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1 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA RESPIRATORY SYSTEM Functions of respiratory system: 1. Interchange of gases: To carry O2 from lungs to the tissues for internal respiration and to bring back CO2 to the lungs for excretion through expiration. 2. Maintenance of pH: This function is carried out by balancing excretion of CO2. 3. Maintenance of Circulation: It affects the heart rate and cardiac output. Blood pressure also changes during respiration. 4. Excretion: Volatile substances like ammonia, ketone bodies, water vapor and certain drugs like diethyl-ether etc. are excreted through expiration. 5. Metabolic function: It helps in maintaining homeostasis of metabolism in the tissue. 6. Temperature regulation: Heat is lost through the expiratory air. 7. Water regulation: Water vapor is partly excreted during expiration from the lungs. ANATOMY OF RESPIRATORY SYSTEM: The respiratory system is divided into two as upper and lower respiratory system. The upper respiratory system consists of nose, pharynx and associated structures. The lower respiratory system consists of larynx, trachea, bronchi and lungs. Study of the pathological conditions and diseases affecting upper respiratory system is known as Oto-Rhino-Laryng- Ology (Oto Ear, Rhino Nose, Larynx Throat, Ology - Study) the doctor who treats such conditions and diseases is known as ENT (Ear, Nose and Throat) specialist. The doctor who treats the diseases of lungs is known as Pulmonologist. 1. NOSE: The nose is divided into external and internal nose. External nose is formed by the supportive frame work of: Bones: frontal bone, nasal bone, maxillae and bony framework of external nose and Hyaline cartilages: septal cartilage forms the anterior portion, lateral cartilage forms the inferior portion and alar cartilage forms the wall of nostrils with muscle, skin and mucus membrane. External opening of the external nose are called external nares (naris singular) or nostrils. Functions: 1. Warming, moistening and filtering of the inspired air. 2. Detecting olfactory stimuli (sense of smell). 3. Modification of speech vibrations by resonating chamber. Rhino - nose, rhinitis - inflammation of the nose, rhinoplasty - surgery of nose.

Respiratory system

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1 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

RESPIRATORY SYSTEM

Functions of respiratory system:

1. Interchange of gases: To carry O2 from lungs to the tissues for internal respiration and

to bring back CO2 to the lungs for excretion through expiration.

2. Maintenance of pH: This function is carried out by balancing excretion of CO2.

3. Maintenance of Circulation: It affects the heart rate and cardiac output. Blood

pressure also changes during respiration.

4. Excretion: Volatile substances like ammonia, ketone bodies, water vapor and certain

drugs like diethyl-ether etc. are excreted through expiration.

5. Metabolic function: It helps in maintaining homeostasis of metabolism in the tissue.

6. Temperature regulation: Heat is lost through the expiratory air.

7. Water regulation: Water vapor is partly excreted during expiration from the lungs.

ANATOMY OF RESPIRATORY SYSTEM:

The respiratory system is divided into two as upper and lower respiratory system. The

upper respiratory system consists of nose, pharynx and associated structures. The lower

respiratory system consists of larynx, trachea, bronchi and lungs. Study of the pathological

conditions and diseases affecting upper respiratory system is known as Oto-Rhino-Laryng-

Ology (Oto – Ear, Rhino – Nose, Larynx – Throat, Ology - Study) – the doctor who treats

such conditions and diseases is known as ENT (Ear, Nose and Throat) specialist. The doctor

who treats the diseases of lungs is known as Pulmonologist.

1. NOSE: The nose is divided into external and internal nose.

• External nose is formed by the supportive frame work of:

– Bones: frontal bone, nasal bone, maxillae and bony framework of external

nose and

– Hyaline cartilages: septal cartilage forms the anterior portion, lateral cartilage

forms the inferior portion and alar cartilage forms the wall of nostrils with

muscle, skin and mucus membrane.

– External opening of the external nose are called external nares (naris –

singular) or nostrils.

