Lung

PBL Wrap-Up

 Case Introduc6on: Jennifer

Garcia an 18 year-old
Hispanic-American female
who presents to an adult
medicine prac6ce for the
rst 6me. She was referred
to the prac6ce by her
pediatrician upon turning
18 years old. Ms. Garcia
has a history of asthma and
allergic rhini6s, but she
feels well today and is here
to establish care.

History of Present illness/ related

symptoms
Denies current shortness of breath or chest 6ghtness.
Occasionally has cough and 6ghtness of the chest that wakes
her at night 3-4 6mes per month.
Has an albuterol inhaler, which she uses approximately 3
6mes per week, but not every day.
Enjoys running for exercise, but oTen develops wheezes,
especially if she runs outside during cold weather.
In addi6on to the informa6on above, her triggers for asthma
include pollen and dust.
Within the past year, she went to the emergency room once
during the spring for an asthma exacerba6on, and she was
given a course of oral steroids, but she did not require
hospitaliza6on at that 6me.
She does not monitor peak ow values at home.

Common Provocative Stimuli

Allergens:

Outdoor allergens- eg pollen, ragweed, etc., pollution

Indoor allergens- * Dermatophagoides (house dust
mites), pets, cockroaches, mice, rats, cigarette smoke

Chemical Mediators
Histamine
Leukotrienes
-Histamines, Leukotrienes, Platelet-activating factor,
Prostaglandins, Bradykinin, Serotonin, Kallikrein, etc.
=Histamine- Preformed, located in the Mast Cell, causes
contraction of the bronchial smooth muscle and airway
edema ****- antihistamines do not improve asthma symptoms
n Late-phase Asthmatic Response - Some patients
have a second delayed asthmatic response- with a
second decrease in FEV1 after initial improvement
n Can last for days
n Depends on presence of antigen-specific IgE

Airway Responses with Allergic Asthma

Airway inflammation, hyperresponsiveness,
and bronchial obstruction
Recruitment of T and B cells and eosinophils

FEV1 (% predicted)

Acute bronchospasm
Ag cross-links IgE on mast cells

100
90
80
70
60
50
40
30
20
10
0

Earlyphase
response

Late-phase
response

6
7
Hours

10

11

12

Common Provocative Stimuli

Inhaled Irritants - irritant
receptors in walls of the larynx,
trachea, and large bronchi
Cigarette smoke
Inorganic dusts- Silica, Hay, gases/
fumes
Occupational exposures- Bakers
Asthma
Environmental pollutants
Respiratory Tract Infections - Viral or
Bacterial

Exercise/Cold Air -Provokes

bronchoconstriction

Asthma Medica6ons: 2 classes

1. Long-term Control (controller medica6ons)

Taken daily to maintain control of persistent

asthma
Reduces markers of airway inamma6on in
airway 6ssue or airway secre6ons and decrease
intensity of airway hyperresponsiveness
Inhaled cor6costeroids
Long ac6ng beta agonists (LABA)
Leukotriene modiers
Mast Cell Stabilizers: Cromolyn, Nedocromil
Methylxanthines: Theophylline
Immunomodulators: Omalizumab

2. Quick-relief (rescue medica6ons)

Provide prompt reversal of airway obstruc6on

and broncho-constric6on

Short-ac6ng inhaled B2 agonists

An6cholinergics
Systemic cor6costeroids

Past Medical History:

Diagnosed with asthma at age 3. Remembers having quite
frequent asthma exacerba6ons and ER visits for asthma as a child,
par6cularly in the winter and spring months. She had 4
hospitaliza6ons for asthma exacerba6ons as a child. She has
never been intubated.
Allergic rhini6s; she develops symptoms (runny nose, itchy
eyes) during pollen season and no6ces more frequent wheezing
episodes during the spring.
Past surgical history: none
Medica8ons: albuterol inhaler as needed

OTC loratadine once a day

Allergies: no medica6on allergies

3 Components of

Bronchial
Hyperresponsiveness

Bronchoconstric8on:

Smooth muscle contrac6on

Measured as increase in airway
resistance/or decrease in forced
exhala6on ow rates
Inammatory cells release mediators
that increase responsiveness of
bronchial smooth muscle to
bronchoconstric6ve s6muli
Prostaglandin and Leukotrienes
Treated by bronchodilators

