Thymus

                                                        Thymus

                                            PKGhatak, MD

In adults, the Thymus gland exists only in name; from the newborn to childhood, till the onset of puberty, the thymus, sitting in front of the heart, dominates. The thymus in children is the largest gland in the chest. The Greeks thought it was the center of anger and named it thymus. The thymus name was derived from thumos meaning anger. Galen was the first physician who correctly described the evolution of the thymus in childhood and greatly reduced in size in adults. In adults, the thymus produces only a few mature   T-cells throughout life.

The thymus grows from the third and fourth pharyngeal pouches, one on each side. As the two lobes of the thymus grow, the cavities in the stalk are closed off and only a vestige remains. The developing thymus lobes descend in the thorax and move close together towards the center and finally join together as one thymus gland.

Several genes encode the development and maturation of the thymus. Deletion of chromosome 22 results in absence of the thymus and clinically the condition is known as DiGeorge syndrome. This syndrome is incompatible with life beyond a few weeks after birth.

Unlike the pancreas and liver, the thymus is just one gland - an endocrine gland. It secretes Thymosin and other hormones. The task of the thymus is to train the immature lymphocytes to become super sleuths like FBI agents. That task has two aspects - a Positive Selection, is the ability to detect any antigen that is foreign to the human body, and the other is a Negative Selection that ensures the quality is not to make a mistake and call normal body antigens as foreign agents. The positive section is delineated by the presence of specific receptors on the T cells surface that have the ability to recognize MHC immune antigen. MHC stands for major histocompatibility complex. Once the lymphocytes are trained properly, they are released into circulation with an official T-Cell designation. T-cells (thymic lymphocytes) take residence in lymph nodes, the spleen and move around the body in the blood. T-cells are further differentiated in CD (cluster differentiation) grouping based on the presence of cell surface proteins. Out of this classification, the CD4 and CD8 T-cells are well known since HIV/AIDs became prevalent. This acquired quality is called the Adaptive Immune System as opposed to Innate immunity, as for example, the macrophages engulf bacteria.

There is a complex relationship between Testosterone and gut bacterial antigen in the development of Positive and Negative Senses. Testosterone modifies gut bacterial antigen that elevates negative sense, whereas Estrogen suppresses negative sense. XX chromosome in females and the master gene AIRE gene (Autoimmune regulator) regulate gene expression that codes autoimmunity are active participants in this process.

 Structure of Thymus.

Each thymus gland has an outer zone of densely packed cells called the cortex and a loose collection of cells in the inner zone called the medulla. Each lobe is made up of several lobules.

The cells of the cortex are mostly thymocytes - newly arrived lymphocytes from the bone marrow waiting to be turned into T-cells. The epithelial cells in the cortex are arranged as a fine network of cells supporting the thymocytes. In the cortex, the thymocytes acquire positive selection.

The medulla has a rough distribution of epithelial cells and fewer thymocytes and collections of whorls of epithelial cell remnants from the stock of the third pouch. These whorls are distinct microscopic features of the thymus and are known as Hassall's corpuscles. In the medulla, the thymocytes acquire negative selection.

 Hormones and Cytokines of Thymus:

Thymosin, Thymulin and Thymopoietin are three secretory hormones of the thymus. The first two are involved in T-cell transformation and the thymopoietin helps to keep the mature T-cells to keep up the acquired adaptive immune property. The cytokines are interleukin class IL-1, IL-6, GM-CSF, zinc- thymulin complex and other polypeptides.

 Diseases associated with Thymus gland disorder:

Myasthenia gravis. In thymoma or hyperplasia of the thymus the T- cell functions are derailed. The body develops antibodies to Acetylcholine receptors. Lack of action of acetylcholine is felt as facial muscle weakness, weakness of legs and fatigue.

 DiGeorge syndrome: Deletion of chromosome 22 results in a congenital abnormality of the heart, hair lip and cleft palate, esophageal tracheal fistula, absence of Thymus gland and total failure of adaptive immunity of T-cells. If the condition is recognized early in infants Thymus gland transplant is indicated.

SCID: Severe combined immunodeficiency disease. This results from the deficient maturation of hemopoietic progenitor cells. T-cells, B-cells, NK (natural killer) cells are deficient.

Autoimmune endocrine syndrome: In this syndrome, T-cells fail to acquire the Negative Selection knowledge while developing in the medulla of the thymus. Thyroid, Parathyroid, and Adrenal cortex are destroyed due to autoantibodies and hormones from these endocrine glands become deficient. Candida infection of the mouth and GI tract is also a common feature of this entity.

Thymoma is associated with multiorgan autoimmunity. In this disorder, thymus growth disturbs the normal development of T-cells. The disease resembles Graft vs Host Disease.

The thymus gland is damaged by radiation of the chest and chemotherapy for cancer. Regeneration of the thymus is possible, shown recently in experimental animals. The CCL11 cells of the damaged thymus stroma initiate the recruitment of peripheral Eosinophils. The natural killer cells and Th2 cells inter-react with eosinophils and restoration of structure and functions resume.

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Liver

Liver

PKGhatak, MD

The liver is an amazing organ. It is the largest solid abdominal organ but hardly noticed. The liver is tucked away underneath the dome of the diaphragm and surrounded by a rib cage. Doctors want to examine the liver have to make it descend down with breathing (breathing out) by asking patients to breathe deep in and out and pushing his/her fingers deep underneath the right side of the rib cage. If the liver is palpable a normal liver is like the relaxed bicep muscle, a cirrhotic liver feels like ear cartilage.

The liver is the largest chemical factory of the body. It gets its raw materials from the GI tract, the digested food and drinks via the portal veins. Then the liver manufactures proteins, fat, cholesterol, glycogen from sugar and glucose from amino acids and fatty acids, hormones, enzymes, and other various chemicals; filters the waste products, detoxifies, absorbs toxins, and then releases these substances at the appropriate time in the blood. The liver is an endocrine cum exocrine gland and much more.

Embryology of Liver:

Liver growth starts early, as early as 2 weeks following fertilization of the ovum. An invagination of endoderm of the foregut, close to the Septum Trasvestum, occurs and that becomes the site of liver development. A liver bud develops and the cells of the head end of the liver bud start to grow in an empty space reserved for the heart and blood vessels. The developing cells destined to be liver cells grow like finger projections and orient in alternating rows with the endothelium of the blood vessels which later become the terminal capillary branches of the portal vein. The septum trasvestum becomes the capsule of the liver and fibrous tissues from the capsule enter the developing liver cells and become the scaffolding and provide stability of the liver. The tail end of the same liver bud forms the gall bladder and extrahepatic bile ducts.

