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Pathophysiology 15 • JP Advis DVM, Ph.D.
Bartlett Hall, Animal Sciences, Cook,
932 - 9240, [email protected]
• Course website: rci.rutgers.edu/~advis
• Lectures, tests, grades, office hours, textbook,
• Material to
be covered:
• About
lecture
slides:
• 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.
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
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
Structure / function of the pulmonary system
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).
Page 2
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
upper
respiratory
tract
lower
respiratory
tract
nasal cavity
pharinx
larynx
traquea
bronquioles
NASAL WALL PHARYNX
TRAQUEA LARYNX
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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
respiratory
unit
pulmonary
venule
pulmonary
arteriole
alveolar
duct alveolar sac
alveoli
lower airways cellular structures
Page 4
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)
capillary
endothelium
red blood cell
(RBC)
alveolar
epithelium
basement
membrane
type 1
alveolar cell
alveolar
macrophage
type 2
alveolar cell
surfactant
layer
intertitial
cell
connective
tissue alveolar
epithelium
surfactant
layer
capillary
endothelium
intertitial
space
basement
membrane
Page 5
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
right primary bronchus
right lung
parietal pleura
viceral pleura
esophagus
diaphragm
pleural space
left lung
mediastinum
left
primary
bronchus
aorta
larynx
Page 6
Page 7
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
voluntary and
higher centers
control centers
pneumotaxic (inspiration)
chemosensitive (H,O2,CO2)
apneustic (insp & exp)
DRG (inspiration)
VRG (inspiration & expiration)
vagus n.
carotide
body
aortic
bodies
(low PO2)
vagus n.
blood-brain
barrier
capillary
inter-
costal n.
phrenicl n.
(to diaphragm)
stretch
irritant
J receptors
Page 8
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
Common clinical manifestations of pulmonary alterations
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.
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 9
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 10
valvular dysfunction
coronary artery disease
left ventricular
dysfunction
increased
left atrial
pressure
increased pulmonary
capillary hydrostatic
pressure
pulmonary
edema
injury to capillary
endothelium
Increased capillary
permeability and
disruption of surfactant production
by alveoli
movement of fluid and plasma
from capillary to intertitial
space (alveolar septum) and alveoli
blockage of
lymphatic vessels
Inability to remove
excess fluid from
interstitial space
accumulation of fluid
in interstitial space
Pulmonary disorders
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
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).
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 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
Atelecthasia (Kohn’s pore), pneumothorax, flail chest are examples
of restrictive disorders
PORES OF KOHN
low inspiratory volume (shallow breathing) high inspiratory volume (deep breathing)
PNEUMOTHORAX FLAT CHEST
normal
alveolus
atelectatic
alveolus
closed pore of Kohn open
pore
of Kohn
inspiration expiration
EXAMPLES OF RESTRICTIVE DISORDERS
Page 12
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
ARDS
acute insult
(e.g. pneumonia, aspiration, smoke inhalation)
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
release of FGFs
(e.g. TGFß, PDGF
atelectasia & decreased
lung complience
non-cardiogenic pulmonary
edema and intrapulmonary
shunting
pulmonary hypertension pulmonary fibrosis
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
Examples of airway obstruction are those caused by
emphysema, chronic bonchitis and asthma
NORMAL LUNG EMPHYSEMA (destruction of alveolar walls)
panlobular centrilobular
CHRONIC BRONCHITIS (inflammation) BRONCHIAL ASTHMA (obstruction)
Obstructive dysfunctions
(B, C, D)
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 asthma, an airway obstruction dysfunction
allergen or irritant exposure
immune activation
(IL-4, IgE production)
vasoactive mediators
vasodilation
Increased capillary permeability
bronchospasm
vascular congestion
mucus secretion impaired mucociliary function
thickening of airway walls
jncreased contractile response of
bronchial smooth muscle
bronchial hyperesponsiveness
airway obstruction
mast cell degranulation
chemotactic mediators
cellular infiltration
(neutrophils, lymphocytes, eosinophils)
autonomic
dysregulation
release of toxic
neuropeptides
epithelial desquamation
and fibrosis
ASTHMA
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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
COPD
tobacco smoke
air pollution
inflammation of the airway epithelium
inherited alpha 1 -
antitrypsin deficiency
inhibition of normal
endogenous anti-
proteases
infiltration of
inflammatory cells and
release of cytokines (neutrophils, macro-
phages, lymphocytes,
leukotriens, interleukins)
systemic effects (muscle
weakness, weight loss)
continuous bronchial
irritation and inflammation
chronic bronchitis (bronchial edema,
hypersecretion of mucus, bacterial
colonization of airways
Emphysema (destruction of alveolar
septo and loss of elastic recoil of
bronchial wall
increased protease activity with
breakdown of elastin in connective
tissue of lungs (elastase, cathepsin)
airway obstruction, air trapping, loss
of surface area for gas exchange,
frequent exacerbations (infections, bronchospasms
dyspnea, cough,
hypoxemia, hypercapnia,
cor pulmonale
Page 16
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 pyelonephri-tis and septic shock, with evidence of bilateral pulmonary
infiltrate, on chest X-ray.
TENTATIVE DIAGNOSIS:
LAB TESTS: FINAL DIAGNOSIS:
TREATMENT:
