Surfactants_AIIMS_Raebareli.pptx

SURFACTANTS: ELIXIR OF
BREATH
Divyanshu Mohan Arya
Roll. M2022029
MBBS 2022 Batch
CREDITS: BING AI IMAGE GENERATOR, MEET D. GAJJAR

CONTENTS
1. Guyton
2. Surface Tension
3. Surfactant Production
4. Composition
5. Surfactant
6. Regulation of Surfactant Production
7. Respiratory Distress Syndrome
Thank you slide
Yawning is powerful stimulus for increasing
lung compliance and reversing the
atelectasis
HOW?
CREDITS: GK PAL

WISDOM FROM GUYTON
“On the inner surfaces of the alveoli the water surface is
also attempting to contract tending to force air out of
the alveoli causes the alveoli to try to collapse. The net
effect is to cause an elastic contractile force of the
entire lungs, which is called the surface tension elastic
force….…..These cells (type 2 pneumocytes)are
granular, containing lipid inclusions that are secreted in
the surfactant into the alveoli. Surfactant is a complex
mixture of several phospholipids, proteins, and ions.
The most important components are the phospholipid
dipalmitoyl phosphatidylcholine, surfactant apoproteins,
and calcium ions. The dipalmitoyl phosphatidylcholine
and several less important phospholipids are
responsible for reducing the surface tension. They
perform this function by not dissolving uniformly in the
fluid lining the alveolar surface. Instead, part of the
INTERNATIONAL GUYTON, PHOTO- MISSISSIPPI CHILDREN'S MUSEUM, WIKIPEDIA
Dr. Arthur Clifton
Guyton
1919-2003
Guyton initially intended to
be a cardiovascular
surgeon but was partially
paralyzed after being
infected with polio.
Then he built the first
motorized wheelchair
controlled by a "joy stick"

WHY SURFACE TESION DEVELOPS?
BORON
We can think of the surface water
molecules as beads connected by
an elastic band. The force that
pulls a water molecule down into
the bulk also creates a tension
between the molecules that
remain at the surface, in a
direction that is parallel to the
surface.

SURFACE TENSION
Force that pulls the surface molecules together of a liquid at
an air-liquid interface is called surface tension.
•At the air-liquid interface, surface tension is created because
water molecules are strongly attracted to one another than to
air molecules.
•The surface tension at the air-liquid interface in the lung
alveoli is a major factor that decreases lung compliance.
•In fact, surface tension at the air-liquid interface of lung
airways accounts for more than half of the elastic recoil of
lungs.
•The surfactant in turn decreases the surface tension in the
alveoli by 2- to 10-fold
CREDITS: BING AI IMAGE GENERATOR, NETTER’S ESSENTIAL
PHYSIOLOGY, GK PAL

SURFACTANT PRODUCTION
CREDITS: : BORON, MEDIA.SPRINGERNATURE.COM, 3D MEDICAL ANIMATION -
YOUTUBE

COMPOSITION OF SURFACTANTS
Lipids
90%
Apoprotein
s…
Carbohydrates…
Lipids
(90%)
Dipalmitoyl phosphatidylcholine
(62%)
Phosphatidylglycerol (5%)
Other phospholipids (10%)
Neutral lipids (13%)- cholesterol
Protei
n
(8%)
Albumin
IgA
Apoproteins (SP-A, SP-B, SP-C, SP-
D)
Not in GK Pal but Ca+2 is important in Guyton
DPPC = Lecithin
CREDITS: GK PAL, GUYTON

SURFACTANT
Pulmonary surfactant is a complex mixture of phospholipids (PL) and
proteins (SP) that reduce surface tension at the air-liquid interface of
the alveolus.
•Principal component: Dipalmitoyl phosphatidyl choline
• Hydrophobic tail faces toward the air in alveolar lumen
•Synthesized in Type II pneumocytes
•Absolute production rate is 4.2 mg/kg/day while the
half-life is 113 ± 25 hours (4-5 days).
CREDITS: BORON, HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC2880575/

EFFECT OF SURFACTANT ON
SURFACE TENSION
70
• Pure air-water
interface
25
• With
Surfactant
Surface Tension
(dyne/cm)
•At zero transpulmonary
pressure, though the
lung is smallest in size,
alveoli are not fully
collapsed due to
surfactant, preventing
atelectasis.
CREDITS: BORON, GK PAL

SURFACE TENSION AND LUNG
COMPLIANCE
BORON, NETTER’S ESSENTIAL PHYSIOLOGY
1. Hints: Differences between two loops
2. Hysteresis, phase of slope due to interplay of
elasticity and surface tension

REGULATION OF SURFACTANT
SYNTHESIS
1. Cortisol: Premature babies are prone to IRDS
2. Thyroxine: Maternal thyroid deficiency and cretinism decrease
surfactant
3. Insulin: Diabetes during pregnancy decreases surfactant
4. Surfactant proteins: depends on concentration of protein in the
plasma.
5. Stretching of Lungs: Yawning and sighing during infancy are
effective stimuli for surfactant synthesis
6. β adrenergic agonists
7. Calcium
8. Exercise: Lung is more compliant during exercise ensuring better
ventilation CREDITS: GK PAL

RESPIRATORY DISTRESS
SYNDROME
Extremely labored breathing by neonate due to high surface tension
of lungs is called infant respiratory distress syndrome (IRDS) or
hyaline membrane disease. Pulmonary edema atelectasis develop.
Surfactant is made in the lungs at about 26 weeks of pregnancy
Risk Factors
1. Prematurity: Surfactant is made in the lungs at about 26 weeks of pregnancy
2. Perinatal Asphixia: Second twin to be delivered
3. Maternal Diabetes
4. Caesarean Section
CREDITS:WWW.NATIONWIDECHILDRENS.ORG

RESPIRATORY DISTRESS
SYNDROME
Signs and Symptoms
•Tachypnea
•Grunting “ugh” sound with
breath
•Changes in color of lips, fingers,
etc.
•Flaring of the nostrils
•Chest retractions
•Cheyne-Stokes Breathing
Treatment
• Oxygen Therapy
• Surfactant Replaceme
nt
• Cortisol
CREDITS: WWW.NATIONWIDECHILDRENS.ORG, RADIOLOGY CASE | RADIOPAEDIA.ORG, WWW.ABOUTKIDSHEALTH.CA

Suggested Questions
1. How surfactants inhibit rapid inspiration?
2. Why less surfactant can cause Pulmonary
Edema?
3. How do surfactants play role in innate
immunity?
4. Why compliance increases during exercise?
5. By law of Laplace, smaller alveoli could drain
into larger alveoli and collapse. How does
that not happen and alveoli coexist?
6. Cause of X ray finding in Hyaline Membrane
Disease?
7. Why Cheyne Stokes breathing in RDS?
Summar
y
Produced by Type 2
pneumocyte and their
most important role is to
lower surface tension
Stored as Lamellar
bodies, secreted as
tubular myelin
Amphipathic due
to phospholipids
Dipalmitoyl
phosphatidylcholi
ne, Calcium ions,
Deficiency causes
Respiratory distress
syndrome
Surfactants

CREDIT: STOCK IMAGES
POST CREDIT
SLIDES AHEAD

SURFACE TENSION AND LAPLACE'S
LAW
BORON

SURFACTANT APOPROTEINS (SP)
BORON
Also in SP-D,
LECTINS-
IMMUNOMODUL
ATORY

COLLECTINS
•Collectins are soluble pattern recognition receptors (PRRs) that bind to lipids
and oligosaccharides on the surface of microorganisms.
•Collectins are a family of collagenous, calcium-dependent (C-type)
lectins. Their polypeptide chains consist of four regions:
1. A cysteine-rich N-terminal domain
2. A collagen-like region
3. An alpha-helical coiled-coil neck domain
4. A C-terminal lectin or carbohydrate-recognition domain
Collectins include:
•MBL, also known as mannose-binding protein
•Surfactant-associated proteins A and D (SP-A and SP-D, respectively)

PNEUMOCYTES
GK PAL
Type 2 pneumocytes (stem cells)
are-
1. Smaller
2. More numerous
3. But occupy less (10%) area
than flattened type 1
pneumocytes.

