Anatomy_SLID_CH06 for respiratory therapist.pptx

Neurologic Control of Breathing, Receptors in the Pulmonary System, and Airway Disease

1. CHAPTER 6 Neurologic Control of Breathing, Receptors in the Pulmonary System, and Airway Disease

2. Objectives Discuss the differences between the sympathetic and parasympathetic nervous systems. Describe the structure and function of a neuron. Identify the nerves that innervate the pulmonary system. Explain the difference between an agonist and an antagonist. Describe the impact of airway inflammation on the pulmonary parenchyma. Define genotypes , phenotypes , and endotypes , and discuss their role in individualizing therapy for chronic respiratory diseases. List the receptors in the pulmonary system that affect respiratory function. Explain the similarities and differences among asthma, chronic obstructive disease, and asthma–chronic obstructive disease overlap (ACO).

3. The Nervous System (1 of 5) The basic structural unit of the nervous system is the nerve cell, or neuron. A group of neurons that run along a specific pathway in the body is called a nerve. Ganglia are groups or bundles of nerve cells located along these pathways that act as relay points for nerve impulses. They may be interconnected with other ganglia to form a complex system of interconnecting nerves and ganglia. This is called a plexus. The parts of the human nervous system are classified according to their location and function. The anatomic classification divides the nervous system into two divisions based on the location of the nerves. These two divisions are the central nervous system (CNS) and the peripheral nervous system (PNS).

4. The Nervous System (2 of 5) FIGURE 6-1 The anatomic divisions of the nervous system are the central nervous system (CNS) and the peripheral nervous system (PNS).

5. The Nervous System (3 of 5) The CNS includes the brain and spinal cord. The PNS includes the nerves that are located outside of the CNS and throughout the rest of the body. The nerves in the PNS are called cranial nerves or spinal nerves based on the area in the CNS from which they originate. The PNS is further subdivided and classified by function into the somatic nervous system (SoNS), the autonomic nervous system (ANS), and the enteric nervous system (ENS). Each of these three subsystems has a specific role in maintaining the functions of the body.

6. The Nervous System (4 of 5) FIGURE 6-2 Divisions of the nervous system.

7. The Nervous System (5 of 5) The functional classification of the nervous system is based on the direction in which the impulses are transmitted through the nerve and the activity the nerve impulse initiates. Most nerves in the body have a mixed function. This means that they contain fibers that can carry impulses away from the CNS and fibers that can carry impulses toward the CNS. The fibers that carry impulses toward the CNS are called afferent nerves, and the fibers that carry impulses away from the CNS to the muscles, organs, and tissues are called efferent nerves.

8. The Central Nervous System (1 of 14) The central nervous system (CNS) includes the brain and the spinal cord and is the primary command-and-control system for the body. Protecting the structures of the CNS from infection and injury is crucial to ensuring optimal function. Bones provide the first structural protection system of the CNS. The brain is surrounded by the bones of the skull, and the spinal cord is supported and surrounded by the vertebral column. Both the brain and the spinal cord are also protected by a three-layered membrane called the meninges. The three layers of the meninges are the dura mater, the arachnoid mater, and the pia mater.

9. The Central Nervous System (2 of 14) Cerebrospinal fluid (CSF) is a clear, colorless liquid found between the arachnoid mater and the pia mater. The function of CSF is to supply nutrients to the CNS tissue, remove waste products from the CNS, and act as a cushion between the bones of the skull and the spine and the neural tissues of the brain and spinal column. The third line of defense for the CNS is a very tight web of microvasculature that prevents toxins, blood cells, and pathogens from entering the brain and spinal column. This microvasculature is called the blood–brain barrier.

