Consensus paper: current state of first- and second-line therapy in advanced clear-cell renal cell carcinoma. – UroToday

The therapy of advanced (clear-cell) renal cell carcinoma (RCC) has recently experienced tremendous changes. Several new treatments have been developed, with PD-1 immune-checkpoint inhibition being the backbone of therapy. Diverse immunotherapy combinations change current first-line standards. These changes also require new approaches in subsequent lines of therapy. In an expert panel, we discussed the new treatment options and how they change clinical practice. While first-line immunotherapies introduce a new level of response rates, data on second-line therapies remains poor. This scenario poses a challenge for clinicians as guideline recommendations are based on historical patient cohorts and agents may lack the appropriate label for their in guidelines recommended use. Here, we summarize relevant clinical data and consider appropriate treatment strategies.

Future oncology (London, England). 2020 Sep 23 [Epub ahead of print]

Peter J Goebell, Philipp Ivanyi, Jens Bedke, Lothar Bergmann, Dominik Berthold, Martin Boegemann, Jonas Busch, Christian Doehn, Susanne Krege, Margitta Retz, Gunhild von Amsberg, Marc-Oliver Grimm, Viktor Gruenwald

Division of Urology, University Hospital Erlangen, D-91054, Erlangen, Germany., Department of Hematology, Hemostaseology, Oncology & Stem Cell Transplantation, Hannover Medical School, D-30625, Hannover, Germany., Department of Urology, Eberhard Karls University, D-72076, Tuebingen, Germany., University Hospital Frankfurt, Medical Clinic II, D-60590, Frankfurt, Germany., Centre Hospitalier Universitaire Vaudois, CH-1011, Lausanne, Switzerland., Department of Urology, University Hospital Mnster, D-48149, Mnster, Germany., Department of Urology, Charit-University Medicine, D-10117, Berlin, Germany., Urologikum Lbeck, D-23566, Lbeck, Germany., Department of Urology, Pediatric Urology & Urologic Oncology, Kliniken Essen-Mitte, D-45136, Essen, Germany., Department of Urology, Technical University of Munich, Rechts der Isar Medical Center, D-81675, Munich, Germany., Department of Oncology & Hematology, University Cancer Center Hamburg & Martini-Clinic, University Medical Center Hamburg-Eppendorf, D-20246, Hamburg, Germany., Department of Urology, Jena University Hospital, D-07747, Jena, Germany., Interdisciplinary GU Oncology, Clinic for Medical Oncology & Clinic for Urology, University Hospital Essen, D-45147, Essen, Germany.

PubMed http://www.ncbi.nlm.nih.gov/pubmed/32964728

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Consensus paper: current state of first- and second-line therapy in advanced clear-cell renal cell carcinoma. - UroToday

Around Town: Life is a series of choices a look at California’s ballot propositions – VVdailypress.com

By Pat Orr | Special to the Victorville Daily Press

Tomorrow marks the start of mailing a ballot to every registered voter in California. And so it begins: The onslaught of mailers, ads, prevarications and outright lies that now constitute campaigns for our votes. If there was ever a year to do your own research, this is it.

The political parties want you to believe this is the most important election in our history, but they say that every four years. What can be important is that we have jobs, taxes, new government spending, crime and racial-preference laws before us in California to vote on.

The impact of the COVID-19 lockdown cannot be underestimated on the attitudes of California voters. Our nave view that the government knows what it is doing has been sorely tested even more than usual.

Proposition 14 is a straightforward request for your approval to issue $5.7 billion in new bonds to fund stem cell research. I ask why this is not funded by big pharma who, along with their academic research partners, will reap the profits from any breakthrough treatments? This bond will cost taxpayers $7.8 billion in principal and interest. Is it good for mankind? Yes, it could be. Is it good for taxpayers? You decide.

Proposition 15 is the attack on Proposition 13s property tax protection passed 40 years ago. Commonly called the Split-roll Initiative, it would revalue commercial property to generate millions from business property owners. This is one issue that the lock-down has helped clarify. This new tax law would cause more business closures and accelerate the departure of businesses who can escape. To intensify the issue further, new work-at-home rules are making large corporate offices obsolete. Couple that with the death of shopping malls and you have a looming business property foreclosure disaster that Prop 15 will only hasten. Voters have turned against 15 despite the hackneyed ads that claim, this is for the schools. Hey, schools are closed!

