Report on Haemopty
Haemoptysis is defined as the expectoration of blood from the respiratory tract that varies from blood- streaking of sputum to coughing up large amounts of pure blood. Blood may be coughed up alone or sputum may be blood stained. Haemoptysis is a common medical problem and may present as an acute life-threatening emergency, which requires immediate attention and intervention. The most common site of bleeding is the airway i.e. trachea , bronchial tree which can be affected by inflammation (acute or chronic bronchitis, bronchiectasis) or, neoplasm (bronchogenic carcinoma, endobrochial metastiatic carcinoma or bronchial carcinoid tumour). Blood originating from the pulmonary parenchyma can be either from a localized source, such as an infection (pneumonia, lung abscess, tuberculosis) or from a process diffusely affecting the parenchyma i.e. coagulopathy. Disorders primarily affecting the pulmonary vasculature include pulmonary embolic disease and those conditions associated with elevation of pulmonary venous and capillary pressure e.g. mitral stenosis or left ventricular failure.
Infectious diseases occur most frequently in Bangladesh due to various sociodemographic factors e.g. socio-economic status, education, nutrition, environmental pollution and sharing of bedroom etc.
Environmental pollution has emerged as a major health hazard in our country, which is likely to increase respiratory diseases and alter the aeitiological pattern of haemoptysis in our country over the years. It is very much fortunate that the patient seeks medical advice as soon as he or she develops haemoptysis, because this symptom is due frequently to serious disease and in many instances is the early sign, which can lead to an early diagnosis if proper investigations are carried out promptly.
Haemoptysis is the common presenting feature of various diseases responsible for major morbidity and mortality. Aetiological pattern in our country is different from that of developed countries. Sophisticated investigation facilities such as CT scan, bronchoscopy, etc. are only available in limited centres and we have to diagnose and treat cases within our limited resources. So a study on haemoptysis will be helpful for prompt diagnosis and management of our patients within limited resources.
Structure of Respiratory System
The main role of the respiratory system is to work closely with the heart and blood to extract oxygen from the external environment and dispose of waste gases, principally carbon dioxide. This requires the lungs to function as an efficient bellows, expelling used air, bringing fresh air in and mixing it efficiently with the air remaining in the lungs. The lungs have to provide a large surface area for gas exchange and the alveolar walls have to present minimal resistance to gas diffusion. This means the lungs have to damage by dusts, gases and infective agents. Host defense is therefore a key priority for the lung and is achieved by a combination of structural and immunological defenses.
The anterior one-third of the nasal cavity is divided into right and left halves by the nasal septum. The nasal vestibule leads to the internal ostium which is the narrowest part of the nasal cavity. This causes a 50% increased resistance to airflow when breathing through the nose rather than through the mouth. The respiratory region is divided by three folds arising from the lateral wall, termed the superior, middle and inferior turbinate. Behind these turbinates are situated the openings of the nasolacrimal duct and the frontal, ethomoidal and maxillary sinuses. The olfactory region for smell is found above the superior turbinate. The nasal cavities communicate with the nasopharynx via the posterior nasal apertures (the choanae) and the Eustachian tube opens into this area just above the soft palate.
The Pharynx and Larynx
The pharynx is divided by the soft palate into an upper nasopharyngeal and lower oropharyngeal region. There are numerous collections of lymphoid tissue arranged in a circular fashion around the nasopharynx , these include the adenoids. The tonsils lie between the anterior and posterior fauces, separating the mouth from the oropharynx.
The larynx consists of a number of articulated cartilages, vocal cords, muscles and ligaments, all of which serve to keep the airway open during breathing and occlude it during swallowing.
The main motor nerve to the larynx is the recurrent laryngeal nerve. The left recurrent laryngeal nerve leaves the vagus at the level of the aortic arch, hooking round it to run upwards through the mediastinum between the trachea and the oesophagus; it can be affected by disease in these areas. The principal tensor of the vocal cords is the external branch of the superior laryngeal nerve, which can be injured during thyroidectomy.
Anatomy of The Lungs
After passing through the nasal passages and pharynx, where it is warmed and takes up water vapor, the inspired air passes down the trachea and through the bronchioles, respiratory bronchioles, and alveolar ducts to the alveoli.
Between the trachea and the alveolar sacs, the airways divide 23 times. The first 16 generations of passages form the conducting zone of the airways that transports gas from and to the exterior. They are made up of bronchi, bronchioles, and terminal bronchioles. The remaining seven generations form the transitional and respiratory zones where gas exchange occurs and are made up of respiratory bronchioles, alveolar ducts, and alveoli. These multiple divisions greatly increase the total cross-sectional area of the airways, from 2.5 cm in the trachea to 11,800 cm in the alveoli. Consequently, the velocity of air flow in the small airways declines to very low values.
The alveoli are surrounded by pulmonary capillaries. In most areas, air and blood are separated only by the alveolar epithelium and the capillary endothelium, so they are about 0.5 mm apart. Humans have 300 million alveoli, and the total area of the alveolar walls in contact with capillaries in both lungs is about 70 m.
The alveoli are lined by two types of epithelial cells. Type I cells are flat cells with large cytoplasmic extensions are the primary lining cells. Type II cells (granular pneumocytes) are thicker and contain numerous lemellar inclusion bodies. These cells secrete surfactant. Other special types of epithelial cells may be present, and the lungs also contain pulmonary alveolar macrophages (PAMs), lymphocytes, plasma cells, APUD cells and mast cells. The mast cells contain heparin, various lipids, histamine, and various proteases that participate in allergic reactions.
The Trachea, Bronchi and Bronchioles
The trachea is 10-12 cm in length. It lies slightly to the right to the midline and divides at the carina into right and left main bronchi. The carina lies under the junction of the manubrium sternum and the second right costal cartilage. The right main bronchus is more vertical than the left and, hence, inhaled material is more likely to pass into it.