Airway Inamma8on:
complex interrelated series of
events- including cellular
inltra6on, cytokine release
and airway remodeling
Airway Remodeling:
due to chronic airway
inamma6on (which is why we
use inhaled cor6costeroids
early in tx of asthma- to avoid
airway remodeling)

Pathophysiology of Asthma
Narrowed and blocked
airway
Air is able to get in easier
(negative pleural pressure
exerts negative external
pressure on airwayssplints them open)
Air is harder to get out
(positive pleural pressure
decreases the diameter of
the airways

Atopic Asthma

TH2 and IgE- mediated type 1 hypersensi6vity reac6on

Asthma airway inamma6on release of potent inammatory mediators
airway dysfunc6on airway remodeling
Mucus gland hypertrophy
Smooth muscle prolifera6on
Angiogenesis
Fibrosis
Nerve prolifera6on

Immunology of
Asthma

Exaggerated Th2 response to harmless environmental an6gens

Th2 secrete cytokines (IL-4, IL-5 and IL-13) inamma6on & s6mulate B
cells to make IgE and Abs
IgE binds Fc receptors on mast cells mast cells release granule contents and
make cytokines early phase and late phase rxns
IL4 s6mulate produc6on of IgE
IL5 ac6vates eosinophils
IL13- s6mulates mucus secre6on

Early Phase Rxn =

Immediate
Hypersensi6vity
Bronchoconstric6on due
to s6mula6on of vagal
parasympathe6c
receptors (mast cells
trigger)
Increased mucus
produc6on
Vasodila6on
Increased vascular
permeability

Late Phase Reac6on

Recruitment of Eosos,
PMNs and T cells
Th2 cells
Th17 cells recruit PMNs

Airway Responses with Allergic Asthma

Airway inflammation, hyperresponsiveness,
and bronchial obstruction
Recruitment of T and B cells and eosinophils

FEV1 (% predicted)

Acute bronchospasm
Ag cross-links IgE on mast cells

100
90
80
70
60
50
40
30
20
10
0

Earlyphase
response

Late-phase
response

6
7
Hours

10

11

12

 Leukotrienes C4, D4, and E4

bronchoconstric6on, inc
vascular permeability, and
inc mucus secre6on
Acetylcholine airway
smooth muscle constric6on
(released by
parasympathe6c nerves)
Histamine
bronchoconstric6on
Prostaglandin D2
bronchoconstric6on and
vasodila6on
Platelet-ac6va6ng factor
aggrega6on of platelets and
release of serotonin from
granules
Other mediators TNF,

Mediators Made
by Leukocytes and
Epithelial Cells

Past Medical History:

Social history: she is a college student and lives in a dormitory.
She does not smoke cigareies, though her father did at home.
She denies alcohol or drug use. She describes her diet as preiy
good and tries to avoid fast food. She jogs or goes to the gym
2-3 6mes per week. She is not currently sexually ac6ve. She has
no pets currently and has not had pets in her house as a child.
Family medical history: Her mother is in good health. Her
father has hypertension. She has two siblings; a younger brother
(age 16) who also has asthma, and a younger sister (age 14) who
does not have asthma, but has eczema. Her maternal
grandmother was diagnosed with breast cancer at age 68.
Review of Systems: no other problems or concerns
Immuniza8ons: are all up to date.

Predisposition to Asthma

Genetic

Many (not all) have + family hx of asthma

Many (not all) with + FHx of asthma have
allergies (allergic rhinits or eczema)Atopic
Long arm of chromosomes 5,11,12 (5q,
11q,12q)
Short arm of chromosome 6 (6p)

Acquired
Environmental factors- most likely
interacting with genetic factors, possibly
exposed during critical time in childhood
House dust mites, domestic animals,
cockroaches, *maternal cigarette
smoking*, viral infections (controversial)

