The major reason why I decided to write this essay was to show you how arterial blood gases and pulmonary function tests can help you in diagnosis and differential diagnosis of respiratory failure, obstructive and restrictive lung diseases.
This not a repetition of Drs Bellot and Jacobus’ lectures in Diseases of Respiratory System, this a comprehensive look on the problem, where I purposefully omitted some details; please excuse me if you find the omissions relevant or significant for the topic covered.
As you have learnt, the majority of pulmonary diseases, according to their major pathophysiologic mechanisms, can be divide two broad categories: obstructive and restrictive. I will start with definitions and major conceptual issues and then we proceed to lab findings.
Obstructive Lung Diseases
Obstructive diseases are characterized by reduction in ventilation due to increased airflow resistance as a result of
o Blockage of airways by mucus plugs (bronchial asthma and chronic bronchitis)
o Narrowing of airway lumina by hypertrophied and/or inflamed mucosa (chronic bronchitis)
o Bronchoconstriction (bronchial asthma)
o Loss of elastic recoil and impairment of expiratory flow (emphysema)
-If you are interested in this mechanism look for a “equal pressure point” concept
Another component of respiration, perfusion, is less affected by obstructive lung diseases (except emphysema, which, by definition, is characterized by reduction in pulmonary vasculature).
How an increased resistance affects lung volumes?
1) Residual volume (RV) increases
-RV – lung volume at the end of maximal exhalation
2) Vital capacity (VC) decreases
-VC – volume that can be exhaled after a maximal inhalation
3) Total lung capacity (TLC) increases too because TLC = RV + VC, and an increase in RV is more that a decrease in VC
4) Forced vital capacity (FVC) moderately decreases because of increased airway resistance
-FVC – volume that can be forcefully exhaled (during 5 sec) after a maximal inhalation. NB: understand the difference in TLC and FVC, which change in opposite directions
5) Forced expiratory volume in 1 sec (FEV1) significantly decreases because forceful expiration induced airflow turbulence with substantial reduction in flow rate
-FEV1 – volume which is exhaled during the first second of FVC measurement
6) FEV1) / FVC ratio decreases [see explanation in 4) and 5)]
How an increased resistance affects ABGs?
Increased resistance to airflow leads to air retention in the lower airways with low PAO2 and high PACO2 (“A” – alveolar). Similar changes can be detected in the arterial blood: decreased PaO2 and increased PaCO2 (hypoxemia and hypercapnia).
How respiratory failure develops in patients with obstructive lung diseases?
At early stages of obstructive lung diseases, high concentration of carbon dioxide activates respiratory center that changes the pattern of breathing and maintains near- normal level of blood gases. With time and increased work of breathing, hypoxemia and hypercapnia rise and reach the levels of PaO2 < 60 mm Hg and PaCO2 > 50 mm, the condition is known as hypercapnic respiratory failure. High PaCO2 level lowers pH (respiratory acidosis) and activates bicarbonates retention by the renal tubules (metabolic compensation).
Restrictive Lung Diseases
This group is quite heterogeneous and is characterized by abnormalities in alveolocapillary interface, such as:
• Edema (pulmonary edema)
• Inflammation (pneumonia, ARDS, aspiration of gastric content)
• Fibrosis (idiopathic pulmonary fibrosis, pneumoconioses, sarcoidosis, etc)
Accumulation of pathologic substances in the pulmonary interstitium leads to an increase in lung elastic recoil, reduction in lung compliance, compression of microvasculature and inhibition of gas diffusion through the air-blood barrier. In such settings, perfusion is affected the most. Ventilation is reduced too, but not so severe as in obstructive lung diseases, and usually allows tachypnea to compensate blood gases abnormalities.
How lung volumes are changed in restrictive lung diseases?
1) Residual volume (RV) decreases due to an increased elastic recoil
2) Total lung capacity (TLC) decreases because of low RV and low VC (reduced compliance)
3) Forced vital capacity (FVC) moderately decreases because of extensive parenchymal fibrosis and preserved airway conductivity
4) Forced expiratory volume in 1 sec (FEV1) slightly-moderately decreases (similar to FVC)
5) FEV1 / FVC ratio remains normal or slightly increases [see explanation in 3) and 4)]
Therefore, TLC and FEV1/FVC are widely used in clinical practice for differentiation of obstructive and restrictive lung diseases.
