[Applause] [Music] hello this is Eric strong once again and today's lecture in this course on understanding abgs will focus on the topic of respiratory acidosis the learning objectives of this lecture are to know the factors which control Alvar ventilation and to know the the differential diagnosis of a respiratory acidosis before I jump into the long list of conditions in the differential diagnosis of a respiratory acidosis a general discussion of the mechanism of respiratory disorders is going to be beneficial towards achieving a more complete understanding of their path of physiology as it relates to acidbase balance almost all primary respiratory disorders arise as a consequence of either one of two general problems either the respiratory centers of the brain failed to appropriately process physiologic data that would otherwise tell the body to increase or decrease ventilation in response to changes in gas exchange or there is an inability to change ventilation in response to appropriate signals from the respiratory sensors another way to look at this is that respiratory disorders originate from either the source of the signal to increase or decrease ventilation the apparatus that responds to this signal or the means of communicating that signal from the former to the latter control of ventilation is a complex process in which the medular respiratory centor integrates input from various locations in the brain as well as sensory impulses from a variety of peripheral chemo receptors and mechano receptors the result of this integration is the medela's direction to the muscles of respiration as to the rate depth and pattern of ventilation the most important of the central respiratory inputs are the central chemo receptors located in a variety of locations but most prominent on the vental surface of the madala these chemo receptors detect changes in PH and stimulate either an increase or decrease in ventilation in order to drive pH back to normal for example detection of a dropping pH from a metabolic process will stimulate an increase in respiratory drive greater ventil will lead to lower P2 as we will discuss more in a minute when reviewing the alular ventilation equation and the lower P2 will push the arterial pH higher as dictated by the Henderson hosbach equation this is the basic mechanism of respiratory compensation that we have frequently referred to in previous lectures the cerebral cortex also provides input first a variety of circumstances can lead lead to increased ventilatory drive from the cereal cortex such as pain anxiety or intentional hyperventilation while it's impossible to consciously hypo ventilate for a sustained period of time the cerebral cortex is thought to provide a lowlevel tonic inhibitory signal the purpose of which is not clear in the ponds are two additional respiratory centers the actions of which are also not completely understood but in the simplest terms they are believed to mildly antagonize one another in order to fine-tune tital volume and respiratory rate these inputs are distinctive and that communication with a meary respiratory Center is bidirectional finally there is significant empiric evidence that there exist progesterone receptors in the CNS and that stimulation of these receptors increases ventilation in the periphery the most important input comes from for peripheral chemo receptors in the Cor in aortic bodies the cored bodies are more active in adults while the aortic bodies are more active in infancy and early childhood these peripheral chemo receptors detect changes in pco2 and pH they also detect changes in po2 sending Pro ventilation signals once po2 drops below 75 mm of mercury which become particularly strong once P2 drops below 50 mm of mercury for tuous Le high po2 levels do not result result in an inhibitory signal otherwise providing excessive supplemental oxygen as which frequently occurs in the hospital could result in patients ceasing to breathe while much less important there are other peripheral receptors ju the capillary receptors were commonly referred to as J receptors are present in the Alvar interstitium and are activated by pulmonary edema and increased interstitial fluid mechanical stretch receptors in the smooth muscle of the Airways ini iate a decrease in respiratory rate in response to over distension a process known as the Herring Brewer reflex finally there are irritant receptors in the aate epithelium which activate in the presence of histamine prostaglandins and a variety of exogenous noxious chemicals so what is the net consequence of this complex process the consequence is that high pco2 low PH low P2 pain anxiety pulmonary edema histamine inhalation of noxious chemicals and elevated levels of progesterone all lead to increased ventilatory drive low pco2 and high pH lead to decrease ventilatory drive another angle from which we can approach the physiology of ventilatory control is to review the alveolar ventilation equation this equation mathematically relates ventilation with the partial pressure of carbon dioxide in arterial blood which is our most significant window into understanding a patient's ventilation status available at the bedside this equation states that the P CO2 is equal to the rate of carbon dioxide production denoted as v. CO2 times the total pressure of inspired air divided by alveolar ventilation denoted as V.A Alvar ventilation which is a measure of the rate of delivery of inspired air to perused alvioli is equal to the respiratory rate times the difference between the tital volume and dead space this equation and these terms are discussed more in lecture two from the course on mechanical ventilation for those of you who are interested in more background but in brief title volume is the total amount of air inspired with each breath the Dead Space is the volume of gas in the lungs which does not participate