Physical Exam

Height: 5-5
Weight: 128 lbs
Pulse: 72 bpm, regular
BP: 100/60 mm Hg
Temp: 37 C
Respira6on: 14/min.
Pulse oximetry: 98% room air
Peak expiratory ow (PEF) = 85% of predicted
General: well appearing female, no acute distress
HEENT: pupils equal, round and reac6ve to light. Oropharynx clear.
Chest: clear to ausculta6on and percussion. No audible wheezes. Normal
inspiratory:expiratory ra6o.
Cardiovascular: normal jugular venous pressure, normal caro6d upstroke, no
caro6d bruits, normal S1 and S2; no murmurs, rubs, or gallops.
Abdomen: normal bowel sounds, no abdominal bruits noted, non-tender,
non-distended no masses or organomegaly palpated or percussed.
Extremi6es: no lower extremity edema. +2 dorsalis pedis pulses bilaterally
Skin: no rashes

Learning Objec6ves

Dene asthma and the various subtypes (atopic, drug-induced and

occupa6onal)
Gather data for the ini6al evalua6on of this pa6ent (iden6fy which
components of the history and physical examina6on should be obtained and
evaluate the signicance of pa6ent informa6on)
Recognize the relevance of this pa6ents race, age, and gender with regards
to epidemiology of asthma.
Recognize gene6c and environmental factors that predispose a person to
developing asthma
Describe the pathophysiology of asthma, including the role of inammatory
cells and mediators and the deni6on of a type I hypersensi6vity reac6on.
Describe the changes that occur in the lungs in pa6ents with asthma with
respect to: acute response, chronic inamma6on, airway remodeling
Understand the associa6on between atopy and asthma in understanding the
pathophysiology of allergic asthma
Iden6fy provoking s6muli for asthma and describe how each agent can
trigger asthma exacerba6ons
Describe how to diagnose a pa6ent with asthma.
Recognize clinical manifesta6ons of asthma, including symptoms, physical
examina6on ndings,

Diagnostic Approach to Asthma

History: Reversible episodes of
bronchoconstriction, usually a trigger,
possible hx of atopy, possible FHx of
asthma/allergies
PE: usually wheeze, usually evidence of
air flow obstruction
CXR: usually neg
Sputum: many eosinophils on smear
Serum: may have elevated eosinophils,
may have elevated IgE total and to
specific allergens
Spirometry- obstruction (peak flow- low)
Bronchoprovication: used to RULE OUT
asthma

Learning Objec6ves
Describe the pathophysiology of asthma,
including the role of inammatory cells and
mediators and the deni6on of a type I
hypersensi6vity reac6on.
Describe the changes that occur in the lungs in
pa6ents with asthma with respect to: acute
response, chronic inamma6on, airway
remodeling

Day 2- Blood Test Results

Complete Blood Count (CBC) with normal ranges
given
WBC 5,700 (4500 11,000/ mm3)
DIFF: 60 SEGS 33 LYMPHS 3 MONOS
3 EOS 1 BASO
Hemoglobin 13.8 (enter reference range for
women)
MCV 90
Platelets 258,000 (150,000-400,000)/mm3

Blood Test Results

Serum Electrolytes, or Chem 7
Sodium: 142 mEq/L
Potassium: 4.0 mEq/L
Chloride: 97 mEq/L
Bicarb: 24 mEq/L
BUN: 12 mg/dl
Crea6nine: 0.8 mg/dl
Glucose: 92 mg/dl

Liver Func8on Tests
Alk Phos: 75 U/L SGOT: 28 U/L SGPT: 30 U/L Bilirubin,
Direct: 0.1 mg/dl Bilirubin, Indirect: 0.8 mg/dl

Spirometry Results
Spirometry Results
Pre-Bronchodilator

Post-Bronchodilator

Pred

Obs

%Pred

Obs

%Change

FVC

4.3

4.1

95

4.2

FEV1

3.4

2.4

72

2.9

21

FEV1/FVC %

77

59

FEV 25-75%

3.78

2.6

69
69

3.1

19

Pathophysiology of Asthma
nPFT
nObstruc6on: FEV1/FVC ra6o= <70 (which should respond
to bronchodilator enough to become >70)
nCan have reduced FEF 25-75:
nMay have response to bronchodilators: 12% change AND
>200mL increase
nMay have air trapping: RV and FRC >120
nMay have hyperina6on: TLC >120
nMay have normal or elevated diusion capacity: DLCO=
80 or >120

Plan for Pa6ent

The pa6ent was started on low-dose
inhaled u6casone to take daily.
She was instructed to use her short-
ac6ng beta-2 agonist (albuterol) as
needed for rescue use. A wriien
ac6on plan was developed and the
pa6ent was also counseled on how
to maintain good control of her
asthma. The pa6ent says she has
been reading more about asthma
on the internet and she would like
you to explain these pictures since
she is gevng confused

www.rad-founda6on.org Asthma Guidelines and Improving Pa6ent

Care

www.rad-founda6on.org Asthma Guidelines and Improving Pa6ent Care

Steps of Therapy: Age 12 Years

Intermittent
Asthma

Persistent Asthma: Daily Medication

Consult with asthma specialist if step 4 care or higher is required.
Consider consultation at step 3.

