Journal Orig

8/6/2019 Journal Orig

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Multi-drug-resistant tuberculosis (MDR-TB) is defined as TB that is resistant at least to

isoniazid (INH) and rifampicin (RMP), the two most powerful first-line anti-TB drugs.[1] Isolates

that are multiply resistant to any other combination of anti-TB drugs but not to INH and RMPare not classed as MDR-TB.

MDR-TB develops during treatment of fully sensitive TB when the course of antibiotics isinterrupted and the levels of drug in the body are insufficient to kill 100% of bacteria. This can

happen for a number of reasons: Patients may feel better and halt their antibiotic course, drugsupplies may run out or become scarce, or patients may forget to take their medication from time

to time. MDR-TB is spread from person to person as readily as drug-sensitive TB and in the

same manner.[2]

Epidemiology

MDR-TB most commonly develops in the course of TB treatment,[3] and is most commonly due

to doctors giving inappropriate treatment, or patients missing doses or failing to complete their

treatment. MDR-TB strains are often less fit and less transmissible, and outbreaks occur morereadily in people with weakened immune systems (e.g., patients with HIV).[4][5][6][7][8] Outbreaks

among non immunocompromised healthy people do occur,[9] but are less common.[3] A 1997

survey of 35 countries found rates above 2% in about a third of the countries surveyed. Thehighest rates were in the former USSR, the Baltic states, Argentina, India, and China, and was

associated with poor or failing national tuberculosis control programmes.

It has been known for many years that INH-resistant TB is less virulent in guinea pigs, and the

epidemiological evidence is that MDR strains of TB do not dominate naturally. A study in LosAngeles, California found that only 6% of cases of MDR-TB were clustered. Likewise, the

appearance of high rates of MDR-TB in New York city in the early 1990s was associated with

the explosion ofAIDSin that area.[10][11]

Treatment of MDR-TB

See also: Tuberculosis treatment

Usually, multidrug-resistant tuberculosis can be cured with long treatments of second-line drugs,

but these are more expensive than first-linedrugs and have more adverse effects.[1]The treatment

and prognosis of MDR-TB are much more akin to that for cancer than to that for infection. It hasa mortality rate of up to 80%, which depends on a number of factors, including

1. How many drugs the organism is resistant to (the fewer the better)

2. How many drugs the patient is given (patients treated with five or more drugs do better)

3. Whether an injectable drug is given or not (it should be given for the first three months atleast)

4. The expertise and experience of the physician responsible

5. How co-operative the patient is with treatment (treatment is arduous and long, andrequires persistence and determination on the part of the patient)
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6. Whether the patient is HIV positive or not (HIV co-infection is associated with an

increased mortality).

The majority of patients suffering from multi-drug-resistant tuberculosis do not receivetreatment, as they tend to live in underdeveloped countries or in a state of poverty. Denial of

treatment remains a difficult human rights issue, as the high cost of second-line medicationsoften precludes individuals unable to afford therapy.[12]

In general, treatment courses are measured in months to years; MDR-TB may require surgery,and death rates remain high despite optimal treatment. However, good outcomes for the patient

are still possible.[13]

The treatment of MDR-TB must be undertaken by a physician experienced in the treatment of

MDR-TB. Mortality and morbidity in patients treated in non-specialist centers are significantlyinferior to those of patients treated in specialist centers.

In addition to the obvious risks (i.e., known exposure to a patient with MDR-TB), risk factors forMDR-TB include HIV infection, previous incarceration, failed TB treatment, failure to respond

to standard TB treatment, and relapse following standard TB treatment.

Treatment of MDR-TB must be done on the basis of sensitivity testing: It is impossible to treatsuch patients without this information. If treating a patient with suspected MDR-TB, the patient

should be started on SHREZ (Streptomycin+isonicotinyl

Hydrazine+Rifampicin+Ethambutol+pyraZinamide)+MXF+cycloserine pending the result oflaboratory sensitivity testing. There is evidence that previous therapy with a drug for more than a

month was associated with diminished efficacy of that drug regardless ofin vitro tests indicating

susceptibility,[14] so, detailed knowledge of the treatment history of that patient is essential.

A gene probe forrpoB is available in some countries, which serves as a useful marker for MDR-TB, because isolated RMP resistance is rare (except when patients have a history of being treated

with rifampicin alone). If the results of a gene probe (rpoB) are known to be positive, then it is

reasonable to omit RMP and to use SHEZ+MXF+cycloserine. The reason for maintaining thepatient on INH is that INH is so potent in treating TB that it is foolish to omit it until there is

microbiological proof that it is ineffective (even though isoniazid resistance so commonly occurs

with rifampicin resistance).

