Single Pulmonary Nodule

 

                                   Single Pulmonary Nodule.

                                          PKGhatak, MD

In certain circumstances, a Chest CT scan is obtained as a part of workup - like a seat belt injury in an automobile accident or an undetermined cause of chest pain or shortness of breath, and to the surprise of the patients and doctors, a single pulmonary nodule is detected on the CT scan.

The incidence of an unsuspected Single Pulmonary Nodule (SPN) is 1 million / year in the USA. The attending doctor must give the patient the most recent information about the possible cause of the SPN. In the USA, there is a 40 % chance that the SPN is a growth at the initial time of detection. The vast majority of these are benign lesions, if the nodule is less than 3 cm, then only about 1 % of all the nodules so detected turn out to be malignant. Whether the SPN is malignant or benign, that depends on many factors including the radiological features of the SPL.

The first question the doctor asks the patient is whether he/she had a CT scan of the chest or chest x-ray previously, if so, that x-ray/CT scan must be reviewed and compared with the recent CT of the chest. Say, 2 years earlier CT, the SPN was of the same size - it was most likely a benign lesion.

This is important because no one wants to miss a diagnosis, Carcinoma of the lung in a very early stage. After all, the cure rate is 90 % at that stage compared with 30 % in stage II CA lung.

How to define a Single Pulmonary Nodule.

This definition is radiological and strictly adhered to.

These are the features: a discrete, well-marginated, rounded opacity, not exceeding 3 cm in diameter, surrounded by normal lung tissue; away from the hilum and mediastinum of the lung and no sign of pleural effusion, atelectasis and lymph node enlargement.

Nodules over 3 cm are called pulmonary masses. It takes 10 years for a nodule to reach the first 1 cm size.

What are common causes of SPN.

The three most common categories of SPN are benign adenoma, granuloma, and malignant tumor. The percentage of these conditions varies according to counties and even different regions of the same country. For example, in the desert region of the USA granulomas from fungal infections are more frequent than tumors, in developing counties granuloma of Tuberculosis is more prevalent.

What are granulomas.

A granuloma is a localized collection of inflammatory cells surrounded by blood vessels.

Granulomas are of two kinds: Inflammatory and Non-Inflammatory.

Infectious causes are Tuberculosis, Histoplasmosis, Coccidioidomycosis, Cryptococcus, Blastomycosis, Nocardiosis, and Hydatid cysts.

Non-infectious granulomas.

Rheumatoid nodules, Granulomatous angiomatosis, Sarcoidosis.

What are benign lung tumors.

Bronchial adenomas, hamartomas, benign tumors originate from cartilage, connective tissues, muscles, etc. And a special group of bronchial adenomas called Carcinoids.

What are the radiological signs of SPN being cancer,

SPN larger than 3 cm in diameter, irregular margin, ground-glass appearance (structure of lung is visible through the lesion), stipple calcification, eccentric calcification; doubling time is short (less than 120 to 600 days). Care must be taken not to call an opacity a nodule if it is located outside the lungs, artifacts, foreign bodies, and nipple shadow.

What are the risk factors for malignancy.

Chance of malignancy increases with 30 + years of smoking history, older age; exposure to radon, asbestos, nickel, chromium, vinyl chloride, polycyclic hydrocarbon; history of previous malignancy and chest radiation.

Nodule size and a chance of malignancy.

 5 cm nodules have a 60 % chance of malignancy, nodules 8 cm are 80-90% malignant.

What lab tests are required to diagnose benign lesions.

Serology test for collagen vascular disease, Rh factor. Serology for fungal infections, and fungal antigen tests where possible. Angiotensin converting enzyme for sarcoidosis., p ANCA and cANCA for angiitis. For Pulmonary Tuberculosis - interferon gamma release assay.

Follow up CT scan when initial CT and other tests are inconclusive.

For less than 3 cm lesions, a yearly CT scan. If stable for 3 years, then no further scans.

For 3 to less than 5 cm lesions, 3 to 6 months interval CT scans.

For 5 to 8 cm lesions an initial biopsy is called for.

How to proceed with SPL.

If history, radiological scans including PET scans, and various blood tests are inconclusive, then a Biopsy of the SPL is called for.

To improve the chance of a better yield by biopsy and with minimum damage of normal lungs, these important additions have taken place.

Skinny needle biopsy (SNB) with fluoroscopy, ultrasound, or CT guidance. Video-assisted thoracoscopic biopsy, GPS guided biopsy.

Bronchoscopic biopsy has also evolved into endobronchial ultrasound (ERUS) biopsy, electromagnetic navigation bronchoscopic biopsy.

At the present time, these modalities of SLN biopsy produced 80 % improvements over skinny needle biopsy.

What to do if SPN is a biopsy proven malignant tumor.

Surgical resection is the treatment of choice.

If the patient is not a candidate for surgical resection but has biopsy proven malignancy, then the following options are available.

External radiation therapy, Stereotactic radiosurgery, Percutaneous radiofrequency ablation.

Single Pulmonary Nodules are mostly asymptomatic when initially detected for unrelated health reasons or during lung cancer surveillance programs for chronic smokers, and the patients are more anxious than sick. A timely investigation and proper counseling must be provided. Most SLNs are benign, but benign lung tumors can cause pneumonia, lung abscess or hemoptysis and in rare instances turn malignant over years if not properly followed.

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                                        Psoriasis

                                   PKGhatak, MD

Psoriasis is a skin disease that manifests as red, itchy scaly patches. Psoriatic lesions commonly appear over the knees, elbows, trunk and scalp. Psoriasis patches can range from a few spots of dandruff-like lesions to scaling lesions covering a large area of the body.

Types of psoriasis:

For descriptive purposes, the psoriatic lesions are called:

Plaque psoriasis, Nail Psoriasis, Guttate psoriasis, Inverse psoriasis, Pustular psoriasis, Erythrodermic psoriasis, and Psoriatic arthritis.

The most common type of psoriasis is plaque psoriasis.

What causes psoriasis.

It is a multifactorial disorder caused by an interaction between Inherited Genetic Mutations and environmental risk factors. The abnormal Immune reaction manifested by very rapid turnover of skin cells, dead skin shedding lags behind the new cells generated, resulting in itching and redness of the skin.

What are the risk factors.

Some of the known triggers are – Streptococcal infection of the skin and throat, dry and cold weather, cuts and bruises of the skin, insect bites, stress, certain medications like - antimalaria drugs, High BP drugs, lithium, etc., sunburns, and rapid withdrawal of prednisone.

Is vaccination safe in Psoriasis.

Childhood vaccination should proceed as usual. All vaccinations, skin injury, and surgery may produce a flare up of psoriasis, this is known as Kobener Phenomenon.

What genetic mutations are associated with Psoriasis.

Genome-wide association studies have identified more than 60 susceptibility regions, those genes are related to Thymic 17(Th-17) cell action. Interleukin-36 -36(IL-36) is an important amplifier of Th-17 signaling.

In addition, Linkage analysis identified 9 different regions - known as PSORS 1 to PSORS 9 - associated with psoriasis.

In North American PSORS 2 is identified as a common variant and psoriasis is inherited as an Autosomal Dominant condition. Mutation of CARD 14 gene identified as the molecular defect underlying cause of psoriasis. Card 14 encodes an adaptor protein that is highly expressed in skin cells known as keratinocytes.

In worldwide studies, PSORS1 locus maps detected an association of PSORS1 to the Major Histocompatibility Complex (MHC) on chromosome 6p21.

Signs and symptoms of psoriasis.

Psoriasis is a chronic remitting skin disease, generally worse in the winter months and improves in summer. About 8 million people in the USA have psoriasis; 40 % of them may also develop arthritis.

Psoriatic skin lesions appear as red patches of skin with thick silvery scales. Psoriasis may appear as raised red or pink plaques with silvery scales called guttate psoriasis. Guttate psoriasis is common in children. In addition, the following symptoms and signs may be present.

Dry, cracked skin that may bleed or itch.

Itching, burning, or soreness.

Thickened, pitted, or ridged nails.

Swollen and stiff joints in Psoriatic arthritis. The clinical picture of psoriatic arthritis resembles Rheumatoid arthritis; arthritis may precede skin lesions and over time becomes resistant to therapy.

Treatment of Psoriasis.

It can be discussed in three categories.

1. Topical 2. Phototherapy, 3. Systemic.

Topical.

Emollients.

Local skin emollients are moisturizers and are effective in early cases involving limited areas of the body. It retains moisture in the skin, thereby reducing itching and scaling.

Hydrocortisone cream/ointment.

Steroid creams of various strengths are available by prescription and the over-the-counter 1% hydrocortisone creams are useful for reducing irritated skin lesions and reducing flaking and itching.

Vitamin D analogs.

It slows down skin cell production and has an anti-inflammatory effect. The ointment can be used on the scalp, the trunk, limbs, and other areas.

Calcineurin inhibitors.

Several compounds are available. They reduce immune reactions. And produce remission of skin lesions, and is useful in lesions over sensitive areas of the body and also the scalp.

Coal tar.

Heavy oil obtained from coal processing is effective in psoriasis. The mechanism of action is unknown. The oil has an odor and can stain clothing and bedding.

Dithranol.

It is used only under medical supervision. Dithranol ointment can be applied over a wide area and allowed to act for 10 to 60 minutes, then washed off. It may burn the skin if used inappropriately.

Phototherapy.

Special light therapy centers use various forms of light therapy. A wide area of the body can be treated. Each session lasts only a few minutes but is repeated 3 -4 times a week and stretched over 6 to 8 weeks. UVB light is invisible to the eyes and is commonly used in phototherapy. Phototherapy can be combined with Dithranol and Coal tar skin ointment.

Phototherapy is effective when other treatments fail.

PUVA.

Psoralen is combined with Ultra Violet A light.

This combination makes the UV A light penetrate deep into the skin. It is useful in cases where other forms of therapy have failed. But repeated use may cause skin cancer.

Systemic therapy.

Drugs are classified as Non-Biological and Biological agents.

Non-Biological.

All these drugs are useful in reducing skin cell proliferation, controlling inflammation, itching, and scaling. Many of them also have significant side effects that require regular follow ups.

Methotrexate.

Initially, the methotrexate is administered IM injections, then switched to oral therapy. Usually given once a week, periodic blood count and renal function are checked for side effects.

Cyclosporine.

This medication is an anti-rejection drug; newer drugs of this category are Sirolimus and Tacrolimus. Drugs are given orally and also locally on the skin as an ointment. Blood levels of these drugs are checked to adjust the dose to keep in the therapeutic range. All of these drugs are useful in suppressing immune reactions.

Acitretin.

It is a retinoid compound and is taken orally. It is widely used but also has side effects including liver damage.

Apremilast.

Apremilast is a Phosphodiesterase inhibitor and the pill is taken by mouth daily. It is effective in both skin lesions and psoriatic arthritis.

Dimethyl fumarate.

This drug is primarily used in Multiple sclerosis. It is also used in Psoriasis.

Biological agents.

Bioactive immunosuppressants are given by injections. Each drug is administered by a given protocol. If significant improvement of psoriasis is not seen in 8 to 12 weeks, then these drugs are discontinued. Since these are used in advanced and resistant cases, the outcomes of use in psoriasis are also variable.

Commonly used biological drugs are -

Etanercept. Administered weekly by IM injection.

Adalimumab. Given every 2 weeks by injection.

Infliximab. Given by intravenous injection.

Ustekinumab. This drug can be given subcutaneously or by IV infusions. Usually given every 4 weeks. It is effective in severe plaque psoriasis.

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Psoriasis  usually appears as red or pink plaques of raised, thick, scaly skin. However, it can also appear as small, flat bumps or large, thick plaques

Lung Abscess

 

                                                             Lung Abscess

                                                  PKGhatak, MD

In any infection, the body tries to limit the spread of infection by pouring in inflammatory cells at the site of entry of the infective organisms. A dense layer of inflammatory cells, white cells and their products are formed around the infection, which is known as a pyogenic membrane. In the center of it, the dead and liquefied cells accumulate. In the lungs, a few smaller branches of bronchioles remain open and air enters the liquefied center giving a distinct picture of air-fluid level on the x-rays. These bronchioles, however, are too narrow to drain the thick accumulated secretion. Unless the cellular derbies are cleared from the site, the repair and healing cannot begin. This may lead to one or more complications - enlargement of abscess, breaking open into a larger bronchiole forming a pulmonary fistula, opening in the pleural space forming empyema, eroding into a blood vessel producing hemoptysis, the distant heterogeneous spread of infection and abscess formation in other organs.

The lung abscess is called primary when the lung is directly infected. An abscess is called a secondary abscess when the lung infection comes from an infected blood clot from below the diaphragm via the inferior vena cava and infected cardiac vegetation. From direct contact with the lung as it happens in amoebic liver abscess, and subphrenic abscess.

The usual source of lung abscess is the aspiration of anaerobic bacteria of the mouth from choking, general anesthesia, dental procedures, alcoholism, seizures, reflux esophagitis, hiatal hernia, esophageal-pulmonary fistula, head and neck cancers, strokes with dysphagia, bulbar palsy, Parkinson's disease, ALS, etc.

Abscess formation can also develop from preexisting cavities in the lungs as cystic fibrosis, emphysema bullae, bronchiectasis, tuberculosis, carcinoma, foreign body- specially partial dentures, loose tooth, small toys in children, and intra- pulmonary sequestration and bronchial cysts - are congenital conditions. Narcotizing vasculitis and infarction of lung from Pulmonary emboli.

Common Bacteria.

Anaerobic gram negative and anaerobic gram positive bacteria predominate in adults. Staphylococcus aureus, including MRSA, is a common bacterium in children. Other rare infections are fungus, nocardia, mycobacteria, actinomyces, lung parasites, and amoeba.

