Saturday, January 9, 2021

Hyperbaric Oxygen Therapy

 

Hyperbaric Oxygen Therapy

PKGhatak,MD

 

In any coastal community where scuba diving activities and commercial sea diving are common, one can find at least one Hyperbaric Oxygen Treatment Center.

Caisson disease, commonly called Bends is an episodic arterial obstruction from Gas bubbles formation due to the release of dissolved Nitrogen and Oxygen in the blood during rapid ascent from a deep dive.

Bends also happen to passengers of an airplane, if the aircraft suddenly loses cabin pressure at an altitude of 35,000 feet or higher. Fighter pilots and submarine sailors are at risk of having bends.

Both nitrogen and oxygen are poorly soluble in blood. In blood, almost all Oxygen (O2) is carried as loosely bound oxyhemoglobin in the RBCs. 1.34 ml of O2 is bound to per 1gram of hemoglobin. O2 is prevented from forming the oxidation of ferrous iron of hemoglobin in the RBC due to the presence of antioxidants and respiratory enzymes. In normal conditions, the O2-carrying-capacity of hemoglobin is 98 to 99% saturated. Increasing either O2 concentration or pressure or both cannot increase O2 saturation any further. Only about 0.3 ml of dissolved O2 is present in 100 ml of blood. Fatty tissues contain most of the dissolved nitrogen (N2).

At one atmospheric pressure and breathing room air, the dissolved O2 is 0.3 ml/dL. When breathing 100% O2, the dissolved O2 increases to 1.5 ml/dL; at a pressure of 3 Bar, the dissolved O2 is 6ml/dL. That much of dissolved O2 is sufficient to supply all the O2 requirements of tissues and then some more.

Characteristics of dissolved O2.

Tissues in the tiny places where capillaries cannot reach and specially in areas where blood vessels are blocked due to infection or diseases, the dissolved O2 easily diffuses out of the blood into the cells. In an O2 rich environment, anaerobic bacteria cannot survive. Phagocytic activities of leukocytes increase due to enhanced peroxide actions. Fibroblast proliferation is enhanced and promotes tissue repair. High O2 generates new blood vessels and is called angiogenesis. Blood vessels are constricted in high PaO2, and that property is utilized in the treatment of thermal burns and crush injuries.

Adverse effects of high O2 environment.

O2 toxicity of the lungs may produce pneumonitis and pulmonary fibrosis. The opacity of eye lenses may develop. Various neurological symptoms including seizures may happen. Retinal changes produce various symptoms but are amenable to treatment.

Adverse Pressure effects.

Pain over nasal sinuses, pain in the inner ear and occasional rupture of eardrums may happen. Temporary vision changes are seen from deformity of the eye lens. Toothaches from the pressure effect of filled cavities are not uncommon.

HBO therapy in Bends.

At 3 Bar pressure and breathing 100% O2, the gas bubbles dissolve back in the plasma. As blood travels to the lungs the dissolved gases diffuse out from blood to the alveolar sacs and are expelled during exhalation. Generally, one treatment of HBO lasts about 4 hrs. with 20-minute break every 2 hrs. in order to minimize O2 toxicity. For the treatment of Bends usually, two sessions are required for the completion of the removal of all dissolved N2.

Various types of Hyperbaric O2 apparatus.

HBO chambers of various sizes are available to accommodate single patients to multiple patients. For the treatment of the localized area of limbs, head-neck and trunk, equipment of various shapes and sizes is available. The body part to be treated is hermetically sealed with inflatable cuffs and has ports for oxygen and other agents. To minimize tourniquet effects on the tissues, the pressure is released periodically.

Indication for HBO therapy.

Besides caisson disease, air embolism is at the top of the list. Other medical conditions are gas gangrene, diabetic foot ulcers, thermal burns, anaerobic resistant infection of the skin and subcutaneous tissues, poorly healing surgical wounds and skin flaps and grafts, resistant osteomyelitis and osteonecrosis, crush injuries, acute hemorrhage in people unwilling to accept blood transfusion because of religious belief. Hard to reach intracranial abscesses, and less well defined circumstances.

Hyperbaric oxygen therapy is a lifesaving treatment device for well-defined conditions and also in the field of experimentation.

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Tuesday, January 5, 2021

Aspergillus and Asthma

 

Aspergillus and Asthma

PKGhatak,MD


Aspergillum is a handheld holy water sprinkler used in church services. The spore forming fungus looks like a holy water sprinkler and the name is derived from there.

 Aspergillus is a mold that can lead to various human infections. Of the illnesses resulting from exposure to aspergillus, respiratory illnesses are common.  A certain group of people is more prone to fungal infection.