ABGs in patients with restrictive lung diseases
Severe inhibition of perfusion along with relatively spared ventilation lead to severe hypoxemia. In such settings, tachypnea becomes a leading compensatory mechanism and a reason of PaCO2 reduction (hypocapnia).
Respiratory failure in patients with restrictive lung diseases
If hypoxemia falls below 60 mm Hg, respiratory failure ensues. But contrary to obstructive diseases, in restrictive diseases hypoxia is not associated with raise in carbon dioxide. In such patients hypocapnia and respiratory alkalosis usually persists, therefore the condition is named hypoxic respiratory failure. If respiratory failure worsens, concentration of carbon dioxide can turn from low to high. Hypercapnia in patients with restrictive lung disease is a grave sign implying an inability to maintain adequate alveolar ventilation.
I hope you found my explanations useful.
Good luck,
Dr. Y.
Wednesday, September 30, 2009
Tuesday, September 29, 2009
Asbestos, Mesothelioma and Lung Cancer
A very interesting question about asbestos-related malignancies was raised today at PACE session. The question was: what is more common asbestos-associated tumor, mesothelioma or bronchogenic carcinoma.
The fact that asbestos exposure tremendously increases risk of mesothelioma is well known and I am not going to discuss it here. But relationship between asbestosis and lung cancer is still obscure, because tobacco smoking masks the influence of asbestos fibers on neoplastic transformation within the bronchial linings. The freshest text in my specialty, Rubin’s Pathology (5th Ed, 2008) states “an association between cancer of the lungs and asbestos exposure is clearly established in smokers. A slight increase in the prevalence of lung cancer has been reported in nonsmokers exposed to asbestos, but small amount of cases renders an association questionable” (P.168).
We can find a reasonable amount of publication browsing the Web. A reputed site, which I trust, “Health and Safety Executive” from the UK contains statistics data about mortality from asbestos-related malignancies; the data indicate that less amount of people die of asbestos-related lung cancer than of mesothelioma (at least not more) http://www.hse.gov.uk/statistics/causdis/asbfaq.htm#mesothelioma..
I hope I answered the question.
Dr. Y.
Monday, September 28, 2009
Is Emphysema a COPD?
I apologize for a long silence; a promised essay about respiratory failure is coming soon, I am just trying to bring my thoughts about it together and meanwhile I discovered a quite intriguing (for medical students) question: why emphysema belongs to a group of chronic obstructive pulmonary diseases? Where is the obstruction? That is the question. Do you have any ideas?
Dr. Y.
Dr. Y.
Monday, September 21, 2009
Heart Failure, Part 5. Mechanisms, Compensatory Mechanisms and Their Adverse Effects
When I finished writing this part, I found it too long, but I decided to post it anyway: on Tuesday and Thursday Semester 4 students will have PACE sessions and after that they will definitely loose any interest in Cardiovascular Pathology. So, before that happened, please read the last part of Heart Failure.
There are three primary physiologic mechanisms that regulate stroke volume: preload, afterload and contractility, which have been (thoroughly?) explained in the previous posts. We have learnt that cardiac failure, as an inability of the heart to maintain stroke volume, can develop either through reduced preload, or increased afterload, or impaired contractility. Each of these factors has its own causes, ways of development, and mechanisms of compensation. It is important to understand that both physiologic mechanisms of heart activity and compensatory mechanisms have their own limits, which, if overwhelmed, may produce adverse effects on cardiac function and structure. Let’s talk again about preload, afterload and contractility but now in terms of heart failure development and compensation.
Preload. Reduced preload of the ventricles (e.g., mitral stenosis, hypertophic or restrictive cardiomyopathy) will automatically lead to decreased stroke volume and subsequently, to ventricular failure. Few physiologic mechanisms can compensate this phenomenon:
1) When the ventricles cannot accommodate all required blood, it will stay in the atria with their distension (preload increase) and activation of Frank Starling mechanism.
a. We always keep in mind limitations of Frank-Starling mechanisms: after a certain point, an increase in EDV will lead to a fall in SV.
