“Biology for Engineers”

Course material
By

Department Of Biotechnology,
Siddaganga Institute Of Technology
Bengaluru - Honnavar Road
Tumakuru-572103 Karnataka, India
 UNIT- 3
HUMAN ORGAN SYSTEMS AND BIO-DESIGNS - 2 (QUALITATIVE):

Lungs as purification system (architecture, gas exchange mechanisms,

spirometry, abnormal lung physiology - COPD, Ventilators, Heart-lung
machine). Kidney as a filtration system (architecture, mechanism of
filtration, CKD, dialysis systems). Muscular and Skeletal Systems as
scaffolds (architecture, mechanisms, bioengineering solutions for
muscular dystrophy and osteoporosis).

Department of Biotechnology,SIT,Tumkur 2
Lungs as purification system: All cells in the body requires oxygen.
Lungs performs gas exchange.

In addition, lungs performs other functions like; Bringing air to the proper body
temperature and maintain humidity.
Protects from harmful substances; like coughing, sneezing etc
Supports sense of smell
The exchange of oxygen and carbon dioxide is
called respiration.

Lung Architecture:
The respiratory system starts at the nose and
mouth, and continues through the air ways and
passes down the throat (pharynx) and voice box,
or larynx.
The entrance to the larynx is covered by a small
flap of tissue called epiglottis, that automatically
closes during swallowing, thus preventing food or
drink from entering the airways.
Trachea (windpipe): Is the largest airway. The
trachea branches into two smaller airways; the left
and right main stem bronchi.
Each lung is divided in to sections (lobes): Three in the right lung and
two in the left lung. Left lung is little compared to right lung.
Branchi: Branched many times into smaller airways, ending in the
narrowest airways
Alveoli: Small air sacs at the each bronchiole. With in the alveolar walls is
a dense network of tiny blood between vessel called capillaries.
The extremely thin barrier between air and capillaries allows oxygen to
move from the alveoli into the blood and allows carbon dioxide to move
from the blood in to the capillaries in to alveoli.
Pleura: Is a slippery membrane that covers the lungs as well as the inside
the chest wall. The two layers of the pleura have only a small amount of
lubricating fluid between them.
Gas exchange mechanism:
Oxygen molecules get carried by the haemoglobin molecules of the red
blood cells, because it has great affinity for oxygen.
Each haemoglobin molecule binds to four molecules of oxygen.
These oxygen molecules are picked up by haemoglobin and get transplanted
by the blood to various tissues.
As carbon dioxide is more soluble in water than oxygen, it is transported in
the dissolved form in our blood.
Not all of the carbon dioxide formed is expelled from the body as some of it
reacts with water to form compounds useful for life processes.

Human bodies have regulatory

system –Medulla region
Ventilators:
Ventillators is a type of breathing apparatus used in medical technology.
It provides mechanical ventillation by moving breathable air into and out of
the lungs.

Different types of mechanical ventilators:

Positive-pressure ventilation: pushes the air into the lungs
Negative-pressure ventilation: Sucks the air into the lungs by making the
chest expand and contract.

Ventillators are required at what

time?
Risk of blood clots, serious
wounds on the skin (bedsours)
and infections etc.
Lung disorders: A respiratory disorder may be temporary or chronic (long
term)
Asthama: Common chronic lung infection. Allergic asthama begins in
childhood. Airways tighten and narrow, slowing down air flow. The lungs
become swollen and inflamed.

Bronchitis: Infection in bronchi. May be due to bacteria or virus.

Chronic obstructive pulmonary disease (COPD): Chronic bronchitis or

emphysema. COPD gets worse over time. It may caused by smoking, air
pollution, chemicals or genetic conditions. COPD leads to fourth most
common cause of death in the US.

Pneumonia: This the infection deep in the bronchioles and alveoli. Pus and
mucus may build up and lunds may swell. This makes difficult to breath.