When sensitivities are known and the isolate is confirmed as resistant to both INH and RMP, fivedrugs should be chosen in the following order (based on known sensitivities):

anaminoglycoside (e.g., amikacin, kanamycin) or polypeptide antibiotic (e.g.,

capreomycin)

PZA EMB

afluoroquinolone: e.g.,moxifloxacin (ciprofloxacin should no longer be used[15]);

rifabutin

cycloserine
http://en.wikipedia.org/wiki/Multi-drug-resistant_tuberculosis#cite_note-Farmer.2C_Paul_2001-11http://en.wikipedia.org/wiki/Multi-drug-resistant_tuberculosis#cite_note-Farmer.2C_Paul_2001-11http://en.wikipedia.org/wiki/Multi-drug-resistant_tuberculosis#cite_note-Mitnick2003-12http://en.wikipedia.org/wiki/Streptomycinhttp://en.wikipedia.org/wiki/INHhttp://en.wikipedia.org/wiki/INHhttp://en.wikipedia.org/wiki/Rifampicinhttp://en.wikipedia.org/wiki/Ethambutolhttp://en.wikipedia.org/wiki/Pyrazinamidehttp://en.wikipedia.org/wiki/Moxifloxacinhttp://en.wikipedia.org/wiki/Cycloserinehttp://en.wikipedia.org/wiki/Multi-drug-resistant_tuberculosis#cite_note-13http://en.wikipedia.org/wiki/RpoBhttp://en.wikipedia.org/wiki/Moxifloxacinhttp://en.wikipedia.org/wiki/Cycloserinehttp://en.wikipedia.org/wiki/Aminoglycosidehttp://en.wikipedia.org/wiki/Aminoglycosidehttp://en.wikipedia.org/wiki/Amikacinhttp://en.wikipedia.org/wiki/Kanamycinhttp://en.wikipedia.org/wiki/Capreomycinhttp://en.wikipedia.org/wiki/Pyrazinamidehttp://en.wikipedia.org/wiki/Ethambutolhttp://en.wikipedia.org/wiki/Fluoroquinolonehttp://en.wikipedia.org/wiki/Fluoroquinolonehttp://en.wikipedia.org/wiki/Moxifloxacinhttp://en.wikipedia.org/wiki/Moxifloxacinhttp://en.wikipedia.org/wiki/Ciprofloxacinhttp://en.wikipedia.org/wiki/Multi-drug-resistant_tuberculosis#cite_note-14http://en.wikipedia.org/wiki/Rifabutinhttp://en.wikipedia.org/wiki/Cycloserinehttp://en.wikipedia.org/wiki/Multi-drug-resistant_tuberculosis#cite_note-Farmer.2C_Paul_2001-11http://en.wikipedia.org/wiki/Multi-drug-resistant_tuberculosis#cite_note-Mitnick2003-12http://en.wikipedia.org/wiki/Streptomycinhttp://en.wikipedia.org/wiki/INHhttp://en.wikipedia.org/wiki/INHhttp://en.wikipedia.org/wiki/Rifampicinhttp://en.wikipedia.org/wiki/Ethambutolhttp://en.wikipedia.org/wiki/Pyrazinamidehttp://en.wikipedia.org/wiki/Moxifloxacinhttp://en.wikipedia.org/wiki/Cycloserinehttp://en.wikipedia.org/wiki/Multi-drug-resistant_tuberculosis#cite_note-13http://en.wikipedia.org/wiki/RpoBhttp://en.wikipedia.org/wiki/Moxifloxacinhttp://en.wikipedia.org/wiki/Cycloserinehttp://en.wikipedia.org/wiki/Aminoglycosidehttp://en.wikipedia.org/wiki/Amikacinhttp://en.wikipedia.org/wiki/Kanamycinhttp://en.wikipedia.org/wiki/Capreomycinhttp://en.wikipedia.org/wiki/Pyrazinamidehttp://en.wikipedia.org/wiki/Ethambutolhttp://en.wikipedia.org/wiki/Fluoroquinolonehttp://en.wikipedia.org/wiki/Moxifloxacinhttp://en.wikipedia.org/wiki/Ciprofloxacinhttp://en.wikipedia.org/wiki/Multi-drug-resistant_tuberculosis#cite_note-14http://en.wikipedia.org/wiki/Rifabutinhttp://en.wikipedia.org/wiki/Cycloserine


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athioamide:prothionamide orethionamide

PAS

amacrolide: e.g., clarithromycin

linezolid

high-doseINH (if low-level resistance)

interferon- thioridazine

Ampicillin

Drugs are placed nearer the top of the list because they are more effective and less toxic; drugs

are placed nearer the bottom of the list because they are less effective or more toxic, or moredifficult to obtain.