Functions:

1. Warming, moistening and filtering of the inspired air.

2. Detecting olfactory stimuli (sense of smell).

3. Modification of speech vibrations by resonating chamber.

Rhino - nose, rhinitis - inflammation of the nose, rhinoplasty - surgery of nose.

2 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

• Internal nose is a large cavity (nasal cavity) in the interior of skull lined with muscle

and mucus membrane.

– Internal nares or choane are the 2 openings for communication with pharynx

it is divided into a series of groove like passages called the superior, middle

and inferior meatuses.

– Four paranasal sinuses run parallel to the external nose. Paranasal sinuses and

nasolacrimal ducts open into the internal nose lined with olfactory epithelium

responsible for sense of taste.

– Paranasal Sinus positioned within some of the bones of the skull, these are

spaces filled with air and lined by mucous membrane. The sinuses comprise

frontal and maxillary (a pair of each), ethmoidal (a group of small spaces), and

two sphenoid sinuses. They drain into the nasal cavities). When a person has

an upper respiratory infection, the sinuses sometimes become infected: this

causes pain, purulent discharge from the nose and obstruction of the nasal

passages causing sinusitis.

– Nasal septum divides nasal cavity into right and left.

3 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

2. Pharynx (throat): Funnel shaped tube approximately 13 cm long which, starts at internal

nares and ends at larynx’s cricoid cartilage. It is situated anterior to cervical vertebrae and

posterior to nasal/oral cavities and composed of skeletal muscles.

Functions:

– As passage of air and food.

– Resonating chamber for sound.

– House of tonsils in immunological reactions.

Anatomically 3 portions are there in the pharynx:

1. Nasopharynx – (helps to adjust pressure b/w pharynx and middle ear) superior portion

with openings to internal nares, ear and oropharynx, contain pharyngeal tonsil.

2. Oropharynx – middle portion, opening called fauces to mouth-possess respiratory and

digestive function, palatine and lingual tonsils are found here.

3. Laryngopharynx – opens down to esophagus also has respiratory and digestive

function.

3. Larynx (voice box): It connects the pharynx and trachea, sited in the midline of neck

anterior to esophagus and made of nine piece of cartilage:

1. Thyroid cartilage/Adam’s apple: consists of 2 fused cartilages in triangular shape, it is

larger in male.

2. Epiglottis (glottis- tongue): It is a large leaf shaped structure with tapered stem and

broad superior leafy portion. Glottis portion consists of pair of folds of mucus

membrane called vocal folds and space between them is called Rima glottides.

3. Cricoid cartilage: They are rings of hyaline cartilage attached with trachea and

thyroid cartilage by ligaments.

4. Arytenoid cartilage (paired): It is triangular attached above the cricoid attached to

vocal folds.

5. Corniculate cartilages (paired): It is found at the apex of arytenoid cartilage and it

supports epiglottis.

6. Cuneiform cartilages (paired): It is a club shaped cartilages above cuneiform which

supports the vocal folds.

4 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

5 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

4. Trachea (wind pipe): It is the tubular passage for air, it is approximately 12 cm long and

2.5 cm in diameter and situated anterior to the esophagus. It starts from larynx and extends to

the 5th thoracic vertebra where it divides into 2 primary bronchi.

• 4 layered:

– Mucosa & sub mucosa - which provide protection from dust particles and

produces mucus.

– Hyaline cartilage: It consists of 16-20 horizontal, incomplete ‘C’ shaped rings

stalked upon each other, open ends has trachealis muscle which, helps to

adjust with esophagus expansion.

– Adventitia connect trachea to other surrounding tissues.

Adventitia is the outermost connective tissue covering of any organ, vessel, or other structure.

5. Bronchi (wind pipe): At the 5th thoracic vertebra trachea divides into 2 i.e. right and left

primary bronchi. The right enters into right lung and left into left lung. Primary bronchi also

consist of incomplete cartilages. The Internal ridge where right and left bronchi divide is

called carina where mucus membrane is most sensitive. The primary bronchi divides to

secondary (lobar) bronchi and then to tertiary (segmental) bronchi then to bronchioles and

then to terminal bronchioles. This extensive branching is called bronchial tree.