Bacteroides fragilis, Fusobacterium capsulatum, and F. necrophorum are the most frequent causes of anaerobic lung abscess. Occasionally gram positive Pepto streptococcus and microaerophilic streptococcus infections are seen. Mixed bacterial infection is also frequent. In rare instances, Gram negative rods like E. coli, Hemophilus influenza, Pseudomonas aeruginosa are seen specially in hospitalized patients with ventilator associated lung abscesses.

Pathology.

In the first 48 hrs. following aspiration, inflammatory exudate takes place. Toxins released by the bacteria initiate vasculitis and venous thrombosis and necrosis of lung tissues.

Common areas of the lung are prone to abscess formation.

Lobes involved in abscesses are the result of aspiration to the most dependent part of the lung. In a bedridden patient, the posterior segment of the right middle lobe generally develops an abscess. In alcoholic and unconscious patients' apical segments of the lower lobes are involved.

Signs and symptoms.

Patients are sick and a distinct foul odor due to anaerobic bacteria is often detected. Chills, fever, night sweats, loss of significant weight are common. Chest pain and shortness of breath are usual. Cough may start as non-productive but soon becomes productive thick pus, at times blood mixed or frank hemoptysis is seen.

Clubbing of fingers is often seen. Fixed rales and other auscultation features may be present based on how close the abscess is to the chest wall.

Diagnosis.

Chest x-ray shows air-fluid level in a thick-walled cavity, rarely, more than one abscess is present. CT scans often are not required for diagnosis but are needed in case surgical treatment is deemed necessary.

Bronchoscopy is mandatory to detect bronchial obstruction by a tumor or foreign body. And to obtain bronchial secretion/pus for both anaerobic and aerobic cultures, gram stain, fungal and mycobacteria cultures, Bronchoscopic biopsy, brushing and cytology are routinely performed.

Cultures.

Aerobic and anaerobic cultures and sensitivity tests are most valuable in selecting proper antibiotics.

Treatment.

As soon as a lung abscess is suspected or detected on x-rays, intravenous antibiotics are initiated. The initial choice of antibiotic is Clindamycin 600 mg given every 8 hrs.; some physicians also add another agent like metronidazole and beta lactam cephalosporin, Fluoroquinolone. Macrolide antibiotic is used in mixed bacterial infections. Antibiotic coverage depends very much on the prevalence of common lung abscess bacteria of the local community and reports of culture and drug sensitivity tests.

It is to be noted that if proper antibiotics are chosen, a clinical improvement is expected in 3 to 5 days – lowering of temperature, less sputum production and a general sense of wellbeing.

The antibiotic coverage should be continued till the patient is afebrile and nearly symptoms free. That may take 3 to 6 weeks. At that stage, antibiotics are usually switched to orally.

In addition to IV antibiotics, chest physiotherapy, postural drainage, chest percussion, bronchodilator therapy, etc. are prescribed, including the attention paid to improve nutrition.

Switching mode of therapy.

If the expected improvement is not forthcoming at the end of 2nd week of therapy, then further assessment is necessary with repeat CT scans and cultures.

If the size of the abscess is seen to have enlarged to 6 cm or more, then some forms of surgical interventions are required. The less invasive procedure was tried first. CT guided or Ultrasound guided transcutaneous drainage of the abscess is performed under local anesthesia.

If more than 12 weeks have passed and the abscess remains, then lobectomy is generally required.

Those patients respond well to the initial therapy, and a complete resolution of abscess takes place in 3 to 6 weeks. Complete resolution of abscess by chest x-ray usually takes 12 weeks, even though the patient is recovered clinically and symptoms free from having an abscess.

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Empyema

 

                                                         Empyema

                                             PKGhatak, MD

Empyema is defined as an accumulation of pus in the pleural space.

The surface of the lung and the inner surface of the chest wall is lined with a thin layer of serous tissue, leaving a minimal space in between known as the pleural space. The pleural membrane is covered by just one layer of mesodermal epithelium upon a connective tissue layer consisting of collagen and elastic fibers. A thin film of pleural fluid bathes both the parietal (chest wall) and visceral(lung) pleura and acts as a lubricant; that makes the lungs expand and contract without any friction during breathing. The pleural fluid is formed by the parietal pleura and the fluid is removed by the lymphatics of this layer, so pleural fluid formation and removal go on continuously. The visceral pleura gets its blood supply from the bronchial arteries and has no sensory nerve supply, so the visceral pleura is pain insensitive, whereas the parietal pleura is richly supplied with pain fibers from the intercostal nerves and also receives blood supply from the intercostal blood vessels.

In pneumonia, usually, more fluid is formed in the pleural space, but the presence of fluid is not easily detected by examination or by simple chest x-rays. CT scan can detect in 15 to 30 % of cases minimal pleural effusion called Parapneumonic pleural effusion. As pneumonia resolves, so also the parapneumonic pleural effusion.

About 6 % of children and 5% of adults with community acquired pneumonia develop parapneumonic empyema. When pleural effusion is infected by the extension of infection, the fluid becomes cloudy and thick. If the infected fluid has the following characteristics, then the effusion is called Empyema: fluid pH is less than 7.2 (normal blood pH is 7.4), glucose less than 60 mg/dl. LDH is three times the upper limit of serum LDH or LDH over 1000 IU/dl, WBC over 50,000/ml, protein over 3,000 mg/dl. Gram stains identify the presence of bacteria.

Risk factors.

In children, empyema often results when pneumonia is treated with inappropriate antibiotics. For those who are not fully immunized, chickenpox is followed by pneumonia, and the use of Ibuprofen in pneumonia.

In adults, the risk factors are homelessness, pulmonary emphysema, Pulmonary tuberculosis, IV drug use, not receiving the pneumonia vaccine, alcoholics, HIV infection, and immunosuppression by disease or therapy, and lung abscess. 35 % of anaerobic lung access is associated with empyema.

Both adults and children are at risk of empyema following prolonged chest tube drainage of bloody pleural effusion from a gunshot wound of the chest/ lung, knife wound, or automobile accident resulting in lung contusion, rib fracture, or pneumothorax.

Post-Surgical Empyema.

Following lobectomy and pneumonectomy due to malignancy or other diseases, if the lung fails to fill up the pleural cavity, then prone to empyema. This may be a special problem in the removal of bullous lesions in emphysema patients. Other causes of Empyema are Bronchopleural fistula, esophageal pleural fistula, perforated duodenal ulcer, amoebic liver abscess, perforated colon diverticulitis, and peritonitis, the infection may spread to the pleural cavity and foreign bodies in the pleural space like infected fragments of a projectile.

Common bacterial empyema.

The common bacteria is Streptococcus pneumonae type1. In community acquired pneumonia, the Streptococcus pneumonae type1 accounts for nearly 50% of postpneumonic empyema, Staphylococcus aureus followed by anaerobic bacteria infections. Viral parapneumonic and tubercular pleural effusion may also lead to empyema.