10. The Central Nervous System (3 of 14) The brain is the largest organ of the nervous system and includes nearly 100 billion neurons that process and control our sensory perception, thoughts, movement, and physiologic functions. The sections of the brain are the: Cerebrum Cerebellum Brain stem

11. The Central Nervous System (4 of 14) FIGURE 6-3 Anatomy of the brain.

12. The Central Nervous System (5 of 14) The cerebrum is the largest portion of the brain. The outermost layer of the cerebrum is the cerebral cortex. This outer layer gives the brain its furrowed appearance. Beneath the cerebral cortex, the cerebrum is divided into right and left hemispheres that are joined by the corpus callosum. Impulses (messages) are transferred between the two hemispheres via the corpus callosum. The right hemisphere of the brain controls the left side of the body and plays a role in creativity, spatial ability, and artistic and musical skills. The left hemisphere of the brain controls the right side of the body and coordinates speech, comprehension, mathematical thinking, and motor skills such as writing. Each hemisphere can be further divided into four lobes: the frontal, temporal, parietal, and occipital lobes.

13. The Central Nervous System (6 of 14) FIGURE 6-4 The cerebrum is divided into four lobes: the frontal, parietal, occipital, and temporal lobes. Each lobe can be further divided into subsections that are responsible for specific bodily functions.

14. The Central Nervous System (7 of 14) Each lobe can be divided into subsections that control specific bodily functions. Some of the functions controlled by subsections of the frontal lobes are personality, behavior, emotions, judgment, problem-solving, and writing. Functions controlled by the temporal lobe include sensory information related to hearing, recognizing musical patterns, some visual processing, and forming memories. Sections of the parietal lobe coordinate and integrate sensory information related to touch, temperature, and pain. The occipital lobe is primarily responsible for receiving and processing visual information from the eyes. Collectively, the functions of the cerebrum include initiation of movement, coordination of movement, temperature control, touch, vision, hearing, judgment, reasoning, problem-solving, emotions, and learning.

15. The Central Nervous System (8 of 14) The cerebellum is the smaller portion of the brain located behind the cerebrum at the base of the skull. This portion of the brain coordinates voluntary muscle movements and has a role in maintaining posture and balance. The brain stem connects the cerebrum, cerebellum, and spinal cord. This area includes the midbrain, the pons, and the medulla. Sensory messages are conducted through the brain stem. The brain stem aids in the coordination of eye movements and also controls involuntary functions such as breathing, heart rate, body temperature, sleep–wake cycles, digestion, sneezing, coughing, and swallowing.

16. The Central Nervous System (9 of 14) Located in the center of the brain, the diencephalon contains several structures that relay information and regulate some bodily functions. The principal structures of the diencephalon are the thalamus, hypothalamus, and the pineal gland. The thalamus, a two-lobed structure, is considered the central sensory and motor relay portion of the brain. It links the relevant parts of the cerebral cortex with the spinal cord and other areas of the brain and also controls sleep and arousal.

17. The Central Nervous System (10 of 14) The hypothalamus is located just underneath the thalamus and is about the size of a pea. The hypothalamus regulates the release of hormones from the pituitary gland and affects body temperature, appetite, sexual behavior, and emotional responses. The hypothalamus responds to a variety of signals and creates hormones that stimulate the pituitary gland to produce other hormones that directly regulate bodily functions.

18. The Central Nervous System (11 of 14)

19. The Central Nervous System (12 of 14) The pineal gland is approximately the size of a grain of rice and is located between the two lobes of the thalamus. This gland produces melatonin, which regulates the body’s sleep–wake cycle. It is suspected that this gland has other functions, although they are unclear at this time.

20. The Central Nervous System (13 of 14) The brain and the spinal cord are composed of tissues called gray matter and white matter. Gray matter is found in the cerebellum, cerebrum, brain stem, and portions of the central spinal cord. Gray matter contains the cell bodies, dendrites, and axon terminals of neurons. The majority of the brain is made up of gray matter. White matter is found in both the brain and the spinal cord and contains axons that connect different parts of gray matter to each other. The axons in the white matter are covered with a layer of protein and lipids called myelin.

21. The Central Nervous System (14 of 14) The function of the spinal cord is to transmit impulses to and from the brain and the peripheral nervous system. The spinal cord is a collection of neural tissue that extends from the medulla oblongata in the brain stem through the vertebral column to the level of the first or second lumbar vertebra. Below that level, spinal nerve roots; meninges; and a fibrous strand, the filum terminale, continue from the spinal cord down to the coccyx. A cross-sectional view of the spinal cord reveals gray matter in the shape of the letter “H” surrounded by white matter.

