Pathophysiology
• JP Advis DVM, Ph.D.
Bartlett Hall, Animal Sciences, Cook,
932 - 9240, advis@aesop.rutgers.edu
15
• Course website: rci.rutgers.edu/~advis
• Lectures, tests, grades, office hours, textbook,
Lectures 1-2: Introduction to Pathophysiology (2)
Lectures 3-4: Mechanisms of Self-Defense and Stress (2)
Lectures 5-8: Endocrine and Nervous System Dysfunctions (4)
Lecture
9: Alterations of Skeletal Muscle Function (1)
REVIEW AND TEST #1
Lectures 12-18: Cardiovascular, Respiratory and Renal Dysfunctions (7)
REVIEW AND TEST #2
Lectures 21-24: Alterations of Digestive Function and Intermediary Metabolism (4)
Lectures 25-26: Alterations of the Reproductive System (2)
REVIEW AND TEST #3
• Material to
be covered:
• About
lecture
slides:
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•
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There are not intended to be the sole source for studying the course material !!!!!!!!!!!!!!!!
Slides are good to review the course material after you have study your course textbook
Slides are a good indicator of the relative importance of lecture topics (see slide # per topic
Group slides by titles when using them to review course material. Match lectures and text.
Respiratory structure / function
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
The pulmonary system consist of the lungs, airways, chest wall,
and pulmonary circulation. Its primary function is the exchange
of gases between environmental air and the blood. The
processes involved are ventilation, diffusion, & perfusion.
The lungs are protected by a series of mechanical barriers from
exogenous contaminants (URT mucosa, nasal hair & turbinates,
mucus blanket, cilia, alveolar macrophages, irritant receptors).
Alveoli are the primary gas exchange units of the lung. Type I
alveolar cells provide support and type 2 provide surfactant.
Ventilation is the mechanical movement of gas or air into and
out of the lungs, It is controlled by the brain respiratory center,
which receives inputs from lung receptors and chemoreceptors.
Airways are controlled by the autonomic nervous system (ANS).
Structure / function of the pulmonary system
Page 1
Respiratory structure / function
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
Structures of pulmonary system and upper airways
NASAL WALL
PHARYNX
nasal cavity
pharinx
upper
respiratory
tract
larynx
traquea
lower
respiratory
tract
bronquioles
TRAQUEA
Page 2
LARYNX
Respiratory structure / function
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
Structures of lower airways, their branching, alveoli
conducting
airways
pulmonary
venule
alveolar
duct
respiratory
unit
lower airways
pulmonary
arteriole
alveolar sac
alveoli
Page 3
cellular structures
Respiratory structure / function
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
Section through the alveolar septum (gas exchange membrane)
type 2
surfactant
alveolar cell
layer
intertitial
cell
connective
tissue
alveolar
epithelium
surfactant
layer
capillary
endothelium
capillary
endothelium
red blood cell
(RBC)
alveolar
epithelium
basement
membrane
type 1
alveolar cell
basement
membrane
alveolar
macrophage
Page 4
intertitial
space
Respiratory structure / function
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
Chest cavity, functional components, and spirogram
trachea
larynx
right primary bronchus
aorta
left
primary
bronchus
right lung
mediastinum
parietal pleura
viceral pleura
left lung
pleural space
diaphragm
esophagus
Page 5
Page 6
Respiratory structure / function
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
Neurochemical respiratory control syste
blood-brain
barrier
capillary
voluntary and
higher centers
control centers
pneumotaxic (inspiration)
chemosensitive (H,O2,CO2)
apneustic (insp & exp)
DRG (inspiration)
VRG (inspiration & expiration)
vagus n.
stretch
irritant
J receptors
vagus n.
carotide
body
intercostal n.
aortic
bodies
(low PO2)
phrenicl n.
(to diaphragm)
Page 7
Respiratory clinical manifestations
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
Pulmonary disease is linked to many signs and symptoms, The
most common are cough and dyspnea. Others are chest pain,
abnormal sputum, hemoptysis, altered breathing patterns,
cyanosis, and fever.
Dyspnea is a subjective sensation of uncomfortable breathing,
as for example, dyspnea on exertion and orthopnea.
Common clinical manifestations include, abnormal breathing
patterns (e.g. Kussmaul and Cheyne-Stokes respirations), hypo
and hyperventilation, cyanosis, clubbing, cough, hemoptysis,
abnormal sputum, and pain.
Conditions caused by pulmonary disease or injury include,
hypercapnia, hypoxemia, acute respiratory failure, pulmonary
edema, aspiration, atelectasis, bronchiectasis, bronchiolitis,
pleural abnormalities, chest wall restrictions, and flat chest.
Common clinical manifestations of pulmonary alterations
Respiratory clinical manifestations
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
Clubbing caused by hypoxemia and v/q abnormalities
Page 8
clubbing - early
clubbing - moderate
clubbing - severe
Respiratory clinical manifestations
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
Pathogenesis of pulmonary edema
Page 9
valvular dysfunction
coronary artery
disease
injury to capillary
endothelium
blockage of
lymphatic vessels
left ventricular
dysfunction
increased
left atrial
pressure
Increased capillary
permeability and
disruption of
surfactant production
by alveoli
Inability to remove
excess fluid from
interstitial space
increased pulmonary
capillary hydrostatic
pressure
movement of fluid and plasma
from capillary to intertitial
space (alveolar septum)
and alveoli
accumulation of fluid
in interstitial space
pulmonary
edema
Pulmonary disorders
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Restrictive lung diseases are characterized by decreased lung
complience and increased work of breathing. The most common
examples are pulmonary fibrosis, inhalational disorders, allergic
alveolitis, pneumoconiosis, and the acute respiratory distress
syndrome (ARDS).
