Week 1 Flashcards
Define single blind study
In a single-blind experiment, the participants do
not know whether they are receiving an
experimental treatment or a placebo
Definite double blind study
In a double-blind experiment, neither the
researchers nor the participants are aware of
which subjects receive the treatment until after
the study is completed
What is the goal of using a placebo?
Eliminate bias that may arise from the expectation that a treatment should produce an effect
B&E: What is Generalizability?
The extent to which the results of a study are
able to be applied to the population of people
that is comparable to the population studied
B&E: What is prevalence?
The number of existing cases of a disease in a
defined population at a specified time
B&E: What is incidence?
The number of new cases of a disease during a given period of time in a defined population
B&E: What is biomedical research?
- Perform scientific investigation
- Experiments
- Observing
- Analyses & Testing
- Find causes of the disease
- Normally wet-lab experiments
B&E: What is applied clinical research?
- Research that benefits humans
- Diagnosis, procedures, medications, devices
- Research effectiveness & safety
B&E: What is epidemiological research?
- Tracking diseases in large population
- Examine association of exposure with disease
What are the preliminary steps to research?
- Topic issue/interest
- Literature search
- Research goal
- Research design
- Data process
B&E: Contrast observational studies from experimental studies ?
- Observational: Don’t have control over exposure
- Experimental: Researchers control exposure & goal is to determine benefit of therapy
B&E: What are three features of a clinical trial?
- Control
- Randomization
- Blinding
B&E: Who is unaware in a triple blind study?
- Subjects, researchers, and data analysts are unaware of who is getting treatment or not
B&E: Describe the parameters of Phase 0 studies
- AKA Human micro-dosing studies
1. Gather preliminary data pharmacodynamics and pharmacokinetics
2. Gives no data on safety or efficacy
3. Small number of subjects (10-15) people
B&E: Describe the parameters of Phase I study
- Increase number of subjects (10-100)
- Designed to assess the safety, toxicity, tolerability, PK, PD, of a drug
- Dose ranging and dose escalation
B&E: Describe the parameters of Phase II studies
- Therapeutic exploratory trial
- Efficacy in patients
- Safety issues
- Optimum dose finding
- Often placebo-controlled and often blinded
B&E: How many persons comprise a phase II study?
Small quantity: 20-300 subjects
B&E: Describe the parameters of Phase IIA & Phase IIB studies
- Phase IIA: designed to assess dosing requirement
- Phase IIB: Designed to study the efficacy of a drug
B&E: What quantity of participants comprise Phase III studies?
- Large # of subjects: 300-3,000 subjects
B&E: What can happen after phase III studies?
Drug may be approved by the FDA
B&E: Describe the parameters of Phase III study
- Therapeutic confirmatory trials
- To establish the efficacy of the drug against existing therapy in a larger number of patients, methods of usage, etc.
B&E: Describe the Phase IIIA & Phase IIIB parameters for study
- Phase IIIA: To get sufficient and significant data
- Phase IIIB: Allows the patient to continue the treatment, label expansion, additional data
B&E: Describe the parameters of a phase IV study
- Post-marketing studies
- After the drug is on the market
- Involves safety surveillance
- Determine behavior of drug in real-life situations
- Evaluate action of drug in a situation of missed dosage or over dosage
- Monitor for long term affects
B&E: Describe how Basic Science and Clinical research differ in their aim/purpose?
- Basic Science: how does something work
- Clinical: aimed at likelihood of events being related or even correlated, humans involved research
B&E: True or False, scientific results does not always match/agree clinical results
True
OPC: What are considered the upper cervical vertebrae?
What are considered the lower cervical vertebrae?
- Upper: OA & C2
- Lower: C3-C7
OPC: What is unique about C7?
- No vertebral artery passing through it
- Spinous process in non-bifid
OPC: How is diagnosis made for cervical spine?
- Using articular pillars
OPC: What level of the spine and chest does the trachea bifurcate?
- Posterior: T4
- Anterior: Sternal angle
OPC: What is pectus carinatum?
Sternum is forming ridge out
OPC: What is Pectus Excavatum?
Sternum sunk in (caved in chest)
OPC: List 5 abnormal lung sounds that may be auscultated
- Wheezing
- Stridor
- Barking cough
- Whistle
- Rattle
OPC: What is tactile fremitus?
- refers to the vibration of the chest wall that results from sound vibrations created by speech or other vocal sounds.
OPC: What is tactile fremitus?
- refers to the vibration of the chest wall that results from sound vibrations created by speech or other vocal sounds.
OPC: What is tactile fremitus?
- refers to the vibration of the chest wall that results from sound vibrations created by speech or other vocal sounds.
OPC: What might cause decreased tactile fremitus?
Decreased intensity of tactile fremitus may occur as a result of excessive amounts of air in the lungs (also known as hyperinflation). Hyperinflation can be seen in individuals with pulmonary emphysema, chronic obstructive pulmonary disease (COPD), asthma, or severe airway obstruction.
OPC: What causes increased Tactile Fremitus?
- increased density within the lung tissue.
- This commonly occurs as a result of lung consolidation, which refers to the replacement of the air within healthy lung tissue with another substance; either inflammatory exudate, blood, pus, or cells.
- most common cause of a consolidated lung is a lung infection, such as pneumonia
- partial or total collapse of a lung (known as atelectasis)
- presence of a solid mass in the lungs, such as a tumor.
OPC: Describe the lung sounds Rales
sounds like hair rubbing between fingers in front of ears
OPC: Describe the lung sounds Rhonchi
snore like wheeze. Loud low pitched on stethoscope auscultation.
OPC: Describe the lung sounds Wheezing
musically type of sound and notes changes with breathing. Usually worse with expiration
OPC: Describe the lung sounds pleural friction rub
dry rubbing sound or a grating sound
OPC: What portion of the stethoscope is used to assess egophony?
- Use the bell since egophony is a lower pitched sound
OPC: What is egophony?