22. The Peripheral Nervous System (1 of 7) The peripheral nervous system (PNS) includes all of the nerves outside of the brain and the spinal column that connect the parts of the body to the CNS. The PNS includes the 12 cranial nerve pairs and the 31 spinal nerve pairs. The PNS is divided into three subsystems: the somatic, autonomic, and enteric nervous systems.

23. The Peripheral Nervous System (2 of 7) The somatic nervous system (SoNS) is also known as the voluntary nervous system. This system transmits impulses between the CNS and the skeletal muscles and enables voluntary movement such as walking or picking up an object. The SoNS includes all the nonsensory neurons connected with skeletal muscles and skin. The SoNS is also responsible for some involuntary muscle responses called reflex arcsneural pathways that control reflexes, such as the rapid withdrawal of a hand or finger when contacting something hot.

24. The Peripheral Nervous System (3 of 7) FIGURE 6-5 Sensory distribution of peripheral nerves: The peripheral nervous system includes the nerves and ganglia outside of the brain and spinal column that run throughout the body. Many of the peripheral nerves are named for the vascular and bony structures that they are closest to. For example, the femoral nerve runs along the femoral bone.

25. The Peripheral Nervous System (4 of 7) The autonomic nervous system (ANS) is the part of the peripheral nervous system that regulates physiologic processes, including heart rate, respiratory rate, pupillary response, urination, blood pressure, and mobilizing the body’s energy stores for emergency response. The ANS is divided into the sympathetic and the parasympathetic nervous systems. These two divisions complement the activities of the other. The sympathetic nervous system responds to stress or stimuli and activates many physiologic processes, including the “fight-or-flight” response. The parasympathetic nervous system reverses the fight-or-flight process and relaxes the body. It is sometimes called the “rest and digest” portion of the nervous system. In the lungs, sympathetic nerve fibers control bronchodilatation of the airways and parasympathetic nerve fibers control bronchoconstriction.

26. The Peripheral Nervous System (5 of 7) The sympathetic nerves arise from the spinal cord in the thoracic and lumbar regions, and the parasympathetic division arises from the cranial nerves and sacral portion of the spinal cord. Nerve fibers in both the sympathetic and the parasympathetic nervous systems can also be classified by their location. The fibers that travel from the CNS to the ganglion are known as preganglionic nerve fibers, and the nerve fibers that travel from the ganglion to the effector organ or muscles are called postganglionic fibers.

27. The Peripheral Nervous System (6 of 7) FIGURE 6-6 Actions of the sympathetic nervous system (fight or flight) and the parasympathetic nervous system (rest and digest).

28. The Peripheral Nervous System (7 of 7) The enteric nervous system (ENS) is considered by some to be part of the ANS, whereas others consider it as a separate entity. This is because the ENS shares some communication pathways with the parasympathetic nervous system via the vagus and pelvic nerves and other pathways with the sympathetic nervous system via the prevertebral ganglia. The ENS controls the gastrointestinal system. Although the ENS communicates with the CNS, it can and does operate independently of the brain and the spinal cord and is often referred to as the “second brain” of the body.

29. The Innervation of the Pulmonary System (1 of 4) The smooth muscles of the airways, blood vessels, and glands of the tracheobronchial tree are innervated by the pulmonary plexus . This network of nerves arises from the vagus nerve on the anterior and posterior side of each lung root. The nerves of the pulmonary plexus follow the bronchi in the lungs and branch to innervate muscle fibers, glands, and blood vessels in the thoracic cavity. Divided into two sections, the anterior pulmonary plexus lies in front of the root of the lung, and the posterior pulmonary plexus lies behind the root of the lung. Both sections are composed of sympathetic and parasympathetic nerve fibers.

30. The Innervation of the Pulmonary System (2 of 4) The sympathetic nerve fibers of the pulmonary plexus stimulate the relaxation of the bronchial smooth muscles and vasoconstriction of the pulmonary vessels. Sympathetic nerve fibers arise in the upper thoracic and cervical ganglia of the sympathetic trunk. The parasympathetic nerve fibers stimulate contraction of the bronchial smooth muscles, vasodilation of the pulmonary vessels, and the production of pulmonary secretions. Parasympathetic nerve fibers arise from the vagus nerve.

