Hypoxia
Dr. Gary Mumaugh – UNW St. Paul
Hypoxia vs. Hypoxemia
 Hypoxia means deficiency of oxygen in the tissues
 Hypoxemia means low oxygen levels in the blood
Hypoxic Injury
 When a cell is deprived of oxygen, it can not longer produce energy without oxygen.
 If the cell must live, it converts to making energy without oxygen – anaerobic.
 Anaerobic metabolism leads to lactic acid as a waste product and lowers the pH of
the cell, making it acidic.
 The acidic environment damages the mitochondria and organelles and changes the
integrity of the cell membrane.
 As the cell loses energy energy, it can’t pump sodium out of the cell and sodium
accumulates inside the cell.
 Because sodium is osmotic, it pulls massive amounts of water into the cell causing
the cell to swell.
 If the hypoxia persists, the acidity of the cell and swelling of the cell causes am
irreversible injury.
 Eventually the lysosome membrane ruptures and the cell dies.
Oxygen Pathway
External atmospheric air  chest wall expansion  bronchial passages
 alveolus  vascular transportation  leaves blood into tissue
fluids diffuses into cellular mitochondria
Four major classifications of hypoxia
1. Extrinsic hypoxia
2. Pulmonary hypoxia
3. Anemic hypoxia
4. Stagnant hypoxia
5. Histotoxic hypoxia
Extrinsic hypoxia
 This describes inadequate oxygenation of the lungs from reason that is OUTSIDE
the lungs.
 The body tissues become hypoxic because there is not enough oxygen entering the
lungs.
 Altitude
o Oxygen levels lower dramatically at higher altitudes.
o Minor Acute Mountain Sickness (AMS) typically only occurs above 8,000 ft.
 Climbers present with symptoms resembling a case of flu, carbon
monoxide poisoning, or a hangover.
o Acute mountain sickness (AMS) can progress to high altitude pulmonary
edema (HAPE) or high altitude cerebral edema (HACE), both of which are
potentially fatal, and can only be cured by immediate descent to lower altitude
or oxygen administration.
o Acclimatization occurs over several months which is an adaptation to high
altitudes. The kidney will make more EPO to stimulate more RBC production
and the number of mitochondria in cells will increase and the amount of
myoglobin will increase in muscle cells.
 Lack of oxygen in the air even at sea level
o This can be seen in certain occupations where the O2 and CO2 levels are
altered such as farmers in silage pits and brewers of alcohol.
 Problems causing hypoventilation
o Anything that interferes with normal chest ventilation and movement will
cause extrinsic hypoxia.
 Can be neurological, orthopedic, respiratory paralysis, chest injuries
 Can be a side effect of medications as in opiate overdose
 Can occur with muscle relaxants and analgesics
o Airway obstruction
o Aspiration
Pulmonary hypoxia
 Lung pathologies are obvious causes of hypoxia.
 Occurs as a result of airway resistance, alveolar issues or reduced membrane
transport of oxygen.
o Asthma, pneumonia, bronchiolitis, lung cancer, COPD and cystic fibrosis
o Lung collapse secondary to pneumothorax, hemothorax or hydrothorax
Normal Pleura – in normal lungs, the visceral pleura is sucked up onto the parietal pleura.
This means that the lungs will fill up all the available space in the thoracic cavity.
Pneumothorax – The parietal pleura will remain attached to the chest wall and the
visceral pleura remains attached to the lung. Because there is air (pneumothorax) or
blood (hemothorax) or fluid (hydrothorax) in the space, the “potential space” has become
an actual space and no suction occurs.
Anemic hypoxia can be caused by anything that can cause anemia or blood loss.
Stagnant hypoxia
 Localized circulatory perfusion reduction will result is a stagnant hypoxia, which can
occur as a result of any arterial disease of trauma.
 Localized hypoxia is referred to as ischemia
 Examples are intermittent claudication, TIA, acute limb ischemia, etc.
Histotoxic hypoxia
 In some cases, the cells are unable to use the oxygen in cellular respiration
 This occurs in poisonings of cellular enzymes, such as with cyanide
o Cyanide blocks enzymes and causes rapid death
 This can occur in sepsis
 Alcohol and carbon monoxide may reduce the efficiency of energy production in the
mitochondria
Response of the body to hypoxia
 Oxygen flux is the flow of oxygen from the lungs to the tissues
o Cardiac output X arterial oxygen concentration X hemoglobin concentration
 Cardiovascular compensatory response
o In hypoxia, the heart rate and stroke volume will increase
o This increases oxygen flux increase
o This is monitored by the chemoreceptors in the aortic bodies and carotids,
which will increase blood pressure
o If the degree of hypoxia continues, the energy production to the myocardium
will eventually be reduced.
 This can lead to decreased cardiac output and death
Response of the body to hypoxia – continued
 Respiratory compensatory response
o In hypoxia, there will be tachypnea with increased respiratory volumes
o At an oxygen saturation rate of 90%, the pulmonary ventilation rate will
increase to 15 liters per minute. (Normal is about 6 liters per minute)
o At an oxygen saturation rate of 80%, the pulmonary ventilation rate will
increase to 25 liters per minute.
 Increase in red blood cell response
Other clinical features of hypoxia
 Cyanosis
o Usually below an oxygen saturation rate of 85%
 CNS effects
o At 85% saturation rate there is fatigue, headache, nausea, vomiting, dizziness
and confusion
o At 75% saturation rate there can become severe mental impairment.
o 65% saturation rate will lead to coma, convulsions and eventually brain death
 Cerebral edema
o The hypoxia causes dilation of the cerebral capillaries which will led to
increased permeability increasing volumes of tissue fluid.
o The increased tissue fluid led to increased intracranial pressure
 Hypoxic damage to organs
o CNS tissue can be damaged in one minute
o The myocardium can be damaged in 5 minutes
o The liver and kidneys can be damaged in 10 minutes
o Skeletal muscles may survive up to 2 hours
Pulmonary Pathophysiology
Dr. Gary Mumaugh – UNW St. Paul
Respiratory Overview
• Respiratory and circulatory systems are closely related structurally and functionally
• External respiration – occurs at the alveoli of the lungs with the capillaries
• This is where the O2 and CO2 exchange with the lung capillaries
• Internal respiration – takes place between the blood capillaries and the tissue cells.
Major Functions of the Respiratory System
 To supply the body with oxygen and dispose of CO2
 Respiration – four distinct processes must happen
o Pulmonary ventilation – moving air into and out of the lungs
o External respiration – gas exchange between the lungs and the blood
o Transport – transport of oxygen and carbon dioxide between the lungs and
tissues
o Internal respiration – gas exchange between systemic blood vessels and
tissues
Respiratory System
 Consists of the respiratory and conducting zones
 Respiratory zone
o Site of gas exchange
o Consists of bronchioles, alveolar ducts, and alveoli
 Conducting zone
o Provides rigid conduits for air to reach the sites of gas exchange
o Includes all other respiratory structures (e.g., nose, nasal cavity, pharynx,
trachea)
 Respiratory muscles – diaphragm and other muscles that promote ventilation
Respiratory Membrane
• Thin layer of cells- alveolar wall, basement membrane, and capillary wall
• Type I and II Pneumocytes- secrete pulmonary surfactant
• Macrophages- take up particles that might interfere with normal function
• Specialized goblet cells- secrete mucous
o Reduces alveolar surface tension
Gas Exchange
 CO2 transported in 3 forms:
o Combined with globin protein in hemoglobin (Hb) of erythrocytes (25%)
o Changed into bicarbonate ion (HCO3-) by carbonic anhydrase (65%)
o Remains as gas dissolved in the plasma (10%)
 O2 transported in 2 forms:
o Binds to heme group in hemoglobin
o Remains as gas dissolved in plasma (1-2%)
Respiratory Defense Mechanisms
•
•
•
•
Warm and humidify incoming air
Branching of bronchial tree increases its contact with airway mucus
Cilia prevents particles form reaching distal airways
Mucus blanket
o Particle clearance (macrophages)
o Antibacterial secretions (lysosome)
o Antiviral secretions (interferons)
Signs and Symptoms of Pulmonary Disease
 Dyspnea
o Subjective sensation of uncomfortable breathing
o Orthopnea
 Dyspnea when a person is lying down
o Paroxysmal nocturnal dyspnea (PND)
 Cough
o Acute cough
o Chronic cough
 Abnormal sputum
 Hemoptysis
 Abnormal breathing patterns:
o Kussmaul respirations (hyperpnea)
o Cheyne-Stokes respirations
 Hypoventilation
o Hypercapnia - Increased CO2 due to hyopventilation
 Hyperventilation
o Hypocapnia - Decreased CO2 due to hyperventilation
Signs and Symptoms of Pulmonary Disease
 Pain
 Cyanosis
 Clubbing
o Finger clubbing is characterized by enlarged fingertips and a loss of the
normal angle at the nail bed.