Liver lobule:

The liver is a mixture of the exocrine gland, endocrine gland, vascular organ and storehouse of many things including every Stem Cell line.

The structural and functional unit of the liver is a lobule – a tiny acinus. The total number of lobules in a liver is estimated to be 300 billion. An understanding of microscopic anatomy is essential to study the physiology of the liver.

A liver lobule is a three dimensional unit. It looks hexagonal under the microscope but in a living state, a lobule is more or less like a circular structure. At the periphery, there is an arcade formed by a branch of the portal vein. Straight branches, the venules of the portal vein – often referred as a lake, originate from the arcade and travel toward the center of the lobule and converse on a central vein. The appearance resembles the spokes of a wheel. Columns of liver cells follow closely the straight portal venules. The other side of the liver cells column is a draining tube – a tiny bile duct. This pattern is repeated in all lobules. The interlobar space is interlaced with fine fibrous tissues attached to the liver capsule. This space contains branches of the hepatic artery and lymph vessels and various mesenchymal cells, including the well known Kupffer's cells.

Branches of the hepatic artery, bile duct and lymphatics follow the branches of the portal vein. a hepatic artery branch to the lobule opens into the lake. The plexus of fine branches of the hepatic artery supplies all the cells of the bile duct and other structures in a lobule. The central vein joins with adjoining veins and ultimately forms 2 to 4 Hepatic veins and hepatic veins terminate in the Superior Vena Cava.

In essence, each hepatic cell is bathed by the blood that is a mixture of arterial blood and venous blood returning from the GI tract. Intrahepatic bile ducts are as profuse as blood vessels are and lobules are drained continuously.

A Hepatocyte:

A liver cell is a large cell and rich in the cytoplasm and nuclear materials. The nucleus is surrounded by a well demarcated nuclear wall. The nuclear chromatin is very prominent and generally contains two nucleoli. The cytoplasm is loaded with mitochondria, smooth and rough endoplasmic reticulum, Golgi apparatus, lysosome, peroxisome, inclusion bodies, stored glycogen, and lipid molecules.

Blood supply: The liver is a very vascular organ. It weighs just 2 % of the body weight but gets 25 % of cardiac output. Of the total blood inside the liver, 75 % is from the portal vein, and the rest is arterial. The liver stores 15 % of total body blood and in hemorrhage, hepatic blood is made available.

Bile secretion: In a day about 1 liter of bile is produced. Bile is produced continuously and finds its way to the gall bladder first and is stored there. After a fatty meal gall bladder discharges bile into the intestine.

Liver Function: It is said that the liver completes 500 different tasks.

The following are just to name some of these functions.

Metabolism of Carbohydrate: Every aspect of carbohydrate metabolic processes from energy production, breakdown of glycogen, making glucose from fat and amino acids and conjugation of the carbohydrate moiety to toxic substances take place in the liver.

Fat metabolism: Cholesterol is synthesized in the liver. The liver converts fatty acid to fat molecules and breaks down fat and releases fatty acid in starved conditions.

Protein synthesis: Albumin and ferritin are made in the liver, so also all the transport proteins - just too many to mention here.

Acute phase positive proteins are about 30 in number. Some important are C- reactive protein, procalcitonin, alpha antitrypsin, heptidine,  IL-1 receptor antagonist, D- dimer. The negative acute phase proteins are albumin, transferrin, transthyretin. 

Blood coagulation: Several anticoagulants and clotting factors are made in the liver. Anticoagulants are protein S and protein C, Antithrombin. Coagulants are fibrinogen, prothrombin, factors- V, VII, IX, X, XI, XII. Von Willebrand and factor VIII are made in the liver but not by the hepatocytes.

Hormone production: Thrombopoietin, Somatomedin, Angiotensinogen, Hepcidin.

Vitamins production: Vitamin D 25-OH. The liver acts as a store of fat-soluble vitamins- A, D, E, K. and B12.

Storage function: Iron, Glycogen, fat, copper.

Detoxification: Most toxins are made less toxic or harmless by conjugation wand made sulfate, glucuronide and simply converted to inert substances.

Execratory function: Bile acids and bilirubin.

Digestive function: Bile acids and bicarbonates.

Myeloid Metaplasia and liver: Several hematological conditions end up destroying bone marrow and replaced it with fibrous tissue, a condition known as myelofibrosis. In such conditions liver and spleen attempt to generate deficient blood cells.

Regenerative power: The liver carries all stem lines. At little as 15 % of the liver remaining from an accident or liver donation, the remaining liver will regenerate to the normal size.

Liver transplant began in 1967, it has become an essential operation in congenital biliary atresia. A liver transplant is performed for liver failure due to many causes including alcoholic cirrhosis and viral hepatitis C.

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Pancreas

                                                            Pancreas

                                              PKGhatak, MD

The pancreas is an important organ but not essential to life since the isolation and purification of Insulin in 1921 by Dr. Banting and a medical student Mr. Best. The pancreas is a mixed gland contains both exocrine (secretion by duct) and endocrine (secretion directly enters blood) glands.

Development of Pancreas:

The pancreas has two sources of origin. Two independent buds develop from the foregut endoderm - one dorsal bud and one ventral bud, at the junction of the foregut and midgut, next to the origin of the biliary bud. The dorsal bud produces the major part of the gland and the main duct, the ventral bud produces a part of the head, the uncinate process and the accessory duct.

Exocrine development:

In the beginning, the primitive pancreatic cells differentiate into the acinar cell line (gland with ducts) and the endocrine cell line. Each acinar duct joins with the adjoining acini and ultimately forms two major ducts as mentioned above. Each acinar duct joins with the adjoining acini and ultimately forms two major ducts as mentioned above. The main pancreatic duct opens into the 2nd part of the duodenum and the duct is a bit dilated, called the ampulla of Vater and is surrounded by smooth muscle sphincter, the sphincter of Oddi. The common bile duct joins the pancreatic duct in the ampulla and the opening in the pancreatic duct is guarded by the sphincter of Boyden. The accessory pancreatic duct opens just proximal to the bile duct + pancreatic duct opening. In adults, many congenital anatomical variations of pancreatic ducts and the occasional head of the pancreas are encountered during surgery.

Endocrine Development:

The developing endocrine cells are grouped together in several clusters and are widely dispersed all through the gland. These clusters are called Langerhans Islands. Endocrine cell populations are further divided into alpha, beta, delta and C cells. All these cells are present on every island. Initial tiny ducts are attached to each islet but soon the ducts disappear.