31. The Innervation of the Pulmonary System (3 of 4) The phrenic nerve innervates the diaphragm. It is both a sensory and a motor nerve that controls and supports breathing. This nerve originates in the spinal column from the ventral rami of the C3, C4, and C5 nerve roots, which are part of the cervical plexus. The left phrenic nerve descends to the left subclavian artery, the arch of the aorta, the left atrium, and the left ventricle and then moves downward toward the left half of the diaphragm. The right phrenic nerve descends to the superior vena cava, right atrium, right ventricle, and inferior vena cava before passing through the vena caval foramen to the right half of the diaphragm.

32. The Innervation of the Pulmonary System (4 of 4) FIGURE 6-7 Innervation of the diaphragm by the phrenic nerve.

33. Neurons (1 of 4) Neurons are the basic units of the nervous system. Like links in a chain, neurons receive, process, and transmit signals from one to another throughout the body. These signals are called action potentials, or nerve impulses. The three basic types of neurons are afferent neurons, efferent neurons, and interneurons. Afferent neurons , also called sensory neurons, transmit nerve impulses from the body to the CNS. Efferent neurons, also called motor neurons, transmit nerve impulses to the body from the CNS. Interneurons are found only in the CNS and form the communication link between sensory neurons and motor neurons. The size of a neuron can vary depending on its location and function in the body. However, all neurons have four basic parts: dendrites; the soma, or cell body; the axon; and the terminal button.

34. Neurons (2 of 4) FIGURE 6-8 Parts of a neuron.

35. Neurons (3 of 4) Dendrites are treelike branches at the end of a neuron that receive nerve impulses from other neurons. Each dendrite has multiple receptors that facilitate the collection of impulses. The dendrite then transmits the impulse to the soma. The soma supports and maintains the function of the neuron. It does not alter or interpret the information; it simply relays the impulse through to the axon. The axon is an elongated fiber that extends from the soma and transmits the neural impulse to the terminal button. The terminal button, located at the end of the neuron, stores chemicals called neurotransmitters.

36. Neurons (4 of 4) When a signal reaches the terminal button, neurotransmitters are released into the space between the current neuron and the next neuron. This space is called the synapse. The neurotransmitter is then collected by the dendrites of the next neuron where the process begins again. If there are any extra neurotransmitters released during this process, the terminal button collects them and keeps the synaptic gap between the two neurons clean.

37. Neurotransmitters (1 of 4) Neurotransmitters are chemicals released by the neurons into the synaptic gap. The neurotransmitter binds to a receptor site on a neighboring neuron, muscle cell, or gland and passes a chemical impulse to the neighboring cell. The type of signal conveyed from one neuron on to another is classified as either an excitatory or inhibitory signal. An excitatory signal from one neuron to another means that the receiving neuron is more likely to transmit the impulse. An inhibitory signal means that the receiving neuron is less likely to transmit the signal. Whether the signal that is transmitted is excitatory or inhibitory is usually is not dependent upon the neurotransmitter, but rather on the type of receptor receiving the signal. Many neurotransmitters can bind to and activate both excitatory and inhibitory receptors.

38. Neurotransmitters (2 of 4) An agonist is a medication or chemical that stimulates binding with a receptor and initiates the same receptor response as the neurotransmitter. Agonists may be direct agonists or indirect agonists. A direct agonist binds directly to a receptor site. An indirect agonist increases the binding of the neurotransmitter to a receptor by stimulating the release of more neurotransmitters or by preventing the reuptake of the released neurotransmitters.

39. Neurotransmitters (3 of 4) An antagonist is a medication or chemical that prevents the neurotransmitter from binding with a receptor and delaying or inhibiting the receptor response. A direct-acting antagonist binds to the receptor and blocks the neurotransmitter, thereby stopping the transmission of the impulse and the subsequent response. An indirect-acting antagonist inhibits the release or production of the neurotransmitter.

