Hepatopulmonary syndrome vs. Portopulmonary hypertension

Often confused as the same syndrome, Hepatopulmonary syndrome and Portopulmonary hypertension are two distinct disease processes. Both are characterized as pulmonary vascular abnormalities in the context of liver disease.

 

Hepatopulmonary Syndrome (HPS): triad of vasodilatation (Intrapulmonary vascular dilatations), abnormal oxygenation (an elevated alveolar-arterial oxygen gradient) and liver disease (any degree of liver disease). *LOOK FOR: digital clubbing, cyanosis and spider angiomas.

 

Portopulmonary hypertension (POPH): vascular obstruction secondary to portal hypertension (varices, splenomegaly, thrombocytopenia, portal vein abnormalities) with concomitant pulmonary arterial hypertension (mean pulmonary artery pressure >25 mmHg at rest, mean pulmonary capillary wedge pressure <15 mmHg, and pulmonary vascular resistance (PVR) >3 Wood units.

 

REFERENCES:

1. Porres-Aguilar M, Altamirano JT, Torre-Delgadillo A, Charlton MR, Duarte-Rojo A. Portopulmonary hypertension and hepatopulmonary syndrome: a clinician-oriented overview. Eur Respir Rev. 2012 Sep 1;21(125):223-33. doi: 10.1183/09059180.00007211.

2. Gupta S, Krowka M J. Hepatopulmonary syndrome. CMAJ Feb 2018, 190 (8) E223; DOI: 10.1503/cmaj.170253

Alpha 1 Anti Trypsin: Pi*MM, Pi*MZ, Pi*ZZ, Pi*null

Alpha1 antitrypsin (α1 AT) deficiency is the only known genetic abnormality that leads to COPD; it accounts for less than 1% of COPD in the United States.

Typically:

  • Basilar-predominant hyperlucency on chest imaging -> early-onset emphysema (eg, before age 55).
  • Occurrence of emphysema in a non- or trivial-smoker, or a family history of liver or lung disease.

WHY? Unimpeded neutrophil elastase contributes to the alveolar destruction of emphysema.

NAMING (disease is inherited co-dominant)

Pi*MM– Normal

Pi*S (essentially normal; leading to a mild decrease in circulating A1-PI)

Pi*null– They do NOT make any alpha-1 antitrypsin. The rare null variants that are characterized by complete absence of AAT synthesis; does not cause liver disease.

Pi*MZ– heterozygous. Heterozygotes are not deemed to be at significant risk of developing emphysema.

PI*ZZ– Homozygotes for the severe deficiency allele Z. Most* but not all severely deficient individuals develop emphysema, risk for which is markedly increased by smoking. For liver disease, the lifetime risk is estimated to be approximately 40%.

Copyright: Craig TJ 2015.

*More than 95% of persons in the severely deficient category are homozygous for the Z allele, designated PiZZ.

REFERENCES

  1. Craig TJ. Suspecting and Testing for Alpha-1 Antitrypsin Deficiency-An Allergist’s and/or Immunologist’s Perspective. J Allergy Clin Immunol Pract. 2015 Jul-Aug;3(4):506-11. doi: 10.1016/j.jaip.2015.04.005. Epub 2015 May 29.
  2. Stoller JK, Aboussouan LS. A review of α1-antitrypsin deficiency. Am J Respir Crit Care Med. 2012;185:246–59.
  3. de Serres F, Blanco I. Role of alpha-1 antitrypsin in human health and disease. J Intern Med. 2014;276:311–35.

What is Hoover Sign?

Hoover’s sign refers to the paradoxical inspiratory retraction of the rib cage and lower intercostal

interspaces. Normally, the costal margin moves minimally during the regular respiratory cycle. However, if it does, it moves outward and upward.

It is commonly seen in COPD. However, it may also be seen in numerous other conditions (i.e congestive heart failure, asthma, severe pneumonia etc.)

It results from alterations in dynamics of diaphragmatic contraction due to hyperinflation, resulting in traction on the rib margins by the flattened diaphragm.

REFERENCES

  1. Klein M: Hoover sign and peripheral airways obstruction. JPediatr 1992, 120:495-496.
  2. Johnston, Chambless R et al. “The Hoover’s Sign of Pulmonary Disease: Molecular Basis and Clinical Relevance” Clinical and molecular allergy: CMA vol. 6 8. 5 Sep. 2008

Hypoxia and pulmonary embolism (PE): Mechanism

The clot CAUSES Dead space; which does not cause hypoxia/hypoxemia on its own.
ALWAYS ASK ABOUT: 
  1. Resp Rate (PE creates dead space, reduced alveolar ventilation, CO2 increases and patient attempts to blow off CO2)
  2. Blood pressure (?Obstructive shock from large saddle PE)
  3. Tachycardia (Left heart trying to increase cardiac output because stroke volume low) 
Image Credit: Dr. Douglas Mckim, MD
Mechanisms by which a PE might cause Hypoxia/Hypoxemia:
  1. Significant V/Q Mismatch (though usually dead space ventilation, but impaired pulmonary oxygen transfer can occur due to vascular re-distribution and release of vaso-active inflammatory molecules such as: serotonin, histamine, prostaglandins, bradykinin etc.)
  2. Pain -> Splinting and atelectasis [caused by loss of surfactant and alveolar hemorrhage]
  3. Inflammation causing infarction [however may be a matched defect] +/- superimposed pneumonia 
  4. Increased pulmonary vascular resistance; potentiating right heart strain and cardiac stunting if (i.e PFO)