Tuberculosis (TB): This is bacterial infection spread through air droplets

from coughs and sneezes. TB can be serious and lead to lung scaring.
Chronic obstructive pulmonary disease (COPD)
COPD: 2 FORMS
Chronic bronchitis, which involves a long term cough with mucus
Emphysema, which involves damage to the walls of the tiny air sacs
(alveoli) at the end of the bronchial tubes.

Causes: Smoking, Lack of protein called alpha-1 antitrypsin, can develop

emphysema even without smoking.

Risk factors: Exposure to certain fumes in the workplace

Signs and symptoms:
Short breath, cough with mucus, exacerbations (breathlessness), difficulty in
taking a deep breath, wheezing, and other conditions like cardiovascular
diseases, osteoporosis, depression anxiety etc.

Treatments:
Vaccination, pulmonary rehabilitation, inhaled bronchodilators and
corticosteroids, oxygen therapy, lung transplantation, antibiotics.

Tests: Spirometry
It is a lung function test to see the
function of lungs.

It determines how well lungs

functions, by measuring how much
air goes into and out of your lungs
when you breath.

Spirometry is safe,
Spirometry
This method also helps to diagnose Asthma, COPD, Cystic fibrosis and
pulmonary fibrosis.

Cystic fibrosis (CF): It is a genetically

inherited disease, causes sticky, tick
mucus to build up in organs, including
lungs and pancreas.

Pulmonary fibrosis: A serious lung

diseases that affects the respiratory
system. Lung damage ( tissues scar and
thicken over time) gradually gets worse
over time. Stiff lung tissues don’t expand
and makes difficult to breathe.
Spirometry
• Spirometry uses a machine called a spirometer. A spirometer is a medical device that
consists of a mouthpiece and a tube. They connect to a machine that measures your
airflow.

• It is the most common of the pulmonary function tests. It measures lung function,
specifically the amount and/or speed of air that can be inhaled and exhaled
• Spirometers can be divided into two basic groups:
• Volume-measurement devices (e.g. wet and dry spirometers).
• Flow-measurement devices (e.g. pneumotachograph systems, mass flow meters
 • A spirometer reading depends on a few factors such as
Age
Height
Race
Sex
Tobacco product use
Weight

Spirometry measures two main components:

Forced vital capacity (FVC). FVC is the highest amount of air that can be
breathed out after taking a deep breath in.

Forced expiratory volume (FEV1). FEV1 is the amount of air

breathed out in one second.

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Requirements of an acceptable spirometer are:
▪ Spirometers must be able to accumulate volume for ≥15 s.
▪ The measuring volume should be ≥8 L (body temperature and pressure,
saturated).
▪ The accuracy of reading should be at least ±3% (or ±0.05 L) with flows from 0–14
L/s.

How to Calculate the Normal rate of Respiration in a Spirometer: The FEV1/FVC

Ratio (FEV1%) parameter is calculated by dividing the measured FEV1 value by the
measured FVC value. The Measured column shows the absolute (numerical) ratio,
and the Predicted column shows the ratio expressed as a percentage. In healthy
adults of the same gender, height, and age, the normal Predicted percentage should
be between 70% and 85%
Heart Lung Machine:
A heart-lung machine is an apparatus that does the work both of the heart (i.e.,
pumps blood) and the lungs (i.e., oxygenates the blood) during, for example,
open-heart surgery The basic function of the machine is to oxygenate the
body's venous supply of blood and then to pump it back into the arterial system.

Blood returning to the heart is diverted through the machine before returning to
the arterial circulation. Some of the more important components of these
machines include pumps, oxygenators, temperature regulators, and filters. The
heart-lung machine also provides intra cardiac suction, filtration, and
temperature control.

