Pathophysiology Flashcards
Lung lobes for reference
Make sure to reference the anatomical location when talking about pneumonia, or cancer
Structure and function 3
Conducting zone path and volume
Respiratory zone path and volume
- Blood-gas interface
- Airways and airflow
- Blood vessels and flow
1. Blood-Gas Interface:
—Oxygen and carbon dioxide —from high to low partial pressure
—Blood-gas barrier is thin (0.2-0.3 um)
—has an area of 50-100 square meters allowing for an enormous surface area of diffusion
—500 million alveoli in the human lung
2. Airways and Airflow
Series of branching tubes that become narrower, shorter, and more numerous as they enter the lung
CONDUCTING ZONE
—trachea ➡️ right and left bronchi ➡️ lobar bronchi ➡️ segmental bronchi ➡️ terminal bronchioles
—= anatomic dead space that receive ventilation but NO blood flow.
—Its volume is 150 cc.
RESPIRATORY ZONE
—terminal bronchioles ➡️ respiratory bronchioles ➡️ alveolar ducts ➡️ alveolar sacs
—where the gas exchange occurs.
—majority of lung with the volume around 2.5- 3L.
INSPIRATION
—(diaphragm, intercostal muscles) draws air into the lung by forward velocity to the terminal bronchioles.
—Afterwards, diffusion of gas takes over in the respiratory zone to ventilate.
3. Blood Vessels and Flow
—Pulmonary artery ➡️ capillaries ➡️ pulmonary veins
—The capillaries form a dense network with the walls of the alveoli providing an efficient arrangement for gas exchange
—Diameter of of the capillaries is 7 - 10 um or just large enough for a red blood cell
—The extreme thinness of the blood-gas barrier makes it prone to damage by either increased pressure within the capillaries or highly inflated lung volume.
—This can cause leakage of plasma/RBCs into the alveolar spaces.
Volumes:
Tidal volume
Anatomical dead space
Alveolar gas
Pulmonary capillary blood
Tidal volume: 500ml
Anatomical dead space: 150ml
Alveolar gas: 3000ml
Pulmonary capillary blood: 70ml
Flows
Total ventilation
Frequency
Alveolar ventilation
Pulmonary blood flow
What are these things?
TIDAL VOLUME
VITAL CAPACITY
RESIDUAL VOLUME
FUNCTIONAL RESIDUAL CAPACITY
TIDAL VOLUME: the amount of air that moves in or out of the lung with each respiratory cycle (500 cc)
VITAL CAPACITY: greatest volume of air that can be expelled from the lungs after taking a maximal inspiration (4800cc)
RESIDUAL VOLUME: amount of gas that remains in the lung after maximal expiration (1200cc)
FUNCTIONAL RESIDUAL CAPACITY: volume of gas in the lung after a normal expiration (2400cc) (ERV+RV)
How do you calculate total ventilation?
How do you calculate alveolar ventilation?
TOTAL VENTILATION or MINUTE VENTILATION:
—tidal volume x RR
—total volume leaving the lung each minute.
—if tidal volume is 500 cc and the respiratory rate is 15, then minute ventilation is 500 x 15 = 7500 cc/min.
However, due to the dead space, not all inhaled air reaches the alveoli where gas exchange occurs.
The volume of fresh gas entering the respiratory zone is the ALVEOLAR VENTILATION.
—TV - dead space volume x RR
—Calculated by (500-150) x 15 = 5,250 cc/min
Diffusion, which law describes it?
What does this law state? What is rate of transfer of gas proportional to and inversely proportional to?
What is the area of the blood-gas barrier and thickness?
—Fick’s law.
—the rate of transfer of a gas through a sheet of tissue (think postage stamp) is proportional to:
—the tissue area
—and the difference in gas partial pressure between the two sides,
—and inversely proportional to the tissue thickness.
—The blood-gas barrier is 50 - 100 square meters
—and the thickness is only 0.3 um therefore the dimensions are ideal for diffusion
Diffusion
What is the PO2 in RBC in the capillary?
What is the alveolar PO2?
Diffusion process is affected by? -3
—The PO2 (partial pressure of O2 dissolved in blood) in a RBC entering a capillary is ~40 mmHg.
—The alveolar PO2 is 100 mmHg.
—O2 flows down pressure gradient (alveolar > capillary RBC) and the PO2 in the red cell rises to that of the alveolar gas.
Diffusion process is affected by
1. Exercise ➡️ pulmonary blood flow is increased and reduces the time the red cell can oxygenate
2. Alveolar Hypoxia ➡️ the alveolar PO2 is lower therefore lowering the diffusion gradient and slowing down oxygenation
3. Thick blood-gas barrier ➡️ impedes diffusion
Water balance in the lung
Which pressure pushes fluid out of the capillary
Which pressure pulls fluid IN to the capillary
—Because only 0.3 um of tissue separates the capillary blood from the air in the lung, the issue of keeping the alveoli free of fluid is critical.
CAPILLARY HYDROSTATIC PRESSURE: the force tending to push fluid out of the capillary (capillary hydrostatic pressure - hydrostatic pressure in the interstitial fluid)
COLLOID OSMOTIC PRESSURE: the force tending to pull fluid in (colloid osmotic pressure of proteins of blood - proteins of interstitial fluid)
Where does fluid go when leaves capillaries?
capillaries → interstitium, perivascular/peribronchial space → lymphatics → if volume exceeded here → crosses alveolar epithelium → alveoli
First
—into the interstitium to the perivascular and peribronchial space within the lung.
—lymphatics in these spaces transport fluid to the hilar lymph nodes.
⚠️EARLIEST SIGN OF EDEMA is identified by engorgement of these peribronchial and perivascular spaces (interstitial edema).
Then
—maximal drainage through interstitial space is exceeded
⚠️fluid crosses the alveolar epithelium into the alveolar spaces (LATER STAGE OF EDEMA).
—the alveoli become filled with fluid, unable to ventilate, and no oxygenation of blood occurs.
Discuss O2 transport and how much O2 we inspire
PO2 of the air we breathe?
PO2 of inspired air?
What is the PO2 in the alveoli? Know this
PO2 coming back to the lungs
—PO2 decreases from atmospheric air to the lung to it is utilized by the mitochondria in the tissues
—PO2 of air is ~21% of the total gas pressure.
—At sea level (760 mmHg barometric pressure), a 37 degree celsius body temperature, and accounting for water vapor (47 mmHg), the PO2 of inspired air is ~ 150 mmHg
= (20.93/100) x (760-47) = 149 mmHG
—The PO2 falls to ~ 100 mmHg in the alveoli due to removal of O2 by pulmonary capillary blood balanced by continued replenishment by alveolar ventilation.
—PO2 in tissues fall considerably as the mitochondria utilize the oxygen
—O2 coming back is about 40mmHg
—hypoventilation could cause a low PO2
What are the 4 causes of hypoxemia?
1.Hypoventilation
2.Diffusion Limitation
3.Shunt
4.Ventilation-perfusion inequality
Hypoxemia: what is happening in these conditions?
Hypoventilation
Diffusion limitation
HYPOVENTILATION:
—if alveolar ventilation is low, the PO2 falls and PCO2 rises
—caused by sedating drugs that depress the central drive to respiratory muscles, damage to the chest wall or paralysis of respiratory muscles, and a high resistance to breathing (diving), and obesity.
—easy to reverse by adding inspired gas (supplemental O2).
DIFFUSION LIMITATION:
—capillary blood PO2 rises close to alveolar PO2 through diffusion however never quite reaches that level although the difference is immeasurably small.
—with exercise, alveolar hypoxia, and/or a thickened blood-gas barrier, the difference can become large.
—note on the diagram, the slightly lowering of PO2 with diffusion and shunt
Hypoxemia
Shunt — important feature, what treatment does NOT work?
SHUNT:
—refers to blood that enters the arterial system without going through ventilated areas of the lung.
—The addition of poorly oxygenated blood lowers arterial PO2.
—Can be due to pulmonary arteriovenous malformation (vascular connection between a pulmonary artery and vein) or a defect between the left and right sides of the heart.
