemical and physical processes in a direction in which total randomness or disorder increases and the energy available for work decreases. In coupled reactions during biosynthesis, part of a system may show a decrease in entropy while another part shows an increase. However, no way exists to circumvent the second law- the entire system always shows a net increase in entropy. In a more global sense, the biochemical reactions within the bodys trillions of cells tilt in the direction of spontaneity that favors disorder and randomness. ( i.e. entropy)

Energy is categorized into one of six forms :

Chemical Mechanical Heat Light Electric Nuclear

The conversion of energy from one form to another occurs readily in the inanimate and animate worlds.

Photosynthesis and Respiration represent the most fundamental examples of energy conversions in living cells.
PHOTOSYNTHESIS In the sun, with a temperature of several million degrees Fahrenheit, nuclear fusion releases part of the potential energy stored in the nucleus of the hydrogen atom. This energy, in the form of gamma radiation, then converts to radiant energy.

CELLULAR RESPIRATION
The reactions of respiration are the reverse of those of photosynthesis as the plants stored energy is recovered for use in biologic work. A portion of the energy released during cellular respirations becomes conserved in other chemical compounds for use in energy requiring processes; the remaining energy flows to the environment as heat.

Biologic work takes one of three forms: Mechanical work of muscle contraction Chemical work that synthesize cellular molecules Transport work that concentrates various substances in the intracellular and extra cellular fluids

It generated by muscle contraction and subsequent movement provides the most obvious example of energy transformation. The molecular motors in a muscle fibers protein filaments directly convert chemical energy into mechanical energy. However, this does not represent the bodys only form of mechanical work. In the cell nucleus, for example, contractile elements literally tug at the chromosomes to facilitate cell division. Specialized structures such as cilia also perform mechanical work in many cells.

All cells perform chemical work for maintenance and growth. Continuous synthesis of cellular components takes place as other components break down. The extreme muscle tissue synthesis that occurs in response to chronic overload in resistance training vividly illustrates chemical work.

The biologic work of concentrating substances in the body progresses much less conspicuously than mechanical or chemical work. Cellular materials normally flow from an area of high concentration to one of lower concentration. This passive process of diffusion requires no energy. For proper physiologic functioning, certain chemicals require transport uphill, against their normal concentration gradients from an area of lower to one of higher concentration. Active transport describes this energy-requiring process.

Secretions and reabsorptions in the kidney tubules use active transport mechanisms, as does neural tissue in establishing the proper electrochemical gradients about its plasma membranes. These quiet forms of biologic work require a continual expenditure of stored chemical energy.

The limits of exercise intensity ultimately depend on the rate that cells extract, conserve, and transfer the chemical energy in the food nutrients to the contractile filaments of skeletal muscle. The sustained pace of marathon runner at close to 90% of maximum aerobic capacity, or the rapid speed achieved by the sprinter in all-out exercises, directly reflects the bodys capacity to transfer chemical energy into mechanical work. Enzymes and coenzymes significantly affect the rate of energy release during chemical reactions.

An enzyme, a highly specific and large protein catalyst, accelerates the forward and reverse rates of chemical reactions within the body without being consumed or changed in the reaction. Enzymes only govern reactions that would normally take place but at a much slower rate. In a way, enzyme reduces the required activation energy. An enzyme-catalyzed reaction proceeds in one direction so that all substrate molecules convert into product molecules with the help of enzyme.

The enzyme first combines with its substrate to form an enzymesubstrate complex

This complex then converts in to an enzyme-intermediate complex

It further changes to an enzyme-product complex that quickly dissociates into free product and the enzyme released unchanged

Enzymes possess the unique property of not being readily altered by the reactions they affect. Consequently, enzyme turnover in the body remains relatively slow, and the specific enzymes are continually reused. A typical mitochondrion may contain up to 10 billion enzyme molecules, each carrying out millions of operations within a brief time. During strenuous exercise, the rate of enzyme activity increases tremendously within the cell, as energy demands increase some 100 times above the resting level. A single cell contains thousands of different enzymes, each with a specific functions that catalyzes a distinct cellular reaction.

Enzymes usually take the names of the functions they perform. The suffix ase appended to the enzyme whose prefix often indicates its mode of operation or the substance with which it interacts.

For example, hydrolase adds water during hydrolysis reactions, protease interacts with protein, oxidase adds oxygen to a substance.

Enzymes do not all operate at the same rate; some operate slowly, others much more rapidly. Enzymes often work cooperatively among their binding sites. While one substance turns on at a particular site, its neighbor turns off until the process completes. Enzymes also can act along small regions of the substrate, each time working at a different rate than previously. Some enzymes delay initiating their work. For some enzymes, peak activity requires relatively high acidity, while others function optionally on the alkaline side of neutrality. This pH effect on enzyme dynamics takes place because changing fluids hydrogen ion concentration alters the balance between positively and negatively changed charged complexes in the enzymes amino acids.Increase in temperature generally accelerate enzyme reactivity.

Step 1 : The active site of the enzyme and substrate line up to achieve a perfect fit, forming an enzymesubstrate complex. Step 2 : The enzyme catalyzes(greatly speeds up) the chemical reaction with the substrate. Note that the hydrolysis reaction adds a water molecule. Step 3 : An end-product (two glucose molecules) forms releasing the enzyme to act on another substrate.

Lock and key mechanism This interactive process ensures that the correct enzyme mates with its specific substrate to perform a particular function. Once the enzyme and substrate join, a conformational change in enzyme shape takes place as it molds to the substrate. Even if an enzyme links with a substrate, unless the specific conformational change occurs in the shape of the enzyme, it will not interact chemically with the substrate. The lock and key mechanism serves a protective function so only the correct enzymes activates a given substrate.

Some enzymes remain totally dormant without activation by additional substances termed coenzymes. The metallic ions iron and zinc play coenzyme roles, as do the B vitamins or their derivatives.

Oxidation-reduction reactions use the B vitamins riboflavin and niacin, while other vitamins serves as transfer agents.
Some advertisements for vitamins imply that taking vitamin supplements provide immediate usable energy for exercise. A coenzyme requires less specificity in its action than an enzyme because the coenzyme affects a number of different reactions.

ENZYME INHIBITION Competitive inhibitors

Closely resemble the structure of the normal substrate for an enzyme, so they bind to the enzymes active site but cannot be changed by the enzyme. The inhibitor repetitively occupies the active site and blunts the enzymes ability to interact with its substrate.

Noncompetitive inhibitors

Do not resemble the enzymes substrate and do not bind to its active sites. Instead, they bind to the enzyme at a site other than the active site, which cause a change in the enzymes structure and ability to catalyze the reaction because of the presence of the bound inhibitor. Many drugs act as noncompetitive enzyme inhibitors.

Hydrolysis Reactions Hydrolysis catabolizes complex organic molecules carbohydrates, lipids, and proteins- into simpler forms the body easily absorbs and assimilates. This basic decomposition process splits chemical bonds by adding H+ and OH- to the reaction by products. Example of hydrolytic reactions include digestion of starches and disaccharides to monosaccharides, proteins to amino acids, and lipids to glycerol and fatty acids. AB + HOH A H + B - OH

Condensation Reactions The reactions illustrated for hydrolysis can occur in the opposite direction.

In the reverse reactions, the compound AB is synthesized from A H and B OH, and a water molecule forms in the building, or anabolic, process of condensation.
The structural components of the nutrients bind together in condensation reactions to form morecomplex molecules and compounds.

Literally thousands of simultaneous chemical reactions occur in the body that involves the transfer of electrons from one substance to another. Oxidation reactions transfer either oxygen atoms, hydrogen atoms, or electrons. A loss of electrons always occurs in oxidative reactions, with a corresponding gain in valence. For example, removing hydrogen from a substance yields a net gain of valence electrons.

Reduction involves any process in which the atoms in an element gain electrons, with a corresponding decrease in valence.

The term reducing agent describes the substance that donates or loses electrons as it oxidizes. The substance being reduced or gaining electrons is called the electron acceptor or oxidizing agent. Electron transfer requires both an oxidizing agent and a reducing agent. Oxidation and Reduction reactions become characteristically coupled. Whenever oxidation occurs, the reverse reduction also takes place; when one substance loses electrons, the other substance gains them. The Redox reaction commonly describes an oxidation-reduction reaction.

The effect of the concentration of chemicals in solution on the occurrence of a particular chemical reaction embodies the law of mass action, often referred to as the mass action effect. In essence, a chemical reaction progresses to the right with the addition of reactants and to the left with the addition of byproducts.
In a simple chemical reaction, the formation of product increases linearly with the concentration of chemicals available to enter the reaction.

In an enzyme-mediated reaction, however, the rate of product formation increases dramatically with a small change in substrate concentration, which generally produces a relatively large effect on product formation.

