Pulmonary blood

Ventilation-perfusion ratio (VA/Q) A comparison of the proportion of lung tissue being ventilated by inhaled air to the rate of oxygenation of pulmonary blood. 

Venous thromboembolism (VTE) results from clot formation in the venous circulation and is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE). A DVT is a thrombus composed of cellular material (red and white blood cells, platelets) bound together with fibrin strands. A PE is a thrombus that arises from the systemic circulation and lodges in the pulmonary artery or one of its branches, causing complete or partial obstruction of pulmonary blood flow. 

The relationship for pulmonary vascular resistance is very non-linear owing to the effect of recruitment and distension of vessels in the pulmonary vascular bed in response to increased pulmonary blood flow. The PVR is usually around 10 times lower than the systemic vascular resistance, at 50-150 dyne.s.cm-5. 

Two different circulatory systems, the bronchial and the pulmonary, supply the lungs with blood [133], The bronchial circulation is a part of the systemic circulation and is under high pressure. It receives about 1% of the cardiac output and supplies the conducting airways, pulmonary blood vessels and lymph nodes [133], It is important for the distribution of systemically administered drugs to the airways and to the absorption of inhaled drugs from the airways [18]. The pulmonary circulation comprises an extensive low-pressure vascular bed, which receives the entire cardiac output. It perfuses the alveolar capillaries to secure efficient gas exchange and supplies nutrients to the alveolar walls. Anastomoses between bronchial and pulmonary arterial circulations have been found in the walls of medium-sized bronchi and bronchioles [18, 65, 67],... 

An immediate response to dust inhalation is the migration of polymorphonuclear leukocytes (PMNs) across epithelial—endothelial junctions to the alveolar space (see Fig. 3.6). Macrophages release a chemotactic factor that mobilizes and attracts PMNs from the pulmonary blood. However, the initial PMN accumulation clears rapidly. 

At present, we suspect that toxin-LR causes heart failure in mice, perhaps due to suddenly increased resistance to pulmonary blood flow. Heart failure in mammals is known to cause engorgement of the liver with blood. Pulmonary vascular occlusion may also cause secondary hypoxemia and shock. However, biochemical pathways that are initiated by toxin-LR and that lead to the onset of discernable signs of illness after 30 min are unidentified. The 30 min asymptomatic period following toxin injection may be associated with a toxin-initiated cascade of biochemical events which lead to overt signs of illness. 

Almitrine, like doxapram, increases the rate and depth of respiration. In addition, it is believed that it redistributes pulmonary blood circulation, increasing it in alveoh, which leads to relatively better pulmonary ventilation. It has a more prolonged effect than doxapram.Synonyms are vectarion, duxil, and others. 

Pharmacology The methyixanthines (theophylline, its soluble salts and derivatives) directly relax the smooth muscle of the bronchi and pulmonary blood vessels, stimulate the CNS, induce diuresis, increase gastric acid secretion, reduce lower esophageal sphincter pressure, and inhibit uterine contractions. Theophylline is also a central respiratory stimulant. Aminophylline has a potent effect on diaphragmatic contractility in healthy people and may then be capable of reducing fatigability and thereby improve contractility in patients with chronic obstructive airways disease. Pharmacokinetics ... 

Any volatile material, irrespective of its route of administration, has the potential for pulmonary excretion. Certainly, gases and other volatile substances that enter the body primarily through the respiratory tract can be expected to be excreted by this route. No specialized transport systems are involved in the loss of substances in expired air simple diffusion across cell membranes is predominant. The rate of loss of gases is not constant it depends on the rate of respiration and pulmonary blood flow. 

Frequently it is desirable to overcome the slow rate of rise of alveolar tension associated with such factors as the high blood solubility of some anesthetics and increased pulmonary blood flow. Since both of these factors retard tension development by increasing the uptake of anesthetic, the most effective way to alleviate the problem is to accelerate the input of gas to the alveoli. A useful technique to increase the input of anesthetic to the lung is to elevate the minute alveolar ventilation. This maneuver, which causes a greater quantity of fresh anesthetic gas to be delivered to the patient per unit of time, is most effective with highly soluble agents (Fig. 25.4). 

