4/10/2016

Regulation of Respiration

• Nervous system regulation – Various levels of activity produce different demands – Medulla – Regulation of respiratory rate Respiratory Regulation and • PaCO 2 normal range 35-45 mmHg Respiratory Disease

Medullary Control Center in Brainstem Regulation of Respiration Pons Medulla Pontine respiratory centers ó Nervous system regulation interact with the medullary respiratory centers to smooth ó Hyperventilation: increased depth and rate of the respiratory pattern. Ventral respiratory group (VRG) breathing that exceeds the body’s need to remove contains rhythm generators whose output drives respiration. CO Pons 2 Medulla ó Causes CO 2 levels to decline (hypocapnia) Dorsal respiratory group (DRG) integrates peripheral sensory ó pH increases (alkalosis) input and modifies the rhythms generated by the VRG. To inspiratory ó Hypoventilation : decreased rate and depth of muscles breathing Diaphragm ó Causes CO 2 levels to increase (hypercapnia) External ó pH decreases (acidosis) intercostal muscles

Figure 22.23

Regulation of Respiration Regulation of Respiration

– Nervous system regulation • Nervous system regulation • Medullary control center – Higher brain centers – Diffuse system of neurons • Cerebral cortex – Direct signals from the cerebral motor cortex bypass medullary » Separate pathways for inspiration and controls expiration – Example: voluntary breath holding • Hypothalamus – Limbic system can modify rate and depth of respiration – Examples: breath holding that occurs in anger or gasping with pain, laughing, crying

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Regulation of Respiration Regulation of Respiration • Chemoreceptors ↑pCO 2 (hypercapnia) • Nervous system control – Central – Peripheral chemoreceptors • pCO 2 most potent stimuli • Carotid and aortic bodies ↑ pCO 2 in the brain • ↑CO 2 levels are the most powerful respiratory stimulant central chemoreceptor in the • Also respond to ↓ pO 2 and pH medulla stimulated

↑ respiratory rate

• Note that pO 2 has no effect here

Arterial P Peripheral Chemoreceptors CO 2

Brain P decreases pH in CO 2 brain extracellular fluid (ECF) Sensory nerve fiber in cranial nerve IX (pharyngeal branch of glossopharyngeal) Central chemoreceptors Peripheral chemoreceptors + External carotid artery in medulla respond to H in carotid and aortic bodies in brain ECF (mediate 70% (mediate 30% of the CO 2 Internal carotid artery of the CO 2 response) response) Carotid body Afferent impulses Common carotid artery Cranial nerve X (vagus nerve) Medullary respiratory centers Sensory nerve fiber in cranial nerve X Efferent impulses Aortic bodies in aortic arch Respiratory muscle Aorta

Ventilation Heart (more CO 2 exhaled) Initial stimulus Arterial P and pH Physiological response CO 2 return to normal Result

Figure 22.26 Figure 22.25

Regulation of Respiration Regulation of Respiration

• High altitude • High altitude – – Quick travel to altitudes above 8000 feet may pO 2 ≤ 60 mm Hg = major stimulus for respiration • produce symptoms of acute mountain sickness Peripheral chemoreceptors sense low O 2 = increase (AMS) respiration rate » Headaches, shortness of breath, nausea and dizziness – Hyperventilate → respiratory alkalosis » In severe cases, lethal cerebral and pulmonary edema

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Regulation of Respiration Regulation of Respiration

• • Chronic CO 2 retention disorders Baroreceptors – CSF buffers reduce central chemoreceptor control – ↓ blood pressure = ↑ respiration • – Rely on paO 2 Relatively small influence and poorly understood • Excessive O 2 administration = apnea! – Example: emphysema

Regulation of Respiration Regulation of Respiration

• Exercise • Neural factors cause increase in ventilation as – Intensity and duration exercise begins – Hyperpnea – increase in depth of breathing – Psychological stimuli • Increase in ventilation (10 to 20 fold) in response to • Anticipation of exercise metabolic needs – Simultaneous cortical motor activation of skeletal • Depth of respiration increases more than rate muscles and respiratory centers • pCO , pO , and pH remain surprisingly constant during 2 2 – Excitatory impulses reaching respiratory centers exercise – from proprioceptors pCO 2 may decrease

Higher brain centers Respiratory Diseases (cerebral cortex—voluntary control over breathing) Other receptors (e.g., pain) + • COPD and emotional stimuli acting – through the hypothalamus – Emphysema + – Respiratory centers – (medulla and pons) Asthma • Pneumonia Peripheral chemoreceptors + • Tuberculosis + O2 , CO 2 , H + – Stretch receptors in lungs • Lung cancer Central Chemoreceptors – • CO , H + Cystic fibrosis 2 + Irritant receptors Receptors in • Smoking muscles and joints

Figure 22.24

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COPD COPD

ó Chronic obstructive pulmonary disease (COPD) – ó End-stage condition of patients with 2 or more of: History of smoking in 80% of patients ó Emphysema – Symptoms ó Asthma • Dyspnea ó Chronic bronchitis – Labored breathing (“air hunger”) • Coughing Irreversible decrease in the ability to force air out • Frequent pulmonary infections of the lungs • Respiratory failure (hypoventilation) accompanied by respiratory acidosis