The right main bronchus divides into the upper lobe brochus and the intermediate bronchus, which further subdivides into the middle and lower lobe bronchi. On the left the main bronchus divides into upper and lower lobe bronchi only. Each lobar bronchus further divides into segmental and sub segmental bronchi. There are about 25 divisions in all between the trachea and the alveoli.
Of the first seven divisions, the bronchi have:
· Walls consisting of cartilage and smooth muscle
· Epithelial lining with cilia and goblet cells
· Submucosal mucus-secreting glands
· Endocrine cells- Kulchitsky or APUD (amine precursor and uptake decarboxylation) containing 4-hydroxytryptamine.
In the next 16-18 divisons the bronchioles have.
· No cartillage and muscular layer that progressively becomes thinner
· A single layer of ciliated cells but very few goblet cells
· Granulated Clara cells that produce a surfactant-like substance.
The ciliated epithelium is an important defence mechanism. Each cell contains approximately 200 cilia beating at 1000 beats per minute in organized waves of contraction. Each cilium consists of nine peripheral parts and two inner longitudinal fibrils in a cytoplasmic matrix. Nexin links join the peripheral pairs. Dynein arms consisting of ATPase protein project towards the adjacent pairs. Bending of the cilia results from a sliding movement between adjacent fibrils powered by an ATP-dependent shearing force developed by the dynein arms. Absence of dynein arms leads to immotile cilia. Mucus, which contains macrophages, cell debris, inhaled particles and bacteria, is moved by the cilia towards the larynx at about 1.5 cm/min.
The bronchioles finally divide within the acinus into smaller respiratory bronchioles that have alveoli arising from the surface. Each respiratory bronchiole supplies approximately 200 alveoli via alveolar ducts. The term small airways refers to bronchioles of less than 2 mm; there are 30000 of these in the average lung.
The Bronchi & their Innervation
The trachea and bronchi have cartilage in their walls but relatively little smooth muscle. They are lined by ciliated epithelium that contains mucous and serous glands. Cilia are present as far as the respiratory bronchioles, but glands are absent from the epithelium of the bronchioles and terminal bronchioles, and their walls do not contain cartilage. However, their walls contain more smooth muscle, of which the largest amount relative to the thickness of the walls is present in the terminal bronchioles.
The walls of the bronchi and bronchioles are innervated by the autonomic nervous system. Muscarinic receptors are abundant, and cholinergic discharge causes bronchoconstriction. The bronchial epithelium and smooth muscle contain b2-adrenergic receptors. Many of these are not innervated. Some may be located on cholinergic endings, where they inhibit acetylcholine release. The b2 receptors mediate bronchodilation. They increase bronchial secretion, while a1 adrenergic receptors inhibit secretion. There is in addition a noncholinergic, nonadrenergic innervation of the bronchioles that produces bronchodilation, and evidence suggests that VIP is the mediator responsible for the dilation.
There approximately 300 million alveoli in each lung. Their total surface area is 40-80 m2. The epithelial lining consists largely of type I pneumocytes. These cells have an extremely attenuated cytoplasm, and thus provide only a thin barrier to gas exchange. They are derived from type II pneumocytes. Type I cells are connected to each other by tight junctions that limit the fluid movements in and out of the alveoli. Type II pneumocytes are slightly more numerous that type I cells but cover less or the epithelial lining. They are found generally in the borders of the alveolus and contain distinctive lamellar vacuoles, which are the source of surfactant. Macrophages are also present in the alveoli and are involved in the defence mechanisms of the lung.
The pores of Kohn are holes in the alveolar wall allowing communication between alveoli of adjoining lobules.
The lungs are separated into lobes by invaginations of the pleura, which are often incomplete. The right lung has three lobes, whereas the left lung has two lobes. The upper lobe lies mainly in front of the lower lobe and therefore signs on the right side in the front of the chest found on physical examination are due to lesions mainly of the upper lobe or part of the middle lobe.
Each lobe is further subdivided into bronchopulmonary segments by fibrous septa that extend inwards from the pleural surface. Each segment receives its own segmental bronchus.
The bronchopulmonary segment is further divided into individual lobules approximately 1 cm in diameter and generally pyramidal in shape, the apex lying towards the bronchioles supplying them. Within each lobule a terminal bronchus supplies an acinus and within this structure further divisions of the bronchioles eventually give rise to the alveoli.
Broncho Pulmonary Segments:
Primary branches of the right and4 left lobar bronchi are termed segmental bronchi because each ramifies in a structurally separate, functionally independent unit of lung tissue called a broncho pulmonary segment. There are typically 10 broncho pulmonary segment in each lung and therefore 10 segmental bronchi. Each lung segment is roughly pyramidal in shape, with its apex towards the hilum and base towards the surface of the lung. The main segments are named and numbered as follows:
Superior Lobe : (i) Apical, (ii) Posterior, (iii) Anterior
Middle lobe : (iv) Lateral (v) Medial.
Inferior Lobe : (v) Superior (apical) (vii) Medial basal
(viii) Anterior basal (ix) Lateral basal (x) Posterior basal.
Superior Lobe : (i) Apical (ii) Posterior (iii) Anterior (iv) Superior lingual
(v) Inferior lingual.
Inferior Lobe : (vi) Superior (apical) (vii) Medial basal (viii) Anterior basal
(ix) Lateral basal (x) Posterior basal.
The pleura is a layer of connective tissue covered by a simple squamous epithelium. The visceral pleura covers the surface of the lung, lines the interlobar fissures, and is continuous at the hilum with the parietal pleura, which lines the inside of the hemithorax. At the hilum the visceral pleura continues alongside the branching bronchial tree for some distance before reflecting back to join the parietal pleura. In health, the pleurae are in apposition apart from a small quantity of lubricating fluid, so the pleural cavity is only a potential space.