Proposition 16 is a weird attempt in this social climate to allow our state to legally discriminate in university admissions, public employment or contracting. We banned discrimination in California once. Now to fight racism, the liberals want to bring legalized institutional racism back. This will never stand up in court if it passes.

Proposition 17 would give 40,000 formerly incarcerated individuals now on parole the right to vote. Proponents see the inability to vote as an example of systemic racism because they claim that two-thirds of parolees are Black or Latino.

Proposition 18 will let 17-year-olds vote in primary elections if they will be 18 before the General Election. This will stop those pesky other parties, like Republicans and Libertarians, from getting a candidate in the top two primary ever again.

Proposition 19 will make it easier for those over 55 to transfer their property tax base to another home. This has overwhelming support particularly as we see so many folks displaced by wildfires this year that must rebuild or relocate. A yes vote is supported by Realtors statewide.

Proposition 20 makes crime a crime again. Theft valued between $250 and $950 will become a felony again if you vote yes on Prop 20. This may reduce the shoplifting plague that has been visited on retailers since the law was changed to allow offenders to steal up to $800 with a slap on the wrist. Every shop owner will vote yes on 20.

Proposition 21 is one more attempt to pass statewide rent control. It failed before and will fail again. Can you imagine there ever being any empty apartments to rent if there was rent control?

Proposition 22 is another issue totally reframed by the COVID-19 lockdown. It is the unions attempt to force independent contractors to become employees. Aimed at ride-share drivers and a host of other gig-economy workers, it is a naked attempt to get new union members. We all have become dependent on food, grocery and drug deliveries so there is zero chance this will pass this year. The value of letting people choose their own work life has become clear and essential for all of us.

Proposition 23 would require a licensed physician on-site at every dialysis clinic. This is good for the big chain clinics, not so good for places like the Victor Valley where the extra cost may force clinics to close.

Proposition 24 strengthens consumer privacy laws. This proposition creates a new state agency full of highly paid managers and unionized state workers to protect your personal credit information from being bought and sold. You decide if the return on investment is worth it.

Proposition 25 is an attempt to enable voters to end the catch-and-release game in the justice system right now. A yes vote keeps our cashless bail system in place under current state law. A no vote returns us to the system wherein the court sets bail requiring assets or cash to secure release until trial.

Meanwhile, every Victor Valley community has a local ballot issue to decide this year. Apple Valley (Measure 0) and Victorville (Measure P) are both asking voters to approve an additional 1% increase in the sales tax to be retained for municipal expenses like police, fire, parks and road maintenance. The impact of COVID-19 lockdowns on local sales tax revenue is significant. The state has signaled it will not be helping with any additional income, so it is either increase revenue or cut more services. We have always been a law-and-order-oriented region, so I expect both measures to pass.

In Hesperia Measure N is an attempt to modify land use and density rules to help keep Hesperia from becoming overbuilt and out-of-character projects from being built in the city.

Adelantos Measure R is a new tax on vacant land parcels that can range from $50-$600 a year depending upon how the property is zoned. I doubt investors or home builders are excited by the prospect of a new tax on unused dirt right now. Has the city made the case to voters they need the money based on past prudent spending?

Measure V is only for Spring Valley Lake residents and it would, if passed, create a new Community Services District. There are long-time residents on both sides of the issue. I expect the vote to be close and trust a majority of SVL voters have paid enough attention to really weigh the pros and cons of creating this new entity.

We all will vote on Measures J and K, which purportedly modernizes the County Charter (J) and imposes a one four-year term limit and salary reduction on our supervisors (K).You should know that J was put on the ballot by the supervisors, while K was put on the ballot by voter petition. Translation: These two may have conflicting provisions.

A yes vote on Measure U repeals the County Fire Tax for those folks living in County Fire Protection District Service Zone 5. The issue here is that many residents in this zone already pay fire fees to other fire agencies and the County sort of snuck up on this area and included it in their tax levy. You will know from your tax bill and your ballot if this issue applies to your property.

This commentary does not reflect the official position of the Daily Press Editorial Board or ownership.

Contact Pat Orr at avreviewopinion@gmail.com.

