Why Oxygen?

by Steve Morgan & Sophie Connolly

"Assume nothing, trust no one, give oxygen."

Anon

In case you haven’t being paying attention, science is cool. Indulge your inner geek by joining us on our pursuit of developing an integrated scientific understanding from which you can develop a clinical practice informed by deeper insights and inoculation against magical thinking.

We are going to take an unashamedly convoluted journey from atmospheric gas to the mitochondria and back again, to examine respiratory physiology and hopefully frame the information in a narrative format that helps you on your inexorable march to examination success.

Have you ever asked yourself what is all the fuss about oxygen? In the first two podcasts we are going to address why oxygen is the foundational slab of our hierarchy of needs and how it got here in the first place. It might just give you a renewed appreciation of nature’s most vital pharmaceutical.

How Oxygen?

by Steve Morgan & Sophie Connolly

"Among the most notable things about fire is that it requires oxygen to burn, exactly like its enemy, life. Thereby are life and flames so often compared."

Otto Weininger

Welcome to the second podcast in the Basic Science Clinic Raw Science series.  In our somewhat circuitous exploration of respiratory physiology we will complete the story of the promiscuously electronegative pharmaceutical gas oxygen.

In the first episode of this series we addressed the ‘why’ of oxygen, exploring its unique physicochemical properties to explain its onerous position as the foundational slab of our hierarchy of needs.  Having traced our way from the presence of oxygen in the atmosphere to the ETC at a mitochondrial level, we now move to the ‘how’ of oxygen.  In this second podcast we return to the atmosphere, examining the contributors to the gaseous composition, as both a signature and supporter of complex biology, and the morphological adaptations necessary to successfully interface with the atmosphere to harvest its oxygen content.

Atmospheric Physics

by Steve Morgan & Sophie Connolly

“Equipped with his five senses, man explores the universe around him and calls the adventure Science.”

Edwin Hubble

Welcome to the third podcast in the Basic Science Clinic Raw Science series.  Following our investigation of the how and why of oxygen, you may be eagerly anticipating the gas’ entry into the respiratory system, prompting a discussion of gas flow, partial pressures and similarly patient-based physiology. Think again.  Resisting the urge to dive down the trachea, we need to describe some foundational concepts to fine tune the resolution of your understanding. Enter atmospheric physics.  Remember physiology is functional biology, biology is effectively applied chemistry, and chemistry is applied physics.

This week we discuss the physics of atmospheric gas in the biosphere.  Such a topic raises discussion of fluid and gauge pressure, heat and temperature, the SI units and clearly, why the sky is blue.

The Gas Laws

by Steve Morgan & Sophie Connolly

"We live in a society exquisitely dependent on science and technology, in which hardly anyone knows anything about science and technology."

Carl Sagan

Welcome to Basic Science Clinic Raw Science episode 4. We are close to embarking on the descent down the oxygen cascade, en route we will examine the key contributors to these stepwise decrements in oxygen partial pressure that coax the gas down to the level of the mitochondria. To grasp the concepts essential to the physiology of this pathway you need to understand the fundamentals of gas behaviour, enter the gas laws.

In this pod we will cover:

Boyle’s, Charles’, Guy-lussac’s laws

Avogadro’s number 

Dalton’s and Henry’s laws

Saturated vapour pressure & boiling point

The concept of in vivo partial pressures

Humidification & Dihydrogen Oxide

by Steve Morgan & Sophie Connolly

“…water is the driving force of all nature….without it, nothing retains its form.”

Leonardo Da Vinci

Welcome to Basic Science Clinic Raw Science episode 5. Let’s get down to business and accompany oxygen on its relentless tumble from nasopharynx to mitochondria down the partial pressure staircase that explains how 160 mmHg of inspired oxygen partial pressure becomes 20 mmHg in the inner mitochondrial matrix. In this pod we will examine step one of this cascade and the science of the humidification of dry, inspired atmospheric gas, whilst paying deference to dihydrogen oxide.

Water is pretty amazing stuff. It is the solvent of life characterized by anomalous idiosyncrasies without which biology wouldn’t even be a thing.  It is the only substance found concurrently in 3 phases on Earth’s surface and is a byproduct of the outpouring of stellar gas and dust produced when a star is born. NASA recently discovered a water vapour cloud surrounding a quasar 12 billion light years away, a celestial snapshot capturing the antiquity of water in the universe.

What to expect:

What makes water so special?

What is water’s role in the first step of the oxygen cascade?

What is the difference between a gas and a vapour?

How do you define humidity?

Fluids & Flow

by Steve Morgan & Sophie Connolly

"If you can’t explain it simply, you do not understand it well enough."

