FISIOLOGI PENUAAN

Dr. Bernhard Arianto Purba, M.Kes., AIFO

 Textbooks
Robert L. Kane, Joseph G. Ouslander, and Itamar B. Abrass. 2004. Essentials of
Clinical Geriatrics. 5th Edition. USA: McGraw-Hill .
Edmund H. Duthie Jr, Paul R. Katz, and Michael L. Malone. 2007. Duthie: Practice of
Geriatrics. 4th ed. USA: Saunders, an imprint of Elsevier Inc.
Christine K. Cassel. 2002. Geriatric Medicine: An Evidence-Base Medicine. 4th ed.
New York, inc : Spinger-Ver-Lag.
Mark H. Beers, and Robert Berkow. 2001. The Merck Manual of Geriatrics. USA:
Whitehouse Station, NJ.
J. Grimely Evans. 2000. Oxford Textbook of Geriatric Medicine (Oxford Medical
Publications). USA: Oxford University Press.
Guyton, A.C & Hall, J.E. 2006. Textbook of Medical Physiology. The 11th edition.
Philadelphia: Elsevier-Saunders.
Marieb, E.N., and Hoehn, K. 2007. Human Anatomy and Physiology. The 7th
edition. USA: Benjamin Cummings, Pearson Educaton, Inc.
Brooks, G.A. & Fahey, T.D. 1985. Exercise Physiology. Human Bioenergetics and Sts
Aplications. New York : Mac Millan Publishing Company.
Foss, M.L. & Keteyian, S.J. 1998. Foxs Physiological Basis for Exercise and Sport.
4th ed. New York : W.B. Saunders Company.
Astrand, P.O. and Rodahl, K. 1986. Textbook of Work Pysiology, Physiological Bases
of Exercise. New York : McGrawHill.
Banerjee, Ashis. 2005. Clinical Physiology. Cambridge: Cambridge University Press.
Fox. 2003. Human Physiology . The 6the dition. New York : McGrawHill
McPhee, S.J, and Ganong, W.F. 2006. Pathophysiology of Disease: An Introduction
to Clinical Medicine. The 5th edition. USA: McGrawHill.
AGING IN SPORT
AND EXERCISE
It Happens to Everyone

Baseball Hall of Fame Members: 2004

From Sports Illustrated
Changing Images & Realities of Aging
Meaning of Age
CHRONOLOGICAL AGE
Count of how many times an
inhabitant has orbited the sun
Minimum age limits for drinking,
driving, voting assume
chronological age barometer of
ability to perform certain
functions
That assumption is not
necessarily accurate!
Mere passage of time does NOT
cause development
I.e. student who is physically
& sexually mature may be
immature when it comes to
knowing how to act in social
situation
Meaning of Age

Functional age
A measure of how well a person can function in a physical & social
environment as compared to other people of the same chronological
age
A 70-year-old who is young at heart may be functionally younger
than a 50 year-old who finds lifes challenges overwhelming
Gerontologists, scientists who study aged people & aging process
divide todays older people into two categories
1. The young-old (55-75) majority of them are vital, vigorous & active
2. The old-old (75 & above) experience more changes in health & may
become more frail or experience major health & psychological
changes (Neugarten & Neugarten, 1987)
Three Components of Functional Age
Psychological age
Ability to deal with demands of environment such a move, accident, change of
job
How well in comparison with same-aged peers, a person can cope with
environmental challenges
A 50-year-old who lives with parents, has no job, & cannot form a meaningful
personal relationship maybe psychologically younger than a 20-year-old who
is independent & exerts control over life choices
Social Age
Depends on how closely behavior conforms to norms, expectancies, & roles a
person of a certain chronological age is expecgted to play in society
A woman having first child in mid-forties is adopting role of parent later than
most of her peers
She thus has a younger social age
Older people who sign up for college courses are socially younger than their
peers
A 23-year-old widow is relatively advanced in social age
Three Components of Functional Age
Biological Age
Measure of how far
person progressed
along potential lifespan
Predicted by persons
physical condition
Measure biological age
by examining how well
vital organ systems
such as respiratory,
cardiovascular systems
are functioning
50-year-old exercised
regularly likely
biologically younger
than 40-year-old
Physiological Changes on Eyes

Skin is loose, loss of muscle tone and elasticity

around the eyelids
baggy lids
ectropion/ entropion/ enophthalmos/ senile ptosis
The fluid contains mucus, antibody, lysozyme (an enzyme destroys bacteria)
 Tear Film

Stability dependant on quality, quantity and blinking

process
loses stability with aging
changes in aqueous, oily and mucin layers decrease
stability
Tear production is reduced to 1/4 to 1/5 of what it was
in the first decade of life
relaxation of eyelid elastic structures- weaker, less
efficient blink
Concentration reduces spontaneous blinking (normal
15-20 X/min to 3-4X/min)
Education!!
Measure Tear quantity

Schirmer's I Test

In Schirmer test, we measure the quantity of tears that

are produced by the eye. If the tears are collected for
some time, lets say 5 minutes or so, then one can
determine whether the amount produced is sufficient for
maintaining eye health or not.

If not much tears are produced, then you have a tear

deficient dry eye. If you produce enough tears, but still
have symptoms of ocular discomfort, then you may have
evaporative dry eye for example due to blepharitis or
Rosacea.
Tear film (quantity of tears)

In Schirmer test a 35 mm x 5 mm size filter paper strip is

used to measure the amount of tears that are produced over
a period of 5 minutes. The strip is placed at the junction of
the middle and lateral thirds of the lower eye lid. The test is
done under ambient light.

The patient is instructed to look forward and to blink

normally during the course of the test. A negative test
(more than 10 mm wetting of the filter paper in 5 minutes)
means you produce normal quantity of tears. Patients with
dry eyes have wetting values of less than 5 mm in 5
minutes.
Tear break up time (TBUT)
Tear stability

Normal tear film is continuous. Blinking

maintains the tear film continuity. If you keep
your eyes open long enough, without blinking,
the tear film will start breaking up. Your eye will
feel uncomfortable forcing you to blink.

