■
Introduction:This is a lengthy article, and some parts may be difficult to understand. It’s okay to skip over the parts you don’t understand and focus on what you can grasp, as this is a treasure of an article!
Since 1985, with funding from the National Natural Science Foundation and other projects, I, along with over twenty graduate students, have conducted research on this topic. Recent findings suggest that the emergence of liver qi stagnation and its related syndromes involves the cerebral cortex, diencephalon, hypothalamus, limbic system, endocrine system, and the functions of the sympathetic and parasympathetic nervous systems. The hypothalamic-pituitary-adrenal (HPA) axis, CRH (Corticotropin-Releasing Hormone), and the locus coeruleus-sympathetic-adrenal medulla system have been studied further in the U.S. in a combined approach of Western and Traditional Chinese Medicine (TCM). We believe that the holistic approach of Western medicine has made significant progress and breakthroughs in recent years, particularly in the field of stress theory. According to Google statistics, daily entries on stress syndrome exceed 4 to 10 million, involving the main mechanisms of internal environmental stability, which are the nervous system, endocrine system, and immune system responding in a three-stage pattern to any pathogenic factors. Some TCM syndromes correspond precisely to the process of internal environmental stability disruption, and the development of diseases in TCM also exhibits three corresponding stages.
The liver qi stagnation and its related syndromes discussed in this article primarily focus on the locus coeruleus-sympathetic-adrenal medulla changes, involving other factors affecting overall internal environmental stability. Liver qi stagnation should be considered the core of all liver syndromes, as almost all existing liver disease syndromes contain it. Today, we will discuss this from the perspective of Western medicine’s understanding of internal environmental stability. We believe that only by starting from a holistic perspective can we grasp the patterns of syndromes. Our research on the evolution of syndromes shows that typical syndromes are relative, while atypical syndromes are common. I will first discuss the liver as an example and continue with a series of reports on the spleen, kidneys, etc.
01
Initial Stage (Equivalent to the Alert Phase of Stress Response)
Based on my clinical observations of a large number of cases, the initial clinical manifestations include instability of the liver and gallbladder, with patients exhibiting:palpitations, anxiety, insomnia with vivid dreams, nightmares, restlessness, and unexplained fears.This stage is primarily characterized by various pathogenic factors causing excitation of the locus coeruleus-sympathetic-adrenal medulla system, leading to disturbances in the locus coeruleus. (The locus coeruleus, also known as the blue nucleus, is a cluster of neurons in the brainstem associated with the stress response, participating in arousal and vigilance.) Disturbances in the limbic system, including the amygdala and hippocampus, trigger sympathetic-adrenal medulla responses, resulting in emotional reactions such as anxiety, restlessness, panic, and insomnia. The sympathetic nervous system causes tension, and increased secretion of norepinephrine and epinephrine from the adrenal medulla leads to palpitations and increased heart rate.In the mid-stage (equivalent to the resistance phase), symptoms of liver qi stagnation are already present, but for the sake of completeness, they are placed in the second stage. If the first stage does not improve, it progresses to the second stage. Pure liver qi stagnation is a stress response, derived from the main symptoms of the first and second stages. Based on our analysis of 800 common syndromes, the five organ syndromes account for 81.5%, with liver qi stagnation and its related syndromes comprising about one-third. Therefore, studying this syndrome is of great clinical significance. An analysis of 40 cases of liver qi stagnation revealed symptoms such as liver yang transforming into fire, liver wind, hyperactive liver yang, and rebellious qi. Among 225 cases of pure liver qi stagnation, those with liver qi invading the spleen and stomach were next in frequency. The main symptoms of liver qi stagnation include:irritability, anxiety, depression, chest tightness, abdominal distension, wandering pain, bitter mouth, and dry throat, with a wiry pulse.Irritability and anxiety:The liver’s function is closely related to the patient’s emotional