The diaphragm is lined by parietal pleura and peritoneum. Its muscle fibres arise from the lower ribs and insert into the central tendon. Motor and sensory nerve fibres go separately to each half of the diaphragm via the phrenic nerves. Fifty percent of the muscle fibres are of the slow-twitch type with a low glycolytic capacity; they are relatively resistant to fatigue.
The amount of air that moves into the lungs with each inspiration (or the amount that moves out with each expriation) is called the tidal volume. The air inspired with a maximal inspiratory effort in excess of the tidal volume is the inspiratory reserve volume. The volume expelled by an active expiratory effort after passive expiration is the expiratory reserve volume, and the air left in the lungs after a maximal expiratory effort is the residual volume. The space in the conducting zone of the airways occupied by gas that does not exchange with blood in the pulmonary vessels is the respiratory dead space. The vital capacity, the largest amount of air that can be expired after a maximal inspiratory effort, is frequently measured clinically as an index of pulmonary function. It gives useful information about the strength of the respiratory muscles and other aspects of pulmonary function. The fraction of the vital capacity expired during, the first second of a forced expiration (FEF, timed vital capacity) gives additional information; the vital capacity may be normal but the FEV, reduced in diseases such as asthma, in which airway resistance is increased because of bronchial constriction. The amount of air inspired per minute (pulmonary ventilation, respiratory minute volume) is normally about 6L (500 mL/breath ´12 breaths/min). The maximal voluntary ventilation (MVV), or as it was formerly called, the maximal breathing capacity, is the largest volume of gas that can be moved into and out of the lungs of 1 minute by voluntary effort. The normal MVV is 125-170 L/min.
Differences in Ventilation & Blood Flow in Different Parts of the Lung:
In the upright position, ventilation per unit lung volume is greater at the base of the lung than at the apex. The reason for this is that at the start of inspiration, intrapleural pressure is less negative at the base than at the apex, and since the intrapulmonaryintrapleural pressure difference is less than at the apex, the lung is less expanded. Conversely, at the apex, the lung is more expanded; ie, the percentage of maximum lung volume is greater. Because of the stiffness of the lung, the increase in lung volume per unit increase in pressure is smaller when the lung is initially more expanded, and ventilation is consequently greater at the base. Blood flow is also greater at the base than the apex. The relative change in blood flow form the apex to the base is greater than the relative change in ventilation, so the ventilation/perfusion ratio is low at the base and high at the apex.
The ventilation and perfusion differences from the apex to the base of the lung have usually been attributed to gravity, they tend to disappear in the supine position , and the weight of the lung would be expected to make the intrapleural pressure lower at the base in the upright position. However, the inequalities of ventilation and blood flow in humans were found to persist to a remarkable degree in the weightlessness of space. Therefore, other as yet unknown factors apparently also play a role in producing the inequalities.
It should be noted that at very low lung volumes such as those after forced expiration, intrapleural pressure at the bases of the lungs can actually exceed the atmospheric pressure in the airways, and the small airways such as respiratory bronchioles collapse (Airway closure). In older people and in those with chronic lung disease, some of the elastic recoil is lost, with a resulting decrease in intrapleural pressure. Consequently, airway closure may occur in the bases of the lungs in the upright position without forced expiration, at volumes as high as the functional residual capacity.
Dead Space & Uneven Ventilation:
Since gaseous exchange in the respiratory system occurs only in the terminal portions of the airways, the gas that occupies the rest of the respiratory system is not available for gas exchange with pulmonary capillary blood. Normally, the volume of this anatomic dead space is approximately equal to the body weight in pounds. Thus, in a man who weighs 150 Ib (68 kg), only the first 350 mL of the 500 mL inspired with each breath at rest mixes with the air in the alveoli. Conversely, with each expiration, the first 150 mL expired is gas that occupied the dead space, and only the last 350 mL is gas from the alveoli. Consequently, the alveolar ventilation, ie, the amount of air reaching the alveoli per minute, is less than the respiratory minute volume. Note in addition that because of the dead space, rapid shallow breathing produces much less alveolar ventilation than slow deep breathing at the same respiratory minute volume.
It is important to distinguish between the anatomic dead space (respiratory system volume exclusive of alveoli) and the total (physiologic) dead space (volume of gas not equilibrating with blood, ie, wasted ventilation). In healthy individuals, the two dead spaces are identical; but in disease states, no exchange may take place between the gas in some of the alveoli and the blood, and some of the alveoli may be over ventilated. The volume of gas in nonperfused alveoli and any volume of air in the alveoli in excess of that necessary to arterialize the blood in the alveolar capillaries is part of the dead space (no equilibrating) gas volume.
Composition of Alveolar Air:
Oxygen continuously diffuses out of the gas in the alveoli into the bloodstream, and CO2 continuously diffuses into the alveoli from the blood. In the steady state, inspired air mixes with the alveolar gas, replacing the O2 that has entered the blood and diluting the CO2 that has entered the alveoli. Part of this mixture is expired. The O2 content of the alveolar gas then falls and its CO2 content rises until the next inspiration. Since the volume of gas in the alveoli is about 2 L at the end of expiration (functional residual capacity); each 350-mL increment of inspired and expired air has relatively little effect on PO2 and PCO2. Indeed, the composition of alveolar gas remains remarkably constant, not only at rest but also under a variety of other conditions.
The alveoli of the lung are essentially hollow spheres. Surface tension acting at the curved internal surface tends to cause the sphere to decrease in size. The surface tension within the alveoli would make the lungs extremely difficult to distend were it not for the presence of surfactant. The type II cells within the alveolus secrete an insoluble lipoprotein largely consisting of dipalmitoyl lecithin, which forms a thin monomolecular layer at the air-fluid interface. Surfactant reduces surface tension so that alveoli remain stable.