40. Neurotransmitters (4 of 4) Epinephrine and norepinephrine are synthesized and stored within the adrenal gland. They have slightly different actions. Epinephrine increases heart rate and arterial blood pressure and acts as a bronchodilator. It binds to both the alpha- and beta-adrenergic receptors, stimulating a broad range of activities throughout the body. Norepinephrine also binds to the alpha- and beta-adrenergic receptors. The actions of norepinephrine are more limited to blood pressure and heart rate control than epinephrine. Norepinephrine causes vasoconstriction, does not dilate the airways, and cannot be used as a treatment target for bronchial constriction.

41. Receptors in the Pulmonary System (1 of 6) The activation or blocking of receptors in the pulmonary system directly impacts ventilation and gas exchange. The ANS has two main receptors types: adrenergic receptors and cholinergic receptors.

42. Receptors in the Pulmonary System (2 of 6) The adrenergic receptors can be divided into the alpha-1 (α1) adrenergic receptors, beta-1 (β1) adrenergic receptors, and beta-2 (β2) adrenergic receptors. The α1 adrenergic receptors are located in the pulmonary vasculature where they regulate vascular tone and maintain ventilation/perfusion matching. When stimulated, they produce bronchial smooth muscle contraction. These receptors are located throughout the body where their vasoconstrictive activity assists in the regulation of blood pressure, body temperature control, and mediate hunger.

43. Receptors in the Pulmonary System (3 of 6) The β1 adrenergic receptors are located in the heart and kidneys, where they regulate heart rate, cardiac contractility, and activation of the renin–angiotensin–aldosterone system. They are also found in the alveolar walls and the submucosal glands. The β2 adrenergic receptors are located in the airway smooth muscle, airway epithelium, vascular smooth muscle, and submucosal glands. Activation of these receptors leads to relaxation of bronchial smooth muscles and bronchodilation.

44. Receptors in the Pulmonary System (4 of 6) The cholinergic receptors , which are also called parasympathetic receptors, are divided into the muscarinic receptors and nicotinic receptors. The cholinergic receptors respond to the neurotransmitter acetylcholine.

45. Receptors in the Pulmonary System (5 of 6) There are five different types of muscarinic receptors (M1–M5). The functions of some of these receptors are unknown. M2 receptors have been found in the postganglionic neurons of the trachea, and M2 and M3 receptors have been identified in the bronchial smooth muscle cells. Stimulation of the parasympathetic nervous system results in the release of acetylcholine, activating these receptors and causing bronchial smooth muscle constriction.

46. Receptors in the Pulmonary System (6 of 6) There are also multiple types of nicotinic receptors. The complete function of some of these receptors is unknown. Nicotinic receptors are located in the neuromuscular junctions of skeletal muscles, the CNS, the sympathetic nervous system, and the parasympathetic nervous system. Acetylcholine binds with the nicotinic receptors in the brain and produces a pleasurable sensation. These receptors also have an affinity for nicotine, which is found in tobacco. This is likely the primary cause of nicotine addiction. Research also indicates that nicotine and the activation of these receptors may be related to the production, proliferation, and survival of malignant cells from multiple cancer types, including lung cancer.

47. Nonnoradrenergic, Noncholinergic Pathways (1 of 4) Neural pathways and receptors have been identified within the airways that do not use adrenergic or cholinergic neurotransmitters. These pathways are known as nonnoradrenergic, noncholinergic (NANC) pathways . When activated, these pathways may induce either contraction of bronchial smooth muscles and bronchoconstriction, known as the excitatory (e-NANC) pathway or relaxation of bronchial smooth muscles and bronchodilation knew as the inhibitory (i-NANC) pathway .

48. Nonnoradrenergic, Noncholinergic Pathways (2 of 4) There are three types of tachykinin receptors : NK-1, NK-2, and NK-3 receptors. Activation of the NK-2 receptors located on bronchial smooth muscle cells has been associated with bronchoconstriction, airway hyperresponsiveness, and airway inflammation. The activation of the e-NANC pathway stimulates the release of tachykinins such as substance P (SP), neurokinin A (NKA), and the peptide calcitonin gene-related peptide (CGRP), which binds and stimulates these receptors.