- Egophony: The basic idea is that normal lungs (filled with air), do not readily transmit sounds, while consolidated lung tissue more readily transmits sounds. To use egophony during an exam, ask the patient to say ‘e’ as you auscultate over the chest wall. Over normal lung areas, you will hear the same ‘e’ tones. Over consolidated tissue, the ‘e’ sound changes to a nasal quality ‘a’ (aaaaay), like a goat’s bleating, indicating positive egophony
OPC: What is egophony?
- Egophony: The basic idea is that normal lungs (filled with air), do not readily transmit sounds, while consolidated lung tissue more readily transmits sounds. To use egophony during an exam, ask the patient to say ‘e’ as you auscultate over the chest wall. Over normal lung areas, you will hear the same ‘e’ tones. Over consolidated tissue, the ‘e’ sound changes to a nasal quality ‘a’ (aaaaay), like a goat’s bleating, indicating positive egophony
OPC: Define Bronchophony
The spoken word sounds louder with auscultation and increase clarity
OPC: What is Pectoriloquy?
Whisper is heard clearly
OPC: Describe the mechanics of cervical spine
- Typically side bending and rotation occur in the same direction but Fryette’s mechanics do not apply to cervical spine
- Can have group dysfunctions that are flexed and extended
OPC: C spine- what sidebending occurs with right translation?
- Right translation = Left sidebending
OPC: C spine- what sidebending occurs in Left translation?
- Left translation induces Right sidebending
OPC: Compare the diagnosis of AA joint vs OA joint
- AA is rotation L or Right only since that is its primary movement
- OA joint is sidebending and rotation occur in opposite directions making it an exception to the C spine diagnosis rules
OPC: Which C spine has nerve roots emerging above and below it?
C7 has C8 emerging below it and T1 even tho C8 is not a vertebrae
OPC: What is Torticollis?
- Where sternocleidomastoid stretch from the sternum to the skull behind the ear
- Either congenital or acquired
- Attachment of this muscle induces sidebending
OPC: Describe sidebending and rotation for the lower cervical unit
Sidebending and rotation occur in the same direction in flexion, extension and neutral in the lower cervical unit
OPC: Describe the nerve roots for C spine
- In the cervical spine, nerve roots emerge above the same numbered vertebrae
OPC: What are the motor functions disturbed by C5 nerve root impingement
Deltoid weakness
OPC: What are the reflexes disturbed by C5 nerve root impingement?
Biceps tendon reflex
OPC: What sensation is disturbed by C5 nerve root impingement?
lateral arm
Axillary nerve
OPC: What motor innervation is disturbed by C6 nerve roots impingement?
- Wrist extension
- Bicpes
OPC: What reflex is disturbed by C6 nerve roots impingement?
Brachioradialis tendon
OPC: What sensory innervation is disturbed by C6 nerve roots impingement?
- Anterior and lateral forearm
- Musculocutaneous nerve
OPC: What motor innervation is disturbed by C7 nerve roots impingement?
- Wrist flexor
- Finger extensors
OPC: What reflex is disturbed by C7 nerve roots impingement?
Triceps reflex
OPC: What sensory function is disturbed by C7 nerve roots impingement?
Middle finger
OPC: What motor innervation is disturbed by C8 nerve roots impingement?
Finger flexion and intrinsic hand muscles
OPC: What sensory innervation is disturbed by C8 nerve roots impingement?
Medial forearm, medial anterior brachial cutaneous nerve
OPC: What motor innervation is disturbed by T1-T2 nerve roots impingement?
Intrinsic hand muscles
OPC: What sensory innervation is disturbed by T1-T2 nerve roots impingement?
Medial arm
Medial brachial cutaneous nerve
OPC: What causes the most serious injuries to the cervical spine?
Due to injury to the vertebral artery in the upper cervical spine including OA, AA, C2 resulting in hemorrhage or stroke
OPC: In what position/movement does vertebral artery injury occur in the C spine?
- Risk when patient is placed in to extreme extension and rotation in the upper cervical area
Where is the thymus found?
Superior mediastinum
What is the function of the thymus?
- Maturation of T & B cells after they are formed in the bone marrow
- Mostly T cells
Describe the histology of the thymus:
- In young age, there are lots of lymphocytes with some support cells-thymic epithelial cells
- Older ages: lymphocytes are more aggregated into islands, less quantity of Lymphocytes due to thymus shrinking
List the layers of the esophagus
- Inner most is Mucosa
- Submucosa
- Muscularis
- Adventitia
Describe the submucosa and muscularis layers of the esophagus
- Submucosa: mucus glands & lymphatic nodules
- Muscularis: striated skeletal tissue proximal to the mouth, then smooth muscle closer to heart
What is the Azygos vein?
- Final vein in the posterior thorax as it provides redundant pathways for drainage to off-set blockages in the system
- Connects between inferior and superior vena cava
- R side of the thorax that will drain the superior vena cava
- Also have the hemiazygos vein
What is the thoracic duct?
- Drains L lymph and lower R lymph
- Empty into jugular vein where the JV joins the subclavian vein
Describe lymphatic drainage of the L and R side of the body
- Entire L side of the patient plus the right lower body will drain into the thoracic duct even tho
- R side of upper body and head will drain into R lymphatic duct
What determines O2 partial pressure of the blood?
Only free, dissolved gas causes a partial pressure
- Does not include O2 attached to Hb
What is oxygen content in the blood
CaO2
- Oxygen in the artery
- Including oxygen as gas in the blood and the HbO2
What is Hb saturation during rest?
75% at tissue
What drives lymphatic fluid movement?
- Via visceral organ contraction including, abdominal and pelvic organs, pulsation of blood vessels, heart, lungs etc.
How does the Bohr effect impact the Oxyhemoglobin dissociation curve
- Decreasing pH/increasing H+ will shift curve right to decrease Hb affinity for O2
- Easier to offload O2
What term matches this description?