Aspergillus in sputum. 

  Aspergillum consists of many species, of which Aspergillum fumigatus (A.fumigatus), A.niger, A.flavus, are important human pathogens. Aspergillum is a saprophytic spore forming warm weather fungus. It can be found in every organic decaying substance in the presence of moisture. Besides causing human diseases, enzymes obtained from aspergillus are used extensively in food industries. Citric acid is obtained from A.Ozoro and A. flabus is hated by farmers because it causes the spoiling of grains.

This fungus multiplies by spores. The spore can withstand a temperature of 70C. The filamentous form of the fungus is called hyphae, and the mass of hyphae is called mycelia. Hyphae and mycelia are destroyed at higher temperatures. Aspergillum produces aflatoxin, which can cause liver cancer. The fungus is easily cultured in the Sabouraud medium. It grows in 5 days.

Aspergillus produces three groups of illnesses in humans. 1. Allergic, 2. Locally infective and 3. Invasive forms.

 In nature, the Aspergillus spore is everywhere and also in the air we breathe. The spores are harmless to humans, except those who are susceptible for the following reasons.  Asthmatics, Cystic Fibrosis, chronic corticosteroids users, taking immunosuppressing medications, bone marrow transplants and solid organ transplants, people with low white cell count (WBC) and cavitary lung diseases.

Wound infection with aspergillus has been a serious problem, particularly following Coronary Graft operations. Less frequently localized infections like that of eyes, nasal sinuses, inner ear, pleura, pericardium, and skin are seen. 

Invasive aspergillosis is generally a very serious disease. It is feared in bone marrow transplantation.

Diagnosis of Aspergillosis.

 In lung diseases.

Identification of aspergillus in sputum stained and observed under the microscope is the most direct way to identify it. Cultures are performed for confirmation. Identifying the fungus in tissues requires a biopsy. Identification of fungus from blood and bodily secretions may not be easy, but cultures are positive. For the invasive lesions, a positive test for the fugal antigens Beta d- glucan and Galactomannan is generally available.

In allergic aspergillosis.

Blood eosinophilia and elevated IgE levels are common, but the tests are non-specific. IgE precipitin test against aspergillus antigen is often positive. A standard skin test is an alternative diagnostic test.

Asthma.

In asthma, airway inflammation is often due to allergies to common house dust, tree and weed pollen, shellfish, animal dandruff, cockroaches and allergy to drugs- specially to the penicillin group. And about 12% are due to hypersensitivity to Aspergillus.

Asthmatics are susceptible to repeated infections and asthma becomes chronic aspergillus spores find a foothold in the small airways.

Worsening of asthma which does not respond to medication, is likely from aspergilla infection. Mucus plugs that are coughed up are loaded with eosinophils and back-brown materials. The brown-black material is the mycelia of aspergillum.

Repeated bouts of aspergillus infection are the rule. Eventually, weakness of bronchial walls produces small areas of bronchiectasis and that produces hemoptysis.  On x-ray, these bronchiectatic areas appear as finger shaped shadows. Usually seen in smaller airways in the central areas of the upper lobes.

Bronchopulmonary aspergillosis.

As the aspergillus began to spread out from the bronchus to the parenchymal of the lung, it takes several clinical pictures as follows-

 1. Nodular lesions – one or more in number. Pathologically these are granulomas.

 2. Pulmonary fibrosis – repeated bouts of infection produce scarring of the lungs.

 3. Cavitary lesions with fungus ball formation are called mycetoma. Mycetoma is more often seen secondary to preexisting cavities of the lungs as in Tubercular cavitary disease, emphysema, and sarcoidosis.

4. Invasion of blood vessels and distant spread.

Aspergilla infection or hypersensitivity disease in asthma are important causes of exacerbation of asthma. In chronic asthmatics, aspergillosis can take several clinical courses. Prompt identification of the fungus and proper fungicidal medication should be prescribed early and in addition to other asthma drugs.


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Monday, January 4, 2021

Cystic Fibrosis and Pseudomonas

 

Cystic Fibrosis and Pseudomonas

       PKGhatak,MD 


Cystic fibrosis (CF) is an inherited disease due to gene mutation and is transmitted by autosomal recessive mode.

Cystic Fibrosis is due to a mutation in the Transmembrane conductance regulator gene (CFTR) on chromosome 7. The CFTR gene provides instructions for making a protein called the cystic fibrosis transmembrane conductance regulator. This protein functions as a channel for Chlorine ion transport across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. In addition to the CFTR gene, another 1,700 gene mutations are associated with CF.