• Right pulmonary bronchus is more vertical, longer and wider. Aspired air enters more

into right lung. Right has 3 lobes.

• Branching of bronchi to bronchioles includes pseudo-stratified cuboidal epithelium.

The columnar becomes non ciliated simple cuboidal epithelium.

• No Goblet cells are present here. Goblet cells are glandular simple columnar epithelial

cells whose function is to secrete mucin a protein, which dissolves in water to form

mucus.

6 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

• Incomplete rings give away to cartilages and cartilage decreases leaving more and

more smooth muscle. This can result in muscle spasm.

6. Lungs: light weight, paired, cone shaped, situated in the thoracic cavity. The heart lies in

between the lungs in the mediastinal space. It has got lobes which are divided by fissures.

The oblique fissure present on both the lungs anteriorly and posteriorly. It divides the lungs

into superior and inferior lobes. The horizontal fissure which is only present in the right lung

divides it into middle and inferior lobes. The pleural membrane which is made up of 2 layers

of serous membrane encloses and protects the lungs. The parietal pleural membrane is

superficial to thoracic wall and the visceral pleural membrane covers the lungs. The pleural

cavity is the space between the pleural membranes lubricates, reduces friction and helps in

breathing.

• Pneumothorax is the condition if the air gets inside the pleural space; hemothorax (or

haemothorax/Haemorrhagic pleural effusion) is a condition that results from blood

accumulating in the pleural cavity. Atelectasis (from Greek: "incomplete" +

"extension") is defined as the collapse or closure of the lung resulting in reduced or

absent gas exchange.

• Lungs are positioned above the diaphragm, just inferior to clavicles. Base is broad and

concave. Apex is narrow and in the superior portion. The coastal surface is the area of

lungs surface which comes in contact with the ribs. Hilum is the place where bronchi,

pulmonary vessels, lymph vessels and blood vessel enter in to the lungs. The root

consists of the above structures, pleura, connective tissue all held together. Cardiac

notch is a concave cavity of left lung where the heart is situated. Right lung has

shorter broader and thicker structure, due to the presence of liver below.

• Left lung is 10 % shorter than right lung as it accommodates the heart.

7 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

• Right lung has 3 lobes and the left lung has 2 lobes. The primary bronchi divide into

secondary bronchi and secondary to tertiary bronchi, each secondary bronchus divides

into 10 tertiary bronchi. Lobules consist of small compartment of bronchopulmonary

segment with lymphatic vessels, arterioles, venules and terminal bronchiole. Each

terminal bronchiole forms respiratory bronchiole which, divides into 2-11 alveolar

ducts.

• Around the alveolar ducts numerous alveoli and alveolar sacs are present. Alveolus is

a single cup shaped pouch. The alveolar sac consists of 2 or more alveolus with a

common opening.

• Alveolar cells are of 2 types. The type 1 simple squamous cells for gases exchange.

The type 2 or septal cells are rounded, few in number and secretes alveolar fluid

containing surfactant which is a mixture of complex phospholipids and lipoproteins. It

also contains alveolar macrophages which protect and remove the dust particles.

8 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

Respiratory membrane: The membrane wall between alveolar and capillary wall, having 0.5

micron thickness and formed of 4 layers.

• One layer of type 1, type 2 cells and macrophages. One layer of epithelial basement

membrane of alveolar wall and the capillary basement membrane fused to the

epithelial membrane.

• The capillary endothelium allows rapid diffusion of gases. The lungs consist of 300

million alveoli having a surface area of 70 m2 for gas exchange.

Blood supply:

• Lungs receive oxygenated blood supply from aorta via bronchial Arteries.

• Pulmonary artery carries deoxygenated blood from heart to lungs for oxygenation.

• Pulmonary Veins carry oxygenated blood from lungs back to heart for systemic

circulation.

