Anatomy and Structure of the

Gaseous Exchange System

(a) [PA] describe the structure

of the human gas exchange

system, including the

microscopic structure of

the walls of the trachea,

bronchioles and alveoli with

their associated blood vessels;

Bronchiole and Trachea in transverse section

Several different types of tissues made of specialised cells work together to form a functional unit whose purpose is to deliver air to and remove air from the gas

exchange surface of the alveoli

(b) [PA] describe the distribution of

cartilage, ciliated epithelium, goblet

cells and smooth muscle in the

trachea, bronchi and bronchioles;

Airway Number Approximate

diameter

Cartilage Goblet

cells

Smooth

muscles

Cilia Site of gas

exchange

Trachea 1 1.8cm Yes Yes Yes Yes No

Bronchus 2 1.2cm Yes Yes Yes Yes No

Terminal

bronchiole

48 000 1.0mm No No Yes Yes No

Respiratory

bronchiole

300000 0.5mm No No No Yes No

Alveolar

duct

9 x 106 400µm No No No No Yes

Alveoli 9 x 109 250µm No No No No Yes

(c) describe the functions of cartilage,

cilia, goblet cells, smooth muscle and

elastic fibres in the gas

exchange system;

Cells:

Ciliated cells - the most numerous of the cell types, extend through the full thickness

of the epithelium. The epithelium is pseudostratified. The base of every cell actually

rests on the basement membrane, therefore it is simple, not stratified. However, the

epithelial cells are of different heights, there are short basal cells and tall columnar

cells, and their nuclei are seen at different levels. This gives the epithelium a stratified

appearance. Because it contains tall cells, it is called a pseudostratified, columnar

epithelium.

Function: provide a coordinated sweeping motion of the mucus coat - "ciliary

escalator" to the pharynx - that serves as an important protective mechanism for

removing small inhaled particles

Mucus (goblet) cells - are interspersed among the ciliated cells and also extend

through the full thickness of the epithelium. Goblet cells are interspersed among the

ciliated cells and also extend the full length of the epithelium. The mucinogen granules

are found in the cytoplasm at the apical end. The thick mucus extends the apical end,

rendering the cell wineglass-shaped (hence its name). The nucleus is flattened at the

base of the mucus cup.

Function: unicellular mucin-secreting

Brush cells - you will not be able to distinguish in standard preparations. Columnar

cells that bear microvilli. The basal surface is in synaptic contact with the

afferent nerve endings that penetrate the basal lamina.

Function: receptor cells of general sensation

Cartilage

Ciliated epithelium

Smooth Muscle

Longitudinal Muscle

Elastic Tissue

Goblet Cells

Pseudostratified ciliated

columnar epithelium

Pseudostratified ciliated

columnar epithelium

Simple squamous epithelium

Submucosa

- serous and mucous glands in the submucosa of the

trachea.

- The serous glands secrete a watery proteinaceous product,

while the mucous glands secrete a viscous, heavier product

called mucus.

- The ducts of the glands pass through the layer(submucosa)

and epithelium to empty into the lumen (surface)

- The lumen is obscured as it approaches the epithelium.

(This is a frequent phenomenon of sectioning.)

Cartilage- The matrix of cartilage typically stains a purplish color

(depending on the preparation).

- Staining is most intense around the cartilage cells, which are

called chondrocytes and sit in spaces called lacunae.

- Chondrocytes are often found in clusters.

- The chondrocytes occupy the whole lacuna, but they

frequently shrink during preparation, and the lacunae appear

as spaces around cells.

- Function: provide flexibility to the tracheal pipe and maintain

the lumen of being opened.

- The trachealis muscle is smooth muscle. Its functions to

narrow the tracheal lumen so when you cough, the narrower

the trachea, the faster the air moves and can propel

whatever is making you cough out of the trachea.

Hyaline cartilage

Smooth muscle- One of three types of muscle found in the body (cardiac and skeletal being the other two). The muscle is involuntary, which means that it is controlled by the autonomic nervous system. Movement alters size of the

bronchial lumen

Elastic fibre- Found in connective tissue, the fibre can stretch up to 1.5 times its normal size and springs back. It works in conjunction with smooth muscle to maintain a ‘stressed’ airway. It is said to give the structure “recoil” ability to return

back to its usual shape and size.

Bronchus Artery Pair

Bronchus

Bronchiole

Respiratory Bronchioles

Respiratory Bronchioles

Respiratory Bronchiole with

alveolar duct

(d) describe the process of gas

exchange between air in the

alveoli and the blood;

Alveoli

• Alveoli have a very thin epithelial lining

• surrounded by many blood capillaries that

carry deoxygenated blood.