Symptoms and Diagnosis.

Persistent temperature elevation- often to 101F or higher, shortness of breath, chest pain, weight loss, anorexia, and general debility are common symptoms. On examination decreased or absent breath sound on one side of the chest, dullness on percussion. Leukocytosis with a shift to the left, toxin granules and Doehle bodies in the neutrophils are present. Chest x-ray shows pleural fluid. Ultrasound detects and delineates empyema easily and is usually repeated for monitoring purposes. CT chest is helpful in trauma cases and also in difficult cases.

Diagnostic thoracentesis is almost universal in all cases of more than minimal pleural effusion. In empyema, the pleural fluid is thick, difficult to aspirate, and cloudy to milky white. The other features will match the characteristics listed above.

Empyema fluid is sent to the lab for aerobic and anaerobic cultures and also for fungi and mycobacteria cultures. Gram stain of empyema fluid shows the presence of bacteria.

Treatment.

Closed tube drainage with a vacuum assisted closure device is inserted by Thoracoscopy. A wide bore chest tube Malicote 10-14F, Pigtail 8 -12F, or 28-32F French catheter is generally suited. Thoracoscopy can also detect septa, loculation, compartmentalization of fluid and that can be removed at the same time. That makes empyema drainage easier. Thoracoscopic lysis of adhesion is generally repeated.

Fibrinolytic enzymes like deoxyribonuclease DNase or tissue plasminogen activator tPA are injected into the pleural cavity and usually repeated to liquefy thick fluid.

Antibiotics are administered by IV and guided by culture and sensitivity tests.

In closed tube drainage of empyema, the lung should expand fully in 14 days.

If the lung fails to expand, then re-culture of fluid, review of the entire case, use of multiple antibiotics, or other surgical measures are called for.

Open drainage.

If the empyema fluid is so thick that even the French 32 size catheters are not draining fluid, then a wide area of the wound is created over the empyema. A large bore chest tube is inserted in the dependent part of the empyema and the other end of the tube is drained into a colostomy bag. The cavity is irrigated daily with mild antiseptic fluid, or the cavity is packed with saline moistened surgical gauge and changed daily. The cavity size should decrease gradually and the wound should seal in 4 to 5 months.

Open flap or Eloesser flap.

In this procedure, a wide incision is made just over the diaphragm, the most dependent part of the pleural cavity. A large skin and muscle flap is created. 1 to 3 ribs are resected to make a large opening into the chest cavity, and the skin-muscle flap is stitched in a way that creates a one-way opening for drainage, eg, making drainage of empyema easier. One way flap prevents air entry at the same time empyema is drained.

Decortication.

In the previous generation, tubercular empyema was the primary reason for this surgical operation. But occasionally some empyema fails to heal by the above methods and decortication is required.

If the lung does not expand to fill the chest cavity in 140 days. This procedure is considered. It is a major open thoracic surgery procedure, and many sick patients may not be able to withstand this procedure.

In this procedure, the entire pleura is stripped away and all cellular/fibrinous materials are removed. The lung with stripped away thick covering expands readily and the operative wound heals in 3 to 4 weeks.

The incidence of empyema has been declining over the past decades but in recent years,  the empyema incidence began creeping upwards. Early diagnosis and proper closed drainage and antibiotic therapy should resolve empyema in 2 to 3 weeks. The decision to open drainage of Empyema should be made after a thorough review of therapy and should be delayed until it is proven to be the only option available.

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Science of High Altitude Pulmonary Edema.

 

                                             Science of High Altitude Pulmonary Edema

                                                      PKGhatak, MD

Airlines are carrying a large number of people to high altitude sky resorts and mountain climbing facilities. These popular recreational activities also put people at risk of mountain sickness and acute pulmonary edema.

At sea level, the partial pressure of oxygen (Pio2) in the air is 160 mm Hg. At 8,000 ft the Pio2 is 120 mmHg, at 11,000 ft. above sea level the Pio2 is 87 mmHg, and at extreme high altitude, 18000 ft., the Pio2 is only 50 mm Hg.

At any altitude above 4,000 ft. the blood level of oxygen is low and becomes lower at higher and higher altitudes.

Air enters the alveoli of the lungs with inhalation. On the way to the alveoli, the air becomes fully saturated with water vapor. At a body temperature of 98.8 degrees F, the partial pressure of H2O is 47 mmHg, PiO2 is diluted as air enters the alveoli and Pi02 becomes (160-47) 113 mmHg. The blood in the capillary is separated from the alveolar air by only one layer of cells. The oxygen(O2) of air first gets dissolved in the alveolar fluid and then rapidly binds with the hemoglobin of blood because of the high affinity of oxygen to hemoglobin and forms a loose compound oxyhemoglobin. The mixed venous blood Pvo2 is 40mmHg, favoring oxygen flow toward the blood due to a pressure gradient of 83 mmHg (113- 40).

When this is happening, carbon dioxide (CO2) of blood is moving in the opposite direction – from blood into the alveoli, again due to the pressure gradient of 40 mmHg of blood to the + 0 mmHg of alveolar air. The CO2 binding is accelerated by the presence of enzymes, carbonic acid anhydrase. As little as 2 to 10 mmHg pressure gradient CO2 can move rapidly and completely.

As the blood leaves the alveoli and returns to the left side of the heart, the O2 carrying capacity of blood is at maximum – the PaO2(partial pressure of arterial blood) is over 90 mmHg and the O2 saturation (O2 sat) is 98 to 100 %.

Let's look at what happens at 8,000 ft. The Pio2 in the alveoli is 73 mmHg (120 – 47). The O2 gradient is (73-40) 43 mmHg. At 43 mmHg, the O2 sat is 75 %. This is significant. Hypoxemia and patients immediately develop symptoms.

Effects of Hypoxia on Local Population.

The people living in the high plateau of Tibet for over 7,000 years. The average altitude of the Tibetan plateau is 11,000 ft. They have developed an advanced adaptive mechanism, and it stands in contrast to the rest of high-altitude residents of Ethiopia and Andes Mountain people. In Peru and Bolivia, the present population moved in about 1,100 to 800 years ago and has yet to adopt the full high-altitude mechanisms of the Tibetan population.

In Peruvians and Bolivians, the hemoglobin level is higher due to the increased Erythropoietin activity, the minute ventilation is decreased, pulmonary arterial pressure is higher, right ventricular hypertrophy is present, Nitric Oxide (NO) levels are lower compared with Tibetans. They have more complications during pregnancy and childbirth, and newborns have lower weight at birth.

In Tibetan, the mutation of EGLN1 and EPAS1 genes carries the adaptive oxygen sensing and high altitude hypoxic adaptive mechanisms. The hypoxic stimuli of carotid and aortic bodies are muted. There is no hyperventilation. At 85 mmHg, the O2 saturation of the air is over 87%, the nitrogen oxide levels in the lungs and blood are high. The hemoglobin levels are not elevated. The resting ventilation is high, and lung volumes are larger. The smooth muscles of the pulmonary artery are not hypertrophic, pulmonary hypertension does not happen. The weight of newborns is normal.