Conditions Caused by Pulmonary Disease or Injury
 Hypercapnia - Hypoxemia Increased CO2 due to hyopventilation
 Hypoxemia
o Hypoxemia versus hypoxia - The body or a region of the body is deprived of
adequate oxygen. Hypoxia may be classified as either generalized, affecting
the whole body, or local.
o Ventilation-perfusion abnormalities
 Shunting A pulmonary shunt is a physiological condition which results
when the alveoli of the lungs are perfused with blood as normal, but
ventilation (the supply of air) fails to supply the perfused region.
 Acute respiratory failure
Hypoperfusion
• Hypoperfusion: inadequate blood flow to pulmonary capillaries
o Heart Failure
• Failing left heart- pulmonary hypertension, reduced blood flow at
higher pressure
 Failing right heart- reduced pulmonary blood flow
o Thromboembolism - blockage of vessel
 Blockage of vessel by embolus
 Release of vasoconstrictors from activated platelets
o Reduced Ventilation
 Vasoconstriction response in arteriole
Chest Wall Disorders
 Chest wall restriction
o Compromised chest wall
 Deformation, immobilization, and/or obesity
 Flail chest
o Instability of a portion of the chest wall
Pleural Abnormalities
 Pneumothorax
o Open pneumothorax
o Tension pneumothorax
o Spontaneous pneumothorax
o Secondary pneumothorax
Pleural Abnormalities
o Pleural effusion
o Transudative effusion
o Exudative effusion
o Hemothorax
o Empyema - Infected pleural effusion
o Chylothorax
Inhalation Disorders
 Toxic Gases
o Pneumoconiosis
 Silica
 Asbestos
 Coal
 Allergic Alveolitis
o Extrinsic allergic alveolitis (hypersensitivity pneumonitis)
 Pulmonary Edema
o Excess water in the lungs
Acute Respiratory Distress Syndrome (ARDS)
 Fulminant form of respiratory failure characterized by acute lung inflammation and
diffuse alveolocapillary injury
 Injury to the pulmonary capillary endothelium
 Inflammation and platelet activation
 Surfactant inactivation
 Atelectasis
 Manifestations:
o Hyperventilation
o Respiratory alkalosis
o Dyspnea and hypoxemia
o Metabolic acidosis
o Hypoventilation
o Respiratory acidosis
o Further hypoxemia
o Hypotension, decreased cardiac output, death
 Evaluation and treatment
o Physical examination, blood gases, and radiologic examination
o Supportive therapy with oxygenation and ventilation and prevention of
infection
o Surfactant to improve compliance
Pulmonary Disorders - Obstructive Lung Diseases
 Airway obstruction that is worse with expiration
 Common signs and symptoms
o Dyspnea and wheezing
 Common obstructive disorders:
o Asthma
o COPD
o Emphysema
o Chronic bronchitis
Obstructive Lung Diseases - Asthma
 Chronic inflammatory disorder of the airways
 Inflammation results from hyper responsiveness of the airways
 Can lead to obstruction and status asthmaticus
 Symptoms include expiratory wheezing, dyspnea, and tachypnea
 Peak flow meters, oral corticosteroids, inhaled beta-agonists, and antiinflammatories used to treat
Two major types of asthma – Intrinsic and extrinsic
Intrinsic Asthma
Extrinsic Asthma
Caused by a virus
Caused by an allergen
Most common in adults
Most common in children
Non allergic factors, viral infection, irritants like
Allergic factors can include dust mites,
epithelial damage, mucosal inflammation,
IgE antibodies, pet dander, and other
emotional upset, parasympathetic input
environmental allergens.
