Pathophysiology Exam 1- common anatomic alterations of the lung and inflammation

what are 6 functions of the lung? explain

1. Gas exchange- primary role of the lung

2. Phagocytic organ- ex: type I and type II pneumocyte, alveolar macrophage, club cells

3. endocrine organ- endothelial cells release substances like nitric oxide and adhesion molecules as part of inflammatory response

4. filter to collect emboli- collects blood clots before they get to the left heart to prevent a stroke

5. regulation of pH- CO2 is volatile gas/ acid, so if we lower the CO2, then pH increases

6. warm and humidfy inhaled air- heat and water loss; prone to environmental injuries

lung compliance: definition, equation, units

- the ease with which the elastic forces of the lungs accept a volume of inspired air (lung expansion)

- Volume (L) / Pressure (cmH2O)

- L/cmH2O

what is the normal lung compliance value? normal respiratory system compliance?

- 0.2 L/cmH2O

- 0.1 L/cmH2O

airways resistance: definition, equation, units?

- The opposition to airflow during inspiration and expiration. ratio of driving pressure to the ratio of airflow

- Pressure / Flow (L/sec)

- cmH2O/L/sec

normal range of airways resistance:

3 factors influencing resistance:

- 0.8 - 2.4 cmH2O/L/sec

- laminar or turbulent flow, dimensions of the airway, and viscosity of the inhaled gas

PAO2 equation:

[(BP - Ph20) * FIO2)] - (PaCO2 / RQ)

minute volume equation-

Resistance equation-

- Tidal volume * respiratory rate

- pressure / flow

respiratory rate-

minute ventilation-

- number of breaths a person takes per minute

- total volume of air inhaled and exhaled by the lungs per min

how does a patient with decreased lung compliance maintain normal PaCO2 levels?

- decrease in tidal volume

- increase in respiratory rate

3 examples of obstructive disease? what becomes difficult?

1. increased airways resistance

2. COPD

3. emphysema

- hard to exhale air

how does a patient with obstructive disease maintain normal PaCO2 levels?

why?

- increased tidal volume

- decreased respiratory rate

- They need a longer time to get gas out at a lower rate, so they have a longer time between breaths. Slow and deep breathing to reduce airway resistance (high amount of air coming in and low amount of air leaving)

2 examples of restrictive disease? what becomes difficult?

1. decreased lung compliance

2. pulmonary fibrosis

- hard to inhale air

how does a patient with restricrtive disease maintain normal PaCO2 levels?

why?

how do you reduce elastic work of breathing?

- decreased tidal volume

- high respiratory rate

- low amount of air coming in but a high amount of air that can leave

- rapid, shallow breathing

what is the normal respiratory rate?

12-15 breaths per minute

3 common presenting respiratory complaints?

1. shortness of breath/ dyspnea

2. cough

3. sputum production

3 types of shortness of breath: explain

1. chronic disease- slowly brought on, patient attributes to aging or deconditioning

2. acute- sudden onset; ex: pulmonary embolus- blood clot in lung or pneumothorax- collapsed lung

3. episodic- nights, lying down; ex: congestive heart failure

3 characteristics of a cough?

1. Abnormal to cough in general

2. Days-to-weeks without coughing

3. Non-productive cough is associated with early bronchitis commonly due to tobacco abuse

deflation reflex-

results-

mechanism-

- compressed or deflated lungs (atelectasis)

- an increased respiratory rate

- unknown

irritant reflex-

respond to-

causes-

- subepithelial mechanoreceptors located on trachea, bronchi, and bronchioles

- compression, exposure to noxious gases

- increase RR, cough, bronchoconstriction, asthma, or high airways resistance

Juxtapulmonary capillary receptors-

located in-

respond to-

causes-

- J receptors

- interstitial tissues between alveoli and capillaries

- pulmonary congestion, pulmonary hypertension, edema, lung deflation, and microemboli

- increased RR and decreased tidal volume

peripheral chemoreceptors-

primary stimulus-

what is their response for?

- oxygen-sensitive cells, located on carotid and aortic bodies

- low PO2 (hypoxia)

- to cause an increase in RR

what do peripheral chemoreceptors respond to?

active-

inactive-

- hypoxia

- active: PaO2 < 60 mmHg (SaO2 < 90%)

- inactive: PaO2 < 30 mmHg

what are 5 other factors that peripheral chemoreceptors respond to?