Effect of Hypoxia on Recent Arrivals.

Acute Mountain Sickness.

On the very day of arrival, symptoms of cerebral anoxia develop. The main symptoms are headaches, dizziness, nausea, anorexia, fatigue and shortness of breath on minimal activities, difficulty sleeping and a mild dry cough. Swelling of the face, hands, and feet develops.

High Altitude Pulmonary Edema (HAPE).

From day 2 to day 4 of arrival, the symptoms are more severe. The shortness of breath at rest develops. The temperature rises to 101F degrees. Palpitation and rapid breathing, mental confusion, incoordination and prostration soon appear. The cough becomes productive of pink frothy sputum and occasionally becomes bloody, labored breathing with gurgling sounds on breathing is heard, cyanosis, a slow heart rate and BP began to fall. Acute respiratory distress and Acute Pulmonary edema set in.

High Altitude Cerebral Edema (HACE).

Anoxia of the brain cells is responsible for increased fluid accumulation in between brain cells and produces persistent headache, dizziness, nausea, the sensation of pins and needles, lethargy, incoordination, loss of sleep, tinnitus, violent behavior and loss of consciousness and seizures.

Pathophysiology of HAPE.

1. Hypoxia producing capillary leaks.

The tight junctions between the type I alveolar cells prevent excess fluid accumulation in the alveolar space. A thin layer of fluid is essential for the normal function of ventilation and gas exchanges. The integrity of the alveolar membrane depends on oxygen; in the hypoxic condition, the alveolar type I cells develop gaps between cell junctions and fluid escapes in the alveolar space. Nitric oxide production is reduced, lack of nitric oxide in the lung results in smooth muscle contraction of the pulmonary arteries and the Pulmonary arterial BP (PBP) is elevated. That produces Right heart strain and hypertrophy. Dr. J.B. Web described the genesis of the capillary leak “The hydrostatic stress that exceeds the load bearing limits of the collagen network [of alveoli] results in rupture of the basement membrane.”

2. Derailed removal of fluid.

Two separate but interrelated paths are present in the lung to ensure fluid removal, these are

A. Starling force driven sodium channels.

B. Na and K iron ATPase dependent trans-epithelial sodium channels.

The functioning of both these channels is defective in hypoxic conditions.

If the foramen ovale was not completely closed the opening of the foramen ovale enlarges and the Right to Left shunt takes place which makes hypoxia more profound and early right heart failure develops. Endothelin-1 activities are reduced and contribute to Pulmonary BP elevation.

 C. Increase in pro-inflammatory markers in the lung.

Analysis of bronchial fluid obtained during the Intubation of HAPE patients shows an increase in pro-inflammatory markers, namely interleukin IL-1 beta, IL-6, IL-8, TNF alpha. In addition, the total cell counts are elevated, and increased lung macrophages are present. Blood levels of LDH, CRP, and total proteins are increased. The monocytes attractive protein1alpha (MIPA1alpha) and monocytes chemo-attractant protein1 and IL8 are significantly higher in Chronic Mountain sickness.

D. The anti-inflammatory markers, IL alpha, IL-10, show no change or levels are decreased.

Chronic Mountain Sickness.

Prolonged stay at high altitude results in the continuation of acute symptoms, in addition, the patients develop sleep disorders. Mental confusion, abnormal behavior, cognitive impairment and various neurological symptoms.

Returnee of a Native of High Altitude.

High altitude people living on a lower plane for an extended period and then on returning to high altitude experience a more severe form of acute Pulmonary edema. The basic reason for this disease is not known.

Diagnosis of HAPE.

Respiratory symptoms in recent arrivals at high altitudes should always alert the possibility of acute mountain sickness or HAPE. This is the primary diagnosis and other possibilities like cardiac failure, PE, and pneumonia should come later.

Shortness of breath at minimal effort, or at rest, temperate elevation, frothy pink sputum, air hunger, cyanosis, tachycardia, and increased rate of respiration are universally present. Moist sounds, rales, on auscultation on both sides, chest x-rays- bilateral mid-zone, bat wing shaped infiltrates, and a low O2 saturation by pulse oximetry should be diagnostic of HAPE.

 

Immediate oxygen is administered by any available source to keep the O2 sat over 90%. Portable Hyperbaric oxygen chambers are generally available or should be made available as soon as possible. An arrangement must be made to take the patients to a lower altitude to a better medical facility.

Medications.

Nifedipine 20 mg tablets are given at 4 hourly to lower Pulmonary hypertension (PAP). Acetazolamide, a diuretic, also lowers PAP by blocking calcium channels, Tadalafil, a phosphodiesterase inhibitor, is also used. A bronchodilator Salmeterol is used to ease breathing.

Dexamethasone is used when cerebral edema is suspected in HAPE with predominant cerebral symptoms.

Prevention of acute mountain sickness and HEPA.

People should consult mountaineering schools/ training centers at the time of preparation for such events. The day before arrival, Nifedipine 80 mg long acting tablets one tablet and on arrival day and onwards one tablet should be taken. No physical activities on the 1^st day. Sleeping at a lower altitude should be considered. Daily hiking/climbing should be limited to 1500 feet.

Use portable oxygen when the pulse oximeter shows saturation below 90 %. And seek advice from the team leader or the guide.

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Non Alcoholic Fatty Liver Disease

 

                                          Non-Alcoholic Fatty Liver

                                        PKGhatak, MD

An ultrasound scan of the abdomen is an unusually simple procedure for investigating abdominal and pelvic conditions. Many patients were found to have fatty liver unexpectedly and unrelated to their symptoms for which ultrasound scans were performed.

Incidence is quite high and is rising not only in the USA but also worldwide. In the USA, about 25 % of people have a fatty liver on ultrasound scan, in India, it is about 35 %.

Chronic alcoholism is a common cause of fatty liver. But it is also detected in high numbers in non-alcoholics. This is now designated as Non-Alcoholic Fatty Liver Disease (NAFLD).

The cause of NAFLD is unknown. People with NAFLD have a high association with Diabetes II, hepatitis C and HIV infections. More causal associations are seen in hepatitis B and A, obesity, physical inactivity, metabolic syndrome - the combination of high BP, obesity around the waist, high triglyceride & LDL cholesterol. Psoriasis, Hypothyroidism, hypopituitarism, Hemochromatosis, sleep apnea, polycystic disease of the ovary, and high fructose soft drinks and prepacked food and frozen TV dinners.

The adverse effect of the medication is known to produce NAFLD -   Acetaminophen. A heavy dose of tetracycline, oral hormone therapy, amiodarone, valproic acid, certain cancer drugs, some HIV drugs.