Rinovirus (during first 3 years of life)
This is why chalkboards are not in schools.
Trigger epithelial cell damage and macrophages
Triggers activate lymphocytes & mast cells.
The affected cells are neutrophils
The affected cells are eosinophils (acidophils)
This is sometimes called Non Eosinophilic Asthma This is sometimes called Eosinophilic Asthma
Histamine reactions causes airway inflammation
Histamine reactions causes airway inflammation
Airway hyper responsiveness, irritation, edema,
Airway hyper responsiveness, irritation, edema,
mucous plugging
mucous plugging
Obstructive Lung Diseases: Chronic Bronchitis
 Hypersecretion of mucus and chronic productive cough that lasts for at least 3
months of the year and for at least 2 consecutive years
 Inspired irritants increase mucus production and the size and number of mucous
glands
 The mucus is thicker than normal
 Bronchodilators, expectorants, and chest physical therapy used to treat
Obstructive Lung Diseases: Emphysema
 Abnormal permanent enlargement of the gas-exchange airways accompanied by
destruction of alveolar walls without obvious fibrosis
 Loss of elastic
recoil
 Centriacinar
emphysema
 Panacinar
emphysema
How COPD Develops
 Smoking causes increased mucus production and bronchial inflammation
 Nicotine paralyzes the mucociliary escalator
o Mucociliary escalator traps mucus, bacteria, irritants
 Nicotine blocks protein inhibitors which will eventually dissolve the alveoli
o Pathophysiology
o Involves all four parts of the respiratory tract
 Bronchi
 Bronchioles
 Alveoli
 Parenchyma
o Specific Pathophysiology
 Increased resistance to airflow
 Loss of elastic recoil
 Decreased expiratory flow rate
 Alveolar walls frequently break because of the increased resistance
of air flows
 The hyper inflated lungs flatten the curvature of the diaphragm and
enlarge the rib cage
 The altered configuration of the chest cavity places the respiratory
muscles, including the diaphragm, at a mechanical disadvantage
and impairs their force-generating capacity
 Consequently, the metabolic work of breathing increases, and
dyspnea increases
Two Types of COPD
 Type A – Pink Puffers
o Have mostly emphysema
o Need to breathe rapidly to exchange O2 and CO2
o Have prominent dyspnea, the fast puffing keeps them from becoming
cyanotic
o Most of the lung is perfused with blood exchange is not efficient because of
fewer alveoli
 Type B – Blue Bloaters
o Have mostly chronic bronchitis with bronchiolar obstruction and nonventilated alveoli
o Results in shunting of cyanotic blood away from the area where there is no air
in the lungs
o Results in pulmonary hypertension which leads to heart failure with peripheral
 Diagnosis
o Smoker with hacking cough, sputum and dyspnea
 Type A – thin, dorsal kyphosis, clubbing, pigeon breast (pectus
carinatum) or funnel chest (pectus excavatum)
 Type B – obese, swollen appearance, cyanotic
o X-ray finding
 Large lung volumes hyperlucent, flat diaphragm, increased AP
diameter
o Pulmonary function tests
 Airway obstruction and decrease, air trapping
o Blood gases
 Type A – normal blood gases
 Type B – marked hypoxemia and CO2 retention
 Treatment of COPD
o Bronchodilators
o Antibiotics & Corticosteroids
o Supplemental oxygen therapy
o Chest physiotherapy to lose secretions
o Surgery to remove diseased lung tissue
o Lung transplantation
Bronchiectasis – Restrictive Lung Disease
 Pathophysiology
o Irreversible dilation of part of the bronchial tree
o Caused by chronic infection of bronchi & bronchioles
o Chronic bronchial infection causes a dilatation of the air passages which are
trapped with muco-purulent material
o Caused by slow-growing bacteria and fungi
 S&S
o Chronic deep hacking cough
o Copious amounts of foul-spelling pus sputum
o Frequent attacks of pneumonia
 Diagnosis
o Localized rales and coarse ronchi