Fluid surfaces covered with surfactant exhibit a phenomenon known as hysteresis, that is, the surface tension lowering effect of the surfactant can be improved by a transient increase in the size of the surface area of the alveoli. During quiet breathing, small areas of the lung undergo collapse, but it is possible to re-expand these rapidly by a deep breath; hence the important of sighs or deep breaths as a feature of normal breathing. Failure of such a mechanism-which can occur, for example, in patients with fractured ribs-gives rise to patchy basal lung collapse. Surfactant levels may be reduced in a number of diseases that cause damage to the lung (e.g. pneumonia). Lack of surfactant plays a central role in the respiratory distress syndrome of the new-born. Severe reduction in perfusion of the lung causes impairment of surfactant activity and may well account for the characteristic areas of collapse associated with pulmonary embolism.
Pulmonary Blood Vessels
The pulmonary vascular bed7 resembles the systemic, except that the walls of the pulmonary artery and its large branches are about 30% as thick as the wall of the aorta, and the small arterial vessels, unlike the systemic arterioles, are endothelial tubes with relatively little muscle in their walls. The walls of the post capillary vessels also contain some smooth muscle. The pulmonary capillaries are large, and there are multiple anastomoses, so that each alveolus sits in a capillary basket.
Pressure, Volume, & Flow
With two quantitatively minor exceptions, the blood put out by the left ventricle returns to the right atrium and is ejected by the right ventricle, making the pulmonary vasculature unique in that it accommodates a blood flow that is almost equal to that of all the other organs in the body. One of the exceptions is part of the bronchial blood flow. As noted above, there are anastomoses between the bronchial capillaries and the pulmonary capillaries and veins, and although some of the bronchial blood enters the bronchial veins, some enters the pulmonary capillaries and veins, bypassing the right ventricle. The other exception is blood that flows from the coronary arteries into the chambers of the left side of the heart. Because of the small physiologic shunt created by those two exceptions, the blood in systemic arteries has a PO2 about 2 mm Hg lower than that of blood that has equilibrated with alveolar air, and the saturation of hemoglobin is 0.5% less.
The pressure gradient in the pulmonary system is about 7 mm Hg, compared with a gradient of about 90 mm Hg in the systemic circulation.
The volume of blood in the pulmonary vessels at any one time is about 1 L, of which less than 100 mL is in the capillaries. The mean velocity of the blood in the root of the pulmonary artery is the same as that in the aorta (about 40 cm/s). It falls off rapidly, then rises slightly again in the larger pulmonary veins. It takes a red cell about 0.75 s to traverse the pulmonary capillaries at rest and 0.3s or less during exercise.
Pulmonary capillary pressure is about 10 mm Hg, whereas the oncotic pressure is 25 mm Hg, so that an inward-directed pressure gradient of about 15 mm Hg keeps the alveoli free of all but a thin film of fluid. When the pulmonary capillary pressure is more than 25 mm Hg-as it may be, for example, in “backward failure” of the left ventricle- pulmonary congestion and edema result. Patients with mitral stenosis also have a chronic, progressive rise in pulmonary capillary pressure and extensive fibrotic changes in the pulmonary vessels.
Effect of Gravity:
Gravity has a relatively marked effect on the pulmonary circulation. In the upright position, the upper portions of the lungs are well above the level of the heart, and the bases are at or below it. Consequently, in the upper part of the lungs, the blood flow is less, the alveoli are larger, and ventilation is less than at the base. The pressure in the capillaries at the top of the lungs is close to the atmospheric pressure in the alveoli. Pulmonary arterial pressure is normally just sufficient to maintain perfusion, but if it is reduced or if alveolar pressure is increased, some of the capillaries collapse. Under these circumstances, no gas exchange takes place in the affected alveoli and they become part of the physiologic dead space.
In the middle portions of the lungs, the pulmonary arterial and capillary pressure exceeds alveolar pressure, but the pressure in the pulmonary venules may be lower than alveolar pressure during normal expiration, so they are collapsed. Under these circumstances, blood flow is determined by the pulmonary artery-alveolar pressure difference rather than the pulmonary artery pulmonary vein difference. Beyond the constriction, blood “falls” into the pulmonary veins, which are compliant and take whatever amount of blood the constriction lets flow into them. This has been called the waterfall effect. Obviously, the compression of vessels produced by alveolar pressure decreases and pulmonary blood flow increases as the arterial pressure increases toward the base of the lung.
In the lower portions of the lungs, alveolar pressure is lower than the pressure in all parts of the pulmonary circulation and blood flow is determined by the arterial-venous pressure difference.
Ventilation and Perfusion Relationships
For efficient gas exchange it is important that there is a match between ventilation of the alveoli (VA) and their perfusion (Q). There is a wide variation in the VA/Q ratio throughout both normal and diseased lung. In the normal lung the extreme relationships between alveolar ventilation and perfusion are:
· Ventilation with reduced perfusion (physiological dead space)
· Perfusion with reduced ventilation (physiological shunting).
In normal lungs there is a tendency for ventilation not to be matched by perfusion towards the apices, with the reverse occurring at the bases.
An increased physiological shunt results in arterial hypoxaemia. The effects of an increased physiological deadspace can usually be overcome by a compensatory increase in the ventilation of normally perfused alveoli. In advanced disease this compensation cannot occur, leading to increased alveolar and arterial PCO2 , together with hypoxaemia which cannot be compensated by increasing ventilation.
Hypoxaemia occurs more readily that hypercapnia because of the different ways in which oxygen and carbondioxide are carried in the blood. Carbondioxide can be considered to be in simple solution in the plasma, the volume carried being proportional to the partial pressure. Oxygen is carried in chemical combination with haemoglobin in the red blood cells, and the relationship between the volume carried and the partial pressure is not linear. Alveolar hyperventilation reduces the alveolar PCO2 and diffusion leads to a proportional fall in the carbondioxide content of the blood. However, as the haemoglobin is already saturated with oxygen, there is no significant increase in the blood oxygen content as a result of increasing the alveolar Po2 through hyperventilation. The hypoxaemia of even a small amount of physiological shunting cannot therefore be compensated for by hyperventilation.