• They provide a short distance and a large surface

area over which oxygen and carbon dioxide can be

exchanged.

• They also contain elastic fibres which expand to

allow air in and snap back to help force out air.

Features of the mammalian lung that enable efficient gas

exchange

• Individual alveoli are only

100-300 micrometers

across, very numerous

(about 300-500 million)

total surface area =

approx 70 m2

• Alveoli walls are one cell

thick, plasma membranes

surround a very thin layer

of cytoplasm.

• Capillary wall is only one

cell thick

Features of the mammalian lung that enable efficient gas

exchange

• Cells are squamous,

flattened

• Capillaries in close

contact with alveolus

wall

• Capillaries very narrow

so RBCs are squeezed

close to the walls and

so close to the air in the

alveoli

Features of the mammalian lung that enable efficient gas

exchange

Surfactant (inner alveolar

lining) produced by cells of

the alveolar surface

(a) lowers the surface tension

of the fluid layer lining the

alveolus, prevent the

alveolus from collapsing;

Easier to breath

(b) Speeds up transport of O2

and CO2 between air and

the liquid lining the

alveolus

(c) Helps to kill any bacteria

which reach the alveoli.

Features of the mammalian lung that enable efficient gas

exchange

• Total diffusion distance

from inside alveolus to

inside RBC is only about

1 micrometer

• Ventilation and blood

transport maintains

concentration gradients

of oxygen and carbon

dioxide for efficient gas

exchange

Gaseous Exchange in the

alveolar

• Oxygen diffuses across

the barrier of epithelium

of the alveolus and the

endothelium of the

capillary.

• Passes into the blood

plasma

• Combines with the

haemoglobin the red

blood cells to form

oxyhaemoglobin.

• CO2 diffuses in the

reverse direction from

the blood to the alveoli.

• Diffusion is efficient because

• Alveoli have a large surface

area

• The gases have a short distance

to travel

• A steep diffusion gradient is

maintained by ventilation

• A good blood supply and the

presence of an oxygen-carrying

compound hemoglobin.

• Surfactant is present.

(e) describe the effects of tar

and carcinogens in tobacco

smoke on the gas exchange

system;

(g) describe the effects of

nicotine and carbon monoxide

on the cardiovascular systems;

Lung diseaseCardiovascular

DiseasesCoronary Heart

Disease

Lung cancer

Emphysema

Chronic bronchitis

COPD

Atherosclerosis

Strokes

Angina

Heart failure

Heart attack

Tobacco smoke

• There are three main components that are

hazardous to health.

(i) Nicotine

(ii) Carbon monoxide

(iii)Tar

• Nicotine - is the addictive element of

cigarettes, stimulates the nervous system

to reduce arteriole diameter and release

adrenaline –

• increasing heart rate and blood

pressure.

• Causes increased stickiness of blood

platelets, which increases the risk of

blood clotting.

• Carbon monoxide - combines irreversibly

with haemoglobin meaning that oxygen

cannot bind effectively.

• This causes a strain on the heart muscle

because it must pump more to provide the

same amount of oxygen

• Tar - settles in the lungs and stimulates a

series of changes that lead to obstructive

lung disease and lung cancer

(f) describe the signs and

symptoms of lung cancer and

chronic obstructive pulmonary

disease (emphysema and

chronic bronchitis);

(h) explain the link between

smoking and atherosclerosis,

coronary heart disease and

strokes;

Lung Cancer

• tar in tobacco smoke contains several

carcinogens.

• These can make DNA in epithelial cells lining

the lungs mutate, which is the first step

towards a malignant tumour.

• This tumour then develops into the lymphatic systemafter spreading through bronchial epithelium

• it is here, in the lymph system where cancerous cells can break away and spread around the organ, causing secondary tumours.

Chronic Obstructive Pulmonary Disease

(a) Chronic bronchitis

- Inflammation of the lining of the air

passages and may be chronic or acute.

- Acute bronchitis usually lasts a few days

only and is a side effect of an infection like a

cold.

- Chronic bronchitis has a gradual onset and

last for a longer duration than its acute

counterpart.

• Most commonly caused by smoking and to a lesser extent air pollution.

• Tars in the cigarette smoke causes the inflammation

• Secretion of excess mucus from the goblet cells in response to the irritation

• Smoking destroys/paralyses the cilia which normally sweep away the nucleus – inhibits the cleaning action of the cilia.

• Frequent coughing of greenish-yellow sputum.

• Breathlessness increase as damaged epithelia are replaced by scar tissues narrowing the bronchi and bronchioles.

(b) Emphysema

• Inflammation of the constantly infected lungs

causes phagocytes to leave blood and line the

airways.

