Aherrera Notes

Dr. Jaime Aherreras Internal Medicine Notes 2009

Aherrera Notes
Dr. Jaime Aherreras Internal Medicine Notes 2009

Aherrera Notes | TAABLE OF CONTENTS

I.
II.
III.
IV.
V.
VI.
VII.
VIII.
IX.
X.

Basic Information
Cardiology
Endocrinology
Gastroenterology
Hematology
Infectious Disease
Nephrology
Neurology
Pulmonology
Rheumatology

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GENERAL
NOTES
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Jaime Alfonso Manalo Aherrera, M.D.

Internal Medicine Notes 2009

WARD NOTES

1) MUST KNOW FORMULAS

I. DOPAMINE DOSAGE COMPUTATION

Dopamine Drip used primarily for stabilization of the Hypotensive Patient

Formulation of Dopamine:
o Dilute 200mg (1 Ampule) in 250cc D5W (Factor used: 13.3)
o Drip at 2.5 10mcg/kg/min
o Maximum Dose of 20mcg/kg/min (Dopa-Max)
o If Double Strength: 2 Ampules in 250cc D5W (use 26.6)

Rate (ugtt/min) = . (mcg/kg/min) x body weight .

13.3

Dose (mcg/kg/min) = .

(ugtt/min) x 13.3
body weight

Dopamine Doses (from Harrisons p1453)

DOSE
< 2 mcg/kg per min

Stimulate DA1 and DA2 Receptors

MECHANISM OF ACTION

2-4 mcg/kg per minute

Stimulate B1-Receptors

> 5 mcg/kg per minute

Effects on A1-Receptors overwhelm the

Dopaminergic Receptors

EFFECT
Vasodilation of Splanchnic and Renal
Vasculature
Increase in Cardiac Output with little or no
change in Heart Rate or SVR
Vasoconstricion, leading to Increase in SVE,
LV Filling Pressures, and Heart Rate

**NOTE: Dopamine is generally the 1st choice for Tx in situations where Modest Inotropy & Pressor Support are required
o
o
o

It is an Endogenous Catecholamine that stimulates B1, A1 Receptors, and Dopaminergic Receptors (DA1, DA2) in
the heart and circulation
Dopamine also releases Norepinephrine from nerve terminals, which itself stimulates A1 and B1 Receptors, thus
raising Blood Pressure
Most useful in treatment of heart failure patients who have Depressed Cardiac Output with Poor Tissue Perfusion

Example) Case on Septic Shock: Patient is a 45kg / F, given 2 amps of Dopamine in 250cc PNSS at a rate of 19uggts/min

In 1 Ampule of Dopamine = 200mg/amp

Strength Factors:

In 1 Ampule of Dobutamine = 250mg/amp

NOTE: 19ugtts/min = 19cc/hr

1 amp of Dopamine = 13.3

2 amps of Dopamine = 26.6

QUESTION: What is the Dose of Dopamine being given to the patient at a rate of 19uggts/min?:
Dose Given (in mcg/kg/min) = Rate (in ugtt/min) x 26.6 = 19 uggt/min x 26.6 =
45 kg
45 kg

11.23 mcg/kg/min

ANSWER: 11.23mcg/kg/min is the dose given to the Patient at a rate of 19uggts/min (or 19cc/hr)
Since we are giving 11.23mcg/kg/min, we have a Vasoconstricting
Effect. This is what we want for a patient with Septic Shock. We
can increase the ugtts/min if patient is still Hypotensive up to
34ugtt/min (20mcg/kg/min) for a 45kg patient (Dopa Max). If still
No Response with Dopa Max, we can give LEVOPHED
(Norepinephrine).
In the computation, we used 26.6 because 2 ampules of dopamine
were used for the patient.

Recall the Action of Dopamine at Different Doses (Dr. Magno Notes):

1. At 1-5mcg = RENAL VASODILATOR

Exerts selective Renal and Mesenteric Vasodilation

Acts on Dopamine Receptors

Improve Renal Blood Flow and Urine Output

2. At 6-10mcg = INOTROPIC

Positive Inotropic Effect

Acts on Beta-1 Adrenergic Receptors

Increase Heart Rate

3. At 10-20mcg = VASOCONSTRICTOR

Peripheral Vasoconstriction

Acts on A-Adrenergic Receptors

Increase Systemic Vascular Resistance

Deleterious for CHF and Low Cardiac Output

II. DOBUTAMINE DOSAGE COMPUTATION

A. Dobutamine Drip selectively stimulates Beta-1 Adrenergic Receptors
o Direct Inotropic Stimulation with Reflex Arterial Vasodilation
o Afterload Reduction and Augmented Cardiac Output
o BP remains constant, HR increases minimally
o For patients with Chronic Refractory Heart Failure
o NOT for Heart Failure resulting from Diastolic Dysfunction or High-Output State
B. Formulation of Dobutamine
o Dilute 250mg (1 amp) in 250cc D5W (use 16.6)
o Drip at 2.5 10mcg/kg/min
o Maximum Dose of 20mcg/kg/min
o If double strength: 2 Ampules in 250cc D5W (use 33.2)
Rate (ugtt/min) = mcg/kg/min x body weight
16.6

mcg/kg/min = .

C. Action of Dobutamine at Different Doses:

o 0 10 mcg/kg/min = INOTROPIC EFFECT
o 10 20 mcg/kg/min = VASOCONSTRICTION

(ugtt/min) x 16.6
body weight

Notes from Harrisons:

Dobutamine has a Positive Inotropic Action and Minimal Positive
Chronotropic Activity at Low Doses (2.5ug/kg/min) but moderate
Chronotropic Activity at Higher Doses

III. NORADRENALINE (LEVOPHED) Rounds

Each ampule has 2mg Noradrenaline per amp
Usual Starting Dose is at 2-4 mcg/min with a maximum of 15 mcg/min
Noradrenaline (LEVOPHED) Drip:
2mg Noradrenaline in 2mL Ampule
Usual Preparation: D5W 250mL + 1 Amp (2mg) Levophed to run at 15-60ugtts/min
Concentration = 2mg = 2,000mcg = 8mcg Noradrenaline per cc (this is the concentration of 1 Amp + 250cc D5W)
250cc 250cc
Drip of 2-8mcg Noradrenaline/min is equivalent to 15-60 ugtts/min
Example: We are using 1 Amp (2mg) in 250cc D5W. If we mix 1 Amp with 250cc D5W, the concentration of Levophed will be 8mcg/cc (as
computed above)
1) If Our desired dose to give patient is 2mcg/min (usual starting dose), what is the Rate?
Step 1: Convert 2mcg/min to mcg/hour
2mcg/min x 60 mins 120mcg/hr
Step 2: If we desire a dose of 120mcg/hr given a concentration of 8mcg Levophed per cc, compute the rate:
120mcg/hr = 15 cc/hr or 15 ugtts/min
8mcg/cc

**NOTE: cc/hr is equal to uggts/min

2) If our desired dose is 8mcg/min 480mcg/hr

480mcg/hr = 60 ugtts/min
8mcg/cc
Example 2) We are using 4 ampules (8mg) in 250cc of D5W. We want to give the patient a dose of 2mcg/min. What is the rate?
Concentration = 8 mg . = 8,000 mcg = 32mcg Noradrenaline per mL (Concentration of 4 Amps + 250cc D5W)
250cc
250cc
Since we initially want to give a dose of 2 mcg/min
.2 mcg x 60 min = 120 mcg / hr
min
hr
120 mcg/hr = 4 cc/hr or 4 uggt/min
32 mcg/cc

III. COMMON FORMULAS USED

A. General Formulas
BMI = kg / m2
Underweight
Normal Weight
Overweight
Obese I
Obese II

< 18.5
18.5 22.9
23 24.9
25 29.9
> 30

Ideal Body Weight:

Females: 100 pounds + (5 pounds per inch over 5 feet)
Males: 106 pounds + (6 pounds per inch over 5 feet)
**NOTE: Divide 2.2 to convert to kilograms

B. Cardiac Output, Mean Arterial Pressure (MAP), Anion Gap, Osmolality, Etc.
Heart Rate x Stroke Volume

Cardiac Output

Systolic BP + (2 x Diastolic BP)

3

Mean Arterial Pressure

Normal Value: 70 100 mmHg

Urine Anion Gap

( Na + K ) Cl

Serum Anion Gap

Na ( HCO3 + Cl )

Urine Osmolality

( SG 1 ) x 40,000
[2 (Na + K)] + RBS (mmol/L) + BUN (mmol/L)

Plasma Osmolality

or
2 (Na in mmol/L) + (Glucose in mg/dL / 18) + (BUN / 2.8)
Normal Value is 280 300 mOsm/L
Normal Value (from Harrisons) = 275-290 mosm/kg
RBS: 1 mmol/L = 18 mg/dL
Effective Plasma
Osmolality

2 Na + RBS in mmol/L
or
2 Na + RBS in mg/dL
18

C. Adequacy of Urine Collection

o M: 20-23mL/kg
o F: 15-20mL/kg
D. 24-Hour Urine Collection Adequacy
o
o
o

Creatinine is produced at a constant rate and in an amount directly proportional to skeletal mass
Creatinine Coefficient = 23mg/kg of IBW (men) and 18mg/kg of IB (women)
If 24 hr urine creatinine is LESS than IBW x Creatinine Coefficient INADEQUATE Collected Specimen
Unpredictable when Serum Crea > 530umol/L

IV. BUN / CREATININE RATIO; CREATININE CLEARANCE

A. BUN / Crea Ratio (SI Units)
Interpretation:
If < 10: Intrinsic Renal Cause
If 10-20: Doubtful Cause
If > 20: Pre-Renal Cause

BUN:Crea Ratio = BUN x 247

Crea
Conversion Factor for Serum BUN: 1 mmol/L = 2.8 mg/dL
B. Fractionated Urine Na (Best test to Diagnose if Renal or Prerenal)

FENa =

[ UNA x PCR ] x 100

[ PNA x UCR ]

Interpretation:
<1
Pre-Renal
>1
Renal (Oliguric ATN)

C. Creatinine Clearance (mL/min): Cockroft and Gault Equation

CreaClearance = . (140 age) x weight in kg .

72 x Serum Crea in mg/dL

CreaClearance = . (140 age) x weight in kg .

72 x (Serum Crea in umol/L / 88.4)

IMPORTANT Notes:
o If Female, multiply everything by 0.85
o If Creatinine is NOT in mg/dL, divide it by 88.4
Normal Creatinine Clearance
o 100-125mL/min in Males
o 85-105mL/min in Females
Staging of Chronic Kidney Disease (CKD)
CKD STAGE
DESCRIPTION
Kidney damage with normal / increased GFT
I
Kidney damage with mildly decreased GFR
II
Moderately decreased GFR
III
Severely decreased GFR
IV
Renal Failure
V

GFR mL/min / 1.73m2

90
60 89
30 50
15 29
< 15 (for dialysis)

V. ELECTROLYTES
A. Calcium
1. Corrected Calcium (mg/dL)

[ (40 Albumin in g/L) x 0.02 ] + Measured Ca2 in mmol/L

OR
( 4 Albumin in g/dL x 0.08 ) + Measured Ca2+ in mg/dL

A Fall in Serum Albumin of

1gm/dL is associated with a Fall
of 0.8mg/dL in Total Calcium

LOW in Renal Failure, Hypoparathyroidism, Severe Hypomagnesemia, Hypermagnesemia, Acute

Pancreatitis, Rhabdomyolysis, Tumor Lysis Syndrome, Vitamin-D Deficiency, Pseudohypoparathyroidism;
Rarely due to Multiple Citrated Blood Transfusions, critically ill patients, Anti-Neoplastic Agents,
Antimicrobials, Agents used to Treat Hypercalcemia
Use with Hypocalcemia ONLY if Ionized Calcium cannot be measured
Make sure that the alteration in Serum Calcium is NOT due to Abnormal Albumin Concentrations
About 50% of Total Calcium is Ionized, and the rest is bound principally to Albumin
When Serum Albumin Levels are REDUCED, a Corrected Calcium Concentration is calculated by
adding 0.2mM (0.8mg/dL) to the Total Calcium Level for every Decrement in Serum Albumin of 1.0g/dL
below the reference value of 4.1 for Albumin, and conversely for elevations in Serum Albumin
Example:

Present Total Calcium = 8mg/dL

Present Serum Albumin = 2.5g/dL (N: 4g/dL)

Corrected Ca2+ = (4 2.5) x 0.8 = 1.2

Corrected Total Calcium = 8 + 1.2 = 9.2 mg/dL

2. Hypocalcemia
Calcium Gluconate 10% Solution of 10mL/amp: 1-2amp Slow IV Push (10-15mins) with Cardiac
Monitoring then incorporate 1amp Calcium Gluconate to present IV Fluids
Chronic Treatment:
Calcium Carbonate 500mg 1 tab BID-TID
Vitamin-D3 Supplements (Calcitriol 0.25mcg/cap OD-BID)
Treat Hypomagnesemia
3. Hypercalcemia
Hydrate: 0.9%NSS at 150-600cc/hr (up to 1-4 Liters in 24 hours)
Furosemide 20-40mg IV q8-12 hours
Bisphosphonates (Pamidronate 30-90mg/day as a single 24-hour Infusion for 3 Days)

B. Sodium
1. Corrected Sodium

0.016 (RBS in mg/dL 100) + Measured Na+ in mmol/L

Plasma Na+ Concentration FALLS by 1.4 mmol/L for every 100 mg/dL RISE in the Plasma
Glucose Concentration

2. Hyponatremia: Sodium Deficit

( Desired Na Actual Na ) x Body Weight in kg x 0.6

Target Na+ = 125 135 mEq/L

NOTE: 0.6 is Total Body Water
NaCl 1 Tab = 17 mEq
NaHCO3 GrX 1 tab = 7 mEq
a. Sodium Correction
Time needed to Infuse = ( Desired Na Measured Na ) / 0.5
Total # of L needed = Na Deficit / 154
Drip Rate = Total # of L needed / Time needed to Infuse

Give Patient 50% of Calculated amount of Na+ in the first 8 hours, and the other 50% in the next
16 hours (correct at a Rate NOT > 0.5meq/L/hr)

b. Sample Case for Hyponatremia

A 70-kg male has a Na+ Value of 105 mmol/L
We want to raise the plasma Na+ concentration from 105 to 115 mmol/L
Formula: Deficit in Plasma Na+ x Total Body Water (TBW)
[115 105] x 70 x 0.6 = 420 mmol
Plain NSS (PNSS) has 154 Na+ Content per Liter; therefore, we can give 2-3 L of PNSS in one day

3. Hypernatremia
a. Water Deficit

Water Deficit =

Plasma Na+ Concentration - 140

140

x 0.6 x BW (kg)

OR
Water Deficit = [ ( Actual Na Desired Na ) ] x 0.6 x BW (kg)
Desired Na

TBW is 0.6 mg/kg for MALES

TBW is 0.5 mg/kg for FEMALES

Desired Na+ is 140

Total Body Water (TBW) in Hypernatremia is due to water loss
Should be corrected SLOWLY over at least 48-72 hours, ideally with hourly Serum Na+
determination to target 0.5mmol/L/h, but NOT > 12mmol/L over the 1 st 24 hours
b. Sample Case on Hypernatremia
A 50 kg woman with a Plasma Na+ Concentration of 160 mmol/L
Water Deficit = 2.9 L
Water deficit should be corrected slowly over at least 48-72

160 140 x 0.4 x 50 kg = 2.9 L

140

hours. Safest route of administration of water is by mouth

or via a nasogastric tube. Alternatively, 5% Dextrose in
Water of Half-Isotonic Saline can be given IV

4. Water Excess

Water Excess =

Normal Na+ x TBW

Actual Na+

- TBW

Hyponatremia

Plasma Na+ Concentration < 135 mmol/L

Clinical Manifestations: Brain Swelling or Cerebral Edema

Stupor, Seizures, and Coma do NOT usually occur unless the Plasma Na+ falls below 120mmol/L of Decreases RAPIDLY

Goals of Therapy: 1) To raise plasma Na+ Concentration by restricting water intake and promoting water loss; and 2) To correct the
underlying disorder

Rx: Plasma Na+ Concentration should be raised by NO more than 0.5-1.0 mmol/L per hour and by LESS than 10-12 mmol/L over the
first 24 hours

For Severe Symptomatic Hyponatremia: Treated with Hypertonic Saline, and Plasma Na + Concentration should be raised by 1-2 mmol/L
per hour for the first 3-4 hours or until seizures subside. It should be raised by no more than 12 mmol/L during the first 24 hours.

Osmotic Demyelination Syndrome (ODS): Risk of correcting Hyponatremia too rapidly Flaccid Paralysis, Dysarthria, Dysphagia
Hypernatremia

Plasma Na+ Concentration > 145 mmol/L

Clinical Features: Water shifts OUT of cells, leading to Contracted ICF Volume Decreased Cell Volume is associated with an Increased
Risk of Subarachnoid or Intracerebral Hemorrhage

Therapeutic Goals: Stop Ongoing Water Loss and to Correct the Water Deficit

C. Potassium
o Hypokalemia = Plasma K+ Concentration < 3.5 mmol/L
o Hyperkalemia = Plasma K+ Concentration > 5.0 mmol/L
1. Potassium Deficit
(Desired K+ - Measured K+)
0.27

x 100

Oral Kcl:
15cc: 10 mEqs
30cc: 20 mEqs

Desired K is 3.5
Target K is 3.5 4.9 mEq/L
If K is 2.0 3.5 mEq/L, replace 10-20 mEq KCl for
every 0.1 mEq/L Drop in K

Maximum Drip: Max 10 mEqs / hr

Central Line: Max 20 mEqs / hr

Desired K is:

Administer as 10% Solution, 15cc + 20mEqs KCl; 1/2 of the dose given within 24 hours,
then the excess within the next 3 days

Kalium Durule:
1 tab = 10 mEqs

4.0 mEq/L for Cardiac Causes, requiring IV administration of K

3.5 mEq/L for Non-Cardiac Causes, requiring Oral Administration of K

Sample Orders for Hypokalemia:

1. Oral Route

Kalium Durule 0.75gm (10 meq) TID PO x 2-3 days; or

Oral KCl Solution 15-30cc TID (1gm KCl = 14meq K+, to be diluted in Oral Feeding or Water
**NOTE: Each Oral Dose should NOT exceed 20-40 meq K+
2. Intravenous Route

Usual Concentration is 20-40 meq K+ in 1L Saline or Dextrose Solution

Ex) Add 20-60 meq KCl in 1L Plain NSS x 12 hours

If K+ Level is <2 and (+) ECG Abnormalities, use Glucose Free Solution

2. Hyperkalemia
Mild (K <5.5)
Moderate (K = 5.5-6.5)

Severe (K > 6.5)

Restrict Potassium Intake

Kayexelate or Sorbisterit 20g; or
Kalmiate 1 Sachet in 50-150cc Water TID x 3 Doses
(up to 4-5 Doses/day)
Furosemide 40-80mg IV Stat or Drip 0.5-20mg/hr
Salbutamol Nebulization
Calcium Gluconate 10mL 1amp in 10% Solution Slow IV Push
Repeat after 10minutes if no improvement
Glucose-Insulin
D50-50mL + 10 units Humulin R Slow IV stat; then q6 0 x 3 Doses
500mL 10% Dextrose + 10 Units Insulin over 30-60minutes
1L 10% Dextrose + 20 Units Insulin with 1/3 solution given in first 30
minutes and the remainder over the subsequent 2-3 hours
Sodium Bicarbonate
1 amp Dilute in 100cc D5W Slow IV Push > 10 minutes
Fastest way to decrease Potassium (K+ shift in <15minutes)

D. Bicarbonate
( Desired HCO3 Actual HCO3 ) x (Weight in Kg) x 0.4

For correction of deficit, administer 1/2 of computed value as Bolus, then remaining 1/2 as IV Drip
Desired HCO3 of 15 18 if patient has Chronic Renal Disease
For Severe Acidosis: < pH 7.20 in Pure HAGMA, Goal is to Increase HCO3 to 10 mEq/L and
pH to 7.15

VI. OTHER CONVERSION FACTORS

To mg/dL

RBS:
BUN:
Crea:
Ca2+:
Bilirubin:

Multiply by 18
Multiply by 2.8
Divide by 88.4
Divide by 0.25
Divide by 17.10

Equivalents

1cc Oral KCl:

15cc Oral KCl:
1 K Durule (750mg):
NaHCO3 50mL:
NaHCO3 Gr X Tab:

1.33 mEqs K
20 mEqs K
10 mEqs K
45 mEqs Na
7 mEqs Na

Regular requirement for NaHCO3 is 21mEq/day,

so we usually give NaHCO3 GrX TID

VII. TEMPERATURE CONVERSION

Degrees Fahrenheit to Degrees Celsius: C = (F 32) x 5/9
Degrees Celsius to Degrees Fahrenheit: F = (C x 9/5) + 32
VIII. INTRAVENOUS FLUIDS
IV SOLUTION
D5W
D10W
0.9 NSS
D5LR
NM
NR
D50.9 NaCl
D5NMK

Na+

GLUCOSE
50 gm/L
100 gm/L

50 gm/L
50 gm/L

154
130
40
140
154
40

Cl154
109
40
98
154
40

K+

4
13
5

Ca2+

HCO3

28

30

IX. PULMONOLOGY FORMULAS

A. Alveolar-Arterial O2 Difference (PAO2 PaO2) or Alveolar-Arterial O2 Gradient (A-a Gradient)
A a Gradient PAO2 PaO2
or

( FiO2 x 713) (PCO2 / 0.8) - PaO2

This formula is derived from:
Alveolar PO2 (PAO2) = FiO2 x (PB PH2O) PaCO2/R
In NORMAL Persons: PAO2 PaO2 < 15 mmHg

Four Basic Mechanisms of Hypoxia:

o Decrease in Inspired PO2
o Hypoventilation
o Shunt
o Ventilation/Perfusion (V/Q) Mismatch
A-a Gradient:
1. Normal Gradient (both reduce Alveolar Oxygenation):

Decrease in Inspired PO2

Hypoventilation
2. Elevated Gradient:

Shunting (ie. Intracardiac Shunt): Low PO2 is NOT correctable with Supplemental O2

V/Q Mismatch: Low PO2 is CORRECTED with Supplemental O2

Shunting VS V/Q Mismatch:
1. Shunt:

Alveolar Collapse (Atelectasis)

Intraalveolar Filling (Pneumonia, Pulmonary Edema)

Intracardiac Shunt

Vascular Shunt within Lungs

2. V/Q Mismatch:

Airway Disease (Asthma, COPD)

Interstitial Lung Disease

Alveolar Disease

Pulmonary Vascular Disease

10

B. Desired FiO2
Desired FiO2

[ ( Desired PO2 / PAO2 ) + ( PACO2 / 0.8) ] x 100

713
Where:
PAO2 = (FiO2 x 713) (PCO2 / 0.8)
Desired PO2 = 80 ( # of yrs > 60 y/o)
= If < 60y/o = 104 (0.43 x age)

Simplified Version (ER Rounds):

Step I: Compute for PAO2

PAO2 = (FiO2 x 713) (PCO2 / 0.8)
Step II: Compute for AaO2
AaO2 = PaO2
PAO2
Step III: Compute for Desired FiO2
. Desired PO2 . + PCO2
AaO2
0.8
713

. x 100

EXAMPLE: COPD Patient with the following values (ABG):

pH = 7.365
PCO2 = 42.4
PO2 = 109
HCO3 = 24.4
FiO2 = 60%
O2 Sat = 90%
Step I: PAO2 = (0.6 x 713) (42.4 / 0.8) = 374.8
Step II: AaO2 = . 109 . = 0.29
374.8
Step III: FiO2 = . 60 . + 42.4
0.29
0.8
713

. x 100 = 36% - therefore, we can decrease FiO2 to 36%

**NOTE: Instead of 80, we used 60 because patient has (+) COPD

**NOTE: Desired PO2:

o Instead of 80 (80 is usually used), we can use 80-100
o In COPD, we can use 60

11

2) NUTRITION (DIET)
I. COMPUTATION OF DIET IN NORMAL PATIENTS (Ambulant, etc)
Total Caloric Requirement
Ideal Body Weight x 35 Kcal
(Kcal/day)
CHO (g/day)

. TCR x 0.6
4

CHON (g/day)

1gm / kg

Fats

The Rest
Subtract CHO + CHON from the TCR

**NOTE: In DM Patients, we give 3 meals + 2 snacks (to avoid Hypoglycemia)

o If we want to Up Build Patients (for thin patients), we can give as much as 40 Kcal 60 Kcal per kg
Example: 70kg Patient
If we use 30 Kcal/kg Patient will need 2,100 Kcal/day
1. Carbohydrates:
2,100 x 0.6
315g/day
4
2. Proteins:
1gm x 70 = 70g/day
If patient has CKD, we may go down to as much as 0.6g/kg
If patient has CKD and is on Dialysis, we can use 0.9g/kg
3. Fats
REST

II. OSTERIZED FEEDING

TCR 1800 Kcal/day (for a 60kg patient)
o CHO 270g/day
o CHON 60g/day
Divided into 6 Equal Feeding
o Fats Rest
1:1 Dilution
III. DM DIET
TCR 1800 Kcal/day (for a 60kg patient)
o CHO 270g/day
o CHON 60g/day
3 Meals, 2 Snacks
o Fats Rest
No Simple Sugars
Low Salt, Low Fat Diet
Na <2g
TC < 200mg
Saturate Fats < 7%
MUFA > PUFA
If CBG >180: give HR 4uSC
If CBG >250: give HR 6uSC
CBG Monitoring pre-meals and at bedtime

12

3) NOTES ON INHERITED PATIENTS

I. GBS vs HYPOKALEMIC PERIODIC PARALYSIS
In Hypokalemic Periodic Paralysis = INTACT Deep Tendon Reflexes (DTR)
In GBS, the DTRs are usually disrupted
II. ORGANOPHOSPHATE POISONING
A. Signs of GOOD Atropinization
Dry Mucosa
HR > 60
Hypoactive BS
Pupils > 4mm

B. Atropine Toxicity
T > 390C
Flushing
(-) Sweating
Psychosis, Restlessness

III. ACUTE MYOCARDIAL INFARCTION

CKMB should be > 2x elevated (Normal is 16, therefore, 32 is already MI)
CKMB / CK Total should be > 5% MI!
IV. HEPARIN DRIP COMPUTATION (Unfractionated Heparin)
A. Initial Therapy
Warfarin = Monitor PT (INR)
o Bolus = 60-80 U/kg
Heparin = Monitor PTT
o Infusion = 14-18 U/kg/hr
aPPT (s)
< 40 s

Bolus
(H)
3000

Stop
(min)
0

Rate Change
(cc/hr)
22

Rpt aPTT
(hrs)
6

40 49

50 75

No Change

Next am

76 85

-1

Next am

86 100

30

-2

101 150

60

-3

> 150

60

-4

aPTT
< 1.25 times

CHANGE
80 Units/kg/Bolus; then
Increase by 4 units/kg/hr

1.25 1.5 times

40 Units/kg/Bolus; then
Increase by 2 units/kg/hr

1.5 2.5 times

NO Change!

2.5 3.0 times

Decrease by 3 Units/kg/hr

> 3.0 times

STOP for 1 Hour; then

Decrease by 3 Units/kg/hr

B. Example Case: 60kg male with Massive MI

o Give 80 U/kg = 4,800 u IV Bolus (initial push)
o Then, maintain on Drip: Add 10,000 Units Heparin with PNSS to make 100cc
o Infusion is at 18 u/kg/hr, therefore, we are giving 1,080 Units per Hour (U/hr)
o Give 10.8 cc/hr 10.8 ugtt/min
o Monitor PTT and make necessary adjustments
C. Example Case 2: PTT: Control is 37.1; then Patient is 33.3
33.3 / 37.1 = 0.9 times
Give 80 Units/kg BOLUS
Then INCREASE the Dose of heparin being given by 4 Units/kg/hr
Computation: 4 x 60kg = 240 Units (therefore, we should ADD 240 units per hour)
**NOTE: In 1 cc, there is 100 u
Therefore, adjust the Heparin Dose by ADDING 2cc/hr (or 2ugtts/min) to the Baseline Drip
D. Deep Vein Thrombosis
o DVT Dose = 12 u UFH BID
o DVT Prophylaxis Dose = 5 u BID

13

ANTICOAGULANT THERAPY WITH LOW-MOLECULAR WEIGHT AND UNFRACTIONATED HEPARIN

(from Harrisons)
CLINICAL INDICATION

HEPARIN DOSE AND SCHEDULE

Venous Thrombosis Pulmonary Embolism

Treatment
5000 U IV Bolus;
1000-1500 U/h
Prophylaxis
5000 U SC q8-12h

TARGET PTT

LMWH DOSE AND SCHEDULE

2-2.5x

100 U/kg SC BID

< 1.5x

100 U/kg SC BID

5000 U IV Bolus;
1000 U/hr
8000 U SC q8 + Warfarin
5000 U IV Bolus;
1000 U/hr

1.5-2.5x

100 U/kg SC BID

1.5-2.0x
1.5-2.5x

100 U/kg SC BID

100 U/kg SC BID

Prophylaxis
General Surgery
Orthopedic Surgery
Px with CHF, MI

5000 U SC BID
10,000 U SC BID
10,000 U SC BID

< 1.5x
1.5x
1.5x

100 U/kg SC BID before & BID

100 U/kg SC BID before & BID
100 U/kg SC BID

PTT at RECHECK
Normal (27-35s)
< 50s
50 60s
60 85s
85 100s
100 120s
> 120s

INTERVENTION
5000 U Bolus; 1300 U/h Infusion
Rebolus with 5000 U and Increase Infusion by 100 U/h
Increase Infusion Rate by 100 U/h
No Change
Decrease Infusion Rate by 100 U/h
Stop Infusion for 30 minutes and Decrease Rate by 100 U/h at Restart
Stop Infusion for 60 minutes and Decrease Rate by 200 U/h at Restart

Acute Myocardial Infarction

With Thrombolytic Tx
With Mural Thrombus
Unstable Angina

**NOTE: LMWH does NOT affect PTT

14

V. OTHER DRIPS (A to E from Blue Book)

A. Nicardepine Drip
1. D5W 250mL + Nicardepine 20mg
Concentration = 0.08mg/mL
Drip of 15-67ugtts/min is equivalent to 1-5mg/hr
OR
2. D5W 90mL + Nicardepine 10mg in Soluset
Concentration = 0.1mg/mL
Drip of 10-50ugtts/min is equivalent to 1-5mg/hr
Maximum Dose = 15mg/hr
NOTE: IV Infusion Site must be changed every 12 hours should a peripheral line be used
B. Noradrenaline (LEVOPHED) Drip: 2mg Noradrenaline in 2mL Ampule
D5W 250mL + 1 Amp Levophed at 15-60ugtts/min
Concentration = 8mcg of Noradrenaline per mL
Drip of 2-8mcg Noradrenaline/min is equivalent to 15-60 ugtts/min
C. Hydralazine (Apresoline) Drip
D5W 250mL + Apresoline 2 Amps (20mg/amp) at 5-30ugtts/min (up to 60 ugtts/min)
Maximum Daily Dose = 3.5mg/kg body weight per 24 hours
D. Isosorbide Dinitrate (ISOKET) Drip
1. D5W 90mL + Isoket 10mg in a Soluset
Drip of 10-50 ugtts/min is equivalent to 1-5 mg/hr
2. If with CHF, may use DOUBLE Dose: D5W 90mL + Isoket 20mg in a Soluset
Drip of 5-25 ugtts/min is equivalent to 1-5 mg/hr
E. Glyceryl Trinitrate (PERLINGANIT) Drip: 1mg/mL in 10mL Vials
1. D5W 90mL + Perlinganit 10mg (1 vial) in a Soluset
Drip of 10-50 ugtts/min is equivalent to 1-5 mg/hr
2. If with CHF, may use DOUBLE Dose: D5W 90mL + Perlinganit 20mg (2 Vials)
Drip of 5-25 ugtts/min is equivalent to 1-5 mg/hr
F. NTG Drip
o 10mg NTG in enough PNSS to make 100cc in Soluset x 10cc/hr
o May increase or decrease by 2cc/hr to achieve Chest Pain-Free State
G. Omeprazole Drip
o 80mg IV Bolus
o 40mg + 100cc PNSS to run for 5 Hours (Continuous Drip)
H. Somatostatin Drip
o 250mg IV Bolus; then
3mg in D5W 250cc x 120
3mg + 500cc PNSS x 42cc/hr (250mg/hr)
I. Electrolytes
1. NaHCO3 Drip
150mg NaHCO3 + 250cc D5W x 240
2. MgSO4 Drip
2-4mg in 250cc D5W x 120
3. KCl Drip (Correction)
Please incorporate 40 meqs KCl to 1L PNSS to run for 80 x __ Cycles
Repeat K+ Post-Correction
J. Insulin Drip (Medicine Notes)

15

o
o

Formulation: Dilute 20 Units of Insulin in 100cc PNSS to concentration of 0.2 Unit/cc

Standard Insulin Concentration is 1 Unit Regular Insulin per 10mL Saline (0.1 unit/cc)
1. For Hyperkalemia (from Blue Book) Glucose-Insulin Drip
a. 50mL of 50% Dextrose in Water + 10 Units Insulin in 2-5 Minutes
Eg. Mix D50-50 mL + 10 Units Humulin-R Slow IV Stat, then q6 hours x 3 Doses
b. 500mL of 10% Dextrose + 10 Units Insulin over 30-60 Minutes
If Volume Overload is NOT a problem
c. 1000mL of 10% Dextrose + 20 Units Insulin with 1/3 of Solution given in the first 30 Minutes and the
remainder over the subsequent 2-3hours
2. For Hyperglycemia
a. Loading Dose
CBG > 200 = 0.075 0.1 Unit/Kg IV Push
CBG > 300 = 0.1 0.125 Unit/Kg IV Push
If DKA = 0.2 Unit/Kg IV Push
b. Maintenance Dose
0.1 Unit/kg/hr, titrate to desired Blood Glucose
3. Dosing Table
a. Intravenous (IV)

CBG
< 70
70 120
121 180
181 240
241 300
> 300

ACTION
Discontinue for 30 minutes, give 15-20mL of D50-50, re-measure in 30 mins
If > 100, resume drip at 1 unit/hr. Continue glucose infusion
Decrease Rate by 0.3 unit/hr
No Change in Rate
Increase Rate by 0.3 unit/hr
Increase Rate by 0.6 unit/hr
Increase Rate by 1.0 unit/hr

b. Subcutaneous (SC)

CBG
< 80
80 180
181 200
201 300
> 300

ACTION
Discontinue for 30 minutes, give 15-20mL of D50-50, re-measure in 30 minutes
No Change in Rate
Humulin-R 6 Units SC
Humulin-R 8 Units SC
Humulin-R 10 Units SC

K. Dopamine, Dobutamine, Heparin

o See above discussion
VI. VIRCHOWS TRIAD: Encompasses the three broad categories of factors that are thought to contribute to thrombosis
The triad consists of:
o Alterations in normal blood flow (Stasis)
o Injuries to the vascular endothelium
o Alterations in the constitution of blood (Hypercoaguability)
VII. METABOLIC SYNDROME (SYNDROME X, INSULIN RESISTANCE SYNDROME)
Consists of a constellation of Metabolic Abnormalities that confer in Risk of Cardiovascular Disease and Diabetes Mellitus
Major Features include:
NCEP:ATPIII 2001 CRITERIA for Metabolic Syndrome: Three or More of the following:
o Central Obesity

Central Obesity: Waist Circumference > 102cm (M), > 88cm (F)
o Hypertriglyceridemia

Hypertryglyceridemia: TG > 150mg/dL or specific medication

o Low HDL Cholesterol

Low HDL Cholesterol: < 40 mg/dL and 50 mg/dL, respectively, or specific medication
o Hyperglycemia

Hypertension: BO > 130 systolic or > 85 Diastolic or specific medication

o Hypertension

Fasting Glucose > 100 mg/dL or specific medication or previously diagnosed T2DM

16

4) ARTERIAL BLOOD GAS (ABG)

Steps in Interpreting ABGs:
1) Check pH and Primary Disturbance
2) Check the Compensatory Mechanism
3) Check for presence of a Mixed Acid-Base Disturbance
4) For Metabolic Acidosis: Compute for Anion Gap (AG)
5) Note if with Good Oxygenation (should be > 90%)

I. FORMULA
A. Metabolic Acidosis
Decrease in PCO2 = 40 (HCO3 x 1.25) +/- 2
B. Metabolic Alkalosis
Increase in PCO2 = 40 + (HCO3 x 0.75) +/- 2
C. Respiratory Acidosis
1. Acute Respiratory Acidosis
HCO3 = 24 + [(PCO2 / 10) x 1] +/- 2
2. Chronic Respiratory Acidosis
HCO3 = 24 + [(PCO2 / 10) x 4] +/- 2
D. Respiratory Alkalosis
1. Acute Respiratory Alkalosis
HCO3 = 24 [(PCO2 / 10) x 2] +/- 2
2. Chronic Respiratory Alkalosis
HCO3 = 24 [(PCO2 / 10) x 4] +/- 2

17

II. COMPENSATORY MECHANISMS

DISORDER
Metabolic Acidosis

PRIMARY
DISTURBANCE
Decrease in HCO3

COMPENSATORY RESPONSE
1.2 mmHg DECREASE in pCO2 for every 1 mEq/L FALL in HCI3

Metabolic Alkalosis

Increase in HCO3

0.7 mmHg INCREASE in pCO2 for every 1 mEq/L RISE in HCO3

Respiratory Acidosis
Acute < 2 weeks
Subacute 2-6 weeks
Chronic > 6 weeks

Increase in pCO2

Acute:
1 mEq/L INCREASE in HCO3 for every 10mmHg RISE in pCO2

Respiratory Alkalosis
Acute
Chronic

Decrease in pCO2

Chronic
3-5 mEq/L INCREASE in HCO3 for every 10mmHg RISE in pCO2
Acute:
2 mEq/L DECREASE in HCO3 for every 10mmHg FALL in pCO2
Chronic:
5 mEq/L DECREASE in HCO3 for every 10mmHg FALL in pCO2

Normal Values:
pH
pCO2 (mmHg)
HCO3 (mEq/L)
Anion Gap
Cl (mEq/L)

7.4 + 0.3
40 + 4
24 + 2
12 + 2
105

III. CASE: An 50/M, 60kg, intubated patient had the following ABG results, post-intubation
pH = 7.2
decreased
pCO2 = 18
decreased
HCO3 = 7
decreased
A. Formula for Metabolic Acidosis:
Decrease in pCO2 = 40 (HCO3 x 1.25)
= 40 ([24 7] x 1.25)
= 18.75

*NOTE: 24 is the desired HCO3; 7 is the actual HCO3

Since the Actual Decrease in PCO2 (18) is within +/- 2 of 18.75 COMPENSATED!!!!!
This means that for every decrease in HCO3, there should be a 1.25 Decrease in PCO2
SAMPLE SCENARIO: If the Actual PCO2 is NOT within +/-2:

If pCO2 is 10 there may be Overcompensation, or a COMBINED Metabolic Acidosis AND Respiratory Alkalosis
If pCO2 is 25 UNCOMPENSATED!

B. Compute for Bicarbonate Deficit:

HCO3 Deficit = (Desired HCO3 Actual HCO3) x weight x 0.4
= (18 7) x 60 kg x 0.4
= 264 mEq Deficit
= Give half dose as IV Bolus, then the remaining in Drip
= Example: Give 100 mEq IV Bolus NOW, then the remaining 150 mEq as Drip
IV. OXYGEN SATURATION
> 80
Adequate Oxygenation
60 80
Mild Hypoxemia
40 60
Moderate Hypoxemia
< 40
Severe Hypoxemia

18

V. METABOLIC ACIDOSIS
A. High Anion Gap Metabolic Acidosis

. AG .
HCO3

If:

= 1 Pure HAGMA
< 1 HAGMA + NAGMA
> 1 HAGMA + Metabolic Alkalosis

B. Normal Anion Gap Metabolic Acidosis

. Cl .
HCO3

If:

= 1 NAGMA
< 1 NAGMA + HAGMA
> 1 NAGMA + Metabolic Alkalosis

VI. ANION GAP

A. High-Anion Gap Metabolic Acidosis (HAGMA)
o Methanol
o Uremia
o DKA
MUDPILES
o Paraldehyde
o Isoniazid
o Lactic Acidosis
o Ethanol
o Salicylates
B. Normal-Anion Gap Metabolic Acidosis (NAGMA)
o Renal
o GI Losses

Diseases with HAGMA:

-Lactic Acidosis
-Ketoacidosis

Diabetic

Alcoholic

Starvation
-Toxins

Ethylene Glycol

Methanol

Salicylates

Propylene Glycol

Pyroglutamic Acid
-Renal Failure (Acute and Chronic)
Diseases with NAGMA
-Renal HCO3 Loss (Proximal RTA Type 2)
-Enhanced NH4 Excretion
-Ingestion of HCl, NH, Cl, Lysine, Arginine
-GI HCO3 Loss (Diarrhea) or Acid Gain
-Impaired NH4 Excretion
-Distal RTA (Type 1)
-Diarrhea
-Urinary Tract Obstruction

VII. SOME EXAMPLES OF MIXED ACID-BASE DISORDERS FROM HARRISONS:

A. Mixed Metabolic and Respiratory
1. Mixed Acidosis Respiratory Alkalosis
Key: High- or Normal-AG Metabolic Acidosis
INTERPRETATION:
Prevailing PCO2 BELOW Predicted Value
Lactic Acidosis, Sepsis in ICU
Example:
Na 140, K 4.0, Cl 106, HCO3 14; AG 20
PCO2 24, pH 7.39
2. Metabolic Acidosis Respiratory Acidosis
Key: High- or Normal-AG Metabolic Acidosis
Prevailing PCO2 is ABOVE Predicted Value
Example:
Na 14, K 4.0, Cl 102; HCO3 18; AG 20
PCO2 38, pH 7.3

INTERPRETATION:
Severe Pneumonia, Pulmonary Edema

3. Metabolic Alkalosis Respiratory Alkalosis

Key: PCO2 does NOT Increase as Predicted; pH is HIGHER than Expected
Example:
Na 140, K 4,0, Cl 91, HCO3 33; AG 16
INTERPRETATION:
PCO2 38, pH 7.55
Liver Disease and Diuretics
4. Metabolic Alkalosis Respiratory Acidosis
Key: PCO2 is HIGHER than Predicted; pH is NORMAL
INTERPRETATION:
Example:
Na 140, K 3.5, Cl 88, HCO3 42; AG 10
COPD on Diuretics
PCO2 67, pH 7.42
B. Mixed Metabolic Disorders
1. Metabolic Acidosis Metabolic Alkalosis
Key: Only detectable with High-AG Acidosis; AG >>> HCO3 INTERPRETATION:
Example:
Na 140, K 3.0, Cl 95, HCO3 25, AG 20
Uremia with Vomiting
PCO2 40, pH 7.42
2. Metabolic Acidosis Metabolic Acidosis
INTERPRETATION:
Key: Mixed High-AG Normal AG Acidosis; HCO3
Diarrhea and Lactic Acidosis
accounted for by combined change in AG & Cl
Toluene Toxicity
Example:
Na 135, K 3.0, Cl 110, HCO3 10, AG 15
Tx of DKA
PCO2 25, pH 7.20

19

ECG TEACHING NOTES (PGH, 2008)

1) INTRODUCTION
I. NORMAL VALUES
< 0.12 sec
P-Wave
< 0.25 Mv in Limb Leads
< 0.1 Mv Terminal Negative Deflection in V1
0.12 0.20 sec (up to 5 small boxes)
PR Interval
< 0.11 0.12 sec
QRS Duration
5 10 mm (0.5 1.0 Mv)
T Wave
< 0.44 (females)
QTc
< 0.48 (males)

Formula of Corrected QT-Interval (QTc)

Corrected QT Interval = . QT Actual .
R-R Interval

Computation of Heart Rate

Rate = .

