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USMLE - Respiratory Part 1

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The conducting zone includes structures that transport air but do not participate in gas exchange.

What makes up the Conducting Zone?

Large airways: Nose, Pharynx, Trachea, Bronchi

Small airways: Bronchioles and Terminal Bronchioles

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Key Terms

Term
Definition

What makes up the Conducting Zone?

Large airways: Nose, Pharynx, Trachea, Bronchi

Small airways: Bronchioles and Terminal Bronchioles

Function of Conducting Zone

Warms and humidifies air but does not participate in gas exchange

Anatomical Dead Space

Cartilage extends until

Bronchi

Goblet cells extend until

End of Bronchi

Pseudostratified, ciliated, columnar cells extend until

What is the cilia’s function?

End of Terminal Bronchioles to beat mucus up and out of lung

Smooth muscle in airway wall extends until

terminal bronchioles

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TermDefinition

What makes up the Conducting Zone?

Large airways: Nose, Pharynx, Trachea, Bronchi

Small airways: Bronchioles and Terminal Bronchioles

Function of Conducting Zone

Warms and humidifies air but does not participate in gas exchange

Anatomical Dead Space

Cartilage extends until

Bronchi

Goblet cells extend until

End of Bronchi

Pseudostratified, ciliated, columnar cells extend until

What is the cilia’s function?

End of Terminal Bronchioles to beat mucus up and out of lung

Smooth muscle in airway wall extends until

terminal bronchioles

What makes up the respiratory zone?

= Lung Parenchyma. Respiratory bronchioles, alveolar ducts and alveoli

participates in gas exchange

What kind of cells are in the Respiratory zone?

Cuboidal cells in respiratory bronchioles, then simple squamous cells up to alveoli

Type I Pneumocytes

Percentage of alveolar surface

Kind of cell

Function

97% of alveolar surface. Squamous cells optimal for gas diffusion

Type II Pneumocytes

Kind of cell

Function

Clustered cuboidal cells. Secrete surfactant and act as precursors

Collapsing Pressure Formula

P = 2 (surface Tension) / Radius

When are alveoli most likely to collapse?

On Expiration

Function of surfactant

Decreased alveolar surface tension to prevent atelectasis

Composition of surfactant

Complex mix of lecithins. The most important of which is dipalmitoylphasphatidylcholine

When does surfactant production begin in the fetus? When does it reach mature levels? What indicates maturity?

Begins at week 26. Mature by week 35. Mature when Lecithin/Sphingomyelin > 2

Clara Cells:

Location

Appearance

Function

In Terminal and Respiratory Bronchioles. Non ciliated columnar cells with secretory granules. Secrete components of surfactant, degrade toxins and act as reserve cells

of lobes in each lung?

R: 3, L: 2 + Lingula

Foreign body most likely to be lodged in

R lung because R mainstem bronchus is wider and more vertical than L

Aspirate a peanut:

While upright?

While supine?

Upright: Lower Portion of R Inferior Lobe

Supine: Superior Portion of R Inferior Lobe

Relationship bet Pul Artery to the Bronchus?

RALS

Right: Anterior, Left Superior

Structures perforating the Diaphragm

I ate 10 eggs at 12

T8: IVC

T10: Vagus and Esophagus

T12: Aorta, Azygous, Thoracic duct (Red White and Blue)

What innervates the Diaphragm? Where is pain from the Diaphragm referred?

C3, 4, 5 keeps you alive

Pain referred to shoulder (C5) and Trapezius ridge (C3, C4)

Muscles of respiration (quiet and exercise)

Inspiration: Quiet –> Diaphragm, Exercise –> SCM, Scalene, External Intercostals

Expiration: Quiet –> Passive, Exercise –> Obliques (Internal and External), Abdominis (Rectus and Transversus) Internal Intercostals

Inspiratory Reserve Vol

Air that can be breathed in after normal inspiration

Tidal Vol

500mL. Air that moves into the lung on quiet inspiration

Expiratory Reserve Vol

Air that can still be breathed out after a normal expiration

Reserve Volume

Air left in lung after maximal expiration

Inspiratory capacity

TV + IRV

Function Residual Capacity

RV + ERV

Vital Capacity

TV + IRV + ERV

Total Lung Capacity

IRV + TV + ERV + RV

Physiological Dead Space

Definition

Calculation

Vol of inspired air that does not participate in gas exchange

VD = Anatomical Dead Space of conducting airways + functional dead space in alveoli

VD = TV [(PaCO2 -PECO2)/PaCO2] Taco Paco Peco Paco

Largest contributor to functional dead space?

Apex of Lung

The tendency is for the lung to … and for the chest wall to …

Lung wants to collapse, Chest wall wants to spring outward

@ FRC: What is happening with the lung - chest wall system? What is the P in the alveoli and airway? What is the P in the Intrapleural space?

@ FRC: Inward pull of lung = outward pull of chest wall and system pressure is atmospheric. P in the alveoli and airway = 0. P in the Intrapleural space is negative to prevent pneumothorax

Alveolar transmural pressure is …

Always positive. Meaning always tending to collapse

What determines the elastic properties of both the chest wall and lungs?