The Pao2 and PaCO2 of some individuals who have mild disease of the lung causing slight VA/Q mismatch may still be normal. Increasing the requirements for gas exchange by exercise will widen the VA/Q mismatch and the Pao2 will fall. VA/Q mismatch is by far the most common cause of arterial hypoxaemia.
Because of their distensibility, the pulmonary veins are an important blood reservoir. When a normal individual lies down, the pulmonary blood volume increases by up to 400 mL, and when the person stands up this blood is discharged into the general circulation. This shift is the cause of the decrease in vital capacity in the supine position and is responsible for the occurrence of orthopnea in heart failure.
Regulation of Pulmonary Blood Flow:
It is unsettled whether pulmonary veins and pulmonary arteries are regulated separately, although constriction of the veins increases pulmonary capillary pressure and constriction of pulmonary arteries increases the load on the right side of the heart.
Plumonary blood flow is affected by both active and passive factors. There is an extensive autonomic innervation of the pulmonary vessels, and stimulation of the cervical sympathetic ganglia reduces pulmonary blood flow by as much as 30%. The vessels also respond to circulating humoral agents. Many of the dialator responses are endothelium dependent and presumably operate via release of NO (Nitric Oxide).
Passive factors such as cardiac output and gravitational forces also have significant effects on pulmonary blood flow. Local adjustments of perfusion to ventilation are determined by local effects of O2 or its lack. With exercise, cardiac output increases and pulmonary arterial pressure rises proportionately with little or no vasodilation. More red cells move through the lungs without any reduction in the O2 saturation of the hemoglobin in them, and consequently, the total amount of O2 delivered to the systemic circulation is increased. Capillaries dilate, and previously underperfused capillaries are “recruited” to carry blood. The net effect is a market increase in pulmonary blood flow with few if any alterations in autonomic outflow to the pulmonary vessels.
133Xe can used to survey local pulmonary blood flow by injecting a saline solution of the gas intravenously while monitoring the chest. The gas rapidly enters the alveoli that are perfused normally but fails to enter those that are not perfused. Another technique for locating poorly perfused areas is injection of macroaggregates of albumin labeled with radioactive iodine. These aggregates are large enough to block capillaries and small arterioles, and they lodge only in vessels in which blood was flowing when they reached the lungs. Although it seems paradoxic to study patients with defective pulmonary blood flow by producing vascular obstruction, the technique is safe because relatively few particles are injected. The particles block only small number of pulmonary vessels and are rapidly removed by the body.
When a bronchus or a bronchiole is obstructed, hypoxia develops in the underventilated alveoli beyond the obstruction. The O2 deficiency apparently acts directly on vascular smooth muscle in the area to produce constriction, shunting blood away from the hypoxic area. Accumulation of CO2 leads to a drop in pH in the area, and a decline in pH also produces vasoconstriction in the lungs, as opposed to the vasodilation it produces in other tissues. Conversely, reduction of the blood flow to a portion of the lung lowers the alveolar PCO2 in that area, and this leads to constriction of bronchi supplying it, shifting ventilation away from the poorly perfused area.
Systemic hypoxia also causes the pulmonary arterioles to constrict, with a resultant increase in pulmonary arterial pressure.
Functions of the Respiratory System
Lung Defense Mechanisms
The respiratory passage that lead from the exterior to the alveoli do more than serve as gas conduits. They humidify and cool or warm the inspired air so that even very hot or very cold air is at or near body temperature by the time it reaches the alveoli. Bronchial secretions contain secretory immunolobulins and substances that help resist infections and maintain the intergrity of the mucosa. In addition, the epithelium of the paranasal sinuses appears to produce NO, which is bacteriostatic and helps prevent infections.
The pulmonary epithelium contains an interesting group of protease-activated receptors (PARs) that when activated trigger release of PGE2, which in turn protects the epithelial cells. These receptors, which are also present in the gastrointestinal tract, are activated when thrombin or trypsin partially digests ligands tethered to them. The PAR2 is form is the form of the receptor in the respiratory tract.
The pulmonary alveolar macrophages (PAMs, “dust cells”) are another important component of the pulmonary defense mechanisms. Like other macrophages, these cells come orginally from the bone marrow. They are actively phagocytic and ingest inhaled bacteria and small particles. They also help process inhaled antigens for immunologic attack, and they secrete substances that attract granulocytes to the lungs as well as substances to stimulate granulocyte and monocyte formation in the bone marrow. When the macrophages ingest large amounts of the substances in cigarette smoke, they may also release lysosomal products into the extracellular space. This causes inflammation. Silica and asbestos particles also cause extracellular release of lysosomal enzymes.
Various mechanisms operate to prevent foreign matter form reaching the alveoli. The hairs in the nostrils strain out many particles larger than 10 mm in diameter. Most of the remaining particles of this size settle on mucous membranes in the nose and pharynx; because of their momentum, they do not follow the airstream as it curves downward into the lungs, and they impact on or near the tonsils and adenoids, large collections of immunologically active lymphoid tissue in the back of the pharynx. Particles 2-10mm in diameter generally fall on the walls of the bronchi as the air flow slows in the smaller passages. There they initiate reflex bronchial constriction and coughing. They are also moved away from the lungs by the “ciliary escalator.” The epithelium of the respiratory passages from the anterior third of the nose to the beginning of the respiratory bronchioles is ciliated, and the cilia, which are covered with mucus, beat in a coordinated fashion at a frequency of 1000-1500 cycles per minute. The ciliary mechanism is capable of moving particles away form the lungs at a rate of at least 16 mm/min. Particles less than 2 mm in diameter generally reach the alveoli, where they are ingested by the macrophages. The importance of these defense mechanisms is evident when one remembers that in modern cities, each liter of air may contain several million particles of dust and irritants.