300
.
# of Big Sq

= . 1500
.
# of Small Sq

Important Notes:
o
o
o

ST Depression: Ischemia
Significant Q-Wave: > 25% of QRS
ST Elevation: Infarction
Significant ST-Segment Depression: > 1mm
Significant ST-Segment Elevation: > 1mm Limb Leads; > 2mm Chest Leads

II. AXIS
Computation of Frontal Axis:
Axis = . 90 x aVF .
|I| + |aVF|

Where:
o
o

Avf and I are integers derived by subtracting the Positive Deflection from the Negative Deflection
The Avf in the numerator is an Integer, while the I and Avf in the Denominator are absolute values of integers
If I is a Negative Integer, then adjust the Axis by adding | 90 |

Interpretation:
Right Axis Deviation (RAD)
Left Axis Deviation (LAD)
Normal Axis
Extreme Axis Deviation

> 1000
< -300
-300 to 1000
-900 to 1800

III. NORMAL ECG

Read As:

Regular Sinus Rhythm (RSR)

Normal Axis (NA)
Within Normal Limits

IV. EJECTION FRACTION ON ECG

Ejection Fraction = (QRS aVr x 2.64) + (Age x 0.645)

20

2) SOME COMMON FINDINGS

I. NON-SPECIFIC ST-T WAVE CHANGES
T-Wave Inversion < 5mm (< 0.5Mv)
ST Segment Depression < 1mm (< 0.1 Mv)
Flattening of ST Segment without the presence of U-Waves
**NOTE: Mention leads where ST-Segment changes and T-Wave inversions occur
II. ISCHEMIA
T-Wave Inversion > 5mm (> 0.5Mv) read as To Consider Ischemia
ST-Segment Depression > 1mm (> 1Mv) in 2 or more contiguous leads read as Ischemia
**NOTE: Significant ST-Segment Depression > 1mm in at least 2 contiguous leads (Horizontal or Downsloping)
III. POOR R-WAVE PROGRESSION
In Leads V1-V3 (R-Wave < 3mm or 0.3Mv) AND Normal R-Wave in V4-V6
Do NOT Read as Poor R-Wave Progression in the following conditions:
o Left Ventricular Hypertrophy
o Left Bundle Branch Block
o Wolff-Parkinson-White Rhythm
o Anteroseptal Wall MI
o Low-Voltage QRS Complexes
**NOTE: NO Clinical Relevance: Do NOT Write:
o Early transition / counterclockwise rotation
o Persistent S V5-V6 or Persistent Posterobasal Forces
IV. ATRIAL ENLARGEMENT
Right Atrial Enlargement
Left Atrial Enlargement

P-Wave with 2.5mm Amplitude (0.25Mv) in any of Lead II, III or Avf
P-Wave Widened > 3mm (> 0.12sec) especially Lead II; OR
Terminal Segment of P-Wave in V1 > 1 small box (>0.04 sec OR 0.1Mv depth)
Do NOT include Notching in Lead II as Criterion

Bi-Atrial Enlargement

RAE
(Tall P-Waves > 2.5mm In Leads II, III, Avf)
PLUS
LAE
(Terminal Segment Of P-Wave > 1 Small Box (0.04 Sec) In V1 Or Widened PWave, Especially Lead II > 3mm (>0.12sec)

21

V. VENTRICULAR ENLARGEMENT
A. Left Ventricular Hypertrophy
1. Sokolow-Lyon Criteria
[S in V1] + [R in V5 or V6] is Greater than 35mm (do NOT use S in V2); OR
Avl > 11mm
**IMPORTANT Notes:
Cut-Off for LVH, regardless of Age > 35mm
No need to Indicate By Voltage
2. Cornell Criteria
S in V3 + R in AvL
Female > 20mm
Male > 28mm
B. Left Ventricular Strain
LVH by Voltage Criteria + Significant Asymmetric ST-Segment Depression with Broad-Inverted T-Wave
Read as LVH with Strain, Cannot Rule Out Concomitant Ischemia
C. Right Ventricular Hypertrophy
RAD + R/S Ratio > 1 in V1 + R/S Ratio < 1 in V6
o
o

RAD is a Prerequisite Criterion for RVH

An Upright V1 or Prominent R in V1 without RAD will NOT be signed out as RVH and need not be
described

D. Biventricular Hypertrophy
Hypertrophy in presence of BBB: RAD + rsR Pattern in V1 (R-Wave Amplitude > 15mm or 1.5Mv)
VI. LOW VOLTAGE COMPLEXES
Chest Leads are more significant
QRS Complexes
< 5mm (0.5Mv) in Limb Leads
< 10mm (1.0Mv) in Chest Leads
Read as Low Voltage Complexes in Limb OR Chest Leads

22

3) ABNORMAL ECG FINDINGS

I. EARLY REPOLARIZATION CHANGES
Embryonic R + ST-Elevation NOT fulfilling criteria for ST-Elevation in MI
Check morphology of ST-Segment if more convex rather than concave
II. BUNDLE BRANCH BLOCKS AND INTRAVENTRICULAR CONDUCTION DEFECT
LBBB
RBBB
Non-Specific Intraventricular Conduction Delay: Widened QRS without Repolarization changes, NOT meeting
the Criteria for LBBB or RBBB
LAFB
LPFB
Bifasicular Block
Trifasicular Block
III. ELECTROLYTE ABNORMALITIES
Low Sensitivity of U Wave
U Wave Prominent + Normal T-Wave Read as Prominent U Wave
Prominent U Wave + Flattened T-Wave Read as T/C Hypokalemia
ST-Segment Depression + U Wave + Normal T-Wave Read as Cannot R/O Ischemia; Prominent U Wave
Flattened T-Waves + Normal QRS-Complex Read as Non-Specific ST-T Wave Changes
QTc Computed to Adjust for Bradycardia (HR < 60bpm) or Tachycardia (HR > 100bpm)
o Normal Value: Female < 0.48
o Normal Value: Male < 0.47
**NOTE: Use the Lead with the longest Absolute QT Interval without Prominent Q-Wave OR Largest Amplitude T-Wave
A. Digitalis Effect
o Seen in patients without Significant ECG Changes due to Organic Disease
o Should describe Drug Effects in leads seen
o Read as Scooping of ST-Segment Depression, Non-Specific ST-T Wave Changes, probably Digitalis Effect
B. Hyperkalemia
o At least > 2 Contiguous Leads with Peaked T-Waves > 10mm (1.0Mv)
o Read as Peaked T-Waves, T/C Hyperkalemia
IV. MYOCARDIAL INFARCTION
A. Timing of MI
Acute
Significant ST-Elevation + T-Wave Inversion +/- Q-Waves
Old
Significant Q-Wave + Isoelectric ST Segment + Upright T-Wave
Age Undetermined
ST-T Wave Change +/- Q-Wave not fulfilled by Criteria for Old and Acute MI
B. Definitions
Significant ST-Segment Elevation

> 1mm Limb Leads

> 2mm Chest Leads

23

Significant Q-Wave
C. Walls of Involvement
LEADS
V1
V1-V2
V1-V3 or V1-V4
V3-V4
V5-V6
V3-V6
V1-V6
II, III, Avf

> 25% of the QRS Complex; or

> 0.04 sec
MYOCARDIAL WALL INVOLVED
Posterior
Septal
Anteroseptal
Anterior
Lateral
Anterolateral
Massive Anterolateral
Inferior

D. Correspondence of Specific ECG Leads (from Medicine Notes)

LEADS
CORRESPONDING LV AREAS
II, III, Avf
Inferior Wall
I, Avl
High Lateral
V1, V2
Septal Wall
V3, V4
Anterior Wall
V5, V6
Lateral Wall
V1 V3
Anteroseptal Wall
V3 V6, I, AvL
Anterolateral Wall
V5, V6, II, III, AvF
Inferolateral Wall
Almost All Leads
Diffuse / Global / Massive
Mirror Image V1, V2
Posterior LV Wall
V3R, V4R
RV Wall
V. INTERPRETING ECGs (Rounds)
A. AV Block
Primary AV Block
Prolonged PR interval (More than 5 small squares or more than 0.2msec)
Secondary AV Block I: There is prolonging PR-Interval, then Drop Beat
II: There is a Regular PR-Interval, then Drop Beat
Tertiary AV Block
With AV dissociation (look for P-waves, look for Q waves DISSOCIATED!)
The PR and QRS Waves are Independent from each other
B. Q-Waves
o 20% of R; Wide OLD Infarct!
o In aVr, there is usually a Q-Wave
C. QRS
o Normal = 0.08 0.12
o If Wider = Bundle Branch Block
D. ST Elevation / Depression
o ST Elevation = at least 2 small boxes in contiguous leads
o ST Depression = at least 1 small box
E. T-Waves
o Peaked T-Waves = 10 boxes in chest leads; 5 boxes in limb leads
o If Inverted T-Waves = CANNOT rule out ischemia

24

VI. VENTRICULAR TACHYCARDIA

A. Ventricular Tachycardia can be classified based on its MORPHOLOGY:
1. Monomorphic Ventricular Tachycardia
Means that the appearance of all the beats match each other in each lead of a surface
electrocardiogram (ECG)
2. Polymorphic Ventricular Tachycardia
Has beat-to-beat variations in morphology
This most commonly appears as a cyclical progressive change in cardiac axis referred to by its French
eponym Torsades de Pointes (literally twisting of the points).
B. Classification Based on Duration of the Episodes:
o Technically, three or more beats in a row on an ECG that originate from the ventricle at a rate of more than
100 beats per minute constitute a ventricular tachycardia
1. Non-Sustained Ventricular Tachycardia
If the fast rhythm self-terminates within 30 seconds, it is considered a non-sustained ventricular
tachycardia
2. Sustained Ventricular Tachycardia
If the rhythm lasts more than 30 seconds it is known as a sustained ventricular tachycardia (even if it
terminates on its own after 30 seconds)
C. Classification Based on SYMPTOMS
1. Pulseless VT
Associated with NO effective cardiac output, hence, no effective pulse, and is a cause of cardiac arrest
In this circumstance it is best treated the same way as ventricular fibrillation (VF) and is recognized as
one of the shockable rhythms on the cardiac arrest protocol
2. Some VT is associated with Reasonable Cardiac Output and may even be Asymptomatic
The heart usually tolerates this rhythm poorly in the medium to long term, and patients may certainly
deteriorate to Pulseless VT or to VF

VII. PACEMAKER
A. Indications for Permanent Pacemaker Insertion (Pacing)
o Permanent Pacemaker Insertion should be implanted in the following conditions (Class-I Indications)
1. Complete Heart Block with:
(+) Symptoms due to the AV Block (eg. Syncope, Heart Failure)
Asystole > 3 seconds by Holter Monitoring even if without symptoms
HR < 40 bpm even without symptoms (any escape rhythm < 40 bpm)
2. Second Degree AV Block, Permanent or Intermittent, with Symptomatic Bradycadia
3. Sinus Node Dysfunction with Symptomatic Bradycardia.
In some patients, this is due to Long-Term Essential Drug Therapy for which there are NO Acceptable
Alternatives Eg. Digoxin for Tachycardia-Bradycardia Syndrome
4. Carotid Sinus Stimulation causing Recurrent Syncope or Asystole > 3 seconds in the absence of any
medication that depresses the Sinus Node or AV Conduction
B. WOF: Pacemaker Syndrome
o Neck vein engorgement, Dizziness, Dyspnea, Chest Pain

25

o This occurs when Atrium pumps against a Closed Mitral Valve due to Asynchronization
VIII. ECG FINDINGS OF PERICARDITIS
Diffuse ST-Segment Elevations = Concave Diffuse ST-Segment Elevation

A. ECG of Pericarditis

B. ST Elevation in Pericarditis is Different from MI: In Myocardial Infarction, it is CONVEX

o In MI = ST-Segment Elevation WITH T-Wave Inversion
o Difference = In Pericarditis, when T-Wave Inversion appears, ST-Segment Elevation disappears

IX. OTHER NOTES (during rounds):

A. ECG Findings of Mitral Stenosis
o LA-Enlargement = WIDE P-Wave
o RAD
o RVH
B. Significant Q-Waves
o 1) Q-Wave > 25% of R-Wave
o 2) Q-Wave is > 0.04 seconds (or 1 small box) duration

26

MECHANICAL VENTILATION

1) BASIC INFORMATION
I. WEANING FROM MECHANICAL VENTILATION
Indications for WEANING:
Mental Status: Awake, Alert, Cooperative
PaCO2 > 60mmHg with FiO2 < 50%
PEEP < 5cm
PaCO2 and pH Acceptable
Spontaneous TV > 5mL
VC > 10mL/kg
MIP > 25cmH2O
RR < 30/min
Rapid Shallow Breathing Index (RBI) < 100
Stable Vital Signs following a 1-2 hour Spontaneous Breathing Trial
A. Removal of Mechanical Ventilator support requires that a number of criteria be met
1. Upper Airway Function must be Intact for a patient to remain extubated
If a patient can breathe on his own through an ET Tube but develops stridor or recurrent aspiration once
tube is removed, Upper Airway Dysfunction or an abnormal swallowing mechanism should be suspected
2. Weaning Index
Respiratory Drive and chest wall function are assessed by observation of RR, Tidal Volume, Inspiratory
Pressure, and Vital Capacity
Weaning Index: Ratio of Breathing Frequency to Tidal Volume (breaths per minute per liter), is both
sensitive and specific for predicting the likelihood of successful extubation
If Ratio < 105 with patient breathing without mechanical assistance through an ET Tube, successful
extubation is likely
3. Alveolar Ventilation is deemed adequate when:
Elimination of CO2 is sufficient to maintain arterial pH in the range of 7.35 to 7.40, and an SaO 2 > 90% can
be achieved with an FiO2 < 0.5 and PEEP < 5cmH2O
B. Approaches to Weaning
o
o

T-Piece and CPAP Weaning are best tolerated by patients who have undergone MV for brief periods and require little respiratory
muscle reconditioning
SIMV and PSV are best for patients intubated for extended periods likely to require gradual respiratory-muscle reconditioning
1. T-Piece and CPAP

Brief spontaneous breathing trials with supplemental O2

Initiated for 5mins/hour followed by a 1-h interval of rest

Trials are increased in 5 to 10 minutes/hour increments until patient can remain ventilator independent for periods of
several hours

Extubation can then be attempted

2. SIMV

Involves gradual tapering the mandatory backup rate in increments of 2 to 4 breaths per minute while monitoring blood
gas parameters and respiratory rates

Rates > 25 / min on withdrawal of mandatory ventilator breaths generally indicate Respiratory Muscle Fatigue and the
need to combine periods of exercise with rest

Exercise periods are gradually increased until a patient remains stable on SIMV at < 4 breaths per minute

A CPAP or T-Piece Trial can then be attempted before extubation

3. PSV

Usually initiated at a level adequate for full ventilator support (PSVMax) ie. PSV is set slightly below the peak
inspiratory pressures required by the patient during volume-cycled ventilation
Level of pressure support is then gradually withdrawn in increments of 3-5cmH2O until a level is reached at which the
RR increases to 25 breaths/min At this point, intermittent periods of higher pressure support are alternated with
periods of lower-pressure support to provide muscle reconditioning while avoiding diaphragmatic fatigue
Gradual withdrawal of PSV continues until the level of support is just adequate to overcome the reistance of the ET
Tube (~5 to 10cmH2O)

27

Support can be discontinued and the patient extubated

II. INDICATIONS FOR INTUBATION (Medicine Notes)

Impending Respiratory Failure; Apnea
RR > 35
PaCO2 > 50
NOTES on FiO2:
PaO2 < 60

FiO2 at Room Air = 21%

TV < 3.5mL/kg

O2 via Nasal Prong = # lpm x 0.4 + 20

VC < 10-15mL/kg
Inspiratory Force < 25cmH2O
FEV < 10mL/kg
The primary indication for initiation of mechanical ventilation is
Respiratory Failure, of which there are 2 basic types:
VQ/VT > 0.6

Hypoxemic Respiratory Failure

To deliver High FiO2

Hypercarbic Respiratory Failure

Absent Gag
pH < 7.35
III. SPONTANEOUS BREATHING TRIAL (Harrisons)
Consists of a Period of breathing through the Endotracheal Tube WITHOUT Ventilator Support (both Continuous Positive
Airway Pressure [CPAP] of 5cmH2O & an Open T-Piece Breathing System can be used) for 30-120 mins
A. If the Following are Present, Patient has passed the Screening Test and should undergo Spontaneous Breathing Trial
o Stable Oxygenation (PaO2/FIO2 > 200) and PEEP < 5cmH2O
o Cough and airway reflexes are intact
o No Vasopressor Agents or Sedatives are being administered
B. Spontaneous Breathing Trial is Declared a FAILURE and STOPPED if any of the following occur:
o 1) RR > 35/min for > 5mins
o 2) O2 Saturation < 90%
o 3) HR > 140/min or a 20% Increase or Decrease from Baseline
o 4) Systolic BP < 90mmHg or > 180mmHg
o 5) Increased Anxiety ot Diaphoresis
If at the end of the Spontaneous Breathing Trial, the ratio of the Respiratory Rate and Tidal Volume in Liters (f/V T)
is < 105, the patient can be EXTUBATED

IV. ASSIST CONTROL MODE (Medicine Notes)

Each breath is assisted by the vent even if the RR exceeds the BUR
Parameters: VT, PEEP, BUR, PFR/IFR, FiO2, Sensitivity Flow Pattern
A. Tidal Volume
o
o

General: 8-10 mL/kg

In ARDS: 6 mL/kg

B. PEEP:
o 5cm H2O
C. Back Up Rate
o 16-20
D. Peak Flow Rate:
o 40-60 mL
o Asthma / COPD: Increase to allow more time to exhale
o ARDS: Decrease to Prevent further injury
E. FiO2 Start at 100%
o If lungs are NORMAL (eg. Trauma patient), start at 50%
o DECREASED to tolerable % as fast as possible (doesnt have to be decreased by 10%)
o Non-Toxic FiO2 = 50% (Golden Time to reach this is 4 hours)
F. Sensitivity (Trigger) 2 L
o Pressure: (-) 1.5 to 2.0 cmH2O (the more negative, the more work patient does)
o Flow: Usually 2L

28

G. Flow Pattern:
o Square Wave

2) BASIC MODES OF VENTILATION (Mech-Vent Work Shop: Dr.Divinagracia Lecture)

Indications for Mechanical Ventilation:
1. Clinical Assessment
Presence of Apnea, Tachypnea (>40/min)
Respiratory Failure that cannot be corrected by any other means
2. Arterial Blood Gases (ABG)
Severe Hypoxemia (PO2 < 50) despite High-Flow Oxygen
Significant CO2 Retention (PCO2 > 50)
3. Worsening Physiological Parameters
Are of limited use since patients with Respiratory Insufficiency are unable to perform PFTs and their Respiratory
Failure mandates immediate intervention
However in some cases especially in Neuromuscular Diseases, these parameters can be used as warnings that the
patient will go into Respiratory Failure sooner rather than later:
o 1) Vital Capacity < 15mL/kg
o 2) Inspiratory Force < -25cm H2O
o 3) FEV1 <10mL/kg
TWO Main Modes of Ventilation:
Volume Cycled / Controlled: we set the Tidal Volume (ex. AC Mode)
Pressure Controlled Ventilation: we set the Peak Airway Pressure (Favorable in ARDS)

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
with EACH patient effort
If patients Respiratory Rate decreases past a Preset Rate, the Ventilator delivers Tidal Breaths at the Preset Rate
EVERY BREATH is assisted
A. Advantages and Disadvantages
ADVANTAGES
Useful in Patients with Neuromuscular Weakness or
CNS Disturbances
The INITIAL Mode usually set upon advent of
Mechanical Ventilation
It totally Unloads (rests) the Respiratory Muscles
requiring NO Work on the Patients part

DISADVANTAGES
Tachypnea may result in Significant Hypocapnea and
Respiratory Alkalosis
Improper setting of Sensitivity to trigger the Ventilator may
result in fighting the ventilator when sensitivity is set too
low
Increases Sensitivity may result in Hyperventilation;
Sensitivity is generally set so that an Inspiratory Effort of
2cmH2O will trigger the Ventilation
Since there is almost NO work involved by the Respiratory
Muscles, Muscle Tone is NOT well Maintained (Atrophy).
Muscle Atrophy starts within 6 hours

29

B. Selection of Ventilator Settings for A/C Mode

SETTING
1) Tidal Volume (VT)

How much volume will the Machine Deliver?

2) Back-Up Rate: Number of Tidal Breaths Delivered per Min

40-60 L/minute

How fast do we deliver the air? 60L/minute is FASTER than

40L/minute (Higher Flow Rates Higher Peak Pressure)
This is the Rate air is delivered to the patient to achieve the Tidal
Volume set
Rate needs to be HIGHER (80L/min) in COPD & Asthma
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)
In Patients with Hypoxemia, deliver the air SLOWER (so that
Inspiration Time is Longer more time to exchange PO2

5) Inspiratory Flow Pattern (IFP)

100%

Initial FiO2 should be 100% unless it is evident that a Lower FiO2

will provide adequate oxygenation
We can start at 50% if Neuromuscular Disease (ex. MG)

4) Inspiratory Flow Rate (IFR)

16 - 22

Minimum number of breaths per minute

Usually set 2 to 4 below the Spontaneous Rate and then the Effect
on the patient of Decreasing Rate is noted (this can be adjusted
depending on the desired PaCO2 or pH
Ex) If set at 8, patient will NOT breath below RR < 8
Faster RR = Blow of CO2 PaCO2 and pH

3) Oxygen Concentration (FiO2)

USUAL VALUE
8-10 mL/kg of Ideal Body Weight
6mL/kg for ALI/ARDS
10-15mL/kg for Neuromuscular Dse

Square Wave

How do you deliver the Air? This is how flow is distributed

throughout the Respiratory Cycle
Normal Person: Sine Wave

Wave Forms usually Available:

a. Sine Wave:

The maximum flow is at Mid Inspiration and resembles a Normal

Spontaneous Tidal Breathing
b. Square Wave

This provides a maximum peak flow throughout the Inspiratory Period

Fast Delivery patients prefer it (but has higher pressures)

c. Decelerating Wave
The flow is maximal at the Start and diminishes as Inspiration ends

6) PEEP

5cm H2O

Physiologic PEEP of about 5cm H2O should be added regardless

of FiO2 to prevent the Alveolar Injury due to the Shearing Effect
of opening and closing the Alveoli
Pressure at End Expiration (it is Positive)

30

Should be Increased in ARDS

7) Sensitivity

Ranges anywhere from 5 to 0.5cmH2O (Pressure Sensitivity) or

1 to 5 Liters (Flow Sensitivity)
The MORE Sensitive (eg. 0.5cm or 1L), the EASIER for the
patient to Trigger the Ventilator which may lead to
Hyperventilation
The LESS Sensitive (eg. 5cm or 5L), the HARDER for the patient
to trigger the Ventilator which may lead to Increased Work of
breathing and thus can cause Patient-Ventilator Desynchrony

-2.0cm or 2L
Different for PGH Vents

a. Pressure Sensitivity

Ex) If set at 1, the patient has to exert a 1cmHg Pressure for the Vent to
Deliver the Tidal Volume
b. Flow Sensitivity

Ex) If set at 1L, patient has to create a negative pressure

Advantage: Patients with COPD (difficult to empty lungs) they will
have LESS work

Sensitivity in PGH Mechanical Ventilators:

o Turn knob Counterclockwise becomes Less Sensitive
o Turn know Clockwise becomes More Sensitive
I:E Ratio:
o Normal is 1:2
o In COPD, adjust to 1:3
o In ARDS, adjust to 1:1
o Ex) In COPD, we Increase the IFR so that the IE Ratio will be 1:3

31

II. SYNCHRONIZED INTERMITTENT MANDATORY VENTILATION (SIMV)

There are two separate circuits for contribution of Minute Ventilation
o One circuit delivers Ventilator Breaths in a manned identical to A/C, with the Ventilator breath being timed or
synchronized to patient effort
o The Mechanical Ventilator breaths are limited to a preset number
Additional patient effort leads to Spontaneous Breaths made through a separate fresh gas system
Allows patient to take as many spontaneous breaths as he chooses around the Intermittent Synchronized Ventilator Breaths
The patients contribution to Minute Ventilation depends on the number of Spontaneous Breaths and Inspiratory Effort
Sample Case: SIMV Mode; BUR set at 12; Patients actual RR is 20

ONLY the 12 of 20 Breaths are Assisted in SIMV

o 12 will Receive the COMPLETE TV set
o 8 will Receive the TV, depending on the Patients efforts

In CONTRAST, in AC Mode ALL 20 will be Assisted

A. Advantages and Disadvantages

ADVANTAGES
Maintains Respiratory Muscle tone due to the continued
use of the Inspiratory Muscles and thus prevents Disuse
Atrophy
There is Decreased Intrathoracic Pressure as compared
to A/C which may lead to improved Hemodynamics
Useful for WEANING because as the Back-Up Rate is
Decreased, the patient gradually assumes the Bulk of
Breathing

DISADVANTAGES
Even with the same Back-Up Rate as the A/C, there is
MORE WORK of Breathing
The Increased Work of breathing results in Increased Oxygen
Consumption which is deleterious in patients with
Myocardial Insufficiency
This mode is NOT useful in patients with Depressed
Respiratory Drive or Impaired Neurologic Status

B. Selection of Ventilator Settings for the SIMV Mode

o Rate: Initial Rate should be Close to the Patients Rate and then the Rate Decreased noting the effect on Patient
Acceptance
o VT, FiO2, IFR, IFP, PEEP SAME of that in A/C
C. A/C Mode VS SIMV:
Assist
Work of Breathing
Can be Used for Weaning

A/C MODE
Total
Almost NONE
NO

SIMV MODE
Partial
Variable
YES

III. RECENT MODALITIES OF MECHANICAL VENTILATION

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

32

3) OTHER NOTES IN MECHANICAL VENTILATION

I. RESPIRATORY MONITORING
Gas Exchange
o Carbon Dioxide and Ventilation
o Oxygen
Lung and Chest Wall Mechanics
o Pressure-Volume Relationships
o Mean Airway Pressure
o Auto-PEEP Effort
Breathing Effort
Ventilatory Drive and Breathing Pattern
Strength and Muscle Reserve
II. SOME FORMULAS:
A. PAO2-PaO2 Gradient
PAO2 = FiO2 (Patm PH2O) (PaCO2 / R)
Normal PAO2-PaO2 Gradient = 10
Increases by 5-6 per decade over 50

At Sea Level:
FiO2 = 0.21
PH2O = 47
PBREATH = 760

PaCO2 = Measured by Labs

R = 0.8

B. Desired FiO2
Desired FiO2 = (PaO2 Desired x FiO2 Known)
PaO2 Known

Example:
Desired FiO2 = 80 x 21%
50

C. Minute Ventilation
Minute Ventilation = Kg x 100
RR
III. WEANING PARAMETERS AND STRATEGIES
Weaning: process of abruptly or gradually withdrawing Ventilatory Support when the cause of the Respiratory Failure is
under resolution
A. When should Weaning be Initiated?
o Liberation from MV in the EARLIEST possible time without compromising the patients safety and recovery is of
prime importance to minimize the complications associated with MV and Intubation
Weaning: Shifting breathing workload from Machine to Patient
Spontaneous Breathing Trials: Testing the patients ability to breath independently
B. Weaning is NOT Synonymous with Extubation
o Need for Mechanical Ventilation is NOT the same as the Need for Artificial Airway
o Weaning Failure: inability to maintain adequate Respiration THROUGH an Artificial Airway
o Extubation Failure: inability to maintain adequate Respiration AFTER removal of Artificial Airway

33

C. Conditions which SHOULD be Met for Weaning

o Resolution or Improvement of the cause of Respiratory Failure
o Cessation of Sedative Drugs
o Cessation of Neuromuscular Blocking Agents
o Absence of Sepsis or marked Fever
o Stable Cardiovascular Status
o Correction of Electrolyte Disorders
o Correction of Metabolic Disorders
o No planned General Anesthesia
o Adequate Gas Exchange
o Adequate Respiratory Pump Capacity
1. Objective Measurements
Adequate Oxygenation
Stable Cardiovascular System (HR < 140; Stable BP; No (or Minimal Pressors)
Afebrile (T <380C)
No significant Respiratory Acidosis
Adequate Hemoglobin (Hgb > 8-10g/dL)
Adequate Mentation (arousable, GCS > 13, no continuous sedative infusion)
Stable Metabolic Status
2. Subjective Clinical Assessment
Resolution of Disease Acute Phase
M.D. believes Discontinuation possible
Adequate Cough
3. Pulmonary Gas Exchange
Minimal PO2 > 60mmHg with:
FiO2 < 0.4 with a PEEP level < 5cmH2O
PaO2/PAO2 > 0.35
PaO2/FiO2 Ratio > 200
Normal PCO2 or back to Baseline for Chronic retainers with Normal pH
4. Rapid Shallow Breathing Index (RSBI)
Overall has the BEST Combination of Sensitivity and Specificity among Weaning Indices
Threshold Value >105

RSBI = f (per minute) / VT (in Liters)

D. Methods of Weaning:
o T-Piece Weaning (abrupt and simple)
o SIMV
o Pressure Support Ventilation
o Noninvasive Ventilation

34

IV. OXYGEN DELIVERY

Low Flow: Nasal Cannula, Face Mask, Reservoir Mask
Indications:
o PaO2 < 60mmHg or SaO2 < 90%
o Acute Situation where Hypoxemia is suspected
o Severe Trauma
o Acute Myocardial Infarction
o Short Term, Post Operative
A. Nasal Cannula
o FiO2 Increases approximately 2-4% / L
o Flowrates >6 lpm do NOT augment the inspired gas
o High Flows can dry the Nasal Mucosa
o Humidification is recommended for Flow Rates > 4 lpm
o Provides 23-45% of O2
o Maximum Flow Rates = 6 lpm
B. Simple Masks
o Provides 31-61% O2
o Flow Rates = between 5-10 lpm
o The reservoir is the space between the mask and the patients face
o Higher Potential FiO2
o Less than 5 lpm is NOT recommended
o 5 lpm is needed to flush exhaled CO2 from the Mask
V. OXYGEN TOXICITY
Injury to the Lung Parenchyma and Airway epithelium due to Cytotoxic Free Oxygen Radicals
Gas exchange abnormalities occur in 24-48 hours with 100% oxygen
FiO2 up to 0.5 for 2-7 days usually does NOT result in Toxicity
If needed, an FiO2 of 100% can be used for up to 24 hours WITHOUT significant Lung Injury

35

LABORATORY WORK UPS AND ANTIBIOTICS

1) NORMAL LABORATORY VALUES (PGH VALUES)

CBC Values
WBC
RBC
Hgb
Hct
MCV
MCH
MCHC
RDW-CV
Platelets

4-11x109/L
4-6 x 1012/L
120-180 g/L
0.370-0.540 %
80-100 fL
27-31 pg
320-360 g/L
11-16%
150-450 x 109/L

Neut%
Lymph%
Mono%
Eo%
Baso%
Pro/Mye/Jv
Stabs
Blasts
Reticulocytes

0.5-0.7
0.2-0.5
0.02-0.09
0.0-0.06
0.0-0.02
0
0.02-0.04
0
0.005-0.015

4-11 x 103/mm3
4-6 x 106/mm3
12.0-18.0g/dL

150-450 x 103/mm3

Thyroid Hormones
Free T4
0.8-2.0 ng/dL
Free T3
2.3-4.2 pg/dL
TSH
0.25-4.30 microunits/mL
Serum T3
70-200 ng//dL
Serum T4
4.0-11.0 ug/dL
ABG
pH
PCO2
PO2
HCO3

7.35-7.45
35-45 mmHg
90-100 mmHg
22-28 mEq/L

Urinalysis
Color
Transparency
SG
PH
Sugar, Albumin

RBC
WBC
Casts
Crystals
Epith cells
Bacteria
Mucus thr

CK-total
CK-MB
CK-MM
Troponin I
Cut Off for MI

Yellow
Clear/hazy
1.016-1.022
4.6-6.5
(-)
0/0-2/hpf
0-2/0-5/hpf

3.9-6.1 mmol/L
2.6-6.4 mmol/L
53-115 umol/L
140-148 mmol/L
3.6-5.2 mmol/L
100-108 mmol/L
2.12-2.52 mmol/L
0.70-1.00 mmol/L
0.9-1.55/0.42-1.97
64-83 g/L
34-50 g/L
23-35 g/L
15-37 U/L
30-65 U/L
36-92 umol/L
0-17.1 umol/L
0 - 5.00 umol/L
3.4-13.7 umol/L
0.13-0.44 mmol/L
30-110 U/L
23-300 U/L
100-190 U/L
M: 0-15 mm/h
0.2-3.0 mg/L
19-60 ug/dL
< 20 IU/mL

75-110 mg/dL
7-20 mg/dL
0.6 1.3 ng/mL
140-148 mEq/L
3.6-5.2 mEq/L
100-108 mEq/L
8.7-10.2 mg/dL
1.5-2.3 mg/dL
6.4-8.3 g/dL
3.4-5.0 g/dL

0.3-1.3 mg/dL
0.1-0.4 mg/dL
0.2-0.9 mg/dL

F: 0-20 mm/h
11-35 umol/L

55-170 U/L
0-16 U/L
8-97 U/L
0-0.09 ng/mL
> 0.4 ng/mL

0-0.09 ug/L
> 0.4 ug/L

0.91-1.56 mmol/L
1.1-3.8 mmol/L
4.2-5.2 mmol/L
0.41-2.37 mmol/L

35-60 mg/dL
40-145 mg/dL
160-200 mg/dL
< 180 mg/dL

Lipid Profile

hyaline, coarse, fine, granular, waxy

Small amounts
Small amounts
(-)
Small amounts

HDL
LDL
Cholesterol
Triglycerides

HDL or LDL divided by 0.0259 to convert to mg/dL

TAG divided by 0.0113 to convert to mg/dL

24 Urine Chemistry

0-8.5 ng/L
0-4 ng/mL
0-35 U/mL
0-37 U/mL
(-)Smoker: 0-3 ug/L

Glucose
BUN
Creatinine
Sodium
Potassium
Chloride
Calcium
Magnesium
Phosphates
Total protein
Albumin
Globulin
AST (SGOT)
ALT (SGPT)
Alk phos
Total bilirubin
Dir bilirubin
Ind bilirubin
Urate
Amylase
Lipase
LDH
ESR
CRP
Ammonia
RF
Cardiac Enzymes

Cancer Markers
AFP
PSA
CA 125
CA 19-9
CEA

BLOOD CHEM

(+)Smoker: 0-5 ug/L

Total volume
Creatinine
Total protein
Na+
K+
ClUric acid
Ca++

500-2000 cc
0.65-0.70 g/L
0-0.1 g/24hour
80-216 mmol/L
25-100 mmol/L
80-340 mmol/L
4.42-5.9 mmol/24hr
2.5-7.5 mmol/24hr

8.8-14 mmol/d
< 100mg/d
Varies with intake

36

Phosphorus
Amylase
Microalbumin

22.4-33.6 mmol/24hr
64.75-490.25 U/L
N: 0.0-0.03 g/d
Microalbuminuria: 0.03-0.30 g/d
Clinical Albuminuria: >0.3g/d

37

2) CLINICALLY USEFUL ANTIBIOTICS (from the Blue Book)

DRUG

GRAM (+)

GRAM (-)

ANAEROBES

Penicillins
Penicillin
Oxacillin PO/IV
Flucloxacillin
Amoxicillin PO, Ampicillin IV
Co-Amoxiclav
Ampi-Sulbactam
Piperacillin / Tazobactam

+++
++
++
++
++ 1/2
++
++

++
++ 1/2
++
++ 1/2

++
+
++ 1/2
++ 1/2
+

Glycopeptide
Vancomycin

+++

Reserve drug & most active for S.aureus and

Enterococcus. Give very slowly as IV infusion

Monobactams
Aztreonam

+++

Alternate to Aminoglycosides in renal failure

Carbapenems
Imipenem-Cilastin
Meropenem

+++

+++

+++

Ertapenem

++

+++

Use as reserve drug

Gm (+) activity as good as Penicillin
For Gm (-): may add Amikacin for Synergism
Anaerobic activity as good as Metronidazole
Very little activity against pseudomonas

++ 1/2
++ 1/2

+ 1/2
++

+
+ 1/2

++

++

For patients > 8 years old

Tetracycline is cheaper, but given QID

+++

With Anti-Pseudomonas activity

Amikacin with Anti-TB action

+++

++ 1/2
++ 1/2
++

++
++
++

+
+
++ 1/2

++
++
++

+++
+++
+++

++
++
++

For multidrug resistant Typhoid

Ceftazidime is best for Pseudomonas
Cefotaxime is best for Meningitis

+++

+++

++

These should be reserved for the very resistant

strains

Macrolides
Erythromycin
Azithromycin
Clarithromycin
Dirithromycin
Tetracycline
Doxycycline
Tetracycline
Aminoglycosides
Amikacin
Gentamicin
Tobramycin
Netilmicin
First Generation Cephalosporins
Cephalexin PO
Cefazolin IV
Second Generation Cephalosporins
Cefuroxime IV
Cefuroxime Axetil PO
Cefoxitin
Third Generation Cephalosporins
Ceftriaxone
Ceftazidime
Cefotaxime
Fourth Generation Cephalosporins
Cefepime
Cefpirome

REMARKS
Narrow spectrum penicillins
Specifically used for Staphylococcus aureus
Broad spectrum penicillin
Good anaerobic coverage
Good anaerobic coverage
Use as reserve drug for Pseudomonas

May cause GI upset

IV drug
Oral drug
Cephalosporin with best Anaerobic coverage

Quinolones

38

Ciprofloxacin
Norfloxacin
Ofloxacin
Fleroxacin
Levofloxacin
Moxifloxacin
Others
Co-Trimoxazole
Co-Trimazine
Chloramphenicol
Clindamycin
Metronidazole
Rifampicin

+++

Used for multidrug resistant Typhoid Fever

Ciprofloxacin is best for Pseudomonas
Norfloxacin is good for Severe UTI

++

+++

Moxifloxacin with better Anaerobic activity

++ 1/2

++ 1/2

++ 1/2
++

++ 1/2
-

++ 1/2
+++

++

++

++ 1/2
+

Drug of choice for Uncomplicated Typhoid

Above diaphragm Anaerobes
Good Gm(+) Activity
Below diaphragm Anaerobes
Used for pulmonary tuberculosis

ADDITIONAL NOTES:
Drugs with Anti-Pseudomonas Properties:
o Aminoglycosides (Tobramycin, Netilmicin, Amikacin, Gentamicin)
o Ceftazidime, Cefoperazone, Quinolones (Ciprofloxacin), Ticarcillin and Piperacillin
o Monobactams (Aztreonam), Carbapenems (Meropenem)
o Fourth Generation Cephalosporins (Cefepime and Cefpirome)

Drugs with Good Anaerobic Properties:

o Clindamycin
o Metronidazole
o Chloramphenicol

Cefoxitin
Meropenem
Ampicillin-Sulbactam

Amoxycillin-Clavulanic Acid
High Dose Penicillin

Drugs with Good Central Nervous System (CNS) Penetration in Meningitis:

o Ceftriaxone

Ampicillin

Penicillin-G
o Ceftazidime

Meropenem

Vancomycin
o Cefuroxime

Ampicillin-Sulbactam
o Cefotaxime

Ciprofloxacin
o Chloramphenicol and Co-Trimoxazole have high diffusion to the CSF even WITHOUT Meningitis

Drugs safe for patients with Liver Disease:

o Aminoglycosides
o Ampicillin
o Amoxicillin
o Cephalexin
o Cefoxitin
o Cefuroxime
o Ofloxacin
o Penicillin-G
o Carbapenems

39

On Cephalosporins
o 4th Generation Cephalosporins have the same indications as 3rd Generation Cephalosporins and should remain as reserved
drugs
o The only two Third Generation Cephalosporins active against Pseudomonas are Ceftazidime and Cefoperazone. Cefaperazone
may cause bleeding in predisposed patients
o Cephalosporins that cross the Blood-Brain Barrier: Ceftriaxone, Ceftazidime, Cefotaxime, Ceftizoxime
o Cephalosporins with Best Anaerobic Coverage: CEFOXITIN. Other Cephalosporins also have some Anaerobic properties
o Cefuroxime Axetil is given with Meals
o Cefazolin is the Drug of Choice ONLY for Surgical Prophylaxis of abdominal operations & implant surgery
On Aminoglycosides:
o Aminoglycosides are given q 8-12 hours in 30 minutes by Slow IV or IM to avoid possible neuromuscular paralysis. They must
have loading doses, and should be given for < 7 days to avoid Nephrotoxicity. Creatinine is measured every 3 days.
o Amikacin: Expensive but it is the most potent and least nephrotoxic

Loading Dose = 7.5mg/kg

Maintenance Dose = 15mg/kg/day in 2 divided doses IM, IV

o Gentamicin, Tobramicin, Netilmycin

Loading Dose = 2mg/kg

Maintenance Dose = 1.5mg/kg/dose q 8hours IM, IV

o Gentamicin is the cheapest aminoglycoside. Spectinomycin is used for Gonorrhea. Streptomycin is used for PTB
On Macrolides
o Erithromycin is given with meals. If with GI upset, lower the dose
o Azithromycin is given 1 hour before meals
Rifampicin
o Aside from Anti-TB properties, Rifampicin may be used synergistically with Oxacillin for S.aureus
o Resistance may develop easily when Rifampicin is used alone

NOTES ON ANTIBIOTICS
1. Methicillin Resistant Staphylococcus aureus (MRSA)

Give Vancomycin, then shift to Oral Zivox (?) when MGH

General Rule:
o If (+) with Bacteremia: 14 days
o If (+) Solid Organ Abscess: 4-6 weeks
2. Two Organisms NOT Targeted by Cephalosporins

Enterococcus

Listeria monocytogenes

**NOTE: Use Penicillins, Ampicillin

3. Ceftriaxone Doses (double check):

2g OD = usual dose

2.5g OD = Gonorrhea

3g OD = Typhoid

2g BID = Meningitis
4. Some Antibiotics to Target Pseudomonas

Ceftazidime

Piperacillin-Tazobactam

Carbapenems (Meropenem) EXCEPT Ertapenem

5. Anaerobic Coverage (ex. If Pneumonia has + Aspiration)

Clindamycin

Metronidazole
6. HLARE

High Level Aminoglycoside Resistance Enterococcus

Mx: Vancomycin
7. ESBL

Extended Spectrum Beta Lactamases

Mx: Carbapenems

40

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CARDIOLOGY
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ertyuiopasdfghjklzxcvbnmqwertyuiop
Jaime Alfonso Manalo Aherrera, M.D.

Internal Medicine Notes 2009

CONGESTIVE HEART FAILURE

CONGESTIVE HEART FAILURE

Heart Failure is a clinical syndrome that occurs in patients who, because of an inherited or acquired abnormality
of cardiac structure and/or function, develop a constellation of clinical symptoms (dyspnea & fatigue) and signs
(edema and rales) that lead to frequent hospitalizations, a poor quality of life, and a shortened life expectancy

Categorized into TWO Groups:

o Systolic Failure: HF with a Depressed Ejection Fraction
o Diastolic Failure: HF with a Preserved Ejection Fraction
Compensatory Mechanisms Activated in the Presence of Cardiac Injury and/or LV Dysfunction:
o 1) Activation of the Renin-Angiotensin-Aldosterone (RAA) and Adrenergic Nervous Systems, which are
responsible for maintaining Cardiac Output through increased retention of salt and water
o 2) Increased Myocardial Contractility
LV Remodeling Changes:
o
o
o
o
o

Myocyte Hypertrophy
Alterations in the Contractile Properties of the Myocyte
Progressive Loss of Myocytes through Necrosis, Apoptosis, and Autophagic Cell Death
B-Adrenergic Desensitization
Abnormal Myocardial Energetics and Metabolism
Reorganization of the Extracellular Matrix with dissolution of the organized structural collagen weave and subsequent
replacement by an interstitial collagen matrix that does not provide structural support to the myocytes

I. FRAMINGHAM CRITERIA FOR DIAGNOSIS OF CONGESTIVE HEART FAILURE

A. Major Criteria
o Paroxysmal Nocturnal Dyspnea
P-R-I-N-C-E-S-P
o Neck Vein Distention
o Rales
o Cardiomegaly
o Acute Pulmonary Edema
1 Major + 2
o S3 Gallop
o Increased Venous Pressure (>16cmH2O)
o Positive Hepatojugular Reflux

Minor Criteria

B. Minor Criteria
o Extremity Edema
D-P-V-T-H-E-N (the private hen)
o Night Cough
o Dyspnea on Exertion
o Hepatomegaly
o Pleural Effusion
o Vital Capacity reduced by 1/3 from Normal
o Tachycardia (>120bpm)
C. Major or Minor
o Weight Loss 4.5kg over 5 days Treatment

II. NYHA CLASSIFICATION OF CHF

FUNCTIONAL
CLASS

I
II
III
IV

DESCRIPTION
Dyspnea occurs with Greater than Ordinary Physical Activity
Dyspnea occurs with Ordinary Physical Activity
Dyspnea occurs with Less than Ordinary Physical Activity
Dyspnea may be present even at Rest

GENERAL GUIDE
Climbs > 2 flights of stairs with Ease
Can climb 2 flights of stairs but with difficulty
Can climb < 1 flight of stairs
Dyspnea at rest

III. CANADIAN CARDIOVASCULAR SOCIETY CLASSIFICATION OF ANGINA

FUNCTIONAL
CLASS
I
II
III
IV

DESCRIPTION
Angina occurs with Greater than Ordinary Physical Activity
Angina occurs with Ordinary Physical Activity
Angina occurs with LESS than ordinary Physical Activity
Angina may be present even at REST

IV. CLUES SUGGESTING DIGITALIS TOXICITY

Digitalis glycosides are given to enhance myocardial performance in situations of chronic heart failure as well as
to control many Supraventricular Dysrhythmias
NORMAL Serum Levels of Digoxin may produce subtle alterations in ECG called the Digitalis Effect
A. Toxic Levels are associated with:
o Potentially Life-Threatening Dysrhythmias
o Heart Blocks
o Etc

Digitalis preparations have a narrow therapeutic range, so maintaining

the desirable serum level of the drug is difficult. HYPOKALEMIA,
a common side effect of diuretic therapy, POTENTIATES the Toxic
Effects of Digitalis.
Antidysrhythmic agents such as Quinidine and Amiodarone, as well

B. Clues PE Suggesting Digitalis Toxicity

as Verapamil, are known to Increase Serum Digoxin Level
o Change in visualization
o Interruption in conduction system (bradycardia, branch blocks)
C. ECG Manifestations of the Dig Effect Include:
o
o
o
o
o

Depressed ST-Segments in leads where the main QRS Deflection is Positive (eg. In the inferior and lateral leads); the STSegments gradually slope downward and look scooped out
Elevated ST-Segments in leads where the main QRS Deflection is Negative (eg. Lead V1)
Flattened or Inverted T-Waves
Shortened QT Interval
Prolongation of the PR-Interval compared with a Pretreatment Baseline; the PR Interval often lengthens by 0.04 to 0.08 seconds
(or more)

D. ECG Manifestations of Digitalis Toxicity include:

o The same ST-Segment and T-Wave changes noted with the Dig Effect
o Significant Prolongation of the PR-Interval
o Supraventricular Dysrhythmias

Ventricular Dysrhythmias

Extreme Sinus Bradycardia

Atrial Premature Complexes (APCs)
Sinoatrial (SA) Block
Junctional Premature Complexes (JPCs)
Junctional Escape Rhythm
Accelerated Junctional Rhythm
Junctional Tachycardia
Atrial Tachycardia with AV Block
Ventricular Premature Complexes (VPCs)
Ventricular Bigeminy
Ventricular Tachycardia (VT)
Ventricular Fibrillation

Bidirectional VT (alternating Polarity of the QRS

Complex) is associated with Poor Prognosis

Atrioventricular (AV) Block

Atrial Tachycardia with AV Block

Second Degree AV Block Type I
Third Degree AV Block

E. Treatment of Digitalis TOXICITY

o
o
o
o

Withholding further Digoxin

Potassium Replacement Therapy (carefully AVOID Hypokalemia)
Digoxin Antibody Fragments (Digoxin Immune Fab)
Temporary Pacing
Diphenylhydantoin (for treatment of Digitalis-Induced Ventricular Dysrhythmias)

V. SOME SIGNS AND SYMPTOMS OF CHF

Cardinal Symptoms of HF: Fatigue and Shortness of Breath
In early stages, DYSPNEA is observed only during exertion
Origin of Dyspnea = Multifactorial (Most Important: Pulmonary Congestion)
A. Orthopnea
o Dyspnea occurring in the RECUMBENT position (later manifestation of HF than is exertional dyspnea)
o Nocturnal Cough: frequent manifestation of this process
o Relieved by sitting upright or by sleeping with additional pillows
B. Paroxysmal Nocturnal Dyspnea
o Acute episodes of severe shortness of breath and coughing that generally occur at night and awaken the patient from
sleep, usually 1-3 hours after patient retires
o Cardiac Asthma: wheezing secondary to bronchospasm
C. Cheyne-Stokes Respiration
o Also referred to as Periodic Respiration or Cyclic Respiration
o Common in advanced HF and is associated with Low Cardiac Output
o Caused by a diminished sensitivity of the respiratory center to Arterial PCO 2
o There is an Apneic Phase, during which the arterial PO2 Falls and PCO2 Rises
o These changes in the arterial blood gas content stimulate the depressed respiratory center, resulting in
Hyperventilation and Hypocapnia, followed in turn by recurrence of Apnea
D. Jugular Venous Pressure (JVP)
o Estimation of the Right Atrial Pressure
o Two main objectives of the examination of the neck veins are inspection of their waveform and estimation of the
central venous pressure (CVP)
o Right Internal Jugular Vein is best for this purpose
o Vertical distance between the top of the oscillating venous column and the level of the sternal angle is determined
generally, it is Less than 3cm (3cm + 5cm = 8cm blood)
o Most Common cause of a high venous pressure is an Elevated Right Ventricular Diastolic Pressure
**IMPORTANT Notes:
CVP = pressure within the right atrium
CVP is equal to [JVP + 5]
E. Abdominojugular Reflux
o Done in patients suspected of having right ventricular failure who have normal CVP at rest
o Palm of examiners hand is placed over the abdomen, and firm pressure is applied for 10s or more
o Normal Persons: maneuver does NOT alter the JVP significantly
o Right Heart Function Impaired: Upper Level of venous pulsation usually INCREASES
o Definition of a Positive Abdominojugular Test: An increase in JVP during 10s of firm midabdominal compression
followed by a rapid drop in pressure of 4cm blood on release of the compression
F. Cardiac Examination
o An S3 (Protodiastolic Gallop) is most commonly present in patients with Volume Overload who have Tachycardia
and Tachypnea, and often signifies Severe Hemodynamic Compromise
o An S4 is NOT a specific indicator for HF, but is usually present in patients with Diastolic Dysfunction
Nice to Know:
Water-bottle Sign = Pericardial Effusion
Electrolytes that can cause arrhythmias = Potassium, Calcium, Magnesium
Kussmauls Sign
An increase, rather than the normal decrease, in CVP during INSPIRATION
Most often caused by Severe Right Sided Heart Failure
Frequent finding in patients with Constrictive Pericarditis or Right Ventricular Infarction
Mitral Stenosis
Normal Mitral Valve Orifice = 4-6cm2
Threshold for Surgical management of Mitral Valve Stenosis < 1.7cm2

VI. TREATMENT FOR HEART FAILURE (Triple Therapy Dr. Abarquez)

Diuretics (Spironolactone: Diuretic of choice because it also blocks aldosterone)
ACE Inhibitors / ARBS
Caution in use of Beta-Blockers = may push patient into further congestion
Digoxin
Management of HF with DEPRESSED Ejection Fraction (<40%)
1. General Measures / Activity / Diet
o Modest exercise
o Salt Restriction (2-3g daily)
o Fluid restriction (<2L/day) if with (+) Hyponatremia or difficult to control fluid retention despite high doses of
diuretics and Na+ Restriction
2. Pharmacologic Management
o Diuretics (only agents that can adequately control fluid retention in advanced HF)
o Preventing Disease Progression
ACE Inhibitors
B-blockers
Effects of Digitalis (Dr. Abarquez Lecture)
o Inotropy
o Lusitropy (attenuates Growth and Collagen Factor)
o Neurogenic
o Preload & Afterload
o Vagotonic
o Less Apoptosis (has Anti-Apoptotic Events)

VII. OTHER SIDE NOTES:

A. Some Trials on Congestive Heart Failure
o RALES: Randomized Aldactone Evaluation Study (Benefits of Spironolactone)
o VHeFT: Vasodilators in Heart Failure
B. Effects of Anti-Hypertensives:
o Enalapril = Preload and Afterload
o Hydralazine = Afterload
o ISDN = Preload
C. Note on HDL VS LDL
o If Decreased HDL but NORMAL LDL = we may give Fibrates to Increase HDL
o If LDL is Increased, we must address the LDL first!
**CONVERSION Factor:

HDL or LDL divided by 0.0259 to convert to mg/dL

TAG divided by 0.0113 convert to mg/dL

HYPERTENSION (from Harrisons)

CLASSIFICATION
Normal
Pre-Hypertension
Stage 1 Hypertension
Stage 2 Hypertension
Isolated Systolic Hypertension

SYSTOLIC (mmHg)
< 120
120 139
140 159
> 160
> 140

DIASTOLIC (mmHg)
And < 80
Or 80 89
Or 90 99
Or > 100
And < 90

Clues for Secondary Hypertension:

o Age of Onset < 20 or > 50
o (-) Family History
o DBP > 110 120
o Sudden Increase in BP in a patient with Stable Stage I HPN
o Poor BP Control, despite Good Compliance
A. Hypertensive Urgency
o Use ORAL Drugs first
o ALA Hypertensive Crisis
o Uncontrolled HPN with NO End-Organ Damage
o Lower BP within 24 hours

B. Hypertensive Emergency
o Use IV Medications, stat
o AKA Malignant Hypertension
o WITH End Organ Damage (Papilledema,
Encephalopathy, Eclampsia, etc)
o Lower BP within 1 Hour

C. Treatment of Hypertensive Urgency / Emergency (Medicine Notes)

1. Oral / Sublingual
Nifedipine
Captopril
Clonidine

5-10 mg SL q30 mins, then 5-10mg PO or SL q6-8hours; OR

30mg/tab PO OD-BID (max 90mg/day)
25 mg/tab 1/2-1 tab SL q30 mins
75 mcg/tab SL q1 (max 700mcg)

2. IV
Nicardipine IV
Hydralazine
ISDN IV
Clonidine
Nitroprusside IV

Initial 5mg/h; titrate by 2.5 mg/h at 5-15 min intervals

Max: 15mg/h
5-10mg IV q3-6 hours (0.1-0.5mg/kg/dose, max 20mg/dose)
Duration: 3-6 hours
Especially for patients with concomitant CAD
1 amp (150mcg/amp) SC, IM or IV with patient supine
Initial 0.3 ug/kg/min; usual 2-4 ug/kg/min;
Max 10 ug/kg/min for 10mins

Stages in the Evolution of Heart Failure (Recommended Therapy by Stage):

STAGE A

STAGE B

At risk for heart

failure, but without
structural heart disease
or symptoms of HF

Structural Heart
Disease but without
Symptoms of HF

Patients with HPN,

CAD, DM
Or
Patients using
Cardiotoxins with FHx
CM

Patients with previous

MI, LV Systolic
Dysfunction,
Asymptomatic
Valvular Disease

Structural Heart Disease

Therapy:
Treat HPN

STAGE C
Structural Heart
Disease with Prior
Current Symptoms
of HF
Patients with known
Structural Heart
Disease, Shortness
of Breath and
Fatigue, Reduced
Exercise Tolerance

Symptoms of HF Develop

Therapy:
All Measures under
Stage-A

Treat Lipid D/O

ACE Inhibitors in
appropriate patients

Encourage regular
exercise

Beta-Blockers

Drugs (Routine Use):

-Diuretics
-ACE Inhibitors
-Beta-Blockers
-Digitalis
-Dietary Salt
Restriction

Discourage Alcohol
Intake, Illicit Drug use
ACE Inhibition

Refractory HF requiring
Specialized Interventions
Patients who have marked
Symptoms at rest despite
maximal therapy (eg. Those
who are recurrently
hospitalized or cannot be
safely discharged from the
hospital without specialized
interventions)

Refractory Symptoms of HF at Rest

Therapy:
All measures under
Stage-A

Encourage smoking
cessation

STAGE D

Therapy:
All measures under Stage
A, B, and C
Mechanical assist devices
Heart Transplant
Continuous (not
intermittent) IV Inotropic
Infusions for Palliation
Hospice Care

ISCHEMIC HEART DISEASE

ISCHEMIC HEART DISEASE

Condition in which there is an Inadequate supply of blood and oxygen to a portion of the Myocardium
IMBALANCE between Myocardial Oxygen Supply and Demand
Most Common Cause: Atherosclerotic Disease of an Epicardial Coronary Artery sufficient to cause a regional reduction in
Myocardial Blood Flow and inadequate perfusion of the Myocardium supplied by involved artery
Obesity, Insulin Resistance, and T2DM are increasing and powerful risk factors for IHD

Patients with IHD fall into Two Large Groups:

o 1) Patients with Chronic Coronary Disease (CAD) who most commonly present with Stable Angina
o 2) Patients with Acute Coronary Syndromes
Acute Coronary Syndromes is Composed of:
o Unstable Angina and Non-ST-Segment Elevation MI
o Acute Myocardial Infarction (MI) with ST-Elevation
I. STABLE ANGINA PECTORIS
This episodic clinical syndrome is due to TRANSIENT Myocardial Ischemia
Males: 70% of all patients with angina pectoris
Typical History: Man older than 50y/o or Woman older than 60y/o who complains of chest discomfort usually described as
heaviness, pressure, squeezing, smothering, or choking, and only rarely as frank pain
Levines Sign: Hand placed over sternum with a clenched fist, to indicate a squeezing, central, substernal discomfort
A. Clinical Presentation
o Angina is usually crescendo-decresendo in nature, typically lasts 2-5 minutes, and can radiate to either shoulder
and to both arms
o Does NOT radiate to Trapezius Muscles (such a radiation pattern is more typical of Pericarditis)
o Episodes of Angina typically caused by Exertion or Emotion, Relieved by Rest and Sublingual Nitroglycerin
B. Electrocardiogram (ECG)
o May be NORMAL (at rest)
o ST-Segment and T-Wave changes as well as LV hypertrophy and intraventricular conduction disturbances are
suggestive of IHD, they are non specific since they can also occur in Pericardial, Myocardial and Valvular Heart
Disease
C. Stress Testing
o Most widely used for both Diagnosis of IHD and estimating prognosis involves recording the 12-Lead ECG before,
during and after exercise

II. MANAGEMENT OF STABLE ANGINA PECTORIS

1) Explanation of he Problem and reassurance about the ability to formulate a Treatment Plan
2) Identification & Treatment of aggravating conditions
3) Recommendations for adaptation of Activity as needed
4) Treatment of Risk Factors that will decrease occurrence of Adverse Coronary Outcomes
5) Drug Therapy for Angina
6) Consideration of Revascularization
A. Dyslipidemia
o Treatment of Dyslipidemia is Central when aiming for Long-Term Relief from Angina, reduced need for
Revascularization, and reduction in MI and death
o HMG-CoA Reductase Inhibitors (Statins): can lower LDL Cholesterol (25-50%), raise HDL Cholesterol, and Lower
Triglycerides
B. Pharmacologic Treatment
1. Drug Therapy
Nitrates

Systemic Venodilation with concomitant reduction in LV End Diastolic Volume and

Pressure, thereby reducing Myocardial Wall Tension and O2 Requirements
Dilation of Epicardial Coronary Vessels
Increased Blood Flow in Collateral Vessels

Long Acting Nitrates

None of the Long Acting Nitrates is as effective as Sublingual Nitroglycerin for the Acute
Relief of Angina

B-Adrenergic Blockers

Reduce Myocardial O2 Demand by inhibiting the increases in HR, arterial pressure, and
myocardial contractility caused by Adrenergic Activation

Ca+ Channel Blockers

Coronary Vasodilators that produce variable and dose dependent reductions in Myocardial
O2 Demand, Contractility, and Arterial Pressure

**NOTE Beta-Blockers VS Ca2+ Channel Blockers

Beta Blockers have been shown to improve Live Expectancy following Acute MI (Ca+ Channel
Blockers have not)
Ca2+ Channel Blockers are indicated in patients with:
Inadequate responsiveness to the combination of B-Blockers & Nitrates
Adverse Reactions to B-Blockers (depression, fatigue, sexual)
Angina and history of Asthma or COPD
Sick Sinus Syndrome or significant AV Conduction Disturbances
Prinzmetals Angina
Sympomatic Peripheral Arterial Disease
2. Anti-Platelet Drugs
Aspirin

Irreversible Inhibitor of Platelet Cyclo-Oxygenase Activity, therefore interferes with Platelet Activation.
Chronic administration of 75 to 325mg PO per day has been shown to reduce coronary events.

