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.

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Please read:   

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

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Cough.

 

                                                                   Cough

                                                     PKGhatak, MD

Cough is a protective action, either voluntary or reflex, to clear the airway of secretion.

The pharynx is a Greek word meaning the throat. The throat is a hollow muscular structure, stretches from the base of the skull to the beginning of the larynx in front and the esophagus behind. Epiglottis is a cartilaginous structure guarding the openings of the larynx and esophagus. The upper posterior part of the pharynx is the nasopharynx where nasal passages open. The middle part is the oropharynx, an extension of the oral cavity and the lower part is the laryngeal pharynx.

The sensation from the nasopharynx is carried by the maxillary branch of the trigeminal nerve (cranial nerve 5). The oropharynx is innervated by the sensory division of the glossopharyngeal nerve. The larynx, vocal cords and nasopharynx are innervated by the sensory fibers of the Vagus nerve –the internal division of the superior laryngeal nerve. A sensory branch of the Vagus also supplies a portion of the external auditory canal and Eustachian tube. Branches from these nerves form a tangle of nerves called the Pharyngeal plexus. The trachea and bronchus down to the respiratory bronchioles are innervated by the recurrent laryngeal nerve of the vagus. These nerves carry sensation to the brain. But the cough center in the brain is not a localized center.

The motor impulse to the muscles involved in the cough reflex is supplied by several nerves. The main muscle is the diaphragm: The phrenic nerve innervates the diaphragm. The intrinsic muscles of the Pharynx are supplied by the recurrent laryngeal nerve, and only the stylopharyngeus muscle is innervated by the motor fibers of the glossopharyngeal nerve. The external intercostal muscles, anterior abdominal muscles, are innervated by the intercostal nerves of the thoracic segments of the spinal motor nerves of the abdomen.

Mechanism of cough.

The initial action is the closure of the glottis (the vocal cords and the space between them), the epiglottis closes the opening to the larynx. The next act is a forceful contraction of all muscles, resulting in positive pressure in the thoracic cavity. The trachea and bronchus become shorter and narrower. The last act is the sudden relaxation of the vocal cord and throat. That results in a sudden gush of air expelled from the airways carrying all irritants captured in the bronchial secretion.

Though coughing and sneezing are triggered simultaneously with some common noxious stimuli, these two reflexes are different. A person can cough in sleep or under light anesthesia. On the other hand, a person who has to be awake to sneeze at the same time cannot sneeze voluntarily.

The force generated by a reflex cough can reach 100 miles/hr. The voluntary cough can vary greatly from just a short repeated cough commonly called a nervous cough to a forceful cough with the use of all muscles including accessory muscles of inspiration as in cases of bringing up thick tenacious sputum. When a cough brings up blood - is called Hemoptysis.

Factors triggering coughs.

Irritants: Irritation of the pharynx, trachea-bronchus from irritant gas, or fine sprays of chemicals like perfume, incense, household cleaners, and detergents.

Infectious agents: respiratory viruses, Covid-19, influenza, bacterial, fungal, mycobacteria.

Allergy and asthma.

Sinus and nasal discharge: Postnasal drip and vasomotor rhinitis, allergic rhinitis are some examples.

Medication: ACE inhibitors.

Pulmonary fibrosis: Idiopathic pulmonary fibrosis, post viral pneumonia fibrosis. Rheumatoid arthritis, SLE and scleroderma.

Malignant lesions: larynx, vocal cord, and Lung.

Aspiration of gastric acid: gastric reflux and aspiration.

Foreign body in airways.

Anxiety and psychosocial: also called nervous cough.

Putting a Q-tip in the ear.

Voluntarily or on request by the examining physician.

Types of Coughs:

Wet cough. In infection and allergy, where a lot of nasal secretion is generated.

Dry cough. Commonly seen in the use of ACE inhibitors, Pulmonary fibrosis.

