Lupine Publishers| Understanding the TCM Role of Liver in the Treatment of Cough

 Lupine Publishers| Journal of Pharmacology & Clinical Research

Abstract

The TCM role of Liver understood with the meridian route and functions shows that the insulting sequence plays a key to understanding the relationship between Liver and Lung in the effective treatment of cough. Liver qi stagnation is the most important and common pattern in clinic that deserves attention, which can be interpreted with scientific evidence. However, there remains a long way to go for the integration of TCM with the conventional medicine.

Keywords: Cough; Liver Qi Stagnation; Liver Meridian; Yin Yang

Introduction

Pathological mucus or foreign irritants are cleared out of the airways in the lung disorders with the protective action coughing when the lung is contracted with the infections. Cough categorized as the acute, the subacute, and the chronic with the duration from less than three weeks to over eight weeks can affect the patients’ life as long as it continues for more than two weeks [1,2]. How to make acupuncture treatments effectively requires an accurate diagnosis following Zang-Fu organs, meridian theories, Yin-Yang, and acupoint indications. Although the stimulations with the acupuncture treatments on the immune system for the infection issue like cough have been verified effective to improve the symptoms resulted from the cough in the recent scientific studies [3,4], the unique technique pattern should deserve attention for the expected successful treatments. Compared to the Western medicine, symptoms in traditional Chinese medicine (TCM) are believed to be broader with the pattern identification. The pathological classifications of diseases in the Western medicine are not generally followed by TCM physicians and acupuncturists, but they strictly depend on the patterns developed with the Yin- Yang balance, Qi-Blood, and the meridian theory [5].

Glance at the Functions of the Liver Meridian

A human body is supported by the three essential and vital treasures Jing (essence), Qi, and Shen. Jing (essence) is viewed as Ying, referring to material that seems to bear high similarity to genes. The damages to Jing may cause serious issues with physiological and psychological developments. Qi is classified as Yang for functions of the body and viewed as the energy to benefit the body to fight against external evil Qi (pathogens), and transports Blood to nourish the all the systems of the body [6,7]. In addition to Jing, Qi, and Shen, spirit, the combination of body and mind, indicates whether or not Yin and Yang are at balance and serves as the foundation for diagnosis and treatment. The concept that the human body in TCM is not only seen as the interaction between humans and Heaven but as a miniature of the universe highlights the importance of Yin-Yang balance. A disease is believed and understood to be the Yin and Yang imbalance in Figure 1. The Yin- Yang balance in TCM has severed as the guideline for explaining the etiology of the diseases and the treatments for over two thousand years in the history of Chinese medicine and the key to the accurate diagnosis and successful treatment outcomes. On the basis of QiBlood, Essence, and fluids, Liver, Heart, Spleen, Lung, and Kidney are five Ying Zang organs that co-work through the meridian systems with the six Fu Yang organs Gall Bladder, Large Intestine, Stomach, Small Intestine, Sanjiao, and Bladder to connect all the body systems. The systems of the body can be affected with the activities of ascent and dispersion of Liver [8]. The Five Elements theory indicates that one of the functions of Liver is to store Blood for regulating the blood volume to nourish the constituents of the body and the Liver qi can affect the Spleen qi to ascend and the Stomach qi descend correctly and the regulation of emotions. On the other hand, whether or not Qi can flow freely within the body in order to ensure the distribution of fluids and blood is also governed by Liver [9]. Qi circulates in the traditional twelve meridians in the body to connect the tissues and organs together, collaborating with Blood to regulate the normal functions of the body and reflect pathology for diagnosis. Meridians are divided into three Hand Yin meridians, three Foot Yin meridians, three Hand Yang meridians, and three-Foot Yang meridians as shown in Table 1 [10]. The Liver meridian classified as Foot Jueyin originates at the lateral side of the big toe, goes upwards along the inner side of the leg meeting with SP12 and SP13, and then encircles the pubic region to connect with the Conception Vessel at CV2, CV3, and CV4. It ascends to Stomach and penetrates Liver to connect with Gallbladder and Lung at PC1, and finally connect with the Governing Vessel at the vertex of the head [11].

Figure 1: Characteristics of Yin and Yang.

Table 1: Twelve meridians and pathways.