Clopidrogel

Oral Agent that blocks ADP Receptor Mediated Platelet Aggregation

3. Other Therapies:
ACE-Inhibitors
Ranolazine
**NOTE: NSAIDS should be AVOIDED!
C. Coronary Revascularization
Percutaneous Coronary
Intervention (PCI)
Coronary Artery Bypass
Grafting (CABG)

Involves Balloon Dilatation usually accompanied by Coronary Stenting. Most common indication for
PCI is Angina Pectoris, despite medical therapy, accompanied by evidence of Ischemia during a
Stress Test
For those with Three-Vessel IHD, Stenosis of the Left Main Coronary Artery

UNSTABLE ANGINA & NSTEMI

Unstable Angina

Angina Pectoris with at least ONE of THREE Features:

o 1) Occurs at rest or with Minimal Exertion lasting > 10 minutes
o 2) Severe and of New Onset
o 3) Occurs with a Crescendo Pattern
Non-ST-Elevation Myocardial Infarction (NSTEMI)

Clinical Features of Unstable Angina (UA) develops evidence of Myocardial Necrosis as reflected by Elevated Cardiac Enzymes

Clinical Features:
o Chest Pain radiating to the Neck, Left Shoulder, and Left Arm
o Dyspnea
o Diaphoresis, Pale Cool Skin, Sinus Tachycardia, S3 or S4, Basilar Rales, Hypotension
Criteria to Document AMI

1) Chest Pain

2) ECG Changes
3) Cardiac Enzymes

I. DEFINITION OF TERMS:
A. Unstable Angina
o STABLE Angina Pectoris is characterized by Chest or Arm Discomfort that may NOT be described as pain, but is
reproducibly associated with Physical Exertion or Stress, and is RELIEVED within 5-10 minutes by REST and/or
Sublingual Nitroglycerin
o UNSTABLE ANGINA is defined as Angina Pectoris or Equivalent Ischemic Discomfort with at least ONE of the
Three Features:
1) Occurs at Rest (or with minimal exertion), usually lasting > 10 Minutes
2) It is Severe and of New Onset (ie. Within the prior 4-6 weeks)
3) Occurs with a Crescendo Pattern (ie. Distinctly more Severe, Prolonged, or frequent than previously)
B. Non-ST-Elevation Myocardial Infarction (NSTEMI)
o Clinical Features of Unstable Angina (UA) + evidence of Myocardial Necrosis as reflected in Elevated Cardiac
Biomarkers
II. PATHOPHYSIOLOGY (Four Pathophysiologic Processes)
1) Plaque Rupture or Erosion with Superimposed Nonocclusive Thrombus (Most Common Cause)
2) Dynamic Obstruction (eg. Coronary Spasm as in Prinzmetals Variant Angina)
3) Progressive Mechanical Obstruction
4) Secondary UA related to Increased Myocardial O2 Demand and/or Decreased Supply (eg. Tachycardia, Anemia)
III. CLINICAL PRESENTATION
Clinical Hallmark: CHEST PAIN substernal region or sometimes epigastrium, radiates to neck, left shoulder, and left arm,
severe enough to be considered painful
Anginal Equivalents: Dyspnea, Epigastric Discomfort
PE: Unremarkable, or if (+) Large Area of Myocardial Ischemia or a Large NSTEMI:
o Diaphoresis
o Pale cool skin
o Sinus tachycardia
o 3rd & 4th heart sound
o Basilar rales
o Hypotension

10

IV. DIAGNOSIS
A. ECG
o ST-Segment Depression
o Transient ST-Segment Elevation
o T-Wave Inversion

In patients with clinical features of UA, the presence of New ST-Segment

Deviation, even of only 0.05 mV, is an important predictor of adverse outcome.
T-Wave changes are sensitive for Ischemia but less specific, unless they are
New, Deep T-Wave Inversions (> 0.3mV)

B. Cardiac Biomarkers
o Patients with UA who have elevated Biomarkers of Necrosis such as CKMB and Troponin (a much more specific
and sensitive marker of Myocardial Necrosis) are at INCREASED Risk for Death or Recurrent MI
o Elevated Levels of these markers distinguish patients with NSTEMI from those with UA
There is a direct relationship between the degree of Troponin Elevation and Mortality. However, in patients WITHOUT a clear clinical
history of Myocardial Ischemia, MINOR Troponin Elevations have been reported and can be caused by Congestive Heart Failure,
Myocarditis, or Pulmonary Embolism, or they may be False Positive Readings.
Thus, in patients with an UNCLEAR History, Small Troponin Elevations may NOT be diagnostic of an ACS

V. DIAGNOSTIC PATHWAYS
Four major diagnostic tools are used in the Diagnosis of UA/NSTEMI in the
Emergency Department: History + ECG + Cardiac Markers + Stress Testing.
Goals are to:

Recognize or exclude MI (using Cardiac Markers)

Evaluate for Rest Ischemia (Chest Pain at rest, serial, or continuous

ECGs)

Evaluate for significant CAD (using provocative stress testing)

QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

First step is to assess the likelihood of Coronary Artery Disease. Patients at high
or intermediate likelihood are admitted to the hospital. Those with clearly atypical
chest pain are sent home. Patients with a Low Likelihood of Ischemia enter the
pathway and are observed in a monitored bed in the ED observation unit over a
period of 6 hours, and 12-Lead ECGs are performed if the patient has recurrent
chest discomfort. A panel of Cardiac Markers (eg, Troponin, CKMB) is drawn at
baseline and 6 hours later. If patient develops recurrent pain, has ST-Segment or
T-Wave Changes, or has Positive Cardiac Markers, he is admitted to the hospital
and treated for UA/NSTEMI. If patient has negative markers and no recurrence of
pain, he is sent for exercise treadmill testing, with imaging reserved for patients
with abnormal baseline ECG. If positive, patient is admitted.

DIFFERENTIALS FOR CHEST PAIN:

Could the Chest Pain be due to an Acute, Potentially Life-Threatening Condition that warrants Immediate Hospitalization?
o Acute Ischemic Heart Disease
o Aortic Dissection
o Pulmonary Embolism
o Spontaneous Pneumothorax

If Not, could it be due to a Chronic condition likely to lead to Serious Complications?

o Stable Angina
o Aortic Stenosis
o Pulmonary Hypertension

If Not, could the Discomfort be due to an Acute Condition that Warrants Specific Treatment?
o Pericarditis
o Pneumonitis / Pleuritis
o Herpes Zoster

If Not, could the Discomfort be due to another Treatable Chronic Condition?

o Esophageal Reflux
Esophageal Spasm
o Peptic Ulcer Disease
Gallbladder Disease
o Other GI Conditions
Cervical Disk Disease
o Arthritis of the Shoulder or Spine
Costochondritis
o Musculoskeletal Disorders
Anxiety State

11

VI. MANAGEMENT OF UA/NSTEMI

A. Medical Treatment
o Bed rest with continuous ECG monitoring for ST-Segment Deviation and cardiac rhythm
o Ambulation is permitted if patient shows NO recurrence of ischemia and does NOT develop a biomarker necrosis
for 12-24 hours
o Medical Therapy: Simultaneous Anti-Ischemic Treatment + Antithrombotic Treatment
DRUG CATEGORY
Nitrates

CLINICAL CONDITION
Administer IV when symptoms are not fully relieved with
three sublingual nitroglycerin tablets and initiation of beta
blocker therapy

WHEN TO AVOID
Hypotension
Patient receiving Sildenafil or other
PDE 5 Inhibitor

Beta Blockers

Unstable Angina

PR Interval (ECG) > 0.24s

20 or 30 Atrioventricular Block
Heart Rate < 60bpm
BP < 90mmHg
Shock
LV Failure with CHF
Severe Reactive Airway Disease

Ca2+ Channel Blockers

Patients whose symptoms are not relieved by adequate

doses of nitrates and Beta Blockers or in patients unable to
tolerate adequate doses of one or both of these agents or in
patients with variant angina

Pulmonary Edema
Evidence of LV Dysfunction (for
Diltiazem or Verapamil)

Morphine Sulfate

Patients whose symptoms are not relieved after three serial

sublingual nitroglycerin tablets or whose symptoms recur
with adequate anti ischemic therapy

Hypotension
Respiratory Depression
Confusion
Obtundation

B. Anti-Ischemic Treatment
o Bed Rest
o Nitrates
o Beta Blockers

Aspirin
Clopidogrel

D. Anticoagulation Therapy
Unfractionated Heparin (Mainstay)
LMWH Enoxaprin

C. Anti-Thrombotic Therapy
E. Invasive VS Conservative Strategy
o High Risk Patients (Multiple Risk Factors): ST-Segment Deviation and/or (+) Biomarkers
o Class I Recommendations for Use of an Early Invasive Strategy:
Recurrent Angina at rest / low level activity despite Rx
Elevated TnT or TnI
New- ST-Segment Depression
Recurrent Angina / Ischemia with CHF symptoms, rales, MR
Positive Stress Test
In this strategy, following treatment with Anti-Ischemic and Anti-Thrombotic
EF < 0.40
Agents, Coronary Arteriography is carried out within ~48 hours of admission,
Decreased BP
followed by Coronary Revascularization (PCI or Coronary Artery Bypass
Sustained VT
Grafting), depending on the coronary anatomy)
PCI < 6 months, prior CABG
VII. LONG TERM MANAGEMENT
Risk Factor Modification
Long Term Tx with Five Classes of Drugs have been shown beneficial:
o Beta Blockers (anti-ischemic tx & reduce triggers for MI)
o Statins (long-term plaque stabilization)
o ACE Inhibitors (long-term plaque stabilization)
o Antiplatelet Therapy (Aspirin + Clopidrogel for at least 9-12 months)
VIII. PRINZMETALS VARIANT ANGINA
Ischemic Pain that occurs at rest, but NOT usually with exertion, and is associated with Transient ST-Segment Elevation (due
to Focal Spasm of an Epicardial Coronary Artery)
Diagnostic Hallmark: Transient Coronary Spasm on Coronary Angiography

12

ACUTE MYOCARDIAL INFARCTION

I. CLINICAL PICTURE
PAIN: Most Common Presenting complaint in patients with STEMI (heavy, squeezing, crushing)
Similar to Angina, but occurs at REST, usually more Severe, and Lasts Longer, does NOT subside with cessation of activity
(in contrast to angina pectoris)
A. Physical Findings:
o Anxious, restless, pallor, diaphoresis
o Anterior Infarction: Tachycardia + Hypertension
o Inferior Infarction: Bradycardia + Hypotension
o Precordium is usually quiet, dyskinetic bulging (in anterior infarct), 4th and 3rd Heart Sounds, pericardial friction rub
(transmural STEMI)
B. Temporal Stages of MI
o Acute (first few hours 7 days)
o Healing (7 28 days)
o Healed (> 29 days)
II. LABORATORY TESTS IN CONFIRMING THE DIAGNOSIS:
ECG
Serum Cardiac Biomarkers
Cardiac Imaging
Non-Specific Indices of Tissue Necrosis and Inflammation
A. Electrocardiogram
o Initial Stage: Total Occlusion of an Epicardial Coronary Artery produces ST-Segment Elevation
o Most patients initially presenting with ST-Segment Elevation ultimately evolve Q Waves

ECG Findings (from Medicine Notes):

INTERPRETATION
Hyperacute
Acute MI
Recent MI
Undetermined
Old MI

Q WAVE
(-)
(-/+)
(++)
(++)
(++)

ST ELEVATION
(-/+)
(++)
(++)
(-)
(-)

B. Molecular Markers in the Diagnosis of AMI (Blue Book)

TESTS
TIME TO
PEAK
DURATION
DETECTION
Troponin-T
Troponin-I
CK-MB

3-12 hrs
3-12 hrs
3-12 hrs

24 hours
24 hours
24 hours

5-14 days
5-10 days
2-3 days

T WAVE
Peaked
(-/+)
Inverted
Inverted
Upright

TIMING
0 6 hours
6 24 hours
24 72 hours
72 hrs 6 wks
> 6 wks

MOST COMMON SAMPLING SCHEDULE

Once at least 12 hrs after chest pain
Once at least 12 hrs after chest pain
Every 12 hrs x 3; Start at 6 hrs after chest pain

Cardiac-Specific Troponin T and Troponin I:

Have amino acid sequences different from those of the skeletal

muscle forms; Highly Specific

Increase after STEMI to levels > 20 times higher

Preferred Biochemical Markers for MI

Remain elevated for 7-10 days after STEMI

QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

Creatine Phosphokinase (CK)

Rises within 4-8 hours and returns to normal by 48-72 h

An important drawback of Total CK measurement is its lack of

Specificity for STEMI

May be elevated with Skeletal Muscle Disease or Trauma,

including IM Injection

MB Isoenzyme of CK has advantage over Total CK that is not

present in significant concentration in extracardiac tissue &
therefore is more specific

CKMB Mass: CK Activity > 2.5 suggests, but is NOT diagnostic

of a Myocardial rather than a Skeletal Muscle Source for the
CKMB Elevation

13

III. CASE: 57/M

CC: Chest Heaviness
HPI: Chest heaviness, 5/10, squeezing, diffuse, midsternum, sudden, with exertion, relieved by rest, radiating
Persistence of chest heaviness, 10/10, diaphoresis, shortness of breath
PMHx: PTB (1998), treated; (-) HPN, DM
Social: Smoker, occasional alcoholic
Pertinents in the History:
o Duration of his initial chest pain = 10 minutes (relieved by rest)
o Duration of his second chest pain = 10 minutes (not relieved by rest)
Pertinents in the Physical Exam:
o Crackles, bilateral to mid
o Apex beat at the 6th ICS MCL; (-) S3/S4
Initial Management and Labs
o ECG revealed ST Elevation on Leads II, III, AvF (Inferior Wall Infarct)
o Aspirin, Streptokinase
o Initial Assessment: Acute Coronary Syndrome
**QUESTION: Why are patients with Inferior Wall MI prone to Hypotension?
o In 90% of patients, the Inferior Wall is supplied by the Right Coronary Artery, which also supplies the SA-Node
Hypotension
IV. KILLIPs CLASSIFICATION OF AMI
CLASS

DESCRIPTION

RISK OF MORTALITY
(Blue Book)
0-5% Risk Mortality

Class I

No Signs of Pulmonary or Venous Congestion (0-5% Mortality Rate)

No Rales
Normal Blood Pressure

Class II

Moderate Heart Failure

(+) Rales at the Lung Bases
Normal Blood Pressure with Basal Congestion
S3-Gallop
Tachypnea or Signs of Right-Sided Heart Failure (Venous & Hepatic Congestion)

10-20% Mortality Rate

Class III

Severe Heart Failure

(+) Midbasal Rales
(+) S3 and S4
Normal Blood Pressure
Pulmonary Edema

35-45% Mortality Rate

Class IV

Shock with Systolic Pressure < 90mmHg & evidence of Peripheral Vasoconstriction
Peripheral Cyanosis
Mental Confusion and Oliguria
Pulmonary Congestion
Hypotension; Cardiogenic Shock

85-95% Mortality Rate

V. CONTRAINDICATIONS TO GIVING BETA-BLOCKERS (METOPROLOL)

Low Cardiac Output State
Evidence of CHF
Hypotension
AV Conduction Block (Relative Contraindication)
Asthma, etc
**NOTE: In Patients with 1st-Degree AV-Blocks (Relative Contraindication):
o Look at PR Interval (Cut-Off is > 0.20s)
o We can give Metoprolol if PR < 0.24s
o We CANNOT give Metoprolol if PR > 0.24s

14

VI. INITIAL MANAGEMENT

A. PreHospital Care:
1. Prognosis in STEMI is largely related to the occurrence of general classes of complications:

Electrical Complications (Arrhythmias)

Mechanical Complications (Pump Failure)

**NOTE: Most Out-of-Hospital Deaths from STEMI = due to Sudden Ventricular Fibrillation
Vast majority of deaths due to V-Fib occur within 24 hours of the onset of symptoms (over half
occur in the 1st hour)
2. Major Elements of Prehospital Care:

Recognition of symptoms
Rapid deployment of an emergency medical team capable of performing resuscitative maneuvers
Expeditious transportation
Expeditious implementation of reperfusion therapy

B. Management in the Emergency Department

o ASPIRIN: rapid action is achieved by chewing 160-325mg tablet, then followed by daily administration of Aspirin
in a dose of 75-162mg
o Supplemental O2 (Nasal Prongs or Face Mask 2-4 L/min)
o Goals in the ER:

Control of Cardiac Discomfort

Rapid identification of patients who are Candidates for Urgent Reperfusion Therapy
Triage of Lower-Risk Patients to appropriate location in the hospital
Avoidance of inappropriate discharge of patients with STEMI

VII. GOALS FOR MANAGEMENT OF ACUTE ST-ELEVATION MI (STEMI)

Reperfusion
When ST-Segment Elevation of at least 2mm in 2
Relief of Chest Pain
contiguous precordial leads and 1 mm in two adjacent
Anti-Platelets / Anti-Coagulants
limb leads is present, a patient should be considered a
candidate for reperfusion therapy
A. Primary Goal in Management in STEMI = REPERFUSION
o Ideally, we do Thrombolysis (Streptokinase)
o Other modes of Reperfusion: Primary Percutaneous Coronary Intervention (PCI), Bypass (CABG)
o Golden Period for Thrombolysis: < 6 hours
Ideally initiated within 30 minutes of presentation (Door to Needle Time < 30 mins)
Although the reduction of mortality rate is more modest, therapy remains of benefit for many patients seen
3-6 hours after onset of infarction
1. Absolute CONTRAINDICATIONS to Thrombolysis

History of Cerebrovascular Hemorrhage at ANYTIME

History of a Non-Hemorrhagic Stroke or other Cerebrovascular Event within the PAST YEAR

Marked hypertension (a reliably detected SBP > 180mmHg and/or DBP > 110mmHg

Suspicion of Aortic Dissection

Active Internal Bleeding (excluding menses)

2. Relative CONTRAINDICATIONS to Thrombolysis (requires assessment of the Risk:Benefit Ratio)

Current use of Anticoagulants (International Normalized Ratio > 2)

Recent (< 2 weeks) Invasive or Surgical Procedure or Prolonged (>10min) Cardiopulmonary Resuscitation

Known bleeding diathesis

Pregnancy

Hemorrhagic Ophthalmic Condition (eg Hemorrhagic Diabetic Retinopathy)

Active Peptic Ulcer Disease

History of Severe Hypertension that is currently adequately controlled

3. Primary Percutaneous Coronary Intervention

Usually Angioplasty and/or Stenting

Effective in restoring perfusion in STEMI when carried out on an emergency basis in the first few hours of MI
Indications For Percutaneous Coronary Intervention (PCI)

Percutaneous Transluminal Coronary Angioplasty (PTCA) alternative to Bypass Surgery

Fundamental Indication for PCI:

o Presence of one or more Coronary Stenoses thought to be responsible for a Clinical Syndrome that
warrant Revascularization
o Approachable by Catheter-Based Techniques
o With Risks and Benefits that compare favorably with those of Bypass Surgery

15

B. Relief of Chest Pain

o Nitrates
o Morphine
o B-Blockers

Avoid giving NSAIDS in the ACUTE Setting of Myocardial Infarction (AMI)

Sublingual
Nitroglycerin

Can be given up to 3 doses of 0.4mg at 5 min intervals. In addition to diminishing or abolishing chest
pain, nitroglycerin can be capable of both decreasing Myocardial O2 Demand (by lowering Preload) and
increasing Myocardial Oxygen Supply (by dilating infarct-related coronary vessels). IV Nitroglycerin
should be considered if there is return of chest pain + ST segment or T wave shifts

Morphine

Very effective analgesic for the pain

IV Beta Blockers

Control pain by diminishing O2 demand. Reduce the risks of reinfarction & ventricular fibrillation

C. Anti-Platelets and Anti-Coagulation

o Aspirin 80mg
o Clopidrogel
o Heparin
1. We give Anti-Coagulants and Anti-Platelets for Secondary Prevention
It has no use in the Acute Ischemic Event
Secondary Prevention = Preventing complications or recurrence
2. Heparin: Anticoagulant
Binds Anti-Thrombin III and activates it (Antithrombotic)
Standard Antithrombin agent used in clinical practice is Unfractionated Heparin or UFH (an alternative to
UFH is Low-Molecular-Weight Heparin / LMWH)
Heparin (Unfractionated Heparin or UFH): Initial Bolus 60-70 U/kg (maximum 5000 U) IV, followed
by infusion of 12-15 U/kg per hour (initial maximum 1000 U/h) titrated to a PTT 1.5-2.5 times control
When UFH is added to a regimen of Aspirin and a non-fibrin-specific thrombolytic (Streptokinase),
additional mortality benefit occurs
**NOTE: Risks of Heparin
Heparin Induced Thrombocytopenia (HIP)
Bleeding (if there is bleeding, we can give Protamine Sulfate)
VIII. HOSPITAL PHASE MANAGEMENT
Activity

Diet
Bowels
Sedation

Patients should be kept at bed rest for the first 12 hours. In the absence of complications, patients should be encouraged to
resume an upright posture by dangling their feet over the side of the bed & sitting in a chair within the first 24 hours, By the 2nd
and 3rd day, patients are ambulating in their room with increasing duration and frequency. By day 3, patients should be increasing
ambulation progressively to a goal of 185 m (600ft) at least 3x a day
Nothing or only clear fluids (due to risk of emesis and aspiration) for the first 4-12 hours
Use of stool softener.
Many patients require sedation during hospitalization to withstand period of enforced inactivity

16

IX. ACC / AHA GUIDELINES FOR MANAGEMENT OF AMI (Medicine Notes)

Initial Recognition and Management in the ER

Initial evaluation of the patient ideally should be accomplished within 10 minutes of his / her arrival at the ER

NO more than 20 minutes should elapse before an assessment is made

At the ER, patient with Suspected MI should immediately Receive:

O2 Support

SL Nitrates (Defer if BP < 90 or HR < 50)

Adequate Analgesia (Morphine or Mependine)

ASA 160-325mg orally

12 L ECG must be done:

o ST Segment Elevation (> 1mV in contiguous leads)
o Presence makes patient a Candidate for Immediate Reperfusion Therapy by Fibrinolysis, PTCA
**IMPORTANT Notes:

Acute MI, LBBB = Manage like ST-Segment Elevation MI

NSTEMI = should NOT receive Thrombolytic Therapy

1) Thrombolysis

Greatest benefit initiated within 6 hours from the onset of symptoms

Benefit also observed when begun 12 hours

Associated with High Risk for ICH, which occurs within 1st day of Therapy

Factors that Increase Risk for ICH:

o Age > 65 y/o
o BW < 70kg
o Systemic HPN
o Administration of Tissue Plasminogen Activator
2) Primary PTCA

May be performed as alternative to Thrombolytics

Provided that it can be accomplished promptly with prompt access to E CABG

HOSPITAL MANAGEMENT
1. First 24 Hours

Confirm MI by Serial ECG and measurement of Cardiac Enzymes

Reinfarction and Death frequently occurs within the 1st 24 hours

Limit Physical Activities for at least 12 hours

Anxiety and Pain appropriate Analgesics

Prophylactic Antiarrhythmias NOT recommended in the 1st 24 hours of Hospitalization

a. Increased Risk for Embolic Stroke:
o Large Anterior Wall MI
**Risk is reduced by Early Administration of Heparin
o LV Mural Thrombus
b. Thrombolytics
o Streptokinase
o Anisoylated Plasminogen Streptokinase Activator Complex (APSAC)
o Urokinase
c. Heparin Administration AFTER Thrombolysis shows:
o Limited evidence of Benefit for Streptokinase, APSAC, Urokinase
o Improved Clinical Outcome with ALTEPLASE IV at least 48 hours after administration of Alteplase
**NOTE: High Dose IV Heparin Recommended when PTCA was done
d. Medications:
o Aspirin
o IV Nitrates for 24-48 hours after hospitalization
o ACE Inhibitors should be continued in patients with impaired LV systolic function (EF < 40%) or CHF
o On Admission: Lipid Profile, Serum Electrolytes including Mg
2. After 1st 24 Hours

Continue ASA, B-Blocker, ACE-Inhibitor

Patients with MI that is spontaneous or provoked in the days to weeks after AMI should undergo:
o Elective Coronary Angio
o Consider PTCA or CABG

However, this does NOT salvage myocardium nor reduce Reinfarction or Death

Thus, reserve the said procedures for survivors who have preserved LV systolic function and spontaneous or provoke Ischemia

17

Temporary Pacemaker Insertion (TPI)

Patients with:
o Sinus Bradycardia, unresponsive to meds
o Mobitz Type II 20 AV Block
o 30 Heart Block
o BBB
o Newly Acquired BBB
o R or LBBB in Conjunction with 10 AV Block
Immediate Surgical Intervention:

Failed PTCA with Persistent Chest Pains or Hemodynamic Instability

Persistent or recurrent ischemia refractory to meds and NOT candidate for catheter intervention

Cardiogenic Shock and Coronary Artery, NOT amendable to PTCA

Mechanical Abnormality, leading to severe Pulmonary Congestion and Hypotension (eg. Papillary Muscle Rupture, MR, VSD)

X. COMPLICATIONS (Medicine Notes)

A. Pericarditis
o Patients with Recurrent Chest Pain
o Should receive High Dose ASA (650mg q4 to 6 hrs)
o If caused by MI, should be treated with:

IV Nitrates

Analgesics

Antithrombotics
B. CHF
o Should receive Diuretics and an Afterload Reducing Agent
C. Cardiogenic Shock
o Intra-Aortic Balloon Pump
o E Coronary Angio PTCA CABG
D. RV Infarction and Dysfunction
o Intravascular Volume Expansion and Inotropic Agent
E. Atrial Fibrillation
o Manifestation of extensive LV systolic dysfunction
o Hemodynamic Compromise
o Direct Cardioversion
o DIGITALIS to Slow the Ventricular Response
F. Ventricular Fibrillation
o Direct Current Countershock
G. Monomorphic Ventricular Tachycardia
o Direct Current Countershock if with associated angina and congestion
o If NOT, should be treated with:

Lidocaine

Procainamide

Amiodarone
H. Symptomatic Bradycardia
o Atropine
XI. PREPARATION FOR DISCHARGE
A. Should undergo Stress-Testing Exercise
o Submaximal at 4-7 day; or symptom limited at 10-14 days
o This is done to:

Assess patients functional capacity and ability to perform test at home or work

Evaluate efficacy of patients current medical regimen

Stratify risk for subsequent cardiac event

B. Long Term Management
o Meds: ASA, Beta-Blocker, Selected Dose of ACE-Inhibitors
o Weight reduction
o Diet Low Fat and Cholesterol (Target LDL < 100mg/dL)
o Smoking cessation

Formal Cardiac Rehab Program or engage in 20 minutes of exercise at least at level of brisk walking at least 3x per week

18

RHEUMATIC HEART DISEASE

RHEUMATIC HEART DISEASE

I. RHEUMATIC FEVER (JONES CRITERIA)
Acute Rheumatic Fever (ARF) is a multisystem disease resulting from Autoimmune Reaction to infection with Group-A
Streptococci (cardiac valvular damage may persist after other features have disappeared)
RF is a Hypersensitivity Reaction induced by Group-A B-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
A. Major Manifestations
Carditis (40-60%)
Migratory Polyarthritis (75%)
Syndenhams Chorea (<10%)
Erythema Marginatum
Subcutaneous Nodules

Pancarditis involving the pericardium, myocardium, and endocardium

Most often affecting the ankles, wrists, knees, elbows
Involuntary jerking movements
Evanescent macular eruption w/ round borders, usually concentrated on trunk
Found over extensor surfaces of joints

B. Minor Manifestations
1. Clinical:
Arthralgia (joint pains)
Fever
2. Laboratory Findings of:
Elevated Acute Phase Reactants (ESR / CRP)
Prolonged PR interval
PLUS Supporting Evidence of Antecedent Group-A Strep Infection
o (+) Throat Culture or Rapid Strep-Antigen Test
o And/or Elevated or Rising Strep-Antibody Test

2 Major Criteria
OR
1 Major and 2 Minor Criteria
PLUS
Evidence of Preceding Infection

Management of Rheumatic Fever

Diagnostics: include ASO Titer, ESR, CRP, Throat Swab CS, ECG, 2D Echo
Treatment

For Infection: Pen-G or Ampicillin IV x 10 days

For Arthritis alone: ASA 75mg/kg/day x 2 weeks (when 1/2 dose for 2-3 weeks)

For Mild Carditis: ASA 75mg/kg/day x 6-8 weeks, then taper

For Mod to Severe Carditis: Add Prednisone 1-2mg/kg/day x 2-3 weeks; continue both ASA and Prednisone until Normal
ESR is reached

For Chorea: Dizepam tab PO

Prophylaxis:

Penicillin-G 1.2 M u q 3-4 weeks

RF without Carditis: 5 years until 30 y/o

Penicillin-V 250mg/cap BID

RF with Mild Carditis: until 45 y/o

Erythromycin 250mg/cap BID

RF with Mod-Sev Carditis: Lifetime

III. PE OF A PATIENT WITH MITRAL STENOSIS (MS)

A. Inspection / Palpation
Malar flush with pinched and blue facies
In patients with sinus rhythm and severe pulmonary hypertension or associated tricuspid stenosis, the JVP reveals prominent a
waves due to vigorous right atrial systole
NOTE: JVP vs CVP
o RV Tap (due to enlarged RV)

JVP is measured from Sternal Angle

B. Auscultation

CVP is measured from Midclavicular Line

o S1 is usually accentuated and slightly delayed

Difference of CVP from JVP is 5 (therefore, 3 + 5 = 8)

o Splitting of S2 (there is Delayed Closure of Pulmonic Valve)

Normal JVP = 3cm

o Opening Snap

Normal CVP = 8cm

o Low pitched rumbling Diastolic Murmur
o
o

IV. PERCUTANEOUS TRANSLUMINAL MITRAL VALVE COMISSUROTOMY (PTMC)

Right Atrium Transluminal approach to Left Atrium Mitral Valve (Creates a whole in the septum between the LA and RA)

19

INFECTIVE ENDOCARDITIS

INFECTIVE ENDOCARDITIS
I. CLASSIFICATION OF INFECTIVE ENDOCARDITIS (IE)
ACUTE BACTERIAL IE
Pathogenic Organism
Staph. Aureus (Virulent)
Clinical Presentation
High Fever, Acute Course
Cardiac Pathology
Normal cardiac valves, No Murmurs
Prognosis
Fatal in 6 weeks if Untreated

SUBACUTE BACTERIAL IE
Strep. Viridans, Enterococci (Less Virulent)
Low Grade Fever, Subacute Course
Damaged Valves, (+) Murmurs
Better Prognosis

II. DUKES CRITERIA FOR INFECTIVE ENDOCARDITIS (IE)

A. Criteria for Infective Endocarditis
o Two Major Criteria, or
o One Major and Three Minor, or
o Five Minor Criteria using definitions for these criteria as listed below
o Possible Infective Endocarditis: findings consistent with Infective Endocarditis that fall short of the criteria listed above
B. MAJOR Criteria
o 1) Positive Blood Culture Results for Infective Endocarditis
Typical Organisms for Infective Endocarditis: Streptococci viridans, HACEK Group, Strep bovis, Staph
aureus, or Enterococci recovered from Two or More Blood Cultures
o

2) Either Positive Echocardiography Study result for Infective Endocarditis: Oscillating Intracardiac Mass,
Abscess or New Dehiscence of Prosthetic Valve or New Valvular Regurgitation
Or Persistently Positive Blood Culture Results: Microorganism consistent with IE recovered from One or
more Blood Cultures drawn more than 12 Hours Apart

C. MINOR Criteria (Mnemonic: PF-VIME)

o 1) Predisposing Heart Condition or Injected Drug User
o 2) Febrile Syndrome
o
o

3) Vascular Phenomena: Arterial embolism, CNS hemorrhage, conjunctival hemorrhage, Janeway lesions
4) Immunologic Phenomena: Immune-complex Glomerulonephritis, rheumatoid factor, false-positive
VDRL test, Oslers nodes, or Roth spots

o
o

5) Microbiologic Evidence: Positive Blood Culture results, but NOT Positive for Major Criterion
6) Echocardiogram: Suggestive of Infective Endocarditis, but NOT Positive for Major Criterion

III. MANAGEMENT
A. Diagnostic
o Blood CS x 3 Sites; CBC, Crea, U/A, RF
o 2D Echo with Doppler, TEE
B. Treatment:
Acute IE
Subacute IE

1) NAFCILLIN or OXACILLIN 2g IV q4 or VANCOMYCIN 500mg IV q6 or 1g IV q12 x 4weeks

2) GENTAMYCIN 100-200mg IV, then 80mg IV q8 x 3-5 days
1) PEN-G 2-4 M u IV q4 x 4 weeks or AMPICILLIN 2g IV q4
2) GENTAMYCIN 80mg IV q8 x 2 weeks

20

OTHER CARDIOVASCULAR DISEASES

CARDIAC TAMPONADE

Life Threatening Condition wherein Pericardial Effusion has compressed the Heart, impairing its Pumping
Most Common Causes: Neoplasm, Idopathic Pericarditis, Uremia
Other Causes: TB, Bacterial, Post-Pericardiostomy Syndrome, Acute MI, Trauma, Iatrogenic

I. CLINICAL FEATURES
A. Three Principal Features
o Increased Intracardiac Pressure
o Limited Ventricular Filling
o Decreased Cardiac Output
B. Symptoms
o Dyspnea, Orthopnea, Fatigue
o Hepatic Engorgement
C. Physical Examination
o Hypotension
o Elevated JVP (Neck Vein Engorgement)
o Pulsus Paradoxus ( > 10mmHg decrease in SBP during Inspiration)
o RR > 20, HR > 100
o Muffled Heart Sounds
II. MANAGEMENT
A. Diagnostics
12-L ECG

Low Voltage QRS Complexes

Electrical Alterans

CXR

Cardiomegaly
No Pulmonary Venous Congestion
RV Collapse with significant Pericardial Effusion

2D Echo (Diagnostic)

BECKS TRIAD:

Hypotension

Engorgement of Neck Veins

Muffled Heart Sounds

B. Treatment
o Emergency Pericardiocentesis
o Emergency Tube Pericardiostomy w/ Creation of Pericardial Window (recurrent cases / chronic cases / infectious cases)

21

PERICARDITIS

Acute Pericarditis most common pathologic process involving the Pericardium

Cardinal Manifestations: Pain, Pericardial Friction Rub, ECG changes, Pericardial Effusion with Cardiac Tamponade and Paradoxical
Pulse (Chest Pain is an important, but not invariable symptom)

I. CLINICAL PRESENTATION

Chest Pain: Severe, Retrosternal, Left Precordial, referred to neck, arms or left shoulder, pleuritic (consequent to accompanying pleural
inflammation)

Pleuritic Chest Pain: Sharp and aggravated by inspiration, coughing, changes in body position

Pain resembles an Acute MI

HOWEVER, Pericardial Pain may be relieved by Sitting Up and Leaning Forward and is intensified by lying supine

Pericardial Friction Rub (85%): may have up to 3 components per cardiac cycle, high pitched, and is described as rasping, scratching or
grating (heard more frequently at end-expiration with patient upright & leaning forward)
Etiologic Classification of Pericarditis:

Infectious (Viral, Pyogenic, TB, Fungal, other infections)

Non-Infectious (AMI, Uremia, Neoplasia, Myxedema, Cholesterol, Chylopericardium, Trauma, Aortic Dissection, etc)

Pericarditis related to Hypersensitivity or Autoimmunity

II. LABORATORY
A. Cardiac Biomarkers
o May have MODEST Increases in Serum Biomarkers of Myocardial Damage (CK and Troponin)
B. ECG
o ECG without Massive Effusion usually displays changes secondary to Acute Subepicardial Inflammation
o Evolves through 4 stages:
Stage 1
Widespread Elevation of ST Segments, with Upward Concavity, involving two or three standard limb leads and V2
to V6; with reciprocal depressions only in aVR & sometimes V1, as well as PR segment depression
Stage 2
After several days, ST Segments return to normal, & only then, or later, do the T waves become inverted (Stage 3)
Stage 3
T Waves become inverted
Stage 4
ECG returns to Normal in Stage 4 (weeks or months after the acute onset)
**NOTE: In contrast, findings in Acute Myocardial Infarction:

ST Elevations CONVEX, and reciprocal depressions are usually more prominent

QRS changes occur, particularly development of Q waves, and notching & loss of R-Wave amplitude

T-Wave are Inversions usually seen within hours BEFORE the ST-Segments have become Isoelectric

Sequential ECGs are useful in distinguishing Acute Pericarditis from AMI (in AMI, Elevated ST-Segments return to
NORMAL within hours)
C. Echocardiography
o Most Effective Imaging Technique
o Can identify accompanying Cardiac Tamponade
D. CT / MRI
o Diagnosis of Pericardial Fluid or Thickening may be confirmed by CT or MRI
III. PERICARDIAL EFFUSION

Effusion is usually associated w/ Pain and/or the above mentioned ECG changes, as well as with an enlargement of the Cardiac Silhouette

Can lead to Cardiac Tamponade

Ewarts Sign: a Patch of Dullness and Increased Fremitus (and Egophony) beneath the angle of the Left Scapula (caused by compression
of the base of the left lung by the pericardial fluid

22

SUPERIOR VENA CAVA SYNDROME

Clinical Manifestation of SVC obstruction causing severe decrease in venous return from head & neck & upper extremities
90% is secondary to malignancy (lung ca 85%)

I. CLINICAL PRESENATION
Neck and Facial Swelling (Periorbital)
Dyspnea, Cough, Hoarseness, Nasal Congestion, Tongue Swelling, Epistaxis, Headaches, Hemoptysis
Dysphagia, Pain, Dizziness, Lethargy, Syncope
Symptoms are aggravated by bending forward or lying down
II. PHYSICAL EXAMINATION
Diagnosis of SVC Syndrome is CLINICAL. Tracheal Obstruction
Neck Vein Engorgement
is the one potentially Life-Threatening Complication
Visible collateral veins on chest wall
Cyanosis, Edema on Face, Arms, Chest
Distant or Unilaterally Absent Breath Sounds (sometimes normal breath sounds)
If Severe: Proprosis, Glossal and Laryngeal Edema, Obtundation
III. MANAGEMENT
A. Diagnostics: Imaging Studies
CXR

Widening of the Superior Mediastinum

Pleural Effusion in 25% of cases

CT Scan

Diminished or Absent Opacification of the Central Venous Structures

Prominent Collateral Venous Circulation
Most Reliable View of Mediastinal Anatomy

MRI

NO Advantage over CT Scan

B. Treatment
o Relieve Symptoms: Decreasing Cardiac Output, Decrease Venous Pressure (Diuretics, Low Salt Diet, Head
Elevation, Oxygen)
o Obtain Histologic Diagnosis
o Other Modalities: Radiation, Chemotherapy, Surgery

CARDIOMYOPATHIES
Dilated

Left and/or Right Ventricular Enlargement, impaired systolic function, CHF, Arrhythmias, Emboli

Restrictive

Endomyocardial scarring or myocardial infiltration resulting in restriction to Left and/or Right Ventricular Filling

Hypertrophic

Disproportionate LV Hypertrophy, typically involving Septum more than free wall, with or without an Intraventricular
Systolic Pressure gradient; usually of a Non-Dilated LV Cavity

23

PHYSIOLOGY OF THE CARDIOVASCULAR SYSTEM

I. CONTROL OF CARDIAC PERFORMANCE AND OUTPUT

Extent of shortening of heart muscle, and therefore, the stroke volume of the ventricle in the intact heart depend on three major influences:
o The Length of the Muscle at Onset of Contractions (Preload)
o The Tension that the Muscle is called upon to Develop during Contraction (Afterload)
o The Contractility of the Muscle (extent and velocity of shortening at any given preload and afterload)

Laplaces Law: When Myocardial Contractility becomes impaired and the ventricle Dilates, Afterload RISES and limits Cardiac Output

II. ASSESSMENT OF CARDIAC FUNCTION

Cardiac Output and Stroke Volume may be depressed in Heart Failure

Ejection Fraction = ratio of Stroke Volume to End-Diastolic Volume (Normal is 67 + 8%)

Ejection Fraction is frequently depressed in Systolic Heart Failure, even when the stroke volume itself is normal
III. CARDIAC DIAGNOSIS:
1) Underlying Etiology
2) Anatomic Abnormalities
3) Physiologic Disturbances
4) Functional Disability

Is the disease congenital, hypertensive, ischemic, or inflammatory in origin?

Which chambers are involved? Are they hypertrophied, dilated, or both? Which valves are affected? Are they
regurgitant and/or stenotic? Is there Pericardial involvement? Has there been a Myocardial Infarction?
Is an arrhythmia present? Is there evidence of congestive heart failure or of myocardial ischemia?
How strenuous is the physical activity require to elicit symptoms?

IV. HEART SOUNDS

A. First Heart Sound (S1)
o Coincides with the Closure of the Mitral Valve and Tricuspid Valve (Systolic Phase)
o Best heard at the APEX
o Start of Systole
B. Second Heart Sound
o Caused by the Closure of the Aortic and Pulmonic Valves (Diastole)
o Indicates End of Systole (or beginning of Diastole)
o Best heard at the BASE
o SPLITTING is normally heard
C. Third Heart Sound (S3)
o Coincides with EARLY DIASTOLE or RAPID VENTRICULAR FILLING
o It is caused by the Flow of Blood during Rapid Ventricular Filling
o Best Heard after S2
o Suggestive of Heart Failure / Left Ventricular Failure
D. Fourth Heart Sound (S4)
o Coincides with LATE DIASTOLE or ATRIAL SYSTOLE (Atrial Contraction / Slow Ventricular Filling)
o Best Heard before S1
o Occurs when diminished Ventricular Compliance Increases the Resistance to Ventricular Filling
o Most Patients with an Acute MI and Sinus Rhythm have an audible S4

V. RENIN-ANGIOTENSIN-ALDOSTERONE AXIS

VI. ACTIVATION OF NEUROHORMONAL SYSTEMS

24

In Heart Failure

The CO in HF results in an
unloading of high pressure
baroreceptors (circles) in the
LV, carotid sinus, and aortic
arch. This unloading leads to
generation of afferent signals to
CNS
that
stimulate
cardioregulatory centers in
brain which release AVP from
posterior pituitary.
AVP
(ADH)
is
a
powerful
vasoconstrictor that increases
permeability of renal collecting
ducts, leading to reabsorption
of free H2O. These afferent
signals to CNS also activate
efferent SNS pathways that
innervate the heart, kidney,
peripheral vasculature, and
skeletal muscles

QuickTim e and a
TIFF (Uncom pres s ed) decom pres s or
are needed to s ee this picture.
QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

Typical Clinical Features of Major Causes of Acute Chest Discomfort

CONDITION

DURATION

QUALITY

LOCATION

ASSOCIATED FEATURES

Angina

More than 2 and less

than 10 mins

Pressure, tightness,
squeezing, heaviness,
burning

Retrosternal, often with radiation to or

isolated discomfort in neck, jaw,
shoulders, or arms frequently on left

Precipitated by exertion, exposure to cold,

psychologic stress

Unstable Angina

10-20 mins

Similar to angina but

often more severe

Similar to angina

Similar to angina but occurs with low levels of

exertion or even at rest

Acute MI

Variable (often >

30mins)

Similar to angina but

often more severe

Similar to angina

Unrelieved by nitroglycerin
May be associated with evidence of heart failure or
arrhythmia

Aortic Stenosis

Recurrent episodes as
described for angina
Hours to Days; may be
episodic

As described for angina

As described for angina

Late-Peaking Systolic Murmur radiating to Carotids

Sharp

Retrosternal or toward Apex

May radiate to left shoulder

May be relieved by sitting up and leaning forward

(+) Pericardial Friction Rub

Aortic Dissection

Abrupt Onset of
unrelenting pain

Tearing or Ripping
Sensation;
Knifelike

Anterior Chest, often radiating to the

back, between shoulder blades

Associated with HPN and/or underlying CT D/O (eg.

Marfan Syndrome)
Murmur of Aortic Insufficiency, Pericardial Rub,
Pericardial Tamponade, or Loss of Peripheral Pulses

Pulmonary
Embolism

Abrupt Onset; Several

Minutes to a Few Hrs

Pleuritc

Often lateral, on the side of Embolism

Dyspnea, Tachypnea, Tachycardia, Hypotension

Pulmonary
Hypertension

Variable

Pressure

Substernal

Dyspnea, signs of increased venous pressure

including edema and JVP distention

Pneumonia or
Pleuritis

Variable

Pleuritic

Unilateral, often localized

Dyspnea, cough, fever, rales, occasional rub

Spontaneous
Pneumothorax

Sudden Onset; Several

Hours

Pleuritic

Lateral to Side of Pneumothorax

Dyspnea, Decreased Breath Sounds on side of

Pneumothorax

Esophageal Reflux

10-60 mins

Burning

Substernal, Epigastric

Worsened by Postprandial Recumbency

Peptic Ulcer

Prolonged

Burning

Epigastric, Substernal

Relieved with food or antacids

Gallbladder Disease

Prolonged

Burning, Pressure

Epigastric, RUQ, Substernal

May follow meal

Musculoskeletal
Disease

Variable

Aching

Variable

Aggravated by movement
May be reproduced by localized pressure on exam

Herpes Zoster

Variable

Sharp or Burning

Dermatomal Distribution

Vesicular Rash

Emotional /
Psychiatric

Variable, may be
fleeting

Variable

Variable; may be retrosternal

Situational factors may precipitate symptoms

Often with anxiety / depression in Hx

Pericarditis

S4 Gallop or MR murmur during pain

25

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ENDOCRINOLOGY
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Jaime Alfonso Manalo Aherrera, M.D.