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Around Town: Life is a series of choices a look at California's ballot propositions - VVdailypress.com

Expansion Therapeutics Names Renato Skerlj, Ph.D., Chief Executive Officer and President – BioSpace

Oct. 5, 2020 12:30 UTC

Experienced life sciences executive to lead Expansion as it advances portfolio of medicines targeting RNA-mediated diseases into the clinic

SAN DIEGO--(BUSINESS WIRE)-- Expansion Therapeutics, Inc., a biotechnology company advancing transformative medicines to patients with RNA-mediated diseases, today announced the appointment of Renato Skerlj, Ph.D., as the companys new Chief Executive Officer and President, effective immediately. Dr. Skerlj will also serve on the companys Board of Directors.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20201005005251/en/

Renato Skerlj, Ph.D., CEO and President, Expansion Therapeutics (Photo: Business Wire)

Renato has a distinguished and proven track record in discovering and developing small molecule drugs for rare diseases which will be invaluable to Expansion as we move our programs targeting expansion repeat disorders toward the clinic, said Scott M. Rocklage, Ph.D., Founding Partner at 5AM Ventures, and Chairman of the Board of Directors of Expansion. Renato shares our vision to bring transformative therapies to patients with severe RNA-mediated diseases.

I am extremely excited about the potential of Expansions pipeline to deliver upon an unmet need for therapies that target a range of serious diseases caused by RNA. I look forward to working with the Expansion team to advance the pioneering work from the lab of Dr. Matt Disney to help patients suffering from these debilitating diseases, such as myotonic dystrophy, for which there are currently no approved therapies, added Dr. Skerlj.

Dr. Skerlj has more than 25 years of experience leading the discovery and development of disease modifying small molecule drugs to treat genetically defined rare diseases. He has authored 67 publications, holds 52 patents and has advanced multiple drug candidates into clinical development.

Most recently, Dr. Skerlj served as Chief Scientific Officer for X4 Pharmaceuticals, Inc., where he also was one of the companys scientific founders and co-inventor of its lead drug candidate, mavorixafor. Prior to joining X4, Dr. Skerlj held leadership roles in drug discovery and development at Lysosomal Therapeutics where he co-invented LTI-291, a CNS drug in clinical development for Parkinsons disease. Previous to that, he was interim Head of Small Molecule Discovery at Genzyme and part of the executive team at AnorMED, a publicly traded company that was acquired by Genzyme in 2006. Dr. Skerlj is an accomplished drug developer with two approved drugs; plerixafor, a CXCR4-targeted stem cell mobilizer approved by the U.S. Food and Drug Administration (FDA) in 2008, and ertapenem, an anti-bacterial approved by the FDA in 2001. Dr. Skerlj received his Ph.D. in synthetic organic chemistry from the University of British Columbia, and completed postdoctoral fellowships at the University of Oxford and Ohio State University.

About Expansion Therapeutics

Expansion Therapeutics is a drug discovery and development company pursuing the vast potential of small molecule medicines for RNA-mediated diseases. Based on exclusive worldwide rights to groundbreaking research from the laboratory of Matthew D. Disney, Ph.D., at The Scripps Research Institute, Expansion has assembled the intellectual property, know-how, and proprietary enabling technologies and tools necessary to facilitate the creation of potent and specific small molecule binders of RNA. Through this unique platform, Expansion is building a portfolio of novel RNA-targeted drug candidates with activity across a broad number of disease indications. The companys initial development focus is on therapies for patients with expansion repeat diseases who have limited and unsatisfactory treatment options. Expansion is relocating its corporate headquarters to the Boston, Massachusetts area and will maintain its research facility in Jupiter, Florida. For more information, visit http://www.expansionrx.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20201005005251/en/

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Expansion Therapeutics Names Renato Skerlj, Ph.D., Chief Executive Officer and President - BioSpace

League of Women Voters Releases Their Proposition recommendations – Valley Voice

The League of Women Voters has been fighting for Democracy for 100 years.The League is a non-partisan, non-profit 501(c)(3) educational organization, dedicated to encouraging active participation in government, and fostering understanding of public policy.

The following are their proposition recommendations for the November 3 General Election.

For more election information, go to VotersEdge.org

PROP 15 SCHOOLS & COMMUNITIES FIRST YES

The Schools & Communities First initiative will raise $12 billion every year for Californias schools, essential workers, and local governments. This will come by ensuring that all corporate properties worth more than $3 million pay their fair share of property taxes while protecting homeowners and renters, small businesses, and agriculture. This money is needed now more than ever and is critical to Californias recovery and reinvestment.