In patients with dry eyes the tear film is unstable,

and breaks up faster. Therefore the tear break up
time in patients who have dry eyes is shorter.
Said in another way, if your tear break up time is
short then you may have dry eyes.
The older patient

Clinically, the older patient may express concern

with short-term visual fluctuations, especially with
tasks requiring increased concentration (refraction,
reading, and driving). The average person blinks
spontaneously 15 tothe
20older
times per minute. During
patient
tasks requiring more concentration, the blink rate
may go down to as little as 3 or 4 blinks per minute.
(Milder, 1987)
The older patient

The reduction in the tear film stability, especially

when combined with a reduction in the blink rate
with concentration, may be a source of irritation or
frustration for the older patient. Educating the
patient on the need to blink more, the use of tear
supplements and lid hygiene may help to minimize
this phenomenon.
Avascular:
Receives O2 from
- Air in front
- Aqueous humor
(also nutrients)

Limbus epithelial stem cells that

continually renew the corneal
epithelium
cornea

A clear cornea is important for the production of a

sharp image on the retina. Fortunately, the
transparency of the cornea does not appear to be
affected greatly by the normal aging process
(Marmor, 1986) The clearness of the cornea is
attributed mostly to the uniformly small diameter
and close spacing of the stromal collagen fibrils and
other smaller corneal cells (Klyce and Beuerman,
1988).
Cornea

The corneal endothelium maintain corneal

hydration. The endothelial cell layer density drops
in the adult cornea.

( Hassal-Hensle Bodies) and accumulation lipids in

peripheral cornea (arcus senilus) maybe due to
sclerosis of the perilimbal vascular plexus
 Cornea

Needs to be smooth and moist by tears and eyelids. Transparency

not affected greatly
Endothelium maintains proper dehydration status:
3500-4000 cells/mm at birth

Drops to 1400 to 2500 cells/mm in adult cornea

By age 90 could be only 900 cells/mm, but the critical number

to maintain proper dehydration is 400-700 cells/mm
Decreased Corneal sensitivity
disadvantages for CL

Increased ATR
horizontal meridian becomes steeper and vertical meridian
varies very little if any
Pupil

Pupil size decreases with age.

Several mechanisms have been suggested to
explain this senile miosis:
** Atrophy of the dilator muscle fibers and thus
loss of their contractile ability is considered a
causative factor.
** Age related degenerative structural changes in
the iris and /or its vascular supply.
** Aging changes in the innervation of the iris
muscles is another theory.
Pupil

This miosis contributes to reduction in retinal

illuminance, and decrease visual function in the
elderly.
Depth of focus improves.
Lens

The density of the ocular media increases with age.

The crystalline lens is considered the major factor in
this age-related change (Werner et al, 1990).
The age-related change in the spectral density and
the yellowing of the lens have been attributed to the
increase in lens thickness and/or the deposition of
pigment.
 Lens

Yellowing
Mellerio (1971 and 1987)
lenticular pigment distribution remains unchanged. Lens
thickness increase cause yellowing
Leberman (1983)
chronic UV exposure induces photochemical generation and
accumulation of at least two chromophores that absorb light
@ 360 and 435nm and fluoresce at 440 and 520 nm
Fluorescent compounds increase in concentration
resulting in a progressive decrease of visible and UV light
transmission, increasing the yellow color of the lens
CATARACT
Refraction and accommodation

A trend toward hyperopia (less myopia) exists after

age 40 years (Exford 1965,Lavery et al., 1988).
This progression of the hyperopia lies somewhere
between +0.25D and +0.50D per decade. After age
70 years the trend appear to reverse, and a slight
shift toward myopia may be noted.
Astigmatic switch from with the rule to against the
rule. Most studies reveal little if any cylinder
power change with increasing age.
Visual Acuity

Visual acuity in the healthy aging eye begins to

change around age 50. The two factors most often
noted as having an adverse effect on the image
quality are the pupil and the lens. The resolution
depends on the quality of the image presented to the
retina, the integrity of the retina, and the neural
capacity.
Normal Age Related Vision Changes

40-44 y.o: 93.5% have cc VA of 20/20 or better

70-74 y.o.: 41.9% have cc VA of 20/20 or better and
56.1 % have cc VA 20/40 or better
Most of these changes are due to degeneration or
from ocular diseases
Neural changes

With age the retina experiences a variety of

changes that some researchers believe may help
contribute to the functional decline in the visual
system.
The number of RPE cells in the posterior pole
decreases significantly with age (Dorey et al., 1989)
The accumulation of RPE lipofuscin increase with
age, and the number of photoreceptors decrease
with age.
THE RETINA
Neural changes

Displacement and loss of photoreceptor nuclei from

the outer nuclear layer (ONL) with increasing age,
reduction in the quantity of the attached rods and
cones and the outer plexiform layer axons.
Loss of retinal ganglion cell axons in the optic nerve.
 RETINA, CHOROID AND SCLERA

4. Collagenous fibers
1. Sclera
5.
2. Choroid Chromatophores
6. Blood vessel

7. Pigment epithelium
8. Rods and cones
9. Outer limiting
membrane
3. Retina 10. Outer nuclear layer

11. Outer plexiform layer

12. Inner nuclear
layer
13. Inner plexiform layer
14. Ganglion cell layer
15. Nerve fiber layer
16. Inner limiting
membrane
 16. Sclera
17. Suprachoroid layer (lamina
1. Blood vessels of fusca)with chromatophores
the choroid 18. Vascular layer of the choroid
2. Chromatophores 19. Choriocapillary layer
3. Pigment cells in
the retina 20. Processes of pigment
cells ectending between
4. Rods rods and cones
21. Cones
5. Cones
22. Rod
6. Outer limiting 23. Outer limiting
membrane 24.membrane
Nuclei of cones
7. Nuclei of cones 25. Nuclei of rods
8. Nuclei of rods
26. Outer processes of
Mullers cells
9. Outer plexiform 27. Synapses between
layer horizontal and visual
28.cells
Synapses between
cones and bipolar
10. Nuclei of cells
bipolar, 29. Bipolar cell
horizontal, 30. Mullers cell
amacrine and 31. Amacrine cell
Mullers cells 32. Synapses between
processes of
11. Inner plexiform bipolar, amacrine
layer and ganglionic cells

12. Ganglion cell 33. Ganglion cell

layer
34. Fiber of optic nerve
13. Mullers fibers
14. Axons of 35. Horizontal fiber
ganglion cells
15. Inner limiting 36. Inner limiting
membrane membrane
37. Inner fibers of Mullers cells
 THE ROD AND
CONE