1. Increased blood H+

2. hypoperfusion

3. increased temperature

4. nicotine

5. PaCO2

central chemoreceptors-

respond to-

- cerebrospinal fluid H+ sensitive cells located bilaterally and ventrally in the substance of the medulla

- hydrogen ions (arterial CO2 affects H+)

what are the 4 steps that result in decreased blood PaCO2 levels?

1. decreased ventilation (hypoventilation) - increased blood PaCO2 levels

2. Increased cerebral spinal fluid CO2 - CSF CO2 forms carbonic acid, which dissociates into H+ and bicarbonate

3. Increased CSF H+ - poor buffering capacity; H+ stimulates central chemoreceptors

4. Increased respiratory rate

absolute shunt-

3 characteristics:

- portion of cardiac output that bypasses lungs and is not exposed to PAO2

1. Refractory to O2 therapy

2. NO ventilation but has perfusion

3. Normally 2-3% of cardiac output

2 common causes to absolute shunt:

1.Bronchial venous drainage

2. Thebesian veins

anatomic shunt-

if you have a hole in your heart, blood goes from the right heart straight to the left heart never coming into contact with alveolus for gas exchange

3 common causes of anatomic shunt-

1. Congenital heart disease

2. Intrapulmonary fistulas

3. Pulmonary vascular tumors

capillary shunt-

1 main characteristic:

- nonoxygenated blood passes through non-ventilated alveoli due to collapse or consolidation, but no ventilation down to that area

1. Refractory to O2 therapy

3 common causes of capillary shunt:

1. alveolar collapse or atelectasis

2. alveolar fluid accumulation

3. alveolar consolidation or pneumonia

relative shunt-

1 main characteristic:

why?

- when pulmonary capillary perfusion is greater than alveolar ventilation due to airway obstruction or alveolar capillary diffusion defect

1. response to O2 therapy

- Has perfusion but low ventilation (obstructive airways disease), its less O2. alveoli are partially ventilated, ventilation is inadequate compared to perfusion

2 causes of relative shunt with examples:

1. Hypoventilation, decreased V/Q ratios; COPD, asthmatic episode, excessive airway secretions

2. increased alveolar-capillary membrane thickness; pulmonary edema, ARDS, chronic interstitial lung disease

alveolar shunt equation-

PAO2 = (BP - PH2O) x FIO2) - (PaCO2 ÷ RQ)

2 characteristics of pulmonary shunting:

examples:

1. Airway obstruction and alveolar capillary diffusion leads to a decreased V/Q ratio due to a decrease in ventilation

2. Anatomic and capillary shunts do NOT respond well to oxygen

- examples of alveolar diffusion defects: edema, asbestosis, scleroderma, cystic fibrosis

shunt-like effect-

main consequence-

- low ventilation but has perfusion and will respond well to oxygen (the more shunt you have, the lower PO2 is)

- venous admixture and reduce PaO2 (hypoxemia)

identify mild, moderate, and severe hypoxemia

1. mild: PaO2 = 60-80 mmHg

2. moderate: PaO2= 40-59 mmHg

3. Severe: PaO2= < 40 mmHg

normal ranges for pH, PaCO2, PaO2, SaO2, and HCO3-

1. pH: 7.35 - 7.45

2. PaCO2: 35-45 mmHg

3. PaO2: 80-100 mmHg

4. SaO2: 93-100%

5. HCO3-: 22-26 mEq/L

4 Diseases that show acute hyperventilation or acute ventilatory failure: sudden onset

Atelectasis, Pneumonia, ARDS, and Asthma

atelectasis caused by:

primary mechanism:

- mucus plugging or upper abdominal surgery, a capillary shunt

- decrease V/Q ratio → pulmonary shunting → venous admixture → hypoxemia AND reversible decreased lung compliance (stiffer lung)

what is the secondary mechanism of atelectasis?

what are the ABG findings (early stage)

- in the effort to correct hypoxia, the body stimulates O2 receptors (peripheral chemoreceptors), deflation and irritant reflexes

- mechanisms increase ventilatory rate, which increases pH and decreases the PaCO2 and HCO3- (ex: respiratory alkalosis)

importance of pneumonia-

primary mechanism:

- there is no effective specific respiratory care treatment modality.

