The Lung:
An Environmentally Embattled Organ
MCB 135K
April 25, 2007
Box 18.1
Pulmonary Respiratory System: Structure
Two lungs activate gas exchange
Chest wall
Respiratory muscles
Activate ventilation
Regulation of respiration by CNS centers
& nerve tracts
Box 18.1
Pulmonary Respiratory System: Major Functions
• Regulation of gaseous exchange
• Immunologic defenses of the body
-by phagocytizing particles from inspired air & blood
• Metabolic functions
-by synthesizing, storing or releasing into blood substances like
surfactant and prostaglandins
• Endocrine functions
-by transforming angiotensin I into angiotensin II
(vasoconstrictor and stimulus for aldosterone secretion)
Lung, “Battered” Organ
Due to:
• Air pollution
• Smoking
• Air borne infections
• Oxygen toxicity
(e.g. with the use of respirators there is increased
free radical production; therefore, simultaneous
administration of antioxidants is recommended)
Major Structural Changes in the
Aveolar Ducts & Aveoli with Age
Amount of elastic tissue
Amount of fibrous tissue
TABLE 18-2
Changes with Aging in Respiratory Muscles
Muscle strength
fatigue when work of breathing
physical exercise)
(as during
Atrophy of some respiratory muscles (primarily
Type I muscle fibers of slow, red muscles as in
long muscles of back, shoulders)
Ratio of glycolytic (anaerobic) to oxidative (aerobic)
metabolism
Blood supply to muscle
Table 1 8- 3 Changes with Age *
Thorax
Morphologic Changes
Calcifi cati on of bronchial and cost al
cart ilage
 cost overteb ral st iffn ess
 rigidit y of chest wall
 ante rior -po st erio r diamet er
Wast ing of respirat or y muscles
Functional Consequences

resist ance t o defor mat ion of chest
wall
 use of diaph ragm in venti lat ion
 t idal volu me *
respons e t o exercise hyperapn ea
 maximal volu nt ary venti lat ion
* Tidal Volume: Amount of in and out air moving out of lungs with quiet
inspiration/expiration
Table 18-3 Changes with Age in the Lung
LUNG
Morphological Changes
Enlarged alveol ar du ct s

suppor t ing du ct fra mewo rk
Alveoli shallow , fl at t er
Thinn ing, separ at ion of alveol ar membrane

mu cous gland

num ber, t hicknes s of elast ic fi bers

t issue ext ensibilit y ( alve ola r wa ll)


pu lmon ary capillary net wo rk
fi br osis of pulm onar y
capillary inti ma
Functional Significance

surf ace area for gas exchange
decreased st ret chability

ph ysiologic dead space ( 4 0%) *

lung elast ic recoil
Vit al Capacit y 1 5 -2 0% **
RV/ TL C  35 -4 0 % **
 ve nt ilato ry fl ow rate
venti lat ion dist ribut ion

resist ance t o fl ow in small airwa ys
 ve nt ilat ion
* Dead Space: Air in the air ways
** Vital Capacity (VC): Greatest amount of air expired after maximal inspiration
** Reserve Volume (RV)/Total Lung Capacity (TLC)
Table 18-1
Signs of Impaired Pulmonary Respiration with Aging
Reduced maximum breathing capacity
Less efficient emptying of the lungs
Premature airway closure
Progressive reduction in blood oxygenation and in PO2 exchanges
between blood and alveolar air
Loss of elastic recoil (i.e. springing back of elastic fibers
after stretching)
Increased rigidity of internal lung structure
Weakening of respiratory muscles
Decreased elasticity of thorax cage and chest wall
Earlier and easier fatigability
Chronic Obstructive Pulmonary Disease
(COPD)
Comprised of three distinct pathologies:
• Chronic bronchitis: inflammation of the bronchi
and accompanied by hypersecretion of mucus &
cough
• Emphysema: characterized by enlargement of
air spaces, destruction of lung parenchyma, loss
of lung elasticity and closure of small airways
• Chronic asthma: constriction of the bronchi
TABLE 18-4
Major Risk Factors for
Chronic Obstructive Pulmonary Disease (COPD)
Cigarette smoking
Air pollution
Genetic factors
Bronchial inflammation
Chronic respiratory tract infections
Old age
Family history of COPD
Male sex
TABLE 18-5
Major Signs of Chronic Obstructive Pulmonary Disease (COPD)
Structural
• Diffuse distention & overaeration of alveoli
• Disruption of interalveolar
septa
• Loss of pulmonary elasticity
• Restructuring of alveoli
• Increased lung volume
• Barrel-shaped chest
Pathophysiologic
• Disturbed ventilation
• Altered air and blood flow
• Frequently partial obstruction
of bronchi
• Wheezing & more work
required for breathing
• Resulting hypoxia (low O2
levels) and hypercapnia (high
CO2 levels)
• Chronic productive cough
with mucus
• Minor respiratory infections
Table 18-6 (con’t.)
Therapeutic strategies:
1. Administration of pharmacological agents
(bronchodilators, mucus liquefiers, anti-inflammatory
agents, protease inhibitors, antibiotics)
2. Administration of O2 to be used cautiously to prevent
acidosis
3. Optimizing function by:
-physical exercise to strengthen abdominal muscles
and diaphragm to aid in lung ventilation
-meeting social, emotional and vocational needs.
-use of respiratory aids in the form or aerosols,
sprays, etc.
Lineages of Mature Blood Cells
Derived from Bone Marrow Stem Cells
White Blood Cells
Granulocytes
Neutrophils
Eosinophils
Basophils
Lymphocytes
B-cells
T-cells
Monocytes
Erythrocytes (Red Blood Cells, RBCs)
Platelets
Some unique characteristics of Red Blood Cells
Red blood cells represent a cell population that:
is easily accessible,
is in continuing renewal,
has a well-defined life span,
has become a popular model
for the study of cell function
at all ages, including old age.
Major Functions of Blood Cells
Efficient oxygen delivery to tissues and cells (erythrocytes, RBCs)
Hemostasis: prevention of blood loss (e.g., through blood clotting,
platelets)
Immune response, primarily white blood cells (Chapter 14)
Responsiveness to environmental stimuli (e.g., increase in cellular
response to hypoxia)
Specificity of responses to demands (only relevant lineage is
stimulated without expansion of irrelevant ones; e.g. hypoxia
selectively stimulates erythroid bone marrow and subsequent
erythropoiesis)
Table 18-13
Hematological Profile of Some Older Individuals
Hemoglobin
Hematocrit
RBC number
Onset of erythropoiesis after
severe bleeding
Erythropoietic responses to
erythropoietin administration
Most of these changes are NOT experienced by
centenarians
Table 18-14
Hormonal Regulators of Erythropoiesis
Erythropoietin
Testosterone
Interleukin-3
Table 18-15
Factors Involved in Earlier and Faster (< 120 days)
Removal of RBCs from Circulation in Old Subjects
Causes
Mechanisms
Earlier and greater fragility
Alteration in membrane lipids
increases cell fragility as well as
decreases glucose transport and
utilization
Greater tendency to aggregate
Membrane alterations may promote
RBC aggregation
Decreased availability of energy for
metabolism
Decreased activity of NA+K+ATPase
Altered ionic balance, especially in
aging associated diseases
Alteration in ionic balance