Rhodopsin
Retinal (11-cis retinal)
Opsin :
- Scotopsin in rods
- Photopsin in cones
Nyctalopia (buta senja)
Macula and fovea
funduscopy with ophthalmoscope
Macula lutea yellow spot
 Neural and Retinal Changes

Tsai, Repka, Quigley, Balassi and others have

found that aging affect the number of retinal
ganglion cell axons available
By age 70, optic nerve have lost about 25% of its axons
therefore there is a loss of some visual transmission from
the retina to the LGN and visual cortex
Devaney and Johnson (1980) reported macular
cell loss of 50% from age 20 to age 80
Only cones cell for sharpening image
Peripheral cone
Dark adaptation

Older patients express concern about the reduction

in their ability to function in poorly illuminated
environments.
The decline in sensitivity is due to media and neural
changes.
Aging changes in the lens and the pupil are
considered to be more detrimental to this function
than neural changes.
Muscular System
The Organization of Skeletal Muscles
 Development of a skeletal
muscle fiber

Sarcomerecontractile unit of a muscle fiber

Organization of the sarcomere
Myofilaments
Thick filaments = myosin filaments
Myosin filaments have heads (cross bridges)
Myosin and actin overlap somewhat
Thin filaments = actin filaments
Anchored to the Z disc
Muscular System
Progressive loss of muscle mass occurs as we age change in
body shape
Accelerated after age 65- causes weight loss
Changes in body shape can affect balance, contributing to falls
Elderly individuals with weak muscles are at greater risk for
mortality than age-matched individuals
Increase in amount and rate of loss of muscle increases risk of
premature death
Physical inactivity is 3rd leading cause of death; plays role in
chronic illnesses of aging
CHANGES IN MUSCLE MASS
Nerve Stimulus to Muscles
Skeletal
muscles must
be stimulated
by a nerve to
contract (motor
neruron)
Motor unit
One neuron
Muscle cells
stimulated by
that neuron
The Events in Muscle Contraction
Muscle Metabolism
Energy yield from
complete aerobic
catabolism of
glucose
Strength Changes With Aging

w Maximal strength decreases

w Muscle mass decreases
w Percentage of ST muscle fibers increases because of
death of fast twitch alpha-motoneurons followed by
reinnervation of the denervated fast muscle fibers by slow
motoneurons, which converts the muscle fibers to ST
w Total number and size of muscle fibers decreases
w Nervous system response slows
w Little change in oxidative enzyme
capacity or number of capillaries
Strength Changes With Aging
Weakness
Contracture
Gait changes
decrease in energy supply (ATP, creatine
phosphate and glycogen
decreased circulation to bring in O2 and
clear lactic acid
Changes at the motor end plate,
therefore decrease in stimulation
potential
reduction in size and number of
mitochondria hence decrease in
available energy
CHANGES IN STRENGTH WITH AGING
Effects of Training on Strength

While endurance training does not prevent the aging loss

in muscle mass, resistance training can maintain or
increase the muscle fiber cross-sectional area in older
men and women.
Use It and Lose Less of It
Resistance training improves strength by
a range of
40-150%
Lean body mass increases 1-3 kg
Muscle fiber area 10-30%
Computed Tomography Scans of Arms of
Three 57-Year-Old Men of Similar Body
Weights Biceps Brachii M.
Humerus

Triceps Brachii M.

Untrained Swim-Trained Strength-Trained

Increased Muscle Mass
Endurance
training emphasis
Walking isnt
enough
Progressive
resistance
training
DM prevention?
Dependency
prevention?
Falls and fractures
Disuse
Sarcopenia
MUSCLE FIBER CHANGES WITH AGING
Healthy perspective?
 Skeletal System

Composed of the bodys bones and

associated ligaments, tendons, and
cartilages.
Functions:
1. Support
The bones of the legs, pelvic girdle, and vertebral
column support the weight of the erect body.
The mandible (jawbone) supports the teeth.
Other bones support various organs and tissues.
2. Protection
The bones of the skull protect the brain.
Ribs and sternum (breastbone) protect the lungs
and heart.
Vertebrae protect the spinal cord.
 Skeletal System
Functions:
3. Movement
Skeletal muscles use the bones as levers to
move the body.
4. Reservoir for minerals and adipose tissue
99% of the bodys calcium is stored in bone.
85% of the bodys phosphorous is stored in
bone.
Adipose tissue is found in the marrow of
certain bones.
What is really being stored in this case? (hint
it starts with an E)
5. Hematopoiesis
A.k.a. blood cell formation.
All blood cells are made in the marrow of
certain bones.
 Bone Structure

Bones are organs. Thus, theyre composed of

multiple tissue types. Bones are composed of:
Bone tissue (a.k.a. osseous tissue).
Fibrous connective tissue.
Cartilage.
Vascular tissue.
Lymphatic tissue.
Adipose tissue.
Nervous tissue.
 Bone Strength
Bone biomechanical properties depend on :

Intrinsic Factors Extrinsic

Factors
Bone material Bone geometry
properties properties (architecture)
Ca2+ related X 1. Loading mechanism
Trabecular
Non Ca2+ related Cortical
2. Loading speed
3. Loading frequency
Bone Structural
Properties
Bone stiffness & strength

Bone remodelling
 Why Do Bones Break?
When load exceeds strength
Loads applied
to the bone

Bone Strength FRACTURE?

Applied Load
>1 FRACTURE
Bone Strength

Bouxsein, 2001
Pathogenesis of Bone Loss Due to
Calcium/Vitamin D Deficiency in
the Aged

Impaired renal Estrogen

function deficiency
Decreased calcium
absorption
Low dietary
Decreased
Calcium intake
vitamin D synthesis
Secondary
hyperparathyroidism

Decreased sunlight
exposure
BONE LOSS

Copyright 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Skeletal System Changes
Manifest changes that affect QOL significantly
Osteoporosis is a common condition characterized by:
progressive loss of bone density
Increased vulnerability to fractures
Thinning of vertebrae loss of height; spontaneous fractures
Reduction in height occurs by1 cm (0.4 inches) every 10 years
after age 40
Height loss is even greater after 70 years
The vertebrae calcify increasing rigidity, making bending difficult
 Trabecular bone (1)

Trabecular
bone with
Normal resorption
trabecular bone areas

Trabecular Osteoporotic
bone with trabecular
microcracks bone
 Microarchitecture and Bone Strength