Location of Pancreas:

The pancreas is located deep inside the abdomen on the posterior abdominal wall, behind the peritoneum. It is firmly anchored on the wall; the head of the pancreas fills the c-shaped space of the duodenal curvature, the main body lies across the abdominal wall, the tail part almost touching the spleen. In front of the pancreas is the Lesser Sac of the Omentum, the stomach slides over it easily.

Exocrine Function of Pancreas:

Pancreatic enzymes are secreted by acini cells and are rich in digestive enzymes -

Pancreatic Amylase, Trypsin, Chymotrypsin, Lipase, Phospholipase, Cholesterol esterase. In addition, the ductal cells secrete Chloride and Bicarbonate.

The total volume of pancreatic secretion is 2 to 3 liters. a day.

The pancreatic juice is very alkaline and acts with bile to neutralize highly acidic gastric discharge in the duodenum.

The action of Pancreatic enzymes on Food:

As the names imply, the amylase digests complex carbohydrates into glucose, trypsin and chymotrypsin digest proteins into simple amino acids and Lipase digest fat into fatty acid and glycerol, cholesterol ester breaks down cholesterol. In the digestive process, duodenal enzymes play a significant part also.

Endocrine Function of Pancreas:

Alpha cells secrete Glucagon.

Beta cells secrete Insulin and Amylin.

Delta cells secrete Somatotropin, Ghrelin and Pancreatic polypeptides. Gastrin is secreted in an early stage of development and later, the stomach secretes gastrin exclusively.

 The C-cell function is not known.

The action of Glucagon. Glucagon breaks down glycogen stores in the liver and skeletal muscles. It stimulates amino acid conversion to glucose (neogluconogenesis). Glycogen turns fatty acids into fat molecules in the liver. Glucagon delays the release of Insulin from the pancreas.

The action of Insulin.  Insulin binds with insulin receptors present on the surface of every cell. A protein molecule GLUT4(glucose transporter 4) comes up to the surface of the cells and an Insulin molecule bound to the receptor fuses with the membrane. This opens up channels for glucose molecules to enter the inside of the cell. The glucose molecule is immediately converted to glucose phosphate by the enzyme phosphatase. This keeps the concentration gradient in favor of glucose crossing inside the cells. Insulin favors glycogen synthesis, the conversion of fatty acids to fat molecules and amino acids to protein. Insulin promotes body growth and increases growth hormone secretion from the pituitary gland. Insulin delays glucagon secretion and thereby reduces glycogen breakdown.

The action of Somatostatin. Somatostatin is a gastrointestinal motility inhibitor. Somatostatin decreases both exocrine and endocrine secretion of the pancreas, decreases secretions from the duodenal and small intestinal glands. It reduces growth hormone release from the pituitary gland. It reduces gastric motility, gastric acid and gastrin secretion.

The action of pancreatic polypeptides. These small molecules suppress pancreatic exocrine secretion, gall bladder contraction and gastric motility.

The action of Ghrelin. Ghrelin promotes growth hormone release, muscle growth, and increases appetite. 

Blood Supply of Pancreas: Pancreas is richly supplied by arterial circulation. Celiac artery and Superior mesenteric artery supply arterial blood. The venous drainage goes to the liver by the Portal vein.

Insulin sensor: The alpha and beta cells act as the sensor of blood glucose levels. Alfa cells modify glucagon release by a negative feedback loop; whereas the beta cells release more insulin when sugar levels are high and shunt down Insulin release when the sugar level is low.

Nerve Supply of Pancreas. Like every abdominal organ, the pancreas has two nervous systems innervation - namely Somatic and Autonomic nervous systems. Nerve fibers going in and out of the pancreas pass through the celiac ganglion but many fibers just pass through.

Somatic sensory. The nerve cells are located in the Dorsal Root Ganglia (DRG) of the spinal nerves T 6 to L 2. The nerve fibers carrying the pain and other sensations enter the spinal cord and travel along the intermediate lateral tract of the spinal cord to the nuclei of the Thalamus. The 2nd order neurons from the thalamus cross the midline to reach the cerebral cortex. The DRG is sensitive to Capsaicin, CGRP (calcitonin gene related peptide). The neurons generate substance P.

Motor division.  The main center for secretary and contractile functions is located in the Nodosa Ganglion of the Vegas nerve. The axions from these neurons directly innervate all the cells of the pancreas.

Autonomic Nervous System:

Sympathetic supply. The nerve cells are located in the Celiac ganglion, the Mesenteric ganglia, and the Paravertebral ganglia. The alpha fibers of sympathetic nerves produce vasoconstriction, delay secretion and decrease endocrine function. Beta fibers stimulate Insulin and glucagon production and release.

Parasympathetic Nervous System:

The nerve cells are located in the Dorsal ganglia of the Vegas nerve. The axon of these nerves makes connections with the neuron present in the pancreas itself. Parasympathetic stimulation increases both exocrine and endocrine secretion and production.

Neurotransmitters:

Somatic nerves are Cholinergic. Sympathetic nerves are noradrenergic, glycinergic, and respond by releasing Neuropeptide gamma. Parasympathetic nerves are nicotinic-cholinergic at the ganglia and muscarine choline at the postganglionic terminal fibers.

The pancreas is fully developed at birth but only the exocrine function is present at birth. At about 15 weeks of life, the endocrine function begins.

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Bronchogenic Cysts.

 

                                                        Bronchogenic Cysts

                                                   PKGhatak, MD

Bronchogenic cysts are rare in adults but not so uncommon in newborns and young children. In a 3 to 6 week old fetus, two independent lateral lung buds develop as outpouchings from the ventral wall of the primitive foregut. (1).  Each of these two lateral buds differentiates as right and left main bronchi. The primitive foregut differentiates into the trachea and esophagus by developing a deep groove and joining the laryngotracheal sulci of the lateral wall of the foregut. Each main bronchi rapidly grows in the surrounding mesenchymal tissue and branches repeatedly and forms the rest of the conductive airways. Bronchogenic cysts arise from the development errors of the bronchogenic cells. Some of the bronchogenic cells remain attached to the developing foregut and that is the reason the bronchogenic cysts appear outside the thorax as these cells form cysts.

The bronchogenic cyst develops as a small solid mass and then as proteinous mucus begins to accumulate and it takes a cystic appearance. The walls of the cysts are thin and cysts have no ducts. As the cyst enlarges it compresses the adjoining structures - trachea, bronchi, and blood vessels in the middle mediastinum. Symptoms vary from being totally asymptomatic to cardiopulmonary compromise.

