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CHAPTER 1

BASIC INFORMATION
I. Introduction to Internal Medicine
II. Core Skills in Internal Medicine
1. Electrocardiography
2. Chest Radiograph Interpretation
3. Arterial Blood Gas Interpretation
4. Thoracentesis
5. Paracentesis
6. Foley Catheter Insertion
7. Intravenous Line Insertion
III. Normal Laboratory Values and Conversion Factors
1. Complete Blood Count
2. Blood Chemistry
3. Urine Studies
4. Equivalent Values
IV. Intravenous Fluids
1. Intravenous Fluids and Common Indications
V. Commonly Used Drips
1. Formulation and Computation of Basic Drips
2. Other Commonly Used Drips
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SECTION 1
INTRODUCTION TO INTERNAL MEDICINE
I. INTRODUCTION

Internal Medicine (IM) can be quite overwhelming because of the complexity of cases and long work hours. Despite these
inherent toxicities, it remains one of the most rewarding fields in Medicine. Students and practitioners alike enjoy the
intellectual stimulation and experience of translating theoretical knowledge into direct patient care. As basic IM principles
cannot be dissociated from the cases we encounter, it is imperative for every practitioner to acquire the core
competencies and skills of an internist. The approach to patient encounter and chart writing are discussed in the
succeeding parts.

II. HISTORY AND PHYSICAL EXAMINATION

Complete history and physical examination are central to hypothetico-deductive reasoning in clinical medicine. Starting
from the chief complaint, problems are elicited from the in chronological order. After completing the details for acute
complaints, probe into the patient’s past medical history, including present medications and pre-morbid functional
capacity. Diseases in the family such as hypertension, diabetes, heart disease, early cardiac death and other
heredofamilial diseases should be elicited as part of the family medical history. History of allergic reactions to drugs and
food should always be elicited. Dietary habits, smoking history, alcohol intake and illicit drug use should also be included
in the personal and social history. Likewise, female patients should be asked about details on menstruation and
pregnancy.

The comprehensive history is followed by the systematic physical examination (PE). This starts with a general survey
followed by checking the patient’s vital signs. Permission should always be asked from the patient before doing any
maneuver, especially the more intrusive ones. A complete PE is carried out with special focus on certain procedures
pertinent to the identified problems of the patient.

III. WRITING THE ORDERS

With the information obtained from the history and PE, a prioritized problem list is then created, with the most urgent
conditions listed first. Based on the problem list, the management list is then outlined.

The orders for the patient usually contain the following:

Diet Dietary preparations (i.e., general liquids, soft diet, full diet) and specific dietary prescriptions
(i.e., low-salt, low-fat, low-purine, DAT)
Fluids and Drips Main IV lines (i.e., plain saline, D5-containing fluids) and side drips (i.e., vasopressors,
electrolyte solutions)
Monitoring BP, HR, RR, temperature, peripheral O2 saturation, neurologic vitals, etc.)
Frequency by which these parameters are checked (i.e., q hourly, q4h, q shift)
Diagnostics Prioritized list of diagnostic procedures such as imaging, blood tests and special procedures
Therapeutics Medications with corresponding doses, frequency of dosing, duration and side effects to
watch out for
Blood products, the amount to be transfused, rate of transfusion and interval between
transfusions
Transfusions Pre-medications and side effects to watch out for
Anticipatory measures: diuretics for possible congestion, anti-pyretics for febrile transfusion
reactions

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DATE/TIME PHYSICIAN’S ORDER SHEET
6/10/2015 Gen Med
7:30am
Diagnosis: Community acquired pneumonia, moderate risk
Hypertension, stage I, controlled

Diet: Low salt, low fat diet; limit oral fluid intake <1.5L day
IVF: PNSS 1L x 10 hours
Side drip1: MgSO4 2g in 250cc D5W x 24 hours

Dx: Chest X-Ray (PA and lateral views)


Complete blood count

Tx:
1. Ceftriaxone 2g IV q24h
2. Azithromycin 500mg/tab 1 tab OD for 3 days
3. Losartan 50mg/tab 1 tab PO OD

Monitor VS q4 with temp and O2 sat


Monitor I&O q shift and record
Refer to dietary for dietary prescription and advice
Watch out for desaturation and BT reaction

Jaime Aherrera MD
Lic. No. 123456

IV. PRESENTING THE CASE

A. General data – begin with the name, followed by the age, sex, chief complaint, reason for admission, and date of
admission or referral
“Juan dela Cruz, 28 years old male, admitted yesterday morning for dyspnea.”

B. History of present illness – review of systems and pertinent information from the past medical, family medical,
personal/social, and obstetric (if applicable) histories

C. Significant diagnostic findings and their interpretations, including pertinent normal findings to rule out the
differentials being considered by the team

D. Hospital course – emphasize the developments or important events that happened to the patient

E. Case summary – two or three sentences

F. Assessment/problem list

G. Plan – based on the assessment/problem list; detailed and specific. Orders for the patient should have their bases
and the expected laboratory findings or trends should be known

H. Entertain clarifications or questions from the audience

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SECTION 2
CORE SKILLS IN INTERNAL MEDICINE
ELECTROCARDIOGRAPHY
I. THE STANDARD 12-LEAD ELECTROCARDIOGRAM (ECG)

A. Limb leads
Standard limb (Bipolar) leads: I, II, III
Augmented limb (Unipolar) leads: aVF, aVR, aVL

B. Chest leads
V1 4th ICS, right parameter border
V2 4th IC, left parasternal border
V3 Between V2 and V4
V4 5th ICS, left midclavicular line
V5 5th ICS, left anterior axillary line
V6 5th ICS, left midaxillary line

II. THE P-QRST WAVES, SEGMENTS AND THE CARDIAC CYCLE

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III. BASIC STEPS IN ECG READING

Step 1: Determine rate


Step 2: Determine rhythm
Step 3: Measure intervals
Step 4: Determine axis
Step 5: Look for chamber enlargements
Step 6: Check for arrhythmias and other abnormalities

STEP 1: DETERMINE HEART RATE


Regular Rhythm

1500_____________
Heart Rate = # of small squares from R to R

Irregular Rhythm

Heart Rate = # of QRS complexes within 30 large boxes x 10

STEP 1: DETERMINE RHYTHM


Regular Sinus Rhythm
Rhythm is determined by the sinus node, which fires at 60-100 bpm
P-wave is normally upright in lead II (and usually in leads I, aVL and aVF)
Each p-wave is followed by a QRS complex, and each QRS complex is preceded by a p-wave
The distances between the R-R intervals should be equal

Sinus Tachycardia and Bradycardia


Tachycardia: HR >100bpm
Bradycardia: HR <60bpm
Sinus Arrhythmia
SA node discharges irregularly (sinus node rate varies with the respiratory cycle)
Rate: normal
Rhythm: varies with respiration, variation in the P-P interval and R-R interval >120 msecs
P-waves, PR interval and QRS: normal

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STEP 3: MEASURE INTERVALS
Normal Values

Wave/Interval Description Normal Values


P-wave Atrial depolarization < 0.12 sec or <120 msec (<3 small boxes)
PR interval Conduction within the AV node 0.12-0.20 sec or 120-200 msec (3-5 small boxes)
QRS duration Ventricular activation < 0.11-0.12 sec or <110-120 msec (<3 small boxes)
QT interval (QTc) Ventricular activation and recovery 0.35-0.43* (males) and 0.45* (females)
*may vary depending on reference
*Source: Kasper DL, et al. Harrison’s Principle of Internal Medicine, 19th edition

Corrected QT-interval (QTc) using the Bazett’s formula


Done to adjust for abnormal heart rates (HR <60 or >100 bpm)

QT actual
Corrected QT interval =
R-R interval in sec

STEP 4: DETERMINE AXIS


Computation of Frontal Axis
Deduct negative deflections form positive deflections in QRS complexes to derive the values for leads I and aVF.
If lead I is a negative integer, subtract the computed axis from 180 to get the final axis.
Note that the value for aVF in the denominator is the absolute value, while that in the numerator takes the sign
(positive or negative) into consideration. This is why a predominantly negative deflection in aVF will make the axis
negative.

____90 aVF____
Axis = | I | + | aVF

Interpretation
Normal Axis -30o to 100o
Right Axis Deviation (RAD) 100o to 180o
Left Axis Deviation (LAD) -30oto -90o
Extreme Axis Deviation -90o to -180o
“Eyeballing” method – can be used to estimate axis

INTERPRETATION LEAD I LEAD aVF


Normal QRS pointing UP QRS pointing UP
Left Axis Deviation QRS pointing UP QRS pointing DOWN
Right Axis Deviation QRS pointing DOWN QRS pointing UP
Extreme Axis Deviation QRS pointing DOWN QRS pointing DOWN

STEP 5: LOOK FOR CHAMBER ENLARGEMENTS


A. Atrial Enlargement

Peaked P-wave with > 2.5mm amplitude (> 2.5 small boxes)
Right Atrial Enlargement (RAE) in leads II, III or aVF
“P-Pulmonale” or peaked P-wave from pulmonary causes
Broad P-wave (> 120ms or > 3 small boxes)
Left Atrial Enlargement (LAE) Biphasic P wave in V1 with a broad negative component
Often notched P-wave in one or more limb leads
“P-Mitrale” or M-shaped P-wave

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B. Left Ventricular Hypertrophy (LVH)

SOKOLOW-LYON CRITERIA CORNELL CRITERIA

[S in V1] + [R in V5 or v6] > 35 mm (>35 small boxes) S in V3 + R in aVL:


Female > 20mm
OR Male > 28mm

R in aVL>11mm

C. Right Ventricular Hypertrophy (RVH)

Relatively tall R wave in lead V1 (R > S wave) with right axis deviation
R in V1 > 0.7mV
R/S in V1 > 1 with R > 0.5 mV
R/S in V5 or V6 < 1

IV. ARRYTHMIAS
JUNCTIONAL AND IDIOVENTRICULAR RHYTHMS
A. Junctional (Atrioventricular) Rhythm

Pacemaker: AV junction with a ventricular rate of 40 to 60 bpm


P wave: may appear before, after, or buried within the QRS complex
Rhythm (RR-interval): regular
QRS complex: narrow (<0.12 sec)

B. Idioventricular Rhythm

Pacemaker: Hiis-Purkinje system (HPS) with a ventricular rate between 15 to 40 bpm


P wave: absent
Rhythm (RR interval): regular
QRS complex: wide (>0.12 sec)

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DISORDERS OF SINUS RHYTHM
A. Sinus Pause

Temporary cessation of sinus node activity


May be synonymous with sinus “arrest” – which pertains to a prolonged sinus pause (definition is arbitrary)
Difference from sinus exit block: the supposed P-P interval of the dropped beat is not a multiple of the normal P-P
interval

B. Sinus Exit Block

Failure of impulse transmission


No visible P-QRS-T complex for >1 cycle, wherein the P-P interval of the pause is a multiple of the normal P-P
interval (differentiating it from sinus pause)

ATRIOVENTRICULAR (AV) BLOCKS


A. First Degree AV Block

Prolonged PR interval
(>0.20 sec or >5 small
boxes)
P-wave is followed by a
QRS complex

B. Second Degree AV Block, Mobitz Type I (Wenckebach)

PR interval progressively
lengthens, then the
impulse is blocked (P is
not followed by QRS,
resulting in a dropped
beat)
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C. Second Degree AV Block, Mobitz Type II

PR intervals of
conducted beats are
constant in length,
however, beats are
dropped with no warning
PR intervals may be
normal or prolonged

D. High Grade AV Block

2 out of every 3 or more


impulses from the atria
are blocked by the AV
node and fail to reach
the ventricles
PR intervals are
constant (in contrast to
complete heart block)

E. Third Degree (Complete) AV Block

P and QRS waves occur


regularly but are
independent of each
other
No consistent
relationship between
atrial and ventricular
activity (AV Dissociation)
PP intervals and RR
intervals are constant

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ATRIAL ARRHYTHMIAS
A. Premature Atrial Contractions (PAC)

Premature P-waves
(earlier than the next
expected sinus P-wave)
P-wave has a different
morphology compared to
the sinus P-wave since
this P-wave is coming
from a different atrial
focus
QRS is usually narrow

B. Atrial Fibrillation (AF)

Description: Rapid,
erratic electrical
discharge from multiple
atrial ectopic foci
Rate: atrial rate >350
bpm; ventricular rate
varies
Rhythm: irregularly
irregular
P-waves: no discernable
P-wave
QRS: usually normal

C. Atrial Flutter

Description: Re-entrant
circuit within the atria,
with variable conduction
of impulses through the
AV node to the ventricles
Rate: atrial rate is 250-
350 bpm; ventricular rate
varies
Rhythm: variable
(depending on
conduction)
P-waves: saw-tooth
appearance
QRS: usually normal

D. Wandering Pacemaker

Description: impulses
originate from different
foci in the atrium
Rate: normal
Rhythm: irregular
P-waves:> 3 different
forms
PR interval: variable
QRS: normal

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E. Multifocal Atrial Tachycardia (MFAT)

Rate: Fast; Irregular


atrial rate (> 100)
Rhythm: irregular
P-wave: >3 different
forms
PR interval: variable
QRS: normal

SUPRAVENTRICULAR TACHYCARDIA (SVT)

Arrhythmia has such a


fast rate that the P
waves may not be seen
Rate: 150-250 bpm
Rhythm: regular
P waves: frequently
buried in preceding T
waves
QRS: normal, but may
be wide if abnormally
conducted through
ventricles (aberrant
conduction)

Atrioventricular Nodal Reentrant Tachycardia (AVNRT)

Most common form of


SVT
Narrow QRS tachycardia
with a short RP interval –
P-waves buried in the
QRS complex
May have a “pseudo-S”
wave (which is actually a
retrogradely conducted
P wave) in inferior leads
or “pseudo-R prime” in
V1

VENTRICULAR ARRHYTHMIAS
Wide QRS tachycardias (>120 ms or 3 small squares): usually ventricular in origin
Differentials for wide QRS tachycardia
o Ventricular tachycardia (VT): more common
o Supraventricular tachycardia (SVT) with aberrancy
When faced with a wide-complex tachycardia and the morphology is in question, it is safer to treat as ventricular
tachycardia (the more life-threatening differential)
A. Premature Ventricular Contractions (PVC)
Prematurely occurring
QRS complex which is
wide and bizarre-looking
Usually no preceding P-
wave
T wave opposite in
Bigeminy: PVCs alternate with sinus beats
deflection to the QRS
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complex

Trigeminy: PVC occurs after every 2 sinus beats

Couplet: two successive PVCs (if three successive PVCs, it is already considered unsustained VT)

B. Ventricular Tachycardia (VT)


1. VT According to Morphology

a. Monomorphic Ventricular
Tachycardia
Rapid, bizarre wide QRS
complex (appearance of
all the beats match each
other in each lead)
No P-wave
Ventricular focus
produces a rapid
sequence of PVC-like
wide ventricular
complexes

b. Polymorphic Ventricular
Tachycardia (Torsades de
Pointes)
Beat-to-beat variations in
appearance
Baseline rhythm
demonstrates long QT
interval
Presents with an
oscillating pattern
mimicking the “turning of
the points” stitching
pattern
2. VT According to Duration

a. Sustained: ventricular tachycardia that lasts for more than 30 seconds


b. Non-sustained: ventricular tachycardia that self-terminates within 30 seconds (presence of at least >3
successive PVCs is considered VT)

3. VT Based on Symptoms

a. Pulseless VT: no effective cardiac output (no pulse, no BP) defibrillate (treat as ventricular fibrillation)
b. Unstable VT: with pulse, but unstable BP cardioversion

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C. Ventricular Fibrillation (VF)
Associated with coarse or fine chaotic undulations
No P-wave
No true QRS complexes

PACEMAKER RHYTHM
A. Ventricular Paced Rhythm

RR interval is regular
QRS complex is wide with an LBBB morphology
Pacemaker spike (“blip”) is followed by a wide QRS complex (good capture)

B. Atrial Paced Rhythm

Atrial pacing appears on the ECG as a single pacemaker stimulus followed by a P wave
PR interval and configuration of the QRS complex are similar to those seen in a sinus rhythm

C. Dual Pacemaker (Atrial and Ventricular)

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V. OTHER ABNORMAL FINDINGS

ISCHEMIA

Findings suggestive of ischemia(should be in 2 or The Contiguous Leads


more contiguous leads)
ST segment depression > 1mm (> 1 small box) II, III, aVF Inferior wall
Deep T-wave inversions > 5 mm (> 5 small I, aVL High lateral wall
boxes) V1, V2 Septal wall
V3, V4 Anterior wall
For example, if there are ST segment V5, V6 Lateral wall
depressions of >1mm in lead V5 and V6: then V1 – V3 Anteroseptal wall
we can say that there is lateral wall ischemia. If V3 – V6, I, aVL Anterolateral wall
ST segment depressions occur in V3 to V6: V5, V6, II, III, aVF Inferolateral wall
then we can say there is anterolateral wall Almost all leads Diffuse, massive
ischemia. V3R, V4R (right-sided Right ventricular wall
leads)

INFARCTION
A. Findings suggestive of injury or infarction

Significant ST elevation:manifestation of myocardial necrosis; the earliest sign of acute infarction


> 1 mm ST elevation in contiguous limb leads, or
> 2 mm ST elevation in contiguous chest leads

B. Pathologic Q-Waves

Indicate myocardial necrosis


Significant Q-wave: > 0.04 secs duration and > 25% of the R wave amplitude
Ignored in lead V1 unless with abnormalities in other precordial leads
Ignored in lead III unless with abnormalities in leads II and aVF

C. Classification as to Timing of Myocardial Infarction

CLASSIFICATION TIMING ECG FINDINGS


(A) Normal
(B) Acute MI Minutes to hours ST elevation + peaked or inverted T-waves + Q waves
(C) Recent MI Hours to days Q-waves +ST elevation + T-wave inversion
(D) Old MI Days to months Q-waves + Isoelectric ST-segment + T-wave inversion

D. Posterior LV wall involvement

Posterior wall ischemia, which is usually associated with lateral or inferior involvement, may be indirectly
recognized by reciprocal or “mirror-image” ST depressions in leads V1 to V3
The posterior LV wall electrical activity is not represented in a typical standard surface ECG
The anteroseptal leads (V1 to V3) are directed form the anterior precordium pointing towards the internal surface
of the posterior myocardium

E. Reciprocal Changes
Pertains to ST-depression in leads opposite those demonstrating ST-elevation
“Ischemia at a distance”
Anterior MI: reciprocal change in inferior wall
Inferior MI: reciprocal change in I, aVL, or anterior wall
Lateral MI: reciprocal change in V1 or inferior wall

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PULMONARY EMBOLISM (PE)

McGinn-White sign: S1Q3T3 pattern (large S-wave in lead I, Q-wave in lead III, and inverted T-wave in lead III)
indicating acute right heart strain
Sinus tachycardia: most commonly cited abnormality
T wave inversion on leads V1-V4: another most commonly cited abnormality (due to RV strain)
Right bundle branch block
Low amplitude deflections

ELECTRICAL ALTERNANS

Beat to beat variation in the QRS amplitude


Seen in massive pericardial effusion and/or cardiac tamponade

BUNDLE BRANCH BLOCKS

V1 V6

Normal

RBBB

LBBB

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A. Left Bundle Branch Block (LBBB)

QRS duration >0.12 sec (complete LBBB)


If <0.12 sec, then it is considered incomplete LBBB
Broad, notched, or slurred R-waves in leads I, aVL,
V5 and V6
Small or absent initial R-waves in right precordial
leads (V1 and V2) followed by deep S-waves
Absent septal Q-waves in leads I, V5 and V6

B. Right Bundle Branch Block (RBBB)

QRS duration >0.12 sec (complete RBBB)


If <0.12 sec, then it is considered incomplete RBBB
Slurred S-wave in leads I and V6
RSR pattern in V1 (“bunny ears”)

PERICARDITIS

Acute Pericarditis

A. Stages of Pericarditis

Stage 1: Widespread ST elevation and PR depression with reciprocal changes in aVR (first two weeks)
Stage 2: Normalization of ST changes; generalized T wave flattening (1 to 3 weeks)
Stage 3: Flattened T waves become inverted (3 to several weeks)
Stage 4: ECG returns to normal (several weeks onwards)

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B. Pericarditis versus Myocardial Infarction
PERICARDITIS MYOCARDIAL INFARCTION
Diffuse ST elevations which are concave upward ST elevations which are convex upward

ST elevation

T-waves T-wave usually not inverted unless ST is T-waves may begin to invert before ST
isoelectric becomes isoelectric
Q-waves Usually absent Present
Reciprocal Change Unusual Common
PR depression Usually present Absent

WOLFF PARKINSON WHITE (WPW) PATTERN

Pre-excitation pattern: atrial impulse activates the


ventricle earlier than would be expected if the
impulse traveled by way of the normal AV
conduction system
o Triad of WPW: PR interval <120 msec,
QRS >120 msec, (+) delta wave (slurred
upstroke or initial portion of QRS complex)
o Secondary ST-T wave abnormalities
opposite that of the delta wave and QRS
forces

ARRHYTHMOGENIC RV DYSPLASIA (ARVD)

Epsilon wave: a small positive deflection (‘blip’)


buried at the end of the QRS complex, representing
delay in depolarization of the right ventricular (RV)
free wall and outflow tract
Epsilon waves, found in 50% of patients with
ARVD, are due to the slowed intraventricular
conduction, hence the terminal notch in the last 1/3
segment of the QRS complex (which represents
the right ventricular activation)

BRUGADA ECG PATTERN

Type 1 Prominent coved ST-elevation displaying J-point amplitude or ST-elevation >2mm,


followed by a negative T-wave
Type 2 >2 mm J-point elevation, >1 mm ST-elevation and a saddleback appearance, followed by
a positive or biphasic T-wave
Type 3

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DEXTROCARDIA (“Right Sided Heart”)

Absent R-wave progression in the chest leads (dominant S-waves throughout)


Predominantly negative P-wave, QRS complex, and T-wave in lead I
Low voltage in leads V3-V6 (because these leads are placed on the left side of the chest)
Accidental reversal of the left and right arm electrodes may produce a similar ECG pattern in the limb leads but
with normal QRS morphology in the precordial leads

OTHER ECG FINDINGS


T-wave inversion, ST segment depression/elevation not fulfilling the
Non-specific ST-T wave changes criteria for ischemia or infarction (as outlined above): flattened or
slightly inverted T-waves, ST segments slightly above or below the
isoelectric line
Poor R wave progression R-wave in leads V1-V3 is < 3 small boxes
Normal R-wave in V4-V6
QRS complexes <5 small boxes in limb leads or < 10 small boxes in
Low voltage complexes chest leads
Example: COPD, anasarca, obesity, myocarditis, moderate-sized to
massive pericardial effusions
Hypokalemia Prominent U wave + flattened T wave
Hyperkalemia Peaked T-waves > 10 mm, wide QRS, sine
Electrolyte abnormalities wave pattern
Hypocalcemia Prolonged QT interval
Hypercalcemia Shortened QT interval

CHEST RADIOGRAPH INTERPRETATION


I. BASIC STEPS IN READING CHEST X-RAYS (CXR)

Step 1: Identify general data


Step 2: Determine view (PA, AP, lateral, decubitus)
Step 3: Assess quality of film
Step 4: Assess anatomy and determine abnormalities

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STEP 1: IDENTIFYING GENERAL DATA OF THE PATIENT

Patient name
Date/Time CXR was taken
Diagnosis of patient
Indication for CXR

STEP 2: DETERMINING THE VIEW

Postero-Anterior View (PA) Antero-Posterior View (AP)


Scapula winged out, ribs and clavicles more angulated Scapula not winged out; clavicles more horizontal
Arms at an angle with the body, with hands at waist Arms parallel to body
Mongolian hat sign appreciated
(formed by the C7 and T1 spinous + transverse Mongolian hat sign not appreciated
processes)
Heart not magnified Heart and other structures magnified

STEP 3: ASSESSING THE QUALITY OF THE FILM

Inclusion Apices of the lungs to the costophrenic angles should be adequately visualized
Inspiratory Effort One should count >8 intercostal spaces, 6-8 anterior ribs, 9-11 posterior ribs
Exposure Upper four thoracic vertebrae should be visualized
Obliquity Medial ends of both clavicles equidistant from midline
The spinous process of the thoracic vertebra should be in the midline

STEP 4: ASSESSING ANATOMY AND ABNORMALITIES


A. General Structure
Soft tissues and bones: soft tissue swellings, rib fractures, breast shadow, osteopenia/osteoporosis
Trachea and mediastinum: carinal angle, tracheal position, mediastinal widening, masses
Vessels: aortic knob and pulmonary arteries
Diaphragm: right hemidiaphragm is usually higher than the left

B. The Heart
Assess CT ratio: >0.50 in PA view suggests cardiomegaly
Cardiomegaly cannot be definitively ascertained on AP films, due to the possibility of magnification effects

CHAMBER PA FILM LATERAL FILM


Left ventricular Apex displaced inferiorly and laterally Obliteration of retrocardiac
enlargement (drooping apex) space
Right ventricular Apex displaced superiorly and Obliteration of retrosternal
enlargement laterally (uplifted apex) space
Prominence of left atrial appendage
Loss of cardiac waistline Posterior displacement of the
Left atrial enlargement Widening of carinal angle (>70o) left mainstem bronchus on
Double density sign on right cardiac lateral film
border
Bulging right heart border (height >1/2
Right atrial enlargement of right cardiac silhouette and width N/A
1/3 of right hemithorax)

C. The Lungs
CP angle: blunting suggests minimal pleural effusion
Pleura: check for pneumothorax, lesions
Parenchyma: check for opacities, densities, infiltrates
Lobes of the lungs:
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o Right Lung (3 lobes): Right upper lobe (RUL) + right middle lobe (RML) + right lower lobe (RLL)
o Left lung (2 lobes): Left upper lobe (LUL) + lingula + left lower lobe (LLL)

II. COMMON CHEST X-RAY PATHOLOGIES

Aortic Aneurysm Mediastinum >30% of thoracic diameter, or mediastinum >8-10 cm


Density in the area of the collapsed lung
Displacement of interlobular fissures (direct sign)
Atelectasis Surrounding structures deviated to the side of the collapsed lung (ipsilateral
mediastinal shift)
Crowding of vessels/bronchi
Ipsilateral diaphragmatic elevation
Bronchiectasis Appears as “bunches of grapes” (ring shadows)
Tram-track lines
Consolidation Inhomogenous opacities
Prominent air bronchogram sign
Hyperaerated lungs
COPD/Emphysema Flattened hemidiaphragms
Tubular heart
Occasionally, bullae
Decreased lung volume
Fibrosis Shift of mediastinum and surrounding structures towards fibrotic area
Blurred heart border or diaphragm with indistinct vascular markings in the areas
of fibrosis
Fungus Ball Homogenous round opacity with a crescent sign
Hamartoma Popcorn ball lesion
Pericardial Effusion Generalized enlargement of the cardiac shadow (“water bottle sign”) with
normal vascular markings
Pleural Effusion Blunting of costophrenic angles
Meniscus sign
Pneumomediastinum Presence of gas between the mediastinal structures
Pneumoperitoneum Presence of gas underneath the diaphragm
Hyperlucent pulmonary area
Pneumothorax Loss of vascular markings beyond the visceral pleural line
Mediastinal structures deviated to contralateral side (tension pneumothorax)
Prominent hilar vessels (hilar fullness) in a bat-wing distribution
Pulmonary edema Cephalization of vessels
Kerley B lines
Pulmonary Metastasis Cannon ball lesions

ARTERIAL BLOOD GAS (ABG) INTERPRETATION


I. BASIC STEPS IN ABG INTERPRETATION

Step 1: Determine the primary acid-base disorder and whether compensation is appropriate
Step 2: Check for secondary acid-base disorders
Step 3: Compute for anion gap and / when needed
Step 4: Check oxygenation status

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STEP 1: DETERMINE THE PRIMARY ACID-BASE DISTURBANCE AND APPROPRIATE COMPENSATION
A. Check the pH, HCO3 and pCO2 levels

NORMAL VALUES IN ARTERIAL BLOOD GAS


Arterial pH 7.40 + 0.05
pCO2 40 +2
HCO3 24 + 2
Anion gap 12 + 2

B. Determine Primary Problem


To assess whether primary problem is respiratory or metabolic in origin, compare changes of HCO 3and pCO2
from baseline
If the change in HCO3 from baseline is larger, then the problem is primarily metabolic and vice versa

Check pH Check HCO3& pCO2 PRIMARY DISTURBANCE


pH <7.4 HCO3> CO2 Metabolic acidosis
CO2>HCO3 Respiratory acidosis
pH >7.4 HCO3> CO2 Metabolic alkalosis
CO2> HCO3 Respiratory acidosis

C. Assess for appropriateness of compensation using the following formulas

PRIMARY DISORDER COMPENSATION


Metabolic acidosis For every 1 meq/L FALL in HCO3,pCO2will DECREASE by 1.2 mmHg
Metabolic alkalosis For every 1 meq/L RISE in HCO3,pCO2will INCREASE by 0.7 mmHg
Respiratory acidosis For every 10 mmHg RISE in pCO2, HCO3will INCREASE by 1 meq/L
Respiratory alkalosis For every 10 mmHg FALL in pCO2, HCO3will DECREASE by 2 meq/L

STEP 2: CHECK FOR SECONDARY ACID-BASE DISORDERS


A. In cases where there is inappropriate compensation, a secondary acid-base disorder should be considered

PRIMARY DISORDER COMPENSATION SECONDARY ACID-BASE DISORDER


Actual reduction of pCO2 from baseline is Secondary RESPIRATORY ALKALOSIS is
Metabolic HIGHER than that of calculated compensation present
Acidosis Actual reduction of pCO2 from baseline is LESS Secondary RESPIRATORY ACIDOSIS is
than that of calculated compensation present
Actual increase of pCO2 from baseline is Secondary RESPIRATORY ACIDOSIS is
Metabolic HIGHER than that of calculated compensation present
Alkalosis Actual increase of pCO2 from baseline is LESS Secondary RESPIRATORY ALKALOSIS is
than that of calculated compensation present
Respiratory Actual increase of HCO3 from baseline is Secondary METABOLIC ALKALOSIS is
Acidosis HIGHER than that of calculated compensation present
Actual increase of HCO3 baseline is LESS than Secondary METABOLIC ACIDOSIS is
that of calculated compensation present
Respiratory Actual decrease of HCO3 from baseline is Secondary METABOLIC ACIDOSIS is
Alkalosis HIGHER than that of calculated compensation present
Actual decrease of HCO3 from baseline is LESS Secondary METABOLIC ALKALOSIS is
than that of calculated compensation present

21
STEP 3: COMPUTE FOR ANION GAP AND / WHEN NECESSARY
A. Formula for Anion Gap

Anion gap = Na – (HCO3 + Cl) Normal anion gap is 8-12


High anion gap is >12

B. Usual Causes of Metabolic Acidosis are as follows:

HIGH-ANION GAP METABOLIC ACIDOSIS (HAGMA) NORMAL ANION GAP METABOLIC ACIDOSIS (NAGMA)
P: Paraldehyde H: Hyperalimentation
M: Methanol I: Isoniazid, Iron A: Acetazolamide
U: Uremia L: Lactic acidosis R: Renal tubular acidosis
D: Diabetic ketoacidosis E: Ethylene glycol, Ethanol D: Diarrhea
S: Salicylates U: Uretero-pelvic shunt
P: Post-hypocapnia

C. Check for /

1. For High-Anion Gap Metabolic Acidosis (HAGMA)


Anion Gap If=1, there is pure HAGMA
If <1, there is HAGMA + NAGMA
HCO3 If >1, there is HAGMA + metabolic alkalosis

2. For Normal-Anion Gap Metabolic Acidosis (NAGMA)


Chloride If=1, there is pure NAGMA
If <1, there is NAGMA + HAGMA
HCO3 If >1, there is NAGMA + metabolic alkalosis

D. Computing for Bicarbonate Deficit

HCO3 deficit = (desired HCO3– actual HCO3) x weight x 0.4

STEP 4: CHECK FOR OXYGENATION STATUS

STATUS PO2 LEVEL ON ABG


Hyperoxemia (more than adequate) >100 mmHg
Normoxemia 80-100 mmHg
Mild hypoxemia 60-79 mmHg
Moderate hypoxemia 45-59 mmHg
Severe hypoxemia

22
THORACENTESIS
MATERIALS METHOD

Thoracentesis set 1. Examine the patient and review available labs (CXR, CBC, blood chemistry,bleeding
Abbocath gauge #16 parameters)
3 way stopcock 2. Explain nature of procedure to patient and obtain consent
Macroset/IV tubing 3. Extract simultaneous serum specimen for LDH, albumin, total protein and glucose
Drapes 4. Position patient in sitting position with the mid-axillary line accessible for needle insertion
50cc syringe 5. Confirm and mark topmost site of insertion by counting ribs based on CXR and percussing
10cc syringe fluid level (usual site of insertion is at the 8th ICS posterior axillary line; alternatively, chest
UTZ with markings can be done)
Lidocaine 2% ampoules
6. Observe sterile technique including sterile gloves, betadine prep and drapes
Clean (non-sterile) gloves
7. Anesthetize skin over insertion site with 2% Lidocaine, including superior surface of the rib
Sterile gloves and pleura
Cotton 8. Insert thoracentesis needle perpendicularly through the anesthetized area to the same depth
Rubbing alcohol as the first needle and observe backflow of pleural fluid
Betadine 9. Once with backflow, leave catheter in place, remove needle and attach three-way stopcock &
Sterile gauze tubing
Micropore 10. Aspirate needed amount, then turn the stopcock and evacuate fluid through the tubing (do not
Sterile specimen remove more than 1.5L to avoid increased risk of re-expansionpulmonary edema or
vials/bottles hypotension)
11. Fill specimen tubes/containers and label properly
12. When draining of fluid is complete, have patient take a deep breath or ask patient to cough
and gently remove needle
13. Cover insertion site with sterile occlusive dressing
14. Send specimen for qualitative studies (pH, specific gravity, cell count and differentials,
protein, LDH, albumin, glucose), gram stain and culture, AFB smear and additional studies as
necessary (i.e., cytology for malignancy, amylase for pancreatitis, triglycerides for
chylothorax)
15. Monitor patient closely and watch out for untoward reactions (chest pain, dyspnea, cough,
infection)
16. Obtain upright CXR to evaluate lung expansion/fluid level and rule out pneumothorax
17. Provide post-procedural analgesics as necessary
18. Document procedure, patient response, side effects, nature of fluid drained and lab tests sent

PARACENTESIS
MATERIALS METHOD

Abbocath gauge #16 1. Examine the patient and review available labs (CXR, CBC, blood chemistry,bleeding
Macroset/IV tubing parameters)
Drapes 2. Explain nature of procedure to patient and obtain consent
50cc syringe 3. Have patient empty bladder prior to procedure
10cc syringe 4. Extract simultaneous serum specimen for LDH, albumin, total protein and glucose
Lidocaine 2% ampoules 5. Assemble materials and prepare sterile field
Clean (non-sterile) gloves 6. Position patient in supine position with the trunk elevated 45 degrees
7. Confirm and mark the site of access (usually midline 3-4 cm below umbilicus, halfway
Sterile gloves
between symphisis pubis and umbilicus)
Cotton
8. Anesthetize skin over insertion site with 2% lidocaine, down to and including the peritoneum
Rubbing alcohol 9. Insert paracentesis needle perpendicularly through the anesthetized area to the same depth
Betadine as the first needle and observe for backflow of fluid
Sterile gauze 10.Once with backflow, leave the catheter in place, remove needle and attach tubing draining into
Micropore specimen needles
Sterile specimen vials/ 11.Remove the necessary amount of ascetic fluid
bottles 12. Monitor the patient for hypotension during the procedure
13. When draining of fluid is complete, remove needle and cover insertion site with sterile
occlusive dressing
14. Fill specimen tubes/containers and label properly
15. Send specimens for qualitative studies (pH, specific gravity, cell count and differentials, LDH,
protein, albumin, glucose), gram stain and culture, AFB smear and additional studies as
necessary (i.e., cytology for malignancy)
16. Provide post-procedural analgesics as necessary
17. Document procedure, patient response, side effects, nature of fluid drained and lab tests sent
23
FOLEY CATHETER INSERTION
MATERIALS METHOD

Foley catheter with urine 1. Hand hygiene


bag 2. Prepare materials
Drapes 3. Identify patient by name and introduce self to patient
10cc syringe 4. Explain nature of procedure
1 vial syringe water 5. Provide as much privacy as possible
Clean (non-sterile) gloves 6. Position patient properly
Sterile gloves 7. Wash and rinse urethral area
Cotton 8. Open foley catheter package, put aside but maintain sterile zone around foley catheter
9. Wear clean gloves
Rubbing alcohol
10.Clean urethral opening aseptically:
Betadine
a. For male – in circular motions inside to out
Lubricant (KY jelly) b. For female – follow a “7” figure then drop
Micropore 11.Change to sterile gloves
Sterile specimen bottles 12. Lubricate tip of catheter liberally
(if for urine collection) 13. Attach drainage end of foley catheter to urine bag
14. Insert lubricated end of catheter into urinary meatus gently then push gently up until you are
sure you are inside the bladder (usually up to the port where you inject water and there is
urine backflow)
15. Observe for urine flow
16. Infuse 5-10ml of sterile water to inflate balloon
17. Pull foley catheter slowly until with some resistance
18. Secure foley catheter with tape
19. Dry patient’s perineum
20. Instruct patient on catheter care
21. Remove gloves
22. Hand hygiene

IV LINE INSERTION
MATERIALS METHOD

IV cathula 1. Hand hygiene


Macroset/IV tubing 2. Prepare materials
Clean (non-sterile) gloves 3. Identify patient by name and introduce self to patient
Tourniquet 4. Explain nature of procedure
Cotton 5. Wear clean gloves
Rubbing alcohol 6. Select position/site of venipuncture
Micropore 7. Swab puncture site with alcohol on concentric circles inside to out
8. Apply tourniquet
Splint (optional)
9. Stabilize the selected site
10.Insert needle bevel up
11.Observe for blood backflow
12. Remove needle while pushing cathula further into the vein
13. Attach infusion set quickly while pressing on vein to prevent excessive escape of blood
14. Release tourniquet
15. Try running the IV line to check that fluid infuses continuously and there is no bulging at the
insertion site
16. Cover the insertion site with a 1x1 sterile gauze and tape securely
17. Loop tubing and secure with tape
18. Apply splint
19. Instruct the patient on care of IV site
20. Discard sharps properly
21. Remove gloves
22. Hand hygiene

24
SECTION 3
NORMAL LABORATORY VALUES AND CONVERSION FACTORS
COMPLETE BLOOD COUNT (CBC)

Monocytes: Neutrophils:
0.02-0.09 Hemoglobin: 0.50-0.70
120-180g/L RBC 4-6 x 1012/L
Platelets: 12.0-18.0 g/dL WBC: (106/mm3)
150-450 x 109/L 4-11 x 109/L MCV 80-100 fL
MCH 27-31 pg
150-450 x 103/mm3 4-11 x 103/mm3 MCHC 320-360 g/L
Hematocrit:
RDW-CV 11-16%
Eosinophils: 0.37-0.54 Reticulocytes 0.005-0.015
0.00-0.06 Lymphocytes:
Basophils: 0.20-0.50
0.00-0.02

BLOOD CHEMISTRY
LABORATORY SI CONVENTIONAL
Glucose 3.9-6.1 mmol/L 75-100 mg/dL LABORATORY SI CONVENTIONAL
BUN 2.6-6.4 mmol/L 7-20 mg/dL Lipase 0.51-0.73 23-300 U/L
Creatinine 53-115 umol/L 0.6-1.3 ng/mL ukat/L
Sodium 136-146 136-146 mEq/L LDH 2.0-3.8 ukat/L 100-190 U/L
mmol/L CRP 0.2-3.0 mg/L 0.2-3.0 mg/L
Potassium 3.5-5.2 mmol/L 3.5-5.2 mEq/L RF < 30 kIU/L < 30 kIU/mL
Chloride 100-108 100-108 mEq/L Free T4 10.3-21.9 0.8-1.7 ng/dL
mmol/L pmol/L
Calcium 2.12-2.52 8.7-10.2 mg/dL Free T3 3.7-6.5 pmol/L 2.4-4.2 pg/mL
mmol/L TSH 0.34-4.25 0.34-4.25
Magnesium 0.70-1.00 1.5-2.3 mg/dL mIU/L uIU/mL
mmol/L PSA < 40 y/o 0.0-2.0 ug/L 0.0-2.0 ng/mL
Phosphorus 0.81-1.4 2.5-4.3 mg/dL PSA > 40 y/o 0.0-4.0 ug/L 0.0-4.0 ng/mL
mmol/L AFP 0.0-8.5 ug/L 0.0-8.5 ng/mL
Total protein 64-83 g/L 6.4-8.3 g/dL CA 125 0-35 kU/L 0-35 U/mL
Albumin 34-50 g/L 3.4-5.0 g/dL CA 19-9 0-37 kU/L 0-37 U/mL
Globulin 23-35 g/L 2.3-3.5 g/dL CEA 0-3.0 ug/L 0-3.0 ng/mL
AST (SGOT) 15-37 U/L 15-37 U/L (nonsmokers)
ALT (SGPT) 30-65 U/L 30-65 U/L CEA 0-5.0 ug/L 0-5.0 ng/mL
Alkaline 36-92 umol/L 36-92 umol/L (smokers)
phosphatase CK-total 55-170 U/L 55-170 U/L
Total bilirubin 0-17.1 umol/L 0.3-1.3 mg/dL CK MB 0-16 U/L 0-16 U/L
Direct bilirubin 0-5.00 umol/L 0.1-0.4 mg/dL CK MM 8-97 U/L 8-97 U/L
Indirect bilirubin 3.4-13.7 umol/L 0.2-0.9 mg/dL Troponin I 0-0.09 ng/mL 0-0.09 ug/L
Uric acid 0.13-0.44 3.1-7.0 mg/dL
umol/L
Ammonia 11-35 umol/L 19-60 ug/dL
Amylase 0.34-1.6 ukat/L 30-110 U/L

25
URINE STUDIES
URINALYSIS 24 HOUR URINE CHEMISTRY
Color Yellow, clear/hazy Total volume 500-2000cc
Specific 1.016-1.022 Creatinine 0.65-0.70 g/L or 8.8-14 mmol/d
gravity Total protein 0-0.1 g/24hr or < 100 mg/d
pH 4.6-6.5 Na+ 80-260 mmol/L
Sugar, (-) K+ 25-100 mmol/L
Albumin Cl- 80-340 mmol/L
RBC 0 / 0-2 / hpf Uric acid 4.42-5.9 mmol/24hr
WBC 0-2 / 0-5 / hpf CA2+ 2.5-7.5 mmol/24hr
Casts Hyaline, coarse, fine, granular, Phosphorus 22.4-33.6 mmol/24hr
waxy Amylase 64.75-490.25 U/L
Crystals Small amounts Mucus thread Small amounts
Epithelial cells Small amounts Microalbumin N: 0.0-0.03 g/d
Bacteria (-) Microalbuminuria: 0.03-0.30 g/d
Mucus thread Small amounts Clinical albuminuria: >0.3 g/d

EQUIVALENT VALUES
To convert to mg/dL Equivalent values of common interventions

PARAMETER FACTOR INTERVENTION EQUIVALENT


RBS (mmol/L) Multiply by 18 1 cc 10% oral KCl 1.33 meqs K+
BUN (mmol/L) Multiply by 2.8 15 cc 10% oral KCl 20 meqs K+
Creatinine (umol/L) Divide by 88.4 30 cc 10% oral KCl 40 meqs K+
Calcium (mmol/L) Divide by 0.25 Kaliumdurule 10 meqs K+
Magnesium (mmol/L) Divide by 0.411 (750mg)
Bilirubin (umol/L) Divide by 17.10 1 medium sized Roughly 7-10 meqs K+
Uric acid (umol/L) Divide by 59.48 banana
HDL or LDL (mmol/L) Divide by 0.0259 NaHCO3 50mL 45 meqs Na+
Triglycerides (mmol/L) Divide by 0.0113 NaHCO3GrX tab 7.7 meqs Na+per tab
(650 mg)
NaCl tab (1g) 17 meqs Na+ per tab
Normal saline 154 meqs Na+per liter
solution (1L)

26
SECTION 4
INTRAVENOUS FLUIDS

INTRAVENOUS FLUIDS AND COMMON INDICATIONS


I. BASIC TYPES OF INTRAVENOUS FLUIDS

IV FLUIDS DESCRIPTIONS EXAMPLES


Balanced salt / electrolyte solutions Normal saline (0.9% NaCl), lactated
Crystalloids which may be isotonic, hypertonic or Ringer’s, hypertonic saline (3, 5, 7.5%),
hypotonic Ringer’s solution
High-molecular weight solutions
which draw fluid into the Albumin, hetastarch, pentastarch,
Colloids intravascular component via oncotic plasma and dextran
pressure
Effective plasma expanders
Provide water that is not bound by D5W (5% dextrose in water), D10W,
Free H2O solutions macromolecules or organelles, thus D20W, D50W, D50-50, dextrose/
is free to pass through membranes crystalloid mixes
Blood products Essentially are also considered Whole blood, pRBC, FFP,
colloids cryoprecipitate, platelet concentrate

II. COMPOSITION OF INTRAVENOUS FLUIDS

IV FLUID Glucose Na+ Cl- K+ CA2+ HCO3 COMMENTS


Useful in dehydrated states and
D5W 50 gm/L hypernatremia
Can be used as diluents
D10W 100 gm/L Used to correct hypoglycemia
0.9 NSS 154 154 Fluid of choice for initial resuscitation
Can be used as diluents
Same as 0.9 NSS but with additional
D5 0.9 NSS 50 gm/L 154 154 glucose
Useful for patients on NPO
LR 130 109 4 3 28 Useful for trauma, surgery and burn
NR 140 98 5 patients
Routine fluid and electrolyte
D5NM 50 gm/L 40 40 13 maintenance with minimal
carbohydrate calories
D5NMK 50 gm/L 40 40 30 Same as D5NM but with additional
potassium content

III. USUAL INDICATIONS FOR IV FLUID ADMINISTRATION

Maintain normal blood pressure: normal or isotonic saline is the initial fluid of choice
Return the intracellular (ICF) volume to normal
o In patients with acute hyponatremia, the ICF volume in the brain rises and could become dangerous high
with more prominent decline in plasma sodium hypertonic saline usually given to raise the plasma
sodium
o When there is a large water deficit in the ICF compartment (e.g. severe hypernatremia), electrolyte-free
water (D5W) is given
Replace ongoing renal losses
Give maintenance fluids to match insensible losses
Provide glucose as fuel substrate for the brain, thereby useful for patients on NPO (dextrose-containing fluids)

27
IV. COMMONLY USED INTRAVENOUS FLUIDS

1. Normal Saline (0,9% NaCl, pNSS)


Least expensive and most commonly used resuscitative crystalloid
High Cl content imposes on the kidneys an excess Cl load that cannot be rapidly excreted risk of
hyperchloremic acidosis
The only solution that may be administered with blood products
Does not provide free water or calories

2. Lactated Ringer’s (LR) Solution


Lactate is converted readily to bicarbonate in the liver
Minimal effects on normal body fluid composition and pH
Most closely resembles the electrolyte composition of normal blood serum
Does not provide calories

3. D5W or ¼ Normal Saline


Provides 170 calories/L from 5% dextrose
Provides free water for insensible losses and some sodium to promote renal function and excretion
With added potassium, this is an excellent maintenance fluid in the immediate postoperative period
Prevents excess catabolism and limits proteolysis

4. Hypertonic Saline (3% NaCl)


1026 mOsm/L, 513 mEq/L Na+
Increases plasma osmolality and thereby acts as a plasma expander, increasing circulatory volume via
movement of intracellular and interstitial water into the intravascular space
Due to high sodium content, poses high risk of hypernatremia

Before proceeding to the next section, here are some general terminologies using drips:

cc/hr equal to mL/hr equal to ugtt/min

ugtt/min (microdrops/min) divided by 4 is EQUAL TO gtt/min (drops/min)

dose (mcg / kg / min) x BW in kg x 60 min


Infusion rate (cc / hr) = solution concentration (mcg / cc)

dose of drug (mcg)_


solution concentration (mcg / cc) = volume of diluent (cc)

28
SECTION 5
COMMONLY USED DRIPS

FORMULATION AND COMPUTATION OF BASIC DRIPS


I. DOPAMINE

Generally used to augment BP and cardiac output in patients with cardiogenic shock
Dopamine releases norepinephrine from nerve terminals, which itself stimulates A1 and B1 receptors
Usually started at an infusion rate of 2-5 mcg/kg/min
Dose is increased every 2-5 minutes to a maximum of 20-50 mcg/kg/min

A. Things to know about Dopamine:

Preparation One ampule contains 200 mg dopamine


Sample order Dopamine drip: 200mg dopamine (1 ampule) + 250 cc D5W to run
for ____ cc/hr
For a formulation of 1 ampule (200mg) in 250 cc D5W factor, used
is 13.3
For a formulation of 2 ampules (400mg) in 250 cc D 5W factor,
Dopamine factor used is 26.6

NOTE: A more concentrated dose is usually chosen for patients who


cannot tolerate fluid overload (e.g. patients with CHF, CKD)

B. Dopamine demonstrates varying Hemodynamic Effects based on the dose

DOSE MECHANISM OF ACTION EFFECT

< 2 mcg/kg/min Activates DA1 and DA2 Renal Vasodilation:


receptors Vasodilation of splanchnic and renal vasculature

Inotropic:
2-10 mcg/kg/min Activates B1-receptors Increase in cardiac output with little or no change in
HR or SVR
Effects on A1-receptors Vasoconstrictor:
> 10 mcg/kg/min overwhelm the dopaminergic Vasoconstriction, leading to increase in SVR, LV
receptors filling pressures, and HR
Source: Fauci, et.al, Harrison’s Principles of Internal Medicine 19th edition, 2015.

C. Computation of Dopamine Drip Rate based on Desired Dose

mcg
Desired dose kg min x Body Weight (kg)
Dopamine drip rate (ugtt/min) = Dopamine factor

D. Sample computation

55/F patient, 45kg, admitted for cardiogenic shock with BP of 80/50 mmHg
If our desired dose is 10mcg/kg/min (chronotropic/inotropic dose) and we decide to give 400mg (2 amps)
dopamine (factor is 26.6), the dopamine rate is computed as follows:
mcg
Dopamine drip rate (ugtt/min) =10 kg min x 45 (kg) = 16.9 = 17 cc/hr = 17 ugtt/min
26.6
Sample chart order:
29
Start dopamine drip: 400mg (2amps dopamine) + 250cc D5W x 17 cc/hr (dose of ~10 mcg/kg/min)
Titrate by 2-3 cc/hr to maintain BP > 90/60
E. Reverse computation: computing for the DOSE of dopamine being administered
Note that when reporting/endorsing a case, it is better to state the dose of dopamine that the patient is
being given and not the drip rate. To compute for the specific dose, use the following formula

Dopamine drip rate ugtt x Dopamine factor


mcg min = min________________
Dopamine dose kg body weight (kg)

Example:
Patient is a 45-kg, 55/F, given 2 amps of Dopamine (200 mg/amp) in 250cc PNSS at a rate of 19 ugtts/min (or
19cc/hr). QUESTION: What is the dose of dopamine being given to the patient?

Dose given (in mcg/kg/min) = rate (in ugtt/min) x 26.6 = 19ugtt/min x 26.6 = 11.23mcg/kg.min
45 kg 45 kg

Answer: 11.23 mcg/kg/min is the dose being given to the patient at a rate of 19 ugtts/min (or 19cc/hr). Since
we are giving 11.23 mcg/kg/min, we have a vasoconstricting effect which is beneficial in a patient with septic
shock. If the patient is still hypotensive, we can increase the ugtt/min (titrate) up 34 ugtt/min (20mcg/kg/min)
for a 45-kg patient (“dopa max”). If still with no response to maximal dopamine dosing, we can start another
inotrope like norepinephrine.

In the computation, we used 26.6 because 2 ampules of dopamine were used for the patient.

F. For quick reference:

1. Dopamine 200 mg + 250 cc D5W preparation

Drip Rate Body Weight in Kg


(ugtt/min or
cc/hr) 40 kg 50 kg 60 kg 70 kg 80 kg 90 kg
2.5 7.5 cc/hr 9.4 cc/hr 11.3 cc/hr 13.1 cc/hr 15.0 cc/hr 16.9 cc/hr
Dose 5.0 15.0 cc/hr 18.8 cc/hr 22.5 cc/hr 26.3 cc/hr 30.0 cc/hr 33.8 cc/hr
(mcg/ 7.5 22.5 cc/hr 28.1 cc/hr 33.8 cc/hr 39.4 cc/hr 45.0 cc/hr 50.6 cc/hr
kg/min) 10.0 30.0 cc/hr 37.5 cc/hr 45.0 cc/hr 52.5 cc/hr 60.0 cc/hr 67.5 cc/hr
15.0 45.0 cc/hr 56.3 cc/hr 67.5 cc/hr 78.8 cc/hr 90.0 cc/hr 101.3 cc/hr
20.0 60.0 cc/hr 75.0 cc/hr 90.0 cc/hr 105.0 cc/hr 120.0 cc/hr 135.0 cc/hr

2. Dopamine 400 mg + 250 cc D5W Preparation

Drip Rate Body Weight in Kg


(ugtt/min or
cc/hr) 40 kg 50 kg 60 kg 70 kg 80 kg 90 kg
2.5 3.8 cc/hr 4.7 cc/hr 5.6 cc/hr 6.6 cc/hr 7.5 cc/hr 8.4 cc/hr
Dose 5.0 7.5 cc/hr 9.4 cc/hr 11.3 cc/hr 13.1 cc/hr 15.0 cc/hr 16.9 cc/hr
(mcg/ 7.5 11.3 cc/hr 14.1 cc/hr 16.9 cc/hr 19.7 cc/hr 22.5 cc/hr 25.3 cc/hr
kg/min) 10.0 15.0 cc/hr 18.8 cc/hr 22.5 cc/hr 26.3 cc/hr 30.0 cc/hr 33.8 cc/hr
15.0 22.5 cc/hr 28.1 cc/hr 33.8 cc/hr 39.4 cc/hr 45.0 cc/hr 50.6 cc/hr
20.0 30.0 cc/hr 37.5 cc/hr 45.0 cc/hr 52.5 cc/hr 60.0 cc/hr 67.5 cc/hr

30
II. DOBUTAMINE
A synthetic sympathomimetic amine with positive inotropic action
Effects are due to selective stimulation of B1 adrenergic receptors

A. Things to know about Dobutamine:

Preparation One ampule contains 250 mg dobutamine


Sample order Dobutamine drip: 250mg dobutamine (1 amp) + 250 cc D5W to run for
___ cc/hr
For a formulation of 1 ampule (250 mg) in 250 cc D 5W, factor used is
16.6
For a formulation of 2 ampules (500 mg) in 250 cc D5W,factor used is
Dobutamine factor 33.2

NOTE: A more complicated dose is usually chosen for patients who cannot
tolerate fluid overload (e.g. patients with CHF, CKD)

B. Effects of Dobutamine (dose-dependent)


Minimal positive chronotropic activity at low doses(2.5 mcg/kg/min) and moderate chronotropic activity at
higher doses
Usually given at 10 mcg/kg/min, however, its vasodilatory effect at this dose precludes its use in patients
with decreased systemic vascular resistance

C. Computation of Dobutamine Drip Rate based on Desired Dose

Desired dose mcg min x Body weight (kg)


Dobutamine Drip Rate (ugtt/min) = kg_____________________
Dobutamine factor

D. Sample computation
60/M patient, 50 kg, in cardiogenic shock from decompensated heart failure with BP of 80/50 mmHg
If our desired dose is 5 mcg/kg/min and we decide to use 500 mg (2 amps) dobutamine (factor is 33.2)

5 mcg min x 50 (kg)


Dobutamine Drip Rate (ugtt/min) = kg_______________ = 7.5 = 8cc/hr = 8 ugtt/min
33.2

Sample chart order:


Start dobutamine drip: 500 mg (2 amps dobutamine) + 250 cc D5W x 8 cc/hr (dose of 5 mcg/kg/min)
Titrate by 2-3 cc/hr to maintain BP >90/60 until 15 cc/hr (~10 mcg/kg/min)

The maximum dose of 15 cc/hr was computed using the dose 10 mcg/kg/min
Note that when endorsing a case, it is better to state the dose of dobutamine that the patient is being
given and not the drip rate
To compute for the specific dose, use the following formula

Dobutamine drip rate ugtt x Dobutamine factor


Dobutamine Dose mcg min = min_____________________
kg body weight (kg)

31
E. For quick reference:

1. Dobutamine 250 mg + 250 cc D5W Preparation

Drip Rate Body Weight in Kg


(ugtt/min or
cc/hr) 40 kg 50 kg 60 kg 70 kg 80 kg 90 kg
2.5 6.0 cc/hr 7.5 cc/hr 9.0 cc/hr 10.5 cc/hr 12.0 cc/hr 13.5 cc/hr
Dose 5.0 12.0 cc/hr 15.0 cc/hr 18.0 cc/hr 21.0 cc/hr 24.0 cc/hr 27.0 cc/hr
(mcg/ 7.5 18.0 cc/hr 22.5 cc/hr 27.0 cc/hr 31.5 cc/hr 36.0 cc/hr 40.5 cc/hr
kg/min) 10.0 24.0 cc/hr 30.0 cc/hr 36.0 cc/hr 42.0 cc/hr 48.0 cc/hr 54.0 cc/hr
15.0 36.0 cc/hr 45.0 cc/hr 54.0 cc/hr 63.0 cc/hr 72.0 cc/hr 81.0 cc/hr
20.0 48.0 cc/hr 60.0 cc/hr 72.0 cc/hr 84.0 cc/hr 96.0 cc/hr 108.0 cc/hr

2. Dobutamine 500 mg + 250 cc D5W Preparation

Drip Rate Body Weight in Kg


(ugtt/min or
cc/hr) 40 kg 50 kg 60 kg 70 kg 80 kg 90 kg
2.5 3.0 cc/hr 3.8 cc/hr 4.5 cc/hr 5.3 cc/hr 6.0 cc/hr 6.8 cc/hr
Dose 5.0 6.0 cc/hr 7.5 cc/hr 9.0 cc/hr 10.5 cc/hr 12.0 cc/hr 13.5 cc/hr
(mcg/ 7.5 9.0 cc/hr 11.3 cc/hr 13.5 cc/hr 15.8 cc/hr 18.0 cc/hr 20.3 cc/hr
kg/min) 10.0 12.0 cc/hr 15.0 cc/hr 18.0 cc/hr 21.0 cc/hr 24.0 cc/hr 27.0 cc/hr
15.0 18.0 cc/hr 22.5 cc/hr 27.0 cc/hr 31.5 cc/hr 36.0 cc/hr 40.5 cc/hr
20.0 24.0 cc/hr 30.0 cc/hr 36.0 cc/hr 42.0 cc/hr 48.0 cc/hr 54.0 cc/hr

III. NORADRENALINE/NOREPINEPHRINE
A potent vasoconstrictor and inotropic stimulant
Despite non-significant improvement in survival compared to patients given dopamine, the relatively safer profile
of norepinephrine makes it a good initial vasopressor therapy
Usually started at a dose of 2 to 4 mcg/minand titrated upward as necessary
If systematic perfusion or systolic pressure cannot be maintained at >90 mmHg with a dose of 15 mcg/min, it is
unlikely that a further increase in dose will be beneficial

A. METHOD 1: Long Method


Step 1: Compute for concentration

EXAMPLE: For 4 mg norepinephrine + 250 cc D5W

stock (mg) x 1000 mcg


Concentration = 250 cc IVF 1 mg 4 mg x 1000 mcg
Concentration = 250 cc 1 mg

Step 2: Compute for infusion rate

mcg / min
Infusion rate cc = dose kg x weight (kg) x 60 min/hr
hr concentration (mcg/cc)

Sample chart order:


To start norepinephrine drip as follows: 4 mg norepinephrine + 250 D 5W x 38 cc/hr (0.2 mcg/kg/min or 10
mcg/min in a 50 kg patient)
Titrate by 5 cc/hr to maintain BP >90/60

32
To compute for the current dose given a certain infusion rate, use the following formula:

Dose mcg / min =Infusion rate (cc/hr) x concentration (mcg/cc)


kg weight (kg) 60 min/hr

B. METHOD 2: Short-Cut Method


Computation for Norepinephrine Drip Rate based on Desired Dose

Desired dose (mcg/min)____


Norepinephrine Drip Rate (ugtt/min) = Norepinephrine factor

Norepinephrine Factor
Norepinephrine drip: 2 mg (1 amp) + 250cc D5W (factor used: 0.133)
Norepinephrine drip: 4 mg (2 amps) + 250cc D5W (factor used: 0.266)
Norepinephrine drip: 8 mg (4 amps) + 250cc D5W (factor used: 0.532)

*A more concentrated dose is usually chosen for patients who cannot tolerate fluid overload

C. For quick reference:


Drip rate Dose (mcg/min)
(ugtt/min or cc/hr) Norepinephrine 2mg + 250 cc D5W Norepinephrine 4mg + 250 cc D5W
Preparation Preparation
5 cc/hr 0.7 mcg/min 1.3 mcg/min
10 cc/hr 1.4 mcg/min 2.7 mcg/min
15 cc/hr 2.0 mcg/min 4.0 mcg/min
20 cc/hr 2.7 mcg/min 5.3 mcg/min
25 cc/hr 3.4 mcg/min 6.7 mcg/min
30 cc/hr 4.0 mcg/min 8.0 mcg/min
40 cc/hr 5.5 mcg/min 10.7 mcg/min
50 cc/hr 6.7 mcg/min 13.3 mcg/min
60 cc/hr 8.0 mcg/min 16.0 mcg/min
70 cc/hr 9.4 mcg/min 18.7 mcg/min
80 cc/hr 10.7 mcg/min 21.3 mcg/min
90 cc/hr 12.0 mcg/min 24.0 mcg/min
100 cc/hr 13.4 mcg/min 26.7 mcg/min

IV. UNFRACTIONED HEPARIN (UFH)


A sulfated polysaccharide usually isolated from mammalian tissues rich in mast cells
Acts as an anticoagulant by activating antithrombin (AT III) and accelerating the rate at which antithrombin inhibits
clotting enzymes, particularly thrombin and factor Xa

A. Usual Formulation of Heparin Drip


Heparin drip: 10,000 units of UFH in enough pNSS to make 100 cc in a soluset (concentration of 10,000
units/100 cc or 100 units/cc)

B. Usual doses for Common Indications


Myocardial infarction = “60-12” 60 units/kg IV push as loading dose then start IV drip at 12 units/kg/hr
Deep vein thrombosis or 80 units/kg IV push as loading does then start IV drip at 18 units/kg/hr
pulmonary embolism = ’80-18”

33
C. Heparin Drip Adjustment:
PTT is ideally monitored every 6 hours (after a dose change) and IV drip adjusted accordingly to reach
target PTT of 1.5-2.5 times the control (46-70 sec)

Raschke’s Protocol

aPTT Heparin Adjustment


<1.2x control 80 u/kg IV bolus then add 4 u/kg/hr to infusion rate
1.2 to 1.5x control 40 u/kg IV bolus then add 2 u/kg/hr to infusion rate
1.5 to 2.3x control No change
2.3 to 3.0x control Decrease infusion rate by 2 u/kg/hr
>3.0x control Discontinue for 1 hour, then decrease infusion rate by 2 u/kg/hr

Mayo Clinic Protocol


aPTT (seconds) Heparin Adjustment
<35 80 u/kg bolus then increase drip rate by 4 u/kg/hr
35-45 40 u/kg bolus then increase drip rate by 2 u/kg/hr
46-70 No change
71-90 Reduce drip rate by 2 u/kg/hr
>90 Withhold heparin for 1 hour then reduce drip rate by 3 u/kg/hr
*Order a PTT 6 hours after any dosage change and adjust accordingly until PTT is therapeutic (~46-70). When two consecutive PTTs are
therapeutic, order PTT every 24 hours

V. INSULIN DRIP (Insulin regimen would depend on the indication)

A. For Hyperkalemia
Insulin causes K+ shift (extracellular potassium goes intracellularly)
Glucose-Insulin (GI) solution: 50 mL of 50% Dextrose in Water (D50-50) + 10 units Regular Insulin in 2-5
minutes
Sample order: Mix 1 amp D50-50 + 10 units Humulin-R IV stat, then q6h x 4 doses

B. For Hyperglycemia
1. Formulation of Insulin drip (depends on physician)
Example (drip 1) 20 units of Insulin (HR) in 100cc pNSS = concentration of 0.2unit/cc (20units/100cc)
Example (drip 2) 50 units of Insulin (HR) in 100cc pNSS = concentration of 0.5unit/cc (50units/100cc)
Example (drip 3) 100 units of Insulin (HR) in 100cc pNSS = concentration of 1unit/cc (100units/100cc)

2. Examples
Example 1: If we decide to give our patient 2 units of insulin per hour (via insulin drip):
For drip 1: give 10 cc per hour (10 cc/hr or 10 gtts/min)
For drip 2: give 4 cc per hour (4 cc/hr or 4 ugtts/min)
For drip 3: give 2 cc per hour (2 cc/hr or 2 ugtts/min)

Example 2: Start drip at 0.1 unit/kg/hr, titrate to desired blood glucose


If the patient is 50kg, start Insulin drip at 5 units/hr. if we decide to use drip #3 form the example
above, the order will be: Insulin drip 100 units HR + 100 cc pNSS at a rate of 5 cc/hr (to deliver 5
units/hr)

V. NICARDIPINE
An intravenous calcium channel blocker used as a first-line agent in the management of hypertensive crises

A. Things to know about Nicardipine:


Preparation One 10 mL ampule contains 10 mg Nicardipine
Drip: 10 mg Nicardipine + 90 mL D5W or pNSS in soluset
Usual formulation
Concentration: 0.1 mg/mL of Nicardipine
Dose Initial dose 5 mg/hr (ex. HPN emergency)

34
5mg/hr = 50 cc/hr (pr 50 ugtt/min)
0.1 mg/cc

Some would give an initial IV bolus prior to starting drip


Titration Titrate by 2,5 mg/hr q15 minutes until target BP is reached
Maximum dose: 15 mg/hr

B. Sample chart order:


Start Nicardipine drip as follows: 10 mg Nicardipine + 90 cc D5W in a soluset x 50 cc/hr, titrate by 2.5 mg/hr every
15 minutes until target BP is reached

VI. NITROGLYCERIN (GLYCERYL TRINITRATE)


Organic nitrate which causes systemic venodilation, decreasing preload and afterload and reducing myocardial
oxygen demand
Also improves coronary collateral circulation

A. Things to know about Nitroglycerin


Preparation One ampule contains 10 mg nitroglycerin
Drip: 10 mg + 90 cc D5W in soluset
Usual formulation
Concentration: 0.1 mg/cc of NTG
100 mcg/cc of NTG
Initial dose 5 mcg/min or 300 mcg/hr
Dose
300 mcg/hr = 3 cc/hr (or 4 uggt/min)
100 mcg/cc
Titration Titrate by 5 mcg.min q5min until pain relief is achieved or BP is controlled

B. Sample chart order:


Start nitroglycerin drip: 10mg nitroglycerin + 90cc D5W in a soluset x 3cc/hr, titrate by 3 cc/hr until chest
pain-free