Mechanism of Action A xanthine derivative that acts as a bronchodilator by directly relaxing smooth muscle of the bronchial airways and pulmonary blood vessels. Therapeutic Effect Relieves bronchospasm and increases vital capacity. Pharmacokinetics Rapidly and well absorbed. Protein binding Moderate (to albumin). Extensively metabolized in liver. Partially excreted in urine. Half-life 6-12 hr (varies). 

The concentration of an inhaled anesthetic in a mixture of gases is proportional to its partial pressure (or tension). These terms are often used interchangeably in discussing the various transfer processes involving anesthetic gases within the body. Achievement of a brain concentration of an inhaled anesthetic necessary to provide an adequate depth of anesthesia requires transfer of the anesthetic from the alveolar air to the blood and from the blood to the brain. The rate at which a therapeutic concentration of the anesthetic is achieved in the brain depends primarily on the solubility properties of the anesthetic, its concentration in the inspired air, the volume of pulmonary ventilation, the pulmonary blood flow, and the partial pressure gradient between arterial and mixed venous blood anesthetic concentrations. 

The advantages of administration by intramuscular injection are that the muscle can act as a depot, and the rate of disappearance of drug from the site of injection can be calculated. Inhalational, intranasal, and intratracheal administration are normally reserved for vapors and aerosols including anesthetics. Absorption is facilitated by small-sized particles, high lipid solubility, sufficient pulmonary blood flow, and a large absorptive surface area, as it is present in healthy lungs. Administration by these routes can be very rapid when several of the factors favoring increased absorption are combined. 

Adenosine affects vascular smooth muscle tone in the pulmonary circulation. In the feline pulmonary vascular bed, under conditions of controlled pulmonary blood flow and constant left atrial pressure, adenosine was shown to produce dose-dependent, tone-dependent responses (Neely and Matot 1996 Cheng et al. 1996). At low baseline pulmonary vascular tone adenosine induces vasoconstriction via A3AR and the release of prostanoids, whereas at elevated pulmonary vascular tone it produces vasodilatation by acting on A2AR, without nitric oxide release or the activation of guanylate cyclase or KATp channels (Neely and Matot 1996 Cheng et al. 1996). 

Reduced pulmonary blood flow and increased pulmonary blood pressure... 

Preliminary studies in animals suggest that airway smooth muscle, like that in the vasculature, is effectively relaxed by nitric oxide. This very lipophilic drug can be inhaled as a gas in acute asthma and dilates the pulmonary blood vessels as well as the airway smooth muscle. Although nitric oxide itself—or nitric oxide donors—may prove of value in acute severe asthma, it appears likely that they will be more useful in pulmonary hypertension (for which nitric oxide is already approved). 

An increase in pulmonary blood flow (increased cardiac output) slows the rate of rise in arterial tension, particularly for those anesthetics with moderate to high blood solubility. This is because increased pulmonary blood flow exposes a larger volume of blood to the anesthetic thus, blood "capacity" increases and the anesthetic tension rises slowly. A decrease in pulmonary blood flow has the opposite effect and increases the rate of rise of arterial tension of inhaled anesthetics. In a patient with circulatory shock, the combined effects of decreased cardiac output (resulting in decreased pulmonary flow) and increased ventilation will accelerate the induction of anesthesia with halothane and isoflurane. This is not likely to occur with nitrous oxide, desflurane, or sevoflurane because of their low blood solubility. 

The lung contains more than 40 different types of cells, amongst which epithelial cells are vital for maintenance of the pulmonary blood-gas barrier. The epithelium also provides absorptive and secretive functions. The diversity of epithelial cell types is summarized as airway epithelium and alveolar epithelium cells. 

Glenny, R. and Robertson, H., Fractal properties of pulmonary blood flow Characterization of spatial heterogeneity, Journal of Applied Physioloqy, Vol. 69, No. 2, 1990, pp. 532-545. 

Q7 What happens to the area of lung whose circulation has been cut off by an embolus in a pulmonary blood vessel ... 

---