responses. Patients with these symptoms are easily agitated and can react strongly to minor stimuli, losing self-control. Sufficiently strong stressors can excite the locus coeruleus and sympathetic nervous system, subsequently stimulating the limbic system, which is closely related to emotions such as fear, anxiety, and depression. Additionally, the excitation of the locus coeruleus and sympathetic nervous system further increases adrenaline secretion, which is a major cause of the aforementioned symptoms.Depression:The hypothalamic-pituitary-adrenal axis increases the secretion of adrenocorticotropic hormone (ACTH), and CRH can induce emotional responses such as anxiety, hopelessness, helplessness, and loss of control. Literature confirms that depression is one of the main manifestations of systemic stress responses, typically appearing after vigilance and anxiety.Chest tightness and a tendency to sigh:Emotional changes due to stress responses and tension in the cortex, hypothalamus, locus coeruleus, adrenal glands, and sympathetic nervous system can lead to changes in the respiratory and circulatory systems (which are also preparations for the fight or flight response), resulting in deep, rapid, irregular breathing, increased heart rate, and even palpitations, with elevated blood pressure. We have previously observed patients who sigh frequently, noting that their respiratory muscle activity is irregular, and after a period, their breathing is affected, leading to insufficient oxygen exchange. Irregular breathing disrupts calm breathing, and after a period of tense and rapid breathing, deep breaths are required to alleviate the situation. Thus, patients often feel that they cannot take a full breath, resulting in insufficient oxygen intake due to tense respiratory muscles. This is the pathophysiological basis for frequent sighing and is also the cause of chest tightness.(Editor’s note: This is interesting because many patients clinically describe feeling like they cannot take a full breath, which is actually due to tense respiratory muscles. What can be done? I wonder if Si Ni San could help relieve smooth muscle tension?)Overventilation, or frequent sighing, can lead to decreased carbon dioxide levels and alkalosis, often accompanied by feelings of excitement and fear. I encountered two cases in the U.S. where patients frequently sighed, experiencing anxiety and numbness in their limbs, along with convulsions. Our research from 1989 showed that most patients with type A liver qi stagnation had autonomic nervous dysfunction, sympathetic nervous system hyperactivity, high blood viscosity, and catecholamine levels above normal.Chest and abdominal pain, wandering pain:The liver governs the smooth flow of qi, and the liver meridian traverses the chest and abdomen. Any obstruction in the qi mechanism in these areas can cause pain, which may be due to organic lesions such as ulcers, chronic gastritis, peritonitis, or colitis, or it may be functional, caused by sympathetic nervous hyperactivity leading to gastrointestinal distension and pain, and digestive dysfunction resulting in bloating. George et al. suggest that stress responses can lead to muscle tension in the pyramidal and extrapyramidal pathways, which can also be a cause of rib pain. Based on literature and our observations, disturbances in the autonomic nervous system along the meridian pathways and sympathetic nervous tension may also be responsible for meridian pain.Wiry pulse:In TCM, a wiry pulse is indicative of liver disease. In our study of 440 cases of liver qi stagnation, 321 cases (73.9%) exhibited a wiry pulse. A wiry pulse is characterized by a tense, elastic feeling, indicating that the blood vessels are in a constricted state. Arterial constriction is caused by sympathetic nervous tension leading to constriction of small arteries.Dry throat and bitter mouth:Stress responses often lead to dry mouth, as sympathetic nervous tension reduces saliva secretion, making it thick and viscous. Saliva not only aids in digestion but also continuously cleanses the oral cavity. When saliva is reduced and thick, food debris, shed epithelial cells, and bacteria accumulate, leading to fermentation and resulting in a bitter taste or even halitosis. Chen et al. suggest that liver qi stagnation is associated with emotional abnormalities, decreased immune function, and abnormal secretion of catecholamines, with increased dopamine, epinephrine, and norepinephrine levels, decreased plasma cAMP, increased cGMP, and elevated plasma cortisol levels, indicating changes in immune function.