The patients cough repeatedly, a short unproductive cough, involuntarily, and at times disturbs sleep.

Paroxysmal cough. The patient coughs uncontrollably and violently followed by a whooping sound in an attempt to resume breathing. Patients soon feel exhausted from coughing as seen in whooping cough(pertussis)

Tickle cough. In vasomotor rhinitis and allergic rhinitis, sudden onset of cough occurs and continues till secretions are completely cleared from the airway.

Nervous cough: repeated attempts to clear the throat when there is no secretion.

Croup. This is seen in children under 5 yrs. old in viral infection because of narrow airways. The swelling in and around the larynx produces raspy and squawking sounds.

Persistent cough. When cough persists over 6-8 weeks, as often seen in allergy and gastric acid aspiration. In delayed diagnosis like eosinophilic bronchitis, carcinoma of the lung, TB, fungal infection, etc.

Night cough. It is usually seen in gastric reflux and asthma.

Features of vasomotor rhinitis:

The precise cause is unknown, various agents are suspected including weather, perfumes, alcohol and spicy food. The cough follows a sudden gush of nasal watery discharge. The disincentive signs are the absence of an itchy nose, watery eyes, or scratchy throat.

Complications of persistent cough:

Most coughs are episodic, related to the upper respiratory tract infection, and are controlled easily. In prolonged vigorous cough, some of the following complications may be seen.

Fainting spells, Subconjunctival hemorrhage, small urine leaks, Inguinal and femoral hernias, Fractured ribs, Sore chest wall and costochondritis. Exhaustion, Sleep deprivation.

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I Can't Breathe

                                                            Dyspnea or Shortness of Breath

                                                           PKGhatak, MD

“ I can't breathe” has become a worldwide cry for social justice after the killing of George Floyd in Minnesota.

I can't breathe, difficulty in breathing, sense of suffocation, air hunger, shortness of breath, short of wind, tightness in the chest, uncomfortable in breathing, not getting enough air, are some of the ways patients describe their difficulty - in medicine known as dyspnea.

The word dyspnea is derived from the Greek word dyspnoia – meaning breathing disorder.

The American Thoracic Society calls dyspnea” a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.”

Can't breathe is one of the most frightening symptoms of human experiences. A sense of impending doom overshadows all other concerns. The patient fights with all his might to right the situation.

A healthy person may experience shortness of breath during strenuous exercise like climbing several flights of stairs or hiking mountains and visiting high altitude places.

Shortness of breath in all other cases is due to an abnormal condition/condition in the lungs or heart or neuropsychiatric causes.

Points to remember that dyspnea is subjective and varies in intensity.

When patients present with dyspnea the doctor categorizes them into groups according to 1. its severity. 2. episodic or chronic.

Some of the conditions of life threatening acute shortness of breath (SOB) are.

1. Allergic and anaphylactic. 2. Asthma. 3. Acute left ventricular failure (commonly called Pulmonary edema). 4. Cardiac tamponade (pericardial effusion or bleeding) 5. Rupture of the lung (pneumothorax). 5. Broken ribs and bloody pleural effusion 6. Pulmonary emboli. 7. Massive hemorrhage. 8. Choking. 9. Bilateral pneumonia like COVID-19. 10. Carbon monoxide poisoning.

Chronic cases of SOB are 1. COPD. 2. Congestive heart failure. 3. Chronic anemia is secondary to systemic diseases. 4. Neuromuscular diseases like ALS, paralysis of the diaphragm, myasthenia gravis. 5. Morbid obesity. 6. Ascites. 7. Large intra-abdominal mass like Wilms tumor. 8. Chronic bilateral pleural effusion. 9. Interstitial pulmonary fibrosis. 9. Deformity of chest wall e.g. Kyphoscoliosis.10. Subphrenic abscess.11. Chronic illness or disability leading to deconditioning.12. Anxiety and psychosis.