Step 5
Step 4
Step 3
Step 2
Preferred:

Step 1
Preferred:
SABA PRN

Low-dose ICS

Alternative:
Cromolyn, LTRA,
Nedocromil, or
Theophylline

Preferred:
Low-dose
ICS + LABA
OR
Medium-dose ICS

Alternative:
Low-dose ICS +
either LTRA,
Theophylline, or
Zileuton

Preferred:
Medium-dose ICS
+ LABA

Alternative:
Medium-dose ICS
+ either LTRA,
Theophylline, or
Zileuton

Preferred:
High-dose
ICS + LABA

Step 6
Preferred:
High-dose
ICS + LABA + oral
corticosteroid

AND

AND

Consider
Omalizumab for
patients who have
allergies

Consider
Omalizumab for
patients who have
allergies

Each step: Patient education, environmental control, and management of comorbidities.

Steps 24:

Consider subcutaneous allergen immunotherapy for patients who have allergic asthma (see notes).

Quick-Relief Medication for All Patients

SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals
as needed. Short course of oral systemic corticosteroids may be needed.
Use of SABA >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to step
up treatment.

Step up if
needed
(first, check
adherence,
environmental
control, and
comorbid
conditions)
Assess
control
Step down if
possible
(and asthma is
well controlled
at least
3 months)

Steps of Therapy: Age 12 Years

Intermittent
Asthma

Persistent Asthma: Daily Medication

Consult with asthma specialist if step 4 care or higher is required.
Consider consultation at step 3.

Step 5
Step 4
Step 3
Step 2
Preferred:

Step 1
Preferred:
SABA PRN

Low-dose ICS

Alternative:
Cromolyn, LTRA,
Nedocromil, or
Theophylline

Preferred:
Low-dose
ICS + LABA
OR
Medium-dose ICS

Alternative:
Low-dose ICS +
either LTRA,
Theophylline, or
Zileuton

Preferred:
Medium-dose ICS
+ LABA

Alternative:
Medium-dose ICS
+ either LTRA,
Theophylline, or
Zileuton

Preferred:
High-dose
ICS + LABA

Step 6
Preferred:
High-dose
ICS + LABA + oral
corticosteroid

AND

AND

Consider
Omalizumab for
patients who have
allergies

Consider
Omalizumab for
patients who have
allergies

Each step: Patient education, environmental control, and management of comorbidities.

Steps 24:

Consider subcutaneous allergen immunotherapy for patients who have allergic asthma (see notes).

Quick-Relief Medication for All Patients

SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals
as needed. Short course of oral systemic corticosteroids may be needed.
Use of SABA >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to step
up treatment.

Step up if
needed
(first, check
adherence,
environmental
control, and
comorbid
conditions)
Assess
control
Step down if
possible
(and asthma is
well controlled
at least
3 months)

Steps of Therapy: Age 12 Years

Intermittent
Asthma

Persistent Asthma: Daily Medication

Consult with asthma specialist if step 4 care or higher is required.
Consider consultation at step 3.

Step 5
Step 4
Step 3
Step 2
Preferred:

Step 1
Preferred:
SABA PRN

Low-dose ICS

Alternative:
Cromolyn, LTRA,
Nedocromil, or
Theophylline

Preferred:
Low-dose
ICS + LABA
OR
Medium-dose ICS

Alternative:
Low-dose ICS +
either LTRA,
Theophylline, or
Zileuton

Preferred:
Medium-dose ICS
+ LABA

Alternative:
Medium-dose ICS
+ either LTRA,
Theophylline, or
Zileuton

Preferred:
High-dose
ICS + LABA

Step 6
Preferred:
High-dose
ICS + LABA + oral
corticosteroid

AND

AND

Consider
Omalizumab for
patients who have
allergies

Consider
Omalizumab for
patients who have
allergies

Each step: Patient education, environmental control, and management of comorbidities.