35
OTHER COMMONLY USED DRIPS
DRUG NAME DOSE PREPARATION HOW TO TITRATE
Amiodarone Continuous infusion: 1 Bolus: 150 mg SIVP Goal is to load 1 g of
(Antiarrhythmic, mg/min for 6hrs, then 0.5 then drip: 150-600 amiodarone within 24
Class III) mg/min infusion mg + 250 cc D5W x hours
16-24 hours
Bolus: 0.5-1 mg SIVP over
Bumetanide 1-2 min Drip: 1 mg + 10 mL Depends on diuretic
(Loop diuretic) Continuous infusion: 1 NSS or D5W response and fluid status
mg/hr
(usually 1 mg/hr or higher)
Bolus: 2-40 mg SIVP x 1-2
Furosemide min Drip: 100 mg + 100 Depends on diuretic
(Loop diuretic) Continuous infusion: 1- mL diluents response and fluid status
10mg/hr
Loading dose: 1 mcg/kg x Drip: 2 mL of Titrate in 0.1 mcg/kg/hr
Dexmedetomedine 10min dexmedetomidine + increments to desired
(A2-Agonist) Continuous infusion: 0.2- 48 mL of 0.9 pNSS level of sedation (max
0.7 mcg/kg/hr (total of 50 mL) dose: 1.5 mcg/kg/hr)
Esmolol Continuous infusion: 50- Drip: 2500 mg + 250 Titrate in 50 mcg/kg/min
(Beta blocker) 200 mcg/kg/min mL diluents increments every four
minutes
May titrate by 1 mg
IsosorbideDinitrate Continuous infusion: 1-5 Drip: 10 mg + 90 mL every 15-30 mins until
(Nitrate) mg/hr diluents chest pain-free (as long
as patient’s BP is
normal)
Rate of infusion should
be reassessed as soon
as basic rhythm appears
Lidocaine Continuous infusion: 1-4 Drip: 1-2 grams + 500 to be stable or at the
(Anti-arrhthymic) mg/min mL diluents (NSS or earliest signs of toxicity.
D5W) It is rarely necessary to
continue IV lidocaine for
prolonged periods
Increase rate by 1 mg/hr
Midazolam Continuous infusion: 1-30 Drip: 125 mg + 125 based on sedation
(Benzodiazepine) mg/min mL diluents (titrate to lowest dose
possible)
Morphine Bolus: 2-4 mg SIVP Drip: 16 mg + 50 cc Depends on type of
(Opioid) Continuous infusion: 1-2 diluent sedation used
mg/hr
Omeprazole Bolus: 40-80 mg IV Bolus: 80 mg IV then Maintain the drip rate
(PPI) Continuous infusion: 8 drip: 40 mg + 90 cc continuously for 72
mg/hr pNSS x 5 hours RTC hours
Pamidronate Continuous infusion: 60-90 Drip: 60-90 mg in 250 Single dose usually
(Biphosphonate) mg IV infusion over 2-24hrs cc pNSS x 2-24 given every 3-4 weeks
hours
Somatostatin Bolus: 250 mcg IV Drip: 3 mg + 250 mL Maintain drip rate
(Splanchnic Continuous infusion: 250 D5W x 12 hours continuously for 72
vasoconstrictor) mcg/hr hours

36
CHAPTER 2
CARDIOLOGY
I. Introduction to Cardiology
II. Approach to Patients with Cardiovascular Conditions
1. Cardiovascular History
2. Cardiovascular Physical Examination
3. The Cardiac Diagnosis
III. Common Conditions in Cardiology
1. Atherosclerosis and Dyslipidemia
2. Hypertension
3. Heart failure
4. Chronic Stable Angina Pectoris
5. Acute Coronary Syndrome
A. Non-ST Elevation Acute Coronary Syndrome
B. ST-elevation Myocardial Infarction
6. Rheumatic Fever
7. Valvular Heart Disease
8. Pericarditis
9. Cardiac tamponade
10. Cardiomyopathy
11. Atrial Fibrillation
12. Peripheral Artery Disease
13. CorPulmonale
37
SECTION 1
INTRODUCTION TO CARDIOLOGY
CARDIOLOGY FORMULAS
STROKE VOLUME (SV)
Volume of blood pumped with each heart beat
Normal range is 55-100mL (for a 70kg man, normal
SV = EDV – ESV is ~70mL)
SV = stroke volume (mL/beat)
EDV = end diastolic volume (N: 65-240 mL)
ESV = end systolic volume (N: 16-143 mL)
EJECTION FRACTION (EF)
EF = SV Most useful index of LV function
Fraction of blood ejected by the LV during systole
EDV EF = ejection fraction
CARDIAC OUTPUT (CO)
Volume of blood being pumped by the heart per
minute
CO = HR X SV Normal CO = 5.0 – 5.5 L/min
CO = cardiac output (L/min)
HR = heart rate (bpm)
BLOOD PRESSURE (BP)

SVR = systematic vascular resistance (resistance


BP = CO x SVR to blood flow through vascular system)

BODY SURFACE AREA (BSA)

Better indicator of metabolic mass than body


BSA = Weight (kg) x Height (cm) weight
3600 BSA = body surface area (m 2)

CARDIAC INDEX (CI)


Marker of cardiac function in relation to BSA, thus
relating heart performance to the size of the
CI = CO individual
BSA Normal CI = 2.6 – 4.2 L/min/m2
If CI < 1.8 L/min/m2 suspect cardiogenic shock
MEAN ARTERIAL PRESSURE (MAP)
Defined as the average arterial pressure during a
single cardiac cycle
SV = EDV – ESV SBP = systolic blood pressure in mmHg
DBP = diastolic blood pressure in mmHg
Normal MAP = > 60mmHg can sustain organ
perfusion (normally 70-110 mmHg)

38
PULSE PRESSURE (PP)
Represents the force that the heart generates each
time it contracts
PP = SP – DP PP = pulse pressure: usually about 30-40 mmHg
SP = systolic pressure (mmHg)
DP = diastolic pressure (mmHg)
Normal PP: if PP < 25% of the systolic value (eg, Low stroke volume, blood loss, aortic stenosis, tamponade)
Wide PP: may reach up to 100mmHg (eg., exercise, atherosclerosis, aortic regurgitation, AV malformation,
hyperthyroidism, aortic dilatation / aneurysm, fever, anemia, pregnancy, anxiety, beri-beri)
MAXIMUM HEART RATE
Maximum HR = 220 – Age Highest HR an individual can achieve without
severe problems through exercise-induced stress

TARGET HEART RATE


Target HR = Maximum HR x 0.85 A specific age-based pulse rate to be maintained
during aerobic exercise to ensure optimal
cardiovascular function

39
SECTION 2
APPROACH TO PATIENTS WITH CARDIOVASCULAR CONDITIONS
CARDIOVASCULAR HISTORY

I. CARDINAL SYMPTOMS OF CARDIOVASCULAR DISEASE


Chest pain or discomfort
Dyspnea, orthopnea, paroxysmal nocturnal dyspnea (PND), wheezing
Palpitations, dizziness, syncope
Cough, hemoptysis
Fatigue, weakness
Pain in extremities with exertion (claudication)

II. COMMON CAUSES OF CHEST PAIN


CONDITION DURATION QUALITY LOCATION ASSOCIATED FEATURES
Cardiac Causes
Retrosternal Precipitated by
Pressure, tightness, Radiation to exertion, exposure to
Angina 2-10 mins squeezing, neck, jaw, cold, psychologic
heaviness, burning shoulders or stress
arms (left)
Similar to angina but Similar to angina but
Unstable Angina 10-20 mins often more severe Similar to angina occurs with low levels
of exertion or at rest
Unrelieved by
Similar to angina but nitroglycerin
Acute MI > 30 mins often more severe Similar to angina May be associated
with evidence of heart
failure or arrhythmia
As described for As described for Late-peaking systolic
Aortic Stenosis Variable angina angina ejection murmur
radiating to carotids
Retrosternal or Relieved by sitting up
toward apex and leaning forward
Pericarditis Hours to days Sharp Left shoulder Pericardial friction rub
and trapezius is present
radiation
Vascular Causes
Anterior chest, Associated with
Acute Aortic Sudden onset of Tearing or ripping often radiating to hypertension and/or
Syndrome unrelenting pain sensation; knife-like the back, underlying connective
(Dissection) between tissue disorder (e.g.,
shoulder blades Marfan syndrome)
Pulmonary Often unilateral, Dyspnea, tachypnea,
Embolism Sudden onset Pressure on the side of tachycardia,
embolism hypotension
Pulmonary Dyspnea
Hypertension Variable Pressure Substernal Signs of increased
venous pressure
Pulmonary Causes
Dyspnea, cough,
Pneumonia or Variable Pleuritic Unilateral, often fever, rales,
Pleuritis localized occasional pleural
friction rub
Spontaneous Sudden onset; Pleuritic Unilateral on Dyspnea
Pneumothorax several hours side of Decreased breath

40
pneumothorax sounds ipsilaterally
Non-Cardiopulmonary Causes
Worsened by
Esophageal 10-60 mins Burning Substernal, postprandial
Reflux epigastric recumbency
Relieved by antacids
Esophageal 2-40 mins Pressure, tightness, Retrosternal Can closely mimic
Spasm burning angina
Peptic Ulcer Prolonged Burning Epigastric. Relieved by food
Substernal intake or antacids
Gallbladder Epigastric, RUQ, May follow meals
Disease Prolonged Aching or colicky substernal Precipitated by fatty
meals
May be reproduced
Costochondritis Variable Aching Sternal by localized or
pinpoint pressure on
exam
Herpes Zoster Variable Sharp or burning Dermatomal Vesicular rash
distribution
Situational factors
Emotional/ Variable; may Variable; may precipitates
Psychiatric be fleeting Variable be retrosternal symptoms
Often with history of
anxiety/depression

CARDIOVASCULAR PHYSICAL EXAMINATION

I. COMMON FINDINGS ON INSPECTION


FINDING REMARKS
Central Cyanosis Cyanosis due to right-to-left shunting, allowing deoxygenated blood to reach
systemic circulation
Peripheral Cyanosis Cyanosis due to reduced extremity blood flow due to small vessel
vasoconstriction
Differential Cyanosis Isolated cyanosis affecting the lower extremities but not the upper (seen in
large PDA)
Homan’s Sign Posterior calf pain on active dorsiflexion of the foot against resistance
(suggestive of DVT)
Kussmaul’s Sign Rise or a lack of JVP with inspiration, associated with constrictive pericarditis
Normally, the venous pressure should fall by at least 3 mmHg with inspiration
Pressure over the upper abdomen (RUQ) for at least 10 seconds
Abdominojugular Reflux Positive response: sustained rise of >3 cm in JVP for at least 15 seconds after
release of the hand

II. COMMON FINDINGS ON PALPATION


FINDING REMARKS
Cardiac Findings
Located in the left 5th ICS, mid-clavicular line
Normal LV Apex Normal apex is a localized systolic outward thrust, less than 2.5 cm in
diameter
LV Enlargement Apical impulse is shifted laterally & downwards
RV Enlargement Sustained systolic lift / heave in the left parasternal area
Peripheral Pulses
PulsusParvus et Tardus A weak and delayed pulse that suggest severe aortic stenosis
Bifid Pulse Two systolic peaks can be appreciated, described in hypertrophic obstructive
cardiomyopathy (HOCM), with inscription of percussion and tidal waves
PulsusParadoxus Refers to a fall in SBP > 10mmHg with inspiration, seen in patients with:
41
pericardial tamponade, massive pulmonary embolism, hemorrhagic shock,
severe obstructive lung disease, tension pneumothorax)
PulsusAlternans Beat-to-beat variability of pulse amplitude seen in severe LV systolic heart
failure

III. COMMON FINDINGS ON AUSCULTATION

A. Heart Sounds
HEART SOUND REMARKS
First Heart Sound (S1) Coincides with closure of the mitral valve and tricuspid valve (Systolic
Pressure)
Caused by the closure of the aortic and pulmonic valves (Diastolic Pressure)
Indicates end of systole (or beginning of diastole)
Best heard at the base; splitting is normally heard
Second Heart Sound (S2) Variations include:
- Widened Interval: RBBB, severe MR
- Narrowly Split or Singular S2: Pulmonary arterial HPN
- Fixed Splitting: ASD secundum
- Paradoxical Splitting: LBBB, RV apical pacing, severe AS, HOCM, MI
Coincides with early diastole or rapid ventricular filling
Third Heart Sound (S3) It is caused by the flow of blood during rapid ventricular filling
Best heard after S2
Coincides with late diastole or atrial systole (atrial contraction/slow ventricular
Fourth Heart Sound (S4) filling)
Diminished ventricular compliance increases resistance to ventricular filling
More common in chronic LCH or active MI

B. Common Auscultatory Areas of the Heart


AREA LOCATION
Aortic Area From the 2nd to 3rd ICS at the right sternal border
Pulmonic Area From the 2nd to 3rd ICS at the left sternal border
Tricuspid Area From the 3rd to 5th ICS at the left sternal border
Mitral Area Near the apex of the heart at the 5th ICS in the left mid-clavicular line

C. Grading of Murmurs
GRADE VOLUME THRILL?
Grade 1 Faint; needs concentration No
Grade 2 Faint but can be heard readily by an experience observer No
Grade 3 Moderately loud No
Grade 4 Loud Yes
Grade 5 Very loud; heard with stethoscope lightly pressed on the skin Yes
Grade 6 Exceptionally loud; heard with stethoscope slightly above the chest wall Yes

D. Common Murmurs
POSSIBLE DIAGNOSIS DESCRIPTION OF MURMUR
Pulmonic / Aortic Stenosis Systolic ejection murmur
Aortic Regurgitation Early diastolic murmur
Tricuspid or Mitral Holosystolic (pansystolic) murmur if chronic
Regurgitation Early systolic murmur if acute
Murmur of TR usually increases with inspiration (Carvallo sign)
Tricuspid or Mitral Stenosis Late diastolic murmur / rumble
Mitral Valve Prolapse Systolic click with mid-to-late systolic murmur

E. Other Sounds
SOUND DESCRIPTION
Opening Snap (OS) High-pitched and occurs after a very short interval following S2
Pericardial Knock From the 2nd to 3rd ICS at the left sternal border
Tumor Plop From the 3rd to 5th ICS at the left sternal border
42
THE CARDIAC DIAGNOSIS
I. COMMON DIAGNOSTIC TESTS IN CARDIOLOGY

DIAGNOSTIC REMARKS
Chest Radiograph (CXR) Widely used to visualize the heart and lungs
12 Lead ECG Graphic recording of electric potentials generated by the heart to detect
arrhythmias, conduction disturbances and ischemia
Holter Monitoring Continuous ECG rhythm pattern for 24 hours or more to document
paroxysmal rhythm abnormalities
Non-invasive tool to evaluate the cardiovascular system’s response to stress
under controlled conditions:
Stress Testing o Exercise stress test: least invasive, makes use of a treadmill
o Pharmacologic stress test: drugs are used to induce stress (e.g.,
dobutamines)
Electrophysiological test of the heart involving intracardiac catheters with
Electrophysiology Study (EPS) electrodes probing the endocardium to test conduction pathways and
electrical activity
Transthoracic Uses ultrasound waves to visualize heart chambers and valves
Echocardiography (TTE) Using Doppler studies, it can visualize blood flow through the heart
Transesophageal Echocardiography that uses a specialized probe with an ultrasound
Echocardiography (TEE) transducer introduced into the esophagus to more accurately visualize
posterior structures
Cardiac Magnetic Resonance Differentiates soft tissues better than CT and allows comprehensive exams
Imaging (MRI) for assessment of size, morphology, function and tissue characteristics
Computed Tomography Displays vessels in the body (e.g., coronaries, aorta)
Angiography (CTA) May also be used to detect calcium in the coronary arteries
Uses radioisotopes (Technetium, Thallium) taken up by viable myocardial
Nuclear Imaging cells to assess myocardial perfusion, viability & function (ischemic
myocardium takes up less isotope)
Intravascular Ultrasound Percutaneous procedure that uses catheters to visualize the lumen and the
interior wall of blood vessels
Coronary Angiography Determines the patency and configuration of the coronary artery lumen by
injecting contrast material into the coronary arteries
Uses invasive monitoring and blood sampling through a catheter inserted into
Cardiac Catheterization the heart to determine function, pressures, oxygenation, flow and volume of
blood within the chambers and great vessels

II. MAKING A CARDIAC DIAGNOSIS


COMPONENT IMPORTANT QUESTIONS
1. Underlying Etiology Congenital, hypertensive, ischemic or inflammatory?
Which chambers are involved? Are they hypertrophied, dilated or both?
2. Anatomic Abnormalities Which valves are affected? Are they regurgitant and/or stenotic?
Is there pericardial involvement?
Has there been a myocardial infarction?
3. Physiologic Disturbances Is an arrhythmia present?
Is there evidence of congestive heart failure or of myocardial ischemia?
4. Functional Disability How strenuous is the physical activity required to elicit symptoms?

Example:
Ischemic Heart Disease, Chronic Stable Angina Pectoris, CCS 3
Congestive Heart Failure NYHA FC III, in Sinus Rhythm

43
SECTION 3
COMMON CONDITIONS IN CARDIOLOGY
ATHEROSCLEROSIS AND DYSLIPIDEMIA

I. THE LIPID PROFILE

A. Total Cholesterol

TC = HDL + Non HDL TC = total cholesterol in mg/dL


HDL = high density lipoprotein in mg/dL
TC = HDL + [LDL + VLDL] LDL = low density lipoprotein in mg/dL
VLDL = very low density lipoprotein in mg/dL (estimated by dividing TG
TC = HDL + LDL + TG level by 5)
5 TG = triglycerides in mg/dL

B. Individual Components
1. High Density Lipoproteins (HDL)
Removes cholesterol from peripheral tissues via the reverse cholesterol transport
Low HDL values < 40 mg/dL increased risk for heart disease

2. Non-High Density Lipoproteins (Non-HDL)


Includes low density lipoproteins (LDL) and very low density lipoproteins (VLDL)
Lower non-HDL cholesterol is desirable and is associated with a lower risk of heart disease
Value can be estimated from other lipid values when non-HDL level is not directly available:
NonHDL = TC – HDL
If VLDL values are not given, it can be
NonHDL = LDL + VLDL estimated by dividing triglyceride levels by 5
Non-HDL are ApoB-100 containing
NonHDL = LDL + TG atherogenic lipoproteins
5

C. The Lipoproteins
Composed of varying proportions of cholesterol, triglycerides and phospholipids
LDL and HDL carry most cholesterol
LIPOPROTEIN REMARKS
Chylomicron Delivers dietary triglyceride to peripheral tissues
Delivers cholesterol to the liver in the form of chylomicron remnants
Delivers hepatic triglycerides to peripheral tissues (TG > cholesterol
VLDL esters)
Secreted by the liver
Formed in the degradation of VLDL
IDL Delivers triglycerides and cholesterol to the liver, where they are
degraded into LDL
Delivers hepatic cholesterol to peripheral tissues
LDL Formed by lipoprotein lipase modification of VLDL in the peripheral
tissues
HDL Mediates reverse cholesterol transport (from periphery back to the liver)

II. THE ACC/AHA 2013 GUIDELINES ON THE TREATMENT OF BLOOD CHOLESTEROL


Statin therapy is recommended for individuals at increased atherosclerotic cardiovascular disease (ASCVD) risk
who are most likely to experience a net benefit (benefit>harm)
There is insufficient evidence to support continued use of specific LDL-C and/or non-HDL-C treatment “targets”
Appropriate intensity of statin therapy should be used to reduce risk in those most likely to benefit

44
Non-statin therapies (e.g., fibrates, niacin), whether alone or in addition to statins, provide little benefit in risk
reduction

A. Four Major Statin Benefits Groups (ASCVD risk reduction outweighs risk of adverse events)
1. Acute coronary syndrome or history of MI
1 Patients with clinical ASCVD 2. Stable or unstable angina
3. Coronary or other arterial revascularization
4. Stroke, TIA or PAD
2 Primary elevations of LDL-cholesterol > 190mg/dL
3 Patients 40-75 years + LDL 70-189 mg/dL + Diabetes (without clinical ASCVD)
4 Patients 40-75 years + LDL 70-189 mg/dL + Estimated 10-year ASCVD risk > 7.5%
(without clinical ASCVD or diabetes)

B. Pooled Cohort Equations for ASCVD Risk Reduction


For the fourth group, risk prediction is done by using the pooled cohort equations for ASCVD risk prediction
(developed by the Risk Assessment Work Group)
Calculator is not appropriate for those with known ASCVD
Calculator is available online at http://tools.cardiosource.org/ASCVD-Risk-Estimator/

Computes for hard ASCVD events, including:

o Non-fatal MI
o Death due to coronary heart disease (CHD)
o Fatal or non-fatal stroke

Data includes:
o Age, sex and race
o Total cholesterol and HDL levels
o Systolic BP
o Treatment for hypertension
o Diabetes
o Smoking history

C. Major Recommendations for Statin Therapy for ASCVD Prevention

Clinical ASCVD LDL > 190 mg/dL Diabetes + 40-75

Age > 75 High Intensity Statin


(Class I) 10 year ASCVD risk >
7.5% and Age 40-75

Moderate Intensity Statin


(Class II) Moderate Intensity
Statin if risk is 5 to
<7.5%
(Class IIa)
High Intensity Statin if 10
year ASCVD Risk > 7.5%
(Class IIa)

45
D. Intensity of Statin Therapy
HIGH-INTENSITY THERAPY MODERATE-INTENSITY THERAPY LOW-INTENSITY THERAPY
Daily dose lowers LDL by > 50% Daily dose lowers LDL by 30 to <50% Daily dose lowers LDL by < 30%
Atorvastatin 10-20 mg
Rosuvastatin 10 mg Simvastatin 10 mg
Atorvastatin 40-80 mg Simvastatin 20-40 mg Pravastatin 10-20 mg
Rosuvastatin 20 mg Pravastatin 40 mg Lovastatin 20 mg
Lovastatin 40 mg Fluvastatin 20-40 mg
Fluvastatin XL 80 mg Pitavastatin 1 mg
Pitavastatin 2-4 mg
INDICATED FOR
Primary Prevention
For 40-75 yrs + LDL 70-189 For 40-75 yrs + LDL 70-189 mg/dL:
mg/dL: With diabetes* , or
With diabetes and > With 5 to <7.5% 10-year risk
7.5% 10-year risk* (without ASCVD or MI)
> 7.5% 10-year ASCVD risk Individualized (e.g., patients who
For LDL-C >190 mg/dL: (without ASCVD or DM); recover from mid-to-moderate
> 21 years + primary moderate-to-high intensity muscle symptoms with higher
LDL-C > 190 mg/dL (risk doses of statins)
estimation is not Individuals in whom high-density statin
required) therapy would be recommended but
have characteristics predisposing them
to statin-associated adverse effects**
Secondary Prevention
< 75 years + clinical > 75 years or safety concerns +
ASCVD clinical ASCVD
*For patients 40-75 years old with LDL 70-189 mg/dL and DM, moderate- (class I recommendation) or high-intensity (class Iia
recommendation if risk for ASCVD is >7.5%) may be considered, depending on the risk-benefit ratio.

**Multiple or serious comorbidities, including impaired renal or hepatic function; history of previous statin intolerance or muscle disorders;
unexplained alanine aminotransferase (ALT) elevations > 3 times the upper limit of normal (ULN); patient characteristics or concomitant use of
drugs affecting statin metabolism; age > 75 years

E. Monitoring
Fasting lipid profile within 4-12 weeks after initiation or dose adjustment and every 3-12 months thereafter
Indicators of anticipated therapeutic response to the recommended intensity of statin therapy (focus is on
the intensity of the statin therapy as an aid to monitoring):
o High-intensity statin therapy: LDL-C reduction of > 50% from the untreated baseline.
o Moderate-intensity statin therapy: LDL-C reduction of 30% to <50% from the untreated baseline.

III. MANAGEMENT

A. Non-Pharmacologic Management (ACC/AHA 2013 Guide for Lifestyle Management for Reducing CV Risk)

1. Diet
High in fruits and vegetables, whole grains; low fat; limit sweets
DASH diet (Dietary Approaches to Stop Hypertension):
o Rich in fruits, vegetables, whole grains, and low-fat dairy foods
o Meat, fish, poultry, nuts and beans
o Limited in sugar-sweetened foods and beverages, red meat, and added fats

2. Physical Activity
3-4 sessions a week, lasting 40 minutes per session
Moderate-to-vigorous intensity physical activity

46
B. Pharmacologic Management

DRUGS MECHANISM OF ACTION LABORATOTY FEATURES ADVERSE EFFECTS


HMG-CoA reductase 1st line of treatment
inhibitor 20-60% LDL reduction Myositis / myopathy
Statins Inhibits melavonate: Doubling of dose: 6% Reversible elevation of
cholesterol precursor additional lowering of AST / ALT
LDL
Ezetimibe Cholesterol absorption 15-20% LDL reduction May increase AST /
inhibitor ALT
Bile acid sequestrant Bad taste, GI
Prevents intestinal discomfort
reabsorption of bile Modest LDL reduction Decreased absorption
Cholestyramine acids, this forcing liver Can increase of fat-soluble vitamins
to use cholesterol to triglycerides Contraindicated if
make more bile acids triglycerides >200
as replacement mg/dL (relative) or 500
mg/dL (absolute)
Upregulates lipoprotein Myositis (increased
Fibrates lipase which increases 35-50% fasting risk if with concomitant
(Gemfibrozil, hydrolysis of VLDL and triglyceride reduction statin use)
Fenofibrate) chylomicrons Increase in AST / ALT
Most common: nausea
Reduces hepatic VLDL
Enhances activity of secretion into Flushing
lipoprotein lipase, circulation and Hyperuricemia
Niacin leading to decreased increases HDL Impaired glucose
VLDL and triglyceride significantly tolerance
levels Only agent proven to
raise HDL levels
Unclear, but it is
thought to decrease Primary use: lower
Omega-3-Fatty catabolism of triglyceride levels (by Bad / fishy taste
Acids (“Fish Oil”) chylomicrons and reducing triglyceride Dyspepsia
increase affinity of LDL synthesis in the liver)
uptake
Increases rate of LDL Reduces LDL levels Can reduce HDL
Probucol catabolism with strong Can reduce HDL levels QT interval
anti-oxidant properties

F. Potency Equivalence of Statins


DOSE OF AGENTS (mg) PERCENT REDUCTION
Rosuvastatin Atorvastatin Simvastatin Pravastatin Total Cholesterol LDL-C
10 20 22% 27%
10 20 40 27% 36%
5 20 40 32% 42%
10 40 80 37% 48%
20 80 42% 54%
Stained doses on same rows are equipotent
(e.g., Rosuvastatin 10 mg is equivalent to atorvastatin 40 mg and both reduce LDL by 48%)

47
HYPERTENSION

I. DIAGNOSIS OF HYPERTENSION
Two or more elevated readings on at least 2 clinic visits over a period of one to several weeks
Definition – adults with:
o SBP > 140 mmHg, or
o DBP > 90 mmHg

II. CLASSIFICATION OF HYPERTENSION

A. Classification as to Etiology
Primary / Essential (most common)
Secondary Hypertension

B. Clues for Suspecting Secondary Hypertension


Age of onset <20 or >50 years
No family history of HPN
DBP >100-120 mmHg
Sudden increase in BP in a patient with stable Stage I HPN
Poor BP control, despite good compliance
Systemic findings (e.g. weight loss/gain, potassium abnormalities)

C. Classification as to Stages
CLASSIFICATION SYSTOLIC (mmHg) DIASTOLIC (mmHg)
Normal <120 and <80
Pre-hypertension 120-139 or 80-89
Stage 1 Hypertension 140-159 or 90-99
Stage 2 Hypertension > 160 or > 100
Isolated Systolic Hypertension > 140 and <90

D. Definition of Terms
VARIATION DESCRIPTION
At least three separate clinic-based measurements >140/90 mmHg and at least
White Coat Hypertension two non-clinic-based measurements <140/90 mmHg in absence of any evident of
target organ damage
Resistant Hypertension Defined as high BP uncontrolled with three drugs or controlled with at least four
anti-hypertensive drugs (including a diuretic)
Orthostatic Hypotension Fall in SBP >20 mmHg or in DBP >10 mmHg in response to assumption of the
upright posture from a supine position within 3 minutes

III. THE EIGHT JOINT NATIONAL COMMITTEE (JNC-8): MANAGEMENT OF HYPERTENSION

A. Simplified Algorithm

Any Age Any Age


Age > 60 Age < 60 (+) Diabetes (+/-) Diabetes
(-) CKD (-) CKD

BP Goal BP Goal BP Goal BP Goal


<150 / <90 <140 / <90 < 140 / <90 < 140 / <90

Initial Drug Initial Drug


Thiazide, or ACEI ACEI or ARB
or ARB, or CCB 48
B. Summary of the JNC-8 Recommendations on Management of Hypertension
RECOMMENDATION PATIENT POPULATION INITIATE THERAPY WHEN GOAL BLOOD PRESSURE
No. 1 Patients > 60 years old SBP > 150 mmHg or SBP < 150 mmHg and
DBP > 90 mmHg DBP < 90 mmHg
No. 2 Patients < 60 years old DBP > 90 mmHg DBP < 90 mmHg
No. 3 SBP > 140 mmHg SBP < 140 mmHg
Patients > 18 years old with SBP > 140 mmHg or SBP < 140 mmHg and
No. 4 CKD DBP > 90 mmHg DBP < 90 mmHg

No. 5 Patients > 18 years old with SBP > 140 mmHg or SBP < 140 mmHg and
DM DBP > 90 mmHg DBP < 90 mmHg
RECOMMENDATION PATIENT POPULATION INITIAL ANTIHYPERTENSIVE AGENT OPTIONS
No. 6 Non-black population Thiazide-type diuretic
(including those with DM) Calcium channel blocker (CCB)
Angiotensin-converting enzyme inhibitor (ACEI)
Angiotensin receptor blocker (ARB)
No. 7 General black population Thiazide-type diuretic
(including those with DM) Calcium channel blocker (CCB)
Patients > 18 years old with Angiotensin-converting enzyme inhibitor (ACEI)
No. 8 CKD (regardless of race or Angiotensin receptor blocker (ARB)
DM status)
The main objective of hypertension treatment is to attain and maintain goal BP:
If goal BP is not reached within a month, increase the dose of the initial drug or add
a second drug (thiazide-type diuretic, CCB, ACEI or ARB)
No. 9 If goal BP cannot be reached with 2 drugs, add and titrate a third drug from the list
Do not use an ACEI and an ARB together in the same patient
If goal BP cannot be reached using only the drugs in recommendation 6 because
of a contraindication or the need to use more than 3 drugs to reach goal, other
classes can be used

IV. MANAGEMENT OF HYPERTENSION

A. Screening for Hypertension:


Us Preventive Services Task Force recommends screening for high blood pressure in adults > 18 years old
Screening:
o Every 2 years if BP < 120/80 (normal)
o Yearly if BP 120-139 / 80-89 (pre-hypertensive)

B. Non-Pharmacologic Management: Lifestyle Management for Hypertension


ASPECT GOAL
Weight Reduction Attain and maintain BMI < 25 kg/m 2
Dietary Salt Reduction < 6 g NaCl/day
Adapt DASH-type Dietary Plan Diet rich in fruits, vegetables, and low-fat dairy products
Reduced content of saturated and total fat
Moderation of Alcohol For those who drink alcohol, consume:
Consumption o < 2 drinks/day in men
o <1 drink/day in women
Physical Activity Regular aerobic activity (e.g., brisk walking for 30 mins/ day)

C. Common Drugs for Hypertension


REPRESENTATIVE
CLASS MECHANISM OF ACTION ADVERSE EFFECTS DRUGS WITH DOSE
RANGE
mg/day (doses per day)
Diuretics
Thiazide diuretics Selectively of Na/Cl Sexual impotence Hydrochlorothiazide
symporter which Hypokalemia 6.25-50 mg OD
49
acts on the distal Dyslipidemia Metolazone 2.5-5
convoluted tubules, Hyperuricemia mg OD
leading to enhanced Hyperglycemia Indapamide 1.5mg
NaCl excretion OD
Hypokalemia Furosemide 40-80
Acts on the thick Metabolic alkalosis mg OD
Loop diuretics ascending limb of Ototoxicity Bumetanide 0.5-2
the Loop of Henle Hypocalcemia mg OD
hypomagnesemia Ethacrynic Acid 25-
100 mg BID
Spironolactone Spironolactone
antagonizes action 12.5-100 mg OD
of aldosterone Hyperkalemia Amiloride 5-20 mg
Potassium-Saving Triamterene & Gynecomastia (only OD
diuretics amiloride inhibit Na- for spironolactone) Eplerenone 25-100
K exchange mg OD-BID
mechanism Triamterene 25-100
mg OD
Beta Blockers (BB)
Atenolol 25-100 mg
OD
Metoprolol 50-400
Selectively inhibits mg/day
Cardioselective BB (B1) B1-Receptors (less Metoprolol XL 50-
pulmonary effects) 200 mg OD
Bronchospasm Bisoprolol 2.5-20
Bradycardia mg OD
AV block Esmolol IV
Metabolic syndrome Propanolol 40-180
Non-Selective BB (B1/B2) Inhibits both B1 and Glucose intolerance mg BID-TID
B2 receptors Sleep disturbance Others: Pindolol,
Depression Timolol, Nadolol
Combined A1 & B- Cardvedilol 6.25-25
adrenergic receptor mg BID
Vasodilating BB (A1/B) blockade Nebivolol 5-10 mg
Nebivolol: additional OD
nitric oxide Others: Labetolol
potentiating effect
Calcium Channel Blockers (CCB)
Amlodipine 2.5-10
Blocks L-type Tachyarrhythmia mg OD
Dihydropyridine calcium channels Edema Felodipine 2.5-20
Vascular effect > Headaches mg/OD
AV-node effect Nifedipine 30-120
mg/day
Blocks L-type AV block (2nd and Diltiazem 120-360
calcium channels 3rd degree) mg/day
Non-Dihydropyridine AV node effect > Trifascicular block Verapamil 120-480
vascular effect Severe LV mg/day
dysfunction
Drugs Acting on the Renin-Angiotensin-Aldosterone-System (RAAS)
Captopril 25-150 mg
Inhibits ACE Cough BID-TID
Result: angiotensin- Angioedema Enalapril 2.5-20
ACE-Inhibitors I is not converted to Hyperkalemia mg/day
angiontensin-II Renal agenesis Lisinopril 5-20
mg/day
Perindopril 2.5-10
50
mg/day
Ramipril 2.5-10 mg
OD
Candesartan 8-32
mg OD
Irbesartan 150-300
mg OD
Hyperkalemia Losartan 25-100 mg
Angiotensin Receptor Competitive Renal agenesis OD
Blockers antagonism with Less cough and Olmesartan 5-40
angiotensin-II angioedema mg OD
Telmisartan 20-80
mg OD
Valsartan 80-320
mg OD
Directly inhibits Angioedema
Direct Renin Inhibitor rennin, the first Hyperkalemia Aliskiren 75-300 mg
enzyme in the Cough OD
RAAS Hyperuricemia
Other Anti-Hypertensives
Blocks the Prazosin 1-5
postsynaptic A1- Postural mg/day
Alpha Blockers receptors found in hypotension Terazosin 1-5
capacitance & Reflex tachycardia mg/day
resistance vessels Doxazosin 1-8 mg
OD
Sedation Clonidine 75-150
Activation of A2- Xerostomia mcg BID-TID
Central Sympatholytics receptors in the Impotence Methyldopa 250-
CNS CNS side effects 500 mg BID-TID
Rebound HPN on
withdrawal
Reflex tachycardia
Headache Hyrdrazaline 25 mg
Release of nitric Hypotension TID
Direct Vasodilators oxide, leading to Lupus-like Minoxidil 2.5-80
arterial vasodilation syndrome (for mg/day
hydralazine)
Hypertrichosis (for
minoxidil)

V. MANAGEMENT OF UNCONTROLLED HYPERTENSION

A. Differentiation Between Types of Uncontrolled Hypertension

SEVERE HYPERTENSION HYPERTENSIVE URGENCY HYPERTENSIVE CRISIS


Usual BP 180-220 / 110-130 mmHg >220/130 mmHg > 220/130 mmHg
Actual Target None (asymptomatic) None Present (brain, heart,
Organ Damage kidney, retina or vessels)
Long-acting oral medication can
Management simple be restarted (usually Short-acting oral medications Immediate reduction of BP
occurs in chronic hypertensives with intravenous medication
who stopped taking medication)
Monitoring Require outpatient follow-up Require outpatient follow-up Admit for monitoring (ICU)
within 24-72 hours within 24 to 72 hours

51
B. Common Intravenous (IV) Drugs for Hypertensive Emergencies
DRUG DOSE CONTRAINDICATIONS & SIDE EFFECTS
5-15 mg/hr as continuous infusion
Nicardipine Starting dose 5 mg/hr, increase q15- Liver failure
30 mins by 2.5 mg until goal BP
achieved
Nitroglycerin 5-200 ug/min Can cause headaches
5 ug/min increase q5 mins
0.3-10 ug/kg/min, increase by 0.5 Liver/kidney failure
Nitroprusside ug/kg/min q5 mins until goal BP Can cause cyanide toxicity
achieved
Esmolol 0.5-10 ug/kg/min as bolus 2nd or 3rd degree AV block, systolic
500-300 ug/kg/min as infusion heart failure, bradycardia, COPD
Labetalol 0.25-0.5 mg/kg; 2-4 mg/min until goal 2nd or 3rd degree AV block, systolic
BP is reached, thereafter 5-20 mg/hr heart failure, bradycardia, COPD

C. Recommended Treatment of Hypertensive Emergencies Based on End-Organ Involvement


TYPE OF EMERGENCY TIMELINE, TARGET BP THERAPY*
HPN Crisis with Several hours Labetalol, Nitroprusside,
Retinopathy or Acute Target MAP: decrease by 20% t0 25% Nicardipine
Renal Insufficiency
HPN Encephalopathy Immediate Labetalol, Nicardipine,
Target MAP: decrease by 20% to 25% Nitroprusside
Acute Aortic Dissection Immediate Nitroprusside + Metoprolol,
Target SBP < 110 mmHg Labetalol
Acute Pulmonary Edema Immediate Nitroprusside + Loop
Target MAP: 60-100 mmHg Diuretic, Nitroglycerin
Acute Coronary Syndrome 1 hour Nitroglycerin, Labetalol
Target MAP: 60-100 mmHg
Acute Ischemic Stroke and 1 hour Labetalol, Nicardipine,
BP > 220/120 mmHg Target MAP: decrease by 5% Nitroprusside
Cerebral Hemorrhage and 1 hour Labetalol, Nicardipine,
SBP > 180 mmHg or MAP > Target SBP: < 180 mmHg and MAP 130 Nitroprusside
130 mmHg mmHg
Several hours Phentolamine (after
Cocaine intoxication Target SBP: < 140 mmHg benzodiazepines),
Nitroprusside
Labetalol + MgSO4 and oral
Severe preeclampsia/ Immediate anti-HPN, Nicardipine
eclampsia Target BP: < 160/105 mmHg Emergency Delivery of
Fetus
*Those underlined: first-line therapy

VI. HYPERTENSION AND PREGNANCY


Four categories of hypertension in pregnancy:
1. Pre-eclampsia: severe progressive multisystem disorder diagnosed by hypertension accompanied by any one
of the following:
o Proteinuria
o BP of 160/110 mmHg or higher despite bed rest
o Thrombocytopenia
o Impaired liver function
o Progressive renal insufficiency
o Pulmonary edema
o New-onset cerebral or visual disturbance
2. Chronic hypertension: hypertension predating pregnancy
3. Chronic hypertension with superimposed preeclampsia
4. Gestational hypertension: BP elevation after 20 weeks gestation in the absence of the additional systemic
features listed above
52
HEART FAILURE (HF)
I. ETIOPATHOGENESIS
A clinical syndrome consisting of a constellation of clinical symptoms (dyspnea & fatigue) and signs (edema and
rales) that lead to frequent hospitalization, a poor quality of life, and a shortened life expectancy.
Etiologies:
o Coronary artery disease (CAD): most common cause of HF in industrialized countries (60-75%)
o Hypertension: cause of HF in 75% of patients
o Idiopathic cardiomyopathy: 20-30% of depressed EF HF
o Pulmonary heart disease: cor pulmonale, pulmonary vascular disorders
o High output states: thyrotoxicosis, nutritional disorders (beriberi), excessive blood flow requirements,
chronic asthma

II. CLASSIFICATION / STAGES OF HEART FAILURE (HF)

A. Classification Based on Function / Ejection Fraction (EF)


TYPE EJECTION DESCRIPTION COMMON EXAMPLES
FRACTION
Progressive disorder initiated by an
Systolic Heart Depressed HF index event (e.g., MI, volume CAD (e.g., MI)
Failure or HF with < 40% overload, chronic anemia) that leads Dilated cardiomyopathy
reduced EF (HfrEF) to a decline in the pumping capacity Valvular heart disease
of the heart
Proposed mechanisms include
Diastolic Heart diastolic dysfunction and extra- Pathologic hypertrophy
Failure or HF with Preserved EF cardiac mechanisms such as (HOCM, HPN)
preserved EF > 40-50% increased vascular stiffness and Aging, fibrosis
(HfpEF) impaired renal function (still Restrictive cardiomyopathy
undefined and evolving)
Occur when the body’s requirements Thyrotoxicosis
Normal at first, then for oxygen and nutrients are Beriberi
High-Output Heart may decrease over increased and the demand outstrips Chronic anemia
Failure time what the heart can provide Systemic arteriovenous
shunting

B. American College of Cardiology / American Heart Association (ACC/AHA) Stages of Heart Failure
STAGE DESCRIPTION EXAMPLES
A At high risk for HF but without structural heart Patients with HPN, CAD, DM or patients using
disease or HF symptoms cardiotoxins or with family history of cardiomyopathy
B Structural heart disease but without signs or Patients with previous MI, LV systolic dysfunction, or
symptoms of HF asymptomatic valvular disease
C Structural heart disease with previous or Patients with known structural heart disease with
current symptoms of HF shortness of breath, fatigue, reduced exercise tolerance
Refractory HF requiring specialized Patient who have marked symptoms at rest despite
interventions maximal therapy (e.g., patients with recurrent
D hospitalizations or cannot be safely discharged without
special interventions)

C. New York Heart Association (NYHA) Functional Classification


NYHA DESCRIPTION COMMENTS
I Symptoms occur with greater than ordinary No limitation of physical activity
physical activity Can climb > 2 flights of stairs with ease
II Symptoms occur with ordinary physical activity Slight limitation of physical activity
Can climb 2 flights of stairs but with difficulty
III Symptoms occur with less than ordinary Marked limitation of physical activity
physical activity Can climb <1 flight of stairs
IV Symptoms may be present even at rest Unable to carry on activity without symptoms
Dyspnea at rest
53
III. CLINICAL MANIFESTATIONS

A. Symptoms
Fatigue and Shortness of Cardinal symptoms
Breath Due to pulmonary congestion juxtacapillary J-receptors are activated
cardiac dyspnea
Orthopnea/Nocturnal Cough Redistribution of fluid from splanchnic and lower extremity into the central
circulation on recumbency
Paroxysmal Nocturnal Severe dyspnea that awakens patient from sleep 1-3 hours after patient retires
Dyspnea Increased pressure in the bronchial arteries
Cheyne-Stokes Respiration In 40% of advanced HF: series of apnea hyperventilation hypocapnia
Diminished sensitivity of the respiratory center to arterial PCO2
GI: anorexia, nausea, early satiety, abdominal fullness which may be due to
Others congested liver and/or bowels
CNS: confusion, disorientation, sleep and mood disturbance may be due to
reduced cerebral perfusion

B. Signs
General Appearance and Uncomfortable when lying flat, labored breathing
Vital Signs Normal or low BP
Cardiac cachexia
Although essential, frequently does not provide information on the severity of
HF
JVP may be > 8 cm H2O
Cardiovascular Sinus tachycardia due to increased adrenergic activity
Point of maximal impulse displaced due to cardiomegaly
S3 (protodiastolic gallop) at the apex: usually in volume overloaded patients
S4: usually in diastolic dysfunction
Crackles: transudation of fluid from intravascular space to alveoli
Pulmonary Expiratory wheezes: cardiac wheezing caused by peribronchial cuffing from
congestion
Pleural effusions: often bilateral; if unilateral, more often on the right
Hepatomegaly with pulsation (if with significant TR)
Abdomen Ascites: increased pressure in the hepatic veins
Jaundice: impairment of hepatic function due to congestion
Peripheral edema: ankles and pre-tibial region
Extremities Indurated and pigmented skin: long standing edema
Peripheral vasoconstriction: cool extremities

IV. DIAGNOSIS OF HEART FAILURE


The diagnosis of HF is straightforward when the patients presents with classic signs and symptoms
Key to diagnosis is a high index of suspicion

A. Framingham Criteria for Heart Failure


MAJOR CRITERIA MINOR CRITERIA
Paroxysmal nocturnal dyspnea (PND) or orthopnea Ankle edema
Neck vein distention Night cough
Rales Dyspnea on exertion
Cardiomegaly Hepatomegaly
Acute pulmonary edema Pleural effusion
S3 gallop Vital capacity decreased by 1/3 from maximal
Increased venous pressure > 16 cm H2O capacity
Hepatojugular reflux Tachycardia > 120 bpm
Major or Minor Criteria: Weight loss > 4.5 kg in 5 days in response to treatment
The diagnosis of HF requires simultaneous presence of at least:
1 Major Criteria, or
1 Major Criterion + 2 Minor Criterion
54
(use of minor criteria acceptable only if they cannot be attributed to another medical condition, such as pulmonary HPN, chronic lung disease, cirrhosis, ascites, nephrotic
syndrome)

B. Diagnostics in HF
DIAGNOSTICS DESCRIPTION
2D Echocardiography with Most useful test, evaluation of ejection fraction (EF)
Doppler Semi-quantitative assessment of LV size, function, wall motion abnormalities,
valvular defects
12-L ECG Assess cardiac rhythm, LV hypertrophy, prior MI
A normal ECG virtually excludes LV systolic dysfunction
Chest Radiography Assess the cardiac size and shape and state of pulmonary vasculature
Identify non-cardiac causes of symptoms
Cardiac Biomarkers (BNP) Relatively sensitive markers for the presence of HF
Increase with age and renal impairment
Complete Blood Count Look for anemia, signs of infection, and bleeding (may precipitate / worsen HF)
Serum Electrolytes, BUN, Assess for electrolyte disturbances, beginning cardiorenal syndrome, ischemic
Crea, AST, ALT hepatitis or chronic passive congestion of the liver
FBS, OGTT Assess for diabetes
Lipid Profile Assess for dyslipidemia
FT4, TSH Assess for thyroid hormone abnormalities

V. MANAGEMENT OF HEART FAILURE

A. Non-Pharmacologic Management and Basic Principles


Sodium restriction: limit Na+ intake to 2-3 g/day in all patients with HF; and to less than 2 g/day in patients with
moderate to severe HF
Fluid restriction: generally unnecessary unless with hyponatremia (< 130 mEq/L) and volume overload
Caloric supplement: for those with cardiac cachexia

B. Pharmacologic Management for Prevention and Treatment of Chronic Heart Failure


DRUG CLASS DESCRIPTION / MECHANISM DOSE
Cornerstone of modern HF treatment
Interferes with RAAS by inhibiting Captopril 25-50 mg TID
the conversion of angiotensin I to Enalapril 2.5-10 mg BID
ACE-Inhibitors angiotensin II Ramipril 2.5-10 mg OD
Inhibits kininase which may lead to Lisinopril 5-20 mg OD
increase in bradykinin (ACE-I
induced cough)
Angiotensin Receptor Use if ACEI intolerant (e.g., cough, Valsartan 40-160 mg BID
Blockers angioedema) Candesartan 8-32 mg OD
Losartan 25-50 mg OD
Another cornerstone of modern HF
treatment Carvedilol 3.125-25 mg BID
Beta Blockers Interferes with sustained activation of Bisoprolol 1.25-10 mg OD
the adrenergic nervous system, Metoprolol succinate 25-200 mg OD
particularly the deleterious effects of
B1 activation
Inhibits action of aldosterone in
Aldosterone Antagonist collecting duct Spironolactone 25-50 mg OD
May also be used for fluid retention Eplerenone 25-50 mg OD
(diuretic)
For symptomatic LV dysfunction +
Digoxin atrial fibrillation Digoxin 0.125-0.375 mg OD
Add-on to standard therapy
Reduces HR by inhibition of the Ivabradine 5-7.5 mg BID
Ivabradine “funny channel” (If) in the SA node
Primarily used for symptomatic
55
stable angina
May be used for HF with systolic
dysfunction in patients with sinus
rhythm and HR > 70 bpm

C. Management of Fluid Retention in Chronic HF


DRUG CLASS DESCRIPTION / MECHANISM DOSE
Act on the loop of Henle by reversibly Furosemide 20-40 mg OD-BID
Loop Diuretics inhibiting the reabsorption of Na+, K+, Cl in Bumetanide 0.5-1.0 mg OD-
the thick ascending limb BID
Reduce the reabsorption of Na+ and Cl in Hydrochlorothiazide 25 OD-
Thiazide and Thiazide- the first half of the distal convoluted tubule BID
Like-Diuretics Tend to lose their efficiency with moderate Indapamide 2.5 mg OD
to severe renal insufficiency (Crea > 2.5 Metolazone 2.5-5.0 mg OD
mg/dL)
Interfere with action at the vasopressin
Arginine Vasopressin receptors Tolvaptan 15 mg OD
Antagonists Primarily used for treatment of Satavaptan 25 mg OD
hyponatremia by stimulating free-water
excretion and improving plasma
Na+concentration

D. Indications for Use of Drugs in HF


CLASS ASYMPTOMATIC LV SYMPTOMATIC HF WORSENING HF END-STAGE HF
DYSFUNCTION (NYHA I) (NYHA II) (NYHA III-IV) (NYHA IV)
ACEI/ARB Yes yes Yes Yes
Diuretic No Yes, if with fluid retention Yes Yes
B-Blocker Yes, if Post-MI Yes Yes Yes
Aldosterone Yes, if Recent MI Yes Yes Yes
Antagonist
Digoxin May be considered* May be considered* Yes Yes
*Digoxin may be considered for patients with NYHA-I for rate control in AF or when improved from more severe HF and in sinus rhythm

E. Devices Used in HF
Cardiac resynchronization therapy (CRT) or biventricular pacing: device used to restore synchrony of the
left ventricle in patients with HF and a widened QRS complex
Implantable cardioverter-defibrillator (ICD): device to treat tachyarrhythmias for primary / secondary
prophylaxis against sudden cardiac death

VI. ACUTE DECOMPENSATED HEART FAILURE (ADHF)

A. Distinctive Phenotypes
ACUTE PRESENTATION MANAGEMENT
DECOMPENSATION
Typical Normo-hypertensive Vasodilators, diuretics
Usually not volume overloaded
Pulmonary Edema Severe pulmonary congestion with hypoxia Vasodilators, diuretics, opiates
O2 non-invasive ventilation
Hypoperfusion with end-organ dysfunction Inotropic therapy
Low Output Low pulse pressure, cool extremities Vasodilators
Cardiorenal syndrome, hepatic congestion Hemodynamic monitoring
Hypotension, low cardiac output, end-organ Inotropic therapy
Cardiogenic Shock failure Mechanical circulatory support
Extreme distress, pulmonary congestion,
renal failure

56
B. Parenteral Therapy for Acute Decompensated HF
DRUG CLASS SAMPLE DRUGS
Inotropic Therapy Dobutamine (2-20 mcg/kg/min)
Others: Milrinone, Levosimendan
Vasodilators Nitroglycerine (10-20 mcg/kg/min)
Others: Nesiritide, Nitroprusside, Serelaxin
Furosemide (20-240 mg/day)
Diuretics Bumetamide (0.5-5 mg/day)
Others: Torsemide, Metolazone, Chlorthalidone, Spironolactone, Acetazolamide

CHRONIC STABLE ANGINA PECTORIS (CSAP)

Patients with ischemic heart disease (IHD) fall into two large groups:
Chronic artery disease (CAD) who commonly present with chronic stable angina pectoris (CSAP)
Acute coronary syndromes (ACS), discussed in the next section, are composed of:
o Non ST-segment elevation acute coronary syndrome (NSTE-ACS)
o ST-segment elevation acute myocardial infarction (STEMI)

I. ETIOPATHOGENESIS
Inadequate supply of blood flow and oxygen to a portion of the myocardium causing inadequate perfusion of
myocardium supplied by an involved artery
Most common cause: atherosclerotic disease of an epicardial coronary artery
Obesity, insulin resistance, and T2DM are increasing and powerful risk factors for IHD

II. CLINICAL MANIFESTATIONS


A. Angina
Typical history involves a man >50 years old or woman >60 years old who complains of chest discomfort:
o Described as heaviness, pressure, squeezing, smothering or choking
o Crescendo-decrescendo in nature
o Usually lasts 2-5 minutes
o Associated with physical exertion or stress
o Radiation to either or both shoulders/arms, but does not radiate to the trapezius muscles
o Relieved within 5-10 minutes by rest and/or sublingual NTG
o Levine’s sign: hand placed over sternum with a clenched fist to indicate discomfort

B. Canadian Cardiovascular Society Classification of Angina


CCS CLASS DESCRIPTION
I Angina occurs with greater than ordinary physical activity
II Angina occurs with ordinary physical activity
III Angina occurs with less than ordinary physical activity
IV Angina may be present even at rest

III. DIAGNOSIS
A. Non-Invasive Diagnostics
DIAGNOSTIC TEST EXPECTED FINDINGS
May be normal at rest
ECG ST-segment and T-wave changes, LV hypertrophy, intraventricular
conduction disturbance (which may be non-specific)
Stress Testing Most widely used for both diagnosis of IHD and estimating prognosis
Involves recording the 12-lead ECG before, during and after exercise
Used to assess left ventricular function in patients with CSAP and
patients with a history of a prior MI, pathologic Q waves or clinical
2D Echo evidence of CHF
Assess for wall motion abnormalities, ejection fraction, presence of
thrombus, etc.

57
B. Indications for Coronary Angiography
Patients with CSAP who are severely symptomatic despite medical therapy and considered for revascularization
Patients with troublesome symptoms that present diagnostic difficulties in whom there is a need to confirm or R/O
the diagnosis of IHD
Patients with known or possible CSAP who have survived cardiac arrest
Patients with CSAP or evidence of ischemia on noninvasive testing with clinical or laboratory evidence of
ventricular dysfunction
Patients at high risk of sustaining coronary events on noninvasive testing, regardless of symptoms

IV. MANAGEMENT OF CSAP

A. Pharmacologic Treatment for Angina


DRUG CLASS EXAMPLES MECHANISM OF ACTION COMMENTS
Anti-Ischemic Drugs
None of the long-
acting nitrates are
as effective as SL
Isosorbide Dinitrate Systemic venodilation NTG for the acute
(ISDN) 10-40 mg BID- with reduction in LV relief of angina
TID end-diastolic volume Used for
Isosorbide Mononitrate and pressure, thereby symptomatic relief
(ISMN) 30-240 mg OD reducing myocardial May be
NTG 0.3-0.6 mg SL, as wall tension and O2 discontinued with
Nitrates needed up to 3 doses, requirements the disappearance
5 mins apart Dilation of epicardial of chest pain
NTG Transdermal coronary vessels Common side effect
Patch 0.2-0.8 mg/hr OD Increased blood flow limiting their use:
(remove at bedtime for in collateral vessels headache
12-14 hrs) At least 8 hour
nitrate-free interval
is recommended to
avoid nitrate
tolerance
Metoprolol 50-100 mg Reduced myocardial
BID-QID O2 demand by Cornerstone
Metoprolol XL 50-200 inhibiting increases in therapy for angina
B-Blockers (BB) mg OD HR, arterial pressure Shown to improve
Carvedilol 3.125-50 mg and myocardial life expectancy
BID contractility caused by following acute MI
Atenolol 50-100 mg OD adrenergic activation
Bisoprolol 5-20 mg OD
Indicated in patients
with:
o Inadequate
responsiveness to
Non-dihydropyridines the combination of
Verapamil 80-120 mg Coronary vasodilators BB and nitrates
TID-QID that produce variable o Adverse reactions
Diltiazem 30-90 mg and dose dependent to BB
Calcium TID-QID reductions in o Angina history of
Channel myocardial O2 asthma or COPD
Blockers (CCB) Dihydropyridines demand, contractility, o Sick sinus
Amlodipine 2.5-10 mg and arterial pressure syndrome or
OD significant AV
Felodpine 2.5-10 mg conduction
OD disturbances
o Prinzmetal’s angina
o Symptomatic
58
peripheral arterial
disease
Other Pharmacologic Agents for Angina
Inhibitor of the IF ion channel (principal determinant of Only works in
Ivabradine the SA node) patients who are in
2.5-7.5 mg BID Slows the heart rate through a mechanism that is not sinus rhythm
associated with negative inotropic effects
Dilates peripheral and coronary resistance vessels via Has anti-anginal
Nicorandil ATP-sensitive K+ channels efficacy similar to
10-20 mg BID Possess a nitrate moiety that promotes venous and BB, nitrates & CCBs
coronary dilation

B. Other Drugs for Stable Angina Pectoris


DRUG CLASS EXAMPLES MECHANISM OF ACTION COMMENTS
Irreversible inhibitor of Chronic administration
Aspirin platelet cyclooxygenase has been shown to
75-162 mg OD activity, interfering with reduce coronary events
platelet activation
Antiplatelets Oral agent that blocks May be substituted for
Clopidogrel ADP receptor-mediated aspirin in those with
75 mg OD platelet aggregation aspirin hypersensitivity
or those who cannot
tolerate aspirin
Can lower LDL
Act as HMG-CoA cholesterol (25-50%),
Rosuvastatin reductase inhibitor raise HDL cholesterol
10-20 mg OD Exhibit pleiotropic and lower triglycerides
Statins Atorvastatin effects: plaque High intensity statin
10-80 mg OD stabilization and anti- therapy should be given
Simvastatin inflammatory effects for patients with
10-40 mg OD established IHD who
are less than 75 years
old, in the absence of
contraindications

C. Coronary Interventions
INTERVENTION DESCRIPTION
Percutaneous Coronary Balloon dilatation usually accompanied by coronary stenting
Intervention (PCI) Most common indication: persistent or symptom-limiting angina pectoris,
despite medical therapy, accompanied by evidence of ischemia during a
stress test
Coronary Artery Bypass Indicated for those with three-vessel CAD or two-vessel CAD with
Grafting (CABG) involvement of the left anterior descending artery (LAD) or stenosis of the
left main coronary artery

ACUTE CORONARY SYNDROMES (ACS)

Operational term that refers to a spectrum of conditions compatible with acute myocardial ischemia and/or
infarction due to an abrupt reduction in coronary blood flow
Patients with ACS are composed of:
o Non-ST segment elevation acute coronary syndrome (NSTE-ACS):
Non-ST segment elevation myocardial infarction (NSTEMI)
Unstable angina (UA)
ST elevation acute myocardial infarction (STEMI)

59
I. UNIVERSAL DEFINITON OF MYOCARDIAL INFARCTION

A. Criteria for Acute MI


“Acute MI” should be used when there is evidence of myocardial necrosis in a clinical setting consistent with acute
myocardial ischemia. Under these conditions, any of the following criteria meet the diagnosis for MI:
Detection of a rise and/or fall in cardiac biomarkers (preferably cardiac troponins/cTn), with at least one value
above the 99th percentile with at least one of the following:
o Symptoms of ischemia
o New or presumed new significant ST-segment and/or T wave changes or new LBBB
o Development of pathologic Q waves on the ECG
o Imaging evidence of new loss of viable myocardium or new wall motion abnormality
o Identification of an intracoronary thrombus by angiography or autopsy
Cardiac death with symptoms suggestive of myocardial ischemia & presumed new ischemic ECG changes or
new LBBB (Type 3)
PCI-related MI (Type 4a)
Stent thrombosis associated with MI (Type 4b)
CABG-related MI (Type 5)

B. Criteria for Previous Myocardial Infarction (any of the following):


Pathologic Q waves with or without symptoms in the absence of non-ischemic causes
Imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract in the absence of a
non-ischemic cause
Pathologic findings of previous MI

II. UNIVERSAL CLASSIFICATION OF TYPES OF MYOCARDIAL INFARCTION


TYPE OF MYOCARDIAL INFARCTION DESCRIPTION
(MI)
Type Related to atherosclerotic plaque rupture, ulceration, fissuring, erosion or
Spontaneous MI dissection with resulting intraluminal thrombus in one or more of the
1 coronary arteries that leads to decreased myocardial blood flow or distal
platelet emboli with ensuing myocyte necrosis
A condition other than CAD contributes to an imbalance between
MI secondary to myocardial oxygen supply and/or demand, e.g., coronary endothelial
Type Ischemic Imbalance dysfunction, coronary artery spasm, coronary embolism,
2 tachyarrhythmias/bradyarrhythmias, anemia, respiratory failure,
hypotension, and hypertension with or without LVH
Type MI resulting in Death Cardiac death with symptoms suggestive of ischemia and presumed new
when Biomarkers are ischemic changes (or new LBBB), but death occurring before blood
3 Unavailable samples could be obtained
MI associated with PCI defined by elevation of cTn values to >5x the 99th
percentile of the upper reference limit in those with normal baseline values
or a rise in cTn values >20% if baseline values are elevated and are stable
or falling; AND either:
Type MI related to PCI Symptoms suggestive of myocardial ischemia
4a New ischemic changes on the ECG or new LBBB
Angiographic loss of patency of a major coronary artery or a side
branch or persistent slow flow or no flow or embolization
Imaging demonstration of new loss of viable myocardium or new
regional wall motion abnormality
Type MI associated with stent thrombosis is detected by coronary angiography
MI related to Stent or autopsy in the setting myocardial ischemia and with a rise and/or fall in
4b Thrombosis cardiac biomarkers with at least one value >99th percentile of the upper
reference limit
MI associated with CABG – defined by elevation of cardiac biomarker
values >10x the 99th percentile of upper reference limit in patients with
Type MI related to CABG normal baseline values; AND either:
5 New pathologic Q waves or new LBBB, or
New graft or new native coronary artery occlusion on angiogram,

60
or
Imaging evidence of new loss of viable myocardium or new
regional wall motion abnormality

NON-ST ELEVATION ACUTE CORONARY SYNDROME (NSTE-ACS)


I. ETIOPATHOGENESIS
Most commonly caused by an imbalance O2 supply and demand, resulting from a partially occluding thrombus
forming on a disrupted atherothrombotic coronary plaque on eroded coronary artery endothelium

A. Four Basic Pathophysiologic Processes:


Most common cause: plaque rupture or erosion with superimposed non-occlusive thrombus
Dynamic obstruction (e.g., coronary spasm as in Prinzmetal’s variant angina)
Severe mechanical obstruction
Increased myocardial O2 demand (e.g., tachycardia) and/or decreased supply (e.g. anemia)

B. Definition of Terms
TERM DEFINITION
Angina or equivalent ischemic discomfort with at least one of the following:
Occurs at rest (or with minimal exertion), usually lasting >10 minutes
Unstable Angina (UA) Severe and of new onset (e.g., within the prior 4-6 weeks) of at least
CCS III severity
Occurs with crescendo pattern (e.g., distinctly more severe, prolonged
or frequent than previous episodes)
NSTEMI Clinical features of UA plus evidence of myocardial necrosis (elevated
cardiac biomarkers)
Ischemic pain that occurs at rest but not usually with exertion,
Prinzmetal Variant Angina associated with transient ST-segment elevation
Due to transient, focal spasm of an epicardial coronary artery

II. CLINICAL MANIFESTATIONS

A. Typical Chest Pain


Chest discomfort is typically severe and has at least one of the following features:
o Occurs at rest (or with minimal exertion), lasting >10 minutes
o Relatively recent onset (within prior 2 weeks)
o Occurs with a crescendo pattern (e.g., more severe, prolonged or frequent)

B. Symptoms & Signs of NSTE-ACS


SYMPTOMS SIGNS
Chest pain radiating to the neck, left Pale cool skin
shoulder, and left arm Sinus tachycardia
Dyspnea S3 or S4
Diaphoresis Basilar rales
Anxiety, restlessness Hypotension

III. DIAGNOSIS OF NSTE-ACS

A. 12-Lead Echocardiogram (ECG)


ST-segment depression, transient ST-segment elevation or T-wave inversion
T-wave changes: sensitive for ischemia but less specific (unless new & deep T-wave inversions > 0.3 mV)
If initial ECG is not diagnostic – serial ECGs should be done to detect ischemic changes if patient remains
symptomatic with a high suspicion for ACS

B. Cardiac Biomarkers
Elevated levels distinguish patterns with NSTE-ACS from UA

61
Serial cardiac troponin I or T levels should be obtained at presentation and 3-6 hours after symptom onset to
identify a rising and/or falling pattern of values
Additional levels should be obtained beyond 6 hours in patients with normal levels on serial examination when
ECG and/or clinical presentation confer an intermediate or high index of suspicion for ACS

1. Advantages and Disadvantages of the Common Cardiac Biomarkers


CARDIAC TROPONINS CK-MB
Powerful tool for risk stratification Rapid, cost-efficient,
Greater sensitivity and specificity than accurate assays
Advantage CK Ability to detect early
Detection of recent MI up to 2 weeks reinfarction
after onset (remain elevated 7-10 days
after MI)
Low sensitivity in very early phase of Loss of specificity in setting
MI (<6 hours after symptom onset) of skeletal muscle disease of
and requires repeat measurement at injury, including surgery and
8-12hours if negative IM injections
Disadvantage Limited ability to detect late minor With contemporary troponin
reinfarction assays, CKMB is not useful
Minor troponin elevations can be for diagnosis of ACS
caused by azotemiz/CKD, CHF,
myocarditis or pulmonary embolism

2. Timing of Cardiac Markers


CARDIAC BIOMARKER TIME TO DETECTION PEAK DURATION
Troponin-T 3-12 hrs 24 hours 5-14 days
Troponin-I 3-12 hrs 24 hours 5-10 days
CK-MB 4-8 hrs 24 hours 2-3 days

C. Risk Stratification: TIMI SCORE for NSTE-ACS


Prognostication scheme, which categorizes patients based on risk of all-cause mortality, new or recurrent MI, or
severe ischemia requiring urgent revascularization

COMPONENTS POINTS INTERPRETATION


Age > 65 years 1 point
> 3 CAD factors 1 point Risk Total Score:
Known CAD (> 50% stenosis) 1 point 0-7 points
Aspirin use in the [ast 7 days 1 point
Severe angina in last 24 hours 1 point High Risk Score:
Elevated cardiac markers 1 point > 3 points
ST deviation > 0.5mm 1 point (13% mortality)

IV. MANAGEMENT OF NSTE-ACS

A. Standard and Anti-Ischemic Therapy


THERAPY DESCRIPTION
Non-Pharmacologic Bed rest with continuous ECG monitoring
Supplemental oxygen if O2 sat <94%
Avoid in:
SL nitrate (ISDN 5 mg/tab) q5 SBP <90 mmHg or >30 mmHg
mins x total of 3 doses below baseline
IV NTG in first 48 hours (5-10 Severe bradychardia <50 bpm
Nitrates mcg/kg/min, max 200 Tachycardia >100 bpm in
mcg/kg/min) for persistent absence of symptomatic HF
ischemia, HF or HPN Suspected RV infarction
Decrease in angina symptoms Those who received sildenafil
for the past 24 hours (may
potentiate hypotension)
62
Not given in patients with:
Signs of acute HF
Low output states (SBP <90,
Started within 24 hours HR <50)
Beta-Blockers (BB) Metoprolol succinate, PR interval > 0.24 secs, 2nd or
carvedilol or bisoprolol 3rd degree AVB without a
pacemaker
Active asthma or reactive
airway disease
Recommended for recurrent ischemia after appropriate use of BB and
Nondihydropyridine Calcium nitrates
Channel Blockers For those with contraindications to beta-blockers
Verapamil or diltiazem
Given orally within 24 hours in patients with congestion and/or LVEF <
ACE Inhibitors 40%
ARBs may be given if patient intolerant to ACE inhibitors
Captopril 6.25-12.5 mg PO q8