Certain substances in the body frequently link to several reaction; thus, the products of one reactions become reactant substances for other reactions. Simply changing the concentration of one substance profoundly affects a number of different reactions. Also some molecules play key roles in a whole chain of chemical events.

Oxygen, for example, exerts a significant mass action effect on reactions required for energy transfer. If oxygen supply to tissue diminishes, several chemical processes cease, and the net energy available for biologic work decreases dramatically.

The gain or loss of heat in the biologic system provide a simple way to determine the energy dynamics of any chemical process. For example, in food catabolism, within the body, a human calorimeter measures the energy change directly as heat (kcal) liberated from the reactions.

Because complete combustion of food takes place at the expense of molecular oxygen, the heat generated in these exergonic reactions can readily be determined from measurements of oxygen consumption.
Oxygen consumption measurement forms the basis of indirect calorimetry and enables one to infer the energy metabolism of humans during rest and diverse physical activities.

Gases moves from one point to another by diffusion & the cause of this movement is always a Pressure difference from the first point to the next. Alveoli [O2 diffusion]

Pulmonary capillary blood

Conversely, when oxygen is metabolized in the cells to form CO2 , the PCO2 rises to a high value, which causes CO2 to diffuse into the tissue capillaries. Pulmonary capillary blood [CO2 diifusion] Alveoli

During strenuous Ex. A persons body may require as much as 20 times the amount of oxygen. Also, because of the increased Cardiac Output, the time that blood remains in the pulmonary capillary maybe reduced to less than one-half normal. O2 diffusion capacity increases almost threefold during Ex. Due to 1. Increased surface area of capillaries participating in the diffusion 2. More nearly ideal Ventilation-Perfusion ratio in the upper part of the lungs.

The blood becomes more saturated with oxygen by the time it has passed through 1/3 of the pulmonary capillary and little additional Oxygen normally enters the blood during the latter 2/3 of its transit. The blood normally stays in the lung capillaries about 3 times as long as necessary to cause full oxygenation. Therefore, In Exercise, even with the shortened time of exposure in the capillaries, the blood can become fully oxygenated or nearly so.

About 98% of blood the blood that enters the left atrium from the lungs has passed through the alveolar capillaries and has become oxygenated up to a PO2 of about 104 mmHg. Another 2% of the blood has passed directly from the Aorta through the bronchial circulation, which supplies mainly the deep tissues of the lungs and is not exposed to the pulmonary air. This blood flow represents shunt flow , meaning blood that is shunted past the gas exchange areas.

On leaving the lungs, the PO2 of the shunt blood is about that of normal venous blood, about 40mmHg.

This blood combines in the Pulmonary veins with the oxygenated blood from alveolar capillaries This mixing of the blood is called Venous Admixture of blood.
It causes the PO2 of the blood pumped by the left side of the heart into the aorta to fall to about 95 mmHg.

When the arterial blood reaches the peripheral tissues, its PO2 in the capillaries is still 95 mmHg.Yet, the PO2 in the interstitial fluid that surrounds the tissue cells average only 40 mmHg.
Thus, There is a tremendous initial pressure difference that causes oxygen to diffuse rapidly from the blood into the tissues, so rapidly that the capillary PO2 falls almost to equal the 40 mmHg pressure in the interstitium. Therefore, the PO2 of the blood leaving the tissue capillaries and entering the veins is also about 40 mmHg.

EFFECT OF RATE OF BLOOD FLOW ON INTERSTITIAL FLUID PO2 If the blood flow through a particular tissue becomes increased, greater quantities of oxygen are transported into the tissues in a given period and the tissue PO2 becomes correspondingly increased.
EFFECT OF RATE OF TISSUE METABOLISM ON INTERSTITIAL FLUID PO 2 If the cells use more O2 for metabolism than normally , this tends to reduce the interstitial fluid PO2.

1. 2.

The rate of oxygen transport to the tissues in the blood The rate at which the oxygen is used by the tissues.

Oxygen is always used by the cells. Therefore the Intracellular PO2 in the peripheral tissue cells remains lower than the Po2 in the peripheral capillaries. Also, there is considerable distance between the capillaries and the cells. The Normal intracellular Po2 ranges from As low as 5 mmHg to as high as 40 mmHg Averaging 23 mmHg Because only 1 to 3 mmHg of Oxygen Pressure is normally required for full support of the chemical processes that use oxygen in the cell. So even this low intracellular Po2 of 23mmHg is more than adequate and provides a large safety factor.