o Appears similar to COPD with clubbing
o Normal blood gases
o History of chronic infection
o CT scan confirms the diagnosis
 Treatment
o Antibiotics – ciprofloxacin
o Bronchopulmonary drainage
 Bending over, almost standing on head, to get the mucus up and out
o Bronchodilators
Cystic Fibrosis
 Inherited disease that causes thick, sticky mucus to build up in the lungs and
digestive tract
 The most common type of chronic lung disease in children and young adults
o 1 in every 3,300 – most children and teenagers
o May result in early death
 S&S
o Pneumonitis, bronchiectasis, lung abscesses, pancreatic insufficiency
 Diagnosis
o Established by the sweat electrolyte test
Pulmonary Fibrosis - Referred to as Interstitial Lung Diseases
 Causes inflammation and fibrosis of the connective tissue between the alveoli
 Most common causes
o Environmental causes – inhaled dusts, asbestosis, silicosis, glass makers,
construction workers
o Antigens – hypersensitivity pneumonitis
o Drugs – Methotrexate
o Radiation injury
o Other diseases – sarcoidosis, RA
o Mimicking disorders similar presentation but vastly different
 CHF, pneumocystis or viral pneumonia, carcinomatosis
 Pathology of interstitial lung disease
o Inflammation of the alveolar wall and inter-alveolar spaces
o Fibrous scarring
o Granuloma formation
o End stage leads to a mass of scar tissue with contraction and the formation of
cystic areas
 Impairment of pulmonary function
o Decreased lung volume
o Decreased compliance (stiff lungs)
o Impairment of diffusion
o Decreased gas exchange
o Shunting and spasm of pulmonary arteries
o Heart failure resulting from pulmonary hypertension
 S & S of pulmonary fibrosis
o Obvious dyspnea
o Chronic nonproductive cough
o Clubbing
o Mild cyanosis
 Diagnosis of pulmonary fibrosis
o CT scan is confirmatory
 Specific diseases that can cause pulmonary fibrosis
o Silicosis – disease of glass makers, sand blasters, rock miners and stone
cutters
 Takes 20 years to develop
o Pneumoconiosis – coal miner’s disease
 Severe lung fibrosis with hypoxia
o Asbestosis – leads to 3 distinct diseases
 Bronchogenic carcinoma
 Mesothelioma of lung (cancer of lung pleura)
 Interstitial fibrosis – takes 20 years to develop
o Drug-induced pulmonary fibrosis – chemotherapy
 Treatment of pulmonary fibrosis
o Very little effective care
o Oxygen 24 / 7
o Corticosteroids
Pulmonary Infections - Pneumonia
 2-3 million cases in USA yearly causing 45,000 deaths
o Mortality is 4 times higher over 65
 Predisposing factors
o Preceded by viral URI causing cilia damage and the production of serous
exudates
o Smoking impairs mucociliary escalation
o Elderly and compromised immune systems
o HIV, AIDS, sickle cell disease, diabetes
o Organ transplant patients
o Close indoor quarters in the winter
o Hypostatic pneumonia can occur from constant laying down
Acute vs. Chronic Pneumonia
 Acute
o Symptoms within 1-2 days after exposure
o Shaking, fever, chills, prostration, dyspnea
o Common cause of death before antibiotics
 Chronic
o More slow progressive form
o Are most viral and fungal pneumonias
o May last several weeks to months
 Diagnosis based on symptoms
o Typical pneumonia
 Rapid onset, productive cough, fever
 X-ray changes
o Atypical pneumonia
 Common with most viral pneumonias
 Diagnosis based on part of the lungs affected
o Lobar pneumonia
 “Classic” pneumonia in which all the alveoli sacs in the lobe are pus
filled or fluid filled
o Bronchopneumonia
 Patchy infiltration throughout the bronchi and bronchioles
o Interstitial pneumonia
 In the connective tissue between the alveoli with granular infiltration
o Lung abscess
 Organisms destroy tissue and form pus abscess
o Empyema
 Prurulent infection in the pleural space
o Nodular lung infections
 TB, coccidiomycosis and histoplasmosis cause nodular infiltrations