49. Nonnoradrenergic, Noncholinergic Pathways (3 of 4) The i-NANC pathway is associated with bronchodilation related to the release of various neuropeptides, including vasoactive intestinal peptide (VIP) and nitric oxide (NO). VIP is co-released upon cholinergic nerve stimulation with acetylcholine. VIP has been shown to be a potent systemic vasodilator and airway bronchodilator, while also decreasing pulmonary artery pressure and pulmonary vascular resistance. VIP binds with the VPAC1 and VPAC2 receptors. The VPAC1 receptor is located in the CNS, primarily in the cerebral cortex and hippocampus, and in peripheral tissues, including the liver, lungs, and intestines. Activation of this receptor facilitates vasodilation and bronchodilation by generating nitric oxide. VPAC2 receptors are located in the thalamus, hippocampus, brain stem, spinal cord and dorsal root ganglia, and smooth muscles of the cardiovascular, gastrointestinal, and reproductive systems

50. Nonnoradrenergic, Noncholinergic Pathways (4 of 4) Nitric oxide (NO) is a potent pulmonary vasodilator synthesized from l-arginine in the pulmonary vascular endothelial cells. It is produced in three isoforms: neuronal (nNOS; NOS I), inducible (iNOS; NOS II), and endothelial (eNOS; NOS III). nNOS has been found to be involved in the regulation of blood pressure and the dilation of certain vascular beds. Excess production of nitric oxide by iNOS has been associated with blood pressure decreases in septic shock. These interactions are not clearly understood. In contrast, eNOS maintains blood vessel dilation, controls blood pressure, and may have vasoprotective and antiatherosclerotic effects.

51. Histamine Receptors (1 of 2) Histamine is a neurotransmitter that is released from neurons in the hypothalamus. It is also an inflammatory mediator that is released in other areas of the body in response to injury, inflammation, or irritation by an allergen trigger. In the lungs, histamine is released by mast cells and causes bronchoconstriction. Histamine activates the histamine receptors that are located throughout the brain, spinal cord, and smooth muscles of the airways and cardiovascular system, endothelial cells, and lymphocytes.

52. Histamine Receptors (2 of 2) There are four types of histamine receptors. The H1, H2, and H3 receptors have been shown to play a role in airway disease. H1 receptors are found in smooth muscle and endothelial cells. When activated, these receptors cause bronchoconstriction and vasoconstriction, which can cause microvascular leaks and pulmonary edema. H2 receptors mediate the effects of histamine and cause limited bronchodilation; they are primarily found in the gastric parietal cells. H3 receptors play a role in bronchoconstriction and the release of neuropeptides from sensory nerves. They are found in the CNS. H4 receptors are found in the mast cells, eosinophils, T cells, and dendritic cells. These receptors regulate immune responses and do not directly affect the lungs.

53. Airway Receptors

54. Neurologic Control of Breathing and Airway Disease When selecting a medication, it is important to understand the pharmacokinetics and pharmacodynamics of the therapy. Pharmacokinetics is how the body processes a substance. In terms of medications, pharmacokinetics may be thought of as what the body does with the drug; that is, how the medication is absorbed, utilized, metabolized, and eliminated by the body. Pharmacodynamics describes what the substance does to the body; that is, whether the medication increases or decreases the heart rate, relaxes the muscles, etc. Clearance is how quickly the medication is removed from the systemic circulation. It is usually measured as the rate of drug elimination divided by plasma concentration.

55. Airway Inflammation (1 of 7) Inflammation is the normal response of the immune system to injuries and harmful substances such as bacteria and various toxins. Inflammation can occur because of an acute condition, such as a cut or infection, or it may be related to a chronic condition, such as asthma, COPD, or arthritis. Acute inflammation may be protective and beneficial; however, chronic airway inflammation may injure and damage the airways and airway anatomy. The three primary pathways that contribute to airway inflammation are the allergic pathway, the eosinophilic pathway, and the neutrophilic pathway.

56. Airway Inflammation (2 of 7) The allergic pathway triggers airway inflammation when an allergen enters the lungs and by activating T-helper type 2 (Th2) lymphocytes and the mast cells in the airways. The Th2 cells direct the release of cytokines that stimulate the B lymphocytes. The B lymphocytes, in turn, produce immunoglobulin (Ig) , a small protein molecule that attaches to the surface of the allergen or irritant and acts as a signal to the rest of the immune system to fight the invader. The term B cell proliferation is used once an Ig protein has bonded with an antigen and triggered the B lymphocytes to reproduce and make more Ig. Several different types of Ig, including IgM, IgG, IgA, IgD, and IgE, are involved in an immune response. The immune response that is associated with allergic asthma initiates the production of IgE.

