Human Respiratory System

• Ventilation (breathing) is the term for the movement of air to (inspiration) and from (expiration) the alveolus.

• Exhalation / expiration is followed by inhalation / inspiration. They are brought about by Nervous System and respiratory muscles.

• Medulla generate impulses to respiratory muscles.

Mechanism of Breathing2

Respiration is the sequence of events that results in gas exchange between the environment and the body cells.

External Respiration

Internal Respiration

A- External respiration: Involves gas exchange (O2 and CO2) with the external environment: exchange between lungs and blood.

B. Involves gas exchange between the blood and tissues.

Internal respiration or Cellular Respiration: is process of ATP production by cells.

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1. Gas exchange between the air in the alveoli and the blood in the pulmonary capillaries is achieved by simple diffusion.

2. The blood coming into pulmonary capillaries is rich in CO2 and poor in oxygen.

External Respirati

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3. CO2 diffuses from higher concentration in the blood across the walls of alveolar capillaries to lower concentration in the air in the alveoli.

4. The blood coming into pulmonary capillaries is oxygen poor and the alveolar air is oxygen-rich.

5. Oxygen diffuses from higher concentration in alveoli across the walls of the alveolar capillaries to the lower concentration in the blood.

6. The end result is that alveoli contain high concentrations of CO2 and low concentration of O2 this situation changes by exhalation.

Exhalation is followed by inhalation of atmospheric air which contains little CO2, and high O2 levels.

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Diffusion is very rapid due to :

Very large surface area of the lungs: Human lungs have at least 50 times the skin’s surface area.

Very small diffusion distance between the air in the alveoli and the blood in the pulmonary capillaries.

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Respiratory Systems

Air–blood barrier contains 2 types of cells:

A-capillary endothelial cell

B-alveolar cell: alveolar cells are two types: type I type II and macrophages.

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• The human respiratory system includes conducting region and respiratory region.

• Conducting region is everything that conducts air to and from the lungs; the lungs lie deep within the thoracic cavity for protection against drying.

• Air moves into the nose, crosses the pharynx, flows through the glottis (an opening into the larynx or voice box) to the trachea, bronchi, bronchioles, and finally the alveoli, where gas exchange occurs.

• This process filters debris, warms the air, and adds moisture (humidification).

• When the air reaches the lungs, it is at body temperature and is saturated with water.

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The larynx, or voice box, is located at the entrance of the trachea. The larynx houses the vocal folds (vocal cords). The vocal folds are situated just below where the tract of the pharynx splits into the trachea and the esophagus. As air passes across vocal cords they vibrate creating sounds.

When food is being swallowed, the glottis is closed by the epiglottis.

Beyond the larynx the trachea divides into two main branches, the right and left bronchi, which enter the right and lift lung respectively.

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Respiratory Systems 1

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Trachea and bronchi are lined with cilia that beat upward carrying mucus, dust, and any food particles that went the wrong route.

The trachea walls are reinforced with C‑shaped rings of cartilage.

Within the lungs, each bronchus branches into numerous bronchioles that conduct air to alveoli.

Alveoli are microscopic air sacs.

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Respiratory Zone:

Function: Gas exchange.

Structures are :

1. Respiratory bronchioles

2. Alveolar duct

3. Alveoli.

Alveoli are microscopic air sacs.

Histology of Alveolar Wall1. Type I pneumocyte (P I cells): Covers 95% of alveolar wall surface area. They are flat cells (too thin to have organelles), which makes them very suitable for gas exchange.

2. Type II pneumocyte (P II cells): Rounded cells, cover 3% of alveolar surface. These are plump / cuboidal with surface microvilli. They produce the surfactant which reduces water surface tension.

3. Alveolar macrophages constitute a small percentage, but represent the main cellular host defense mechanism in the alveolar space. They are part of the mononuclear phagocyte system and are derived primarily from blood Monocytes.

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Each alveolus is surrounded by a network of pulmonary capillary

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In late fetal life: Type II cells start to develop at about 24 weeks of gestation, secreting small amounts of surfactant. However, adequate amounts of surfactant are not secreted until about 35 weeks of gestation - this is the main reason for increased incidence rates of infant respiratory distress syndrome (IRDS).

P-II cells secrete a phospholipid (like phosphatidyl choline, phosphatidyl glycerol,…) that lowers surface tension; called surfactant (surface active agent), that prevents alveoli from collapsing during expiration.

IRDS: Premature babies are sometimes born with lungs with insufficient surfactant, and their alveoli collapse.