B. Anti-Platelet Therapy
Initial treatment should begin with aspirin
In the absence of a high risk of bleeding, patients with NSTE-ACS should also receive a P2Y12 inhibitor for up to
12 months (at least 12 months if patient is to undergo PCI with stenting): clopidgrel, ticagrelor, prasugrel
THERAPY DESCRIPTION
Platelet cyclooxygenase inhibitor
Aspirin Dose: 165-325 mg loading dose, then 80-162 mg OD maintenance dose
indefinitely
Thienopyridine
Clopidogrel Inactive prodrug that is converted into an active metabolite that causes
irreversible blockade of the platelet ADP P2Y12inhibitor
Dose: 300-600 mg loading dose, then 75 mg OD
Non-thienopyridine
Novel, potent, reversible platelet ADP P2Y12inhibitor
Ticagrelor May be used in patients who are treated either by an invasive or conservative
strategy
Dose: 180 mg loading dose, then 90 mg BID
Thienopyridine
Also a platelet ADP P2Y12 antagonist, but achieves a more rapid onset and
higher level of platelet inhibition than clopidogrel
Approved for ACS patients following angiography in whom PCI is planned (it
Prasugrel has not been found to be effective in patients treated by a conservative
strategy)
Contraindicated in patients with prior stroke / TIA or a high risk of bleeding
Dose: 60 mg loading dose, then 10 mg OD (if patient is to undergo early
invasive management)

C. Anticoagulation Therapy
THERAPY DESCRIPTION
Unfractioned Heparin Mainstay of therapy
(UFH) Target aPTT 50-70 seconds (ratio of 1.5-2.5)
Dose: 60 U/kg IV bolus (maximum 4,000 U), then 12 U/kg infusion (1000
units/hour) for 48 hours or until PCI is performed (most trials continued therapy
for 2-5 days)
Enoxaparin Superior to UFH in reducing recurrent cardiac events, especially in patients
managed conservatively
Dose: 30 mg IV loading dose, then 1 mg/kg SC q12 for the duration of
hospitalization or until PCI is performed
Fondaparinux Indirect factor Xa inhibitor

63
Equivalent in efficacy to enoxaparin, but with lower risk of major bleeding
Dose: 2.5 mg SC OD for duration of hospitalization or until PCI is performed

D. Statins
High intensity statin therapy should be initiated or continued
Early administration of statins (e.g., Atorvastatin 80 mg/day) has been shown to reduce adverse outcomes
E. Conservative versus Early Invasive Strategy
Conservative strategy (low risk patients): anti-ischemic therapy and antithrombotic therapy followed by “watchful
waiting” (close observation)
Early-invasive strategy (for high risk patients): following treatment with anti-ischemic and antithrombotic agents,
angiography is carried out within 48 hours, followed by coronary revascularization (PCI or CABG)
CONSERVATIVE MEDICAL MANAGEMENT EARLY INVASIVE MANAGEMENT
(Ischemia-Guided Strategy) (Revascularization)
Low risk score (TIMI 0 or 1) Recurrent angina or ischemia at rest or with low-
Low risk troponin-negative female patients level activities despite intensive medical therapy
Patient or physician preference in the Elevated cardiac biomarkers (TnT or Tnl)
absence of high-risk features New or presumably new ST segment depression
CHF symptoms, rales, MR
Reduced left ventricular function (LVEF < 40%)
Sustained ventricular tachycardia
PCI < 6 months or prior CABG
High-risk findings from noninvasive testing
Hemodynamic instability
Mild-to-moderate renal dysfunction
DM
High TIMI risk score > 3

IV. PRINZMETAL’S VARIANT ANGINA


Syndrome of severe ischemic pain that usually occurs at rest and associated with transient ST elevation
Caused by focal spasm of an epicardial coronary artery (most commonly the right coronary artery)
Diagnostic hallmark: coronary arteriography demonstrates transient coronary spasm
Main therapeutic agents: nitrates and calcium channel blockers
Aspirin may increase severity of ischemic episodes

ST-ELEVATION MYOCARDIAL INFARCTION (STEMI)


I. ETIOPATHOGENESIS
Acute plaque rupture is central to the pathogenesis of STEMI
Occurs when coronary blood blow decreases abruptly after a thrombotic occlusion of a coronary artery previously
affected by atherosclerosis

II. CLINICAL MANIFESTATIONS


Diagnosed similarly as NSTE-ACS (e.g., clinical features, increased cardiac biomarkers) but with ECG findings
evolving in a temporal pattern (see ECG Reading in Chapter 1)

III. DIAGNOSIS AND RISK STRATIFICATION FOR STEMI


A. Killip Scoring for STEMI
CLASS DESCRIPTION RISK OF MORTALITY
Class No rales or signs of pulmonary or venous congestion
I Normal BP 0-5%
Moderate HF, bibasal rales
Class Normal BP
S3 gallop 10-20%
II
Tachypnea or signs of right-sided CHF (venous or hepatic
congestion)
Severe HF
64
Class (+) mid-basal rales and pulmonary edema 35-45%
III (+) S3 and S4
Normal BP
Shock with SBP <90 mmHg & evidence of peripheral
Class vasoconstriction 85-95%
Peripheral cyanosis
IV
Mental confusion and oliguria

B. TIMI Risk Score for STEMI


TIMI risk score for STEMI: predicts 30-day mortality
Designed for risk assessment early after patient presentation and thus does not incorporate noninvasive and
invasive data
COMPONENTS POINTS INTERPRETATION
Historical
Age 65-74 2 points
Age > 75 3 points
DM, Hypertension, Angina 1 point Risk Total Score:
Examination 0-14 points
SBP < 100 mmHg 3 points
HR > 100 bpm 2 points High Risk Score:
Killip II-IV 2 points > 5 points
Weight < 67 kg 1 point (12% mortality)
Presentation
Anterior ST elevation or LBBB on ECG 1 point
Time to Treatment > 4 hours 1 point

IV. MANAGEMENT OF STEMI

A. Pre-hospital Management of STEMI


Major components:
o Recognition of symptoms
o Rapid deployment of an emergency medical team capable of performing resuscitative maneuvers
o Expeditious transportation
o Expeditious implementation of reperfusion therapy
Most out-of-hospital deaths from STEMI are due to sudden ventricular fibrillation
Majority of deaths occur within 24 hours of the onset of symptoms (over half occur in the 1st hour)

B. Reperfusion Therapy: Primary Goal of Management


Reperfusion Therapy (fibrinolysis or PCI) should be administered to all eligible patients with STEMI with
symptom onset within the last 12 hours
o Primary PCI: recommended method of reperfusion when it can be performed in a timely fashion
o Fibrinolysis: administered at non-PCI-capable centers
FIBRINOLYSIS / THROMBOLYSIS INVASIVE STRATEGY (PCI)
Generally preferred if: Generally preferred if:
Early presentation (< 3 hours of symptom onset) Available PCI laboratory with surgical backup
Invasive strategy is not available: o Medical contact-to-balloon or door-to-balloon
Delay to invasive strategy: < 90 minutes
o Prolonged transport o Door-to-balloon minus door-to-needle < 1 hr
o Door-to-balloon minus door-to-needle High risk STEMI (cardiogenic shock, Killip > 3)
time >1 hr Contraindications to fibrinolysis
o Medical contact-to-balloon or door-to- Late presentation (symptom onset > 3 hours)
balloon time >90 minutes Diagnosis of STEMI is in doubt
Fibrinolytic agents: Percutaneous coronary intervention (PCI) or
o Streptokinase percutaneous transluminal coronary angioplasty
o Tissue plasminogen activators (PTCA): balloon angioplasty and stenting

Adjunct anti-platelet therapy with fibrinolysis: Anti-platelet therapy during Primary PCI:
Aspirin continued indefinitely
65
Clopidogrel for at least 14 days up to 1 o Aspirin indefinitely after PCI
year o One P2Y12-receptor inhibitor continued for 1 year
for those who receive a stent:
Adjunctive anticoagulant therapy with Clopidogrel
fibrinolysis: given for a minimum of 48 hours or Prasugrel (not used if + prior stroke/TIA)
until revascularization is performed (same dose Ticagrelor
as in NSTE-ACS)
o Unfractioned heparin (UFH) Anticoagulant therapy during primary PCI:
o Enoxaparin o UFH
o Fondaparinux o Bivalirudin
Fibrinolysis is still reasonable if symptom onset is within 12-24 hours as long as there is evidence of ongoing
ischemia (although primary PCI is preferred for this population)

CONTRAINDICATIONS TO FIBRINOLYSIS
ABSOLUTE CONTRAINDICATIONS RELATIVE CONTRAINDICATIONS
Previous intracranial hemorrhage History of chronic, severe, poorly controlled HPN
Structural cerebral vascular lesion (e.g., Significant HPN at initial evaluation (SBP > 180
AVM) mmHg or DBP > 110 mmHg)
Malignant intracranial neoplasm History of previous ischemia stroke > 3 months
Ischemic stroke within 3 months except Dementia
acute ischemic stroke within 4.5 hours Intracranial pathology not covered in absolute
Suspected aortic dissection contraindications
Active bleeding / bleeding diathesis (except Traumatic or prolonged (>10 minutes) CPR
mense) Major surgery (<3 weeks)
Closed-head or facial trauma within 3 months Recent (within 2-4 weeks) internal bleeding
Intracranial/intraspinal surgery within 2 Noncompressible vascular punctures
months Pregnancy
Severe uncontrolled hypertension Active peptic ulcer
(unresponsive to emergency therapy) Oral anticoagulant therapy
For streptokinase, previous treatment within
the previous 6 months
AVM: Arteriovenous malformation
CPR: cardiopulmonary resuscitation

C. Other Routine Medications for STEMI


THERAPY DESCRIPTION
Should be initiated in the first 24 hours, except if
with signs of HF, low output state, increased risk for
Beta Blockers cardiogenic shock, or other contraindications (PR
interval > 0.24, 2nd or 3rd degree AVB, active
asthma, reactive airway disease)
ACE-inhibitors should be initiated in the first 24
hours to all patients with anterior wall STEMI, HF or
RAAS Inhibitors EF < 40%
ARB may be used for those intolerant to ACE-
inhibitors
Statins High intensity statin therapy should be initiated or
continued

D. Supportive Care
THERAPY DESCRIPTION
First 12 hours: bed rest
Next 12 hours: dangling of feet at bedside and
Activity sitting in a chair
2nd and 3rd day: ambulation in the room with
increasing duration and frequency to a goal of 185
cm (600 ft) at least 3x a day
2 weeks: resumption of work and sexual activity

66
Nothing or only clear liquids (due to risk of emesis
Diet and aspiration) for the first 4-12 hours
Use of stool softener
Sedation Many require sedation during hospitalization to
withstand period of enforced inactivity

E. Secondary Prevention and Long Term Management


THERAPY DESCRIPTION
Smoking Complete cessation
BP Control BP <140/90 or <130/80 if CKD or DM
Lipid Management High dose statins
<7% of total calories as saturated fats and <200 mg/day total cholesterol
Physical Activity 30 minutes of moderate intensity aerobic exercise, 3 to 4 days per week
Weight BMI 18.5 – 24.9 kg/m2
Management Waist circumference: women <35 inches, men <40 inches
DM Management HbA1c <7%
Anti-platelets Aspirin or P2Y12-receptor inhibitors
RAAS Blockers ACEI in stable high-risk patients (anterior MI, previous MI, Killip > II, EF <40%)
Beta Blockers Continued indefinitely

IV. USUAL COMPLICATIONS OF STEMI


COMPLICATION FREQUENCY DESCRIPTION
Ventricular 1-3% in those who Bimodal peak (within 24 hours & 3-5 days; can range from 1-14 days)
Septal Rupture did not undergo Presents with chest pain, SOB and hypotension
(VSR) reperfusion Holosystolic murmur, S3, accentuated 2 nd heart sound, pulmonary
edema, RV and LV failure, cardiogenic shock
Bimodal peal (within 24 hours & 3-5 days; can range from 1-14 days)
Presents with angina, pleuritic or pericardial chest pain, syncope,
Ventricular Free 0.8-6.2% hypotension, arrhythmia, nausea, restlessness, hypotension and
Wall Rupture sudden death
JV distention (29%), pulsus paradoxus (47%), electromechanical
dissociation and cardiogenic shock
1% (posteromedial Bimodal peak (within 24 hours & 3-5 days; can range from 1-14 days)
Papillary Muscle more frequently Abrupt onset of dyspnea, pulmonary edema, and hypotension
Rupture affected than Soft murmur in most cases, no thrill, variable signs of RV overload,
anterolateral severe pulmonary edema, cardiogenic shock
muscle) Hypercontractile LV, torn papillary muscle or chordae tendinae, flail
leaflet and severe MR on echo with color flow

RHEUMATIC FEVER (RF)


I. ETIOPATHOGENESIS
Multi-system disease resulting from autoimmune reaction to infection with Group A Beta-Hemolytic
Streptococcus
In RF, antibodies against M-proteins of certain strains of Streptococcus cross-react with tissue glycoproteins in
the heart, joints and other tissues (“molecular mimicry”)

II. CLINICAL MANIFESTATIONS


Latent period of 3 weeks (ranges from 1 to 5 weeks) between the precipitating infection and the appearance of
the clinical features of ARF with the exception of chorea and indolent carditis which may follow prolonged talent
period lasting up to 6 months
Most common clinical presentation: polyarthritis and fever

A. Major Manifestations
Carditis Pancarditis involving the pericardium, myocardium and endocardium
(up to 60%) Hallmark is valvular damage
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Characteristic manifestation is mitral regurgitation
Migratory Typically migratory over a period of hours
Polyarthritis Most often asymmetric and affecting large joints (ankles, wrists, knees, elbows)
(75%) Highly responsive to salicylates and NSAIDs
Sydenham’s Involuntary jerking movements mostly affecting the head and upper limbs
Chorea (<10%) Commonly occurs in females and in the absence of other manifestations
Usually resolves completely within 6 weeks
Erythema Evanescent pink macular eruption with round borders and central clearing
Marginatum Usually concentrated on the trunk, sometimes on the limbs, but almost never on the
face
Subcutaneous Painless small lumps found over extensor surfaces of joints
Nodules Usually a delayed manifestation (2-3 weeks after onset)
Commonly associated with carditis

B. Minor Manifestations
Clinical Arthralgia (joint pains), fever
Laboratory findings Elevated acute phase reactants (ESR/CRP), prolonged PR interval on ECG

C. Supporting Evidence of a Preceding Streptococcal Infection within the last 45 days


Elevated or rising anti-streptolysin-O or other streptococcal antibody, or
A positive throat culture, or
Rapid antigen test for group-A Streptococcus, or
Recent scarlet fever

III. DIAGNOSIS

A. The Revised Jones Criteria: Diagnosis of Rheumatic Fever (RF) and Rheumatic Heart Disease (RHD)
DIAGNOSTIC CATEGORIES CRITERIA
Primary episode of RF Evidence of preceding group-A streptococcal infection; PLUS:
2 major criteria, or
1 major + 2 minor criteria
Recurrent RF in a patient Evidence of preceding group-A streptococcal infection; PLUS:
without established RHD 2 major criteria, or
1 major + 2 minor criteria
Recurrent RF in a patient with Evidence of preceding group-A streptococcal infection; PLUS:
established RHD 2 minor criteria
Rheumatic chorea Other major manifestations or evidence of group-A streptococcal infection not
Insidious onset rheumatic required
carditis
Chronic valve lesions of RHD
(patients presenting for the 1st
time with pure MS or mixed Do not require any other criteria to be diagnose as having RHD
MV disease and/or AV
disease)

B. Criteria for Echocardiographic Diagnosis of Rheumatic Heart Disease (RHD) in Individuals <20 years of age
Definite RHD (either A, B, C or D)
A. Pathologic MR + > 2 morphologic features of RHD of the mitral valve (MV)
B. MS mean gradient >4 mmHg
C. Pathologic AR + > 2 morphologic features of RHD of the aortic valve (AV)
D. Borderline disease of both the MV and AV
Borderline RHD (either A, B, C)
A. > 2 morphologic features of RHD of the MV without pathologic MR or MS
B. Pathologic MR
C. Pathologic AR
Normal Echocardiographic Findings (all of A, B, C and D)
A. MR that does not meet all four Doppler criteria (physiologic MR)
B. AR that does not meet all four Doppler criteria (physiologic AR)
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C. An isolated morphologic feature of RHD of the MV (e.g., valvular thickening), without any associated pathologic
stenosis or regurgitation
D. Morphologic feature of RHD of the AV (e.g., valvular thickening), without any associated pathologic stenosis or
regurgitation
Definitions of Pathologic Regurgitation & Morphologic Features of RHD
Pathologic MR: all of the following – seen in 2 weeks; in at least 1 view, jet length 2 cm; peak velocity > 3 m/s;
pansystolic jet in at least 1 envelope
Pathologic AR: all of the following – seen in 2 views; in at least, jet length > 1 cm; peak velocity > 3 m/s’
pandiastolic jet in at least 1 envelope
Morphologic features of RHD in MV: anterior MV leaflet thickening > 3 mm; chordal thickening; restricted
leaflet motion; excessive leaflet tip motion during systole
Morphologic features of RHD in AV: irregular of focal thickening; coaptation defect; restricted leaflet motion;
prolapse

IV. MANAGEMENT OF RHEUMATIC FEVER

A. For Acute Management


Penicillin:
For Infection o PO: Pen V 500 mg BID or Amoxicillin 50 mg/kg daily x 10
days
o IM: single dose of 1.2 M units Benzathine Penicillin G
For Arthritis / Mild Carditis Aspirin 4-8 g/d in 4-5 divided doses up to 2 weeks
For Moderate-Severe Carditis May add prednisone 1-2 mg/kg/day up to 4 max of 3 weeks
For Severe Chorea Carbamazepine or valproic acid

B. For Prophylaxis of Rheumatic Fever


Primary prophylaxis for RH: to treat group-A streptococcal URTI and eradicate the organism to prevent an initial
attack of acute RF
Secondary prophylaxis for RF: to prevent colonization and/or infection in patients who had a previous attack of
RF to prevent recurrence of RF

1. Drugs Available for Secondary Prophylaxis


Benzathine Penicillin G 1.2 M units q 2-4 weeks (best)
Penicillin VK 250 mg/cap BID
Erythromycin 250 mg/cap BID (if allergic to Penicillin)

2. Duration of Secondary Prophylaxis


CATEGORY DURATION OF PROPHYLAXIS
RF without Carditis 5 years after last attack or until 21 y/o (whichever is longer)
RF with Carditis, but no residual 10 years after last attack or until 21 y/o (whichever is longer)
valvular disease
RF with persistent valvular disease 10 years after last attack or until 40 y/o (sometimes lifetime)

VALVULAR HEART DISEASE (VHD)


I. STAGES OF PROGRESSION OF VHD
CLASS STAGE A STAGE B STAGE C STAGE D
(At Risk) (Progressive) (Asymptomatic Severe) (Symptomatic Severe)
General Definition
Risk + + + +
Symptoms - - - +
Severity - Mild-to-Moderate Severe Severe
Individual Valvular Heart Disease Staging
Asymptomatic Severe Symptomatic Severe
AS At risk Asymptomatic C1: normal LVEF D1: high gradient
Progressive C2: low LVEF D2: low flow, low gradient, low
LVEF

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D3: low flow, low gradient,
preserved LVEF (paradoxical low-
flow severe AS)
Asymptomatic Severe
AR At risk Asymptomatic C1: normal LVEF Symptomatic Severe
Progressive C2: low LVEF or dilated
LVEF
MS At risk Asymptomatic Asymptomatic Severe Symptomatic Severe
Progressive
Asymptomatic Severe
MR At risk Asymptomatic C1: normal LVEF Symptomatic Severe
Progressive C2: low LVEF & dilated
LVEF
TR At risk Asymptomatic Asymptomatic Severe Symptomatic Severe
Progressive

II. INDIVIDUAL VALVULAR HEART DISEASES (VHD)

A. Aortic Stenosis (AS)


Most common cause: degenerative calcification of aortic cusps in adults
Most common congenital defect: bicuspid aortic valve (BAV)
Symptoms (dyspnea, angina, exertional syncope) are rarely present until valve orifice <1 cm 2
Death usually at 7th-8th decades, and may depend on the presence of symptoms:
o If with syncope I angina: death in 3 years
o If with dyspnea: death in 2 years
o If with CHF: death in 1.5-2 years

Pulsus parvus et tardus: weak and late pulse


Physical Exam Low pitched midsystolic ejection murmur at 2nd R ICS
Murmur may be transmitted to the apex, resembling murmur of MR (Gallavardin
effect)
Diagnostics CXR / ECG: LVH (with strain pattern on ECG)
2D Echo: calcified aortic valve with restriction in opening
Avoidance of strenuous activity and competitive sports
Diuretics for CHF
Caution with the use of nitrates and afterload unloaders (ACEI/ARBs) as these
Therapy may precipitate hypotension
Statins for slower progression of leaflet calcification
Intervention: Transcatheter Aortic Valve Implantation (TAVI), aortic valve
replacement (surgery)

B. Aortic Regurgitation (AR)


Austin Flint murmur: soft low-pitched rumbling mid-to-late diastolic murmur
De Musset sign: jarring of the body & bobbing of the head with each systole in
severe AR
Quincke’s pulse: visible capillary pulsations at the root of the nail with pressure
Physical Exam Traube sign: booming pistol shot sound over femoral arteries
Duroziez sign: to and from murmur when femoral artery is compressed
Water hammer (Corrigan’s) pulse: bounding and forceful pulse, rapidly
increasing and subsequently collapsing
Others: widened pulse pressure, absence of A2 in severe AR
ECG: LVH usually with ST depression and T wave inversion in I, aVL, V5-6 (lateral
Diagnostics leads)
2D Echo: mosaic color flow across the aortic valve during diastole
Therapy Diuretics, ACEI and vasodilators for CHF
Intervention: aortic valve replacement (surgery)

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C. Mitral Stenosis (MS)
Rheumatic heart disease is the leading cause
Poor prognosis for those >65 y/o, marked cardiac output depression, RV dysfunction and pulmonary
hypertension
Loud S1 and accentuated P2
Physical Exam Apical diastolic rumble and murmur
Opening snap
CXR: LAE, RAE, RVH
Diagnostics ECG: LAE, RAE, RVH; atrial fibrillation in severe cases
2D ECHO: doming motion of the mitral valve (anterior leaflet) during diastole
For fluid retention: sodium, restriction, diuretics
For rate control: beta-blockers, non-dihydropyridine calcium channel blockers,
digoxin
Therapy For secondary prophylaxis of rheumatic heart disease: penicillin
For prevention of stroke: warfarin (target INR 2-3)
Intervention: percutaneous transseptal mitral commisurotomy (PTMC) or mitral
valve replacement therapy (surgery)

D. Mitral Regurgitation (MR)


Soft S1; S4 in acute severe MR
Physical Exam Apical holosystolic murmur radiating to axilla (characteristic finding)
Hyperdynamic LV with brisk systolic impulse and laterally displaced apex beat
CXR: LAE, LVH
Diagnostics ECG: LAE, LVH; atrial fibrillation in severe cases
2D ECHO: mosaic color flow across the mitral valve during systole
For fluid retention: sodium, restriction, diuretics
Therapy For acute MR:vasodilators (decreases afterload and helps reduce severity of MR)
Intervention:mitral valve repair or replacement (surgery)

E. Mitral Valve Prolapse (MVP, Floppy Valve Syndrome, Barlow’s Syndrome)


More common in women 15-30 years old
More severe in men and >50 years old
Most patients are asymptomatic
Frequent finding in heritable connective tissue disease
Apical mid- or late non-ejection systolic click (characteristic finding)
Physical Exam High pitched late crescendo-decrescendo murmur after systolic click
Murmur is accentuated by standing and strain phase of Valsalva, diminished by
squatting and isometric exercises
CXR / ECG: usually normal; but may have biphasic or inverted T in II, III, aVF
Diagnostics (inferior leads) on ECG
2D ECHO: systolic displacement of MV leaflets (prolapse) at least 2 mm into LA
superior to mitral plane
IE prophylaxis for patients with prior endocarditis
Therapy Symptoms: beat-blockers for palpitations; warfarin if with AF
Intervention: mitral valve repair or replacement (surgery) if with severe MR

F. Tricuspid Stenosis (TS)


Generally rheumatic in origin; does not occur in isolation and usually associated with MS
Almost always accompanied by severe TR
Symptoms of right-sided CHF (ascites, edema, hepatosplenomegaly)
Physical Exam Opening snap of TV ~0.06 sec after PV closure
Diastolic murmur at LLSB, augmented during inspiration and reduced during
expiration & strain phase of Valsalva
Diagnostics ECG: RAE, RVH
2D ECHO: restriction in opening of the TV
Therapy Salt restriction, bed rest and diuretics
Interventions: surgery
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G. Tricuspid Regurgitation (TR)
Distended neck veins, hepatomegaly, ascites, (+) hepatojugular reflux
Physical Exam Prominent RV pulsation along left parasternal region
Carvallo sign: blowing holosystolic murmur at LPSB intensified by inspiration
Diagnostics ECG: RAE, RVH
2D ECHO: mosaic color flow across tricuspid valve during systole
Isolated TR is usually tolerated and does not require surgery
Therapy Intervention: valve annuloplasty or replacement for severe cases

H. Pulmonic Regurgitation (PR)


Most common acquired abnormality is regurgitation from severe pulmonary arterial HPN
Graham Steell murmur: high-pitched, decrescendo, diastolic blowing murmur along left sternal border
Intervention: percutaneous pulmonic valve replacement for severe PR

PERICARDITIS
I. ETIOPATHOGENESIS
Most common pathology affecting the pericardium and classified clinically and etiologically
May be infectious, non-infectious (MI, uremia, neoplasia, myxedema, cholesterol, chylopericardium, trauma, aortic
dissection, post-irradiation, acute idiopathic, sarcoidosis) or presumably related to hypersensitivity or
autoimmunity (rheumatic fever, collagen valvular disease, drug-induced, post-cardiac injury)

II. CLINICAL MANIFESTATIONS

A. Acute Pericarditis (< 6 weeks)


Pain resembles that of acute MI
Chest pain: severe, pleuritic, may be retrosternal or left pericordial and may be referred to neck and, arms or
left shoulder
Pericardial pain may be relieved by sitting up and leaning forward and is intensified by lying supine
PE may reveal pericardial friction rub (85%): high-pitched and is described as rasping, scratching or grating
and heard most frequently at end-expiration with patient upright and leaning forward

B. Chronic (Constrictive) Pericarditis (> 6 months)


Results when the healing of an acute fibrinous or serofibrinous pericarditis or the resorption of a chronic
pericardial effusion is followed by obliteration of the pericardial cavity with formation of granulation tissue
Weakness, weight gain, fatigue, increased abdominal girth / ascites and edema
Common in the Philippines: tuberculosis, malignancy and radiation-induced
Kussmaul’s sign: increase in systemic venous pressure with inspiration (in normal conditions, there should
be a decrease in pressure with inspiration)
Pericardial knock: early diastolic sound in the left sternal border

III. DIAGNOSIS AND MANAGEMENT


DIAGNOSTICS ACUTE PERICARDITIS CHRONIC (CONSTRICTIVE
PERICARDITIS)
Cardiac biomarkers Modest increase May be normal-minimally
increased
Subepicardial inflammation displays: Low voltage QRS complexes
Stage 1: Diffuse SST-elevation Diffuse flattening or inversion
ECG with upward concavity and PR of T-waves
segment depression Atrial fibrillation in 1/3 of
Stage 2: ST segments patients
normalize
Stage 3: T-wave inversions
Stage 4: ECG returns to

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normal (weeks or months)

This is in contrast with ECG findings in


AMI wherein ST-elevations are
convex, QRS changes occur and T-
wave inversion is seen within hours
before the ST-segments become
isoelectric
Pericardial thickening
Septal bounce
Pericardial fluid or thickening Dilation of the IVC and hepatic
Differentiate pericarditis from veins
Echocardiography MI: assessment of wall motion Normal ventricular systolic
function
Flattening of the LV posterior
wall
CT/MRI Pericardial fluid collection Pericardial thickening (more
Pericardial thickening accurate)
Bed rest Pericardial resection /
NSAIDs, colchicine pericardectomy
Management Pericardiocentesis if with Sodium restriction & diuretics
tamponade Anti-Koch’s for TB patients
Steroids (uncertain benefi)

CARDIAC TAMPONADE
I. ETIOPATHOGENESIS
Accumulation of fluid in the pericardial space causes increased intracardiac pressures causing limited ventricular
filling and decreased cardiac output
Three most common causes are neoplastic disease, idiopathic pericarditis and renal failure

II. CLINICAL MANIFESTATIONS


Dyspnea, orthopnea and fatigue
Beck’s triad: hypotension, neck vein engorgement and muffled heart sounds
Tachycardia, tachypnea and pulsus paradoxus (>10 mmHg decrease in SBP during inspiration)

A. Diagnostics for Cardiac Tamponade


DIAGNOSTICS COMMENTS/EXPECTED FINDINGS
12-L ECG Low voltage QRS complexes with electrical alternans
Chest Radiograph Multi-chambered cardiomegaly “water-bottle” sign
2D Echocardiography Large pericardial effusion
Right atrial and right ventricular diastolic collapse

B. Differentials for Cardiac Tamponade


CHARACTERISTIC CARDIAC CONSTRICTIVE RESTRICTIVE RV MI EFFUSIVE
TAMPONADE PERICARDITIS CMP CONSTRUCTIVE
Clinical Features
Pulsus Paradoxus +++ + + + +++
Jugular Veins
Prominent y-descent - ++ + + -
Prominent x-descent +++ ++ +++ + +++
Kussmaul’s sign - +++ + +++ ++
Third Heart Sound - - + + +
Pericardial Knock - ++ - - -

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Electrocardiogram
Low ECG voltage ++ ++ ++ - ++
Electrical Alternans ++ - - - +
Echocardiography
Thick pericardium - +++ - - ++
Pericardial effusion +++ - - ++
RV size Usually small Usually normal Usually normal Enlarged
Exaggerated +++ +++ - +++
Respiratory Variation
CT-MRI
Thick pericardium - +++ - ++
Equalization of Diastolic +++ +++ - ++
Pressure
Cardiac Biopsy Helpful? No No Sometimes No No
CMP: Cardiomyopathy; RVMI: right ventricular myocardial infarction

IV. MANAGEMENT
Emergency pericardiocentesis
Tube pericardiostomy with pericardial window (for recurrent, infectious, malignant and other chronic causes)

CARDIOMYOPATHY (CMP)
Heterogenous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that
usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilatation and are due to a variety of
causes that frequently are genetic
It excludes cardiac dysfunction that results from other structural heart diseases such as CAD, valvular disease or
severe hypertension
DILATED RESTRICTIVE HYPERTROPHY
CARDIOMYOPATHY CARDIOMYOPATHY CARDIOMYOPATHY
Cardiac enlargement, Endomyocardial scarring or Disproportionate
resulting in impaired systolic myocardial infiltration hypertrophy, typically
Pathophysiology function, HF, arrhythmia, resulting in restriction of involving the interventricular
emboli ventricular filling septum more than the free
wall
Ejection Fraction Usually <30% 25-50% >60%
LV Dimension Dilated >60mm >60mm (may be decreased) Often decreased
LV Wall Thickness Decreased Normal or increased Markedly increased
Atrial Size Increased Increased; may be massive Increased
Valvular Regurgitation Related to annular dilation Related to endocardial Related to valve-septum
involvement interaction
Common First Symptoms Exertional intolerance Exertional intolerance, fluid Exertional intolerance; may
retention early have chest pain
Congestive Symptoms Left before right Right often predominates Left-sided congestion may
develop late
Viral, parasitic Amyloidosis Most common abnormality
Common examples Peripartum Loeffler’s found at autopsy in young
Alcohol, MAP, cocaine Endomyocardial competitive athletes who die
Chemotherapy suddenly
Normal LVEF: > 50%
Normal LV dimension: < 55mm

ATRIAL FIBRILLATION (AF)


I. TYPES OF ATRIAL FIBRILLATION
TYPE DEFINITION
Lone AF AF in a patient <60 years old with the absence of clinical findings of other
cardiovascular disease, related pulmonary disease, or cardiac abnormalities
First Diagnosed AF Every patient who present with AF for the first time, irrespective of duration or
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presence / severity of symptoms
Self-terminating, usually within 48 hours
Paroxysms may continue for up to 7 days
Paroxysmal AF 48 hour time point is important: after this, likelihood of spontaneous conversion
is low
Anticoagulation must be considered
Persistent AF AF episode either lasts >7 days or require termination by cardioversion
Long-standing Persistent AF Lasted for > 1 year when it is decided to adopt a rhythm control strategy
Permanent AF Presence of arrhythmia is accepted by the patient – rhythm control interventions
are not pursued

II. STROKE PREVENTION IN AF


Efficacy of stroke prevention with aspirin is weak and the risk of major bleeding with aspirin is not significantly
different from oral anticoagulants (OACs)
Usually has two scoring systems:
o CHA2DS2-VASc Score: to determine the risk of having a stroke in the presence of AF
o HAS-BLED: to determine the risk of bleeding (since patients with AF will be given anticoagulants)

A. CHA2DS2-VASc Score
Estimates the risk of ischemic stroke in patients with non-rheumatic / non-valvular atrial fibrillation
Better than CHADS2 in identifying “truly low risk” patients with AF
Components and corresponding points:
VARIABLE SCORE (POINTS) RISK
C Congestive HF / left ventricular dysfunction 1 0: 0%
1: 1.3%
H Hypertension (>140/9 mmHg) 1 2: 2.2%
A2 Age > 75years 2 3: 3.2%
D Diabetes 1 4: 4.0%
S2 Prior stroke / TIA / thromboembolism 2 5: 6.7%
6: 9.8%
V Vascular disease (prior MI, PAD, aortic plaque) 1 7: 9.6%
A Age 65-74 1 8: 12.5%
Sc Female sex 1 9: 15.2%

B. HAS-BLED Score
Bleeding risk score to aid in decision-making for thromboprophylaxis (to balance the risk of stroke versus risk of
major bleeding)
High risk for bleeding: HAS-BLED score > 3 (regular monitoring and correction of potentially reversible risk factors
for bleeding)
VARIABLE SCORE (POINTS)
Hypertension (SBP > 160 mmHg) 1
Abnormal renal / liver function
Renal: Chronic dialysis or renal transplantation or creatinine > 200 umol/L 1
Liver: CLD, bilirubin >2x ULN with AST / ALT / Alk Phos >3x ULN 1
Previous Stroke 1
Bleeding history or predisposition (bleeding diathesis, anemia, etc) 1
Labile INR (unstable or high INR) 1
Elderly (age >65) 1
Use of Drugs predisposing to bleeding (e.g., antiplatelets, NSAIDs) 1
Alcohol use (>8 drinks per week) 1
CLD: Chronic Liver Disease
ULN: Upper Limit of Normal

III. MANAGEMENT OF ATRIAL FIBRILLATION


A. Drugs for Rate Control:
B-blockers: metoprolol, bisoprolol, atenolol, esmolol, propranolol, carvedilol
Non-dihydropyridine CCB: verapamil, diltiazem
Digitalis / Digoxin
Others: amiodarone, dronedarone

75
B. Pharmacological Cardioversion:
If with structural heart disease: Amiodarone
If without structural heart disease: Flecainide, Ibutilide, Propafenone

C. Electrical Cardioversion:
Used for patients with recent-onset AF (<48 hours) and with hemodynamic instability

IV. ANTICOAGULATION FOR STROKE PREVENTION


POPULATION ANTITHROMBOTIC THERAPY FOR STROKE PREVENTION
Valvular AF (RHD, prosthetic valves) Warfarin only
Non-Valvular AF + <65 years old + Lone AF No antithrombotic therapy
Non-Valvulvar AF + CHA2DS2-VASc Score 0 No antithrombotic therapy
Non-Valvular AF + CHA2DS2-VASc Score 1 Class Iia: consider oral anticoagulant therapy (NOAC/warfarin)
Non-Valvular AF + CHA2DS2-VASc Score > 2 Class I: start oral anticoagulant therapy (NOAC or warfarin)

A. Warfarin (Vitamin-K Antagonist)


Considered for patients with AF with >1 stroke risk factor(s) provided there are no contraindications
Superior to antiplatelets in preventing stroke
Usual INR target: 2.0-3.0

B. Non-Vitamin K Oral Anticoagulants (NOACs)


Non-inferior to warfarin, but with better safety profile
Broadly preferably to warfarin in the vast majority of patients with non-valvular AF
Assessment of renal function is mandatory for all NOACs, especially for Dabigatran
Do not require dose adjustment on the basis of a specific coagulation test (in contrast to INR in warfarin)
Do not have specific antidotes, and management of bleeding is supportive
Not recommended in patients with severe renal impairment (creatinine clearance < 30 mL/min)
DRUG MECHANISM OF ACTION DOSE
Oral direct thrombin inhibitor
150 mg BID superior to warfarin 150 mg BID
with same risk as warfarin to cause 110 mg BID for> age > 80,
Dabigatran major bleeding concomitant interacting drugs,
110 mg BID non-inferior to warfarin HAS-BLED > 3, creatinine
with fewer major bleeds (compared clearance 30-40 mL/min
to warfarin)
Oral direct factor Xa inhibitor 20 mg OD
Rivaroxaban Non-inferior to warfarin in 15 mg OD if: HAS-BLED > 3,
preventing stroke creatinine clearance 30-49
mL/min
5 mg BID
Apixaban Oral direct factor Xa inhibitor 2.5 mg BID if : age > 80 years,
weight < 60 kg, or creatinine >
133 umol/L

PERIPHERAL ARTERY DISEASE (PAD)

I. ETIOPATHOGENESIS
Clinical disorder characterized by stenosis or occlusion in the aorta or arteries of the limbs
Atherosclerosis is the leading cause of PAD in patients >40 years old

II. CLINICAL MANIFESTATIONS


A. History and Symptoms
More than half of patients with PAD are actually asymptomatic, though some may present with slow gait
Most common symptoms: intermittent claudication (pain, ache, cramp, numbness, or sense of fatigue in the
muscles which occurs during exercise and is relieved by rest)
Other symptoms are rest pain or feeling of coldness or numbness in the feet and toes

76
B. Physical Examination
Decreased or absent pulses distal to obstruction
Bruits over narrowed artery
Muscle atrophy, hair loss, thickened nails, smooth and shiny skin
Reduced skin temperature
Pallor, cyanosis,, ulcers or gangrene

III. DIAGNOSIS
DIAGNOSTICS COMMENTS / EXPECTED FINDINGS
ABI: ratio of ankle to brachial artery pressure
ABI Assessment by Doppler o >1.0: normal individuals
o <0.9: in patients with PAD
o <0.5: signifies severe ischemia (at risk for critical limb ischemia)
Segmental pressure measurements: presence of pressure gradients between
sequential cuffs signify stenosis
Segmental pulse volume recordings: amplitude of pulse volume contour
Other Non-Invasive Tests becomes blunted in significant PAD
Duplex ultrasonography: images and detects stenosis
Transcutaneous oximetry
Treadmill testing: assesses functional limitations objectively

IV. MANAGEMENT
A. Non-Pharmacologic Management
Goals: reduce the risk of associated CV events, improve limb symptoms, prevent progression to critical ischemia,
and preserve limb viability
Risk factor modification: cigarette smoking cessation, BP control
Supportive: feet care, elastic supports should be avoided, regular exercise (walk until nearly maximum
claudication discomfort is experience, and then rest until symptoms resolve before resuming ambulation)
Revascularization is usually indicated for patients with disabling, progressive or severe symptoms despite medical
therapy and for those critical limb ischemia

B. Physical Examination
Antiplatelet Therapy Aspirin and clopidogrel dual therapy is not more effective than aspirin alone in
reducing CV morbidity and mortality in patients with PAD
Anticoagulant Therapy Not indicated to improve outcomes in patients with chronic PAD
ACE-Inhibitors Reduce CV risks in patients with PAD
Statins Target LDL <100 mg/dL
Increases claudication distance by 40-60% and improves measured quality of
Cilostazol life
Contraindicated in patients with CHF
Pentoxifylline Increases blood flow to the microcirculation and enhances tissue oxygenation

COR PULMONALE
I. ETIOPATHOGENESIS
Often referred to as “pulmonary heart disease”
Defined as altered RV structure and/or function in the context of chronic lung disease and is triggered by the
onset of pulmonary hypertension
Acute Cor Pulmonale Acute RV dilatation and failure occurs (e.g., massive pulmonary embolism) but RV does
not hypertrophy
Chronic Cor Pulmonale More slowly evolving and progressive pulmonary hypertension leads to both RV
hypertrophy and dilation

II. CLINICAL MANIFESTATIONS


Dyspnea: most common symptom and occurs due to increased work of breathing

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Tussive or effort-related syncope happens due to inability of RV to deliver adequate blood volume to the LV
Abdominal pain and ascites: happens due to backflow from right-sided HF
Orthopnea and PND: uncommon and occurs only with concurrent LV failure
RV heave: points to RV volume and pressure overload
Carvallo’s sign: increase in the intensity of the holosystolic murmur of tricuspid regurgitation with inspiration
Cyanosis: a late finding and is secondary to low cardiac output

III. DIAGNOSIS
DIAGNOSTICS COMMENTS / EXPECTED FINDINGS
12-L ECG P pulmonale (p waves > 2.5 mV in leads II and/or V1)
Right axis deviation and RV hypertrophy
Chest Radiography Enlargement of main pulmonary artery, hilar vessels & descending right
pulmonary artery
2D Echocardiography Right-sided chamber enlargement with dysfunction; pulmonary hypertension
Spirometry Identifies obstructive and restrictive parenchymal diseases
CT scan Identifies thromboembolic diseases, interstitial diseases

IV. MANAGEMENT
Target the underlying pulmonary disease to decrease the underlying pulmonary valvular resistance and lessen
RV afterload
Non-invasive mechanical ventilation, bronchodilators and correction of respiratory acidosis
Correction of infection, anemia and polycythemia and other extra-cardiac problems
Pulmonary vasodilators: modest reduction of pulmonary pressure and RV afterload

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CHAPTER 3
PULMONARY MEDICINE
I. Introduction to Pulmonology
II. Approach to Patients with Pulmonary Conditions
1. Clinical History and Physical Examination
2. Diagnostic Procedures
III. Common Pulmonary Conditions
1. Bronchial Asthma
2. Chronic Obstructive Pulmonary Disease
3. Community-Acquired Pneumonia
4. Health Care-Associated Pneumonia
5. Pulmonary Tuberculosis
6. Pleural Effusion
7. Pneumothorax
8. Superior Vena Cava Syndrome

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SECTION 1
INTRODUCTION TO PULMONOLOGY
PULMONOLOGY FORMULAS AND REFERENCE VALUES
ALVEOLAR-ARTERIAL OXYGEN GRADIENT (Aa-Gradient)
To compute the A-a gradient appropriate for age:

age The normal A – a gradient for a young person


Normal A – a gradient = 4 + 4 is -5 -10 mmHg (normally increases with age).
Example: A 60 year old patient should have an
The A-a gradient is the difference between the alveolar oxygen (PAO 2) A-a gradient < 19.
and the arterial oxygen (PaO2)1 computed as follows:
An increased computed A-a gradient
A – a gradient = PAO2 – PaO2 (compared to the A-a gradient appropriate for
age) suggests defect in diffusion, V/Q
PaO2 is derived from patient’s ABG ; while PAO2 is computed as mismatch or right-to-lung shunting.
follows:
PaO2: arterial oxygen partial pressure: obtained
PaCO2 from ABG
PAO2 = FiO2(Patm- PH2O) – 0.8
PAO2: alveolar oxygen partial pressure
If FiO2 at room air is 21%, Patm at sea level is 760 mmHg and PH2O is 47
mmHg, the formula for A-a gradient can be simplified to: PaCO2: arterial carbo dioxide pressure: also
obtained from ABG
5
A – a gradient = 150 – 4 (PaCO2) - PaO2

PaO2 – FiO2 RATION (PFR)


PaO2: arterial oxygen partial pressure: obtained
PaO2 from ABG
PFR = FiO2 FiO2: fraction of inspired oxygen

DESIRED PaO2
If age < 60 years old:

Desired PaO2= 104 – (0.43 x age)


*Used for adjust for ventilator FiO2 settings
If age 60 years and above:

Desired PaO2= 80 – (age – 60)


DESIRED FiO2

Current FiO2 x Computed desired PaO2 Current PaO2: obtained from ABG
Desired FiO2 = Current PaO2 Computed desired PaO2: obtained using
previous formula
O2 FLOW SYSTEM OXYGEN FLOW RATES ESTIMATED FiO2 in %
1 24
2 28
Nasal cannula 3 32
4 36
5 40
6 44
5-6 40
Simple face mask 6-7 50
7-8 60

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SECTION 2
APPROACH TO PATIENTS WITH PULMONARY CONDITIONS
CLINICAL HISTORY AND PHYSICAL EXAMINATION
I. DYSPNEA

A. Pathogenesis of Dyspnea
DESCRIPTION PATHOPHYSIOLOGY
Chest tightness or constriction Bronchoconstriction
Interstitial edema (asthma, myocardial ischemia)
Increased work or effort of breathing Airway obstruction (COPD, uncontrolled asthma)
Neuromuscular disease (myopathy, kyphoscoliosis)
Air hunger, need to breathe, urge to breathe Increased drive to breathe (CHF, pulmonary
embolism, moderate-severe airflow obstruction)
Hyperinflation (asthma, COPD)
Cannot get a deep breath, unsatisfying breath Restricted tidal volume (pulmonary fibrosis, chest
wall restriction)
Heavy breathing, rapid breathing, breathing more Deconditioning

B. Variations of Dyspnea
SYMPTOM COMMENTS
Common indicator of CHF, mechanical impairment
Orthopnea of the diaphragm associated with obesity, or
asthma triggered by esophageal reflux
Paroxysmal nocturnal dyspnea Highly suggestive of CHF
Acute, intermittent episodes of dyspnea More likely to reflect episodes of myocardial
ischemia, bronchospasm, or pulmonary embolism
Chronic persistent of dyspnea Typical of COPD, interstitial lung disease, and
chronic thromboembolic disease
Platypnea Left atrial myxoma or hepatopulmonary syndrome

II. COUGH

A. Duration of cough
DURATION COMMON CAUSES
Respiratory tract infection, aspiration
Acute cough <3 weeks event, inhalation or noxious chemicals
or smoke
Residuum from a tracheobronchitis,
Subacute cough 3-8 weeks duration such as in pertussis or “post-viral
tussive syndrome”
Chronic cough >8 weeks Inflammatory, infectious, neoplastic
and cardiovascular etiologies

B. Differential diagnoses for cough with normal chest physical examination and radiography
Cough-variant asthma
Gastroesophageal reflux
Nasopharyngeal drainage
Medications (angiotensin converting enzyme [ACE] inhibitors)

III. HEMOPTYSIS
70-90% due to bronchitis, bronchiectasis, necrotizing pneumonia, tuberculosis (owing to high prevalence and its
predilection to cavity formation)
“BATTLE CAMP”
o Bronchitis, Bronchiectasis

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o Aspergilloma
o Tumor
o Tuberculosis
o Lung abscess
o Emboli
o Coagulopathy
o Autoimmune disorders, AVM, Alveolar hemorrhage
o Mitral stenosis
o Pneumonia
The origin of blood can be identified by observing its color
o Bright-red, foamy blood: usually from the respiratory tract
o Dark-red, coffee-colored blood: usually from the gastrointestinal tract
Principles of management:
o Maintain airway patency and oxygenation
o Localize the source of bleeding
o Control hemorrhage: may give racemic epinephrine ET flushing (if intubated), concocted as 1 ampule of
epinephrine in 9 mL normal saline solution, as 2 mL flushing q6

IV. CHEST EXAMINATION FINDINGS


CONDITION PERCUSSION FREMITUS BREATH VOICE ADVENTITIOUS
SOUNDS TRANSMISSION SOUNDS
Normal Resonant Normal Vesicular Normal Absent
(lung bases)
Consolidation or Bronchophony,
Atelectasis (with Dull Increased Bronchial Egophony Crackles
patent airway)
Consolidation or
Atelectasis (with Dull Decreased Decreased Decreased Absent
blocked airway)
Asthma Resonant Normal Vesicular Normal Wheezing
Emphysema Hyperresonant Decreased Decreased Decreased Absent or
Wheezing
Pneumothorax Hyperresonant Decreased Decreased Decreased Absent
Pleural effusion Dull Decreased Decreased Decreased Absent or Pleural
Friction Rub
Pulmonary mass Dull normal Normal normal Decreased
(over the mass) (over the mass)

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DIAGNOSTIC PROCEDURES
DIAGNOSTIC DESCRIPTION
Routine chest radiography (posterioanterior and lateral views)
Integral part of the diagnostic evaluation involving the parenchyma, pleura, airways
Chest Radiograph or and mediastinum
Chest X-Ray (CXR) Lateral decubitus: determine whether pleural abnormalities represent freely flowing
fluid
Apical lordotic views: visualize disease at the lung apices
Produces images using echoes or reflection of the US beam
Ultrasound (US) Can detect and localize pleural abnormalities
Quick and effective way of guiding percutaneous needle biopsy of peripheral lung,
pleural or chest wall lesions
Allows distinction between densities that would be superimpose on plain
Computed Tomography radiographs
(CT) Better in characterizing tissue density and providing accurate size assessment of
lesions
Commonly used for evaluation of pulmonary embolism (PE)
Ventilation-Perfusion PE produces 1 or more regions of VQ mismatch (e.g. regions in which there is a
(VQ) Lung Scanning defect in perfusion that follows the distribution of a vessel & that is not accompanied
by a corresponding defect in ventilation)
Helical CT and Helical CT: faster scans with improved contrast enhancement and thinner
Multidetector CT collimation
Multidetector CT: obtains multiple slices in a single rotation that are thinner
CT Pulmonary Allows simultaneous detection of parenchymal abnormalities
Angiography Test of choice for many clinicians in the evaluation of pulmonary embolism
Magnetic Resonance Role is less well defined than that of CT
Imaging (MRI) Poorer spatial resolutions and less detail of the pulmonary parenchyma
Pulmonary Angiography Radiopaque contrast medium is injected through a catheter placed in the pulmonary
artery
Bronchoscopy Direct visualization of the tracheobronchial tree
Performed usually with flexible fiberoptic instruments
Video-Associated Standard technique for diagnosis and management of pleural and parenchyma lung
Thoracoscopic Surgery disease
(VATS)

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SECTION 3
COMMON PULMONARY CONDITIONS
BRONCHIAL ASTHMA
I. ETIOPATHOGENESIS
Syndrome characterized by airflow obstruction that varies markedly, both spontaneously and with treatment
Associated with airway hyperresponsiveness and airflow inflammation
Symptoms usually demonstrate reversibility and variability
o Reversibility applies to rapid improvements in FEV1 (or PEF)1 measured within minutes after inhalation of
a rapid-acting bronchodilator or more sustained improvement over days or weeks after controller
treatment
o Variability refers to improvement or deterioration in symptoms and lung function occurring over time
Mast cells, eosinophils, T-lymphocytes, and neutrophils all play a role in the pathogenesis

II. CLINICAL MANIFESTATIONS


History of variable respiratory symptoms AND confirmed variable expiratory airflow limitation
III. History of Variable Respiratory Symptoms
Typical symptoms include cough, dyspnea, shortness of breath and wheezing
o May be worse at night and in the early morning hours
o Triggered by exercise, laughter, allergens and cold air
o Often appear or worsen with viral infections
Signs include rhonchi & wheezing throughout the chest but may be normal when asthma is controlled
III. Evidence of Variable Expiratory Airflow Limitation
At least once during the diagnostic process when FEV1 is low, confirm that FEV1 /FVC is reduced (it is normally
0.75-0.80 in adults)
Document that variation in lung function is greater than in healthy people (examples include the following):
o FEV1 increases by >12% and 200 mL after inhaling a bronchodilator (bronchodilator reversibility)
o Average diurnal PEF variability is >10%
o FEV1 increases by >12% and 200 mL from baseline after 4 weeks of anti-inflammatory treatment
PEF variability is calculated from twice daily readings (best of 3 each time), averaged over 1-2 weeks:

Day’s highest PEF – Day’s lowest PEF


PEF Variability = mean of the day’s highest and lowest PEF

III. DIAGNOSIS

A. Classification of Asthma Severity by Level of Control


CONTROLLED PARTYLY CONTROLLED UNCONTROLLED
(all of the following) (any measure present)
Daytime Symptoms None (2x or less/week) >2x/week
Limitation of Activities None Any
Nocturnal Symptoms None Any Three or more symptoms of
(Awakening) partly controlled asthma in
Need for Reliever None (2x or less/week) >2x/week any week
Lung Function Normal <80% predicted
Exacerbation None 1 or more per year One in any week

B. Asthma Phenotypes
PHENOTYPE DESCRIPTION
Most easily recognizable phenotype
Most often commences in childhood
Allergic Asthma Associated with a personal or family history of atopy
(eczema, allergic rhinitis, food and drug allergy)
Eosinophilic airway inflammation
Responds well to inhaled corticosteroids (ICS)
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Non-allergic Asthma Neutrophilic or paucigranulocytic airway inflammation
Less responsive to ICS
Common in women, presenting symptoms usually in
Late-onset Asthma adulthood
Requires higher doses of ICS or are relatively refractory to
ICS
Asthma with Fixed Airflow Limitation Seen in patients with long-standing asthma who develop
fixed airflow limitation due to airway wall remodeling

IV. MANAGEMENT
Goals of asthma therapy:
o Minimal (ideally no) chronic symptoms, including nocturnal symptoms
o Minimal (infrequent) exacerbations
o No emergency visits
o Minimal (ideally no) use of as-required B2-agonist
o No limitations on activities, including exercise
o PEF circadian variation <20%
o (near) normal PEF
o Minimal (or no) adverse effects from medicine

A. Pharmacologic Therapy for Asthma


DRUG CLASS EXAMPLES MECHANISM OF ACTION COMMENTS/ADVERSE
EFFECTS
RELIEVERS
Stimulates adenylyl cyclase,
increasing cAMP, causing
Salbutamol bronchodilation Tremors and palpitations
Short Acting B2 Procaterol Rapid onset of (usually in the elderly)
Agonists Terbutaline bronchodilation Minimal decrease in serum
(SABA) Albuterol Best used to relief of K+
symptoms
No effect on chronic
inflammation
Muscarinic receptor
antagonists Dry mouth (most common)
Short Acting Ipratropium Inhibit only the cholinergic Urinary retention and
Anticholinergics reflex components and glaucoma may be
thereby less effective than observed in the elderly
B2-agonists
Inhibit phosphodiesterase Nausea, vomiting and
Methylxanthines Theophylline activity causing increase in headache (most common)
Aminophylline cAMP levels and Arrhythmia, seizures and
bronchodilation death at high concentration
CONTROLLERS
Most effective anti-
Inhaled Beclomethasone inflammatory agents for
Corticosteroids Budesonide asthma control Hoarseness / dysphonia
(ICS) Fluticasone Reduce inflammatory cell and oral candidiasis
numbers and eosinophils in
airway mucosa
Truncal obesity, easy
Prednisone bruisability, osteoporosis,
Systemic Methylprednisolone Useful for treatment of acute DM, HPN, gastric
Steroids Hydrocortisone exacerbations ulceration, proximal
myopathy, depression,
cataracts
Long Acting B2 Formoterol Improve asthma control and Should not be given in the
Agonists Salmeterol reduce inflammation when absence of ICS

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(LABA) Bambuterol added to ICS, thereby
allowing lower doses of ICS
to be given
Less effective than ICS in
controlling asthma and
Leukotriene Montelukast Block leukotriene receptors have less effect on airway
Modifying Zafirlukast (montelukast, zafirlukast) or inflammation
Drugs Zileuton inhibit lipoxygenase Useful as an add-on
(zileuton) therapy in some patients
not controlled with low
doses of ICS
Very short duration of
Cromones Cromolyn sodium Inhibit mast cell and sensory action needing frequent
Nedocromil sodium nerve activation dosing
Favorable safety profile
Anti-IgE Omalizumab Inhibits IgE-mediated Very expensive

B. Initial Controlled Treatment


Asthma treatment is a continuous cycle: assess, adjust treatment and review response
For the best outcomes, regular controller treatment should be initiated as soon as possible after the diagnosis of
asthma is made
After starting initial controller treatment, review response after 2-3 months, or according to urgency
o Consider stepping up if: uncontrolled symptoms, exacerbations or risks
o Consider stepping down if: symptoms controlled for 3 months, low risk for exacerbations
Indicated only if:
Symptoms are rare
Step 1 As-needed SABA with no controller No night-walking due to asthma
No exacerbations in the last year
Normal FEV1
Step 2 Low-dose ICS + as-needed SABA
Step 3 Low-dose ICS/LABA + as-needed SABA or
ICS/Formoterol maintenance + reliever therapy
Step 4 Low-dose ICS/Formoterol maintenance + reliever therapy, or
Medium dose ICS/LABA + as-needed SABA
Step 5 Refer for expert investigation
Add-on treatments: anti-IgE (Omalizumab), low dose oral steroids

C. Non-Pharmacologic Therapy of Asthma


Smoking cessation
Regular physical activity
Occupational aspects
Breathing techniques

V. CLASSIFICATION AND MANAGEMENT OF EXACERBATIONS


MILD OR MODERATE SEVERE LIFE THREATENING
Clinical Talks in phrases Talks in words
manifestations Prefers sitting to lying Sits hunched forward
Not agitated Agitated
Respiratory rate Increased >30/min Drowsy,
Accessory Not used Used Confused,
muscles Silent chest
Pulse rate 100-120 bpm >120 bpm
O2 saturations 90-95% <90%
Peak Expiratory >50% predicted or best < 50% predicted or best
Flow (PEF)
SABA Transfer to acute care facility
Treatment Ipratropium bromide SABA
Prednisolone 1mg/kg PO Ipratropium bromide

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Controlled oxygen Controlled oxygen
Oral or IV corticosteroids
Consider IV magnesium
Consider high dose ICS

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

I. ETIOPATHOGENESIS
Characterized by expiratory airflow limitation that is not fully reversible (hallmark: airflow obstruction)
Unusual in the absence of smoking or prior history of smoking, except for patients with A1-antitrypsin deficiency
Elastase-Antielastase Hypothesis: remains a prevailing mechanism for its pathophysiology

A. The Pathological Changes include:


Chronic inflammation
Increased numbers of specific inflammatory cell types in different parts of the lung
Structural changes resulting from repeated injury and repair

B. Encompasses the Following Conditions:


Emphysema: anatomically-defined condition characterized by enlargement and destruction of alveoli “pink
puffers”)
Chronic bronchitis: clinical condition characterized by chronic cough and phlegm (“blue bloaters”)
Small airways disease: condition where bronchioles are narrowed

II. CLINICAL MANIFESTATIONS


CARDINAL SYMPTOMS SIGNS
May be normal in early stages
Pink puffers (predominantly emphysema): thin, non-cyanotic,
prominent use of accessory muscles
Blue bloaters (predominantly chronic bronchitis): heavy and cyanotic
Most common symptoms: “Tripod position”: to facilitate use of accessory muscles
Cough, sputum production, exertional Signs of hyperinflation: barrel chest, enlarged lung volumes on
dyspnea percussion (hyperresonance)
Others: pursed-lip breathing, expiratory wheezing, systemic wasting,
weight loss
Signs of cor pulmonale (bipedal edema, ascites) in severe cases
Clubbing is not a sign of COPD and should alert the clinician to other
causes of clubbing

III. DIAGNOSIS
A clinical diagnosis of COPD should be considered in any patient who has dyspnea, chronic cough or sputum
production, and a history of exposure to risk factors for the disease
Risk factors: tobacco smoke (including popular local preparations), smoke from home cooking and heating
fuels, occupational dusts and chemical
DIAGNOSTIC TEST COMMENTS/EXPECTED FINDINGS
Required to make the diagnosis
Post-bronchodilator FEV1/FVC <0.70 confirms presence of persistent
airflow limitation
Degree of reversibility of airflow limitation after bronchodilators /
steroids is no longer recommended (it has never been shown to add
Spirometry to the diagnosis, differential diagnosis, or to predicting the response
to long-term treatment with bronchodilators or corticosteroids)
FEV1, FEV1/FVC and all other measures of expiratory airflow are
reduced
TLC, FRC and RV may be increased indicating air trapping
DLCO may be reduced
Chest radiograph Useful for excluding other differential diagnoses
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Low flattened diaphragms, increase in the volume of retrosternal
airspace (hyperinflation)
Hyperlucent lung zones with possible bullae formation and diminished
vascular markings
Not routinely requested
May be helpful when the diagnosis is in doubt to rule out concomitant
CT scan diseases
Useful if surgical procedure such as lung volume reduction is
contemplated
To evaluate a patient’s oxygen saturation and need for supplemental
oxygen therapy
Pulse oximetry Should be used to assess all stable patients with FEV1<35%
predicted or with clinical signs suggestive of respiratory failure or right
heart failure
If peripheral saturation is <92%, ABGs should be assessed
Resting or exertional hypoxemia
Increased alveolar-arterial oxygen tension gradient
Arterial blood gas (ABG) In long-standing disease, may have chronically increased arterial
PaCO2 but metabolic compensation (increased HCO 3) maintains pH
near normal

IV. CLASSIFICATION OF COPD


PATIENT CHARACTERISTIC SPIROMETRIC EXACERBATIONS PER mMRC
CLASSIFICATION YEAR
A Low risk GOLD 1-2 <1 0-1
Less symptoms
B Low risk GOLD 1-2 <1 >2
More symptoms
C High risk GOLD 3-4 >2 0-1
Less symptoms
D High risk GOLD 3-4 >2 >2
More symptoms

A. Classification based on Severity of Airflow Limitation in COPD using Spirometry (Post-Bronchodilator FEV1)
Spirometry should be performed after the administration of an adequate dose of a short-acting inhaled
bronchodilator (to minimize variability)
STAGE CLINICAL FINDINGS SPIROMETRY FINDINGS
FEV1/FVC FEV1
Chronic cough and
GOLD 1 sputum production FEV1> 80% predicted
Mild Patient unaware that lung
function is abnormal
Chronic cough and sputum
production
GOLD 2 Shortness of breath on FEV1 50 to <80%
Moderate exertion predicted
FEV1 / FVC
Stage patients typically seek
medical attention <0.70
Greater shortness of breath
GOLD 3 Reduced exercise capacity FEV130 to <50%
Severe Fatigue predicted
Repeated exacerbations
Signs or symptoms of
GOLD 4 respiratory failure (PaO2< 60 FEV1<30% predicted
Very Severe mmHg + PaCO2>50 mmHg)
Cor pulmonale

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B. Classification Based on Exacerbation
Exacerbation of COPD: defined as an acute event characterized by worsening of the patient’s
respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication
Best predictor of having frequent exacerbations (2 or more per year) is a history of previously treated
events

C. Modified Medical Research Council (mMMRC) Questionnaire for Assessing the Severity of Breathlessness
mMMRC DESCRIPTION
0 I only get breathless with strenuous exercise
1 I get short of breath when hurrying of the level or walking up a slight hill
2 I walk slower than people of the same age on the level because of breathlessness, or I
stop for breath when walking on my own pace on the level
3 I stop for breath after walking 100 meters or after a few minutes on the level
4 I am too breathless or I am breathless when I’m dressing or undressing

V. OVERVIEW OF MANAGEMENT

A. Only Three Interventions have been demonstrated to influence the natural history of COPD
Biggest impact in the natural history of COPD
Nicotine replacement therapy (gum, inhaler, nasal spray, transdermal
Smoking Cessation patch) reliably increases long term smoking abstinence rates
Brief (3-minute) period of counseling to urge a smoker to quit results in
smoking cessation rates of 5-10%
Only pharmacologic therapy demonstrated to unequivocally decrease
Oxygen Therapy mortality rates in COPD
For chronically hypoxemic patients
>15 hours / day (long term oxygen therapy)
Lung Volume Reduction Surgery Segmentectomy or lobectomy of focal emphysematous areas of the
lung

B. Pharmacologic Therapy for Stable COPD


None of the existing medications for COPD have been shown to modify the long-term decline in lung function
Bronchodilator medications are central to the symptomatic management of COPD (principal bronchodilator
treatment includes B2-agonists, anticholinergics and methylxanthines)
MEDICATIONS COMMENTS ADVERSE EFFECTS
Alters airway smooth muscle tone improving
emptying of the lungs
Effects usually wear off within 4-6 hours (short Sinus tachycardia
acting) and >12 hours (long acting) Arrhythmias
Beta2 – Agonists Regular treatment with LABA is more effective Tremors
and convenient than treatment with SABA Hypokalemia
Appears to provide subjective benefit in acute
episodes but is not necessarily helpful in stable
disease
Blocks acetylcholine’s effect on muscarinic
receptors
Example: ipratropium, oxitropium, and Dryness of the mouth
Anticholinergics tiotropium bromide Bitter metallic taste
Bronchodilating effects of short-acting inhaled Arrhythmias
anticholinergics lasts longer than that of short-
acting B2-agonists
Tachycardia
Acts as nonselective phosphodiesterase Arrhythmias
Methylxanthines inhibitor Seizures
Examples: theophylline, doxofylline Headaches
Insomnia
Inhaled Addition of ICS to bronchodilator treatment Hoarseness
corticosteroids appropriate for: Oral candidiasis
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o Symptomatic patients with FEV1<50%
predicted (Stages III and IV)
o Repeated exacerbations
Chronic treatment with systemic glucocorticoids
should be avoided

VI. MANAGEMENT OF STABLE COPD

A. Pharmacologic Management of COPD


PATIENT RECOMMENDED FIRST ALTERNATIVE CHOICE OTHER POSSIBLE
GROUP CHOICE TREATMENT
LAMA
SAMA pm or
A or LABA Theophylline
SABA pm or
SABA and SAMA
B LAMA SABA and/or SAMA
or LAMA and LABA Theophylline
LABA
LAMA and LABA
ICS + LABA or SABA and/or SAMA
C or LAMA and PDE-4 inhibitor Theophylline
LAMA or
LABA and PDE-4 inhibitor
ICS + LABA and LAMA
or
ICS + LABA ICS + LABA and PDE-4 inhibitor Carbocisteine
D and/or or SABA and/or SAMA
LAMA LAMA and LABA theophylline
or
LAMA and PDE-4 inhibitor
SAMA: Short acting muscarinic antagonist (e.g., Ipratropium)
SABA: Short acting beta agonist (e.g. Salbutamol)
LAMA: Long acting muscarinic agonist (e.g., Tiotropium)
LABA: Long acting beta agonist (e.g., Salmeterol)
ICS: Inhaled corticosteroid (e.g. Budesonide)
PDE-4 inhibitor (e.g., Roflumilast)

B. Non-Pharmacologic Management of COPD


PATIENT GROUP ESSENTIAL RECOMMENDED DEPENDING ON LOCAL
GUIDELINE
A Smoking cessation Physical activity Flu vaccination
Pneumococcal vaccination
B-D Smoking cessation Physical activity Flu vaccination
Pulmonary rehabilitation Pneumococcal vaccination

VII. MANAGEMENT OF ACUTE EXACERBATIONS


Exacerbation: event in the natural course of the disease characterized by a change in patient’s baseline
dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a
change in regular medication in patients with underlying COPD
Change in mental status is the most important sign of a severe exacerbation in patients with very severe COPD