Their combined volume

What is compliance?

What increases compliance?

What decreases compliance?

Change in lung vol for a given change in pressure

Increases in emphysema and normal aging

Decreases in fibrosis, pneumonia and edema

Hemoglobin

Composed of

Exists in 2 forms

Exhibits

Composed of 2 alpha and 2 beta subunits

Exists in Taut form in tissues (low affinity) and Relaxed form in lungs (high affinity)

Exhibits positive cooperativeity and negative allostery

What shifts Hemoglobin dissociation curve to the R (towards T form)

CADET! Turn R!

| CO2 and Cl, Acidosis and Altitude, BPG, Exercise, Increased Temp

Fetal Hemoglobin

Consists of

Different affinities?

Consists of 2 alpha and 2 gamma subunits

| Lower affinity for BPG = higher affinity for O2 --> curve shifted to the L

Methemoglobin

What is it ?

Change in affinity?

Shift in curve?

Treat with

Oxidized Iron 3+ (ferric) instead of Iron 2+ (ferrous)

Lower affinity for O2, Higher affinity for cyanide

Shifts curve to R

Treat with Methylene Blue

Nitrite poisoning causes

Oxidization of Fe2+ to Fe3+

How to treat cyanide poisoning?

Use nitrites to oxidize Hemoglobin to methemoglobin. MetHem with bind cyanide and allow cytochrome oxidase to function. Then use Thiosulfate to bind cyanide --> forms thiocynate which is renally excreted

Carboxyhemoglobin

What is it

Affect on O2 binding curve

Hemoglobin bound to CO

| Shifts curve to L --> decreased O2 unloading in tissues

Appearance of Hemoglobin O2 binding curve?

Sigmoidal because of cooperativity

Pulmonary Circulation Re Resistance and Compliance

Low Resistance and High Compliance

How does a decrease in PA02 (= increase in PACO2) affect pulmonary circulation?

Vasoconstriction to shift blood away from poorly ventilated areas

Which gases are perfusion limited? What does that mean?

O2 (normally), CO2, N2O. Diffusion Increases if Blood Flow Increases

Which gasses are diffusion limited? What does that mean?

O2 (in fibrosis or emphysema), CO. Gas does not equilibrate by the time the blood reaches the end of the capillary.

Gas diffusion equation

What happens in Emphysema?

What happens in Fibrosis?

Vgas = (A/T) x D(P1-P2)

Emphysema --> Area decreases

Fibrosis --> Thickness increases

Pulmonary artery pressure: Normal? PHTN?

Normal: 10-14mmHg, PHTN: >/= 25 (rest) or >/= 35 (exercise)

PHTN affect on pulmonary artery

Arteriosclerosis, Medial Hypertrophy, Intimal Fibrosis

Cause of Primary PHTN

Inactivation of BMPR2 gene which normally functions to inhibit vascular smooth muscle proliferation

What causes secondary PHTN? What is the course of the disease?

COPD (destruction of lung parenchyma), Mitral Stenosis (Increased resistance --> increased P), Recurrent thromboemboli (decreased cross sectional area of pulmonary vascular bed), autoimmune disease, L --> R shunt (increased sheer stress --> endothelial injury), Sleep Apnea, Living at high altitude

Respiratory distress --> Cyanosis and RVH --> cor pulmonale --> death

Pulmonary Vascular Resistance formula

PVR = (P pulmonary artery - P left atrium) / CO

O2 content of blood formula

| What is normal O2 binding capacity?

O2 binding capacity x saturation + dissolved O2

| O2 binding capacity normally 20ml/dL

1g Hb can bind how much O2?

How much Hb is normally in blood?

When does cyanosis occur?

1.34m
15 g Hb/dL

Cyanosis occurs when deoxygenated Hb > 5g/dL

What happens to O2 content of blood, O2 sat and PaO2 when Hb decreases?

O2 content decreases but O2 sat and PaO2 remain the same

Formula for oxygen delivery to tissues

CO x O2 content of blood

Alveolar gas equation

PAO2 = PIO2 - PaCO2/R

PAO2 = 150 - PaCO2/.8

R = CO2 produced/O2 consumed

A-a gradient

Normal value

Increased in?

Causes?

Normal A-a gradient = 10-15mmHg

Increased in hypoxemia due to lesion in Lung

Causes: Shunting, V/Q mismatch, Fibrosis

Causes of hypoxemia with normal A-a gradient?

High altitude, hypoventilation

What causes hypoxemia with increased A-a gradient?

V/Q mismatch, Diffusion limitation, R-L shunt

Causes of Hypoxia

Decreased cardiac output, Hypoxemia, Anemia, CO poisoning

What can cause ischemia?

Arterial flow or venous drainage blocked

V/Q at apex? base?

apex = 3 (wasted ventilation). base = .6 (wasted perfusion)

Where in the lung is ventilation greatest? Where is perfusion greatest?

Both at base

What happens to V/Q during exercise?

Vasodilation of apical capillaries --> V/Q approaches 1 at apex

What kind of organisms thrive in the apex of the lung?