180 kg 20 kg

(unsupported trabecular length)2 determines resistance against buckling load

 Microarchitecture and Bone Strength

180 kg 20 kg

(unsupported trabecular length)2 determines resistance against buckling load

The Importance of Connections
in Maintaining Strength
Loss of Connections
Results in a Loss of Strength
 Joints
Loss of hyaline cartilage
decreased water content with increased
calcium salts, crosslinking of fibers
therefore more stiff and less elastic
can reform fibrocartilage
 Joints
Synovial fluid decreased in volume
secondary to decreased blood flow,
Synovial membrane less elastic as are
adjacent ligament structure
with less movement-joint (ligaments)
contract to position
Osteoarthritis

 Physiological Changes
Heterogeneityof various values and functions
Many associated with physical inactivity
 Systole: (0.3sec)

ventricles contracting

Diastole: (0.5sec)

ventricles relaxing

Pressure & volume change, valve

activity, heart sound & ECG
 Phases of the Cardiac Cycle
Wiggers Curve

START
(f) Ventricular diastolelate:
All chambers are relaxed.
Ventricles fill passively. 800
msec
(e) Ventricular diastoleearly:
As ventricles relax, pressure
in ventricles drops; blood
flows back against cusps of
semilunar valves and forces
them closed. Blood flows
into the relaxed atria.
(a) Atriole systole begins:
Atrial contraction forces
a small amount of additional
blood into relaxed ventricles.
(b) Atriole systole ends
0 atrial diastole begins
msec 100
msec
(c) Ventricular systole
Cardiac first phase: Ventricular
cycle contraction pushes AV
valves closed but does
not create enough pressure
to open semilunar valves.
370
msec (d) Ventricular systole
second phase: As ventricular
pressure rises and exceeds
pressure in the arteries, the
semilunar valves open and
blood is ejected.
Cardiac Output (CO) and Cardiac Reserve

CO is the amount of blood pumped by

each ventricle in one minute
CO is the product of heart rate (HR) and
stroke volume (SV)
CO = HR x SV
(ml/min) = (beats/min) x ml/beat
HR is the number of heart beats per
minute (+ 75 beat per minute/bpm)
SV is the amount of blood pumped out
by a ventricle with each beat (+70 mL
per beat)
Cardiac reserve is the difference
between resting and maximal CO
The Cardiovascular
System
Overall reduction in blood flow occurs as we age
Heart of a 20-year old can pump 10 times the
amount actually needed to preserve life
After age 30, about 1% of reserve is lost/ year

Results in:
Normal atrophy of the heart muscle
Calcification of the heart valves
Arteriosclerosis ("hardening of the arteries")
Atherosclerosis (intra-artery deposits)
Cardiovascular Function and Aging

w Aerobic capacity decreases about 1% per year after age 25

w Maximum heart rate decreases about 1 beat per year
w Maximum stroke volume decreases, though it can be well
maintained with training
w Maximum cardiac output decreases
w Muscle blood flow decreases are offset in trained
individuals by an increased submaximal a-vO
2
difference
Maximal HR and Age

Maximal heart rate can be estimated with the following

equation:
HRmax = [208 0.7 age]
COVER

BP = CO X pR
 Extrinsic Innervation of the Heart
Vital centers of medulla
Cardiac Center
Cardioaccelerator center
Activates sympathetic
neurons that increase HR
Cardioinhibitory center
Activates parasympathetic
neurons that decrease HR
Cardiac center receives input
from higher centers (hypotha-
lamus), monitoring blood
pressure and dissolved gas
concentrations
 Slower
Healing rate

Reduced
Brain, Liver Poor Response
and Kidney to Stress
Function
CVD Changes

Poorer Cell
Oxygen

Risk of HBP,
Vulnerable to Heart Attack,
Drug Toxicity Stroke, Heart
Failure
 Natural
Natural History
History and
and Main
Main
Consequences
Consequences

American
American Heart
Heart Association
Association classification
classification of of human
human athero-sclerotic
athero-sclerotic
lesions
lesions from
from the
the fatty
fatty dot
dot (type
(type I)I) to
to the
the complicated
complicated type
type VI
VI
Varicose Veins
Heart to Heart
 Acute Myocardial
Infarction
Silent MI more common
Commonly presents with dyspnea only
May present with signs, symptoms of
acute abdomen--including tenderness,
rigidity
 Acute Myocardial

Infarction
Possibly just vague symptoms
Weakness
Fatigue
Syncope
Incontinence
Confusion
TIA/CVA
Acute Myocardial Infarction

If adding chest pain to their list of

symptoms would make you think MI,

ITS AN MI!
HEART FAILURE
Mechanics of Muscle Contraction:
Tension Sarcomere Length Relationship

Thin Filaments
Thick Filaments
 Hypovolemia & Shock

Decreased ability to compensate

Progress to irreversible shock rapidly
Tolerate hypoperfusion poorly, even for
short periods
 Hypovolemia & Shock

Hypoperfusion may occur at normal

pressures
Medications (beta blockers) may mask
signs of shock
Why can older persons be hypoperfusing at a
normal blood pressure?
 Anatomy Overview
Nasal cavity The respiratory tract includes:
Pharynx
Nose (nasal cavity) Pharynx
(nasopharynx, oropharynx,
laryngopharynx) Larynx Trachea
Bronchi (primary, secondary (lobar),
Larynx tertiary (segmental) Bronchioles
Terminal bronchioles Respiratory
Trachea
bronchioles Alveolar ducts
Alveoli
Bronchi

Bronchioles

Respiratory
bronchioles
Right Left
Alveolar duct
Lung Lung

Alveoli
 The Muscles of
Breathing
Inspiratory muscles
Diaphragm (75%)
External
Intercostalis
Sternocleido-
mastodeus
Scalenus
Seratus (anterior)

Expiratory muscles
Internal
Intercostalis
Abdominal
Muscles
Spirometry
LUNG VOLUMES Dead space

Residual
Volume

Tidal volume Total

lung
Expiratory reserve capacity
volume

Tidal volume
Vital capacity

Inspiratory reserve
volume
Changes in Respiratory System
Maximum lung function decreases with age
Diminished elasticity of airways and lung tissue
Reduced ciliary activity decreased oxygen uptake/exchange
Muscles of the rib cage atrophy, further reducing the ability to:
breathe deeply
cough
expel carbon dioxide
Aggravating factors: Smoking, Pollution
Results in:
Lower stamina for work; easily fatigued
Shortness of breath
Oxygen lack can increase anxiety
Susceptibility to pneumonia increased
Respiratory Changes With Aging

w Vital capacity (VC) and forced expiratory volume in 1 s

(FEV1.0) decrease linearly with age
w Residual volume (RV) increases
w Total lung capacity (TLC) remains unchanged
w RV:TLC increases (less air can be exchanged)
.
w VEmax decreases after maturity
w Elasticity in lung tissue and chest walls
decreases, which is the primary mechanism
for the above listed changes; there may also
be a decreased function of the respiratory
muscles
 .
Changes in VO2max With Aging
Among Normally Active Men

.
Age VO2max % change from
(years) (ml . kg -1. min -1 ) 25 years

25 47.7
35 43.1 -9.6
45 39.5 -17.2
52 38.4 -19.5
63 34.5 -27.7
75 25.5 -46.5
Changes in Aerobic Capacity and Maximal
Heart Rates With Aging in a Group of 10
Highly Trained Masters Distance Runners

.
VO2max
Age Weight HRmax
(years) (kg) (L/min) (ml kg1 min 1) (beats/min)
21.3 63.9 4.41 69.0 189
(1.6) (2.2) (0.09) (1.4) (6)
46.3 66.0 4.25 64.3 180
(1.3) (0.6) (0.05) (0.8) (6)

Note. Values are mean SE.

 .
CHANGES IN VO2MAX WITH AGE
Aging versus Inactivity

Aging alone might decrease cardiorespiratory fitness less

than the deconditioning that occurs with inactivity,
decreased activity, or decreased intensity of training. If
body
. composition and physical activity are kept constant,
VO2max decreases only 2% to 5% per decade, rather than
the 10% per decade normally attributed to aging.
The Components of the Digestive System
Digestive Process
 Age-Related Changes in the
Gastrointestinal Tract

Areas
Areas identified as
Motility Hormone
Hormone
Motility
responsiveness
responsiveness important
important to
to aging
aging
are:
are:
Pathophysiology
Pathophysiology of
of
Visceral
Visceral
sensitivity
sensitivity
Drug
Drug
metabolism
swallowing
swallowing disorders
disorders
metabolism
Esophageal
Esophageal reflux
reflux
Dysmotility
Dysmotility symptoms
symptoms
Liver
Liversensitivity
sensitivity Pancreas:
Pancreas:
to
tostress
stress Structure
and
Structure GI
GI immunobiology
immunobiology
andfunction
function
Cellular
Cellular mechanisms
mechanisms
of
of neoplasia
neoplasia in
in the
the GI
GI
Immunity
Immunity Lithogenic
Lithogenic tract
tract
bile
bile
Decreased
Decreased visceral
visceral
Colonic
Colonic
function
function
sensitivity
sensitivity

Hall
Hall KE,
KE, et
et al.
al. Gastroenterology.
Gastroenterology. 2005;129:1305-1338.
2005;129:1305-1338.
CURRENT
CURRENT HOT TOPICS
 Esophageal Aging

Dysphagia, regurgitation, chest pain, heartburn-

associated nausea are common in the elderly
Presbyesophagus: (age-related changes in
esophageal function)
Decreased
Decreased contractile
contractile amplitude
amplitude
Polyphasic
Polyphasic waves
Incomplete
Incomplete relaxation of the lower esophageal sphincter (LES)
Esophageal
Esophageal dilation
dilation
GERD
Common
Common in in the elderly
Impaired
Impaired clearance
clearance ofof acid
acid
Longer
Longer duration
duration of
of reflux
reflux episodes
Atypical
Atypical symptom presentation
Hall
Hall KE,
KE, et
et al.
al. Gastroenterology.
Gastroenterology. 2005;129:1305-1338.
2005;129:1305-1338.
CURRENT
CURRENT HOT TOPICS
 Aging and the Stomach

Decreased
Clearance of liquids from
stomach
Perception of gastric distention
Cytoprotective factors
Mucosal blood flow and
impaired sensory neuron
function in animal models
Increased
Contact time with NSAIDs or
other noxious agents in delayed
emptying
Tendency for gastric mucosal
injury in delayed emptying
Prevalence of H. pylori
associated with increased risk
of bleeding peptic ulcer,
pernicious anemia, and
lymphoma

Hall
Hall KE,
KE, et
et al.
al. Gastroenterology.
Gastroenterology. 2005;129:1305-1338.
2005;129:1305-1338.
Cullen
Cullen DJE,
DJE, et
et al.
al. Gut.
Gut. 1997;41:459-462.
1997;41:459-462.
CURRENT
CURRENT HOT TOPICS
 PPIs in the elderly
Overuse of PPIs is associated with

- Increased incidence of pneumonia

- Increased incidence of hip fractures
- Increased incidence of C. Difficile

Wean patients off PPIs and H2 Blockers if possible

CMAJ
CMAJ August
August 12,
12, 2008;
2008; 179 (4).Targonik LE,
LE, Lix
Lix LM,
LM, et
et al
al
CMAJ
CMAJ September
September 26,
26, 2006;
2006; 175
175 (7)
(7) Dial S, Delaney
Delaney C,
C, et alal

CURRENT
CURRENT HOT TOPICS
 Gastric Acidity

Reduced gastric secretions lead to an

increased post prandial gastric pH (6.5)
Fasting pH (1.3) in over 75 yr olds is
statistically different from average young
patients and 11% had a median fasting pH
of >5
The rate of return to pH 2.0 was
significantly longer than in younger
cohorts (> 4 hrs)
Pharm Res 1993 Feb;10(2):187-96.
Upper gastrointestinal pH in seventy-nine healthy, elderly,
North American men and women. Russell TL, Berardi RR,
CURRENT
et al.
CURRENT HOT TOPICS
 Gastrointestinal Bleeding Is
Common in the Elderly

75% GI bleeding in the

upper tract
Esophagus
Stomach
Small bowel

20%-25% GI bleeding
in the lower tract
Terminal ileum
Colon
Rectum

Hall
Hall KE,
KE, et
et al.
al. Gastroenterology.
Gastroenterology. 2005;129:1305-1338.
2005;129:1305-1338.
CURRENT
CURRENT HOT TOPICS
 Gastrointestinal Bleeding in the
Elderly