- decreases the V/Q ratio, which leads to pulmonary shunting- venous admixture- hypoxemia (which decreases PaO2). It decreases lung capacity

what is the secondary mechanism to pneumonia (consolidation)

in an effort to correct hypoxemia, the body may lead to deflation and irritant reflex and the stimulation of O2 receptors

what are the ABG findings for pneumonia

- increase respiratory rate (hyperventilation) to expel more CO2. this leads to INCREASE pH, DECREASE PaCO2, DECREASE HCO3-

increase alveolar-capillary membrane thickness disease examples:

primary mechanism:

- ARDS and pulmonary fibrosis: excessive scar tissue in lungs

- this causes an alveolar capillary (A-C) block, hypoxemia, and decreased lung capacity

what is the secondary mechanism for an increased alveolar-capillary membrane thickness?

the body stimulates O2 receptors (specifically the carotid bodies because they are sensitive to changes in O2 levels) and deflation and irritant reflex

what are the ABG findings of increased alveolar-capillary membrane thickness?

- increase pH

- decrease PaCO2

- decrease HCO3-

bronchospasms (asthma) primary mechanism:

secondary mechanism:

- decrease the V/Q ratio, leading to pulmonary shunting which leads to venous admixture, hypoxemia, and increased airway resistance.

- body stimulates O2 receptors and irritant reflex

ABG findings for bronchospasms:

- increase pH

- decrease PaCO2

- decrease HCO3-

what is the main stimulus that increases RR? why?

- hypoxemia (low PaO2)

- hypoxemia increases the activation of pH, PaCO2, and HCO3- and we over-ventilate to try to compensate

- minute ventilation does down

what are the stable levels of PaO2, pH, PaCO2, HCO3- for chronic ventilatory failure: COPD- emphysema and chronic bronchitis

1. Low PaO2

2. Low to normal pH

3. Elevated PaCO2

4. Elevated HCO3-

what protocol and examples does the distal airway and alveolar weakening (emphysema) disease use?

- pulmonary rehabilitation protocol

- breathing exercises, pursed lip breathing training

what is emphysemas primary mechanism?

secondary mechanism?

- decrease the V/Q ratio, pulmonary shunting leads to venous admixture, hypoxemia, and increased airways resistance

- the body stimulates O2 receptors and irritant reflex

emphysema ABG findings:

- increase pH

- decrease PaCO2

- decrease HCO3-

ABG findings of acute alveolar hyperventilation:

pH, PaCO2, HCO3-, PaO2

what kind of protocol is this?

example?

1. High pH

2. Low PaCO2

3. Normal to slightly reduced HCO3-

4. Low PaO2

- O2 therapy protocol

- respiratory alkalosis

ABG findings of acute ventilatory failure:

pH, PaCO2, HCO3-, PaO2

what kind of protocol is this?

example?

1. Low pH

2. High PaCO2

3. Normal to slightly increased HCO3-

4. Lower PaO2

- Mechanical ventilation protocol

- Acute respiratory acidosis

ABG findings of chronic ventilatory failure:

pH, PaCO2, HCO3-, PaO2

what kind of protocol is this?

example?

1. Low to normal pH

2. High PaCO2

3. High HCO3-

4. Low PaO2

- O2 therapy protocol

- Compensated respiratory acidosis

ABG findings of Acute alveolar hyperventilation superimposed on chronic ventilatory failure:

pH, PaCO2, HCO3-, PaO2

what kind of protocol is this?

1. High pH

2. PaCO2 slightly below patient's elevated baseline

3. HCO3- slightly lower than baseline

4. PaO2 lower than the patient's normal baseline

- Mechanical ventilation protocol

ABG findings of Acute ventilatory failure superimposed on chronic ventilatory failure: :

pH, PaCO2, HCO3-, PaO2

what kind of protocol is this?

1. Low pH

2. High PaCO2 (above the patient's baseline "high")

3. Low PaO2 (lower than the patient's normal baseline "low")

4. High HCO3-

- mechanical ventilation protocol

inflammation-

characterized by:

requires:

the body's attempt to remove:

- microvascular response to injury

- movement of fluid, leukocytes, and molecules of host defense from the intravascular to the extravascular space

- vascularized connective tissue

- an injurious agent and to begin the reparative process

inflammation does NOT = ?

why? (2 reasons)

- infection

1. Because infection is accompanied by inflammation, but inflammation can occur without infection

2. Infection requires a living organism

What is the hallmark sign of inflammation?