When O2 is used by the cells CO2

increases the intracellular Pco2. [CO2 diffuses] Cells Tissue Capillaries [By blood] Lungs Pulmonary Capillaries Alveoli

At each point in the gas transport chain, CO2 diffuses in a direction exactly opposite that of O2 diffusion.
Major difference between diffusion of O2 and CO2 : CO2 can diffuse about 20 times as rapidly as O2. Therefore, The Pressure differences required to cause CO2 diffusion are far less than the pressure differences required to cause O2 diffusion.

1. Intracellular Pco2 about 46 mmHg & Interstitial Pco2 about 45 mmHg. 2. Pco2 of arterial blood entering the tissue 40 mmHg & Pco2 of venous blood leaving the tissue - about 45 mmHg

[UPTAKE OF CO2 BY THE BLOOD IN THE TISSUE CAPILLARIES]

DIFFUSION OF CARBON DIOXIDE FROM THE PULMONARY BLOOD INTO THE ALVEOLUS

 Exactly opposite from the ways in which they affect tissue Po2.

1.

A decrease in blood flow

one quarter normal (Point B)

from Normal (Point A)

increases the tissue Pco2

from the normal value of 45 mmHg

Elevated level of 60mmHg

Conversely, Increasing the blood flow to 6 times normal (Point C)

Decreases the Pco2

from the normal value of 45 mmHg 41 mmHg

2. 10- fold increase in metabolic rate

greatly elevates the interstitial fluid Pco2 at all levels of blood flow Decreasing the Metabolism to one quarter normal Interstitial fluid Pco2 to fall to about 41 mmHg. Closely approaching that of the arterial blood , 40 mmHg.

Normally, about 97% of the oxygen transported from the lungs to the tissues is carried in chemical combination with hemoglobin in RBC.
The remaining 3% is transported in the dissolved state in the water of the plasma and cells.

Thus, under normal conditions, oxygen is carried to the tissues almost entirely by Hemoglobin.

The Oxygen molecules combine loosely and reversibly with the heme portion of the hemoglobin. When Po2 is high, as in the Pulmonary capillaries

O2 binds with the hemoglobin When Po2 is low, as in the tissue capillaries O2 is released from the hemoglobin

The blood of a normal person contains about 15 grams of hemoglobin in each 100 ml of blood and each gram of hemoglobin can bind with a maximum of 1.34 ml of oxygen. 15 * 1.34 = 20.1 which means on an average, The hemoglobin in 100 ml of blood can combine with a total of almost Exactly 20 ml of O2, when the hemoglobin is 100% saturated, usually expressed as 20 volumes percent.

[Effect of blood Po2 on the quantity of oxygen bound with hemoglobin in each 100 ml of blood]

During heavy Exercise, the muscle cells use O2 at a rapid rate, which , in extreme cases, can cause the interstitial fluid Po2 to fall to as 15 mmHg. At this pressure only 4.4 ml of O2 remain bound with the hemoglobin in each 100 ml of blood. Thus, 19.4- 4.4=15h ml, is the quantity actually delivered to the tissues by each 100 ml of blood. 3 times as much as O2 as normal is delivered in each volume of blood that passes through the tissues & Cardiac Output can increase to 6 to 7 times normal in well-trained Marathon runner

The percentage of the blood that gives up its oxygen as it passes through the tissue capillaries is called the utilization coefficient. The normal value for this is about 25%, i.e 25% of the oxygenated hemoglobin gives its oxygen to the tissues.

During strenuous Exercise, the Utilization coefficient in the entire body can increase to 75 to 85 percent.
And in the local tissue areas where the blood flow is extremely slow or the metabolic rate high, utilization coefficients approaching 100% have been recorded i.e. essentially all the oxygen is given to the tissues.

 Another

major function essential to life as a tissue Oxygen buffer system. i.e. the Hemoglobin in the blood is mainly responsible for stabilizing the oxygen pressure in the tissues.

Role

of hemoglobin in maintaining Constant Po2 in the tissues The hemoglobin in the blood automatically delivers O2 to the tissues at a pressure that is held rather tightly between about 15 and 40 mmHg.

A shift of the Oxygen hemoglobin dissociation curve in response to changes in the blood CO2 and Hydrogen ions has a significant effect in enhancing oxygenation of the blood in the lungs and then again in enhancing release of O2 from the blood in the tissues .