REFERENCES

  1. Huet Y, Lemaire F, Brun-Buisson C, Knaus WA, Teisseire B, Payen D, Mathieu D. Hypoxemia in acute pulmonary embolism. Chest. 1985 Dec;88(6):829-36.
  2. Santolicandro A, Prediletto R, Fornai E, Formichi B, Begliomini E, Giannella-Neto A, Giuntini C. Mechanisms of hypoxemia and hypocapnia in pulmonary embolism. Am J Respir Crit Care Med. 1995 Jul;152(1):336-47.
  3. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008 Sep;29(18):2276-315. 

Why is LDH elevated in pleural fluid from Diuretics: Mechanism

It is common teaching to be judicious when interpreting the thoracentesis results of patients receiving diuretic therapy. It is stated, their pleural LDH will often be elevated and result in them being misclassified as exudative effusions when they are in fact transudative.

WHY?

Currently, the mechanism is not entirely clear, but proposed mechanisms include:

  • Lactate dehydrogenase (LDH) is an intracellular protein responsible for catalysing the conversion of lactate to pyruvic acid. It tends to leak during cellular injury or lysis.
  • Thus, any patient with repeated or bloody thoracentesis, the LDH may be elevated secondary to RBC lysis (blood) or local trauma from the thoracentesis; repeated attempts augmenting that damage.
  • LDH is primarily created by the liver, and in patients with CHF, hepatic congestion/ release upon diuresis may play a role in its elevation in pleural fluid.
  • Diuretics move water via diffusion; from the extravascular (pleural space) to the blood, leading to an increase in the protein and LDH concentration in the pleural cavity.

REFERENCES

  • Bielsa, J.M. Porcel, J. Castellote, et al. Solving the Light’s criteria misclassification rate of cardiac and hepatic transudates. Respirology, 17 (2012), pp. 721-726
  • Mitrouska I, Bouros D. The Trans-Exudative Pleural Effusion. CHEST, Volume 122, Issue 5, 1503 – 1505
  • Broaddus, V. Diuresis and transudative effusions—changing the rules of the game. The American Journal of Medicine, Volume 110 , Issue 9 , 732 – 735

Lung lobes most commonly affected by Aspiration (Upright vs. Supine)

Aspiration events have a gravity-based predilection, meaning the lobes/ lung segments in the most dependent positions are likely affected. Also, the right main bronchus has a larger luminal diameter and more vertical trajectory than the left main bronchus making it more susceptible to aspirated content.

Lobes of the lungs most likely to be affected by aspiration include:

Upright: The lower lobes (Right>Left)

Supine: Superior segments of the lower lobes (Right>Left) or posterior segment of the RIGHT upper lobe. This is typically in patients with altered LoC (i.e Alcoholics, Intubated patients etc.).  

REFERENCES:

  1. Kuhajda, Ivan et al. “Lung Abscess-Etiology, Diagnostic and Treatment Options.” Annals of Translational Medicine 3.13 (2015): 183. PMC. Web. 14 Sept. 2018.
  2. Kim M, Lee KY, Lee KW et-al. MDCT evaluation of foreign bodies and liquid aspiration pneumonia in adults. AJR Am J Roentgenol. 2008;190 (4): 907-15.
  3. Moreira Jda S, Camargo Jde J, Felicetti JC, et al. Lung abscess: analysis of 252 consecutive cases diagnosed between 1968 and 2004. J Bras Pneumol 2006;32:136-43.

Consolidation vs. Ground Glass Opacities

Ground glass opacities are hazy increases in lung opacity without obscuration of the underlying parenchymal vessels.

Whereas, Consolidation is an increase in lung opacity that does obscure the vessels.

REFERENCES

  1. radiologyassistant.nl
  2. Chest Radiology (Seventh Edition), 2019

COPD and Hypoxic Drive: Mechanism

It is common dogma on the wards that oxygen therapy for chronic CO2 retainers should be targeted between 88-92% during an COPD exacerbation.

The mechanism often quoted is the “hypoxic drive to breath”. The idea is that COPD patients tend to have chronically elevated levels of carbon dioxide due to the nature of their illness. As such, administration of oxygen to these patients with COPD can be dangerous.

Their chronically elevated carbon dioxide levels result in loss of the hypercapneic mediated respiratory drive and they rely solely on their “hypoxic” drive to breath. The patient’s chemo-receptors are already tolerant of high levels of carbon dioxide.

However, also contributory to the desaturation seen with higher oxygen levels is the Haldane effect. The Haldane effect states that deoxygenated hemoglobin has a higher affinity for CO2 because it is a better proton acceptor than oxygenated hemoglobin.