• The circulation of blood from heart through pulmonary artery to lungs for

oxygenation and the circulation of the oxygenated blood back to heart by pulmonary

veins are known as pulmonary circulation.

• Ventilation perfusion coupling: It is constriction of arterioles in response to hypoxia

resulting in diversion of blood flow from poorly ventilated area to highly ventilated

areas for oxygenation.

9 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

3. (A) Voice production:

Structures:

Glottis portion of larynx consists of pair of folds of mucus membrane. The superior

pair of folds is called ventricular/false vocal folds and the inferior pair is called true vocal

cords and the space between ventricular folds is called rima glottides. The laryngeal muscles

are attached to cartilages and vocal folds to produce vibrations.

Process:

1. When laryngeal muscles contracts they pull posterior cricoarytenoid muscles and

moves vocal folds apart (abduction) and the rima glottidis becomes open.

2. When lateral cricoarytenoid muscles contracts moving the vocal folds together and

rima glottidis become narrow/closed (adduction). Other intrinsic muscles also can

elongate or shorten vocal folds.

3. Increased tension on vocal folds causes folds to vibrate rapidly at high pitch and vice

versa. Androgens cause male vocal folds to be thicker, so that it vibrates slowly and

have low pitch in males when compared with females. Pharynx, mouth, nasal cavity,

paranasal sinuses acts as resonating chambers and gives voice the individual quality.

Respiration: It is the process of gas exchange in our body. It includes 3 processes:

1. Pulmonary ventilation/breathing: It includes inhalation (inflow) of atmospheric air for

oxygenation and exhalation (outflow) of alveolar air of lungs after oxygenation.

2. External pulmonary respiration: It includes exchange of gases between alveoli of

lungs and blood in pulmonary capillaries across respiratory membrane. In this process

blood gains O2 and blood loses CO2.

10 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

3. Internal tissue respiration: It includes the exchange of gases between blood in

capillaries and tissue cells. In this process blood loses O2 and gains CO2.

Inhalation/inspiration/breathing in:

• It is an active process breathing in the atmospheric air is called inhalation/inspiration.

As per Boyle’s law, when volume increases the pressure decreases. Before respiration

the pressure inside the lungs is equal to air pressure of atmosphere which is equal to

760 mm of hg i.e. equal to1 atmosphere (1 atm.) Then pressure inside the lung

decreases by increased lung volume causing air to flow in. For inhalations lungs must

expand, this needs the contraction of muscles of inspiration.

Muscles of inspiration:

1. Diaphragm: It is a dome shaped skeletal muscle at the floor of thoracic cavity innervated

by phrenic nerve. The contraction causes the flattening and lowering of its dome, increasing

vertical diameter of thoracic cavity. In normal breath the diaphragm descends downwards by

1 cm. and in strenuous breath by 10 cm. The pressure difference ranges from 1-3 mm of hg to

100 mm of Hg. The volume of air inhaled during normal breath is 500ml and in strenuous

breath it is 2-3 Liters. Diaphragm is responsible for the 75 % of air entering lungs during

inhalation.

2. External intercostal muscles: Its contraction causes elevation of ribs, increased anterio-

posterior and lateral diameter of chest cavity and is responsible for the 25 % of air entering

lungs during inhalation. Accessory muscles are contracted during deep forceful inhalation.

The sternocleidomastoid muscle elevates the sternum and the scalene muscle elevates the first

2 ribs.

11 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

Intra pleural pressure during the quiet inhalation is always sub atmospheric i.e. 756 mm of

hg, contraction of diaphragm and external inter coastal muscles further decreases it to 754

mm of Hg. Expansions of the parietal and visceral pleura occur and are pulled along the

thoracic cavity. The alveolar pressure of 760 also drops to 758 mm of Hg and a pressure

difference is established and the air enters into the lungs.