 Diagnosis according to where the pneumonia was acquired
o Community acquired
 Acquired anywhere in the community, but not in a hospital
o Nosocomial
 Acquired in a hospitalized setting
 Diagnosis according to etiologic agent
o Pneumococcal pneumonia
 Classic bacterial pneumonia
 AKA streptococcal pneumonia
o Aspiration pneumonia
 Common in elderly from swallowing gastric or food contents in the
trachea
 Often vomiting with loss on consciousness
o Hemophilus pneumonia
 Common on smokers with COPD
o Staphlococci pneumonia
 Virulent infection often after influenza
Pneumonia – continued
 Diagnosis according to etiologic agent - continued
o Viral pneumonia
 Most common form
 S & S of pneumonia
o Cough, sore throat, fever, chills, rapid breathing, wheezing, dyspnea, chest or
abdominal pain, exhaustion, vomiting
 DX of pneumonia
o Medical history, physical examination, x-ray
 TX of pneumonia
o Antibiotics, respiratory therapy with oxygen
o Amoxicillin is first-line therapy
o Steroids for wheezing
o Expectorates and lots of fluids
o Codeine for severe pain
Tuberculosis - TB
 One third of world population have active or latent infection resulting in 3 million
deaths per year
 Pathology and course of TB
o A chronic destruction of the lung with scarring
o Slow progressive lung damage and possible death
o Systemic symptoms of wasting, fatigue, night sweats, appetite loss – used to
be called consumption
 S&S
o Cough, sputum, hemoptysis, TB spread to organs leads to destruction of
organs and organ systems
Tuberculosis – TB - continued
 DX of classic triad
o Lung infiltrate, calcified node enlargement, pleural effusion
 TX of TB
o When it comes to treatment of TB, think slow
o Slow growth of organisms, slow destruction of lung tissue, prolonged
treatment and slow recovery
o Lasts at least year and is treated with extensive drug therapy with isoniazid
and rifampin
 Symptoms
o Chronic illness
o Symptoms include
 Slight fever with night sweats
 Progressive weight loss
 Chronic productive cough
 Sputum often blood streaked
 Causative Agent - Mycobacterium tuberculosis
o Gram-positive cell wall type
o Slender bacillus
o Slow growing
 Generation time 12 hours or more
o Resists most prevention methods of control
 Pathogenesis
o Usually contracted by inhalation of airborne organisms
o Bacteria are taken up by pulmonary macrophages in the lungs
o Resists destruction within phagocyte
 Pathogenesis
o Organisms are carried to lymph nodes
o About 2 weeks post infection intense immune reaction occurs
 Macrophages fuse together to make large multinucleated cell
 Macrophages and lymphocytes surround large cell
 This is an effort to wall off infected tissue
o Activated macrophages release into infected tissue
 Causes death of tissue resulting in formation of “cheesy” material
 Epidemiology
o Estimated 10 million Americans infected
 Rate highest among non-white, elderly poor people
o Small infecting dose
 As little as ten inhaled organisms
o Factors important in transmission
 Frequency of coughing, adequacy of ventilation, degree of crowding
 Tuberculin test used to detect those infected
o Small amount of tuberculosis antigen is injected under the skin
o Injection site becomes red and firm if infected
o Positive test does not indicate active disease
Tuberculosis - continued
 Prevention
o Vaccination for tuberculosis widely used in many parts of the world
 Vaccine not given in United States because it eliminates use of
tuberculin test as diagnostic tool
 Treatment
o Antibiotic treatment is given in cases of active TB
 Two or more medications are given together to reduce potential
antimicrobial resistance
 Antimicrobials include
 Rifampin and Isoniazid (INH)
 Both target actively growing organisms and metabolically
inactive intracellular organisms
 Therapy is pronged
 Lasting at least 6 months