• To reach the lining of the lungs from the

capillaries, phagocytes release elastase

• This enzyme destroys elastin in the walls of

the alveoli

• Elastin is responsible for the recoil of the

alveoli when we breathe out

• Bronchioles collapse during exhalation,

trapping air in the alveoli, which burst

• Hence there is a reduced of surface area for

gaseous exchange, causing breathlessness.

Cardiovascular Disease

• Cardiovascular diseases are degenerative

diseases of the heart and circulatory system

• And are caused by many factor -

multifactorial

• diseases that involve the heart or blood

vessels (arteries and veins)

(a) Artherosclerosis

(b) Coronary heart disease

(c) Strokes

• Related to nicotine and carbon monoxide

found in cigarette smoke.

Nicotine and Cardiovascular Disease

• NICOTINE is a CENTRAL NERVOUS SYSTEM

stimulant that acts on nerves throughout the

body.

• In the cardiovascular system, nicotine

stimulates the nerves that regulate smooth

MUSCLE tissue, causing smooth muscle cells

to contract.

• This constricts blood vessels, notably arteries,

reducing the channel for blood flow.

• Nicotine further stimulates the baroreflexsensors (clusters of NERVE cells in the major arteries and the heart that sense the flow and pressure of blood).

• These actions result in increased blood pressure, HEART RATE, and cardiac workload.

• Nicotine further acts as an irritant within the arteries, causing INFLAMMATION of the inner layer of the arterial wall.

• Researchers believe such inflammation may be the foundation for atherosclerosis.

CO and cardiovascular disease

• Carbon monoxide is a poison. It has a greater

affinity than oxygen for HAEMOGLOBIN and

binds with hemoglobin to form

carboxyhaemoglobin, blocking haemoglobin

from carrying oxygen.

• This reduces the amount of oxygen that

enters the bloodstream from the LUNGS.

CO and cardiovascular disease

• By the end of a cigarette, a smoker can have

concentrations of carbon monoxide as high as

7%; 10% is the level at which symptoms of

carbon monoxide poisoning begin to become

apparent.

• Carbon monoxide in the bloodstream deprives

cells in the BRAIN and heart, which rely on

oxygen for fuel

Atherosclerosis

• Starts with accumulation of fatty materials in

artery walls.

• Reduces flow of blood to tissues and may also

increase the chance of blood clots forming

within the artery, obstructing the flow of

blood entirely.

• Build up which contains cholesterol, fibres,

dead muscle cells and platelets is called

atheroma.

• Once fibers are deposited in the cholesterol,

and these often start to calcify and become

hard, a process known as arteriosclerosis.

Normal

cross

section

of the

artery

wall.

Damage to

artery wall

possibly by

high blood

pressure,

CO or

nicotine

Fatty

material is

deposited in

vessel wall.

Atheroma

deposits in

the inner

wall and

roughening

the artery

Narrowed

artery

becomes

blocked by

a blood clot

Stroke

• A stroke occurs when an artery in the brain

(a) Bursts so that blood leaks into brain tissues

(brain haemorrhage)

(b) Is blocked due to artherosclerosis or a

thrombus.

Stroke

• The brain tissue in the area supplied by the

artery is starved of oxygen and dies (cerebral

infarction)

• A stroke may be fatal or cause mild or severe

disability.

• Depending on how large the area of brain

infected.

Coronary Heart Disease

• Two coronary arteries branch from the aorta

to supply all the muscles of the atria and the

ventricles.

• Coronary heart disease is a disease of these

arteries that causes damage to or malfunction

of the heart.

• Three forms of coronary heart disease:

(a) Angina pectoris

(b) Heart attack

(c) Heart failure

Angina pectoris

• Severe chest pain brought on by exertion (e.g.

exercise)

• Pain is caused by severe shortage of blood to the

heart muscle, but there is no death to the heart

tissue.

Heart Attack

• A.k.a myocardial infarction.

• Part of the heart is starved of oxygen and dies

• Causes sudden and severe chest pain

• May survive if treated immediately.

Heart failure

• Due to blockage of a main coronary artery

• Result in gradual damage of heart muscle

• The heart weakens and fails to pump

efficiently.

(i) evaluate the epidemiological

and experimental evidence

linking cigarette smoking to

disease and early

death;

Epidemiology

• Epidemiology is the study

of health-event patterns

in a society.

• It is the cornerstone

method of public

health research.

Original map by John

Snow showing

the clusters of cholera

cases in the London

epidemic of 1854

Epidemiological Evidence

• Cigarette smoking began in the

1900. Doctors started noticing a

huge increase in cases of lung

cancer from 1930 onwards, and

by 1950s it was declared an

epidemic.