57. Airway Inflammation (3 of 7) In allergic asthma, IgE attaches to receptor sites on the mast cells. The mast cells release chemical mediators, histamine and leukotrienes, which stimulate the contraction of bronchial smooth muscles, increase vascular permeability, and attract and activate leukocytes. The mast cells and Th2 cells also release cytokines, which are signaling proteins that provide cellular communication during the inflammatory response. Among the many different types of cytokines are the lymphokines, which include interleukin-2 (IL-2), IL-3, IL-4, IL-5, IL-7, IL-9, IL-15, IL-16, and IL-17. These cytokines attract additional immune cells to join in the immune response.

58. Airway Inflammation (4 of 7) Proinflammatory cytokines such as IL-1, IL-6, IL-11, tumor necrosis factor- α ( TNF- α), granulocyte-macrophage colony-stimulating factor (GM-CSF), and stem cell factor (SCF) amplify and continue the inflammatory response. Anti-inflammatory cytokines, including IL-10, IL-12, IL-18, and interferon- γ ( INF- γ) inhibit inflammation. Chemokines such as β- chemokines, α- chemokines, and regulated upon activation normal T cell expressed and secreted (RANTES); monocyte chemoattractant protein 1 (MCP-1), MCP-2, MCP-3, MCP-4, MCP-5, MIP-1 α; eotaxin; and IL-8 attract leukocytes into tissues and regulate cell trafficking.

59. Airway Inflammation (5 of 7) Eosinophilic airway inflammation overlaps with the allergic allergen pathway. Eosinophils originate in the bone marrow and are released into the circulation. They are regulated by cytokines, particularly IL-5. Eosinophils are lured from the bloodstream to the airways by chemoattractants, such as eotaxin. The eosinophils infiltrate the airway tissue and undergo cell activation. When activated, eosinophils release leukotrienes and other substances such as growth factors and metalloproteinases that have been shown to be involved in airway remodeling.

60. Airway Inflammation (6 of 7) Neutrophilic inflammation is triggered, neutrophils are recruited to the airways by various mediators, including IL-8, IL-1β, TNF-α, and leukotriene B4. In the lungs, these neutrophils become activated and release proteins, including human neutrophil elastase (HNE) and myeloperoxidase (MPO), which contribute to bronchial inflammation and to structural changes such as peribronchiolar fibrosis and emphysema. The exact mechanism and triggers of the neutrophilic inflammation pathway are unknown. However, neutrophilic inflammation in COPD has been associated with thicker secretions, a poor response to corticosteroid treatment, and a poor prognosis.

61. Airway Inflammation (7 of 7) FIGURE 6-9 Airway inflammation and mucus production in asthma, COPD, and CF. Rogers DF. Physiology of airway mucus secretion and pathophysiology of hypersecretion . Respir Care 2007;52(9):1134–1149.

62. Genotypes, Phenotypes, and Endotypes Observable characteristics or traits such as an organism’s morphology, development, and biochemical or physiologic properties are known as its phenotype . The underlying set of genes that an individual has is the person’s genotype . The interaction of the environment with an individual’s genotype is what determines their phenotype, or the characteristics of the disease that they have. An endotype is a specific biologic pathway that explains the observable properties of a disease or condition. The difference between a phenotype and an endotype is that a phenotype is defined by observable characteristics, whereas an endotype is defined by a distinct pathophysiologic mechanism or pathway that is usually measurable in some way by a laboratory test or scan. The terms are, however, often used interchangeably in some references, which can be confusing.

63. Chronic Respiratory Diseases (1 of 5) Researchers and clinicians are increasingly able to identify the specific endotypes of bronchial constrictions, airway remodeling, and inflammation, thereby developing therapeutic measures that interrupt these pathways and enabling the creation of an individualized treatment plan for a patient. The development of individualized treatment plans based on endotypes is becoming the standard of care for several pulmonary diseases, including asthma and COPD.