Those that thrive on high O2 like TB

V/Q = 0

Shunt (airway obstruction). 100% O2 wont help

V/Q = infinity

Blood flow obstruction (physiological dead space) Assuming <100% dead space, O2 will help

PAO2, PaO2, and PvO2 in apex, middle and base

Apex: PA>Pa>Pv

Middle: Pa>PA>Pv

Base: Pa>Pv>PA

In what forms is CO2 transported in the blood?

Bicarb: 90%, CarbaminoHb (binds at N terminus and binding favors T form): 5%, Dissolved CO2: 5%

How does oxygenation of Hb affect CO2 in blood?

Oxygenation --> dissociation of H from Hb. H + bicarb = CO2 thus more CO2 is released from RBC

Haldane Effect

Bohr Effect

Increased H in periphery --> Hb O2 curve shifted to R and O2 unloading favored

Response to high altitude?

Increased Mito, Increased renal excretion of bicarb (to combat alkalosis) Increase in ventilation, decreased PO2 + PCO2, Increased EPO --> Increased Hb and Hc, Increased BPG, RVH

"Mr. V. Deb"

Response to exercise

CO2 production

O2 consumption

Ventilation

V/Q

Pulmonary blood flow

pH

PaO2, PaCO2, venous CO2, venous O2

CO2 production increases, O2 consumption increases, Ventilation increases, V/Q becomes more uniform, Pulmonary blood flow increases, pH decreases (lactic acidosis), PaO2 NC, PaCO2 NC, venous CO2 increase, venous O2 decreases

DVT

What predisposes to it?

What can it lead to?

Physical Exam sign?

Treatment and prevention?

Virchow's triad of Vascular damage (exposed collagen), Increased coagulability (defect in coagulation cascade, most commonly factor V Leiden), Reduced flow [VIR]

Leads to Pul embolus

Homan's Sign --> Dorsiflexion of foot --> calf pain

Heparin for prevention and acute management. Warfarin for long-term prevention of recurrence

Sudden onset of dyspnea, chest pain, and tachypnea

Pulmonary embolism

Types of PE?

FAT BAT

| Fat, Air, Thrombus, Bacteria, Amnionic fluid, Tumor

Fat embolus associated with…

| Presents as…

Long bone fracture and liposuction

| Presents as hypoxemia, neurological abnormalities, petechial rash

Major risk with Amnionic fluid embolus?

Can lead to DIC especially post partum

Imaging test of choice for PE?

CT pulmonary angiography

Where do most PEs arise from?

95% from deep leg veins

Most dangerous location for PE?

Saddle Embolus of Pulmonary Artery

Histology of thromboembolus formed premortem?

Lines of Zahn: interdigitating areas of pink (platelets, fibirn) and red (RBCs)

Obstructive Lung Disease: Names, RV, FVC, PFTs, V/Q, PO2, PCO2

Chronic Bronchitis, Emphysema, Asthma, Bronchiectasis

RV: Increases, FVC: Decreases

FEV1 decrease, FVC decreases, FEV1/FVC decreases

V/Q decreases, PO2 decreases, PCO2 increases

Chronic Bronchitis: Clinical definition

Productive Cough for >3 months (not necessarily consecutive) for >2 years

Chronic Bronchitis: Pathology and Physical Findings

Harry Reid Won 50% Securing Complete Democratic Control

Hypertrophy of Mucus secreting glands in bronchi, Reid Index > 50%, Wheezing, Small airway disease, Crackles (early) Dyspnea (late), Cyanosis (early onset hypoxemia due to shunting)

Emphysema: pathology and findings

PERCE

Pursed lip breathing (increased airway pressure prevents collapse), Enlarged airspace, Recoil decreased, Compliance increased, Elastase activity increased

Two types of emphysema

Centriacinar = smoking

Panacinar = alpha-1-antitrypsin deficiency

Alpha Agonists

Names

Uses

Tox

Pseudoephedrine, Phenylephrine

Reduce hyperemia, edema, nasal congestion.

Open up Eustachian tube.

Pseudoephedrine is a stimulant. Can cause HTN. Pseudoephedrine can cause CNS stimulation/anxiety

Dextromethorphan

Class

MoA

Uses

Risk

Antidote

Opioid (synthetic codeine analog)

Antagonizes NMDAR

Antitussive

Mild abuse potential

Naloxone treats OD

Bosentan

MoA

Uses

Competative antagonist of endothelin 1 receptor

Decreases Pulmonary Vascular Resistance

Used to treat Pulmonary Arterial HTN

N Acetylcysteine

Type of drug

Action

Uses

Mucolytic expectorant

Loosens mucus plugs in CF

Antidote for acetaminophen OD

Guaifenesin

Type of drug

Action

Expectorant that thins the respiratory secretions but does not suppress the cough reflex

Molecules that cause bronchoconstriction?

Adenosine, ACh

Molecules that cause Bronchodilation

cAMP

Ab Asthma therapy

Name

MoA

Uses

Omalizumab

Monoclonal IgE Ab that binds up serum IgE

Used in allergic asthma resistant to steroids and long acting beta2 agonists