When ciliary motility is defective, mucus transport is virtually absent. This leads to chronic sinusitis, recurrent lung infections, and bronchiectasis. Ciliary immotility may be produced by various air pollutants, or it may be congenital. One congenital form is Kartagener’s syndrome, in which the axonemal dynein, the ATPase molecular motor that produces ciliary beating, is absent. Patients with this condition also are infertile because they lack motile sperm, and they often have situs inversus, presumably because the cilia necessary for rotating the viscera are nonfunctional during embryonic development.
Metabolic & Endocrine Functions of the Lungs
In addition to their functions in gas exchange, the lungs have a number of metabolic functions. They manufacture surfactant for local use as noted above. They also contain a fibrinolytic system that lyses clots in the pulmonary vessels. They release a variety of substances that enter the systemic arterial blood, and they remove other substances form the systemic venous blood that reach them via the pulmonary artery. Prostaglandins are removed from the circulation, but they are also synthesized in the lungs and released into the blood when lung tissue is stretched.
The lungs also activate one hormone; the physiologically inactive decapeptide angiotensin I is converted to the pressor, aldosterone-stimulating octapeptide angiotension II in the pulmonary circulation. The reaction occurs in other tissues as well, but it is particularly prominent in the lungs. Large amounts of the angiotensin-converting enzyme responsible for this activation are located on the surface of the endothelial cells of the pulmonary capillaries. The converting
enzyme also inactivates bradykinin. About 70% of the angiotensin I reaching the lungs , is converted to angiotensin II in a single trip through the capillaries.
Removal of serotonin and norepinephrine reduces the amounts of these vasoactive substances reaching the systemic circulation. However, many other vasoactive hormones pass through the lungs without being metabolized. These include epinephrine, dopamine, oxytocin, vasopressin, and angiotensin II. In addition, as noted in various amines and polypeptides are secreted by neuroendocrine cells in the lungs.
Defence mechanisms of the respiratory tract:
Pulmonary disease often results form a failure of the many defence mechanisms that usually protect the lung in a healthy individual. These can be divided into :
§ Physical and Physiological Mechanisms
§ Humoral and Cellular Mechanisms.
Physical and Physiological mechanisms
This prevents dehydration of the epithelium.
Over 90% of particles greater than 10 mm diameter are removed in the nostril or nasophrynx. This includes most pollen grains which are typically > 20 microns in diameter. Particles between 5-10 microns become impacted in the carina. Particles smaller than 1 micron tend to remain airborne, thus the particles capable of reaching the deep lung are confined to the 1-5 micron range.
This is affected by coughing, sneezing or gagging.
Respiratory Tract Secretions
The mucus of the respiratory8 tract is a gelatinous sub-stance consisting chiefly of acid and neutral polysaccharides. The mucus consists of 5 mm thick get that is relatively impermeable to water. This floats on a liquid or sol layer that is present around the cilia of the epithelial cells. The gel layer is secreted form goblet cells and mucous glands as distinct globules that coalesce increasingly in the central airways to form a more or less continuous mucus blanket. Under normal conditions the tips of the cilia are in contact with the under surface of the gel phase and coordinate their movement to push the mucus blanket upwards. Whilst it may only take 30-60 minutes for mucus to be cleared from the large bronchi, there may be a delay of several days before clearance is achieved from respiratory bronchioles. One of the major long-term effects of cigarette smoking is a reduction in mucociliary transport. This contributes to recurrent infection and in the larger airways it prolongs contact with carcinogens. Air pollutants, local and general anesthetics and bacterial and viral infections also reduce mucociliary clearance.
Congenital defects in mucociliary transport occur. In the immotile cilia syndrome there is an absence of the dynein arms in the cilia themselves, and in cystic fibrosis an abnormal mucus is associated with ciliary dyskinesia. Both diseases are characterized by recurrent infections and eventually with the development of bronchiectasis.
Humoral and cellular mechanisms
Non- Specific soluble factors
· a1 Antitrypsin is present in lung secretions derived from plasma. It inhibits chymotrypsin and trypsin and neutralizes proteases and elastase.
· Lysozyme is an enzyme found in granulocytes that has bactericidal properties.
· Lactoferrin is synthesized from epithelial cells and neutrophil granulocytes and has bactericidal properties.
· Interferon is produced by most cells in response to viral infection. It is a potent modulator of lymphocyte function. It renders other cells resistant to infection by a other virus.
· Complement is present in secretions and is derived by diffusion from plasma. In association with antibodies, it plays an importnt cytotoxic role.
· Surfactant protein A (SPA) is one of four species of surfactant proteins which opsonizes bacteria/ particles, enhancing phagocytosis by macrophages.
· Defensins are bactericidal peptides present in the azurophil granules of neutrophils.
Pulmonary Alveolar Macrophages
These are derived from precursors in the bone marrow and migrate to the lungs via the bloodstream. They phagocytose particles, including bacteria, and are removed by the mucociliary escalator, lymphatics and bloodstream. They are the dominant cell in the airways at the level of the alveoli and comprise 90% of all cells obtained by bronchoalveolar lavage.
Alveolar macrophages work principally as scavengers and are not particularly good at presenting antigens to the immune system. Dendritic cells form a network throughout the airways and are thought to be the key antigen-presenting cell in the airway.
The lung contains large numbers of lymphocytes which are scattered throughout the airways. In animals, aggregates of bronchus-associated lymphoid tissue (BALT) can be identified but these are not normally found in humans. Sensitized lymphocytes contribute to local immunity through differentiation into IgA-secreting plasma cells. IgG and IgE are found in low concentrations in airway secretions from a combination of local and systemic production.