In general, resistance to one drug within a class means resistance to all drugs within that class,

but a notable exception is rifabutin: Rifampicin-resistance does not always mean rifabutin-

resistance, and the laboratory should be asked to test for it. It is possible only to use one drug

within each drug class. If it is difficult finding five drugs to treat then the clinician can requestthat high-level INH-resistance be looked for. If the strain has only low-level INH-resistance

(resistance at 0.2 mg/l INH, but sensitive at 1.0 mg/l INH), then high dose INH can be used aspart of the regimen. When counting drugs, PZA and interferon count as zero; that is to say, when

adding PZA to a four-drug regimen, another drug must be chosen to make five. It is not possible

to use more than one injectable (STM, capreomycin or amikacin), because the toxic effect ofthese drugs is additive: If possible, the aminoglycoside should be given daily for a minimum of

three months (and perhaps thrice weekly thereafter). Ciprofloxacin should not be used in the

treatment of tuberculosis if other fluoroquinolones are available.[16]

There is no intermittent regimen validated for use in MDR-TB, but clinical experience is that

giving injectable drugs for five days a week (because there is no-one available to give the drug atweekends) does not seem to result in inferior results. Directly observed therapy helps to improve

outcomes in MDR-TB and should be considered an integral part of the treatment of MDR-TB.[17]

Response to treatment must be obtained by repeated sputum cultures (monthly if possible).Treatment for MDR-TB must be given for a minimum of 18 months and cannot be stopped until

the patient has been culture-negative for a minimum of nine months. It is not unusual for patients

with MDR-TB to be on treatment for two years or more.

Patients with MDR-TB should be isolated in negative-pressure rooms, if possible. Patients withMDR-TB should not be accommodated on the same ward as immunosuppressed patients (HIV-

infected patients, or patients on immunosuppressive drugs). Careful monitoring of compliance

with treatment is crucial to the management of MDR-TB (and some physicians insist onhospitalisation if only for this reason). Some physicians will insist that these patients remain

isolated until their sputum is smear-negative, or even culture-negative (which may take many

months, or even years). Keeping these patients in hospital for weeks (or months) on end may be

a practical or physical impossibility, and the final decision depends on the clinical judgement ofthe physician treating that patient. The attending physician should make full use of therapeutic
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drug monitoring (in particular, of the aminoglycosides) both to monitor compliance and to avoid

toxic effects.

Some supplements may be useful as adjuncts in the treatment of tuberculosis, but, for thepurposes of counting drugs for MDR-TB, they count as zero (if four drugs are already in the

regimen, it may be beneficial to add arginine or vitamin D or both, but another drug will beneeded to make five).

arginine[18] (peanuts are a good source)

Vitamin D[19]

Immunoxel/Dzherelo[20]

V5 Immunitor[21]

The drugs listed below have been used in desperation, and it is uncertain as to whether they areeffective at all. They are used when it is not possible to find five drugs from the list above.

imipenem

[22]

co-amoxiclav[23] [24]

clofazimine[25] [26] [27]

prochlorperazine[28]

metronidazole[29]

The following drugs are experimental compounds that are not commercially available, but may

be obtained from the manufacturer as part of a clinical trial or on a compassionate basis. Theirefficacy and safety are unknown:

PA-824[30] (manufactured by PathoGenesis Corporation, Seattle, Washington)

R207910

[31]

(Koen Andries et al., under development by Johnson & Johnson)

In cases of extremely resistant disease, surgery to remove infection portions of the lung is, ingeneral, the final option. The center with the largest experience in this is theNational Jewish

Medical and Research Centerin Denver, Colorado. In 17 years of experience, they have

performed 180 operations; of these, 98 were lobectomies and 82 were pneumonectomies. There

is a 3.3% operative mortality, with an additional 6.8% dying following the operation; 12%experienced significant morbidity (in particular, extreme breathlessness). Of 91 patients who

were culture-positive before surgery, only 4 were culture-positive after surgery.

The Lungs
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FIG. 970Front view of heart and lungs.