Of the 75% bleeding in the upper

tract
50%
50% bleeding
bleeding is due
due to
to NSAID
NSAID use
use
50%
50% bleeding
bleeding is due
due to
to ulceration
ulceration or
or
erosions
erosions (peptic
(peptic or
or esophageal)
Females are at higher risk than
males
Continued bleeding and rebleeding
are the highest predictors of
mortality and morbidity in older
patients

Hall
Hall KE,
KE, et
et al.
al. Gastroenterology.
Gastroenterology. 2005;129:1305-1338.
2005;129:1305-1338.
Image
Image courtesy
courtesy of
of David
David C.
C. Metz,
Metz, MD.
MD.
CURRENT
CURRENT HOT TOPICS
 Colorectal Cancer in the Elderly

An estimated 106,680
cases of colon and 41,930
cases of rectal cancer
were expected to occur in
2006
90% of all cases occur in
individuals aged > 50
years

American
American Cancer
Cancer Society.
Society. Cancer
Cancer Facts
Facts and
and Figures
Figures 2006.
2006. Atlanta:
Atlanta: American
American Cancer
Cancer Society;
Society; 2006.
2006.
Burt RW. Gastroenterology. 2000;119:837-853.
Burt RW. Gastroenterology. 2000;119:837-853.
Image
Image courtesy
courtesy of
of Subhas
Subhas Banerjee,
Banerjee, MD.
MD.
CURRENT
CURRENT HOT TOPICS
 Colorectal Cancer in the Elderly
In
In aa study
study of
of 1244
1244 participants divided into 3 age groups who
underwent
underwent screening
screening colonoscopy, increasing age may be
associated
associated with
with an
an increased
increased prevalence
prevalence of neoplasia
of neoplasia
Prevalence of
Prevalence (%)
neoplasia (%)

n = 1034 n = 147 n = 63

Age
Age group
group (years)
(years)
Lin
Lin OS,
OS, et
et al.
al. JAMA.
JAMA. 2006;295:2357-2365.
2006;295:2357-2365.
CURRENT
CURRENT HOT TOPICS
 Aging-Associated Changes in
Colonic Motility

Common disorders observed in the elderly that are

correlated with colonic motility are:
Constipation
Constipation
Diverticular
Diverticular disease
disease
Diarrhea
Diarrhea
Fecal
Fecal incontinence
incontinence
There are age-associated reductions in myenteric
neurons, calcium influx, and tensile strength of the
collagen and muscle fibers
No clear effect of age on colonic transit, as many
constipated older patients appear to have normal
transit times

Hall
Hall KE,
KE, et
et al.
al. Gastroenterology.
Gastroenterology. 2005;129:1305-1338.
2005;129:1305-1338.
Petruzziello
Petruzziello L, et al. Aliment Pharmacol Ther. 2006;23:1379-1391.
L, et al. Aliment Pharmacol Ther. 2006;23:1379-1391.
CURRENT
CURRENT HOT TOPICS
 Prevalence of Constipation Compared
to Other Common Diseases
Prevalence
Prevalence of
of Selected Diseases in US Adults
Coronary
Coronary heart
heart disease
disease 14
14

Asthma
Asthma 16
16

Diabetes
Diabetes 16
16

Migraines
Migraines 33
33

Hypertension
Hypertension 49
49

Constipation
Constipation 63*
63*

00 20
20 40
40 60
60 80
80
Prevalence
Prevalence in
in millions
millions
Pleis JR and Lethbridge-Cejku M. Summary health statistics for U.S. adults:
National health interview survey, 2005. National Center for Health Statistics.
*Prevalence
*Prevalence in
in North
North Americans
Americans Vital Health Stat 10(232). 2006. Available at:
http://www.cdc.gov/nchs/data/series/sr_10/sr10_232.pdf. Accessed 3.5.07.
Higgins PDR, et al. Am J Gastroenterol. 2004;99:750-759.
CURRENT
CURRENT HOT TOPICS
 Diverticular Disease
An
An abnormality in the aging colon
involving
involving decreased tensile strength of
the
the muscle
muscle wall
By
By age
age 50
50 years,
years, one third of Americans
will
will have
have diverticulosis
diverticulosis coli;
coli; by
by age
age 80
80
years,
years, two
two thirds
thirds will be affected
Incidence
Incidence less
less than
than 5%
5% among
among those
those aged
aged
<< 40
40 years
years
Incidence
Incidence greater
greater than
than 60%
60% byby age
age 85
85 years
years
Mean
Mean age
age atat presentation
presentation is
is 60
60 years
years
The
The majority
majority of those affected are
asymptomatic
asymptomatic
Hall
Hall KE,
KE, et
et al.
al. Gastroenterology.
Gastroenterology. 2005;129:1305-1338.
2005;129:1305-1338.
Cooperman
Cooperman A,
A, et
et al.
al. Diverticulitis.
Diverticulitis. eMedicine
eMedicine Web
Web Site.
Site. Available
Available at:
at:
www.emedicine.com/MED/topic578.htm. Accessed
www.emedicine.com/MED/topic578.htm. Accessed 11/3/06. 11/3/06.
Image
Image courtesy
courtesy of
of Jennifer
Jennifer Christie,
Christie, MD.
MD.
CURRENT
CURRENT HOT TOPICS
 Diverticular Disease (Cont.)

Other factors in diverticular disease:

Slow
Slow colonic
colonic transit
transit
Increased
Increased frequency
frequency of
of segmenting
segmenting contractions
contractions resulting
resulting in
in
increased
increased water
water reabsorption
reabsorption and hard feces

According to data from the National Demographic

and Health Survey (NDHS) between 1997 and 2002
Hospital
Hospital admissions
admissions increased
increased by by 14% to 261,180
261,180
Office
Office visits
visits increased
increased by
by 14%
14% to to 1,493,865
1,493,865
Emergency
Emergency department
department visits
visits increased
increased byby 84%
84% to
to 161,364
161,364

Hall
Hall KE,
KE, et
et al.
al. Gastroenterology.
Gastroenterology. 2005;129:1305-1338.
2005;129:1305-1338.
CURRENT
CURRENT HOT TOPICS
 Diarrhea

Definition:
Loose
Loose stools
stools of
of more
more than 200 grams per day in at least
33 bowel
bowel movements
movements per
per day
day