—An important feature of a shunt is that the hypoxemia can not be abolished by giving 100% O2 to breathe because the shunted blood never is exposed to the higher alveolar PO2
Hypoxemia
VENTILATION-PERFUSION INEQUALITY
(Most common)
What could cause a reduced V/Q ratio (i.e reduced ventilation?)
What could cause an increase V/Q ratio? (I.e decrease perfusion?)
MOST COMMON and results when ventilation and blood flow are mismatched (affecting the ratio between them) resulting in impairment of both O2 and CO2 transfer
Ratio: Ventilation (V) / Perfusion (Q)
—Can reduce the ratio by obstructing ventilation, causing PO2 to fall and CO2 to rise.
••example: pneumonia, COPD, edema = ventilation issue
—Can increase the ratio by obstructing blood flow, causing the PO2 to rise and CO2 to fall
••example: PE obstructing full flow of pulmonary artery leading to absolute dead space: no perfusion Q and okay ventilation V
In diagram B, black block is an obstruction preventing airflow. Nothing wrong with circulation.
In C, black blob is impeding blood flow. 150 comes in but ends up being 100 b/c pulmonary circulation through perfusion gradient drops it to 100. No CO2 because blockage in vessel.
A-a gradient: a measure of hypoxemia
What does it measure?
What is normal?
What is abnormal?
What are you trying to determine?
A-a gradient =
∆ in alveolar concentration of oxygen (PAO2) and the arterial concentration of oxygen, or (PaO2) = PAO2 - PaO2
>10 is abnormal
(FiO2) x (atmospheric pressure - H2O pressure) - (PaCO2/0.8) - PaO2 from ABG (pull it up on MedCalc)
Useful to determine if hypoxemia is intrapulmonary or extrapulmonary
In a perfect lung there would not be an A-a gradient as oxygen would diffuse and equalize across the capillary membrane. Therefore pressure in the alveolar and arterial system would be equal. However, due to the effect of gravity there is perfusion differences in the base of the lung compared to the apices, resulting in about a 5 - 10 mmHg physiologic V/Q mismatch
Normal is 5-10 mmHg and increases 1 mmHg per decade of life. Rule of thumb is the A-a gradient is (age in years +10)/4 so a 40 year old would have a gradient of 12.5 mmHg
A-a gradient
Elevated gradient suggests? 3
What is the impact of hypoventilation and high altitude
Remember: ∆ in alveolar concentration of oxygen (PAO2) and the arterial concentration of oxygen, or (PaO2) = PAO2 - PaO2
An ELEVATED gradient suggests:
1. Diffusion defects
•••interstitial lung disease
•••environmental lung disease
•••PNA (pneumonia)
2. V/Q mismatch
•••PNA, CHF, PE, ARDS, atelectasis
3. Shunt
•••PFO, ASD, pulmonary AVMs
HYPOVENTILATION and HIGH ALTITUDE would have mild depression to no change (both the alveolar and arterial PO2 decrease together producing no gradient)
Gas transport by the blood
What are the two ways oxygen is carried?
What is O2 saturation? ⭐️
Blood is the carriage for the respiratory gases, oxygen and carbon dioxide.
OXYGEN:
—Carried in 2 forms: 1) dissolved and 2) combined with hemoglobin
—0.003 mL of O2 will be dissolved in each 100 mL of blood (inadequate)
Hemoglobin
—is an iron compound that has 4 sites to bind oxygen;
—2 alpha and 2 beta.
—Oxygen forms a reversible combination with hemoglobin (Hb) to give oxyhemoglobin:
—O2 + Hb <> HbO2
The O2 SATURATION of Hb is the percentage of the available binding sites that have O2 attached.
⭐️ The O2 saturation of arterial blood with PO2 of 100 mmHg is 97.5%; as opposed to mixed venous blood with a PO2 of 40 mmHg is 75%
Discuss the oxygen dissociation curve
What does the initial steep part represent? Where in the body are we?
What does the plateau later part represent, where are we in the body?
Right shift means?