Blood drains by gravity or with the use of gentle suction into the oxygenator
venous reservoir. (A)The arterial pump that pumps the blood from the venous
reservoir (B) and delivers blood to the membrane oxygenator which is attached
to the lower part of the venous reservoir. Once oxygen, carbon dioxide, and
heat exchange have occurred the blood is directed through an arterial blood
filter (C). A purge line to the uppermost part of the filter serves for the removal of
any micro emboli that may have been introduced into the blood during its
passage through the circuit
 Heart lung Machine
• The tube is attached to a large blood that allows oxygen-depleted blood to leave the
body and travel to the bypass machine.

• There, the machine oxygenates the blood and returns it to the body through the
second set of tubing, also attached to the body.

Department of Biotechnology,SIT,Tumkur 17
• The two tubes ensure that blood leaves the body before
reaching the heart and returns to the body after the heart.

• A third tube is also inserted very near or directly into the

heart. It is used to flush the heart with cardioplegia, a
potassium solution which stops the heart and takes over the
heart and lung function.

• The risks of being on heart and lung bypass include blood

clots, bleeding after surgery, surgical injury to the phrenic
nerve, acute kidney injury, and decreased lung and/or heart
function.

Department of Biotechnology,SIT,Tumkur 18
Kidney as a filtration system
The kidneys are two bean-shaped organs, each about the size of a fist. They are
located just below the rib cage, one on each side of your spine.

Healthy kidneys filter about a half cup of blood every minute, removing wastes and
extra water to make urine. The urine flows from the kidneys to the bladder through
two thin tubes of muscle called ureters, one on each side of your bladder. Your
bladder stores urine. Your kidneys, ureters, and bladder are part of your urinary
tract.

Why kidney is important ?

• Removes extra waste and extra

fluids
• Removes acids produced by the
cells.
• Controls blood pressure
• Makes RBCs
• Keep bones strong and healthy

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Each of your kidneys is made up of about a million filtering units called
nephrons. Each nephron includes a filter, called the glomerulus, and
a tubule. The nephrons work through a two-step process: the glomerulus
filters your blood, and the tubule returns needed substances to your blood
and removes wastes.

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Kidney as filtration system

Glomerular filtration: First step in making urine. It is the process that your kidneys use to filter excess
fluid and waste products out of the blood into the urine collecting tubules of the kidney., hence it is
eliminated from the body..

During body metabolism, various toxic compounds gets produced. It cannot be stored or used, later it
must be eliminated to prevent toxic build-up. In addition, our diets contain substances (carbohydrates,
fats etc.). Waste material goes out of the body in the form of feces (undigested food and bacteria).
Water soluble waste products in urine (ex; urea and electrolytes like sodium, potassium).

The main substances present in urine:

• Metabolic waste products eg; urea and creatinine
• Electrolytes; sodium, potassium, calcium, chloride and bicarbonate etc.
• Water

Kidney contains a million of specialized cells called Nephrons.

First, separation of liquid part from the blood (plasma), which contains all the dissolved solutes from
the blood cells. Each nephrons has a microscopic filters called glomerulus that is constantly filtering
the blood.
 Mechanism of filtration in nephrons:

Filtration: Filtration is the mass movement of water and solutes from plasma to the renal tubule that occurs in the
renal corpuscle. About 20% of the plasma volume passing through the glomerulus at any given time is filtered. This
means that about 180 liters of fluid are filtered by the kidneys every day. Thus, the entire plasma volume (about 3
liters) is filtered 60 times a day!
Reabsorption: Reabsorption is the movement of water and solutes from the tubule back into the plasma.
Reabsorption of water and specific solutes occurs to varying degrees over the entire length of the renal tubule. Bulk
reabsorption, which is not under hormonal control, occurs largely in the proximal tubule. Over 70% the filtrate is
reabsorbed here. In addition, many important solutes (glucose, amino acids, bicarbonate) are actively transported
out of the proximal tubule such that their concentrations are normally extremely low in the remaining fluid. Further
bulk reabsorption of sodium occurs in the loop of Henle.
Regulated reabsorption, in which hormones control the rate of transport of sodium and water depending on
systemic conditions, takes place in the distal tubule and collecting duct.
Secretion
Even after filtration has occured, the tubules continue to secrete additional substances into the tubular fluid. This
enhances the kidney's ability to eliminate certain wastes and toxins. It is also essential to regulation of plasma
potassium concentrations and pH. (See Fluid and electrolyte balance).
Excretion
Excretion is what goes into the urine, the end result of the above three processes. Although the
original concentration of a substance in the tubule fluid may initially be close to that of plasma,
subsequent reabsorption and/or secretion can dramatically alter the final concentration in the urine.