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Infant respiratory distress syndrome: also called Hyaline membrane syndrome.

Without surfactant the surface tension causes the alveolus to collapse after each breath rather than remain inflated. Each breath therefore is difficult.

Lungs are covered by double layer membrane called PLEURA,

Parietal pleura that is attached to the bony thorax

and

Visceral pleura that is attached to the lung surface.

In between the parietal and visceral pleura exists a cavity containing a thin fluid named pleural cavity.

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Air movement into and out of the lungs occurs due to pressure differences induced by changes in lung volumes.

Air flows from higher to lower pressure areas. It is directly proportional to pressure difference.

When intrapulmonary pressure is lower than atmospheric pressure it is called subatmospheric pressure OR negative pressure.

Humans respire using a tidal ventilation mechanism; negative pressure in the lungs allows for air flow during inspiration.

During inhalation, lowering the diaphragm and raising the ribs forms a negative pressure by increasing the volume of the thoracic cavity; the air–under greater outside pressure–flows into the lung.

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Boyle's law

Pressure of a gas is inversely proportional to its volume (at fixed temp.).

During (inspiration)

Lung volume intrapulmonary pressure air goes in.

Create negative pressure in the thoracic cavity and lungs, and then air flows into the lungs.

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Mechanics of Breathing (pulmonary ventilation)

Phases of Breathing:

1- inspiration (inhalation)

2-expiration (exhalation)

They are due to increasing and decreasing thorax and lungs volumes.

For inspiration to occur, lungs must be able to expand/stretch (compliance); for expiration to occur, lungs must get smaller (elasticity). The tendency to get smaller is also aided by surfactant.

Increasing volumes by muscle contractions that lower the diaphragm and raise the ribs.

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24Inspiration Versus Expiration

Contraction of diaphragm & external intercostal muscles lung volume intrapulmonary pressure forces air into lungs.

• Inhalation

• Active process

During quiet breathing contraction of diaphragm and external intercostals expands thoracic cavity

Decreases pressure (Boyle’s law – volume inversely related to pressure)

Air flows down pressure gradient.

Mechanics of inspiration

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Forced / deep inspiration

Contraction of accessory respiratory muscles: these are

1-Scalene

2-Pectoralis minor

3-Sternocleidomastiod

Which will increase the volume anteriorly and posteriorly.

Mechanics of expiration Quiet expiration totally passive mechanism lungs recoil (elasticity) to their original size due to muscles relaxation.

Diaphragm relaxation &external interalcostal muscles relaxation lung volume intrapulmonary pressure forces air out of lungs.

• Exhalation during quiet breathing is passive process due to: Recoil of elastic fibres & inward pull of surface tension of alveolar fluid

• Forced expiration: results from:

1-The contraction of internal intercostal muscles depresses the rib cage.

2- Abdominal muscles contract putting pressure on the internal organs which push against the diaphragm moving it up which decrease the volume of thorax.

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Pulmonary Function Test.

Pulmonary function may be assessed clinically by means of a technique known as spirometry, the record of the breathing is called a spirogram.

It records:

1- lung volume

2- lung capacity

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Lung Volumes.1. Tidal volume (TV; 500 ml): volume of gas inspired/expired of restful breathing. 2. Inspiratory reserve volume (IRV; 3000 ml): maximum volume that can be inspired during forced breathing other than tidal volume.3. Expiratory reserve volume (ERV; 1300 ml): maximum volume of gas that can be expired during forced breathing other than tidal volume.4. Residual volume (RV; 1200 ml): volume of gas remaining in the lungs after vital capacity (VC) expiration.

Lung Capacities: sum of two or more lung volumes.

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7. Vital capacity (VC; 4700 ml): maximum air that can be expired after a maximum inspiration.

8. Forced Expiratory volume (FEV): amount of gas that can be expired forcedly in 1s, 2s, 3s.

Gas Exchange in the LungsAt sea level, one atmosphere = 760 mmHg (or 760 torr).

760 mmHg was measured by Barometer.

Atmospheric pressure is made of a mixture of gases so its pressure is equal to the sum of the pressures exerted by each gas.

Dalton's law: In a mixture of gases, each gas exerts pressure (partial pressure; P) in proportion to its percentage in the total mixture.

Since O2 percentage in atmosphere is 21% then

PO2= 760 × 21/100= 160 mmHg.