Left shift means
(See notebook)
—Steep at the beginning because hemoglobin WANTS to unload O2 at the tissues, venous blood.
—If you’re high up, it’s not unloading the O2
—Wants to hold on to the oxygen when you’re hypoxia, if O2 is dropping, you can see you can drop from 100-80 without much difference in O2 sat.
—You won’t desaturate.
—But then you can decompensate fast.
—The curved shape has the physiologic advantage with the flat upper portion indicating that even if PO2 in alveolar gas falls slightly, loading of O2 will be relatively unaffected.
—The oxygen dissociation curve is shifted to the right (O2 affinity of Hb is reduced; more unloading of O2 in the capillary) by an increase in H+, PCO2, temperature, and the concentration of 2,3 diphosphoglycerate (DPG) in red cells (byproduct of RBC metabolism, shift the curve to the right and unload more O2)
—Shift to the left, carbon monoxide, binds to hemoglobin more easily then O2
—Simple way to remember: an exercising muscle is acidotic, hypercarbic, and hot … benefits from increased unloading of O2 from its capillaries⭐️
How is CO2 carried? 3
CO2 is carried in the blood in three forms:
1.Dissolved
—24x more soluble than O2 therefore 10% is dissolved in blood
dissolve as bicarbonate ions:
⭐️CO2 + H2O <> H2CO3 <> H+ and HCO3-⭐️
3.Carbamino Compounds:
—formed from combination of CO2 with amine groups in blood, most importantly globin of Hb
Acid base status
Which organ has a rapid effect on acid base balance
What is the bicarbonate buffering equation
—Transport of CO2 has a profound effect on the acid-base status of the blood and body
—The lung excretes 10,000 meq of carbonic acid per day as opposed to a 100 meq of fixed acids by the kidney.
—Lungs can have a rapid correction of CO2. Kidneys there is a delay
—Therefore alveolar ventilation and elimination of CO2 can greatly affect the acid-base balance.
—Can use the HENDERSON-HASSELBALCH equation to then describe the relationship between blood pH and the components of the H2 and CO3 buffering system.
⭐️CO2 + H2O <> H2CO3 <> H+ + HCO3-⭐️
carbon dioxide + water <> carbonic acid <> hydrogen ions + bicarbonate
—Allows the metabolic component to be separated from the respiratory component.
Acid base
What is normal body pH
What does the ratio of bicarbonate concentration to arterial PCO2 need to equal in order for pH to remain physiologically in balance?
What are the 4 pH disturbances?
The normal body pH is 7.35 - 7.45 with the average 7.4
As long as the RATIO of BICARBONATE concentration (HCO3-) to arterial PCO2 remains equal to 20, the pH will remain at 7.4.
The bicarbonate is chiefly determined by the kidney and the PCO2 by the lung.
The ratio of the bicarbonate to PCO2 can be disturbed in 4 ways, both PCO2 and bicarbonate can be raised or lowered leading to a characteristic acid-base change
- Respiratory Acidosis
- Respiratory Alkalosis
- Metabolic Acidosis
- Metabolic Alkalosis
Respiratory acidosis
Respiratory alkalosis
RESPIRATORY ACIDOSIS:
—Caused by an increase in PCO2 which reduces the HCO3-/PCO2 ratio and therefore decreases the pH.
—CO2 retention can be caused by HYPOVENTILATION or V-Q mismatch.
—If respiratory acidosis persists, the kidneys conserve HCO3- resulting in increased plasma levels and restores the ratio of HCO3-/PCO2.
RESPIRATORY ALKALOSIS:
—Caused by a decrease in PCO2 which increases the HCO3-/PCO2 ratio and increases the pH.
—A decrease in PCO2 is caused by HYPERVENTILATION (high altitude, anxiety attack).
—Renal excretion of HCO3- results returning the HCO3-/PCO2 ratio back to normal.
Metabolic acidosis
Metabolic alkalosis
METABOLIC ACIDOSIS:
—caused by a metabolic decrease in HCO3- causing the HCO3- /PCO2 ratio to fall and therefore decreasing the pH.
—Results from the accumulation of acids in the blood (diabetic ketoacidosis or lactic acidosis).