64. Chronic Respiratory Diseases (2 of 5) Asthma is a complex, heterogeneous, chronic disease characterized by airway inflammation, airway hyperresponsiveness, and reversible airflow limitation. Through an improved understanding of the pathophysiology of asthma, several asthma phenotypes have been identified. These include allergic asthma, nonallergic asthma, late-onset asthma, and asthma with fixed airflow limitation. These phenotypic classifications enable clinicians to treat the underlying pathophysiology, predict the patient’s likely response to therapy, and tailor treatment plans to maximize therapeutic outcomes.

65. Airway Inflammation FIGURE 6-10 Asthma is characterized by airway inflammation and hypersecretions of mucous. Both of these conditions lead to airway narrowing and obstruction of airflow.

66. Chronic Respiratory Diseases (3 of 5) Chronic obstructive pulmonary disease (COPD) is an umbrella term that describes several preventable and treatable diseases that are characterized by airflow limitation; airway inflammation; and persistent symptoms of dyspnea, cough, and sputum production. COPD occurs as a result of airway and/or alveolar abnormalities related to exposure to tobacco smoke or other noxious particles or gases in the environment. The airflow limitation in COPD is related to small airways disease and damage that has occurred to the gas-exchanging surfaces of the lung alveoli. Patients with COPD are often classified as having chronic bronchitis, emphysema, or both.

67. Chronic Respiratory Diseases (4 of 5) Chronic bronchitis is a persistent long-term inflammation of the airway and increased mucus production. This contribute to airflow limitation by narrowing the inner diameter and restricting airflow into and out of the lungs. Emphysema is characterized by damage that occurs in the alveoli in patients with COPD. In a normal lung, the alveoli look like grapelike clusters. In an individual with emphysema, the walls of the alveoli become damaged and the alveoli become one enlarged sac, rather than multiple small grapelike sacs. The loss of alveolar wall structures translates to a loss in surface area for gas exchange. Physiologically, this means the individual with COPD is not able to get a full volume/amount of oxygen into their body with a normal breath. The work of breathing increases, and in many instances arterial oxygen saturation levels decrease.

68. Chronic Respiratory Diseases (5 of 5) Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder that is caused by a mutation in the SERPINA1 gene. This mutation increases an individual’s risk of developing COPD, along with liver cirrhosis and skin and vascular disorders. Diagnosis may be done by a blood test.

69. COPD FIGURE 6-11 COPD may be characterized by chronic bronchitis, emphysema, or both. © Alila Medical Media/ Shutterstock .

70. Asthma–Chronic Obstructive Disease Overlap The term asthma–chronic obstructive disease overlap (ACO) is used to describe patients who have characteristics of both asthma and COPD. Previously, the term asthma COPD overlap syndrome (ACOS) was used to describe these individuals. However, this led to confusion, as some clinician believed ACOS to be a separate disease state.

71. Asthma–Chronic Obstructive Disease Overlap

72. Summary (1 of 2) The physical act of breathing is controlled by the nervous system. Anatomically, the human nervous system is divided into two parts: the central nervous system (CNS), which includes the brain and spinal cord, and the peripheral nervous system (PNS), which includes the nerves that are located outside of the CNS and throughout the rest of the body. The nervous system can also be classified according to its function. The sympathetic nervous system controls the fight-or-flight response that is triggered by stress or stimuli. The parasympathetic nervous system reverses the fight-or-flight process and is known as the “rest and digest” portion of the nervous system. Neurons are the basic cellular units of the nervous system.

73. Summary (2 of 2) Neurotransmitters are chemicals that carry impulses from one neuron to the receptor of another neuron. Nerves are bundles of neurons that run along specific pathways in the body. The phrenic nerve is the nerve that originates in the C3 to C5 region of the neck and then passes between the lungs and heart to reach the diaphragm. It contains motor, sensory, and sympathetic nerve fibers, but provides only motor nerves to the diaphragm. The collection of nerves that innervate the smooth muscle of the airways, blood vessels, and glands of the tracheobronchial tree is called the pulmonary plexus. The neural pathways in the lungs play a role in several airway diseases, particularly those that are characterized by airway inflammation.