Steps 24:

Consider subcutaneous allergen immunotherapy for patients who have allergic asthma (see notes).

Quick-Relief Medication for All Patients

SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals
as needed. Short course of oral systemic corticosteroids may be needed.
Use of SABA >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to step
up treatment.

Step up if
needed
(first, check
adherence,
environmental
control, and
comorbid
conditions)
Assess
control
Step down if
possible
(and asthma is
well controlled
at least
3 months)

Steps of Therapy: Age 12 Years

Intermittent
Asthma

Persistent Asthma: Daily Medication

Consult with asthma specialist if step 4 care or higher is required.
Consider consultation at step 3.

Step 5
Step 4
Step 3
Step 2
Preferred:

Step 1
Preferred:
SABA PRN

Low-dose ICS

Alternative:
Cromolyn, LTRA,
Nedocromil, or
Theophylline

Preferred:
Low-dose
ICS + LABA
OR
Medium-dose ICS

Alternative:
Low-dose ICS +
either LTRA,
Theophylline, or
Zileuton

Preferred:
Medium-dose ICS
+ LABA

Alternative:
Medium-dose ICS
+ either LTRA,
Theophylline, or
Zileuton

Preferred:
High-dose
ICS + LABA

Step 6
Preferred:
High-dose
ICS + LABA + oral
corticosteroid

AND

AND

Consider
Omalizumab for
patients who have
allergies

Consider
Omalizumab for
patients who have
allergies

Each step: Patient education, environmental control, and management of comorbidities.

Steps 24:

Consider subcutaneous allergen immunotherapy for patients who have allergic asthma (see notes).

Quick-Relief Medication for All Patients

SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals
as needed. Short course of oral systemic corticosteroids may be needed.
Use of SABA >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to step
up treatment.

Step up if
needed
(first, check
adherence,
environmental
control, and
comorbid
conditions)
Assess
control
Step down if
possible
(and asthma is
well controlled
at least
3 months)

Steps of Therapy: Age 12 Years

Intermittent
Asthma

Persistent Asthma: Daily Medication

Consult with asthma specialist if step 4 care or higher is required.
Consider consultation at step 3.

Step 5
Step 4
Step 3
Step 2
Preferred:

Step 1
Preferred:
SABA PRN

Low-dose ICS

Alternative:
Cromolyn, LTRA,
Nedocromil, or
Theophylline

Preferred:
Low-dose
ICS + LABA
OR
Medium-dose ICS

Alternative:
Low-dose ICS +
either LTRA,
Theophylline, or
Zileuton

Preferred:
Medium-dose ICS
+ LABA

Alternative:
Medium-dose ICS
+ either LTRA,
Theophylline, or
Zileuton

Preferred:
High-dose
ICS + LABA

Step 6
Preferred:
High-dose
ICS + LABA + oral
corticosteroid

AND

AND

Consider
Omalizumab for
patients who have
allergies

Consider
Omalizumab for
patients who have
allergies

Each step: Patient education, environmental control, and management of comorbidities.

Steps 24:

Consider subcutaneous allergen immunotherapy for patients who have allergic asthma (see notes).

Quick-Relief Medication for All Patients

SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals
as needed. Short course of oral systemic corticosteroids may be needed.
Use of SABA >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to step
up treatment.

Step up if
needed
(first, check
adherence,
environmental
control, and
comorbid
conditions)
Assess
control
Step down if
possible
(and asthma is
well controlled
at least
3 months)

Low Power

Basement membrane brosis

Increased goblet cells and inc size of submucosal glands
Hypertrophy/hyperplasia of bronchial wall muscle

High Power

Basement membrane brosis

Increased goblet cells and inc size of submucosal glands
Hypertrophy/hyperplasia of bronchial wall muscle