Exhalation or expiration: The process of breathing out is called exhalation and it is based

on the pressure gradient in the opposite direction i.e. the pressure inside the lung is more than

the atmospheric pressure of 760 mm of Hg.

Normal exhalation: It is a passive process and no muscle contraction is involved. It results

from elastic recoil of chest wall and lungs. Recoiling of the elastic fibers stretched during

inhalation occurs and inward pulls of surface tension due to the fill of alveolar fluid in the

alveoli. The relaxation of muscles of inhalation, diaphragm and the external intercostal

muscles decreases the lung volume. Hence the alveolar pressure increases to 762 mm of Hg

and as a result the air flows out.

During forceful exhalation: During the forceful exhalation like playing the wind instruments,

contracts the muscles of exhalation like the rectus abdominus and other abdominal muscles.

The contraction moves the inferior rib downwards and compresses the abdominal viscera

forcing diaphragm superiorly. The contraction of the internal Intercostal muscles pulls the rib

anteriorly and thereby reduces the surface area and volume which forces out the air inside the

lungs.

The other factors affecting the pulmonary ventilation are:

1. Surface tension of alveolar fluid: It causes the alveoli to assume the smallest possible

diameter and it also accounts for 2/3rd of elastic recoil of the lungs, which decreases the

size of alveoli during exhalation.

2. Compliance of lungs: It is the effort required to stretch the lung and chest wall. Higher

the compliance, the lungs expands rapidly and normally. In TB and pulmonary edema

the intercostal muscles are paralyzed, which decreases the compliance of the lungs.

3. Air way resistance: The resistance to the flow of air especially by bronchioles with the

signals from sympathetic system results in relaxation of air wall. The pathological

conditions like COPD, asthma and chronic bronchitis constricts/contracts the air ways.

4. Eupnoea: It is the normal pattern of breathing (inhalation and exhalation).

5. Coastal breathing: It is the shallow (not deep) chest breathing.

6. Diaphragmatic breathing: It is the deep abdominal breathing, where strong contraction

of diaphragm occurs.

7. Modified respiratory movements: It includes the movements like coughing, sneezing,

sighing, yawning, sobbing, crying, laughing, hiccoughing, valsalua maneuer.

12 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

Lung volumes: The normal respiratory rate is 12 breathes per minute.

1. Tidal volume: It is the volume of one breath which is approximately equal to 500 ml.

2. Minute ventilation: It is the total volume air that enters in each minute which is equal to

the normal respirator rate multiplied by tidal volume (12 x 500 = 6 L).

3. Anatomic dead space: It is the conducting air ways where the air present does not

undergo respiratory exchange (30% of air = 150 ml).

4. Alveolar ventilation rate: It is the volume of air that reaches respiratory zone per

minute (350x12 =4200 ml).

5. Inspiratory reserve volume: It is the additional volume of air that can be inhaled by

taking a very deep breath (3100ml in male, 1900ml in female).

6. Expiratory reserve volume: It is the additional volume of air that can be exhaled

forcibly as far as possible after a normal inhalation (1200 ml in male, 700 ml in

female).

7. Forced expiratory volume FEV 1.01 second: The volume of air that can be exhaled

from the lungs in one second with maximal effort following a maximal inhalation.

8. Residual volume: The considerable volume of air remaining in the lungs even after

expiratory reserve volume cannot be measured by spirometer (1200 male, 1100

female).

9. Minimal volume: If thoracic cavity is cut opened, intra-pleural pressure rises and forces

out some residual volume, the air remaining after this is called minimal volume.

Fetal lung: If there is no air in the lungs of fetus, the condition is knows as still born and the

lung will not float in water.

Lung capacities: They are combinations of various or specific lung volumes.

• Inspiratory capacity: It is the sum of tidal volume and inspiratory reserve volume

(500+3100/1900).

• Functional residual capacity: It is the sum of residual volume and expiratory

reserve volume (1200+1200/1100+700).

• Vital capacity: It is the sum of inspiratory reserve volume, tidal volume and

expiratory reserve volume (3100+500+1200/1900+500+700=4800/3100).