A scientific process of answering a question
using data from a population.
A study is a scientific process of answering a question
using data from a population.
What is an Epidemiologic study
▪ Studies of populations of patients
▪ Examine the association of exposure with
disease
Why is clinical research different from epidemiological research?
- No control over exposure in epidemiology studies -Researchers control exposure in clinical studies
Compare Experimental vs. Observational Studies
- Experimental: random division of samples, two groups, tx & alternative, compare results
- Observational: without treatment or control, observe and collect data, identify source of risk, prospective or retrospective
List 2 forms of secondary research
- Meta analysis
- Systematic reviews
Why are meta analysis and systematic reviews considered high quality evidence?
Can perform statistical analysis using the data presented
What is a major use of case reports?
- Identification of new trends, symptoms, or diseases that do not fit the known/traditional diagnostic criteria
List 4 advantages of case report studies
- Can help in the identification of new trends or diseases
- Can help detect new drug side effects and potential uses (adverse or beneficial)
- Educational- a way of sharing lessons learned
- Identifies manifestations of a rare disease
What are 4 disadvantagers of case studies?
- May not be generalizable
- Not based on systematic reviews
- Causes or associations may have other explanations
- Can be seen as emphasizing the bizarre or focusing on misleading elements
T/F: Case reports and case studies have statistical analysis since case studies have multiple patients
False, since there is no control group there is no statistical analysis
B&E: What is a case series? What to look for?
- Collections of reports on several patients with unique or interesting conditions
- Is solely observational study, cannot add recommendations or opinions
BSE: What is the lowest hierarchy of evidence?
Case reports/studies since they have no statistical analysis
BSE: Describe cross sectional studies
- Patients studied as a part of a group with a particular identifier
- Frequency of disease and risk factors identified at the same time
BSE: Do cross-sectional studies follow groups studies over a period of time? What can be determined from a cross-sectional study?
- No, this is a prevalence study that is seen during a snapshot of time
- Can determine the prevalence of disease
BSE: List 3 descriptive studies
- Case reports
- Case series
- Cross-sectional studies
BSE: What type of study are case-control studies? What is their purpose?
- Observational study
- Compares the group with the disease to the group without the disease
- Loos retrospective over time for exposure or risk factors
- Opposite of cohort study
- Better for rare diseases
BSE: When picking a control group, what is the best parameter to look for?
The only difference between groups is the presence or absence of disease to limit confounding results
BSE: What is the main results gained from case-controls studies?
- Main outcome measure is the odds ratio
- Odds of disease in exposed vs odds of disease in not exposed
BSE: What are disadvantages of case-control studies?
- Retrospective studies have more problems with data quality becuase they rely on memory
- Not good for evaluating diagnostic tests because it’s already clear that the cases have the condition and the controls do not
- It can be difficult to find a suitable control group
- Insufficient for rare exposures (smaller sample than cohort study)
- Recall may be a a problem
BSE: What are advantages of case-control studies?
- Less time needed to conduct the study because the condition or disease has already occured
- Allow you to simultaneously look at multiple risk factors
- Good for studying rare conditions or diseases
- Useful as intial studies to establish an association
- Relatively inexpensive
BSE: What is another name for cohort studies?
Incidence study
BSE: What do cohort studies do?
- Compare exposure groups to nonexposure groups
- Either retrospective or prospective
- Good for common disorders/disease
- Gives information about incidence of disease in groups
- Exposure determined before the outcome is known
BSE: What is the main out come of cohort studies?
Relative risk: How much does exposure increase risk of disease
BSE: How can you identify a cross-sectional study vs. a retrospective cohort study?
- CCS: The outcome is the prevalence of disease
- Retrospective cohort: the outcome is the incidence of disease
BSE: Why are Randomised controlled studies considered “gold standard”?
- Researcher can control the exposure to a particular set of participants
- Randomization of participants who get treatment vs. those who do not
- Eliminates bias
BSE: T/F: Systematic reviews can include published and unpublished data of only RTC studies
False, systematic reviews can include publishes and unpublished data of varying study designs
BSE: What is meta analysis?
- Subset of systematic reviews that pools data from several studies together
- Increases the number of subjects and controls
- Increases statistical power
BSE: Aside from being a subset of systematic review, how do meta analysis differ from SR?
- Both use unpublished and published data
- Meta Analysis is numbers only and must use data from study designs that are the same
BSE:
CPR: Describe the cells found in the mucosal layer of the trachea
- Respiratory epithelium containing pseduostratified w/cilia cells & goblet cells
- Lamina propria: loose CT with lymphocytes
CPR: Describe the Submucosal layer of the trachea
- Dense irregular CT
- Elastic fibers
- Submucosal glands with acinar cells that secrete seromucus
- Tracheal cartilage
- Tracheal muscle
- Blood vessels
CPR: What kind of muscle is trachealis muscle? Where is it found?
- Smooth muscle
- Found in submucosal layer of trachea
CPR: What type of cartilage is found in the ___________ layer of the trachea? Describe it
- Hyaline cartilage
- Submucosal layer
- Basophilic matrix b/c lots of GAGs
CPR: What are the start and end of the conducting portion of the respiratory system?
Nose to Terminal bronchile
CPR: What is the starting point and ending point of the respiratory portion of the respiratory system?
Starts at respiratory bronchioles and extends to alveolar sacs
CPR: List the 5 types of cells that can be found in the respiratory epithelium
- Ciliated columnar cells
- Goblet cells
- Brush cells
- Basal cells
- Small granule cells
CPR: What are the most abundant type of cell found in respiratory epithelium? Where is respiratory epithelium found?
- Ciliated columnar cells are the most abundant cell type
- Respiratory epithelium is found in the mucosal layer of respiratory tissues
CPR: Primary ciliar dyskinesia AKA Immotile-cilia syndrome AKA ______________ syndrome is:
& is caused by:
- Kartagener’s syndrome
- Defective dynein arms of the cilia
- Not only prevents mucociliary clearance in airways but also reduces sperm motility and egg transport
- Autosomal recessive disorder associated with bronchiectasis
CPR: Why does decreased mucociliary clearance lead to increased respiratory infections?