2) Sympathetic activation will enhance force of atrial contraction and tone of venous compartment of systemic circulation with augmented venous return to the heart (=increased preload)
a. An increment in sympathetic tone will induce a considerable amount of adverse effects:
i. Increased heart rate that is not always good, e.g., tachycardia will reduce preload
ii. Calcium influx with possible arrhythmia and ischemia
iii. Too much venous return will overwhelm the pulmonary circuit with possible development of pulmonary edema
iv. A raise in arteriolar resistance will increase afterload and ca cause multisystem organ ischemia
3) Activation of renin-angiotensin system as well as synthesis and secretion of antidiuretic hormone with water and salt retention count for a great deal in cases of cardiac failure caused by hypovolemia
a. Adverse effects of renin and ADH surplus:
i. An excess in EDV – a fall in SV (see above)
ii. Activation of myocardial fibrosis
iii. An increase in arteriolar tone with elevation in afterload
Afterload. Increased afterload is always bad: pressure or volume overload, or thinning of the heart wall always have unfavorable effects on cardiac function. Pressure and volume overload induce the following compensatory mechanisms:
1) An increase in preload
a. See the adverse effects of preload above
2) Myocardial hypertrophy with augemented force of contraction and reduction of overall afterload (see LaPlace law)
a. Adverse effects of myocardial hypertrophy:
i. Growth of cardimyocytes is always accompanied by production of extracellular matrix with subsequent myocardiosclerosis
ii. Inadequate growth of blood vessels with diminished oxygen and nutrient supply
iii. Changed geometry of cardimyocytes: larger diameter – less surface/volume ratio with insufficient metabolite transport through the sarcolemma.
3) Release of natriuretic peptides with reduction in arteriolar tone and volume of circulating blood (inhibition of sodium reabsorption).
Contractility. Impaired contractility often becomes a cause of heart failure, for example in patients with acute MI or chronic ischemic heart disease. Affected contractility can be partially compensated by
1) An increase in preload
2) Activation of adrenergic nervous system
3) Medications, e.g., beta-adrenoceptor agonists or phosphodiesterase inhibitors.
Adverse effects of too high preload and activated sympathetic nervous system have been covered above. About side effects of the mentioned drugs, please refer to Dr. Babbini’s lectures.
With this post I finish my talk about heart failure and I truly hope that my work helped you a little to understand this pathology. Going through my posts you had chances to appreciate this problem in all its complexity, and I believed it would influence in good way your approach in diagnosis and management of heart failure, a very serious medical problem in the modern world.
Very soon I will start to work on respiratory failure, I guess, I have a few words to say about it.
Good luck,
Dr. Y.
There are three primary physiologic mechanisms that regulate stroke volume: preload, afterload and contractility, which have been (thoroughly?) explained in the previous posts. We have learnt that cardiac failure, as an inability of the heart to maintain stroke volume, can develop either through reduced preload, or increased afterload, or impaired contractility. Each of these factors has its own causes, ways of development, and mechanisms of compensation. It is important to understand that both physiologic mechanisms of heart activity and compensatory mechanisms have their own limits, which, if overwhelmed, may produce adverse effects on cardiac function and structure. Let’s talk again about preload, afterload and contractility but now in terms of heart failure development and compensation.
Preload. Reduced preload of the ventricles (e.g., mitral stenosis, hypertophic or restrictive cardiomyopathy) will automatically lead to decreased stroke volume and subsequently, to ventricular failure. Few physiologic mechanisms can compensate this phenomenon:
1) When the ventricles cannot accommodate all required blood, it will stay in the atria with their distension (preload increase) and activation of Frank Starling mechanism.
a. We always keep in mind limitations of Frank-Starling mechanisms: after a certain point, an increase in EDV will lead to a fall in SV.