Pathology

Charcot-Leyden Crystals galec6n-10 protein

In background of eosinophils
Can be found in sputum

Pathology

Curshmans Spirals mucus plugs from mucus gland

ducts or bronchioles
Can be found in the sputum

Lung Hyperina6on

Learning Objec6ves

Describe the expected spirometry results for a

pa6ent with asthma
Describe why asthma is classied as an obstruc6ve
lung disease
Describe the classica6on of asthma based upon
severity of symptoms and lung func6on
Recognize the four essen6al components of asthma
care: 1) assessment and monitoring of severity and
control; 2) pa6ent educa6on and partnership; 3)
control of environmental factors leading to asthma
severity; 4) pharmacologic therapy
Review the stepwise approach to asthma
management with pharmacologic therapy

Learning Objec6ves

Iden6fy the dierent classes of medica6ons used to

treat asthma and describe their: indica6ons for use,
mechanism of ac6on, side eects, and
contraindica6ons. Dis6nguish between medica6ons
used for rescue vs. control
Describe the microscopic changes that occur in the
airway, bronchus, and the sputum.
Describe which cells are involved in airway
remodeling? (specically thickening of the airway
wall, sub-basement membrane brosis, increased
vascularity, increased goblet cells, increased size of
submucosal glands and hypertrophy/hyperplasia of
bronchial wall muscle)
Describe what a mucus plug is, Curschmann spirals,
and Charcot-Leyden crystals?

Day 3
Six months have passed since Ms.
Garcias rst visit to her new primary
care doctor. She had been taking the
prescribed inhaled u6casone daily
and no6ced a signicant decrease in
her nighvme symptoms of asthma
as well as a decrease in her need for
albuterol. However, she now
presents to the Emergency room,
complaining of shortness of breath
for one day.

 Had symptoms of a cold for 3 days;

sneezing, nonproduc8ve cough, nasal
conges8on.
During this 8me, she has felt
increased wheezing, so she has
increase the use of her albuterol
inhaler. She has now used it 5 8mes in
the past 24 hours.
She denies fever, chest pain, or sinus
pressure.
She awoke in the middle of the night
with a lot of diculty breathing that
did not respond with her inhaler. She
felt scared by her symptoms, so her
roommate brought her to the
emergency room.
She states that a lot of people in her
dorm have had bad colds
She has been taking all of her
medica6ons as prescribed.

History of
Present illness/
related
symptoms

 Her past medical history,

allergies, family history,
social history is unchanged
from the informa6on that
was previously given in the
case.
Current medica8ons:
Inhaled u6casone daily
Loratadine once a day
Albuterol inhaler as
needed

Physical Exam

Height: 5-5
Weight: 126 lbs
Pulse: 115 bpm, regular
BP: 138/84
Temp: 37.9 C
Respira8on: 32/min.
Pulse oximetry: 90% room air
Peak expiratory ow (PEF) = 30% of pa8ents baseline
Gen: uncomfortable appearing, diculty speaking full
sentences, + use of accessory muscles of respira8on
HEENT: pupils equal, round and reac6ve to light.
Chest: decreases breath sounds bilaterally; diuse high-
pitches wheezing noted; prolonged I:E ra8o; no focal
dullness to percussion
Cardiovascular: tachycardic S1, S2, no murmurs, rubs,
or gallops
Abdomen: normal bowel sounds, soT, non-tender, non-
distended
Extremi6es: no edema
Neuro: awake and alert x 3,

Laboratory and Diagnos8c Tests from

Emergency Room:

Complete Blood Count (CBC) with normal ranges

given
WBC 6,500 (4500 11,000/ mm3)
Hemoglobin 13.8 (13.5 -17.5g/dL)
Platelets 300,000 (150,000-400,000)/mm3
Serum Electrolytes, or Chem 7
Sodium 142 mEq/L (136-145 mEq/L)
Potassium 4.6 mEq/L (3.5-5.0 mEq/L)
Chloride 103 mEq/L (95-105 mEq/L)
HC03 22 mEq/L (22-28 mEq/L)
Glucose 102 (fas6ng normal 70-110 mg/dL)
Serum urea nitrogen 22 mg/dL (7-18 mg/dL)
Serum Crea6nine 0.8 mg/dL (0.6-1.2 mg/dL)
Calcium 9.5 mg/dL (8.4-10.2 mg/dL)