PROP 16 OPPORTUNITY FOR ALL YES

Affirmative action in state hiring, contracting, and education was banned in California by Prop 209 in 1996. Prop 16 will reverse that ban and allow schools and public institutions to take race, ethnicity, color, national origin, and gender into consideration when admitting students to colleges, hiring employees for public jobs, and selecting contractors for public projects. Equal opportunity programs are a time-tested way to fight systemic racism and gender discrimination by leveling the playing field and giving everyone a chance at good public jobs and wages and quality public schools. Prop 16 provides all Californians a fair opportunity in education, employment, and contracting.

PROP 17 RESTORE VOTING RIGHTS YES

Restoring voting rights to Californians who have completed their prison term is a matter of justice, equity, and fundamental fairness. Right now, nearly 50,000 people who have been released from prison and are on parole are denied the right to vote a right that is owed to every citizen and important to successful reintegration into the community. Our neighbors who are working, paying taxes, raising families, and rebuilding their livesdeserve a voice in the policy-making that shapes their lives. And including their voices will help California achieve a more representative democracy.

PROP 18 VOTING RIGHTS FOR 17-YEAR OLDS YES

Seventeen-year-olds who will be 18 by the next general election should be able to vote in primary and special elections. Prop 18 will give them that right. Young people are significantly underrepresented in Californias electorate.Allowing 17-year-olds to vote in primary and special elections will engage young voters while they are studying the issues in high school and have a strong interest in participation. Once voting begins it becomes a life-long habit. Furthermore, fairness dictates that people who will be eligible to vote in a general election should be able to help choose the candidates who will be on that ballot. Finally, many 17-year-olds are civically engaged and at the forefront of movements to improve the communities in which they live. We would all benefit from their voices at the ballot box.

PROP 19 PROPERTY TAX BREAKS NO

Prop 19 exacerbates an already inequitable property tax system offering tax breaks to people who do not need them. Providing tax breaks to homeowners over 55 who purchase a replacement home and allowing them to transfer their current tax assessment to a new home anywhere in the state does nothing to help low-income seniors or families struggling to find housing. This proposition would allow not just one, but three such transfers. Senior citizens are already allowed to keep their current tax assessment when they purchase a home of equal or lesser value.And while the plan to put state revenuefrom increased home sales into a fund to support firefighting may sound appealing, it will make it more difficult for the legislature to fund the states response to other natural disasters or public health crises.While Prop 19 eliminates a tax break for some property inherited by children from parents, this beneficial element is not sufficient to merit support.

PROP 20 ROLLBACK ON CRIMINAL JUSTICE REFORMS NO

Over the past decade, California has made progress enacting laws that reduce the prison population and create a more effective and equitable public safety system. Prop 20 would roll back many advances in criminal justice reforms and reinstate a get tough law enforcement system that believes longer incarceration is a solution to crime. It would make minor theft of some goods worth over $250 punishable as a felony. It allows the state to collect DNA from people convicted of misdemeanors like shoplifting and drug possession. Prop 20 sends California in the wrong direction at a time when there is forward momentum toward smart justice approaches that increase public safety and reduce costs to the state.

PROP 24 CONSUMER DATA PRIVACY NO

The League of Women Voters supports the protection of consumers private data. Prop 24 includes some beneficial elements, but we oppose due to the complexity of a 52-page initiative with impacts and nuances that are difficult for voters to discern and rollbacks to existing protections. Among the troubling aspects of Prop 24 is its expansion of pay for privacy through the addition of loyalty and rewards programs, allowing businesses to charge consumers more or provide worse service if they choose to exercise their privacy rights. The initiative also allows businesses to require consumers to direct each individual website and app not to sell information weakening the current legal requirement that companies respect a global opt-out for all services. These burdens are fundamentally inequitable, placing the onus on the average consumer to protect their own privacy. Working people dont have the time to do the paperwork and they cant afford to pay companies to respect their wishes. Finally, the initiative comes less than a year after the 2018 California Consumer Privacy Rights Act went into effect,before we have had an opportunity to see how the new law works or the legislature has had a chance to address any defects.