In addition to these resident cells, the lung has the usual range of acute inflammatory responses and can mobilize neutrophils promptly in response to injury or infection and play a major part in inflammatory conditions such as asthma.
Haemoptysis is defined as the expectoration of blood from the respiratory tract, a spectrum that varies from blood-streaking of sputum to coughing up large amounts of pure blood. Massive haemoptysis is variably defined as the expectoration of >100 to > 600 mL of blood over a 24-h period, although the patient’s estimation of the amount of blood is notoriously unreliable. Expectoration of even relatively small amounts of blood is a frightening symptom and can be a marker for potentially serious disease, such as bronchogenic carcinoma. Massive haemoptysis, on the other hand, can represent an acutely life-threatening problem. Large amounts of blood can fill the airways and the alveolar spaces, not only seriously disturbing gas exchange but potentially causing the patient to suffocate.
Because blood originating from the nasopharynx or the gastrointestinal tract can mimic blood coming from the lower respiratory tract, it is important to determine initially that the blood is not coming from one of these alternative sites. Clues that the blood is originating from the gastrointestinal tract include a dark red appearance and an acidic pH, in contrast to the typical bright red appearance and alkaline pH of true haemoptysis.
The bronchial arteries, which are part of the high-pressure systemic circulation, originate either from the aorta or from intercostal arteries and are the source of bleeding in bronchitis or bronchiectasis or with endobronchial tumours.
The most common site of bleeding is the airways, i.e., the tracheobronchial tree, which can be affected by inflammation (acute or chronic bronchitis, bronchiectasis) or by neoplasm (bronchogenic carcinoma, endobronchial metastatic carcinoma, or bronchial carcinoid tumor). Blood orginating from the pulmonary parenchyma can be either from a localized source, such as an infection (pneumonia, lung abscess, tuberculosis, or from a process diffusely affecting the parenchyma (as with a coagulopathy or with an autoimmune process such as Goodpasture’s syndrome). Disorders primarily affecting the pulmonary vasculature include pulmonary embolic disease and those conditions associated with elevated pulmonary venous and capillary pressures, such as mitral stenosis or left ventricular failure.
Although the relative frequency of the different etiologies of hemoptysis varies, most recent studies indicate that bronchitis and bronchogenic carcinoma are the two most common causes. Tuberculosis and bronchiectasis are the most common causes of massive haemoptysis. Even after extensive evaluation, a sizable proportion of patients (up to 30%) have no identifiable aetiology for their haemoptysis. These patients are classified as having idiopathic or cryptogenic haemoptysis, and subtle airway or paranchymal disease is presumably responsible for the bleeding.
Aetiology of Haemoptysis
1. Diseases of the respiratory system
A. Infective and inflammatory conditions
i. Pulmonary tuberculosis
iii. Lung abscess
iv. Chronic bronchitis.
v. Pulmonary infarction
vii. Primary pulmonary hypertension
viii. Acute bronchitis
ix. Mycotic infection of the lung
x. Parasitic diseases of the lung-
a. Pulmonary amoebiasis.
b. Hydatid cyst
c. Lung fluke
ix. Viral infection:
Small pox, chicken pox, measles
B. Neoplastic conditions
I. Bronchial carcinoma
II. Bronchial adenoma
III. Metastatic tumours.
IV. Cavernous haemangioma.
V. Alveolar cell carcinoma.
VI. Mediastinal turnours.
VII. Carcinoma of the trachea.
2. Diseases of the cardiovascular system:
I. Mitral stenosis
II. Left heart failure
III. Aortic aneurysm
V. Hereditary telangiectasia
VI. Left atrial tumours.
VII. Congenital heart disease.
VIII. Infective endocarditis.
3. Connective tissue diseases:
i) Systemic lupus erythematosus.
ii) Poly arteritis nodosa.
iii) Wegener’s granulomatosis.
4. Haemorrhagic diseases:
i) Idiopathic thrombocytopenic purpura.
iii) Aplastic anaemia.
II. Foreign body
III. Idiopathic pulmonary haemosiderosis
IV. Good Pasteur’s syndrome
VI. Cystic fibrosis
VII. Pulmonary alveolar microlithiasis.
VIII. Middle lobe syndrome
IX. Pulmonary eosinophilia
X. Pulmonary endometriosis
Haemoptysis in Different Diseases:
Haemoptysis is a classical symptom of pulmonary tuberculosis and may vary from mere blood staining of the sputum to the rarer occurrence of sudden eruption of half a litre or more of blood, occasionally immediately fatal. The mechanism of bleeding depends upon the site, type and the stage of lesion. In exudative lesion small pulmonary vessels are necrosed due to softening of the lung parenchyma.
In tuberculosis, abscess formation and cavitations may occur. The blood vessels that traverse through the wall of the cavity or through the cavity undergo aneurysmal dilation which rupture on straining and may result in profuse haemoptysis. A healed and calcified tuberculous lymph node may impinge into the bronchial wall. Erosion and later ulceration occurs due to pressure of the hard lymph node resulting in haemoptysis. The haemoptysis usually proceed the coughing out of a broncholith or accompany it. If the lymph node contains tubercle bacilli, there may result in bronchial spread of tuberculosis. Tuberculous ulceration of the trachea or bronchi may be the result of primary infection or a part of wide spread parenchymal infection. This ulceration of the mucosa erodes the smaller bronchial vessels and cause haemoptysis. Occasionally severe and repeated haemoptysis may be due to quite localized apical fibrosis associated with healed tuberculosis. Radiologically calcified spots may be found. Sometimes bronchiectatic changes are found in these area where bleeding occurs from the granulation tissue on the wall of the dilated bronchi that may or may not be tubercolous.
Bronchiectasis is the term used to describe abnormal dilatation of the bronchi. It is usually acquired but may result from an underlying genetic or congenital defect of airway defences.Bronchiectasis is usually caused by chronic inflammation and infection in the airways.