 Incidence: one in 50,000 hospital admissions. Location: 10 % of bronchogenic cysts are located in the middle mediastinum. The mediastinal cysts account for 50 % of all lung cysts and are seen in the paratracheal, carinal, para-esophageal and hilar region. 20 % of bronchogenic cysts are intrapulmonary and develop late and are seen in adults. Other locations are the neck, pericardial, pleural, diaphragm, and retroperitoneal. Size of the cysts: 2 to 10 cm in diameter, usually single.

Cysts are lined with ciliated pseudostratified columnar respiratory epithelium and squamous metaplasia is rarely present. In addition to mucus glands, cartilage, smooth muscle and blood may be present.

 Symptoms in children: Stridor, shortness of breath, dysphagia, superior vena cava syndrome, pneumothorax and pneumonia. In adults: Most cysts are asymptomatic and detected in chest x-rays, and recurrent pneumonia.

 Complications: Fistula formation in the tracheobronchial tree, malignancy. Diagnosis: The present generation of sonograms is very sensitive and can detect bronchogenic cysts in utero. In newborns to adults, the chest x-ray and CT scan detect all bronchogenic cysts, rarely MRI is needed.

Treatment: Surgery is the only option in symptomatic cases and in adults, lobectomy is usually required for intrapulmonary cysts. Surgery is also recommended for asymptomatic cysts before the start of complications.

Reference: 1.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320013/

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Spontaneous Pneumothorax.

                         Spontaneous Pneumothorax

                                           PKGhatak, MD

A slender, tall young man around 20 years old. old suddenly feels sharp chest pain and soon develops shortness of breath. He is told in the ER that he has pneumothorax. His medical and family history does not point to the cause of his illness and the term Spontaneous pneumothorax is used to describe the incidence.

Most frequently, chest wall injuries from an automobile accident and rib fractures, gunshot wounds, and knife attacks, are the common traumatic causes of pneumothorax; pulmonary emphysema, cystic diseases of the lung, and use of ventilators are other main causes of pneumothorax.

Spontaneous pneumothorax results from the rupture of a small subpleural bleb. Usually, 10 to 30 subpleural blebs develop due to inherited diseases or poorly repaired deceased lung tissue. Any one of these blebs may open up during straining, lifting heavyweight, or without an apparent reason. The outside air pressure is higher than normal pleural cavity pressure.  Any breach in the integrity of lung tissue or airways, the outside air freely enters the pleural cavity. The air around the lung tissues sneezes, the lung and a lobe of the lung or the entire one side may collapse and that causes shortness of breath. 

Incidence of spontaneous pneumothorax.

The incidence in men is 10 per 100,000 male population per year; in women, the incidence is 4 per 100,000 per year. A tall young person's growth spurts out spaces the growth of lungs, the resultant lung connective tissues are thinly spread out and air sacs can easily form.

Inherited conditions.

Mutation of the FLCN gene accounts for 40 % of spontaneous pneumothorax. FLCN gene codes for a protein Folliculin. Folliculin promotes cell division and cell growth and in addition confers elastic properties. The disease was previously known as Birt-Hogg-Dube syndrome - a constellation of skin tumors, renal cancer, multiple pulmonary cysts and recurrent pneumothorax. The disease is inherited by an autosomal dominant pattern.

Machado- Joseph Disease. It is also inherited by the autosomal dominant mode. This disease manifests as spinocerebellar ataxia and recurrent spontaneous pneumothorax.

Other disease associations are - Marfan syndrome and Homocystinuria.

Management of spontaneous pneumothorax.

Once the diagnosis is confirmed and if the pneumothorax is small (less than 15 % of the chest cavity) the patient is watched in the ER for 4 to 6 hrs. Oxygen therapy and pain medication may or may not be required. If the patient is stable and comfortable, then the patient is discharged with instructions and subsequent follow-up telephone calls.

A larger pneumothorax is evacuated by inserting an intercostal chest tube at the most dependent site. The chest tube usually is self retained and secured at the insertion site by a retention suture. The wound is dressed by a sterile dressing impregnated with medical Vaseline. The distal end of the chest tube is positioned underwater seal and a suction device is used. A Series of air bubbles is seen to come out initially and the lung expands, and healing starts. When the air bubble ceases, then a clamp is applied to the chest tube and after several hours a chest x-ray is obtained to confirm the full expansion of the lung and absent pneumothorax. Then the patient is ready for discharge.

Recurrence rate in non-gene spontaneous pneumothorax.  

  In about 10 to 30 % of cases, the pneumothorax may recur.

Complications.

Check valve formation and Tension Pneumothorax. 

  This is an emergency situation. The pleural pressure keeps increasing with each breath and the air outlet is blocked by a tissue flap. The other normal lung is displaced laterally and the heart and larger blood vessels are compressed and displaced. Cardiac output falls and severe hypoxemia and hypotension and shock follow. The situation must be corrected by inserting a wide bore needle in the chest cavity and then thoracic surgery is required.

Prolonged healing or no improvement of pneumothorax.

 Repair, resection, or segmental lobectomy may be required to ensure a permanent closure of the damaged lung tissue.

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Stunned Myocardium.

 

                                                Stunned Myocardium

                                            PKGhatak, MD

Coronary arterial occlusion causes chest pain and demands an immediate ER visit. Often family members are told it is a heart attack or myocardial infarction using a medical term. Not all coronary occlusions result in infarctions thanks to timely angioplasty, thrombolytic therapy, or having only partial obstruction of circulation. Immediately after a successful full restoration of circulation, the cardiac enzymes and ECG return to normal. However, an echocardiogram may show a decrease in the contractile function of ventricles and the ejection fraction (EF) less than normal (75 – 55 %). Serial studies show a remarkable improvement of EF in the next 2 days, then a slow improvement over several weeks. Dr. Braunwald and Kolner in 1982 described this condition and called it Stunned Myocardium. However, years earlier Dr. Heydrickx showed, in experimental dogs by occluding coronary circulation temporarily for 2 to 15 minutes followed by full restoration of blood flow, decreased myocardial contractility but his peers did not believe this experiment and rejected his paper submitted for publication.

Difficulties in studying the living human heart.   

 Stunned myocardium is a functional abnormality of the heart muscles and is reversible. Changes in heart muscles do not faithfully reflect changes seen in blood and require the study of heart muscle cells. Biopsy of the heart for a reversible disease is out of the question. Experiments are carried out on dogs and pigs for that purpose. The metabolic paths, cytokines and sympathetic control of the human heart are different from those of animals. And not all that is known from animal studies applies to humans.