PROP 25 END CASH MONEY BAIL YES

A YES vote on Prop 25 is a vote to replace the money bail system with the use of pretrial risk assessment tools that focus on safety and flight risk. It is estimated that almost 46,000 Californians, a disproportionate number of whom are Black and Latinx, are being held in jail but not yet sentenced. Cash bail both criminalizes poverty and reflects the systemic racism that plagues our criminal legal process. California must move away from the money bail system to create a fairer and more equitable criminal legal system that balances public safety with the presumption of innocence. People who pose little threat to public safety should not be subject to losing their jobs, homes, and families simply because they lack the money to pay for release from jail while awaiting their day in court. While the new law that would go into effect with a YES vote is not perfect, it can be amended by the legislature.A NO vote, however, could enshrine cash bail and prevent future legislative action to curtail the commercial bail industry.

NO RECOMMENDATIONS ON OTHER STATE PROPOSITIONS ON NOVEMBERS BALLOT

PROP 14 STEM CELL RESEARCH NEUTRAL

While the League of Women Voters of California supports ongoing stem cell research, we are neutral on Prop 14 because of the funding mechanism used and because of the requirement for a supermajority vote to amend its provisions. Prop 14 would authorize the use of general obligation bonds to continue funding stem cell research through the California Institute for Regenerative Medicine (CIRM).However, general obligation bonds are designed for long-term financing of capital projects, purchase of facilities for public use, and repair or retrofitting of public facilities and structures not for funding specialized research by an entity that has little state oversight.Furthermore, the legislature is prohibited from changing the law without a 70 percent supermajority vote, thereby restricting state representatives ability to carry out their responsibilities. Finally, profits from intellectual property agreements could only be spent on CIRM-funded research treatments, limiting the states flexibility to spend funds on matters that might be more urgent.

PROP 21 LOCAL GOVERNMENTS & RENT CONTROL NEUTRAL

The League supports efforts to help resolve Californias housing crisis. We promote solutions aimed at increasing housing production in a sustainable, accessible, and equitable manner. Rent control policies are one strategy to address Californias housing challenges, offer tenant protections, and prevent displacement. Rent control may be an effective short-term solution but studies suggest that its longer-term impact may, in certain cases, stifle the building of high-density and more affordable housing.Some of the modifications in Prop 21 have alreadybeen addressed through recently passed legislation. Because there are benefits and drawbacks to rent control, the League has chosen to be neutral on Prop 21.

PROP 23 KIDNEY DIALYSIS CLINICS NEUTRAL

This measure will require operators of chronic dialysis clinics to have a minimum of one licensed physician at the clinic whenever patients are being treated, offer the same level of care to all patients regardless of how payment is being made, and make reports about dialysis-related infections to the states health department and the National Healthcare Safety Network (NHSN). There is disagreement about whether the presence of a doctor is always necessary or could exacerbate a doctor shortage, and over whether costs are manageable or prohibitively high. Furthermore, the League questions why voters should be deciding questions of recordkeeping and medical staffing. The uncertainty of the costs and benefits of the measure leads the League to take a neutral position.

PROP 22 RIDESHARE AND DELIVERY DRIVERS NO POSITION

The League of Women Voters of Californias positions do not cover the issues in Prop 22. We therefore take no stand on the proposition.

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League of Women Voters Releases Their Proposition recommendations - Valley Voice

What is the difference between ventilation and respiration? – EMS1.com

By Chris Ebright

You were taught from day one of taking vital signs to countrespirations. However, I am here to say that your stellar EMT instructor let you down because thats wrong. The same incorrect terminology is also written in numerous textbooks, on run reports, and spoken everyday between medical professionals. So now youre asking: OK, smartypants, then what is the proper term? The appropriate term, my fellow professionals, is, you count ventilations.

Arent these terms essentially the same? The easy answer is no. The harder question is: Well, why not? This installment of Back to the Basics discusses these physiological processes and how they differ. So please, read on.

Simply put, ventilation is breathing the physical movement of air between the outside environment and the lungs. Air travels through the mouth and nasal passages, then down the pharynx. Upon reaching the vocal cords, air flows into the trachea, transitioning from the upper airway into the lower airway. Here, it continues distally to the carina, then through the primary bronchi, various branches of bronchioles, and eventually arriving in the alveoli. This is inhalation. Air movement in a reverse pathway from alveoli to mouth and nose, is exhalation. Inhalation, followed by exhalation, equals one ventilation. This is what you observe (chest rise and fall) when determining the breathing rate.