Peak Flow Meter Emphysema

Used to assess rate of exhalation in • Word literally means “inflation” obstructive lung disease • Destruction of alveolar walls – Leads to large but inelastic alveolar spaces – Consequences 1. Must work hard during expiration (enlist accessory muscles)

2. Bronchioles collapse during expiration (CO 2 trapping) 3. Pulmonary capillaries damaged → increased pulmonary resistance → decreased blood flow to lung → right ventricular systolic dysfunction

Emphysema Emphysema • Almost exclusively associated with smoking – Exception: pre-term infants • Smoking inhibits production of alpha- antitrypsin which normally stabilizes lysosomes of alveolar marcrophages • Without it, lysosomes rupture and release destructive enzymes

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Asthma Asthma • “To pant” • Active airway inflammation – Immune response caused by production of IgE and recruitment of inflammatory cells • Smooth muscle spasms of bronchioles → reduced air flow • Often associated with bronchiolar edema – Increased wall thickness = impaired diffusion

Asthma Asthma

ó Affects 1/10 in USA • Treatment ó More common in children – Short term relief: inhibit bronchiolar smooth ó Triggers muscle ó Allergens • Epinephrine not usually first line ó Stressful state • Inhaled beta-2 agonists ó Exercise – i.e. albuterol • Inhaled corticosteroids ó Viral infection – Long term control • Removal of allergen or trigger

Pneumonia Pneumonia

• Infection &/or inflammation within the lung • – Pathogens Usually treated with antibiotics • Bacterial, viral, or fungal • Eighth most common cause of death in U.S. – Aspiration • Chemicals • Ingested material

• Edema/inflammation → increase wall thickness → impaired diffusion

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Tuberculosis (TB) Tuberculosis (TB)

– Caused by the bacterium Mycobacterium tuberculosis ó Symptoms • Related to the organism that causes leprosy ó Fever, night sweats, weight loss, racking cough, spitting up blood – Airborne • Affects lungs but may become systemic ó Treatment • May remain dormant in lungs ó 12-month course of antibiotics – Phagocytosis by macrophage → M. tuberculosis ó Extensively drug resistant resists destrucon → survives in macrophage phagolysosome → carried throughout body → infects other organs → reactivates during periods of immune suppression

Lung Cancer • Leading cause of cancer death • Most common types – Adenocarcinoma • From glandular structures in epithelial tissue – Squamous cell carcinoma • From squamous epithelial cells • Slow-growing – Small cell carcinoma • Immature, undifferentiated Tuberculosis creates cavities visible in x-rays cells of neuroendocrine nature like this one in the patient's right upper lobe . • Fast-growing

Lung Cancer Lung Cancer • Highly metastatic • Mesothelioma – Early detection is crucial – Cancer of the plurae of the lung • Most common sites of metastasis – Almost exclusively caused by exposure to – Other lung asbestos • Naturally-occurring, highly durable fiber – Adrenals • Once used for many purposes - fire-proof vests, – Bone building insulation, fabric, added to concrete – Brain – Asbestos fibers are inhaled and become – Liver embedded in the lungs

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Cystic Fibrosis Cystic Fibrosis

ó Secretion of abnormally viscous mucus • Most common lethal genetic disease in North ó Respiratory America ó Clogged airways, infections • Lung disease accounts for most deaths ó Digestive • Some now living into their 40’s ó Clogged ducts, decreased enzyme function ó Excretory ó Electrolyte imbalances

Smoking Smoking

• Effects • Lung cancer leading cause of cancer death in – Nicotine constricts terminal bronchioles U.S. for men and women – Systemic vasoconstriction – Most die within one year after diagnosis – Increased mucus secretion by goblet cells • COPD – Impairment of cilia – Inhibits alpha-antitrypsin production – Carbon monoxide binds Hb – Decrease in collagen production

Acid-Base Disturbances Respiratory • óCauses Acidosis – ó Abnormal control of breathing Hypoventilation → low pH, elevated CO 2 ó Accumulation of acidic or basic chemicals in body – Causes • óRespiratory vs. metabolic CNS depression (head injury, drugs) • Impaired respiratory muscle function (spinal cord óArterial blood gases injury, neuromuscular disease, muscle relaxants) • Pulmonary diseases

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Respiratory Metabolic • Alkalosis • Acidosis – – + Hyperventilation → high pH, low CO 2 Excessive H – Causes • Organic acid production, loss of base, reduced excretion → low pH, low HCO - • Psychological (fear, pain, anxiety) 3 • Causes • Respiratory stimulants – Renal failure • Increased metabolic states (fever, pregnancy, sepsis) – DKA – Starvation – Ingestion of salicylates

Metabolic Compensation • Alkalosis • Respiratory acidosis – Deficient H + – • Loss of acid, low K +, Cl -, consumption of alkaline Kidneys retain base - • substances → high pH, high HCO 3 Respiratory alkalosis • Causes – Kidneys excrete base – Excessive use of antacids or bicarbonates • Metabolic acidosis – Protracted vomiting – – Gastric suction Hyperventilation will lower paCO 2 – Use of diuretics • Metabolic alkalosis – Excess aldosterone – Hypoventilation will raise paCO 2

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