- Without the movement of mucus, the bacteria are stagnant and can invade respiratory cells
CPR: Why do goblet cells stain light color?
- Secretory granules called mucins within the cell
- Once the product is moved extracellularly-becomes hydrated to form mucus
CPR: Presence of goblet cells begins to taper off where in the respiratory sytem
- Population of goblet cells tapers off in the terminal bronchioles
CPR: What type of metaplasia occurs in the respiratory epithelium of smokers? What are the physiologic repercussions of this?
- Ciliated columnar epithelium changes to stratified squamous and increase in goblet cells
- There is decreased movement of mucous
- Congestion of smaller airways
CPR: What is Smoker’s melanosis?
Benign focal pigmentation of the oral mucosa caused by toxic, carcinogenic, and mutagenic chemicals in tobacco smoke activate melanocytes to produce melanin
CPR: Describe the adventia of the trachea
- Containing dense irregular CT for anchoring
CPR: What are brush cells? Where are they found?
- Found in respiratory epithelium of mucosal layer respiratory tissue
- Chemosensory receptors with afferent nerve endings that are specialized in identifying potentially harmful substances
- i.e. detecting small particles of bacterial proteins
CPR: Describe the mechanism of action of brush cells
- Identify potentially harmful substances
- Release Ach that affects neighboring ciliated columnar cells
- This in turn increases mucociliary clearance by increasing beating, ensuring the removal of bacteria
CPR: What are basal cells? Where are they found?
- Basal cells are mitotically active small round stem cells that give rise to ciliated columnar, goblet, and brush cells
- Lie on the basal lamina of the mucosal layer of respiratory tissue but do not reach the lumen
CPR: What are small granule cells? Where are they found?
- Contain numerous granules that produce peptides to regulate bronchial and vascular muscle tone in response to stimuli such as hypoxia
- Found in mucosal layer of respiratory tissue
CPR: T/F: fluid secreted by submucosal glands is synonymous to surfactant
- F, has similar purpose to surfactant but is not the same
CPR: Descending the conducting and respiratory pathway, what happens to elastic fibers?
- Increasing quantity of elastic fibers
CPR: Where does the presence of smooth muscle start to decrease in respiratory tract?
- Smooth muscle regulates luminal diameter
- Begins in trachea and starts to decrease at bronchiole tree and completely absent at alveolar sacs
CPR: List the anatomic structures from the trachea to the alveolar sacs
Start: Trachea > Primary Bronchi (L&R) > Secondary/Lobar Bronchi (2 L, 3 R) > Tertiary/Segmental Bronchi > Terminal Bronchiole > Respiratory bronchiole > Alveolar ducts > Alveolar sacs
CPR: Where does the conducting portion of the respiratory system stop?
Terminal bronchioles are the final conduction portion
CPR: How does the cartilage structure compare in the bronchi vs. the trachea?
- Trachea: C shaped hyaline cartilage rings surrounded by tracheal muscle
- Bronchi: Cartilage rings that completely encircle the lumen of the primary bronchi. And as the diamter of the bronchi decreases the cartilage becomes cartilage plates
CPR: Where does lung tissue start appearing along the respiratory tract?
- Lung tissue present and surrounding the adventitia in the bronchi since they enter the lungs
CPR: Contrast the histological features of acute vs. chronic bronchitis
Acute: mucosal inflammation and thickening and increased mucous secretion
Chronic: Mucous hypersecretion with enlargement of tracheobronchial submucosal glands and a disproportionate increase of mucous acini
CPR: Describe the symptoms of acute vs chronic bronchitis
- Acute: deep productive cough, nasal congestion, and chest pain
- Chronic: mucus production, chest pain, wheezing, SOA, low fever
CPR: Where does the majority of lung cancers originate?
- From the lining of the airways, specifically the bronchi
CPR: What are the two main types of lung cancer?
- Non-small cell lung cancer (~85%)
- Small cell lung cancer
CPR: List the three sub types of Non-small cell lung cancer
- Adenocarcinoma
- Squamous cell carcinoma
- Large cell carcinoma
CPR: What is the most common form of lung cancer in non smokers?
Adenocarcinoma
CPR: Describe Adenocarinoma of the lung. Is it small cell or non-small cell cancer?
- Non-small cell lung cancer
- Arising from glands of bronchioles and alveoli epithelial cells
- Well differentiated columnar cells that proliferate along the framework of alveolar septa
- More common in Women & caused by abnormalities of the tumor protein p53
CPR: Describe Squamous cell carcinoma of the lung. Is it non-small cell or small cell?
- Non-small cell lung cancer
- Smoking causes change of respiratory epithelium to stratified squamous epithelium that exhibit dysplasia
- Does not usually spread beyond the lungs or its lymph nodes
- Keratin perales present due to accumulations of keratin made by malignant squamous cells
CPR: What are keratin pearles?
- Islands of brightly color eosinophilic neoplastic epithelial cells
- Whorl-shaped accumulations of keratin that are made by malignant squamous cells
- Seen in squamous cell carcinoma
CPR: Describe large cell carcinoma. Where does it come from?
- Origin includes basal cells, club cells, type II pneumocytes, & pulmonary neuroendocrine cells
- Poorly differentiaed tumor cells with large cells that contain ample cytoplasm and prominent nucleoli and vesicular chromatin
- Tend to grow more quickly and spread faster than other forms of non-small cells lung cancers
- Metastasize outside the lungs to lymph nodes
CPR: Describe small cell carcinoma?