A. Management of Severe but Not Life-Threatening Exacerbations of COPD at the ER


Assess severity of symptoms, blood gases, and CXR
Administer controlled oxygen therapy and repeat ABG after 30-60 minutes
Increase doses and/or frequency of bronchodilator use
Add oral or IV glucocorticoids
Consider antibiotics (oral or occasionally IV) when there are signs of bacterial infection
Consider non-invasive mechanical ventilation

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B. Therapy for Acute Exacerbation
MANAGEMENT COMMENTS
Bronchodilators Inhaled B-agonists often with addition of anticholinergic agent
Frequency depends on severity of exacerbation
Bacteria frequently implicated in exacerbations: Streptococcus pneumoniae,
Antibiotics Haemophilius influenza, Moraxella catarrhalis
Most clinicians treat patients with moderate or severe exacerbations with
antibiotics, even in the absence of data implicating a specific pathogen
Reduces hospital stay, hastens recovery and reduces chances of subsequent
Glucocorticoids exacerbations / relapses
Prednisone 40 mg/day or its equivalent for 5 days
Most common acute complication for steroids: hyperglycemia
Oxygen Maintain O2 saturation > 90%
Administration of oxygen does not reduce minute ventilation

C. Indications for Ventilator Support


NON-INVASIVE VENTILATION INVASIVE MECHANICAL VENTILATION
Selection Criteria
Moderate to severe dyspnea with use of
accessory muscles and paradoxical abdominal Indications
motion Unable to tolerate NIV or NIV failure
Moderate to severe acidosis (pH <7.35) and/or Severe dyspnea with use of accessory muscles
hypercapnia (PaCO2>45mmHg) and paradoxical abdominal motion
RR >25/min RR >35/min
Exclusion Criteria (any may be present) Life-threatening hypoxemia
Respiratory arrest Severe acidosis (pH <7.25) and/or hypercapnia
Cardiovascular instability (PaCO2>60 mmHg)
Change in mental status; uncooperative patient Respiratory arrest
High aspiration risk Somnolence, impaired mental status
Viscous or copious secretions Cardiovascular complications
Recent facial or gastroesophageal surgery Other complications (e.g., metabolic abnormalities,
Craniofacial trauma sepsis, pneumonia, pulmonary embolism,
Fixed nasopharyngeal abnormalities barotrauma, massive pleural effusion)
Burns
Extreme obesity

D. Discharge Criteria
Inhaled beta-agonist use no more frequent than q4h
Patient is able to walk across room
Patient able to eat and sleep without frequent awakening by dyspnea
Patient has been clinically stable for 12-24 hours
ABG have been stable for 12-24 hours
Patient (or home caregiver) fully understands the use of meds
Follow-up plans have been finalized and home care arrangements have been completed

COMMUNITY-ACQUIRED PNEUMONIA (CAP)


I. ETIOPATHOGENESIS
Lower respiratory tract infection (pulmonary parenchyma) acquired in the community within 24 hours to less than
2 weeks
Results from the proliferation of microbial pathogens at the alveolar level and the host’s response to those
pathogens
Most common access of microorganisms to the lower respiratory tract is through aspiration from the oropharynx
Classic pneumonia (lobar pneumococcal) evolves through a series of changes

91
PHASE DESCRIPTION
Edema Initial phase with the presence of a proteinaceous exudate and often of bacteria
in the alveoli
Erythrocytes in the cellular intraalveolar exudate
Red Hepatization Neutrophil influx is more important from the standpoint of host defense
Bacteria are occasionally seen in pathologic specimens
No new erythrocytes are extravasating and those already present have been
lysed and degraded
Gray Hepatization The neutrophilis the predominant cell, fibrin deposition is abundant and bacteria
have disappeared
This phase corresponds with successful containment of the infection and
improvement in gas exchange
Resolution (Final Macrophage reappears as the dominant cell type in the alveolar space and the
Phase) debris of neutrophils, bacteria and fibrin has been cleared, as has the
inflammatory response

II. CLINICAL MANIFESTATIONS


Commonly presents with acute cough, abnormal vital signs of tachypnea, tachycardia, and fever with at least one
abnormal chest finding of diminished breath sounds, rhonchi, crackles or wheezes

III. DIAGNOSIS

A. Classification and Disposition


LOW-RISK CAP MODERATE-RISK CAP HIGH-RISK CAP
Stable Unstable
RR <30/min RR > 30/min
Vital Signs PR <125bpm PR >12bpm
Temp 36-40oC Temp > 40oC or
BP > 90/60mmHg <36oC Any of the criteria under
BP < 90/60 mm/Hg Moderate Risk CAP, plus:
No altered mental Altered mental state Severe sepsis and
state of acute onset of acute onset septic shock
Features No suspected Suspected Need for
aspiration aspiration mechanical
No or stable Decompensated co- ventilation
comorbids morbidities
Localized infiltrates Multilobar infiltrates
Chest X-Ray No pleural effusion Pleural effusion
No abscess Abscess
Disposition outpatient ward admission ICU admission

B. Diagnostics for CAP


DIAGNOSTICS COMMENTS
Essential in the diagnosis of CAP, assessing
severity, differentiating pneumonia from other
Chest Radiography conditions and in prognostication
Best radiologic evaluation consists of standing
posterioanterior and lateral views of the chest
Does not predict the likely etiologic agent
Microbiologic Studies Optional in low-risk CAP
(sputum and blood cultures) Necessary in moderate- and high-risk CAP
Options for non-resolving pneumonia,
Invasive Procedures immunocompromised patients and in whom no
(e.g., transtracheal, transthoracic, biopsy, adequate respiratory specimens can be sent
bronchoalveolar lavage, protected brush specimen) despite sputum induction and routine diagnostic
testing

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IV. MANAGEMENT
For patients requiring hospitalization, empiric therapy should be initiated as soon as possible after a diagnosis
Empiric microbial therapy for CAP:
RISK STRATIFICATION POTENTIAL PATHOGENS EMPIRIC THERAPY
Previously healthy:
Amoxicillin or extended macrolides
(suspected atypical pathogen)
Streptococcus pneumoniae
Haemophilus influenza With stable comorbid illness:
Chlamydphila pneumoniae β-lactam / β-lactamase inhibitor
Low-Risk CAP Mycoplasma pneumoniae combination (BLIC) or second-
Moraxella catarrhalis generation oral cephalosporin +
Enteric Gram-negative bacilli extended macrolides
(among those with co-morbids)
Alternative:
Third-generation oral cephalosporin
+ extended macrolide
Streptococcus pneumoniae
Haemophilus influenza IV non-antipseudomonal β-lactam
Chlamydphila pneumoniae (BLIC, cephalosporin or carbapenem)
Moderate-Risk Mycoplasma pneumoniae + extended macrolide
Moraxella catarrhalis or
CAP Enteric Gram-negative bacilli IV non-antipseudomonal β-lactam +IV
Legionella pneumophila extended macrolide or IV respiratory
Anaerobes (risk of aspiration) FQ

No risk for P. aeruginosa:

Streptococcus pneumoniae IV non-antipseudomonal β-lactam +IV


Haemophilus influenza extended macrolide or IV respiratory
Chlamydphila pneumoniae FQ
Mycoplasma pneumoniae
Moraxella catarrhalis With risk for P. aeruginosa:
High-Risk CAP Enteric Gram-negative bacilli
Legionella pneumophila IV antipneumococcal antipseudomonal
Anaerobes (risk of aspiration) β-lactam + IV extended macrolide +
Staphylococcus aureus aminoglycoside
Pseudomonas aeruginosa or
IV antipneumococal antipseudomonal
β-lactam + IV ciprofloxacin/levofloxacin
(high-dose)
1. Extended macrolides: azithromycin dehydrate, clarithromycin
2. Oral β-lactam/β-lactamase inhibitor (BLIC): amoxicillin-clavulanic acid, amoxicillin-sulbactam, sultamicillin
3. Oral second-generation cephalosporin: cefaclor, cefuroxime axetil
4. Oral third-generation cephalosporin: cefdinir, cefixime, cefpodoxime proxetil
5. IV non-antipseudomonal β-lactam (BLIC, cephalosporin or carbapenem): amoxicillin-clavulanic acid, ampicillin-sulbactam, cefotiam,
cefoxitin, cefuroxime Na, cefotaxime, ceftizoxime, ceftriaxone, ertapenem
6. Respiratory fluoroquinolones: levofloxacin, moxifloxacin
7. IV antipneumococal, antipseudomonal β-lactam (BLIC, cephalosporin or carbapenem): cefoperazone-sulbactam, piperacillin-tazobactam,
ticarcillin-clavulanic acid, cefipime, cefpirome, imipenem-cilastatin, meropenem
8. Aminoglycosides: gentamicin, tobramycin, netilmicin, amikacin

V. PNEUMONIA RISK SCORE (CURB-65) PREDICTS MORTALITY IN CAP


C Confusion of new onset Interpretation:
U Urea (BUN) > 7 mmol/L (19 mg/dL) 0-1: treat as outpatient
R Respiratory rate > 30 bpm 2: admit patient
B Blood pressure <90/60 mmHg >3: consider ICU admission
65 Age >65 years old

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VI. ASSESSING RESPONSE TO THERAPY

A. Response to therapy is expected within 24-72 hours of initiating treatment:


Temperature, RR, HR, BP, sensorium, O2 saturation, and inspired oxygen concentration should be monitored
to assess response to therapy
A patient is considered to have responded to treatment if:
o Fever decreases within 72 hours;
o Temperature normalizes within 5 days; and,
o Respiratory signs, particularly tachypnea, return to normal
Follow-up cultures of blood and sputum are not indicated for patients who are responding to treatment

B. De-escalation of antibiotic therapy once the patient is improving, stable and has a functioning GI tract:
Resolution of fever more than 24 hours
Less cough and resolution of respiratory distress (normalization of RR)
Improving WBC count, no bacteremia
Etiologic agent is not a high-risk (virulent/resistant) pathogen (e.g. Legionella, S. aureus, or gram-negative
enteric bacilli)
No unstable comorbid condition or life-threatening complications such as MI, CHF, complete heart block, new
atrial fibrillation, supraventricular tachycardia, etc.
No sign of organ dysfunction such as hypotension, acute mental changes, BUN to creatinine ratio of >10:1,
hypoxemia, and metabolic acidosis
Patient is clinically hydrated, taking oral fluids and is able to take oral medications

C. Duration of Treatment
ETIOLOGIC ORGANISMS DURATION OF TREATMENT (days)
Most bacterial pneumonias 5-7
Enteric Gram-negative pathogens, S. aureus, and P. 14
aeruginosa
Mycoplasma and Chlamydophila 10-14
Legionella 14-21

D. Failure to improve after 72 hours of treatment is an indication of reassessment


Incorrect diagnosis or presence of complicating noninfectious condition (e.g., pulmonary embolism, CHF,
vasculitis, MI)
A resistant microorganism or an unexpected pathogen that is not covered by the antibiotic of choice
Antibiotic is ineffective or causing an allergic reaction
Impaired local or systemic host defenses (e.g., aspiration, endobronchial obstruction, bronchiectasis)
Local or distant complications of pneumonia (e.g., parapneumonic effusion, empyema, lung absecess, ARDS,
metastatic infection, endocarditis)
Overwhelming infection
Slow response in the elderly patient (S. pneumoniae and L. pneumophila)
Exacerbation of co-morbid illness
Nosocomial superinfection
E. Hospital Discharge
In the absence of any unstable coexisting illness or other life-threatening complication, the patient may be
discharged once clinical stability occurs and oral therapy is initiated
1. During the 24 hours before discharge, the patient should have the following characteristics:
Temperature of 36-37.5oC
Pulse <100/min
RR between 16-14/min
SBP >90 mmHg
Blood O2 saturation >90%
Functioning GI tract
2. Repeat Chest Radiograph
Not needed in patients who are clinically improving
Recommended during a follow-up visit, approximately 4 to 6 weeks after hospital discharge
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HEALTH CARE-ACQUIRED PNEUMONIA (HCAP)
I. ETIOPATHOGENESIS
Transition between classic CAP and typical HAP

A. Ventilator-Associated Pneumonia (VAP)


The greatest difference between VAP and HCAP/HAP is the return to dependence on expectorated sputum for a
microbiologic diagnosis of VAP, which is further complicated by frequent colonization by pathogens in patients
with HAP or HCAP
Common pathogenic mechanisms include oropharyngeal colonization with pathogenic bacteria, cross-infection
from other colonized patients, large volume aspiration, microaspiration around ET tub and altered lower
respiratory host defenses
Clinical manifestations: same in VAP as with any other forms of pneumonia: fever, leukocytosis, increase in
secretions, and pulmonary consolidation on PE, along with a new or changing radiographic infiltrate
NON-MDR PATHOGENS MDR PATHOGENS
Streptococcus pneumoniae Pseudomonas aeruginosa
Other Streptococcus spp. MRSA
Haemophilius 95nfluenza Acinetobacter spp.
MSSA Antibiotic-resistant Enterobacteraceae
Antibiotic-sensitive Enterobacteriaceae Enterobacter spp.
Escherichia coli ESBL-positive strains
Klebsiella pneumoniae Klebsiella spp.
Proteus spp. Legionella pneumophila
Enterobacter spp. Burkholderia cepacia
Serratia marcescens Aspergillus spp.

B. Hospital-Acquired Pneumonia (HAP)


HAP in non-intubated patients, both inside and outside the ICU, is similar to VAP save for the higher frequency of
non-MDR pathogens and better underlying host immunity in non-intubated patients the lower frequency of
MDR pathogens allows monotherapy in a majority of HAP cases
The only pathogens that may be more common in the non-VAP population are the anaerobes (due to a higher risk
of macroaspiration)
More difficult to obtain lower respiratory samples appropriate for culture in non-intubated patients

II. CLINICAL CONDITIONS ASSOCIATED WITH MDR PATHOGENS IN HCAP


Hospitalization for > 48 hours
Hospitalization for > 2 days in prior 3 months
Nursing home or extended-care-facility residence
Antibiotic therapy in preceding 3 months
Chronic dialysis
Home infusion therapy
Home wound care
Family member with MDR infection

III. MANAGEMENT
Once an etiologic diagnosis is made, broad-spectrum empirical therapy can be modified to address the known
pathogen specifically
Empirical antibiotic treatment of HCAP
WITHOUT RISK FACTORS FOR MDR PATHOGENS WITH RISK FACTIRS FOR MDR PATHOGENS
Standard recommendation is treatment with three
Majority can be treated with a single agent antibiotics: two directed at P. aeruginosa and one at
MRSA
Ceftriaxone 2g IV q24 A beta-lactam:
Moxifloxacin 400 mg IV q24 Ceftazidime 2g IV q8 or Cefepime 2g IV q8-12
Ciprofloxacin 400 mg IV q8 or
Levofloxacin 750 mg IV q24 Piperacillin/tazobactam 4.5g IV q6, Imipenem
Ampicillin/sulbactam 3g IV q6 500 mg IV q6 or 1g IV q8, plus
Ertapenem 1g IV q24

95
A second agent against gram-negative bacteria:
Gentamicin or Tobramycib 7 mg/kg IV q24 or
Amikacin 20 mg/kg IV q24, or
Ciprofloxacin 400 mg IV q8 or Levofloxacin 750
mg IV q24, plus

An agent against gram-positive bacteria:


Linezolid 600 mg IV q12, or
Vancomycin 15mg/kg, up to 1 g IV q12

PULMONARY TUBERCULOSIS (PTB)

I. ETIOPATHOGENESIS
Caused by Mycobacterium tuberculosis
Most common site for the development of TB is the lungs (85% of patients)
Most commonly transmitted from person with infectious PTB to others by droplet nuclei, which are aerosolized by
coughing, sneezing or speaking. Aerosolized droplets are 1-5 µm in diameter. A single cough can generate 3000
infective droplets, with as few as 10 bacilli needed to initiate infection
Most infectious patients: those with cavitary pulmonary disease and laryngeal TB
Typical TB lesion: epitheloid granuloma with central caseation necrosis

II. CLINICAL MANIFESTATIONS


In the Philippines, cough of two weeks or more should lead to high index of suspicion for PTB
Cough may be accompanied by night sweats, weight loss, unexplained fever and chills, chest pain, fatigue and
body malaise
Absence of fever does not exclude TB
Physical findings are of little utility in PTB

A. General Classification of Tuberculosis


CLASSIFICATION DEFINITIONS
Cough of at least 2 weeks in an adult (age > 15 y/o)
A child (< 15 y/o) fitting criteria for TB
Presumptive TB Radiologic imaging suggestive of tuberculosis
Any person who presents with symptoms or signs suggestive of TB
Cough of any duration in a high risk individual or a close contact of an
active TB case
Definite case A patient with MTB complex identified from a clinical specimen either by
culture or by a newer method such as molecular line probe assay
New case Patient who never had treatment for TB or who has taken anti-TB
medications for < 1 month
Retreatment case (patient previously treated with anti-TB drugs for at least 1 month in the past)
Patient who was previously treated for TB, and was declared cured for has
Relapse completed treatment; and is now bacteriologically or clinically diagnosed
TB
Patient who was previously treated for TB, and treatment failed at the end
of the most recent course:
o Sputum smear or sputum culture positive at 5 months or later
Treatment after failure during treatment
o Clinically diagnosed in a patient in whom sputum studies cannot
be done, without clinical improvement anytime during the course
of treatment
Treatment after lost to follow- A patient who returns to treatment with positive bacteriology (smear or
up (TALF) culture) or clinically diagnosed, following interruption of treatment for two
months or more
Previous treatment outcome A previously treated patient whose outcome was not known or not
unknown (PTOU) documented

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B. Classification of Tuberculosis based on Anatomical Site Affected

At least 1 (or 2) sputum


Smear-positive specimen positive for AFB,
with or without radiographic
abnormalities
Patient with sputum culture,
Bacteriologically- Culture-positive with or without radiographic
Confirmed abnormalities
Pulmonary TB Patient with positive sputum
Rapid Diagnostic test- for MTB using a rapid
positive diagnostic test (e.g. Xpert
MTB/Rif) with or without
radiographic abnormalities
Two sputum specimens negative for AFB or MTB; but with
Clinically-Diagnosed clinical or radiologic evidence consistent with active TB and
there is a decision by a physician to treat as tuberculosis
Bacteriologically- Smear/culture/rapid diagnostic test from an extra-
Extra-Pulmonary TB Confirmed pulmonary site positive for AFB
(EPTB) A patient with histologic and/or clinical or radiologic
Clinically-Diagnosed evidence consistent with active extra-pulmonary TB and
there is a decision by a physician to treat as tuberculosis

III. DIAGNOSIS
DIAGNOSTICS COMMENTS / EXPECTED FINDINGS
At least two sputum specimens should be sent
Sputum collection:
Sputum Microscopy for AFB o Two sputum specimens of good quality shall be collected, either
as frontloading (e.g., spot-spot one-hour apart) or spot-early
morning specimens, based on the patient’s preference
o The two specimens should be collected at most within 3 days
Primarily recommended for patients at risk for drug resistance
It is recommended in the following smear positive patients:
o All cases of retreatment
Sputum TB Culture o All cases of treatment failure
o All other cases of smear positive patients suspected to have one
or more multi-drug resistant TB
o All household contacts of patients with MDR-TB
o In patients with HIV
Recommended for patients suspected to have PTB whose sputum
Chest Radiograph smears are negative
Initiating TB treatment based on chest radiographs alone is discouraged
Rapid Diagnostic Test (Xpert Gene Xpert testing for the presence of Mycobacterium tuberculosis and
MTB/Rif Assay) Rifampicin resistance

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Presumptive TB
Cough of at least 2 years in an adult > 15 years old
CXR suggestive of tuberculosis
Cough of any duration in a high risk individual or close contact of an active TB case

Sputum smear microscopy

Positive* Negative or not done

Chest Radiograph
If not suggestive of TB Not TB
If suggestive of TB proceed to nest step

Bacteriology confirmed TB
MTB (+)
Rif-sensitive
Xpert MTB/Rif**
History of previous TB treatment? MTB Negative Not TB
MTB Positive Next step

No Yes MTB (+)


Rif-Resistant
Bacteriologically Bacteriologically
If no access to Xpert
confirmed TB confirmed TB
New Case Retreatment MTB/Rif:
Decision of MD or TBDC+?
Either “Not TB” or “Clinically
Clinically Diagnosed TB”
Refer to PMDT$ Diagnosed TB
Services for Retreatment
Evaluation

Yes

Category I Category II Treatment History of If clinically


previous TB diagnosed
Treatment (for Rif-sensitive)
treatment? TB
No

Clinically
Diagnosed TB
New Case

*Positive: at least 1 (of 2) specimen for acid fast bacilli


** Xpert MTB/Rif: Rapid diagnostic test for the presence of Mycobacteria tuberculosis and Rifampicin resistance
+ TBDC: Tuberculosis diagnostic committee
$ PMDT: Programmatic Management of Drug-Resistant Tuberculosis (possible MDR-TB treatment if Rifampicin Resistant TB)

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IV. MANAGEMENT

A. Treatment Regimen for TB


CATEGORY TB PATIENTS ALTERNATIVE TB TREATMENT REGIMEN
Initial Phase Continuation Phase
New pulmonary TB (bacteriologically-
confirmed or clinically diagnosed)
I New extra-pulmonary TB (bacteriologically- 2 HRZE* 4 HR or 4HRE*
confirmed or clinically-diagnosed), except
CNS / bones or joints
Ia New extra-pulmonary TB (CNS / bones or 2 HRZE 10 HR
joints)
Pulmonary or extra-pulmonary, previously
treated drug-susceptible TB (whether
bacteriologically-confirmed or clinically-
diagnosed), except CNS / bones or joints
o Relapse 2 HRZES and 1 5 HRE
II o Treatment after failure HRZE
o Treatment after lost to follow-up
(TALF)
o Previous treatment outcome
unknown (PTOU)
o Other
Extra-pulmonary (CNS / bones or joints),
previously treated, drug susceptible TB 2 HRZES and 1 9 HRE
IIa (whether bacteriologically-confirmed or HRZE
clinically-diagnosed)
Standard regime drug-resistant (SRDR):
Drug rifampicin resistant TB or multi-drug Individualized based on previous treatment
Resistant resistant TB courses and drug sensitivity testing
TB XDR TB regimen: extensively drug-
resistant TB
*if with cavitary disease, give streptomycin IM alternate days (60 days) instead of ethambutol
# based on the WHO guideline, in populations with known or suspected high levels of isoniazid resistance, new TB patients may receive HRE as
therapy in the continuation phase as an acceptable alternative to HR

B. Drugs used for Tuberculosis


DRUG DOSE MECHANISM OF ACTION
(daily)
Inhibits fatty acid synthase and mycolic acid synthesis
Isoniazid 5 mg/kg, Excellent bactericidal activity against both intracellular and extracellular
(H/INH) max 300 mg actively dividing MTB
Bacteriostatic against slowly dividing organisms
Binds to and inhibits mycobacterial DNA-dependent RNA polymerase
thereby blocking RNA synthesis
Rifampicin 10 mg/kg, Has both intracellular and extracellular bactericidal activity, both in
(R) max 600 mg dividing and non-dividing MTB
Also has sterilizing activity
Most active antimycobacterial agent available and therefore the
cornerstone of first-line TB treatment
Exact mechanism is unclear (fatty acid synthetase-) may be the primary
target)
Pyrazinamide 25 mg/kg, More active against slowly replicating organisms than against actively
(Z) max 2 g replicating organisms
Active only in acidic environment (pH<6.0) and are found within
phagocytes or granulomas
Ethambutol Inhibits arabinosyltransferases involved in cell wall synthesis, which
(E) 15 mg/kg probably inhibits the formation of arabinogalactan and
lipoarabinomannan
99
Bacteriostatic antimycobacterial agent which provides synergy with
other drugs
Least potent against MTB
Inhibits protein synthesis by binding at a site in #)S mycobacterial
Streptomycin 15 mg/kg, ribosome
(S) max 1 g Bactericidal against dividing MTB but has only low-level early
bactericidal activity

C. Managing Side-Effects
SIDE EFFECTS DRUGS RESPONSIBLE WHAT TO DO?
Minor Side Effects (Patient should be encouraged to continue taking medications)
Gastrointestinal intolerance Rifampicin Give medication at bedtime
Mild skin reactions Any kind of drug Give antihistamines
Orange/red-colored urine Rifampicin Reassure the patient
Pain at injection site Streptomycin Apply warm compress
Give pyridoxine (Vitamin B6)
Burning sensation in feet IsoniazId 100-200 mg daily for
(peripheral neuropathy) treatment; 10 mg daily for
prevention
Give aspirin or NSAID
Arthralgia due to hyperuricemia Pyrazinamide If symptoms persist, consider
gout
Flu-like symptoms (e.g., fever, Rifampicin Give anti-pyretics
muscle pain)
Major Side Effects (discontinue taking the medications)
Severe skin rash Any drug (especially Discontinue anti TB drugs &
(hypersensitivity) streptomycin) refer
Discontinue anti TB drugs &
Jaundice due to hepatitis Any drug (especially isoniazid, refer
rifampicin, pyrazinamide) If symptoms subside, resume
treatment & monitor clinically
Impairment of visual acuity and Discontinue ethambutol &
color vision due to optic Ethambutol refer to an ophthalmologist
neuritis
Hearing impairment, tinnitus Discontinue streptomycin &
and dizziness due to damage of Streptomycin refer
CN VIII
Oliguria or albuminuria due to Streptomycin Discontinue anti TB drugs &
renal disorder Rifampicin refer
Psychosis and convulsion Isoniazid Discontinue isoniazid & refer
Thrombocytopenia, anemia, Rifampicin Discontinue anti TB drugs &
shock refer

D. Treatment Outcomes
OUTCOME DESCRIPTION
Cured A sputum smear positive patient who has completed treatment and is sputum smear
negative in the last month of treatment and on at least one previous occasion
Treatment completed A patient who has completed treatment, but does not meet the criteria to be
classified as “cured” or “failure”
Died A patient who dies for any reason during the course of the treatment
Patient who is sputum smear positive at five months o later during treatment
Treatment failure A sputum smear negative patient initially who turned out to be positive during
treatment
Lost to follow-up Patient whose treatment was interrupted for two consecutive months or more
Transfer out Patient who has been transferred to another facility with proper referral/transfer slip
for continuation of treatment

100
Not evaluated A patient for whom no treatment outcome is assigned
Patients transferred to another treatment facility with outcome unknown

PLEURAL EFFUSION
I. ETIOPATHOGENESIS
Excess quantity of fluid in the pleural space
Most common cause of pleural effusion is left ventricular failure
Transudative effusion: occurs when systematic factors that influence the absorption of pleural fluid are altered
Exudative effusion: occurs when local factors that influence formation and absorption of pleural fluid are altered

II. CLINICAL MANIFESTATIONS


Patients may present with pleuritic pain, cough and dyspnea
Findings include decreased breath sounds with decreased or absent tactile fremiti and dullness on percussion
Tracheal deviation and pleural rub may also be noted

III. DIAGNOSIS AND MANAGEMENT


First step: determine if effusion is exudative or transudative (use the Light’s criteria by obtaining LDH and protein
level from serum and pleural fluid)
Other diagnostics for exudative pleural effusions:
o Description of the appearance of the fluid
o Glucose & protein level
o Differential cell count
o Microbiologic studies and cytology
o Work up for tuberculosis

A. Light’s Criteria

Exudative pleural effusions meet at least one of the following criteria:


Pleural fluid protein / serum protein >0.5
Pleural fluid LDH/serum LDH >0.6
Pleural fluid LDH more than two-thirds normal upper limit for serum

These criteria misidentify -25% of transudates as exudates. If one or more of the exudative criteria arte met and the patient is
clinically thought to have a condition producing a transudative effusion, the difference between the protein levels in the serum and
the pleural fluid should be measured. If this gradient >31 g/L, the exudative categorization by these criteria can be ignored because
almost all such patients have transudative pleural effusion

B. Common causes of pleural effusion


Transudative Pleural Effusions
Most common cause of pleural effusion
Diagnostic thoracentesis should be performed:
o If effusions are not bilateral and comparable in
size
Effusion due to Heart Failure o If patient is febrile
o If patient has pleuritic chest pain, to verify that
the patient has a transudative effusion;
otherwise, the heart failure is treated
Pleural fluid N-terminal pro-brain natriuretic peptide
(NT-proBNP) >1500 pg/mL is virtually diagnostic
Liver cirrhosis may give rise to pleural effusion
Cirrhosis Usually on the right side (passage of fluid from
abdomen through diaphragm)
Other Transudative Effusions Nephritic syndrome, myxedema, urinothorax
Pulmonary embolism (may also be exudative)
Exudative Pleural Efusions
Parapneumonic Effusion Most common cause of exudative pleural effusion
Bacterial Pneumonia (in the US)
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Lung Abscess Presents with acute febrile illness consisting of
Bronchiectasis chest pain, sputum production and leukocytosis
Empyema If free fluid separates the lung from the chest wall
by >10mm, a therapeutic thoracentesis should be
performed
The following factors indicate the need for a more
invasive procedure (e.g., CTT insertion)
o Loculated pleural fluid
o Pleural fluid pH <7.20
o Pleural fluid glucose <3.3 mmol/L (<60mg/dL)
o Positive gram stain or culture of the pleural fluid
o Presence of gross pus in the pleural space
If fluid recurs, a repeat thoracentesis should be
performed
If fluid cannot be completely removed, consider
CTT insertion and instilling fibrinolytics or
performing thoracoscopy to break own adhesions
If above procedures remain ineffective,
decortications should be considered
Three most common causes: lung CA, breast CA
and lymphoma
Diagnosis usually clinched by cytologic exam of
fluid if negative, thoracoscopy is the next best
procedure
Effusion secondary to Malignancy Glucose levels may be low if tumor burden is high
Patients with malignant effusions are treated
symptomatically for the most part
If patient’s QOL is compromised by dyspnea,
pleurodesis or insertion of a small indwelling
catheter may be considered
Diagnosis most commonly overlooked in the
differential diagnosis of a patient with undiagnosed
pleural effusion
Effusion secondary to Pulmonary Embolism Diagnosis is established by spiral CT scan or
pulmonary arteriography
If the pleural effusion increases in size after
anticoagulation, consider recurrent emboli,
hemothorax or a pleural infection
Most common cause of an exudative pleural
effusion in most parts of the world
Usually associated with primary TB and thought to
be primarily due to a hypersensitivity reaction to TB
Tuberculosis Pleuritis protein in pleural space
Cytology shows predominantly small lymphocytes
Diagnosis is established by high levels of
adenosine deaminase (>40 IU/L) or interferon
gamma (>140 pg/mL) in the pleural fluid
Treatment of pleural TB is identical to PTB
Hematocrit should be obtained on pleural fluid if
initial tap reveals bloody pleural fluid
If hematocrit is more than ½ of that in peripheral
Hemothorax blood, hemothorax should be considered and tube
thoracostomy should be inserted
If pleural hemorrhage >200 mL/h, consider
thoracoscopy or thoracotomy

102
PNEUMOTHORAX (PTX)

Presence of gas in the pleural space

I. ETIOPATHOGENESIS
TYPE ETIOLOGY/PATHOGENESIS MANAGEMENT
Occurs in the absence of underlying
lung disease Simple aspiration: initial treatment
Primary Spontaneous Usually due to rupture of apical pleural If lung does not expand or PTX
PTX blebs recurs, thoracoscopic stapling of
Occurs almost exclusively in smokers blebs and pleural abrasion
(those with subclinical disease)
Occurs in the presence of underlying Tube thoracostomy or thoracoscopy
lung disease or thoracotomy with bleb stapling
Secondary PTX Mostly due to COPD (but have been and plural abrasion
reported in all lung disease) If patient refuses surgery,
pleurodesis is an option
Penetrating or non-penetrating chest Tube thoracostomy unless very small
injuries and can be managed with
Traumatic PTX Iatrogenic PTX is a subtype which is supplemental oxygen or aspiration
increasingly becoming more common If hemopneumothorax: two chest
tubes directed at each lesion
Medical emergency
Large-bore needle should be
Tension PTX Pressure in the pleural inserted into the pleural space
through the 2nd anterior ICS and
should be left in place until a
thoracostomy tube can be inserted

SUPERIOR VENA CAVA (SVC) SYNDROME


I. ETIOPATHOGENESIS
Clinical manifestation of superior vena caval obstruction with severe reduction in venous return from the heart,
neck and upper extremities
Most common etiologies are lung CA, lymphoma and metastatic tumors
o Lung CA (small cell and squamous cell) accounts for 85% of all cases of malignant origin
o Malignant lymphoma is the leading cause of SVCs in adults
The increasing use of intravascular devices has led to increasing prevalence of benign causes of SVC
Other benign causes: aneursyms, thyromegaly, thrombosis, fibrosing mediastinitis, histoplasmosis or Behcet’s
syndrome

II. CLINICAL MANIFESTATIONS


SVCs usually present with neck and facial swelling (especially around the eyes), dyspnea and cough
Other symptoms are hoarseness, tongue swelling, headaches, nasal congestion, epistaxis, hemoptysis,
dysphagia, pain, dizziness, syncope and lethargy which are aggravated by bending forward or lying down
PE findings include dilated neck veins, increased number of collateral veins over the anterior chest wall, cyanosis
and edema of the face, arms and chest
More severe cases present with proptosis, glossal and laryngeal edema, obtundation and signs of cerebral
edema
Cardiorespiratory symptoms may occur at rest when significant airway and vascular obstruction occurs
Rarely, esophageal varices may develop

III. DIAGNOSIS OF SVC SYNDROME


DIAGNOSTICS COMMENTS / EXPECTED FINDINGS
Most significant finding is widening of the superior mediastinum (more
Chest Radiography commonly on the right side)
Pleural effusion occurs in 25% (often on the right side) - majority are
103
exudative and occasionally chylous
May be normal in some cases
Provides the most reliable view of the mediastinal anatomy
Chest CT Diminished or absent opacification of central venous structure with
prominent collateral venous circulation
Chest MRI No advantages over CT
Invasive Procedures
(e.g., broncoscopy, percutaneous Necessary for etiologic diagnosis / histologic diagnosis
core needle biopsy, mediastinoscopy
and thoracotomy)

IV. MANAGEMENT
Upper airway obstruction demands emergent therapy:
o Diuretics with low salt diet
o Head elevation
o Oxygen support
o Glucocorticoids for lymphoma (no benefit in lung CA)
Radiation therapy is the primary treatment for SVCs caused by NSCLC and other metastatic solid tumors
Chemotherapy is effective when the underlying CA is SCLS of the lung, lymphoma or germ cell tumor
Recurrent SVC may be palliated with use of intravascular self-expanding stents (however, may precipitate heart
failure and pulmonary edema)
The mortality with SVC does not relate to caval obstruction but rather to underlying cause

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CHAPTER 4
CRITICAL CARE
I. Shock in the Intensive Care Setting
1. Overview of the Types of Shock
2. Cardiogenic Shock
3. Sepsis and Septic Shock
4. Other Forms of Shock
II. Common Conditions Encountered in the ICU
1. Respiratory Failure
2. Acute Respiratory Distress Syndrome
3. Venous Thromboembolism
III. Overview of Mechanical Ventilation
1. Non-Invasive Ventilation (NIV)
2. Basic Modes of Mechanical Ventilation
3. Oxygen Delivery, Spontaneous Breathing Trial and
Weaning

105
SECTION 1
SHOCK IN THE INTENSIVE CARE SETTING
OVERVIEW OF THE TYPES OF SHOCK
TYPE OF SHOCK CVP & PCWP CARDIAC OUTPUT SYSTEMIC VASCULAR
(CO) RESISTANCE (SVR)
Cardiogenic Shock ↑ ↓ ↑
Septic Shock
Hyperdynamic phase (Early) ↑↓ ↑ ↓
Hypodynamic phase (Late) ↑↓ ↓ ↑
Hypovolemic Shock ↓ ↓ ↑
Hypoadrenal Shock ↓ ↓ ↓
Neurogenic Shock ↓ ↓ ↓
CVP: central venous pressure (N: 3-10 mmHg)
PCWP: pulmonary capillary wedge pressure (N: 4-12 mmHg)
CO: cardiac output (N: 4-8 L/min)
SVR: systemic vascular resistance (N: 700-1600 dynes.s/cm2)

CARDIOGENIC SHOCK
I. ETIOPATHOGENESIS
Characterized by systemic hypoperfusion due to severe depression of cardiac index (<2.2 L/min/m2) and
sustained systolic arterial hypotension (<90 mmHg) despite an elevated filling pressure (PCWP >18 mmHg)
Most common cause: severe LV dysfunction

II. MANAGEMENT OF PATIENTS WITH CARDIOGENIC SHOCK


ACUTE PULMONARY EDEMA LOW-OUTPUT ARRYHTMIA
CARIDOGENIC SHOCK
Furosemide IV 0.5-1 mg/kg SBP >100 mmHg:
Morphine IV 2-4 mg NTG 10-20 mcg/min IV
Oxygen/intubation as needed
NTG SL then 10-20 mcg/min IV if SBP 70-100 mmHg and no
SBP >100 mmHg signs/symptoms of shock: If with bradycardia or
Norepinephrine 0.5-30 mcg/min Dobutamine 2-20 tachycardia:
First Line of IV or Dopamine 5015 mcg/kg/min IV Manage accordingly
Action mcg/kg/min IV if SBP <100 based on ACLS
mmHg and signs/symptoms of SBP <100 mmHg or with guidelines
shock present signs/symptoms of shock:
Dobutamine 2-20 mcg/kg/min IV Norepinephrine 0.5-30
if SBP >70-100 mmHg and no mcg/min IV, or
signs/symptoms of shock Dopamine 5-15
mcg/kg/min IV
Second Line of If SBP >100 mmHg and not less than 20 mmHg below baseline: consider ACE-inhibitors such
Action as Captopril 1-6.25 mg
The following should be considered in non-hypovolemic shock
Third Line of o Diagnostics: pulmonary artery catheter, echocardiography, angiography for MI/ischemia
Action and other additional diagnostic studies
o Therapeutics: intra-aortic balloon pump, reperfusion/revascularization

SEPSIS AND SEPTIC SHOCK


I. ETIOPATHOGENESIS
TNF-alpha is a central mediator
Intravascular thrombosis is the hallmark of the local inflammatory response
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Endothelial injury is the major mechanism of multi-organ dysfunction

II. DIAGNOSIS AND DEFINITIONS

A. Bacteremia Versus Septicemia


Bacteremia Presence of bacteria in blood, as evidenced by positive blood culture
Septicemia Presence of microbes or their toxins in blood

B. Definition in Terms
SYNDROME DEFINITION
Two or more of the following conditions (may have a noninfectional etiology):
Signs of Possible Harmful o Fever (oral temperature >38oC) or hypothermia (<36oC)
Systemic Response (SIRS) o Tachypnea (>24 breaths/min)
o Tachycardia (HR >90 bpm)
o Leukocytosis >12,000 or leukopenia <4,000 or >10% bands
The harmful host response is infection
Sepsis with one or more signs of organ dysfunction:
o CVS: arterial SBP < 90 mmHg or MAP <70 mmHg that responds to
administration of IV fluids
Sepsis o Renal: urine output <0.5 mL/kg/hr for 1 hour despite adequate fluids
(or Severe Sepsis) o Respiratory: PaO2/FiO2 <250 (or <200 if lung is the only dysfunctional
organ)
o Hematologic: platelet count <80,000/uL or 50% decrease in platelet count
from highest value recorded over precious 3 days
o Unexplained metabolic acidosis: a pH <7.30 or a base deficit >5.0 mEq/L
and a plasma lactate level >70 mmHg
Sepsis with hypotension (SBP <90 mmHg or 40 mmHg less than patient’s normal
Septic Shock BP) for at least 1 hour despite adequate fluid resuscitation, OR
Need for vasopressors to maintain SBP >90 mmHg or MAP >70 mmHg
Refractory Septic Shock Septic shock that lasts for >1 hour and does not respond to fluid or pressor
administration
Multiple-Organ Dysfunction Dysfunction of more than one organ, requiring intervention to maintain
Syndrome (MODS) homeostasis
SIRS: Systemic Inflammatory Response Syndrome
ULN: Upper Limit of Normal
“Adequate” fluid resuscitation: when the pulmonary artery wedge pressure is >12 mmHg or central venous pressure >8 mmHg

III. MANAGEMENT
A. Initial Resuscitation (first 6 hours)
CVP 8-12 mmHg
Resuscitation Goals MAP > 65 mmHg
Urine output >0.5 mL/kg/hour
Obtain appropriate blood cultures
Broad-spectrum IV antibiotics with good penetration into presumed source of infection
Antibiotic Therapy Combination therapy in Pseudomonas infections and neutropenic patients for at least
3-5 days and de-escalation following susceptibility studies
Duration of therapy typically 7-10 days; longer if response is slow or there are
undrainable foci of infection or immunologic deficiencies

B. Hemodynamic Support and Adjunctive Therapy


Fluid Therapy Crystalloids or colloid with target CVP of 8-12 mmHg (>12 mmHg if mechanically
ventilated)
Vasopressors Maintain MAP >65 mmHg
Norepinephrine and Dopamine are the initial vasopressors of choice
Inotropic Therapy Dobutamine in patients with myocardial dysfunction as supported by elevated cardiac
filling pressures and low CO
Steroids Consider IV hydrocortisone for adult septic shock when hypotension responds poorly
to adequate fluid resuscitation and vasopressors
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C. Other Supportive Therapy
RBC transfusion if hemoglobin is: Platelet transfusion if platelet count is:
<7.0 g/dL to target Hgb 7.0-9.0 g/dL <5000/mm3 (5x109/L) regardless of
in adults bleeding
Blood Transfusion Higher level required in special 5,000-30,000/mm3 (5-30x109/L) and
circumstances like MI, acute there is significant bleeding risk
hemorrhage, cyanotic CHD Higher platelet counts
(>50,000/mm3) are required for
surgery or invasive procedures
Target tidal volume of 6 mL/kg with an initial upper limit plateau pressure <30 cm
H2O (for ARDS)
Mechanical Ventilation Set PEEP to avoid extensive lung collapse at end-expiration
of Sepsis-Induced AL/ Maintain in a semi-recumbent position (bed raised to 45o) unless contraindicated
ARDS Noninvasive ventilation in patients with mild to moderate hypoxemic respiratory
failure with no contraindications for its use
Weaning protocol and an SBT regularly
Glucose Control May use IV insulin (e.g., drip) to control hyperglycemia
Low-dose UFH or LMWH, unless contraindicated
DVT Prophylaxis Compression stockings or an intermittent compression device, when heparin is
contraindicated
Sedation, analgesia, neuromuscular blockade (intermittent bolus or continuous
infusion)
Others Renal replacement therapy (intermittent hemodialysis & continuous veno-veno
hemofiltration)
Stress ulcer prophylaxis (H2 blocker or PPI)
Consideration for limitation of support (advanced care planning)

OTHER FORMS OF SHOCK


I. HYPOVOLEMIC SHOCK
Most common form of shock resulting from either the loss of RBC mass and plasma from hemorrhage or from
loss of plasma volume alone due to extravascular or GI, urinary and insensible losses

MILD MODERATE SEVERE


(<20% blood volume) (20-40% blood volume) (>40% blood volume)
Cool extremities Same as “mild”, PLUS: Same as “moderate”, PLUS:
Increased capillary refill time Tachycardia Hemodynamic instability
Diaphoresis Tachypnea Marked tachycardia
Collapsed veins Oliguria Hypotension
Anxiety Postural changes Mental status deterioration

II. HYPOADRENAL SHOCK/ADRENAL INSUFFICIENCY


Occurs in a setting where unrecognized adrenal insufficiency complicates the host response to the stress induced
by acute illness or major surgery
Can occur as a consequence of the chronic administration of high dose exogenous steroids
Shock is categorized by loss of homeostasis with reductions in systemic vascular resistance, hypovolemia and
reduced cardiac output
Diagnosis may be established by an ACTH stimulation test, but this may be inconsistent
Management:
o Hemodynamically unstable + diagnosis is not established Dexamethasone 4 mg IV (does not interfere
with the ACTH stimulation test)
o Diagnosis is established Hydrocortisone 100 mg IV q6-8h (leads to reduce mortality)
o Simultaneous volume resuscitation and pressor support are required

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SECTION 2
COMMON CONDITIONS ENCOUNTERED IN THE ICU
RESPIRATORY FAILURE
A condition in which the respiratory system fails in one or both of its gas exchanging functions
o Oxygenation
o CO2 elimination

I. TYPE I RESPIRATORY FAILURE


Acute hypoxemic respiratory failure (generally PO2 <55-60 mmHg)
Usually from alveolar flooding and subsequent intrapulmonary shunting
Alveolar flooding may be a consequence of:
o Pulmonary edema (cardiogenic or non-cardiogenic)
o Pneumona
o Alveolar hemorrhage
o ARDS (low pressure pulmonary edema)

II. TYPE II RESPIRATORY FAILURE


Hypercarbic respiratory failure (generally pCO2 >45-50 mmHg)
Result of alveolar hypoventilation and leads to the inability to eliminate carbon dioxide effectively
Mechanisms by which this occurs are categorized by:
Drug overdose
Diminished CNS drive Brainstem injury
to breathe Sleep-disordered breathing
Hypothyroidism
Impaired neuromuscular transmission
Reduced strength of o Myasthenia gravis
neuromuscular o Guillain-Barre syndrome
function o Amyotrophic lateral sclerosis
o Phrenic nerve injury
Respiratory muscle weakness (myopathy, electrolyte derangements, fatigue)
Increased resistive loads
o Bronchospasm
Loads due to reduced lung compliance
o Alveolar edema
o Atelectasis
Increased overall load o Intrinsic positive end-expiratory pressure (auto-PEEP)
on the respiratory Loads due to reduced chest wall compliance
system o Pneumothorax
o Pleural effusion
o Abdominal distention
Loads due to increased minute ventilation requirements
o Pulmonary embolus with increased dead space fraction
o Sepsis

III. TYPE III RESPIRATORY FAILURE


This form of respiratory failure occurs as a result of lung atelectasis
Also called perioperative respiratory failure: commonly found in the perioperative period (usually from pain)

IV. TYPE IV RESPIRATORY FAILURE


Results from hypoperfusion of respiratory muscles in patients in shock (respiratory muscles normally consume
<5% of the total cardiac output and O2 delivery)
Patients in shock often experience respiratory distress due to pulmonary edema (e.g., patients in cardiogenic
shock), lactic acidosis and anemia – up to 40% of CO may be distributed to the respiratory muscles
Intubation and mechanical ventilation can allow redistribution of the CO away from the respiratory muscles and
back to vital organs while the shock is treated

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ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)
I. ETIOPATHOGENESIS
ARDS is a clinical syndrome of:
o Severe dyspnea of rapid onset
o Hypoxemia
o Diffuse pulmonary infiltrates

A. Etiology of ARDS
DIRECT LUNG INJURY INDIRECT LUNG INJURY
Pneumonia Sepsis
Aspiration of gastric contents Severe trauma (multiple bone fractures, flail chest, head trauma, burns)
Pulmonary contusion Multiple transfusions
Near-drowning Drug overdose
Toxic inhalation injury Pancreatitis
Postcardiopulmonary bypass

B. Three Phases in the Natural History of ARDS


Alveolar capillary endothelial cells and type I pneumocytes (alveolar epithelial cells)
are injured, leading to loss of the normally tight alveolar barrier to fluid and
Exudative Phase macromolecules
(Day 1-7) Edema fluid rich in protein accumulates in the interstitial and alveolar spaces
X-ray reveals alveolar and interstitial opacities involving at least three-quarters of
the lung fields
Most are liberated from mechanical ventilation during this phase
Proliferative Phase Histologically, the first signs of resolution are often evident in this phase
(Day 7-21) Lymphocyte-predominant pulmonary infiltrate
Approximately 3 weeks after the initial pulmonary injury, most patients recover
While many patients with ARDS recover lung function 3-4 weeks after the initial
Fibrotic Phase pulmonary injury, some will enter a fibrotic phase
Biopsy evidence for pulmonary fibrosis in any phase of ARDS is associated with
increased mortality

II. CLINICAL MANIFESTATIONS & DIAGNOSIS OF ARDS


OXYGENATION IN ARDS ONSET CHEST ABSENCE OF HIGH LEFT
PaO2 / FiO2 IMAGING ATRIAL PRESSURES
Mild 200 mmHg < PaO2/FiO2 < 300 mmHg Within 1 week Bilateral PCWP < 18 mmHg or no
Moderate 100 mmHg < PaO2/FiO2 < 200 mmHg of known alveolar or clinical evidence of
Severe PaO2/FiO2 < 100 mmHg clinical insult interstitial increased left atrial
infiltrates pressure

III. MANAGEMENT
Aim is to protect the lung and is basically done by decreasing tidal volume and giving adequate positive end-
expiratory pressure

A. Mechanical Ventilation
Frequently needed due to fatigue from increased work of breathing and progressive hypoxemia
However, mechanical ventilation can aggravate lung injury
Lower tidal volume (VT) would protect against ventilator-induced lung injury and improve clinical outcomes
o Low VT = 6 mL/kg predicted body weight (preferred in ARDS)
o Conventional VT = 12 mL/kg (8-10 mL/kg in Asians)
This improvement in survival represents the most substantial benefit in ARDS mortality demonstrated for any
therapeutic intervention in ARDS to date

B. Summary of Evidence-Based Recommendation for Management of ARDS


Management Level of Evidence
Low tidal volume Grade A – best evidence
Minimize left atrial filling pressures Grade B
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High-PEEP Grade C
Prone position Grade C
Recruitment maneuvers Grade C
ECMO Grade C

VENOUS THROMBOEMBOLISM (VTE)


Encompasses deep venous thrombosis (DVT) and pulmonary embolism (PE)
Virchow’s triad: inflammation + hypercoagulability + endothelial injury

I. DEEP VENOUS THROMBOSIS (DVT)


Presence of thrombus in one of the deep venous conduits that return blood to the heart
Most commonly involves the deep veins of the leg or arm, often resulting in potentially life-threatening emboli to
the lungs (e.g., pulmonary embolism) or debilitating valvular dysfunction and chronic leg swelling

A. Clinical Manifestations
Most frequent symptom: cramp in the lower calf
Leg swelling and pain
Patients at risk: older age, prolonged immobilization, paralysis, hyperviscosity syndromes, etc.

B. Diagnostic Tests
Venous duplex scan: best non-invasive diagnostic method which detects “vein incompressibility” (most definite
sign of thrombosis)
D-dimer: high negative predictive value (“rule out test”)

C. Padua Prediction Score for Identification of Hospitalized Patients at Risk for Venous Thromboembolism
Most widely used risk assessment tool to decide whether to administer VTE prophylaxis to hospitalized medical
patients (e.g., those at risk for venous thromboembolism)
High risk for developing PE: > 4 points
RISK FACTOR SCORING
Cancer 3
Previous VTE 3
Immobility 3
Thrombophilia 3
Trauma / surgery 2
Age > 70 years 1
Heart / respiratory failure 1
Acute MI or stroke 1
Infection / rheumatologic disorder 1
Obesity 1
Hormonal treatment 1

D. Common Regimens for VTE Prevention


UFH 5,000 units SC BID-TID
Enoxaparin 40 mg SC OD
Fondaparinux 2.5 mg SC OD
Compression stockings or intermittent pneumatic compression devices

II. PULMONARY EMBOLISM (PE)


Blockage of the main artery of the lung (or its branches) by a substance from elsewhere in the body (embolism)
Increase in pulmonary vascular resistance from pulmonary embolism causes increase in RV wall tension leading
to progressive right HF (the usual cause of death from PE)
One of the three major cardiovascular causes of death, along with MI and stroke

A. Sources of Embolism
Pelvic vein thrombosis or proximal leg DVT
Isolated calf thrombi (most common source of paradoxical embolism – e.g., through an ASD)
Upper extremity venous thrombosis (rarely embolize and cause PE)
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Others: air embolus, fat embolus, amniotic fluid

B. Pathophysiology
Most common gas exchange abnormalities:
o Hypoxemia (decreased arterial PO2)
o Increased alveolar-arterial O2 tension gradient (represents inefficiency of O2 transfer across the lungs)
Increase in anatomic dead space: because breathed gas does not enter gas exchange units
Increase in physiologic dead space: because ventilation to gas exchange exceeds venous blood
flow through pulmonary capillaries

C. Clinical Manifestations
PE: most frequent history is unexplained breathlessness
Dyspnea is the most frequent symptom of PE and tachypnea is the most frequent sign of PE
Clinical presentation depends on the size of PE
RISK FACTOR SMALL PE MODERATE PE MASSIVE PE
(70-75%) (20-25%) (5-10%)
Usual symptoms Pleuritic pain, cough, Varied Dyspnea, syncope
hemoptysis
Usual signs Varied Varied Hypotension, cyanosis
BP Normal Normal Low (<90 mmHg SBP)
RV on 2D Echo Normal right heart function RV hypokinesis / RV hypokinesis /
dysfunction dysfunction
Anticoagulation: IV anticoagulation; IV anticoagulation;
Management Heparin + Warfarin; or Controversy regarding consider advanced
Rivaroxaban advanced therapy therapy
*advanced therapy: systemic thrombolysis, catheter-directed therapy, surgical embolectomy, IVC filter

III. DIAGNOSIS OF VENOUS THROMBOEMBOLISM

A. Determine the likelihood of a venous thromboembolism (Well’s Scoring)


DEEP VENOUS THROMBOSIS PULMONARY EMBOLISM
Parameter Score Parameter Score
Active cancer 1
Paralysis, paresis or recent cast 1 Signs and symptoms of DVT 3
Bedridden for >3 days; major surgery <12 1 Alternative diagnosis less likely than PE 3
weeks HR >100bpm 1.5
Tenderness along distribution of deep veins 1 Immobilization >3 days; surgery within 4 weeks 1.5
Entire leg swelling 1 Prior PE or DVT 1.5
Unilateral calf swelling >3 cm 1 Hemoptysis 1
Pitting edema 1 Cancer 1
Collateral superficial non-varicose veins 1
Alternative diagnosis at least as likely as DVT -2
Low clinical likelihood of DVT: < 0 points
Moderate clinical likelihood of DVT: 1-2 points High clinical likelihood of PE: >4
High clinical likelihood of DVT: > 3 points

B. Approach to Diagnosis
1. Request for a D-Dimer (rule out test) if:
Likelihood for DVT is low
Likelihood for PE is not high

2. Request for an Imaging Test if:


Likelihood for DVT is not low
Likelihood for PE is high

C. Diagnostics for PE
DIAGNOSTICS COMMENTS / EXPECTED FINDINGS
Plasma D-dimer High sensitivity for PE
ELISA Useful rule-out test: patients with normal D-dimer do not have PE
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It is not specific as levels can increase with MI, pneumonia, sepsis, cancer, postoperative
state, 2nd and 3rd trimester of pregnancy
ABG Both PO2 and PCO2 may be decreased in PE
Most common abnormality in PE is T-wave inversion in leads V1 to V4
Most frequently cited abnormality in PE (in addition to sinus tachycardia): S1 Q3 T3
ECG o S wave in Lead I
o Q wave in Lead III
o Inverted T wave in Lead III
Cardiac May be increased in RV microinfarction
Biomarkers
Westermark’s sign: focal oligemia
CXR Hampton’s Hump: peripheral wedged-shaped density above the diaphragm
Palla’s Sign: enlarged right descending pulmonary artery
Chest CT Scan Principal imaging test for the diagnosis of PE
with IV Contrast Can image small peripheral emboli
(high-resolution)
Second-line diagnostic test for PE
Lung scanning High probability scan for PE: two or more segmental perfusion defects in the presence of
normal ventilation
Echocardiography McConnell’s Sign: hypokinesis of the RV free wall with normal motion of the RV apex
(best known indirect sign of PE on transthoracic echo)
Pulmonary Definitive diagnosis of PE depends upon visualization of an intraluminal filling defect in
angiography more than one projection

IV. MANAGEMENT OF VENOUS THROMBOEMBOLISM (DVT AND PE)

A. Anticoagulation
Foundation of successful treatment of DVT and PE
Parenteral agents are continued as a transition or bridge to stable, long-term anticoagulation with warfarin
ANTICOAGULANT REMARKS DOSE FOR VTE
Parenteral Anticoagulation
Binds and accelerates activity of
antithrombin, thus preventing additional
thrombus formation & permitting
Unfractioned Heparin endogenous fibrinolytic mechanisms to IV bolus 80 units/kg, then 18
(UFH) lyse the clot that has already formed units/kg/hour (maintain PTT ratio
Major advantage: short half-life 1.2-2.5x normal)
Major disadvantage: repeated sampling
for PTT and dose adjustment (every 4-6
hours)
Low Molecular Weight No monitoring or dose adjustment 1 mg/kg q12 SC
Heparin (LMWH) needed, unless obese or has CKD 0.5mg/kg if CrCl <30 mL/min
Fondarparinux Anti-Xa pentasaccharide 5-10 mg OD
Oral Anticoagulants
Vitamin-K antagonist which prevents
carboxylation activation of factors II, VII, 5 mg OD overlapped with
IX, X parenteral anticoagulation (to be
Full effect requires 5 days started on day 1-2 of LMWH or
Warfarin Overlapping UFH, LMWH, or UFH)
fondaparinux with warfarin for at least 5 Maintain overlap with parenteral
days can counteract early procoagulant anticoagulation for 5 days until
effect of unopposed warfarin INR is 2-3 for at least 24 hours
Monitor prothrombin time (PT) with a
target INR 2.5 (range of 2.0 to 3.0)
Direct thrombin inhibitor 150 mg BID (to be started on the
Dabigatran Indicated for DVT and PE in those who day after last dose of enoxaparin
have been treated with a parenteral is given)

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anticoagulant for 5-10 days
Rivaroxaban Factor Xa inhibitor 15 mg BID x 3 weeks, followed
by 20 mg OD
Apixaban Factor Xa inhibitor 10 mg BID x 7 days, then 5 mg
BID

DURATION OF ANTICOAGULATION
3 months Proximal or isolated distal provoked DVT (e.g., provoked by surgery or a non-
surgical transient risk factor)
3-6 months Unprovoked DVT (3 months if risk of bleeding is high)
Indefinite / Extended Idiopathic DVT
DVT with cancer, APAS, antithrombin III, protein C and protein S deficiencies
CONTRAINDICATIONS TO ANTICOAGULATION
Severe uncontrolled hypertension Cerebral lesions at high risk for bleeding
Acute bacterial endocarditis Major bleeding diathesis
Hemorrhagic stroke Allergy to anticoagulants
Active ulverative condition Severe liver and renal failure
Uncontrolled active bleeding Impaired bleeding parameters (platelet count
<50x109/L, INR >3, PTT >2x normal)

B. Fibrinolysis / Thrombolysis
The only FDA-approved indication for PE fibrinolysis is massive pulmonary embolism
Rapidly reverses right heart failure and may result in a lower rate of death and recurrent PE
Preferred agent: Recombinant Tissue Plasminogen Activator (r-tPA)

C. Other Modalities
Inferior vena cava (IVC) filters
Pulmonary embolectomy
Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension
Maintenance of adequate circulation (for patients with massive PE and hypotension)
Graduated compression stockings (30-40 mmHg) for DVT (if without significant peripheral arterial disease)
Emotional support

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SECTION 3
OVERVIEW OF MECHANICAL VENTILATION
NON-INVASIVE VENTILATION (NIV)
I. MECHANISM

Provided by using a tight fitting mask or nasal mask


Highly effective in patients with acute exacerbations of COPD
Uses bilevel positive airway pressure ventilation (“BiPAP”)
If there are contraindications to NIV, invasive ventilation should be used (e.g., may require intubation)

II. CONTRAINDICATIONS FOR NIV


Cardiac or respiratory arrest
Severe encephalopathy
Severe GI bleed
Hemodynamic instability
Acute coronary syndrome
Facial surgery or trauma
Upper airway obstruction
High-risk aspiration and/or inability to protect airways
Inability to clear secretions

NON-INVASIVE VENTILATION (NIV)


I. ASSIST/CONTROL MODE (A/C MODE)
The patient breathes at his own rate and the ventilator senses the inspiratory effort and delivers a preset tidal
volume of each patient effort
If patient’s RR decreases at preset rate, the ventilator delivers tidal breaths at the preset rate
Since every breath is assisted, tachypnea may result in significant hypocapnia and respiratory alkalosis
Uses initial mechanical ventilation settings
1. Tidal Volume (TV) 8-10 mL/kg of ideal body weight
“How much volume will the machine deliver?” 6 mL/kg for ALI/ARDS
10-12 mL/kg for neuromuscular disease
2. Back-up Rate (BUR)
Minimum number of breaths per minute
Usually set 2-4 counts below the spontaneous rate (this can be 14-22 breaths/min
adjusted depending on the desired PaCO2 or pH)
Faster RR = ↑ exhalation of CO2 ↓PaCO2 and ↑pH
3. Oxygen Concentration (FiO2)
Initial FiO2 should be 100% unless it is evident that a lower FiO2
will provide adequate oxygenation
We can start at 50% if with neuromuscular disease (e.g.,
myasthenia gravis) 100%
Eventually downtitrated based on desired PO2
Prolonged exposure to high oxygen concentrations is avoided
as it may lead to O2 narcosis and development of more free O2
radicals
4. Inspiratory Flow Rate (IFR)
“How fast do we deliver the air?”
This is the rate at which air is delivered to the patient to achieve
the set tidal volume 40-60 L/minute
Rate needs to be higher (80 L/min) in obstructive diseases such
as COPD or asthma to allow for a longer time for expiration
Rate needs to be lower in patients with severe hypoxemia to

115
deliver air slower, prolonging inspiration time & allowing more
gas exchange
An IFR lower than the patient demand will increase the work of
breathing and is a common cause of patient-ventilator
discordance (fighting or bucking the ventilator)
5. Inspiratory Flow Pattern (IFP)
“How do you deliver the air?” Decelerating wave
How flow is distributed throughout the respiratory cycle
A normal person has a sine wave pattern
6. Positive End-Expiratory Pressure (PEEP)
“Physiologic PEEP” of about 5cm H2O should be added
regardless of FiO2 to prevent alveolar injury due to the shearing
effect of opening and closing the alveoli and therefore should
be increased in ARDS 5 cm H2O
Lower PEEP is usually given to patients with hypotension as
higher values increase intrathoracic pressures which can
impede venous return, thereby reducing preload and
subsequent CO
7. Sensitivity
Ranges anywhere from -5 to -0.5 cm H2O (pressure sensitivity)
or 1 to 5 liters (flow sensitivity)
The more sensitive (e.g., 0.5 cm or 1L), the easier for the
patient to trigger the ventilator which may lead to
hyperventilation
The less sensitive (e.g., 5 cm or 5L), the harder for the patient
to trigger the ventilator which may lead to increased work of
breathing and may cause patient-ventilator dyssynchrony
-2.0 cm or 2 L
a. Pressure Sensitivity
If set -1, the patient has to exert a -1cm Hg pressure for the
ventilator to deliver the tidal volume

b. Flow Sensitivity
If set at 1L, the patient has to exert an air flow of at least 1L
Advantageous in COPD since it affords less work of
breathing for patients

II. SYNCHRONIZED INTERMITTENT MANDATORY VENTILATION (SIMV)


Allows the patient to have spontaneous breaths around the intermittent synchronized ventilator breaths beyond
the set respiratory rate
Patient’s contribution to minute ventilation depends on the number of spontaneous breaths & inspiratory effort

EXAMPLE:
Patient’s MV set on SIMV mode; BUR set at 12; patient’s actual RR is 20
Only 12 of the 20 breaths are assisted in SIMV
o 12 will receive the complete (assisted) tidal volume set
o 8 will receive the tidal volume depending on the patient’s effort
In contrast, in AC mode all 20 breaths will be assisted

A. A/C Mode versus SIMV


A/C MODE SIMV MODE
Assist Total Partial
Work of Breathing Almost none Variable
Can be used for weaning? No Yes
Patient breathes at his own Allows patient to breathe on
rate his/her own if the RR exceeds
In simple terms Ventilator delivers a preset the preset back-up rate
tidal volume with each (all
effort)
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B. Advantages and Disadvantages of SIMV
ADVANTAGES DISADVANTAGES
Maintains respiratory muscle tone due to the
continued use of the inspiratory muscles Even with the same back-up rate as the A/C, there
preventing disuse atrophy is more work of breathing
There is decreased intrathoracic pressure as The increased work of breathing results in
compared to A/C which may lead to improved increased oxygen consumption which is deleterious
hemodynamics in patients with myocardial insufficiency
Useful for weaning because as the back-up This mode is not useful in patients with depressed
rate is decreased, the patient gradually respiratory drive or impaired neurologic status
assumes the bulk of breathing

C. Selection of Ventilator Settings for the SIMV mode


Rate: initial rate should be close to the patient’s inherent rate and eventually adjusted depending on patient
tolerance
VT, FiO2, IFR, IFP, PEEP selection is similar to that in A/C mode

III. NEWER MODALITIES OF MECHANICAL VENTILATION


Pressure Limited Ventilation Pressure Support Ventilation (PSV)
Pressure Controlled Ventilation (PC)
Combination of Volume-Cycled and Pressure-Limited SIMV with PSV
Ventilation
Inverse Ratio Ventilation PCV with Inverse Ratio
A/C with Very Low Flow Rates

OXYGEN DELIVERY, SPONTANEOUS BREATHING TRIAL & WEANING


I. OXYGEN DELIVERY
Indications:
o PaO2 <60 mmHg or SaO2 <90%
o Acute conditions where hypoxemia is suspected
o Severe trauma
o Acute MI
o Short-term, post-operative states

A. Nasal Cannula
FiO2 increases approximately 2-4%/L
Provides 23-45% of O2
Maximum flow rate of 6 lpm (flow rates >6 lpm do not augment the inspired gas)
High flows can dry the nasal mucosa
Humidification is recommended for flow rates >4 lpm

B. Simple Masks
Higher potential FiO2 (provides 31-61% O2)
Flow rates between 5-10 lpm
The reservoir is the space between the mask and the patient’s face
5 lpm is needed to flush exhaled CO2 from the mask (<5 lpm is not recommended)

II. SPONTANEOUS BREATHING TRIAL (SBT)


Consists of a period of breathing through endotracheal tube without ventilator support (both continuous
positive airway pressure [CPAP] of 5 cmH2O & an open T-piece breathing system can be used] for 30-120
minutes

A. If the following are present, the patient has passed the screening test and should undergo SBT:
Stable oxygenation (PaO2/FiO2 >200) and PEEP > 5 cmH2O
Cough and airway reflexes intact
No vasopressor agents or sedatives being administered
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B. SBT is declared a failure and stopped if any of the following occur:
RR >35/min for >5 minutes
O2 saturation <90%
HR >140/min or a 20% increase or decrease from baseline
SBP <90 mmHg or >180 mmHg
Increased anxiety or diaphoresis
If at the end of the spontaneous breathing trial, the rapid shallowing breathing index (RSBI) or ratio of the RR
to tidal volume in liters (f/VT) is <105: patient has higher chances of successful extubation