Pathological View of Liver with Cough

It is stated that “Five Zang organs and six Fu organs make people cough, in addition to Lung.” in the 38th Chapter On cough of the volume Su Wen (Essential Questions) of the Huang-Di-Nei- Jing (Essential Questions of Yellow Emperor’s Inner Classic). This warning suggests that a TCM practitioner and an acupuncturist must consider the relationship of the other organs in treating cough based on the Five Elements theory to gain the whole picture of the etiology. Liver in the Five Elements theory refers to Wood while Lung is Metal to govern Qi in TCM. The meridian route of Liver indicates that the Liver meridian passes Lung and the insulting sequence that Liver can invade Lung explains that Liver can affect the functions of Lung with its failure in free flow of Qi to descend Lung qi, which can result in such symptoms as cough, dyspnea, and asthma. Blood regulation and dispersing stagnated Qi rely on the smooth flow of Liver qi [12,13]. Unfortunately, Liver qi stagnation, presented with the symptoms of swelling in the breast, frequent sighs, the tightness in the chest, tension in the epigastric region, the sensation of a lump in the throat called Plum Pit Qi, or sometimes stabbing pain in the hypochondriac region, is the extremely common TCM pattern in clinic and one of the pathological changes of Liver. The circulation of Qi is impeded with this change when Liver is depressed with the negative emotions like anger, worry, depression, and resentment [14,15]. Scientific studies of depression, which is understood to be the presentation of negative Shen in TCM, have shown that the neurotransmitter signaling in transforming macronutrients into molecules is dysregulated with the stagnated Liver qi. Stagnated Liver qi leads the molecules to be delivered insufficiently to the brain with the disrupted mitochondrial ATP production in neurons [16]. In addition, the failure in controlling the ratio of lymphocytes and granulocytes that can be seen as Yin and Yang by the autonomic nervous system is viewed as Liver qi stagnation [17]. On the other hand, the sympathetic nervous system controls the Natural Killer cell while the parasympathetic nervous system is assumed to be closely connected to the release of cytotoxic substances [18,19].

Discussion

The quotation “Qi is the commander of Blood and Blood acts as the mother of Qi” highlights the collaboration of Blood and Qi. Blood is seen as Yin and Qi can be classified into Yang, which can result in diseases when the imbalance of Yin-Yang occurs. Blood, produced with food qi (gu qi) by Spleen, circulates in the veins governed by Heart to nourish the organs and the systems. Blood, in addition to food qi, is also generated by the mother of Liver based on the Generating sequence Kidney, which stores prenatal Jing and produces marrow that generates to manufacture Blood. Qi circulates in the traditional twelve meridians to support the life, interacting with Blood for the Zang-Fu organs to function normally in harmony [20,21]. The studies on the relation between Qi in the twelve meridians and the oxygen metabolism highlight that one may be short of breath and experience wheezing or coughing when the normal level of blood oxygen is below, presenting the high similarity of physiological functions and pathological reactions between Qi and oxygen [22]. In other words, this suggested that oxygen, to some extent, is equivalent to Qi [23]. The Generating Sequence of the Five Elements theory shows Kidney is the mother of Liver, which suggests that Kidney’s problems can affect its child Liver. The maximum oxygen is delivered with the normal value of 45% of hematocrit [24]. Kidney produces Erythropoietin to promote the number of red blood cells to increase the capacity of the blood to carry more oxygen. In addition, the circulation of oxygen in the Kidney is closely associated with the production of Erythropoietin determined by tissue oxygen pressure [25]. In other words, stagnated Liver qi can be dispersed as long as Kidney can function normally with the delivery of the healthy Qi to Liver. In a word, the inflammation resulted from the infection can be reduced with much more oxygen delivered upwards with the blood to Lung.

Conclusion

Inductive logic thinking is the basis of the developments of TCM and acupuncture theories. TCM practitioners and acupuncturists must stick to the pattern identification developed based on Yin-Yang and the Five Elements theories that act as the two key principles in practice to the accurate diagnosis and the expected outcomes. With the collaboration of Liver and Kidney, it is suggested in this study that Qi may be viewed as oxygen in the blood and Kidney is the key to producing Qi, which makes Liver an anti-inflammatory role eventually to reduce the inflammation of the Lung. The integration of the western medicine and TCM has gained much more attention, which suggests that the trend may be the optimal choice for the public health system. However, how to link each other together needs more research and shows that there is a long way to go.