TYPE II PNEUMOCYTE INNATE
IMMUNITY
They secrete
•Defensins and other peptides and proteases
•ROS
•RNS
•Collectins
CREDITS: DR.ARVIND CHAUDHARY SIR SLIDES

LAPLACE’S LAW
If the air passages leading from the alveoli of the lungs are blocked,
the surface tension in the alveoli tends to collapse the alveoli. This
collapse creates positive pressure in the alveoli, attempting to push
the air out. This pressure can be calculated from the Laplace’s Law:
Pressure = 2 × Surface tension/Radius of alveolus For the average-
sized alveolus with a radius of about 100 micrometers and
1. lined with normal surfactant, about 4 cm H2O pressure (3 mm Hg).
2. lined with pure water, about 18 cm H2O.
Premature babies have alveolar radius less than 25%, hence collapsing
tendency sometimes as much as six to eight times than that in a
normal adult person.
GUYTON

FIRST FEW BREATHS
NETTER’S ESSENTIAL PHYSIOLOGY

CATABOLISM OF SURFACTANTS
•Surfactant is secreted into the alveolus where it is degraded and then
recycled.
•Metabolism of surfactant is slower in newborns, especially preterm,
than in adults.
•respiratory distress occurs due to accelerated breakdown by
oxidation, proteolytic degradation, inhibition or inherited defects of
surfactant metabolism.
CREDITS : HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/PMC2880575/

FATE OF SURFACTANT
COMPONENTS
•Surfactant components are removed from air spaces through uptake
by Type II cells and alveolar macrophages, with the bulk done by the
Type II cells.
•The phospholipids are taken up by endocytosis into the Type II cells
where they are recycled and re-secreted.
•The SPs are recycled back into the lamellar bodies for re-secretion
with surfactant.
•Surfactant is also transformed during the cyclic compression and
expansion of alveoli from large, highly surface active aggregates into
smaller, less active subtypes.

FROM BORON
SYNTHESIS OF
SURFACTANT

SURFACTANT SYNTHESIS
BORON, GK PAL

STIMULANTS OF SURFACTANT
PRODUCTION
•Type II cells have beta-adrenergic receptors and respond to beta-agonists
with increased surfactant secretion.
•Purines, such as adenosine triphosphate are potent stimulators of surfactant
secretion and may be important for its secretion at birth.
•Mechanical stretch such as lung distension and hyperventilation, have also
been found to be involved in stimulating surfactant secretion. Stretch-
mediated enhancement of surfactant secretion during exercise prevents a
loss of alveolar surfactant.
•Hormones also play a role in surfactant secretion. Thyroxine accelerates
Type II cell differentiation while acting synergistically with glucocorticoids to
enhance the distensibility of the lung and DPPC synthesis.
•However, glucocorticoids alone are used in clinical practice to induce lung
maturity because studies have not shown that the synergistic effect with
thyroxine is greater than the effect achieved by glucocorticoids alone.