—Respiratory compensation occurs by an increase in ventilation that lowers PCO2 and raises the HCO3/PCO2 ratio.
METABOLIC ALKALOSIS:
—Increase in HCO3 raises the HCO3-/PCO2 ratio and therefore the pH.
—Excessive ingestion of alkalis or loss of gastric acid (ex: from vomiting) are potential causes.
—Respiratory compensation by a reduction in ventilation that raises the PCO2 (although this is usual a small effect)
ABG
How do you interpret in a step wise manner?
What are the normal ABG values?
1.pH
2.PaCO2
3.HCO3
4.PaO2
Normal ABG Values
1.pH 7.35 - 7.45
2.PaCO2 35 - 45 mmHg
3.HCO3 22 - 26 meq/L
4.PaO2 80 - 100 mmHG
Examine the pH
Examine the PaCO2 (which has the issue, CO2 or HCO3?)
Examine the HCO3 and PaO2 levels
Inspiration
Expiration
Inspiration:
1. Diaphragm (innervated by phrenic nerve)
2. External Intercostal Muscles connect adjacent ribs
3. Accessory Muscles include the scalene muscles (elevate first 2 ribs) and the sternomastoids (raise the sternum)
Expiration:
4. Typically passive; the lung and chest wall are elastic return to equilibrium after actively being expanded during inspiration
5. During exercise or voluntary hyperventilation, expiration becomes active and utilize the muscles of the abdominal wall. They contract and push the diaphragm upwards.
6.Internal Intercostals: assist active expiration by pulling ribs down and decrease thoracic volume
Compliance — what is this?
Examples of decreased compliance? 3
What does pulmonary surfactant do?
Increased compliance? 2 examples
Measure of the lung expandability and is calculated by change in volume / change in pressure. Determined by elastin in the connective tissue and surface tension.
Decreased compliance is a stiff lung
1. Pulmonary Fibrosis or increased fibrous tissue
2. Alveolar Edema which prevents inflation of the alveoli
3. Atelectasis or collapse of alveoli: small air sac, less compliance, collapse.
Increased compliance is a pliable lung and occurs with increased volume and degeneration of lung tissue.
Pulmonary surfactant increases compliance by decreasing the surface tension of water and preventing the collapse of the alveoli.
- Emphysema/COPD — lost the recoil, super compliant
- Aging lung
Control of Ventilation - how gas exchange is regulated
What are the 3 respiratory control systems?
Where in the brain?
Respiratory control system:
1. Sensors: chemo receptors gather information and feed it to the:
2. Central Controller: pons & medulla in the brain which coordinates the information and sends impulses to theL
3. Effectors (respiratory muscles): causes ventilation
Breathing can be under voluntary control with the cortex overriding the function of the brainstem
Central chemoreceptors:
—located?
—sensitive to?
Peripheral chemoreceptors
—located?
—sensitive/responds to?
CENTRAL CHEMORECEPTORS:
—Located near the ventral surface of the medulla and are surrounded by brain extracellular fluid
—Sensitive to the PCO2 but not the PO2 of blood
(when the blood PCO2 rises, CO2 diffuses into the CSF from the cerebral blood vessels and liberate H+ ions thereby stimulating chemoreceptors to increase ventilation)
PERIPHERAL CHEMORECEPTORS:
—Located in carotids and aortic arch
—Respond to decreased arterial PO2, increased PCO2, and H+
—Rapid response
Ventilatory Response to CO2
What is the most important stimulus to ventilation? Controlled within how many mmHG?
What does it come from?
—Arterial PCO2 is the most important stimulus to ventilation and is tightly controlled w/i 3mmHG
—Majority of the stimulus comes from the central chemoreceptors but the peripheral chemoreceptors also contribute and their response is faster
—The response is magnified if the arterial PO2 is lowered
Ventilatory Response to Hypoxia
—when is the role of PO2 and the hypoxic drive high? 2 (as opposed to the normal mechanism of PCO2 driving ventilation)
—in the case of severe lung disease, why might it be a problem to give them a high O2 mixture?