NAFLD is the initial stage of fatty liver, a more advanced stage of inflammation of the liver leads to a state called Non-Alcoholic Steatohepatitis (NASH). The incidence of NASH in the USA is about 6% of the population and in India, it is about 12 %.

Symptoms.

The majority of patients are symptoms free. Some complaints of vague upper abdominal discomfort, right upper abdominal pain, bloating, and anorexia. Some other patients with more advanced diseases have a loss of weight, enlargement of the liver, anemia, frequent infections, and gastrointestinal bleeding.

Investigation and diagnosis.

Liver enzymes - ALT and AST are elevated, due to liver damage. Platelet count falls due to decreased production of Thrombopoietin, a hormone produced in the liver and needed for platelet generation in the bone marrow.

Later, vitamin K-dependent clotting factor deficiency leads to the prolongation of Prothrombin time. Serum albumin level falls.

MRI of the liver clearly delineates pathological changes in liver cells. A new generation of Ultrasound scans – Fibroscan of the liver is also very sensitive like MRI and detects the degree of fibrosis. Fibrosis is the result of deaths of hepatocytes and inflammatory cell infiltration of the liver. Hepatic cirrhosis is the end stage.

Fibrosis Calculation.

Several institutions have developed a Fibrosis score, corroborated by liver biopsy, based on Age, ASL and ALT, and Platelet count. It is very useful for patients and the treating physician for monitoring progress. This practice has decreased the need for liver biopsy.

Formula : 

 Age ([yr] x AST [U/L])   /   ((PLT [10(9)/L]) x (ALT [U/L])(1/2)). 

Using this formula, patients with a score > 3.25 are likely to have advanced fibrosis whereas those with a score < 1.45 are unlikely to have advanced fibrosis.

A biopsy of the liver is the final confirmatory test, but biopsy is not necessary in the majority of cases.

Complications.

As the NAFLD progresses, the inflammation leads to the development of Steatohepatitis, the next step and ultimately to hepatic cirrhosis. Complications of cirrhosis are bleeding esophageal varices, hypoalbuminemia, ascites, hypersplenism, thrombocytopenia, and hepatic failure.

About 5 % of NAFLD patients with hepatic cirrhosis develop Hepatocellular carcinoma.

Treatment.

No effective drug treatment is available.

A weight reduction of 5 to 7 % of body weight is associated with improvement.

Daily physical exercise or 45 45-minute walk is advocated.

Elimination of Fructose from food and drinks should be done.

Vitamin E as high as 700 IU was advised, but worsening Diabetes and increased prostate cancer risk should be taken into consideration before undertaking such therapy.

Liraglutide with vitamin E is also tried.

Aramchol a combined fatty acid and bile acid conjugate is approved in Israel and in India for use in NASH.

Several anti-fibrosis agents are undergoing trial in the final stages.

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Embolus

                                                               EMBOLUS

                                                   PKGhatak, MD

The word embolus is derived from Greek: en + ballein = in + to throw. In short, it means a wedge or plug. Obstruction of blood vessels by a wedge or plug may result from any of these - a piece of a detached blood clot, a fat globule, air bubble, a broken piece of the indwelling venous catheter, amniotic fluid and IV drug addicts injected contaminated drugs, and in rare instances broken piece of bones and metal fragments during orthopedic surgery.

What happens with the venous embolus/ emboli.

Venous blood returns to the right side of the heart, then goes to the lungs. All formed substances having a size larger than an RBC (red blood cell) are caught in the pulmonary capillaries. The living tissues beyond the site of obstruction suffer severe oxygen lack, undergo various degrees of structural damage or die (infarction).

In patients, with an open foramen ovale or right atrial septal defect, the emboli enter the left atrium, pushed to the left ventricle, from there into the general circulation. Clots can block arteries of the brain, kidneys, GI tract, etc. and result in substantial damage to the organs.

Fat embolism.

Bone marrow contains a large amount of fat and may release fat globules in the blood. Fractured bone or orthopedic surgery, fat molecules are released in the circulation. The fat globules, like venous blood clots, get tangled up in the lung capillaries or go via an open foramen ovale and enter the arterial side bypassing the lungs. In addition, the fat molecules can flatten out and may enter the arterial side of the circulation by one of these mechanisms. 1. The cells of the alveoli are disrupted and allow fat to enter pulmonary veins. 2. Fat molecules thinned out and assume elongated narrow shapes and go past the capillary bed to the venous side and then to the left heart and travel everywhere with the arterial blood,

Air embolism.

In an underwater dive, in a submarine or scuba diving, the nitrogen of air dissolves in a large volume in the blood due to higher pressure – the deeper the depth, the higher the pressure. In a rapid ascent, the nitrogen emerges from blood as gas and forms bubbles in the arteries and veins. Air bubbles obstruct blood circulation and deprive organs of oxygen. In the lungs, the rapid release of dissolved nitrogen can produce enough pressure to rupture the lungs and the lungs may collapse.

In high altitude flying, if the cabin pressure is lost suddenly, then air bubbles form in the blood vessels.

The intravenous line attached to the Porto Cath in the central vein may get disconnected and air can enter. In some instances, the air from the IV tubing is not purged completely; a small amount of air can enter, in most such cases the air will diffuse out via the alveoli and expired breaths but in other instances may produce serious consequences.

Chance of air embolism is a concern in every case involving direct access to central veins - like coronary bypass operation, heart-lung machine, extracorporeal membrane oxygenation, etc.

In childbirth, the freshly separated placental site may allow air to enter the veins of the mother.

Amniotic Fluid Embolism.

In late pregnancy, the placental membrane along the veins can tear open, allowing amniotic fluid to enter the mother's circulation. Amniotic fluid carries cellular debris, hair, urine and meconium of the fetus. In spontaneous miscarriage/abortion/ Caesarean section, amniotic fluid embolism may happen.

Foreign Body Embolism.

IV drug users inject crushed tablets, some of the ingredients of tablets are kaolin, a kind of earth, gum and inert substances. All these are pushed into the vein.

Many of these chemicals produce inflammation and granuloma in the lungs. Repeated exposures produce pulmonary fibrosis. Broken needles, at times, find their way into the lungs causing hemorrhage, pneumothorax and hemothorax.

Venous Thrombus and Pulmonary Embolism.

Blood contains several clotting factors and also clot preventing factors. Blood circulates constantly, that movement prevents blood from clotting. Just like concrete carrying trucks constantly rotate the cement drum to prevent the concrete from solidifying.

Tissue clot promoting factors.

Deep vein thrombosis is seen frequently in these conditions - post surgical patients, multiple fractures, pregnancy and childbirth, cancer chemotherapy. These conditions produce tissue damage and release the Tissue clotting factor.

Stasis of blood in veins.

A prolonged period of sitting, as happens on a long flight on airlines, and in certain jobs, like watching monitor screens constantly, promotes venous clots in the leg and pelvic veins. When blood is stagnant, the tissues use up oxygen and produce anorexic injury to the endothelium of veins and release clot-promoting factors. In congestive heart failure, return of venous blood from below the diaphragm is delayed due to higher pressure in the right atrium. Immobilized fracture of the leg is another risk factor, so also varicose veins.