The amount of a particular substance that is excreted is determined by the formula:

amount excreted = amount filtered - amount reabsorbed + amount secreted

The glomerular filtration water and other substances from blood.

The filtration membrane keeps blood cells and large proteins in to bloodstream.
Reabsorption moves nutrients and water back into bloodstream
Waste ions and hydrogen ions secreted from the blood in the formation of urine.

Urine contains 95% water.

Chronic kidney disease (CKD):

Both acute and chronic kidney disease are linked with high health care.

Chronic kidney disease , also called chronic kidney failure, involves a gradual loss of kidney function.

In advanced chronic kidney disease causes a dangerous levels of fluid, electrolytes and wastes to build up in the
body.

At early stages, CKD may not recognized but showing symptoms.

At later stages, kidney failure; it is fatal
Dialysis and kidney transplant

Symptoms: Nausea, vomiting/ loss of appetite, weakness, sleep problem, urinate more / less, muscular cramps,
dry skin,

• Diseases that are associated with CKD are;

• Type 1 or Type 2 diabetes
• High blood pressure
• Glomerulonephritis (inflammation in kidney)
• Polycystic kidney disease
• Prolonged obstruction of the urinary tract
Complications:

CKD affect all parts of the body. Includes;

fluid retention, could lead to swelling in arms and legs, high pressure or fluid in the legs ( pulmonary

edema)

• A suddon rise in potassium levels in the blood (hyperkalaemia)

• Anaemia

• Heart disease

• Weak bones and associated with bone fractures.

• Damages CNS, cause difficulty in concentration

• Decreased immune response

• Pericarditis (inflammation at the heart; pericardium

Dialysis
Dialysis is a procedure to remove waste products and excess fluid from the
blood when the kidney stops working.

Uses:
Acute kidney injury (AKI): A sudden episode of kidney failure or kidney damage
that happens within a few hours to days. AKI treated in a hospital settings with
intravenous fluids. In severe cases, dialysis may be needed for a short time until the
kidney get better.

Kidney failure: When 10-15% of kidney works, if the glomerular filtration rate
(eGFR) is less than 15 ml/min. At this stage, kidney are no longer able to keep alive
without some extra help. This is known as end stage kidney disease (ESKD). At this
stage dialysis is needed for the rest of the life or until kidney transplantation.
Dialysis performs the functions of kidneys.
• Removal of waste and extra fluids in the body to prevent them from building up in the body.
• Keeping waste and extra fluids in the body to prevent them from building up in the body.
• Keeping safe levels of minerals in the blood such as potassium, sodium, calcium and bicarbonate.
• Regulate blood pressure.
Muscular and skeletal system

The skeleton includes bones, ligaments, tendons and cartilage

Muscles are attached to skeletal system to make musculoskeletal system.
Functions: movement, sustain body posture and position, maintain body temperature, store nutrients and
stabilize joints.

Parts of muscle tissue: Skeletal muscle tissue, connective tissue, nerve tissue and blood or vascular tissue.

There are 3 types of muscles: Skeletal, cardiac

and smooth.