At High altitudes: total atmospheric pressure is low (PO2 is low)

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Partial Pressures of Gases in Blood, Lungs & Tissues

Alveoli air PO2 = 105 mmHg (only 60 mmHg O2 can saturate Hb) and PCO2 = 40 mmHg.

Arterial blood PO2 = 100 mmHg; PCO2 = 40 mmHg.

Peripheral tissue PO2 = 40 mmHg; PCO2 = 46 mmHg.

Venous blood PO2 = 40 mmHg; PCO2 = 45 mmHg.

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Regulation of respiration

1. Neural regulation

2. Chemical regulation

• Nervous regulation

There are respiratory centers in the

Medulla oblangata----rhythmicity center that controls automatic breathing.

Pons----- pneumotaxic and apneustic centers (fine tuning of breathing).

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Medulla oblangataThe inspiration center automatically generates impulses in rhythmatic spurts رشات .

These impulses travel along nerves to respiratory muscles to stimulate their contraction. The result is inhalation.

As lung inflate baroreceptors in the lung tissue detect this stretching, and generate sensory impulses to medulla. These impulses depress the inspiration center .This is named Hering–Breuer inflation reflex.

As inspiration center is depressed the result is decrease in impulse to respiratory muscles which relax to bring about exhalation.Then inspiration center become active again in another cycle.

When the is more forceful exhalation as during exercise, the inspiration center activates the expiration center, which generate impulses to internal intercostal muscles and abdominal muscles.

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Pons----- pneumotaxic and apneustic centers (fine tuning of breathing).

Apneustic center promotes inspiration.

Pneumotaxic center inhibits inspiration .

These centers receive impulses from the cerebral cortex, hypothalamus, spinal cord, periphery and from stretch and compression receptors in the lung.

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Factors that influence respiration39

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Respiratory Systems

There are 2 groups of chemoreceptors that monitor changes in blood PCO2, pH, and PO2:

1. Central chemoreceptors in medulla oblongata

2. Peripheral chemoreceptors in the aorta and carotid arteries.

Regulation of respiration cont.2. Chemical regulation

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• Peripheral chemoreceptors include: aortic bodies, located around aortic arch (send sensory information to medulla in the vagus nerve), and carotid bodies (send sensory signals via glossopharyngeal nerve; IX) located at the point where each common carotid artery branches into internal and external carotid arteries .

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Peripheral chemoreceptors

Chemoreceptor input to the brain stem modifies the rate and depth of breathing so that arterial PCO2, pH & PO2 remain relatively constant

Respiratory Systems

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1-Hypoventilation PCO2 & pH (due to formation of carbonic acid, which splits releasing H+). However, blood O2 content decreases much more slowly because of the large “reservoir” of O2 attached to hemoglobin (Hb).

CO2 + H2O → H2CO3 → H+ + HCO3

Hyperventilation PCO2 & pH, but does not significantly increase O2 content, as Hb in arterial blood is 97% saturated with O2 during normal ventilation.

Thus, Aortic & carotid bodies are not stimulated directly by blood CO2, but are stimulated by a rise in [H+] of arterial blood, which occurs when blood CO2 (and thus H2CO3), is raised.

Peripheral Chemoreceptor

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MedullarychemoreceptorsArterial PCO2 blood H+, however,

H+ cannot cross blood-brain barrier (cannot influence medullary chemoreceptors), but CO2 can and through the formation of H2CO3, lowers cerebrospinal fluid pH.

Medullary chemoreceptor response requires few minutes before it gets into action. The immediate increase in ventilation that occurs when PCO2 rises is due to peripheral chemoreceptors stimulation.

Respiratory Systems 4

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Respiratory Systems

• Hypercapnia (increase of CO2 in arterial blood).

• PCO2 & pH (due to formation of carbonic acid, which splits releasing H+).

• Blood and other body fluids are more acidic, medulla respond by increasing ventilation.

• Hypercapnia normally triggers a reflex which increases breathing and access to oxygen, such as arousal and turning the head during sleep. A failure of this reflex can be fatal, as in sudden infant death syndrome.

• hypercapnia can be accompanied by respiratory acidosis.

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Respiratory Systems

• Respiratory acidosis is a medical condition in which decreased ventilation (hypoventilation) causes increased blood carbon dioxide concentration and decreased pH.

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Respiratory acidosis –

occurs when the rate or

efficiency of respiration decreases.

Respiratory Systems

Hypocapnia

• Is a isiiis stateof reduced carbon dioxide in the arterial blood. Hypocapnia usually results from deep or rapid breathing, known as hyperventilation.