• Total lung capacity: It is the sum of vital capacity and residual volume

(6000/4200).

Spirometer: A device to test how the lung is working (used for Pulmonary Function Tests)

to assess the effects of lung disease or the progress of treatment and the procedure is called

spirometry. The spirometer records the total volume of air breathed out – the forced vital

capacity. The machine also records the volume of air breathed out in one second i.e. the

forced expiratory volume. In diseases such as asthma, in which the airways are obstructed,

the ratio of the forced expiratory volume to the forced vital capacity is reduced.

13 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

Transport of gases:

Oxygen transport:

• O2 does not easily dissolve in water and hence only 1.5% in dissolves in blood plasma

which is 95% of water. Rest of the oxygen i.e. 98.5% gets bound with Hb in RBC. In

100 ml of blood there is 20 ml gaseous O2 out of which 19.7 ml bound to Hb, 0.3 ml

in is dissolved in blood plasma.

• Hb is made up of a haem part and a protein globulin part. Haem has 4 iron atoms and

each combines with 1 O2. So only that 1.5 % dissolved in plasma diffuses out of tissue

capillaries into tissue cells.

Determinants /factors of O2 transport:

1. Partial pressure of O2: If the partial pressure of oxygen high then more O2 binds to Haem.

Binding of Hb with O2 forms HbO2 (oxyheamoglobin). If Hb is fully saturated then it is

completely bound. In the pulmonary capillaries PO2 is high i.e. 100-105 mm of Hg hence O2

binds to Hb easily. In tissue capillaries PO2 is low hence dissolved O2 is unloaded, diffused to

tissue cells and only 95 % of the O2 gets unloaded from Hb.

• If PO2 is between 60-100 mm of Hg. Hb is 90 % saturated with O2.

• If 40 mm of Hg. Hb is 75% saturated.

• If 20 mm of Hg. Hb saturation is 35%.

• So that people can still perform at higher altitudes where PO2 is less.

In active tissues PO2 reaches below 40 mm of Hg. The O2 gets unloaded from HbO2, and

hence more O2 available for tissue respiration.

14 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

2. Acidity & PH:

• As the acidity increases pH of blood decreases. As a result more O2 dissociates from

Hb because affinity of Hb decreases. Lactic acid, carbonic acid etc. get increases

during exercise hence the O2 dissociation. Due to high concentration of H+ it will get

bind to Hb at the same time O2 diffuses out from Hb.

• Bohr Effect states that when pH increases Hb dissociation curve shifts to right side i.e.

at given PO2 Hb is less saturated with O2.

3. Partial pressure of CO2:

• The effect is similar to that of H+ as PCO2 increases, Hb releases O2 more readily, and

because CO2 also binds to Hb. CO2 itself increases acidity by formation of carbonic

acid.

• CO2 enters to the blood and temporarily converted to carbonic acid, by the enzyme

carbonic anhydrase, so that H+ is increased and O2 affinity gets decreased.

• CO2+H2O (water in plasma)H2CO3 (Carbonic acid)H++HCO3 (Bicarbonate ions).

4. Temperature:

• Increase in temperature leads to increased O2 release from Hb and heat is the

byproduct of all metabolic reactions. Metabolically active cells release acid along

with heat during metabolism which results in increased O2 release.

• In hypothermia only less O2 is released, so more O2 remain bounded to Hb.

5. BPG – 2, 3 BIPHOSPHOGLYCERATE:

• It is found in RBC, formed during glycolysis. When BPG binds to Hb – O2 binding to

Hb is decreased.

– Greater the BPG more O2 gets diffuses into the plasma. Thyroxine, Growth

Hormone, Nor-Adrenalin, Adrenalin, Testosterone increases BPG formation.

– At Higher altitudes people will have more BPG.