Cause of stunned myocardium.      

  The precise reason is still debated even today. High energy ATP (adenosine triphosphate) generation, the sympathetic neural response is delayed or deficient. ACE (angiotensin I enzyme), bradykinin, and prostacyclin actions on the myocardium are complex. Restoration of circulation restores the oxygen supply to the myocardium, which generated free radicals that break down contractile protein troponin I and paradoxically depresses myocardial contractility further. The use of Superoxide Dismutase, an inactivating agent, improves stunned myocardium. In stunned myocardium, the Mitochondrial electron transfer is delayed, oxidation of catecholamines depresses contraction, ATP derived energy generation is suppressed, action potential generation is prolonged, energy dependent on calcium channels interfere with calcium ion movements and calcium overload of the sarcoplasmic reticulum and myocardium results in depressed contractility. Prophylactic use of calcium channel blockers prevents stunned myocardium.

 ACE, bradykinin and prostacyclin.

 An increase in ACE activity increases angiotensin I and bradykinin. Angiotensin II is a potent vasoconstrictor and positive inotrope results in increased ischemia. On the other hand, an increase in bradykinins generates more prostacyclin and nitrous oxide (NO),   both are known to minimize stunning.

Clinical situation producing stunning.                                                      

  Cardiac surgery. During inflating and deflating a balloon at the time of angioplasty. Cardiac stress test in chronic angina. Emotional stress. Dialysis.

Hibernating myocardium.

Decreased myocardial contractility over a longer period from chronic coronary disease or repeated stunned myocardium is known as hibernating myocardium. The myocardial cells are viable but require weeks or months to return to normal function.

 Takotsubo cardiomyopathy.

This is another example of myocardial wall motion abnormality in temporary myocardial ischemia. Patients are postmenopausal women subjected to severe mental stress prior to the development of chest pain and shortness of breath. ST-T is elevated in ECG and also cardiac enzymes are elevated. However, the Coronary angiogram shows no abnormality. An echocardiogram reveals Left ventricular apical ballooning, but a normal wall motion of the base ofthe  ventricles is an indication of more than a single coronary artery spasm. The excised myocardiocytes show vacuoles filled with lipids, damaged mitochondria, edema and mononuclear cell infiltration, local necrosis and fibrosis. Patients usually fully recover in 2 to 5 weeks.

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Slow Growing Carcinomas of Lungs.

                                                     Slow growing carcinoma of the lungs

                                                                 PKGhatak, MD

Carcinoma is a cancerous growth of the cell that lines the inside of the glands and ducts of glands, it also includes surface cells (epithelial cells) of internal organs like the liver and intestine. The cancerous growth of the connective tissues is called sarcoma and cancers of blood cells are known as Leukemia.

Slow growing carcinomas and potentially malignant carcinomas of lungs were previously grouped under Bronchial Adenoma. Now they are in a separate group.

List of slow growing carcinomas and tumors, benign in appearance with a tendency of recurrence and distant metastases.

1. Carcinoid tumors.

2. Adenocystic carcinoma.

3. Mucoepidermoid carcinoma.

Carcinoids.

Carcinoids of the lungs are the major lung tumor of this group, accounting for 85 % of all cancers of the lungs when Small Cell Cancer (SCC) and Non-Small Cell Cancers (NSCC) of the lungs are not included.

Carcinoid tumors also grow in all parts of the gastrointestinal tract, pancreas, ovaries, testis, appendix, thymus gland, and Meckel's diverticulum. Carcinoid tumors develop from Kulchitsky's cells, otherwise called neuroendocrine cells. These cells closely resemble nerve cells but secrete a wide variety of hormones and polypeptides which produce many symptoms due to excess hormone like actions.

This discussion on the endocrine effects of carcinoids will be limited to bronchial carcinoids. 

Symptoms of bronchial carcinoids.

Centrally located tumors are located in the trachea and in equal frequency in the right and left main bronchi. Peripheral carcinoids are much less frequent, and patients are mostly asymptomatic; often detected on chest CT or plain X-ray, an incidental finding. Peripheral carcinoids also cause pneumonia. Because of delayed diagnosis, many peripheral carcinoids are cancerous at the time of biopsy.

The centrally located carcinoid usually is a single lesion. They produce hemoptysis, cough, and episodic wheezing. Under the bronchoscope, the carcinoid tumor appears as a small cherry red, very vascular mucosal tumor. Both sexes are equally affected, usually in people over 50 yrs. of age but all age groups are known to have carcinoids.

The tumor cells are small polyhedral cells arranged in sheets, ribbons, and alveolar or glandular architecture. The nucleus of cells is mostly regular but irregular nuclei and mitotic activities indicate malignancy.

The blood circulation of bronchi is systemic, secretion from carcinoid drains directly into the bronchial veins and bypasses the liver. As a result, even a small amount of hormones/ hormone like substances produced generate significant and persistent symptoms. Carcinoid tumors secrete mostly serotonin and to a lesser amount of histamine, kallikrein, prostaglandins, tachykinins, and various amounts of 40 other chemicals. 

Midgut carcinoids produce a large amount of GI secretory and motility polypeptides.

About 10 % of bronchial carcinoids produce carcinoid syndrome.

Carcinoid syndrome and carcinoid crisis.

Serotonin is 5-hydroxytryptophan (5TP). 5TP is produced from an amino acid - tryptophan. Platelets store serotonin.

Bronchial carcinoids produce intense flushing of the face, neck and upper torsos and become red and itchy. Watery eyes and runny nose develop. Salivation is increased. Wheezing, watery diarrhea, and marked hypotension develop. Carcinoid syndromes are periodic and unpredictable, they may last 2 mins to several minutes and are usually prolonged in bronchial carcinoids.

Carcinoid Crisis.

Symptoms of carcinoid crisis are basically the same but more severe and sustained. Usually, it leads to cardiovascular collapse and cardiac arrhythmias, and death.

Carcinoid crises are precipitated by general anesthesia, tumor manipulation, biopsy, and surgery.

Pellagra.

Niacin is also called vitamin B3, It is also derived from tryptophan. In carcinoids, most of the tryptophan is shunted away for serotonin production. Vitamin B3 deficiency leads to pellagra. The symptoms are known by 3Ds - dementia, dermatitis, and diarrhea.

Increased Fibrosis.

Thickening of the right sided heart valves, the intraventricular septum, leads to congestive heart failure. Retroperitoneal fibrosis, urethral obstruction, Pyronine's syndrome may develop.