• hypocapnia causes cerebral vasoconstriction, leading to cerebral hypoxia and this can cause transient dizziness, visual disturbances, and anxiety. A low partial pressure of carbon dioxide in the blood also causes alkalosis, leading to lowered plasma calcium ions and increased nerve and muscle excitability. This explains the other common symptoms of hyperventilation, muscle cramps and tetany in the extremities, especially hands and feet.

• Because the brain stem regulates breathing by monitoring the level of blood CO2, hypocapnia can suppress breathing to the point of blackout from cerebral hypoxia.

• Respiratory alkalosis – occurs when the rate of respiration increases.

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Effects of Blood PO2 on VentilationThe O2 content of the blood decreases much more slowly because of the large reservoir of O2 attached to Hb.

So blood PO2 has little effect on breathing.

(low PO2 chemoreceptor sensitivity to PCO2 changes).

PO2 of arterial blood must fall from 100 mmHg to 50 mmHg before ventilation is stimulated.

This stimulation is due to a direct PO2 effect on carotid bodies. Since this degree of hypoxemia does not occur at sea level, PO2 does not normally exert direct effect on breathing because of the large reservoir of attached to Hb.

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Gas Exchange and Transport1. Gas exchange between the air in the alveoli and the blood in the pulmonary capillaries is primarily by diffusion.

2. Atmospheric air contains little CO2, but blood flowing in the pulmonary capillaries has a higher concentration of CO2.

3. CO2 diffuses from higher concentration in the blood across the walls of alveolar capillaries to lower concentration in the air in the alveoli.

4. The blood coming into pulmonary capillaries is oxygen poor and the alveolar air is oxygen-rich.

5. Oxygen diffuses from higher concentration in alveoli across the walls of the alveolar capillaries to the lower concentration in the blood.

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Hemoglobin (Hb) & O2 Transport

In each 100 mL of oxygenated blood:

1.5% of O2 is dissolved in plasma

98.5% is bound to Hb; oxyhemoglobin (Hb-O2).

Hb consists of 4 polypeptides; 2 -chains & 2 -chains. Each chain contains a heme group with Fe2+ (ferrous iron). The iron atom of a heme group loosely binds with an O2 molecule.

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3 Types of Hemoglobin1- oxyhemoglobin

2-Methemoglobin (met-Hb) : Oxidized Hb has Fe++ in the oxidized (Fe3+/ferric) state. Met-Hb thus lacks the e- it needs to form a bond with O2 and cannot participate in O2 transport. Blood normally contains only a small amount of met-Hb, but certain drugs can increase this amount.

3- Carboxyhemoglobin: the reduced heme is combined with CO instead of O2. Since the bond with CO is 210 times stronger than the bond with O2, CO remains attached to Hb.

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Oxygen-binding ability of hemoglobin a. The percentage of oxygen-binding sites of hemoglobin carrying O2 varies with partial pressure of O2 in the immediate environment.

b. At a normal partial pressure of O2 in lungs, hemoglobin becomes practically saturated with O2.

d. At the O2 partial pressures in the tissues, oxyhemoglobin quickly unloads much of its O2.

e. The acid pH and warmer temperature of the tissues also promote this dissociation.

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Loading and Unloading Reactions

In the lungs: loading reaction

Deoxy-Hb + O2 oxy-Hb;

In tissues (unloading reaction) occurs.

Oxy-Hb Deoxy-Hb + O2

Loading/unloading reactions are affected by: PO2 and Hb affinity to O2.

In the lungs, the oxy-Hb saturation is 97% (20 ml O2 /100 ml blood). This is reduced to 75% (15.5 ml O2 /100 ml) in blood leaving tissues.

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CO2 Transport

Carbon dioxide transport:

~9% dissolved in plasma

~13% attached to Hb as carbaminohemoglobin

~78% converted to bicarbonate ion HC03-

CO2 + H2O H2CO3 H+ + HCO3-

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Body tissue

Capillarywall

Interstitialfluid

Plasmawithin capillary

CO2 transport

from tissuesCO2 produced

CO2

H2O

H2CO3 HbRedbloodcell Carbonic

acid

Hemoglobin (Hb)picks up

CO2 and H+.

H+HCO3

Bicarbonate

HCO3

To lungs

CO2

CO2

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HCO3 CO2 transport

to lungs

H2CO3

H2O

H+

HbHemoglobin

releasesCO2 and H+.

CO2

Alveolar space in lung

To lungs

HCO3

CO2

CO2

CO2

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