Internal Medicine Notes 2009

ENDOCRINE DISORDERS

1) THYROID STORM

Clinical presentation of Uncomplicated Thyrotoxicosis are generally present and accentuated in Thyroid Storm
Known Precipitants of Thyroid Storm (associated with Rapid Rise in Thyroid Hormone Levels)
o
o
o
o
o
o
o
o
o
o
o

Thyroid Surgery
Withdrawal to Therapy, Radioiodine Therapy
Iodinated Contrast Dye
Condition associated with an Acute or Subacute Nonthyroidal Illness
Nonthyroidal Surgery
Infection, CVA
Pulmonary Embolism
Parturition
DKA
Emotional Stress
Trauma

I. BURCH AND WARTOFSKYS DIAGNOSTIC CRITERIA FOR THYROID STORM

A. Thermoregulatory Dysfunction (Temperature)
37.2 37.7 0C
37.8 38.2 0C
38.3 38.8 0C
38.9 39.3 0C
39.4 39.9 0C
> 40.0 0C

5
10
15
20
25
30

B. Central Nervous System Effects

Absent
Mild (Agitation)
Moderate (Delirium, Psychosis, Extreme Lethargy)
Severe (Seizure, Coma)

0
10
20
30

C. Gastrointestinal-Hepatic Dysfunction
Absent
Moderate (Diarrhea, Nausea/Vomiting, Abdominal Pain)
Severe (Unexplained Jaundice)

0
10
20

D. Cardiovascular Dysfunction
1. Tachycardia (Beats Per Minute)
99 109
110 119
120 129
130 139
> 140
2. Congestive Heart Failure
Absent
Mild (Pedal Edema)
Moderate (Bibasilar Rales)
Severe (Pulmonary Edema)
Atrial Fibrillation
3. Precipitant History
Negative
Positive

Scoring:
< 25
Unlikely Storm
25 44 Impending Storm
> 45

Highly Suggestive of
Thyroid Storm

5
10
15
20
25
0
5
10
15
10
0
10

II. NOTES FROM LECTURE ON THYROID STORM

A. Thyrotoxicosis VS Hyperthyroid
o Thyrotoxicosis: Clinical Syndrome resulting from Cellular Responses to Excessive Thyroid Hormone (may be
EXOGENOUS or ENDOGENOUS)
o Hyperthyroid: Thyrotoxicosis that results from Increased Production of Thyroid Hormones from the Thyroid Gland
itself (ENDOGENOUS)
B. Causes of Thyrotoxicosis:
PRIMARY THYROTOXICOSIS
Graves Disease
Toxic Multinodular Goiter
Toxic Adenoma
Thyroid CA / Mets
Struma Ovarii

SECONDARY THYROTOXICOSIS
TSH Secreting Pituitary Adenoma
Thyroid Hormone Resistance Syndrome
H-Mole

THYROTOXICOSIS WITHOUT
HYPERTHYROIDISM
Leakage

Subacute Thyroiditis

Painless Thyroiditis

Suppurative Thyroiditis
Thyrotoxicosis Factitia

Exogenous Thyroid Hormone

Diet Pills
Other Causes of Thyroid Gland Destruction:

Amiodarone

Radiation

Infarction of Adenoma
Ectopic Thyroid Gland
Struma Ovarii (Thyroid Tissue in ovary)

C. Thyroid Storm
o Extreme Accentuation of Hyperthyroidism, usually with Graves Disease of Toxic Multinodular Goiter
o < 10% of Hospital Admissions for Thyrotoxicosis
o Mortality Rate = 20-30%
o Point of which Thyrotoxicosis transforms to Storm is controversial
1. Precipitants of Thyroid Storm
Pre-Existing Thyrotoxicosis, Untreated or Partially Treated
Infection, Trauma, Surgery
Due to poorly prepared Thyroidectomy in Graves Disease patient
Other conditions associated with a Rapid Rise in Hormone Levels:
Withdrawal of Antithyroid Drug Therapy
Radioiodine Therapy
Vigorous Thyroid Palpation
Iodinated Contrast Dyes
Salicylates (competes with Albumin Binding Increase in Free Thyroid Hormone Levels)
Conditions associated with an Acute or Subacute Non-Thyroidal Illness
Infection
CVA
Trauma
DKA
2. Pathophysiology
No evidence that there is an Increased Production of T3 or T4 causing the Storm
Magnitude of Increase in Thyroid Hormones does NOT appear to be Critical
Increased Catecholamine Receptors (Key Role)
Decreased Binding to TBG (Increased Free T3/T4)
3. Atypical Presentation
Suspect Hyperthyroid in patients with Fever and Atrial Fibrillation NOT controlled with appropriate
Cardiac Management
Apathy and Coma RARE Manifestation of storm

 Key to Management = EARLY Recognition

Graves Ophthalmopathy
4. Some Laboratory Findings:
90% will NOT go back to Normal
Increased FT4, Increased FT3
RAI can Worsen Ophthalmopathy if still in
Decreased TSH
the Active Phase (wait until Ophthalmopathy is
12 L ECG
more stable before giving RAI)
Leukocytosis, shift to the Left if (+) Infection
Mild Hypercalcemia
Liver Function Test Abnormalities
Hyperglycemia (Mild to Moderate)

III. MANAGEMENT OF STORM

Goals in Management:

1) Stop Synthesis of New Hormones within the Thyroid

2) Halt release of stored Thyroid Hormone from Thyroid Gland

3) Prevent conversion of T4 to T3

4) Control Adrenergic Symptoms associated with Thyrotoxicosis

5) control systemic Decompensation with Treatment

6) Treat Underlying cause

Key Notes:

Thyroid Hormone Levels will Normalize after 4-Weeks (TSH longer time to Normalize)

Some Tests done in the PGH Lab:

o Total T4/T3
o Free T4/T3
o Tsh
o Thyroglobulin Assay
o Anti-TPO
o TgAb
Liver Function Tests:

In Thyroid Storm, we give High Doses of PTU Monitor Liver Function Tests, Agranulocytosis

If Storm is resolving, Liver Function Tests should have a Decreasing Trend

If LFTs are still increasing, DECREASE the Dose of PTU

A. Inhibit New Hormone Production

1. Propylthiouracil (PTU)
Inhibits Thyroid Peroxidase (which is involved in organification and coupling)
Drug of choice because it inhibits Peripheral Conversion of T4T3 (in HIGH doses)
Given in Large Doses: 600-1000mg Loading Dose and 200-300mg every 6 hours given orally or by
nasogastric tube or per rectum
Mechanism Of Action
Inhibit synthesis of thyroid hormones by inhibiting organification of iodine and coupling of
the iodotyrosinases
Inhibit Peripheral Conversion of T4 to T3
Proposed to have direct effects on the immune system producing a decrease in circulating
thyroid-stimulating antibodies and restoration of normal suppressor cell activity
2. Methimazole
20-25mg PO q6
Inhibit Hormone Synthesis

B. Inhibit Hormone Release

1. Stable Iodide (SSKI)
Given 1 hour after PTU it blocks the release of hormone from the gland (block the synthesis first before
giving Iodine)
Wolff-Chaikoff Effect: One hour after the first dose of PTU, Stable Iodide is given to BLOCK Thyroid
Hormone Synthesis via the Wolff-Chaikoff Effect (the DELAY allows the Antithyroid Drug to prevent the
excess Iodine from being incorporated into new hormone)
Administration: A saturated solution of Potassium Iodide (5 drops SSKI every 6 hours), or Ipodate or
Iopanoic Acid (0.5mg every 12h), may be given orally
**NOTE: Opposite of Wolff-Chaikoff = Jod Basedow (worsens)
2. Others:
Lugols Solution 4-8 Drops PO q6-8
Sodium Ipodate 1-3g PO QID
Iopanoic Acid 1g PO q8
Mechanism of Iodine:

Decreases Fractional Turnover of Thyroid Iodine and T4 Secretion Rate

Blocks Thyroid Hormone release

C. Beta-Blockers:
1. Propranolol
To reduce tachycardia and other adrenergic manifestations
60-80mg PO q4 or 80-120mg q6
High doses or Propranolol decrease T4T3 conversion
CAUTION is needed to avoid Acute Negative Inotropic Effects, but controlling the heart rate is important,
as some patients develop a form of High-Output Heart Failure
2. Cardioselective Agents (for patients with Pulmonary Diseases)
Atenolol 500-200mg PO QID
Metoprolol 100-200mg
Nadolol
3. Esmolol (IV)
50-100 ug/kg/min
D. Supportive
o Acetaminophen 325-650mg PO/PRN q4-q6
o Hydrocortisone 100mg IV q8 (decreases T4 to T3 conversion; Vasomotor Stability)
o Volume Depletion and Poor Nutrition:
IV Fluids / Electrolytes
Glucose 5-10%
Vitamins
Oxygen
Vasopressors
Treatment of CHF (Digoxin, Diuretics)
Glucocorticoids to correct Relative Adrenal Insufficiency
E. Alternative Treatment
Lithium Carbonate:
o Lithium Carbonate 300mg PO q8 (mimics iodine)

Inhibits Coupling of Iodotyrosines

Inhibits release of Thyroid Hormones

o Potassium Perchlorate 1g PO QID

Inhibit conversion of T4 to T3 by decreasing Type-1

o Cholestyramine 4g PO QID
F. Removal of T4 and T3 from the Serum:
o Cholestyramine
o Plasmapheresis
o Hemodialysis
o Hemoperfusion

Deiodinase Activity

2) HYPERTHYROIDISM / HYPOTHYROIDISM
I. HYPERTHYROIDISM
Consequence of Excessive Thyroid Hormone Action
Thyrotoxicosis is defined as a state of Thyroid Hormone Excess and is NOT synonymous with Hyperthyroidism
(which is the result of excessive thyroid function) however, the major etiologies of Thyrotoxicosis are
Hyperthyroidism caused by Graves Disease, Toxic MNG, and Toxic Adenomas
Causes:
o
o
o
o
o
o
o
o

Toxic Diffuse Goiter (Graves Disease)

Toxic Adenoma
Toxic Multinodular Goiter (Plummers Disease)
Painful Subacute Thyroiditis
Silent Thyroiditis, including Lymphocytic and Postpartum variations
Iodine Induced Hyperthyroidism
Excessive Pituitary TSH or Trophoblastic Disease
Excessive Ingestion of Thyroid Hormone

A. Clinical Manifestations (Attributable to the effects of EXCESS Thyroid Hormones in the circulation)
SYMPTOMS
Hyperactivity, Irritability, Dysphoria
Heat Intolerance and Sweating
Palpitations
Fatigue and Weakness
Weight Loss with Increased Appetite
Diarrhea
Polyuria
Oligomenorrhea, Loss of Libido

SIGNS
Tachycardia; Atrial Fibrillation in the elderly
Tremor
Goiter
Warm, Moist Skin
Muscle Weakness, Proximal Myopathy
Lid Retraction or Lag
Gynecomastia

B. Laboratory Examinations
o
o
o
o
o

Sensitive TSH Analysis: single best screening test for Hyperthyroidism

T4 or Free T4
Triiodothyronine T3 Radioimmunoassay (RIA) or Free T3
Thyroid Autoantibodies not routinely necessary
Radioactive Iodine Uptake
Thyroid Scan done to help determine the cause of Hyperthyroidism

TSH level is suppressed and total

and unbound Thyroid Hormone
Levels are increased. In 2-5% of
patients, only T3 is increased (T3
Toxicosis). The converse state of
T4 Toxicosis, with elevated Total
and Unbound T4 and Normal T3
Levels, is occasionally seen when
Hyperthyroidism is induced by
Excess Iodine, providing surplus
substrate for Thyroid Hormone
Synthesis.

QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

C. Treatment (Surgical + Antithyroid Drugs + Radioactive Iodine)

1. Surgical Intervention
No uncommonly performed, unless Coexistent Thyroid Cancer
Common candidates include pregnant patients who are intolerant to medications or non-pregnant
during definitive therapy, but refuses Radioactive Iodine
Those with very large goiters
Pediatric patient
Complications: Hypoparathyroidism, Vocal Cord Paralysis
2. Anti-Thyroid Drugs
a. Methimazole 5mg/tab
Dose: 10-20mg PO q8
Maximum Dose: 80mg/d
b. PTU 50mg/tab
Dose: 50-150mg/tab PO q8 starting dose
Maximum Dose: 1200mg/day
Adverse Reactions: Rash, Agranulocytosis
Indicated in patients with Graves Disease, elderly patients who require post treatment
prior to radioactive iodine therapy
C. Radioactive Iodine Therapy
Yields quickest resolution of the Hyperthyroidism
Leads to Hypothyroidism and require lifelong Thyroid Replacement Therapy
Pharmacology Notes (Med School)
1. Prophylthiouracil (PTU)

Inhibits Organification and Coupling

Inhibits Peripheral Conversion of T4 to T3

2. Methimazole

Inhibits Organification and Coupling (only)

3. Iodide

Inhibits Hormone Release

Decrease Vascularity of Thyroid Gland

4. Anion Inhibitors

Competitive Inhibitor of Iodide Transport Mechanism

Ex) Perchlorate; Thiocyanate

5. B-Adrenergic Antagonists

Reduces Activity of Thyroid Hormone on Target Tissues

Ex) Propranolol
6. Radioactive Iodine

Damages the Gland thru Cytotoxic Effects

It is ONLY used for Hyperthyroid!!! NOT Hypothyroid!!!

II. HYPOTHYROIDISM
Results from Undersecretion of Thyroid Hormone
Iodine Deficiency remains the Most Common Cause of Hypothyroidism worldwide
In areas of Iodine Sufficiency, Autoimmune Disease (Hashimotos Thyroiditis) and Iatrogenic Causes are most
common (treatment of Hyperthyroidism)
Secondary Causes: Pituitary Disease, Hypothalamic Disease
A. Clinical Features (Descending Order of Frequency)
SYMPTOMS
Tiredness, Weakness
Dry Skin
Feeling Cold
Hair Loss
Difficulty Concentrating and Poor Memory
Constipation
Weight Gain with Poor Appetite
Dyspnea
Hoarse Voice
Menorrhagia (later Oligomenorrhagia or Amenorrhea)
Paresthesia
Impaired Hearing

B. Laboratory Examinations
o TSH immunoassay
o Free T4
o Thyroid Autoantibodies
o Thyroid Scan
o UTZ

SIGNS
Dry coarse skin; Cool Peripheral Extremities
Puffy Face, hands, and feet (Myxedema)
Diffuse Alopecia
Bradycardia
Peripheral Edema
Delayed Tendon Reflex Relaxation
Carpal Tunnel Syndrome
Serous Cavity Effusions

In Hypothyroid: Increased TSH IRMA; Decreased FT4

A normal TSH Level Excludes Primary (but NOT Secondary) Hypothyroidism. If the TSH is
elevated, an Unbound T4 level is needed to confirm the presence of Clinical Hypothyroidism,
but T4 is Inferior to TSH when used as a screening test, because it will not detect Subclinical
Hypothyroidism. Circulating Unbound T3 Levels are NORMAL in 25% of patients. T3
measurements are therefore, NOT indicated

QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

C. Treatment
1. Primary Hypothyroidism
a. Levothyroxine Na 25mcg, 50mcg, and 100mcg
Start usually with 25-50mcg/d use Lower Dosages 12.5-25mcg for patients > 60y/o and
those with cardiac disease
Treatment for Life
WOF Adrenal Failure, Hypotension, nausea and vomiting
b. Course:
Symptoms improve in weeks
WOF for heart failure from too aggressive therapy
c. Plan
Increase Dose by 25-50mcg every 4 weeks until patient is Euthyroid
d. Goal of Treatment:
Maintain Plasma TSH in the Normal Range. Monitor Plasma TSH q3-4 months
2. Secondary Hypothyroidism
Monitor Serum T4 and other Pituitary Hormones
Give steroid replacement first prior to L-Thyroxine Treatment
III. GOITER AND NODULAR THYROID DISEASE
GOITER: Enlarged Thyroid Gland
Biosynthetic Defects, Iodine Deficiency, Autoimmune Disease, and Nodular Diseases can each lead to Goiter
A. Diffuse Non-Toxic (Simple) Goiter
o When Diffuse Enlargement of the Thyroid occurs in the absence of Nodules and Hyperthyroidism, it is
referred to as Diffuse Non Toxic Goiter (Simple Goiter or Colloid Goiter)
o Thyroid Function is preserved, most Goiters are Asymptomatic
o Pembertons Sign: refers to symptoms of faintness with evidence of facial congestion and external
jugular venous obstruction when arms are raised above the head
o Tx: Iodine or Thyroid Hormone Replacement induces variable regression of goiter in iodine deficiency
o Levothyroxine can be started to suppress the TSH into Low-Normal, but detectable range
B. Non-Toxic Multinodular Goiter
o Most are Asymptomatic EUTHYROID
o Thyroid Architecture is distorted, and multiple nodules can be appreciated
C. Toxic Multinodular Goiter
o Presence of Functional Autonomy in Toxic MNG (in contrast to Non Toxic MNG)
o Clinical Presentation: Subclinical Hyperthyroidism or Mild Thyrotoxicosis
o Tx: Antithyroid Drugs often with B-Blockers can normalize Thyroid Function
o Laboratory:
TSH is Low
T4 Level is normal or minimally increased
T3 is often elevated to a greater degree than T4

3) DIABETES MELLITUS
I. CLINICAL FEATURES (Notes from Rounds)
A. Symptoms of DM
o Polyuria
o Polydypsia
o Unexplained Weight Loss

**NOTE: Polyphagia was removed

Target BP if (+) DM: < 130/80

B. Note that Patients with DM are on the following drugs

o Aspirin
o Statins
o Anti-Hypertensives
**NOTE: Studies have shown benefits in using these drugs
C. Nice To Knows:
o Metformin = CONTRAINDICATED in patients with Renal Insufficiency
o Target Glucose in patients with Infection = 110-130 (?)
o Human Biphasic Insulin
30% SHORT Acting + 70% INTERMEDIATE Acting
Short Acting = Onset of Action is after 30 minutes therefore, give it 30 minutes before meals
Intermediate Acting = Onset is after 2 hours therefore, give it 2 hours before meals
**NOTE: Lispro / Aspart (Analogs) = when given SC, it acts IMMEDIATELY
Therefore, give it IMMEDIATELY before meals, to AVOID Hypoglycemia
Ex) Lispro 30u immediately before meals

II. DIAGNOSIS OF DM
A. Diagnostic Criteria for DM is Based on the following Premises:
o 1) Spectrum of Fasting Plasma Glucose (FPG) and the Response to an Oral Glucose Load (OGTT)
o 2) DM is Defined as the Level of Glycemia at which Diabetes-Specific Complications occur, rather than
on the deviations from a Population-Based Mean
1. Glucose Tolerance is Classified into THREE Categories Based on FPG:
Normal
FPG < 5.6 mmol/L (100 mg/dL)
Impaired Fasting Glucose
FPG = 5.66.9 mmol/L (100-125 mg/dL)
Diabetes Mellitus
FPG > 7.0 mmol/L (126 mg/dL)
2. Based on Response to Oral Glucose Tolerance Test (OGTT)
Impaired Glucose Tolerance
7.8 to 11.1 mmol/L (140 to 199 mg/dL)
Diabetes Mellitus
Glucose > 11.1 mmol/L (200 mg/dL)
**NOTE: This is 2 hours after a 75-g Oral Glucose Load
B. Criteria for the Diagnosis of Diabetes Mellitus:
Symptoms of Diabetes PLUS Random Blood Glucose Concentration > 11.1 mmol/L (200 mg/dL); or
Fasting Plasma Glucose > 7.0 mmol/L (126 mg/dL); or
Two Hour Plasma Glucose > 11.1 mmol/L (200 mg/dL) during an Oral Glucose Tolerance Test

Random is defined as without regard to time since the last meal

Fasting is defined as No Caloric Intake for at least 8 hours
Current Criteria for Diagnosis of DM emphasize that the FPG is the MOST reliable and convenient test for
identifying DM in asymptomatic individuals

10

III. OVERVIEW OF SOME DRUGS USED:

A. Insulin
INSULIN PREPARATION
Lispro (Rapid)
Aspart (Rapid)
Regular (Short)
Isophane (Intermediate)
Glargine (Long)
Detemir (Long)

ONSET OF ACTION
5-15 mins
5-15 mins
30-60 mins
2-4 hours
2-4 hours
3-8 hours

PEAK
30-90 mins
30-90 mins
2-3 hours
4-10 hours
Peakless
Peakless

DURATION
4-6 hours
4-6 hours
6-10 hours
10-20 hours
24 hours

1. Intermediate Acting
Humulin-N (Brand Name) = NPH or Humulin Isophane (Generic)
Given at a dose of 0.3 0.5 units/kg SC (2/3 given am; 1/3 given pm)
Ex) In a 60 kg patient at a dose of 0.4 units/kg, we can give HN 20 0 4
2. Short Acting
Humulin-R (Brand Name) = Regular Insulin
Usually given 30 minutes before meals
Ex) 4 u Pre-Breakfast
3. Rapid Acting
Usually given 5 minutes before meals
B. Insulin Secretagogues
1. Sulfonylureas
Gliclazide
Glibenclamide
2. Non-Sulfonylureas
Repaglinide
Nateglinide
C. Insulin Sensitizers (Enhance Insulin Sensitivity)
1. Biguanide
Metformin
2. Thiazolidinedione
Rosiglitazone
Pioglitazone
D. Intestinal Absorption Inhibitors
1. Carbohydrase Inhibitor
Acarbose
Miglitol
2. Lipase Inhibitor
Orlistat

11

IV. LECTURE ON DIABETES MELLITUS

A. Type 1 VS Type 2 CM
o T1DM: Absolute Insulin Deficiency
o T2DM: Relative Insulin Deficiency with Insulin Resistance
o In T2DM, the Insulin Dose is usually higher because of Insulin Resistance
B. Diagnosis of DM:
o Recent Studies suggest that HbA1c > 6.5: usually Diabetic already (not yet a recommendation)
C. Complications of DM:
o Acute: DKA, HHS, Hypoglycemia
o Chronic:
Microvascular: Neuropathy, Retinopathy, Nephropathy
Macrovascular: MI, Stroke, PAOD
D. Treatment Goals (according to ADA 2009)
HbAIc
Fasting / Preprandial Plasma Glucose
Postprandial Plasma Glucose
Bedtime Plasma Glucose

<7
70-130mg/dL (3.9-7.2mmol/L)
<180mg/dL (<10mmol/L)
110-150mg/dL (6-8.3mmol/L)

**IMPORTANT NOTES:
According to AACE: HbA1c should be <6.5
When monitoring Glucose, include FBS, HbA1c, and Postprandial Glucose (PPG)
E. Management of Diabetes
1. Consider the Mechanism of Action of the Drug:
PATHOPHYSIOLOGY OF DM
Islet Cell Dysfunction (A and B)
A: Increased Glucagon
B: Decreased Insulin
Non-Suppressable Hepatic Glucose Output
(responsible for Fasting Hyperglycemia)
Insulin Resistance
High Carbohydrate Diet
Decreased Incretin Levels / Activity
GLT
GIP

DRUGS USED
Sulfonylureas
Meglitinides
Insulin
DPP-IV Inhibitors
GLP-1 Analogues
Metformin
Thiazolidinediones
Incretin Agents
Metformin
Thiazolidinediones
A-Glucosidase Inhibitors
DDP-IV Inhibitor
GLP-1 Analogues
Metformin

12

2. Consider Side Effects (Two Most Common Side Effects = Hypoglycemia and Weight Gain)
a. Common Side Effects
Insulin
Sulfonylureas
Metiglinides
Thiazolidinediones

Metformin

Acarbose

GLP-1 Agonist
DP-IV Inhibitors

Hypoglycemia
Weight Gain
Hypoglycemia
Weight Gain
Few Hypoglycemia
Weight Gain
No Hypoglycemia if MonoTx
Weight Gain
Edema, CHF, Osteoporosis, Anemia
No Hypoglycemia if MonoTx
Weight Loss
Lactic Acidosis (especially if with CKD, Heart Problem, Hypoxia)
No Hypoglycemia if MonoTx
Weight Loss
Diarrhea, Flatulence, Abdominal Pain
No Hypoglycemia if MonoTx
Weight Loss
No Hypoglycemia if MonoTx
Headache, Nasopharyngitis

**IMPORTANT Notes:
-Reason for Weight Loss in DM (symptom of DM) due to Lipolytic Actions in DM
-Hypoglycemia in SU:
o Glyburide > Glibenclamide > Glimepiride > Gliclazide > Glipizide
o Glyburide is not available in the Philippines
o Glibenclamide: used in the Philippines, but NOT advisable for elderly it is prone to
Hypoglycemia due to its Long Action
b. Some Contraindications:
Metformin: Hypoxia, Renal Dysfunction, Liver Disease, CHF
Glibenclamide: CKD
Some Drugs that can be used in CKD: Meglitinides, Acarbose, etc

3. Consider MonoTx or Combination Tx or Insulin

Recent Studies show: Do Combination Therapy Earlier to achieve Goals earlier
Current Suggestions:
HbA1c LEVELS
6 7%
7 10%

> 10%

MANAGEMENT
Oral Monotherapy
Combination Therapy

Oral + Oral

Oral + Basal Insulin

Biphasic Insulin
Insulin

The following REQUIRE Replacement Therapy (Institute Insulin Therapy)

Type 1 DM
History of Pancreatectomy or Pancreatic Dysfunction
Wide fluctuations in Glucose (Brittle Diabetes)
History of DKA
Insulin use > 5 years
Diabetes > 10 years (because of Progressive B-Cell Destruction)

13

4. Consider Primary Effect of Drug (either Preprandial or Postprandial)

a. Monotherapy
DRUG GROUP
Sulfonylureas
Meglitinides
Metformin
Thiazolidinediones
Incretin
Acarbose
DDP-IV Inhibitor
b. Combination Therapy
Sulfonylureas + Metformin
Sulfonylureas + Rosiglitazone
Sulfonylureas + Acarbose
Repaglinide + Metformin

PRIMARY CONTROL
Fasting Plasma Glucose
Postprandial Plasma Glucose
Fasting Plasma Glucose
Fasting Plasma Glucose
Postprandial Plasma Glucose
Postprandial Plasma Glucose
Postprandial Plasma Glucose
Fasting Plasma Glucose
Fasting Plasma Glucose
Fasting Plasma Glucose, Postprandial Plasma Glucose
Fasting Plasma Glucose, Postprandial Plasma Glucose

c. Suggested Regimen based on HbA1c

If HbA1c is
<7%
Control Postprandial first
7-9%
Control either Preprandial and Postprandial
>9%
Control Preprandial (fasting) first
d. Insulin
INSULIN PREPARATION
Lispro (Rapid)
Aspart (Rapid)
Regular (Short)
Isophane (Intermediate)
Glargine (Long)
Detemir (Long)

PRIMARY CONTROL
Postprandial Plasma Glucose
Postprandial Plasma Glucose
Postprandial Plasma Glucose
Fasting Plasma Glucose
Fasting Plasma Glucose
Fasting Plasma Glucose

5. Evaluate at the Appropriate Time (based on Peak Effect)

DRUG STARTED
Sulfonylureas

WHEN WILL DRUG TAKE

EFFECT?
1-2 Weeks

WHEN TO MONITOR RESPONSE?

(Clinical Monitoring)
FPG at 2 Weeks
HbA1c at 3 Months

Meglitinide

1-2 Weeks

FPG at 2 Weeks
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

DPPV-IV Inhibitors

2 Weeks (?)

FPG at 2 Weeks
HbA1c at 3 Months
PPG at Initiation

Annual Laboratories:
o Lipid Profile
o Liver Function Tests
o Urine Albumin:Creatinine Ratio
o Serum Creatinine / GFR
o TSH in T1DM, Dysplipidemia, and women > 50
o Dilated Eye Exam

14

6. Other Notes on Management

Approved Drugs for Management of Pre-Diabetes (Impaired Glucose Tolerance)
Acarbose
Metformin
TZD
If (+) Hypoglycemia Stop SU:
Glucose levels will normalize after 3-5 days
If (+) Renal Disease, Glucose will normalize after 1 wk
V. DIABETIC FOOT (NEUROISCHEMIC FOOT ULCER / NIFU)
A. University of Texas Grading:
0
Stage A
Stage B

Stage C

Stage D

Pre or Postulcerative
Lesion, completely
epithelialized
Pre or Postulcerative
Lesion, completely
epithelialized with
Infection
Pre or Postulcerative
Lesion, completely
epithelialized with
Ischemia
Pre or Postulcerative
Lesion, completely
epithelialized with
Infection and Ischemia

II

III

Superficial Wound, not

involving Tendon Capsule
or Bone
Superficial Wound, not
involving Tendon Capsule
or Bone with Infection

Wound Penetrating to
Tendon or Capsule

Wound Penetrating to
Bone or Joint

Wound Penetrating to
Tendon or Capsule with
Infection

Wound Penetrating to
Bone or Joint with
Infection

Superficial Wound, not

involving Tendon Capsule
or Bone with Ischemia

Wound Penetrating to
Tendon or Capsule with
Ischemia

Wound Penetrating to
Bone or Joint with
Ischemia

Superficial Wound, not

involving Tendon Capsule
or Bone with Infection and
Ischemia

Wound Penetrating to
Tendon or Capsule with
Infection and Ischemia

Wound Penetrating to
Bone or Joint with
Infection and Ischemia

I: Change in color; Pre-ulcerative; Post-ulcer

II: Dermal involvement
III: Deep tissues (Muscle and bone)

A: Non-infected; Non-ischemic
B: Infected; Non-ischemic
C: Non-infected; Ischemic
D: Infected; Ischemic

B. Wagner
0

No Open Lesion but may have deformity or cellulites

Superficial Ulcer, partial or full thickness

Dermis only (Gram Positive: Cloxacillin, Ampi-Sul, 1st Gen Cephalosporins

II

Ulcer extends to ligament, tendon, joint capsule or deep fascia without abscess / osteomyelitis
Tendon, Joint Capsule (Gram Negative: Aminoglycosides

III

Deep Ulcer with abscess, osteomyelitis, or joint sepsis

Bone (Anaerobic Coverage)

IV

Localized Gangrene (localized to forefoot or heel)

Advanced Gangrene

15

4) DIABETIC EMERGENCIES
I. DIABETIC KETOACIDOSIS
DKA and Hyperglycemic Hyperosmolar State (HHS) are ACUTE Complications of Diabetes
DKA was formerly considered a Hallmark of DM Type 1
HHS is primarily seen in individuals with DM Type 2
BOTH disorders are associated with Absolute or Relative Insulin Deficiency, Volume Depletion, and Acid-Base
Abnormalities
A. DKA vs HHS
Glucose mmol/L (mg/dL)
Na+ mEq/L
K+
Mg2+
ClP
Creatinine
Osmolality (mOsm/mL)
Plasma Ketones
Serum Bicarbonate mEq/L
Arterial pH
Arterial PCO2 mmHg
Anion Gap [Na-(Cl+HCO3)]

DKA
13.9 33.3 (250 600)
125 135
Normal to Increased
Normal
Normal
Decreased
Slightly Increased
300 320
++++
< 15 mEq/L
6.8 7.3
20 30
High

HHS
33.3 66.6 (600 1200)
135 145
Normal
Normal
Normal
Normal
Moderately Increased
330 380
+/Normal to Slightly Decreased
> 7.3
Normal
Normal to Slightly High

B. Clinical Features of DKA

SYMPTOMS
Nausea / Vomiting
Thirst / Polyuria
Abdominal Pain
Shortness of Breath

PRECIPITATING EVENTS
Inadequate Insulin Administration
Infection (PNA / UTI / Gastroenteritis / Sepsis)
Infarction (Cerebral, Coronary, Mesenteric, Peripheral)
Drugs (Cocaine)
Pregnancy

PHYSICAL FINDINGS
Tachycardia
Dehydration / Hypotension
Tachypnea / Kussmaul Respirations
Respiratory Distress
Abdominal Tenderness (may resemble
Acute Pancreatitis / Surgical Abdomen)
Lethargy / Obtundation / Cerebral Edema
Possibly Coma

Symptoms / Signs of DKA usually develop over 24 hours

Hyperglycemia Glucosuria, Volume Depletion, Tachycardia
Classic Signs: Kussmaul Respiration and a Fruity Odor of patients breath (secondary to Metabolic
Acidosis and Increased Acetone)
C. Pathophysiology
o Results from RELATIVE or ABSOLUTE Insulin Deficiency combined with counterregulatory hormone
excess (Glucagon, Catecholamines, Cortisol and Growth Hormone)
o BOTH Insulin Deficiency and Glucagon Excess are necessary for DKA to develop
o Decreased Ratio of Insulin to Glucagon promotes Gluconeogenesis, Glycogenolysis, Ketone Body
Laboratory evaluation of DKA shows an Increased Ion Gap Metabolic
formation in the Liver
Acidosis and Positive Serum Ketones. Plasma Glucose is usually elevated,
D. Differential Diagnosis:
but the degree of Hyperglycemia may be moderate (~300mg/dL or lower).
o Starvation Ketosis
Urine Ketone reaction correlates poorly with Ketonemia, but is usually
o Alcoholic ketoacidosis
Positive in DKA
o Other Increased Anion Gap Acidosis
o
o
o

E. Complications of DKA
o Lactic Acidosis
o Arterial Thrombosis
o Cerebral Edema

Hyponatremia, Hyperkalemia, Azotemia, and Hyperosmolality are other

findings. Serum Amylase and Transaminases may be elevated, again
raising suspicion for Intra-Abdominal Pathology.

16

F. Management of DKA
o

1) Confirm diagnosis (High Plasma Glucose, (+) Serum Ketones, Metabolic Acidosis)

2) Admit to Hospital; Intensive Care Setting may be necessary for frequent monitoring or if pH < 7.00 or
Unconscious
3) Assess:
Serum Electrolytes (K, Na, Mg, Cl, Bicarbonate, Phosphate)
Acid-Base Status pH, HCO3, pCO2, B-Hydroxybutyrate
Renal Function (Creatinine, Urine Output)

Notes on Potassium:

If < 3.3: Hold Insulin; Add 40meq K/L

If 3.3 5: 20-30 meq K/L

If >5: Re-check Potassium q20

Potassium Drips:

Peripheral Line: Maximum Rate is 10 meq/hr (Maximum of 60meq/L)

Central Line: Maximum Rate is 20 meq/hr

o
o
o

4) Replace Fluids: 2-3 L of 0.9% Saline over first 1-3 hours (10-15mL/kg per hour); subsequently, 0.45% Saline at
150-300mL/h; change to 5% Glucose and 0.45% Saline at 100-200mL/h when Plasma Glucose reaches 250mg/dL
(14mmol/L)
5) Administer Short-Acting Insulin: IV (0.1 units/kg) or IM (0.3units/kg), then 0.1 units/kg per hour by continuous
IV infusion; Increase 2 to 3 fold if NO response by 2-4 hours. If initial Serum K + is < 3.3mmol/L (3.3mEq/L), do
NOT administer Insulin until the K+ is corrected to > 3.3mmol/L (3.3mEq/L)
6) Assess patient: What precipitated episode (noncompliance, infection, trauma, infarction, cocaine)? Initiate
appropriate workup for precipitating event (cultures, CXR, ECG)
7) Measure capillary glucose every 1-2 h; measure electrolytes (especially K+, bicarbonate, phosphate) and Anion
Gap every 4 h for first 24 hours
8) Monitor BP, pulse, respirations, mental status, fluid intake and output every 1-4 hours

9) Replace K+: 10 mEq/h when Plasma K+ < 5.5mEq/L, ECG normal, urine flow and normal creatinine documented;
Administer 40-80 mEq/h when Plasma K+ <3.5mEq/L or if Bicarbonate is given

10) Continue above until patient is stable, glucose goal is 150 250 mg/dL, and acidosis is resolved, Insulin
Infusion may be decreased to 0.05 0.1 units/kg/hour
11) Administer Intermediate or Long-Acting Insulin as soon as patient is eating. Allow for overlap in Insulin
Infusion and Subcutaneous Insulin Injection

G. Criteria For Resolving DKA

o Normalization of Serum Anion Gap
o Normalization of Acidosis
o (-) Ketones
**IMPORTANT Notes:
Serum Ketones: B Hydroxybutyrate (which is converted to Acetoacetate)
Urine Ketones: Acetoacetate

17

MANAGEMENT OF DIABETIC KETOACIDOSIS (Dr. Gatchalian)

CASE: 60kg Patient comes in with a CBG of 500
1st thing to do is HYDRATE (up to 3 L can be given) however, if there is NO Improvement, start Insulin
1. Hydration
Monitor CBG every 1 hour
We can give as much as 3 L, before giving Insulin
2. Insulin Regimen
Give a Bolus Dose of 0.15 U/kg
Maintain on a Drip at 0.10 U/kg range of 0.1 to 0.6 (Ex. Mix 20 U Insulin in 100cc PNSS)
Ex) In a 60 kg patient, we give 9 Units/Hour
. 20 U . = . 9 U .
100cc
X

X = 45 cc / hour or 45 ugtts/min (which is equivalent to 9 U/hour)

3. Adjusting Insulin
Monitor CBG every hour and get the difference
Ex) If CBG is 500, then decreases to 300 after one hour, the difference is 200
If Difference is:

> 75
50-75

Decrease by HALF
MAINTAIN Dose

< 50

Double Insulin Dose

Ex) If we are giving 9 U/hr, give 4.5 U/hr

4. RULE (Subjective for PGH)

If you get a CBG Value of LESS than 250 for 2-3 Consecutive Times, we may:
o 1) Start D5NR + 20 mEqs KCl x 10 Hours
o 2) Start Fixed Dose of Insulin at HN 0.4-0.6 u / kg / hr
II. HYPERGLYCEMIC HYPEROSMOLAR STATE (HHS)
A. Clinical Presentation:
o Prototype patient: Elderly with Type 2 DM, with a several weeks history of Polyuria, Weight Loss, and diminished
Oral Intake that culminates in Mental Confusion, Lethargy, or Coma
o PE: reflects profound Dehydration and Hyperosmolality and reveals Hypotension, Tachycardia, and an altered
mental status
o Notable ABSENT are symptoms of Nausea, Vomiting, and abdominal pain, and the Kussmaul Respirations
characteristic of DKA
o Often precipitated by a serious, concurrent illness such as MI or stroke, sepsis, pneumonia & other serious infections
o Results from Severe Dehydration and Hyperglycemia clinical evidence of Severe Dehydration is the rule
o Ketoacidosis is ABSENT because Residual Insulin Secretion, though inadequate for Glycemic Control, effectively
inhibits Lipolysis and Ketogenesis
B. Pathophysiology
o Relative Insulin Deficiency and Inadequate Fluid Intake are the underlying causes of HHS
o Hyperglycemia Osmotic Diuresis Volume Depletion, exacerbated by inadequate fluid intake
o Insulin Deficiency is only RELATIVE (probably) and less severe than in DKA
C. Management
o 1) Fluid Replacement
o 2) Insulin Therapy
o 3) Collection of Electrolyte Deficits

18

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GASTROENTEROLOGY
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Jaime Alfonso Manalo Aherrera, M.D.

Internal Medicine Notes 2009

COMMON GASTROINTESTINAL DISEASES

1) UPPER GASTROINTESTINAL BLEEDING (UGIB)

Hemorrhage may develop from any gut organ

Upper GI Bleeding presents with MELENA or HEMATEMESIS
Lower GI Bleeding produces passage of Bright Red or Maroon Stools

I. TERMINOLOGIES
Hematemesis
Melena
Hematochezia
Occult GI Bleeding
Symptoms of Blood Loss or Anemia
II. SOURCES OF BLEEDING
PUD (Duodenal and Gastric)
Gastritis (Stress, Alcohol, Drugs)
Esophagitis, Duodenitis
Esophageal Varices, Gastroduodenal Varices
Mallory-Weiss Tears
Angiodysplasia or Telengiectasia
Gastro-Esophageal Carcinoma
Hemophilia
Gastroduodenal Fistula
Bleeding Disorders (Leukemia, Aplastic Anemia)

The Most Common Upper GI Causes of Bleeding are Ulcer

Disease, Gastroduodenitis, and Esophagitis.
Other etiologies include Portal HPN, Malignancy, Tears across the
Gastroesophageal Junction, and Vascular Lesions

III. MANAGEMENT
Antacids
H2 Blockers / PPI
AntBx: Metronidazole, Amoxicillin, Tetracycline,
Clarithromycin
Anticholinergics
Sucralfate
Bismuth
PGE2

IV. CLINICAL PRESENTATION

Overt GI Bleeding: presents with passage of fresh or altered blood through the mouth or in the stool
Occult Bleeding: refers to (+) Fecal Occult Blood Test or Iron-Deficiency Anemia without visible blood in stool
Obscure Bleeding: refers to GI blood loss of unknown origin that persists or recurs after negative initial endoscopic
evaluation (obscure bleeding can either be Overt or Occult)
V. GENERAL CONSIDERATIONS IN OVERT BLEEDING
A. Initial Evaluation
o Intravascular Volume and Hemodynamic Status
o Laboratory Evaluation (CBC, PT/PTT, Blood Type, Liver & Renal Function Tests
B. Initial Resuscitation
1. Restoration of Intravascular Volume:
Isotonic Saline, LR, or Hetastarch can be used

Blood should be used for volume replacement whenever possible and should be initiated as soon as it is
evident that patients bleeding is massive, ongoing, or severe enough that Colloid Infusion alone is NOT
adequate for Tissue Oxygenation
Packed RBC Transfusion: should be continued until patients condition is hemodynamically stable and
hematocrit reaches 25% or greater
2. Correction of Coagulopathy
Discontinuation of offending anti-coagulants followed by infusion of FFP can be used to correct prolonged
coagulation parameters
Protamine Infusion: 1mg antagonizes 100 units of heparin
Parenteral Vitamin-K (10mg SC or IM) for prolonged PT from Warfarin Tx or Hepatobiliary Disease
Platelet Infusion if Platelet Count < 50,000mm3
3. Airway Protection
Intubation to prevent aspiration should be considered in diminished mental status (shock, hepatic
encephalopathy), massive hematemesis, or active variceal hemorrhage

VI. APPROACH TO PATIENT

A. History & PE
Degree of Volume Loss
Level of Bleeding
Etiology of Bleeding

Patients with Lower GI Bleed have less hemodynamic compromise than those with Upper GI Bleed
Hematemesis or Coffee-Ground Emesis, Melena, Hematochezia
Important points in history include prior bleeding episodes, alcohol use, liver disease, coagulation
disorders, and bleeding tendencies:

History of emesis prior to GI bleed = suggest Mallory-Weiss Tear

NSAIDs and Aspirin

Hypotension and Hypovolemic Shock preceding bleed suggests Ischemic Injury to the gut

Radiation Therapy to prostate or pelvis suggests radiation proctitis

Prior Aortic Graft Surgery possibility of Aortoenteric or Aortocolonic Fistula

Precipitating Factors
Abnormalities in coagulation (liver disease, von-willebrands disease, vitamin-K deficiency, DIC)
Medications (warfarin, heparin, aspirin, NSAIDs, thromboytics),
Color of Stool
Can provide important clues
NG Aspiration
Useful in diagnosing Upper GI Bleeding
Anoscopy/Sigmoidosocpy DRE may identify potential source of bleeding in anorectum

B. Further Evaluation and Therapy

Esophagogastroduodenoscopy (EGD)
Colonoscopy
Tagged RBC Scanning
Arteriography
Surgery

Preferred method of investigation and therapy of upper GI bleed

All patients with acute Lower GI bleed from unknown source should undergo endoscopic
evaluation of colon
RBCs labeled with technetium 99m remain in circulation for as long as 48 hours and
extravasate into the bowel lumen with active bleeding
Allows rapid localization and potential therapy of GI bleeding when bleeding rates exceed
0.5mL/min
Emergent total colectomy may be a lifesaving maneuver for massive, unlocalized lower GI
bleed; this should be preceded by EGD to rule out rapidly bleeding upper source

VII. THERAPY FOR SPECIFIC LESIONS

Peptic Ulcer Disease
(PUD)

High Dose-Proton Pump Inhibitors (Omeprazole 40mg PO BID) reduces rate of recurrent bleeding & need for
surgery. Use of High Dose PPIs has documented utility in patients who are awaiting endoscopic treatment or in those
whom endoscopy is contraindicated or postponed
Therapeutic Endoscopy: advantage of immediate treatment & should be implemented in all patients early in the
hospital course (within 24 hours). Fluid resuscitation & hemodynamic stability are essential prior to endoscopy.
Surgery for intractable or recurrent bleeding
Risk Factors for increased morbidity & mortality:

Age > 60 y/o

More than one comorbid illness

Blood Loss > 5 units

Shock on Admission

Bright-Red Hematemesis with Hypotension

Variceal Hemorrhage

Coagulopathy
Large (>2cm) Ulcers
Recurrent Hemorrhage (within 72 hours)
Requirement for Emergency Surgery

ICU admission and Intubation for airway protection in patients who are actively bleeding from varices. Octreotide
Infusion to reduce Portal Pressures acutely.
Esophageal Varices

Variceal Ligation of Banding = Endoscopic Therapy of Choice (controls active hemorrhage)

Sclerotherapy (used less frequently because of complications)

TIPS / Transjugular Intrahepatic Portosystemic Shunt to decompress the portal pressure

Shunt Surgery

Balloon Tamponade
Gastric Varices

Octreotide Infusion or other pharmacologic therapy should be initiated early (as for Esophageal Varices)

Variceal Ligation or Banding usually NOT successful

Sclerotherapy can be attempted, TIPS, Balloon Tamponade

Pharmacologic Prophylaxis with B-Adrenergic Antagonists

Shown to REDUCE Portal Pressure & lower risk of recurrent bleeding

Propranolol and Nadolol reduce resting heart rate by 25%

Hepatic Transplantation

Stress Ulcer

Encountered in ICU setting, especially those who require mechanical ventilation > 48 hours, with coagulopathy,
sepsis, burns, or CNS processes
Prophylactic Therapy: Histamine-Receptor Antagonists and Sucralfate, PPIs

2) PANCREATITIS

Pathologic Spectrum varies from Edematous Pancreatitis (Mild & Self-Limited) to Necrotizing Pancreatitis (correlates
with the Severity of the attack)

I. RANSONS CRITERIA IN PANCREATITIS

POOR Predictive Power!
> 3 Factors at time of Admission (1) or during initial 48 hours (2) indicates an Increased Mortality Rate
These patients need closer monitoring in an ICU stting
FIRST 24 HOURS
Patients age > 55 y/o
Leukocytosis or WBC > 16,000 mm3
Hyperglycemia or FBS > 200 mg/dL
Serum LDH > 400 units/mL
Serum AST or SGOT > 250 units/mL

AFTER 48 HOURS OF ADMISSION

Fall in Hematocrit by > 10%
Fluid Deficit of > 4000 mL
Hypocalcemia (<8mg/dL)
Hypoxemia (PO2 < 60mmHg)
Increase in BUN to > 1.8 mmol/L after IV-Administration
Hypoalbuminemia

Severe Acute Pancreatitis: Risk Factors that Adversely Affect Survival in Acute Pancreatitis:
o
o

o
o

1) Associated with Organ Failure and/or Local Complications such as Necrosis

2) Clinical Manifestations

Obesity BMI > 30

Hemoconcentration (Hct > 44%)

Age > 70
3) Organ Failure

Shock

Pulmonary Insufficiecny (PO2 < 60)

Renal Failure (CR > 2.0mg%)

GI Bleeding
4) > 3 Ransom Criteria (not fully utilizable until 48 hours)
5) Apache II Score > 8 (Cumbersome)

II. ACUTE PANCREATITIS

AUTODIGESTION: One of the pathogenic theories of pancreatitis wherein pancreatitis results when Proteolytic Enzymes
(Trypsinogen, Chymotrypsinogen, Proelastase, and Phospholipase-A) are activated IN the Pancreas, rather than in the
Intestinal Lumen
A. Common Causes of Acute Pancreatitis
o Gallstones, Alcohol = MOST COMMON
o HyperTriglyceridemia, Hypercalcemia
o ERCP, Trauma, Post-Op, Sphincter of Oddi Obstruction
o Drugs (MEAT-V) Mercaptopurine, Estrogen, Azathioprine, Tetracycline, Valproic Acid
B. Clinical Features
o Steady and Boring Abdominal Pain, Epigastric or Periumbilical in location, radiating to the BACK
o Pain is more intense when SUPINE
o Relieved by sitting with the Trunk Flexed and Knees drawn up (Fetal Position / Prostration)
o Associated with nausea, vomiting, and abdominal distention
Abdominal Pain (Major Symptom)

BORING and Steady in Character (in Epigastrium & Periumbilical Region)

Radiates to the Back (in 50% of Cases) or other Parts of the Abdomen (Chest, Flanks)

ACUTE in Onset (Sudden)

Lasts for Several Hours

Moderate to Severe

**NOTE: It is Frequently more Intense when patient is SUPINE, and relieved by

Sitting

C. Physical Examinations
o Distressed & anxious patient, Low Grade Fever, Tachycardia
o Hypotension: which may be due to:
Hypovolemia 20 to exudation of Blood and Plasma CHON into retroperitoneal space
Increased formation and release of Kinin Peptides which cause Vasodilation and Increased Vascular
Permeability
Systemic Effects of Proteolytic and Lipolytic Enzymes
o Obstructive Jaundice due to Edema of the Head of the Pancreas
o Erythematous Skin Nodules 2 0 to Subcutaneous Fat Necrosis
o Bibasilar Rales, Atelectasis, Pleural Effusion
o Hypoactive Bowel Sounds
o Findings in Severe Necrotizing Pancreatitis:
Cullens Sign = Faint blue discoloration around umbilicus which occurs as the result of Hemoperitoneum
Turners Sign = blue-red-purple / green-brown discoloration of flanks due to tissue catabolism of Hemoglobin
D. Diagnosis of Acute Pancreatitis
o Any severe acute pain in abdomen or back should suggest Acute Pancreatitis
o Diagnosis confirmed by a Threefold or Greater Elevated Level of Serum Amylase and/or Lipase
o Strong Indicators include: Hemoconcentration (Hct > 44%), Signs of Organ Failure
E. Differential Diagnosis = Any Disease with (+) Abdominal Pain
Perforated Viscus
(especially Peptic Ulcer)
Acute Cholecystitis and
Biliary Colic
Acute Intestinal Obstruction
Mesenteric Vascular
Occlusion
Connective Tissue Disorders
with Vasculitis
Pneumonia
Diabetic Ketoacidosis
Other Differentials

Can usually identified by imaging studies or endoscopy

Readily diagnosed by the presence of Free Intraperitoneal Air
Pain of Biliary Tract in Origin is usually right-sided or epigastric than periumbilical, and is gradual in
onset; Ileus is usually absent; UTZ is helpful in diagnosing Cholelithiasis and Cholecystitis
Both Pancreatitis and Acute Cholecystitis can have elevated serum amylase
Should be colicky pain, xrays showing mechanical obstruction
Evident in elderly debilitated patients with brisk leukocytosis, abdominal distention, and bloody
diarrheal; Angiography shows vascular occlusion
SLE, Polyarteritis Nodosa
Pain referred in Upper Abdomen
Serum Lipase Level is NOT Elevated in DKA (however, Amylase is elevated)
Renal Colic, Myocardial Infarction, Dissecting Aortic Aneurysm

Serum Amylase & Lipase levels are widely used as Screening Tests for Acute Pancreatitis in patients with Abdominal Pain or Back
Pain. Values greater than THREE TIMES the upper limit of Normal virtually clinch the Diagnosis if Gut Perforation or Infarction is
excluded. In the absence of objective evidence of pancreatitis by abdominal UTZ, CT, ERCP, or EUS, mild to moderate elevations of
Amylase and/or Lipase are problematic in making a diagnosis of Pancreatitis.
In Acute Pancreatitis, Serum Amylase is usually elevated within 24 hours of onset and remains so for 1-3 days. Levels return to
normal within 3-5 days unless there is extensive pancreatic necrosis, incomplete ductal obstruction, or pseudocyts formation.
Approximately 85% of patients with acute pancreatitis have an elevated serum amylase level.
Serum Amylase is often elevated in other conditions (because enzyme is found in many organs pancreas, salivary glands, liver, small
intestine, kidney, fallopian tube and can be produced by various tumors carcinomas of the lung, esophagus, breast, ovary.