A ventilation can only take place if the brainstem, cranial and associated peripheral nerves, the diaphragm, intercostal musculature and lungs are all functional. Combining the function of all these structures, the pulmonary ventilation mechanism establishes two gas pressure gradients. One, in which the pressure within the alveoli is lower than atmospheric pressure this produces inhalation. The other, in which the pressure in the alveoli is higher than atmospheric pressure this produces exhalation. These necessary changes in intrapulmonary pressure occur because of changes in lung volume.

So, how does the lung volume change? Quite simply, it is a combination of muscle contractions stimulated by the central nervous system, and the movement of a serous membrane within the thorax called the pleura. The pleura is made of two layers: a parietal layer that lines the inside of the thorax and a visceral layer that covers the lungs and adjoining structures (blood vessels, bronchi, and nerves). Between the visceral and parietal layers is a small, fluid-filled space, called the pleural cavity.

The initiation of ventilation begins with the brainstem, where impulses (action potentials) generate within the medulla oblongata, then travel distally within the spinal cord. The impulse traverses individually through cervical nerves three, four and five until just above the clavicle. Here, the three cervical nerves merge into one large nerve called the phrenic nerve, which attaches distally to the diaphragm. Imagine these two nerves resembling a pair of suspenders on the anterior chest. The delivered impulse from the phrenic nerve initiates diaphragm contraction.

The intercostal muscles are a group of intrinsic chest wall muscles occupying the intercostal spaces. They are arranged separately in three distinct layers (external intercostal muscles, internal intercostal muscles, and innermost intercostal muscles). The intercostal nerves that stimulate these muscles originate from the spinal cord thoracic nerves 1-11.

Inhalation is initiated as the dome-shaped diaphragm is stimulated. As it contracts and flattens, the thorax expands inferiorly. The internal and innermost intercostal muscles relax, while the external intercostal muscles contract from stimulus by the thoracic nerves. This produces an upward and outward movement of the ribs (similar to the movement of a bucket handle), and the sternum (similar to when pulling upward on a handle of a water pump). The fluid in the pleural cavity acts like glue, adhering the thorax to the lungs. Hence, as the thorax expands vertically and laterally, the parietal layer drags the visceral layer along with it, causing the lungs to expand. Adequate expansion of the lungs results in a decreased pressure within the alveoli. Therefore, when the alveolar pressure drops below atmospheric pressure, air rushes into the lungs.

Remember, inhalation requires a stimulus initiated from the central nervous system. Think of it like turning on a light. The light stays unlit until you flip a switch (CNS), releasing electricity and stimulating the components of the light bulb. As long as the switch is on and there is an impulse, the light stays lit. However, if you turn off the switch, the stimulus ceases, and the light shuts down. Exhalation is akin to turning off the switch, so to speak.

Thoracic stretch receptors constantly monitor chest expansion. Once an acceptable limit of expansion develops, they send a message to the central nervous system to turn off the switch. All the nerves stimulating diaphragmatic and external intercostal muscle contraction temporarily stop conducting. Consequently, the diaphragm and the external intercostal muscles relax, decreasing the thoracic volume like letting air out of a balloon. Assisting with this passive process, the internal and innermost intercostal muscles are stimulated. Their contraction pulls the ribcage and attached pleura further downward and inward, compressing the lungs and increasing the air pressure within the alveoli. Once the alveolar pressure exceeds the atmospheric pressure, air moves out of the lungs.

That is all there is to it simple, right? Adults normally ventilate between 12 to 20 times per minute, thanks to the autonomic nervous system. We do not even have to think about it! Nonetheless, what becomes a problem (and why EMS gets a call) is when the nervous system, the thoracic musculature, or the lungs become diseased or disabled. Here is a partial list of pathologies that impair ventilation:

Respiration is the movement of gas across a membrane. The gas exchange in the lungs is referred to as external respiration. The very thin membrane gas crosses is called the respiratory membrane, separating the air within the alveoli from the blood within pulmonary capillaries. Its structure consists of the alveolar wall, the capillary wall, and eachs respective basement membrane. A basement membrane is a thin, fibrous structure that separates the lining of an internal or external body surface from underlying connective tissue. Think of it like Christmas wrapping paper around a box.