Antithrombotic protein Thrombomodulin and Endothelial Protein Receptors are downregulated in infections, injuries and hypoxia. The same mechanism also up-regulates the Leukocyte adhesion molecule - P-selectin.

Blood viscosity.

In blood diseases, like polycythemia vera and leukemia, the blood cell volume is elevated. In multiple myeloma, the globulin levels are high. These conditions result in high viscosity which slows circulation and promotes blood clots.

Congenital absence/ deficiency of anticoagulants.

Protein C in association with V Leiden is a potent anticoagulant. About 5% of the Caucasian population of North America has a congenital deficiency of V Leiden. Several other anticoagulation factors like Protein S, protein C, antithrombin, and prothrombin are also inherited. Congenital deficiency of vitamin K dependent factors occurs due to mutation of the VKORC-1 gene.

Acquired clotting factor abnormalities.

Anti-phospholipid syndrome, Nephrotic syndrome, Lupus antibodies to antiphospholipid and in homocysteinemia, Paroxysmal Nocturnal hemoglobinuria promote blood clots. Carcinoma produces various coagulation factor abnormalities. Central venous indwelling catheters - the tip of the catheter often form clots and a clot can propagate. Estrogen therapy - increases liver production of several clotting factors.

Infected Blood clots.

In infections of the heart valves and endothelium (inner layer of the heart) the bacteria produce colonies known as vegetation. These vegetations are fragile and break loose. Arterial blood carries these infected vegetations to the brain, kidney, liver, spleen and other organs.

Detached arterial plaques.

In coronary angiogram/angioplasty procedures, the catheter tips may knock off arterial plaques. These plaques are made up of calcium-cholesterol-cellular derbies and these travel downstream to the pelvis, legs, kidney, etc. Carotid artery plaques may go directly to the brain and cause strokes. Similarly, during surgical repairs of Atrial aneurysms emboli can easily happen.

Consequences of Pulmonary Embolism.

Pulmonary embolism (PE) from breaks away clots from the deep veins is the most common cause of pulmonary embolism. About 400,000 cases are recorded each year in the USA and 40,000 patients die from PE.

The symptoms, diagnosis and treatment.

It is easier to discuss this aspect as 1. Massive pulmonary emboli, 2. Recurrent small multiple pulmonary emboli and, 3. Mixed type.

1. Massive pulmonary emboli.

 It is a life ending event if immediate treatment is not available. Sudden acute onset of shortness of breath, chest pain followed by loss of consciousness and ventricular arrhythmia results from lack of oxygen to vital organs. A chest x-ray may show a lack of the usual darkness of blood in the lung and is called an oligemic lung. EKG shows sinus tachycardia in excess of 120/ min, right axis, RBBB, right ventricular strain and ventricular premature beats or tachycardia. Marked hypoxemia, cyanosis, shock, feeble /absent pulse at the wrist, altered consciousness, and poor renal output are usual findings. Angio CT/ angiogram shows clots in the pulmonary trunk/ main branch and sudden tapering of the caliber of the pulmonary artery.

Treatment is very urgent. A pulmonary artery catheter is inserted and advanced to the site of obstruction. Thrombolytic agents are infused. Otherwise, open chest operation and removal of clots have to be undertaken. A six-month direct oral anticoagulant or vitamin K-dependent \ clotting factors (factor VII, IX, X, protein C, protein S, and Prothrombin inhibition) coumadin are recommended. Underlying clotting factor modification where possible should be done.

2. Chronic small repeated Pulmonary emboli.

The initial episodes of pulmonary emboli may be misdiagnosed as mild asthma attacks, undetermined chest pain, and anxiety attacks. Shortness of breath with mild physical activities develops. Evidence of Pulmonary hypertension develops. Long term anticoagulation is essential to prevent future emboli. In recurrent PE an Inferior vena cava filter is inserted that block the upward movements of clots.

3. Mixed types are the combination of these classes. Thrombolytic therapy and long term direct acting anti-coagulation is appropriate therapy.

Fat embolism.

Fat embolism is underreported. The risk factors of fat embolism are - all major multiple bone fractures, crush injuries, bone marrow transplantation, orthopedic surgery of major joints, IV hyperalimentations, liposuction, acute and chronic pancreatitis, prolonged CPR, splitting sternum in open heart surgery, major burn victims, prolonged use of corticosteroid, fatty liver, sickle cell anemia, thalassemia, etc. When a small amount of fat globules enters the circulation, it may not produce any adverse effect on the body. When intermediary pins were used in hip fractures, fat embolism was common.

More than occasionally, the fat embolism is misdiagnosed as something else and only by autopsy examination is the fat embolism established. 15 % of all autopsies show fat embolism. Fat is a neurotoxin. Cerebral fat embolism produces significant CNS symptoms. Skin petechiae are very characteristic of fat emboli of the skin. A fluoroscopic eye examination is one direct evidence of any embolism.

 A chest x-ray may show only nonspecific vascular congestion. MRI of the brain is most helpful for cerebral fat emboli. Centrum putamen and subarachnoid show edema due to the toxic effect of fat.

Treatment of fat embolism has gone through many therapeutic trials, but none are specific. General vascular support and adequate oxygenation of vital organs decide the treatment outcomes. Mortality is about 10%.

Air Embolism.

Air embolism produces two distinct groups of medical problems.

One that produces pain in joints is known as caisson disease or bends. The other is major symptoms due to blockage of blood flow to vital organs. Occasionally air can block blood entry to the heart chambers. These incidences are not common but time is short for the reversal of the block. Less severe but significant symptoms are due to cerebral anoxia.

Treatment consists of giving oxygen immediately and then oxygen delivered in Hyperbaric chambers. This aspect is discussed in an earlier blog.

Amniotic Fluid Embolism.

Amniotic fluid embolism is a near fatal complication during childbirth and in the 48 hours postpartum period. Sudden cardiovascular collapse, air hunger, loss of consciousness and disseminated intramuscular coagulation are usual presentations. Acute pulmonary hypertension from arterial obstruction is complicated by the release of cytokines and complements that produce multisystem failure. Complement C3 and C4 are low in serum, and zinc coproporphyrin levels are elevated. There is no specific therapy for amniotic fluid embolism. Extracorporeal membrane oxygenation and correction of acidosis and other metabolic derailments are therapeutically maintained as well as possible under the circumstance. The pregnancy is terminated by C-section and the prognosis of the newborn is good. Air embolism happens in about 4 per 100,000 childbirths. The mortality is 60 to 80%.

 Embolisms are of several kinds and emboli can originate from various sources. Deep vein thrombosis resulting in pulmonary embolism is common among various groups and in a selected population, like nursing homes, cancer hospitals and ICU units, the incidence is high.

The current nursing practice of early mobilization following surgery, trauma, and childbirth has substantially lowered the incidence of PE. The direct acting anticoagulant improved patients' compliance with therapy.