Albert Einstein

Welcome to Basic Science Clinic Raw Science episode 6. The next step on the oxygen cascade relates to the composition of alveolar gas, how and why it differs from that in the upper respiratory tract and conducting airways. This composition is determined by the components of the alveolar gas equation (AGE). We will examine the AGE in more detail in the next podcast, but for now we can take it to be PAO2 = PiO2 – PaCO2/RQ. In this conceptual model the PiO2 describes the gas entering the alveolus and the second half, the minus PaCO2/RQ, is the net gas leaving the alveolus as oxygen is exchanged with CO2 across the alveolar capillary membrane. The PAO2 is therefore the net alveolar oxygen partial pressure reflecting the interaction of these two processes. The composition of PiO2 we ascertained in the last podcast where humidification and warming of inspiratory gas at 1 atm leaves us with approximately 150 mmHg of oxygen partial pressure at the carina. Before we analyse the gas in the alveolus we are going to examine how it gets there and the factors that affect pulmonary ventilation and respiratory gas flow.

Remember deranged physiology at each transition point on the oxygen cascade may limit the efficacy of oxygen transfer and hence reduce the amount of oxygen delivered to the mitochondria. It is important to understand the ways in which these steps can be disrupted and then systematically consider them all in your assessment of undifferentiated hypoxia. Step 1 is calculating the PiO2, which is FiO2 multiplied by Patm – PH2O. Therefore reduced FiO2, for example when oxygen is consumed in a house fire, or reduced barometric pressure, for example on the peak of mount Everest, are both potential causes in reduced oxygen partial pressure at step 1 and hence are causes of downstream tissue hypoxia.

For step 2 a comprehensive understanding of the complex of interrelated factors that affect respiratory gas flow and the provision of oxygen replete inspired gas to the alveolus is crucial core knowledge for a budding critical care physician. To bear the responsibility of mechanically ventilating a patient’s potentially injured lung, it is incumbent on us to be fortified by a high fidelity conceptual model.

In this pod we will cover:

Fluids and Flow

How can you predict the type of flow in a fluid system?

How do you define viscosity?

What about the specifics of gas flow in the airways?

What is ventilation?

So how does the respiratory apparatus generate a pressure differential?

Oppositional Forces

by Steve Morgan & Sophie Connolly

"What we know is not much. What we do not know is immense." 

Pierre-Simon Laplace

Welcome to Basic Science Clinic Raw Science 7. As a prelude to deconstructing gas exchange we have been examining how humans, as tidal ventilators, replenish the composition of the gas in the functional residual capacity to provide a plentiful oxygen repository to buffer fluctuations in the oxygen content of blood leaving the lung with every beat of the heart.

Convective, pressure gradient driven, bulk gas volume displacement can only occur if the displacing force is greater than the forces that oppose gas flow. These oppositional forces are the physiological targets of pathological processes that affect the lung, that alter pulmonary mechanics, increase work of breathing eventually critically compromising respiratory function and indicating the need for respiratory support measures. To effectively manage organ system dysfunction it is vital to develop an intimate understanding of your enemy so today we will examine the oppositional forces to gas flow that are among the key perpetrators of respiratory failure.

In this pod we’ll cover:

What are the oppositional forces to gas flow?

What is elastance?

What is elastic recoil and what are its determinants?

How does the lung prevent surface tension induced alveolar instability?

What is the 2nd major oppositional force to gas flow?

How do these driving and oppositional forces relate to work of breathing?

Adaptation & Alveoli

by Steve Morgan & Sophie Connolly

"An expert is a person who has made all the mistakes that can be made in a very narrow field."

Niels Bohr

Welcome to Basic Science Clinic Raw Science 8. Convective gas flow through the tracheobronchial tree is the end-point of pulmonary mechanics but the fundamental purpose of the lung is gas exchange, comprised of three interlinked physiological processes: ventilation, diffusion and perfusion. Today we examine the incredible structural adaptation of the human lung down to the alveolus as the centrepoint of gas exchange, a process itself best conceptualized via the elegant physiological model of the alveolar gas equation.

The unraveling of the procession of pulmonary blood flow from right ventricle to lung to facilitate the mingling of blood and air involved protagonists that spanned epochs from Hippocrates to Galen and eventually in 1661 to Marcello Malpighi. He was the first person to view the pulmonary capillaries and alveoli through the augmented reality offered by the light microscope that had been invented in 1590.

The composition of gas in the alveoli determines and represents the process of pulmonary gas exchange and provides a framework for understanding the mechanisms and practical physiological limitations. Alveolar gas is practically inaccessible in vivo and hence requires an accurate and precise model to ascertain its configuration under specific conditions.

The alveolar gas equation relates the alveolar partial pressure of oxygen to inspired partial pressure of oxygen, alveolar and hence arterial partial pressure of carbon dioxide and the respiratory quotient.

How is the lung adapted to optimise gas exchange?

So how does the alveolus fit in?

What are the cell populations in the alveolar region?

How can we model pulmonary gas exchange?