Renal Insufficiency

Salivary Gland Lesions: Mumps, Calculus, Irraiation Sialadenitis, Maxilofacial Surgery

Tumor Hyperamylasemia: CA of Lung, Esophagus, Breast, Ovarian

Macroamylasemia, Burns, DKA, Pregnancy, Renal Transplantation, Cerebral Trauma, Drugs (Morphine)

Cholecystitis, Choledocholithiasis, Perforated / Penetrating Peptic Ulcer, Intestinal Obstruction / Infarction, Ruptured
Ectopic Pregnancy, Peritonitis, Aortic Aneurysm, Chronic Liver Disease, Postoperative Hyperamylasemia
Serum LIPASE may now be the Single Best Enzyme to measure for the diagnosis of Acute Pancreatitis.
An Assay for Trypsinogen has a theoretical advantage over Amylase and Lipase determinations in that the pancreas is the ONLY organ
that contains this enzyme.
No single blood test is reliable for the diagnosis of Acute Pancreatitis in patients with Renal Failure.

F. Diagnostics:
1. Amylase

Diagnosis of Pancreatitis is usually established by detection of an INCREASED Level of Serum Amylase (Salivary
Gland Disease and Gut Perforation or Infarction should be EXCLUDED!)
There is NO Definite Correlation between the Severity of Pancreatitis & Degree of Elevation
After 48 to 72 hours, Amylase tend to RETURN to NORMAL (even with continuing evidence of pancreatitis)

2. Lipase

Elevated Levels may remain for 7 to 14 days

Three Fold Elevation of Serum Lipase is usually Diagnostic of Acute Pancreatitis
Markedly Increased Levels of Peritoneal or Pleural Fluid Amylase (>1500nmol/L or > 5000U/dL)

3. Other Findings:

Leukocytosis (15,000 20,000 per uL)

Hemoconcentration in more severe disease (Hematocrit > 44%)
Hyperglycemia, Hypocalcemia, Hyperbilirubinemia
Elevated Serum Lactate Dehydrogenase (LDL) Levels > 8.5umol or > 500 U/dL POOR Prognosis
Hypertriglyceridemia in 15-20% (Amylase and Lipase are normal in these patients)
Hypoxemia
ECG: ST-Segment and T-Wave Abnormalities, simulating Myocardial Ischemia

4. Plain Films of the Abdomen in Acute Pancreatitis

1) Localized Ileus, usually involving the jejunum (Sentinel Loop)

2) Generalized Ileus with Air-Fluid Levels
3) Colon Cut-Off Sign, which results from isolated distention of Transverse Colon
4) Duodenal Distention with Air-Fluid Levels
5) A Mass, which is frequently a Pseudocyst

5. CT-Scan

Can confirm clinical impression of Acute Pancreatitis, even if Amylase is NORMAL

Can indicate severity

6. Sonography

Useful in Acute Pancreatitis to evaluate the gallbladder

Pancreas is enlarged in Acute Pancreatitis

7. Endoscopic Ultrasonography (EUS)

High resolution imaging of the Pancreatic Parenchyma and Pancreatic Duct with a trasducer fixed to an endoscope that
can be directed onto the surface of the pancreas through stomach or duodenum

8. Endoscopic Retrograde Cholangiopancreatography (ERCP)

May provide useful information on the status of pancreatic ductal system

G. Complications:
Local
Systemic

Necrosis, Abscess, Pseudocyst, Ascites, Obstructive Jaundice

Pleural Effusion, ARDS, Hypotension, DIC, GI Hemorrhage, Oliguria, Hyperglycemia, Fat Necrosis, Encephalopathy

1. Necrotizing Pancreatitis

Represents a severe form of Acute Pancreatitis, usually identified on Dynamic Dual-Phase CT Scanning with Contrast

Infected Pancreatic Necrosis: (+) Increasing Abdominal Pain, marked Leukocytosis, Bacteremia

Mx for Infected Necrosis: CT-Guided Percutaneous Aspiration for GS/CS to Confirm

2. Pseudocysts

Suggested by persistent pain or hyperamylasemia

Complications: Infection, Hemorrhage, Rupture (Pancreatic Ascites), Obstruction of adjacent structures

Asymptomatic Non-Enlarging Pseudocyts < 6cm: followed clinically with serial imaging studies

Symptomatic / Complicated Pseudocysts: decompression by Percutaneous, Endoscopic, Surgical Technique

3. Infection

Sources of Fever: Pancreatic Necrosis, Abscess, Infected Pseudocyst, Cholangitis, Aspiration Pneumonia

Cultures should be obtained and Broad-Spectrum Antibiotics should be administered

4. Pulmonary Complications

Atelectasis, Pleural Effusion, Pneumonia, ARDS

Cellular Injury & death result in liberation of bradykinin peptides, vasoactive substances, & histamine that can produce
vasodilation, increased vascular permeability, and edema with profound effects on many organs, most notably: LUNG
5. Renal Failure
Due to Severe Intravascular Volume Depletion or Acute Tubular Necrosis

H. Indicators of Organ Failure

Cardiovascular
Pulmonary
Renal
GIT

Hypotension (BP < 90mmHg) or Tachycardia ( > 130 beats/min)

PO2 < 60mmHg
Oliguria (<50ml/h) or Increasing BUN, Creatinine
Gastrointestinal Bleeding

I. Treatment = Supportive (Disease is Self-Limited & subsides spontaneously, usually 3-7 days after treatment is instituted)
1. Aggressive Volume Repletion with IV Fluids
Serum Electrolytes, Ca2+, Glucose levels should be monitored and supplemented
2. Narcotic Analgesics: For PAIN Relief
Most Commonly used agent because it has the least effect on the Sphincter of Oddi
Meperidine
Morphine & Pantazocine

It is the DOC because it does NOT cause Spasm of the Sphincter of Oddi)
However, it is Contraindicated in Renal Failure.
Should be avoided if possible

3. Nothing Per Orem (NPO)

NPO until they are free of pain and nausea
NG Suction is reserved for patients with Ileus or Protracted Nausea & Vomiting and is not routine
(Nasogastric Suction to Decrease Gastrin Release from the Stomach and Prevent Gastric Contents from
Entering the Duodenum)
When can we Start giving Food (Med School Notes)?
When patient is Stable already (+) Abdominal Sounds, etc
Start with CARBOHYDRATES
4. Urgent ERCP and Biliary Sphincterotomy
Within 72 Hours of presentation can improve the outcome of Severe Gallstone Pancreatitis
Thought to result from reduced biliary sepsis, rather than being a true improvement of pancreatic inflammation
5. Acid Suppression
May be necessary in severely ill patients with risk factors for Stress Ulcer Bleeding
6. Prophylactic Antibiotics
For SEVERE Pancreatitis (Nectrotizing Acute Pancreatitis)

III. CHRONIC PANCREATITIS

Chronic Inflammatory Disease of the Pancreas commonly seen with Chronic Alcohol Abuse
Characterized by Irreversible Damage to the Pancreas, as distinct from the Reversible Changes noted in Acute Pancreatitis
Presence of histologic abnormalities, including chronic inflammation, fibrosis and progressive destruction in both Exocrine
and eventually Endocrine Tissue
A. Clinical Features (Symptoms are IDENTICAL to Acute Pancreatitis)
o PAIN = may be Continuous, Intermittent or Absent
o WEIGHT LOSS
o Abnormal Stools, MALABSORPTION

Signs of Malabsorption are Common in

Chronic Pancreatitis

B. Diagnosis
1. Amylase and Lipase
They are NOT Elevated (in contrast to Relapsing Acute Pancreatitis)
2. Classic Triad (seen in < 1/3 or Patients)
Pancreatic Calcification
Steatorrhea
Diabetes Mellitus
3. Intubation Test
Secretin Stimulation Test
Usually gives Abnormal Results when 60% or More of Pancreatic Exocrine Function has been lost
4. Cobalamin Malabsorption
Corrected by the Administration of Oral Pancreatic Enzymes
40% of Patients have Cobalamin (Vitamin B12) Malabsorption
5. Marked Excretion of Fecal Fat
Corrected by Administration of Oral Pancreatic Enzymes
6. Serum Trypsinogen Level
DECREASED
In the presence of Steatorrhea, a Serum Trypsinogen Level < 10ng/mL = Diagnostic of Chronic Pancreatitis
7. Radiographic Hallmark = (+) CALCIFICATION throughout the Pancreas
Ultrasound
CT-Scan
ERCP
C. Treatment (Directed to TWO MAJOR Problems = Pain + Malabsorption)
1. Management of Pain (Critical in Chronic Pancreatitis)
ABSTINENCE from Alcohol and Fatty meals
Use of Narcotics
Pancreatic Enzymes
Surgery
ERCP and Sphincterotomy if (+) Pancreatic Duct Obstruction from stones, structures, papillary stenosis
2. Management of Malabsorption (Exocrine Insufficiency)
Pancreatic Enzyme Replacement
Supportive Measures
Diet should be Moderate in Fat (30%), High in protein (24%), and Low in CHO (40%)
Restriction of Long-Chain Triglyceride Intake can help Patients who DONT respond
satisfactorily to Pancreatic Enzyme

3) PEPTIC ULCER DISEASE

Most Common Cause of UGIB

Ulcer: Break in the Mucosal Surface > 5mm, with Depth into the Mucosa
Burning Epigastric Pain exacerbated by Fasting and improved with Meals

I. FEATURES
Epigastric Burning Pain
Bloatedness, Nausea, Vomiting, Insomnia
UGIB

Alarming Symptoms: Weight Loss, Early Satiety, Bleeding, Anemia,

and lack of appropriate response to Acid Suppression

II. DIAGNOSIS
X Ray

Double contrast upper GI series.

Benign: Smooth, regular, round ulcer, ulcer crater beyond gastric wall, gastric folds into the base, collar of edema /
Hamptons line around the base, distensible gastric wall in the ulcer area

Endoscopy

Primary Diagnostic Maneuver (usually with biopsy of the ulcer)

Gastric Acid Analysis

Achlorydia usually in malignant

III. COMPLICATIONS
Hemorrhage: Most Serious
Perforation (intense pain, rigid abdomen, decreased BS, direct & rebound tenderness
Gastric Outlet Obstruction: early satiety, epigastric fullness, nausea and vomiting of undigested food, weight loss
Penetration (into adjacent organ): sudden onset of pain radiating to the back, High Amylase and Lipase (treatment is
surgical)
IV. TREATMENT PROTOCOLS FOR H. pylori
NO Single Agent is effective in eradicating the Organism
Combination Therapy for 14 days provides the GREATEST Efficacy
Goals in Treating PUD:
o 1) Relief of Symptoms (Pain or Dyspepsia)
o 2) Promote Ulcer Healing
o 3) Prevent Ulcer Recurrence & Complications
DRUG
Triple Therapy
1. Bismuth Subsalicylate PLUS
Metronidazole PLUS
Tetracycline

DOSE
2 tablets QID
250mg QID
500mg QID

2. Ranitidine Bismuth Citrate PLUS

Tetracycline PLUS
Clarithromycin or Metronidazole

400mg BID
500mg BID
500mg BID

3. Omeprazole (Lansoprazole) PLUS

Clarithromycin PLUS
Metronidazole OR
Amoxicillin

20mg BID (30mg BID)

250 or 500mg BID
500mg BID
1g BID

Quadruple Therapy
Omeprazole (Lansoprazole)
Bismuth Subsalicylate
Metronidazole
Tetracycline

20mg (30mg) daily

2 tablets QID
250mg QID
500mg QID

4) ACUTE CHOLANGITIS
I. CHARCOTS TRIAD AND REYNOLDS PENTAD
A. Charcots Triad
o Right Upper Quadrant Pain
o Jaundice
o Fever
**NOTE: Seen in 70% of patients with Bacterial Cholangitis
B. Reynolds Pentad
o Right Upper Quadrant Pain
o Jaundice
o Fever
o Altered Mental Status
o Shock
II. TREATMENT OF ACUTE CHOLANGITIS
Mild (Grade I)
Moderate (Grade II)
Non responsive to medical management
Severe (Grade III)
Patients with acute cholangitis and organ failure

Observation
(Antibiotic, Analgesia, prevention of organ damage)
Early Biliary Drainage
Urgent Biliary Drainage

**NOTE: Treatment for all = Treatment of ETIOLOGY

10

5) COMMON CAUSES OF GI SYMPTOMS

ABDOMINAL PAIN
Appendicitis
Gallstone Disease
Pancreatitis
Diverticulitis
Ulcer Disease
Esophagitis
GI Obstruction
Inflammatory Bowel Dse
Functional Bowel D/O
Vascular Disease
Gynecologic
Renal Stone

NAUSEA & VOMITING

Medications
GI Obstruction
Motor Disorders
Functional Bowel D/O
Enteric Infection
Pregnancy
Endocrine Disease
Motion Sickness
CNS Disease

DIARRHEA
Infection
Poorly Absorbed Sugars
Inflammatory Bowel Dse
Microscopic Colitis
Functional Bowel D/O
Celiac Disease
Pancreatic Insufficiency
Hyperthyroidism
Ischemia
Endocrine Tumor

GI-BLEEDING
Ulcer Disease
Esophagitis
Varices
Vascular Lesions
Neoplasm
Diverticula
Hemorrhoids
Fissures
Inflammatory Bowel Dse
Infectious Colitis

OBSTRUCTIVE
JAUNDICE
Bile Duct Stones
Cholangiocarcinoma
Cholangitis
Sclerosing Cholangitis
Ampullary Stenosis
Ampullary Carcinoma
Pancreatitis
Pancreatic Tumor

11

6) OTHER GI DISEASES
I. ACHALASIA
Motor disorder of the Esophageal Smooth Muscle in which the LES does NOT relax normally with swallowing, and the
Esophageal Body undergoes Non-Peristaltic Contractions
Underlying Abnormality = Loss of Intramural Neurons (Inhibitory Neurons containing VIP and Nitric Oxide Synthase are
predominantly involved, but Cholinergic Neurons are also affected in Advanced Disease)
A. Primary VS Secondary
o Primary Idiopathic Achalasia: Most of the patients (in the US)
o Secondary Achalsia: May be caused by:
Gastric Carcinoma that infiltrates Esophagus
Lymphoma
Chagas Disease
Certain Viral Infections
Eosinophilic Gastroenteritis
Neurodegenerative Disorders
B. Clinical Features
o Main Symptoms: Dysphagia, Chest Pain, Regurgitation
o Dysphagia:
Appears early
Occurs with BOTH Liquids and Solids
Worsened by Emotional Stress and Hurried Eating
**NOTE: The presence of Gastroesophageal Reflux argues AGAINST Achalasia
In patients with Long-Standing Heartburn, cessation of Heartburn and appearance of Dysphagia suggest
development of Achalasia on top of Reflux Esophagitis
C. Diagnosis
Chest X-Ray

Absence of Gastric Air Bubble

Tubular Mediastinal Mass beside the Aorta (sometimes)
Air-Fluid Level in Mediastinum in Upright Position represents Retained Food in Esophagus

Barium Swallow

Esophageal Dilatation
Sigmoid Esophagus (in advanced cases)

Fluoroscopy

Normal Peristalsis is LOST in the Lower 2/3 of Esophagus

Terminal Part shows a Persistent Beaklike Narrowing (represents Non-Relaxing LES)

Manometry

Basal LES Pressure NORMAL or ELEVATED

Swallow-Induced Relaxation either does NOT occur or is Reduced in Degree, Duration, Consistency
Esophageal Body shows an Elevated Resting Pressure
In Response to Swallows, Primary Peristaltic Waves are Replaced by Simultaneous-Onset Contractions

These contractions may be of Poor Amplitude (Classic Achalasia) or of Large Amplitude and Long
Duration (Vigorous Achalasia)

CCK Test

Cholecystokinin (CCK), which normally causes a Fall in the Sphincter Pressure, Paradoxically causes
Contraction of the LES
This paradoxical response occurs because, in Achalasia, the Neurally Transmitted Inhibitory Effect of CCK is
Absent, owing to the loss of Inhibitory Neurons

Endoscopy

To exclude Secondary Causes of Achalasia, particularly Gastric Carcinoma

12

II. DIFFUSE ESOPHAGEAL SPASMS and RELATED MOTOR DISORDERS

Symptoms: Chest Pain and Dysphagia

Recognized by Manometric Features

DES: Characterized by Non-Peristaltic Contractions, usually of Large Amplitude and Long Duration

An Esophageal Motility Pattern showing Hypertensive but Peristaltic Contractions has been called Nutcracker Esophagus
A. Clinical Features
o Non-Peristaltic Patterns are dye to Dysfunction of Inhibitory Nerves
o Histopathology: Patchy Neural Degeneration localized to Nerve Processes, rather than the Prominent Degeneration of Nerve
Cell Bodies seen in Achalasia (Diffuse Esophageal Spasm may progress to Achalasia)
B. Diagnosis of Diffuse Esophageal Spasm
Barium Swallow
The Normal Sequential Peristalsis below the Aortic Arch is REPLACED by Uncoordinated
Simultaneous Contractions that produce the appearance of Curling or Multiple Ripples in the Wall,
Sacculations, and Pseudodiverticula the Corkscrew Wsophagus
Barium Swallow is frequently Normal in DES and Mostly Normal in Related Disorders
Manometry

DES and other related disorders are Manometric Diagnoses

Several Techniques to Provoke Esophageal Spasms:

Cold Swallows (produce Chest Pain but do NOT produce Spasm on Manometry)

Solid Boluses

Pharmacologic Agents (Edrophonium) induce both Chest Pain and Motor Abnormalities
C. Treatment = Agents that Relax Smooth Muscle
o Sublingual Nitroglycerin (0.3 to 0.6mg)
o Long-Acting Agents: Isosorbide Dinitrate (10-30mg PO before meals), Nifedipine (10-20mg PO before meals)
III. DIARRHEA

Loosely defined as Passage of Abnormally Liquid or Unformed Stools at an Increased Frequency

For adults: Stool Weight > 200g/d can be generally considered Diarrheal
A. Acute VS Chronic
o Acute: < 2 Weeks
o Persistent: 2-4 Weeks
o Chronic: > 4 Weeks

**NOTE: More than 90% of Acute Diarrhea are caused by INFECTIOUS AGENTS

Remaining 10% are caused by Medications, Toxic Ingestions, Ischemia, etc

B. Pathology of Causative Agents

1) Toxin-Producers

Pre-Formed Toxins: Bacillus cereus, Staphylococcus aureus, Clostridium perfringens

Enterotoxin: Vibrio cholerae, Enterotoxigenic E.coli, Klebsiella pneumoniae, Aeromonas

2) Enteroadherent

Enteropathogenic and Enteroadherent E.coli

Giardia organisms

Cryptosporidiosis

Helminths
3) Cytotoxin-Producers

Clostridium difficile

Hemorrhagic E.coli
4) Invasive Organisms

Minimal Inflammation: Rotavirus and Norwalk

Variable Inflammation: Salmonella, Campylobacter and Aeronomas Species, Vibrio parahaemolyticus, Yersinia

Severe Inflammation: Shigella Species, Enteroinvasive E.coli, Entamoeba histolytica

**REITERs SYNDROME = Arthritis, Urethritis, Conjunctivitis

Salmonella

Campylobacter
Reiters Syndrome may accompany or follow infections by

Shigella
the following

Yersinia

13

LIVER DISEASES

1) VIRAL HEPATITIS
I. CLINICAL & EPIDEMIOLOGIC FEATURES OF VIRAL HEPATITIS
A. Hepatitis-A Virus
Antigen (s)
Antibodies
Features
Diagnosis
Age Preference
Transmission

Fecal-Oral

Percutaneous

Perinatal

Sexual
Clinical

Severity

Fulminant

Progress to Chronicity

Carrier

Cancer

Prognosis
Prophylaxis
Therapy

HAV
Anti-HAV
Early Fecal Shedding
Acute Infection = IgM and Anti-HAV
Previous Infection = IgG Anti-HAV
Children, Young Adults
+++
Unusual
+/-

Some Points:
There is NO Progression to
Chronicity!
No Carrier State!
No Predisposition to
Development of
Hepatocellular Cancer

Mild
0.1%
None
None
None
Excellent
Immunoglobulin
Inactivated Vaccine
NONE (No Specific Treatment it is just Supportive)

B. Hepatitis-B Virus
Features
Age Preference
Transmission

Fecal-Oral

Percutaneous

Perinatal

Sexual
Clinical

Severity

Fulminant

Progress to Chronicity

Carrier

Cancer

Prognosis
Prophylaxis
Therapy

Blood-Borne Virus, Carrier State

Young Adults (Sexual and Percutaneous)
Babies, Toddlers
+++
+++
++
Occasionally Severe
0.1-1%
Occasional (1-10%) 90% of Neonates
0.1 30%
(+) Neonatal Infection
Worse with Age, Debility

Some Points:
It CAN Progress to
CHRONICITY (especially if it
is Transmitted Perinatally
from mother to neonate)
There is a Recombinant
Vaccine!
Prognosis is WORSE with Age
It is a DNA Virus (unlike
Hepatitis-A)
If we are Vaccinated = we will
be (+) Anti-HBs

Recombinant Vaccine
Interferon (Immunomodulator); Lamivudine (Antiviral)

C. Hepatitis-C Virus
Antigen (s)
Antibodies
Features
Diagnosis
Age Preference
Transmission

Fecal-Oral

Percutaneous

Perinatal

Sexual
Clinical

Severity

Fulminant

Progress to Chronicity

Carrier

Cancer

Prognosis
Prophylaxis
Therapy

HCV, C100-3, C33c, C22-3, NS5

Anti-HCV
Blood-Borne Agent
(formerly labeled as Non-A, Non-B Hepatitis)
Acute Diagnosis = Anti-HCV
Chronic Diagnosis = Anti-HCV and HCV RNA
Any Age, but More Common in Adults
+++
+/+/Moderate
0.1%
Common: 50-70% chronic hepatitis; 80-90% chronic infection
1.5-3.2%
+
Moderate

Some Points:
NO Vaccine Yet (because of the
Several Subtypes!)
Formerly labeled as Non-A NonB Hepatitis
Most Common: Blood
Transfusion Infection
Complications and Sequalae

RARELY = Fulminant
Hepatitis-C

Chronic Hepatitis-C

NONE
Interferon + Ribavirin

14

D. Hepatitis-D Virus
HBsAg, HDV Antigen
Anti-HBs, Anti-HDV
Defective RNA-Virus requires Helper Function of HBV
(Hepadnaviruses)

Antigen (s)
Antibodies
Features

Diagnosis

Age Preference
Transmission

Fecal-Oral

Percutaneous

Perinatal

Sexual
Clinical

Severity

Fulminant

Progress to Chronicity

Carrier

Cancer

Prognosis
Prophylaxis
Therapy

HDV Antigen present in Hepatocyte Nucleus

Anti-HDV, HDV-RNA
HBV/HDV Coinfection:
-IgM Anti-HBc and Anti-HDV
HDV Superinfection:
-IgG Anti-HBc and Anti-HDV
Any Age (Similar to HBV)

Complications and Sequelae

Fulminant Hepatitis

Mild Disease

Asymptomatic Carriers

+++
+
++
Occasionally Severe
5-20%
Common
Variable
+/Acute = Good
Chronic = Poor
HBV-Vaccine (None for HBV Carriers)
Interferon +/-

E. Hepatitis-E Virus
Antigen (s)
Antibodies
Features
Diagnosis
Age Preference
Transmission

Fecal-Oral

Percutaneous

Perinatal

Sexual
Clinical

Severity

Fulminant

Progress to Chronicity

Carrier

Cancer

Prognosis
Prophylaxis
Therapy

HEV Antigen
Anti-HEV
Agent of Enterically Transmitted Hepatitis
IgM/IgG Anti-HEV (assays being developed)
Virus in Stool, Hepatocyte, Cytoplasm, Bile
Young Adults (20-40 years)
+++
Mild
1-2%
None
None
None
Good
Unknown
None

Summary of Some Differences:

Incubation
Onset
Vaccination
Transmission

A
15-45
Acute
IG, Inactivated
Feco-Oral

Therapy

None

B
30-180
Insidious or Acute
Recombinant
Percutaneous (+++)
Perinatal (+++)
Sexual (++)
Interferon
Lamivudine

C
15-160
Insidious
NONE
Percutaneous (+++)
Sexual (+/-)
Interferon
Ribavirin

D
30-180
Insidious or Acute
HBV Vaccine
Percutaneous (+++)
Perinatal (+)
Sexual (++)
Interferon

E
14-16
Acute
Unknown
Feco-Oral
None

15

II. SIMPLIFIED DIAGNOSTIC APPROACH IN PATIENTS PRESENTING WITH ACUTE HEPATITIS (Medicine Notes)
INTERPRETATION
HBsAg
IgM Anti HAV
IgM Anti HBC
Anti HCV
Acute Hepa B
+
+
Chronic Hepa B
+
Acute Hepa A
+
+
Superimposed on Chronic Hepa B
Acute Hepa A & B
+
+
+
Acute Hepa B
+
Acute Hepa A & B
+
(HBsAg below detection threshold)
Acute Hepa B
+
(HBsAg below detection threshold)
Acute Hepa C
+
III. COMMONLY ENCOUNTERED SEROLOGIC PATTERNS OF HEPATITIS-B INFECTION
HBsAg

Anti-HBs

Anti-HBc

HBeAg

Anti-HBe

Acute HBV Infection

(High Infectivity)

INTERPRETATION

IgM

Chronic HBV Infection

(High Infectivity)

IgG

1) Late-Acute or Chronic HBV Infection

(Low Infectivity)

IgG

2) Process of Seroconversion from HBsAg to AntiHBs (RARE)

+/-

+/-

1) Acute HBV Infection

2) Anti-HBc Window

IgM

+/-

+/-

1) Low Level Hepatitis B Carrier

2) Hep B in Remote Past Infection

IgG

+/-

Recovery from HBV Infection

+
+

IgG
-

+/-

2) HBeAg-Negative (Precore-Mutant) Hepatitis B

(Chronic or, rarely, Acute)
1) HBsAg of one Subtype and Heterotypic Anti-HBs
(Common)

1) Immunization w/ HBsAg (Vaccination)

2) Remote Past Infection (?)
3) False Positive

**NOTE: Anti-HBc Window = period wherein only the IgM Anti-HBc (Core Antigen) is POSITIVE!

16

A. Genomic Structure of HBV

o HBs = Surface Antigen
o HBV-DNA = DNA Polymerase
o HBc = Core Antigen
o HBe = Envelope
a. Antigen = HBsAg
HBsAg is detectable in > 95% of Patients with Acute Hepatitis-B
It is found in Serum, Body Fluids, Hepatocyte Cytoplasm
b. Antibody = Anti-HBs
Appears following Infection
Protective Antibody!
B. Scheme of TYPICAL Clinical and Laboratory for Hepatitis-B
o Jaundice will come LATER than the Increase in ALT (unlike in Hepatitis-A)
o (+) HBsAg
IMPORTANT Notes:
When patient presents with Jaundice, look out
for HBeAg, IgM Anti-HBc and HBeAg

QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

If after 6 months, the HBsAg is still present,

then the Patient already has CHRONIC
Hepatitis-B
ALT Increase PRECEDES Jaundice

1. Antigens and Antibodies

HBs Anti-HBs
HBc Anti-HBc (IgM; IgG)
HBe Anti-HBe
2. Golden Period = 24-WEEKS
ALL the ANTIGENS must DECREASE in 24-Weeks otherwise, it progresses to Chronicity!
Chronic Hepatitis = Persistence of Antigen (HBsAg) BEYOND 6-Months or 24 Weeks
**Window Period = BOTH HBs and HBe Antigens are NEGATIVE
The only marker which is positive would be IgM Anti-HBc

17

C. Complications and Sequelae

1. Serum-Sickness Like Syndrome
During the PRODROMAL PHASE
Signs and Symptoms:
Arthralgia / Arthritis
Rash
Angioedema
Hematuria, Proteinuria (5-10%)
2. Fulminant Hepatitis (90% will die)
Massive Hepatic Necrosis
It is a RARE Event
Signs and Symptoms = ENCEPHALOPATHY Coma
Small Liver
Excessively Prolonged Prothrombin Time (PT)
**Hepatic Failure with Encephalopathy:
SMALL Liver = Rapidly SHRINKING Liver Size
Rapidly Rising Bilirubin Level
Markedly Prolonged PT even as Transaminases FALL
Clinical Signs:
o Confusion
o Disorientation
o Somnolence
o Ascites & Edema
**Terminal Events for Fulminant Hepatic Failure (Causes of Death)
Cerebral Edema (Most Common)
Brainstem Compression
GIT-Bleeding
Sepsis
Respiratory Failure
Cardiovascular Collapse
Renal Failure
**NOTE: Mortality Rate > 80%
3. Chronic Hepatitis
There is an INCREASED Risk to develop Hepatocellular Carcinoma
95% of Patients with Hepatocellular Carcinoma will be Positive for Hepatitis-B
**NOTE: Chronic if (+) HBsAg Persisting > 6 MONTHS
4. Increased Risk for Hepatocellular Carcinoma
Hepatitis-B = Most Common Cause of Hepatocellular Carcinoma

18

D. Chronic Hepatitis-B (Antigens PERSIST > 6 Months)

o Clinical and Laboratory Features, suggesting Progression from ACUTE to CHRONIC Hepatitis-B:
1) Lack and Complete Resolution of Clinical Symptoms of Anorexia, Weight Loss, Fatigue and Persistence
of Hepatomegaly
2) Presence of Bridging or Multilobular Hepatic Necrosis on Liver Biopsy during Protracted, Severe Acute
Viral Hepatitis
3) Failure of Serum Transaminase, Bilirubin and Globulin Levels to return to Normal within 6-12 months
after Acute illness
4) Persistence of HBeAg beyond 3 months or HBsAg beyond 6 Months after Acute Hepatitis
IMPORTANT Notes:
In Chronic Hepatitis B, HBsAg does NOT
down (Anti-HBC may go down & be replaced
by IgG)
QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

ALT may be Fluctuating if it is Elevated,

it may signify Activity

**NOTE: Chronic Hepatitis-B is (+) HBsAg Persisting > 6-MONTHS:

1. Active Chronic Hepatitis = TREAT!
(+) HBs Antigen
(+) HBeAg
ALT is Abnormal (Increased)
**IMPORTANT Notes:
o HBeAg = Marker for Infectivity!
o Anti-HBe = Marker of Recovery!
2. Inactive Chronic Hepatitis
(+) HBs Antigen
(-) HBe Antigen
(+) Anti-HBe (Marker of Recovery)
ALT is NORMAL
We DONT have to Treat just Observe
3. Precore Type (Mutant Strain)
(+) HBs Antigen
(-) HBe Antigen
(+) Anti-HBe (Antibody)
ALT is ABNORMAL
We have to Treat!

19

2) CASE ON LIVER MASS

50/M with a chief complaint of Right Lower Lobe Liver Mass

Dx: T/C Hepatocellular Carcinoma (HCCA)

I. NOTES ON LIVER DISEASES

Fatigue: Common symptom of liver pathologies
Jaundice: Common feature in Severe / Advanced cases
Importance of Digital Rectal Examination (DRE) in Liver Diseases:
o Hemorrhoids would indicate portal hypertension
o Melena would come from bleeding varices, due to portal hypertension
II. ALCOHOLIC LIVER DISEASE
Pathology of Alcoholic Liver Disease comprises THREE Major Lesions
o Fatty Liver
o Alcoholic Hepatitis
o Cirrhosis
The following contain ~12 g of Alcohol:
o One Beer
o Four Ounces of Wine
o One Ounce of 80% Spirits
Threshold for Developing Alcoholic Liver Disease:
o MEN: > 60-80 g/day for 10 YEARS (approximately 4 beers; because in 1 beer = 12g)
o WOMEN: 20-40 g/day for 10 YEARS
III. HEPATOCELLULAR CARCINOMA
Most metastatic CA to the liver would come from the GI tract because of Hematogenous spread
Signs of Cirrhosis (CLD) = Palmar Erythema, Gynecomastia in males, Testicular Atrophy
Signs of Portal HPN = Caput medusae, Telangiectasia, Spider angiomata
IV. DIFFERENTIALS
A. Focal Nodular Hyperplasia
o Considered because of the mass
o However, rule out a more serious pathology, before considering a benign one
o Size of the mass would point to a malignancy
B. Renal Cell Carcinoma
o TRIAD: Hematuria + Flank Mass + Flank Pain
o Not considered because these are absent in the patient

20

V. DIAGNOSTICS
A. Triphasic CT-Scan (for Liver Masses)
o Three Phases = Arterial + Venous + Plain
o Done to see the vascularity of the mass, because it would light up in the arterial phase Highly Vascular
Masses would suggest a Malignancy
B. Dynamic Ultrasound
C. AFP Levels
o Before doing a biopsy, get AFP levels first
o If AFP is > 200, the mass is most probably MALIGNANT
**NOTE: If the following are present, there is NO need for a BIOPSY
1) Mass > 2cm detected by any imaging modality
2) Elevated AFP > 200
3) Features of Malignancy in Dynamic Scan (Triphasic CT, Dynamic UTZ)
**NOTE: If the following are present, treat as HEPATOCELLULAR CA!!!!
Read algorithm in harrisons
D. Biopsy
o Biopsy is NOT done in all cases of Hepatic Masses to avoid Invasive Procedure and its complications
o If we do a biopsy, check PT/PTT
E. Chest X-Ray
o To check for any masses, pathologies, etc
o Pleural Effusion:
On CXR, we would see Blunting of Costophrenic Angles, Meniscus Sign
On CXR, for pleural effusion to blunt the Costophrenic Sulci, there must be 175cc of Fluid
Reactive Pleural Effusion: Pleural effusion on the right in cases of liver abscess, liver mass, etc
VI. EXAMS TO EVALUATE LIVER FUNCTION
Albumin
Bleeding Parameters
Bilirubin
**NOTE: ALT / AST are NOT markers of Liver Function!
o They are Functions of HEPATOCELLULAR DAMAGE

21

VII. DIAGNOSTICS TO EVALUATE LIVER DISEASES

A. Tests Based on Detoxification and Excretory Functions
o Serum Bilirubin
o Urine Bilirubin
o Blood Ammonia
o Serum Enzymes
SERUM ENZYMES
1. Enzymes the Reflect DAMAGE to Hepatocytes
Aminotransferases (Transaminases) are sensitive indicators of Liver Cell Injury and are most helpful in
recognizing Acute Hepatocellular Diseases such as Hepatitis
Includes: Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)
o AST = found in the liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes (in decreasing order of concentration)
o ALT = found primarily in the LIVER
Any type of Liver Cell Injury can cause modest elevations in the Serum Aminotransferases
Aminotransferases > 1000 U/L occur almost exclusively in disorders associated with Extensive Hepatocellular
Injury (Viral Hepatitis, Ischemic Liver Injury, Toxin/Drug Induced Liver Injury)
Important Notes:
o In most Acute Hepatocellular Disorders: ALT > AST
o AST:ALT Ratio > 2:1 is suggestive, while a Ratio of > 3:1 is Highly Suggestive of Alcoholic Liver
Disease
o The AST in Alcoholic Liver Disease is rarely > 300U/L and the ALT is often normal (a low level of
ALT in serum is due to Alcohol Induced Deficiency of Pyridoxal Phosphate)
2. Enzymes that Reflect Cholestasis
Alkaline Phosphatase, 5Nucleotidase, and -Glutamyl Transpeptidase are usually elevated in Cholestasis

B. Tests that Measure Biosynthetic Function of the Liver

1. Serum Albumin
Frequently decreased in Chronic Liver Disease
Half Life is relatively long (~20 days) therefore, Serum Levels may be NORMAL in Acute Liver Disease
2. Serum Globulins

C. Coagulation Factors
o
o
o

With the EXCEPTION of Factor-VIII, the blood clotting factors are made exclusively in HEPATOCYTES
Useful for this purpose is the Serum Prothrombin Time (Factors II, V, VII, X)
Biosynthesis of Factors II, VII, IX, X depends on Vitamin-K

VIII. RADIOGRAPHIC EVALUATION

Ultrasoonography

Used to screen for dilation of Biliary Tree and to detect Gallstones & Cholecystitis in patients with right
sided abdominal pain associated with Abnormal Liver Blood Tests
Can detect and characterize Liver Masses, Abscesses, and Cysts
Diagnostic Modality of Choice for Hepatocellular Carcinoma SCREENING

Helical CT Scan with Contrast

Useful in evaluation of Parenchymal Liver Disease

Has the added feature of Contrast Enhancement to define space-occupying lesions (Abscess and Tumor)

MRI

Allows calculation of Liver Volume

Similar information as the CT Scan, but visualizes vessels without use of IV contrast
Helpful in diagnosis of Benign Masses such as Focal Nodular Hyperplasia & Hamngioma

22

3) LIVER ABSCESS

Liver is the organ most subject to the development of abscesses

FEVER: Most Common presenting sign of Liver Abscess

I. CLINICAL PRESENTATION
Right Upper Quadrant signs / symptoms: Pain, guarding, punch tenderness, rebound tenderness
Chills, anorexia, weight loss, nausea, vomiting; 50% of patients have Hepatomegaly, Right Upper Quadrant Pain, Jaundice
II. PYOGENIC VS AMEBIC
A. Pyogenic Abscess
o Result from hematogenous infection, spread from intra-abdominal infection or ascending infection from biliary tract
o Clinical Features: Fever, chills, weight loss, abdominal pain from tender hepatomegaly
o 50% of patients are jaundiced
o Laboratory Studies: Leukocytosis, Elevated AP
In Pyogenic Abscesses, UTZ examination will demonstrate a cystic
o Diagnosis: Confirmed by CT or UTZ
mass in the liver, often with multiple complex septations or
inhomogenous fluid characteristics. CT findings will include a
complex hypodense mass with peripheral enhancement. In patients
with a solitary dominant abscess, percutaneous aspiration with
evaluation by GS/CS is essential to direct further antimicrobial &
drainage therapy

B. Amebic Liver Abscess

o Should be considered in patients from endemic areas
o Diagnosis requires high index of clinical suspicion
o Tx: Metronidazole, Chloroquine

III. DIAGNOSIS
Single Most Reliable Laboratory Finding: Elevated Serum Alkaline Phosphatase
50% have elevated Bilirubin, and 48% have elevated Aspartate Aminotransferase
Other Labs: Leukocytosis, Anemia (Normo-Normo), Hypoalbuminemia, concomitant Bacteremia
On Radiography: (+) Elevation of the Right Hemidaphragm, right basilar infiltrate, right pleural effusion
Imaging Methods (CT, MRI, UTZ): most reliable methods
IV. PYOGENIC LIVER ABSCESS

70% MIXED Flora

Pyogenic Liver Abscess is MORE Toxic than an Amoebic Mass

Commonly caused by: Anaerobes, E. coli, Klebsiella, Enterococcus, Bacteroides, Staphylococcus aureus, Streptococcus
A. Etiology
o Biliary Tract Disease (Acute Cholecystitis; Cholangitis)
o Appendicitis
o Diverticulitis
o Intrinsic Hepatic Lesion
General Management
o Undetermined (10%)
Drainage (Percutaneous or Surgical) = Mainstay of Therapy

Empirical Therapy

B. Clinical features
o Fever, Chills, RUQ Pain, Anorexia, Nausea
Several Factors predicting Failure of Percutaneous Drainage
o Tender Hepatomegaly (50%)
(favors Surgical Intervention):
C. Diagnosis
Presence of Multiple, Sizable Abscesses
1. Laboratory
Viscous Abscess contents that tend to plug the catheter

80% Elevated Alkaline Phosphatase

Associated Disease requiring surgery

33% Jaundice = Increased Bilirubin

Lack of a clinical response to percutaneous drainage in 4-7 days

40% = (+) Blood Culture

2. Diagnostic Procedures:

Ultrasound: Cystic mass, multiple complex septations, hypoechogenic, inhomogenous fluid characteristics

CT-Scan: Complex hypodense mass with peripheral enhancement

Ultrasound Guided Aspiration

D. Treatment
o Broad Spectrum Antibiotics = for Gram (-) Anaerobes
o Aspiration = Percutaneous or Surgical Drainage
o Drugs used for Empirical Therapy include the same ones used in Intraabdominal Sepsis and 2 0 Bacterial Peritonitis
o Aerobic Gram (-) Bacilli and Anaerobes:

Broad Spectrum Penicillin: Ticarcillin / Clav 3.1g q4-6

Cefoxitin 2g q4-6 IV

Imipenem 500mg q6 IV

Meropenem 1g q8 IV

Combination: Ampicillin + Metronidazole + Ciprofloxacin

23

V. AMOEBIC LIVER ABSCESS

Etiology: Entamoeba histolytica there is local proteolytic destruction of the liver parenchyma with focal infarction (invasion of the
colonic mucosa into the portal system)

Clinical Features: RUQ Pain, Fever, Chills, Pleuritic Pain, Night Sweats, Intestinal Amoebiasis (50%), Hx of Diarrhea Jaundice is not
common in Ameobic Liver Disease, in contrast to Pyogenic Liver Abscess (Med Notes)

Laboratory: Leukocytosis (50%), Increased Transaminases, Increased Serum Bilirubin, Increased Alkaline Phosphatase (80%)
A. Diagnosis
1. Ultrasound = COMPLEX MASS (Most Commonly seen)

Usually Solitary

RIGHT Lobe (90%)

2. CT-Scan

Complex Hypodense Mass with Peripheral Enhancement

3. Gallium Scan

(+) Filling Defect

4. Aspiration Biopsy

ANCHOVY PASTE Fluid with TROPHOZOITES (when we Aspirate)

5. Serologic Test

(+) in 95% of Case

Indirect Hemagglutination Gel Diffusion

B. Therapy = AMOEBICIDES:
o METRONIDAZOLE 750mg PO or IV 5-10 days
o Choloroquine
C. Complications = CYST RUPTURE into the following:
o Pleural Space
o Lungs
o Bowel
o Retroperitoneum

VI. HEPATOBILIARY TUBERCULOSIS

Aspiration & Drainage is rarely indicated. It is indicated only if there is

(+) Secondary Pyogenic Infection
More than 90% respond to Metronidazole Tx, with Decrease in Pain and
Fever within 72 hours
Indications for Aspiration of Liver Abscess:

Need to rule out Pyogenic Abscess

No Clinical Response in 3-5 days

Threat of Imminent Rupture

Need to prevent Rupture of Left Lobe Abscess into

Pericardium

A. Presentation
o 1) Miliary Hepatic Tuberculosis (Disseminated)
o 2) Focal or Nodular Tuberculosis = Single or Multiple Conglomerate Tubercles
o 3) Tuberculosis of Bile Ducts (or Tubular Tuberculosis)
B. Presenting Complaints
o JAUNDICE (Most Common Complaint)
o Abdominal Pain, Abdominal Mass, Fever, Abdominal Enlargement, Weight Loss
C. Clinical & Laboratory Features:
A. Physical Examination Findings

Jaundice = ALL Patients

Abdominal Tenderness (RUQ, Epigastric, RLQ)

Cervical Lymphadenopathy, Scrofuloderma, Fluid Wave, Abdominal Distention, Normal Physical Examination,
Hepatosplenomegaly
B. Chest X-Ray Findings

Pulmonary TB

Normal

Pneumonia, Pulmonary Congestion, Elevated Right-Hemidiaphragm

**NOTE: We do NOT need a Pulmonary Tuberculosis to have a Diagnosis of Liver Tuberculosis!
C. Sonographic Findings
o Biliary Obstruction: Intrahepatic Duct, Common Bile Duct, Common Hepatic Duct, Unspecified
o Hepatomegaly: With Calcification (Liver Calcifications = MOST Common) or Without Calcification
o Others: Contracted Gallbladder, Cholecystitis, Cholelithiasis, Choledocholithiasis, TB-Liver, Pancreatic Head Mass, Pancreatitis,
Portal Hypertension, Splenomegaly
D. Treatment of Hepatobiliary Tuberculosis
o Anti-TB Therapy (12-18 Months Triple / Quadruple Treatment)
o Surgery

24

4) TUMORS OF THE LIVER

Hepatocellular Carcinoma (HCC) is one of the most common malignancies worldwide

I. CLINICAL FEATURES
Abdominal Pain, Weight Loss, Weakness, Abdominal Fullness & Swelling, Jaundice & Nausea
Most Common Symptom = Abdominal Pain
Jaundice is usually due to obstruction of Intrahepatic Ducts by the underlying liver disease
Hepatomegaly = Most Common Physical Sign (50-90%)
Abdominal Bruits, Ascites (should be examined by cytology), Splenomegaly, Weight Loss, Wasting
Signs of Chronic Liver Disease: Jaundice, Dilated Abdominal Veins, Palmar Erythema, Gynecomastia, Testicular Atrophy,
Peripheral Edema
II. APPROACH TO THE PATIENT
A. Serologic Assays
o A-Fetoprotein (AFP): Serum Tumor Marker in HCC
o In a patient presenting with either a new hepatic mass or other indications of recent hepatic decompensation, CEA,
Vitamin B12, AFP, Ferritin, PIVKA-2 and Antimitochondrial Ab should be measured, and Standard Liver Function
Tests should be performed (including PT, PTT, Albumin, Transaminases, Alk Phos, G-Glutamyl Transpeptidase)
B. Radiology
o UTZ Examination of liver is an excellent screening tool
o Two Characteristic Vascular Abnormalities are:
1) Hypervascularity of the Tumor Mass (Neovascularization or Abnormal Tumor-Feeding Arteries)
2) Thrombosis by Tumor invasion of otherwise normal portal veins
To determine Tumor Size and Extent, and the presence of Portal Vein Invasion accurately, a Helical / Triphasic CT Scan of the
Abdomen and Pelvis with Fast Contrast Bolus Technique should be performed to detect the vascular lesions typical of HCC.