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Lupine Publishers| Complex and Severe Amiodarone-Induced Pleuro- Pulmonary Toxicity

 Lupine Publishers| Journal of Pharmacology & Clinical Research

Abstract

Introduction: Pulmonary complications related to amiodarone have become exceptional with the doses currently used; their frequency is estimated at 1.6-2%. Acute or subacute pneumonia is the most classic manifestation. Pleural involvement under amiodarone is exceptional and unusual. We report an original observation of triple toxicity to amiodarone with concomitant pulmonary parenchymal, pleural and hepatic involvement and which was spontaneously resolved.

Case Report: 71-years-old patient, hypertensive and diabetic type 2, without degenerative complications, treated with amiodarone for four years for atrial fibrillation, was hospitalized because of severe acute pneumopathy evolving for ten days. Biology revealed moderate cytolytic hepatitis (ASAT at 130 IU/l and ALAT at 243 IU/l) without cholestasis or liver failure. Chest X-ray and thoracic CT showed bilateral and diffuse interstitial infiltrates, severe bilateral pneumonitis of both upper lobes, diffuse patchy infiltrates and ground–glass opacity, and bilateral pleural effusion. Abdominal ultrasound and CT showed moderate homogeneous and hyperdense hepatomegaly without focal lesions. The infectious, immunological, and tumoral investigations were negative. The hypothesis of drug toxicity was retained, and the evolution was rapidly favorable after stopping amiodarone with disappearance of respiratory complaints, normalization of liver tests, and progressive radiological cleansing. Chest radiography and thoracic CT scan were substantially normal at six months.

Conclusion: Amiodarone-induced complex pulmonary toxicity with parenchymal and pleural involvement remains exceptional and not well known by clinicians. Regular clinical and radiological monitoring are recommended to detect and manage them in time, and improve the prognosis given the risk of irreversible fibrosis evaluated at 5-7% of cases.

Keywords: Amiodarone; Pneumonitis; Pleuritis; Amiodarone Pulmonary Toxicity; Hepatitis; Toxicity

Abbrevations:ASAT: Aspartate Aminotransferase; ALAT: Alanine Aminotransferase; Ana: Antinuclear Antibodies; P-Anca: Perinuclear Antineutrophil Cytoplasmic Antibodies; C-Anca: Cytoplasmic Antineutrophil Cytoplasmic Antibodies; Anti-Lkm1: Anti- Liver/Kidney Microsome Antibodies; Anti-M2: Anti-Mitochondrial Antibodies M2 Subtype

Introduction

Amiodarone is a class III antiarrhythmic agent widely used for the treatment of ventricular and supraventricular rhythm disorders [1,2]; its spectrum of toxicity is wide: thyroid, heart, lung, eye, skin, liver, gastrointestinal tract, and central nervous system [3]. All these effects are mediated by the mitochondrial toxicity of the drug and its lipophilicity. This toxicity is not dose-dependent, can occur even very early, and men seems to be more exposed than women [4]. The current incidence of amiodarone pneumonia is estimated at 1.6-2% [5,6]. His most classic presentation is acute or subacute pneumonia, while pleural involvement is exceptional [3,7] and often described as an unusual manifestation of amiodarone-induced pneumopathy [7,8]; similarly, acute hepatitis under amiodarone is very rare (<3%) [6]. We are reporting an original observation of triple toxicity to amiodarone with concomitant bilateral pleural, pulmonary parenchymal and hepatic involvement.

Case Report

71-years-old patient, hypertensive and diabetic type 2, without degenerative complications, treated with amiodarone for four years for atrial fibrillation, was hospitalized because of severe acute pneumopathy evolving for ten days. The examination found apyretic patient, dyspneic (polypnea at 26 cycles/min and spontaneous oxygen saturation at 82%) with diffuse crepitant rales, bilateral pleuritis, and moderate hepatomegaly. The electrocardiogram showed slower atrial arrhythmia (mean frequency at 90/min) and the cardiac enzymes were not elevated. Chest X-ray showed bilateral and diffuse interstitial infiltrates (Figure 1). Thoracic CT revealed severe bilateral pneumonitis of both upper lobes (Figure 2) with diffuse patchy infiltrates and ground–glass opacity (Figure 3), and bilateral pleural effusion (Figure 4). Abdominal ultrasound and CT showed moderate homogeneous and hyperdense hepatomegaly without focal lesions.