(Pulmones)

The lungs are the essential organs of respiration; they are two in number, placed one on

either side within the thorax, and separated from each other by the heart and other contents of

the mediastinum (Fig. 970). The substance of the lung is of a light, porous, spongy texture; itfloats in water, and crepitates when handled, owing to the presence of air in the alveoli; it is

also highly elastic; hence the retracted state of these organs when they are removed from the

closed cavity of the thorax. The surface is smooth, shining, and marked out into numerouspolyhedral areas, indicating the lobules of the organ: each of these areas is crossed by

numerous lighter lines.

At birth the lungs are pinkish white in color; in adult life the color is a dark slaty gray,mottled in patches; and as age advances, this mottling assumes a black color. The coloring

matter consists of granules of a carbonaceous substance deposited in the areolar tissue near

the surface of the organ. It increases in quantity as age advances, and is more abundant inmales than in females. As a rule, the posterior border of the lung is darker than the anterior.

The right lung usually weighs about 625 gm., the left 567 gm., but much variation is met

with according to the amount of blood or serous fluid they may contain. The lungs are


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7/14

Surfaces.The costal surface (facies costalis; external or thoracic surface) is smooth,

convex, of considerable extent, and corresponds to the form of the cavity of the chest, being

deeper behind than in front. It is in contact with the costal pleura, and presents, in specimenswhich have been hardened in situ, slight grooves corresponding with the overlying ribs.

The mediastinal surface (facies mediastinalis; inner surface) is in contact with the

mediastinal pleura. It presents a deep concavity, the cardiac impression, whichaccommodates the pericardium; this is larger and deeper on the left than on the right lung, on

account of the heart projecting farther to the left than to the right side of the median plane.

Above and behind this concavity is a triangular depression named the hilum, where thestructures which form the root of the lung enter and leave the viscus. These structures are

invested by pleura, which, below the hilus and behind the pericardial impression, forms the

pulmonary ligament. On the rightlung (Fig. 972), immediately above the hilus, is an arched

furrow which accommodates the azygos vein; while running upward, and then archinglateralward some little distance below the apex, is a wide groove for the superior vena cava

and right innominate vein; behind this, and nearer the apex, is a furrow for the innominate

artery. Behind the hilus and the attachment of the pulmonary ligament is a vertical groove for

the esophagus; this groove becomes less distinct below, owing to the inclination of the lowerpart of the esophagus to the left of the middle line. In front and to the right of the lower part

of the esophageal groove is a deep concavity for the extrapericardiac portion of the thoracicpart of the inferior vena cava. On the leftlung (Fig. 973), immediately above the hilus, is a

well-marked curved furrow produced by the aortic arch, and running upward from this

toward the apex is a groove accommodating the left subclavian artery; a slight impression in

front of the latter and close to the margin of the lung lodges the left innominate vein. Behindthe hilus and pulmonary ligament is a vertical furrow produced by the descending aorta, and

in front of this, near the base of the lung, the lower part of the esophagus causes a shallow

impression.


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FIG. 972Mediastinal surface of right lung.

Borders.The inferior border (margo inferior) is thin and sharp where it separates the basefrom the costal surface and extends into the phrenicocostal sinus; medially where it divides

the base from the mediastinal surface it is blunt and rounded.

The posterior border (margo posterior) is broad and rounded, and is received into the deepconcavity on either side of the vertebral column. It is much longer than the anterior border,

and projects, below, into the phrenicocostal sinus.

The anterior border (margo anterior) is thin and sharp, and overlaps the front of thepericardium. The anterior border of the rightlung is almost vertical, and projects into the

costomediastinal sinus; that of the leftpresents, below, an angular notch, the cardiac notch,

in which the pericardium is exposed. Opposite this notch the anterior margin of the left lung

is situated some little distance lateral to the line of reflection of the corresponding part of the

pleura.


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FIG. 973Mediastinal surface of left lung.

