Faisal I. Mohammed, MD, PhD Yanal A. Shafagoj MD, PhD

1

Respiratory systemL5

Faisal I. Mohammed, MD, PhDYanal A. Shafagoj MD, PhD

University of Jordan

Control of Breathing….Introduction Q: What the controller system is going to do? A: Homeostasis of O2, CO2, H+ Q: How? A: by: Hyperventilation or hypoventilation Q: What is the feedback system? A: ↓ PaCO2, ↑PaCO2, ↓ PaO2 (below 60 mmHg),

↓ H+, and finally ↑H+ Note: ↑PaO2 has almost no effect on the controller

system

Regulation of Respiration ….Introduction

• Sensors– gather information

• Central controller– integrate signals

• Effectors– Respiratory muscles

How alveolar ventilation VA affects PAO2 and PACO2

PAO2 depends on : 1. O2 delivery to alveoli (Alveolar Ventilation VA).2. Rate of O2 absorption to blood (O2 Consumption VO2)

PAO2 (VA/VO2)HYPERVENTILATION is when alveolar ventilation is more than CO2 production decrease PaCO2HYPOVENTILATION is when alveolar ventilation is LESS than CO2 production increase PaCO2

PACO2 = (VO2/VA)* KK”= constant (= 0.863 mmHg. lit/ml).If ventilation is doubled then PCO2 is ½If ventilation is halved then PCO2 is doubled…keeping CO2 production constant.....See the two graphs in the next two slide.

Partial pressure of oxygen in alveoli

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0 5 10 15 20 25 30Alveolar Ventilation

250 ml/min1000 ml/min

Metabolic rate

Po2

Copyright © 2011 by Saunders, an imprint of Elsevier Inc.

Partial pressure of CO2 in alveoli

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2 5 10 15 20 25 30Alveolar Ventilation

200 ml/min800 ml/min

Metabolic rate

Pco2


Objectives

Describe the respiratory centerCompare and contrast the effect of carbon dioxide and oxygen on the chemosensitive areaExplain the role of peripheral chemoreceptorsDescribe how rate and depth are controlledSummarize the process of control of respiration

REGULATION OF PULMONARY FUNCTION

Respiratory control centers: the main integrators controlling the nerves that affect the inspiratory and expiratory muscles are located in the brainstem Medullary rhythmicity center: generates the basic

rhythm of the respiratory cycle Consists of two interconnected control centers

Inspiratory center stimulates inspiration Expiratory center stimulates expiration

8University of Jordan

REGULATION OF PULMONARY FUNCTION (cont.)

The basic breathing rhythm can be altered by different inputs to the medullary rhythmicity center Input from the apneustic center in the pons

stimulates the inspiratory center to increase the length and depth of inspiration

Pneumotaxic center in the pons inhibits the apneustic center and inspiratory center to prevent overinflation of the lungs



A. Location of Respiratory Centers & Control Units1. Medullary Respiratory Centers

a. Inspiratory Area - DRG - dorsal respiratory group neurons b. Expiratory Area - VRG - ventral respiratory group neurons

2. Pontine Centers: a. Pneumotaxic Center - located in upper pons (“off switch”)b. Apneustic Center - located in lower pons (prevents turn-off)

3. Pulmonary Receptorsa. pulmonary stretch receptors (Hering-Breuer reflex)b. other receptors??

B. Control of Respiratory Activity1. Central or Medullary Chemoreceptors

2. Peripheral Chemoreceptors

3. Interaction between Central and Peripheral Chemoreceptors.

4. Cortical Factors

THE RESPIRATORY CENTER It is a loose collection of inspiratory and

expiratory neurons situated in the medulla oblongata of the brain stem. Is not a discrete identifiable center in the strict anatomical sense. When inspiratory neurons are active, expiratory neurons are inhibited and vise versa.

Brain Stem Respiratory Centers

Neurons in the reticular formation of the medulla oblongata form the rhythmicity center: Controls automatic

breathing. Consists of interacting

neurons that fire either during inspiration (I neurons) or expiration (E neurons).