III. BENIGN TUMORS (found predominantly in women)

Hemangiomas
Considerable effort has gone into differentiating these three entities radiologically. The most
Adenomas
useful diagnostic differentiating tool is a Triphasic CT-Scan performed with HCC fast Bolus
Focal Nodular Hyperplasia (FNH)
Protocol for Arterial-Phase Imaging, together with subsequent delayed venous-phase imaging.
A. Hemangioma
o Most Common BENIGN Liver Tumor (5-7% Autopsy; Women > Men)
o Treatment is unnecessary unless their expansion causes symptoms
B. Hepatic Adenoma
o Usually in Women (Childbearing Age) Common in Contraceptive Pill Use
o They can cause pain and can bleed or rupture, causing acute problems. Low potential for Malignant Change and a 30%
risk of Bleeding.
o Symptoms: RUQ Fullness, Intraabdominal Hemorrhage (25%)
Biopsy is not Suggested due to Hypervascularity
o Treatment: STOP Pill; Surgery
o Diagnosis:
CT Scan = Hepatic Mass; Cold Spot
Abnormal Liver Function Test, Abnormal Alpha Fetoprotein
C. Hepatic Cyst (Can be Multiple or Solitary): Problems = Bleeding and Infection
Solitary Cyst
RIGHT Liver Lobe
Asymptomatic; Occasionally = PAIN & FEVER (Secondary Bleeding, Infection or Rupture)
Polycystic Liver
Multiple Cysts (Several mm to 10-15cm); ASYMPTOMATIC
Disease
Complications: Hemorrhage, Infection, Rupture
(+) Cyst: Pancreas, Spleen, Lungs
Laboratory Findings: Liver Function Tests are NORMAL, Mild in Alkaline Phosphatase
Treatment: Surgical Aspiration / Decompression
D. Focal Nodular Hyperplasia
o Typically benign, and usually no treatment is needed

25

IV. PRIMARY HEPATOCELLULAR CARCINOMA

80-90% of all Primary Liver Carcinoma
Most Commonly due to Cirrhosis prior to a Chronic Hepatitis-B
Incidence: 4x Men > Women
A. Etiologic Factors
o Chronic Liver Disease: Alpha-1 Antitrypsin Deficiency, Tyrosinosis (40% Risk), Hemochromatosis, Primary Biliary
Cirrhosis
o Previous Hepatitis-B Infection
90-95% of Hepatocellular Carcinoma = (+) HBV Infection
60-70% of Hepatocellular Carcinoma = Chronic Hepatitis / Cirrhosis
o Others: Mycotoxins, Humoral Factors (Increased Androgen), Schistosomiasis (?), Clonorchiasis (?)
B. Clinical Features
o Hepatomegaly
o Hepatic Bruit or Fruction Rub
o Ascites (Bloody in 50%)
o Non-Specific Symptoms (Malaise, Weight Loss, Anorexia, Abdominal Pain)
o Clinical Deterioration or SUDDEN Increase in Transaminases in a STABLE Cirrhotic Patient
C. Diagnosis
o Laboratory: Alkaline Phosphatase, Transaminases
o Gallium Scan: Focal Filling Defects
o Alpha Fetoprotein Elevation: 85-90%
o Angiography: Hypervascularity, Tumor Blush
o Liver Biopsy
D. Treatment
o NO Effective Treatment (Survival Rate < 6 months)
o Surgery = 5-year Survival Rate < 10%
o Radiotherapy & Chemotherapy = RARE Response
V. METASTATIC HEPATIC MALIGNANCY
It is MORE COMMON Than Primary Hepatocellular Carcinoma (MOST COMMON MALIGNANT Neoplasm)
Primary Source = Gastrointestinal Carcinoma (Colon, Stomach, etc)
A. Tumors Metastatic to the Liver:
o Colon
These three are predominantly the primary sites, however, metastatic tumors to the liver
o Pancreas
can originate from any organ primary.
o Breast
**Other Sources may be from:
GIT Carcinoma
Malignant Melanoma
Carcinoma of the Pancreas, Lungs, Breast, Kidney, Ovary
Lymphoma
B. Clinical Features
o Fever, RUQ Pain
o Hepatomegaly, Friction Rub, Jaundice
C. Diagnosis
o Liver Biopsy
o CT or Ultrasound Guided Aspiration Biopsy
D. TREATMENT (Depends on the Underlying Primary Source)
o Radiotherapy, Chemotherapy
o Hepatic Artery Infusion
o Surgery

VI. APPROACH TO PATIENTS WITH JAUNDICE

Yellowish discoloration of tissue resulting from the Deposition of Bilirubin

26

Hepatocellular Conditions producing Jaundice:

Viral Hepatitis

Hepatitis A, B, C, D, E

Epstein-Barr Virus

Cytomegalovirus

Herpes Simplex
Alcohol
Drug Toxicity

Predictable Dose Dependent: Acetaminophen

Unpredictable, Idosyncratic: Isoniazid

Environmental Toxins (Vinyl Chloride)
Wilsons Disease
Autoimmune Hepatitis
QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

27

LECTURE ON LIVER CIRRHOSIS

Additional Notes from Harrisons

LIVER CIRRHOSIS

Characterized pathologically as IRREVERSIBLE Chronic Injury of the Hepatic Parenchyma

Include extensive fibrosis in association with the formation of Regenerative Nodules
Central Event leading to Hepatic Fibrosis: Cytokine-Mediated (tgf-B) Activation of the Hepatic Stellate Cells producing
Fibrin Forming Type-1 Collagen
Results from:
o Hepatocyte Necrosis
o Collapse of the supporting network with subsequent connective tissue deposition
o Distortion of Vascular Bed, and Nodular Regeneration of remaining Liver Parenchyma

I. ALCOHOLIC CIRRHOSIS
Excessive chronic alcohol use can cause different types of Chronic Liver Disease: Alcoholic Fatty Liver, Alcoholic Hepatitis,
and Alcoholic Cirrhosis
Diagnosis requires an accurate history regarding amount and duration of alcohol consumption
Laboratory Tests can be completely normal in patients with Early Compensated Alcoholic Cirrhosis
In Advanced Liver Disease, patient may be:
LIVER ENZYMES:
o Anemic from either Chronic GI Blood Loss
AST / ALT
>2
Alcoholic Liver Disease
o Nutritional Deficiencies
AST / ALT
<1
Viral
o Hypersplenism related to Portal Hypertension
Alk Phos > Liver Enzymes
Cholestatic
o Direct Suppressive Effect of Alcohol on the Bone Marrow
II. CAUSES AND COMPLICATIONS OF CIRRHOSIS
COMPLICATIONS OF CIRRHOSIS:
Portal Hypertension (Gastroesophageal Varices, Portal Hypertensive
Gastropathy, Splenomegaly, Hypersplenism, Ascites / SBP
Hepatorenal Syndrome (Type 1, Type 2)
Hepatic Encephalopathy
Portopulmonary Hypertension

Coagulopathy (Factor Deficiency, Fibrinoysis, Thrombocytopenia)

Bone Disease (Osteopenia, Osteoporosis, Osteomalacia)
Hematologic Abnormalities (Anemia, Hemolysis, Neutropenia, Thrombocytopenia)
Malnutrition
Hepatopulmonary Syndrome

CAUSES OF CIRRHOSIS
Alcoholism
Chronic Viral Hepatitis (Hep-B, Hep-C)
Autoimmune Hepatitis
Non-Alcoholic Steatohepatitis
Biliary Cirrhosis

Primary Biliary Cirrhosis

Primary Sclerosing Cholangitis

Autoimmune Cholangiopathy

Cardiac Cirrhosis
Inherited metabolic Liver Disease
- Hemochromatosis
- Wilsons Disease
- A1-Antitrypsin Deficiency
- Cystic Fibrosis
Cryptogenic Cirrhosis

III. LABORATORY FINDINGS IN CIRRHOSIS (from the Lecture)

Liver Insufficiency:
o Decreased Albumin: < 3.8 g/dL
o Prolonged PT (INR > 1.3)
o Increased Bilirubin: > 1.5 mg/dL
Portal Hypertension
o Decreased Platelet Count: < 175,000
AST / ALT Ratio > 1
Imaging (CT or UTZ)
o Nodular Liver
o Splenomegaly
o Venocollaterals
Liver Biopsy: NOT always necessary if:
o 1) Decompensated Cirrhosis (Variceal Hemorrhage, Ascites, etc)
o 2) Liver/Spleen imaging diagnostic of Cirrhosis

28

IV. SEVERITY OF LIVER DISEASE:

Child Turcotte Pugh
MELD Score
A. Child Pugh Criteria for Hepatic Functional Reserve
A
Serum Bilirubin
Serum Albumin
Prothrombin Time

(mg/dL)
(umol/L)
(g/dL)
(g/L)
Seconds Prolonged
INR

Ascites
Neurologic Disorder

< 2.0
< 34
> 3.5
> 35
0-4
< 1.7
None
None

B
2.0-3.0
34-51
3.0-3.5
30-35
4-6
1.7 2.3
Easily controlled
Minimal

C
> 3.0
> 51
< 3.0
< 30
>6
> 2.3
Poorly controlled
Advanced Coma

B. MELD Score
o Estimates the Risk of 3 month Mortality (higher the MELD score likely to die in three months)
o Three Laboratory Values used:
Serum Total Bilirubin
Serum Creatinine
INR
6.4 + 9.8 x log(INR) + 11.2 x log(Cr) + 3.8 x log(Bilirubin)

V. HISTORY OF CHRONIC LIVER DISEASE

Chronic Liver Disease

Compensated Cirrhosis

Decompensated Cirrhosis

Death

Compensated VS Decompensated: Presence of Complications!

Variceal Hemorrhage
Ascites
Encephalopathy
Jaundice

VI. COMPLICATIONS OF CIRRHOSIS

Portal Hypertension

Liver Insufficiency

Variceal Hemorrhage

Encephalopathy
SBP

Ascites

Jaundice
Hepatorenal Syndrome

Encephalopathy

29

VII. INVESTIGATING ASCITES

CONDITION

GROSS APPEARANCE

PROTEIN
(g/L)

Cirrhosis

Straw colored or bile stained

< 25 (95%)

> 1.1

Neoplasm

Straw colored, hemorrhagic,

mucinous, or chylous
Clear, Turbid, Hemorrhagic,
Chylous
Turbid or purulent

> 25 (75%)

< 1.1

> 25 (50%)

< 1.1

If purulent,
> 25

< 1.1

CHF

Straw-colored

Variable
(15-53)

> 1.1

10%

< 1000 (90%)

Usually Mesothelial,
Mononuclear

Nephrosis

Straw-colored or chylous

< 25 (100%)

< 1.1

Unusual

< 250
Mesothelial,
Mononuclear

If chylous, ether
extraction, sudan staining

Pancreatic
Ascites

Turbid, Hemorrhagic, or
Chylous

Variable,
often >25

Variable, may
be blood stained

Variable

Amylase in Ascitic
Fluid & Serum

TB Peritonitis
Pyogenic
Peritonitis

SAAG
(g/dL)

CELL COUNT
RBC,
WBC, per uL
>10,000u/L
1%
< 250 (90%)
Predominantly
Mesothelial
20%
> 1000 (50%)
Variable Cell types
7%
> 1000 (70%)
Usually > 70% L
Unusual
Predominantly PMN
Leukocytes

OTHER TESTS

Cytology, cell block,

peritoneal biopsy
Peritoneal Biopsy, Stain
and Culture for AFB
Positive Gram Stain,
Culture

A. SAAG: Serum to Ascites Albumin Gradient

o Serum Albumin [minus] Albumin in Ascitic Fluid (Gradient)
o The gradient correlates DIRECTLY with Portal Pressure
1. If SAAG is > 1.1g/dL (or 11 g/L)
Cause of Ascites is PORTAL HYPERTENSION with (97% Specificity):
Cirrhosis
Cardiac Ascites
Budd Chiari Syndrome
Management of Ascites:
Portal Vein Thrombosis

Dietary Salt Restriction (2g Salt/day)

Veno-Occlusive Disease

Diuretic Therapy
Fatty Liver of Pregnancy

Paracntesis
2. If SAAG is < 1.1g/dL (or 11 g/L)

TIPS
Peritoneal Carcinomatosis
Spontaneous Bacterial Peritonitis:
Infection (Peritonitis, TB)

Infectious complication of Portal HPN-Related

Nephrotic Syndrome
Ascites
Pancreatic or Biliary Ascites
B. Absolute WBC Count (PMN) > 250/mm3
o Infection
o When Mononuclear Cells are predominant: TB, Fungal
3

C. RBC Count > 50,000/mm = Hemorrhagic Ascites

o Malignancy
o TB
o Trauma
D. Others:
Amylase
TAG
Cytology
Gram Stain or Culture
pH < 7

Abdominal Pain & Distention, Fever,

Decreased Bowel Sounds, Worsening of
Hepatic Encephalopathy
Diagnosis is likely when Ascitic Fluid has >
250 neutrophils/u/L

Increased in Pancreatic Ascites

Increased in Chylous Ascites
Positive in Malignancy
Bacterial Infections
Bacterial Infection

E. Management of Ascites
o Removal of > 1 L at a time (Paracentesis) may lead to Hypovolemia, Shock
o Unless 10grams Albumin is replaced IV for each 1 L Ascitic Fluid removed

30

VIII. HEPATIC ENCEPHALOPATHY: Grading System for Hepatic Encephalopathy:

GRADE

LEVEL OF
CONSCIOUSNESS
Normal

PERSONALITY AND
INTELLECT
Normal

Normal

Normal

Inverted Sleep
Pattern, Restless

Forgetful, Mild Confusion,

Agitation, Irritable

Tremor, Apraxia, Incoordination,

Impaired handwriting

Slowing Triphasic Waves

Lethargic, Slow
Responses

Disorientation from time, amnesia,

decreased inhibitions,
inappropriate behavior

Asterixis, Dysarthria, Hypoactive

Reflexes

Slowing Triphasic Waves

Somnolent but can be

aroused, confused

Disorientation for place, aggressive

Asterixis, Hyperactive Reflexes,

Babinskis Sign. Muscle Rigidity

Slowing Triphasic Waves

Coma

Nil

Decrebrate

Slowing Delta Waves

NEUROLOGIC
ABNORMALITIES

**NOTE: Asterixis is POSITIVE in Stage I, II, and III but Negative on IV!
o There will be NO Asterixis when patients is already in COMA
o First Manifestation is the Reversal of the Sleep-Wake Pattern
Treatment is multifactorial and includes management of the precipitating factors.
Sometimes hydration & correction of electrolyte imbalance is all that is necessary.
Mainstay of Treatment (in addition to correction of precipitating factors) is to use
Lactulose, which result in Colonic Acidification. Catharsis ensues, contributing to
the elimination of waste products in the gut. Goal: 2-3 Stools per day.

EEG ABNORMALITIES

Portosystemic Encephalopathy is a serious

complication of chronic liver disease and is broadly
defined as an alteration in mental status & cognitive
function occurring in the presence of liver failure.
Encephalopathy is more commonly seen in patients
with chronic liver disease. Gut-derived neurotoxins
are not removed by the liver because of vascular
shunting and decreased hepatic mass get to the brain
& cause symptoms. Ammonia levels are typically
elevated in patients with hepatic encephalopathy.

Treatment of Hepatic Encephalopathy (Washington)

Treat Precipitating Factors

Dietary Protein Restriction (Controversial)

Non-Absorbable Disaccharide (Lactulose, Lactitol)

Neomycin

Metronidazole (250mg PO q8h)

A. Pathogenesis (Most Important):
o SEVERE Hepatocellular Dysfunction and/or Intrahepatic & Extrahepatic Shunting of Portal Venous Blood into the Systemic
Circulation BYPASSING the Liver (There is FAILURE to DETOXIFY the substances)
B. Common Precipitants of Hepatic Encephalopathy:
o Increased Nitrogen Load: Gastrointestinal Bleeding, Excess Dietary Protein, Azotemia, Constipation
o Electrolyte and Metabolic Imbalance: Hypokalemia, Alkalosis, Hypoxia, Hyponatremia, Hypovolemia
o Drugs: Narcotics, Tranquilizers, Sedatives, Diuretics
o Miscellaneous: Infection, Surgery, Superimposed Acute Liver Disease, Progressive Liver Disease, Portal-Systemic Shunts
C. Aims of Treatment:
o 1) Eliminate or Treat the Precipitating Factors
o 2) Lower Blood Ammonia (and other Toxins): Decreases Absorption of Proteins and Nitrogenous Products from the Intestine
D. Approach to the Patient with Hepatic Encephalopathy, BUN (Blood Urea Nitrogen)
Initial Evaluation:
Exclude other Causes of Disordered Mentation, Identify Precipitants and Correct
Determine Electrolytes, BUN, Creatinine, NH3 (Optional), Glucose

Protein Restriction

Inadequate Response (?)

Laxative (eg. LACTULOSE 30-120mL, 1 to 4x daily until 4 stools/day)

Broad-Spectrum Antibiotics
(eg. Neomycin 500-1000mg qid; or Metronidazole 250mg tid)

Inadequate Response (?)

Consider Liver Transplantation

31

MANAGEMENT OF COMPLICATIONS (Lecture)

I. VARICES
Gastroesophageal Varices: Most important complication of cirrhosis
Dilation of Coronary and Gastric Veins
Can lead to bleeding
A. Pathophysiology
Resistance to Portal Flow

Decreased Splanchnic Arteriolar Resistance

Increased Resistance to Portal Pressure

Increased Splanchnic Flow (Increased Portal Blood Inflow)

VARICES!
o
o
o
o

Varices increase progressively by 7-8% per year

Determinant of Severity of Varices = Severity of Liver Disease
Everyone with Cirrhosis should be Endoscoped!
Two Year probability of FIRST Bleed:
7% in Small Varices
30% in Large Varices

B. Principles in Treatment of Varices:

1. Vasoconstrictors
Examples: Non-Selective B-Blockers, Terlipressin, Vasopressin, Octreotide
Mechanism: Increases Splanchinc Arteriolar Resistance
Note on Beta-Blockers:
Selective B-Blockers (B1): Metoprolol, Atenolol
Non-Selective B-Blockers (B1 + B2): Propranolol, Nadolol, Esmolol
Rationale for Use of Non-Selective B-Blockers:
If you Block the B2-Receptors in Vessels Unopposed A1-Receptor Action Constriction of
Splanchnic Vessels Increased Resistance
Terlipressin:
Dose: 2mg q40 (very expensive)
BUT, there is increased survival
2. Venodilators
ISMN (NOT used alone usually combined with B-Blockers)
Mechanism: Decreases Intrahepatic Resistance to Decrease Portal Pressure AND Decreases Systemic
Pressure to Decrease Portal Blood Inflow
3. Shunt
TIPS, Surgical Shunts
Mechanism: Decreases resistance to Portal Flow Decrease Portal Pressure
4. Endoscopic Therapy
Sclerotherapy
Band Ligation

32

C. Management of the Different Stages of Cirrhosis:

STAGE
MANAGEMENT
No Varices
Pre-Primary Prophylaxis: Prevention of Variceal Development
There is NO Specific Treatment
Recommendation: Repeat Endoscopy in 2-3 years (sooner if with Decompensated Liver
Disease)
In studies, B-Blockers did NOT prevent the development of Varices (Timolol actually
increases adverse effects)
Varices, but NO
Hemorrhage

Primary Prophylaxis: Prevention of First Variceal Hemorrhage

1) Small Varices
Recommendation: Repeat Endoscopy in 1-2 years
B-Blockers (?) data are not clear
2) Medium to Large Varices
Recommendation: Beta-Blockers + Endoscopic Variceal Ligation

Variceal
Hemorrhage

Treatment of Acute Variceal Hemorrhage:

1) General Management:
IV Fluids
Do NOT overtransfuse (this can actually increase Portal Volume Increase bleeding)
Antibiotic Prophylaxis
2) Specific Treatment:
Pharmacologic: Terlipressin, Somatostatin, Vasopressin + Nitroglycerin
Endoscopic: Ligation, Sclerotherapy
Shunt: TIPS, Surgical Shunts
3) TIPS (Transjugular Intrahepatic Portal Shunt)
Rescue treatment for recurrent Variceal Hemorrhage
Indicated in patients who re-bleed on Combination Endoscopic Management and
Pharmacologic Treatment
Problem: Hepatic Encephalopathy (may be decreased by giving Lactulose)

Recurrent
Hemorrhage

Secondary Prophylaxis: Prevent Recurrent Hemorrhage

1) B-Blockers Plus Endoscopic Variceal Ligation (BEST)
2) B-Blockers + ISMN or Endoscopic Variceal Ligation
3) TIPS / Shunt

33

II. ASCITES
Cirrhosis: Most Common Cause of Ascites
Other Causes: Peritoneal Malignancy, Heart Failure, Peritoneal TB
A. Diagnostic Tap = 30-60cc
o PMN Count, Culture (SBP)
o Albumin, Protein (Cirrhotic Ascites)
o Glucose or LDH (Secondary Infection)
o Amylase (Pancreatic Ascites)
o Cytology (Malignant Ascites)
B. Indication for Diagnostic Paracentesis
o New Onset Ascites
o Admission to Hospital
o S/Sx of SBP
o Renal Dysfunction
o Unexplained Encephalopathi
**NOTE: Contraindications: NONE!
Do we give FFP before Paracentesis? There are NO Recommendations!
Avoid the RIGHT side in Paracentesis (because these patients are usually maintained on Lactulose which
causes Dilation of the Cecum)
LLQ is the better site (Lateral to the Inferior Epigastric Vessels)
C. Differential Diagnoses:
Hepatic Sinusoids
SAAG > 1.1

Peritoneum
SAAG < 1.1

Capillarized Sinusoid
Ascites Protein < 2.5

Normal Leaky Sinusoid

Ascites Protein > 2.5

Sinusoidal HPN:
-Cirrhosis
-Late Budd-Chiari

Post-Sinusoidal HPN
-Cardiac Ascites
-Early Budd-Chiari
-Venoocclusive

Peritoneal Lymph
Ascites Protein > 2.5
Malignancy
TB

34

D. Management of the Different Stages of Ascites:

STAGE
MANAGEMENT
Portal Hypertension
No Specific Therapy! Salt Restriction
without Ascites
Uncomplicated Ascites
Definition: Ascites responsive to Diuretics in the absence of Infection & Renal Dysfunction
Goal: to achieve Negative Sodium Balance
1) Salt Restriction
Effective in 10-20% of cases
2g salt/day (or 5.2g of Dietary Salt)
Fluid Restriction NOT necessary, unless there is Hyponatremia (Na <125)
2) Diuretics
Should be Spironolactone-Based (Furosemide should NOT be used alone!)
Dose: Spironolactone 100-400mg/day
Furosemide 40-160mg/day for Inadequate Weight Loss or if (+) HyperK +
Diuretics if Weight Loss < 1kg in the 1st week and < 2kg thereafter
Diuretics if Weight Loss > 0.5kg/day in patient without edema; or
> 1kg/day in those with edema

Note:

Side Effects: Renal Dysfunction, Hyponatremia, Hyperkalemia, Encephalopathy,

Gynecomastia

3) Large Volume Paracentesis (LVP) VS Diuretics in Uncomplicated Ascites

LVP: Faster resolution and Fewer Complications!
Refractory Ascites

LVP + Albumin (Mainstay)

TIPS
PVS
Definition of Terms:
Diuretic-Intractable Ascites: Maximum doses of Diuretics could NOT be reached
because of Side-Effects
Diuretic-Resistant Ascites: No response to Maximum Doses of Diuretics
Volume Expanders:
Albumin
Dextran-70
Polygeline
Albumin:
Decreases the Incidence of Post-Paracentesis Circulatory Dysfunction
Use Albumin if > 5L of Ascites is removed (if < 5 L, may use Synthetic Expanders)
Dose: 6-8 g per Liter of Ascitic Fluid Removed

Hepatorenal Syndrome

Discussed in Another Lecture

35

III. SPONTANEOUS BACTERIAL PERITONITIS (SBP)

Most Common Infection in Cirrhotic Patients
S/Sx: Fever, Jaundice, Abdominal Pain
A. Early Diagnosis: Diagnostic Paracentesis
o PMN Count > 250/mm3
o Done if Sx of SBP occur
B. Pharmacologic Management
o Antibiotics: 3rd Generation Cephalosporins, Quinolone (Ciprofloxacin) or B-Lactams (Co-Amoxiclav)
o Usually Cefotaxime 2g q120 2g q60
o Duration: 5-10 days
o Repeat Paracentesis in 48 hours if NO clinical Improvement with Antibiotics (no need to repeat if with Clinical
Improvement in repeat paracentesis, there should be a 25% decrease in the PMN count)
C. Albumin (Plus Antibiotics) Indicated if:
o BUN > 30 mg/dL
o Creatinine > 1.0
o Bilirubin > 4 g/dL
**NOTE; Albumin is NOT indicated if (+) 100% Predicted Cure and Survival!
D. Prophylaxis for SBP:
o Indicated for these Patients:
1) Cirrhotic with Active Variceal Hemorrhage
2) Patient Recovered from SBP (Long-Term)
o Tx: Norfloxacin 400mg PO BID x 7 days
IV. HEPATIC ENCEPHALOPATHY
Ammonia Levels are NOT reliable NOT necessary!
Clinical Diagnosis
Ammonia has good correlation with Severity, but is NOT good in Diagnosis
A. Precipitants of Hepatic Encephalopathy
o Excess Protein, Infection, Constipation
o TIPS
o GI Bleeding
o Sedation
o Diuretics ( Serum K+, Plasma Volume Azotemia)
B. Mechanisms of Action of Lactulose
o Colonic Acidification
o Catharsis
C. Protein Restriction (?)
o NOT necessary in Hepatic Encephalopathy
o Do NOT restrict protein, unless patient is in Stage IV

36

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HEMATOLOGY
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Jaime Alfonso Manalo Aherrera, M.D.

Internal Medicine Notes 2009

LECTURE ON RATIONAL BLOOD USE

INTRODUCTION
Whole Blood
Red Cells

Platelet-Rich Plasma
Platelets

Plasma
Cryoprecipitate

Derivatives

I. ADVANTAGES OF COMPONENT THERAPY

Less volume transfused
Correct dose
Lower risk for immunologic transfusion reactions (Plasma = responsible for reactions)
Coagulation Factors are preserved
Decreased disease transmission
Unwanted Leukocyte and Platelet Aggregates eliminated
More patients can benefit
II. AVAILABILITY
Red Cell Products (Whole Blood, PRBC, Washed RBC, Leukocyte Depleted Red Cells)
FFP
Cryosupernate
Cryoprecipitate
Platelets (Random Donor Platelets or Apheresed)
III. KEY NOTES
There are only TWO Indications for Whole Blood Transfusion:
o Massive Hemorrhage / Bleeding
o Exchange Transfusion
Whole Blood:
o No more Viable Platelets, Fibrinogen if stored for several days
o Massive Blood Loss means Loss of >30% acutely
Most Common Fatal Hemolytic Transfusion Reaction: Clerical Error!
o Donor should have Hgb > 125
o Risks: Early ( < 5 days) or Late ( > 7 days)
In Transfusion Reactions, there are only TWO Conditions when we can Continue Transfusion:
o Mild Allergic Reaction
o Febrile Non-Hemolytic Reaction (continue when Fever subsides)
All Blood Units should be Infused within 4 Hours
o If (+) Risks (such as Congestion), we can divide the units into Aliquots
Each unit should be tested for ABO and Rh Group
o Tested in the Philippines: HIV 1 & 2, HBV, HCV, Syphilis, Malaria
o Others: HTLV 1 & 2, CMV, etc (Plasma can transmit most infections)

BLOOD PRODUCTS
I. PACKED RED BLOOD CELL (PRBC)
A. Humans have Profound Capacity to Tolerate Anemia
o Increase CO
o Decrease Blood Viscosity
o Redistribution
o 2,3-DPG (change in affinity of Hgb to O2)
B. Current Standards (NIH Consensus Conference Report, 1988)
HEMOGLOBIN
< 7 g/dL
PRBC is Justified

MANAGEMENT

6 10 g/dL

Individualized signs and symptoms of O2 Deprivation, Risks vs Benefits

If (-) Cardiac / Neuro / Pulmo patient can tolerate this level without transfusion

> 10 g/dL

Almost Never (more Harmful to transfuse)

Sample Case:
32 year old female for Elective Cholecystectomy. Hgb: 84, Hct: 0.23, MCV: 65, MCH: 23. Do you transfuse?
Blood Loss in Elective Cholecystectomy: ~300-500cc
Most would opt to Type and Screen (if Blood Loss is < 500cc) this means that there is no need for crossmatching yet, no need for transfusion
**NOTE: In Cancer Patients: Quality of Life is improved at Hemoglobin Level of 11 12 g/dL
C. Revised (Local) Guidelines for Adult BT of PRBC (~250cc): NVBSP Guidelines
o 1) Hgb < 7 g/dL or Hct < 21% (If not due to a treatable cause, such as Fe deficiency)
o

2) Symptomatic Anemia, regardless of Hemoglobin Level (usually < 10g/dL)

Dyspnea
Syncope
Postural Hypotension
Tachycardia
Chest Pain
TIA

3) Hgb < 7 g/dL or <21% with concomitant hemorrhage, COPD, CAD, Hemoglobinopathy, Sepsis

4) Patients receiving General Anesthesia, if:

a) Pre-Op Hemoglobin < 7 g/dL or Hct < 21%
b) Major Blood Letting Operation and Hemoglobin < 10 g/dL or Hct < 30% (Open Heart, Laminectomy)
c) Signs of Hemodynamic Instability or Inadequate O2 Carrying Capacity (Symptomatic Anemia)

D. Classification of Hypovolemic Shock according to Blood Loss

Blood Loss (mL)
Blood Loss (% BV)
Pulse Rate
Blood Pressure
Pulse Pressure
Respiratory Rate
Urine Output (cc/h)
CNS / Mental Status

CLASS I
Up to 750 mL
Up to 15 %
< 100
Normal
Normal or Decreased
14 20
> 30
Slightly anxious

CLASS II
750 1500 mL
15 30 %
> 100
Normal
Decreased
20 30
20 30
Mildly anxious

CLASS III
1500 2000 mL
30 40 %
> 120
Decreased
Decreased
30 40
5 15
Anxious and confused

CLASS IV
> 2000 mL
> 40 %
> 140
Normal
Decreased
> 35
Negligible
Confused, Lethargic

E. CONTRAINDICATIONS to Red Cell Transfusion:

o Volume Expansion when O2 Carrying Capacity is adequate
o Prophylaxis: No signs/symptoms of Anemia
o Enhance General Sense of Well-Being
o Promote Wound Healing
F. Indications of Prophylactic Paracetamol / Anti-Histamines
o Paracetamol: give only if (+) Febrile
o Anti-Histamine: give only if (+) previous history of Allergy
o Tx; Give Leukocyte Depleted Products
G. Transfusion of PRBC:
o Give Blood Transfusion over 4 Hours after proper Blood Typing and Crossmatching
o 1 Unit raises Hemoglobin by 1g/dL or Hematocrit by 3%
II. PLATELET TRANSFUSION
Indications: Therapeutic and Prophylactic
o Therapeutic: ex) Bleeding
o Prophylactic: ex) Patient undergoing surgery (indications are controversial)
In Patients with Decreased Platelet Production:
o At > 100,000: Bleeding Time is NOT affected
o At 10,000: Bleeding Time is Prolonged
o At < 10,000: Bleeding Time is > 30 minutes and NOT related to Platelet Count
o At < 5,000: Spontaneous Bleeding
Example: Case on ITP
o Tx is Steroids
o If Platelet Count is 12,000 do NOT Transfuse yet Platelet Count will Increase in response to the Steroids
Dose and Response:
POOLED / RANDOM DONOR PLATELETS
1 Unit / 10kg BW
Dose

Response

1 Unit increases PC by 5,000 10,000 cells/uL

SINGLE DONOR / APHERESIS PLATELETS

1 Pack (equivalent to 4-8 Units of RDP)
Advantage: may reduce Infectious Disease
Transmission by reducing the number of Donor
Exposures
Corrected Count Increment (CCI) > 10,000 within 1
Hour and > 7,500 within 24 Hours Post-Transfusion

Platelets are NOT useful in the following (these are due to Increased Platelet Destruction):
o Drug Induced Thrombocytopenia
o TTP, HUS, ITP
o Heparin Induced Thrombocytopenia
Note on Dengue Hemorrhagic Fever:
o If (-) Bleeding, NO Transfusion!
A. Random Donor Platelets (RDP)
o Volume: 50 cc
o Dose: 1 Unit / 10 kg Body Weight (ex: if 60kg, give 6 units)
o Content: > 5.5 x 1010 Platelets/bag
o Can carry Organisms (bacteria from the environment can go into the blood induce Sepsis)
B. Single Donor Platelets (SDP) / Apheresed Platelets
o Volume: 200 600 cc
o Dose: 1 Apheresis Product / Transfusion Episode

 Some Generalizations:
o If Platelet Count < 10,000 give Prophylaxis (EXCEPT in Immune Mediated Diseases)
o If Major Surgeries maintain > 50,000
o In Minor Surgeries maintain > 30,000
o Cross Matching is NOT required prior to Platelet Transfusion, but should be ABO Type-Specific
o Pre-Medications NOT necessary
CCI = Posttransfusion Count Pretransfusion Count
. x Body Surface Area
Number of Platelets Transfused x 10

III. FRESH FROZEN PLASMA (FFP) TRANSFUSION

Indication: Control or Prevention of Bleeding in Multiple Coagulation Defects
o Liver Disease with Coagulopathy
o Hemophilia
o DIC
o Reversal of Warfarin Effect
Dose: 4-7 Units for an Average Adult (15-20 mL/kg)
o Response: Increase Coagulation Factors by about 2%
Shelf Life: 1 year when frozen at 300C

IV. CRYOPRECIPITATE TRANSFUSION

Indications:
o Hemophilia-A with Bleeding or Anticipated
o VonWB Disease
o Fibrinogen Deficiency in DIC
o Factor XIII Deficiency
Shelf Life: 1 year when Frozen at 300C
Dose: In Pools of 6 Units each
o Response: Increase Fibrinogen by 30-60 mg/dL
V. CRYOSUPERNATE TRANSFUSION
Indications:
o Hemophilia-B
o Factor II, VII. . . . .
VII. GRANULOCYTE CONCENTRATE TRANSFUSION
Indications:
o Gram (-) Sepsis with ANC at < 500, NOT responding to Antibiotics

BASIC HEMATOLOGY NOTES

INTRODUCTION
I. SOME FORMULAS
Hemoglobin:
Hematocrit:
Serum Fe:
TIBC:
Serum Ferritin

M: 16 + 2
F: 13 + 2
M: 47 + 6
F: 40 + 6
50 150 mg/dL
54 64 mmol/dL
M: 100
F: 30

A. Reticulocyte Count (0.005 0.015)

o To know if with Marrow Problem or Anemia secondary to Hemodialysis or Blood Loss
o Reticulocyte Count % = PGH Value x 100%
o Corrected Reticulocyte Count:
Patients Reticulocyte Count x Patients Hct / Normal Hct x 1000
Normal Hct Values = 0.4-0.5 for Males; 0.38-0.48 for Females (usually 0.45)
**NOTE: Reticulocyte Index: Corrected Reticulocyte Count / 2
Interpretation:

LOW Retic Count = Marrow problem because of decreased production

HIGH Retic Count = Compensatory or Destruction or Blood Loss

Absolute Reticulocyte Count = Patients Reticulocyte x Patients Reticulocyte

45
Corrected Reticulocyte Count = Absolute Reticulocyte Count
Maturation Time (MT)
MT is 1
1.5
2.0
2.5

when Hct is

45%
35%
25%
15%

Interpretation:
CRC

< 1%
> 2%

Hypoproliferative BM
Hemolysis or
100,000mm2 Blood Loss

B. Hematology Formulas
o MCH = Hgb/RBC
o MCV = Hct (100)/RBC
o MCHC = Hgb/Hct

N: 27 31
N: 76 100
N: 330 390

Chromic
Cytic

MCH = Hypo / Hyperchromic

MCV = Micro / Macrocytic
IMPORTANT Notes:

Microcytic, Hypochromic = Iron Deficiency, Thalassemia, Chronic Inflammatory Disease, Myelodysplastic

Macrocytic = Megaloblastic Anemia, Hemolysis, Liver Disease, Alcoholism, Hypothyroidism, Aplastic Anemia

Normocytic, Normochromic = Anemia of Chronic Disease

o Anemia of Endocrine Failure = Mild Normocytic Normochromic Anemia
o Anemia of Chronic Renal Failure = Normocytic, Normochromic Anemia (Reticulocytes are DECREASED)
Aplastic Anemia, Pure Red Cell Aplasia, Myelophthisic Anemia, Myelodysplastic Syndromes

These are the Hypoproliferative Anemias associated with Marrow Damage

The have the following Characteristics:

o Normochromic, Normocytic or Macrocytic
o Characterized by LOW Reticulocyte Count

Microcytic Anemia

Macrocytic Anemia
(Macrocytosis: MCV > 100Fl)

Iron Deficiency Anemia

Thalassemia
Lead Poisoning
Chronic Infection

Macrocytosis
Reticulocytosis
Liver Disease
Downs Syndrome
Megaloblastic

Folic Acid Deficiency

B12 Deficiency

C. Absolute Neutrophil Count (ANC)

(Neutrophils + Stabs) x WBC x 1,000

< 500 = NEUTROPENIC!

II. TRANSFUSION THERAPY (Medicine Notes)

A. Packed RBC (pRBC)
o Indications:
1) Hgb < 7g/Dl or Hct < 21% in Hemodynamically STABLE Patients or without CVD
2) Hgb < 8g/Dl or Hct < 24% in UNSTABLE and CVD Patients
% Increase: 1 Unit Prbc x 4 hours increases Hemoglobin by 10
B. Fresh Frozen Plasma (FFP)
o Volume = 200Ml
o Content: Normal Levels of all Coagulating Factors
o Dose: 15mL/kg (each unit will raise factors by 3-5% or 10-15u/kg)
o Indications:
PT INR > 1.5x Normal
PTT > 5 sec of Upper Limit of Control
Active Bleeding
Coagulation Deficit of Factor II, V, VII, X, XII
Reversal of Warfarin
TTP
C. Platelet
o Volume: 50cc
o Dose: 1 unit / 10 kg
o Indication: PC < 10-20,000 (Prophylaxis)
If PC < 50,000 in Bleeding Patients or undergoing Procedure
Massive Bleeding
**NOTE: Given over 30 minutes; NO Pre-BT Meds
D. Cryoprecipitate
o Volume: 15-20mL
o Dose: Pool of 2 or 6 u (each unit Increase by 5-10%) 1 bag/10kg BW
o Pre-Med Tx: Paracetamol 500mg; Diphenhydramine 25-50mg PO/IV
o In Non-Hemolytic Febrile Transfusion: Meperidine 25-50mg IV to prevent chills
E. Whole Blood
o Volume: 500Ml
o Dose: 20mL/kg x 4 hours
o Contains 1/2g of Fe per mL
o Therefore, 500mL = 250g Iron
III. HEMA CLEARANCE
A. Transfusion Threshold
o NO Cardiac Disease: Hgb 70
o With Cardiac Disease: Hgb 80 100
**NOTE: How do you know if enough was transfused? Check Symptoms
B. Platelet (50cc) Fast Drip
o With Bleeding: < 100 T (NOT Purpura nor Petechiae)
o W/O Bleeding: < 20 T
C. RBC: Run x 4 hours
D. FFP

FD
15cc/kg
2 Units q 12 (if you expect bleeding)
4 units FD

IV. SCREENING ASSAYS (from Harrisons)

Commonly used Screening Tests are:

o PT
o aPTT
o Platelet Count

Interpreting PT
1. INR

If > 1: means that blood is LESS Coaguable, prone to bleeding, ideal for ACS px

If < 1: coaguable blood

2. Activity
> 70% = needed if you will do Invasive Procedures / Surgeries

A. Prothrombin Time (PT)

o PT assesses Factor I (Fibrinogen), II (Prothrombin), V, VII, and X
o Measures the time for clot formation of the citrated plasma after recalcification and addition of Thromboplastin
o International Normalized Ratio (INR) is determined by: (PTPATIENT / PTNormal.Mean)ISI
o INR was developed to assess Anticoagulation due to reduction of Vitamin-K Dependent Coagulation Factors, it is commonly
used in the evaluation of patients with Liver Disease
B. Activated Partial Thromboplastin Time (aPTT)
o Assesses the Intrinsic and Common Coagulation Pathways: Factors XI, IX, VIII, X, V, II, Fibrinogen, and also Prekallikrein,
High Molecular Weight Kininogen and Factor XII
Prolonged PT:

Factor VII Deficiency

Vitamin-K Deficiency Early

Warfarin Anticoagulation
Prolonged aPTT and PT

Factor II, V, or X Deficiency

Vitamin-K Deficiency Late

Direct Thrombin Inhibitors

Prolonged aPTT:
1. No Clinical Bleeding

Factors XII, High Molecular Weight Kininogen, Protein Kinase

2. Variable, but usually Mild Bleeding

Factor XI

Mild in Factor VIII & IX

3. Frequent Severe Bleeding

Severe Deficiencies of Factor VIII and IX

4. Heparin

COMMON HEMATOLOGIC CASES

I. PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)

Main Defect = MUTATION in Pig-A Gene (in the X-Chromosome), which is necessary for GPI Anchor

Without this Anchor, Cell Membranes are Easily Destroyed (there are proteins which attach to this glycoprotein)

It is a DISTINCTIVE Disorder because it is an Intracorpuscular Defect acquired at the Stem Cell Level
A. Characterized by Three Common Manifestations:
o Hemolytic Anemia
o Venous Thrombosis
o Deficient Hematopoiesis
B. Diagnosis
o Clinical Symptoms = Ictericia, Pallor, Thrombosis
o PERIPHERAL CYTOPENIAS
**NOTE: Other Findings (from the book)

Anemia is highly Variable

Hematocrit from < 20% to Normal

NORMOCHROMIC and NORMOCYTIC

Bone Marrow appears NORMOCELLULAR

C. Treatment
Washed Packed-RBC Transfusion
Corticosteroids 15-30mg EOD
Iron Replacement for IDA
Heparin / Warfarin
ATG 150mg/kg (Total) over 4-10 days
Hematopoietic Stem Cell Transplant (HSCT)

To Avoid further HEMOLYSIS

To Control the Hemolysis
Questionable because if we give more Iron, we can promote Hemolysis
If with History of Thrombosis
For Marrow Hypoplasia
Transplant

II. APLASTIC ANEMIA

PANCYTOPENIA with Bone Marrow HYPOCELLULARITY (Fats > Cellular Elements)

Acquired Aplastic Anemia = Abrupt Onset of Low Blood Counts in a previously Well Young Adult

Pancytopenia = it means DIMINISHED Amounts of RBC, WBC, Platelets (all the blood elements)
A. Clinical Course & Signs/Symptoms = Depends on SEVERITY
o Anemia = Pallor, EF, Weakness
o Bleeding = Most Common EARLY Symptom
o Thrombocytopenia = Bleeding Diathesis
o Leukopenia = Fever, Signs of Infections
o (-) Organomegaly (in General)
B. Pathogenesis of Aplastic Anemia
o Bone Marrow results from SEVERE Damage to the Hematopoietic Cell Compartment
o In Aplastic Anemia = there is Replacement of the Bone Marrow by Fat (HYPOCELLULAR Marrow)
C. Laboratory Diagnosis
o NORMOCYTIC, NORMOCHROMIC or MACROCYTIC RBC
o Reticulocytopenia
o Pancytopenia
D. Treatment of Aplastic Anemia
o HSCT (Hematopoietic Stem Cell Transplant)
o Horse ATG 40mg/kg/d x 4 days or Rabbit ALG 3.5mg/kg/d x 5 days
o Cyclosporin 12mg/kg/d Orally
o Androgens / Steroids / Growth Factors
o Transfusions
o Avoidance / Treatment of Infections
o Removal of Suspected Etiologic Agent
o Treatment for Severe & Very Severe = BONE MARROW Transplant

10

III. ANEMIA (from Medicine Notes)

A. Three Major Classes of Anemia
o Marrow Production Defects (Hypoproliferative)
o Red Cell Maturation Defects (Ineffective Erythropoiesis)
o Decreased Red Cell Survival (Blood Loss / Hemolysis)
Anemia

CBC; Reticulocyte Count

Reticulocyte Index < 2.5

Red Cell Morphology
Normocytic
Normochromic

Micro or Macrocytic

Reticulocyte Index > 2.5

Hemolysis / Hemorrhage
Blood Loss
Intravascular Hemolysis
Metabolic Defect
Membrane Abnormality

Hypoproliferative
Marrow Damage
*Infiltration / Fibrosis
*Aplasia

Maturation Disorder
Cytoplasmic Defects
*Iron Deficiency
*Thalassemia
*Sideroblastic Anemia

Hemoglobinopathy
Immune Destruction
Fragmentation Hemolysis

Iron Deficiency
Decreased Stimulation
*Inflammation
*Metabolic Defect
*Renal Disease

Nuclear Defects
*Folate Deficiency
*Vitamin B12 Deficiency
*Drug Toxicity
*Refractory Anemia

B. Signs and Symptoms

o Most often recognized by Abnormal Screening Lab Tests
o Acute Leukemia: Always due to Blood Loss
o 30% Loss of Blood Volume: Unable to compensate w/ Vascular Contractions and changes in Regional Blood Flow
o 40% Blood Loss: will manifest signs and symptoms of Hypovolemic Shock
o Hgb of 7-8 mg/Dl = Signs and Symptoms of Anemia will develop:
Bleeding
Easy Fatigability
Malaise
Fever
Weight Loss
Night Sweats
C. Physical Examination
o Findings of infection, blood in stool, lymphadenopathy, petechiae, splenomegaly
o Forceful heartbeat, strong peripheral pulses, systolic flow murmur (Hemic)
o Pale skin and mucous membranes

11

D. Laboratory Examinations:
1. CBC
Hemoglobin, Hematocrit
Red Cell Indices
MCV (N: 90 + 8)
MCH (N: 30 + 3)

Microcytosis: MCV < 80

Macrocytosis: MCV > 100
MCV and MCH reflect defects in Hemoglobin Synthesis

2. Peripheral Blood Smear

Anisocytosis = change in Cell Size
Poikilocytosis = changes in Cell Shape (suggests defect in maturation of RBC precursors in BM or
fragmentation of circulating RBCs)
Polychromasia = Reticulocytes which are released Prematurely from the BM (slightly larger than normal
and grayish blue), seen in Fibrosis, Infiltration of BM by Malignant Cells
3. Reticulocyte Count
Key to the initial classification of Anemia
< 2-3x the normal = Inadequate Marrow Response
An accurate Reticulocyte Count is key to the initial classification of Anemia. Normally, Reticulocyte Count ranges
from 1-2% and reflects the daily replacement of 0.8-1.0% of the circuloating red cell population. A reticulocyte count
provides a reliable measure of red cell production
In order to use the Reticulocyte Count to estimate marrow response, two corrections are necessary. The first correction
adjusts the reticulocyte count based on the reduced number of circuloating red cells. With anemia, the % of
reticulocytes may be increased while the absolute number is unchanged. To correct for this effect, the reticulocyte
percentage (%) is multiplied by the ratio of the patients hemoglobin or hematocrit to the expected
hemoglobin/hematocrit for age and gender of the patient. This provides an estimate of reticulocyte count corrected for
anemia. In order to convert the corrected reticulocyte count to an index of marrow production, a further correction is
required, depending on whether some of the reticulocytes in circulation have been released from the marrow
prematurely. For this second correction, the peripheral blood smear is examined to see if there are polychromatophilic
macrocytes present. These cells, representing prematurely released reticulocytes, are referred to as shift cells, and the
relationship between the degree of shift. The correction is necessary because these prematurely released cells survive as
reticulocytes in circulation for > 1 day, thereby providing a falsely high estimate of daily red cell production.
If the Reticulocyte Production Index is < 2 in the face of established Anemia, a Defect in Erythroid Marrow
Proliferation or Maturation must be present

E. Calculation of Reticulocyte Production Index (Medicine Notes)

1. Correction #1 for Anemia (Produces the Absolute Reticulocyte Count)
Abs. Ret Ct = Ret Count x .

Hemoglobin of Patient
.
Expected Hgb for the Age and Gender

Example: Person whose reticulocyte count is 9%; Hgb 7.5g/Dl, Hct 23%
Absolute Reticulocyte Count = 9 x (7.5/15) OR 9 x (23/45) = 4.5%
2. Correction #2 for Anemia (Produces the Reticulocyte Index)
Reticulocyte Production Index = Retic Count x . Hemoglobin of Patient / Expected Hemoglobin .
Maturation Time Correction
**NOTE: Maturation Time Correction varies from 1-3, but 2 is usually used
Example: IN a person whose Reticulocyte Count is 9%, Hgb 7.5gm/Dl, Hct 23%
Reticulocyte Production Index = 9 x 7.5 / 15 = 2.25
2

12

F. Bone Marrow Examination

Hypoproliferative Anemia
Hemolytic Disease
Maturation Disorder

RETICULOCYTE PRODUCTION INDEX

<2
>3
Decreased

E/G RATIO
1:2 or 1:3
At least 1:1
Increased

**NOTE: E/G Ratio or Erythroid / Granulocytic Ratio

1. Hypoproliferative Anemia
Reticulocyte Production Index with little or no change in RBC morphology (Normocytic, Normochromic)
At least 75% of all cases of Anemia
Majority due to Mild to Moderate Deficiency or Inflammation
Other Causes: Marrow damage, inadequate EPO stimulation in Renal Failure
Key Labs: Serum Iron, TIBC, Evaluation of Renal and Thyroid Function, Marrow Biopsy Serum Ferritin
Acute or Chronic Inflammation
In Mild to Moderate Deficiency

Serum Iron
Serum Iron

% Transferrin Saturation
% Transferrin Saturation

N or TIBC
TIBC

Ferritin
Ferritin

**NOTE: Anemia of Chronic Disease

Cytokines causes ANEMIA

This is in contrast to Anemia of Iron Deficiency

2. Red Cell Maturation Defects / Ineffective Erythropoiesis

Slight to Moderately Elevated Reticulocyte Production Index that is accompanied by either Macrocytic or Microcytic
Red Cell Indices
Marrow Morphology: E/G Ratio > 1:1 (Erythroid Hyperplasia)
Has TWO Types:

Nuclear Maturation Defects (From Vitamin B12, Folic Acid Deficiency, Drug Damage, Myelodysplasia)

Cytoplasmic Maturation Defects (Defects from Severe Iron Deficiency)

3. Blood Loss / Hemolytic Anemia

RBC Production Indices > 2.5x the Normal

There is INCREASED Erythropoiesis: presence of Polychromatophilic Macrocytes in PBS

13

HEMATOLOGIC MALIGNANCIES
I. ACUTE LEUKEMIA
Present with manifestations of CYTOPENIAS
Anemia: Fatigue and Dyspnea
Thrombocytopenia: Cutaneous or Mucosal Hemorrhages
Neutropenia: Fever and Infection
Leukemic Infiltration of organs: Lymphadenopathies, Splenomegaly (common in ALL), Gingival Hyperplasia and Skin
Nodules (common in AML)
A. Acute Myeloid Leukemia (AML)
o 80% of adult Acute Leukemia
o Characterized by predominance of Blasts (Myeloblasts and Early Promyelocyte) in the BM and PBS
o
o

Etiology: Hereditary, radiation, chemical and other occupational exposures, drugs

Classifications: WHO Classification + FAB Classification (see harrisons)
1. Clinical Presentation
Non-Specific Symptoms that begin gradually or abruptly and are the consequence of Anemia,
Leuokcytosis, Leukopenia, or Leukocyte Dysfunction, or Thrombocytopenia
Fatigue, weakness, anorexia, weight loss, fever, abnormal hemostasis, bone pain, lymphadenopathy,
nonspecific cough, headache, or diaphoresis
2. On Physical Examination
Fever, Splenomegaly, Hepatomegaly, Lymphadenopathy, Sternal Tenderness, evidence of Infection &
Hemorrhage
3. Hematologic Findings
Anemia (can be severe) Normocytic Normochromic
Decreased Erythropoiesis often results in a Reduced Reticulocyte Count
Decreased RBC survival by accelerated destruction
Active Blood Loss
Median Presenting Leukocyte Count is ~15,000u/L
Auer Rods: if present, the Myeloid Lineage is virtually certain
Platelet Counts < 100,000/uL
Elevation of Serum Uric Acid (50%)
4. Treatment: Induction + Postremission Management
Goal: to quickly induce Complete Remission (CR)
Once CR is obtained, further therapy must be used to prolong survival and achieve cure

B. Acute Lymphoblastic Leukemia

o Characterized by predominance of Lymphoblasts
o Occurs most often in children
o Form of Acute Leukemia that is MOST Responsive to Therapy
o
o
o

Common in children ALL is NOT a common Leukemia in Adults

ALL cell origin is in the Lymphoid Line
Most Common ALL Variant (75%) = B-Cell Lineage

14

II. CHRONIC LEUKEMIA

Characterized by Proliferation of Lymphoid or Hematopoietic Cells that are more mature than those of Acute Leukemia
Have a longer, less devastating Clinical Course than acute leukemia
A. Chronic Lymphocytic Leukemia (CLL)
o Proliferation of neoplastic lymphoid cells (almost always B-Cells) with widespread infiltrations of BM, PBS,
Lymph Node, Spleen and Liver
o Incapable of producing into Antibody-Producing Plasma Cells
o Often occurs in persons > 60 y/o
o Presence of Smudge Cells in PBS
o Leukemic Cells resemble Normal Mature, Peripheral Blood Lymphocytes
o Increased Number of MATURE Lymphocytes (CD-5 B-Cells 95%) in Peripheral Blood & Bone Marrow
o Males > Females
1. Complications:
Warm Antibody Autoimmune Hemolytic Anemia (AIHA)
Hypoagammaglobulinemia and Increased Susceptibility to Bacterial Infection
2. Clinical Features
Indolent Clinical Course
Generalized Lymphadenopathy and Moderate Hepatosplenomegaly

Asymptomatic or +/- Lymphadenopathy

Pallor, Signs of Bleeding, Infections

3. Treatment of Chronic Lymphocytic Leukemia

Indications for Treatment: Hemolytic Anemia, Important Cytopenias, Disfiguring Lymphadenopathy,
Symptomatic Organomegalies, Marked Systemic Symptoms
Treatment / Management:
Chlorambucil + Prednisone
COP or CHOP
Mainstay of Treatment = Fludarabine +/- Chemotherapeutic Agents
HSCT (for younger patients)
IVIG

B. Chronic Myeloid Leukemia (CML)

o Neoplastic Clonal Proliferation of Myeloid Stem Cells
o Characterized by reciprocal chromosomal translocation between chromosomes 1 and 2 Philadelphia
Chromosome
o Marked Leukocytosis (50,000 to 200,000)
o Reduction in Leukocyte Alkaline Phosphatase activity in the Leukemic Leukocytes
o Clinical Features:
Prominent Splenomegaly
Modestly Enlarged Liver and Lymph Nodes
Terminates in Accelerated Phase (BLASTIC CRISIS) with Increasing number of Blast Cells and
Promyelocytes
o
o

Diagnosis is established by identifying a Clonal Expansion of a Hematopoietic Stem Cell possessing a reciprocal
translocation between Chromosomes 9 and 22
Untreated, the disease is characterized by the inevitable transition from a Chronic Phase to an Accelerated Phase and
on to Blast Crisis in a Median Time of 4 years
1. Clinical Presentation
Clinical Onset of the Chronic Phase is generally insidious
Fatigue, malaise, and weight loss, splenic enlargement (early satiety, left upper quadrant mass)
2. Physical Examination
Minimal to Moderate Splenomegaly = Most Common
Mild Hepatomegaly

15

3. Laboratory Hematologic Findings

Elevated WBC, with increases in both immature and mature granulocytes
Platelet Counts are almost always elevated at diagnosis
Mild Normocytic Normochromic Anemia
Bone Marrow Cellularity is Increased (at diagnosis) Increased Myeloid to Erythroid Ratio
Disease Acceleration: defined by development of increasing degrees of anemia unaccounted for by the
bleeding or therapy; cytogenetic clonal evolution; or blood marrow blasts between 10-20%, blood or
marrow basophils >20%, or platelet count < 100,000/uL
Blast Crisis: defined as Acute Leukemia, with Blood or Marrow Blasts > 20%
**NOTE: Cytogenic Hallmark of CML (90-95%) = t(9;22)(q34;q11.2)
Originally, this was recognized by the presence of a shortened chromosome 22 (22q-), designated
as the Philadelphia Chromosome
4. Treatment
Goal of Tx: To achieve prolonged, durable, nonneoplastic, nonclonal hematopoiesis, which entails the
eradication of any residual cells containing the BCR/ABL Transcript
Hence, goal is complete molecular remission and cure
If Blasts > 20% Blastic Crisis
10-20% Accelerated Phase
< 10% Chronic Phase
Hydroxyurea
o Given as management action of Leukocytes Rupture
o Problem: Ruptured WBCs may cause an Increase in Uric Acid Levels therefore, we give Allopurinol AND
we give NaHCO3 to Alkalinize the Urine

III. LYMPHOMAS
Incidence: Males > Females (3:2)
Etiology: Viral (EBV), Chemicals (Benzene Herbicides), Hereditary, Immunodeficiency
A. Signs / Symptoms
o Painless Enlarged Lymphadenopathy
o With or Without Fever, Night Sweats, Weight Loss
B. Hodgkins VS Non-Hodgkins Lymphoma:
Spread
Extranodal Site Involvement
Systemic Symptoms
Involvement

HODGKINS LYMPHOMA
Orderly Spread by Contiguity
RARE
Of Prognostic Importance
Axial and Central Lymph Nodes

Cure

POSSIBLE for All Types

NON-HODGKINS LYMPHOMA
Random, Hematogenous Spread
In UNFAVORABLE Types
Less Common
Peripheral, Mesenteric Lymph Nodes
Blood; Waldermyers Ring
RARE in Low Grade Tumors

C. Diagnosis
o Lymph Node or Extra-Nodal Mass BIOPSY
o FNAB (+) Limitations (very painful)
o Histopathology = (+) REEDSTERNBERG CELL in Hodgkins Lymphoma
o Immunohistochemistry
D. Differential Diagnosis
o Reactive Lymph Node Hyperplasia (as in INFECTIONS)
o Undifferentiated Carcinoma
E. Prognosis
o Hodgkins Lymphoma is BETTER than Non-Hodgkins Lymphoma
o International Prognostic Index (IPI) for Non-Hodgkins Lymphoma (FIVE Clinical Factors):
Age 60 or Above
Serum LDH Levels ELEVATED
Performance Status
Ann-Arbor Stage III or IV
Extranodal Site Involvement

16

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Jaime Alfonso Manalo Aherrera, M.D.