Skeletal muscles help us move and are

voluntary. Cardiac muscles make our heart
beat and are involuntary. Smooth muscles are
in hollow organs and blood vessels, working
automatically. Each muscle type has unique
features and functions.
Muscular and skeletal system
The muscle tissues are derived from
mesoderm.
Myoblasts differentiation (embryonic
muscle cells) lead to formation of
elongated and contractile cells with
specific morpho functional
characteristics; they are classified as
smooth, cardiac striated and skeletal
striated muscle tissue.
Muscle architecture
The striated skeletal muscle tissue (abundantly present in the body) is
organized by epimysium, perimysium and endomysium, through which blood
capillaries, lymphatic vessels and nerve endings flow.
Each myocyte (muscle fibre) is made up of elongated, multinucleated,
cylindrical cells joined by connective tissue sheaths, organized in to repetitive
arrangements of sarcomeres, actin and myosin filaments (myofibrils).

Myofibrils are post-mitotic cells (quiescent

cells). These cells are located adjacent to
the muscle fibre. In the adults, the cells may
return to self-renewal and proliferation
capacity in response to stress or injury.

Structure of skeletal muscle cells

Microscopic organization of a skeletal muscle:
The sarcoplasm (cytoplasm) of a muscle fibre is filled with bundle of long contractile
protein fibres called the myofibrils. The fibrils run along the entire length of a muscle
cell.
The sarcoplasmic reticulum forms
a network around every single
myofibrils.

The terminal sacs of it, called the

terminal cisternae, store calcium
ions, which play a very important
role in muscle contraction.

Each myofibril is made of several

repeating units, referred as
Sarcomere

The striated appearance is due to

the repeated bands of the actin
(forms light I bands) and myosin
(forms dark A bands) proteins
present along the length of
myofibrils
Mechanism of muscle contraction
Each I band has a dense line running vertically through the middle called a Z disc or Z
line.

The sarcomere itself is bundled with in the myofibrils that runs the entire length of the
muscle fibre.

The actin filaments: The thin filaments, major components of the I-band and
extended into the A-band.
Myosin filaments are thick filaments, are bipolar and extend throughout the A-band.
They are cross-linked at the centre by the M-band.

Contraction: By the sliding

action of thick and thin filaments
present in sarcomere structure.
Architecture of skeletal system

• The muscular and skeletal systems are separate but interconnected systems that
work together to provide support, stability and movement.
• Skeletal system is composed of bones, cartilages and ligaments.
• Bones provide rigid frame work for the body, protecting the organs.
• Cartilage acts as a cushion between bones, reducing friction and absorbing shock
during movements.
• Ligaments connect bones to other bones, providing stability and preventing
excessive movement.

The architecture of muscle and skeletal

system is very complex.
Muscles attached to bones via tendons,
which transmit the force produced by the
muscles to work against and protects
body organs and tissues.
Muscular system as scaffolds
Muscular system as scaffolds in regenerative medicine is an area of active
research.

Muscles have potential to be used as scaffolds for the regeneration of tissues due
to inherent mechanical properties and ability to support cell growth and tissue
regeneration.

Example: Muscular scaffolds are used in the treatment of damaged or diseased

heart tissue. Researchers have developed methods for using muscle cells to create
a functional, 3D scaffolds, that can support the growth of new heart tissue. In this
approach, muscle cells are harvested from the patient and seeded on scaffold, such
as hydrogel or artificial matrix. The scaffold provides a framework for the cells to
grow and differentiate into new heart tissue, which can help to repair the damaged
or diseased tissue.

While the use of muscular system as scaffolds is still in the experimental stage.
Muscle cells as scaffolds

Muscle cells can be used as a scaffolds for tissue generation by removing the living cells
from the muscle tissue. Leaving behind the structure known as extracellular matrix.

This decellularized muscle scaffold provides a framework that can guide and support the
growth of new tissues.