Treatment:

The goal is to restore the normal functioning of the lung, heart, blood and brain as soon as possible.

Pulse oximetry is in wide use since the covid pandemic, it is the initial test and any lack of oxygen should be immediately corrected by giving oxygen.

The other conditions are just too many to discuss here. But the best place is the emergency room for severe acute situations and the doctor's office for non-life-threatening conditions.

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Chest Pain.

 

                                                               Chest Pain.

                                                (Pain Pathways of the Heart).

                                                 PKGhatak, MD

The American Heart Association and its affiliates have been very successful in educating people on the significance of chest pain and its relation to an acute heart attack.

Heart muscles are not richly supplied with pain nerve fibers (called Afferent or sensory fibers) compared with the pericardium (fibrous covering of the heart). A wider area of the heart muscles has to be injured to elicit pain sensation. Even then, the pain is not felt in the heart but projected on the Central chest wall, neck, Lower jaw, and arms down to the fingers, upper abdomen, or on the back in between the shoulder blades.

This peculiarity of projection of visceral pain onto the skin is limited to organs innervated by the Vagus nerve.

In the early stage of fetal development, the human body was a segmented tube; each segment had its own pair of blood vessels and pair of nerves. In the later phase of development, as limbs and internal organs developed, that representation remained intact.

In the case of the heart, the location of pain felt on the skin is due to the fact that the heart developed from the pair of blood vessels from Cervical 7 to Thoracic 3 segments. The sensory nerve fibers of the heart join the vagus and sympathetic nerves to carry pain sensation to the brain.

In 1991 Dr. Armor described a new concept – Heart-Brain, consisting of 40,000 neurons situated in the heart and functioning as a mini brain. Nerve fibers from these neurons make direct connections with the amygdala, hypothalamus, thalamus and relay information to the cerebral cortex. The sensation from these neurons modifies effects of both the sympathetic and parasympathetic nervous system, and according to Dr. Armor, generates memory, emotion and modulates pain sensation.

Sensory nerves of the heart.

The Vagus nerve and nerves of the sympathetic nervous system carry Pain sensation to the brain.

The sensory nervous system of the heart is distinct. The nerve cells, nerve fibers, and ganglions are separate from the outflow tracts of both the parasympathetic (vagus) and sympathetic systems.

Vagus nerve.

The sensory fibers of the heart originated in the Nodose Ganglion of the Vagus, situated in the Jugular foramen. These fibers travel with the vagus nerve into the chest. Fibers destined to innervate the heart pass through the cardiac plexus without making any connection. The pain sensation from the heart is carried to the sensory nucleus of the vagus – Nucleus Tactus Soliterious, situated in the dorsomedial medulla. From there, the 2nd order neuron carries the sensation to the thalamus. From the thalamus, the pain sensation reaches the cerebral cortex.

80 % of pain sensation is carried by a pair of the vagus nerve. The right vagus nerve innervates the sinoatrial node, atrioventricular node, and atrial walls. The left vagus nerve innervates these structures and also from the rest of the heart. There is a considerable overlap of innervation of the heart from both vagus nerves.

Sympathetic innervation of the heart.

The neurons, that carry the pain sensation from the heat in the sympathetic nervous system, are situated in the Dorsal Ganglion from the 8th cervical to the 3^rd thoracic segment. The axon of the nerve enters the spinal cord via the Dorsal root and makes a connection with the neuron situated in the dorsal horn of the spinal cord. The second order neuron carries the pain sensation upward to the Thalamus. And from the Thalamus the sensation carries to the cerebral cortex by the 3^rd order neuron.

Nerve supply to the pericardium.

The pericardium has two sets of innervations.

The surface or parietal pericardium is supplied with neurons situated in cervical 3 to cervical 5 segments. The pain fibers travel via the Phrenic nerve.

The visceral pericardium is supplied by nerves that travel to the brain via both sympathetic and parasympathetic nerves.

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