Carbon Dioxide & Dead Space

by Steve Morgan & Sophie Connolly

In the words of the canonical Roman poet Ovid: “Sickness seizes the body from bad ventilation”.

Welcome to Basic Science Clinic Raw Science 9. Convective gas flow provides the substrate to interface with alveolar structural and functional adaptation in orchestrating gas exchange. Gas exchange is the serial interconnection of ventilation, diffusion and perfusion. Alveolar gas composition is determined by amount and type of gases delivered by ventilation, the rate and direction of gas diffusion, and the pulmonary blood flow which continuously recalibrates partial pressure gradients to direct oxygen and carbon dioxide movement. Bulk gas volume displacement is the mechanism of ventilation, but how do we conceptualise and quantify its contribution to gas exchange and its associated abnormalities? In this pod we will examine the quantification of ventilation and parse its correspondence with variance in the dead space volume and central role in carbon dioxide homeostasis.

In this podcast we will cover:

How do we define pulmonary ventilation?

What is the relationship between alveolar minute ventilation and alveolar gas composition?

What are the determinants of arterial carbon dioxide partial pressure?

What are the physiological sequelae of hypercapnia?

What is permissive hypercarpnia?

What is dead space?

How do we quantify dead space volume?

What are the factors that affect dead space?

Pulmonary Diffusion

by Steve Morgan & Sophie Connolly

“It is of great advantage to the student of any subject to read the original memoirs on that subject, for science is always most completely assimilated when it is in the nascent state.”

James Clerk Maxwell

Welcome to Basic Science Clinic Raw Science 10. Not before time we are ready to approach the alveolar-capillary membrane to substantiate the factors that determine the reciprocal exchange of biologically operative respiratory gases. For all the demonstrable complexity of transport and signaling mechanisms in the human body, the energetically neutral transaction of simple passive diffusion is culpable for the cascading maintenance of gas exchange homeostasis and oxidative phosphorylation, with its explosive potential for driving the evolution of ostentatious biological complexity. The adaptive imperative to exploit diffusion for gas exchange imposes certain anatomical demands on the respiratory system. Namely the requirement for a huge tissue surface area of negligible thickness, and minimising diffusion impedance, whilst ensuring dependable partitioning of air space and blood compartments, even in conditions of extreme flow and pressure fluctuations. In this pod we will detail the determinants of diffusion and unravel its antecedence to the segregation of the pulmonary and systemic circulations as a prelude to dissecting the emblematic features of pulmonary perfusion.

In this podcast:

What is Graham’s Law?

How does diffusion proceed in the human lung?

So where does Fick’s law fit in?

What is meant by diffusion and perfusion limitation?

How do we quantify pulmonary diffusion?

What are the physiological components of the diffusing capacity?

How is diffusion responsible for the pulmonary circulation?

Pulmonary perfusion

By Steve Morgan & Sophie Connolly

“The physiology of today is the medicine of tomorrow.”

Ernest H. Starling

Welcome back to the basic science clinic podcast on ICN. Post-hiatus we are ready to reinvigorate the examination of oxygen cascade physiology, from the prevailing atmosphere down to the only organelle that boasts its own bespoke genome, the mitochondrion. In the last podcast we decomposed the minutiae of passive respiratory gas diffusion across the alveolar capillary membrane. Prior to expounding the pre-eminence of V/Q ratios in determining gas exchange sufficiency, we need to publically vivisect the pulmonary circulation to bring you the belated Raw Science 11, pulmonary perfusion.

This detailed inspection of pulmonary perfusion is the longest podcast yet, no doubt we got slightly carried away and thus we have broken it up into three more comfortably digested sections. Section 1 will include the historical bit and both adult and fetal anatomy. Section 2 examines pulmonary haemodynamics and the integrated control of pulmonary vascular tone. Section 3 details the protean functions of the pulmonary endothelium and endothelial glycocalyx, the determinants of transvascular fluid flux in the lung, all with reference to the pathophysiology of acute lung injury.

The pulmonary circulation participates in gas exchange, blood filtration, metabolic regulation of endogenous vasoactive mediators, drug uptake, metabolism and excretion and the regulation of lung interstitial fluid homeostasis, a dexterous function devastated by the clinical syndrome of ARDS. Understanding the idiosyncracies of the pulmonary circuit is imperative for interpreting heart-lung interactions that influence V/Q distribution & gas exchange efficiency as well as overall cardiovascular performance, particularly during positive pressure ventilation in the context of concomitant shock states.

Section 1 (start to 18:24)

The historical bit. Galen to Harvey.

Fetal development & neonatal adaptation

Adult anatomical considerations

Section 2 (18:30-40:26)

Pulmonary haemodynamics

PVR determinants

Regulation of pulmonary vasomotor tone

Section 3 (40:35 to end)

Functions of the pulmonary endothelium

Control of EVLW & Starling's forces

Endothelial glycocalyx