in gas exchange either because it is not adjacent to a diffusing membrane or because that section of the lung is not being adequately profused from this equation we can see that mathematically there are four types of derangements that will lead to increased P2 low respiratory rate low title volume High Dead Space and high rate of CO2 production of these the the first two account for the overwhelming majority of respiratory acidoses and the last two very rarely although the equation suggests that high pressure of inspired air can also lead to high P2 this would only occur in unusual non-physiologic situations such as hyperbaric chambers and we won't consider it further in this lecture at this point I'm going to move on to the list of specific ideologies of a respiratory acidosis unfortunately this is by a large margin the longest differential diagnosis among the five fundamental acid-based disorders and not every ideology will be explicitly listed first there is obstructive lung disease such as COPD and Asthma while moderate to severe COPD is frequently associated with a chronic respiratory acidosis asthma only leads to this during severe exacerbations next is the category of central hypoventilation these are primary problems located in the brain stem the most common of these is drug intoxication the list of drugs which can lead to respiratory depression in toxic levels is very long in itself the big three drug classes here are alcohol narcotics and benzodiazapines other classes occasionally implicated in respiratory depression and at subsequent acidosis include the so-called non- benzoin such as zadam or ambian histamines gabapentin and the similarly structured pregabalin and various anti-depressants and antipsychotics there are various brain stem lesions which can occur as a consequence of trauma or stroke obesity HP hypoventilation syndrome is also associated with Central hypoventilation and finally Central hypoventilation syndrome also known as andin curse the next category is neuromusc ular diseases these can be seen in the spinal cord peripheral nerves the neuromuscular Junction or the muscles I won't go through every cause listed especially since this represents only a small subset of these conditions the next category is diseases associated with poor compliance of the total respiratory system they can be further divided into those which result in low lung compliance such as the various forms of interstitial lung disease acute lung injury in ards and the Lesser degrees of pulmonary edema and those diseases which result in low chest wall compliance just such kyos scoliosis obesity hyperventilation syndrome also belongs here as I'll discuss in a few minutes the final category is not a problem with ventilation at all per se but is rather hyper metabolism that is rare situations which the rate of CO2 production is significantly elevated over normal this has been reported in extreme fever prolonged seizures and hyperalimentation this list is obviously very long and it may be a little bit intimidating also there is no clear algorithm to follow in order to reach a diagnosis like there was with each of the metabolic disorders luckily however the vast majority of conditions listed here are either individually quite rare or have other features of the presentation which will drive the diagnostic workup towards something rather specific therefore I'd like to focus on just those entities which I most frequently encounter in my clinical practice which are COPD drug overdose and the Obesity hypoventilation syndrome COPD is a complicated disease which could be discussed for hours so I'm just going to focus on how COPD leads to a respiratory acidosis to get there however I need to First review the two classic subtypes of COPD there is chronic bronchitis represented by this man here who was historically referred to as a blue bloater and there is empyema represented by this guy known as a pink puffer while many textbooks and medical school lectures may give the impression that it is easy to distinguish these two subtypes at the bedside in reality most COPD patients fall along a spectrum between these two extremes the primary physiologic problem from the chronic bronchitis component is Airway inflammation while the primary problem from the empyema component is paranal destruction aay inflammation leads to increased aay mucus and some degree of fibrosis while destruction of parena leads to decreased outward traction applied to the Airways these two processes together lead to Airway obstruction since this obstruction is more pronounced during expiration there is subsequent air trapping and hyperinflation this hyperinflation causes the development of positive end expiratory pressure which can help to improve oxygenation but which also creates additional work for the respiratory system during inspiration it also leads to flattening of the diaphragm which through multiple mechanisms also increases respiratory work and decreases overall efficiency of ventilation the consequence of this is lower tital volumes while the body attempts to compensate for this with increased respiratory rate when the progression of COPD has moved past the earlier stages this compensation will be incomplete incomplete compensation for low tital volumes necessarily means decreased Alvar ventilation the destruction of lung pranka mentioned earlier also leads to decreased surface area of the Alvar capillary membrane which can directly contribute to decreased Alvar ventilation by increasing Dead Space lower Alvar ventilation as we know from the Alvar ventilation equation must result in higher P2 chronically elevated P2 may result in decreased sensitivity in the central respiratory centers to further changes in pac2 which then feeds back and can increase pac2 still further all in all the process by which a respiratory acidosis develops in COPD is fairly