WHY “HYALINE MEMBRANE”
DISEASE
•The alveoli of infants with IRDS at death contain large quantities of
proteinaceous fluid, almost as if pure plasma had leaked out of the
capillaries into the alveoli.
•The fluid also contains desquamated alveolar epithelial cells.
•This condition is called hyaline membrane disease because
microscopic slides of the lung show that the material filling the
alveoli looks like a hyaline membrane.
•Hyaline membrane disease is also called respiratory distress
syndrome.
INTERNATIONAL GUYTON

BRAKING OF SUDDEN
RESPIRATION
BORON

MECONIUM ASPIRATION
SYNDROME
•In the fetal distress, gasping may be initiated in utero leading
to aspiration of amniotic fluid and its contents, which includes
meconium, into the large airways.
•Meconium has Phospholipase-A2, competitive displacement of
surfactant from the alveolar film. It is also known to induce
hydrolysis of DPPC, releasing free fatty acids and lyso-PC which
damage the alveolar capillary membrane and induce
intrapulmonary sequestration of neutrophils.

PULMONARY HEMORRHAGE
•Following endothelial damage, neutrophils are released. They, in turn, express
proteases, oxygen free-radicals and cytokines.
•These damage the Type II cells that produce SPs,
•Elastase damages and degrades SP-A, thereby inhibiting SP-A mediated
surfactant lipid aggregation and adsorption in vitro .
•A rare adverse event associated with surfactant replacement therapy as it
rapidly lowers intrapulmonary pressure.

ACUTE RESPIRATORY DISTRESS
SYNDROME
•Acute Respiratory Distress Syndrome (ARDS) is a significant cause of morbidity
and mortality in all age groups following sepsis, hemorrhage, or other forms of
lung injury.
•It is defined as a severe form of acute lung injury (ALI) and a syndrome of acute
pulmonary inflammation.
•ALI/ARDS is characterized by sudden onset, impaired gas exchange, decreased
static compliance, and by a non-hydrostatic pulmonary edema.

PULMONARY ALVEOLAR
PROTEINOSIS
•Alveoli fill with PL-rich proteinaceous material.
•Due to absolute deficiency of alveolar cells or hypo-responsiveness of the
alveolar immune cells to Granulocyte-Macrophage Colony Stimulating Factor
(GM-CSF).

HEREDITARY SP-B DEFICIENCY
•Autosomal recessive
•Surfactant replacement is not effective.
•Lung transplant has provided relief in some of these patients and it has been
found that long-term outcomes after lung transplantation for SP-B–deficient
infants are similar to those of infants transplanted for other indications

HEREDITARY SP-C ASSOCIATED
DISORDER
•Autosomal dominant
•The mutation could be familial or de novo.
•SP-C is derived from a precursor protein, proSP-C.

ABCA3 TRANSPORTER GENE
MUTATION
•ABCA3 is a member of the ATP-Binding Cassette (ABC) transporter family
•Expressed in the Type II epithelial cells
•ABCA3 is critical for the proper formation of lamellar bodies and intracellular
lipid homeostasis
•Autosomal recessive

SUMMARY OF APPLIED ASPECTS
An understanding of the complex metabolic process involving
phospholipids and surfactant proteins is the key in the management of
respiratory failure secondary to defects in surfactant metabolism. The
combined use of prenatal corticosteroids and postnatal surfactant
replacement therapy can be credited with a dramatic improvement in the
outcome of patients with RDS. Lung transplantation has been successful in
treating infants with inherited SP-B deficiency and has also afforded the
opportunity to investigate surfactant composition and function. Whole
lung lavage is currently the mainstay of treatment in Pulmonary Alveolar
Proteinosis and further studies to ascertain the role of SP-B and GM-CSF
will help in advancing further ground breaking therapy for this disease.
Gene therapy could overcome the limitations of surfactant replacement
therapy in inherited defects of surfactant metabolism.

RESPIRATORY MEMBRANE
GUYTON(L), GK PAL (R)

Surfactants_AIIMS_Raebareli.pptx

Recommended

Recommended

More Related Content

Similar to Surfactants_AIIMS_Raebareli.pptx

Similar to Surfactants_AIIMS_Raebareli.pptx (20)

Recently uploaded

Recently uploaded (20)

Surfactants_AIIMS_Raebareli.pptx