• Hb – HbA- adult, HbF-foetal differ in structure and affinity for O2, HbF more affinity

to O2, transfer more O2 at human placenta

• Carbon monoxide (CO) is 200 times stronger than O2; even at lower concentration

CO of 0.1% and PCO of 0.5 mm of hg it combines with half of Hb in blood hence can

be fatal. If CO is inhaled and intoxicated the lips, oral mucosa appears in bright red

color. Antidote includes giving pure O2.

Carbon dioxide transport:

• Deoxygenated blood, 100 ml = 53 ml gaseous CO2

15 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

• Transport in 3 forms

– Dissolved CO2 - 7 % in dissolution in blood plasma – diffuse in alveoli

– Carbamino compounds – 23% with amino groups of amino acids in protein in

Hb, Hb+CO2HbCO2 carboxyhaemoglobin. Carbaminohaemoglobin formed

at high PCO2 as high in tissues.

– Bicarbonate ions – 70 % as bicarbonate in plasma HCO3-

– CO2 enters RBC

– CO2 + H2O H2CO3 H+ + HCO3- by enzyme carbonic anhydrase.

16 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

• HCO3- diffuses out RBC

1. Down the concentration gradient &

2. Exchange – Cl- enters the cell.

• This exchange maintains the electrical balance b/w plasma and RBC – called chloride

shift.

• HCO3- in blood plasma reaches lungs, reaction reverses CO2 out.

• Haldane effect – relationship b/w CO2 transport and CO2 carrying capacity.

• Lower the oxyhaemoglobin higher the CO2 carrying capacity.

• Deoxy Hb binds to CO2 transport more CO2.

• Deoxy Hb buffers H+ more than O2, so remove H+ ions from solution and promote

CO2H2CO3

17 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

External and Internal Respiration:

External respiration:

• Process of external respiration happens in the pulmonary capillaries. Oxygen from

inhaled air crosses the pulmonary capillaries across the respiratory membrane into the

RBC and at the same time CO2 diffuses out into alveoli and then to the expired air.

Internal respiration:

• Process of respiration happens in systemic capillaries where oxygen from RBC

diffuses into tissue cells and carbon dioxide from tissue cells escapes into RBC.

Control of respiration:

• Each minute 200 ml O2 is used. The exercise increases it to 15 - 20 folds and in

trained athletes it increased to 30 times.

Control by:

– Respiratory center and medullary rhythmicity area in the medulla.

– Pneumotaxic area situated in the upper pons.

– Apneustic area situated in the lower pons.

18 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

Regulated by:

– Cortex of brain.

– Chemoreceptors situated centrally in the medulla, aorta and carotid bodies.

– Proprioceptors.

– Inflation reflux (HERING BREUR reflex).

Respiratory Centre: The nerve impulse from widely dispersed clusters of neurons alters the

size of thorax.

1. Medullary rhythmicity area: It is situated in medulla oblongata and controls the basic

rhythm of respiration. There are 2 areas: The inspiratory area responsible for inspiration and

the expiratory area responsible for expiration.

Quiet breathing (Duration is 5 seconds):

• First 2 seconds: The inspiration area nerve impulses are active for first 2 seconds

resulting in external intercostal and diaphragm contraction, which results in breathing

in and it gets inactive after 2 seconds stopping the inspiratory process.

• Last 3 seconds: Both inspiratory area and expiratory area are inactive and hence there

is no impulse, which results in the relaxation of muscles for inspiration and results in

breathing out.

Forceful breathing: At first the inspiratory area followed by active expiratory area are

triggered causing first contraction of external intercostal muscles and diaphragm followed

by contraction of internal intercostal and abdominal muscle during. The external

intercostal muscles and diaphragm relaxes during contraction of internal intercostal and

abdominal muscles.

2. Pneumotaxic area: It is present in the upper pons and coordinates transition between

inhalation and exhalation. It transmit inhibitory impulse to inspiratory area i.e. turn off

inspiratory area which makes the duration of inhalation shorter and breathing rate becomes

rapid.

3. Apnuestic area: It is present in the lower pons and sends stimulatory impulses to

inspiratory area which activates and prolongs inhalation resulting in long deep inhalations.