- Highly malignant form
- Cancer looks like oats under the microscope
- Neoplastic transformation of small granule Kulchitsky cells in bronchial respiratory epithelium
- Highly aggressive carcinoma
- Metastasizes far and has poor prognosis
CPR: Describe the tumors of small cell (___) carcinoma
- Oat carcinoma
- Tumor consists of: sheets of small round, oval, or spindle-shaped cells with scant cytoplasm
- Finely granular nuclear chromatin
- Conspicous mitoses
- Neuroendocrine markers
CPR: T/F bronchioles lack mucosal glands and cartilage but have smooth muscle
True
CPR: Describe the epithelium of terminal bronchioles
- Simple cuboidal cells or ciliated simple columnar
- Club/Clara cells
- BALT
CPR: What are club cells?
- Exocrine cells that are nonciliated, dome-shaped apical ends containing secretory granules with various surfactants
- Secrete of some surfactant components that reduce surface tension and help prevent collapse of bronchioles
- Detoxification of inhaled xenobiotic compounds by SER enzymes
- Secretion of antimicrobial peptides and cytokines for local immune defense
CPR: What is bronchiolitis?
- Common large infection in babies and infants
- Commonly caused by RSV, Influenza, Rhinovirus
CPR: What is the difference between alveolar ducts and alveolar sacs?
- Alveolar proceed alveolar sacs
CPR: Describe the mucosal layer of the terminal bronchioles
- Lamina propria: Smooth muscle and elastic connective tissue
- Epithelium: club cells, simple squamous cells
CPR: Describe the epithelium of respiratory bronchioles
- Simple squamous epithelium
- 1-2 layers
CPR: Describe alveolar septum
- B/T alveoli and capillary where the alveoli are made of Type I pneumocytes (majority) and Type II pneumocytes
- Formation of alveolar pores b/t Type I pneumocytes
CPR: ________________ is characterized by the destruction of the intralveolar wall, reducing the surface area available for gas exchange
- Emphysema is characterized by the destruction of the interalveolar wall, reducing the surface area available for gas exchange
- Destruction and/or impaired synthesis of elastic fibers disallowing expiration due to decreased elasticity
CPR: How does cigarette smoke impact elastase?
Cigarette smoke inhibits α1-antitrypsin, a protein that normally protects the lungs from elastase produced by alveolar macrophages
CPR: What prevents tissue fluid leakage into alveolar air space in the alveoli?
- Desmosomes and occluding junctions between type I pneumocytes in the alveoli
CPR: What is another name for Type II pneumocytes?
Alveolar spetal cells
CPR: What are lamellar bodies?
Organelles in the Type II pneumocytes that store surfactant
CPR: What causes infant respiratory distress syndrome?
- Incomplete differentiation of type II alveolar cells due to premature birth. Decreased surfactant production and increased surface tension that allows for alveolar collapse
CPR: What are dust cells?
- Referred to as heart failure cells in CHF
- Lungs get congested with blood
- RBCs pass into the alveoli and are phagocytized by alveolar macrophages
- Identified by hemosiderin
CPR: What is the hilum?
Region on mediastinal surface of the lung where main bronchus, pulmonary arteries and veins, bronchial vessels, nerves & lymphatics
CPR: Compare the L hilum to the R hilum
- Left Lung Hilum: Bronchi is posterior to pulmonary veins with pulmonary arteries superior to bronchi
- Right Lung Hilum: Bronchi is the most posterior structure with pulmonary artery anterior to the bronchi
CPR: Where does aspiration pneumonia occur when patient is in the supine position
- Posterior segment of the right upper lobe and superior segment of right lower lobe
CPR: Where does aspiration pneumonia occur when patient is upright?
The basilar segment of the right lower lobe
CPR: Where do bronchial arteries come from?
Arise from the thoracic aorta and supply oxygenated blood to the bronchi, connective tissue of the lungs, and vasa vasorum of the pulmonary vessels
CPR: Most bronchial veins drain into pulmonary veins. What is the exception?
Some posterior bronchial veins may drain into the azygos system that returns to the R atrium
CPR: Describe the lymphatic drainage of the lungs
- Deep lymphatic plexus found alongside bronchi, blood vessels, and in interlobular septa
- This plexus drains the deeper lung tissues and communicates with the superficial plexus
CPR: Describe the lung lymphatic superficial plexus
- In connective tissue beneath visceral pleura that drains to hilar nodes
CPR: Describe the sensory innervation of the phrenic nerve related to the lung
- Phrenic nerve innervates the fibrous pericardium, mediastinal pleura, diaphragmatic peritoneum
CPR: What innervates the visceral pleura?
Innervated by autonomic fibers
Insensitive to pain
CPR: What innervates the parietal pleura?
- Innervated by somatic afferent fibers
- Pain sensitive
- Costal pleura is supplied by intercostal nerves
CPR: Describe normal finding of percussion of the thorax
- Normally percussion produces a resonant sound
CPR: Describe abnormal findings of percussion of the thorax
- Hyperresonance suggests overinflation, i.e. emphysema or pneumothorax
- Dullness may indicate consolidation, pleural effusion, or tumor
CPR: Where might normal dullness be found during percussion of the thorax?
- Dullness may be normal over the heart and liver
CPR: What is pneumothorax?
Air in the pleural cavity
CPR: Describe clinical presentation of pneumothorax
- Sudden-onset chest pain and dyspnea
- PE may reveal decreased breath sounds, hyperresonance to percussion, and decreased chest wall movement on the affected side
CPR: What happens to the trachea during pneumothorax?
The trachea deviates to the opposite side that the pneumothorax occurs
CPR: What is pleural effusion?
- Fluid in the pleural cavity
- Transudates or exudates
CPR: What causes transudates in pleural effusion?
Imbalances in hydrostatic or oncotic pressures
CPR: What causes exudates in pleural effusion?
Inflammation or malignancy
CPR: What are symptoms of pleural effusion?
- Dyspnea
- Pleuritic chest pain
- Dry cough
- PE may reveal dullness to percussion and decreased breath sounds at the lung bases
CPR: Describe how Obstructive diseases differ from Restrictive diseases regarding gas diffusion
- Obstructive: Reduce the surface area available for gas diffusion into blood
- Restrictive: Decrease capacity for gas diffusion due to the thickening of alveolar walls
CPR: What is FEV1?