Insert fig. 16.25

Respiratory Center

Figure 41-1

Chemoreceptors

2 groups of chemo-receptors that monitor changes in blood PCO2, PO2, and pH.

Central: Medulla…chemosensitive

area…sensitive to H+ Peripheral:

Carotid and aortic bodies. Control breathing indirectly

via sensory nerve fibers to the medulla (X, IX). Sensitive to O2

Insert fig. 16.27

Chemoreceptor Control

Central chemoreceptors:More sensitive to changes in arterial PC02 through H+

H20 + CO2

H+ cannot cross the blood brain barrier. C02 can cross the blood brain barrier and

will form H2C03.Lowers pH of CSF fasters than it lowers blood pH

Directly stimulates central chemoreceptors.

H+H2C03

Peripheral Chemoreceptors

• Carotid body-bifurcation of the carotids–responds to oxygen (PO2<60 mmHg)–-responds to carbon dioxide and hydrogen ion…one seventh of–The central respons but 5 times faster

0200400600800

0 200 400 600

PO2

nerv

e im

puls

es



Brain Stem Respiratory Centers

Neurons in the reticular formation of the medulla oblongata form the rhythmicity center: Controls automatic

breathing. Consists of interacting

neurons that fire either during inspiration (I neurons) or expiration (E neurons).

Insert fig. 16.25


REGULATION OF PULMONARY FUNCTION (cont.)

Factors that influence breathing: sensors from the nervous system provide feedback to the medullary rhythmicity center Changes in the PO2, PCO2, and pH of arterial blood influence the medullary

rhythmicity area PCO2 acts on central chemoreceptors in the medulla—if it increases, the

result is faster breathing; if it decreases, the result is slower breathing A decrease in blood pH stimulates peripheral chemoreceptors in the

carotid and aortic bodies and, even more so, stimulates the central chemoreceptors (because they are surrounded by unbuffered fluid) (Figure 24-32)

Arterial blood PO2 presumably has little influence if it stays above a certain level

Low arterial blood PO2 is the main stimulus for breathing in chronic smokers


Controls of rate and depth of respiration Arterial PO2

When PO2 is below 60mmHg, ventilation increases Arterial PCO2

It is the most important regulator of ventilation, small increases in PCO2, greatly increases ventilation

Arterial pH As hydrogen ions increase, alveolar ventilation

increases, but hydrogen ions cannot diffuse into CSF as well as CO2

Central (medullary) Chemoreceptors (mechanisms) the H+ (CO2) sensors

H+

blood here

brain here

cerebrospinal fluid between

25

Peripheral Chemoreceptors


A Summary of Chemoreceptor Reflexes

Brain Stem Respiratory Centers (continued)

I neurons project to, and stimulate spinal motor neurons that innervate respiratory muscles.

Expiration is a passive process that occurs when the I neurons are inhibited.

Activity varies in a reciprocal way.

Rhythmicity Center I neurons located primarily in dorsal respiratory group (DRG):

Regulate activity of phrenic nerve. Project to and stimulate spinal interneurons that innervate

respiratory muscles. E neurons located in ventral respiratory group (VRG):

Passive process. Controls motor neurons to the internal intercostal muscles.

Activity of E neurons inhibit I neurons. Rhythmicity of I and E neurons may be due to pacemaker

neurons.

Activities of medullary rhythmicity center is influenced by pons.

Apneustic center: Promotes inspiration by stimulating the I neurons

in the medulla. Pneumotaxic center:

Antagonizes the apneustic center. Inhibits inspiration.

Pons Respiratory Centers

Chemoreceptors

2 groups of chemo-receptors that monitor changes in blood PC02, P02, and pH.

Central: Medulla.

Peripheral: Carotid and aortic bodies.

Control breathing indirectly via sensory nerve fibers to the medulla (X, IX).

Insert fig. 16.27

Effects of Blood PC02 and pH on Ventilation Chemoreceptor input modifies the rate and depth of

breathing. Oxygen content of blood decreases more slowly because

of the large “reservoir” of oxygen attached to hemoglobin.

Chemoreceptors are more sensitive to changes in PC02. H20 + C02

Rate and depth of ventilation adjusted to maintain arterial PC02 of 40 mm Hg. H2C03 H+ + HC03

-

Chemoreceptor Control

Central chemoreceptors: More sensitive to changes in arterial PC02.