Other Endocrine Manifestations of bronchial carcinoids.

Neurosecretory products of carcinoids are varied - some are Pituitary hormones like GI secretory and motility polypeptides.

Type I Kulchitsky's carcinoid cells produce mostly bronchial obstructive symptoms.

Type II Kulchitsky's cells produce serotonin and other vasoactive and secretory polypeptides. And responsible for Serotonin syndrome and serotonin crisis.

Type III Kulchitsky's cell carcinoids are large cell carcinoma of the lung and Type IV cells are small cell carcinoma of the lung (SCC).   Type III and IV cell tumors secrete hormones and hormone like products.

The effects of these hormones produce the following syndrome/ entities.

1. Cushing's syndrome from excess ACTH.

2. Hyperpigmentation from melanocytes stimulating hormone.

3. Acromegaly and gigantism from excess growth hormone.

4. Hypoglycemia from insulin like products.

5. Hyperglycemia, hypertension, osteoporosis, renal stones and various other conditions.

 Metastases.

Bronchial carcinoid metastasizes to hilar lymph nodes, bones, and occasionally to distant places via blood.

Adeno Cystic Carcinoma.

Adeno cystic carcinoma is also known as Cylindroma. The tumor arises from the mucus glands of the trachea and main bronchi. The tumor is invasive in nature, spread along the airway underneath the surface layer cells and invades the hilum. and blood vessels. The tumor cells are small pleomorphic, the cells are arranged like tubes. The surrounding stroma shows myxomatous changes. The symptom is hemoptysis. Other symptoms are wheezing and partial bronchial obstruction.

Mucoepidermoid carcinoma.

Mucoepidermoid carcinomas are rare carcinomas and arise from the mucus glands of the trachea and major bronchi. The tumor is a mixture of several cellular types - well differentiated mucus cells, sheets of squamous cells with varying degrees of keratinization, and cellular bridges. Tumors are well circumscribed but noncapsulated and usually project into the lumen of the trachea or bronchi.

Symptoms. Hemoptysis, cough, fever, chest pain.

The tumor is a slow growing that does not invade local issues. Mitotic figures are few.

Diagnosis and treatment of slow growing carcinoma.

Bronchoscopy and biopsy give the proper diagnosis. The choice of treatment is surgical. Various techniques of surgery and the amount of tissues removed depend on the extent of lesions and degree of malignancy. The prognosis is generally good.

For diagnosis and treatment of bronchial carcinoid -please see a previous blog.

https://humihealth.blogspot.com/2011/06/carcinoid-and-other-neuroendocrine.html

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Benign Tumors of Lungs.

                                                   Benign tumors of the lungs

                                                        PKGhatak, MD

The Lung cancer surveillance program using a low dose CT scan has resulted in an increase in the detection of lung nodules/ masses. One in every 100 CT scans detects a benign lesion, only a fraction of these nodules are true benign tumors, and the majority are due to infectious granulomas. The plain chest x-ray detects one benign nodule out of 500 chest x-rays.

The previous generation of clinicians included low grade malignant tumors and also benign looking tumors with the tendency of local recurrence and distant metastasis, under the Bronchial Adenomas. Now the malignant and potentially malignant tumors are excluded from the adenoma of the lungs and naturally, the incidence of adenoma has changed.

Benign tumors of the lungs are diverse. All of these tumors, however, have a common mode of presentation, symptoms, methods of diagnosis and options for treatment modalities.

Tumors originating in other structures of the chest are excluded in this discussion.

Mode of presentation.

Incidental.  Patients are symptoms free at the time of detection of a tumor on a CT scan or plain chest x-ray. These tumors are located peripherally.

Symptomatic.  Patients' symptoms are of two categories.

Symptoms of airway obstruction. Patients complain of wheezing, hemoptysis, shortness of breath. These tumors are centrally located in the major bronchi and trachea.

Symptoms of alveoli damage. Repeated pneumonia in the location, lung abscess, chest pain. The tumors are peripherally located.

Work up.

Bronchoscopy and biopsy of lesions are all that are required to make a final diagnosis.

Treatment options.

Tumors are slow growing and often the patients are asymptomatic - waiting with follow up is generally advised.

Surgery.  Most patients are better off having the tumor removed by a limited surgery by video-assisted thoracoscopic surgery.

Other modes of tumor ablations are rarely advised.

Classification and some aspects of Benign Tumors of Lungs.

Hamartomas.

Hematomas are the most common benign tumor of the lung. Hamartoma originates from the retained totipotent fetal cells in the lung. The pathological pictures are of a mixed cellular type. Normal lung tissues are mixed with growths from cartilage, fat cells, muscles and mucus glands.

10 % of patients complain of obstructive symptoms. X-ray shows a single mass with a very clear defined border. Occasionally seen as a lobulated nodule of 3cm size A popcorn calcification is a very distinct feature, but diffuse, stippled, or macular calcification may be present. The average age of patients is 40 -60 yrs; the male-female ratio is 2:1.

Bronchial Adenoma.

These benign tumors originate from the lining epithelial cells of the mucus glands of the bronchus. The tumor usually projects into the lumen of the airways. Symptoms are from airway obstruction. The pathological picture consists of mucus filled small acini lined with columnar cells.

Hemangiomas.

This is usually a single lung lesion, when lung hemangioma is a part of hemangioma of the face, the tumor behaves differently and is discussed in an earlier blog. Most patients are symptom free, when they have symptoms, they are from infection and hemoptysis. Histologically, there are sheets of rounded endothelial cells lining blood filled spaces, occasional papillary cellular pattern is present.

Leiomyomas.

Leiomyomas arise from smooth muscle cells of the bronchi. All age groups of patients are involved. Female patients are specially prone to leiomyoma. The microscopic picture is bundles of spindle cells with elongated pale nuclei. Rare calcification is seen.

Lipomas.

Lipomas are seen in the major airways, as polypoidal mass projecting into the lumen usually has a morrow base but some lipomas take an hourglass appearance due to intrabronchial and extra bronchial parts. Lipomas originated from the fat cells of the bronchus or from fat cells of the connective tissue situated in between the cartilage rings. The male-female ratio is 5 :1, and the onset of symptoms is at 50 yrs. or older age. The histological picture is a fat cell mixed with some muscle cells and glands.

Lymphangiomyelomatosis.