- Forced expiratory volume in 1 second
- A PFT test
CPR: What is VC?
- VC = vital capacity measured during forced exhalation (FVC)
CPR: What are some forces that contribute to lung compliance?
- Lung tissue: elastin & collagen fibers
- Surface tension
CPR: What does surfactant do?
- Binds to H2O water molecules that are tightly bound to break up the tight bonds so the lungs have better compliance
CPR: Compare the chest wall movement vs. lung movment?
- Chest wall wants to expand
- Lung wants to collapse/recoil
CPR: What contributes to the recoil forces of the lung? What is recoil force?
- Elastin and surface tension contribute to lung recoil forces
- Recoil force is what makes the want to tend to collapse
CPR: Describe the pleural pressure change during inspiration
Volume increases and pleural pressure becomes more negative to overcome recoiling of lungs
CPR: Why is expiration faster than inspiration?
- Related to compliance, lungs tend to want to collapse which is conducive to expiration where volume decreases and pleural pressure becomes less negative
CPR: Describe how compliance is changed in emphysema? How does contribute to physical appearance?
- Emphysema has increased compliance due to decreased elastic recoil the air sacs to lose their shape and become floppy
- Since there is increased residual volume, overtime contributes to barrel chest
CPR: Describe how the alveolar and pleural pressure changes during inspiration?
- Alveolar pressure becomes a little bit negative to draw in air from ATM of higher pressure
- Pleural pressure is -6 mmHg
- Transpulmonary pressure increases
CPR: Describe how pressures change during expiration
- Alveolar pressure rises
- Intrapleural pressure becomes less negative
- Transpulmonary pressure lowers
CPR: How to calculate transpulmonary pressure and how it contributes to equal pressure point
- Transpulmonary pressure = Alveolar pressure - intrapleural pressure
- When transpulmonary pressure is + or alveolar pressure > intrapleural pressure = inspiration
- When transpulmonary pressure is - pr alveolar pressure < intrapleural pressure = expiration alveolar collapse
CPR: Emphysema is an _______________ lung disease and involves the destruction of:
Emphysema is an obstructive lung disease that involves the destruction of elastin fibers in the lungs which contribute to normal recoil in healthy lung
CPR: Describe how emphysema contributes to early airway collapse during expiration and what is the repurcussion
- In emphysema there is little collapsing force in the alveoli meaning the transpulmonary pressure is lower than it should be during expiration (TPP should be -)
- Alveolar pressure < Intrapleural pressure = airway collapse
- Less air is able to leave which increases residual volume
CPR: Describe the work of alveoli in fibrotic lung diseases
- Easy to recoil with increased elastic fibers
- Hard to stretch & must use muscles to overcome resistance
- Want a lower tidal volume so that it is easier to overcome resistance
CPR: What is the passive resting point?
- At FRC the recoil of both lungs and chest wall is equal
- Lung recoiling inward is balanced by chest wall spring out
CPR: How do can you measure FEV1? What is it?
- Forced expiratory volume in 1 second
- Inhale and then force exhalation until physically unable to which is the forced vital capacity
- usually 80% of vital capacity
- <70% indicative of obstructive ventilatory defect
CPR: What is FVC?
Forced vital capacity (FVC) refers to the maximum amount of air a person can forcefully exhale from their lungs after taking the deepest breath possible
CPR: Describe how FEV1/FVC ratio will be changed in obstructive diseases and why?
- Both FEV1 and FVC are lowered overall, leading to a decreased ratio
- In obstructive diseases: increased resistance, reduced expiratory flow, cannot get air out
CPR: Describe how Restrictive diseases changes FEV1/FVC
- Reduced compliance
- Reduced lung volumes but normal FEV1/FVC
- Cant get air in
- Ratio increases
CPR: In obstructive diseases, the ratio FEV1/FVC both are lowered, which is reduced more?
- FEV1 is more reduced than FVC
CPR: In which type of lung diseases may FEV1 may or may not decrease?
In restrictive diseases, FEV1 may or may not decrease since recoil effect is okay
CPR: List 4 obstructive lung diseases
- Emphysema
- Chronic bronchitis
- Bronchiectasis
- Asthma
CPR: What class of diseases does this match:
Reduced expansion of lung parenchyma accompanied by decreased total lung capacity
Restrictive lung disease
CPR:
1. What class of diseases does this match:
Limitation of airflow due to partial or complete obstruction.
2. Describe the changes to FVC and FEV1
- Obstructive air diseaess
- Both are reduced but FEV1 is more reduced
CPR: What is normal FEV1/FVC ratio?
0.8 or 80% as the most amount of air is expired at the beginning of respiration
CPR: What is PEF?
Measured during a maximally forceful and rapid exhalation that immediately follows a maximal inhalation
CPR: What is FEF50?
- Forced Expiratory Fraction 50
- The flow rate at the midpoint of vital capacity
CPR: What is FIF50?
- Forced Inspiratory Flow-50
- Flow rate at the midpoint of vital capacity in inspiration
CPR: Why is FEF50 < FIF50 normally?
- Because expiration occurs at a faster rate than inspiration due to elastic recoil of lungs so rate of change in volume is faster in expiration = less volume in lungs faster
CPR: Why do restrictive lung diseases have a long/ tall/thin/narrow flow-volume loop?
- Because restrictive disorders the total lung volume and residual volume make the loop thin
- Vital capacity is small since lungs do not want to expand
- Since there is nothing wrong with the airway, the expiring rate is fast since not as much air to expire
CPR: What is the most soluble in in lungs?
CO2 is 20 times more soluble in blood than that of O2
CPR: How do partial pressure and concentration relate to each other in the lungs?
Partial pressure and concentration are directly correlated
CPR: According to Fick’s law, what 4 factors contribute to diffusion?