  

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Arterio Venous Malformation

 

                                              Arteriovenous malformation

                                               PKGhatak, MD

In 2011, Mike Patterson, a prominent Philadelphia Eagles football player, had a seizure on the playing field. Later in the day, it was determined that Mike's seizure was due to an arteriovenous malformation in the brain. In the succeeding months, more known cases of arteriovenous malformation (AVM) in celebrities became known. It is estimated that 1 in every 100,000 world population has AVM, however, most of them did not have any symptoms.

AVM develops when the artery makes a direct path to the veins without first connecting with capillaries. AVM may arise in any place in the body, however, when present in the brain or spinal cord they tend to be symptomatic. When AVM in the brain enlarges, it produces pulsating pain, nausea, vomiting, and various neurological symptoms depending on the location and seizures. When AVM ruptures, it becomes a catastrophic event.

AVM is an inherited condition but also occurs due to somatic gene mutations, and occasionally following injuries and stab wounds. In some cases, AVM develops from cavitary pulmonary tuberculosis, schistosomiasis, and juvenile hepatic cirrhosis. It is a difficult task to determine the mode of inheritance in every case of AVM. There are about 600 mutations of genes associated with AVM. The well known Osler- Rendu- Weber syndrome or hereditary hemorrhagic telangiectasia (HHT) is due to autosomal dominant inheritance. The mutated genes are two:

 No1. Endigin gene mutation is present on chromosome 9.

 No 2. Activin receptor kinase gene mutation is present on chromosome 12.

Just one copy of one of the two mutated genes will manifest as HHT. The MADH4 gene mutation is associated with colon polyps and AVM. These genes are under the control of the RASA1 gene. In normal circumstances, the RASA1 gene transcribes a protein kinase controlling capillary formation. In HHT blood vessel developments are defective at several levels due to abnormal cytokine function.

At birth, most of the AVMs are small and may not be visible but as the child grows, the AVM enlarges and in adolescence, the enlargement accelerates. AVMs on the face, neck, and chest wall are often associated with visceral AVM. AVMs tend to grow for a period and then regress spontaneously, in some cases, continue to slow growth.

Besides AVM, congenital abnormalities of veins, capillaries and lymphatics are known. But the incidence of these abnormalities is less frequent.

Pulmonary AVM.

The AVM of the lung is usually small and remains asymptomatic. Multiple or larger AVMs are detected in chest x-rays. In rare instances, a large AVM occupies an entire lobe or two lobes of the lungs, called diffuse AVM. AVM of the lung is seen in 40% of hereditary hemorrhagic telangiectasia.

Pulmonary AVM usually produces recurrent hemoptysis, pneumothorax, hemothorax, recurrent pneumonia, septicemia and TB, and other infections. Large and diffuse AVM produces low oxygen saturation of the arterial blood (PaO2). Low PaO2 is due to pulmonary arterial blood, instead of going to the alveoli, drains directly into the pulmonary veins. A Right to Left shunt develops. Hypoxic symptoms arising from the brain, liver and kidneys begin early, and congestive heart failure is a late development.

Cerebro-spinal AVM.

AVM of the brain is present in 30% of HHT and about 1 % of AVM is located in the spinal cord. Most of these AVMs are symptomatic. Initially, the symptoms are mild and nonspecific - headache, seizures, visual or speech problems, balance and ambulation abnormalities. Any increase in the size of the AVM either due to growth or infection or bleeding/ clot formation produces a symptom depending on the location of the AVM. Visual field loss, diplopia, cranial nerve palsy, weakness of limbs or incoordination are usual symptoms. Pulsating noise in the head is a distinct symptom due to the rapid flow of blood from an artery to a vein. Infections and rupture of AVM are real possibilities. Rupture of AVM may be the first presenting symptom and such incidences are as high as 50%. Intense headaches and rapid onset of coma usually follow. If treatment is delayed, the outcome is bad. Infected emboli from the lung result in brain abscesses. Meningoencephalitis, high pressure hydrocephalus, seizures, cranial nerve palsy and hemiparesis are complications from the infection.

Renal and genitourinary AVM.

Hematuria, repeated UTI and vaginal bleeding and uterine infection in women are seen but less frequently.

Hepatic AVM.

Most of the AVMs are small and maybe multiple and remain silent. In HHT the incidence of hepatic AVMs is 40%. The chances of infection of AVM in the liver are high. Pain in the upper right quadrant of the abdomen is the presenting symptom. Infection of the liver, cholangiohepatitis, hepatic insufficiency, and intra-abdominal bleeding occur. Portal hypertension, esophageal varies and GI bleeding is seen.

Hereditary Hemorrhagic Telangiectasia.

HHT is an autosomal dominant hereditary disease, in North America, the incidence of HHT is 1 in 10,000 population. Mucocutaneous telangiectasia of lips is a distinct feature and is present in 95% of HHT. The bluish dilated venules of the lips and floor of the mouth and tongue are present at ages 10 to 20. Telangiectasia of the fingertips and chest wall develops in the 30s to 40s. Nose bleeding in HHT is a daily occurrence and leads to iron deficiency anemia and occasionally requires a blood transfusion.

Another feature of HHT is bleeding AVM from the stomach and small intestine. The GI bleeding may be massive. Hemoptysis and neurological symptoms develop from AVM of the lungs and brain respectively.

One word of caution – bronchoscopy or endoscopy procedures must be conducted with extreme care. Biopsy of tissue is strictly prohibited, once bleeding starts, the control of bleeding is nearly impossible except removal of the organ by immediate surgery.

Cutaneous AVM.

The port-wine stain of the face, chest wall, and other areas of the body is due to skin capillary AVM, often cutaneous AVM is associated with visceral AVM.

Diagnosis and Treatment.

Recurrent hemoptysis, GI, or genitourinary bleeding, when accompanied by cutaneous telangiectasia, diagnosis is not difficult. Most large sized pulmonary AVMs are symptomatic. Bluish discoloration of lips and fingers, clubbing of fingers and a distinct humming noise on chest auscultation, presence of right heart enlargement and congestive heart failure, features of neurological symptoms when present together, the clinical diagnosis is almost certain.

Imaging is very helpful. Contrast enhanced CT is very specific. MRI, Angio-CT and the new generation of Doppler Ultrasound scans have replaced most other diagnostic tools of the earlier days - like Bubble tests and Angiograms. In the bubble test, several microbubbles are injected on the venous side and microbubbles are detected by ultrasound scans of the arteries.

Controlling bleeding where possible is attempted first, but in most cases immediate embolization of the artery is necessary. Other therapeutic options are - sclerotherapy or laser coagulation. If non-surgical treatment to control bleeding fails, then surgery is the only option that remains. In cases of distressing nose bleeds, various forms of plastic surgery procedures are attempted to patch over the location of telangiectasia.

In HHT the family members are strongly encouraged to undergo genetic testing and counseling.

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