 The origin of this tumor is the smooth muscle of lymphatics. The tumor may extend to the bronchial wall, venules, arterioles and alveolar sacs. The patients are females of childbearing age, present with shortness of breath. At times patients have persistent chylous pleural effusion and hemoptysis. Female reproductive hormones are perhaps responsible. X-ray shows lower lobe infiltrates of linear or fine nodular infiltrates with hyperinflations of the remaining lung. The diffusion capacity of CO (carbon monoxide) is reduced, so also the ventilation-perfusion ratio, and dead space of the lung is increased, and also the total lung capacity.

Pathological picture - hypertrophy of the smooth muscles of the entire lung and obstruction of all smaller airways.

Lymphangiomas. 

These tumors originate from the wall of lymph channels, tumor consists of lymph filled spaces lined by columnar or cuboidal cells and rarely of stratified squamous cells, making an appearance of a honeycomb. An occasional collection of lymphocytes is also present.

Papillomas.

The tumors are present in the larynx, trachea and main bronchus. Human papillomavirus infection may be responsible. Mixed cell papillary growths are a common pathological picture. In rare instances carcinoma in situ is present. Hoarseness of voice and cough are presenting symptoms.

Neurofibromas.

These benign tumors originate in nerve tissues of the lung, and lesions are round, oval, or lobulated. They are located outside the bronchus. Tumors compress the airways. Tumors are composed of bundles of elongated nerve fibers with palisading nuclei. The bundles are separated by fine fibers called Antoni A tissue.

Myoblasts. The tumor cells have fine granular eosinophilic cytoplasm, and cells are ovoid and polygonal. patients are young and both sexes are equally affected.

Chondromas.

These tumors are not to be confused with hamartomas. Tumor originates from the cartilage cells of the rings of the major airways.

Pseudotumor. 

This is a radiological finding, not a tumor as such. When fluid accumulates in the horizontal fissure between the right upper and middle lobes of the lung, on PA chest X-ray, it shows a spindle shaped tumor and on the right lateral view, the mass appears as a triangle. The tumor disappears as fluid dissipates from improved congestive heart failure. For this reason, the tumor is also called a phantom tumor and a vanishing tumor.

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FEVER

                                                                       Fever

                                                       PKGhatak, MD

Merriam Webster dictionary defines fever as the elevation of the body temperature above normal.

The question then, what is a normal body temperature.

It may come as a surprise to many that a normal body temperature is not so easily defined or universally accepted. Human body temperature varies - it is highest at sundown, reaches 37.4C (99.3F) then slowly decreases and drops to 35.2C (95.6F) at sunrise. This is known as Diurnal Variation.

CDC (Center for Disease Control, USA) defines normal body temperature 37C (98.6F) and fever 38C (100.4F). In 1868 Carl Wuderlich wanted to answer that question and studied one million fever charts. He concluded that a normal axillary (under the armpit) temperature was 37 (+ -) 0.9C and any temperature over 38C as fever. A similar study conducted by Mackowiak concluded that a normal oral temperature was 99.9°F and anything above that was fever. Small and Clements reviewed over 120,000 ER visit charts and reported a temperature of 1.8F above the diurnal variation was fever.

Causes of fever.

These are several causes of fever and can be mentioned here very briefly under External and Internal causes.

External causes. -

Infection. Viruses, bacteria, fungi, inhalation of fungal spores, parasites.

Inflammation.  Damage to body tissue by sprains, bone fractures, childbirth, surgery, crush injuries,

Snakebite, insect bites, plant poison.

Autoimmune disease/condition.  Rheumatoid arthritis and other collagen vascular diseases. Crohn's disease, ulcerative colitis. Mismatched blood and blood product transfusion, rejection of organ transplants.

Allergy.  Hay fever.

Malignancy.  Lymphoma, sarcoma, acute leukemia.

Food and Drinks.   Uncooked shellfish, unpasteurized milk and milk products, poorly cooked meat and eggs.

Drugs.  Fever from drugs is due to the development of antibodies or direct action of the heat controlling center of the brain. Penicillin tops the list followed by cephalosporins, anti-TB drugs, quinidine, procainamide, methyldopa, phenytoin.

Hear stroke.  Exposure to high ambient temperature and humidity, working in the boiler room, and steam engine locomotive. 

Post anesthetic malignant hyperthermia. Certain anesthetic drugs can precipitate uncontrollable high temperatures in people with a rare inherited disorder.

Internal factors from damage to the temperature center.

Brain damage from strokes. Methamphetamine intoxication, Traumatic Brain Injury (TBI).

Malignant hyperthermia. When body temperature reaches 109°F (43 °C), the temperature center breaks down and unless medical attention is given immediately, death becomes imminent. Examples are Parkinson's hyperpyrexia syndrome, Serotonin syndrome.

FUO (fever of unknown origin).  FUO in the earlier days due to subacute bacterial endocarditis or lymphoma. Now it is highly unlikely that a fever will not have a discernable cause.

Physiology of Fever.

The Temperature Regulating Center (TCR) is located in the Hypothalamus of the brain. The hypothalamus is also the nerve center of the sympathetic nervous system. The TCR is connected with other centers of the brain and via the Hypothalamus - pituitary portal circulation with the Pituitary gland. Through these pathways, the hypothalamus controls the metabolic rate, heat generation and heat dissipation of the body. Regulation of heart rate, breathing, and hormone levels is under the autonomic nervous system.

The setpoint of Temperature.

The hypothalamic auto-regulatory mechanism sets the normal core body temperature.

Pathology of fever.

Chemicals secreted by the phagocytic WBCs, immunocytes are called Cytokines, Interleukins, Prostaglandins. These are the chemical messengers that can turn the TCR up or down. Cytokines and interleukins promote Prostaglandin E2(PGE2) secretion. PGE2 acts directly on TCR.

Some bacterial degradation products can directly act on the TCR and cause fever(pyrogenic).

Effect of fever:

Higher body temperature enhances the phagocytic action (ability to engulf) of WBC.

Immunocytic activities increase - production of IL-1(interleukin 1) and IL-6 are promoters of inflammation.

Inhibition of Bacterial growth. Most human pathogenic bacteria grow best at a normal body temperature; fever slows down the bacterial growth rate.

Metabolic reset.  At a higher temperature, glucose utilization, glycogen breakdown and glucose generation from fat and amino acids are accelerated.

Generation of body heat or Thermogenesis is under the control of the hypothalamus:

Shivering is a common method of thermogenesis; the release of adrenaline and thyroxine are other ways.

Loss of heat is achieved through vasodilatation and increased sweat production via the sympathetic nervous system.