In normal circumstances, the proper hydration of the surface layer and the viscosity of mucus secreted by the Goblet cells of the respiratory tract are mainlined by keeping the electrolyte concentration constant. The movement of sodium ions across the cells is maintained by ATP derived active sodium channels. In Cystic Fibrosis the Sodium channel is normal. Due to defective CFTR protein, the conductance regulator of the chloride channel and calcium activated chloride channel fail. Chloride ions are not absorbed back into the cells from the surrounding water layer. Sodium concentration also increases in the fluid secondarily in maintaining the balance of cations and anions. In a recent study, the CFTR gene mutation is identified in the cilia. The abnormal motility of cilia is due to thick sticky mucus and not in the ciliary protein that moves the cilia.

A thin layer of low viscosity fluid separates the ciliary epithelium from a 5 micron thick mucus layer of the respiratory tract and functions as a lubricant for ciliary movement. Maintenance of normal concentrations of sodium and chloride and the resultant osmolarity of this fluid layer is essential for the coordinated ciliary movement that propels the mucus toward the vocal cord for elimination from the airways.

Patients homozygous for the abnormal CF genes show defective ciliary movement due to the high concentration of Na + Cl ions in the surrounding fluid. This abnormality leads to thick mucus accumulation in the respiratory tract, pancreas, liver, intestine and reproductive ducts. The degree of severity of the clinical states varies. CF newborns are likely to be born preterm, have a lower birth weight, lower life expectancy and occasionally a life threatening condition called meconium illus. Most CF cases are diagnosed in early childhood, but occasional young adults present with chronic cough, recurrent sinusitis and failure to gain weight.

All newborns are required to have state mandated genetic tests on the heel blood obtained at the time of birth. Those newborns with positive genetic screening tests are followed by the Sweat Chloride test. If chloride levels are high - the diagnosis of CF is confirmed.

People carriers of one copy of the mutated CFTR gene are slightly more susceptible to URI, sinusitis, bronchiectasis and pancreatic cancer.

What is the relation of sweat chloride with the ciliary motility of respiratory epithelium.

In CF the chloride ion fails to be absorbed back into the cells from the surrounding hyperosmolar fluid and water from the cells moves out leading to the dehydration of cells. As sodium chloride concentration also increases in the fluid, the fluid viscosity increases and ciliary movement becomes disorganized and ineffective to propel mucus upward along the mucociliary escalate for clearing. If bacteria, like Pseudomonas aeruginosa, find their way into the lungs then Pseudomonas bacteria can stay in contact with the epithelium longer and have time to attach themselves and invade the tissues. And inflammation begins. As the process becomes frequent the pseudomonas change from being swimmers to swarmers. The biofilms they produce help them to coalesce together tighter and resist Beta lactamase antibiotics and then pseudomonas become resistant to Beta lactamase antibiotics.

Pseudomonas.

 

Pseudomonas is a gram negative rod shaped encapsulated organism. It is present ubiquitously in the soil, water, man-made materials including hospital equipment, catheters and ventilators. In culture media, it produces surface growth and produces various shades of green color, and emits a tortilla-like odor. It is aerobic bacteria but also a facultative anaerobe. It has a flagellum at one end and is a free swimmer. The colony can form biofilms that become resistant to antibiotics. The bacteria produce exotoxin A, which can inhibit protein synthesis in the immunocytes and immunocytes die as a consequence. The organism produces catalase, oxidase and citrate.

Pseudomonas aeruginosa, infection in the early phase, is phagocytized. But pseudomonas survives in the phagocytes by blocking the digestive enzymes of phagocytes. It also neutralizes IL1 beta and capsae1 as a result of the inflammation and control of the spread of infection becomes inadequate. In repeated infections the pseudomonas form biofilms and the colony becomes compact. And pseudomonas changes from being free swimmers to swarmers. A subunit FilC, of the flagellar protein- flagellin is a chloride sensor, mutate. In CF the pseudomonas mutation of the FilC gene makes pseudomonas grow more aggressively in the high chloride environment.

Cystic fibrosis, a debilitating and difficult to treat, inherited disease. Chloride ion transport disorder results in thick sticky mucus in the respiratory tract that is an opportunity for pseudomonas to colonize and then infect the lungs and cause repeated bouts of pneumonia. Pseudomonas aeruginosa thrives inside the macrophages, kills Immunocytes and neutralizes inflammatory response and inherently develops resistance to antibiotics.

This is a rare lethal combination for people suffering from CF.

In every community, the Cystic Fibrosis Foundation and the American Lung Association provide support, updated information and assistance in varieties of ways to help unfortunate sufferers and their families.

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Leprosy

                                                  Leprosy                                              P.K.Ghatak, MD It is the perception ...