H20 + C02

H+ cannot cross the blood brain barrier. C02 can cross the blood brain barrier and will form

H2C03. Lowers pH of CSF.

Directly stimulates central chemoreceptors.

H+H2C03

Chemoreceptor Control (continued)

Peripheral chemoreceptors: Are not stimulated directly by changes in arterial

PC02. H20 + C02 H2C03 H+ + HCO3

-

Stimulated by rise in [H+] of arterial blood. Increased [H+] stimulates peripheral

chemoreceptors.

Chemoreceptor Control of Breathing

Insert fig. 16.29

Effects of Blood P02 on Ventilation

Blood P02 affected by breathing indirectly. Influences chemoreceptor sensitivity to changes in PC02.

Hypoxic drive: Emphysema blunts the chemoreceptor response to PC02. Choroid plexus secrete more HC03

- into CSF, buffering the fall in CSF pH.

Abnormally high PC02 enhances sensitivity of carotid bodies to fall in P02.

Effects of Pulmonary Receptors on Ventilation Lungs contain receptors that influence the brain stem respiratory

control centers via sensory fibers in vagus. Unmyelinated C fibers can be stimulated by:

Capsaicin: Produces apnea followed by rapid, shallow breathing.

Histamine and bradykinin: Released in response to noxious agents.

Irritant receptors are rapidly adaptive receptors. Hering-Breuer reflex:

Pulmonary stretch receptors activated during inspiration. Inhibits respiratory centers to prevent undue tension on lungs.

Pulmonary Disorders Dyspnea:

Shortness of breath. COPD (chronic obstructive pulmonary

disease): Asthma:

Obstructive air flow through bronchioles. Caused by inflammation and mucus secretion.

Inflammation contributes to increased airway responsiveness to agents that promote bronchial constriction.

IgE, exercise.

Pulmonary Disorders (continued) Emphysema:

Alveolar tissue is destroyed. Chronic progressive condition that reduces surface area for gas

exchange. Decreases ability of bronchioles to remain open during

expiration. Cigarette smoking stimulates macrophages and leukocytes

to secrete protein digesting enzymes that destroy tissue. Pulmonary fibrosis:

Normal structure of lungs disrupted by accumulation of fibrous connective tissue proteins. Anthracosis.

Disorders Caused by High Partial Pressures of Gases

Nitrogen narcosis: At sea level nitrogen is physiologically inert. Under hyperbaric conditions:

Nitrogen dissolves slowly. Can have deleterious effects.

Resembles alcohol intoxication. Decompression sickness:

Amount of nitrogen dissolved in blood as a diver ascends decreases due to a decrease in PN2. If occurs rapidly, bubbles of nitrogen gas can form in tissues and

enter the blood. Block small blood vessels producing the “bends.”

Hypoxia - O2 deficiency at the tissue level. There could be several causes.

1. Hypoxic-hypoxia (PO2 of arterial blood is reduced). e.g., breathing O2-poor gas or at reduced atmospheric pressures. When PO2 of inspired air falls to about 60-70 mmHg there is loss of consciousness (alv. PO2 ~35-40 mm Hg).

At sea level when breathing in an environment with 10% or less O2, you are in trouble. With altitude, composition of air remains about same but there are pressure changes. Delayed effects of altitude Acclimatization

2. Anemic-hypoxiaEssentially low Hb content. Also in CO poisoning, effective Hb content is reduced by HbCO

complexing.

3. Stagnant-hypoxiaHypoxia due to circulation that is so slow that tissue does not receive its necessary "flow" of

O2. Shock, congestive heart failure (or localized restriction) can lead to damage of important organs.

4. Histotoxic-hypoxiaInhibition of tissue oxidative processes by poisons. e.g., Cyanide poisoning - combines with

cytochrome oxidase preventing O2 from serving as the ultimate electron acceptor.

RESPONSES TO CHANGE IN RESPIRATORY GASES

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Faisal I. Mohammed, MD, PhD Yanal A. Shafagoj MD, PhD