Internal Medicine Notes 2009

COMMON INFECTIOUS DISEASES

1) DENGUE INFECTION
I. DENGUE FEVER
Acute febrile illness with NO Identifiable Focus of Infection of 2-7 days Duration (sometimes Biphasic)
With Two or More of the following:
o Headache
Tourniquet Test:

Inflate cuff midway between Systolic and

o Retro-Orbital Pain
Diastolic for 5 minutes
o Myalgia / Arthralgia

(+) If > 20 Petechiae in a 1 square inch area

o Rash (Petechial)
1.5 inches from Volar Aspect of Antecubital
o Hemorrhagic Manifestations (Petechiae + Tourniquet Test)
Fossa
o Leukopenia
A. Microbiology
o Aedes Aegypti = Principal Vector (All four distinct dengue viruses Dengue 1-4 have Aedes Aegypti as their
principal vector, and all cause a similar clinical syndrome
o Breeds near human habitation relatively fresh water source such as water jars, discarded containers
o In rare cases, SECOND infection with a Serotype of Dengue Virus different from that involved in the Primary
Infection leads to Dengue Hemorrhagic Fever (HF) with Severe Shock
o Incubation Period 2-7 Days
B. Clinical Presentation
o Sudden Onset of Fever, headache, retroorbital pain, and back pain along with the severe myalgia that gave rise to the
colloquial desegnation Break Bone Fever
o D1: Macular rash, adenopathy, palatal vesicles and sclerae injection
o Others: Anorexia, nausea, vomiting, cutaneous hypersensitivity, maculopapular rash beginning on the trunk and
spreading to extremities and face
o Epistaxis and scaterred petechiae are often noted in uncomplicated dengue, and preexisting gastrointestinal lesions
may bleed during the Acute Illness
C. Laboratory Findings
o Leukopenia, Thrombocytopenia, Serum Aminotransferase Elevation
o Dx: IgM ELISA or Paired Serology during Recovery or by Antigen-Detection ELISA or RT-PCR during the Acute Phase
II. DENGUE HEMORRHAGIC FEVER / DENGUE SHOCK SYNDROME
Usually with a background of Previous Exposure to another Serotype the transient protection after Dengue Virus Infection
is replaced within several weeks by the potential for Heterotypic Infection resulting in Typical Dengue Fever or
uncommonly for ENHANCED Disease (Secondary DHF / DSS)
Macrophage Infection is CENTRAL to the pathogenesis of Dengue Fever and to the Origin of DHF / DSS
A. Pathogenesis
Previous Infection with a Heterologous Dengue Virus Serotype

Production of Nonprotective Antiviral Antibodies

Bind to Virions Surface and through interaction with the Fc Receptor focus Secondary
Dengue Viruses on the Target Cell

Enhanced Infection
B. Induction of Vascular Permeability and Shock depends on Multiple Factors:
o 1) Presence of Enhancing and Non-Neutralizing Antibodies
o 2) Age (susceptibility to DHF/DSS drops after 12y/o)
o 3) Sex (F > M)
o 4) Race
o 5) Nutritional Status (Malnutrition is Protective)
o 6) Sequence of Infection (Serotype 1 followed by Serotype 2 is More DANGEROUS than Serotype 4 followed by
Serotype 2)
o 7) Infecting Serotype (Serotype 2 is MORE DANGEROUS)

C. Clinical Presentation of DHF

o
o

Identified by detection of Bleeding Tendencies (Torniquet Test, Petechiae) or Overt Bleeding in Absence of underlying causes
Dengue Shock Syndrome: accompanied by Hemorrhagic Signs & results from Increased Vascular Permeability leading to shock
Mild DHF / DSS
More Severe Cases

Restlessness, Letharghy, Thrombocytopenia < 100,000/uL, Hemoconcentration are detected 2 to 5

days after onset of Typical Dengue Fever, usually at the time of Defervescence
Frank Shock is apparent, with Low Pulse Pressure, Cyanosis, Hepatomegaly, Pleural Effusions,
Ascites, and in some cases Severe Ecchymoses and GI-Bleeding
Period of Shock lasts only 1 or 2 days, and most patients respond promptly to close monitoring,
oxygen administration, and infusion of Crystalloid or in severe cases Colloid

1. Dengue Hemorrhagic Fever (DHF)

Fever or Hx of Fever lasting for 2-7 days

Hemorrhagic Manifestations such as:

(+) Tourniquet Test

Petechiae, Ecchymosis, Purpura

Bleeding from Mucosa, GI Tract, IV Sites or other sites, Hematemesis or Melena

Thrombocytopenia (100,000 or 1-2 Platelets / OIF)

Evidence of Plasma Leakage due to Increased Capillary Permeability

Any Hematocrit > 40% of Rise of > 20% in Hematocrit for age and sex

A Drop in 20% Hematocrit following volume replacement treatment as compared to baseline

Signs of Plasma Leakage (Pleural Effusion, Ascites)

2. Dengue Shock Syndrome (DSS): All the criteria of DHF, PLUS Signs of Circulatory Failure

Rapid and Weak Pulses

Narrow Pulse Pressure (< 20mmHg)

Hypotension for Age (< 60mmHg Systolic for < 5y/o and < 90mmHg Systolic for > 50 y/o)

Cold Clammy Extremities

D. Diagnosis
o Virologic Diagnosis can be made by the usual means, although Multiple Flavivirus Infections lead to a broad immune response to
several members of the group, and this situation may result in a lack of Virus Specificity of the IgM and IgG Immune Responses
o A secondary Antibody Response can be sought with tests against several Flavivirus Antigens to deminstrate the characteristic
Wide Spectrum of Reactivity

III. GRADING OF DENGUE (Medicine Notes)

GRADE 1
Fever with Non-Specific Sx

GRADE 2

GRADE 3

GRADE 4

Grade 1 PLUS:

Grade 1 + 2 PLUS:

Grade 1 + 2 + 3 PLUS

Hemorrhagic Manifestations:

(+) Torniquet Test

Easy Bruisability

Gum Bleeding

Epistaxis, Rashes

Petechiae on Palate

Petechiae on Axillae

Circulatory Failure

Rapid Weak Pulse

Narrowing Pulse Pressure

Hypotension

Cold, Clammy Skin

Restlessness

Profound SHOCK
Undetectable BP or Pulse

IV. MANAGEMENT OF DENGUE HEMORRHAGIC FEVER

A. Diagnostics
o CBC with PC, PT, PTT; Torniquet Test
o Dengue Serology if Illness LONGER Than 4 days
o Others: AST/ALT, urinalysis, CXR

Monitor Platelet Count + Hematocrit Levels q12-24 hours

B. Therapeutics
o Supportive Hydration
o Optional Medications: H2-Blockers if with Abdominal Pain or GI Bleeding
o Watch out for Complications:

If there is Frank, Uncontrollable Bleeding Fresh Whole Blood is indicated

If PT, PTT are prolonged and with Thrombocytopenia, Fresh Frozen Plasma Transfusion is indicated

If there is DIC, Platelet Transfusion is indicated

**NOTE: In the Absence of Bleeding, there is NO need to administer Platelet Transfusion, even if PC is LOW
C. Prevention

2) TYPHOID FEVER

Gram (-) S. typhi and S. paratyphi

3 Major Antigenic Determinants: Somatic-O Antigen, Surface V1 Antigen, Flagellar H-Antigen
Incubation Period: varies with the size of infecting dose and averages 10-20 days (range 3-55 days)
I. PATHOGENESIS
Hallmark: Invasion and Multiplication within the Mononuclear Phagocytic Cells in the liver, spleen, lymph nodes and Peyer
Patches of the Ileum
Transmitted to humans orally by contaminated food or water
II. CLINICAL MANIFESTATION
NON-SPECIFIC SYMPTOMS
PHYSICAL FINDINGS
Chills
Diaphoresis
Anorexia
Myalgia
Cough
Weakness / Malaise
Sore Throat
Dizziness
Constipation / Diarrhea
Abdominal Pain
Abdominal Distention

III. CRITERIA FOR ADMISSION (Medicine Notes)

All Patients Suspected of Having Typhoid Fever with
ONE or More of the Following:
Persistent Vomiting or Unable to take Oral Fluids
Severe Dehydration
Spontaneous Bleeding
Persistent Abdominal Pain
Listlessness
Changes in Mental Status
Weak, Rapid Pulse
Cold, Clammy Skin
Circumoral Cyanosis
Seizures
Hypotension or Narrowing Pulses

Persistent High Fever

Relative Bradycardia
Rose Spots (Rashes primarily trunk area)
Abdominal Tenderness
Hepatomegaly
Splenomegaly
Thyroid Psychosis / Encephalitis
Epistaxis

All Patients suspected of having Complicated Typhoid Fever

Intestinal Perforation
GI Hemorrhages
Peritonitis
Pericarditis
Hepatic and Splenic Abscesses
DIC
Myocarditis
Meningitis

III. LABORATORY WORK-UP

A. Complete Blood Count (CBC)
o Leukopenia / Leukocytosis
o Thrombocytopenia
o Normochromic Anemia; Hypochromia with Blood Loss
o Neutropenia
B. Culture of Appropriate Specimen
1. Blood Culture
Gold Standard
Should be taken anytime during the illness, but yield is HIGHERST during the first 2 Weeks
Should be taken at least from different sites
2. Stool Culture
(+) 2nd 4th Week of Illness
3. Bone Marrow Culture
NOT likely done, but indicated in high suspicious cases with (-) Blood or Stool Culture
Can be done anytime during t he illness
Isolation Rate is around 90%

IV. LABORATORY FINDINGS (from Blue Book)

IgM
IgG
(+)
(-)
Acute Infection
(+)
(+)
Recent Infection
(-)
(+)
Equivocal: Past Infection or Acute Infection
V. TREATMENT
A. UNCOMPLICATED Typhoid Fever: Conventional Therapy
o Chloramphenicol 3-4g in 4 divided doses x 14 days; Or
o Co-Trimoxazole Forte 1-1.5 tabs BID x 14 days; Or
o Amoxicillin 4-5g/day in 3 divided doses x 14 days
B. For COMPLICATED Cases, Presence of Severe Symptoms, Clinical Deterioration despite Conventional Therapy:
(Empiric Therapy for Suspected Resistant Typhoid Fever)
o Ceftriaxone (Rocephin) 3gm IV Infusion OD x 5-7 days; or
Ceftriaxone may be used for Pregnant
o Fluoroquinolones:
Women and Children
Ciprofloxacin (Cibprobay) 500mg tab PO BID x 7-10 days
Ofloxacin (Inoflox) 400mg tab PO BID x 7-10 days
Pefloxacin (Floxin) 400mg tab PO BID x 7-10 days
VI. PREVENTION
Whole Cell Vaccine (Heat Killed) = 2 parenteral doses
Purified Vi Polysaccharide fro Capsule = 1 parenteral dise (ViCPS)
Attenuated S. typhi = 4 oral doses (Ty21a)
VII. COMPLICATIONS:
Intestinal Perforation
GI Hemorrhage and Peritonitis may occur in the 3 rd to 4th Week of Illness
Pancreatitis, Hepatic & Splenic Abscess, Disseminated Intravascular Coagulation, Myocarditis, Meningitis, Encephalitis

3) LEPTOSPIROSIS

MILD FORM = Leptospirosis may present as an Influenza-Like Illness with Headache and Myalgia
SEVERE FORM (Weils Syndrome) = characterized by Jaundice, Renal Dysfunction, & Hemorrhagic Diathesis

I. EPIDEMIOLOGY
A ZOONOSIS with a worldwide distribution
Rodents (especially Rats) = Most Important reservoir, although other Wild Mammals, Dogs, Fish and Birds may also harbor
these Microorganisms
Transmission of Leptospires:
o Direct Contact with Urine, Blood or Tissue from an Infected Animal
o Exposure to a Contaminated Environment
o Human-to-Human Transmission is RARE!
o Since Leptospires are Excreted in the Urine and can survive in water for many months, WATER is an
Important Vehicle in their Transmission
II. CLINICAL MANIFESTATIONS
A. Anicteric Leptospirosis
o Leptospirosis may present as an Acute Influenza-Like Illness with Fever, Chills, Severe Headache, etc
o Muscle Pain (Calves, Back, Abdomen) = IMPORTANT Feature of Leptospiral Infection
1. Leptospiremic Phase
Acute Influenza-Like Illness = Fever, Chills, Severe Headache, Nausea, Vomiting, Myalgias
IMPORTANT Feature of Leptospiral Infection = MUSCLE PAIN, which especially affects the Calves,
Back and Abdomen
Mental Confusion may be Evident
Pulmonary Involvement (is not Uncommon) = Manifested in most cases by COUGH and Chest Pain and in
a few cases by Hemoptysis
MOST COMMON Finding on Physical Examination = FEVER with Conjunctival Suffusion
Mild Jaundice may be Present
2. Immune Phase
Most Patients become ASYMPTOMATIC within 1-week
After an Interval of 1 to 3 days, the Illness recurs in a number of cases
The Start of this Second (Immune) Phase COINCIDES with the Development of Antibodies
Symptoms are more VARIABLE than during the First (Leptospiremic) Phase
Fever is LESS Pronounced and Myalgias are LESS Severe than in the Leptospiremic Phase
NOTE: This is where we see the Inflammation Stages
**An Important Event during the Immune Phase is the Development of Aseptic Meningitis:
Meningeal Symptoms usually DISAPPEAR within a few days, but may persist for weeks
Iritis, Iridocyclitis and Chorioretinitis = Late Complications that may persist for years (can become
apparent as early as the third week, but often present several months after the initial illness)

B. Severe Leptospirosis (WEILS SYNDROME = Most Severe Form)

o Characterized by Jaundice, Renal Dysfunction, Hemorrhagic Diathesis, and HIGH MORTALITY
o Mortality = usually due to HEMORRHAGE!
o Frequently (but NOT exclusively) associated with Serovar Icterohaemorrhagiae / Copenhageni
o Serovar Icterohaemorrhagiae / Copenhageni = Causes the INFECTION (from RATS)
o The onset of Illness is NO Different from that of Less Severe Leptospirosis; however, after 4-9 days, Jaundice as
well as Renal & Vascular Dysfunction generally develop
o NOTE: It has NO Biphasic Disease Pattern like that seen in Anicteric Leptospirosis!
**Physical Examination and Other Findings:
The Jaundice of Weils Syndrome, which can be profound and give an Orange Cast to the Skin, is usually
NOT Associated with Severe Hepatic Necrosis
(+) Hepatomegaly & Tenderness in the Right Upper Quadrant (usually detected)
(+) Splenomegaly (in 20% of cases)
**Findings in Weils Syndrome:
1. Renal Failure
Develop during 2nd week of illness (respond to treatment if there is NO Hemorrhage)
Hypovolemia and Decreased Renal Perfusion = contribute to the Development of Acute
Tubular Necrosis with Oliguria or Anuria
Dialysis is sometimes required, although a Fair Number of cases can be managed without Dialysis
(Renal Function may be completely regained)
2. Pulmonary Involvement
Occurs frequently
Presents with Cough, Dyspnea, Chest Pain, and Blood-Stained Sputum
Sometimes = Hemoptysis or even Respiratory Failure
3. Hemorrhagic Manifestations (seen in Weils Syndrome)
Common Manifestations = Epistaxis, Petechiae, Purpura, Ecchymoses
RARE Manifestations = Severe GI-Bleeding, Adrenal or Subarachnoid Hemorrhage
4. Other Manifestations described in SEVERE Leptospirosis:
Rhabdomyolysis, Hemolysis, Myocarditis, Pericarditis
Congestive Heart Failure, Cardiogenic Shock
Adult Respiratory Distress Syndrome
Multi-Organ Failure

III. LABORATORY DIAGNOSIS OF LEPTOSPIROSIS

Isolation of Leptospires in Culture

CERTAIN

(+) Serology: Endemic

Single (+), Low Titer
Single (+), High Titer
Paired Sera, Rising Titer

2
10
25

(+) Serology, NOT Endemic

Single (+), Low Titer
Single (+), High Titer
Paired Sera, Rising Titer

5
15
25

Scoring System:

(+) = Isolation of Leptospires from Culture

Presumptive:
o A or A + B = 26
o A + B + C = 25

Suggestive
o A or A + B = 20 25
o A + B + C = 20 25

A. Culture Isolation
o GOLD Standard
o Isolated from Blood / CSF = during the First 10 days
o Isolated from Urine = several weeks (beginning around the 1 st week)
o Ellinghausen-McCullough-Johnson-Harris (EMJH) Medium, Fletcher Medium, Korthof Medium
B. Others
o Direct Darkfield Microscopy (Blood or Urine) Usually results in Misdiagnosis and should NOT be used
o Serology = Antibody Detection: Microagglutination Test (MAT), Complement Fixation, ELISA, IFA,
Microcapsule Agglutination Test (MCAT)
o DNA Technology (eg. PCR)
C. Renal Changes
o Kidneys are Invariably Involved in Leptospirosis
o Related Findings Range from:
Urinary Sediment Changes (Leukocytes, Erythrocytes, Hyaline or Granular Casts)
Anicteric Leprospirosis = Mild Proteinuria
Severe Leptospirosis = Renal Failure and Azotemia
IV. TREATMENT
The Effectiveness of Antimicrobial Therapy for the Mild Febrile form of Leptospirosis is CONTROVERSIAL, but such
Treatment is INDICATED for MORE SEVERE FORMS
Treatment should be initiated as EARLY as possible; nevertheless, contrary to previous reports, treatment started after the
first 4 days of illness is effective.
A. In Milder Cases: Oral Treatment with Tetracycline, Doxycycline, Ampicillin, or Amoxicillin should be considered
o Amoxicillin 500mg QID PO
o Ampicillin 500-750mg IV q6
B. For Severe Cases: IV Administration of Penicillin G, Amoxicillin, Ampicillin, or Erythromycin is recommended
o Pen G 1.5 M q6 1 week
Jarisch-Herxheimer Reaction
o After the start of Antimicrobial Treatment for Leptospirosis, a Jarisch-Herxheimer Reaction similar to that seen in
other Spirochetal Diseases may develop
o It is a Dramatic, though usually Mild Reaction, consisting of Fever, Chills, Myalgias, Headache, Tachycardia,
Increased Respiratory Rate, Increased Circulating Neutrophil Count, and Vasodilation with Mild Hypotension

3) MALARIA

Protozoan Disease transmitted by the Bite of Infected Anopheles Mosquitoes

It is a Parasitic Infection caused by a Protozoan Plasmodium spp
It is presented with CYCLIC FEVER and CHILLS with SPLENOMEGALY leading to serious illness

I. EPIDEMIOLOGY OF MALARIA
MOST IMPORTANT Parasitic Disease in Humans
Four Species of Malaria: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae
Of the 4 Species of Human Malaria, Plasmodium falciparum causes nearly ALL DEATHS and NEUROLOGICAL
COMPLICATION
Transmission of P. falciparum = Transmitted by the BITE of an Infected Anopheline mosquito (Anopheles flavirostris in
the Philippines)
II. LIFE CYCLE OF MALARIA
In Humans, although Parasite undergoes development in the Liver, it is the Erythrocytic Cycle thats responsible for disease!
o Erythrocytic Cycle = Responsible for the Development of the Disease
o Schizonts Rupture & Merozoites are Released = causes PAROXYSM of Malaria

Erythrocyte Changes in Malaria

After INVADING an Erythrocyte, the growing Malarial Parasite progressively consumes and degrades Intracellular
Proteins, principally HEMOGLOBIN
Potentially Toxic Heme Biologically Inert HEMOZOIN or Malarial Pigment
Parasite also alters RBC membrane Irregular Shape More Antigenic & Less Deformable
Result: Shortened RBC survival

III. CLINICAL MANIFESTATIONS

Initial Symptoms: NON-SPECIFIC and NOT Reliable (Incubation Period = 8-40 days)
Headache may be SEVERE, there is NO Neck Stiffness or Photophobia resembling Meningitis
A. High Index of Suspicion
o Travel to and Overnight Stay in Malarious Area (palawan)
o Blood Transfusion in the past 6 months
o Intravenous Drug Use
**NOTE: Significant Travel History
Significant Exposure = at most, 1 Month (Incubation Period = as long as 30-45 days)
Ex) If patient had a History of Travel to Palawan 2 years ago, it is NOT Significant
B. Other Features:
o
o
o
o
o
o

Nausea, Vomiting, and Orthostatic Hypotension

Classic Malarial Paroxysms
Anemia
Splenic Enlargement
Slight Enlargement of the Liver
Mild Jaundice

1. Classical Malaria Paroxysm:

Cold Stage (Chills)
Hot Stage (Fever Spikes)
Sweating Stage
**IMPORTANT Notes:
The CLASSIC Malarial Paroxysms (Fever Spikes, Chills and Rigors) occur at REGULAR
Intervals are relatively Unusual and suggest Infection with P. vivax & ovale
Fever is IRREGULAR at First (P. falciparum may NEVER become Regular)
2. Periodicity of Attacks ONLY if the Patient is UNTREATED
Periodicity = every 3 days, 4 days, etc (it does NOT occur if patient is Treated)
Eg. Every 48-Hours for Plasmodium falciparum
3. Periodicity of Malaria:
Tertian Periodicity

Cyclic Fever occurring every 48 Hours

Includes Plasmodium falciparum, vivax, ovale

Quartan Periodicity

MALIGNANT VS BENIGN TERTIAN

Malignant Tertian Malaria = severe w/ complications (Plasmodium falciparum)

Benign Tertian Malaria = mild (Plasmodium ovale, vivax)

Cyclic Fever occurring every 72 Hours
Includes Plasmodium malariae

C. Severe FALCIPARUM MALARIA

1. CEREBRAL MALARIA (MOST Life-Threatening)
COMA is a characteristic and ominous feature of Falciparum Malaria
Death Rate = 20% among adults; 15% in children
Diffuse Symmetric Encephalopathy (Focal Neurologic Signs are UNUSUAL
2. Others:

Severe Normocytic Anemia

Hypoglycemia, Metabolic Acidosis with Respiratory Distress, Fluid and Electrolyte Disturbance, Acute Renal Failure
Acute Pulmonary Edema and Adult Respiratory Distress Syndrome (ARDS)

10

Circulatory Collapse, Shock, Septicemia, Abnormal Bleeding

Jaundice, Haemoglobinuria
High Fever, Hyperparasitaemia (>100,000 Ring Stage/uL)

IV. DIAGNOSIS
A. Thick and Thin Smears
o GOLD STANDARD Actual Demonstration of the Parasite in the Blood Smear
o Thick Smear = for Quantification of Parasitemia
o Thin Smear = for Species Identification
B. Others
o Rapid Diagnostic Tests
o Serology (IFAT, ELISA, IHA)
C. Other Findings (Medicine Notes)
o Normochromic, Normocytic Anemia
o ESR, Plasma Viscosity, CRP
o Prolonged PT/PTT, Severe Thrombocytopenia, Metabolic Acidosis
o Plasma Glucose, Na, HCO3, Ca2+, Phosphate, Albumin
o Lactate, BUN, Crea, Urate, Muscle & Liver Enzymes, Bilirubin (DB & IB)
D. For Cerebral Malaria
o Mean Opening Pressure at Lumbar Puncture is ~180mmHg of CSF
o Normal or has slightly Total Protein and Cell Count
V. TREATMENT

We Treat Malaria with COMBINATION Drugs this is because of Chloroquine-Resistance

Severe Malaria = DOC is QUININE (for Severe Malaria: Cerebral Malaria, etc)
A. First Line of Treatment = Chloroquine + Sulfadoxine / Pyrimethamine (CQ + SP)
o First Line in the Drug Treatment of PROBABLE Malaria and CONFIRMED P. falciparum provided that the Disease is NOT
Severe
B. Artemether-Lumefantrin (Co-ArtemTM)
o SECOND Line Drug
o Given ONLY to Microscopically CONFIRMED P. falciparum which did NOT respond to Adequate CQ + SP Treatment
o It is NOT recommended for PREGNANT Women and children < 8y/o
C. Quinine + Tetracycline / Doxycycline
o THIRD Line Drug
o Should be given to those who did NOT Respond to Co-ArtemTM
o DRUG of CHOICE in the Treatment of SEVERE MALARIA!
**IMPORTANT Notes:

Tetracycline and Doxycycline are CONTRAINDICATED for Pregnant Women and children < 8y/o

Instead, give Quinine + Clindamycin

D. Primaquine
o Given in single dose to CONFIRMED P. falciparum cases to PREVENT Transmission
o Given for 14 days to CONFIRMED P. vivax to PREVENT RELAPSE
E. Chloroquine
o Drug to be used in the Treatment of CONFIRMED P. vivax

11

4) SCHISTOSOMIASIS

Endemic in 24-Provinces in the Philippines

HIGHEST Prevalence of Infection in children 5-15 years of age

I. EPIDEMIOLOGY
Schistosoma japonicum = MAJOR Species involved in Schistosomiasis (in the Philippines)
Snail Vector = Oncomelania quadrasi (Skin Penetration)
Transmission = requires CONTACT between Humans and other Animal Hosts with the Breeding Sites for Snails (there
should be SKIN PENETRATION of the Cercaria!)
II. CLINICAL ASPECTS
Main Pathology and Manifestations = due to Granulomatous Reaction to Eggs deposited in the Liver and other organs
Most Serious Consequence in the Liver is OBSTRUCTION of Intrahepatic Portal Branches leading to:
o Portal Hypertension with Splenomegaly
o Collateral Circulation
o Ascites
**IMPORTANT Notes:
o End of Infection = LIVER CIRRHOSIS
o Usually, patients would come for consult due to Signs of Liver Failure (Ascites, Hepatomegaly, etc)

12

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Jaime Alfonso Manalo Aherrera, M.D.

Internal Medicine Notes 2009

COMMON RENAL (NEPHROLOGY) DISEASES

1) RENAL TUBULAR ACIDOSIS

Disorder of Renal Acidification out of proportion to the Reduction in GFR

Characterized by Hyperchloremic Metabolic Acidosis with Normal Anion Gap

I. TYPE-1 RTA (DISTAL)

Distal Nephron does NOT lower Urine pH normally due to excessive back diffusion of H + Ions from the Lumen to the Blood
Chronic Acidosis:
o Decreased Tissue Reabsorption of Ca2+
o Renal Calciuria (Increasing Osteoclast Activity) Alkaline Urine
o Decreased Urine Citrate Excretion
A. Diagnosis:
o Suggested by Normal Anion Gap Metabolic Acidosis with Urine pH > 5.5
o (-) Bicarbonaturia
B. Treatment
o NaHCO3 100mEq + 400cc H2O
II. TYPE-II RTA (PROXIMAL)
Hyperchloremic Acidosis
Bicarbonate Reabsorption in the Promximal Tubule is defective leading to Bicarbonaturia
Distinguished from Type-I by the ability to Normally Acidify Urine during Spontaneous or Induced Ammonium Acidosis
Treatment: NaHCO3 5-15 mmol/kg/day
III. TYPE-IV RTA
Distal Tubule Secretion of K+ and H+ ions are Abnormal, resulting in Hyperchloremic Acidosis with Hyperkalemia
Hyponatremic Hypoaldosteronism = MOST COMMON Cause of Type IV RTA
Treatment: Fludrocortisone 0.1-0.2mg/kg/day

2) URINARY TRACT INFECTIONS

Acute Infections of the Urinary Tract can be subdivided into TWO Categories:
o Lower Tract Infections = Urethritis and Cystitis
o Upper Tract Infection = Acute Pyelonephritis, Prostatitis, and Intrarenal & Perinephric Abscesses

I. CLINICAL FEATURES OF URINARY TRACT INFECTIONS:

UTIs exist when Pathogenic Microorganisms are detected in Urine, Uretha, Bladder, Kidney or Prostate
Growth of > 105 Organisms/mL of Urine = signifies INFECTION
III. URINALYSIS
NOT Recommended for Young Females presenting with Typical Symptoms of LOWER Urinary Tract Infection
5 WBC / hpf
Routine Screening is NOT recommended for Diabetics, Indwelling Foley Catheters, Cancer Patients (taking Chemotherapy)
III. EIGHT CLINICAL SYNDROMES OF UTI
Acute Uncomplicated Cystitis in Women
Acute Uncomplicated Pyelonephritis
Asymptomatic Bacteriuria
UTI in Pregnancy
Recurrent UTI (recurred > 2x Annually)
Complicated UTI (patients with Anatomic, Structural or Functional Abnormality)
UTI in Men (almost ALWAYS Complicated)
Catheter-Associated UTI

3) ACUTE RENAL FAILURE

Syndrome characterized by Rapid Decline in GFR (hours to days)

Diagnosed when Biochemical Screening of Hospitalized Patients reveals a Recent INCREASE in Plasma Urea and
Creatinine Concentrations
Frequent Clinical Features: Retention of Nitrogenous Waste Products, Oliguria (UO < 400mL/d contributing to extracellular
fluid overload), and electrolyte and acid-base abnormalities

I. ACUTE VS CHRONIC RENAL FAILURE

First step in evaluating a patient with renal failure

is to determine if the disease is Acute or Chronic
Findings Suggestive of Chronic Renal Failure:
o Anemia
o Neuropathy
o Renal Osteodystrophy
o Small, Scarred Kidneys

ARF is often considered to be reversible, although a return to baseline serum

creatinine concentrations postinjury might not be sufficiently sensitive to detect
clinically significant irreversible damage that may ultimately contribute to CKD.
Kidney Size may be Normal or Increased in some CKD:

Diabetic Nephropathy

Amyloidosis

Polycystic Kidney Disease

HIV Associated Nephropathy

Kidney Size
Carbamylated Hemoglobin
Broad Casts on Urinalysis
History of Kidney Disease, HPN, Abnormal Urinalysis
Anemia, Metabolic Acidosis, Hyperkalemia, Hyperphosphatemia
Reversibility with Time

ACUTE KIDNEY DISEASE

Normal
Normal
Absent
Absent
Often Present
Usually Complete

CHRONIC KIDNEY DISEASE

Small
High
Present
Present
Usually Present
Sometimes Partial

II. TYPES OF RENAL FAILURE

Pre-Renal ARF: Diseases that cause Renal Hypoperfusion
Intrinsic ARF: Diseases that directly involve the Renal Parenchyma
Post-Renal ARF: Diseases associated with urinary tract obstruction
TYPE
Pre-Renal

DESCRIPTION
Most Common Form, which occurs in the setting of Renal Hypoperfusion
Prolonged Hypoperfusion leads to Acute Tubular Necrosis (Ischemic)
Clinical Features: thirst, orthostatic dizziness, orthostatic hypotension,
tachycardia, reduced jugular venous pressure, decreased skin turgor, dry
mucous membranes

SOME EXAMPLES
Hypovolemia (GI losses, decreased intake, etc)
Low Cardiac Output
Systemic Vasodilation
Selective Intrarenal Vasoconstriction
Hepatorenal Syndrome

Intrinsic

Can be conceptually divided based on the Predominant Compartment:

1) Ischemic or Nephrotoxic Tubular Injury

2) Tubulointerstitial Diseases

3) Diseases of the Renal Microcirculation & Glomeruli

4) Diseases of Larger Renal Vessels

Ischemic Acute Tubular Necrosis

Nephrotoxic ARF

Post-Renal

Urinary Tract Obstruction accounts for < 5% of hospital acquired ARF

Bladder Neck Obstruction (Most Common)

Prostatic Disease

Neurogenic Bladder

Therapy with Anticholinergics

Because one kidney has sufficient reserve to handle generated nitrogenous

waste products, ARF from obstruction requires:

Obstruction to Urine Flow between external urethral meatus and

bladder neck

Bilateral Ureteric Obstruction

Unilateral Unreteric Obstruction with one functioning kidney

Hepatorenal Syndrome (HRS)

o Unique form of Prerenal ARF that frequently complicates Advanced Cirrhosis as well as Acute Liver Failure
o Kidneys are structurally normal but fail due to splanchnic vasodilation and arteriovenous shunting, resulting in
provound renal vasoconstriction

III. URINALYSIS
Anuria suggests complete urinary tract obstruction but may complicate severe cases of Prerenal or Intrinsic Renal ARF
Findings in Urinalysis (from Med-School Notes)
Prerenal ARF

Low Volume
Concentrated Urine (High Specific Gravity)
No RBC, No WBC (ACELLULAR)
(+) Hyaline Casts (Fine Granular Casts) = Tamm Horsfall Protein

Post Renal ARF

Usually due to Obstructions, Stones, Prostatic Enlargement, etc

NORMAL RBC (this means that the RBC does NOT come from the Glomerulus)

Acute Tubular Necrosis (ATN)

Muddy Brown Granular Cast = PATHOGNOMONIC

Microscopic Hematuria
Mild Tubular Proteinuria (protein is < 1 gram/day)

Glomerulnephritis (GN)

Dysmorphic RBC (the RBC has to pass thru the Glomerulus Distortion of Shape)
(+) RBC Casts
> 1g Proteinuria (Glomerular Proteinuria)

Allergic Interstitial Nephritis

WBC Casts; Granular Cast

Eosinophiluria

Chronic Kidney Disease (CKD)

(+) Broad Cast

Broad Casts reflect Total Fibrosis and Dilatation of Tubules

IV. DIAGNOSTICS
A. Serial Serum Creatinine Measurements
o Prerenal ARF: Fluctuating Creatinine Levels that parallel changes in Hemodynamic Status
o Renal Ischemia, Atheroembolization, Radiocontrast Exposure: Creatinine rises rapidly (within 24-48 hours)
Contrast Nephropathy: Peaks in 3-5 days
ATN, Atheroembolic: Peaks later 7-10 days
B. Approach to Patients with Azotemia

Radiologic Findings:

UTZ: Useful to exclude Post-Renal

CT, MRI: Alternative

Retrograte / Anterograde Pyelography

Plain Film of Abdomen

Renal Biopsy:

Reserved for patients in whom

prerenal and postrenal ARF have
been excluded, and the cause of
Intrinsic ARF is unclear
Complications:
ARF impairs renal excretion of Na, K. and H2O
and perturbs divalent cation homeostasis and
urinary acidification mechanisms

QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

As a result, complications include:

Intravascular Volume Overload

Hyponatremia

Hyperkalemia

Hyperphosphatemia

Hypocalcemia

Hypermagnesemia

Metabolic Acidosis
Uremic Syndrome:
Develops because patients are unable to excrete
nitrogenous waster products

V. MANAGEMENT
MANAGEMENT ISSUE
Reversal of Renal Insult
Ischemic ATN
Nephrotoxic ATN

THERAPY
Restore systemic hemodynamics and renal perfusion through volume resuscitation and use of vasopressors
Eliminate Nephrotoxic agents
Consider toxin-specific measures (eg. Forced alkaline diuresis for rhabdomyolysis, allopurinol for tumor lysis sx)

Prevention and Treatment of Complications

Intravascular Volume
Salt and H2O Restriction
Overload
Diuretics, Ultrafiltration
Hyponatremia

Restruction of Enteral Free Water Intake

Avoidance of Hypotonic IV solutions, including dextrose-containing solutions

Hyperkalemia

Restriction of Dietary K+ Intake

Eliminate K+ supplements and K+-Sparing diuretics
Loop Diuretics to promote K+ Excretion
Potassium Binding Ion-Exchange Resins (eg. Sodium Polystyrene Sulfonate or Kayexelate)
Insulin (10 units regular) and Glucose (50mL of 50% Dextrose) to promote Intracellular Mobilization
Inhaled B-Agonist Therapy to promote intracellular mobilization
Calcium Gluconate or Calcium Chloride (1g) to stabilize the Myocardium
Dialysis

Metabolic Acidosis

Sodium Bicarbonate (maintain Serum HCO3 > 15mmol/L or Arterial pH > 7.2)
Administration of other bases (eg. THAM)
Dialysis

Hyperphosphatemia

Restriction of dietary phosphate intake

Phosphate-Binding Agents (Calcium Carbonate, Calcium Acetate, Sevelamer Hydrochloride, Aluminum OH)

Hypocalcemia

Calcium Carbonate or Gluconate (if symptomatic)

Hypermagnesemia

Discontinue Mg++ Containing Antacids

Hyperuricemia

Treatment usually not necessary if < 890umol/L or < 15mg/dL

Allopurinol, forced Alkaline Diuresis, Rasburicase

Nutrition

Protein and Calorie intake to avoid net negative nitrogen balance

Dialysis

To prevent complications of ARF

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

VI. ABSOLUTE INDICATIONS FOR DIALYSIS:

Symptoms or Signs of the Uremic Syndrome
Management of Refractory Hypervolemia, Hyperkalemia, or Acidosis
VII. BUN / Crea Ratio (SI Units)

BUN:Crea Ratio = BUN x 247

Crea
Conversion Factor for Serum BUN: 1 mmol/L = 2.8 mg/dL

Interpretation:
If < 10: Intrinsic Renal Cause
If 10-20: Doubtful Cause
If > 20: Pre-Renal Cause

VIII. CREATININE CLEARANCE (mL/min): Cockroft and Gault Equation

CreaClearance = . (140 age) x weight in kg .

72 x Serum Crea in mg/dL

CreaClearance = . (140 age) x weight in kg .