Approximately 85% of all mortality associated with

diarrhea involves the elderly
73
73 million
million consultations
consultations for
for acute
acute diarrhea
diarrhea in the
the United States
States
each
each year
year

Between 1997 and 2002

Office
Office visits
visits for
for chronic
chronic diarrhea increased by
by 115%
115% from
from
991,886
991,886 toto 2,132,272
2,132,272

Hoffmann
Hoffmann JC,
JC, et
et al.
al. Best
Best Pract
Pract Res
Res Clin
Clin Gastroenterol.
Gastroenterol. 2002;16:17-36.
2002;16:17-36.
Hall
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
KE, et al. Gastroenterology. 2005;129:1305-1338.
CURRENT
CURRENT HOT TOPICS
 Causes of Diarrhea in the Elderly

Common Causes Less Common Causes

Infections Celiac disease
Drug-induced diarrhea Inflammatory bowel disease

Malabsorption Thyrotoxicosis

Fecal impaction Scleroderma with systemic

manifestations
Colonic carcinoma
Whipples disease
Small bowel bacterial overgrowth
Amyloidosis with small bowel
Diabetic diarrhea involvement
Pancreatic insufficiency
Small bowel tumors

Hoffmann
Hoffmann JC,
JC, et
et al.
al. Best
Best Pract
Pract Res
Res Clin
Clin Gastroenterol.
Gastroenterol. 2002;16:17-36.
2002;16:17-36.
Hall
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
KE, et al. Gastroenterology. 2005;129:1305-1338.
CURRENT
CURRENT HOT TOPICS
 Fecal Incontinence
Fecal
Fecal incontinence
incontinence isis uncommon
uncommon in in the
the general
general population
population
(2.2%)
(2.2%) but
but has
has aa significantly
significantly higher
higher prevalence
prevalence (10%)
(10%) in
in the
the
older
older population
population

Anorectal damage Structural

from surgery or impairments in
irradiation the pelvic floor

Fecal incontinence
can result from:
Fecal impaction Decreased
and subsequent rectal or anal
overflow sensation

Internal anal
sphincter
incompetence

Hall
Hall KE,
KE, et
et al.
al. Gastroenterology.
Gastroenterology. 2005;129:1305-1338.
2005;129:1305-1338.
CURRENT
CURRENT HOT TOPICS
 Fecal Incontinence

Risk factors identified are:

Advancing
Advancing age
Diabetes
Diabetes mellitus
mellitus
Urinary
Urinary incontinence
incontinence
Stroke
Stroke
Physical
Physical limitations
limitations
Female
Female gender
gender
Gynecological
Gynecological surgery
surgery
Perianal
Perianal injury or surgery
surgery
Hypertension
Hypertension
Poor
Poor general health
Bowel-related
Bowel-related factors
factors (incomplete
(incomplete defecation,
defecation, constipation,
constipation,
straining,
straining, fecal
fecal urgency)
urgency)
Goode
Goode PS,
PS, et
et al.
al. JJ Am
Am Geriatr
Geriatr Soc.
Soc. 2005;53:629-635.
2005;53:629-635.
CURRENT
CURRENT HOT TOPICS
 Implications for Elderly Suffering from
Diarrhea and/or Fecal Incontinence

Both can become a chronic problem resulting in

social isolation and decreased activity out of the
home
It is important to obtain a good history to determine if
fecal incontinence is due to diarrhea, urgency,
obstruction, or rectal dysfunction

Hall
Hall KE,
KE, et
et al.
al. Gastroenterology.
Gastroenterology. 2005;129:1305-1338.
2005;129:1305-1338.
Akhtar
Akhtar AJ, et al. JJ Amer
AJ, et al. Amer Med
Med Dir
Dir Assoc.
Assoc. 2005;6:54-60.
2005;6:54-60.
CURRENT
CURRENT HOT TOPICS
 Hepatobiliary Function With Aging
Dynamic
Dynamic assessments
assessments of of liver function decrease with aging
Compared
Compared to
to younger
younger adults, in healthy subjects
subjects there
there is
is a
decrease
decrease of
of 30%
30% -- 40%*
40%* in:
in:
Liver
Liver size
size
Blood
Blood flow
flow
Perfusion
Perfusion
Nonalcoholic
Nonalcoholic steatohepatitis (NASH) is a common
complication
complication of
of obesity
obesity and
and diabetes
diabetes mellitus
mellitus
Diabetes
Diabetes affects
affects 12%
12% ofof the
the US
US population;
population; >> 70%
70% ofof affected
affected
individuals
individuals are
are in
in the
the geriatric
geriatric age
age range
range
NASH
NASH may
may progress
progress toto cirrhosis
cirrhosis in
in up
up to
to ~25%
~25% ofof patients
patients
NASH
NASH increases
increases the
the risk
risk of
of hepatic
hepatic side
side effects
effects of
of certain
certain drugs
drugs

*Decreases
*Decreases occur
occur between
between the
the 33rdrd and
and 10
10thth decade
decade of
of life
life
Hall
Hall KE,
KE, et
et al.
al. Gastroenterology.
Gastroenterology. 2005;129:1305-1338.
2005;129:1305-1338.
Reynaert
Reynaert H, et al. Aliment Pharmacol
H, et al. Aliment Pharmacol Ther.
Ther. 2005;22:897-905.
2005;22:897-905.
CURRENT
CURRENT HOT TOPICS
 Gallbladder Function with Aging

Bile becomes increasingly lithogenic with aging

Precipitation
Precipitation of
of supersaturated
supersaturated bile
bile and
and concomitant
concomitant
crystallization
crystallization of
of cholesterol
cholesterol or
or calcium bilirubinate
bilirubinate
In subjects aged > 35 years, fasting and postprandial
gallbladder volumes increased
In
In older
older individuals,
individuals, there
there was
was less
less complete
complete gallbladder
gallbladder
emptying
emptying following
following aa meal
meal
Aging women may be more susceptible to impaired
gallbladder contractility
Compared to young patients, cholecystitis and
cholangitis in older patients have increased morbidity
and mortality
Hall
Hall KE,
KE, et
et al.
al. Gastroenterology.
Gastroenterology. 2005;129:1305-1338.
2005;129:1305-1338.
CURRENT
CURRENT HOT TOPICS
 Pancreatic Function With Aging