 

In the pre-antibiotic era, the study of fever was an important subject in medical school. Paying meticulous attention to the characteristics of the fever chart, a physician could guess the bacteria responsible for the infection.

The fever was categorized as- 

Continuous, remittent (the temperature remained above normal throughout the day but fluctuated more than 2 C in 24 hrs.), intermittent, quotidian (every day), tertian (every 2-day interval), quartan (every 3-day interval).

Typhoid fever was diagnosed on the basis of remittent fever, and a palpable spleen. Other examples of intermittent fever are Malaria, Kala-azar, TB, Rat bite fever, EB virus.

The post antibiotic era changed the enthusiasm for fever study. At present, antigen testing for pathogens includes viruses, bacteria, and many fungal and parasitic diseases. Antibody tests are also widely available. Present day clinicians look at the fever cart but rely less on it to make a diagnosis.

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Common Cold

                                                              Common cold

                                                    PKGhatak, MD

The common cold is really very common. It is said that every adult gets 2 attacks and every child 6 attacks of the common cold every year. The common cold is the number one viral disease of humans.

There are approximately 200 different viruses responsible for the common cold, including three groups of coronaviruses; however, Rhinovirus is responsible for about 50% of the common cold cases. The common cold is also called a Head Cold and a Viral URI (viral upper respiratory infection)

Rhinovirus is an RNA virus. It thrives in the nose because the virus prefers a temperature of 89 degrees F, and the nose's temperature is very close to this, as opposed to the core body temperature of 98.6 degrees F. It is also true that exposure to cold makes a person susceptible to rhinovirus infection.

The COVID-19 pandemic made people aware of viral infections. The mode of the viral spread and symptoms of illness are understood by most people. Public health officials repeatedly advised people how to protect themselves from this respiratory viral infection and to minimize the spread of the virus to others.

People have learned that viruses are inert particles, like darts, until the virus gets a foothold in a living individual. The virus then enters inside the cell and directs the cell's DNA / RNA to copy virus particles. In the end, the cell walls are broken open and viruses are released, newly released viruses infect more healthy cells. The rhinovirus uses ICAM receptors to attach to the nasal epithelium and then enter inside the cell.

The COVID-19 pandemic has produced havoc in the way we live, work, socialize, and carry out other activities. Most of these are detrimental to human society, except for one benefit: during the period of social distancing and hand washing, the common cold has almost disappeared.

In early human history, the common cold viruses found humans an easy target to attack, infect, multiply, and live in perpetuity. The human immune system is unable to maintain a good defense against the common cold viruses. A vaccine, for the same reason, has not been effective. Recently, MedUnite of Vienna found that the human immune system produces antibodies against the RNA genome of rhinovirus but not against the capsid protein, which is necessary to kill the rhinovirus. That is responsible for repeated rhinovirus infections.

Children are nursery-going age, young adults on college campuses, military recruits, people in cruise ships, sailors on submarines and other ocean-going vessels, and institutional residents are prone to repeated common colds.

Infants and young children suffer the most because their airways are narrow and they are not able to cough up sputum. Elderly and disabled nursing home patients develop complications more often than any other group and also die in a higher proportion.

The diagnosis.

Viral URI is diagnosed by eliminating bacterial URI.  The most common bacteria causing URI is GAS (group A streptococcus). The textbook lists certain signs like  - a temperature of 104 degrees F or higher, swollen red tonsils, strawberry tongue, petechiae on the hard palate, and cervical lymph node enlargement, which are usually findings in bacterial URI; but physicians depend on the Rapid Strep Test (RST). The RST detects a GAS antigen, taken from the throat by a swab and mixing it with known GAS antibodies; and at times, a blood WBC count is necessary.

Complications.

A middle ear infection is common in children, and difficulty in breathing may require hospitalization. Elderly people may develop viral pneumonia, and at times, viral URI makes them susceptible to bacterial pneumonia.

Prevention.

A molecule, SETD3 (set domain protein 3), has shown promise in blocking rhinovirus replication by interfering with the methyltransferase of rhinovirus.

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Sternutation

                                                                Sternutation

                                                     PKGhatak, MD

Sternutation is an unusual way to say sneezing. The Latin root is a verb, Sternuere, meaning to sneeze.  The term, Sternutation, is hardly used in medicine.

Sneezing is a reflex involuntary action of forceful expulsion of a large volume of air through the nose and mouth containing the nasal discharge and mucus containing the nasal irritant.

The sensory pathway of this reflex is the maxillary division of the trigeminal nerve.  The sensory nucleus is situated in the medulla, close to the lateral reticular formation, called the spinal trigeminal nucleus. The neurotransmitter is Histamine. The motor pathways are extensive because a large number of muscle groups are involved. Many of the muscles are also used in coughing. The muscles used in sneezing are the pharyngeal, tongue, laryngeal, diaphragm, bronchial, facial including eyelids, muscles of respiration, accessory muscles of respiration, and anterior abdominal muscles. The motor impulse is carried by the facial, glossopharyngeal, Vagus, phrenic, intercostal, and spinal motor nerves.

The act of sneezing.

Initially, the mouth and nasal passages are widely opened to draw in a large volume of air. Next, the base of the tongue is elevated and the epiglottis is depressed partially closing the oropharynx. Finally, a sudden volant contraction of all muscles forces out air through the nose and mouth containing nasal secretions and mucus. A sneeze generates aerosol particles of 0.5 to 5.0 micrometers in size of about 40,000 in one sneeze.

A person must be awake to sneeze but cannot voluntarily sneeze or sneeze on demand. 

Special categories of sneezing.

Snatiation. 

Snatiation is a combination of two words - sneeze and satiety. This is a hereditary condition, inherited by autosomal dominant mode. A full stomach brings uncontrollable sneezing.

Photic sneeze.

It is also inherited by an autosomal dominant mode, also known as ACOHOO (autosomal dominant compulsive helio ophthalmic outburst of sneezing). People carrying this gene sneeze as soon as they step out of dark places into a brightly lit place,

The usual cause of a sneeze.

Nasal irritants: foreign body, irritant gases, household cleaning agents, detergents, perfume, incense burning.

Allergic rhinitis. Vasomotor rhinitis, chronic sinusitis.

Nasal infection: viruses, bacteria, etc.

Nasal polyp.

Injury to nose, CSF leak, Nose bleeds.

Withdrawal of addictive drugs like opioids.

The history of sneezing is nothing to sneeze about. The subject is full of historical facts, religious beliefs and practices, tradition and lots of intrigues.

_______________________________

Please read:   

https://en.wikipedia.org/wiki/Sneeze

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