Fissures and Lobes of the Lungs.The left lung is divided into two lobes, an upper and a

lower, by an interlobular fissure, which extends from the costal to the mediastinal surface of

the lung both above and below the hilus. As seen on the surface, this fissure begins on themediastinal surface of the lung at the upper and posterior part of the hilus, and runs backward

and upward to the posterior border, which it crosses at a point about 6 cm. below the apex. It

then extends downward and forward over the costal surface, and reaches the lower border a

little behind its anterior extremity, and its further course can be followed upward andbackward across the mediastinal surface as far as the lower part of the hilus. The superior

lobe lies above and in front of this fissure, and includes the apex, the anterior border, and a

considerable part of the costal surface and the greater part of the mediastinal surface of thelung. The inferior lobe, the larger of the two, is situated below and behind the fissure, and

comprises almost the whole of the base, a large portion of the costal surface, and the greater

part of the posterior border.The right lung is divided into three lobes, superior, middle, and inferior, by two interlobular

fissures. One of these separates the inferior from the middle and superior lobes, and

corresponds closely with the fissure in the left lung. Its direction is, however, more vertical,

and it cuts the lower border about 7.5 cm. behind its anterior extremity. The other fissureseparates the superior from the middle lobe. It begins in the previous fissure near the

posterior border of the lung, and, running horizontally forward, cuts the anterior border on a

level with the sternal end of the fourth costal cartilage; on the mediastinal surface it may be


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traced backward to the hilus. The middle lobe, the smallest lobe of the right lung, is wedge-

shaped, and includes the lower part of the anterior border and the anterior part of the base of

the lung.The right lung, although shorter by 2.5 cm. than the left, in consequence of the diaphragm

rising higher on the right side to accommodate the liver, is broader, owing to the inclination

of the heart to the left side; its total capacity is greater and it weighs more than the left lung.

The Root of the Lung (radix pulmonis).A little above the middle of the mediastinal

surface of each lung, and nearer its posterior than its anterior border, is its root, by which thelung is connected to the heart and the trachea. The root is formed by the bronchus, the

pulmonary artery, the pulmonary veins, the bronchial arteries and veins, the pulmonary

plexuses of nerves, lymphatic vessels, bronchial lymph glands, and areolar tissue, all of

which are enclosed by a reflection of the pleura. The root of the right lung lies behind thesuperior vena cava and part of the right atrium, and below the azygos vein. That of the left

lung passes beneath the aortic arch and in front of the descending aorta; the phrenic nerve, the

pericardiacophrenic artery and vein, and the anterior pulmonary plexus, lie in front of each,

and the vagus and posterior pulmonary plexus behind each; below each is the pulmonaryligament.

The chief structures composing the root of each lung are arranged in a similar manner frombefore backward on both sides, viz., the upper of the two pulmonary veins in front; the

pulmonary artery in the middle; and the bronchus, together with the bronchial vessels,

behind. From above downward, on the two sides, their arrangement differs, thus:

On the right side their position iseparterial bronchus, pulmonary artery, hyparterialbronchus, pulmonary veins, but on the left side their position ispulmonary artery, bronchus,

pulmonary veins. The lower of the two pulmonary veins, is situated below the bronchus, at

the apex or lowest part of the hilus (Figs. 972, 973).

Divisions of the Bronchi.Just as the lungs differ from each other in the number of their

lobes, so the bronchi differ in their mode of subdivision.The right bronchus gives off, about 2.5 cm. from the bifurcation of the trachea, a branch

for the superior lobe. This branch arises above the level of the pulmonary artery, and is

therefore named the eparterial bronchus. All the other divisions of the main stem come offbelow the pulmonary artery, and consequently are termed hyparterial bronchi. The first of

these is distributed to the middle lobe, and the main tube then passes downward and

backward into the inferior lobe, giving off in its course a series of large ventral and small

dorsal branches. The ventral and dorsal branches arise alternately, and are usually eight innumberfour of each kind. The branch to the middle lobe is regarded as the first of the

ventral series.

The left bronchus passes below the level of the pulmonary artery before it divides, andhence all its branches are hyparterial; it may therefore be looked upon as equivalent to that

portion of the right bronchus which lies on the distal side of its eparterial branch. The first

branch of the left bronchus arises about 5 cm. from the bifurcation of the trachea, and isdistributed to the superior lobe. The main stem then enters the inferior lobe, where it divides

into ventral and dorsal branches similar to those in the right lung. The branch to the superior

lobe of the left lung is regarded as the first of the ventral series.


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Structure.The lungs are composed of an external serous coat, a subserous areolar tissue

and the pulmonary substance or parenchyma.

The serous coat is the pulmonary pleura (page 1090); it is thin, transparent, and invests theentire organ as far as the root.