Arterial Blood Gas

pH =7.5
paCO2 =27
paO2 =75

Acid-Base Physiology
REMEMBER
Henderson Hasselbalch equation:
pH = 6.1 + log [HCO3] / (0.03)PCO2
A rearranged form:
[H+] = 24 X pCO2 / [HCO3]
pH/ pCO2/ pO2/ calculated Bicarbonate/ O2 satura6on
Normal pH = 7.38-7.42
Normal pCO2 = 40 mmHg
Normal pO2 = 100 mmHg

Primary Acid-Base Disturbance

Acid-Base Physiology- Compensatory Mechanisms

The kidneys and lungs act as defense or compensatory mechanisms

The first defense is buffering
Once buffering is exhausted, the kidneys and lungs work to compensate
for an imbalance in the ratio of HCO3/CO2
Acute- Minutes- Respiratory:PCO2 regulation
Chronic- Hours to Days- Renal: Bicarbonate regulation
The pH will never normalize with a compensatory mechanism i.e. gets
close to normal

6 Step Approach to Acid Base

Analysis- STEP 1
1.Is the pH acidemic or alkalemic
acidemia = pH < 7.35
alkalemia = pH > 7.45

Remember- acidosis and alkalosis refer to the

process only
When referring to the pH of blood, we always
refer to it as acidemic or alkalemic
A pH of 7.4 would be neutral

STEP 2
2. Is the primary disturbance respiratory or
metabolic?
- How would you figure this out?

By looking at the PCO2

Normal PCO2= 40 mm Hg
(Normal Bicarbonate = 24 meq/L)
If acidemic: Then either the HCO3 < 24 AND/OR PCO2 > 40
If alkalemic: Then either the HCO3 > 24 AND/OR PCO2 < 40
Another way of thinking about it:
If the PCO2 is deranged in the same direction as the pH- the acidbase disorder is metabolic in origin
If the PCO2 is deranged in opposite direction to pH- the acid-base
disorder is respiratory in origin

STEP 3
3. If primary is respiratory, is it acute or
chronic?
Acute: pH= 0.08 X (pCO2-40)/10
Chronic: pH= 0.03 X (pCO2-40)/10

STEP 4
If primary is metabolic acidosis, is it
anion gap or non-anion gap?
Anion gap = [Na] ([Cl-] + [HCO3-])
Elevated: AG>12

STEP 5
If primary is metabolic, is there adequate
respiratory compensation?
- Winters Formula
Expected pCO2 = (1.5 [HCO3-]) + 8 2

STEP 6
If anion gap acidosis exists, is there a
second metabolic disorder?
Delta-Delta = HCO3 + (AG-12)
If this is > 24: Primary metabolic alkalosis
= 24: Normal
< 24: Primary metabolic acidosis
(non-gap)

Important Equa8ons to measure

compensa8on

Acid-Base approach
acidemia or alkalemia?

1
2

metabolic

mixed
both PaCO2 and
HCO3 can
independently
account for pH
change

respiratory

AG

? respiratory compensation

? metabolic compensation

(immediate)

(depends on kidneys)

NAG

MET ACID
MET ALK
PaCO2 = 1.5(HCO3) +8 +/-2
PaCO2 inc 0.75 per inc HCO3
PaCO2 dec 1.25 per dec HCO3 PaCO2 = 0.7(HCO3) + 20 +/-2
PaCO2 = last 2 digits of pH

acute

chronic

RESP ACID
Acute
pH dec 0.008 per inc PaCO2
HCO3 inc 0.1 per inc PaCO2

RESP ALK
Acute
pH inc 0.008 per dec PaCO2
HCO3 dec 0.2 per dec PaCO2

Chronic
Chronic
pH dec 0.003 per inc PaCO2 pH inc 0.0017 per dec PaCO2
HCO3 inc 0.4 per inc PaCO2 HCO3 dec 0.5 per dec PaCO2

if AG

20 then AG met acidosis is likely present

(NEJM.1980.303.854, ArchIM.1990.150.311, NEJM.1979.300.1421)