Biology revealed moderate cytolytic hepatitis (ASAT at 130 IU/l and ALAT at 243 IU/l) without cholestasis or liver failure. The other basic biological tests were within normal limits: Leucocytes, platelet, hemoglobin, erythrocyte sedimentation rate, C-reactive protein, creatinine, ionogram, glycemic parameters, muscle enzymes, electrophoresis of serum proteins, and urine analysis. The infectious (bacteriological, viral and tuberculous), immunological (ANA, p-ANCA, c-ANCA, anti LKM1, anti M2 antibodies) and tumor investigation was negative. The diagnosis of drug toxicity was retained, and the evolution was rapidly favorable after stopping amiodarone with disappearance of respiratory complaints, normalization of liver tests, and progressive radiological cleansing. Chest radiography and thoracic CT scan were substantially normal at six months.

Discussion

Although rarely observed, toxic pulmonary involvement caused by amiodarone is a major cause of discontinuation of this treatment [1,7,9]. Classically assessed at 5-7% [2,10], amiodaroneinduced pneumopathy appears to be clinically overestimated [5,6]. Indeed, in the large controlled and double-blind study, including 3439 patients receiving daily 400 mg or less amiodarone, pulmonary toxicity was noted only in 1.6% [5]. This pulmonary toxicity of amiodarone has been markedly reduced using lower doses of the drug but can occur with any dose [3]. Clinically, amiodarone-induced pneumopathy may manifest itself as: cough, chest discomfort, often progressive dyspnea, chest pain, and more rarely hemoptysis or acute respiratory failure in the exceptional forms of intra-alveolar haemorrhage or acute respiratory distress syndrome [2,9,11]. However, it can remain totally infra-clinical (insidious), and would only be found in pulmonary imaging [2,9,11]. Radiologically, this toxic pneumopathy may be in the form of: diffuse interstitial lung disease, acute or chronic organizing pneumonia, eosinophilic pneumonia, single or multiple nodules or mass-like lesions, desquamative interstitial pneumonia, and diffuse alveolar haemorrhage [3,11,12]. These lesions can be rapidly progressive [2] with the risk of irreversible pulmonary fibrosis [2,9,12]. Pleural effusion/pleurisy remains exceptional during amiodarone pulmonary toxicity [3,7,8]. It is classically bilateral and exudative [8,13]. It is rarely isolated [7], most often associated with parenchymal pulmonary toxicity or other toxic organ damage [8,13], and may exceptionally be, as in our observation, the first sign indicative of this toxicity [8,13]. Hepatic injury with amiodarone is rare and often unpredictable. Its frequency is estimated at 15-30% for elevated liver enzymes and less than 3% for acute hepatitis [6]. It can be irreversible in 50% of cases and even lead to severe forms of steatohepatitis with cirrhosis and portal hypertension [6]. Similarly, pulmonary involvement can also progress to irreversible fibrosis in 5 to 7% of cases [14] with a mortality estimated at 9% [2]. Treatment is based on discontinuation of the drug and, in severe cases, systemic corticosteroids for 4 to 12 months; the initial dose is 40-60mg/day followed by a gradual decline [3]. Corticosteroid therapy allows rapid improvement of pulmonary gas exchange and reversibility of radiological abnormalities [10]. Relapse after discontinuation of corticosteroid therapy has been reported mainly in obese subjects. Early detection of amiodaroneinduced pulmonary toxicity significantly improves its prognosis which can be fatal [2,9,12] (50% of cases if acute respiratory distress syndrome [2]), and clinical recommendations are currently well established for this [5,6].

Conclusion

The pulmonary toxicity of amiodarone has become rare with the use of lower doses; it can happen even early enough and with any dose. Regular clinical, radiological and biological monitoring makes it possible to detect and take these complications in time. Our observation is characterized by the association of a triple toxicity with amiodarone: pulmonary, hepatic, and pleural which is exceptional, and by its spontaneous resolution. It is necessary to think of the iatrogenic cause due to amiodarone in front of any bilateral pleurisy that is not proven in patient under amiodarone.

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