02
Second Stage: Resistance Phase of Stress Response
This stage develops when the initial phase is not controlled. In this phase, the body mobilizes systemically, and adrenal cortical responses increase, leading to elevated metabolism, weakened inflammatory and immune responses, and shrinkage of the thymus and lymphatic tissues, depleting defensive reserves. The typical TCM syndrome is liver qi stagnation.2.1 Liver Qi Invading the SpleenPatients in this category exhibit symptoms of spleen deficiency alongside liver qi stagnation, such as poor appetite, heaviness in the limbs, edema, diarrhea, a slow pulse, a swollen tongue, and a white, greasy coating. Observations indicate that spleen deficiency symptoms are often accompanied by parasympathetic nervous hyperactivity. Edema is common without identifiable causes in modern medicine related to the kidneys, heart, or liver. Geonge et al. suggest that adrenocorticotropic hormone stimulates the adrenal cortex to secrete electrolyte steroids like aldosterone and deoxycorticosterone into the systemic circulation, increasing sodium and water reabsorption in the renal tubules, and increasing capillary permeability, leading to fluid retention due to connective tissue relaxation.Liver qi invading the spleen can cause intestinal colic and increased peristalsis, leading to what is known as irritable bowel syndrome, a typical gastrointestinal stress syndrome.2.2 Liver Qi Invading the StomachSymptoms of liver qi stagnation may also include stomach pain, vomiting, and acid reflux, which can be associated with organic lesions such as ulcers or chronic gastritis, or functional disorders, primarily accompanied by autonomic nervous dysfunction and sympathetic nervous hyperactivity.2.3 Qi Stagnation and Blood StasisQi stagnation can lead to blood stasis, and blood stasis can further obstruct the meridians, exacerbating qi stagnation. We have found that many cases of liver and spleen enlargement exhibit symptoms of qi stagnation and blood stasis, indicating that blood stasis can lead to accumulation. The tongue may show stasis spots, or the tongue color may be purplish, with stabbing pain in the hypochondrium. Blood stasis is a common clinical manifestation. Due to microcirculation disorders, autoimmune deficiencies, and disrupted coagulation mechanisms, changes such as hyperplasia, chronic inflammation, thrombosis, and edema can be observed.2.4 Qi Stagnation Transforming into HeatIn TCM, excess qi can transform into fire. Prolonged stagnation can lead to heat symptoms such as five hearts heat, red tongue, even crimson tongue, yellow coating, rapid pulse, yellow urine, and dry stools. These can be seen in organic lesions with low-grade fever, such as chronic hepatitis, or can appear without organic lesions, presenting with heat symptoms, rapid pulse, palpitations, and insomnia, primarily due to sympathetic nervous hyperactivity. Liver fire can invade the lungs, causing lung inflammation and hemoptysis, or liver fire can invade the stomach, leading to hematemesis. Sympathetic nervous hyperactivity affects the temperature center, resulting in heat production, increased basal metabolism, and accelerated heart rate. Such patients may experience low-grade fever, but mild cases may only present with heat in the hands and feet or slightly elevated body temperature, not exceeding normal levels. The liver fire syndrome is reported in many literatures as a stress state, with adrenal hyperfunction leading to vasodilation and increased metabolism. Jin’s five types of liver diseases include liver qi stagnation, hyperactive liver yang, liver wind transformation, liver fire, and liver blood deficiency, indicating that liver wind transformation, plasma norepinephrine and epinephrine levels are highest, while liver yang hyperactivity, liver fire, and liver-gallbladder damp-heat are higher than in the normal group, with liver qi stagnation and liver qi stagnation with spleen deficiency resembling healthy individuals.2.5 The Interconversion of Liver Qi Stagnation, Hyperactive Liver Yang, Internal Wind, Liver Excess Fire, and Liver-Gallbladder Damp-Heat Syndromes.Liver qi stagnation, rebellious liver qi, and excessive rising can often lead to hyperactive liver yang. Prolonged liver qi stagnation can also transform into fire and generate wind. Hyperactive liver yang can also transform into wind. Domestic studies combining Western and TCM, such as those by Li Jiqun, report that multiple indicators show common pathological changes in patients with liver fire and liver-gallbladder damp-heat syndromes. One is that the body is in a stress state, with elevated plasma norepinephrine, epinephrine, dopamine, and decreased T3, T4, and elevated TSH, indicating hyperfunction of the sympathetic-adrenal medulla and adrenal cortex. Secondly, inflammatory mediators are released, increasing tumor necrosis factors in the blood, and changes in the content of active substances related to vascular cell activation and damage to vasodilatory