- Pressure gradient
- Area
- Distance
- Solubility
CPR: Why does CO2 have a lower partial pressure gradient?
-
CPR: What does sympathetic innervation of the lungs do?
- Beta 1 is SNS innervation of the lungs
- Vasoconstricts and bronchodilates
CPR: What does parasympathetic innervation do in the lungs?
- PNS: M3
- Vasodilates and bronchoconstricts
CPR: Describe the concentration of O2 & CO2 in the venous system
- O2 is much less compared to arterial, but is still present because not 100% is delivered to the tissues at the capillaries
- CO2 concentration is higher
CPR: Describe O2 and CO2 concentration in systemic arteries
- High O2 content to oxygenate the tissues and get O2 to the mitochondria
- Low C02 concentration: but note not all CO2 is exchanged at the alveoli so some CO2 is still present
CPR: What is normal shunt?
5%
CPR: In high altitude, why will pulmonary blood flow resistance increased?
- Low O2 induces vasodilation systemic, lung experiences vasoCONSTRICTION
- Increase constriction increases resistance and pressure with constriction
CPR: Pulmonary hypertension will cause:
R ventricular hypertrophy
CPR: What hormone is increased in hypoxemia?
- Increased erythropoietin so that more RBC are present and more HbA to carry oxygen
CPR: What occurs at high altitudes?
- Hypoxemia due to lowered atmospheric pressure
- Less oxygen content in the blood because less oxygen to be extracted from the blood
CPR: Compare the Hb binding of CO vs O2
- CO binds to Hb 250 times greater than O2
- Can kick off O2 & CO can make binding between remaining O2-Hb stronger so O2 cannot be released to tissues
- CO needs much less partial pressure to bind to Hb
CPR: When tissue lacks oxygen, what happens?
- Tissues will switch to anaerobic metabolism which will increase lactic acid production
- Acidic increases = Acidosis
CPR: What does a Left shift on the Hb-Dissociation curve mean?
- The Hb has greater affinity for O2
- Cannot release O2 at tissues in capillaries
CPR: How is CO2 transported in the blood?
- 10% is physically dissolved in the plasma
- 30% bound to Hb as carbamino hemoglobin (HbCO2)
- 60% in the form Bicarbonate (HCO 3- )
CPR: 60% of CO2 is transported in RBC in the form: Bicarbonate (HCO 3- ).
1. What enzyme is responsible for changing CO2?
2. What happens to Bicarbonate in RBCs?
- Carbonic anhydrase
- Bicarb effluxes from RBC to exchange for influx of Cl- ions to balance charges. When gets back to the lung, they will switch back so that bicarb can be transported out of the body
CPR: What effects take place at the lung and tissues to allow RBC to uptake/release CO2?
- Lung: Haldane Effect says that removing O2 from Hb increases the ability of Hb to pick up CO2 and CO2 generated H+
- Tissue: Bohr effect influences CO2 and H+ on the release of O2
CPR: What are 2 ways to limit gas exchange?
- Diffusion limited gas exchange
- Perfusion limited
CPR: Describe Perfusion limitation regarding Oxygen binding
- At the alveoli, O2 enters the blood and binds to Hb
- When O2 is bound to Hb it does not contribute to partial pressure
- At the lungs PA and Pa need to equilibrate to 100 mmHg
- So it takes extra time and more O2 equilibrate in the blood
CPR: Describe Perfusion limitation related to Nitrous oxide (NO2)
- Nitrous oxide doesn’t bind to Hb at the level of the alveoli
- Therefore, it stays in the blood and contributes to partial pressure
- This allows fast equilibration b/t PA and Pa
CPR: Among the 4 gases, which are always perfusion limited, which are usually perfusion limited, and which are always diffusion limited
NO2
CO2
CO
O2
- Always perfusion: NO2
- Usually perfusion: CO2 & O2
- Always diffusion: CO
CPR: Describe diffusion limited gas exchange of CO
- PA doesn’t equilibrate with PiCO because when it gets into blood it quickly binds to Hb which decreases Pa
CPR: Describe perfusion vs diffusion in the lungs
- Perfusion: gas uptake in blood directed by Q
- Diffusion: gas uptake in blood from alveoli determined by diffusion capacity
CPR: Describe diffusion capacity changes for O2 transport in the alveoli (remember under normal circumstances O2 is normally ___________ limited)
- Strenuous exercise: the blood flow is fast so there is not enough time for A-a gradient to equilibrate
- Fibrosis: diffusion limited b/c alveolar thickening takes even longer for PaO2 = Pa O2
- O2 is normally perfusion limited
CPR: In the respiratory center of the brain, what controls inspiration?
Where is the respiratory center of the brain?
- Dorsal respiratory group
- This is in the dorsal portion of the medulla, which mainly causes inspiration
CPR: In the respiratory center of the brain, what controls forced expiration?
Where is this located?
- Ventral respiratory group, located in the ventrolateral part of the medulla, which mainly causes forced expiration
CPR: What is the pneumotaxic center? Where is it?
- Located in upper pons
- Limits inspiration by inhibiting DRG
- Limits tidal volume, increases respiratory rate
- Receives input from cerebral cortex
CPR: What do β2 receptors do in the lungs?
β2 receptors dilate the lungs
CPR: What do M3 receptors do in the lungs?
- PNS cholinergic M3 receptors constrict
CPR: What do muscarinic antagonists do in the lungs?
- Cause vasodilation due to to blocking M3 receptors that normally bronchoconstrict
CPR: What is Atelectasis?
Collapsed lung
CPR: What is tidal volume?
The tidal volume is the volume of air inspired or expired with each normal breath; it amounts to about 500 milliliters in the average adult male
CPR: What is inspiratory reserve volume?
The inspiratory reserve volume is the extra volume of air that can be inspired over and above the normal tidal volume when the person inspires with full force; it is usually equal to about 3000 milliliters.
CPR: What is the expiratory reserve volume?