AG
HCO3
~1 pure AG met acid
<1.1 underlying NAG met acid ( HCO3>AG)
>2.1 underlying met alk ( HOC3<AG)
~1.1 ketosis
~1.6 lactic acidosis

or

AG + HCO3

<23
underlying
NAG met acid

>30
underlying
met alk

Pathophysiology of Asthma
nABG
nMost common abnormality- low CO2 and low O2
nLow O2- V/Q mismatch
nLow CO2- tachypnea

nIf CO2 normalizes- BE VERY WARY

nEither pa6ent is gevng beier (breathing beier- so
slower respiratory rate)
nOr gevng much worse (gevng 6red- so slower
respiratory rate)

nIf CO2 is elevated- need to intervene

nNoninvasive posi6ve pressure ven6la6on or intuba6on

Chest X-Ray
Hyper-
inated lungs,
no opaci6es
or eusions
noted

Pa8ent Progress
The pa6ent received albuterol via con6nuous
nebulizer for one hour. She was also given 60
mg methylprednisolone IV. ATer one hour,
her lung sounds improved on physical
examina6on with clearing of breath sounds
and improved airow. Her PEF aTer
treatment improved to 60% of predicted. RR
was 24 at this 6me and HR 105. The pa6ent
was monitored in the emergency room for
another hour. Her symptoms resolved and her
vital signs stabilized. The pa6ent was given
prescrip6on for a brief course of oral steroids
to be taken at home. In addi6on, her low-
dose u6casone was changed to medium-
dose u6casone with long ac6ng beta agonist,
to be added to her typical home medica6ons.
The pa6ent also received a wriien asthma
ac6on plan, which she reviewed with the ER
sta. She was discharged home and was
no6ed to contact her primary care provider
within 3-5 days.

Learning Objec6ves
Recognize causes for acute asthma exacerba6ons
(including infec6ons, allergens and pollutants)
Describe the pathological changes that are occurring in the
lungs in the sevng of an acute asthma exacerba6on
Explain the mechanisms by which wheezes are heard on
lung examina6on
Describe the medical treatment for acute asthma
exacerba6ons and describe the physiologic response for
each treatment (drug therapy).
What is dierence between Asthma exacerba8on versus
an status asthma8cus?
Dene status asthma6cus and recognize its clinical features
and risk of mortality.

Steps of Therapy: Age 12 Years

Intermittent
Asthma

Persistent Asthma: Daily Medication

Consult with asthma specialist if step 4 care or higher is required.
Consider consultation at step 3.

Step 5
Step 4
Step 3
Step 2
Preferred:

Step 1
Preferred:
SABA PRN

Low-dose ICS

Alternative:
Cromolyn, LTRA,
Nedocromil, or
Theophylline

Preferred:
Low-dose
ICS + LABA
OR
Medium-dose ICS

Alternative:
Low-dose ICS +
either LTRA,
Theophylline, or
Zileuton

Preferred:
Medium-dose ICS
+ LABA

Alternative:
Medium-dose ICS
+ either LTRA,
Theophylline, or
Zileuton

Preferred:
High-dose
ICS + LABA

Step 6
Preferred:
High-dose
ICS + LABA + oral
corticosteroid

AND

AND

Consider
Omalizumab for
patients who have
allergies

Consider
Omalizumab for
patients who have
allergies

Each step: Patient education, environmental control, and management of comorbidities.

Steps 24:

Consider subcutaneous allergen immunotherapy for patients who have allergic asthma (see notes).

Quick-Relief Medication for All Patients

SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals
as needed. Short course of oral systemic corticosteroids may be needed.
Use of SABA >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to step
up treatment.

Step up if
needed
(first, check
adherence,
environmental
control, and
comorbid
conditions)
Assess
control
Step down if
possible
(and asthma is
well controlled
at least
3 months)

 Acute Exacerba8on no
consensus deni6on but
involves:
need for tx w/ systemic
steroids,
hospital admission,
hospital treatment for
worsening asthma,
airway inamma6on w/
SOB,
cough,
wheezing,
chest 6ghtness
dec morning peak ow
>25% baseline on 2
consecu6ve days

Status Asthma6cus a
paroxysm that persists for days
or even weeks that can cause
airway obstruc6on so extreme
marked cyanosis or DEATH
Unresponsive to tx w/
bronchodilators (and steroids)
Persistent shortness of breath
The inability to speak in full
sentences
Breathlessness even while lying
down
Chest that feels closed
Bluish 6nt to your lips
Agita6on, confusion, or an
inability to concentrate
Hunched shoulders and
strained abdominal and neck
muscles
A need to sit or stand up to
breathe more easily