• The active pneumotaxic area overrides apneustic area.

Regulation of respiration: The basic rhythm of inspiratory area is modified by various

influences like:

The influence of cortex:

• Voluntarily we can inhibit the reflux to breathe, for a short time, protection from

water, irritating gases entering lungs etc. but is limited because increased CO2 and H+

activate inspiratory area overriding voluntary control.

19 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

• By hypothalamus and limbic system with emotional stimuli (laughing and crying)

modifies the respiratory rhythm.

Chemoreceptor regulations:

• Central chemoreceptors in medulla in CNS sense the changes in H+, PCO2 in CSF and

make changes in respiration rate and depth.

Peripheral nervous system:

• Aortic bodies are cluster of chemoreceptors in wall of arch of aorta part of

vagus nerve sense the percentage of oxygen in the oxygenated blood and

adjust the rate and depth of respiration by giving feedback mechanisms.

• Carotid bodies are oval nodules in wall of left and right common carotid

arteries, part of glossopharyngeal nerve sense the percentage of oxygen in the

oxygenated blood and adjust the rate and depth of respiration by giving

feedback mechanisms.

Sensitive to the changes of PO2, H+, PCO2 in blood:

• Normal PCO2 is 40 mm of Hg in the arteries and any short change in PCO2 leads to

hypercapnea, hypercarbia and regulates respiration.

Responds to deficiency of O2: If PCO2 falls below 50 mm of Hg and increase in PCO2 & H+,

participate in -ve feedback system cause hyperventilation till PCO2 & PO2 becomes normal.

Hypoxia: The condition in which there is a lower O2 level in tissues.

Proprioceptor stimulation:

• Exercise: It stimulates respiration (as PCO2 increase, PO2 decrease and H+ increase).

• From proprioceptors: The proprioceptor in joints and muscles stimulates respiration.

• Stretch sensitive: Sensitive to pressure differences e.g. baroreceptors in walls of

alveoli.

Proprioceptors: Sensory nerve endings in the muscles, tendons and joints which signal to the

brain their position relative to the outside world and the state of contraction of the muscle.

During movement, a regular flow of information to the brain from the proprioceptors, the

eyes and ears ensures that actions are coordinated and the body’s balance maintained.

Inflation reflex (Hering breur reflex): The over inflation of lungs during inspiration

stimulates stretch receptors and inspiratory area and stops further inhalation, as exhalation

begins lungs deplete and stretch receptors no longer stimulated. The inspiratory and apneustic

area are no longer inhibited and a new inflation begins, this protective mechanism for

preventing excessive inflation of lung is called inflation reflex.

20 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA

Other factors influencing respiration:

1. Limbic system stimulation: The emotional changes activates excitatory signal to

inspiratory area.

2. Temperature: The increased temperature increases respiration.

3. Pain: Sudden pain and apnea or prolonged somatic pain can increase respiration.

4. Stretching of anal sphincter: The stretching of anal sphincter muscle increases

respiration. It is a technique used in the new born to increase respiration.

5. Irritation of airways: There are 2 types of irritations based on irritating agents: The

physical and chemical irritation, which will decrease respiration.

6. Blood pressure: The sudden rise in BP decreases respiration and drop in BP increases

respiration.

IMPORTANT QUESTIONS OF RESPIRATORY SYSTEM.

1. Describe the right lung. (5)

2. Regulation of respiration. (10)

3. Anatomy of respiratory tract and mention the functions of trachea. (5)

4. Explain the events that occur in inhalation and exhalation. (5)

5. Explain the exchange of gases in external and internal respiration. (5)

6. Mechanism of respiration. (5)

7. Draw and label the parts of respiratory system. Discuss the mechanism of respiration.

(10)

8. Structure and function of respiratory system. (5)

9. With the help of a neat labelled diagram outline the parts of respiratory system and

illustrate the process involved in CO2 transport in our body. (10)