Therefore, increasing oxygen concentration in the blood by giving patients supplemental oxygen means carbon dioxide molecules will be displaced in favour of the oxygen, thereby reducing alveolar expulsion. 

Finally, another important mechanism is: hypoxic mediated vasoconstriction (aka V/Q mismatch).

When alveolar oxygen tension is reduced (i.e bronchoconstriction, mucus plugging), it induces vasoconstriction of pulmonary capillaries supporting the effected alveoli. This is meant to counteract possible shunting and normalize the V/Q ratio, a mechanism called hypoxic pulmonary vasoconstriction (see figure). The strongest determinant for hypoxic pulmonary vasoconstriction is alveolar partial pressure of oxygen.

Therefore, providing a high fraction of inspired O2 (FiO2) will increase O2 tension in alveoli with a low level of ventilation (i.e scarred alveoli in setting of COPD), inhibiting hypoxic pulmonary vasoconstriction. As a result, alveoli with relatively impaired ventilation (which would be vasoconstriction normally) are no longer, leading to an increase in V/Q mismatch.

Therefore in summary (Abdo et al. 2012):

“In patients with COPD, hypoxic pulmonary vasoconstriction is the most efficient way to alter the V/Q ratios to improve gas exchange. This physiological mechanism is counteracted by oxygen therapy and accounts for the largest increase of oxygen-induced hypercapnia. A titrated oxygen therapy to achieve saturations of 88% to 92% is recommended in patients with an acute exacerbation of COPD to avoid hypoxemia and reduce the risk of oxygen-induced hypercapnia.”

REFERENCES

  1. Abdo WF, Heunks LM. Oxygen-induced hypercapnia in COPD: myths and facts. Critical Care. 2012;16(5):323. doi:10.1186/cc11475.
  2. Aubier M, Murciano D, Milic-Emili J, Touaty E, Daghfous J, Pariente R, Derenne JP. Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure. Am Rev Respir Dis. 1980;16:747–754.
  3. organ, G.E., Mikhail, M.S., Murray, M.J. Clinical Anesthesiology: Fourth Edition. Chapter 22 Respiratory Physiology: The Effects of Anesthesia. Pg. 565.

Paradoxical breathing (abdominal paradox): Mechanism

During a Respiratory exam, the question of paradoxical breathing commonly comes up. The more accurate and correct term is actually abdominal paradox (as paradoxical breathing may also refer to the deranged breathing seen during an injury resulting in flail chest).

During a normal respiratory cycle, in the supine position, the anterior abdominal wall displays a prominent outward movement during inspiration. This is secondary to diaphragm movement and displacement of abdominal viscera. The opposite is seen during expiration.

However, during abdominal paradox, as the diaphragm fatigues, it is unable to contract and move downwards. Instead of the expected outward movement of the abdominal wall, there is an inward movement instead (hence the term paradox).

MECHANISM: The paradoxical inward movement of the abdominal wall during inhalation is due to the cephalic (upward) movement of the fatiguing diaphragm in response to the negative intra-thoracic pressure generated by the inspiratory action of the neck and intercostal muscles.

EXAMPLE: Video

 REFERENCES

  1. Chapter 9. Pulmonary Evaluation. Lawrence P. Cahalin. Cardiovascular and Pulmonary Physical Therapy: An Evidence-Based Approach.
  2. Civetta, Taylor, & Kirby’s: Critical Care, 4th Edition Section II – Monitoring Chapter 20 – Bedside Assessment and Monitoring of Pulmonary Function and Power of Breathing in the Critically.
  3. Chapter 143: Pump Failure: The Pathogenesis of Hypercapnic Respiratory Failure in Patients with Lung and Chest Wall Disease. Steven G. Kelsen. Fishman’s Pulmonary Diseases and Disorders, 5e.

PFTs: What is pseudorestriction?

Sometimes when interpreting spiromtery, a patient may have what appears to be a mixed obstructive/ restrictive picture. (Reduced FEV1/FVC and Reduced FVC).

Patients with an obstructive process (i.e COPD) may have gas trapping, which will reduce their FVC due to increased residual volume (RV). This may falsely lead a clinician to interpret it as a mixed obstructive/ restrictive process, while it is truly just obstructive.

NOTE: The next step to confirm pseudo-restriction, is to get a TLC. If normal (and therefore not restrictive) it highly suggests this pathology. Also look at the RV and RV/TLC ratio.

Img Cred: Cleve Clin J Med

REFERENCES

  1. Sorino, C et al. Physician’s mistakes in the interpretation of spirometry. European Respiratory Journal 2012 40: P1131
  2. Ranu H, Wilde M, Madden B. Pulmonary Function Tests. The Ulster Medical Journal. 2011;80(2):84-90.
  3. As-Ashkar, F, Mehra, R, Mazzone, PJ. Interpreting pulmonary function tests: recognize the pattern, and the diagnosis will follow. Cleve Clin J Med. 2003;70:866–881.