III. WEANING FROM MECHANICAL VENTILATION


Weaning is the process of abruptly or gradually withdrawing ventilator support when the cause of respiratory
failure is resolving (weaning is not synonymous with extubation)
Need for mechanical ventilation is not the same as the need for artificial airway
o Weaning failure is the inability to maintain adequate respiration through an artificial airway
o Extubation failure is the inability to maintain adequate respiration after removal of artificial airway
A. Removal of Mechanical Ventilator Support Requires that a Number of Criteria be met:
Upper airway function must be intact for a patient to remain extubated
RSBI <105
Reversal of underlying cause of respiratory failure
Adequate oxygenation:
o P/F ratio >150-200 at PEEP 5-8 cm H2O
o FiO2 40-50%
o pH > 7.25
o PO2 > 60 at FiO2 < 40%
Hemodynamic stability: HR < 140, stable BP, Hgb > 8-10
Capability to initiate inspiratory effort: GCS > 13
Acceptable electrolytes
B. Additional conditions which should be met for weaning
Cessation of sedative drugs
Cessation of neuromuscular blocking agents
Absence of sepsis or marked fever
No planned general anesthesia
Adequate gas exchange
Adequate respiratory pump capacity
C. Methods of Weaning
METHOD DESCRIPTION
Brief spontaneous breathing trials with supplemental O 2
Best tolerated by patients who have undergone M for brief periods and require little
T-Piece respiratory muscle reconditioning
Initiated for 5 minutes/hour followed by a1-hour interval of rest
Trials are increased in 5-10 min/hour increments until the patient can remain
ventilator independent for 60-120 minutes, and then extubation can be attempted
CPAP Mode of weaning where patient-initiated breaths are supported with preset
pressure that is eventually titrated down until discontinuation
Mandatory backup rate is decreased by 2 to 4 breaths per minute while monitoring
blood gas parameters & RRs until < 4-6 breaths per minute are achieved
Best for patients intubated for extended periods who are likely to require gradual
SIMV respiratory muscle reconditioning
Rates > 25/min on withdrawal of mandatory ventilator breaths generally indicate
respiratory muscle fatigue and the need to combine periods of exercise with rest
Shifting to PSV, CPAP, or T-Piece trial can then be attempted before extubation
Mode of ventilation that is patient-triggered, pressure-limited and flow-cycled to
Pressure Support augment spontaneous respiratory effort
Ventilation (PSV) Well tolerated by patients who are gradually being weaned by decreasing set
pressures until 4-6 cm H2O and eventual withdrawal of ventilator support

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CHAPTER 5
GASTROENTEROLOGY
I. Approach to Patients with Gastrointestinal Conditions
1. History Taking in Gastroenterology
2. Physical Examination in Gastroenterology
3. Gastrointestinal Endoscopy
4. Approach to Ascites
II. Common Conditions in Gastroenterology
1. Peptic Ulcer Disease
2. Gastrointestinal Bleeding
3. Overview of Liver Disease
4. Viral Hepatitis
5. Alcoholic Liver Disease
6. Liver Cirrhosis
7. Acute Pancreatitis
8. Surgical Causes of Right Upper Quadrant Pain

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SECTION 1
APPROACH TO PATIENTS WITH GASTROINTESTINAL CONDITIONS
HISTORY TAKING IN GASTROENTEROLOGY
I. COMMON GASTROINTESTINAL COMPLAINTS
TERM DEFINITION
Anorexia Loss or lack of appetite
Early satiety Inability to eat a full meal
Heartburn Retrosternal burning sensation resulting from excess gastroesophageal reflux
Dysphagia Difficulty in swallowing
Odynophagia Painful swallowing
Diarrhea Condition in which feces are discharged from the bowels frequently and in a liquid form
Constipation Condition in which there is difficulty in emptying the bowels, usually associated with hardened
feces
Obstipation Complete constipation with no passage of either feces or gas
Tenesmus Intense urge with straining but little or no result
Hematemesis Vomitus of red blood or coffee-ground material
Melena Black, tarry, foul-smelling stool which usually implies bleeding proximal to the ligament of Treitz
(upper GI bleed) and that blood has been in the GI tract for at least 14 hours
Hematochezia Passage of bright red or maroon blood form the rectum which usually implies bleeding from the
colon (lower GI bleed); may also come from an upper GI source, with rapid intestinal transit
Occult GI bleeding Identified in the absence of overt bleeding by a fecal occult blood test or the presence of iron
deficiency
Jaundice Yellowing of the skin or sclerae, arising from obstruction in bile duct, liver disease, hemolysis, etc.
Other complaints Indigestion, nausea, retching, regurgitation, vomiting, excessive gas, fullness, pain, weight loss

II. DIFFERENTIALS FOR THE COMMON GASTROINTESTINAL COMPLAINTS


ABDOMINAL PAIN DIARRHEA GI BLEEDING OBSTRUCTIVE JAUNDICE
Appendicitis Infection Ulcer disease Bile duct stones
Gallstone disease Poorly absorbed sugars Esophagitis Cholangiocarcinoma
Pancreatitis Inflammatory Bowel Disease Varices Cholangitis
Diverticulitis Microscopic Colitis Vascular lesions Sclerosing cholangitis
Ulcer disease Functional Bowel Disorders Neoplasm Ampullary stenosis
Esophagitis Celiac Disease Diverticula Ampularry carcinoma
GI obstruction Pancreatic Insufficiency Hemorrhoids Pancreatitis
Inflammatory Bowel Disease Hyperthyroidism Fissures Pancreatic tumor
Functional Bowel Disorders Ischemia Inflammatory Bowel Disease
Vascular disease Endocrine tumor Infectious Colitis
Gynecologic
Renal Stone

PHYSICAL EXAMINATION IN GASTROENTEROLOGY


I. INSPECTION
Violaceous Striae Usually seen in Cushing’s syndrome
Dilated Veins May be seen in portal hypertension and in inferior vena cava obstruction
Bulging Flanks Associated with ascites
Prominent Peristaltic May be seen in patients with intestinal obstruction
Waves Can also be seen in thin individuals

II. AUSCULTATION (done prior to percussion or palpation as these may alter frequency of bowel sounds)
Borborygmi Prolonged gurgles of hyperperistalsis, aka “stomach growling”
Bruits with audible systolic and diastolic components heard near the midline
Bruits almost midway between subxiphoid area and umbilicus may suggest renal artery
stenosis
Epigastric bruits heard only during systole may be present in normal individuals
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III. PERCUSSION
Tympany Predominant percussion tone
Due to gas in the abdomen
Dullness Scattered all over the abdomen
Signifies presence of underlying mass, organ, fluid and/or feces
Obliterated Trauble’s Percussion of left lower anterior chest wall between lung resonance above and
Space the costal margin
Signifies splenomegaly
Change in the percussion note from tympany to dullness (over lowest interspace
Splenic Percussion Sign in left anterior axillary line) on inspiration
Also signifies splenomegaly

IV. PALPATION
Involuntary rigidity Associated with peritoneal inflammation
Rebound tenderness
Shifting dullness Dullness shifting to the more dependent side is seen in ascites
Fluid wave Easily palpable impulse on the side opposite the pressure (with hands pressed
firmly on the midline of the abdomen) suggest ascites
Pain in right lower quadrant during left-sided pressure suggests appendicitis
Rovsing’s sign Also associated with referred rebound tenderness (right lower quadrant pain on
withdrawal of pressure on left side)
Psoas sign Abdominal pain on hip flexion and/or extension secondary to irritation of psoas
muscle by an inflamed appendix
Obturator sign Right hypogastric pain on internal rotation of right hip suggests irritation of
obturator muscle by an inflamed appendix
Cutaneous Hyperesthesia May also be seen in appendicitis
Sharp increase in right upper quadrant tenderness with a sudden stop in
inspiratory effort (while pressure is applied under the costal margin lateral to the
Murphy’s sign border of the rectus muscle) is seen in acute cholecystitis
Same procedure may enhance hepatic tenderness (due to multiple causes) but
pain is usually less localized

V. DIGITAL RECTAL EXAMINATION (DRE)


Sphincter Tightness May be noted in anxiety, inflammation or scaring
Sphincter Laxity May be seen in some neurologic diseases
Induration May be due to inflammation, scarring or malignancy
Skin Tags Soft, pliable tags of redundant skin at anal margin seen in some individuals

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GASTROINTESTINAL ENDOSCOPY
DIAGNOSTIC REMARKS COMMON INDICATIONS
Endoscope inserted through the mouth Dyspepsia despite treatment
Esophagogastroduo- into the esophagus, stomach, duodenal or with signs of alarm
denoscopy (Upper bulb, and second part of the duodenum UGIB, dysphagia, refractory
Endoscopy, EGD) Best method of examining the upper vomiting
gastrointestinal mucosa Anemia, weight loss,
malabsorption
Scope inserted through anal canal into Cancer screening
the rectum and colon LGIB
Colonoscopy Gold standard for diagnosis of colonic Anemia
mucosal disease Diarrhea
Obstruction
Visualizes only the rectum and a portion Primarily used for evaluation
Flexible Sigmoidoscopy of the left colon, typically up to 60 cm of diarrhea and rectal outlet
from the anal verge bleeding
Capsule endoscopy
Small Bowel Endoscopy Push enteroscopy Obscure GI bleeding
Single- or Double-Balloon Enteroscopy Suspected Crohn’s disease
or Spiral Enteroscopy
Scope passed through the mouth to the
Endoscopic Retrograde duodenum; the ampulla of Vater is Jaundice
Cholangiopancreatography identified and cannulated; and Cholangitis
(ERCP) radiographic contrast material is injected Gallstone pancreatitis
into the bile duct and pancreatic duct Pancreatic/biliary tumor
under fluoroscopic guidance
High-frequency ultrasound transducers
Endoscopic Ultrasound incorporated into the tip of endoscope
(EUS) Obtains images of the gut wall and Staging of malignancy
adjacent organs, vessels and lymph
nodes

APPROACH TO ASCITES
I. COMMON CAUSES OF ASCITES
CONDITION GROSS APPEARANCE OF ASCITIC FLUID PROTEIN (g/L) SAAG (g/dL)
Cirrhosis Straw-colored <25 > 1.1
CHF Straw-colored Variable
Neoplasm Straw-colored, hemorrhagic, mucinous or chylous >25
TB Peritonitis Clear, turbid, hemorrhagic, chylous >25
Pyogenic Peritonitis Turbid or purulent >25 < 1.1
Nephrosis Straw-colored or chylous <25

II. PERITONEAL FLUID ANALYSIS


LABORATORY FINDING ASSOCIATED CAUSE OF ASCITES
Absolute PMN count > 250/uL
Positive gram stain or culture Infection (e.g. spontaneous/primary bacterial peritonitis)
pH < 7.0
RBC count > 50,000 Hemorrhagic ascites
(malignancy, tuberculosis, trauma, ruptured omental varix)
Increased amylase Pancreatic ascites, pancreatitis
Increased triglycerides Chylous ascites
Positive malignant cells in cytology Malignancy

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III. SERUM ASCITES-ALBUMIN GRADIENT (SAAG)
Replaced the description of exudative or transudative ascitic fluid
The gradient correlates directly with portal pressures
SAAG = serum albumin – ascitic fluid albumin
SAAG > 1.1 g/dL (or 11 g/L) SAAG < 1.1 g/dL (or 11 g/L)
Portal Hypertension:
Cirrhosis Peritoneal carcinomatosis
Cardiac ascites Infection (peritonitis, TB)
Budd-Chari Syndrome Nephrotic Syndrome
Portal Vein Thrombosis Pancreatic or biliary ascites
Venoocclusive Disease
Fatty Liver of Pregnancy

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SECTION 2
COMMON CONDITIONS IN GASTROENTEROLOGY
PEPTIC ULCER DISEASE (PUD)
I. GASTRIC MUCOSAL DEFENSE SYSTEM

A. Preepithelial
Mucus-bicarbonate-phospholipid layer to neutralize/buffer gastric acid

B. Epithelial
Mucus production
Ionic transporters for maintaining intracellular pH and bicarbonate production
Intracellular tight junctions
Heat shock proteins prevent protein denaturation and protect cells
Restitution: epithelial cells bordering a site of injury migrate to restore a damaged region

C. Subepithelial
Microvascular system/bed
Capable of angiogenesis in the event of injury
Provides micronutrients and O2
Removes toxic metabolic by-products

II. OVERVIEW OF ULCERS


GASTRIC ULCER (GU) DUODENAL ULCER (DU)
Distal to the junction between First portion of the duodenum
Usual location antrum and acid secretory (within 3 cm of pylorus)
mucosa
Risk of malignancy Common (should be biopsied) Extremely rare
Usual etiology H. pylori, NSAID-induced H. pylori, NSAID-induced
injury injury
Gastric acid secretion appears
Pathophysiology Gastric acid output normal or to be increased
decreased HCO3 secretion is significantly
decreased
Burning or gnawing discomfort
Pain that awakens the patient
Character of abdominal pain Burning or gnawing discomfort from sleep (between midnight
and 3 AM) is the most
discriminating symptom
Occurs 90 minutes to 3 hours
Pain in relation to food intake Precipitated by food after a meal
Relieved by antacids or food
Bleeding: melena or coffee-ground emesis
Penetrating ulcer: pain becomes constant, no longer relieved by
Complications antacids, radiates to the back
Perforation: sudden severe, generalized abdominal pain
Gastric output obstruction: pain worsening with meals, vomiting of
undigested food

III. HELICOBACTER PYLORI AND NSAIDS

A. Helicobacter pylori
S-shaped gram-negative microaerophilic rod with multiple sheathed flagella which can transform into coccoid form
(dormant state)
Bacterial urease aids in infection by producing ammonia from urea, which then alkalinizes surrounding pH

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RISK FACTORS FOR HIGHER COLONIZATION PLAYS A ROLE IN THE DEVELOPMENT OF
RATES
Poor socioeconomic status PUD
Low educational attainment Gastric mucosa-associated lymphoid tissue
Crowded and unsanitary conditions (MALT) lymphoma
Gastric adenocarcinoma

B. NSAID-induced Disease
Interruption of prostaglandin synthesis can impair mucosal defense and repair leading to mucosal injury
Established risk factors
o Advanced age
o History of ulcer
o Concomitant glucocorticoid/anticoagulant/clopigodrel use
o High-dose/multiple NSAIDs
o Serious/multisystem disease

IV. FORREST CLASSIFICATION OF ULCERS


Classification of Upper GI Bleed (UGIB) used for selecting patients for endoscopic treatment
CLASSIFICATION DESCRIPTION RISK OF REBLEED
Acute Hemorrhage
Type IA Arterial spurting 100%
Type IB Arterial oozing 50%
Signs of recent hemorrhage
Type IIA Visible vessel 43%
Type IIB Adherent clot 22%
Type IIC Pigmented flat spot 10%
Lesions without active bleeding
Type III No stigmata of recent bleed; or 5%
fibrin-coated clean ulcer base

V. DIAGNOSTICS
Commonly used as a first test for documenting an ulcer
Barium studies of o DU: appears as a well-demarcated crater, most often seen in the bulb
proximal GIT o GU: discrete crater with radiating mucosal folds originating from the ulcer
margin
Allows direct visualization of the mucosa
Endoscopy (EGD) Most sensitive and specific approach for examining the upper GIT
Facilitates documentation of a mucosal defect and tissue biopsy to rule out
malignancy (GU) or H. pylori
Invasive tests (Endoscopy/Biopsy required)
Rapid Urease (prone to false negatives with recent therapy)
Histology
Tests for detection of H. Culture
pylori Non-Invasive Tests
Urea Breath Test (test of choice for documenting eradication)
Serology
Stool antigen

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VI. MANAGEMENT OF PUD
Relief of symptoms
Promote ulcer healing
Prevent ulcer recurrence and complications

A. Acid Neutralizing/Inhibitory Drugs


CLASS EXAMPLES MECHANISM OF ACTION SIDE EFFECTS
Aluminum hydroxide Constipation
Neutralizes intragastric Diarrhea
Antacids Magnesium hydroxide acidity Avoid in patients with
CKD
Cimetidine Competitive inhibition at Headache, fatigue,
H2 Receptor Ranitidine the parietal cell H2- myalgias
Antagonists Famotidine receptor, suppresses Relatively safe
acid secretion
Covalently bind and Headache, abdominal
Omeprazole irreversibly inhibit H+, pain, diarrhea,
Proton Pump Esomeprazole K+-ATPase flatulence, dermatitis,
Inhibitors Lansoprazole Most potent acid pruritus, dry mouth,
(PPIs) Rabeprazole inhibitory agent blurred vision,
Pantoprazole Maximum efficacy if angioedema
taken before a meal

B. Cytoprotective Agents
CLASS EXAMPLES MECHANISM OF ACTION SIDE EFFECTS
Becomes a viscous
paste within the stomach
and duodenum, binding
Sucralfate Sucralfate primarily to sites of Constipation
active ulceration
Act as a physiochemical
barrier
Black stools
Bismuth- Bismuth subsalicylate Constipation
Containing (BSS, Pepto-Bismol) Mechanism is unclear Darkening of the tongue
Preparations Neurotoxicity (long-
term)
Enhancement of Diarrhea
Prostaglandin Misoprostol mucosal defense and Contraindicate in
Analogues repair pregnancy
(Misoprostol)

C. Helicobacter pylori Eradication


Antibiotic resistant strains are the most common cause for treatment failure in compliant patients
Dual therapy and shorter regimens (7-10 days) are not as effective and are not recommended
1. Triple Therapy for 14 days
DRUG DOSE
Omeprazole 20 mg BID
Any Proton Pump Inhibitor (PPI), Lansoprazole 30 mg BID
plus Esomeprazole 40 mg OD
Pantoprazole 40 mg OD
Rabeprazole 20 mg BID
Either of the following, plus Clarithromycin (first line) 500 mg BID
Metronidazole 500 mg BID
2. Non-Bismuth Quadruple (Sequential) Therapy for 14 days
PPI plus Amoxicillin for 5-7 days, followed by
PPI plus Clarithromycin and Metronidazole for 5-7 days
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VII. PUD-RELATED COMPLICATIONS
Gastrointestinal Bleeding Most common complication of PUD
Second most common ulcer-related complication
Penetration: form of perforation in which ulcer bed tunnels into
Perforation adjacent organ
o DU: tends to penetrate posteriorly into the pancreas, leading
to pancreatitis
o GU: tends to penetrate into the left hepatic lobe
Least common ulcer-related complication
Gastric Outlet Obstruction Relative obstruction secondary to ulcer-related inflammation and
edema in the prepyloric region

GASTROINTESTINAL BLEEDING
I. COMMON CAUSES OF UPPER GASTROINTESTINAL BLEEDING (UGIB)
Most common upper GI causes: ulcer disease, gastroduodenitis, and esophagitis
Usually presents with hematemesis or melena (massive UGIB can also present with hematochezia)

A. Bleeding Peptic Ulcer Disease (BPUD)


Most common cause of UGIB
Usually secondary to NSAID use or H. pylori infection
Ulcer: a break in the mucosal surface >5mm
ECG FINDINGS RISK OF RE- MANAGEMENT DISPOSITION
BLEEDING
Clean-based ulcer -/+ No IV PPI or endoscopic Discharge
treatment
Flat pigmented spots +
Ward for 3 days
Adherent clots covering ulcer base ++ IV PPI +/- endoscopic
treatment
Platelet plug protruding from a vessel +++
wall in the base of an ulcer (sentinel IV PPI + endoscopic ICU for a day then
clot) treatment ward for 2 more
Active spurting from an ulcer ++++ days

B. Bleeding Esophageal Varices (BEV)


Second most common cause of UGIB
Usually arises due to portal hypertension from liver cirrhosis
Poorer outcomes compared to patients with other sources of UGIB

C. Hemorrhagic and Erosive Gastropathy (“Gastritis”)


Endoscopically visualized subepithelial hemorrhages and erosions
Usually seen with NSAIDs, alcohol intake and stress (serious trauma, major surgery, extensive burns, major
intracranial disease, or severe medical illness)

D. Mallory-Weiss Tear
A linear mucosal rent near or across the gastroesophageal junction that is often associated with retching, vomiting
or incessant coughing

E. Dieulafoy’s Lesion
Large-caliber arteriole that runs immediately beneath GI mucosa and bleeds via a pinpoint mucosal erosion
Seen most commonly on the lesser curvature of the proximal stomach

II. COMMON CAUSES OF LOWER GASTROINTESTINAL BLEEDING (LGIB)


Most common lower GI causes: hemorrhoids, anal fissures, diverticula, neoplasms (adenocarcinoma), ischemic
colitis, and arteriovenous malformations
Usually presents with hematochezia

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A. Hemorrhoidal Disease
Patients commonly present for two reasons: bleeding and protruding rectal mass
Severe pain may indicate a thrombosed hemorrhoid
STAGE CHARACTERISTICS TREATMENT
Fiber supplementation
I Enlargement with bleeding Cortisone suppository
Sclerotherapy
II Protrusion with spontaneous reduction Fiber supplementation
Cortisone suppository
Fiber supplementation
Protrusion requiring manual reduction Cortisone suppository
III Banding
Operative hemorrhoidectomy
IV Fiber supplementation
Irreducible protrusion Cortisone suppository
Operative hemorrhoidectomy

B. Diverticular Disease
Hemorrhage from a colonic diverticulum: most common cause of hematochezia in patients >60 years old
Bleeding more often seen from the right colon, usually abrupt and painless
Minor/occult bleeding is not characteristic
Localization of diverticular bleeding should include colonoscopy, which may be diagnostic and therapeutic

C. Anal Fissure
Most common cause of rectal bleeding in infancy
Acquired from trauma to the anal canal following defecation
More common in the posterior anal canal
Relative ischemia in the region of the fissure leads to poor healing

III. MANAGEMENT OF BLEEDING

A. Initial Resuscitation

1. Airway Protection (intubation to prevent aspiration)


Decreased sensorium (shock, hepatic encephalopathy)
Massive hematemesis
Active variceal bleeding

2. Restoration of Intravascular Volume


IV fluids: isotonic state; lactated Ringer’s solution
Transfusion with packed RBCs (or whole blood if necessary)

3. Correction of Coagulopathy (if present)


Discontinuation of offending anti-coagulants followed by infusion of FFP
Parenteral vitamin K for prolonged PT (INR) from warfarin, liver disease
Platelet infusion if with significant thrombocytopenia

128
B. Therapy for Specific Lesions
DISEASE TREATMENT
High-dose PPIs: Omeprazole 80 mg IV bolus followed by 8 mg/hour
infusion for 72 hours (See also chapter 1)
Therapeutic endoscopy (advantage of immediate treatment)
Peptic Ulcer Disease (PUD) Surgery for intractable or recurrent bleeding
H. pylori eradication if with evidence of infection (14-day antibiotic
regimens)
Avoidance of NSAIDs if possible
1. Vasoactive Agents
Reduce portal venous pressures acutely by splanchnic vasoconstriction
Somatostatin 275 mcg IV bolus followed by 3 mg infusion over 12 hours
Octreotide 50 mcg/hour infusion

2. Non-selective Beta-Blockers
Decrease rates of recurrent bleeding
β-blockade allows unopposed alpha-receptor mediated vasoconstriction of
splanchnic vessels
propranolol 10 mg PO TID (starting dose)

3. Antibiotics for Patients with Cirrhosis to Decrease Infections (7-day course)


Ceftriaxone 1 g IV OD
Ciprofloxacin 400 mg IV q12
Variceal Hemorrhage
Levofloxacin 500 mg IV OD
Norfloxacin 400 mg PO BID

4. Endoscopic / Surgical Options


Ligation or banding: endoscopic therapy of choice as it controls active
hemorrhage (lower rates of success for gastric compared to esophageal
varices)
Sclerotherapy
Cyanoacrylate “glue” injection
Balloon tamponade with a Sengstaken-Blakemore tube or Minnesota tube
Transjugular Intrahepatic Portosystemic Shunt (TIPS)
Liver transplantation

5. Judicious Blood Transfusion (overtransfusion may further increase portal pressures)


Stress Ulcer Prophylactic therapy: PPIs, Histamine-Receptor Antagonists and
Sucralfate
Colonic Diverticulum Mesenteric angiography with coiling
Segmental resection of the colon
Sitz baths, high-fiber diet, stool softeners
Hemorrhoids Banding
Sclerotherapy
Hemorrhoidectomy (excisional vs stapled)
Sitz baths, high-fiber diet, stool softeners, topical anesthetics
Anal Fissures For chronic fissures (>6 weeks): nifedipine or NTG ointment applied TID,
botulinum toxin type A injections
Surgery: anal dilatation and lateral internal sphincterotomy

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OVERVIEW OF LIVER DISEASE
I. BASIC PATTERNS OF LIVER DISEASE
Hepatocellular (viral, alcoholic liver disease): features of liver injury, inflammation & necrosis predominate
Cholestatic (obstructive diseases): features of inhibition of bile flow predominate
Mixed (drug-induced liver diseases): features of both

II. MAJOR RISK FACTORS FOR LIVER DISEASE


Alcohol use, personal habits, sexual activity, travel, occupation, injection drug use
Medications (including herbal compounds, birth control pills, and over-the-counter medications)
Exposure to jaundiced or other high-risk persons
Recent surgery
Remote or recent transfusion with blood and blood products
Accidental exposure to blood or needle-stick
Familial history of liver disease

III. CLINICAL MANIFESTATIONS


SYMPTOMS OF HEPATIC DISEASE
Constitutional Symptoms Fatigue, poor appetite, weakness, nausea and malaise
Fatigue: most common and most characteristic symptom of liver disease
Liver-specific Symptoms Dark urine, light stools, itching, abdominal pain and bloating
Jaundice: hallmark of liver disease and the most reliable marker of severity
SIGNS OF HEPATIC DISEASE
Icterus Check sclerae, skin, mucous membrane below the tongue
Palmar erythema Occurs in acute and chronic liver disease; prominent in persons with cirrhosis
Spider angioma Superficial tortuous arterioles seen on the arms, face, upper torso; fill outwards
from the center (unlike telangiectasis)
See in venoocclusive disease, infiltrative disorders, hepatic malignancy,
Hepatomegaly alcoholic hepatitis
Hepatic tenderness: the most reliable physical finding in examining the liver
Splenomegaly Subtle significant finding in liver disease
Ascites Best appreciated by percussing for shifting dullness
Peripheral edema Contributing factors: hypoalbuminemia, venous insufficiency, heart failure, and
medications
First signs: change in sleep patterns, change in personality, irritability, mental
Hepatic encephalopathy dullness
Confusion, disorientation, stupor and eventually coma supervene
Acute liver failure: excitability, mania
Fetor hepaticus Slightly sweet, ammonia-like odor in patients, especially if there is porto-
venous shunting of blood
Umbilical hernia Secondary to increased intraabdominal pressures from ascites
Caput medusa Results from recannulation of umbilical vein: collateral veins radiating from
umbilicus
Hyperestrogenemia For males: gynecomastia, testicular atrophy, loss of male-pattern hair
distribution
DISEASE-ASSOCIATED FINDINGS
Wilson’s disease Kayser-Fleischer rings (golden-brown copper pigment deposited in periphery
of cornea)
Alcoholic liver disease Dupuytren contracture and parotid enlargement
Hemochromatosis Slate-gray pigmentation of skin

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IV. DIAGNOSTICS
TESTS BASED ON DETOXIFICATION & EXCRETORY FUNCTIONS
Unconjugated (indirect) bilirubin: seen in hemolytic disorders, Crigler-Najjar and
Gilbert’s syndrome
Serum Bilirubin Conjugated (direct) bilirubin: almost always implies liver or biliary tract disease
Higher levels indicate more severe hepatocellular damage/injury in viral
hepatitis and drug-induced liver disease
Enzymes that reflect damage to hepatocytes
ALT is more specific as an indicator of liver injury than AST
Elevations of >1000 U/L occur almost exclusively in:
o Viral hepatitis
o Ischemic liver injury (prolonged hypotension or acute heart failure)
Aminotransferases o Toxin- or drug-induced liver injury
o Acute phase of biliary obstruction caused by passage of gallstone into
CBD
Patterns of liver injury:
o AST:ALT<1 in chronic viral hepatitis, non-alcoholic fatty liver disease
o AST:ALT>2 in alcoholic liver disease
o Alkaline phosphatase > aminotransferases in cholestatic conditions
Alkaline Phosphatase (ALP) Enzymes that reflect cholestasis
5’Nucleotidase Elevations of ALP greater than 4 times seen in cholestatic liver disease,
y-glutamyl Transpeptidase infiltrative liver diseases, rapid bone turnover
(GGT) Elevations in both GGT and alkaline phosphatase indicative of biliary disease
TESTS THAT MEASURE BIOSYNTHETIC FUNCTION OF LIVER
Synthesized exclusively by the hepatocytes
Half-life of 18-20 days, therefore not a good indicator of acute or mild
Serum Albumin dysfunction
Hypoalbuminema is more common in chronic liver disorders such as cirrhosis,
reflecting severe liver damage and decreased albumin synthesis
y-globulins are increased in CLD due to increased antibody synthesis to fight off
Serum Globulins intestinal bacteria that the cirrhotic liver failed to clear from the hepatic
circulation
Single best acute measure of hepatic synthetic function
All clotting factors are synthesized in the liver except for factor VIII (produced by
endothelial cells)
Clotting Factors Prothrombin time measures factors II, V, VII, X
Vitamin K-dependent factors: II, VII, IIX, X
Marked prolongation of PT >5 sec above control not corrected by IV Vitamin K
is a poor prognostic sign
IMAGING AND OTHER TESTS
Most commonly employed for imaging of the liver
Ultrasound, CT, MRI Ultrasound is first-line if initial blood tests suggest cholestasis (to check for
dilated ducts/gallstones)
MRCP, ERCP Procedures of choice for visualization of the biliary tree
Doppler US and MRI Hepatic vasculature and hemodynamics
Doppler US is first test ordered if suspecting Budd-Chari syndrome
The criterion standard in the evaluation of patients with liver disease
Subject to sampling error in focal infiltrative disorders such as hepatic
Liver Biopsy metastasis
Should not be the initial procedure in the diagnosis of cholestasis
Contraindications to percutaneous approach: significant ascites and prolonged
INR (may use transjugular approach instead)

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V. DISEASE-SPECIFIC LABORATORY TESTS
DISEASE DIAGNOSTIC TESTS AND EXPECTED FINDINGS
Autoimmune Hepatitis Antinuclear antibody (ANA) or anti-smooth muscle antibody (SMA)
Elevated IgG levels
Primary Biliary Cirrhosis AMA (anti-mitochondrial antibody); elevated IgM levels
Primary Sclerosing p-ANCA; cholangiography
Cholangitis
Wilson’s Disease Decreased serum ceruloplasmin and increased urinary copper
Increased hepatic copper level
Hemochromatosis Elevated iron saturation and serum ferritin
Genetic testing for HFE gene mutations
Hepatocellular Cancer Elevated alpha-fetoprotein level >500; US or CT image of mass

VI. OVERVIEW OF SEROLOGY FOR VIRAL HEPATITIS


HEPATITIS A (HAV)
Anti-HAV (IgM) Diagnosis of hepatitis A during acute illness and persists for several months
(Antibody to HAV) Detected when aminotransferase activity is elevated & fecal HAV shedding still
occurring
Anti-HAV (IgG) After acute illness, anti-HAV of the IgG class remains detectable indefinitely
(Antibody to HAV) Predominates during convalescence
Marker of immunity to reinfection
HEPATITIS B (HBV)
HBsAg (Hepatitis B Surface First virologic marker detectable in serum within 1-12 weeks after infection with
Agent) HBV
Chronic HBV infection: HBsAg remains detectable beyond six months
After HBsAg disappears, anti-HBsAg becomes detectable and remains
Anti-HBs detectable indefinitely thereafter (protective antibody)
Also seen after immunization with hepatitis B vaccine (anti-HBs would be the
only serologic marker to appear)
IgM anti-HBc: predominates during the first six months after acute infection,
Anti-HBc (IgM or IgG) including anti-HBc window period
IgG anti-HBc: predominant class of anti-HBc beyond six months
An isolated reactive anti-HBc can be seen in the gap or window period
Appears concurrently with or shortly after HBsAg
Qualitative marker on HBV replication and relative infectivity
HBeAg (Hepatitis B ‘e’ HBsAg-positive serum containing HBsAg is more likely to be highly infectious
Antigen) Its disappearance may be a harbinger of clinical improvement and resolution of
infection
Persistence beyond the first 3 months of acute infection is predictive of
development of chronic infection
Anti-HBe Its appearance coincides with a period of relatively lower infectivity
HBV DNA More sensitive and quantitative indicator of HBV replication
HEPATITIS C (HCV)
Anti-HCV Diagnosis of Hepatitis C
HCV RNA Most sensitive test for HCV infection: “gold standard” in establishing a diagnosis
of HCV
HEPATITIS D (HDV)
Anti-HDV Testing for anti-HDV is useful in those with hepatitis B and severe/fulminant
disease
HEPATITIS E (HEV)
Anti-HEV (IgM/IgG) Not routinely available

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VII. SUMMARY OF TESTS FOR VIRAL HEPATITIS
DISEASE DIAGNOSTIC TESTS AND EXPECTED FINDINGS
Hepatitis A Anti-HAV IgM
Hepatitis B
Acute infection HBsAg, IgM anti-HBc
Chronic infection HBsAg, IgG anti-HBc
Markers of replication HBeAg, HBV DNA
Hepatitis C Anti-HCV and HCV RNA
Hepatitis D (Delta) HBsAg and anti-HDV
HBV/HDV coinfection IgM anti-HBc and anti-HDV
HDV superinfection IgG anti-HBc and anti-HDV
Hepatitis E Anti-HEV

VIRAL HEPATITIS
I. ACUTE VIRAL HEPATITIS

A. Overview of Clinical Profile


FEATURE HAV HBV HCV HDV HEV
Onset Acute Insidious or acute Insidious Insidious or Acute
acute
Predominant Percutaneous, perinatal, Percutaneous,
Mode/s of Fecal-oral sexual Percutaneous sexual Fecal-oral
Transmission
Severity Mild Occasionally severe Moderate Occasionally Mild
severe
Progression to None Occasional (common if Common Common None
Chronicity perinatal)
Prognosis Excellent Variable Moderate Variable Good
IG HBIG
Prophylaxis Inactivated Recombinant vaccine None HBV vaccine Vaccine
Vaccine
Interferon, Lamivudine, PEG-IFN +
Therapy None Adefovir, PEG-IFN, Ribavirin Interferon None
Entecavir, Telbivudine, Telaprevir,
Tenofovir Boceprevir
More Chronic liver Defective virus Usually from
symptomatic/ disease from that requires contaminated
severe The only hepatitis virus chronic helper water supply
Additional Notes infection in with a DNA genome (other hepatitis C is function of after monsoon
adults types have an RNA the most HBV for flooding in
compared to genome) frequent replication and endemic areas
children indication for expression
liver transplant

B. Clinical Manifestations
SYMPTOMS AND SIGNS
Prodromal Anorexia, nausea and vomiting, fatigue, malaise, arthralgias, myalgias, headache,
Symptoms photophobia, pharyngitis, cough & coryza may precede the onset of jaundice by 1-2
weeks
Jaundice With the onset of jaundice, the constitutional prodromal symptoms usually diminish
Complete clinical and biochemical recovery occurs:
o 1-2 months after hepatitis A and E
Recovery Phase o 3-4 months after the onset of jaundice in hepatitis B and C (among healthy
adults, acute hepatitis B is self-limited in 95-99% while hepatitis C is self-
limited in only 15%)

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LABORATORY FEATURES
AST and ALT Increase during the prodromal phase of acute viral hepatitis and precede the rise in
bilirubin level
Peak levels vary from 400-4000 IU or more
Bilirubin When jaundice appears, bilirubin typically rises
Prothrombin Time Prolonged values reflect a severe hepatic synthetic defect
Alkaline Normal or mildly elevated
Phosphatase
Hypoalbuminemia Uncommon in uncomplicated acute viral hepatitis

C. Diagnosis of Acute Hepatitis


DIAGNOSTIC INTERPRETATION HBsAg IgM Anti-HAV IgM Anti-HBc Anti-HCV
Acute hepatitis B + - + -
Acute hepatitis A superimposed on + + - -
chronic hepatitis B
Acute hepatitis A and B + + + -
Acute hepatitis A - + - -
Acute hepatitis A and B (HBsAg below - + + -
detection threshold)
Acute hepatitis B (HBsAg below - - + -
detection threshold)
Acute hepatitis C - - - +

D. Sequelae of Acute Viral Hepatitis

1. Fulminant Hepatitis
Most feared complication of viral hepatitis (massive hepatic necrosis)
Primarily seen in hepatitis B, E and D (mnemonic: B-E-D-ridden for fulminant hepatitis)
Signs and symptoms of encephalopathy that may evolve to deep coma
Terminal events: brainstem compression, GI bleeding, sepsis, respiratory failure, cardiovascular collapse,
renal failure
Management: restriction of protein intake, oral lactulose or neomycin, supportive (fluids, circulation,
respiration, correction of bleeding and hypoglycemia), liver transplantation may be life-saving

2. Chronic Liver Disease (CLD)


Hepatitis A or E Neither HAV nor HEV causes chronic liver disease
Hepatitis B Chronic: persistence of HBeAg for >3 months or HBsAg for >6 months after acute hepatitis
Hepatitis C After acute HCV infection, the likelihood of remaining chronically infected approaches 90%

II. CHRONIC VIRAL HEPATITIS

A. Interpretation of Hepatitis B Serologic Markers


INTERPRETATION HBsAg Anti-HBs Anti-HBc HBeAg Anti-HBe
Acute hepatitis B, high infectivity + - IgM + -
Chronic hepatitis B, high infectivity + - IgG + -
Chronic hepatitis B, low infectivity + - IgG - +
Anti-HBc “window” - - IgM +/- +/-
Hepatitis B in remote past - - IgG - +/-
Recovery from hepatitis B - + IgG - +/-
Immunization with HBsAg (after - + - - -
vaccination)

B. Sequelae
Liver cirrhosis (see separate section on Liver Cirrhosis for more information)
Hepatocellular carcinoma (hepatitis B and C), especially for individuals who acquired hepatitis B perinatally

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C. Management
FACTORS THAT AFFECT DECISION TO TREAT AND/OR DURATION OF TREATMENT
HEPATITIS B HEPATITIS C
Clinical status (presence of cirrhosis,
compensated vs. decompensated)
Family history of hepatocellular carcinoma Detectable HCV RNA in serum
HBsAg status HCV genotype
HBV DNA titers
ALT levels
TREATMENT
Pegylated interferon (PEG IFN) once weekly Pegylated interferon (PEG IFN) + Ribavirin
SC injection o Genotype 1: 48 weeks
Lamivudine 100 mg PO OD (first successful o Genotype 2: 24 weeks
oral antiviral agent) o Most pronounced side effect of ribavirin is
Entecavir 0.5 mg PO OD (most potent of the hemolysis
antivirals)
Tenofovir 300 mg PO OD

ALCOHOLIC LIVER DISEASE


I. ETIOPATHOGENESIS
Threshold for developing alcoholic liver disease
o Men: >60-80 g/day of alcohol for 10 years
o Women: >20-40 g/day of alcohol for 10 years
o >160 g/day has a 25x increased risk of alcoholic cirrhosis
The following all contain ~12 g of alcohol:
o One bottle of beer
o Four ounces of wine
o One ounce of 80% spirits

II. CLINICAL MANIFESTATIONS


PATHOLOGY SYMPTOMS AND SIGNS SOME LABORATORY FINDINGS
Fatty liver RUQ pain, nausea, fatigue AST or ALT increased 2 to 7-fold
AST/ALT ratio >1
Fever, spider nevi, jaundice and Bilirubin may be markedly increased
abdominal pain in alcoholic hepatitis despite only
Alcoholic hepatitis Portal hypertension, ascites, or modest elevation in alkaline
variceal bleeding can occur in the phosphatase
absence of cirrhosis PMN >5500/uL predicts severe
alcoholic hepatitis when discriminant
function >32
RUQ pain, fever, nausea and vomiting,
diarrhea, anorexia and malaise
More specific complications: ascites,
edema or upper GI hemorrhage Hypoalbuminemia
Jaundice, encephalopathy, Prolonged PT
hepatomegaly, splenomegaly Increased bilirubin
Alcoholic cirrhosis Liver edge may be firm and nodular Anemia
Scleral icterus, palmar erythema, Thrombocytopenia (due to portal HPN
spider angiomas, parotid gland and hypersplenism)
enlargement, digital clubbing, muscle CT/UTZ: nodular liver, splenomegaly,
wasting, edema and ascites venous collaterals
Males: decreased body hair, testicular
atrophy, gynecomastia
Females: menstrual abnormalities

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III. MANAGEMENT
Complete abstinence from alcohol is the cornerstone in the treatment of alcoholic liver disease
Glucocorticoids may be used for severe alcoholic hepatitis (discriminant function >32 or MELD >20)

Discriminant function = 4.6 x [PT prolongation above control in seconds] +serum bilirubin mg
dL
o Steroid dosing: prednisone 40 mg/day or prednisolone 32 mg/day for 4 weeks, then tapered over 4 weeks
o Exclusion criteria: active GI bleeding, renal failure, pancreatitis
TNF inhibitor pentoxifylline (400 mg PO TID x 4 weeks) has demonstrated improved survival in severe cases

LIVER CIRRHOSIS
I. NATURAL HISTORY

Chronic liver disease compensated cirrhosis decompensated cirrhosis death


The presence of complications differentiates decompensated from compensated cirrhosis:
o Variceal hemorrhage
o Ascites
o Hepatic encephalopathy
o Jaundice

II. CAUSES OF CIRRHOSIS


Alcoholic cirrhosis
Chronic viral hepatitis B or C
Autoimmune hepatitis
Nonalcoholic steatohepatitis
Biliary cirrhosis
Cardiac cirrhosis
Inherited metabolic liver disease (e.g., hematochromatosis, Wilson’s Disease)

III. COMPLICATIONS OF CIRRHOSIS


Spontaneous bacterial peritonitis
Hepatic encephalopathy
Portal hypertension
Portopulmonary hypertension
Hepatorenal syndrome
Hepatopulmonary syndrome
Others: malnutrition, bone disease, coagulopathy, hematologic (thrombocytopenia, neutropenia)

A. Spontaneous Bacterial Peritonitis (SBP)


Spontaneous infection of the ascitic fluid without an intra-abdominal source
Usually occurs in the setting of liver cirrhosis

Clinical features of Spontaneous Bacterial Peritonitis


o Presents as fever, altered mental status, elevated WBC, and abdominal pain/discomfort
o Most common organisms are Escherichia coli and other gut bacteria
o Isolation/growth of more than 2 organisms should raise suspicion for perforated viscus (secondary
bacterial peritonitis)
o Diagnosis: fluid sample has an absolute neutrophil count >250/uL

Treatment: Cephalosporins or Quinolones


o Cefotaxime 2 g IV q8 x 5 days
o Ofloxacin 400 mg PO BID x 8 days
o Ciprofloxacin 200 mg IV q12 x 2 days followed by ciprofloxacin 500 mg PO q 12 x 5 days
o Ceftriaxone 1 g IV q8 x 5 days

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B. Hepatic Encephalopathy
Alteration in mental status and cognitive function occurring in the presence of liver failure
In acute liver injury, development of encephalopathy is a requirement for diagnosis of fulminant hepatic failure
Encephalopathy is more commonly seen in chronic liver disease
Symptoms are due to neurotoxins that are not removed by the liver because of vascular shunting

Clinical features of Hepatic Encephalopathy


o Symptoms: confused, changes in behavior, violent, difficult to manage, sleepy and difficult to rouse
o Asterixis or liver flap: sudden forward movement of the wrist after it is bent back on an extended arm
(cannot be elicited if already comatose)
o Cerebral herniation is a feared companion of brain edema
o Correlation between severity of liver disease and serum ammonia levels is often poor
GRADE LEVEL OF PERSONALITY AND INTELLECT NEUROLOGIC
CONSCIOUSNESS ABNORMALITIES
0 Normal Normal Normal
1 Inverted sleep pattern, Forgetful, mild confusion, agitation, Tremor, apraxia,
restless irritable incoordination, impaired
handwriting
Disorientation to time, amnesia, Asterixis, dysarthria,
2 Lethargic, slow responses decreased inhibitions, inappropriate hypoactive reflexes
behavior
Somnolent but can be Asterixis, hyperactive
3 aroused, confused Disorientation to place, aggressive reflexes, Babinski’s
sign, muscle rigidity
4 Coma Nil Decerebrate

Precipitating Events in Hepatic Encephalopathy


o Hypokalemia: hypokalemia causes increased ammoniagenesis (alkaline tide)
o Infection
o Increased dietary protein load
o Electrolyte disturbances
o GI bleeding

Treatment of Hepatic Encephalopathy


Nutrition Protein restriction is discouraged as it has negative impact on overall nutrition
Replace animal-based protein with vegetable-based protein in the diet
Mainstay of treatment for encephalopathy
Initial dose: 30-40 mL orally, once or twice daily (dose may be increased as
tolerated)
Lactulose Goal is to promote 2-3 soft stools per day
Mechanisms of action:
o Colonic acidification
o Catharsis
Adjunctive to lactulose
Poorly absorbed antibiotics:
Antibiotics o Neomycin 250 mg BID-QID
o Metronidazole 250-500 mg TID (given alternately to reduce individual side
effects)
Rifamixin 550 mg BID has been very effective as well, with a better safety profile
Supportive Management/correction of the above-mentioned precipitating factors
Zinc supplementation may be helpful

C. Portal Hypertension (HPN)


Elevation of hepatic venous pressure gradient >5 mmHg
Development of portal hypertension is usually revealed by the presence of thrombocytopenia, splenomegaly and
development of ascites, encephalopathy and/or esophageal varices with or without bleeding

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Classification of Portal Hypertension
PRE-HEPATIC HEPATIC POST-HEPATIC
Affects the portal venous system Most common: can be presinusoidal, Affects the hepatic veins and venous
before it enters the liver sinusoidal, postsinusoidal damage to the heart
Presinusoidal Budd-Chiari syndrome
Schistosomiasis Inferior vena caval webs
Portal vein thrombosis Congenital hepatic fibrosis Cardiac causes
Splenic vein thrombosis Sinusoidal Restrictive cardiomyopathy
Massive splenomegaly (Banti’s Cirrhosis Constrictive pericarditis
syndrome) Alcoholic hepatitis Severe CHF
Postsinusoidal
Hepatic sinusoidal obstruction
(venoocclusive syndrome)

Complications of Portal Hypertension


GASTROESOPHAGEAL VARICES
Resistance to portal flow leads to increased resistance in portal pressure
Mechanism Decreased splanchnic arteriolar resistance leads to increased splanchnic flow (increased
portal blood flow)
Treatment See table in separate section on Management on GI bleeding
ASCITES
Due to portal HPN, there will be vasodilation of the splanchnic arterial system, resulting in:
Increased splanchnic pressure due to increased portal venous flow ascites
Mechanism Underfilling of arterial system RAAS activation hyperaldosternism Na+/H2O
retention ascites
Decreased synthetic function of the liver hypoalbuminemia decreased oncotic
pressure ascites
Small amount of ascites: dietary sodium restriction (<2 g of sodium/day, avoid canned or
processed foods)
Moderate amount of ascites: diuretics with 100 mg spironolactone and 40 mg furosemide
Treatment as the isokalemic dose (up to a maximum of 600 mg/day and 160 mg/day, respectively)
Refractory ascites: repeated large-volume paracentesis with albumin infusion, TIPS
procedure (TIPS does not improve survival and may precipitate hepatic encephalopathy,
liver transplantation)
HYPERSPLENISM
Mechanism Hypersplenism with the development of thrombocytopenia is a common feature of
patients with cirrhosis and is usually the first indication of portal hypertension
Splenomegaly itself usually requires no specific treatment
Treatment Supportive transfusion with platelet concentrate as necessary during episodes of
bleeding

IV. RISK STRATIFICATION IN HEPATIC DISEASES

A. Child Pugh Score


Stratifies patients in risk groups
Predicts likelihood of major complications of cirrhosis (e.g., variceal bleeding, SBP)
PARAMETER 1 2 3
Serum Bilirubin umol/L <34 34-51 >51
mg/dL <2.0 2.0 – 3.0 >3.0
Serum Albumin g/L >35 30 - 35 < 30
g/dL >3.5 3.0 – 3.5 < 3.0
Prothrombin Time Seconds 0–4 4–6 >6
INR < 1.7 1.7 – 2.3 > 2.3
Ascites None Easily controlled Poorly controlled
Hepatic Encephalopathy None Minimal Advanced

Interpretation:
o Class A = scores 5-6
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o Class B = score of 7-9
o Class C = scores of 10-15

Decompensation indicates cirrhosis with a score of > 7 (this level has been the accepted criterion for listing a
patient for liver transplantation)

B. Model for End-Stage Liver Disease MELD) Score


Scoring system to predict prognosis of patients with liver disease and portal hypertension
This score is now used for prioritizing allocation for liver transplantation
Calculated using three non-invasive variables:
o PT-INR
o Serum bilirubin
o Serum creatinine

ACUTE PANCREATITIS
I. ETIOPATHOGENESIS
Inflammation of the pancreas due to activation of pancreatic enzymes within the pancreas
The pathologic spectrum of acute pancreatitis
o Interstitial pancreatitis: mild and self-limited disorder
o Necrotizing pancreatitis: more severe form
Common etiologies (G-A-T-E-D):
o Gallstones: most common cause
o Alcohol: 2nd most common cause
o HyperTriglycerides (usually with serum triglycerides >1000 mg/dL)
o Endoscopic retrograde cholangiopancratography (ERCP)
o Drugs
o Trauma
o Postoperative
o Sphincter of Oddi dysfunction
For recurrent attacks of pancreatitis, the two most common etiologies: alcohol and cholelithiasis
Autodigestion: currently accepted pathogenic theory
Proteolytic enzymes (e.g., trypsinogen, chymotrypsinogen, proelastase) are activated in the pancreas rather than
in the intestinal lumen

II. CLINICAL MANIFESTATIONS OF PANCREATITIS

A. Symptoms and Signs of Acute Pancreatitis


SYMPTOMS
Major symptom of acute pancreatitis
Quality: steady and boring in character
Abdominal pain Location: epigastrium and peiumbilical region
Radiation: back, chest, flanks, lower abdomen
More intense when supine
Relieved upon sitting with the trunk flexed and knees drawn up
Other symptoms Nausea, vomiting, and abdominal distention
SIGNS
General PE Distressed and anxious patient
Low-grade fever, tachycardia, and hypotension are fairly common
Hypovolemia secondary to exudation of blood and plasma proteins into
Shock the retroperitoneum
Systemic effects of proteolytic and lipolytic enzymes released into the
circulation
Abdominal Tenderness Compared with the intense pain, this sign may be unimpressive
Bowel Sounds Decreased or absent
Jaundice (infrequent) Due to edema of the pancreatic head with compression of the
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intrapancreatic portion of the common bile duct (CBD)
Pulmonary findings Basilar rates, atelectasis, pleural effusion (most frequently left sided)
Cullen’s Sign Blue discoloration around the umbilicus (results from hemoperitoneum)
Turner’s Sign Blue-red-purple or green-brown discoloration of the flanks (reflects tissue
catabolism of hemoglobin)

B. Revised Atlanta Definitions of Morphologic Features of Acute Pancreatitis


MORPHOLOGIC FEATURE DEFINITION
Interstitial Pancreatitis Acute inflammation of pancreatic parenchyma & peripancreatic tissues
No recognizable tissue necrosis
Necrotizing Pancreatitis Inflammation associated with parenchymal and/or peripancreatic necrosis
Peripancreatic fluid associated with interstitial edematous pancreatitis
Acute Pancreatic Fluid No associated necrosis
Collection Applies only to areas of fluid seen within the first 4 weeks after onset of
interstitial edematous pancreatitis and without features of a pseudocyst
Encapsulated collection of fluid with a well-defined inflammatory wall
Pancreatic pseudocyst usually outside the pancreas with minimal or no necrosis
Occurs > 4 weeks after onset of interstitial edematous pancreatitis
Acute necrotic collection Collection containing variable amounts of both fluid and necrosis
(ANC) associated with necrotizing pancreatitis
Mature, encapsulated collection of pancreatic and/or peripancreatic
Walled-off Necrosis (WON) necrosis that has developed a well-defined inflammatory wall
Usually occurs > 4 weeks after onset of necrotizing pancreatitis

C. Revised Atlanta Classification: Clinical Course, Definitions and Classifications

1. Phases of Acute Pancreatitis


Severity is defined by clinical parameters, rather than morphologic
findings
Early Most exhibit SIRS and are predisposed to organ failure
(<2 weeks) Three organ systems should be assessed to define organ failure:
respiratory, cardiovascular, and renal
Persistent organ failure (>48 hours): most important clinical finding with
regard to severity of the acute pancreatitis episode
Characterized by a protracted course of illness and may require imaging
Late to evaluate for local complications
(>2 weeks) Important clinical parameter of severity: persistent organ failure
May require supportive measures (dialysis, ventilator support, TPN)

2. Severity of Acute Pancreatitis


Without local complications or organ failure
Self-limited disease and subsides within 3-7 days after treatment is
Mild instituted
Oral intake may be resumed if patient is hungry, has normal bowel
function and has no nausea/vomiting
Moderately Severe Characterized by transient organ failure (resolves in <48 hours) or local or
systemic complications in the absence of persistent organ failure
Persistent organ failure (>48 hours)
Severe CT scan or MRI should be obtained to assess for necrosis and/or
complications

3. Imaging in Acute Pancreatitis


Two types of pancreatitis are recognized on imaging: interstitial or necrotizing
CT imaging: best evaluated 3-5 days into hospitalization when patients are not responding to
supportive care to look for local complications such as necrosis

III. DIAGNOSTICS

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Acute pancreatitis: increased level of serum amylase and lipase (more than 3-fold)
Amylase Returns to normal after 3-7 days
Amylase elevations in serum and urine occur in many conditions other than
pancreatitis
Acute pancreatitis: increased level of serum amylase and lipase (more than 3-fold)
Lipase Preferred test (more specific than amylase)
Elevated for 7-14 days
Complete blood count Leukocytosis (15,000-20,000/uL)
Hemoconcentration with hematocrit values >44%
Renal function Azotemia with BUN > 22mg/dL: due to loss of plasma into the retroperitoneal space
and peritoneal cavity
Hyperglycemia: due to decreased insulin release, increased glucagon release,
increase output of adrenal glucocorticoids and catecholamines
Hypocalcemia: saponification
Serum chemistry Hyperbilirubinemia
Serum alkaline phosphatase and aspartate aminotransferase levels are transiently
elevated
Markedly elevated serum LDH levels: poor prognosis
Hypertriglyceridemia
ABG Hypoxemia (arterial PO2 < 60 mmHg): may herald the onset of ARDS
Helpful in indicating the severity of acute pancreatitis and the risk of morbidity and
Abdominal CT Scan mortality
Aids in evaluating for complications of acute pancreatitis
Sonography Useful in acute pancreatitis to evaluate the gallbladder if gallstone disease is
suspected

IV. DEFINING SEVERE ACUTE PANCREATITIS


RISK FACTORS FOR SEVERE DISEASE
Age > 60 years
Obesity, BMI >30
Comorbid disease (Charlson Comorbidity Index)
MARKERS OF SEVERITY AT ADMISSION OR WITHIN 24 HOURS
SIRS
APACHE II
Hemoconcentration (Hematocrit > 44%)
Admission BUN (>22 mg/dL)
BISAP (> 3 of these factors: associated with increased risk for in-hospital mortality)
o B: BUN >25 mg/dL
o I: Impaired Mental Status (GCS <15)
o S: SIRS: > 2 of 4 present
o A: Age > 60 years
o P: Pleural effusion
Organ Failure (Modified Marshall Score)
o Cardiovascular: SBP < 90 mmHg, HR > 130 bpm
o Pulmonary: PaO2 < 60 mmHg
o Renal: serum creatinine > 2.0 mg/dL
MARKERS OF SEVERITY DURING HOSPITALIZATION
Persistent organ failure (>48 hours)
Pancreatic necrosis

V. MANAGEMENT
Usually, the disease is self-limited and subsides spontaneously
Resolution occurs within 3-7 days after treatment is instituted
Conventional Analgesics for pain
Measures No oral alimentation (NPO)
Fluid Resuscitation The most important treatment intervention: safe, aggressive IV fluid resuscitation
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Initial IVF: LR or pNSS at 15-20 cc/kg bolus, followed by 3mg/kg/hr to maintain urine
output >0.5cc/kg/hr
Targeted resuscitation strategy: measure hematocrit and BUN every 8-12 hours to
ensure adequacy of fluid resuscitation and monitor response to therapy
Antibiotics Prophylactic antibiotics have no role in either interstitial or necrotizing pancreatitis
ERCP For severe acute biliary pancreatitis with organ failure and/or cholangitis
No abdominal pain, nausea or vomiting
Resumption of Diet Patient is hungry
Normal bowel sounds

VI. COMPLICATIONS
LOCAL COMPLICATIONS SYSTEMIC COMPLICATIONS
Pulmonary: ARDS, effusion, pneumonitis
Necrosis (sterile or infected) Cardiovascular: hypotension, sudden death
Pancreatic fluid collections (pseudocyst, abscess) Hematologic: disseminated intravascular coagulation
Pancreatic ascites Gastrointestinal: ulcer formation, gastritis
Obstructive jaundice Renal: oliguria, azotemia, acute tubular necrosis
Metabolic: hyperglycemia, hypocalcemia

SURGICAL CAUSES OF RIGHT UPPER QUADRANT PAIN


I. DIFFERENTIALS FOR RIGHT UPPER QUADRANT PAIN
DIFFERENTIAL DESCRIPTION
Divided into two major types:
Cholelithiasis o Cholesterol stones (80%)
(“Gallstones”) o Pigment stones (< 20%)
Ultrasonography: very accurate in the identification of cholelithiasis
Most specific and characteristic symptom of gallstone disease: biliary colic
Passage of stones in the common bile duct (CBD)
CBD stones should be suspected in gallstone patients who have any of the following
Choledocholelithiasis risk factors:
o History of jaundice or pancreatitis
o Abnormal tests of liver function
o Ultrasonographic or MRCP evidence of a dilated CBD or stones in the duct
Acute inflammation of the gallbladder wall usually follow obstruction of the cystic duct
by a stone
Acute Cholecystitis Ultrasonography demonstrates calculi in 90-95% and is useful for detection of signs of
gallbladder inflammation: thickening of the wall, pericholecystic fluid and dilation of the
bile duct
Bacterial infection superimposed on an obstruction of the biliary tree most commonly
Ascending Cholangitis from a gallstone
Medical +/- surgical emergency

II. CLINICAL MANIFESTATIONS OF BILIARY TRACT PATHOLOGIES


Most specific and characteristic symptom of gallstone disease
Steady epigastric or RUQ pain, radiation to intrascapular area, right scapula or
shoulder
Begins quite suddenly and may persist with severe intensity for 15 minutes to 5 hours
Biliary colic Subsides gradually or rapidly
Persistence of pain beyond 5 hours should raise the suspicion of acute cholecystitis
May be precipitated by:
o Eating a fatty meal
o Consumption of a large meal following a period of prolonged fasting
o Eating a normal meal
Murphy’s sign Deep inspiration or cough during subcostal palpation of the RUQ usually produces
increased pain and inspiratory arrest
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Usually in acute cholecystitis
Rare complication
Mirizzi’s Syndrome Gallstone becomes impacted in the cystic duct or neck of the gallbladder causing
compression of the common bile duct (CBD), resulting in CBD obstruction and
jaundice
Courvoisier’s Law A palpable enlarged gall bladder suggests that the biliary obstruction is secondary to
underlying malignancy
Triad of Acute Sudden RUQ tenderness
Cholecystitis Fever
Leukocytosis
Charcot’s Triad of Biliary (RUQ) pain
Acute Cholangitis Jaundice
Spiking fevers with chills
Biliary (RUQ) pain
Reynolds’ Pentad of Jaundice
Acute Cholangitis Fever
Shock
Altered mental status
Nausea and vomiting
Other symptoms Jaundice usually if with CBD obstruction
Fever or chills with biliary pain imply a complication: cholecystitis, pancreatitis,
cholangitis

III. DIAGNOSTICS
Bilirubin, Alkaline Elevated levels suggest common bile duct stone
Phosphatase
Rapid, accurate identification of gallstones (>95%)
Gallbladder Ultrasound Procedure of choice for detection of stones
Limitations: bowel gas, massive obesity, ascites
Pathognomonic findings in:
o Calcified gallstones
Plain Abdominal X-Ray o Limey bile, porcelain GB
o Emphysematous cholecystitis
o Gallstone ileus
Limitations: generally low-yield; contraindicated in pregnancy
Magnetic Resonance Useful modality for visualizing pancreatic and biliary ducts
Cholangiopancreatography Cannot offer therapeutic intervention
(MRCP)
Endoscopic Retrograde Best visualization of distal biliary tract
Cholangiopancreatography Cholangiogram of choice in: absence of dilated ducts, pancreatic or ampullary
(ERCP) disease, prior biliary surgery, endoscopic sphincterotomy is a treatment possibility
Can be complicated by pancreatitis, cholangitis or perforation
Pecutaneous Transhepatic Best visualization of proximal biliary tract
Cholangiogram Can provide biliary of drainage
Indicated when ERCP is contraindicated or has failed

IV. MANAGEMENT

A. Cholelithiasis (Gallstones)
Laparoscopic cholecystectomy: “gold standard” for treating symptomatic cholelithiasis
Ursodeoxycholic acid (UDCA) 10-15 mg/kg per day
o Used for cholesterol stones: therapy should be limited to radiolucent stones <5mm in diameter
o Mechanism: decreases cholesterol saturation of bile and retards cholesterol crystal nucleation
o Pigment stones are not responsive to UDCA therapy
o Relatively expensive and requires long-term treatment (up to 2 years for complete dissolution)

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B. Choledocholithiasis
Endoscopic biliary sphincterotomy (EBS) followed by spontaneous passage or stone extraction: treatment of
choice, especially in elderly or poor-risk patients
Laparoscopic cholecystectomy and ERCP have decreased the incidence of complicated biliary tract disease and
the need for choledocholithotomy and T-tube drainage of the bile ducts

C. Acute Cholecystitis
Cholecystectomy: mainstay of therapy for acute cholecystitis and its complications
Meperidine or NSAIDs: usually employed for analgesia because they may produce less spasm of the sphincter of
Oddi than drugs such as morphine
Intravenous antibiotic therapy for severe acute cholecystitis: guided by the most common organisms likely to be
present (E. coli, Klebseilla spp., and Streptococcus spp.)