The subserous areolar tissue contains a large proportion of elastic fibers; it invests the

entire surface of the lung, and extends inward between the lobules.The parenchyma is composed of secondary lobules which, although closely connected

together by an interlobular areolar tissue, are quite distinct from one another, and may be

teased asunder without much difficulty in the fetus. The secondary lobules vary in size; thoseon the surface are large, of pyramidal form, the base turned toward the surface; those in the

interior smaller, and of various forms. Each secondary lobule is composed of several primary

lobules, the anatomical units of the lung. The primary lobule consists of an alveolar duct, the

air spaces connected with it and their bloodvessels, lymphatics and nerves.The intrapulmonary bronchi divide and subdivide throughout the entire organ, the

smallest subdivisions constituting the lobular bronchioles. The larger divisions consist of: (1)

an outer coat of fibrous tissue in which are found at intervals irregular plates of hyaline

cartilage, most developed at the points of division; (2) internal to the fibrous coat, a layer ofcircularly disposed smooth muscle fibers, the bronchial muscle; and (3) most internally, the

mucous membrane, lined by columnar ciliated epithelium resting on a basement membrane.The corium of the mucous membrane contains numerous elastic fibers running longitudinally,

and a certain amount of lymphoid tissue; it also contains the ducts of mucous glands, the

acini of which lie in the fibrous coat. The lobular bronchioles differ from the larger tubes in

containing no cartilage and in the fact that the ciliated epithelial cells are cubical in shape.The lobular bronchioles are about 0.2 mm. in diameter.


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FIG. 975Schematic longitudinal section of a primary lobule of the lung (anatomical unit); r.

b., respiratory bronchiole; al. d., alveolar duct; at., atria; a. s., alveolar sac; a, alveolus or aircell;p. a.: pulmonary artery:p. v., pulmonary vein; l., lymphatic; l. n., lymph node. (Miller.)

FIG. 976Section of lung of pig embryo, 13 cm. long, showing the glandular character of the

developing alveoli (J. M. Flint.) X 70. a. Interstitial connective tissue. b. A bronchial tube. c.

An Alveolus. l. lymphatic clefts. q. Pleura.


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The fetal lung resembles a gland in that the alveoli have a small lumen and are lined by

cubical epithelium (Fig. 976). After the first respiration the alveoli become distended, and theepithelium takes on the characters described above.

Vessels and Nerves.The pulmonary artery conveys the venous blood to the lungs; itdivides into branches which accompany the bronchial tubes and end in a dense capillary net-

work in the walls of the alveoli. In the lung the branches of the pulmonary artery are usually

above and in front of a bronchial tube, the vein below.The pulmonary capillaries form plexuses which lie immediately beneath the lining

epithelium, in the walls and septa of the alveoli and of the infundibula. In the septa between

the alveoli the capillary net-work forms a single layer. The capillaries form a very minute net-

work, the meshes of which are smaller than the vessels themselves; their walls are alsoexceedingly thin. The arteries of neighboring lobules are independent of each other, but the

veins freely anastomose.

The pulmonary veins commence in the pulmonary capillaries, the radicles coalescing into

larger branches which run through the substance of the lung, independently of the pulmonaryarteries and bronchi. After freely communicating with other branches they form large vessels,

which ultimately come into relation with the arteries and bronchial tubes, and accompanythem to the hilus of the organ. Finally they open into the left atrium of the heart, conveying

oxygenated blood to be distributed to all parts of the body by the aorta.

The bronchial arteries supply blood for the nutrition of the lung; they are derived from the

thoracic aorta or from the upper aortic intercostal arteries, and, accompanying the bronchialtubes, are distributed to the bronchial glands and upon the walls of the larger bronchial tubes

and pulmonary vessels. Those supplying the bronchial tubes form a capillary plexus in the

muscular coat, from which branches are given off to form a second plexus in the mucouscoat; this plexus communicates with small venous trunks that empty into the pulmonary

veins. Others are distributed in the interlobular areolar tissue, and end partly in the deep,

partly in the superficial, bronchial veins. Lastly, some ramify upon the surface of the lung,beneath the pleura, where they form a capillary network.

The bronchial vein is formed at the root of the lung, receiving superficial and deep veins

corresponding to branches of the bronchial artery. It does not, however, receive all the bloodsupplied by the artery, as some of it passes into the pulmonary veins. It ends on the right side

in the azygos vein, and on the left side in the highest intercostal or in the accessory

hemiazygos vein.

The lymphatics are described on page 718.

Nerves.The lungs are supplied from the anterior and posterior pulmonary plexuses, formed

chiefly by branches from the sympathetic and vagus. The filaments from these plexusesaccompany the bronchial tubes, supplying efferent fibers to the bronchial muscle and afferent

fibers to the bronchial mucous membrane and probably to the alveoli of the lung. Small

ganglia are found upon these nerves.

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