The expiratory reserve volume is the maximum extra volume of air that can be expired by forceful expiration after the end of a normal tidal expiration; this volume normally amounts to about 1100 milliliters.
CPR: What is residual volume?
The residual volume is the volume of air remaining in the lungs after the most forceful expiration; this volume averages about 1200 milliliters.
CPR: What is inspiratory capacity?
The inspiratory capacity equals the tidal volume plus the inspiratory reserve volume. This capacity is the amount of air (about 3500 milliliters) a person can breathe in, beginning at the normal expiratory level and distending the lungs to the maximum amount
CPR: What is the functional residual capacity?
The functional residual capacity equals the expiratory reserve volume plus the residual volume. This capacity is the amount of air that remains in the lungs at the end of normal expiration (about 2300 milliliters).
CPR: What is vital capacity?
The vital capacity equals the inspiratory reserve volume plus the tidal volume plus the expiratory reserve volume. This capacity is the maximum amount of air a person can expel from the lungs after first filling the lungs to their maximum extent and then expiring to the maximum extent (about 4600 milliliters).
CPR: What is the total lung capacity?
The total lung capacity is the maximum volume to which the lungs can be expanded with the greatest possible effort (about 5800 milliliters); it is equal to the vital capacity plus the residual volume
CPR: What are the most commonly used spirometric indices?
- FEV1: Forced expiratory volume in 1 s
- FVC: Forced vital capacity
CPR: What volumes or capacities can you measure?
- Forced residual capacity
- Residual volume
- Total lung capacity
CPR: What is the preferred way to measure functional residual capacity, residual volume, and/or total lung capacity?
Body plethsymography
CPR: How to calculate alveolar ventilation?
Alveolar ventilation = (tidal volume - dead space volume) * respiratory rate
CPR: How to calculate pulmonary ventilation?
Pulmonary ventilation = tidal volume * respiratory rate
Describe gas equilibration at the end of the pulmonary capillary
- At the end of pulm capillary is when vessel moving past alveoli for the blood to become oxygenated
- PA O2 is 100 mmHg but at the end of the capillary the O2 will have diffused out and the PaO2 is 100 mmHg so they math
- Blood gas pressure = Alveolar gas pressure at the end of the pulmonary capillary
Contrast NO2 perfusion limited gas exchange compared to O2
- Since NO2 doesn’t bind to Hb, the equilibration b/t alveoli and blood occurs quickly
- Takes longer for O2 to equilibrate due to it binding to Hb while it flows past the alveoli, requires more O2 and time to build up partial pressure for equilibrium to be reached b/t alveoli and capillary
Is oxygen normally perfusion or diffusion limited?
Oxygen is normally perfusion limited
- This is because during gas exchange at the alveoli there is rapid uptake of O2 by the Hb.
- If O2 is bound to Hb it does not contribute to partial pressure
- So as blood moves around the alveoli it continues to exchange O2 until the Hb is saturated and then the Pa O2 can start to equilibrate with the PA O2
Define perfusion limited gas exchange
Gas uptake into blood is affected by blood flow
- If inc. blood flow can increase perfusion limited
Blood always equilibrates with alveolar pressure
Define diffusion limited gas exchange
Gas uptake into blood is affected by diffusion capacity
blood never equilibrates with alveolar pressure
O2 is normally perfusion limited, under what circumstances is it diffusion limted?
- In pathology wherein the PaO2 cannot equilibrate with PA O2
- I.e. pulmonary fibrosis where alveolar membrane thickness increases such that gas cannot as easily travel from high to low concentration so takes longer for Pa O2 to become equal to PA O2
Give an example of a gas that is diffusion limited
- CO
- This is because CO so readily binds to Hb as soon as it enters the Pa, it is removed as a contributor to partial pressure
- So no matter how far get, the CO will still be not considered part of a partial pressure contributor
Explain the normal A-a gradient
- Due to physiologic shunt
- Remember the bronchial vein dumps into the pulmonary veins with deoxygenated blood which lowers the the PaO2 that is entering the heart
- So even though the PaO2 equilibrates with Pa after leaving the alveoli, the later PaO2 is lowered
Describe the A-a gradient in pulmonary fibrosis
- A type of diffusion defect
- The PAO2 is reaching 100 mmHg
- There is fibrosis of the alveoli causes difficulty for O2 to cross the alveolar membrane and thus the equilibration is not reached
- A-a gradient is changed to PA02 - PaO2 = 100 mmHg - PaO2 60 mmHg = 40 mmHg
Do you want a high or low oxygen A-a gradient, why?
Want lower b/c want the PAO2 and PaO2 should be equilibrated
The only lowering factor is the natural shunt lower PaO2 when deoxygenated bronchial blood dumps into pulmonary veins
Why is PaCO2 unchanged in diffusion defects?
B/c CO2 is a very soluble gas that easily crosses the alveoli membrane
- O2 is less dissolvable
Why is PaCO2 unchanged in V/Q mismatch?
- B/c not all alveoli are compromised & ventilation is reduced , not 0
- I.e. mucus plug in one of the alveoli, but the rest of the alveoli are able to equilibrate PaO2 with PAO2 so A-a gradient is not much changed overall
For testing purposes, R-L shunt is equivalent to:
- Full blockage of an alveoli
- i.e. airway obstruction
- Does not respond to O2 adminstration
What type of G proteins are in β 1 & β 2 nerves?
β 1 & β 2 are Gs proteins which means they increase cAMP production
What type of proteins are α 1 nerves?
α 1 are Gq proteins so they increase Ca+2 & PKC
What receptors cause bronchodilation in the lungs?
β 2 are Gs proteins which means they increase cAMP production but cause bronchodilation
What cause bronchoconstriction in the lungs?
M3 receptors
BSE: T/F Prevalence increasing, increases PPV, Sensitivity, Specificity and decreases NPV
Technically yes, but mostly Prevalence influences PPV and NPV only