D. Ascending Cholangitis
ERCP with endoscopic sphincterotomy: preferred initial procedure for both establishing a definitive diagnosis and
providing effective therapy
Endoscopic management of bacterial cholangitis is as effective as surgical intervention

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CHAPTER 6
INFECTIOUS DISEASES
I. Introduction to Infectious Diseases
1. Antibacterial Agents
2. Fever of Unknown Origin
3. Fever and Rash
II. Common Infectious Disease Conditions
1. Dengue
2. Malaria
3. Typhoid Fever
4. Leptospirosis
5. Schistosomiasis
6. Tetanus
7. Rabies
8. Infective Endocarditis
9. Human Immunodeficiency Virus: AIDS and Related
Disorders
10. Sexually Transmitted Infections
III. Immunization

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SECTION 1
INTRODUCTION TO INFECTIOUS DISEASES
ANTI-BACTERIAL AGENTS
I. BETA-LACTAMS
EXAMPLES MECHANISM ORGANISMS COVERED COMMON DOSAGES
OF ACTION
PENICILLINS
Narrow Spectrum Syphilis:
Penicillins: Highly effective against gram-positive cocci Pen G 2.4 Million units IM as
except penicillinase-producing bacteria, single dose (SD)
Penicillin G (IV form) meningococci, spirochetes, anaerobic
Penicillin V (Oral) cocci Prophylaxis for Recurrent
Rheumatic Fever:
Pen V 250 mg PO BID
Very Narrow
Spectrum Penicillins:
Active against most penicillinase-producing Cellulitis:
Nafcillin staphylococci Cloxacillin 500 mg QID
Oxacillin Inhibit cell wall
Cloxacillin synthesis:
Dicloxacillin
Extended-Spectrum Binds to
Penicillins: penicillin binding Effective against gram-positive cocci, Cellulitis:
proteins (PBP) enterococci and Listeria monocytogenes Amoxicillin 500 mg TIC
Ampicillin
Amoxicillin
Bone & Joint; Skin Structure
Antipseudomonal Sulbenicillin, Carbenicillin and Ticarcillin – Infections:
Penicillins: active against P. aeruginosa, P. vulgaris, Ticarcillin/Clavulanate 3.1 g IV
Providencia, Morganella and Enterobacter q4-q6
Sulbencillin sp. but less potent than the extended-
Carbenicillin spectrum penicillins against Streptococci Severe infections;
Ticarcillin and Enterococci Nosocomial Pneumonia:
Piperacillin Piperacilllin/Tazobactam 4.5 g
IV q6 (CrCl >40 mL/min)
CEPHALOSPORINS
Prophylaxis for
First-Generation: Cardiovascular and General
Active against most gram-positive cocci Surgeries (Biliary Tract,
Cefazolin including penicillin-resistant S. aureus but Esophageal, Appendectomy
Cephalexin not against enterococcus, Methicillin- or Laparoscopic Surgery):
Cephalothin resistant S. aureus (MRSA) and Methicillin- Usually Cefazolin 1-2 g IV pre-
Cefadroxil resistant S. epidermidis (MRSE) op (single dose)
Cephapirin
Inhibit cell wall Respiratory infections:
synthesis, but Cephalexin 250 mg PO q6
Second-Generation: are less Cefoxitin – resistant to beta-lactamase-
susceptible to producing gram-negative bacilli Prophylaxis for Non-
Cefoxitin penicillinase Perforated Appendicitis:
Cefaclor Improved activity against H. influenza, M. Cefoxicillin 1-2 g IV pre-op
Cefuroxime catarrhalis, Neisseria meningitides and N.
Cefamandole gonorrhea Pharyngitis/Tonsillitis:
Cefonizid Cefuroxime 250 mg PO q12 for
Cefotetan Enhanced activity against staphylococci, 10 days
Cefprozil non-enterococci streptococci and some
Enterbacteriaceae
146
Third-Generation: Effective against S. pneumoniae, S.
pyrogenes and other streptococci (with the
Ceftriaxone exception of Ceftazidime) and have CAP Mod risk:
Ceftazidime modest activity against Methicillin-sensitive Ceftriaxone 2g IV q24
Cefixime S. aureus (MSSA)
Ceftizoxime CAP High risk + Risk for P.
Cefpodoxime proxetil Excellent activity against N. gonorrhea, H. aeruginosa infection:
Cefotaxime influenza, M. catarrhalis and Ceftazidime 2 g Iv q8
Cefoperazone Enterobacteriaceae
Moxalactam
Active against both aerobic gram-positive
Fourth-generation: organisms (but not MRSA) and gram- CAP High risk + Risk for P.
(widest spectrum) negative organisms, including P. aeruginosa infection:
aeruginosa Cefepime 1-2 g IV q8-12 up to
Cefepime 21 days
Cefpirome Inactive against MRSA, MRSE,
Enterococcus sp., B. fragilis and ESBL
Specifically developed to target resistant
strains of bacteria

Ceftobiprole – active against MRSA,


Fifth-generation: Penicillin-resistant S. pneumoniae, P.
aeruginosa and enterococci Skin & soft tissue infections:
Ceftobiprole Ceftobiprole 500 mg IV
Ceftaroline fosamil Ceftaroline fosamil – for acute bacterial infusion q12
skin and skin structure infections (ABSSSI)
caused by MSSA, MRSA, S. pyrogenes, E.
coli, K. pneumoniae and CAP caused by S.
pneumoniae, S. aureus, H. influenxa, K.
pneumoniae and E. coli
CARBAPENEM
Nosocomial infections caused by multiple-
Inhibit cell wall resistant and complicated polymicrobial Intraabdominal infections:
Meropenem synthesis, and infections caused by aerobic gram-positive, Meropenem 1 g IV q8;
Imipenem are highly gram-negative organisms, anaerobic Imipenem 500 mg IV q6 or 1 g
Doripenem resistant to bacteria and ESBL-positive organisms. IV q8 for 4-7 days
Ertapenem degradation by
beta-lactamases All are recommended for pseudomonal Complicated skin/skin
infections except Ertapenem structure infections:
Meropenem 500 mg IV q8
MONOBACTAMS
Inhibit cell wall Activity limited to gram-negative bacilli
Aztreonam synthesis (binds including most Enterobacteriaceae, Pseudomonal infections:
to PBP3) Aeromonas sp., N. gonorrhea, H. influenza Aztreonam 2 g IV/IM q6-8
and P. aeruginosa

II. AMINOCYCLITOLS AND AMINOGLYCOSIDES


EXAMPLES MECHANISM OF ORGANISMS COVERED COMMON DOSAGES
ACTION
AMINOCYCLITOLS
Prophylaxis for Colorectal
Inhibit formation Active against aerobic gram-negative bacilli; Surgery:
of initiation most are active against P. aeruginosa, E. coli, Neomycin + Erythromycin
complex and Klebsiella and Proteus sp. base 1 g each PO at 1, 2,
Neomycin cause misreading and 11 pm on the day
of mRNA (30S Synergistic against staphylococcal, before surgery or Neomycin
inhibitor) streptococcal and enterococcal endocarditis 2 g + Metronidazole 2 g at 7
and 11 pm on the day
before surgery

147
AMINOGLYCOSIDES
In addition to an
Active against aerobic gram-negative bacilli; antipseudomonal beta-
Amikacin Inhibit formation most are active against P. aeruginosa, E. coli, lactam or carbapenem in
Streptomycin of initiation Klebsiella and Proteus sp. HAP:
Tobramycin complex and Useful combination treatment for serious Amikacin 20 mg/kg/day IV
Kanamycin cause misreading gram-negative infections
Netilmycin of mRNA (30S Tuberculosis:
inhibitor) Synergistic against Staphylococcal, Streptomycin 15 (12-18)
Streptococcal and Enterococcal endocarditis mg/kg IM per day (max 1
g/day)

III. BETA-LACTAMASE INHIBITORS


EXAMPLES MECHANISM OF ORGANISMS COVERED COMMON DOSAGES
ACTION
Clavulanic acid
(usually with Inhibits beta- Exacerbation of chronic
Amoxicillin, Ticarcillin) lactamases which bronchitis:
then restores the Against Beta-lactamase producing strains of Co-amoxiclav 1 g BID
Sulbactam antibacterial staphylococci, gonococci, H. influenza, M.
(usually with activity of catarrhalis, Bacteroides, Klebsiella sp. and E. Severe infections;
Ampicillin) amoxicillin, coli Nosocomial Pneumonia:
ampicillin, Piperacillin/Tazobactam 4.5
Tazobactam ticarcillin and g IV q6 (CrCl >40 mL/min)
(usually with piperacillin
Piperacillin)

IV. CHLORAMPHENICOL
EXAMPLES MECHANISM OF ORGANISMS COVERED COMMON DOSAGES
ACTION
Fully susceptible typhoid:
Inhibition of Aerobic and anaerobic bacteria
peptide bond Severe and complicated:
Chloramphenicol formation at the Standard therapy for typhoid fever, ampicillin- 100 mg/kg IV x 14-21 days
50S subunit resistant H. influenza and intraocular
infections Uncomplicated:
50-75 mg/kg x 14-21 days

V. MACROLIDES
EXAMPLES MECHANISM OF ORGANISMS COVERED COMMON DOSAGES
ACTION
Acute bronchitis:
Azithromycin 500 mg PO
BID day 1 then 250 mg PO
Azithromycin OD for days 2-5

Cervicitis; Chancroid:
Azithromycin 500 mg PO
Prevents Active against aerobic gram-positive cocci single dose
translocation at and bacilli, Legionella, Mycoplasma, Chancroid:
the 50S subunit Chlamydia and some gram-negative Erythromycin 500 mg PO
organisms including Bordetella pertussis, H. QID for 7 days
ducreyi and C. jejuni
Erythromycin Alternative for
nongonococcal urethritis:
Erythromycin base 500 mg
PO QID for 7 days;
Erythromycin ethylsuccinate
800 mg PO QID for 7 days

148
Exacerbation of chronic
Newer Macrolides bronchitis:
Clarithromycin Clarithromycin 500 mg PO
Roxithromycin BID for 7 days
Josamycin
Telithromycin H. pylori: (together with
Fidaxomicin Bismuth and Amoxicillin)
Clarithromycin 500 mg BID
for 2 weeks

VI. GLYCOPEPTIDES
EXAMPLES MECHANISM OF ORGANISMS COVERED COMMON DOSAGES
ACTION
Inhibit cell wall MRSA Infections:
mucopeptide Active against MSSA, MRSA, coagulase- Vancomycin 15-20 mg/kg IV
Vancomycin formation by negative staphylococci, enterococci, q12 (adjust accordingly
binding D-ala D- streptococci, C. diphtheria (JK Group), C. based on creatinine
ala portion cell difficile and Listeria clearance)
wall precursors

VII. LINCOSAMIDES
EXAMPLES MECHANISM OF ORGANISMS COVERED COMMON DOSAGES
ACTION
CA MRSA:
Clindamycin 600 mg IV q6-8

Bacterial vaginosis: Clindamycin cream 2%,


Useful for aerobic and 1 full applicator (5g) intravaginally HS for 7
Clindamycin Blocks peptide anaerobic gram-positive days
Lincomycin bond formation at cocci, some anaerobic Alternative: Clindamycin 300 mg PO BID for 7
50S ribosomal gram-negative bacilli and days or Clindamycin ovules 100 mg
subunit protozoans intravaginally HS for 3 days

Add-on therapy to Aspiration Pneumonia


(except in B-lactams that already have
anaerobic activity):
Clindamycin 450-900 mg IV q8

VIII. NITROMIDAZOLES
EXAMPLES MECHANISM OF ORGANISMS COVERED COMMON DOSAGES
ACTION
Bacterial Vaginosis:
Metronidazole 500 mg PO BID for 7 days or
Metronidazole gel 0.75%, 1 full applicator (5
g) intravaginally OD for 7 days

Forms toxic Trichomoniasis:


Metronizadole metabolites in the Excellent activity against Metronidazole 2 g PO SD
Secnidazole bacterial cell that anaerobes and protozoans Alternative: Metronidazole 500 mg BID x 7
damage DNA days

Acute gastroenteritis by B. hominis:


Metronidazole 750 mg PO TID x 10 days

Pseudomembranous colitis (C. difficile):


Metronidazole 500 mg PO TID for 10 days

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IX. OXAZOLIDINONES
EXAMPLES MECHANISM OF ORGANISMS COVERED COMMON DOSAGES
ACTION
Protein synthesis Active against S. aureus, S.
Linezolid inhibitors: epidermidis, S. Soft tissue infections:
disrupts mRNA pneumoniae, E. faecalis, Linezolid 600 mg PO/IV q12
translation and E. faecium

X. QUINOLONES
EXAMPLES MECHANISM OF ORGANISMS COMMON DOSAGES
ACTION COVERED
First Generation:
Usually for UTI and
Cinoxacin diarrheal diseases Not available locally
Nalidixic acid among children
Oxolinic acid
Pipemidic acid
Alternative for acute uncomplicated cystitis:
Ciprofloxacin 250 mg BID PO for 3 days;
Second Generation: Active against Norfloxacin 400 mg BID PO for 3 days
Enterobacteriaceae and
Ciprofloxacin Haemophilus sp., N. Primary treatment for uncomplicated acute
Norfloxacin gonorrhea & M. pyelonephritis:
Ofloxacin catarrhalis, C. Ciprofloxacin 500 mg BID for 7-10 days
Lomefloxacin Blocks bacterial trachomatis, and H.
Pefloxacin DNA synthesis by ducreyi Salmonella gastroenteritis:
Rufloxacin inhibiting Ciprofloxacin 500 mg PO OD for 7-10 days
bacterial
topoisomerase II Shigellosis:
(DNA gyrase) Ciprofloxacin 750 mg PO OD for 3 days
and Add-on to an IV non-antipseudomonal beta-
topoisomerase IV lactam in Moderate or High Risk CAP:
Levofloxacin 500 mg PO/IV OD for 7-14 days or
Broadened activity 750 mg PO/IV for 5 days
Third Generation: against anaerobes,
intracellular pathogens & Primary treatment for uncomplicated acute
Levofloxacin some gram-positive and pyelonephritis:
gram-negative aerobes Levofloxacin 250 mg OD PO for 7-10 days or 750
mg OD PO for 5 days

Salmonella gastroenteritis:
Levofloxacin 500 mg PO OD x 7-10 days
Highly effective against
Fourth Generation: both typical and atypical
respiratory pathogens Add-on to an IV non-antipseudomonal beta-
Moxifloxacin lactam in Moderate or High Risk CAP:
Gatifloxacin Moxifloxacin – most Moxifloxacin 400 mg PO/IV OD x 10 days
potent against S.
pneumoniae

XI. NITROFURANS
EXAMPLES MECHANISM OF ORGANISMS COMMON DOSAGES
ACTION COVERED
Inactivates
Nitrofurantoin bacterial Usually for the treatment Acute uncomplicated cystitis:
Nifuroxazide ribosomal of uncomplicated lower Nitrofurantoin monohydrate 100 mg BID PO x 5
Furazolidone proteins and UTI days or Nitrofurantoin macrocrystals 100 mg QID
other PO x 5 days
macromolecules

150
resulting to
inhibition of DNA,
RNA, protein and
cell wall
synthesis

XII. TETRACYCLINES
EXAMPLES MECHANISM OF ORGANISMS COMMON DOSAGES
ACTION COVERED
Drug of choice for V.
cholera, V. vulnificus, B.
burgdorferi, some Cervicitis/Nongonococcal urethritis/
Aeromonas and Chlamydia infections:
Doxycycline Binds to 30S Xanthomas sp., Doxycycline 100 mg PO BID x 7days
Minocycline subunit to block Mycoplasmas
Oxytetracycline binding of Donovanosis:
Tetracycline aminoacyl-tRNA Penicillin allergic Doxycycline 100 mg PO BID x 3-4 weeks until all
Tigecycline to acceptor site patients with lesions have completely healed
ribosome-mRNA leptospirosis, syphilis,
complex actinomycosis, Lymphogranuloma venereum:
tularemia, meliodosis Doxycycline 100 mg PO BID x 21 days
and skin and soft tissue
infections

XIII. TRIMETHOPRIM/SULFONAMIDES
EXAMPLES MECHANISM OF ORGANISMS COMMON DOSAGES
ACTION COVERED
Cotrimoxazole: Excellent activity against Pneumocystitis jiroveci Pneumonia
Trimethoprim- S. typhi, some strains of For prophylaxis:
Sulfamethoxazole Folic acid Shigella, V. cholera, H. TMP-SMX 160/800 mg 3x weekly, or
(TMP-SMX) synthesis influenza TMP-SMX 80/400 mg PO OD
inhibitors
Cotrimazine: Use in Pneumocystitis For treatment:
Trimethoprim- jiroveci infection TMP-SMX 15-20 mg TMP/kg/day PO or IV q6-q8
Sulfadiazine

FEVER OF UNKNOWN ORIGIN (FUO)


Any febrile illness without an initially obvious etiology
The term FUO should be reserved for prolonged febrile illness without an established etiology, despite intensive
evaluation & diagnostic testing
TYPE DEFINITION
Fever of Unknown Origin Temperature > 38.3oC on several occasions
(Petersdorf & Beeson Definition 1961) Duration of fever > 3 weeks on two occasions
Uncertain diagnosis despite 1 week of inpatient investigation
Fever > 38.3oC on at least two occasions
Illness duration of > 3 weeks
No known immunocompromised state
Diagnosis uncertain after a thorough history-taking, physical
exam and the following obligatory investigations:
o ESR, CRP
Recent Definition of FUO o Platelet count, leukocyte count and differential,
hemoglobin
o Electrolytes, creatinine, total protein
o Alkaline phosphatase, ALT, AST
o LDH, creatinine kinase
o Ferritin
o ANA and RF
o Protein electrophoresis
151
o Urinalysis
o Blood culture (x3), urine culture
o Imagine (CXR and abdominal ultrasound)
o Tuberculin skin test

FEVER AND RASH


Infectious diseases associated with a rash
DISEASE ETIOLOGY DESCRIPTION
Begins as erythematous macules behind the ears, neck and
Rubeola: hairline then progresses to face, trunk and extremities
Measles Paramyxovirus Koplik’s spots: pathognomonic for measles; bluish white
(1st disease) dots surrounded by erythema; appears first on the buccal
mucosa opposite the lower molars
Scarlet fever Group A Streptococcus Rash is made up of minute papules giving the “sandpaper”
(2nd disease) (pyrogenic exotoxin A, B, C) feel of the skin
Pastia’s lines: accentuation of the rash in skin folds
Rubella: Spreads from hairline downward, with clearing as it spreads
German Measles Togavirus Forschheimer spots: petechiae on the soft palate, present
(3rd disease) in 20% of patients
Erythema Erythematous macular rash that spreads to the extremities
infectiosum (5th Human parvovirus B19 in a lacy reticular pattern “Slapped-cheeks” disease;
disease) “Glove-and-socks” syndrome
Exanthema subitum: Diffuse maculopapular rash over trunk and neck
Roseola Human herpesvirus 6
(6th disease)
Infectious 5% of patients develop morbilliform or popular rash usually
Mononucleosis Epstein-Barr virus on the arms and trunk
Most patients given ampicillin may develop a macular rash
Macular rash usually presents on the fifth day, begins on
Epidemic Typhus Rickettsia prowazekii the upper trunk and becomes generalized sparing the face,
palms and soles
Endemic (Murine) Initial macular rash usually detected in the axilla or inner
Typhus Rickettsia typhi arm
Most patients given ampicillin may develop a macular rash
Scrub Typhus Orientia tsutsugamushi Maculopapular rash and presence of the characteristic
eschar (site where the chigger has fed)
Leptospirosis Leptospira interrogans Rash may be macular, maculopapular, erythematous,
petechial or ecchymotic
Lyme Disease Borrelia burgdorferi Presence of erythema migrans (central clearing, red outer
border and a target center) at the site of tick bite
Typhoid Fever Salmonella typhi Rose spots: faint, salmon-colored, blanching
maculopapular rash usually seen on the trunk and chest
Dengue virus (4 serotypes; Maculopapular rash beginning on the trunk and spreads to
Dengue Fever flavivirus) the extremities and face which usually presents near the
time of defervescence
Petechiae on the trunk, extremities and mucous
Relapsing Fever Borrelia species membranes seen in 18% of patients at the end of febrile
episode
African Trypanosoma rhodesiense Blotchy or erythematous maculopapular rash on the trunk
Trypanosomiasis (East Africa)/ gambiense Presence of a painful trypanosomal chancre in some
(West Africa) patients at the site of inoculation
Initially pale red or pink macules on the trunk and proximal
Secondary Syphilis Treponema pallidum extremities which progresses to popular lesions usually on
the palms and soles
Condyloma lata: papules that enlarged to form broad,

152
moist, pink or gray-white highly infectious lesions usually in
warm, intertriginous areas
Chikungunya Fever Chikungunya virus Maculopapular rash on upper extremities and face,
appearing at the time of defervescence
Hand-Foot-and- Coxsackie virus A16 Painful vesicles in the mouth; papules on hands and feet
Mouth Disease (most common cause)
Group A streptococcus
Streptococcal Toxic (associated with pyrogenic Scarlatiniform rash
Shock Syndrome exotoxin A and/or B or
certain M types)
Staphylococcal Toxic S. aureus (toxic shock Erythroderma of variable intensity
Shock Syndrome syndrome toxin 1, Desquamation of the skin occurs during convalescence
enterotoxin B or C)
Staphylococcal Localized blister formation and exfoliation of the skin
Scalded-Skin S. aureus, phagr group II Nikolsky’s sign: rupture of the lesions with gentle pressure
Syndrome
Varicella: Varicella-zoster virus Macules evolving into papules then vesicles on an
Chickenpox erythematous base (the classic “dew on a rose petal”)
Pseudomonas “hot- Pseudomonas aeruginosa Pruritic erythematous follicular, popular, vesicular or
tub” folliculitis pustular lesions
Primary Herpes Hallmark: painful grouped vesicles that may progress to
Simplex Virus (HSV) HSV pustules and ulcerate
infection
Initially pink maculopapular lesions and later evolves into
nonblanching petechial rash usually in the trunk and
Acute extremities
Meningococcemia Neisseria meningitides May have purpura fulminans (large ecchymoses with
sharply irregular shapes evolving into hemorrhagic bullae
and then into black necrotic lesions; reflects disseminated
intravascular coagulation)
Chronic Neisseria meningitides May have pink maculopapular, nodular, petechial and
Meningococcemia purpuric lesions with pale blue-gray centers; recurrent
Tularemia Francisella tularensis Ulceroglandular form: erythematous, tender papule
evolves into necrotic, tender ulcer with raised borders
Anthrax Bacillus anthracis Typically begins as a papule which evolves to a painless
vesicle then later on to a coal-black, necrotic eschar

153
SECTION 2
COMMON INFECTIOUS DISEASES CONDITIONS
DENGUE

I. ETIOPATHOGENESIS
Acute febrile illness of 2-7 days duration (sometimes biphasic), with no identifiable focus of infection
Four (types 1 to 4) distinct viruses (type 2 is more dangerous)
Principal vector: Aedes aegypti, which breeds near human habitation
Macrophage/monocyte infection is central to the pathogenesis
Second infection with a serotype different from that involved in the primary infection leads to dengue hemorrhagic
fever (HF) with severe shock
Incubation period: 2-7 days

II. CLINICAL MANIFESTATIONS


Classic symptoms: sudden onset of fever, headache, retro-orbital pain, and back pain along with severe myalgia
“break-bone fever”
Initial symptoms: macular rash, adenopathy, palatal vesicles and scleral injection
Other signs and symptoms: anorexia, nausea, vomiting, cutaneous hypersensitivity, maculopapular rash
beginning on the truck and spreading to extremities and face
Epistaxis and scattered peterchiae are often noted in uncomplicated dengue and preexisting gastrointestinal
lesions may bleed during the acute illness

III. DIAGNOSIS

A. Common Diagnostic Tests


DIAGNOSTICS COMMENTS/EXPECTED FINDINGS
Complete blood count Leukopenia, thrombocytopenia, elevated hematocrit
Dengue IgM and IgG (ELISA) IgM antibody: usually detected by day five of illness
IgG antibody: detects past dengue infection
Immunoassay for the detection of non-structural protein 1 (NS1) antigens
NS1 Antigen (Rapid) Test Aids in screening and diagnosis as early as 1 day post-onset of symptoms
(prior to the detection of IgM or IgG antibodies)
BP cuff is inflated midway between systolic and diastolic pressures for 5
Tourniquet test minutes
Considered positive if >20 petechiae per square inch, 1.5 inches from the
volar aspect of the antecubital fossa

B. WHO Classification of Dengue


DENGUE + WARNING SIGNS SEVERE DENGUE
DENGUE FEVER WARNING SIGNS
Probable Dengue Abdominal pain or Severe Plasma Leakage
Lives in/travels to dengue endemic area tenderness Leads to shock and fluid
Fever and any 2 of the following: Persistent vomiting accumulation with respiratory
Nausea, vomiting Clinical fluid collection distress
Rash Mucosal bleed
Aches and pains Lethargy, restlessness Severe Bleeding
Positive Tourniquet test Liver enlargement >2 cm As evaluated by physician
Leukopenia Increase in Hct concurrent
Any warning signs with rapid decrease in Severe Organ Involvement
platelet count Liver: AST or ALT > 1000
Laboratory-Confirmed Dengue CNS: impaired consciousness
Important when there are no signs *requiring strict observation and Heart and other organs
of plasma leakage medical intervention

154
IV. MANAGEMENT
GROUP A GROUP B GROUP C
DENGUE FEVER WITHOUT DENGUE FEVER WITH WARNING SEVERE DENGUE
WARNING SIGNS SIGNS
Patients with co-existing conditions*
May be sent home and have social circumstances** Require emergency treatment
Referred for in-patient management
Advise: Hydration: Initial resuscitation: isotonic crystalloid
Adequate bed rest Encourage OFI if tolerated. If not, solutions at 5-10 ml/kg/hr over 1 hour
Adequate fluid intake start IVF If patient improves: IVE may be
Paracetamol PRN (4g max per Start with 5-7 ml/kg/hr for 1-2 hrs reduced to 5-7 ml/kg/hr for 1-2
day) Reduce to 3-5 ml/kg/hr for 2-4 hours, 3-5 ml/kg/hr for 2-4 hrs and
hrs then reduced further depending
Patients with stable hematocrit can be Reduce to 2-3 ml/kg/hr or less on hemodynamic status; IVF can
sent home; advise return to hospital if according to clinical response be maintained over 24 to 48 hrs
with development of warning signs o If Hct remains the same or If unstable: recheck Hct after 1st IV
rises minimally, continue with bolus
Daily review for disease progression: 2-3 ml/kg/hr for another 2-4 o If Hct increases/still high
decreasing WBC, defervescence, hrs (>50%), repeat a second
warning signs until out of critical period o If with worsening of vitals and bolus of crystalloid solution or
rapidly rising Hct, increase 10-20 ml/kg/hr for 1 hour (if
rate to 5-10 ml/kg/hr for 1-2hrs there is improvement, reduce
Reduce IVF until adequate UO rate to 7-10 ml/kg/hr and
and/or fluid intake or Hct continue to reduce as above)
decreases below baseline value o If Hct decreases, this
indicates bleeding and need
Monitoring to cross-match & transfuse
VS q1-4 hrs until out of critical
phase Treatment of hypotensive shock:
Hct at baseline and q6-12 hrs initiate resuscitation with crystalloid or
Blood glucose and other organ colloid solution at 20 ml/kg as bolus for
function tests 15 mins
If patient improves, give IVF at 10
ml/kg/hr for 1 hr then reduce
gradually
If still unstable: review Hct, assess
need for further fluid resuscitation
(if persistently high) or need for
bllod transfusion

Treatment of hemorrhagic
complications:
Give 5-10 ml/kg of pRBC or 10-20
ml/kg fresh whole blood
*such as pregnancy, infancy and old age, obesity, diabetes, renal failure, chronic hemolytic disease, etc.
**such as living alone, or living far from health facilities

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MALARIA
I. ETIOPATHOGENESIS

A. Pathogenesis
Most important parasitic disease in humans
In humans, the erythrocytic cycle is responsible for disease
o Rupture of schizonts and release of merozoites present clinically as paroxysms of malaria
o Hypnozoites are responsible for disease relapses

B. Etiology
Protozoan disease caused by 4 species of Plasmodium (falciparum, vivax, ovale and malariae) and transmitted
by the bite of infected Anopheles mosquitoes (Anopheles flavirostris in the Philippines)
Plasmodium falciparum causes nearly all deaths and neurological complications

II. CLINICAL MANIFESTATIONS

A. Classic Malaria Paroxysm: cold stage (chills), hot stage (fever spikes), sweating stage
Tertian Periodicity Cyclic fever occurring Plasmodium falciparum (malignant tertian)
every 48 hours Plasmodium vivac, ovale (benign tertian)
Quartan Periodicity Cyclic fever occurring Plasmodium malariae
every 72 hours

B. Symptoms Ranging from Mild Constitutional Symptoms to Organ Failure


MILD / NON-LIFE THREATENING MALARIA SEVERE FALCIPARUM MALARIA
Unarousable coma / cerebral malaria
Academia / acidosis
Nonspecific constitutional symptoms Severe normochromic, normocytic anemia
Headache without neck stiffness or photophobia Renal failure
Nausea and vomiting Pulmonary edema / ARDS
Classic malaria symptoms Hypoglycemia
Anemia Hypotension / shock
Hepatosplenomegaly Bleeding / disseminated intravascular coagulation
Mild jaundice (DIC)
Convulsions
Others: hemoglobinuria, extreme weakness,
hyperparasitemia, jaundice

III. DIAGNOSIS OF MALARIA


DIAGNOSTICS COMMENTS/EXPECTED FINDINGS
Thick and thin smear: gold standard for laboratory confirmation of Malaria
Microscopic Acute demonstration of the parasite in the smear
Examination o Thick smear: for quantification of parasitemia
o Thin smear: for species identification
Complete blood count Normocytic normochromic anemia, thrombocytopenia
(CBC)
Blood chemistry Decreased plasma glucose, ↓Na, ↓HCO3, ↓Ca2+, ↓phosphate, ↓albumin, ↑lactate,
↑BUN, ↑creatinine, ↑urate, ↑muscle & liver enzymes, ↑bilirubin (DB & IB)
ABG Metabolic acidosis (usually high anion gap)
PT/PTT Prolonged in severe cases
Lumbar tap (for Mean opening pressure ~180 mmHg of CSF
cerebral malaria) Normal or slightly ↑total protein and cell count

IV. MANAGEMENT OF MALARIA

A. Malaria is treated with Combination Drugs (due to widespread chloroquine resistance)


DRUG REGIMEN CLINICAL USE SIDE EFFECTS
Chloroquine + Sulfadoxine First line of treatment in Pyrimethamine: megaloblastic
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Pyrimethamine (CQ + SP) probable and confirmed anemia, pancytopenia,
falciparum malaria that is not pulmonary infiltration
severe
Second line drug for cases
which did not respond to Artemether: anaphylaxis,
Artemether-Lumefantrine adequate CQ + SP therapy utricaria, fever
Not recommended for Lumefantrine: none identified
pregnant women and children
<8y/o
Quinine + Tetracycline/ Third line of drug for those
Doxycycline who did not respond to Co- Quinine: cinchonism, tinnitus,
(Quinine + Clindamycin for ArtemTM high-tone hearing loss,
pregnant women and children Drug of choice for severe hypoglycemia, very bitter taste
<8y/o) malaria
Given as single dose to
confirmed P. falciparum cases
to prevent transmission
Primaquine Given for 14 days to confirmed Massive hemolysis in G6PD
P. vivax to prevent relapse deficiency
The only drug which can
eradicate extrahepatic stages
of the parasite
Chloroquine Drug of choice for P. vivax Nausea, dysphoria, pruritus,
cases retinopathy (>100 g)

B. Drugs used for severe Falciparum malaria


Artesunate
Artemether
Quinine dyhydrochloride
Quinidine

C. Drugs for prophylaxis


Doxycycline, primaquine, atovaquone/proguanil, chloroquine
Mefloquine (only prophylaxis permitted in pregnancy)

TYPHOID FEVER (ENTERIC FEVER)


I. ETIOPATHOGENESIS
A potentially fatal multisystemic illness caused by gram-negative Salmonella typhi and Salmonella paratyphi
Hallmark: invasion and multiplication within the mononuclear phagocytic cells in the liver, spleen, lymph nodes
and Peyer’s patches of the ileum
Transmission: orally by contaminated food or water (humans are the only known hosts)
Incubation: varies with amount of infecting dose but averages 10-20 days (range of 3 to 55 days)

II. CLINICAL MANIFESTATIONS


NON-SPECIFIC SYMPTOMS PHYSICAL FINDINGS FINDINGS NECESSITATING HOSPITAL
ADMISSION
Chills Persistent high fever Persistent vomiting / unable to take
Diaphoresis Relative bradycardia fluids
Anorexia Rose spots (rash at Severe dehydration
Myalgia trunk area) Spontaneous bleeding
Cough Abdominal tenderness Persistent abdominal pain
Weakness/malaise Hepatomegaly Listlessness
Sore throat Splenomegaly Changes in mental status
Dizziness Typhoid psychosis/ Weak, rapid pulse
Constipation/diarrhea encephalitis Cold, clammy skin
Abdominal pain Epistaxis Circumoral cyanosis
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Abdominal distention Seizures
Hypotension or narrow pulse pressure
*complications include intestinal perforation leading to GI hemorrhage and peritonitis (3rd to 4th week of illness), pancreatitis, hepatic and splenic
abscess, DIC, myocarditis, meningitis and encephalitis

III. DIAGNOSIS OF TYPHOID FEVER


DIAGNOSTICS COMMENTS/EXPECTED FINDINGS
CBC Neutropenia / leukopenia / leukocytosis / thrombocytopenia
Normochromic anemia; hypochromia with blood loss
Blood culture Gold standard: should be taken from at least 2 different sites
Can be taken anytime during the illness but yield is highest during the first 2 weeks
Stool culture May be positive during the 3rd week of illness in untreated patients
Not usually done, but indicated in highly suspicious cases or of negative blood/stool culture
Bone marrow culture Can be done anytime during the illness
Yield is high (~90%): yield not reduced by up to 5 days of prior antibiotic therapy
Serology Several serologic tests, though available, are not sufficiently sensitive or specific to replace
culture-based methods for diagnosis of enteric fever

IV. MANAGEMENT OF TYPHOID FEVER


INDICATION AGENTS DOSAGE & ROUTE DURATION (DAYS)
Empirical Ceftriaxone 2 g/d IV 10-14
Treatment Azithromycin 1 g/d PO 5
Ciprofloxacin (first line) 500 mg BID PO or 400 mg q12h IV 5-7
Azithromycin 1 g/d PO 5
Fully Susceptible Amoxicillin 1 g TID PO or 2 g q6h IV 14
Chloramphenicol 25 mg/kg TID PO or IV 14-21
TMP-SMX 160/800 mg BID PO 7-14
Multidrug- Ceftriaxone 2 g/d IV 10-14
resistant Azithromycin 1 g/d PO 5
Quinolone- Ceftriaxone 2 g/d IV 10-14
resistant Azithromycin 1 g/d PO 5

LEPTOSPIROSIS

I. ETIOPATHOGENESIS

A. Etiology
Caused by the pathogenic spirochete Leptospira interrogans (zoonosis with a worldwide distribution)
Rodents (especially rats): most important reservoir (others are wild mammals, dogs, fish and birds)
Incubation period: 2-28 days

B. Transmission
Direct contact with urine, blood or tissue of an infected animal
Exposure to a contaminated environment
Human-to-human transmission is rare
Leptospires may persist in water for many months

II. CLINICAL MANIFESTATIONS


SUSPECTED LEPTOSPIROSIS MILD OR ANICTERIC MODERATE-SEVERE LEPTOSPIROSIS
LEPTOSPIROSIS OR WEIL’S SYNDROME
Individual presenting with acute Any suspected case of leptospirosis Any suspected case of leptospirosis
febrile illness of at least 2 days, and presenting with acute febrile illness presenting with acute febrile illness with:
and various manifestations but Unstable vital signs
Residing in a flooded area or has with: Jaundice
high-risk exposure (wading in floods Stable vital signs Abdominal pain, nausea, vomiting,
and contaminated water, contact Aniceteric sclerae diarrhea
with animal fluids, swimming in Good urine output Oliguria/anuria
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flood water or ingestion of No evidence of Meningismus/mengineal irritation
contaminated water, with or without meningismus/meningeal Sepsis/septic shock or altered
cuts or wounds), and irritation, sepsis/septic sensorium
shock, difficulty of breathing Difficulty of breathing or hemoptysis
At least 2 of the following: or jaundice
Myalgia The following findings should alert the
Calf tenderness May have other nonspecific findings clinician to possible severe leptospirosis:
Conjunctival suffusion such as nausea/vomiting, diarrhea, WBC >12,000 with neutrophilia and
Chills non-productive cough and thrombocytopenia
Abdominal pain maculopapular rash Serum creatinine >3 mg/dL (or CrCl
Headache <20 ml/min) and BUN >23 mg/dL
Jaundice AST/ALT ratio >4x, Bilirubin >190
Oliguria umol/L
Prolonged PT <85%
Serum K+ >4 mmol/L
ABG: severe metabolic acidosis (pH
<7.2, HCO3 <10) and hypoxemia
(PaO2 <60 mmHg, SaO2 <90%, PF
ratio <250)
CXR: extensive alveolar infiltrates
ECG: heart block, repolarization
abnormalities

III. DIAGNOSIS OF LEPTOSPIROSIS

DIAGNOSTICS COMMENTS/EXPECTED FINDINGS


Microscopic Dark-field microscope or immunofluorescence or light microscopy after appropriate staining
Demonstration Only of value during the 1st 7-10 days of acute illness during leptospiremia
(Direct Detection) Insensitive and lacks specificity
Culture and Isolation Gold standard
(Direct Detection) Time-consuming, labor –intensive, requires 6-8 weeks for the result
Low diagnostic yield
Polymerase Chain Early confirmation of diagnosis especially during the acute leptospiremic phase before the
Reaction or PCR appearance of antibodies
(Direct Detection) Limited clinical use due to cost
Fourfold rise in titer from acute to convalescent sera is confirmatory
Microagglutination In endemic areas (like the Philippines), a single titer of at least 1:1600 in symptomatic
Test or MAT patients is indicative of leptospirosis
(Indirect Detection) Highly sensitive and specific but time-consuming and hazardous to perform
Cross-reacts with syphilis, viral hepatitis, HIV, relapsing fever, Lyme disease, legionellosis
and autoimmune disease
Specific IgM Rapid Quick detection of Leptospira genus-specific IgM antibodies in human sera
Diagnostics Sensitivity of 63-72% and specificity of 93-96% if tested in illness <7 days; if taken >7 days,
(Indirect Detection) sensitivity improves to >90%
Non-specific Rapid Detects leptospira antibody in human serum through agglutination reaction which may
Diagnostics persist for years
(Indirect Detection) A positive result should be confirmed with MAT
CBC Peripheral leukocytosis, neutrophilia, thrombocytopenia
Urinalysis Proteinuria, pyuria and often hematuria
Hyaline and granular casts may also be present during the first week of illness
Serum Creatinine Can be initially normal but can be elevated during the course (sign of acute kidney injury)
Serum Creatinine Elevated in patients with severe myalgia
Phosphokinase
Liver Function Tests Bilirubins, ALT, AST and alkaline phosphatase may show slight elevation

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IV. MANAGEMENT OF LEPTOSPIROSIS
Jarisch-Herxheimer reaction: dramatic, mild reaction consisting of fever, chills, myalgia, headache, tachycardia,
tachypnea, neutrophilia and vasodilation with mild hypotension after initiation of antibiotic therapy

A. Treatment of Leptospirosis
INDICATION DRUGS DOSE
Doxycycline (first line) 100 mg BID PO
Mild Cases Amoxicillin (alternative) 500 mg q6h or 1 g q8h PO
Azithromycin (alternative) 1 g initially, followed by 500 ng OD PO for 2 more days
Penicillin G (first line) 1.5 MU q6-8h IV for 7 days
Ampicillin (alternative) 0.5 to 1 g q6h IV for 7 days
Severe Cases Cefotaxime (alternative) 1 g q6h IV for 7 days
Ceftriaxone (alternative) 1 g q24h IV for 7 days
Azithromycin (alternative) 500 mg OD PO for 3-5 days
Renal replacement therapy for patients in uremia, increasing creatinine or K + levels,
Acute Kidney Injury fluid overload, pulmonary hemorrhage or ARDS, metabolic acidosis, intractable
oliguria
Patients should be admitted to the ICU for close monitoring and/or invasive
ventilation
Pulmonary Hemorrhage/ Bolus methylprednisolone within the first 12 hours of onset of respiratory involvement
ARDS may be considered
o Methylprednisolone 1 g IV/day for 3 days, then
o Oral prednisolone 1 mg/kg/day for 7 days

B. Chemoprophylaxis
Most effective measure is avoidance of high-risk exposure and use of appropriate protective equipment
Currently, there is no recommended pre-exposure prophylaxis that is safe for pregnant/lactating women

SINGLE EXPOSURE CONTINUOUS EXPOSURE


Low Risk: Moderate Risk: High Risk:
(-) wounds/cuts/skin lesions (+) wounds/cuts/skin lesions (+/-) wounds/cuts/skin lesions
Doxycycline 100 mg 2 caps single Doxycycline 100 mg 2 caps OD for 3- Doxycycline 100 mg 2 caps once
dose within 24-72 hours of exposure 5 days started immediately within 24- weekly until the end of exposure
72 hours of exposure

SCHISTOSOMIASIS
I. ETIOPATHOGENESIS
Parasitic disease endemic in 24 provinces In the Philippines; highest prevalence in children 5-15 years of age
Schistosoma japonicum: major species involved in the Philippines
Oncomelania hupensis quadrasi: snail vector
Transmission: requires skin penetration of the cercaria
Main pathology & manifestations caused by granulomatous reaction to eggs deposited in liver & other organs

II. CLINICAL MANIFESTATIONS


ACUTE SCHISTOSOMIASIS CHRONIC SCHISTOSOMIASIS
Cercarial dermatitis / swimmer’s itch Liver cirrhosis
Katayama fever (serum sickness-like syndrome with fever, Portal hypertension
generalized lymphadenopathy and hepatosplenomegaly) Ascites

III. DIAGNOSIS
DIAGNOSTICS COMMENTS/EXPECTED FINDINGS
Liver Ultrasound Clay pipestem fibrosis with lacelike pattern
CBC High level peripheral eosinophilia in Katayama fever
Fecalysis (Kato Katz Method) Demonstration of parasite eggs
Rectal Imprint Biopsy of rectal tissue with the aid of proctoscopy
Circumoval Precipitin Test (COPT) Detects circulating schistosome antigens
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IV. MANAGEMENT
SPECIES MANAGEMENT
S. mansoni
S. haematobium Praziquantel 40 mg/kg/day PO in 2 divided doses in 1 day
S. intercalatum
S. japonicum Praziquantel 60 mg/kg/day PO in 3 divided doses in 1 day
S. mekongki

TETANUS
I. ETIOPATHOGENESIS
Acute disease manifested by hypertonia or muscle spasms with or without autonomic nervous disturbance
Caused by a powerful neurotoxin (tetanospasm) produced by Clostridium tetani, a gram-positive spore-forming
anaerobic rod which can enter the skin through abrasions, wounds or in neonates, the umbilical stump

II. CLINICAL MANIFESTATIONS


Wound infection, multiplication of C. tetani No symptoms
↓ in 7 to 10 days
Tetanus toxin uptake into nervous system and VAMP Initial symptoms: muscle aches, trismus and myalgia
cleavage in GABA inhibitory neurons
↓ after 24 to 72 hours
Muscle spasm: local and generalized
Further toxin effects causing widespread disinhibition of Cardiovascular instability: labile BP, tachycardia or
motor and autonomic nervous system bradycardia
Pyrexia: increased respiratory and GI secretions
↓ after 4 to 6 weeks
Toxin degradation Cessation of spasms, restoration of normal muscle tone
Cardiovascular and autonomic control
III. DIAGNOSIS AND CLASSIFICATION OF TETANUS

A. RITM Classification
STAGE I STAGE II STAGE III
Incubation Period >14 days 10-14 days <10 days
Period of Onset >6 days 3-6 days <3 days
Trismus Mild Moderate Severe
Dysphagia Absent Present Present
Muscular stiffness Mild / localized Pronounced Severe/board-like
Paroxysmal spasm Absent Mild and short Frequent, violent, prolonged & with
asphyxia
Dyspnea of cyanosis Absent Absent Present
Unstable BP
Sympathetic overactivity Absent Absent or mild ↑↓Paroxysmal
tachycardia/arrhythmias
Profuse sweating, hyperpyrexia

B. Classification Based on Extent of Involvement


1. Localized Cephalic Tetanus
o Only isolated areas of the body are involved and only localized muscle spasms occur
o Prognosis is poor if cranial nerves are involved, leading to respiratory/pharyngeal muscle spasm with
consequent aspiration or airway obstruction

2. Generalized Tetanus
o Typical presentation involved face and jaw muscles first followed by generalized muscle spasm

IV. MANAGEMENT

A. Non-Pharmacologic Management

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Entry wound should be identified, cleaned and debrided of necrotic material to remove any remaining source of
anaerobic foci and prevent further toxin production
Secure airway early in severe cases; if necessary, mechanical ventilation should be instituted
Patients should ideally be nursed in calm, quiet, dark environments with close cardiovascular monitoring

B. Pharmacologic Management
Appropriate antibiotics Metronidazole 500 mg IV q6h for 7 days (preferred antibiotic)
Penicillin 100,000 – 200,000 IU/kg per day (alternative)
Tetanus Toxoid For cases of suspected tetanus
(e.g. Td vaccine) Can be given with or without tetanus immunoglobulin
Tetanus immunoglobulin (TIG) Human tetanus Ig (TIG) 3,000-6,000 IU, or
or Tetanus Antitoxin Equine antitoxin 10,000 – 20,000 U as single IM dose
Control of Spasms Sedatives (e.g., benzodiazepines) and muscle relaxants

C. Recommendations for Post-Exposure Tetanus Prophylaxis


VACCINATION HISTORY Clean, Minor Wounds All Other Wounds*
Td TIG Td TIG
Unknown number or < 3 doses received Yes No Yes Yes
For those with > 3 doses received:
> 10 years since most recent dose Yes No Yes No
5-9 years since most recent dose No No Yes No
<5 years since most recent dose No No No No
*wounds >1 cm, in depth, incurred >6 hrs earlier, or with stellate or avulsion configuration; crush injuries or burn injuries; devitalized tissue; and
wounds contaminated with dirt, feces or saliva

D. Prognosis: Factors Associated with a Worse Outcome in Adult Tetanus:


Age > 70 years
Incubation period < 7 days
Short time from first symptom to admission
Puerperal, IV, post-surgery and burn entry site
Period of onset < 48 hours
HR >140 bpm
SBP >14 mmHg
Severe disease or spasms
Temperature >38.5oC

RABIES
I. ETIOPATHOGENESIS
Rapidly progressive, acute infectious disease of the CNS, caused by the rabies virus (family Rhabdoviridae)
Incubation: 20-90 days
Transmission: via bite of an infected animal
Prognosis: recovery is rare

II. CLINICAL MANIFESTATIONS


Combativeness, seizures, autonomic dysfunction (hypersalivation, gooseflesh,
Encephalithic (Furious) cardiac arrhythmia, priapism)
Rabies (80% Hydrophobia: involuntary, painful contraction of the diaphragm and accessory
respiratory/laryngeal/pharyngeal muscles in response to swallowing liquids
Aerophobia: same features cause by stimulation from a draft of air
Paralytic Rabies (20%) Early and prominent flaccid muscles weakness predominates

III. CATEGORIZATION OF EXPOSURE AND RESPECTIVE MANAGEMENT (WHO CLASSIFICATION)


EXPOSURE MANAGEMENT
Feeding/touching an animal Wash exposed skin immediately with soap and
Licking of intact skin water

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I Exposure to patient with signs of rabies by sharing No vaccine or RIG needed
or eating or drinking utensils Pre-exposure vaccination may be considered
Casual contact with patient with signs of rabies
Start vaccine immediately
o Complete regimen until day 28/30 if:
Animal is rabid, killed, died or unavailable for
Nibbling/nipping of uncovered skin with bruising 14 day observation and examination; or
Minor scratches / abrasions / abrasions without Animal under observation died within 14 days
II bleeding (includes wounds that are induced to and was IFAT positive or no IFAT testing was
bleed) done or has signs of rabies
Licks on broken skin o Complete vaccine regimen until:
Animal is alive and remains healthy after 14-
day observation period
Animal under observation died within 14 days
but had no signs of rabies and was IFAT
negative
Transdermal bites or scratches (includes puncture Start vaccine and RIG immediately:
wounds, lacerations and abrasions) o Complete regimen until day 28/30 if:
Contamination of mucous membranes with saliva Animal is rabid, killed, died or unavailable for
(e.g., licks) 14 day observation and examination; or
Exposure to rabies patient through bites, Animal under observation died within 14 days
III contamination of mucous membranes or open skin and was IFAT positive or no IFAT testing was
lesions with body fluids (except blood/ feces) done or had signs of rabies
through splattering, mouth-to-mouth resuscitation, o Complete vaccine regimen until day 7 if:
licks of eyes, lips, vulva, sexual activity, exchanging Animal is alive & remains healthy after 14 day
kisses on the mouth or other direct mucous observation period
membrane contact with saliva Animal under observation died within 14 days
Handling of infected carcass or ingestion of raw but had no signs of rabies and was IFAT
infected meat negative

INFECTIVE ENDOCARDITIS (IE)


I. ETIOPATHOGENESIS
Prototypic lesion: vegetation
The analogous process involving AV shunts, PDAs or coarctation of the aorta is called infective endarteritis
Endothelial injury may also lead to development of an uninfected platelet-fibrin thrombus called non-bacterial
thrombotic endocarditis (NBTE) or as a result of a hypercoagulable state called marantic endocarditis

II. DIAGNOSIS: THE MODIFIED DUKE’S CRITERIA

A. Criteria for Diagnosis


Two major criteria; or
Definite Endocarditis One major criteria and three minor criteria; or
Five minor criteria
Possible Endocarditis One major + one minor, or
Three minor criteria
Alternative diagnosis is established
Diagnosis of IE is Rejected Symptoms resolved & do not recur with < 4 days of antibiotic therapy
Surgery or autopsy after < 4 days of antimicrobial therapy yields no
histologic evidence of endocarditis

B. Major and Minor Criteria (from the Modified Duke’s Criteria)


Blood cultures: three 2-bottle sets separated from one another by at least 1 hour and obtained from different sites
over 24 hours
If cultures remain negative after 48-72 hours, 2 to 3 additional blood culture sets should be obtained
Predisposing heart conditions include: valvular disease with stenosis or regurgitation, prosthetic valves,
congenital heart defects, prior endocarditis, hypertrophic cardiomyopathy
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MAJOR CRITERIA MINOR CRITERIA
1) Positive blood culture: Predisposing heart condition or
Typical organisms for IE from >2 cultures: injection drug use
o S. viridans
o HACEK Fever > 38.0oC
o S. gallolyticus (previously S. bovis)
o S. aureus Vascular phenomena: major arterial
o Enterococcus emboli, septic pulmonary infarcts, mycotic
OR, Persistently positive, defined as recovery of a aneurysms, intracranial hemorrhage,
microorganism consistent with IE from: conjunctival hemorrhages, Janeway
o Blood cultures drawn >12 hours apart, or lesions
o All of 3 or a majority of >4 separate cultures
with first and last drawn at least 1 hour apart Immunologic phenomena:
OR, Single positive blood culture for Coxiella burnetii or glomerulonephritis, Osler’s nodes, Roth’s
phase I IgG antibody titer of >1:800 spots, rheumatoid factor
2) Evidence of endocardial involvement:
Positive echocardiogram: Microbiologic evidence: positive blood
o Oscillating intracardiac mass culture but not meeting major criterion or
o Abscess serologic evidence of active infection with
o New dehiscence of prosthetic valve organism consistent of IE
Or, New valvular regurgitation
*HACEK: Haemophilius sp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella sp.

III. CLINICAL MANIFESTATIONS

A. Acute Versus Subacute Endocarditis


ACUTE BACTERIAL IE SUBACUTE BACTERIAL IE
Streptococcus viridans
Usual S. aureus Enterococci
Etiology B-Hemolytic Streptococci Coagulase-negative staphylococcus (prosthetic
Pneumococci valve)
HACEK
Fever High grade fever (39.4-40oC) Low grade fever (rarely >39.4oC)
Course Rapid Indolent
Acute / decompensated heart failure common Rarely metastasizes
Hematogenously seeds extracardiac sites
Prognosis Poor (if untreated) Better prognosis

B. Non-Cardiac Manifestations
MANIFESTATION DESCRIPTION
Janeway lesions Nontender, slightly raised hemorrhages on the palms and soles (seen in endocarditis)
Osler’s nodes Tender, raised nodules on the pads of the fingers or toes (seen in endocarditis)
Splinter Small blood clots that run vertically under the nails
hemorrhages
Glomerulonephritis Caused by immune complex deposition at the glomerular basement membrane
Minor emboli: splinter hemorrhages, Janeway lesions, conjunctival hemorrhages
Embolic events Major emboli: arterial emboli, intracranial hemorrhage, pulmonary infarct, mycotic
aneurysm
Mycotic aneurysms Focal dilations in the artery wall that have been weakened by infection or septic emboli

IV. MANAGEMENT
ORGANISM RECOMMENDED REGIMEN
Penicillin G (2-3 mU IV q4h) for 4 weeks
Ceftriaxone (2 g/d IV OD) for 4 weeks
Streptococci Vancomycin (15 mg/kg IV q12h) for 4 weeks
(Penicillin-sensitive) Penicillin G (2-3 mU IV q4h) OR Ceftriaxone (2 g IV OD) for 2 weeks PLUS
Gentamicin (3 mg/kg IV or IM OD) as a single dose or divided into equal doses q8h for 2
weeks

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Penicillin G (4-5 mU IV q4h) OR Ceftriaxone (2 g IV OD) for 6 weeks PLUS
Streptococci Gentamicin (3 mg/kg IV or IM OD) as a single dose or divided into equal doses q8h for 2
(Penicillin-resistant) weeks
Vancomycin (15 mg/kg IV q12h) for 4 weeks
Penicillin G (4-5 mU IV q4h) PLUS Gentamicin (1 mg/kg IV q8h) both for 4-6 weeks
Enterococci Ampicillin (2 g IV q4h) PLUS Gentamicin (1 mg/kg IV q8h) both for 4-6 weeks
Vancomycin (15 mg/kg IV q12h) PLUS Gentamicin (1 mg/kg IV q8h) both for 4-6 weeks
Staphylococci Nafcillin OR Oxacillin (2 g IV q4h) for 4-6 weeks
(Methicillin-sensitive) Cefazolin (2 g IV q8h) for 4-6 weeks
Vancomycin (15 mg/kg IV q12h) for 4-6 weeks
Staphylococci Vancomycin (15 mg/kg IV q8-12h) for 4-6 weeks
(Methicillin-resistant)
HACEK organisms Ceftriaxone (2 g/d IV OD) for 4 weeks
Ampicillin/sulbactam (3 g IV q6h) for 4 weeks
Culture Negative Ampicillin/sulbactam (3 g IV q6h) PLUS Gentamicin (1 mg/kg IV q8h) for 4-6 weeks

V. PROPHYLAXIS IN ADULTS WITH HIGH RISK CARDIAC LESIONS


Amoxicillin 2 g PO 1 hour before procedure (standard oral regimen)
Ampicillin 2 g IV or IM 1 hour before procedure (unable to take oral medication)
For Penicillin allergy:
o Clarithromycin or azithromycin 500 mg PO 1 hour before procedure
o Cephalexin 2 g PO 1 hour before procedure
o Clindamycin 600 mg PO 1 hour before procedure
o Cefazolin or Ceftriaxone 1 g IV or IM 30 minutes before procedure
HIGH RISK CARDIAC LESIONS
Prosthetic valves Completely repaired congenital defects
Prior endocarditis during the 6 months after repair
Unrepaired cyanotic congenital defects Incompletely repaired congenital defects

HUMAN IMMUNODEFICIENCY VIRUS: AIDS AND RELATED DISORDERS


I. ETIOPATHOGENESIS

A. Etiologic Agent
Etiologic agent: Human Immunodeficiency Virus (HIV)
Four retroviruses known to cause human disease
o Human T lymphotropic viruses (HTLV)-1 and HTLV-II: transforming retroviruses
o Human immunodeficiency viruses, HIV-1 and HIV-2: cause cytopathic effects
HIV-1 is the most common cause of HIV disease throughout the world
Hallmark of HIV disease: profound immunodeficiency resulting primarily from a progressive quantitative and
qualitative deficiency of helper T cells, occurring in a setting of polyclonal immune activation

B. Transmission
Primarily by sexual contact: worldwide, heterosexual transmission is still the most common mode
Blood and blood products
Occupational transmission of HIV
Infected mothers to infants intrapartum, perinatally or via breast milk
No evidence that HIV is transmitted by casual contact or that the virus can be spread by insect, such as by a
mosquito bite

II. CLINICAL MANIFESTATIONS


ACUTE HIV SYNDROME ASYMPTOMATIC STAGE SYMPTOMATIC STAGE
(CLINICAL LATENCY)
Occurs 3-6 weeks after primary Median time: 10 years (for Symptoms can appear at any time
infection along with a burst of untreated patients) More severe and life-threatening
plasma viremia Ongoing and progressive HIV complications of HIV infection
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Symptoms: fever, skin rash, disease with active virus occur in patients with CD4+ T cell
pharyngitis, myalgia replication counts <200/uL
Most patients recover Rate of disease progression is
spontaneously from this syndrome directly correlated with HIV RNA AIDS:
Many have only a mildly levels HIV + CD4+ T cell count <200/uL;
depressed CD4+ T cell count that or
remains stable for a variable HIV + HIV-associated diseases
period before beginning its decline indicative of a severe defect in cell-
mediated immunity

III. DIAGNOSIS OF HIV


A. Diagnostics Used
DIAGNOSTIC DESCRIPTION
Standard blood screening test for HIV infection
ELISA or Enzyme Immunoassay Sensitivity of >99.5% (not optimal with regard to specificity)
(EIA) Commercial EIA kit contains antigens from both HIV-1 and HIV-2
Scored as positive (highly reactive), negative (nonreactive), or indeterminate
(partially reactive)
Most commonly used confirmatory test
Western blot Western blot demonstrating antibodies to products of all three of the major
genes of HIV (gag, pol and env) is conclusive evidence of infection with HIV
EIA-type assay: consists of antibodies to the p24 antigen of HIV
p24 Antigen Capture Assay Detects the viral protein p24 in the blood of HIV-infected individuals
Greatest use as a screening test for HIV infection in patients suspected of
having the acute HIV syndrome
B. Laboratory Monitoring of HIV Infection
DIAGNOSTIC DESCRIPTION
Measured directly or calculated as the product of the percent of CD4 + T-cells and the
total lymphocyte count
Best indicator of and correlated with the level of immunologic competence
CD4+ T Cell Count o CD4+ T cell counts <200/uL: high risk of disease from P. jiroveci
o CD4+ T cell counts <50/uL: high risk of CMV, mycobacteria of the M. avium
complex (MAC), and/or T. gondii
Measured at the time of diagnosis and every 3-6 months thereafter
HIV RNA Determination Number of copies of HIV RNA per milliliter of serum or plasma
HIV RNA can be detected in virtually every patient with HIV infection
HIV Resistance Testing Drug resistance testing in the setting of virologic failure should be performed while
the patient is still on the failing regimen

IV. MANAGEMENT OF HIV AND AIDS

A. Clinical Settings where Initial Antiretroviral Therapy (ART) is recommended in the Philippines:
NNRTI-based regimen = 2 NRTI + 1 NNRTI
First line NNRTI Zidovudine (AZT) 300 mg BID + Lamivudine (3TC) 150 mg BID
Alternative first line NNRTI Tenofovir (TDF) 300 mg OD + Lamivudine (3TC) 150 mg BID
First line NRTI Nevirapine (NVP) 200 mg BID
Alternative first line NRTI Efavirenz (EFV) 600 mg OD HS (for patients with hypersensitivity to NVP)
NRTI: Nucleoside Reverse Transcriptase Inhibitor
NNRTI: Non-Nucleoside Reverse Transcriptase Inhibitor

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SEXUALLY TRANSMITTED DISEASES (STD)
DISEASE/ETIOLOGY FEATURES TREATMENT
Treat gonorrhea (unless excluded)
Urethritis in Men Ceftriaxone 250 mg IM; or
N. gonorrhea Urethral discharge Cefpodoxime 400 mg Pol or
C. trachomatis Dysuria Cefixime 400 mg PO
M. genitalium Usually without frequency
U. urealyticum PLUS treatment for chlamydial infection
T. vaginalis Azithromycin 1 g PO; or
Doxycycline 100 mg BID PO for 7 days
Epididymitis Unilateral pain Ceftriaxone 250 mg IM + Doxycycline 100
C. trachomatis Swelling and tenderness of mg BID x 10 days
N. gonorrhea (less commonly) the epididymis Levofloxacin 500 mg OD x 10 days (for
Enterobacteriaceae)
Treat gonorrhea (unless excluded)
Ceftriaxone 250 mg IM; or
Mucopurulent cervicitis (MPC) Presence of yellow Cefpodoxime 400 mg PO; or
N. gonorrhea mucopurulent discharge from Cefixime 400 mg PO
C. trachomatis the cervical os
M. genitalium PLUS treatment for chlamydial infection
Azithromycin 1 g PO; or
Doxycycline 100 mg BID PO for 7 days
Outpatient
Ceftriaxone 350 mg IM once; PLUS
Doxycycline 100 mg PO BID for 14 days;

Acute PID Inpatient*


Lower abdominal pain <3 Regimen A
Pelvic Inflammatory Disease weeks duration o Cefotetan 2 g IV q12; or
N. gonorrhea Pelvic tenderness on o Cefoxitin 2 g IV q6; PLUS
C. trachomatis bimanual pelvic examination o Doxycycline 200 mg IV or PO q12
Evidence of lower genital tract Regimen B
infection o Clindamycin 900 mg IV q8; PLUS
o Gentamicin 1.5 mg/kg q8

Continued parenteral therapy until 48 hrs after clinical


improvement, then change to outpatient therapy
Vulvovaginal Infections
Vulvovaginal candidiasis Vulvar itching and/or irritation Fluconazole 150 mg PO single dose
C. albicans Scanty, white, clumped Azole cream, tab or suppository:
discharge miconazole, clotrimazole
Trichomonal vaginitis Vulvar itching
T. vaginalis Often profuse white or yellow Metronidazole 500 mg PO BID for 7 days
homogenous discharge
Malodorous
Slightly increased discharge
Bacterial vaginosis (+) Clue cells: vaginal Metronidazole 500 mg PO BID for 7 days
Gardnerella vaginalis epithelial cells coated with Topical: metronidazole gel, clindamycin
coccobacillary organisms
giving it a granular
appearance
Ulcerative Genital or Perianal Lesions
Sharply demarcated, elevated
Syphilitic Chancre and round ulcers Benzathine penicillin 2.4 million units IM as
T. pallidum Lymph nodes are bilateral, single dose
firm and non-tender
Herpes Acyclovir 400 mg PO TID x 7-10 days; or

167
HSV Erythematous ulcers Acyclovir 200 mg PO 5x a day x 7-10 days;
Lymph nodes are firm, tender, or
often bilateral Valacyclovir 1 g PO 2x a day for 7-10 days;
or
Famciclovir 250 mg PO TID for 7-10 days
Undermined, ragged &
Chancroid irregular ulcers Ciprofloxacin 500 mg PO as single dose; or
H. ducreyi Lymph nodes are tender, may Ceftriaxone 250 mg IM as single dose; or
suppurate, loculated & usually Azithromycin 1 g PO as single dose
unilateral
Elevated, round or oval ulcers
Lymphogranous venereum Lymph nodes are tender, may Doxycycline 100 mg PO BID for 21 days
C. trachomatis suppurate, loculated & usually
unilateral
Donovanosis Elevated, irregular ulcers Doxycycline 100 mg BID for at least 3
K. granulomatis Pseudobuboes weeks and until all lesions have completely
healed

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SECTION 3
IMMUNIZATION
VACCINE TYPE/ROUTE INDICATION SCHEDULE
Single dose

Comorbidities (chronic lung disease, asthma, Booster may be given to:


Pneumococcal cardiovascular disease, DM, liver disease) o > 65 years old if first
Polysaccharide (PPSV23): Immunocompromised (asplenia, HIV) dose >5 years ago and
IM or SC Residents of nursing homes or long-term care before age 65
Conjugate (PCV 13): IM facilities o <65 years old who
Smokers and alcoholics received vaccine >5
years ago and
immunocompromised
Human Papilloma Virus (HPV) Females:
Bivalent (Types 16, 18) for 3 doses at age 11 or 12 and those aged 13 3 doses
females only: IM through 26 if not previously vaccinated Bivalent – 0, 1, 6 months
Quadrivalent (Types 6, 11, Quadrivalent – 0, 2, 6
16, 18) for females and Males: months
males: IM 3 doses at age 11 or 12 and those aged 13
through 26, if not previously vaccinated
Meningococcal Two doses if immunocompromised (asplenia, HIV,
Polysaccharide vaccine complement deficiency) Single dose
(MPSV): IM or SC Single dose for unvaccinated students in (revaccination after 5
Conjugate vaccine dormitories, microbiologists routinely exposed to years if with risk of
(MCV4): IM Neisseria meningitides, military recruits, travelers exposure)
or inhabitants in endemic areas
ViPS
1 dose should be given >
2 weeks before exposure
Typhoid Travelers to outbreak areas Booster dose – 1 dose IM
Vi Polysaccharide (ViPS): Health care workers and lab technicians every 3 years for travelers
IM Exposed to S. typhi cases and patients
Live attenuated: Oral Those in refugee camps & disaster areas Live attenuated (oral)
Enteric-coated capsules
every other day for 1
week
Influenza
Trivalent inactivated All persons >6 months Single dose annually
vaccine: IM or intradermal
(microneedle)
MSM and illicit drug users
Persons working with HAV in a research Single dose
Hepatitis A laboratory setting Booster dose between 6-
Inactivated vaccine: IM Chronic liver disease and recipients of clotting 12 months after primary
factor concentrates course
Travelers to endemic countries
Sexually active persons not in a long-term,
mutually monogamous relationship and those with
STD
MSM and injection-drug users
Hepatitis B Exposed healthcare personnel 3 doses: 0, 1, 6 months
Inactivated vaccine: IM ESRD, chronic liver disease, HIV
Household contacts and sex partners of
chronically-infected persons
Clients and staff of institutions for developmental
disabilities
169
Close contact with persons at high risk for severe
disease (e.g., health personnel and family
contacts of immunocompromised persons) or at 2 doses: 0, 1-2 months
Varicella high risk for exposure or transmission (e.g. Single dose post-
Live attenuated vaccine: teachers, day care staff) exposure prophylaxis:
SC Residents and staff of correctional institutions within 72 hours of
Military personnel exposure
Adolescents and adults living in households with
children
Non-pregnant women of childbearing age
Measles, Mumps, Rubella Measles and mumps component: college
(MMR) students, health care workers, travelers 2 doses: 0, 1 month
Live attenuated: SC Rubella component: non-pregnant women of
childbearing age should be vaccinated

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CHAPTER 7
ENDOCRINOLOGY
I. Introduction to Endocrinology
II. Common Conditions in Endocrinology
1. The Metabolic Syndrome
2. Diabetes Mellitus
3. Gestational Diabetes Mellitus
4. Hyperglycemic Crises in Diabetes
5. Diabetic Foot Ulcer
6. Hypoglycemia
7. Hyperthyroidism
8. Thyroid Storm
9. Goiter and Nodular Thyroid Disease
10. Osteoporosis
11. Multiple Endocrine Neoplasia
12. Cushing’s Syndrome
13. Mineralocorticoid Excess
14. Pituitary Diseases

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SECTION 1
INTRODUCTION TO ENDOCRINOLOGY
I. GENERAL FORMULAS
BODY MASS INDEX
BMI = Weight in kg
(height in m)2
IDEAL BODY WEIGHT (IBW)
IBW Males = 106 lbs + (6 lbs per inch over 5 feet)

IBW Females = 100 lbs + (5 lbs per inch over 5 feet)

*Divide by 2.2 to convert to kilograms

WAIST-HIP RATIO (WHR)


WHR = Waist circumference in cm
Hip circumference in cm
Waist circumference should be measured at the midpoint between the lower margin of the last palpable rib and
the top of the iliac crest
Hip circumference should be measured around the widest portion of the buttocks
Used as an indicator or measure of the health of a person, and the risk of developing serious health conditions
Abdominal obesity: defined as a waist-hip ratio >0.90 for males and >0.85 for females

A1C APPROXIMATES THE FOLLOWING MEAN PLASMA GLUCOSE VALUES


HBA1C APPROXIMATE PLASMA GLUCOSE VALUE
6% 7.0 mmol/L (126 mg/dL)
7% 8.6 mmol/L (154 mg/dL)
8% 10.2 mmol/L (183 mg/dL)
9% 11.8 mmol/L (212 mg/dL)
10% 13.4 mmol/L (240 mg/dL)
11% 14.9 mmol/L (269 mg/dL)
12% 16.5 mmol/L (298 mg/dL)

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SECTION 2
COMMON CONDITIONS IN ENDOCRINOLOGY
THE METABOLIC SYNDROME
I. ETIOLOGY
Metabolic abnormalities that confer an increased risk of cardiovascular disease and diabetes mellitus
Insulin resistance: most accepted an unifying hypothesis in metabolic syndrome
Hypertriglycerides is an excellent marker of insulin resistance
Other associated conditions: non-alcoholic fatty liver, hyperuricemia, polycystic ovarian syndrome and obstructive
sleep apnea
II. DIAGNOSIS
A. BMI Classification
CLASSIFICATION OF BMI WHO INTERNATIONAL CLASSIFICATION IN ASIANS
(kg/m2) CLASSIFICATION
Underweight < 18.5 < 18.5
Normal 18.5 – 24.99 18.5 – 22.9
Overweight > 25 23 – 24.9
Obese I > 30 25 – 29.9
Obese II > 35 > 30
Obese III > 40

B. NCEP: ATP III 2001 Criteria for the Metabolic Syndrome (requires 3 or more of the following)
Central Obesity Waist circumference >102 cm (M) or >88cm (F)
Hypertriglyceridemia TG > 150 mg/dL or use of specific medication
Low HDL Cholesterol <40 mg/dL (M) or <50 mg/dL (F) or use of specific medication
Hypertension BP > 130 systolic or > 85 diastolic or use of specific medication
Fasting Glucose > 100 mg/dL or specific medication or preciously diagnosed T2DM

C. Harmonizing Definition for the Metabolic Syndrome (requires 3 or more of the following)
> 90 cm (M) or > 80 cm (F) in South Asian, Chinese, and Ethnic
South and Central American
Waist circumference > 85 cm (M) or > 90 cm (F) in Japanese
> 94 cm (M) or > 80 cm (F) in Europe, Sub-Saharan African, Eastern
and Middle Eastern
Hypertriglyceridemia TG > 150mg/dL or use of specific medication
Low HDL Cholesterol < 40 mg/dL (M) or < 50 mg/dL (F) or use of specific medication
Hypertension BP > 130 systolic or > 85 diastolic or use of specific medication
Fasting Glucose > 100 mg/dL or specific medication or previously diagnosed T2DM
TG: Triglycerides
M: Males; F: Females

III. MANAGEMENT OF OBESITY


TREATMENT BMI CATEGORY (kg/m2)
25 – 26.9 27 – 29.9 30 – 34.9 35 – 39.9 > 40
Diet & Exercise + if with + if with + + +
comorbids comorbids
Pharmacotherapy - + if with + + +
comorbids
Surgery - - - + if with +
comorbids

Dietary therapy: primary focus is reduction in overall calorie consumption


Diet and exercise: combination of dietary modification and exercise is the most effective behavioral approach
Pharmacotherapy: appetite suppressants (e.g., phentermine) and gastrointestinal fat blockers (e.g., orlistat)
Surgery: classified into three (restrictive, restrictive-malabsorptive, and malabsorptive)
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DIABETES MELLITUS
I. ETIOPATHOGENESIS
Group of metabolic disorders that share the common phenotype of hyperglycemia
DM is defined as the level of glycemia at which diabetes-specific combinations occur

A. Classification of Diabetes (based on the pathogenic process that leads to hyperglycemia)


Type 1 DM: result of interactions of genetic, environmental and immunologic factors that ultimately lead to
destruction of pancreatic beta cells and insulin deficiency
Type 2 DM: heterogenous group of disorders characterized by variable degrees of insulin resistance, impaired
insulin secretion and excessive hepatice glucose production

B. Risk Factors for Type 2 DM


Physical inactivity
Family history of diabetes (e.g., parent or sibling with T2DM)
Obesity (BMI > 25 kg/m2 or ethnically relevant definition for overweight)
High-risk ethnicity (e.g. African American, Latino, Native American, Asian American, Pacific Islander)
GDM or delivery of a baby > 9 lbs (4 kg)
History of cardiovascular disease or hypertension (> 140/90 mmHg)
HDL cholesterol < 35mg/dL (0.90 mmol/L) and/or triglycerides >250 mg/dL (2.82 mmol/L)
HbA1C 5.7-6.4%, IGT or IFG on previous testing
Conditions with insulin resistance (e.g. acanthrosis nigricans, polycystic ovary syndrome)