—The role of PO2 in the day-to-day control of ventilation is small except at HIGH ALTITUDE and SEVERE LUNG DISEASE where the hypoxic drive becomes important
—Chronic PCO2 retention reduces the normal stimulus to ventilation as the pH of the extracellular fluid has adjusted to normal range.
—The blood pH has been regulated by the kidneys reducing stimulation from peripheral receptors.
—⭐️Therefore arterial hypoxemia becomes the chief stimulus to ventilation.
—🔺If a patient is given a high O2 mixture to breathe and relieve the hypoxemia, ventilation may become depressed, they will decompensate because you’re taking away their drive to breathe (sensing O2)🔺
Cheyne-Stokes Respiration
What is the breathing pattern?
Seen in patients with which conditions?
Seen in severe hypoxemia and get a breathing pattern characterized by
periods of apnea (10 - 20 seconds) followed by periods of hyperventilation equally as long.
Seen in patients wit:
—severe heart failure
—brain injury
—high altitude
—and near death
Central chemoreceptors have a delay in sensing the alteration in CO2 following the change in ventilation. As a result, the respiratory center hunts for the equilibrium condition but overshoots it.
What are the tests of ventilators capacity
FEV1 define
FVC define
FEV1 to FVC (FEV1/FVC) normal?
Forced Expiratory Volume (FEV1)
—is the volume of gas exhaled in one second by a forced expiration from full inspiration.
Forced Vital Capacity (FVC)
—is the total volume of gas that can be exhaled after a full inspiration.
—These values are are reported as absolute numbers and as a percentage of what one would predict for an individual of the same age, gender, and height.
The ratio of FEV1 to FVC (FEV1/FVC) is also reported with normal ~80%
=The percentage of the FVC expired in one second
Note in obstructive: prolonged expiration, can’t get the air OUT. It is trapped
https://www.aafp.org/pubs/afp/issues/2004/0301/p1107.html
Tests of ventilators capacity
Forced expiratory flow
Peak expiratory flow
Overall PFTs
Forced Expiratory Flow:
—the middle half (25-75% volume in litres) of the total expiration is marked and its duration is measured.
—The FEF 25-75% is the volume in liters divided by the time in seconds.
Peak Expiratory Flow (PEF)
—is the maximal flow that can be exhaled when blowing out at a steady state
Overall PFTs (pulmonary function tests)
—have limited role in clinical practice and are rarely useful to make a diagnosis.
—They provide supporting data to H&P, exam, labs, and imaging.
—They are useful for following a patient especially on bronchodilator therapy.
[PATIENT OSCE — DIFFERENTIALS]
Diseases of the lung
Just for reference
OBSTRUCTIVE disease
Airway Obstruction
a.Tracheal
b.Bronchial
c.Generalized
2.COPD
a.Emphysema
b.Chronic Bronchitis
3.Asthma
RESTRICTIVE disease
1.Diseases of the Lung Parenchyma
a.Interstitial Pulmonary Fibrosis
b.Sarcoidosis
c.Hypersensitivity Pneumonitis
d.Asbestosis
e.Collagen Vascular Disease
2.Diseases of the Pleura
a.Pneumothorax
b.Pleural Effusion
c.Pleural Thickening
3.Diseases of the Chest Wall
a.Scoliosis
b.Ankylosing Spondylitis
4.Neuromuscular Disorders
VASCULAR disease
Pulmonary Edema
a.Increased Capillary Hydrostatic Pressure
b.Increased Capillary Permeability
c.Reduced Lymph Drainage
2.Pulmonary Embolism
3.Pulmonary Hypertension
4.Pulmonary Arteriovenous Malformation
ENVIRONMENTAL, NEOPLASTIC, and INFECTIOUS diseases
Diseases caused by inhaled particles
a.Pollutants
b.Coal Workers’ Pneumoconiosis
c.Silicosis
d.Asbestosis
e.Occupational Asthma
2.Neoplastic
3.Infectious
a.Pneumonia
b.TB
c.Fungal
d.HIV
4.Suppurative Diseases
a.Bronchiectasis
b.Cystic Fibrosis