Recall that adequate ventilation enables air to reach the alveoli and establish a pressure gradient. The alveolar pressure of oxygen typically ranges from 80 to 100 mmHg, whereas the alveolar pressure of inspired carbon dioxide is very low (typically 40 mmHg). Oxygen-depleted blood, transported from the bodys cells and back to the right side of the heart, is pumped into the pulmonary trunk and through the pulmonary arteries. Eventually, the blood makes its way through the distal pulmonary capillaries surrounding the alveoli. Oxygen within the pulmonary bloodstream typically has a pressure of 40 mmHg, and carbon dioxide has a pressure of 45 mmHg. These differences in pressure allow for diffusion of oxygen from alveolar air, across the respiratory membrane and onto the hemoglobin of red blood cells. Carbon dioxide diffuses off hemoglobin, crosses the respiratory membrane, and enters the alveolar space.

The result of external respiration establishes a hemoglobin oxygen pressure in excess of 100 mmHg, and a decreased pressure of carbon dioxide of 40 mmHg. The exchange of oxygen and carbon dioxide continues across the respiratory membrane until the equilibrium of each gas is established. Oxygen-rich blood then flows from the lungs via the pulmonary veins back to the left side of the heart. Here, it is pumped out through the aorta to all body tissues.

Blood flows from the systemic circulation, down through arteries, arterioles, and eventually to the capillaries. Capillaries are only large enough to accommodate one red blood cell at a time, and blood flow at this level is very slow. This maximizes the time for the release of oxygen and reabsorption of carbon dioxide. Cells require high concentration oxygen to function correctly. Thus, another membrane exchange of gas must take place between individual body cells and the systemic capillaries.

This transaction occurs with gas already within the body, so it is termed internal respiration. Organelles within a cell take oxygen and combine it with glucose, fat, or protein, and make energy (ATP) through a series of complex chemical reactions. The resultant waste product is a high concentration of carbon dioxide. So, as arterial blood flows into capillaries, an awaiting cell has low oxygen pressure (40 mmHg, typically) and a high carbon dioxide pressure (45 mmHg).

Oxygen that is attached to hemoglobin maintains a pressure of around 100 mmHg, and carbon dioxide a pressure of 40 mmHg. A diffusion gradient is established once again, only this time in the opposite direction that occurred in the lungs. At the cellular level, the exchange of oxygen and carbon dioxide commences across the cellular/capillary membrane until an equilibrium of each gas is established. Blood flow continues through the venules, veins, vena cava, heart, and back into the lungs with a hemoglobin oxygen pressure of 40 mmHg and a carbon dioxide pressure of 45 mmHg. Rinse and repeat, every minute, of every day, for life.

Unfortunately, external and internal respiration can also be negatively influenced and inhibited by various disease processes. At the time of this article, the most notable respiratory pathology is caused by COVID-19, the coronavirus. View the YouTube video from the Cleveland Clinics Dr. Sanjay Mukhopadhyay (found in the reference listings) to get a first-hand view of what COVID-19 does to the alveolar-capillary membrane.

Additionally, here are some other common respiration pathologies:

Hopefully, now you understand the difference between ventilation and respiration. Even though these are independent physiological processes, they are also mutually dependent to ensure the survival of the human body. So, the next time someone misuses one of these terms set them straight with a smile. Tell em Chris told you.

Chris Ebright is an EMS education specialist with ProMedica Air and Mobile in Toledo, Ohio, managing all aspects of internal continuing EMS education as well as for numerous EMS systems in northwest Ohio and southeast Michigan. He has been a nationally registered paramedic for 25 years, providing primary EMS response, land and air critical care transportation. Chris has educated hundreds of first responders, EMTs, paramedics, and nurses for 24 years with his trademark whiteboard artistry sessions, including natives from the Cayman Islands and Australia. Chris passion for education is also currently featured as a monthly article contributor, published on the Limmer Education website. He has been a featured presenter at numerous local, state and national EMS conferences over the past 13 years, and enjoys traveling annually throughout the United States meeting EMS professionals from all walks of life. Chris is a self-proclaimed sports, movie and rollercoaster junkie and holds Bachelor of Education degree from the University of Toledo in Toledo, Ohio. He can be contacted via email at c.ebrightnremtp@gmail.com or through his website http://www.christopherebright.com.

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What is the difference between ventilation and respiration? - EMS1.com