Exocrine and endocrine pancreatic function in

nondiabetic patients is preserved with aging
Incidence of pancreatic cancer is increasing in
patients aged > 65 years
Significantly
Significantly worse
worse surgical
surgical outcomes in patients > 74 years
Median
Median survival
survival is
is 11
11 months
months vs. 25 months in patients aged
64
64 to
to 74
74 years
years
Approximately half of acute pancreatitis cases are
patients aged > 60 years
Gallstones
Gallstones are
are most
most common
common etiology
etiology (60%)
40%:
40%: surgery,
surgery, drugs,
drugs, trauma,
trauma, infection,
infection, alcohol
alcohol
Mortality
Mortality in elderly is 20%; twice that of general population
Hall
Hall KE,
KE, et
et al.
al. Gastroenterology.
Gastroenterology. 2005;129:1305-1338.
2005;129:1305-1338.
CURRENT
CURRENT HOT TOPICS
Skin and Its Tissues

Composed of several tissue types

Maintains homeostasis
Protective covering
Retards water loss
Regulates body temperature
Houses sensory receptors
Contains immune system cells
Synthesizes chemicals
Excretes small amounts of wastes

149
Skin Cells

Help produce Vitamin D needed for normal

bone and tooth development

Some cells (keratinocytes) produce substances

that simulate development of some white
blood cells

150
 Layers of Skin (3)
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Epidermis Stratified
squamous

Dermis epithelium

Subcutaneous layer
AKA hypodermis Dense irregular
connective
tissue
Beneath dermis
Some also call it the
superficial fascia
Some consider it not
Adipose tissue
part of the skin
The McGraw-Hill Companies, Inc./Al Telser, photographer

151
PHYSICAL IMPLICATIONS OF AGING
Skin:
Exhibits most obvious sign of aging
Loss of underlying connective tissue, fat and oil
glands wrinkles, sagging skin
Aging skin appears thinner, paler, and translucent
Increased sensitivity to heat/cold, bruising, and
bedsores
Develops "age spots" due to deposits of melanin
pigment
Ability to perspire is decreased
Contributing factors: nutrition; exposure to sun,
chemicals/toxins; hormones, and heredity
 Epidermis
Lacks blood vessels
Keratinized
Thickest on palms and
soles (0.8-1.4mm)
Melanocytes provide melanin
Rests on basement membrane
Stratified squamous epithelium

With aging less able to keep out

substances; chemicals,
microorganisms
athletes foot, fissures
 Dermis
On average 1.0-2.0mm thick
Contains dermal papillae Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Binds epidermis to underlying Hair shaft

Sweat gland pore

tissues
Sweat
Stratum corneum
Epidermis Stratum basale
Capillary

Irregular dense connective tissue Dermal papilla

Basement membrane
Tactile (Meissners) corpuscle
Muscle cells Dermis Sebaceous gland
Arrector pili muscle
Sweat gland duct

Nerve cell processes Lamellated (Pacinian) corpuscle

Hair follicle

Specialized sensory receptors SubcutaneousSubcutaneous

layer
Sweat gland
Nerve cell process
Adipose tissue
Blood vessels
Blood vessels Muscle layer

(a)

Hair follicles
With aging less h20 more
Glands crosslinking of collagen therefore
155
thinner and less elastic- fissures
 Subcutaneous Layer
AKA hypodermis Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Loose connective Hair shaft

Sweat gland pore

tissue and
Sweat
Stratum corneum
Epidermis Stratum basale
Capillary
Dermal papilla

Adipose tissue is Basement membrane

Tactile (Meissners) corpuscle

present
Dermis Sebaceous gland
Arrector pili muscle
Sweat gland duct
Lamellated (Pacinian) corpuscle

Insulates Subcutaneous
Hair follicle
Sweat gland
layer Nerve cell process
Adipose tissue

Major blood vessels Blood vessels

Muscle layer

present

With aging
decreased fat: decreased cushion, callous/corns
less skin support: increased sheer force 156
***Typically the subcutaneous tissue is poorly vascularized.
DEFINITION OF A PRESSURE ULCER

Localized area of
tissue breakdown
resulting from
compression of soft
tissue between a bony
prominence and an
external surface
Touch
Hair:
Shows obvious signs of aging
Hair color is due to pigment melanin- gradually decreases after
age 30-40
Loses pigmentation turns hair gray/white
Manifests earliest in scalp, followed by facial/body hair
Occurs earlier in Caucasians compared to Asians
Alopecia- baldness/ hair loss is the norm
Coarsening of hair common

Nails:
Become dull, brittle, ridged, thickened, grow slower
due to reduced blood flow to connective tissues
 Nails
Lunula Nail bed Nail plate
Protective coverings

Three (3) parts:

Nail plate
Nail bed
Lunula

160
Body Defenses
Immune System

Overall effectiveness decreases, leading to:

Increased infection risk

Decreased ability to fight diseases

Slowed wound healing

Autoimmune disorders

Cancers
Geriatric Abuse & Neglect
Physical, psychological injury of
older person by their children or
care providers
Knows no socioeconomic bounds
Acting with Empathy:

Empathy recognizing and understanding

the state of mind, beliefs, desires and
emotions of another person without
interjecting your own.

Putting yourself in anothers shoes

Sympathy feeling sorry another person.

Empathy Sympathy
Avoid patronizing speech remarks that
reflect stereotypes of incompetence and
dependence.

Avoid infantalization e.g., using terms

of endearment, using simple language,
etc.
 Ideal ageing
Preconception
Obstetrics Prevention & Well-being perspective
Health CHC cure Participation
QoL
Wellbeing
etc.

Intervention

Age
Birth Chronic disorder 1 Complication
Chronic disorder 2
Food
intake

Food
intake

pro-opiomelanocortin (POMC)

paraventricular nuclei (PVN)

cocaine- and amphetamine-regulated transcript (CART)

Balance in aging
Anorexie:many factors contribute
Cytokines Muscle
N - loss Hormones wasting
Lipolysis Low albumin

Social factors Modulators / mediators

Mechanical barrages Serotonin, NE
Leptin, NPY, CRF
Sensory changes
IL-1, IL-6l, TNF-alpha
Taste, smell, texture, appearance
MSH
Illness (Cancer, Infectious CCK, GRP, Amylin,
diseases, COPD, gastrointestinal
diseases, heart failure, pressure Glucagon, GLP
sores) Somatostatin
Ghrelin
Psychiatric illnesses
The End
TERIMAKASIH