2) Sympathetic activation will enhance force of atrial contraction and tone of venous compartment of systemic circulation with augmented venous return to the heart (=increased preload)
a. An increment in sympathetic tone will induce a considerable amount of adverse effects:
i. Increased heart rate that is not always good, e.g., tachycardia will reduce preload
ii. Calcium influx with possible arrhythmia and ischemia
iii. Too much venous return will overwhelm the pulmonary circuit with possible development of pulmonary edema
iv. A raise in arteriolar resistance will increase afterload and ca cause multisystem organ ischemia
3) Activation of renin-angiotensin system as well as synthesis and secretion of antidiuretic hormone with water and salt retention count for a great deal in cases of cardiac failure caused by hypovolemia
a. Adverse effects of renin and ADH surplus:
i. An excess in EDV – a fall in SV (see above)
ii. Activation of myocardial fibrosis
iii. An increase in arteriolar tone with elevation in afterload
Afterload. Increased afterload is always bad: pressure or volume overload, or thinning of the heart wall always have unfavorable effects on cardiac function. Pressure and volume overload induce the following compensatory mechanisms:
1) An increase in preload
a. See the adverse effects of preload above
2) Myocardial hypertrophy with augemented force of contraction and reduction of overall afterload (see LaPlace law)
a. Adverse effects of myocardial hypertrophy:
i. Growth of cardimyocytes is always accompanied by production of extracellular matrix with subsequent myocardiosclerosis
ii. Inadequate growth of blood vessels with diminished oxygen and nutrient supply
iii. Changed geometry of cardimyocytes: larger diameter – less surface/volume ratio with insufficient metabolite transport through the sarcolemma.
3) Release of natriuretic peptides with reduction in arteriolar tone and volume of circulating blood (inhibition of sodium reabsorption).
Contractility. Impaired contractility often becomes a cause of heart failure, for example in patients with acute MI or chronic ischemic heart disease. Affected contractility can be partially compensated by
1) An increase in preload
2) Activation of adrenergic nervous system
3) Medications, e.g., beta-adrenoceptor agonists or phosphodiesterase inhibitors.
Adverse effects of too high preload and activated sympathetic nervous system have been covered above. About side effects of the mentioned drugs, please refer to Dr. Babbini’s lectures.
With this post I finish my talk about heart failure and I truly hope that my work helped you a little to understand this pathology. Going through my posts you had chances to appreciate this problem in all its complexity, and I believed it would influence in good way your approach in diagnosis and management of heart failure, a very serious medical problem in the modern world.
Very soon I will start to work on respiratory failure, I guess, I have a few words to say about it.
Good luck,
Dr. Y.
Saturday, September 19, 2009
Squatting in TOF, an Answer to Nathan's Question
Hi Everybody,
Nathan asked me so intersting question, that I decided to post it:” Dr. Yakubovskyy, I was wondering if you could elaborate on why the squatting position is common in pts with Tetrology of Fallot. The only explanation I have found is that it presumably lessens the right to left shunt. I've tried to dig deep into my physio knowledge to explain it but can't come up with an answer that is satisfying. Thanks”.
The answer: As you know, TOF is a relatively common and very serious congenital heart defect. The major problem in patients with TOF is severe cyanosis (hypoxemia) associated with right ventricular outflow tract obstruction (RVOTO) and reduction in pulmonary blood flow. Squatting is a mechanism that helps patients to cope with an acute attack of cyanosis. There are not very many recent publications, which shed light on the protective mechanisms of squatting in the patients with TOF; the last one appeared in 2002 with the major postulated mechanism as the reduction of amount of deoxygenated blood entering the systemic circulation through VSD. Besides that, there are few more possible protective mechanisms, which deserve to be mentioned here. To save space I combined all known (for me) effects of squatting in the patients with TOF and presented in the diagram below. Enjoy.
Dr. Y.
Nathan asked me so intersting question, that I decided to post it:” Dr. Yakubovskyy, I was wondering if you could elaborate on why the squatting position is common in pts with Tetrology of Fallot. The only explanation I have found is that it presumably lessens the right to left shunt. I've tried to dig deep into my physio knowledge to explain it but can't come up with an answer that is satisfying. Thanks”.