Localized bronchiectasis may be due to bronchial distension resulting from the accumulation of pus beyond an obstructing bronchial lesion, such as enlarged tuberculous hilar lymph nodes, a bronchial tumour or an inhaled foreign body (e.g. an aspirated peanut.)
The bronchiectatic cavities are lined by granulation tissue, squamous epithelium or normal ciliated epithelium.
There may be also inflammatory changes in the deeper layers of the bronchial wall and hypertrophy of the bronchial arteries. Chronic inflammatory and fibrotic changes are usually found in the surrounding lung tissue.
SYMPTOMS OF BRONCHIECTASIS:
1). Due to accumulation of pus in dilated bronchi:
Chronic productive cough is usually worse in morning and often brought on by changes of posture. Sputum is often copious and persistently purulent in advanced disease. Halitosis is a common accompanying feature.
Due to inflammatory changes in lung and pleura surrounding dilated bronchi:
Fever, malaise, and increased cough and sputum production and when spread of infection causes pneumonia, which may be associated with pleurisy. Recurrent pleurisy in the same site often occurs in bronchiectasis.
Can be slight or massive and is often recurrent. Usually associated with purulent sputum or an increase in sputum production, which can be the only symptom in dry bronchiectasis.
When disease is extensive and sputum persistently purulent a decline in general health occurs with weight loss, anorexia, lassitude, low-grade fever, and failure to thrive in children. In these patients digital clubbing is common.
In bronchiectasis there are three varieties of dilations. These are cylindrical, fusiform and saccular. Haemoptysis is more common in saccular variety. Bleeding may occur from highly vascular granulation tissue that appears in the wall of dilated bronchi. There is anatomical communication between the pulmonary and bronchial arteries. In the wall of the dilated bronchi these vessels get wide aneurysmal dilatation. The walls become thin. Severe haemoptysis may result from the rupture of these anastomosing aneurysms. The dilated and deformed bronchi are the site of chronic infection which causes mucosal ulceration and erosion of blood vessels causing bleeding.
Suppurative pneumonia is the term used to describe a form of penumonic consolidation in which there is destruction of the lung parenchyma by the inflammatory process. Although microabscess formation is a characteristic histological feature of suppurative pneumonia, it is usual to restrict the term pulmonary abscess to lesions in which there is a large localized collection of pus or a cavity lined by chronic inflammatory issue, from which pus has escaped by rupture into a bronchus.
Suppurative pneumonia and pulmonary abscess may be produced by infection of previously healthy lung tissue with Staphylococcus aureus or Klebsiella pneumoniae. These are, in effect, primary bacterial pneumonias associated with pulmonary suppuration. More frequently, suppurative pneumonia10 and pulmonary abscess develop after the inhalation of septic material during operations on the nose, mouth or throat under general anaesthesia, or of vomitus during anaesthesia or coma. In such circumstances gross oral sepsis may be a predisposing factor. Additional risk factors for aspiration pneumonia include vocal cord palsy, achalasia or oesophageal reflux and alcoholism. Aspiration into the lungs of acid gastric contents can give rise to a severe haemorrhagic pneumonia often complicated by the acute respiratory distress syndrome. Intravenous drug-users are at particular risk of developing haematogenous lung abscess, often in association with endocarditis affecting the pulmonary and tricuspid valves.
Bacterial infection of a pulmonary infarct or of a collapsed lobe may also produce a suppurative pneumonia or a lung abscess. The organism isolated from the sputum include Strep. pneumoniae, staph. aureus, strep. pyogenes, H. influenzae and in some cases, anaerobic bacteria. In many cases, however, no pathogen can be isolated, particularly when antibiotics have been given.
The clinical features of suppurative pneumonia are :
· Cough productive of large amounts of sputum which is sometimes fetid and blood stained.
· Pleural pain common.
· Sudden expectoration of copious amounts of foul smelling sputum occurs if abscess ruptures into a bronchus.
2) Clinical signs:
· High remittent pyrexia.
· Profound systemic upset.
· Digital clubbing may develop quickly (10-14 days).
· Chest examination usually reveals signs of consolidation or sings of cavitation may found.
· Pleural rub is common.
· Rapid deterioration in general health with marked weight loss can occur if disease not adequately treated.
Acute Bronchitis and Tracheitis:
Initially irritating unproductive cough accompanied by retrosternal discomfort present in tracheitis. Chest tightness, wheeze and breathlessness when bronchi become involved. Tracheitis causes pain on coughing. Sputum is initially scanty or mucoid. After a day or so sputum becomes mucopurulent, more copious and, in tracheitis, often blood-stained. Acute bronchial infection may be associated with a pyrexia of 38-390C and a neutrophil leucocytosis. Spontaneous recovery occurs over a few days.
b) Exacerbation of chronic bronchitis which often results in type II Respiratory failure in patients with severe COPD.
c) Acute exacerbation of bronchial asthma.
Pneumonia is defined as an acute respiratory illness associated with recently developed radiological pulmonary shadowing which may be segmental, lobar or multilobar. The clinical context in which a pneumonia develops is highly suggestive of the likely organism involved and hence the immediate choice of antibiotics; pneumonias are therefore usually classified as community acquired, hospital acquired (nosocomial), or those occurring in immunocompromised hosts or patients with underlying damaged lung (including suppurative and aspirational pneumonias). Lobar pneumonia is a radiological and pathological term referering to homogeneous consolidation of one or more lung lobes, often with associated pleural inflammation; bronchopneumonia refers to more patchy alveolar consolidation associated with bronchial and bronchiolar inflammation often affecting both lower lobes.
Community-Acquired pneumonia (CAP)
The incidence varies with age, being much higher in the very young and the elderly. Pneumonia accounts for almost one-fifth of childhood deaths world-wide, with approximately 2 million children under 5 dying each year. Most patients may be safely managed at home, but hospital admission is necessary in 20