edema

what are the 5 cardinal signs of inflammation? explain

1. RUBOR= redness in capillaries and venules because they are dilating and an increase in blood flow to those areas

2. CALOR= heat; increase in blood flow

3. DOLAR= pain

4. TUMOR= swelling due to leaking into interstitial space

5. STUPOR= loss of function

3 causes of inflammation? explain

1. living agents: bacteria, viruses, parasites, fungi, infectious diseases

2. non-living agents: trauma, ionizing radiation, chemical agents, electricity

3. immune mechanisms

what are the 3 stages of inflammation? explain

1. edema (swelling)

2. early stages- we see neutrophils infiltrate in congested blood vessels *after fluid moves to the site of inflammation*

3. later stages- we see monocytes/ macrophages appear; apoptosis is programmed cell death

4 types of cells in the blood: what is each involved in?

1. Neutrophils- involved in early response to inflammation

2. Lymphocytes and monocytes- come in the later stages

3. Eosinophils and basophils- involved in acidic infection or allergic reactions

4. Platelets- clotting

4 types of cells in the tissue:

explain

1. Mast cells- release histamine and located outside blood cells and the airway

2. Macrophages and multinucleated giant cells- if there is a chronic infection, the body tries to kill it, then they recruit macrophages into one big thing to kill

3. Plasma cells- B lymphocytes that have matured in the tissue

4. Endothelial cells- vascular system

relative percentage of WBC:

*never leave medical education building*

1. neutrophil: 50-70%

2. lymphocyte: 20-40%

3. monocyte: 1-6%

4. neutrophil band: 1-5%

5. eosinophil: 1-5%

6. basophil: 0-1%

Overview of Inflammation Response can be remembered as the 5 Rs:

1. Recognition of the injurious agent

2. Recruitment of leukocytes

3. Removal of the agent

4. Regulation (control) of the response

5. Repair (resolution)

what 3 structures are included in Exudate edema?

what is it due to?

result in?

1. high protein content 2. some WBC 3. RBC from blood

- inflammation, so gaps widen and protein, leukocytes, and RBC can move into extravascular space

- vasodilation, fluid and protein leakage

what is transudate edema?

what does this increase? ex:

result in?

- low protein content, few cells

- hydrostatic pressure and low osmotic pressure

- venous outflow and congestive heart failure

- fluid leakage

what are 4 examples of the result of fluid leakage in transudate edema?

1. Decreased colloid osmotic pressure, 2. decrease protein synthesis (liver disease)

3. increase protein loss (kidney disease)

4. protein malnutrition (kwashiorkor)

what is vascular permeability in inflammation increased by?

how?

- chemically induced retraction of endothelial cells and endothelial injury

- Endothelial contraction due to hormones like histamine which causes the opening of gaps or endothelial injury that will cause destruction of the endothelial cells and produce gaps

define margination-

Migration of leukocytes and neutrophils, from the center of the bloodstream to the periphery (vessel walls) during slowed blood flow

define diapedesis-

After adhesion, leukocytes flatten, polarize, and squeeze between or through the endothelial cells and pierce the basement membrane to enter the tissue

define opsonization-

When pathogens are coated with molecules called opsonins (IgG and IgM), making them more easily recognized and engulfed by phagocytic cells (macrophages and neutrophils)

define chemotaxis-

Directed movement of a cell towards or away from chemical concentration gradient. Crucial for guiding leukocytes to sites of infection or inflammation

define extravasation-

Leukocytes moving from bloodstream (blood vessels) into surrounding tissues, which encompasses a series of margination, rolling, adhesion, diapedesis, and migration

thromboxane A2 stimulates?

what does it bind to?

- platelet aggregation

- receptors on their surface, forms a platelet plug, and crucial step in clotting

thromboxane A2 promotes?

what does it cause?

- vasoconstriction

- blood vessels to narrow, restricts blood flow to the injured area, and aids in reducing blood loss

nitric oxide inhibits: explain

promotes? explain

- platelet aggregation; inhibits the formation of a thrombus (blood clot)

- vasodilation; relaxes smooth muscle in blood vessel walls and causes vessels to widen

Prostacyclin (PGI2) produced by?

inhibits?

promotes?

- endothelial cells

- platelet aggregation; by increasing levels of cyclic AMP within platelet

- vasodilation

why is a balance between NO, PGI2, and Thromboxane A2 crucial?

to prevent excessive bleeding and clot formation

E and P-selectin mediates:

released from:

mediators cause:

- leukocyte rolling adhesion

- Weibel-Palade bodies

- activation of endothelial cells

what does the activation of endothelial cells lead to?

triggered by:

- rapid expression of P-selectin on the surface of endothelial cells

- histamine, thrombin, PAF

what do leukocytes express?

ligands like P-selectin glycoprotein, allowing them to slow down and roll.

what are 3 roles ICAM-1 and VCAM-1 play in extravasation?

1. Chemokines are released at the site of inflammation and activate the rolling leukocytes, inducing a change in B2-integrins

2. the change: upregulated by inflammatory cytokines (IL-1, TNF) on endothelial cells to mediate firm adhesion

3. This high-affinity binding between integrins and ICAM-1/VCAM-1, causes the leukocytes to stop rolling and adhere firmly to the endothelium

what are 2 roles that B2-integrins play in extravasation?

1. through junctions between endothelial cells

2. Interactions between the leukocyte and endothelial cell, helps guide the leukocyte through the endothelium and into the underlying tissues

P-selectin initiates? allows?

ICAM-1 and VCAM-1 critical for?

B2-integrins bind?

- the rolling process; leukocytes to slow down

- firm adhesion

- stable adhesion, stop the rolling, and facilitate transmigration of leukocytes across the endothelial barrier during extravasation

chemotaxis-

6 steps:

- leukocytes and neutrophils follow chemical signals made by chemoattractant to the site of infection

1. cellular locomotion along a chemical gradient

2. ligand-receptor binding

3. activation of Phospholipase C

4. release of intracellular calcium

5. assembly of contractile elements

6. cell movement

Exogenous chemoattractant-

bacterial products: explain

lipopolysaccharide membrane-

- from outside the body, some foreign came in

- N-formyl-methionine; The first amino acid in bacterial protein synthesis

- Major component of the outer membrane of gram-negative bacteria

endogenous-

3 examples:

- we create it in our body

1. complement components (C5a)- protein that floats in blood in inactivated form, when activated, proteins leak out blood vessel and tissues and signal other leukocytes to follow

2. arachidonic acid metabolites, leukotrienes- lipid in leukocyte wall that releases signals

3. cytokines (IL-8)

acute inflammation-

predominant cells:

- Occurs suddenly (minutes or hours) and has a short duration (hours to days), emigration of leukocytes into tissue

- neutrophils

chronic inflammation-

predominant cells:

- Onset is slow (days) and has longer duration (weeks-to-months)

- monocytes, macrophages, lymphocytes

5 chemical mediators of inflammation: explain

1. Increased vascular permeability- Histamine (released by mast cells), anaphylatoxins (C3 & C5a), kinins, Leukotrienes (C, D, & E)- cause vascular permeability, and platelet activating factor (PAF)

2. Chemotaxis- C5a and Leukotriene B4

3. Endothelial-leukocyte interactions and acute phase response- TNF and Interleukin-I (IL-1)

4. Tissue destruction- Lysosomal products and oxygen-derived free radicals

5. Nitric oxide- vasodilation and cytotoxicity

3 performed mediators during acute inflammation-

5 newly synthesized-

- histamine, serotonin, lysosomal enzymes

- prostaglandins, leukotrienes, platelet-activating factor (PAF), cytokines (IL-1, TNF), nitric oxide (NO)

4 consequences of phospholipase A2 activation

1. breaks down the cell wall and releases arachidonic acid from membrane phospholipids

2. it's metabolized into prostaglandins, leukotrienes, and lipoxins

3. These mediators can trigger further inflammatory responses, potentially damaging tissue

4. can lead to a cascade of events that contribute to inflammation and other cellular processes

What are the 5 consequences of leukocyte activation (ligand-receptor binding)?

1. locomotion

2. modulate adhesion molecules

3. A.A. metabolites

4. Degranulation & secretion lysosomal enzymes

5. Activation of oxidative burst

how is locomotion a consequence of leukocyte activation?

Leukocyte activation associated with increased cell migration and chemotaxis, guided by chemokines, allowing them to leave the bloodstream and move to the site of inflammation

how is modulate adhesion molecules a consequence of leukocyte activation?

Leukocytes increase the expression of adhesion molecules like integrins, enabling stronger binding to cells and helping their recruitment to sites of inflammation.