C. Classification of Glucose Tolerance


GLUCOSE FASTING PLASMA GLUCOSE GLUCOSE AFTER ORAL HbA1C
TOLERANCE (FPG) GLUCOSE CHALLENGE
Normal < 10 mg/dL (5.6 mmol/L) < 140 mg/dL (7.8 mmol/L) < 5.7%
Impaired Glucose 100-125 mg/dL (5.6-6.9 mmol/L) 140-199 mg/dL (7.8-11 mmol/L) 5.7-6.4%
Homeostasis Impaired Fasting Glucose (IFG) Impaired Glucose Tolerance (IGT)
Diabetes Mellitus > 126 mg/dL (7.0 mmol/L) > 200 mg/dL (11.1 mmol/L) > 6.5%

II. CLINICAL FEATURES OF DIABETES


Classic symptoms: polyuria, polydipsia, polyphagia, nocturia, weight loss
Others: fatigue, weakness, blurred vision, frequent superficial infections and poor wound healing

A. Acute Complications of DM
Diabetic Acidosis
Hypoglycemic hyperosmolar state

B. Chronic Complications of DM
MICROVASCULAR MACROVASCULAR OTHERS
Eye disease
Retinopathy (nonproliferative/ Gastrointestinal (gastroparesis, diarrhea)
proliferative) Genitourinary (uropathy, sexual dysfunction
Macular edema Dermatologic
Coronary artery disease Cataracts and glaucoma
Neuropathy Peripheral arterial disease Periodontal disease
Sensory and motor (mono-/ Cerebrovascular disease Hearing loss
polyneuropathy) Increased risk for infection
Autonomic Cheiroarthropathy (thick skin + reduced joint
mobility)
Nephropathy (albuminuria, declining
renal function)

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III. DIAGNOSIS OF DIABETES MELLITUS

A. Criteria for the Diagnosis of DM


Note:
Either of the following: Current criteria emphasize the HbA1C or the FPG as
Hemoglobin A1C > 6.5%, or the most reliable and convenient tests
FPG > 126 mg/dL (7.0 mmol/L), or Perform HbA1C with an assay-standardized method
2-hour plasma glucose > 200 mg/dL (11.1 mmol/L) “Fasting”: no caloric intake for at least 8 hours
during 75 g OGTT, or “Random”: without regard to time since last meal
Symptoms of DM + RBS > 200 mg/dL (11.1 In the absence of unequivocal hyperglycemia, these
mmol/L) criteria should be confirmed by repeat testing on a
different day
FPG: Fasting Plasma Glucose
OGTT: Oral Glucose Tolerance Test (performed using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water)

B. Screening for DM
Begin at age 45 years every 3 years
Earlier age if they are overweight (BMI > 23) + one additional risk factor for DM (see above)
May use A1C FPG, or 2-hour plasma glucose after 75 g OGTT for screening

IV. MANAGEMENT OF DIABETES

A. Insulin Therapy
Common side effects are hypoglycemia and weight gain
Adjust doses in renal insufficiency
INSULIN PREPARATION ONSET OF ACTION PEAK DURATION
Rapid and Short Acting Insulin
Lispro (Rapid)
Aspart (Rapid) < 15 mins 30-90 mins 2-4 hours
Glulisin (Rapid)
Regular (Short) 30-60 mins 2-3 hours 3-6 hours
Intermediate and Long Acting Insulin
Isophane/NPH (Intermediate) 2-4 hours 4-10 hours 10-16 hours
Glargine (Long) Minimal peak activity Up t0 24 hours
Detemir (Long) 1-4 hours

1. Three Major Components of Exogenous Insulin Therapy


Required to regulate metabolic processes even in the absence of meals
Basal Insulin Usual “basal insulin”: given as intermediate or long-acting insulin
Intermediate-acting insulin usually given in portions of 2/3 in AM and 1/3 in PM
Required to cover glycemic excursions following a meal
Bolus Insulin Usual “bolus insulin”: given as short or rapid-acting insulin
Rapid-acting insulin given within 15-20 minutes or immediately before meals
Short-acting insulin given within 30-45 minutes before meals
Correctional Insulin Supplemental doses of short or rapid-acting insulin given to correct elevations in
blood glucose that occur despite the use of basal and bolus insulin

2. Initiating Insulin Therapy in T1DM


Calculate total insulin requirement: usually 0.5-1 units/kg per day
50% of computed value given as basal insulin

3. Initiating Insulin Therapy in T2DM


Basal Insulin Calculate dose at 0.2 units/kg/day for insulin-naïve patients
Bolus Insulin Initiated if unable to achieve target A1C with basal insulin alone
Start with 4 units before each meal OR calculate each dose at 0.1 units/kg
Calculate dose at 0.3 to 0.5 units/kg/day:
Basal-bolus Insulin o 50% of dose will be given as basal insulin
NPH: 2/3 pre-breakfast, 1/3 pre-dinner
175
Glargine or Detemir: give at bedtime
o 50% of dose will be given as bolus insulin in equal divided doses pre-meals
Example:
Intermediate acting insulin: 20-0-10 (this means, 20 units given pre-breakfast +
Sample Order 10 units given pre-supper)
Regular acting insulin: 4-4-4 (this means, 4 units given pre-breakfast, 4 units
given pre-lunch, and 4 units given pre-supper)

B. Common Hypoglycemic Agents (OHAs)


DRUG CLASS SUBTYPES EXAMPLES GENERAL MECHANISM OF COMMON SIDE
ACTION EFFECTS
Gliclazide
Sulfonylureas Glibenclamide
Insulin Glimepride Increases insulin secretion Hypoglycemia
Secretagogues Glipizide Weight gain
Non-sulfonylureas Repaglinide
Nateglinide
Decreases hepatic
Biguanides Metformin glucose production and Weight loss
improves peripheral Lactic acidosis
Insulin glucose utilization
Sensitizers Decreases insulin Edema
Thiazolidinediones Rosiglitazone resistance, increases Weight gain
Pioglitazone glucose utilization Osteoporosis
Anemia
Intestinal Alpha-glucosidase Acarbose Inhibits intestinal Weight loss
Absorption Inhibitors Miglitol absorption of sugars Diarrhea
Inhibitors Lipase Inhibitors Orlistat Flatulence
Sitagliptin
DPP-IV Inhibitors Saxagliptin
Incretin- Linagliptin Prolongs endogenous Headache
Related Drugs Vildagliptin GLP-1 action Nasopharyngitis
GLP-1 Agonists Exenatide
(Parenteral) Liraglutide
Increases, urinary glucose Glucosuria
excretion Urinary tract &
Na+ -Glucose Dapagliflozin Inhibits subtype 2 Na+- vaginal infections
Co-Transporter-2 Canagliflozin glucose transport protein Dehydration
Others Inhibitors Empagliflozin which is responsible for at Hyperkalemia
least 90% of glucose (limited clinical
reabsorption in the kidney experience)
Amylin Agonists Pramlinitide Slows gastric emptying Nausea
(Parenteral) Decreases glucagon hypoglycemia

176
C. Drugs and their Primary Areas of Control
goals of treatment based on HbA1C
o If HbA1C is <7% Control PPG first
o If HbA1C is 7-9% Control both FPG and PPG
o If HbA1C is >9% Control FPG first
MONOTHERAPY COMBINATION THERAPY INSULIN

Sulfonylureas Sulfonylurea + Lispro


Metformin FPG Metformin FPG Aspart PPG
Thiazoldinediones Sulfonylurea + Regular
Meglitinides Thiazolidinedione NPH
GLP-1 agonists Sulfonylurea + GLP-1 FPG, Glargine FPG
Acarbose PPG agonist PPG Detemir
DPP-IV Metformin + Meglitinide
inhibitors

FPG: Fasting Plasma Glucose


PPG: Postprandial Glucose

D. Goals of Treatment
INDEX GOAL
Glycemic Control
HbA1C (primary goal) < 7.0%
Preprandial capillary plasma glucose 80-130 mg/dL (4.4 – 7.2 mmol/L)
Peak postprandial capillary plasma glucose* < 180 mg/dL (10.0 mmol/L)
Blood Pressure ** < 140/90 mmHg (130/80 for younger patients)
Lipids**
Low-density lipoprotein (LDL) < 100 mg/dL (2.6 mmol/L)
High-density lipoprotein (HDL) >40 mg/dL (1 mmol/L) [M] or > 50 mg/dL (1.3
Triglycerides mmol/L) [F}
< 150 mg/dL (1.7 mmol/L)
*Peak postprandial capillary plasma glucose: 1-2 hours after beginning a meal
**see JNC-8 and Dyslipidemia Guidelines in Cardiology Chapter (values indicated are from the ADA)

E. Self-Monitoring of Blood Glucose (SMBG): For patients on multiple-dose insulin or insulin pump
Prior to meals and snacks, occasionally postprandially, and at bedtime
Prior to exercise or critical tasks such as driving
When they suspect low blood glucose
After treating low blood glucose until they are normoglycemic

F. Monitoring Response
DRUG PEAK EFFECT WHEN TO MONITOR RESPONSE?
Sulfonylureas FPG at 2 weeks
HbA1C at 3 months
1-2 weeks FPG at 2 weeks
Meglitinides HbA1C at 3 months
PPG at initiation
Metformin 2-3 weeks FPG at 2 weeks
HbA1C at 3 months
Acarbose 2-4 weeks HbA1C at 3 months
PPG at initiation
Thiazolidinediones 1-2 months FPG at 4 weeks
HbA1C at 3-6 months
FPG at 2 weeks
DPP-IV Inhibitors 2 weeks HbA1C at 3 months
PPG at initiation

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V. ANTICIPATORY CARE
A. Recommended Annual Laboratories
LABORATORY FREQUENCY
HbA1C testing 2-4 times / year
Screening for Diabetic Neuropathy Annual
Lipid profile & Serum Creatinine Annual

B. Cornerstones of Anticipatore Care


Moderate weight loss of 7% of body weight
150 min/week moderate intensity aerobic exercise, spread over at least 3
Lifestyle Changes days/week, with no more than 2 consecutive days without exercise
Dietary fiber intake of 14 g of fiber/1,000 kcal; saturated fat intake <7%
Smoking cessation and moderation of alcohol intake
Hypertension Best treated with ACE inhibitor (ARB for ACEI intolerant patients)
DASH-style diet by reducing sodium and increasing potassium intake
Dyslipidemia Maximally-tolerated statin therapy regardless of baseline lipid levels for all
diabetics
Antiplatelet Agents Consider for primary prevention in men >50 years or women >60 years with
at least one major risk factor
Diabetic Kidney Disease Recommended daily protein allowance of 0.8 g/kg/day
Screening (comprehensive eye examination by an ophthalmologist or
Retinopathy optometrist)
o Type 1 diabetes: within 5 years after diagnosis
o Type 2 diabetes: shortly after diagnosis
Influenza vaccine to all diabetics > 6 months of age
Immunizations Pneumococcal vaccine if > 2 years old, revaccination if >64 years old
Hepatitis B vaccine in unvaccinated adult diabetic 19-59 years old

C. Approved Drugs for Management of Pre-diabetes (IGT, IFG, HbA1C 5.7-6.4%)


Metformin (strongest evidence)
Acarbose
Thiazolidinediones

GESTATIONAL DIABETES MELLITUS (GDM)


I. DEFINITIONS
Overt DM: pregnant woman who meets the criteria for diagnosis of DM
Pre-Gestational DM: diagnosed in a woman even before pregnancy
GDM: diagnosed in the 2nd and 3rd trimester of pregnancy that is not clearly overt DM

II. DIAGNOSIS (ONE-STEP STRATEGY)


Screen at first prenatal visit based on the International Association of the Diabetes and Pregnancy Study Groups
(IADPSG) criteria using the 75 g OGTT
Any of the following:
FPG: > 92 mg/dL (5.1 mmol/L)
1 hr PPG: > 180 mg/dL (10.0 mmol/L)
2 hr PPG: > 153 mg/dL (8.5 mmol/L)

III. MONITORING
Do SMBG before and 1 hr or 2 hrs after the start of each meal/after the first bite
Glycemic targets in pregnancy
GDM PREEXISTING TYPE 1 AND TYPE 2 DM
FPG < 95 mg/dL (5.3 mmol/L) FPG 60-99 mg/dL (3.3-5.4 mmol/L)
1-hr PPG < 140 mg/dL (7.8 mmol/L) PPG 100-129 mg/dL (5.4-7.1 mmol/L)
2-hr PPG < 120 mg/dL (6.7 mmol/L) HbA1C <6.0%

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IV. MANAGEMENT

A. Medical Nutrition Therapy (MNT)

1. Recommended Daily Caloric Intake and Weight Gain


PREGRAVID BMI CATERGORY Kcal/kg/day TOTAL WEIGHT GAIN
Low (BMI < 18.5) 36-40 <28-40
Normal (BMI 18.5-24.9) 30 25-35
High (BMI 25-29.9) 24 15-25
Obese (BMI >29.9) 12 11-20

2. General Diet Structure


3 meals and 3 snacks
o 50-60% complex high fiber carbohydrates
o 18-20% protein of high biologic value
o < 30% fats
Avoid concentrated sweets and convenience foods

B. Insulin Therapy
Implemented if glycemic goals not met after 1 week MNT
May use NPH, regular insulin, lispro or aspart insulin

V. POSTPARTUM SCREENING
Screen for persistent diabetes and prediabetes using FBS and 75 g OGTT
Done at 6-12 weeks postpartum and 1-3 years thereafter depending on risk factors
Use non-pregnancy criteria

HYPERGLYCEMIC CRISES IN DIABETES

I. ETIOPATHOGENESIS
Associated with absolute or relative insulin deficiency combined with counterregulatory hormone excess volume
depletion, and acid base abnormalities
Decreased insulin-glucagon ratio promotes gluconeogenesis, glycogenolysis and ketogenesis

A. Precipitating Factors
Infection: most common
Discontinuation of or inadequate insulin therapy
Comorbidities such as pancreatitis, MI, stroke
Restricted water intake (bedridden, altered thirst response of the elderly)
Drugs that affect carbohydrate metabolism: steroids, thiazides, sympathomimetic agents, pentamidine,
antipsychotics

B. Types of Hyperglycemic Crisis

1. Diabetic Ketoacidosis (DKA)


Results from increased gluconeogenesis and glycogenolysis and impaired glucose utilization by
peripheral tissues
Formerly a hallmark of DM type 1
Ketones (indicator of DKA) should be measured in individuals with T1DM when glucose > 300 mg/dL

2. Hyperosmotic Hyperglycemic State (HHS)


Greater degree of dehydration and higher endogenous insulin secretion compared with DKA
Primarily seen in individuals in T2DM
Insulin levels inadequate to facilitate glucose utilization by insulin-sensitive tissues but adequate to
prevent lipolysis and ketogenesis

179
II. CLINICAL MANIFESTATIONS

A. Diagnostic Criteria for DKA and HHS


DKA HHS
MILD MODERATE SEVERE
Plasma Glucose (mg/dL) >250 >250 >250 >600
Arterial pH 7.25-7.30 7.00-7.24 <7.00 >7.30
Serum bicarbonate (mEq/L) 15-18 10 to <15 <10 >15
Urine ketones Positive Positive Positive Small
Serum ketones Positive Positive Positive Small
Effective serum osmolality (mOsm/kg) Variable Variable Variable >320
Anion gap >10 >12 >12 Variable
Alteration in Sensorium Alert Alert/drowsy Stupor/coma Stupor/coma

B. Differentiating Features of DKA and HHS


INDEX DKA HHS
CLINICAL FEATURES
Symptoms Nausea, vomiting, thirst, polyuria, Polyuria, weight loss, diminished oral
abdominal pain, dyspnea intake, mental confusion, lethargy, coma
Tachycardia, dehydration, tachypnea, Profound dehydration, hypotension,
Signs Kussmaul respirations, abdominal tachycardia, altered mental status (No
tenderness, decreased sensorium nausea, vomiting, abdominal pain or
Kussmaul respiration unlike DKA)
Development of Over 24 hours Several weeks
manifestations
LABORATORY VALUES
Glucose mmol/L (mg/dL) 13.9 – 33.3 (250-600) 33.3 – 66.6 (600-1200)
Na+ (mEq/L) 125-135 135-145
K+ Normal to increased Normal
Mg2+ Normal Normal
Cl- Normal Normal
Phosphate Decreased Normal
Creatinine Slightly increased Moderately increased
Osmolality (mOsm/mL) 300-320 330-380
Plasma ketones ++++ +/-
Serum bicarbonate < 15 mEq/L Normal to slightly decreased
(mEq/L)
Arterial pH 6.8 – 7.3 > 7.3
Arterial PCO2 (mmHg) 20-30 Normal
Anion Gap (Na- [Cl + High Normal to slightly high
HCO3])

III. MANAGEMENT
A. General Management
Admit to ICU
Measure capillary blood glucose (CBG) every 1-2 hours
Monitor BP, pulse, respirations, mental status and fluid I & O every 1-4 hours
Assess serum electrolytes, ABG and renal function
15-20 mL/kg/hr or 1-1.5 L of pNSS during the first hour (unless with risk of congestion)
Once CBG is ~200-250 mg/dL, shift fluids to D5-IVF (glucose-containing)
Fluid Therapy IVF replacement should correct estimated deficits within the first 34 hours
In renal/cardiac patients, monitor serum osmolality and cardiac, renal and mental status to
avoid iatrogenic overload
Regular insulin preferably by IV route (short half-life & easy titration): mainstay of therapy
Initial IV bolus (0.1 unit/kg) is given, then infusion started at 0.1 units/kg/hr (see algorithm)
Insulin Therapy If CBG does not decrease ~50-75 mg/dL/hr, increase insulin infusion rate (two to three-
fold) hourly until with a steady glucose decline
When CBG ~200 mg/dL in DKA or 300 mg/dL in HHS, may decrease insulin infusion rate
180
to 0.02-0.05 units/kg/hr to maintain CBG 150-200 mg/dL in DKA or 250-300 mg/dL in HHS
Potassium Despite depletion of total body potassium, mild-moderate hyperkalemia is common
Insulin therapy, correction of acidosis & volume expansion decrease serum K +
If pH <6.9, start 100 mmol HCO3 in 400 ml sterile water with 20 mEq KCl at 200 ml/h for 2
Bicarbonate hrs until venous pH >7.0
Repeat every 2 hours until pH reaches >7.0

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Complete initial evaluation. Check capillary glucose and serum/urine ketones to confirm hyperglycemia and ketonemia/ketonuria. Obtain blood for metabolic
profile. Start IV fluids: 1.0 L of 0.9% NaCl per hour1

IV Fluids Bicarbonate Insulin: Regular Potassium

pH > 6.9 pH < 6.9 IV Route IV Route


Determine hydration status (DKA and HHS) (DKA and HHS) Establish adequate renal
function (urine output – 50
No 100 mmol in 0.1 U/kg/B. Wt. ml/hr)
Severe Cardiogenic
HCO3- 400 ml H2O as IV bolus
Hypovolemia Shock
+ 20mEq 0.14 U/kg
Mild KCL, infuse Bwt/hr as IV
dehydration for 2 hours 0.1 U/kg/hr IV continuous insul
Hemodynamic continuous infusion K+ <3.3 mEq/L K+ >5.2 mEq/L
Administer
0.9% Nacl monitoring/ insulin infusion
pressors Repeat
(1.0L/hr)
every 2
hours until Hold insulin and give Do not give K+, but
pH > 7. If serum glucose does not fall by 20 – 30 mEq/hr check serum K+ every 2
Monitor at least 10% in first hour, give 0.14 Until K+ >3.3 mEq/L hours
Elevated corrected serum
Na+ serum K+ U/kg as IV bolus, then continue
every 2 previous Rx
hours
Serum Serum Na+ Serum
Na+ high normal Na+ low DKA HHS
K+ = 3.3 – 5.2 mEq/L
When serum glucose reacges 200 When serum glucose reaches 300
mg/dL, reduce regular insulin mg/dl, reduce regular insulin
0.45% NaCl 0.9% NaCl infusion to 0.02-0.05 U/kg/hr IV, or infusion to 0.02-0.05 U/kg/hr
(250-500 ml/hr) (250-500 ml/hr) Give 20 – 30 mEq K+ in each
give rapid-acting insulin at 0.1 between 200 and 300 mg/dl until
depending on depending on liter of IV fluid to keep serum
U/kg SC every 2 hours. Keep patient is mentall alert. K+ between 4-5 mEq/L
hydration state hydration state serum glucose between 150 and
200 mg/dl until resolution of DKA.

When serum glucose reaches 200


mg/dl (DKA) or 300 mg/dl (HHS),
change to 5% dextrose with Check electrolytes, BUN, venous pH, creatinine and glucose every 2-4 hrs until stable. After
0.45% NaCl at 150-250 ml/hr resolution of DKA or HHS and when patient is able to eat, initiate SC multidose insulin regime.
To transfer from IV to SC, continue IV insulin infusion for 1-2 hrs after SC insulin begun to
ensure adequate plasma insulin levels. In insulin naïve patients, start at 0.5 U/kg to 0.8 U/kg
body weight per day and adjust insulin as needed. Look for precipitating cause(s).

182
B. Transition to Subcutaneous (SQ) insulin
Overlap 1-2 hours between IV and SQ insulin to prevent recurrence of hyperglycemia or ketoacidosis
If the patient remains on NPO, continue IV insulin
Patients with known DM may be given insulin at the dose they were receiving before the onset of DKA so long as
it was controlling glucose properly
For insulin-naïve patients, start insulin regimen at 0.5-0.8 units/kg/day

C. Criteria for Resolution


DKA HHS
Plasma glucose <200 mg/dL and two of the following: Normal serum osmolality
Serum bicarbonate level > 15 mEq/L Improvement of normal mental status
Venous pH >7.3
Calculated anion gap < 12 mEq/L

IV. COMPLICATIONS

A. Hypoglycemia and Hypokalemia


Due to overzealous treatment of DKA with insulin and bicarbonate

B. Hyperchloremic Non-Anion Gap Acidosis


Usually seen during the recovery phase of DKA
Caused by loss of ketoanions plus excess infusion of chloride-containing fluids during treatment

C. Cerebral Edema
Occurs in ~0.3-1% of DKA in children but rare in adults
Associated with 20-40% mortality rate
Symptoms: headache, gradual deterioration in level of consciousness, seizures, sphincter incontinence, pupillary
changes, papilledema, bradycardia, elevation in BP and respiratory arrest
Treated with mannitol and mechanical ventilation

DIABETIC FOOT ULCER


I. ETIOPATHOGENESIS
Diabetics are prone to foot ulcers
Development is attributed to: neuropathy, ischemia, infection and immune impairment
Neuropathy: most common underlying etiology of foot ulceration

II. CLASSIFICATION OF DIABETIC FOOT ULCERS


A. Wagner Classification System
Assesses ulcer depth and the presence of osteomyelitis or gangrene
o Grade 0: pre- or post-ulcerative lesion, completely epithelialized
o Grade 1: partial / full thickness ulcer; superficial wound
o Grade 2: penetrates the tendon or capsule
o Grade 3: deep with osteitis
o Grade 4: partial foot gangrene
o Grade 5: whole foot gangrene

B. University of Texas System


Assesses ulcer depth, presence of wound infection, and presence of signs of lower-extremity ischemia
Within each wound grade, there are four stages
Example: A superficial wound that is ischemic but not infected is classified as Grade 1, Stage C
DEPTH OF ULCER PRESENCE OF INFECTION / ISCHEMIA
Grade 0: pre- or post-ulcerative lesion, epithelialized Stage A: (-) infection, (-) ischemia
Grade 1: superficial wound Stage B: (+) infection, (-) ischemia
Grade 2: wound penetrates tendon or capsule Stage C: (-) infection, (+) ischemia

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Grade 3: wound penetrates bone and joint Stage D: (+) infection, (+) ischemia

III. DIFFERENTIALS FOR A FOOT ULCER


FOOT ULCER USUAL ETIOLOGY DESCRIPTION
Diabetic neuropathy (“DM Located at the sites of trauma, such as areas of callus
Neuropathic Ulcer foot”) formation, bony prominence or parts of foot exposed to mild
chronic trauma
Small, annular, pale, tender, circumscribed and dessicated
Arterial (Ischemic) Peripheral arterial Located on distal areas of limbs (e.g., toes, heels,
Ulcer occlusive disease fingertips)
(PAOD) May progress to tissue necrosis & gangrene
May co-exist in diabetic patients with PAOD
Large, irregular borders, erythematous & moist (shiny
Chronic venous appearance)
Venous Ulcer insufficiency (CVI) Located near the medial or lateral malleolus
Chronic venous edema may impart hemosiderin deposition
in the skin, giving rise to a “brawny appearance”

IV. MANAGEMENT

A. Screening & Surveillance


Screen for distal polyneuropathy at diagnosis and at least annually thereafter
Annual comprehensive foot examination
o Inspection
o Assessment of foot pulses and ankle brachial index (ABI)
o Tests for loss of protective sensation: 10-g monofilament plus either: vibration using 128-Hz tuning fork,
pinprick sensation, ankle reflexes, and vibration perception threshold

B. General Management
Medications for relief of symptoms from polyneuropathy or autonomic neuropathy are recommended
General foot self-care education
Use multi-disciplinary approach:
o Refer patients to foot care specialists for ongoing preventive care and surveillance
o Refer patients with significant claudication or positive ABI for further vascular assessment

HYPOGLYCEMIA
I. ETIOPATHOGENESIS
Defined as glucose levels <55 mg/dL with symptoms that are relieved promptly after the glucose level is raised
Recurrent hypoglycemia can induce a vicious cycle of hypoglycemia-associated autonomic failure
hypoglycemia unawareness and defective glucose counterregulation
Hepatic glycogen stores usually last only in 48 hours

A. Physiologic Response to Hypoglycemia


1ST line of defense Decreased insulin (primary glucose regulatory factor)
2nd line of defense Increased glucagon (primary glucose counterregulatory factor)
3rd line of defense Increased epinephrine (critical when glucagon is deficient)
Other defenses Increased cortisol and growth hormone

B. Common Causes of Hypoglycemia


Drugs used to treat DM (insulin/insulin secretagogues)
Alcohol intake
Critical illness (hepatic, renal, cardiac failure, sepsis, inanition)
Hormone deficiencies (cortisol, glucagon, epinephrine)
Endogenous hyperinsulinism (includes islet- and non-islet cell tumors)
Accidental, surrpetious or malicious hypoglycemia

184
II. DIAGNOSIS (WHIPPLE’S TRIAD)
1. Symptoms consistent with hypoglycemia
o Neuroglycopenic symptoms: behavioral changes, confusion, fatigue, seizures, loss of consciousness
o Adrenergic symptoms: palpitations, tremors, anxiety, sweating
2. Low plasma glucose measured with a precise method (not a glucose monitor)
3. Relief of symptoms after the plasma glucose level is raised

III. TREATMENT
If awake initial dose of 20 g oral glucose
If unconscious or unwilling parenteral glucose 25 g, if not practical SC or IM glucagon (1.0 mg in adults)
Manage primary reason for hypoglycemia

HYPERTHYROIDISM
I. ETIOPATHOGENESIS
Consequence of excessive thyroid function

II. CLASSIFICATION
Thyrotoxicosis: clinical syndrome resulting from cellular responses to excessive thyroid hormone (may be
exogenous or endogenous)
Hyperthyroidism: clinical state resulting from increased production of thyroid hormones from the thyroid gland
itself (endogenous)
PRIMARY THYROTOXICOSIS SECONDARY THYROTOXICOSIS THYROTOXICOSIS WITHOUT
HYPERTHYROIDISM
Graves’ disease TSH-secreting pituitary adenoma Subacute thyroiditis
Toxic multinodular goiter Thyroid hormone resistance Silent thyroiditis
Toxic adenoma syndrome Thyroid destruction: amiodarone,
Functioning thyroid Ca Chorionic gonadotropin-secreting radiation, infarction of adenoma
metastasis tumors Ingestion of excess thyroid
Activating mutation of TSH Gestational thyrotoxicosis hormone (thyrotoxicosis factitia)
receptor or thyroid tissue
McCune-Albright syndrome
Struma ovarii
Drugs: iodine excess (Jod-
Basedow)

A. Graves’ Disease
Accounts for 60-80% of thyrotoxicosis
Typically occurs between 20 and 50 years of age; also occurs in the elderly
Caused by thyroid-stimulating immunoglobulin (antibodies to the receptor for TSH chronically stimulate TSH
receptor)
Diagnosis is straightforward in a patient with:
o Biochemically-confirmed thyrotoxicosis
o Diffuse goiter on palpation
o Ophthalmopathy
o Dermopathy

B. Toxic Multinodular Goiter (MNG)


Presence of functional autonomy (in contrast to nontoxic MNG)
Includes subclinical hyperthyroidism or mild thyrotoxicosis

C. Hyperfunctioning Solitary Nodule (Toxic Adenoma)


Mutations lead to enhanced thyroid follicular cell proliferation and function
Thyrotoxicosis is usually mild
Disorder is suggested by:
o Thyroid nodule: generally large enough to be palpable
o Absence of clinical features suggestive of Graves’ or other causes of thyrotoxicosis
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Radioiodine Ablation (RAI): treatment of choice

III. CLINICAL MANIFESTATIONS


SYMPTOMS SIGNS
Hyperactivity, irritability, Weight loss with increased Tachycardia Warm, moist skin
dysphoria appetite Atrial fibrillation in the Muscle weakness, proximal
Heat intolerance and Diarrhea elderly myopathy
sweating Polyuria Tremor Lid retraction or lag
Palpitations Oligomenorrhea Goiter Gynecomastia
Fatigue and weakness Loss of libido

IV. DIAGNOSTICS

A. Common Diagnostics Used:


DIAGNOSTICS COMMENTS/EXPECTED FINDINGS
Sensitive TSH analysis Single best screening test for hyperthyroidism
TSH is suppressed
Free T4 RIA Elevated (isolated T4 toxicosis is occasionally seen when hyperthyroidism is
induced by excess iodine)
Free T3 RIA Elevated (may be the only thyroid hormone elevated T3 toxicosis)
Thyroid-Stimulating Elevated (not routinely necessary)
Antibodies
Graves’ Disease: enlarged gland and increased tracer uptake that is distributed
homogenously
Toxic Adenoma: focal areas of increased uptake with suppressed tracer uptake in
Radioactive Iodine the rest of the gland
Uptake and Thyroid Toxic MNG: gland is enlarged often with distorted architecture and multiple areas
Scan of relatively increased or decreased tracer uptake
Subacute Thyroiditis: very low uptake because of follicular cell damage and TSH
suppression
Thyrotoxicosis factitia: low uptake

B. Interpretation of Thyroid Function Test Results


RESULT DIFFERENTIALS
TSH FT4
Low High Primary thyrotoxicosis: Graves’ disease, multinodular goiter, toxic adenoma
Destructive thyroiditis, excess iodine intake, excess thyroid hormone
Low Normal Subclinical hyperthyroidism (if normal FT3)
T3 toxicosis (if high FT3)
Normal / High High Secondary thyrotoxicosis: TSH-secreting pituitary adenoma or thyroid hormone
resistance syndrome

V. MANAGEMENT

A. Medical Management
CLASS EXAMPLES MECHANISM SIDE EFFECTS
Inhibit thyroid peroxidase Common side effects: rash,
Propylthiouracil (PTU) 50- (TPO), reducing oxidation urticarial, arthralgia
150 mg PO q8h and organification of iodide Rare but major side effects:
Thionamides Methimazole 10-20 mg PO Reduce thyroid antibody hepatitis, SLE-like
q8-24h levels (unclear mechanism) syndrome, agranulocytosis
Carbimazole 15-40 mg PO PTU has added benefit in (sore throat, fever, oral
OD thyroid storm (see below) ulcers)
Control adrenergic
Beta- Propranolol 20-40 mg q6h symptoms, especially in the Bradycardia, AV block,
Blockers early stages before anti- bronchospasm, hypotension
thyroid drugs take effect

186
B. Radioactive Iodine Therapy (RAI)
Damages gland through cytotoxic effects
Yields quickest resolution of the hyperthyroidism
Leads to post-procedural hypothyroidism and requires lifelong thyroid hormone replacement therapy
Carbimazole or methimazole must be stopped at least 2 days before RAI
PTU has prolonged radioprotective effect and should be stopped several weeks before RAI
Absolute contraindications: pregnancy and breast-feeding

C. Surgical Management
Now uncommonly performed, unless with coexistent thyroid cancer
Surgical candidates:
o Pregnant patients who are intolerant to medications
o Non-pregnant patients how refuse RAI
o Patients with very large goiters
o Pediatric patients
Complications include hypoparathyroidism and vocal cord paralysis

THYROID STORM
I. ETIOPATHOGENESIS
Extreme accentuation of hyperthyroidism, usually with Graves’ Disease or Toxic Multinodular Goiter
<10% of hospital admissions for thyrotoxicosis but reaches mortality rate of 20-30%

A. Pathophysiology
Point at which thyrotoxicosis transforms to storm is controversial
o No evidence that there is an increased production of T3 or T4 causing the storm
o Magnitude of increase in thyroid hormones does not appear to be critical
Increased catecholamine receptors have been noted
Decreased binding to thyroid-stimulating globulin (increased free T3/T4) is a possible mechanism

B. Precipitants of Thyroid Storm


Pre-existing thyrotoxicosis, untreated or partially treated
Surgery (e.g., poorly prepared thyroidectomy in a patient with diffuse toxic goiter)
Other conditions associated with a rapid rise in hormone levels
o Withdrawal of anti-thyroid drug therapy
o Radioiodine therapy
o Vigorous thyroid palpation
o Iodinated contrast dyes
o Salicylates (competes with albumin binding thus increasing free thyroid hormone levels)
Conditions associated with an acute or subacute non-thyroidal illness: infection, stroke, trauma, DKA

II. DIAGNOSIS (Burch and Wartofsky’s Criteria)


A. Thermoregulatory Dysfunction D. Cardiovascular Dysfunction
37.2 – 37.7oC 5 1. Tachycardia (bpm)
37.8 – 38.2oC 10 99 - 109 5
38.3 – 38.8oC 15 110 – 119 10
38.9 – 39.3oC 20 120 – 129 15
39.4 – 39.9oC 25 130 – 139 20
> 40.0oC 30 > 140 25
B. Central Nervous System Effects 2. Congestive Heart Failure / Atrial Fibrillation
Absent 0 Absent 0
Mild (agitation) 10 Mild (pedal edema) 5
Moderate (delirium, psychosis, extreme 20 Moderate (bibasilar rales) 10
lethargy)
Severe (seizure, coma) 30 Severe (pulmonary edema) 15
C. Gastrointestinal-Hepatic Dysfunction Atrial Fibrillation 10
Absent 0 3. Precipitant History
187
Moderate (diarrhea, vomiting, abdominal 10 Negative 0
pain)
Severe (unexplained jaundice) 20 Positive 10
INTERPRETATION
<25 Storm unlikely 25-44 Impending Storm >45 Highly suggestive of storm

IV. MANAGEMENT
Goals of Management
o Stop synthesis of new thyroid hormones
o Halt release of preformed thyroid hormones
o Prevent conversion of T4 to T3
o Control adrenergic symptoms associated with thyrotoxicosis
o Control systemic decompensation
o Treat underlying cause
MECHANISM DRUG DOSE ACTION
Inhibits thyroid peroxidase (TPO)
Inhibition of 600-1000 mg LD and Inhibits peripheral conversion of T4 to T3 on
new PTU 200-300 mg q6h high doses
hormone PO/NGT/PR Decreases circulating TSI
production Restores normal suppressor cell activity
Methimazole 20-25 mg PO q6h Inhibits thyroid peroxidase (TPO)
Supersaturated 5 drops q6h 1 hour after
Inhibit Solution of PTU (Wolff-Chaikoff
preformed Potassium Iodide Effect) Blocks thyroid hormone release
hormone (SSKI) Decrease fractional turnover of thyroid iodine
release Lugol’s Solution 4-8 drops PO q6-8h and T4 secretion rate
Sodium ipodate 1-3 g PO QID
Iopanoic acid 1 g PO q8h
60-80 mg PO q4g or 80- Reduces sympathetic overdrive
Control of Propranolol 120 mg q6h High doses also decrease peripheral
adrenergic conversion of T4 to T3
symptoms Atenolol 50-200 mg PO QID Cardioselective
Metoprolol 100-200 mg (may be used in COPD and asthma)
Esmolol 50-100 mcg/kg/min
Acetaminophen 325-650 mg PO q4-6h
Supportive Hydrocortisone 100 mg IV q8 Decreases peripheral conversion of T4
management Addresses relative adrenal insufficiency
Glucose 5-10% solution
Mimics iodine
Lithium 300 mg PO q8h Inhibits coupling of iodotyrosinases and
Alternatives peripheral conversion of T4
Potassium 1 g PO QID
perchlorate
cholestyramine 4 g PO QID Hastens removal of T4 and T4 from serum

HYPOTHYROIDISM
I. ETIOPATHOGENESIS
Results from undersecretion of thyroid hormone
Iodine deficiency remains the most common cause worldwide
Most common causes in areas of iodine insufficiency: autoimmune disease (Hashimoto’s thyroiditis) & iatrogenic
Secondary causes include pituitary and hypothalamic disease

188
II. CLINICAL MANIFESTATIONS
SYMPTOMS SIGNS
Tiredness, weakness
Dry skin Dry coarse skin
Cold intolerance Cool peripheral extremities
Hair loss Puffy face, hands and feet (myxedema)
Difficulty concentrating and poor memory Diffuse alopecia
Constipation Bradycardia
Weight gain with poor appetite Peripheral edema
Dyspnea & hoarse voice Delayed tendon reflex relaxation
Menorrhagia (later oligomenorrhagia or amenorrhea) Carpal tunnel syndrome
Paresthesia Serous cavity effusions
Impaired hearing
Arranged in Decreasing Order of Frequency

III. COMMON DIAGNOSTICS

A. Common Diagnostics Used:


DIAGNOSTICS COMMENTS/EXPECTED FINDINGS
Sensitive TSH analysis Elevated in primary hypothyroidism
May be normal in secondary hypothyroidism (pituitary disease)
Free T4 Low in primary hypothyroidism
May be normal in mild hypothyroidism
Thyroid autoantibodies May be noted in autoimmune etiologies
Thyroid scan ultrasound To determine the specific cause of hypothyroidism

B. Interpretation of Thyroid Function Test Results


RESULTS DIFFERENTIALS
TSH FT4
High Normal Mild hypothyroidism
High Low Primary hypothyroidism
Autoimmune hypothyroidism (if thyroid autoantibodies are positive)
Normal Low Drug effects, sick euthyroid syndrome, pituitary disease

IV. MANAGEMENT: LEVOTHYROXINE (LT4)


A. Dosage
Start usually with 25-50 mcg/day (1.6 mcg/kg/day)
Use lower dosages of 12.5-25 mcg for patients >60 y/o and those with cardiac disease

B. Duration
Symptoms improve in weeks; lifelong treatment is necessary
Increase dose by 25-50mcg every 4 weeks until patient is clinically and biochemically euthyroid

C. Monitoring
Monitor plasma TSH q3-4 months (maintain in normal range)
For secondary hypothyroidism, monitor serum T4 and other pituitary hormones and give steroid replacement prior
to LT4

GOITER AND NODULAR THYROID DISEASE

I. ETIOPATHOGENESIS
Goiter is defined as an enlarge thyroid gland
Causes include biosynthetic defects, iodine deficiency, autoimmune disease and nodular diseases

II. CLASSIFICATION

A. Diffuse Non-Toxic (Simple or Colloid) Goiter


189
Diffuse enlargement of the thyroid occurs in the absence of nodules and hyperthyroidism
Thyroid function is preserved and most patients are asymptomatic
Pemberton’s sign: symptoms of faintness with facial congestion and external jugular venous obstruction when
arms are raised above the head
Levothyroxine can be started to suppress the TSH into the low-normal, but detectable, range

B. Non-Toxic MNG
Most are asymptomatic
Thyroid architecture is distorted and multiple nodules can be appreciated

C. Toxic MNG
Presence of functional autonomy in contrast to non-toxic MNG
TSH is low, T4 level is normal or minimally increased, and T3 is often elevated to a greater degree than T4
Antithyroid drugs often given with beta-blockers can normalize thyroid function

III. APPROACH TO A THYROID NODULE

Thyroid Ablate, resect or


Scan “Hot” Nodule medically manage

Surgery if further growth


or suspicious cytology
Low “Cold”
TSH Nodule
or
Released by
Intermediate Non inadequate “Hot”
Solitary or Diagnostic Monitor
Nodule

Suspicious TSH (17%) by US


Nodule
Normal Benign
TSH
(69%)
Consider
US Guided Cytopathology Thyroid
FNA Suspicious Scan
or Follicular “Cold” or
(10%) Intermediate

Surgery
Malignant
(4%)

190
OSTEOPOROSIS
I. ETIOPATHOGENESIS AND DIAGNOSIS
A reduction in the strength of bone that leads to an increased fracture risk
Diagnosed based on WHO classification criteria for bone mass using dual-energy x-ray absorptiometry (DXA) as
gold standard
Presence of vertebral fractures on either radiograph or VFA examination confirms clinical diagnosis of
osteoporosis
Recommended DXA sites: femoral neck or total femur and/or lumbar spine (distal third of radius if cannot
evaluate spine/hips)
Peripheral BMD technologies (quantitative UTZ, CT scan, single x-ray absorptiometry) done in sites like the
calcaneus, wrist and metatarsals and bone turnover markers should not be used in the diagnosis of osteoporosis
(but can be used in fracture risk assessment and assessing adherence to and effectiveness of therapy)
BONE MINERAL DENSITY (T-Score)
Normal > -1 SD
Osteopenia / Low bone mass Between -1 and -2.5 SD
Osteoporosis < -2.5 SD
Severe osteoporosis < -2.5 SD and > 1 fragility fracture/s

II. SCREENING

A. Osteoporosis Screening Tool for Asian (OSTA)


Used to identify an individual’s risk for osteoporosis in areas where DXA is not widely available

Weight (kg) 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-94
(lbs) 88-98 99-109 110-119 120-130 131-141 142-152 153-164 165-174 175-185 186-196 197-208
Age
40-44
45-49
50-54
55-59 LOW
60-64
65-69
70-74
75-79 MEDIUM
80-84
85-89 HIGH
90-94
95-99
A simple tool to identify Asian women at increased risk of osteoporosis.

B. Fracture Risk Assessment Tool (FRAX)


Used to assess fracture probability in all postmenopausal women with at least one WHO risk factor, prior to
undergoing central DXA:
o Low BMI
o Previous fragility fracture
o Parental history of hip fracture
o Glucocorticoid treatment
o Current smoking
o Alcohol intake (at least 3 units/day)
o Rheumatoid arthritis
o Other secondary causes of osteoporosis (e.g., CKD, liver disease, malabsorption, IBD, hypogonadism,
hyperparathyroidism, Cushing’s disease, COPD, androgen deprivation therapy, malignancies)

C. Indications for Bone Density Testing (consider BMD testing):


Women > 65 years and men > 70 years (regardless of risk factors)
Younger postmenopausal women, women in menopausal transition and men 50-69 years with risk factors for
fracture
Adults who have a fracture after age 50
191
Adults with a condition associated with low bone mass or bone loss (e.g., RA, on steroids > 3 months)

III. MANAGEMENT OF OSTEOPOROSIS

A. Indications to Treat
IF WITH BMD MEASUREMENT, TREAT IF: IF WITHOUT BMD MEASUREMENT, TREAT IF:
Vertebral compression fracture evident on VFA or Belongs to high-risk category based on OSTA tool
confirmed through radiograph (clinical where central BMD cannot be done or not available
osteoporosis) 10-year probability of hip fracture >3% or any major
BMD T-score of < -2.5 SD osteoporosis related fracture >20% based on FRAX
estimates

B. Pharmacologic Therapies
Biphosphonates
Hormonal replacement therapy
Selective estrogen receptor modulators (SERM)
Strontium ranelate
Parathyroid hormone or its analog (teriparatide)
Calcitonin
Tibolone
RANKL inhibitor (denosumab)
Vitamin D or its analog, in combination with calcium, is used as mandatory adjunct

IV. PREVENTION
Calcium supplementation at least 750-800 mg daily for a minimum of 2 years to prevent bone loss
Calcium Vitamin D3 10-20 mcg to be given with 1000 mg calcium, especially for those with limited sun
exposure
Exercise Supervised high intensity resistance exercise (8-12 repetitions at least 2-3 days/week)
Moderate levels of walking (24 METs/week or 8 h/week of walking at an average pace)
Lifestyle Smoking cessation and limiting alcohol consumption

MULTIPLE ENDOCRINE NEOPLASIA (MEN)


MEN 1 MEN 2
MEN 2A MEN 2B
Parathyroid hyperplasia / adenoma Medullary thyroid carcinoma
Pancreatic islet cell hyperplasia / Pheochromocytoma Medullary thyroid carcinoma
adenoma / carcinoma Parathyroid hyperplasia/adenoma Pheochromocytoma
Pituitary hyperplasia / adenoma MEN 2A + cutaneous lichen Mucosal and gastrointestinal
amyloidosis neuromas
Less common manifestations: foregut MEN 2A + Hirschprung’s disease Marfanoid features
carcinoid, pheochromocytoma, Familial medullary thyroid carcinoma
subcutaneous or visceral lipomas

CUSHING’S SYNDROME
I. ETIOPATHOGENESIS
Constellation of clinical features that result from chronic exposure to excess glucocorticoids of any etiology
Iatrogenic use of glucocorticoids (for immunosuppression or treatment of inflammatory disorders) is the most
common cause
Cushing’s disease refers specifically to Cushing’s syndrome caused by a pituitary corticotrope adenoma

II. CLASSIFICATION

A. ACTH-Dependent
Means that Cushing’s syndrome is due to excess ACTH
192
Possible sources of ACTH excess:
o Pituitary corticotrope adenoma (Cushing’s disease)
o Ectopic secretion of ACTH by nonpituitary tumor (paraneoplastic syndrome)

B. ACTH-Independent
Means that Cushing’s syndrome is not due to excess ACTH
Majority of patients with ACTH-independent cortisol excess harbor a cortisol-producing adrenal adenoma
Other causes include adrenocortical carcinoma and nodular adrenal hyperplasia

III. CLINICAL FEATURES


BODY COMPARTMENT/SYSTEM SIGNS AND SYMPTOMS
Body fat Weight gain, central obesity, rounded face, fat pad on back of neck (“buffalo
hump”)
Skin Facial plethora, thin and brittle skin, easy bruising, broad and purple stretch
marks, acne, hirsutism
Bone Osteopenia, osteoporosis (vertebral fractures)
Decreased linear growth in children
Muscle Weakness, proximal myopathy (prominent atrophy of gluteal and upper leg
muscles)
Cardiovascular System Hypertension, edema, atherosclerosis
Metabolism Glucose intolerance/diabetes, dyslipidemia, hypokalemia
Reproductive System Decreased libido, amenorrhea in women (duet to cortisol-mediated inhibition of
gonadotropin release)
Central Nervous System Irritability, emotional lability, depression, cognitive defects, paranoid psychosis
in severe cases
Blood and immune System Increased susceptibility to infections, leukocytosis with eosinopenia and
lymphopenia, hypercoagulability

MINERALOCORTICOID EXCESS
Excess activation of mineralocorticoid receptor leads to:
o Potassium depletion (hypokalemia)
o Increased sodium retention (expansion of extracellular and plasma volume hypertension)
Most common cause is primary hypertension
Clinical hallmark is hypokalemic hypertension
Conn’s Syndrome = aldosterone-producing adrenal adenoma

PITUITARY DISEASES
DISEASE PATHOPHYSIOLOGY CLINICAL MANIFESTATIONS TREATMENT
Frontal bossing Transphenoidal surgery (TSS)
Increased hand and Somatostatin analogs
mandibular enlargement with (Octreotidem, Lanreotide)
Acromegaly Growth hormone prognathism GH receptor antagonist
excess Widened space between (Pegvisomant)
lower incisors Dopamine agonists
Gigantism in children and (Cabergoline, Bromocriptine)
adolescents radiation
Prolactin-producing Galactorrhea Dopamine agonists
Hyperprolactinemia pituitary tumor Amenorrhea (Cabergoline, Bromocriptine)
(prolactinoma), stalk Infertility Surgery (TSS)
compression
Obesity Surgery (selective TSS)
Thick skin Pituitary irradiation
Cushing’s Disease ACTH-producing Moon facies Ketoconazole
adenoma Hypertension Metyrapone
Purple skin striae Mitotane
193
Hirsutism
Menstrual disorders
Acne
Bruising
Truncal obesity
Proximal muscle weakness
Oligomenorrhea
Amenorrhea
Infertility
Decreased vaginal secretions
Gonadotropin Decreased libido and potency Hormone replacement
Hypogonadism deficiency Infertility, decreased muscle (testosterone, estrogen,
mass progesterone)
Reduced beard and body hair
growth
Soft testes
Fine facial wrinkles

III. TESTS OF PITUITARY INSUFFICIENCY


HORMONE TEST INTERPRETATION
Insulin Tolerance Test Insulin-induced hypoglycemia should normally induce a rise in GH;
Growth lack thereof suggest GH deficiency
Hormone GHRH test, L-arginine Normal response is a rise in GH
test, L-dopa test Lack thereof suggest GH deficiency
Prolactin TRH test TRH should normally induce a rise in prolactin levels
Insulin Tolerance Test Insulin-induced hypoglycemia induces a rise in ACTH and
subsequently cortisol
CRH test Lack of rise in both ACTH and cortisol suggests ACTH deficiency
Metyrapone blocks cortisol synthesis causing decreased cortisol and
ACTH Metyparone Test increased ACTH
Lack of rise in ACTH suggests ACTH deficiency
Standard ACTH Normal response is an increase in cortisol
Stimulation (Co-syntropin) Lack of rise in cortisol plus low ACTH suggests ACTH deficiency
Test
Basal Thyroid Function TSH normally induces a rise in T3 and T4 levels
Tests: T4, T3, TSH Low TSH with low free thyroid hormones indicate TSH deficiency
TSH Normal response is a rise in TSH (unless thyroid hormone levels are
TRH Test increased)
Lack thereof suggest TSH deficiency
Basal LH and FSH should normally be increased in postmenopausal
LH, FSH, Testosterone, women
LH, FSH Estrogen Low sex hormones in the setting of low LH and FSH indicate pituitary
insufficiency
GnRH Test Normal response is a rise in FSH and LH (most adults); lack thereof
suggests pituitary insufficiency

194
CHAPTER 8
NEPHROLOGY
I. Introduction to Nephrology
II. Fluids and Electrolytes
1. Water Balance
2. Sodium
3. Potassium
4. Calcium
5. Magnesium
6. Bicarbonate
III. Common Renal Conditions
1. Abnormalities in Nephrology
2. Acute Kidney Injury
3. Chronic Kidney Disease
4. Urinary Tract Infections
5. Nephrolithiasis
6. Renal Tubular Acidosis
7. Glomerular Diseases

195
SECTION 1
INTRODUCTION TO NEPHROLOGY
NEPHROLOGY FORMULAS
ANION GAP (SERUM)
Na+ = serum sodium
Anion Gap = Na – (Cl + HCO3) Cl- = serum chloride
HCO3 = serum bicarbonate
ANION GAP (URINE)
Na+ = urine sodium
Urine Anion Gap = Na + K – Cl K+ = urine potassium
Cl- = urine chloride
BUN CREATININE RATIO
BUN = serum BUN in mmol/L
Crea = serum creatinine in umol/L
BUN
BCR = Crea x 247 Interpretation:
Pre-renal azotemia: BCR > 20:1
Oliguric renal failure: BCR 10-15:1
ESTIMATED CREATININE CLEARANCE (COCKROFT – GAULT FORMULA)
(140 – age) x BW BW = body weight in kg
Crea = serum creatinine in mg/dL
CrCl = 72 x Crea *For females, multiply result by 0.85

SERUM OSMOLALITY
Balance between the water and the chemicals dissolved in blood
Find out if severe dehydration or overhydration is present

SERUM OSMOLALITY
Serum Osmolality = 2(Na + K) + RBS + BUN
Na+ = serum sodium; K+ = serum potassium; RBS = serum random blood sugar in mmol/L
BUN = serum BUN in mmol/L

Interpretation:
Normal osmolality: 280 – 295 mosmol/kg
Increased serum osmolality’ dehydration, poorly controlled DM (DKA, HHS), diabetes insipidus
Decreased serum osmolality: overhydration, diuretic use, SIADH

URINE OSMOLALITY (ESTIMATE)


Measure of urine concentration
Large values indicate concentrated urine (i.e., heart failure, dehydration, shock, SIADH)
Small values indicate diluted urine (e.g., diabetes insipidus, renal tubular necrosis, renal failure, pyelonephritis)
URINE OSMOLALITY (ESTIMATE)
Urine Osmolality = (Urine SG – 1) x Urine SG = urine specific gravity
Normal 24-hour urine osmolality = 50-800 mOsm/kg
40,000
FRACTIONAL EXCRETION OF SODIUM (FE Na)
Urine Na+ = urine sodium
Plasma Na+ = plasma sodium
Urine Na x Plasma Crea Urine Crea = urine creatinine
FE Na = Plasma Na x Urine Crea Plasma Crea = plasma creatinine
Interpretation:
FENa < 1%: seen in pre-renal azotemia
FENa > 2%: seen in oliguric acute renal failure
196
WATER EXCESS
Water excess = (0.6 x BW in kg) - 0.6 x BW in kg x Actual Na BW = body weight in kg
Na+ = serum sodium
Desired Na
CORRECTED CALCIUM
Calcium must be “corrected” when the albumin is abnormal
This is to correct for the change in total calcium due to the change in albumin-bound calcium/
Corrected Calcium = Actual Ca + [(40 – Albumin) x 0.02] Actual Ca+ = serum calcium in mmol/L
Albumin = serum albumin in g/L
CORRECTED SODIUM
In marked hyperglycemia, ECF osmolality increases
Serum Na+ falls in proportion to ECF dilution, declining 1.6 mEq/L per 100 mg/dL increase in RBS
Corrected Sodium = Actual Na + 0.016 (RBS – 100) Actual Na+ = serum sodium
RBS = random blood sugar in mg/dL

OVERVIEW OF ELECTROLYTE CORRECTION


Hyponatremia
Na deficit = (Desired Na – Actual Na) x BW in kg x 0.6
Hypokalemia
Potassium deficit = Desired K – Actual K 100%
0.27
Hypernatremia (Water Deficit)
Water deficit = Na – 140 x TBW TBW in Males = 0.6 x Body Weight in kg
140 TBW in Females = 0.5 x Body Weight in kg
Bicarbonate Deficit
Bicarbonate deficit = (Desired HCO3 – Actual HCO3) x BW in kg x 0.4

197
SECTION 2
FLUIDS AND ELECTROLYTES
WATER BALANCE
I. COMPOSITION OF BODY FLUIDS
Water is the most abundant constituent in the body [50% of body weight in women and 60% in men]
Total body water (TBW): 55-75% intracellular fluid (ICF) and 25-45% extracellular fluid (ECF)
ECF: 25% intravascular [plasma water] and 75% extravascular [interstitial]
Fluid movement between spaces determined by Starling forces
Osmolality: solute or particle concentration of a fluid (mosmol/kg of water)
o Major ECF particles: Na+, Cl-, HCO3
o Major ICF particles: K+, organic phosphate esters
o Effective osmoles: solutes restricted to ECF or ICF and thus determine the effective osmolality of that
compartment
o Ineffective osmoles: solutes that do not contribute to water shifts (e.g., urea) across most membranes

II. HYPOVOLEMIA

A. Causes of Hypovolemia
RENAL CAUSES EXTRARENAL CAUSES
Osmotic diuresis (e.g., mannitol)
Pharmacologic diuresis/natriuresis (e.g.,
furosemide) Fluid loss from GI tract (e.g., impaired GI reabsorption,
Hereditary defects in renal transport proteins, enhanced fluid secretion)
mineralocorticoid defects (e.g., deficiency, Insensible losses (evaporation of water from skin and
resistance) respiratory tract)
Tubulointerstitial injury (e.g., interstitial nephritis, Accumulation of fluid within specific tissue compartments
acute tubular injury, obstructive uropathy) (e.g., interstitium, peritoneum, GI tract)
Excessive renal water excretion (e.g., diabetes
insipidus)

B. Clinical Manifestations
Nonspecific: fatigue, weakness, thirst, postural dizziness, oliguria, cyanosis, abdominal and chest pain, confusion,
obtundation
May be accompanied by symptoms of additional electrolyte abnormalities

C. Physical Examination Findings


LESS RELIABLE MORE RELIABLE
Decreased jugular venous pressure (JVP)
Diminished skin turgor Orthostatic hypotension
Dry oral mucous membranes Orthostatic tachycardia
In severe cases: peripheral cyanosis, cold extremities,
oliguria, altered mental status

D. Diagnostics
DIAGNOSTICS EXPECTED FINDINGS
Increased due to a decrease in glomerular filtration rate (GFR)
Serum BUN, Creatinine Creatinine is more dependable since BUN is influenced by changes in
tubular reabsorption (prerenal azotemia), catabolic states, hyperalimentation,
GI bleeding and protein intake
Serum Aminotransferases May be elevate in hypovolemic shock from hepatic ischemia
(AST, ALT)
Cardiac Biomarkers May be elevated in hypovolemic shock from cardiac ischemia
Routine Chemistries and/or Will reveal acid-base disorders depending on the etiology and severity of
Arterial Blood Gases hypovolemia (e.g. normal anion gap metabolic acidosis from diarrheal illness,
elevated anion gap metabolic acidosis from lactic acidosis)
198
E. Management involves Restoration of Normovolemia and Replacement of Ongoing Losses
Mild hypovolemia: oral hydration and resumption of normal maintenance diet
Severe hypovolemia: IV hydration
CLINICAL SCENARIO APPROPRIATE MANAGEMENT
Normonatremic / Normal saline (0.9% NaCl) is the most appropriate resuscitation fluid
Hyponatremic Patients
Hypotonic solutions:
Hypernatremic Patients o 5% dextrose if water loss only (e.g. diabetes mellitus)
o Hypotonic saline if both water and Na+-Cl loss
Patients with Bicarbonate IV bicarbonate (150 mEq of NaHCO3 in 5% dextrose)
Loss and Metabolic Acidosis
Patients with Severe pRBC transfusions without increasing hematocrit beyond 35%
Hemorrhage or Anemia

SODIUM
Disorders are due to abnormalities in water homeostasis that lead to changes in the relative ratio of sodium to boy
water (the absolute plasma sodium concentration tells nothing about a patient’s volume status)

I. HYPONATREMIA
Defined as plasma Na+ <135 mM
Almost always due to increased circulating AVP and/or increased renal sensitivity to AVP combined with any
intake of free water (exception is hyponatremia due to low solute intake, e.g. beer potomania)
Causes generalized cellular swing

A. Approach to and causes of Hyponatremia


HYPOVOLEMIC HYPONATREMIA EUVOLEMIC HYPERVOLEMIC HYPONATREMIA
HYPONATREMIA
Decrease in total body sodium greater Subclinically volume Increase in total body water greater than
than decrease in total body water expanded patients increase in total body sodium
UNa >20 mM UNa <20 mM UNa >20 mM UNa >20 mM UNa <20 mM
Renal losses
Diuretic excess Extrarenal
Mineralocorticoid losses Glucocorticoid deficiency
deficiency Vomiting Hypothyroidism
Salt-losing deficiency Diarrhea Stress Nephrotic
Bicarbonaturia with Third Drugs Acute or chronic syndrome
RTA and metabolic spacing of Syndrome of renal failure Cirrhosis
alkalosis fluids inappropriate antidiuretic Cardiac failure
Ketonuria Burns hormone (SIADH)
Osmotic diuresis Pancreatitis secretion
Cerebral salt wasting Trauma
syndrome

B. Clinical Manifestations (primarily neurologic)


Early symptoms: nausea, headache and vomiting
Severe cases: seizures, brainstem herniation, coma and death
Key complication is normocapnic or hypercapnic respiratory failure (associated hypoxemia may amplify
neurologic injury)

C. Management
1. Clinical Assessment should Focus on the Underlying Cause:
Check for intake of drugs and supplements
Assessment of volume status (see above) is central to the diagnostic approach
Consider all possible causes of excessive circulating AVP

2. Major Considerations in Management


Presence/severity of symptoms determine the urgency and goals of therapy
199
Patients with chronic hyponatremia are at risk for osmotic demyelination syndrome (ODS) if plasma
Na+ corrected >8-10 mM within the first 24 hours and/or by >18mM within the first 48 hours
Response to therapy is unpredictable: ergo, frequent Na monitoring is needed
Once therapy instituted, focus on treatment or withdrawal of underlying cause

D. Correcting Sodium Deficit and Hyponatremia (Sample Problem)


CORRECT SODIUM DEFICIT SAMPLE CASE
1. Compute for the sodium deficit AP, 60/M, 60 kg, complaining of 3-day history of diarrhea.
Na deficit = (desired Na – actual Na) x BW in kg x 0.6 Serum Na+ 123. Ongoing losses of 200 cc/LBM, -8
*desired Na is usually pegged at 125-135 mEq/L
times/day [Na+ losses in LBM = 25-50 mEqs/L)
2. Compute for the time needed to infuse Na deficit = (133 – 123) x 60 x 0.6 = 360 + 80 mEqs/L
Desired Na – Actual Na
Time needed in infuse = 0.5 mEq / hr
*Desired Na of 133 was calculated by adding 10 mEqs to actual Na + (limit
L
to prevent ODS). We add another 80 mEqs/L deficit to our calculated
value since our patient has ongoing losses of 1.6L LBM/day, equivalent to
3. Compute for the amount of pNSS needed 80 mEqs per day.
Amount of pNSS needed = Computed Na deficit / 154
133 - 123
Time needed to infuse = 0.5 mEqs / hr = 20 hours
4. Calculate the drip rate L
Amount of pNSS needed
Drip rate = time needed to infuse
Amount of pNSS needed = 440 / 154 = 2.9 L

Drip rate = 2.9L / 20 hours = 145 cc/hour


Sample chart order: Start pNSS 1L x 145 cc/hr for a total of 3 liters, re-check serum sodium q6 to 12 hours

II. HYPERNATREMIA
Defined as an increase in plasma Na+ concentration to >145mM
Usually the result of a combined water and electrolyte deficit, with losses of water in excess of those of sodium

A. Causes
GI water loss / diarrhea: most common gastrointestinal cause
Insensible water loss
Renal water loss: osmotic diuresis from hyperglycemia, excess urea, post-obstructive diuresis, mannitol
Diabetes insipidus

B. Symptoms
Symptoms are explained by cellular shrinkage due to efflux of intracellular water
Primarily neurologic: change in sensorium is the most common manifestation

C. Management
Central to the management is correction of the underlying cause:
o Chronic hypernatremia (>48 hours): correction must be carried out slowly to avoid central cerebral edema
(e.g., correct deficit over 48 hours); plasma sodium should not be corrected >10 mM/d
o Acute hypernatremia due to sodium loading can be safely corrected at the rate of 1 mM/h
Water, as much as possible, must be administered per orem or by NGT
Alternatively, D5W can be used with corresponding CBG monitoring

D. Correcting Hypernatremia (Sample Problem)


CORRECT WATER DEFICIT SAMPLE CASE
1. Compute for the water deficit JR, 80/M, 50 kg, bedridden patient presented with
decrease in sensorium at the ER. Na was 155. 24-hour
Water deficit =Na – 140 TBW urine tests showed 1800 cc volume, urine Na+ of 35, urine
140 K+ 72.
Total body water (TBW) is 50% of body weight in
Water deficit = 155 – 140 x 50 x 0.6 = 3.2 L
women and 60% in men
140
2. Compute for ongoing water losses (optional) aka
electrolyte-free water clearance CeH2O = 1.8 (1 – 35 + 72) = 0.4 L
155

200
CeH2O = Urine Volume (1 – Urine Na + Urine K)
Insensible losses = 10 x 50 = 0.5 L
Plasma Na

3. Compute for insensible losses = ~10 mL/kg/day We therefore correct the water deficit of 3.2 L over 48 hours
(less if ventilated, more if febrile) which is roughly 67 cc/hr (1.6 L/day) of free-water
replacement + 0.9 L per day to account for ongoing water
4. Correct the deficit over 48-72 hours (incorporate losses and insensible losses.
insensible losses and ongoing water losses to daily
water replacement) avoiding correction of >10 mM/day

Sample chart order:


Choice 1: Replacement via enteral route: Give 270 cc free-water flushes q6 after feeding
Choice 2: Replacement via parenteral route: to start IVF D5W (or 0.3 NaCl) 1 L x 67 cc/hr
Please do serum sodium q6

POTASSIUM
I. HYPOKALEMIA
Defined as plasma K+ <3.6 mM
Long-standing hypokalemia may predispose to acute kidney injury and lead to ESRD

A. Causes of Hypokalemia
DECREASED INTAKE CELLULAR REDISTRIBUTION INCREASED LOSS
Metabolic alkalosis Non-renal
Insulin o Gastrointestinal loss (diarrhea)
B2-adrenergic activation o Integumentary loss (sweat)
(bronchodilators, tocolytics)
Alpha-adrenergic antagonists Renal
Thyrotoxic periodic paralysis o Increased distal delivery (diuretics,
Starvation Downstream stimulation of Na/K osmotic diuresis, salt-wasting
Clay ingestion ATPase pump (theophylline, nephropathies)
caffeine) o Increased potassium secretion
Anabolic state: vitamin B12 or folic Mineralocorticoid excess
acid administration, GM-CSF, TPN Distal delivery of
Familial hypokalemic periodic nonreabsorbed anions
paralysis (vomiting, NGT suction,
proximal RTA, DKA)
Magnesium deficiency

B. Clinical Manifestations
History: medications, diet, and/or symptoms pointing to a probable cause such as diarrhea and periodic weakness
Presents as cardiac, skeletal and intestinal disturbances
o Muscle weakness and paralysis due to hyperpolarization of skeletal muscles
o Ileus secondary to paralytic effects on intestinal smooth muscle cells
ECG changes include broad flat T waves, ST depression and QT prolongation (usually prominent at levels <2.7
mmol/L)
Predisposes to digoxin toxicity

C. Transtubular Potassium Gradient (TTKG)


TTKG >4 during hypokalemia points to renal loss
The transtubular potassium gradient (TTKG) can also be computed using the following formula

Urine K x Serum Osm


TTKG = Serum K Urine Osm

201
D. Management
1. Goal of Therapy
Prevent life-threatening and/or chronic consequences
Replace the potassium deficit
Correct the underlying cause and/or mitigate future hypokalemia

2. Correcting the Potassium Deficit


Urgency of therapy depends on severity of hypokalemia, associated clinical factors & rate of decline
Oral replacement is the mainstay of therapy
Concomitant magnesium deficiency should always be corrected

E. Correcting Hypokalemia (Sample Problem)


CORRECTING POTASSIUM DEFICIT SAMPLE CASE
1. Calculate for potassium deficit JR, 24/M, presented at the ER with bilateral lower extremity
weakness. His siblings share the same symptoms, which
Desired K – Actual K 100% according to them occur usually after heavy meals. Serum
Potassium deficit = 0.27
K+ was noted to be 2.5 mM.
*This formula is used for non-redistributive hypokalemia. For other
cases, the potassium deficit is estimated as 400-800 mmol reduction 3.5 – 2.5
for a 2.0 mM fall in serum K. Potassium deficit = 0.27 100% = 370 mEqs

2. Target K+ for cardiac patients is usually 4.0; Since our patient can actually tolerate feeding, we prefer
otherwise a target of 3.5 is used. the oral route.
If we prefer to correct purely via the oral route we
3. Oral K correction is the preferred therapy for can provide the deficit using 10% oral KCl solution
hypokalemia. The IV route is limited to patients unable (30 cc = 40 mEqs K+). With this formulation, we can
to utilize the enteral route or in the setting of severe give 30cc of 10% oral KCl for a total of 9 doses at
complications (e.g., paralysis, arrhythmia). QID intervals.
Alternatively, to speed up the correcition, we can
4. Use saline solutions rather than dextrose since correct using the oral and IV route simultaneously
dextrose-induced increase in insulin can acutely o pNSS 1L + 30 mEqs KCl x 8 hrs x 3 cycles
exacerbate hypokalemia. (=90 mEqs/day)
o oral KCl 10% solution 30 cc TID x 7 cycles
5. The peripheral IV dose is usually 20-40 mmol of KCl (=120 mEqs/day)
per liter; higher concentrations can cause chemical
phlebitis, irritation and sclerosis. If hypokalemia is There are no hard and fast rules in choosing the method of
severe, IV KCl may be given through a central vein correction, always rely on clinical judgment!
(femoral veins are preferable) with cardiac monitoring
at rates of 10-20 mmol/hour.