Obstructive lung diseases are characterized by airway obstruction
that is worst with expiration. The most common examples are
asthma, chronic bronquitis and emphysema. When the last two
occur together, it is often called chronic obstructive pulmonary
disease (COPD).
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
The most common respiratory tract infections involved the upper
tract (common cold, pharingitis, laryngitis). Infections of the lower
respiratory tract occur most often in individuals whose normal
defenses mechanisms are impaired.
Pulmonary vascular disease ls linked to pulmonary embolism,
pulmonary hypertension, and cor pulmonale (right side failure).
Pulmonary disorders
Page 10
Respiratory dysfunctions
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
Atelecthasia (Kohn’s pore), pneumothorax, flail chest are examples
of restrictive disorders
normal
alveolus
closed pore of Kohn
open
pore
of Kohn
atelectatic
alveolus
PORES OF KOHN
low inspiratory volume (shallow breathing)
high inspiratory volume (deep breathing)
EXAMPLES OF RESTRICTIVE DISORDERS
inspiration
PNEUMOTHORAX
expiration
FLAT CHEST
Page 11
Respiratory dysfunctions
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
mechanism for acute respiratory distress syndrome (ARDS) is
another example of a restrictive disorder
acute insult
(e.g. pneumonia, aspiration, smoke inhalation)
ARDS
Release of cytokines
( e.g. IL, Tß, TNF)
influx of inflammatory cells to lung
( e.g. neutrophils, macrophages, activated platelets )
release of ROS and cytokines
activation of complement system
damage to type 2
pneumocytes
disruption of alveolar
capillary membrane
microthrombi in
pulmonary circulation
atelectasia & decreased non-cardiogenic pulmonary pulmonary hypertension
edema and intrapulmonary
lung complience
shunting
Page 12
release of FGFs
(e.g. TGFß, PDGF
pulmonary fibrosis
Respiratory dysfunctions
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
Examples of airway obstruction are those caused by
emphysema, chronic bonchitis and asthma
Obstructive dysfunctions
(B, C, D)
panlobular
centrilobular
NORMAL LUNG
EMPHYSEMA (destruction of alveolar walls)
CHRONIC BRONCHITIS (inflammation)
BRONCHIAL ASTHMA (obstruction)
Page 13
Respiratory dysfunctions
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
Pathophysiology of asthma, an airway obstruction dysfunction
allergen or irritant exposure
immune activation
(IL-4, IgE production)
mast cell degranulation
vasoactive mediators
chemotactic mediators
ASTHMA
vasodilation
Increased capillary permeability
cellular infiltration
(neutrophils, lymphocytes, eosinophils)
autonomic
dysregulation
bronchospasm
vascular congestion
mucus secretion
impaired mucociliary function
thickening of airway walls
jncreased contractile response of
bronchial smooth muscle
release of toxic
neuropeptides
bronchial hyperesponsiveness
airway obstruction
epithelial desquamation
and fibrosis
Page 14
Respiratory dysfunctions
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
Pathophysiology of chronic bronchitis and emphysema (COPD),
another example of an obstructive respiratory dysfunction
tobacco smoke
air pollution
inflammation of the airway epithelium
systemic effects (muscle
weakness, weight loss)
continuous bronchial
irritation and inflammation
infiltration of
inflammatory cells and
release of cytokines
(neutrophils, macrophages, lymphocytes,
leukotriens, interleukins)
inhibition of normal
endogenous antiproteases
increased protease activity with
breakdown of elastin in connective
tissue of lungs (elastase, cathepsin)
Emphysema (destruction of alveolar
septo and loss of elastic recoil of
bronchial wall
chronic bronchitis (bronchial edema,
hypersecretion of mucus, bacterial
colonization of airways
airway obstruction, air trapping, loss
of surface area for gas exchange,
frequent exacerbations (infections,
bronchospasms
COPD
inherited alpha 1 antitrypsin deficiency
dyspnea, cough,
hypoxemia, hypercapnia,
cor pulmonale
Page 15
Your eigth case study
Structure / Function
airways, chest wall & pleura,
ventilation, breathing, gas
transport, lung circulation
Clinical manifestations
signs, symptoms and
consequences of pulmonary
disease
Pulmonary disorders
restrictive and obstructive
lung disease, infections,
pulmonary vascular disease,
respiratory tract malignancies
Case studies
examples of case files on
respiratory function disorders
SUMMARY:
A 34-year-old woman with diabetes presents to the emergency
department with complaints of fever, chills, back pain,
dizziness, and shortness of breath. She reports a new onset
non-productive cough and denies having chest pain. She
reports no sick contacts. On examination, she is ill-appearing,
febrile, hypotensive, and tachycardic. She has marked right
costovertebral (flank) tenderness. Her lung examination
demonstrates course rales and rhonchj throughout both lung
fields. Her heart rate is tachcardic but with a regular rhythm.
Her O2 saturation on room air is very low at 80% (normal is
>94%). Urinalysis reveals numerous bacteria and leukocytes,
consistent with an urinary tract infection. She has pyelonephritis and septic shock, with evidence of bilateral pulmonary
infiltrate, on chest X-ray.
TENTATIVE DIAGNOSIS:
LAB TESTS:
FINAL DIAGNOSIS:
TREATMENT:
Page 16