• In 1912 there were 374 lung

cancer cases(per 100k), and now

there are over 35,000 deaths a

year, an increase of nearly 100

times.

• The correlation between lung cancer and cigarette smoking is plain in the chart to the right - it shows the 20 year 'lag' between the rise of cigarettes and the rise of lung cancer.

• Epidemiological data links smoking and cancer, and up to 50% of smokers may die of smoking-related diseases.

• About 1/3 of cancer deaths are as a result of

cigarette smoking, and a quarter of smokers die

of lung cancer.

• Chronic obstructive pulmonary disease is very

rare in non smokers, less than 10% of victims are

non-smokers, and less than 2% of people with

emphysema are non-smokers.

• Approx. 1/5 of smokers suffer from emphysema,

and as a result deaths from pneumonia and

influenza are twice as high amongst smokers.

• Epidemiological studies have ruled out other

factors, that is to say that they cannot find any

other factor with a close correlation with

smoking.

• Smoking has been found to have a direct link

with lung cancer, as smoking is the common

fact in almost all cases.

• Smoking also contributes to many other

cancers of the mouth, larynx, bladder, kidney

and pancreas.

Possible links between CHD and diet

• Saturated fats in food

are not easily

metabolized and

contains LDL.

• These saturated fats

will remain in the

circulation

Experimental studies

• Epidemiological evidence is sometimes questioned, as it does not 'prove' sufficiently for some that there is a definite link between lung cancer and smoking.

• However, there is also experimental evidence to prove a direct causative link between smoking and lung cancer.

Beagles used in experiments (1960s) to

investigate the link between smoking and lung

cancer.

• When there is a damage of the lining of the coronary arteries, atheroma (fatty plaques) will be formed

• This increases the chance of blood clots formation within the arteries, closing the lumen eventually, blocking arteries and capillaries.

• High intake of salts in food increase blood pressure by lowering water potential of the blood.

Effects of smoking on

cardiovascular disease

• CO and nicotine are

both toxic to the

endothelium (the thin

lining of the blood

vessels) by damaging

the lining and making

penetration by fats and

cholesterol.

• CO combines with Hb and reduces the O2

transport. Oxygen deficiency is a cause of

angina and may induce heart attack.

• Nicotine increases blood pressure, heart rate

and constriction of blood vessels.

• Cigarette smokers produce more fibrinogen

(blood clotting protein) and reduced levels of

the enzymes involved in removing blood clots.

• Smoking greatly stimulates the sticking of

blood platelets to the surface of the

endothelium and these are involved in blood

clotting.

• Nicotine has a direct effect on raising blood

fat levels.

(j) discuss the difficulties in

achieving a balance between

preventions and cure with

reference to coronary

heart disease, coronary by-pass

surgery and heart transplant

surgery;

Treatment to coronary heart

disease (CHD)• Drugs.

• Coronary artery by-pass surgery.

• Heart Transplant.

• Angioplasty.

Drugs

• Used to lower blood pressure, decrease risk of blood clotting,

prevent abnormal heart rhythms, reduce retention of fluids and

decrease the cholesterol

– ACE (angiotensin-converting enzyme) inhibitors. ACE inhibitors

are commonly used to treat high blood pressure. Examples

include captopril and enalapril.

– If you have a high blood cholesterol level, cholesterol-lowering

medicine called statins may be prescribed. Examples include

simvastatin, pravastatin and atorvastatin. They work by blocking

the formation of cholesterol and increasing the number of LDL

receptors in the liver, which help to remove the LDL cholesterol

from your blood

Coronary artery bypass surgery

• Invasive surgery involves replacing the

damaged artery by blood vessels from the

leg.

• The bypass carries blood from the aorta to

a place on the heart beyond the blockage

in the coronary artery. Sometimes two or

three bypass is necessary.

Heart Transplant

• Very high cost

• Difficulties in finding suitable donor

• Make sure that the host do not reject donor’s tissue.

• Drugs are used to suppress the immune system

after the transplant which may produce unpleasant

side effects and may not entirely prevent rejection.

• There are strict rules on deciding who should

receive transplant. Smokers who didn’t listen to

advice will be rejected from being in the transplant

list.

Angioplasty

• Less invasive procedure.

• Involves stretching the coronary arteries

by inserting a deflated balloon in the

femoral artery in the leg, positioning it in

the narrowed coronary artery and

expanding the balloon several times.

Prevention of CHD

• Prevention is more cost effective than

treatment.

• Two major ways;

– Screen for population at risk

– Adopting healthy lifestyle