functions indicate increased content of vasodilatory substances, leading to vasodilation. Plasma catecholamines, liver yang hyperactivity, liver fire syndrome, and liver-gallbladder damp-heat syndrome all increase sequentially, indicating sympathetic nervous hyperactivity. The nucleic acid content in red blood cells in liver fire syndrome shows decreased ATP and increased AMP, indicating increased metabolism and energy consumption, with elevated inflammatory mediators such as LTC4 in allergic reactions.In liver-gallbladder damp-heat syndrome, multiple indicators show that the main feature is an exogenous inflammatory response, with endothelial cell damage and increased release of inflammatory vascular active substances, increased platelet aggregation factors, and liver-gallbladder damp-heat often exhibiting characteristics of liver fire combined with exudative inflammation, sometimes with exogenous inflammation, and increased capillary permeability.2.6 Dizziness, Headache, and Dry Eyes.All belong to the same mechanism of liver fire and hyperactive liver yang.2.7 Damage to the Chong and Ren MeridiansMenstrual cycle irregularities, dysmenorrhea, amenorrhea, and breast lumps and tenderness are closely related to the Chong and Ren meridian functions in TCM. Liver qi stagnation can disrupt these meridians, leading to the aforementioned symptoms, which may worsen in some patients before menstruation, often diagnosed as premenstrual syndrome. This condition is primarily caused by excessive mental stress, leading to dysfunction of the subcortical centers, including the pituitary and other endocrine glands, resulting in elevated estrogen levels, insufficient luteal phase, or relative increases in estrogen, along with sympathetic nervous hyperactivity. This condition has been classified as a stress-related disease, with menstrual blood often showing purple clots and reduced volume, possibly due to sympathetic nervous hyperactivity affecting coagulation mechanisms, shortening coagulation time, and prolonging the retention time of clots in the uterus.Additionally, CRH can inhibit the release of gonadotropin-releasing hormone, indirectly lowering follicle-stimulating hormone and progesterone levels, leading to amenorrhea and menstrual irregularities in women. CRH can promote the secretion of ACTH, inhibiting glucocorticoids (which can also inhibit estrogen).2.8 Qi StagnationEmotional stimuli and sudden fainting, limb numbness, chest fullness, and throat constriction, with a feeling of choking, clenched fists, and limb convulsions. Seizures triggered by anger are typical stress responses.2.9 Running Piglet QiThe running piglet qi we observe arises from the foundation of liver qi stagnation and can coexist with plum pit qi, both falling within the disease spectrum. The Soviet neurologist Seip described that due to functional reasons or organic lesions in the abdominal cavity, damage to the abdominal nerve plexus can lead to sensations that rise from the lower abdomen to the head. This sensation typically spreads to the left side, reaching the occiput and then the face, causing patients to feel a rush of blood to the face, with facial flushing, often accompanied by persistent palpitations and a fear of death. Patients often describe an indescribable feeling of extreme distress, resembling the symptoms of running piglet qi, indicating that this condition likely arises from such causes. It also reflects autonomic nervous dysfunction.2.10 Plum Pit Qi – Phlegm Qi ObstructionThroat blockage, chest fullness, and difficulty in qi flow, with a sensation of obstruction or inability to expel or swallow. This plum pit qi often has no identifiable organic lesions in the throat, and some patients with seizures may initially feel a small ball rolling to the throat, referred to as the “seizure ball.” This is primarily due to autonomic nervous dysfunction and visceral dysfunction. Sometimes, temporary changes in the throat, such as foreign body sensations, can form excitatory foci under weakened cortical conditions, leading to a prolonged sensation of obstruction. Soviet neurology records indicate that dysfunction of the abdominal autonomic nerve plexus can also cause this specific symptom. (Editor’s note: Therefore, can our Ban Xia Hou Po Tang and Hou Po Su Ye improve the function of the abdominal autonomic nerve plexus? Experts say it can also lead to such sensory disturbances, so Ban Xia Hou Po Tang is not a panacea for plum pit qi; it has its indications.)The abdominal nerve plexus is distributed among abdominal organs such as the liver, pancreas, stomach, duodenum, small intestine, colon, and kidneys. Organic lesions in these organs can lead to dysfunction of the abdominal nerve plexus, and dysfunction of the abdominal nerve plexus can also cause lesions in these organs. When the abdominal nerve plexus is dysfunctional, it can produce various indescribable sensations, as if food is approaching the throat (due to esophageal retroperistalsis).