Blood passes through the lungs Alveoli

Co2 diffuses : From the blood

Reduces the blood Pco2 and Decreases the H+ ion Concentration [because of the decrease in blood carbonic acid] Shift of Oxygen-Hemoglobin dissociation curve to the left & upwards

Therefore, the quantity of the Oxygen that binds with hemoglobin at any given alveolar Po2 now becomes considerably increased. Allows greater O2 transport to the tissues.

The normal DPG in the blood keeps the Oxygen-Hemoglobin dissociation curve shifted slightly to the right all the time.

In Hypoxic conditions, that last longer than a few hours, the quantity of DPG in the blood increases considerably. That shifts Oxygen Hemoglobin dissociation curve even farther to the right.
This causes oxygen to be released to the tissues at as much as 10 mmHg higher tissue oxygen pressure than would be the case without this increased DPG. DPG mechanism important for adaptation to hypoxia, especially caused by poor tissue blood flow.

In exercise, several factors shift the dissociation curve to the right, delivering extra amounts of Oxygen to the active , exercising muscle fibers. The exercising muscle release large quantities of CO2, also several other acids released by the muscles, increases the hydrogen ion concentration in the muscle capillary blood.

Increase in Muscle Temp. to 2 to 3 degrees increases O2 delivery to muscle fibers.

This right hand shift of the curve allows oxygen to be released to the muscle at Po2 levels as great as 40 mmHg, even after removing 7580% of O2 from the Hemoglobin. Then, in the lungs, the shift occurs in the opposite direction , allowing pickup of extra amounts of O2 from the Alveoli.

EFFECT OF INTRACELLULAR Po2 ON RATE OF OXYGEN USAGE : Only a minute level of oxygen pressure is required in the cells for normal intracellular cellular chemical reactions to take place

The reason : The respiratory enzyme systems of the cell, are generated so that when cellular Po2 is >1 mmHg, O2 availability is no longer a limiting factor in the rates of chemical reactions, Instead the main limiting factor is the concentration of (ADP) in the cells.

[Effect of intracellular po2 on rate of oxygen usage by the cells ] Note : Increasing the intracellular concentration of Adenosine diphosphate(ADP) increases the rate of oxygen usage.

ATP used in the cells to provide energy ADP

Increase in concentration of ADP

Increases the metabolic usage of both oxygen and various nutrients that combine with the Oxygen to release energy This energy used to convert ADP ATP

Under Normal operating conditions, the rate of oxygen usage by the cells is controlled ultimately by the rate of energy expenditure within the cells i.e. by the rate at which ADP is formed from ATP.
Only at very low intracellular Po2 (<1mmHg) does the availability of oxygen become a limiting condition.

Tissue cells are seldom more than 50 mm away from a capillary & O2 normally can diffuse readily enough from the cells to supply all the required amounts of oxygen for metabolism. Occasionally, cells are located farther from the capillaries rate of O2 diffusion to these cells becomes so low Intracellular Po2 falls below the critical level of 1 mmHg i.e. required to maintain maximal intracellular metabolism. Under these conditions, O2 usage by cells is said to be diffusion limited and is no longer determined by the amount of ADP formed in the cells. Almost never occurs in Pathological states.

1. 2.

The total amount of O2 available each minute for use in any given tissue is determined by : The quantity of O2 transported in each 100 ml of blood The rate of blood flow If the rate of blood flow falls to 0

Amount of available O2 - falls to 0 There are times when the rate of blood flow through a tissue can be so low that the tissue Po2 falls below the critical 1 mmHg required for maximal intracellular metabolism. Under these conditions, The rate of tissue usage of O2 is Blood flow limited

At the normal arterial Po2 of 95 mmHg, about 0.29 ml of O2 is dissolved in every 100 ml of water in the blood. When the Po2 of the blood falls to 40 mmHg in the tissue capillaries only 0.12 ml of O2 remains dissolved. In other words : ).17 ml of O2 is normally transported in the dissolved state to the tissues by each 100 ml of blood.

During Strenuous Exercise Hemoglobin release of O2 to the tissues Increases Threefold

The relative quantity of O2 Transported in the dissolved state falls to as little as 1.5 %

But if a Person breathes O2 at very high alveolar Po2 levels

The amount transported in the dissolved state czan become much greater Sometimes so much so that serious excesses of O2 occur in the tissues and Oxygen Poisoning ensues. Seizures and Death In relation to High Pressure breathing of O2, as occurs in deep-sea divers

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