The answer: As you know, TOF is a relatively common and very serious congenital heart defect. The major problem in patients with TOF is severe cyanosis (hypoxemia) associated with right ventricular outflow tract obstruction (RVOTO) and reduction in pulmonary blood flow. Squatting is a mechanism that helps patients to cope with an acute attack of cyanosis. There are not very many recent publications, which shed light on the protective mechanisms of squatting in the patients with TOF; the last one appeared in 2002 with the major postulated mechanism as the reduction of amount of deoxygenated blood entering the systemic circulation through VSD. Besides that, there are few more possible protective mechanisms, which deserve to be mentioned here. To save space I combined all known (for me) effects of squatting in the patients with TOF and presented in the diagram below. Enjoy.
Dr. Y.
Thursday, September 17, 2009
Heart Failure, Part 4. Contractility
Contractility (syn.: inotropy) is a unique feature of cardiac muscle that provide cardiomyocytes with ability to generate force, which is independent of preload and afterload. In addition to force, contractility also influences velocity of sarcomere shortening during the phase of isovolumetric contraction. An increase in generated force and velocity of cardiomyocyte shortening will enhance the ejection velocity and, correspondingly, ejection fraction and stroke volume (with concomitant reduction in end systolic and end diastolic volume).
Factors enhancing contractility
Factors enhancing contractility
- Sympathetic stimulation
- Catecholamines
- Inotropic drugs (see below)
- Physiologic
- Vagal (parasympathetic) stimulation
- Pathologic
- Advanced heart failure (unknown mechanism)
- Acute MI
- Chronic ischemic heart disease
- Drugs used for cardiac failure treatment
- Beta-adrenoceptor agonists (dopamine, dobutamine, etc)
- + peripheral vasodilation with resoration of end-organ perfusion and reduction of afterload
- Phosphodiesterase inhibitors (milrinone)
- + veno and arterial vasodilation with a decrease in preload and afterload
- Digoxin
- Caffeine
- Theophylline
To be continued
Heart Failure, Part 3. Afterload
Afterload can be defined as stress (or tension, T) that cardiac wall experiences during systolic ejection. According to LaPlace law, wall tension is directly proportional to intrachamber pressure (P) and radius (r) and inversely proportional to wall thickness (h): T=PXr/2h.Therefore, changes in chamber pressure, volume and/or wall thickness will affect afterload and, correspondingly, stroke volume.
Factors influencing pressure (P)
Amendment: Pharmacologic correction of afterload
Factors influencing pressure (P)
- Blood pressure. Intrachamber (left/right ventricular) pressure during systolic ejection is very close to the pressure in the aorta or pulmonary trunk. That means, in cases of systemic or pulmonary hypertension, elevation in ventricular pressure will automatically increase afterload. And visa versa, reduction in blood pressure will reduce afterload.
- Valvular stenosis interferes with chamber empting and causes accumulation of blood with subsequent increase in pressure (and volume)
- Congenital heart defects. E.g., atrial and ventricular septal defects, and patent ductus arteriosus increase pressure (and volume) load on the right chambers
- Valvular insufficiency leads to reverse blood flow with an increase in chamber volume
- Dilated cardiomyopathy
- Valvular stenosis (see above)
- Congenital heart defects (see above)
- Myocardial hypertrophy with an increase in sarcomere mass and reduction of wall stress
- Physiologic myocardial hypertrophy seen in athletes
- Pathologic myocardial hypertrophy as a compensatory process in patients with cardiovascular diseases, e.g., systemic hypertension
- Ventricular aneurysm, e.g., in old MI, with sclerosis and thinning of the wall
- Advanced heart failure with volume overload (thinning of the myocardial wall)
Amendment: Pharmacologic correction of afterload
- Vasodilators: reduction of blood pressure with subsequent afterload decrease
- Beta-blockers
- ACEI/ARBs
- Nitrites: potent venodilators, used in acute heart failure (e.g., pulmonary edema) to reduce preload
- Human BNP analogs: vasodilatory and diuretic effects
- Diuretics: reduction of volume of circulating blood and blood pressure with subsequent diminishing in afterload
- + preload reduction
To be continued
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