6. Careful monitoring of serum K+ during correction.

II. HYPERKALEMIA
Defined as plasma K+ > 5.5mM
A decrease in renal potassium excretion is the most common cause

A. Causes
“PSEUDO” HYPERKALEMIA INTRA- TO EXTRACELLULAR SHIFT INADEQUATE EXCRETION
Acidosis Inhibition of the RAAS
Hyperosmolality (radiocontrast, ACE inhibitors / ARBs / direct renin
hypertronic dextrose, mannitol) inhibitors
Cellular efflux (thrombocytosis, Beta-adrenergic antagonists Blockade of mineralocorticoid
erythrocytosis, leukocytosis, in (noncardioselective agents) receptors (spironolactone,
vitro hemolysis) Digoxin and related glycosides eplerenone)
Hereditary defects in red cell Hyperkalemia periodic paralysis Blockade of ENaC (amiloride,
membrane transport Lysine, arginine, aminocaproic acid triamterene)
Succinylcholine, thermal trauma, Decreased distal delivery
neuromuscular injury, disuse CHF
atrophy, mucositis or prolonged Volume depletion
202
immobilization Hyporeninemic hypoaldosteronism
Rapid tumor lysis Tubulointerstitial disease
Diabetes
Drugs (NSAIDs, COX-2 inhibitors,
beta blockers, cyclosporine,
tacrolimus)
Advanced age
Renal resistance to mineralocorticoid
Tubulointerstitial diseases
Hereditary (defects in ENaC)
Advanced renal insufficiency (CKD,
ESRD, AKI)
Primary adrenal insufficiency

B. Clinical Manifestations
Clinical manifestations are predominantly cardiac in nature
Associated cardiac arrhythmias include sinus bradycardia, sinus arrest, slow idioventricular rhythms, ventricular
tachycardia, ventricular fibrillation and asystole
Classic ECG findings are:
o Tall peaked T waves (5.5-6.5 mM)
o Loss of P waves (6.5-7.5 mM)
o Widened QRS complexes (7-8 mM)
o Sinusoidal pattern (>8 mM)

C. Management
The first priority is assessment of need for emergency treatment followed by comprehensive workup:
o ECG manifestations should be considered as an emergency
o Patients with plasma K+ >6.5, even without ECG changes, should be managed aggressively
o Patients should be placed on continuous cardiac monitoring
The management of hyperkalemia is divided into stages:

1. Cardioprotection (from arrhythmic effects of hyperkalemia)


Calcium raises the action potential threshold and reduces excitability without changing the resting
membrane potential
10 mL of 10% calcium gluconate IV over 2-3 mins with cardiac monitoring
Effect starts in 1-3 minutes and lasts 30-60 minutes
Dose should be repeated if there is no change in ECG findings or if they recur

2. Cellular Redistribution (shifts K+ inside the cells)


TREATMENT DOSING PHARMACOKINETICS OTHERS
Hypoglycemia is a common side
10 units regular insulin + Effect in 10-20 mins effect, therefore follow with D10W
Insulin D50-50 Peaks at 30-60 mins at 5075 ml/h
Lasts for 4-6 hours If glucose > 250 mg/dL, insulin
should be given without glucose
Beta 10-20 mg nebulized Effect in 30 mins Use with caution in patients with
Agonists salbutamol in 4 ml pNSS Peaks at 90 mins cardiac disease
inhaled over 10 minutes Lasts for 2-6 hours
No role in routine treatment of
Bicarbonate hyperkalemia
(IV) 150 mEqs + 1 L D5W Reserved for patients with
hyperkalemia and concomitant
metabolic acidosis

3. Potassium Excretion
TREATMENT IMPORTANT POINTS
Cation Sodium polystyrene sulfonate (SPS) exchanges Na+ for K+ in the GI tract and increased
Exchange fecal K+ excretion
203
Resins Given as 15-30 g premade suspension with 33% sorbitol or 30 cc lactulose
Full effect only after 24 hours and usually requires repeated dosing every 4-6 hours
Diuretics Loop and thiazide diuretics can be utilized to reduce K+ in volume-replete or hypervolemic
patients with sufficient renal function
Dialysis Hemodialysis: most effective and reliable method to reduce plasma K+ concentration

CALCIUM

I. HYPOCALCEMIA

A. Causes
LOW PARATHYROID HORMONE LEVELS HIGH PARATHYROID HORMONE LEVELS (SECONDARY
(HYPOPARATHYROIDISM) HYPERPARATHYROIDISM)
Vitamin D deficiency or impaired 1,25(OH)2D production/action
Nutritional
Renal insufficiency
Parathyroid agenesis Vitamin D resistance
Isolated
DiGeorge syndrome Parathyroid hormone resistance syndromes
PTH receptor mutations
Parathyroid destruction Pseudohypoparathyroidism
Surgical
Radiation Drugs
Infiltration by metastases or systemic Calcium chelators
diseases Inhibitors of bone resorption (bisphosphonates,
Autoimmune plicamycin)
Altered vitamin D metabolism (phenytoin,
Reduced parathyroid function ketoconazole)
Hypomagnesemia
Activating CaSR mutations Miscellaneous
Acute pancreatitis
Acute rhabdomyolysis
Hungry bone syndrome after parathyroidectomy
Osteoblastic metastases (e.g., prostate cancer)

B. Clinical Manifestations
Patients may be asymptomatic (if decreases in calcium are relatively mild and chronic) or may present with life-
threatening complications
Moderate to severe hypocalcemia presents with paresthesias caused by neuromuscular activity
Chvostek’s Sign: twitching of circumoral muscles in response to tapping of the facial nerve anterior to the ear
Trousseau’s Sign: carpal spasms induced by inflation of BP cuff to 20 mmHg above the patient’s SBP for 3
minutes
Severe hypocalcemia can induce seizures, carpopedal spasm, bronchospasm, laryngospasm and prolongation of
QT interval in the ECG

C. Management
OVERVIEW OF CORRECTION (some examples)
Acute Symptomatic Calcium gluconate, 10 mL 10% wt/vol (90 mg or 2.2 mmol) IV, diluted in 50 mL of
Hypocalcemia 5% dextrose solution or pNSS, given IV over 5 mins
Calcium gluconate 10% solution 10 mL 1-2 amp SIVP (10-15 mins)
Continuing Constant IV infusion (10 amps calcium gluconate or 900 mg calcium in 1 L D 5W or
Hypocalcemia pNSS x 24 hours)
Chronic Hypocalcemia Elemental calcium 1,000-1,500 mg/day in divided doses (Calcium carbonate 500 mg
due to 1 tab BID-TID)
Hypoparathyroidism Vitamin D2 or D3 25,000-100,000 U daily or calcitriol [1,25(OH)2D] 0.25-2 mcg/day
(Calcitriol 0.25 mcg/cap OD-BID)
204
III. HYPERCALCEMIA

A. Causes of Hypercalcemia
COMMON CAUSES OF HYPERCALCEMIA
1. Excessive PTH production
Primary hyperparathyroidism (adenoma, hyperplasia, rarely carcinoma)
Tertiary hyperparathyroidism (long-term stimulation of PTH secretion in renal insufficiency)
Ectopic PTH secretion
Inactivating mutation in the CaSR
2. Hypercalcemia of malignancy
Overproduction of PTHrP (many solid tumors)
Lytic skeletal metastases (breast cancer, myoma)
3. Excessive 1,25(OH)2D production
Granulomatous diseases (sarcoidosis, tuberculosis, silicosis)
Lymphomas
Vitamin D intoxication
4. Primary increase in bone resorption
Hyperparathyroidism
Immobilization
5. Excessive calcium intake
Milk-alkali syndrome
Total parenteral nutrition
6. Other causes
Endocrine disorders (adrenal insufficiency, pheochromocytoma, VIPoma)
Medications (thiazides, vitamin A, antiestrogens)

B. Clinical Manifestations
SIGNS AND SYMPTOMS OF HYPERCALCEMIA
Usually asymptomatic and recognized only on routine calcium
Mild Hypercalcemia measurements
(up to 11-11.5 mg/dL) Vague neuropsychiatric symptoms (trouble concentrating, personality
changes, depression), peptic ulcer disease, nephrolithiasis or increased
fracture risk
More Severe Hypercalcemia Lethargy, stupor or coma
(>12-13mg/dL) GI symptoms (nausea, anorexia, constipation, pancreatitis)
ECG Changes Bradycardia, AV block, arrhythmias and shortened QT-interval

C. Mechanism of Hypercalcemia in Various Diseases


MECHANISM EXAMPLES
Excessive PTH Production Hyperparathyroidism, ectopic PTH secretion
Parathyroid Hormone Related Humoral hypercalcemia of malignancy
Peptide (PTHrP) Mediated
Excessive 1,25(OH)2D Tuberculosis, lymphoma, Vitamin D toxicity
Increased Bone Resorption Prolonged immobilization, hyperthyroidism, some malignancies
Drugs Thiazides, anti-estrogens, Vitamin A
Excessive Calcium Intake Iatrogenic, calcium supplements

D. Management
OVERVIEW OF MANAGEMENT
Volume Expansion First line treatment of hypercalcemia
(Hydration) pNSS x 8 hours (may go up to 1-4 L in 24 hours)
Furosemide 20-40 mg IV q8-12h
Forced Diuresis Loop diuretics may be used to enhance Ca excretion but should not be
initiated until volume status has been restored to normal
Diuresis in a dehydrated patient may worsen hypercalcemia
Bisphosphonates Pamidronate 60-90 mg IV over 2-4 hrs
May take up to 24-40 hrs to take effect
205
Acts within a few hours of its administration (used for life-threatening
Calcitonin hypercalcemia)
Principally acts through osteoclasts, blocking bone resorption
Steroids for malignancies (e.g., multiple myeloma, lymphoma)
Others Dialysis for severe hypercalcemia complicated by renal failure refractory to
medical management

MAGNESIUM
Second most abundant intracellular cation
Important in different processes which include:
o Energy transfer, storage and use
o Protein, carbohydrate and fat metabolism
o Maintenance of normal cell membrane function
o Regulation of PTH

I. HYPOMAGNESEMIA
May present with muscular weakness, tremors, seizures, paresthesias, tetany and nystagmus
ECG findings: nonspecific ST-T changes, prolonged QT interval, PVCs, torsades de pointes and ventricular
fibrillation
Usually coexists with hypokalemia and hypocalcemia
CORRECTING MAGNESIUM DEFICIT SAMPLE CASE
1. Calculate for magnesium deficit PR, 40/M, diagnosed cased of CHF, presented with Mg2+
of 0.5
Magnesium deficit = Desired Mg – Actual Mg
Magnesium deficit = 1 – 0.5 = 0.5
Target Mg2+ is usually 1.0 for patients with cardiac
conditions. Otherwise, a target of 0.8 is used Correct the deficit by starting MgSO4 drip as follows:
Start MgSO4 drip: 5g in 250cc D5W x 24 hours (faster drip
2. In correcting for the deficit, 1 g MgSO4 is given per rates can be used for patients with no volume overload)
0.1 mg Mg2+ deficit

BICARBONATE
Usually given in patients with severe metabolic acidosis (except hypercarbic acidosis)
Reacts with H+ ions to form water and carbon dioxide and acts as a buffer against acidosis by raising blood pH
CORRECTING BICARBONATE DEFICIT SAMPLE CASE
1. Compute for the estimated bicarbonate deficit PC, 56/M, 60 kg, diagnosed case of CKD V, lost to
follow-up after initiation HD, presented at the ER gasping
Bicarbonate deficit = (Desired HCO3 – Actual HCO3) x weight in kg x 0.4 ABG showed HCO3 of 9
Desired HCO3 is usually 20-23 in patients with CKD Bicarbonate deficit = (20 – 9) x 60 x 0.4 = 264 mEqs

2. Oral alkali supplementation may be initiated


Sample orders:
There is no hard and fast rule in choosing the method NaHCO3 50 mEqs IV bolus q6h x 3 doses, or
of correction, always rely on clinical judgment (caution NaHCO3 50 mEqs in 250 cc D5W x 8h x 3 cycles
with use of NaHCO3)! NaHCO3 GrX (650 mg) tabs can be given as well

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SECTION 3
COMMON RENAL CONDITIONS
ABNORMALITIES IN NEPHROLOGY
I. DEFINITION OF TERMS
TERM DEFINITION
Azotemia Reduction in GFR
Abnormal excretion of serum protein
Proteinuria o Microalbuminuria: 30-300 mg/d (or mg/g)
o Macroalbuminuria: 300-3500 mg/d (or mg/g)
o Nephrotic range proteinuria: >3500 mg/d (or mg/g)
Polyuria 24 hour-urine output >3000 mL
Oliguria 24 hour-urine output <400 mL
Anuria Complete absence of urine formation (<100 mL in 24 hours)
Dysuria Pain that occurs during urination; perceived as burning or stinging in the urethra

II. CLUES FOR DIAGNOSIS OF RENAL DISEASES


TERM DEFINITION
Acute Renal Failure Anuria, oliguria, documented recent decline in GFR
Chronic Renal Azotemia > 3 months, prolonges signs of uremia, kidneys reduced in size, broad casts in
Failure urinary sentiment
Acute Nephritis Hematuria, RBC casts, azotemia, oliguria, edema, hypertension
Nephrotic Syndrome Proteinuria > 3.5g/24 h per 1.73m 2, hypoalbuminemia, edema, hyperlipidemia
Urinary Tract Bacteriuria >105 CFU/mL, infectious agent documented in urine, pyuria, leukocyte casts,
Infection frequency, urgency, tenderness
Nephrolithiasis Previous history of stone passage, stone seen on x-ray, renal colic
Renal Tubular Electrolyte disorders, polyuria, nocturia, rencal calcification, large kidneys, renal transport
Defects defects

ACUTE KIDNEY INJURY (AKI)

I. ETIOPATHOGENESIS
Sudden impairment of kidney function resulting in the retention of nitrogenous and other waste products
Defined by:
o Rise from baseline creatinine of at least 0.3 mg/dL within 48 hours or at least 50% higher within 1 week
o Reduction in urine output to less than 0.5 mL/kg per hour for longer than 6 hours
TYPE DESCRIPTION SOME EXAMPLES
Most common form Hypovolemia (e.g. GI losses, poor intake)
Due to inadequate renal plasma flow and Low cardiac output
intraglomerular hydrostatic pressure to Decreased effective circulating volume
Pre-renal support GFR (CHF, liver failure)
Involves no parenchymal damage to the Impaired renal autoregulation (NSAIDs,
kidney; rapidly reversed once ACEi, ARBs, cyclosporine)
intraglomerular hemodynamics are
restored
Most common causes are Glomerular (Acute GN)
o Sepsis Tubules and interstitium
o Ischemia o Ischemia
o Nephrotoxins o Sepsis/infection
Intrinsic Ischemia: hypoxia in the renal medulla o Nephrotoxins
leads to impaired autoregulation, Exogenous (iodinated
endothelial and vascular smooth muscle contrast, aminoglycosides,
damage and leukocyte-endothelial crisplatin, ampho B)
adhesion, vascular obstruction and Endogenous (hemolysis,
207
inflammation rhadbomyolysis, myeloma,
intratubular crystals)
Vascular
o Vasculitis
o Malignant hypertension
o TTP-HUS
Occurs when unidirectional flow of urine Bladder neck obstruction (most common)
Post-renal is acutely blocked, leading to increased Prostatic disease
retrograde hydrostatic pressure and Neurogenic bladder
interference with GFR Therapy with anticholinergics

II. MAJOR CAUSES, CLINICAL FEATURES AND DIAGNOSTICS


ETIOLOGY CLINICAL FEATURES LABORATORY FEATURES COMMENTS
Poor fluid intake / fluid loss BCR >20% Low FeNa, high SG and
Heart failure FeNa <1% urine osmolality may
Evidence of volume Hyaline casts in urine not be seen in CKD &
Pre-renal Azotemia depletion (tachycardia, Urine SG >1.018 diuretic use
hypotension, dry mucous Urine osmolality >500 Most diagnostic:
membranes) mOsm/kg Response to restoration
of hemodynamics
(+) culture from normally FeNa may be low
Sepsis-associated Overt hypotension not sterile body fluids particularly early in the
AKI always seen in mild to Granular casts and renal course but is usually
moderate AKI tubular epithelial cell >1% and osmolality
casts on urinalysis <500 mOsm/kg
Systemic hypotension, often Granular casts, renal
Ischemia-associated superimposed on sepsis tubular epithelial cell
AKI and those with limited renal casts
reserve such as old age and FeNa >1%
CKD
Nephroxtoxin-Associated AKI (Endogenous)
Elevated myoglobin and
Rhabdomyolysis Traumatic crush injuries, CK FeNa may be low
seizures, immobilization Heme (+) with few RBC
on U/A
Anemia FeNa may be low
Hemolysis Recent blood transfusion Elevated LDH Evaluation for
with transfusion reaction Low haptoglobin transfusion reaction
must be done
High turnover disease Hyperphosphatemia,
Tumor Lysis (leukemia, lymphoma) hypocalcemia,
Recent chemotherapy hyperyuricemia
Age > 60 years Monoclonal spike in Bone marrow or renal
Multiple myeloma Constitutional symptoms urine or serum biopsy can be
Bone pain electrophoresis diagnostic
Low anion gap
Nephrotoxin-Associated AKI (Exogenous)
Rise in serum creatinine
Contrast Exposure to iodinated in 1-2 days FeNa may be low
Nephropathy contrast Peak within 3-5 days
Recovery within 7 days
Granular casts, renal
Tubular injury Aminoglycosides, cisplatin, tubular epithelial cell
tenofovir, zoledronate casts
FeNa >1% typically
Recent medication exposure Eosinophilia Urine eosinophils of
Interstitial Nephritis Fever, rash, arthralgias Sterile pyuria limited diagnostic
accuracy
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Non-drug causes: Often non-oliguric Systemic signs of drug
tubulointerstitial nephritis- reaction often absent
uveitis syndrome, Legionella Kidney biopsy may be
infection helpful
Other causes of Intrinsic AKI
Variable features of skin ANA, ANCA, anti-GBM
rash, arthralgias, sinusitis antibody
Glomerulonephritis/ (anti-GBM disease), lung Hepatitis serologies, Kidney biopsy may be
Vasculitis hemorrhage (anti-GBM, cryoglobulins helpful
ANCA-associated, lupus), Blood culture
recent skin infection or Hypocomplementemia
pharyngitis ASO titer
Schistocytes on PBS
TTP/HUS Recent GI infection or use of Elevate LDH Kidney biopsy may be
calcineurin inhibitors Anemia, helpful
thrombocytopenia
Recent manipulation of the
aorta or other large vessels Hypocomplementemia
Atheroembolic May occur spontaneously or Eosinophiluria (variable) Skin or kidney biopsy
disease after anticoagulation Variable amounts of can be diagnostic
Retinal plaques, palpable proteinuria
purpura, livedo reticularis,
GI bleed
History of kidney stones, No specific findings Imaging with computed
Post-renal AKI prostate disease, other than AKI tomography or
obstructed bladder catheter May have pyuria or ultrasound
or pelvic neoplasm hematuria

III. MANAGEMENT
MANAGEMENT THERAPY
ISSUE
Reversal of Renal Insult
Ischemic AKI Restore systemic hemodynamics and renal perfusion through volume resuscitation and use
of vasopressors
Nephrotoxic AKI Eliminate nephrotoxic agents
Consider toxin-specific measures
Prevention and Treatment of Complications
Intravascular volume Salt and H2O restriction
overload Diuretics, ultrafiltration
Hyponatremia Please see selection on “Sodium”
Hyperkalemia Please see selection on “Potassium”
Metabolic acidosis Sodium bicarbonate (maintain serum HCO3 >15 mmol/L or arterial pH >7.2)
Dialysis in severe cases
Restriction of dietary phosphate intake
Hyperphosphatemia Phosphate-binding agents (e.g., calcium carbonate, calcium acetate, sevelamer
hydrochloride, aluminum OH)
Hypocalcemia Calcium carbonate or gluconate (if symptomatic)
Hypermagnesemia Discontinue Mg2+-containing antacids
Hyperuricemia Treatment usually not necessary if <890 umol/L or <15 mg/dL
Allopurinol for tumor lysis, forced alkaline diuresis for rhadbomyolysis
Nutrition Protein and calorie intake to avoid net negative nitrogen balance
Indicated when medical managements fails to control volume overload, hyperkalemia,
Dialysis acidosis and when there are severe complications of uremia (asterixis, pericardial rub or
effusion, encephalopathy, uremic bleeding)
Choice of agents Avoid other nephrotoxins: ACE inhibitors/ARBs, aminoglycosides, NSAIDs, radiocontrast
Drug dosing Adjust doses and frequency of administration for degree of renal impairment

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IV. R-I-F-L-E CRITERIA FOR AKI
STAGE GFR CRITERIA URINE OUTPUT CRITERIA
RISK Serum creatinine increased 1.5x; or Urine output <0.5 mL/kg/h x 6 hours
GFR decreased >25%
IINJURY Serum creatinine increased 2x; or Urine output <0.5 mL/kg/h x 12 hours
GFR decreased >50%
Serum creatinine increased 3x; or Urine output <0.3 ml/kg/h x 24 hours
GFR decreased >75%; or (oliguria); or
FAILURE Serum creatinine > 4 mg/dL; or Anuria x 12 hours
Acute rise > 0.5 mg/dL
LOSS Persistent acute renal failure; complete loss of kidney function >4 weeks

ESRD Complete loss of kidney function >3 months

CHRONIC KIDNEY INJURY (CKD)


I. ETIOPATHOGENESIS
Spectrum of different pathophysiologic processes associated with abnormal kidney function and a progressive
decline in GFR
Defined by the KDOQI as kidney damage for > 3 months, as defined by structural or functional abnormalities of
the kidney, with or without decreased GFR, manifested by either of the following or GFR <60 mL/min/1.73 m 2 for
> 3 months with or without damage
o Pathologic abnormalities
o Markers of kidney damage, including abnormalities in the composition of the blood or urine, or
abnormalities in imaging tests
A. Leading Categories of Etiologies of CKD
Diabetic nephropathy
Glomerulonephritis
Hypertension-associated CKD (vascular and ischemic kidney disease)
Autosomal dominant polycystic kidney disease
Other cystic and tubulointerstitial nephropathies
B. Pathophysiology of CKD
Initiating mechanism specific to the underlying etiology
Progressive mechanisms involving hyperfiltration & hypertrophy of the remaining viable nephrons
II. STAGING OF CKD
CKD is alternatively defined by KDIGO as abnormalities of kidney structure or function present for >3 months,
with implications for health and is classified (for prognostication/risk for outcome of CKD) based on case, GFR
category and albuminuria category (CGA)
ESRD: represents a stage of CKD where the accumulation of toxins, fluid and electrolytes normally excreted by
the kidneys results in the uremic syndrome
A. Prognosis of CKD by GFR and Albuminuria Categories: KDIGO 2013
PERSISTENT ALBUMINURIA CATEGORIES
A1 A2 A3
Normal to mildly Moderately Severely
increased increased increased
<30 mg/g 30-300 mg/g >300 mg/g
<3 mg/mmol 3-30 mg/mmol >30 mg/mmol
G1 Normal or high >90 Low risk Moderately High risk
increased risk
GFR G2 Mildly decreased 60-89 Low risk Moderately High risk
categories increased risk
(ml/min/ G3a Mildly to moderately decreased 45-59 Moderately High risk Very high risk
1.73m2) increased risk
G3b Moderately to severely decreased 30-44 High risk Very high risk Very high risk
G4 Severely decreased 15-29 Very high risk Very high risk Very high risk
G5 Kidney failure <15 Very high risk Very high risk Very high risk
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B. Previous Staging of CKD
STAGE DESCRIPTION GFR mL/min/1.73m2 ACTION
Diagnosis and treatment of
I Kidney damage with normal / increased GFR 90 comorbid, slowing progression,
CVD risk reduction
II Kidney damage with mildly decreased GFR 60 – 89 Estimating progression

III Moderately decreased GFR 30 – 59 Evaluating and treating


complications
IV Severely decreased GFR 15 – 29 Preparation for renal
replacement therapy
V Renal failure < 15 (or dialysis) Renal replacement
(if uremia is present)

III. DIAGNOSIS

A. Differentiating Acute Kidney Injury from Chronic Kidney Disease


ACUTE KIDNEY INJURY CHRONIC KIDNEY DISEASE
Kidney size Normal Small
Carbamylated Hemoglobin Normal High
Broad Casts on Urinalysis Absent Present
Histor of Kidney Disease, HPN, Absent Present
Abnormal Urinalysis
Anemia, Metabolic Acidosis, Often present Usually present
Hyperkalemia, Hyperphosphatemia
Reversibility with Time Usually complete Sometimes partial

B. Diagnostics
DIAGNOSTICS EXPECTED FINDINGS
Verifies presence of 2 kidneys, determines symmetry, estimates size and rules out
Renal Ultrasound masses/obstruction
Finding of bilaterally small kidneys supports CKD (expect for early DM
nephropathy, amyloidosis, HIV nephropathy, polycystic kidney disease)
Not advised for bilaterally small kidneys
Renal Biopsy Other contraindications: uncontrolled hypertension, active UTI, bleeding diathesis
(including ongoing anticoagulation) and severe obesity
Other Tests Perform specific tests to assess for specific target organ damage (see above)

IV. CLINICAL MANIFESTATIONS


Uremia leads to disturbances in the function of virtually every organ system
SYSTEMIC FINDINGS COMMENTS / TREATMENT
Fluid, Electrolyte and Acid-Base Disorders
Sodium and Water Homeostasis
o Total body content of Na+ and H2O are modestly
increased Hyponatremia responds to water restriction
o Hyponatremia not commonly seen Salt restriction if with evidence of ECFV
Potassium Homeostasis expansion
o Decline in urinary K+ excretion Diuretics +/- metolazone in CKD III-V
o Increase in K+ due to dietary intake, protein catabolism, Kaliuretic diuretics for hyperkalemia
hemolysis, hemorrhage, transfusion of RBC, acidosis Intractable hyperkalemia is an indication for
o Hypokalemia is uncommon (reduced dietary intake, dialysis
excessive diuretics, GI loss) Alkali supplementation when HCO3 falls below
Metabolic Acidosis 20-23 mmol/L
o Impaired ammoniagenesis
o NAGMA in early stages HAGMA in later stages
Disorders of Calcium and Phosphate Metabolism
Bone manifestations Optimal management is prevention
o High bone turnover with increased PTH levels: osteitis Low-phosphate diet
fibrosa cystica (classic lesion of secondary Use of phosphate-binding agents
211
hyperparathyroidism) Calcitriol suppresses PTH secretion directly
o Low bone turnover with low or normal PTH levels:
adynamic bone disease and osteomalacia
Calcium, Phosphorus and Cardiovascular System
o Strong association between hyperphosphatemia and
increased CV mortality
Other complications
o Calciphylaxis (calcific uremic arteriolopathy): almost
exclusive to advanced CKD; livedo reticularis, patches
of ischemic necrosis especially on legs, thighs,
abdomen and breasts (warfarin treatment is at risk
factor)
Cardiovascular Abnormalities (leading cause of morbidity and mortality in CKD patients)
Ischemic Vascular Disease
o CKD is a major risk factor for ischemic CVD
Heart Failure In CKD + DM or proteinuria >1 g/day, BP goal
o Abnormal cardiac function from myocardial ischemia, left is <130/80 with salt restriction as first-line
ventricular hypertrophy and frank cardiomyopathy therapy
o “low-pressure” pulmonary edema in advanced CKD ACEi and ARBs may slow rate of decline of
Hypertension and Left Ventricular Hypertrophy kidney function but can precipitate AKI and
o Hypertension develops early in CKD hyperkalemia
o Absence of hypertension may signify a salt-wasting form Lifestyle changes
of CKD, effect of anti-HPN therapy, volume depletion or Management of hyperlipidemia using dietary
poor left ventricular function measures and statins
o Use of EPO can also increase BP Uremic pericarditis is an absolute indication for
Pericardial Disease urgent initiation or intensification of dialysis
o Chest pain with respiratory accentuation accompanied (heparin-free)
by friction rub
o Observed in advanced uremia (underdialyzed, non-
adherent patients)
Hematologic Abnormalities
Anemia
o Normocytic, normochromic anemia observed as early as
CKD III and universal in CKD IV
o Causes include:
Relative EPO deficiency
Diminished RBC survival Recombinant human EPO should be initiated
Bleeding diathesis once there are adequate bone marrow iron
Iron deficiency stores
Hyperparathyroidism/marrow fibrosis Iron supplementation
Chronic inflammation Vitamin B12 and folate supplementation
Folate or vitamin B12 deficiency Target hemoglobin of 100-115 g/L
Hemoglobinopathy Desmopressin, cryoprecipitate, IV conjugated
Co-morbids such as hypo/hyperthyroidism, estrogen and EPO for abnormal bleeding time
pregnancy, HIV, autoimmune disease and and coagulopathy
immunosuppressive drugs Optimal dialysis corrects prolonged bleeding
Abnormal hemostasis time
o Prolonged bleeding time, decreased activity of platelet
factor III, abnormal platelet aggregation and adhesion
and impaired prothrombin consumption
o Greater susceptibility to thromboembolism especially if
with nephrotic-range proteinuria
Neuromuscular Abnormalities
CNS, Peripheral and Autonomic Neuropathy Most resolve with dialysis
o Early signs seen at CKD III Successful renal transplantation may reverse
o Usually clinically evident at CKD IV residual neurologic changes
Gastrointestinal and Nutritional Abnormalities
Uremic Fetor: urine-like breath odor with dysgeusia Protein restriction may slow the rate of renal
(unpleasant metallic taste) decline at earlier stages
212
Gastritis: peptic disease or mucosal ulcerations at any level o Daily protein intake 0.60-0.75 g/kg/day with
of the GI tract at least 50% provided by high-biologic
Anorexia due to retention of uremic toxins value proteins
Protein-Energy Malnutrition (PEM) o 0.90 g/kg/day for CKD IV and those with
PEM; daily total caloric intake of 35 kcal/kg
Calcium and iron supplements may aggravate
constipation and anorexia
PEM: indication for renal replacement therapy
Endocrine-Metabolic Disturbances
Glucose metabolism
o Slowed response to glucose loading Goals: FBS 90-130 mg/dL, HbA1Z <7%
o FBS normal or slightly elevated Reduction in insulin and hypoglycemic agent
o Diminished renal degradation of insulin doses
Sexual dysfunction Intensive dialysis and successful renal
Low estrogen, menstrual abnormalities, inability to carry transplantation may reverse sexual dysfunction
pregnancies to term
Reduced plasma testosterone, oligospermia
Dermatologic Abnormalities
Local moisturizers, mild topical steroids, UV
Pruritus, hyperpigmentation radiation
Nephrogenic fibrosing dermopathy: progressive Minimizing exposure to gadolinium in CKD II
subcutaneous induration especially on the arms and legs and avoidance in CKD III to V
associated with exposure to gadolonium Rapid removal of gadolinium by immediate
dialysis for patients in whom MRI is highly
necessary

IV. MANAGEMENT

A. Slowing Progression of CKD


MANAGEMENT REMARKS
Control of BP and Proteinuria Use anti-HPN therapy with a goal of <140/90 mmHg (see JNC-8 guidelines)
Use ACEi and ARBs for their proteinuria-lowering effects
Control of Blood Glucose FBS 90-130 mg/dL
HbA1C <7%
May slow rate of renal decline at earlier stages
Protein Restriction Daily protein intake 0.60-0.75 g/kg/day with at least 50% provided by high
biologic value proteins
For CKD V and those with PEM: may increase to 0.90g/kg/day

B. Hemodialysis or Renal Replacement Therapy


Relies on the principles of solute diffusion across a semipermeable membrane
Movement of waste products takes place down a concentration gradient from circulation into the dialysate
Clear indications for initiation of renal replacement therapy
o Uremic pericarditis
o Encephalopathy
o Intractable muscle cramping
o Anorexia and nausea not attributable to reversible causes such as peptic ulcer disease
o Evidence of malnutrition
o Fluid and electrolyte abnormalities refractory to other measures

URINARY TRACT INFECTIONS (UTI)


I. ETIOPATHOGENESIS
UTI may be asymptomatic (subclinical infection) or symptomatic (disease)
Both UTI and asymptomatic bacteriuria connote the presence of bacteria in the urinary tract, usually accompanied
by WBCs and inflammatory cytokines in the future

213
A. Encompasses a Variety of Clinical Entities
Asymptomatic Bacteriuria Presence of bacteria in the urinary tract in the absence of symptoms attribute
(ABU) to the presence of bacteria and does not usually require treatment
Definition: > 105 bacterial CFU/mL in urine
Acute cystitis or pyelonephritis in premenopausal non-pregnant outpatient
women without anatomic abnormalities or instrumentation of the urinary tract
Acute uncomplicated cystitis (AUC): symptomatic infection in the urinary
Uncomplicated UTI bladder (acute onset dysuria, urgency, frequency, hematuria without vaginal
discharge)
Acute complicated pyelonephritis (AUP): symptomatic infection in the
kidneys (fever > 38oC, flank pain, costoverbal tenderness, +/- symptoms of
lower UTI)
Catch-all term that encompasses all other types of UTI, defined as:
o Presence of indwelling urinary catheter or intermittent catheterization
o Incomplete emptying of the bladder with >100mL retained urine post-
voiding
o Impaired voiding due to neurologic bladder or cystocoele, obstructive
uropathy, vesicoureteral reflux and toher urologic abnormalities including
surgical, ischemic or radiation injuries of the uroepithelium, peri-/post-
Complicated UTI operative UTI
o Intrinsic renal azotemia, renal transplantation, DM, immunosuppression
(febrile neutropenia, HIV/AIDS)
o UTI caused by unusual (M. tuberculosis, Candida spp) UTI or MDR
pathogens
o UTI in males except in young males presenting exclusively with lower UTI
symptoms
o Urosepsis
Recurrent UTI Not necessarily complicated
Catheter-Associated Can by symptomatic (CAUTI) or asymptomatic
Bacteriuria / UTI Definition: >102 bacterial CFU/mL in urine

B. Etiology
Uropathogens causing UTI: usually enteric gram-negative rods that have migrated to the urinary tract
Common pathogens
o E. coli
o Staphylococcus saprophyticus
o Klebsiella spp.
o Proteus spp.
o Enterococcus spp.
In majority of cases, bacteria establish infection by ascending from urethra to bladder
Bacteria can also gain access to the urinary tract by hematogenous spread

II. CLINICAL MANIFESTATIONS


Cystitis Dysuria, urinary frequency, nocturia, hesitancy, suprapubic discomfort, gross
hematuria (without vaginal discharge)
Mild cases present with low-grade fever with or without lower-back or
costovertebral-angle pain
Pyelonephritis Severe cases present with high fever, rigors, nausea, vomiting and flank/loin pain
Urinalysis reveals pyuria (> 5 wbc/hpf of centrifuged urine) & bacteriuria (> 10,000
CFU of uropathogen/mL)
Emphysematous Severe form characterized by production of gas in renal and perinephric tissues
Pyelonephritis Almost exclusive in DM patients
Xanthrogranulomatous Occurs when chronic urinary obstruction, together with chronic infection, leads to
Pyelonephritis suppurative destruction of renal tissue

214
III. DIAGNOSIS
DIAGNOSTIC EXPECTED FINDINGS
Urinalysis and Urine Urine microscopy reveals pyuria (~100%) and hematuria (~30%)
Dipstick Test Dipstick test for nitrite and leukocyte esterase test can be used in certain areas
Urine Culture Detection of bacteria in urine culture is the “gold standard” for UTI
Recommended in cases of pyelonephritis to facilitate cost-effective use of antibiotics
Blood Culture Not routinely recommended unless the patient presents with signs of sepsis
Biomarkers Procalcitonin, mid-regional pro-atrial natriuretic peptide and CRP all not
recommended
Not routinely recommended
Considered for patients with:
Radiologic Imaging o History of urolithiasis, urine pH > 7.0 or renal insufficiency
o Who remain febrile despite 72 hours of treatment
o Whose symptoms recur (to rule out nephrolithiasis, obstruction, abscess
formation or other complications of pyelonephritis)
Other tests Perform specific tests to assess for specific target organ damage (see above)

IV. MANAGEMENT OF UTI


A. Acute Uncomplicated Cystitis
Empiric antibiotic treatment: most cost-effective management approach (pre-treatment urine culture and
sensitivity is not recommended and urine microscopy and dipstick test are not prerequisites for treatment)
Patients whose symptoms worsen or do not improve after completion of initial treatment should have a culture
done and antibiotics empirically changed pending result of sensitivity testing
Patients in whom symptoms fail to resolve after treatment should be managed as complicated UTI
DRUG DOSE
Primary Nitrofurantoin macrocrystals (first line) 100 mg QID x 7 days PO
Treatment Fostomycin trometamol 3 g PO single dose
Fluoroquinolones
Ofloxacin 200 mg BID x 3 days PO
Ciprofloxacin 250 mg BID x 3 days PO
Levofloxacin 250 mg OD x 3 days PO
Alternative Norfloxacin 400 mg BID x 3 days PO
Treatment Beta-Lactams
Amoxicillin-clavulanate 625 mg BID x 7 days PO
Cefuroxime 250 mg BID x 7 days PO
Cefixime 200 mg BID x 7 days PO
Cefpoxodime proxetil 100 mg BID x 7 days PO

B. Acute Uncomplicated Pyelonephritis


Hospital admission (and IV antibiotic use, as necessary) is recommended for patients with:
o Inability to maintain oral hydration or take medications / concern with compliance
o Presence of possible complicating conditions
o Severe illnesses with high fever, severe pain, marked debility and signs of sepsis
ORAL PARENTERAL
Ciprofloxacin 500 mg BID x 7-10 days Ceftriaxone 1-2 g q24h
Ciprofloxacin 1000 mg BOD x 7 days Ciprofloxacin 400 mg q12h
Extended-Release
Levofloxacin 250 mg OD x 7-10 days Levofloxacin 250-750 mg q24h
750 mg OD x 5 days
Ofloxacin 400 mg BID x 14 days Ofloxacin 200-400 mg q12h
IV antibiotics can be shifted to any of the above oral antibiotics once Amikacin 15 mg/kg q24h
afebrile (day 3) and can tolerate drugs PO (guided by GS/CS results) Gentamicin +/- Ampicillin 3-5 mg/kg q24h

Multi-drug resistant organisms: ertapenem 1 g q24h or piperacillin-tazobactam 2.25-4.5 g q6-8h


Aminopenicillins and first-generation cephalosporins: not recommended (high prevalence of resistance)
TMP-SMX must be used only if the uropathogen is proven to be susceptible
Routine post-treatment culture in patients who are clinically improved is not recommended

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C. UTI in Pregnancy
Screening should be done between 9th-17th week AOG, preferably on the 16th week for all pregnant women
The following are considered relatively safe in early pregnancy:
o Nitrofurantoin
o Ampicillin
o Cephalosporins

D. UTI in Males
Men with uncomplicated UTI 7 to 14 days of fluoroquinolone or TMP-SMX
Acute bacterial prostatitis Get cultures and tailor therapy and continue for 2-4 weeks
Chronic bacterial prostatitis 4-6 weeks of antibiotics
Recurrent bacterial prostatitis 12 weeks of antibiotics
Retreatment in the absence of 2 weeks
urologic abnormalities 4-6 weeks if repeat culture reveals same organism as initial infecting organism

NEPHROLITHIASIS
Calcium salts, uric acid, cysteine and struvite are the common constituents
May be asymptomatic and incidentally noted during radiographic studies undertaken for unrelated reasons
Common cause of isolated hematuria
As the stone traverses the ureter, it may present with pain (beginning at the flank, gradually increasing in severity
over the next 20-60 mins, may radiate to ipsilateral groin, testis or vulva) and bleeding
Stone <0.5 cm may pass spontaneously
Helical CT scan without radiocontrast is the standard diagnostic procedure
TYPE COMMON ETIOLOGIES DIAGNOSIS TREATMENT
Low-sodium and protein diet
Idiopathic hypercalciuria Serum and urine Thiazides (idiopathic
Calcium Stones Hypocitraturia calcium hypercalciuria)
(75-85%) Dietary hyperoxaluria Urine oxalate Alkali supplements (hypocitraturia)
Low-oxalate, normal calcium
(dietary hyperoxaluria)
Metabolic syndrome Glucose intolerance
Uric Acid Gout Obesity Alkali and allopurinol if daily urine
Stones (5-10%) Idiopathic Hyperlipidemia uric acid > 1000 mg
Clinical for gout
Cysteine Stone type Fluids and alkali
Stones (1%) Hereditary Elevated cysteine D-penicillamine if needed
excretion
Struvite Stones Infection Stone type (Mg2+, Antibiotics and judicious surgery
(5%) PO4-, NH3)

RENAL TUBULAR ACIDOSIS (RTA)


Disorder of renal acidification out of proportion to the reduction in GFR
Characterized by hyperchloremic metabolic acidosis with normal anion gap
TYPE CLINICAL FEATURES TREATMENT
Kidneys unable to acidify urine to pH <5.5 in
presence of systemic metabolic acidosis or after acid
loading Alkali replacement 1-3 mmol/kg/day in
Due to impaired hydrogen ion secretion or HCO 3 divided doses
Type 1 reabsorption in distal nephron Citrate tolerated better than sodium
Distal Features: hypokalemia, hypocitraturia, hypercalciuria, bicarbonate
nephrocalcinosis and/or nephrolithiasis
Most patients are asymptomatic; usually discovered
incidentally during evaluation for kidney stones
Type 2 Result of impaired bicarbonate reabsorption in the Alkali supplementation 5-15
Proximal proximal tubule where the bulk of filtered HCO 3 is mmol/kg/day with supplemental

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recovered potassium
Features: hyperphosphaturia, hyperuricosuria,
hypercalciuria, non-selective aminoaciduria &
glycosuria
Distal tubule secretion of K+ and H+ ions are impaired,
Type 4 resulting in hyperchloremic acidosis with Correction of hyperkalemia
hyperkalemia Management of renal dysfunction
Most common form of RTA

GLOMERULAR DISEASES
Acute Nephritic Syndrome Pulmonary-Renal Syndromes Nephrotic Syndrome
1-2 g/24h proteinuria >3 g/24h proteinuria
Hematuria with RBC casts Hypertension
Pyuria RPGN with lung hemorrhage Hypercholesterolemia
Hypertension Hypoalbuminemia
Fluid retention Edema/anasarca
Rise in serum creatinine Microscopic hematuria
PROTOTYPE DISEASES
Post-streptococcal GN Minimal change disease
Subacute bacterial IE Goodpasture’s syndrome Focal segmental glomerulosclerosis
Lupus nephritis ANCA small-vessel vasculitis Membranous glomerulonephritis
Anti-GBM (Wegener’s, Churg-Strauss, Diabetic neuropathy
IgA nephropathy Microscopic polyangitis) AL and AA amyloidosis
ANCA small-vessel vasculitis HSP Light-chain deposition disease
Henoch-Schonlein purpura (HSP) Cryoglobulinemia Fibrillary-immunotactoid disease
Cryoglobulinemia Fabry’s disease
MPGN

Basement Membrane Syndromes Glomerular Vascular Symptoms Infectious Disease-Associated


Syndromes
Microscopic hematuria Vascular injury Variety of inflammatory reactions in
Mild to heavy proteinuria Hematuria glomerular capillaries
Hypertension with variable Moderate proteinuria Combination of hematuria and
elevations in serum creatinine proteinuria
PROTOTYPE DISEASE
Atherosclerotic nephropathy Post-streptococcal GN
Hypertensive nephropathy Subacute bacterial IE
Anti-GBM disease Cholesterol emboli HIV
Alport’s syndrome Sickle cell disease Hepatitis B and C
Thin basement membrane disease Thrombotic microangiopathies Syphilis
Nail-patella syndrome APAS Leprosy
ANCA small-vessel vasculitis Malaria
HSP schistosomiasis
Cryoglobulinemia

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CHAPTER 9
RHEUMATOLOGY
I. Approach to Patients with Joint Pains
II. Common Conditions in Rheumatology
1. Osteoarthritis
2. Gouty Arthritis
3. Systemic Lupus Erythematosus
4. Rheumatoid Arthritis
5. Infectious Arthritis
6. Antiphospholipid Antibody Syndrome

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SECTION 1
APPROACH TO PATIENTS WITH JOINT PAINS
I. HISTORY TAKING OF PATIENTS WITH JOINT PAIN
QUESTIONS TO ASK REMARKS
Monoarthritis: gout, septic arthritis, knee osteoarthritis (OA), reactive arthritis (ReA)
Oligoarthritis (2-4 joints involved): OA, reactive arthritis, gout
What is the number Polyarthritis (> 5 joints involved): rheumatoid arthritis (RA), systemic lupu erythematosus
of joints affected? (SLE), hand OA, chronic gout

Note: psoriatic arthritis has 5 types and can therefore be mono- to polyarticular
Acute versus chronic:
o Acute onset examples: gout, septic arthritis
What is the mode of o Chronic onset examples: OA; RA; TB arthritis; connective tissue disease (CTD)-related
onset? arthritis, e.g., SLE

Note: chronic diseases may have acute onset or “flares”, e.g., OA flare, while some acute
diseases can become chronic, e.g., chronic tophaceous gout
Inflammation usually presents with at least one of the following: dolor (pain), calor
Is there presence or (warmth), rubor (redness), tumor (swelling), and function laesa (loss of function)
absence of joint Inflammatory arthritis: pain and stiffness in involved joints; worse in the morning or after
inflammation? periods of inactivity (“gel phenomenon”); improves with mild to moderate activity
Non-inflammatory arthritis: pain that worsens with activity and improves with rest
Is it articular or non- Non-articular causes: bursitis, tendinitis, other soft tissue conditions
articular?
Pattern of onset: migratory, additive, intermittent
o Migratory: joints are sequentially affected where, as one joint settles, another
What is the pattern of becomes inflamed (e.g. acute rheumatic fever)
joint involvement? o Additive: subsequent joints are involved while preceding ones are still inflamed; most
common but least specific (e.g., RA)
o Intermittent: the same joint is involved in different episodes of inflammation, but the
joint is quiescent during intervening periods (e.g., gout)
Is there systemic Most commonly involves the eyes and skin, e.g., uveitis, scleritis, malar rash, oral ulcers,
involvement? photosensitivity

II. PHYSICAL EXAMINATION


Goal is to ascertain the structures involved, nature of the underlying pathology, functional consequences, and
presence of systemic or extraarticular manifestations
There are 28 easily examined joints (to be palpated):
o Proximal interphalangeal joints (PIPs)
o Metacarpophalangeal joints (MCPs)
o Wrists
o Elbows
o Shoulders
o Knees

A. Pain Differentiation Based on Range of Motion


SITE OF PATHOLOGY ACTIVE ROM PASSIVE ROM
Referred pain Normal Normal
Periarticular pain Decreased Can be normal
Intraarticular pain Decreased Decreased

B. Definition of Terms
SITE OF PATHOLOGY DEFINITION
Crepitus Palpable vibratory or crackling sensation elicited with joint motion
Subluxation Alteration of joint alignment such that articulating surfaces incompletely
approximate each other
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Dislocation Abnormal displacement of articulating surfaces such that the surfaces are
not in contact
Range of Motion For diarthrodial joints, the arc of measurable movement through which the
joint moves in a single plane
Contracture Loss of full movement resulting from bony hypertrophy, malalignment of
articulating structures, or damage to periarticular supportive structures
Deformity Abnormal shape or size resulting from bony hypertrophy, malalignment of
articulating structures, or damage to periarticular supportive structures
Enthesitis Inflammation of the enthuses (tendinous or ligamentous insertions in bone)
Epicondylitis Infection or inflammation involving an epicondyle

C. Grading of Muscle Strength (5-point scale)


0 No movement
1 Trace movement or twitch
2 Movement with gravity eliminated
3 Movement against gravity only
4 Movement against gravity and some resistance
5 Normal strength

III. DIAGNOSTICS
Cannot substitute for clinical evaluation and should never be used as a “screen” for disease
Positive predictive value of many rheumatologic tests is low when these tests are ordered indiscriminately
DIAGNOSTICS COMMENTS / EXPECTED FINDINGS
Add little to the evaluation of acute presentations of arthritis (except in cases of
Radiographs suspected trauma) but often critical for the assessment of chronic arthritis
Plain radiography is the imaging method of choice
Most reliable means of distinguishing between inflammatory and non-
inflammatory arthritis is analysis of the WBC in the synovial fluid
Arthrocentesis and Important diagnostic test to rule out septic arthritis and gout
Synovial Fluid Analysis Determine the WBC; detect bacteria by gram stain; look for uric acid crystals
under polarized light
Synovial fluid WBC count <2000/mcL in non-inflammatory arthritis
Useful in detection of soft tissue abnormalities (e.g., tendinitis, tenosynovitis,
Ultrasonography enthesitis, bursitis, rotator cuff lesions)
Preferred method for evaluation of synovial (Baker’s) cysts, rotator cuff tears,
tendinitis, and crystal deposition in cartilage
CT: provides detailed visualization of the axial skeleton, articulations, lung
disease
MRI: images musculoskeletal structures such as fascia, vessels, nerves,
CT or MRI muscle, cartilage, ligaments, tendons, pannus, synovial effusions and bone
marrow
MRI can better define the nature and the extent of joint, bone and surrounding
soft tissue changes
Erythrocyte Inflammatory marker; usually elevated in inflammatory arthritis
Sedimentation Rate (ESR) Can be elevated due to many other factors, e.g., menstruation, pregnancy
Inflammatory marker; usually elevated in inflammatory arthritis
C-Reactive Protein (CRP) Generally lacks specificity except when the value is >100 mg/dL, in which case
septic arthritis or gout should be excluded
Values range from 238-516 umol/L (4.0-8.6 mg/dL) in men; 178-351 umol/L
(3.0-5.9 mg/dL) in women
Hyperuricemia is associated with gout and nephrolithiasis but levels may not
Serum Uric Acid correlate with severity of articular disease
50% of patients with an acute gouty attack will have normal serum uric acid
levels
Monitoring may be useful in assessing response to therapy (target: <6 mg/dL)
Complete Blood Count Anemia is common in chronic inflammatory conditions
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Leukocytosis is common in septic arthritis, acute gout and juvenile arthritis
Leukopenia & lymphopenia in a patient with polyarthritis is suggestive of SLE
Reactive thrombocytosis is common with active chronic inflammatory arthritis,
e.g., RA and juvenile idiopathic arthritis
Thrombocytopenia can be a presenting feature of SLE
Histones: drug-induced lupus
ds-DNA: 50% of SLE (specific)
U1-RNP: >90% of mixed connective tissue disease
Sm: 30% of SLE (specific)
Antinuclear Antibody Ro (SS-A): 60% of Sjogren’s, subacute cutaneous lupus, neonatal lupus
(ANA) Patterns La (SS-B): 50% of Sjogren’s, 15% of lupus
Scl-70: 40% of diffuse scleroderma
PM-1: polymyositis, dermatomyositis
Jo-1: polymyositis with pneumonitis + arthritis
RNA polymerase I: 40% of progressive systemic sclerosis
Centromere / kinetochore: 75% of CREST (limited scleroderma)

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SECTION 2
COMMON CONDITIONS IN RHEUMATOLOGY
OSTEOARTHRITIS (OA)
I. ETIOPATHOGENESIS
Most common joint disease and a leading cause of disability in the elderly
Sine qua non is hyaline articular cartilage loss
o Commonly affected joints are the cervical and lumbosacral spine, hip, knee and first metatarsophalangeal
(MTP) joints
o In the hands, the distal and proximal interphalangeal joints (IPs) and base of the thumb are often affected
o Wrist, elbow and ankle are usually spared
Risk factors include age (most important), obesity, repeated joint use
Joint pain is activity-related, starting as episodic and progressing continuously with accompanying brief morning
stiffness (<30 min) that gradually resolves

II. DIAGNOSTICS
No blood tests are routinely indicated
Synovial fluid analysis reveals a non-inflammatory pattern
Joint imaging correlates poorly with presence and severity of pain:
o May be normal in early stages
o Advanced stages may show joint space narrowing, subchondral sclerosis, osteophytes

III. MANAGEMENT
Goal is relief of pain and prevention of disability

A. Non-Pharmacologic and Adjunctive Management


Exercise with brief periods of rest for the involved joint
Weight management (weight loss of 5 kg translates to 50% reduction in pain): core treatment for obese and
overweight adults with knee OA
Correction of possible malalignment (knee braces, orthotics)
Acupuncture
Concentrated standardized ginger preparation

B. Pharmacologic Management
MANAGEMENT COMMENTS
Maximum dose of 4 g daily
Paracetamol First-line drug therapy for reduction of mild knee OA pain
Close monitoring for upper GI adverse effects for doses >2 g per day
Low-dose NSAIDs or Up to 2 weeks duration
Selective COX-2 Inhibitors
Topical NSAIDs Less systemic side effects compared to oral preparations
Intra-articular Injections Steroids: should not exceed 3 times per year in the same joint
Hyaluronans: more effective: longer duration of pain control
Glucosamine and chondroitin sulfate
Others Opioids (tramadol)
Topical capsaicin
Surgery (arthroscopic debridement and lavage, meniscectomy, arthroplasty)

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GOUTY ARTHRITIS
I. ETIOPATHOGENESIS
Metabolic disease that usually affects middle-aged to elderly men and postmenopausal women
Results from increased body urate pool with hyperuricemia
Precipitants of gout: dietary excess, trauma, surgery, excessive ethanol ingestion, hypouricemic therapy and
comorbid illness (e.g., stroke, ACS)
Asymptomatic Defined as hyperuricemia in the absence of gouty arthritis and uric nephrolithiasis
Hyperuricemia Hyperuricemia; defined as serum uric acid >7 mg/dL (416 umol/L) in men and >6
mg/dL (357 umol/L) in women
Acute Gouty Arthritis Characterized by acute arthritis initially affecting the MTP of the first toe
(podagra) followed by recurring episodes of acute mono- or oligoarthritis
Intercritical Gout Referred to as “interval gout”: the asymptomatic periods between gouty attacks
Chronic Tophaceous Occurs in untreated gouty arthritis, characterized by persistent low grade
Gout (CTG) inflammation of joints with sporadic flares
Joint deformities: due to deposition of massive urate crystals forming visible tophi

II. DIAGNOSTICS
DIAGNOSTICS COMMENTS / EXPECTED FINDINGS
Strongly negative birefringent needle-shaped monosodium urate (MSU) crystals
Synovial Fluid Analysis both intra- and extracellularly
Thick chalky paste fluid; WBC 2,000-60,000/uL
Joint Imaging Joint swelling early in the disease; soft tissue masses
Cystic changes with well-defined erosions and overhanging sclerotic margins
Serum Uric Acid May be low or normal at the time of attacks
24h Uric Acid Urine >800 mg/24h (over-producers)
Collection <600 mg/24h (under-excretors)

III. MANAGEMENT
A. Non-Pharmacologic and Adjunctive Management
General Adequate hydration & increase oral fluid intake (at least 8 glasses of water per day)
Avoid diuretics unless benefits outweigh the risks
Hypouricemic Diet Low purine diet, avoid red meals, alcoholic drinks (especially beer)
Limit seafood, sweetened fruit juice / fructose-containing food and beverages

B. Medical Management
Asymptomatic Do not routinely treat with urate lowering medications
Hyperuricemia Indications for urate lowering therapy: serum uric acid >11-13 mg/dL, presence of
tophi, arthropathy on radiography, nephrolithiasis, tumor lysis syndrome, CKD 2-3
NSAIDS, glucocorticoids, ice compress
Acute Attacks Colchicine: unless contraindicated (e.g., renal insufficiency), colchicine 0.5 mg TID
may be given, then decreased to OD after the acute attack and maintained until uric
acid <6 mg/dL and at least 3 months without gout flare recurrence
Started 1-2 weeks after acute attacks and continued until uric acid is controlled
Treatment goal is to reduce uric acid to <6 mg/dL
Hypouricemic Uric acid under-excretion treated with uricosuric drugs (probenecid,
Therapy benzbromarone, sulfinpyrazone)
Uric acid over-production treated with xanthine oxidase inhibitors:
o Allopurinol 100 mg/tab PO OD initial dose (adjust accordingly)
o Febuxostat 40 mg/tab ½ tab PO OD initial dose (adjust accordingly)

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SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
I. ETIOPATHOGENESIS
Autoimmune disease in which organs and cells undergo damage mediated by tissue-binding autoantibodies and
immune complexes
Diagnosis is based on characteristic clinical features and autoantibodies

II. DIAGNOSTICS
A. 1982 Original American College of Rheumatology (ACR) Criteria
4 out of 11 criteria
Mnemonic: “SOAP BRAIN MD”
CRITERIA DESCRIPTION / REMARKS
Serositis Pleuritic, pericarditis
Oral/ Nephropharyngeal ulcers Observed by physician
Arthritis Non-erosive, 2 or more peripheral joints
Photosensitivity Sensitivity to UV rays from sunlight
Blood / Hematologic disorder Anemia, leukopenia <4000, lymphopenia <1500 or thrombocytopenia <100,000
Renal disorder +3 or >0.5 g/d proteinuria or cellular casts
Ana (+) Best screening test for SLE
Positive in >98% of patients during the course of the disease
Immunologic disorder Anti-dsDNA, anti-Sm, aPL
Neurologic disorder Cerebritis: seizures, psychosis
Malar Rash Butterfly rash: fixed erythema over the malar eminence which spares
nasolabial folds
Discoid Rash Erythematous circular patches with adherent keratotic scaling and follicular
plugging

B. 2012 Systemic Lupus International Collaborating Clinics (SLICC) Revised Criteria


4 criteria (at least 1 immunologic, 1 clinical) or biopsy-proven lupus nephritis
Presence of any 4 criteria (must have at least 1 in each category) qualifies patient to be classified as having SLE
with 93% specificity and 92% sensitivity
CLINICAL CRITERIA IMMUNOLOGIC CRITERIA
Skin
Acute, subacute cutaneous SLE
Chronic cutaneous SLE
Oral ulcers
Alopecia
Synovitis (arthritis) ANA (ANA > reference negative value)
Renal disorder Anti-dsDNA
Prot/Cr > 0.5 Anti-Sm
RBC casts Antiphospholipid antibodies
Biopsy Hypocomplementemia
Neurologic disorder Positive Direct Coombs test
Seizures, psychosis, mononeuritis, myelitis, peripheral
or cranial neuropathies, acute confusional state
hemolytic anemia
leukopenia <4,000 or lymphopenia <1,000
thrombocytopenia <100,000

III. MANAGEMENT
Analgesics and antimalarials are the mainstays of treatment for mild disease
Systemic steroids are the mainstays for severe disease
DRUG INDICATION ADVERSE EFFECTS / COMMENTS
NSAIDS Arthritis Increased risk for aseptic meningitis, renal insufficiency, elevated
transminases and cardiovascular events
Topical Steroids Dermatitis Skin atrophy, hypopigmentation, contact dermatitis

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Sunscreens Photosensitivity At least SPF 15 (SPF 30 preferred)
Reapply throughout the day
Bone health (to
Calcium and help counter
Vitamin D sun avoidance None when taken in appropriate doses
and steroid
intake)
Dermatitis, Hepatotoxicity, BM suppression, pulmonary fibrosis
Methotrexate arthritis Contraindicated in pregnancy; stop 3-6 months before trying to
conceive
Hydroxychloroquine Dermatitis, Potential retinal toxicity at high and prolonged doses
arthritis Helps prevent flares
Systemic Steroids/ Immunosuppression, hypertension, hyperglycemia, hypokalemia,
MPPT* acne, aseptic necrosis of bone/osteoporosis, fragile skin, mood
swings/psychosis, Cushing’s syndrome
Predisposition to infection, BM suppression, hemorrhagic cystitis,
Cyclophosphamide bladder CA, ovarian/testicular failure
Control of Contraindicated in pregnancy
disease activity Predisposition to infection, BM suppression, alopecia, GI symptoms,
Azathioprine hepatotoxicity, flulike illness
Contraindicated in pregnancy unless benefits outweigh risks
(evidence from prospective cohort studies suggests fetal safety)
Mycophenolate Predisposition to infection, BM suppression, lymphoproliferative
Mofetil disorders, GI symptoms, tremors, rash
Biologics Predisposition to infections, TB reactivation
**MPPT: Methylprednisolone Pulse Therapy

RHEUMATOID ARTHRITIS (RA)


I. ETIOPATHOGENESIS
Chronic inflammatory disease of unknown etiology marked by symmetric, peripheral polyarthritis
Most common form of inflammatory polyarthritis which may result in joint damage and physical disability
May result in a variety of extraarticular manifestations (e.g., fatigue, subcutaneous nodules, lung involvement,
pericarditis, peripheral neuropathy, vasculitis, and hematologic abnormalities)

II. CLINICAL MANIFESTATIONS


MANIFESTATIONS REMARKS
Initially involves small joints of hands and feet
Early morning stiffness >1 hour easing with physical activity
Most frequently involved joints: wrists, MCP, PIP (DIP involvement usually a sign of
Joint Involvement coexistent OA)
Swan neck deformity: hyperextension of the PIP with flexion of the DIP joint
Boutonniere deformity: flexion of the PIP with hyperextension of the DIP joint
Z-line deformity: subluxation of the first MCP with hyperextension of 1st IP joint
Flexor tendon tenosynovitis: frequent hallmark of RA
Subcutaneous Nodules Seen in 30-40%
Usually benign, firm, nontender and adherent to periosteum, tendons or bursae
Pleuritic/Pericarditis Most frequent site of cardiac involvement in RA is the pericardium
Vasculitis Fever of >38.3oC during the clinical course should raise suspicion of systemic vasculitis
Others Weight loss, fever, fatigue, malaise, depression, cachexia in the most severe cases

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III. DIAGNOSIS

A. Classification Criteria for RA: Score > 6 fulfills the requirements for Definite RA
CRITERIA SCORE
1 large joint (shoulder, elbow, hip, knee, ankle) 0
2-10 large joints 1
Joint Involvement 1-2 small joints (MCP, PIP, thumb, IP, MTP, wrists) 2
4-10 small joints 3
>10 joints (at least 1 small joint) 5
Serology Negative RF and negative anti-CCP antibodies 0
Low-positive RF or low-positive anti-CCP antibodies (< 3 times ULN) 2
High-positive RF or high-positive anti-CCP antibodies (> 3 times ULN) 3
Acute-phase Normal CRP and normal ESR 0
Reactants Abnormal CRP or abnormal ESR 1
Duration of < 6 weeks 0
Symptoms > 6 weeks 1

B. Diagnostic Tests
DIAGNOSTICS COMMENTS / EXPECTED FINDINGS
Serum Markers (+) RF or anti-CCP, elevated acute phase reactants
CBC Normocytic normochromic anemia
Synovial Fluid Consistent with inflammatory arthritis
Analysis
Joint Imaging Juxtaarticular osteopenia (initial finding), soft tissue swelling, joint effusions, symmetric joint
space narrowing, joint subluxation & collapse in severe cases

III. MANAGEMENT

A. NSAIDS
Formerly viewed as the core of all other RA therapy
Now considered as adjunctive therapy

B. Glucocorticoids
Low-moderate doses for rapid disease control before the onset of fully effective DMARD therapy
1- to 2-week burst of glucocorticoids for acute disease flares

C. Disease-Modifying Anti-Rheumatic Agents (DMARDS)


Slow or prevent structural progression of RA
Cornerstone of therapy
DMARD DOSING ADVERSE EFFECTS / COMMENTS
Methotrexate 10-25 mg/week PO or SQ Hepatotoxicity, myelosuppression, infection, nauseam
(DMARD of choice) Folic acid 1 mg/day given to diarrhea, interstitial pneumonitis
reduce toxicities Contraindicated in pregnancy
Hydroxychloroquine 200-400 mg/day PO Irreversible retinal damage, rash, cardiotoxicity, blood
dyscrasia, nausea, diarrhea
Sulfasalazine 500-1500 mg BID PO Granulocytopenia, hemolytic anemia in persons with
G6PD deficiency, nausea, diarrhea
Hepatotoxicity, myelosuppression, infection, alopecia,
Leflunomide 10-20 mg/day diarrhea
Contraindicated in pregnancy

D. Biologics
Protein therapeutics designed mostly to target cytokines and cell-surface molecules
Share the common adverse effect of a potentially increased risk for infection
BIOLOGIC MECHANISM
Infliximab Chimeric (part-mouse, part-human) anti-TNF monoclonal antibody
Adalimumab, Fully humanized anti-TNF monoclonal antibody
Golimumab
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Certolizumab pegol Pegylated Fc-free fragment of a humanized monoclonal antibody with binding
specificity for TNF
Etanercept Soluble fusion protein comprising the TNF receptor-2 in a covalent linkage with the Fc
portion of IgG1
Anakinra Recombinant form 1L-1 receptor antagonist
Abatacept Soluble fusion protein consisting of a domain of human CTLA-4 linked to a portion of
human IgG
Rituximab Chimeric monoclonal antibody against CD-20
Tocilizumab Humanized monoclonal antibody against the IL-6 receptor

INFECTIOUS ARTHRITIS

I. ETIOPATHOGENESIS

A. Pathogenesis
Hematogenous route is the most common route in all age groups
The knee is the most commonly involved joint
Acute bacterial infection typically involves a single joint or a few joints
Subacute or chronic monoarthritis or oligoarthritis suggests mycobacterial or fungal infection
Polyarticular involvement may be seen in RA

B. Etiologic Agents
Infants: Group B Streptococcus, Gram (-) enteric bacilli, and Staphylococcus aureus
Young adults & adolescents: N. gonorrhea
Staphylococcus aureus accounts for most non-gonococcal isolates in adults of all ages

II. CLINICAL MANIFESTATIONS


Fever (may be absent in immunosuppressed people)
Moderate-severe pain that is uniform around the joint
Musculoskeletal: joint effusion, muscle spasm, decreased range of motion

III. DIAGNOSTICS
DIAGNOSTICS COMMENTS / EXPECTED FINDINGS
Acute Phase Reactants Elevated ESR, CRP
CBC Elevated WBC counts with leftward shift
Cell counts averaging 100,000/uL with >90% PMN (acute bacterial infection)
Synovial Fluid Analysis 10,000-30,000/uL with 5-70% PMN and remainder lympchocytes (TB/fungal infection)
Elevated LDH and total protein; decreased glucose
Early findings: soft tissue swelling, joint space widening, displacement of tissue planes
Joint Imaging by distended capsule
Late findings: effusions, symmetric joint space narrowing, joint subluxation and
collapse in severe cases
Cultures Blood CS will be (+) for Staphylococcus aureus in 50% of cases
Synovial fluid CS will be (+) for Stap