03
Third Stage (Exhaustion Phase): Liver Yang Deficiency and Others
This syndrome ultimately presents with symptoms of yang deficiency, as any liver syndrome will eventually end in yang deficiency. This is similar to the reports from the Shanghai Hypertension Research Institute on the evolution of hypertension syndromes, where initial liver yang hyperactivity and yin deficiency lead to both yin and yang deficiency, ultimately resulting in yang deficiency.This is the final stage of the stress response, where systemic endocrine failure and atrophy can occur.In summary, liver disease syndromes primarily reflect disturbances in the internal environment. Domestic literature also suggests that the stress response system, particularly the locus coeruleus-sympathetic nervous system-adrenal medulla, is the main change. In the first stage, liver and gallbladder instability and pure liver qi stagnation primarily involve emotional, psychological, and physiological responses from the cerebral cortex and limbic system, with increased secretion from the sympathetic nervous system and adrenal medulla, but this is unstable, as examinations of the aforementioned endocrine glands and autonomic nervous functions are also unstable. As the syndrome progresses to the second stage, liver qi invading the spleen occurs, with both sympathetic and parasympathetic nervous systems hyperactive. The hyperactivity of the parasympathetic nervous system is often due to spleen deficiency, where liver qi invades the spleen or spleen deficiency leads to liver qi stagnation (earth countering wood), resulting in liver qi stagnation and spleen deficiency, with disharmony between the liver and spleen. The relationship between the liver and spleen is complex, with varying states of sympathetic and parasympathetic nervous systems, leading to a very complicated situation. Liver qi invading the stomach, along with the different clinical manifestations influenced by the sympathetic and parasympathetic nervous systems, further complicates the picture. Hyperactive liver yang, liver excess fire, liver qi transforming into heat, and internal wind movement are a group of liver excess syndromes driven by sympathetic nervous system hyperactivity and increased secretion from the adrenal medulla, with corresponding increases in norepinephrine and epinephrine secretion. The manifestations differ, with hyperactive liver yang primarily affecting systemic blood vessels, leading to elevated blood pressure due to increased norepinephrine. Liver qi stagnation transforming into fire manifests as sympathetic-adrenal medulla hyperactivity, leading to congestive inflammation, such as liver fire invading the lungs causing lung inflammation and hemoptysis, or liver fire invading the stomach leading to hematemesis. These are systemic changes related to inflammation in associated organs. Liver excess fire can present as conjunctival symptoms, otitis media, and herpes zoster, while internal wind movement can lead to cerebrovascular diseases, including cerebral hemorrhage and infarction. In fact, the syndromes of liver disease involve a stress system that is not solely the adrenal-sympathetic system but also includes the hypothalamic-pituitary-adrenal system, with these neuroendocrine activities interacting to form a very complex local environment.The third stage is yang deficiency, where liver yang deficiency will occur alongside yang deficiency in other organs, leading to systemic endocrine and nervous atrophy and failure, not just in the liver. As seen, the Western stress system is intricate, and clinical manifestations are also complex, yet they exhibit common patterns. However, Western research and discussion on this are limited, as it requires a holistic perspective to classify these important clinical manifestations, which have been thoroughly practiced and developed in Chinese medicine. This is the essence of TCM syndrome differentiation.Applying the patterns of TCM syndromes to the theory of holistic stability can reasonably elucidate the essence of syndromes, providing a shortcut for integrating TCM and Western theories. The next step is to establish diagnostic criteria for syndromes based on this perspective, including psychiatry, psychology, endocrinology (including the pituitary, adrenal, gonads, thyroid, etc.), neurology (including sympathetic and parasympathetic nervous systems, limbic system, etc.), and immunology testing indicators. A comprehensive study of diagnostic elements will contribute to the formation of integrated TCM and Western theories.· END ·Copyright StatementThis article is excerpted from a discussion on the pathophysiological basis of liver qi stagnation and its related syndromes, authored by Huang Bingshan. Edited by: Bacon. Copyright belongs to the relevant rights holders. Sharing this article is for the purpose of dissemination and learning exchange. Non-professionals should not blindly self-medicate. If there are any improper uses of the article or images, please feel free to contact us for removal.