complicated the next ideology of a respiratory acidosis is drug overdose as with COPD this is far too expansive a diagnosis to discuss in depth however let's just focus on the depression of respiration as a general rule drugs that depress respiratory drive first lower the respiratory rates and only at higher levels lower tital volume as well the risk of significant respiratory acidosis and death is relatively low when a single drug is present but each additional drug that's added synergistically impacts ventilation particularly when the additional drugs are in different classes for example mixing alcohol narcotics and benzodiazapines here's a simple qualitative graph in which the relative risk of fatal drug overdose will be plotted in arbitrary units as a function of the number of drug classes simultaneously present in a person's circulation with only one drug class the risk as mentioned is small with two classes the risk is substantially higher higher in fact than simply adding the risk of each individual class together finally with alcohol narcotics and benzos all present simultaneously the risk of accidental fatal overdose is high if you're unconvinced by this arbitrarily qualitative graph I'll put together um another scent of non-scientific qualitative data a list of some of the major celebrities who have suffered accidental overdoses after combining multiple respiratory depressants these drugs were all available either over the counter or were provided by a physici Marilyn Monroe who some make uh claim actually committed suicide uh died after mixing the prescription sleep aid chlorohydrate with barbituates Jimmy Hendrick died after mixing barbituates with alcohol Anna Nicole Smith makes chlorohydra multiple benzodiazapines and badril Michael Jackson in a Highly Questionable move by his now disgraced physician was given the powerful anesthetic Popa fall mixed with multiple benzo diazines Heath Ledger who in my opinion is the most unfortunate soul in this list made a fatal miscalculation when he combined multiple narcotics multiple benzos and the over-the-counter antihistamine damine Whitney Houston mixed the benzo Xanax with badril and the dating muscle relaxant Flexeril though it may have arguably been the stimulant cocaine that dealt her the Fatal blow finally and most recently the American Artist Thomas canc died after mixing alcohol and the benzo aspine volume while this list isn't exactly a rigorous scientific study it supports the notion that accidental death as a consequence of mixing multiple respiratory depressants isn't a rare phenomenon next I'd like to talk about the obesity hypoventilation syndrome which may be much less common among the Rich and Famous but which is not rare in the general population and which frequently goes unrecognized obesity hypoventilation syndrome or OHS is simply defined as the combination of obesity and chronic hypoventilation while awake that occurs in the absence of other explanations hypoventilation occurs due to two factors first there is poor compliance of the chest wall that leads to a form of restrictive lung disease second there is decreased Central responsiveness to changes in pac2 and pa2 it's as if the brain decides that too much physical effort is required for the body to maintain normal ventilation and it resets itself to accept a higher pco2 before triggering a sensation of shortness of breath despite a frequent assumption to the contrary obesity hypoventilation is not the same thing as obstructive sleep apnea obstructive sleep apnea or Osa is caused by physical upper Airway obstruction during sleep and is characterized by normal gas exchange while a wake there is however substantial overlap between the two syndromes which we can demonstrate with a simple ven diagram this blue circle will represent patients with Osa and the red circle patients with OHS this demonstrates three things first that Osa is much more common than OHS second that the majority of patients with Osa do not have OHS and third the majority of patients with OHS do have Osa frequent complications of OHS include chronic hypoxia pulmonary hypertension right heart failure and a predisposition to develop hypercapnic respiratory failure often without any clear precipitant I'd like to conclude this lecture with a brief discussion of the rare but historically interesting condition Central hypoventilation syndrome which is also known as undy curse this is a rare impairment of autonomic control ventilation but with intact voluntary control affected patients are sometimes said to forget to breathe when they fall asleep it's best described in its congenital variant but it can also be acquired as a consequence of surgery trauma or stroke the interesting part of this condition is the origin of the eponym which is one of the few medical eponyms that is not the name of a physician the name Andy's curse actually comes from a German folk tale in a story known as sleep of undy undy is a beautiful and Immortal water nymph Who falls in love with a mortal man he swears faithfulness to her with every waking breath and they are married unfortunately after bearing his child undy loses her immortality and begins to show signs of aging a little too stereotypically the man then has an affair with a younger woman when undy discovers them together she uses hers magical powers to curse him that since he swore faithfulness with every waking breath if he should fall asleep that breath would be taken away and he would die which of course he eventually did since Central hypoventilation syndrome wasn't described until the 1960s it is unlikely the writers of the folk tale were referencing a specific medical condition that's it for this lecture on the causes of respiratory acidosis please continue to the next lecture that will briefly discuss the causes of respiratory alkalosis the list of which is much shorter [Music]