Process: Harvest muscle tissue: A small sample of muscle tissue is taken, typically from
a donor or an animal model
Cell removal: The living cells within the muscle tissue are removed using a process
called decellularization. This involves the tissue with specific chemical solutions

ECM scaffold: The

remaining ECM acts as
scaffold
Cell seeding: Seeded with
stem cells
Tissue integration: Cells
continue to grow, populate
in the scaffold and form a
new tissue
Bioengineered skeletal muscle construct

Natural and synthetic biomaterials are used in muscle tissue scaffold development.

• From the tissue biopsy,

Fibroblasts are isolated and
reprogrammed to produce
Induced myogenic
progenitor cells (iMPC)
using several transcriptional
factors.

• Polycaprolactone (PCL)
material as porous scaffold.
Alone PCL don’t provide
muscle microenvironment.
Hence, construction of a
hybrid scaffolds were
engineered using
decellularized muscle
extracellular matrix (ECM)
Bioengineering solutions for muscular dystrophy

• Muscular dystrophy is a group of genetic disorders that results in

progressive weakness and degeneration of skeletal muscles, which are
responsible for movement.

• Caused by mutations in genes that encode proteins needed for muscle

function.

Most common type of muscular dystrophy:

• Duchenne muscular dystrophy, Becker muscular dystrophy, limb-gridle

muscular dystrophy and facioscapulohumeral dystrophy etc.

• There is currently no cure for muscular dystrophy.

Bioengineering solutions for muscular dystrophy

Approaches like,

1. Gene therapy: This delivering a functional copy of missing or mutated

gene to the affected muscle cells. The goal is to restore the production of the
missing protein and improve muscle function.

2. Exoskeleton technology: This involves using wearable devices, such as

robotic exoskeletons, to support and enhance the movement of individuals
with muscular dystrophy. The devices use motors and sensors to mimic the
movements of the wearer and help improve mobility.
3. Stem cell therapy: This involves using stem cells to replace the damaged
muscles and promote repair and regeneration of the muscle tissue. Stem cells
can be taken from the patients own body or from a donor.

A promising strategy:

• By use of satellite cells

(muscle stem cells),

• Embryonic stem cells

(ESCs)

• Mesenchymal stem cells

(MSCs)

• Adipose derived stem

cells (ADSCs)
4. Tissue engineering: This involves a combination of materials such as
scaffolds and growth factors to promote the growth and repair of muscle
tissue.
5. Artificial muscles

Artificial muscle refers to a type of technology that aims to mimic the properties nad
functions of natural muscles.

Artificial muscles (prosthetics) can be made from various materials, includes shape
memory alloys, electroactive polymers and carbon nanotubes.

Shape memory alloys (SMAs) are materials with the ability to remember and recover
their original shape after being deformed. SMAs, like NiTi alloys commonly used in
artificial muscle applications. When exposed to heat or an electrical current, SMAs
undergo a phase transformation, enabling them to contract and generate force. This
property makes them suitable for mimicking muscle-like movements in devices such
as prosthetics, robotics and actuators.
Osteoporosis

Osteoporosis is a bone disease, develops due to decrease in bone density. This

decreases bone strength and increases the risk of bone fractures

Causes: Low calcium intake, decrese in estrogen in women, decrease in

testosterone in men.

Early signs: low bone density, bone fractures, loss of height, a curved upper back,
suddon back pain, gastrointestinal issues, dental problems etc.
Bioengineering approaches to cure osteoporosis:

1. Stem cell therapies, using

bone tissue engineering.

Tissue engineering involves
growing and replacement of
tissues in the lab and
implanting them into the
patients body.
2. Drug delivery: New drug
delivery system that can
target the bone tissue
directly.
3. 3D printing technology
to create artificial bone tissue
4. Stem cells for generation of a new bone

Ultrasound and gene therapy to stimulate the stem cells in the collagen scaffolds to
repair the bone fractures.
Ultrasound pulses, temporary creates small holes in the cell membranes allowing the
delivery of the genes therapy-containing microbubbles into the stem cells.

Animals received the

collagen transplant
and ultrasound gene
therapy repaired their
fractured leg bones
with in 2 months.