72 x (Serum Crea in umol/L / 88.4)

IMPORTANT Notes:
o If Female, multiply everything by 0.85
o If Crea is NOT in mg/dL, divide it by 88.4

4) CHRONIC RENAL DISEASE

CKD Encompasses a spectrum of different pathophysiologic processes associated with abnormal kidney function, and a
progressive decline in GFR

I. DEFINITION OF TERMS
A. Chronic Renal Disease
o Pathophysiologic Process resulting to IRREVERSIBLE Reduction in Renal Mass and Function occurring MORE
than 3 MONTHS
o Pathophysiologic Process with Multiple Etiologies, resulting in the Inexorable Attrition of Nephron Number and
Function, and frequently leading to End-Stage Renal Disease (ESRD)
B. End-Stage Renal Disease (ESRD) or Stage 5 CKD
o Irreversible Loss of Renal Function rendering an Individual PERMANENTLY dependent upon RRT
o Represents a Clinical State or Condition in which there has been an Irreversible Loss of Endogenous Renal
Function, of a Degree Sufficient to render the patient permanently dependent upon Renal Replacement Therapy /
RRT (Dialysis or Transplantation) in order to avoid Life-Threatening Uremia
Staging of Chronic Kidney Disease (CKD)
STAGE
I

DESCRIPTION
Kidney damage with normal / increased GFT

GFR mL/min / 1.73m2

90

II
III

Kidney damage with mildly decreased GFR

Moderately decreased GFR

60 89
30 50

IV

Severely decreased GFR

15 29

Renal Failure

< 15 (for dialysis)

ACTION
Diagnosis and Treatment, Tx of
comorbid conditions, slowing
progression, CVD risk reduction
Estimating progression
Evaluating and Treating
complications
Preparation for kidney
replacement therapy
Kidney Replacement (if uremia
is present)

 NOTES from Harrisons:

o
o
o

The normal annual mean decline in GFR with age from the peak GFR (~120mL/min per 1.73m2) attained during
the third decade of life is ~1mL/min per year per 1.73m2, reaching a mean value of 70mL/min per 1.73m2 at 70y/o
Measurement of Albuminuria is also helpful for monitoring nephron injury and the response to therapy in many
forms of CKD, especially chronic glomerular diseases
An Accurate 24-Hour Urine Collection is the Gold Standard for measurement of Albuminuria
Microalbuminuria refers to the excretion of amounts of Albumin too small to detect by urinary dipstick

o
C. Azotemia
o LABORATORY Finding of an Elevated BUN and Creatinine
o May or May NOT have Symptoms
o Retention of Nitrogenous Waste as Renal Insufficiency develops
D. Uremia
o Syndrome Reflecting DYSFUNCTION of all Organ Systems as a result of Untreated or Undertreated ARF or CRF
o It is the Clinical and Laboratory Syndrome, reflecting Dysfunction of all Organ Systems as a result of Untreated or
Undertreated Acute or Chronic Renal Failure
o Refers to more Advanced Stages of Progressive Renal Insufficiency when the Complex, Multiorgan System
derangements become CLINICALLY MANIFEST
II. ETIOLOGY & EPIDEMIOLOGY

Most Frequent cause of CKD = Diabetic Nephropathy

Hypertensive Nephropathy
Progressive Nephrosclerosis

The uremic syndrome and the disease state associated with advanced renal impairment involve more than renal excretory failure. A host
of metabolic and endocrine functions normally undertaken by the kidneys are also impaired, and this results in Anemia, Malnutrition,
and Abnormal Metabolism of carbohydrates, fats, and proteins.
In summary, the pathophysiology of the Uremic Syndrome can be divided into manifestations in three spheres of dysfunction:
1) Those consequent to the accumulation of toxins normally undergoing renal excretion, including products of protein metabolism
2) Those consequent to the loss of other renal functions, such as fluid and electrolyte homeostasis and hormone regulation
3) Progressive systemic inflammation and its vascular and nutritional consequences

II. CLINICAL ABNORMALITIES IN UREMIA

Fluid and Electrolyte

Endocrine-Metabolic
Neuromuscular
Cardiovascular and Pulmonary
Dermatologic
Gastrointestinal
Hematologic and Immunologic

Chronic Renal Failure applies to the process of continuing significant irreversible

reduction in nephron number, and typically corresponds to CKD Stages 3-5.
Pathophysiology of CKD involves 2 Broad Sets of Mechanisms of Damage:

1) Initiating mechanisms specific to underlying etiology

2) Set of progressive mechanisms, involving hyperfiltration and

hypertrophy of the remaining viable nephrons

A. Fluid and Electrolyte, Acid-Base Balance

o Sodium and Water Homeostasis
o Potassium Homeostasis
o Metabolic Acidosis
B. Bone Disease and Disorders of Calcium & Phosphate (PO4 Metabolism)
Those Associated with:

HIGH Bone Turnover

HIGH PTH Levels

Osteitis Fibrosa (classic lesion of secondary hyperparathyroidism)

Those Associated with:

LOW Bone Turnover

NORMAL PTH Levels

Osteomalacia
Adynamic Bone Disease

C. Cardiovascular Abnormalities (leading cause of Morbidity and Mortality)

o Ischemic Heart Disease
o Congestive Heart Failure
o Hypertension and LVH
o Pericarditis (Pericardial Pain with respiratory accentuation, fruction rub)

D. Hematologic Abnormalities
o Anemia = Normocytic, Normochromic Type (Cause = Insufficient EPO-Production)
o Abnormal Hemostasis
Prolonged BT
Decreased Activity of Platelet Factor-III
Abnormal Platelet Aggregation and Adhesiveness
Impaired Prothrombin Consumption
E. Neuromuscular Abnormalities
o Central, Peripheral and Autonomic Neuropathy starting at STAGE-III CRD
o Mild Disturbance in Memory and Concentration and Sleep Disturbances
o Indication to Start RRT
F. Gastrointestinal and Nutritional Abnormalities
o Uremic Fetor: Urineferous Odor of the Breath due to breakdown of UREA to NH 3 in Saliva associated with a
Metallic Taste
o Gastritis, PUD, Diverticulosis, Pancreatitis
G. Endocrine-Metabolic Abnormalities
o Glucose Metabolism: Plasma-Insulin is ELEVATED
o Low Estrogen Level (Amenorrhea, Inability to carry Pregnancy to Term
o In Males: Oligospermia, Germinal Cell Dysplasia, Reduced Testosterone Level
H. Dermatologic Abnormalities
o Pallor
o Ecchymosis and Hematoma (defective Hemostasis)
o Pruritus, Excoriations (Calcium Deposition and Secondary Hyperparathyroidism)
o Uremic Frost (White Sediments on the Skin)
III. EVALUATION OF CKD
A. Initial Approach
o Symptoms and overt signs of kidney disease are often absent until renal failure supervenes
o Particular aspects in the history include: HPN, DM, abnormal urinalysis, problems with pregnancy
o PE should focus on BP and target organ damage from HPN, fundoscopy, precordial examination, edema, sensory
polyneuropathy, asterixis, pericardial friction rub
o The finding of Asterixis or a Pericardial Friction Rub not attributable to other causes usually signifies the presence
of the Uremic Syndrome
B. Laboratory Studies
o Underlying cause / aggravating disease process and degree of renal damage and its consequences
o A 24 hour urine collection may be helpful, as protein Excretion > 300mg may be an indication for therapy with ACE
Inhibitors or ARBS
C. Imaging Studies
o Renal Ultrasound: the finding of Bilaterally SMALL Kidneys supports the diagnosis of CKD of long-standing
duration, with an Irreversible component of Scarring
o Doppler Sonography, Nuclear Medicine Studies, CT or MRI Studies
o Voiding Cystogram (for Reflux Nephropathy)
D. Renal Biopsy
o In a patient with Bilaterally Small kidneys, Renal Biopsy is NOT advised because:
1) It is technically difficult and has a greater likelihood of causing bleeding and other adverse consequences
2) There is usually so much scarring that the underlying disease may not be apparent
3) The window of opportunity to render disease-specific therapy has passed

Other Contraindications to Renal Biopsy:

o Uncontrolled Hypertension
o Active Urinary Tract Infection
o Bleeding Diathesis
o Morbid Obesity

**NOTE: Ultrasound-Guided Percutaneous Biopsy is favored

IV. ESTABLISHING THE DIAGNOSIS & ETIOLOGY OF CKD

Most Important Initial Step in evaluation of Elevated Serum Creatinine = to distinguish newly diagnosed CKD from Acute
or Subacute Renal Failure (because the latter two conditions may respond to therapy specific to the disease)
Evidence of Metabolic Bone disease with Hyperphosphatemia, Hypocalcemia, and elevated PTH and bone Alkaline
Phosphatase levels suggests chronicity
Normochromic, Normocytic Anemia suggests that the process has been ongoing for some time
The finding of bilaterally reduced kidney size (<8.5cm in all but the smallest adults) favors CKD
V. MANAGEMENT OF CKD
A. Slowing the Progression of CKD
o Protein Restriction (intake of 0.60 to 0.75g/kg/day)
o Reducing Intraglomerular Hyperension and Proteinuria
B. Slowing Progression of Diabetic Renal Disease
o Control of Blood Glucose (Preprandial Glucose = 90-130mg/dL and HgbA1c < 7%)
o Control of Blood Pressure and Proteinuria
C. Managing Other Complications of Chronic Kidney Disease (CKD)
o Medication Dose Adjustment
o Preparation for Renal Replacement Therapy
VI. COMPLICATIONS OF HEMODIALYSIS
Hypotension = Most Common Acute Complication of Hemodialysis
High Output Cardiac Failure
Muscle Cramps
Anaphylactoid Reactions, etc

5) NEPHRITIC / NEPHROTIC SYNDROME

I. NEPHRITIC SYNDROME
Hematuria
RBC Casts
Proteinuria
Hypertension
Edema
Deteriorating Renal Function
II. NEPHROTIC SYNDROME
Proteinuria > 3.5 g/m+/24h
Hypoalbuminemia
Hyperlipidemia
Hypercoaguability
Edema

Nephrotic Syndrome classically presents with Heavy Proteinuria, Minimal Hematuria,

Hypoalbuminemia, Hypercholesterolemia, Edema, and Hypertension

Most Common Cause in Adults = Membranous Glomerulonephritis

Most Common in Chilren = Minimal Change Disease

Diabetic Nephropathy
o Single Most Common Cause of Chronic Renal Failure in the US
o Majority of patients with Diabetic Nephropathy have Type 2 DM

III. APPROACH TO PATIENTS WITH PROTEINURIA

> 3 g per day = NEPHROTIC SYNDROME (Non-Selective Proteinuria)
In Early DM Patients = (+) Microalbuminuria

10

FLUID & ELECTROLYTE / METABOLIC DERANGEMENTS

CAUSES OF HYPONATREMIA vs HYPERNATREMIA
HYPONATREMIA
I. Pseudohyponatremia
A. Normal Plasma Osmolality

Hyperlipidemia

Hyperproteinemia

Post-TURP
B. Increased Plasma Osmolality

Hyperglycemia

Mannitol
II. Hypoosmolal Hyponatremia
A. Primary Na+ Loss (20 H2O Gain)

Integumentary Loss: sweating, burns

GI Loss: vomiting, tube drainage, fistula, obstruction, diarrhea

Renal Loss: diuretics, osmotic diuresis, hypoaldosteronism, salt-wasting

nephropathy, postobstructive diuresis, nonoliguric acute tubular necrosis
B. Primary H2O Gain (20 Na+ Loss)

Primary Polydipsia

Decreased Solute Intake (eg. Beer Protomania)

AVP release due to pain, nausea, drugs

Syndrome of Inappropriate AVP Secretion

Glucocortidoid Deficiency

Hypothyroidism

Chronic Renal Insufficiency

C. Primary Na+ Gain (Exceeded by 20 Water Gain)

Heart Failure

Hepatic Cirrhosis

Nephrotic Syndrome

HYPERNATREMIA
I. Nonrenal Water Loss

Evaporation from the skin and respiratory tract (insensible

losses)

GI Losses: diarrhea (most common)

Increased Insensible Loss due to fever, exercise, heat

exposure, severe burns, mechanically ventilated patients
Na+ concentration of sweat decreases with profuse perspiration,
thereby increasing solute-free water loss
II. Renal Water Loss (Most Common Cause of Hypernatremia)

Drug Induced Diuresis

Osmotic Diuresis (Hyperglycemia, Glucosuria, IV Mannitol)

Diabetes Insipidus
III. Primary Na+ Gain

CAUSES OF HYPOKALEMIA VS. HYPERKALEMIA

HYPOKALEMIA
I. Decreased Intake
A. Starvation
B. Clay Ingestion
II. Redistribution into Cells
A. Acid-Base: Metabolic Alkalosis
B. Hormonal

Insulin

B2-Adrenergic Agonists (Endogenous or Exogenous)

A-Adrenergic Antagonists
C. Anabolic State

Vitamin B12 or Folic Acid (RBC production)

Granulocyte-Macrophage Colony Stimulating Factor (WBC production)

Total Parenteral Nutrition

D. Other

Pseudohypokalemia

Hypothermia

Hypokalemic Periodic Paralysis

Barium Toxicity
II. Increased Loss
A. Non-Renal

GI Loss (Diarrhea)

Integumentary Loss (Sweat)

B. Renal

HYPERKALEMIA
I. Renal Failure
II. Decreased Distal Flow
(ie. Decreased Effective Circularing Arterial Volume)
III. Decreased K+ Secretion
A. Impaired Na+ Reabsorption

Primary Hypoaldosteronism: Adrenal insufficiency,

Adrenal enzyme deficiency (21-Hydroxylase, 3BHydroxysteroid Dehydrogenase, Corticosterone Methyl
Oxidase)

Secondary Hypoaldosteronism: Hyporeninemia, Drugs

(ACE inhibitors, NSAIDs, Heparin)

Resistance to Aldosterone: Pseudohypoaldosteronism,

Tubulo-Interstitial Disease, Drugs (K+ Sparing
Diuretics, Trimethroprim, Pentamidine)
B. Enhanced Cl- Reabsorption (Chloride Shunt)

Gordons Syndrome

Cyclosporine

Increased Distal Flow: Diuretics, Osmotic Diuresis, Salt Wasting Nephropathies

Increased Secretion of K+
- Mineralocorticoid Excess: 10 Hyperaldosteronism, 20 Hyperaldosteronism
(Malignant HPN, Renin-Secreting Tumors, Renal Artery Stenosis, Hypovolemia),
apparent Mineralocorticoid Excess (Licorice, chewing tobacco, carbenoxolone),
Congenital Adrenal Hyperplasia, Cushing Syndrome, Bartters Syndrome)
- Distal Delivery of Non-Reabsorbed Anions: Vomiting, Nasogastric Suction,
Proximal (Type 2) Renal Tubular Acidosis, DKA, Glue-Sniffing (Toluene Abuse),
Penicillin Derivatives
- Other: Amphotericin-B, Liddles Syndrome, Hypomagnesemia

11

1) SODIUM & WATER

Water is the Most Abundant Constituent of the body, comprising approximately 50% in Women and 60% in Men
Total Body Water = 55-75% Intracellular Fluid + 25-45% Extracellular Fluid
Osmolality: Solute or Particle Concentration of a fluid

I. EXTRACELLULAR FLUID
Extracellular Fluid = Intravascular (Plasma Water) + Extravascular (Interstitial) Spaces
Major ECF Particles = Na+ and Anions (Cl- and HCO3)
Major ICF Particles = K+ and Organic Phosphate Esters (ATP, Creatine Phosphate, and Phospholipids)
Solutes that are restricted to the ECF or the ICF determine the Effective Osmolality (or Tonicity) of that compartment. Since Na+ is largely
restricted to the ECF, Total Body Na+ Content is a reflection of ECF Volume. Likewise, K+ and its attendant anions are predominantly
limited to the ICF and are necessary for Normal Cell Function

II. WATER BALANCE

Normal Plasma Osmolality is 275 290 mosmol/kg
Disorders of water homeostasis result in Hypo- or Hypernatremia
Normally, about 600 mosmols must be Excreted per day, and since the maximal urine osmolality is 1200 mosmol/kg, a
Minimum Urine Output of 500 mL/d is required for neutral solute balance
**NOTE: Arginine Vasopressin (AVP, ADH)
o Synthesized in the Supraoptic and Paraventricular Nuclei of Hypothalamus; Secreted by Posterior Pituitary
o Net Effect: Passive Water Reabsorption along an Osmotic Gradient
o Major Stimulus for AVP Secretion: HYPERTONICITY
III. SODIUM BALANCE
Sodium is actively pumped out of cells by the Na-K-ATPase Pump
Result = 85-95% of Na+ is EXTRACELLULAR

2) HYPOVOLEMIA

True Volume Depletion refers to a state of combined Salt and Water Loss exceeding intake, leading to ECF Volume
Contraction (loss of Na+ may be Renal or Extrarenal)

Causes of HYPOVOLEMIA
1. ECF Volume Contracted:

Extrarenal Na+ Loss: GI (vomiting, diarrhea, etc), Skin/Respiratory (insensible losses, sweat, burns), Hemorrhage

Renal Na+ and Water Loss: Diuretics, Osmotic Diuresis, Hypoaldosteronism, Salt-Wasting Nephropathies

Renal Water Loss: Diabetes Insipidus (Central or Nephrogenic)

2. ECF Volume NORMAL or Expanded:

Decreased Cardiac Output: Muyocardial, Valvular or Pericardial Disease

Redistribution: Hypoalbuminemia (Hepatic Cirrhosis, Nephrotic Syndrome), Capillary Leak (Acute Pancreatitis, Ischemic
Bowel, Rhabdomyolysis)

Increased Venous Capacitance: Sepsis

A. Pathophysiology
o ECF Volume Contraction is manifest by a decreased plasma volume and HYPOTENSION
o Hypotension: due to Decreased Venous Return (Preload) and diminished Cardiac Output
B. Clinical Features
o Most Symptoms: non specific and secondary to electrolyte imbalances and tissue hypoperfusion
o More Severe Volume Contraction: End Organ Ischemia (Oliguria, Abdominal and Chest Pain, Confusion)

12

3) HYPONATREMIA / HYPERNATREMIA
I. HYPONATREMIA: Plasma Na+ < 135 mmol/L
Clinical Features: related to Osmotic Water Shift, leading to Increased ICF Volume, specifically Brain Cell Swelling or
Cerebral Edema (symptoms are primarily neurologic)
Stupor, Seizures & Coma do NOT usually occur unless the Plasma Na + concentration falls < 120mmol/L or decreases rapidly
II. HYPERNATREMIA: Plasma Na+ > 145 mmol/L
Hypernatremia is a state of HYPEROSMOLALITY
Majority of cases result from the LOSS of WATER
Clinical Features: As a consequence of Hypertonicity, water shifts OUT of cells, leading to a Contracted ICF Volume a
decrease in Brain Cell Volume is associated with an Increased Risk of Subarachnoid or Intracerebral Hemorrhage

4) HYPOKALEMIA / HYPERKALEMIA
I. HYPOKALEMIA: Plasma K+ Concentration < 3.5 mmol/L
May result from: Decreased Net Intake, Shift into Cells, Increased Net Loss
Clinical Features: Symptoms seldom occur unless the Plasma K+ Concentration is < 3 mmol/L
A. ECG Changes:
o Due to Delayed Ventricular Repolarization and do NOT correlate well with Plasma K + Concentration
o Severe K+ Depletion: Increased Risk of Ventricular Arrhythmias
o Hypokalemia also predispose to Digitalis Toxicity
1. Early Changes:

Flattening or Inversion of T-Wave

Prominent U Wave
ST-Segment Depression
Prolonged QU Interval

2. Severe K+ Depletion

Prolonged PR Interval
Decreased Voltage
Widening of QRS Complex

B. Management
o Correct K+ Deficit and Minimize ongoing losses
II. HYPERKALEMIA: Plasma K+ Concentration > 5.0 mmol/L
Occurs as a result of either K+ Release from Cells or Decreased Renal Loss
Most Serious Effect: Cardiac Toxicity
Potentially Fatal Hyperkalemia RARELY occurs unless the Plasma K + is > 7.5 mmol/L and is usually associated with:
o
o
o

Profound Weakness
Absent P-Waves
QRS Widening
Ventricular Arrhythmias

A. ECG Changes
o Earliest Finding: Increased T-Wave Amplitude (Peaked T-Waves)
o More Severe Degrees of Hyperkalemia:

Prolonged PR Interval & QRS duration

AV Conduction Delay
Loss of P-Waves

**NOTE: Progressive Widening of QRS Complex & merging with the T-Wave produces a Sine Wave Pattern
Terminal Event is usually Ventricular Fibrillation or Aystole
B. Treatment
o Calcium Gluconate: decreases membrane excitability
o Insulin: causes K+ to shift into cells
o IV NaHCO3: can also shift K+ into cells
o B2-Adrenergic Agonists: promote cellular uptake of K
o Loop and Thiazide Diuretics
o Sodium Polystyrene Sulfonate (Cation-Exchange Resin)
o Hemodialysis

13

5) HYPOCALCEMIA / HYPERCALCEMIA

Calcium Ion plays a critical role in normal cellular function and signaling, regulating diverse physiologic processes such as
neuromuscular signaling, cardiac contractility, hormone secretion, and blood coagulation
Extracellular Ca2+ Concentrations are maintained w/in exquisitely narrow range thru a series of feedback mechanisms that involve:
o
o

Parathyroid Hormone (PTH)

Active Vitamin-D Metabolite 1,25-Dihydroxyvitmin-D (1,25(OH)2D)

QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

A decrease in ECF Ca2+ triggers an Increase in Parathyroid Hormone

Secretion (1) via Activation of the Calcium Sensor Receptor on
Parathyroid Cells.
PTH, in turn, results in Increased Tubular
Reabsorption of Ca2+ by the Kidney (2) and Resorption of Calcium from
Bone (2) and also stimulates Renal 1,25(OH)2D Production (3).
1,25(OH)2D, in turn, acts principally on the Intestine to Increase
Calcium Absorption (4). Collectively, these homeostatic mechanisms
serve to restore Serum Ca2+ Levels to Normal.

I. HYPOCALCEMIA
May be asymptomatic if the decreases in Serum Ca2+ are relatively Mild and Chronic, or they may present with LifeThreatening Complications
Moderate to Severe Hypocalcemia: Paresthesias, usually of the fingers, toes, and circumoral regions, and is caused by
Increased Neuromuscular Irritability
Chvosteks Sign: Twitching of the Circumoral Muscles in response to gentle tapping of the facial nerve just anterior to the
ear may be elicited
Trousseaus Sign: Carpal Spasm may be induced by inflation of a BP cuff to 20mmHg above patients systolic BP for 3mins
Severe Hypocalcemia can induce Seizures, Carpopedal Spasm, Bronchospasm, Laryngospasm, and Prolongation of QT-Interval
II. HYPERCALCEMIA
A. Clinical Manifesations
Mild Hypercalcemia
(up to 11 11.5 mg/dL

More Severe Hypercalcemia

(>12-13 mg/dL)

Usually Asymptomatic and recognized only on routine Calcium Measurements

Some may complain of vague Neuropsychiatric Symptoms
Trouble concentrating, personality changes, or depression
Peptic Ulcer Disease or Nephrolithiasis, Increased Fracture Risk
Lethargy, Stupor, Coma
GI Symptoms: nausea, anorexia, constipation, pancreatitis
Decreased Renal Concentrating Ability Polyuria and Polydipsia

B. Hypercalcemia can present with ECG Changes:

o
o

Bradycardia
AV Block
Short QT Interval

o
C. Management (from Endorsements)
1. IV-Hydration

Patients presenting with Hypercalcemia are volume-depleted already by ~2L

If we hydrate, we improve perfusion to kidneys, we Increase Calcium Excretion

2. Bisphosphanates

Inhibits activity of Osteoclasts, thereby inhibiting RESORPTION

3. Diuretics

Give Loop Diuretics

This will enhance excretion of Ca2+ -- when you give Diuretics, make sure to hydrate the patient
4. Dialysis (In Severe Hypercalcemia, refractory to the usual therapy)

C. Complications of Hypercalcemia
o

Arrhythmias
Deposition of Calcium in Vessels, Nephrocalcinosis, etc

14

6) HYPOGLYCEMIA

Most commonly caused by drugs used to treat DM or by exposure to other drugs, including alcohol
The lower limit of the Fasting Plasma Glucose in NORMALLY 70mg/dL (3.9mmol/L)
Glucose Levels < 55mg/dL (3.0mmol/L) with symptoms that are relieved promptly after the glucose level is raised
document Hypoglycemia

I. WHIPPLES TRIAD
1) Symptoms consistent with Hypoglycemia
2) Low Plasma Glucose concentration measured with a precise method (Not a Glucose Monitor)
3) Relief of those symptoms after the Plasma Glucose Level is raised
II. ENDORSEMENT NOTES:
If there is Hypoglycemia, catecholamines will ELEVATE (ex. jittery, tachycardia, palpitations, sweating, tremors)
Late Phase: Patient is already Obtunded
III. CLINICAL MANIFESTATIONS
Neuroglycopenic Symptoms of hypoglycemia are the direct result of CNS Glucose Deprivation
Symptoms: Behavioral changes, confusion, fatigue, seizure, loss of consciousness, and if severe death
Neurogenic (or Autonomic) Symptoms of Hypoglycemia are the result of the perception of physiologic changes caused by
the CNS-Mediated Sympathoadrenal Discharge triggered by Hypoglycemia
IV. TREATMENT OF HYPOGLYCEMIA
Readily absorbable Carbohydrates (eg. Glucose and Sugar-Containing Beverages)
IV Dextrose Initial Bolus of 20-50mL 50% Dextrose should be given immediately, followed by Infusion of D5W (or
D10W) to maintain Blood Glucose above 100mg/dL
Glucagon 1mg IM (or SC)

NOTES ON RENAL ABNORMALITIES

I. REMEMBER: 2-3-4-5
> 2x a night is Nocturia
> 3 L/day is Polyuria
< 400 mL is Oliguria
< 50 mL is Anuria

Furosemide = Binds to ALBUMIN

Therefore, do NOT give Furosemide in patients with Hypoalbuminemia

Instead, we can give Bumetamide

In Harrisons: Oliguria refers to a 24 hours urine output of < 500mL, and Anuria is the
complete absence of urine formation (< 50mL)

II. IN CKD, WE GIVE BLOCKING THERAPY

1) CaCO3
**NOTE: If Calcium x Phosphate x 12 is < 70 we can give CaCO3

If > 70, we DONT given CaCO3, because we run the risk of Metastatic Calcification
2) NaHCO3
3) FeSO4
III. ACE INHIBITORS AND CKD
For Diabetic Patients and those with Chronic Kidney Disease = choice of HPN is ACE Inhibitors or
Angiotensin-II Antagonists to delay Diabetic Nephropathy
For End-Stage Renal Disease Patients: CAUTION on ACE-Inhibitors use Calcium-Antagonists, Diureticsm and
Centrally Acting Agents
In giving ACE Inhibitors, watch out for HYPERKALEMIA (especially in End Stage Renal Disease Patients)
Potassium Homeostasis in CKD
In CKD, the decline in GFR is NOT necessarily accompanied by a parallel decline in urinary K + Excretion, which is predominantly
mediated by aldosterone-dependent secretory events in the distal nephron segments.
Some medications can inhibit potassium entry into cells and renal K+ excretion. The most important medications in this respect in
clued ACE-Inhibitors, ARBs, Spironolactone and other K+-sparing diuretics such as amiloride, eplerone, triamterene.

15

IV. CRITERIA FOR INITIATING PATIENTS ON MAINTENANCE DIALYSIS

Presence of Uremic Symptoms
Presence of Hyperkalemia unresponsive to Conservative Measures
Persistent Extracellular Volume Expansion despite Diuretic Therapy
Acidosis Refractory to Medical Therapy
Bleeding Diathesis
Creatinine Clearance or Estimated GFR below 10 mL/min per 1.73m2
Clinical Abnormalities in UREMIA (page 1763 for complete list)
o
o
o
o
o
o
o

Fluid and Electrolyte Disturbance

Endocrine Metabolic Disturbances (Hyperuricemia, 2 0 Hyperparathyroidism, Osteomalacia)
Neuromuscular Disturbances (fatigue, headache, sleep disorders, lethargy, etc)
Cardiovascular & Pulmonary Disturbances (Pericarditis, CHF, Pulmonary Edema, etc)
Dermatologic Disturbances (pallor, pruritus, ecchymoses, hyperpigmentation, uremic frost)
Gastrointestinal Disturbances (anorexia, nausea, vomiting, uremic fetor, GI bleeding)
Hematologic and Immunologic Disturbances (anemia, lymphocytopenia)

V. ALBUMIN (IN URINALYSIS)

Trace = 0.05 0.2 g/L
+1 = 0.3 g/L
+2 = 1.0 g/L
+3 = 3.0 g/L
+4 = > 20 g/L

VI. SUGAR (IN URINALYSIS)

Trace = 5mmol/L
+1 = 15
+2 = 30
+3 = 60
+4 = 120

Polyuria > 3L/d. A 24 hour urine collection is

needed for this evaluation. Results from either:

1) Excretion of nonabsorbable solutes (eg.

Glucose); or

2) Excretion of water (usually from a

defect in ADH production or renal
responsiveness)

16

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NEUROLOGY
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Jaime Alfonso Manalo Aherrera, M.D.

Internal Medicine Notes 2009

NEUROLOGIC SYMPTOMS

1) NERVOUS SYSTEM DYSFUNCTION

I. SYNCOPE
Transient loss of consciousness & postural tone due to reduced Cerebral Blood Flow (associated with spontaneous recovery)
Causes of Syncope:
o Disorders of Vascular Tone or Blood Volume
o Cardiovascular Disorders (Obstructive Lesions, Cardiac Arrhythmias)
o Cerebrovascular Disease
II. CONFUSION AND DELIRIUM
Confusion: Mental and behavioral state of reduced comprehension, coherence, and capacity to reason
Delirium: Acute confusional state
A. Common Etiologies of Delirium (page 160):
o
o
o
o
o
o
o
o
o

Toxins
Metabolic Conditions
Infections
Endocrinologic Conditions
Cerebrovascular Disorders
Autoimmune Disorders
Seizure-Related Disorders
Neoplastic Disorders
Hospitalization
Terminal End of Life Delirium

B. Step-Wise Evaluation of a Patient with Delirium:

1. Initial Evaluation

History, PE

CBC, Electrolytes (including Ca2+, Mg2+, P)

Liver Function Tests including Albumin

Renal Function Tests

2. First Tier Further Evaluation Guided by Initial Evaluation

Systemic Infection Screen: U/A and Culture, CXR, Blood Culture

ECG, ABG, Toxcology Screen

Brain Imaging

If suspecting a CNS Infection: Lumbar Puncture following Brain Imaging

If suspecting Seizure-Related Etiology: EEG

3. Second Tier Further Evaluation

Vitamin levels: B12, Folate, Thiamine

Endocrinologic: TSH, FT4, Cortisol

Serum Ammonia

Sedimentation Rate

ANA, Complement Levels, p-ANCA, c-ANCA

Infectious Serologies: RPR, Fungal & Viral, HIV

Lumbar Puncture
Brain MRI

III. UPPER MOTOR NUERON LESION VS LOWER MOTOR NEURON LESIONS

SIGN
UPPER MOTOR NEURON LOWER MOTOR NEURON
Atrophy
None
Severe
Fasciculations
None
Common
Tone
Spastic
Decreased
Distribution of Weakness
Pyramidal / Regional
Distal / Segmental
Tendon Reflexes
Hyperactive
Hypoactive / Absent
Babinskis Sign
Present
Absent

MYOPATHIC
Mild
None
Normal / Decreased
Proximal
Normal / Hypoactive
Absent

2) SEIZURES
I. SYNCOPE VS SEIZURES

The diagnostic dilemma encountered most often is the distinction between a Generalized Seizure and Syncope

Features that distinguish Generalized Tonic Clonic Seizure from Syncope include:
FEATURES
SEIZURE
SYNCOPE
Immediate Precipitating Factors
Usually none
Emotional stress, Valsalva, Orthostatic
Hypotension, Cardiac Etiologies
Premonitory Symptoms
None or Aura (eg. Odd Odor)
Tiredness, nausea, diaphoresis, tunneling of vision
Posture at Onset
Variable
Usually erect
Transition to Unconsciousness
Often Immediate
Gradual over seconds
Duration of Unconsciousness
Minutes
Seconds
Duration of Tonic or Clonic Movements
30 60 s
Never more than 15 s
Facial Appearance during event
Cyanosis, Frothing of Mouth
Pallor
Disorientation & Sleepiness after event
Many minutes to hours
< 5 minutes
Aching of Muscles after event
Often
Sometimes
Biting of Tongue
Sometimes
Rarely
Incontinence
Sometimes
Sometimes
Headache
Sometimes
Rarely
II. CLASSIFICATION OF SEIZURES
A. Partial Seizures
o Seizures occur within Discrete Regions of the brain
o Divided into: Simple Partial Seizures + Complex Partial Seizures
Simple Partial Seizures
If Consciousness is FULLY PRESERVED during the seizure, the clinical manifestations are
considered relatively SIMPLE and the seizure is termed Simple Partial Seizures
Complex Partial Seizures

If Consciousness is IMPAIRED, the symptomatology is more complex and the seizure is termed
Complex Partial Seizure

B. Generalized Seizures
o Arise from BOTH Cerebral Hemispheres simultaneously
o Defined as bilateral clinical and electrographic events without any detectable focal onset
Absence Seizures
Sudden, brief, lapses of consciousness without loss of postural control.
(Petit Mal)
Lasts for only a few seconds, consciousness returns as suddenly as it was lost, and there is NO
postictal confusion
Atypical Absence
Have features that deviate both clinically and electrophysiologicaly from typical absence seizures (ex.
Seizures
Lapse of consciousness is usually of longer duration & less abrupt in onset and cessation, and the
seizure is accompanied by more obvious motor signs that may include focal or lateralizing features)
Generalized Tonic
Clonic Seizures
(Grand Mal)

Primary generalized, tonic-clonic seizures are the main seizure type in ~10% of all persons with
Epilepsy. Most common seizure type resulting from metabolic derangements. Begins abruptly
without warning, although some with vague premonitory symptoms in the hours leading up to the
seizure.
Initial Phase (Tonic Phase): Tonic contraction of muscles throughout the body. Respiration
impaired, secretions pool in oropharynx, cyanosis develops. Marked enhancement of sympathetics
leads to increased HR, BP and papillary size.
Clonic Phase: After 10-20 sec, Tonic phase evolves into the Clonic Phase. Produced by
superimposition of periods of muscle relaxation on the tonic muscle contraction. The periods of
relaxation progressively increase until the end of the Ictal Phase, which lasts no more than 1 minute.
Post Ictal Phase: unresposinveness, muscular flaccidity, excessive salivation, bladder / bowel
incontinence. Patients gradually regain consciousness over minutes to hours (there is a period of
postictal confusion)

Atonic Seizures

Sudden loss of postural muscle tone lasting 1 to 2 seconds. Consciousness is briefly impaired, but
there is usually no post ictal confusion

Myoclonic Seizures

Sudden and brief muscle contraction that may involve one part of the body or the entire body.

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PULMONOLOGY
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Jaime Alfonso Manalo Aherrera, M.D.

Internal Medicine Notes 2009

PULMONARY DISEASES

1) PULMONARY TUBERCULOSIS
I. CLASSIFICATION OF TB (ATS)
CLASS
DESCRIPTION
ATS Class 0
No Exposure
(-) PPD
ATS Class 1
(+) Exposure
(-) PPD

ATS Class 2:
TB Infection

(+) Exposure
(+) PPD
(-) Target Organ TB Lesion

ATS Class 3:
PTB Active

See Table Below

ATS Class 4:
Previous PTB
Disease

ATS Class 5:
PTB Suspect

TREATMENT
BCG in high prevalence area
If with recent exposure:
Give Primary Prophylaxis: HR for 4 months or HE for 6 months
Repeat PPD in 2 Months
-if (+): Treat as Class 2
-if (-): Stop Primary Prophylaxis
70% of adult Filipinos are (+) for PPD, and are therefore naturally infected
If with recent PPD Conversion, give Primary Prophylaxis HR for 4 months or
HE for 6 months
If NOT a recent PPD converter, but currently exposed to a TB Case, give
primarily Prophylaxis as above
If NOT a recent PPD converter and NO Family member has Active TB, may
NOT give Primary Prophylaxis
See Table Below

ATC Class 3 patients are

further subdivided into
WHO Category I, II, III
Eg. CXR with Minimal
Infiltrates, but NO
Symptoms of Active
Disease or Previously
treated PTB
Check previous CXR
Reclassify patient into Class III or Class IV in 2-3 Months using Sputum Bacteriology or Serial X-Ray Changes

II. TREATMENT REGIMEN FOR ATS CLASS 3 PATIENTS (TB ACTIVE)

WHO
TB PATIENTS
ALTERNATIVE TB TREATMENT REGIMEN
CATEGORY
Initial Phase
Continuation Phase
I*
New Smear-Positive PTB
New Smear-Negative PTB w/ extended parenchymal
involvement
New cases of Severe Forms of Extra-Pulmonary TB
II

2 HRZE

4 HR

2 HRZES and 1 HRZE

5 HRE

2 HRZE

4 HR

Sputum Smear-Positive: Relapse

Treatment Failure
Treatment after Interruption

III **

New Smear-Negative PTB (other than in Category I)

New Less Severe Forms of Extra-Pulmonary TB

* Give this regimen if with High Bacterial Load, Cavitary Lesions, AFB + 4 Smears, or High Community Resistance (eg NCR,
Davao, Zamboanga, Cavite, Pampanga)
If with Cavitary Disease, give Streptomycin IM Alternate Days (60 Doses) instead of Ethambutol
** May give this cheaper regimen for Newly Diagnosed TB and those cases found in Low Community Resistance

III. NOTES FROM BLUE BOOK

A. Indications of Active Disease
o (+) AFB Sputum Smear (at least 2+) or (+) TB Culture
o (+) Symptoms: Constitutional symptoms are more reliable than local symptoms
o Increase in CXR Infiltrates (usually apical)
B. Indications of Inactive Disease
o Six Months interval with NO change in CXR infiltrates and NO constitutional symptoms
o Preferable with History of Completed TB Therapy
C. Indications of Favorable Disease Response
o Completion of prescribed treatment
o Conversion of Sputum Smear and Culture to Negative
o Resolution of Constitutional Symptoms
o Resolution or Improvement of Local Symptoms
D. Multiple Drug Resistant TB (MDRTB) and Extremely Drug Resistant Tuberculosis (XDRTB)
1. Multiple Drug Resistant Tuberculosis (MDRTB)
Infection with strain of M. tuberculosis which shows in-vitro resistance to at least Isoniazid ad Rifampicin
Suspect in TB patients who are still Sputum Smear or Culture Positive despite 3 months of adequate Tx
2. Extremely Drug Resistant Tuberculosis (XDRTB)
MDRTB Plus Resistance to Fluoroquinolones and an IV Aminoglycoside
NOTE: NO Effective Treatment regimen avilable
IV. DOSAGE OF DRUGS
DRUG
H: Isoniazid (INH)

CHILDREN
5 mg/kg/day

300-400mg PO

ADULTS

R: Rifampicin (R)

10-20 mg/kg/day

450-600mg PO

Z: Pyrazinamide (Z)

20-30 mg/kg/day

1500mg/day PO

E: Ethambutol (E)

15-20 mg/kg/day

800-1000mg/day PO

S: Streptomycin (S)

10-18 mg/kg/day

1gram IM

V. ALGORITHM FOR DIAGNOSIS OF PTB: CPM GUIDELINES (2008)

TB SYMPTOMATIC
(COUGH for 2 weeks of more)
Three (3) Sputum Collection
2 or 3 Smear (+)

Only ONE (1) Smear Positive

Classify as
SMEAR POSITIVE TB

All THREE (3) Smear Negative

Collect another 3 Sputum Specimens

Immediately

Refer to Physician (Symptomatic Tx for 2-3 wks)

If Symptoms Persist, request for CXR

At least ONE Smear Positive?

Abnormal Findings on CXR
Yes

No
Request for CXR

Yes

No

TB Diagnostic Committee

No Abnormal Findings
on CXR

Consistent with Active TB?

Yes

No

Consistent with Active TB

Observation / Further Exam,

If necessary
Yes
Classify as
SMEAR NEGATIVE TB

No
Not Consistent with
Active TB

Collection of Sputum Specimens

o First Specimen (Spot Specimen): collected at time of consultation, or as soon as the TB symptomatic is identified
o Second Specimen: very first sputum produced early in the morning immediately after waking up. It is collected by
the patient according to instructions given by the DOTS facility staff
o Third Specimen (Second Spot Specimen): collected when TB symptomatic comes back to the DOTS facility to
submit the second specimen
**NOTE: Pulmonary Nodule VS Mass:
o Pulmonary Nodule is < 3 cm on CXR

VI. NATIONAL TB CONTROL PROGRAM MANUAL OF PROCEDURES, 2005

A. Definition of Terms
TB Symptomatic

Active Case Finding

Passive Case Finding

Any person with cough for two or more weeks with or without the following symptoms:

Chest and/or back pains not referable to any other musculo-skeletal disorders

Hemoptysis or recurrent blood streaked sputum

Significant weight loss

Other symptoms: Sweating, fatigue, body malaise, shortness of breath

A health workers purposive effort to find TB cases who do not consult with personnel in a DOTS Facility
Finding TB cases among TB symptomatics who present themselves in a DOTS facility

B. Formulation of Anti-TB Drugs

o Fixed Dose Combination (FDCs) two or more first line drugs are combined in one tablet
o Single Drug Formulation (SDF) each drug is prepared individually
C. Classification of TB Cases
LOCATION OF
SPUTUM SMEAR
LESION
EXAMINATION
Pulmonary TB (PTB) Smear Positive

Smear Negative

DEFINITION OF TERMS
1.

A patient with at least 2 Sputum Specimens Positive for AFB, with or

without Radiographic Abnormalities consistent with Active TB;
or
2. A patient with 1 Sputum Specimen Positive for AFB and with
Radiographic Abnormalities consistent with Active TB as determined by a
Clinician;
or
3. A Patient with one Sputum Specimen positive for AFB with Sodium
Culture Positive for M. tuberculosis
A Patient with at least 3 Sputum Specimens Negative for AFB with Radiographic
Abnormalities consistent with Active TB, AND
There has been no Response to a Course of Antibiotics and/or Symptomatic
Medications, AND
There is a Decision by a Medical Officer to Treat the Patient with Anti-TB Drugs

Extrapulmonary TB

1.

2.

A patient with at least one Mycobacterial Smear / Culture Positive from an Extra-Pulmonary Site
(organs other than the Lungs = Pleura, Lymph Nodes, Genitourinary Tract, Skin, Joints & Bones,
Meninges, Intestines, Peritoneum and Pericardium, among others);
or
A patient with Histological and / or Clinical Evidence consistent with Active TB and there is a
Decision by a Medical Officer to Treat Patient with Anti-TB Drugs

D. Types of TB Cases
o TB Cases shall be Categorized based on the History of Anti-TB Treatment
o A thorough understanding on the Types of TB Cases is necessary in determining the correct Treatment Regimen
TYPE
New

DEFINITION OF TERMS
A patient who has NEVER had Treatment for TB or who has taken Anti-TB Drugs for LESS than One Month

Relapse

A patient previously treated for Tuberculosis, who has been declared Cured or Treatment Completed, and is
Diagnosed with Bacteriologically Positive (Smear or Culture) Tuberculosis

Failure

A patient who, while on Treatment, is Sputum Smear Positive at 5 Months or Later during the Course of Tx

Return after Default

(RAD)

A patient who returns to Treatment with Positive Bacteriology (Smear or Culture), following Interruption of
Treatment for Two Months or More

Transfer-In

A Patient who has been Transferred from another Facility with proper Referral Slip to continue Treatment

Other

All Cases who do NOT fit into any of the above definitions
This Group includes:

1) Patient who is Starting Treatment again after Interrupting Treatment for more than 2 Months and
has remained or became Smear-Negative

2) A Patient, who was initially Registered as New Smear-Negative Case, turned out to be Smear
Positive during Treatment, (The Treatment Outcome of this case is Treatment Failure. ReRegister as Other for the next treatment

3) Chronic Case: a Patient who is Sputum Positive at the End of a Re-Treatment Regimen

VII. SUMMARY OF TREATMENT MODIFICATION BASED ON T HE SPUTUM FOLLOW-UP RESULTS

A. Category-I
First 2 Months: HRZE
If (-)

If (+)

4 Months of HR
o
o

Another 1 Month of HRZE

If after 2 Months of HRZE you have Sputum Smear Negative, go directly to 4 Months of HR
BUT, if you still have Sputum Smear Positive, take HRZE for another month, then go to HR for 4 Months. This makes the
Intensive Phase 3 Months and a Total of 7 Months of Treatment

B. Category-II
First 2 Months: HRZES
1 Month of HRZE
If (-)

If (+)

5 Months of HRE

Another 1 Month of HRZE

C. Category-III

First 2 Months: HRZ

4 Months of HR
Sputum Smear is done at the end of 2nd Month

VIII. GUIDE IN MANAGING SCC DRUGS SIDE EFFECTS

SIDE EFFECTS
DRUGS RESPONSIBLE

WHAT TO DO?

Minor Side Effects Patient should be Encouraged to CONTINUE taking Medications

Gastro-Intestinal Intolerance
Rifampicin
Give medication at bedtime
Mild Skin Reactions
Any kind of Drugs
Give Anti-Histamines
Orange / Red Colored Urine
Rifampicin
Reassure the patient
Pain at Injection Site
Streptomycin
Apply Warm Compress
Burning Sensation in Feet due to
Isoniazid
Give Pyridoxine (Vitamin B6)
Peripheral Neuropathy
100-200mg daily for Treatment; 10mg daily for prevention
Arthralgia due to Hyperuricemia
Pyrazinamide
Give Aspirin or NSAID
If symptoms persist, consider Gout & give Allopurinol
Flu-Like Symptoms (Fever, Muscle Pain) Rifampicin
Give Anti-Pyretics
Major Side Effects Discontinue Taking the Medicines and refer to MHO / CHO immediately
Severe Skin Rash (Hypersensitivity)
Any Drug (especially Streptomycin)
Discontinue Anti-TB Drugs and refer to MHO / CHO
Jaundice due to Hepatitis
Any Drug (especially Isoniazid,
Discontinue Anti-TB Drugs and refer to MHO / CHO. If
Rifampicin. Pyrazinamide)
symptoms subside, resume treatment & monitor clinically
Impairment of Visual Acuity and Color
Vision due to Optic Neuritis
Hearing Impairment, Ringing of Ear and
Dizziness due to Damage of CN-VIII
Oliguria or Albuminuria due to Renal
Disorder

Ethambutol

Discontinue Ethambutol and refer to Ophthalmologist

Streptomycin

Discontinue Streptomycin and refer to MHO / CHO

Streptomycin
Rifampicin

Discontinue Anti-TB Drugs and refer to MHO / CHO

Psychosis and Convulsion

Thrombocytopenia, Anemia, Shock

Isoniazid
Rifampicin

Discontinue Isoniazid and refer to MHO / CHO

Discontinue Anti-TB Drugs and refer to MHO / CHO

IX. OUTCOME OF TREATMENT

Cured
A Sputum Smear Positive Patient 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 the Treatment, but does NOT meet the Criteria to be Classified as Cured of Failure

Died

Patient who DIES for any Reason during the Course of the Treatment

Treatment Failure

Patient who is Sputum Smear POSITIVE at Five Months or LATER during the Treatment. A Sputum Smear
Negative Patient initially who turned out to be Positive during Treatment

Defaulter

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

2) BRONCHIAL ASTHMA

Chronic inflammatory Disorder of the Airways; cells play a role: Mat Cells, Eosinophils, T-Lymphocytes, and Neutrophils
Monitoring Severity of Asthma: Peak Expiratory Flow Meter is practical and is recommended for use in both initial
assessment and in monitoring severity of asthma

I. CLASSIFICATION OF ASTHMA (ACCORDING TO SEVERITY)

Mild Intermittent
Mild Moderate Persistent
Severe Persistent
PARAMETERS
Mild Intermittent

CHRONIC ASTHMA SEVERITY

Mild-Moderate Persistent

Severe Persistent

Daytime Symptoms

Monthly

Weekly

Daily

Night Awakening

Less than Monthly

Monthly to Weekly

Nightly

Rescue B2-Agonist Use

Less than Weekly

Weekly to Daily

Several Daily

PEF or FEV1

> 80% of Predicted

60-80% of Predicted

< 60% of Predicted

Treatment needed to
control

Occasional use of B2 Agonists

Regular use of Inhaled

Corticosteroid and Long-Acting
B2 Agonists

Use of Combination of Inhaled

Corticosteroids, Long-Acting B2
Agonist Plus Oral Steroids

II. TREATMENT
Control of Triggers
Goals of Pharmacologic Treatment: Achieve CONTROL of Asthma
o 1) Minimal (ideally none) chronic symptoms, including nocturnal symptoms
o 2) Minimal (Infrequent) Exacerbations
o 3) Minimal need for PRN B2-Agonists, ideally none
o 4) No Limitations on activities, including exercise
o 5) Near Normal PEFR
o 6) PEF Variability < 20%
o 7) Minimal (or no) adverse effects from treatment
III. GINA CLASSIFICATION (Levels of Asthma Control)
CONTROLLED
Daytime Symptoms
None (twice or less/week)
Limitation of Activities
None
Nocturnal Symptoms (Awakening)
None
Need for Reliever
None (twice or less/week)
Lung Function
Normal
Exacerbation
None

PARTLY CONTROLLED
> 2x / week
Any
Any
More than twice/week
< 80% Predicted
> 1x / year

UNCONTROLLED
Three or more symptoms
of Partly Controlled
Asthma in any week

One in any week

IV. DRUGS USED TO TREAT ASTHMA

A. Controllers:
o Useful in achieving and keeping Persistent Asthma under control
o They are also called Preventers
o Include the following:
Anti-Inflammatory Agents (Corticosteroids)
Anti-Allergic Medications
Long Acting Bronchodilators
Anti Inflammatory Agents
(Corticosteroids)

Inhaled:
Beclomethasone Dipropionate (Qvar Metered Dose Inhaler)
Budesonide (Budecort Turbuhaler / Primavent Metered Dose Inhaler)
Oral / Systemic:
Prednisone (Orasone)
Methylprednisolone (Medrol)

Long Acting Bronchodilators

Long Acting B2 Agonist

Formoterol Fumarate (Inhaled)
Salbutamol (Oral / Systemic)
Bambuterol (Oral / Systemic)
Long Acting Theophylline (Sustained Release Formulation)
Nuelin SR

Combined Corticosteroids and

Long Acting Bronchidilators

Formoterol and Budenoside (Symbicort Turbuhaler)

Salmeterol and Fluticasone

Leukotriene Receptor
Antagonists

Montelukast Na (Kastair, Singulair)

Zafirlukast (Accolate)

B. Relievers
o Reverse Airflow Obstruction and QUICKLY relieve its accompanying symptoms such as cough, dyspnea, wheezing
and chest tightness
o Consists mainly of Short Acting Bronchodilators
Short-Acting Bronchodilators

Short Acting B2-Agonists

1. Inhaled:
Salbutamol (Ventolin / Asmalin / Librentin Metered Dose Inhaler)
Procaterol (Meptin Air MDI)
Terbutaline Sulfate (Bricanyl Turbuhaler)
Terbutaline Sulfate (Bricanyl Metered Dose Inhaler)
2. Oral / Systemic
Salbutamol (Ventolin)
Procaterol (Meptin)
Terbutaline Sulfate (Bricanyl)
Terbutaline Sulfate, Guiafenesin (Bricanyl Expectorant Syrup)
Short Acting Theophylline (Regular Formulations)
Neulin Tab
Brondil Tab

Anti-Cholinergic Agents

Ipratropuim Bromide (Atrovent)

Combined Anti-Cholinergics
and Short Acting B2 Agonists

Ipratropium Bromide + Salbutamol (Combivent Metered Dose Inhaler)

IV. MANAGEMENT OF CHRONIC ASTHMA: HOME TREATMENT

CLASSIFICATION
CONTROLLER USED
Step 1: Mild Intermittent
NONE
Step 2: Mild-Moderate Persistent

Step 3: Severe, Persistent

RELIEVER USED
Inhaled Short Acting B2 Agonist
PRN Only, NOT > 3x/week

Daily Medication:
Inhaled Corticosteroids PLUS Long Acting
B2 Agonists

Inhaled Short Acting B2 Agonist, NOT to

exceed 3-4x/day

Daily Medication:

Inhaled Short-Acting B2 Agonist, NOT to

exceed 3-4x/day

Inhaled Corticosteroids PLUS Long Acting

B2 Agonists (eg. Seretide or Symbicort
Inhaler)
Oral Steroid > 7.5mg daily or alternate days

Consider Inhaled Ipratropium Bromide

(Seretide or Symbicort Inhaler)

Add inhaled Ipratropium Bromide

Guide to Treatment Plan:

Patients should start treatment at the step most appropriate to the initial severity of the condition. A Rescue Course of prednisone
may be needed at any time and any step

When to Step Up: If control is not achieved, consider step up. But first review patient medication technique, compliance and
environmental control

When to Step Down: Review treatment every 3-6 months. If control is sustained for at least 3 months, a gradual stepwise reduction
in treatment may be started

V. CLASSIFICATION OF ANTI-ASTHMA DRUGS

A. Sympathetic Agonists:
1. A1, B1, B2 Agonists
Epinephrine
Ephedrine

**NOTE: Epinephrine & Isoproterenol are not commonly used

because of their effect on the Heart (B1 Receptors)

2. B1, B2 Agonists
Isoproterenol
3. Selective B2-Agonists
SHORT ACTING
Terbutaline
Albuterol
Levalbuterol
Mataproterenol
Pirbuterol
B. Methylxanthines
o Theophylline
o Aminophylline
o Anhydrous Theophylline
o Theobromine
o Caffeine

LONG ACTING
Salmeterol
Bitolterol
Formeterol

Zileuton

C. Anticholinergics
o Ipatropium Bromide
o Atropine Methylnitrate
D. Leukotriene Modifying Drugs
o Zafirlukast
o Montelukast

E. Glucocorticoids
INHALED CORTICOSTEROIDS
Beclomethasone Dipropionate
Triamcinolone Acetonide
Flunisolide
Budesonide
Fluticasone propionate

SYSTEMIC CORTICOSTEROIDS
Prednisone
Hydrocortisone Sodium Succinate

F. Cromolyn Sodium

VI. BASIC MECHANISMS OF SOME DRUGS IN ASTHMA

ATP
Adenylyl Cyclase

Beta Agonists

Bronchodilation
(+)
cAMP
BRONCHIAL TONE

Phosphodiesterase

Antimuscarinics
Acetylcholine

Theophylline
(+)

AMP

(+)
Adenosine
Theophylline
Bronchoconstriction
A. Beta Agonists
o Stimulates the enzyme Adenylyl Cyclase to enhance cAMP
o Increased cAMP causes BRONCHODILATION
B. Theophylline
o Inhibits Phosphodiesterase so that there is an accumulation of cAMP BRONCHODILATION
o Inhibits Adenosine from causing Bronchoconstriction
o Disadvantage = lots of side effects
C. Antimuscarinics (Muscarinic Antagonists)
o Block the effects of Acetylcholine from causing Bronchoconstriction
o Includes: Ipratropium and Atropine

10

VII. MANAGEMENT OF ACUTE EXCACERBATIONS OF ASTHMA: HOME TREATMENT

Assess SEVERITY:
Clinical Features: Cough, Breathlessness, Wheeze, Chest Tightness, Use of Accessory Muscles and Suprasternal Retractions
PEF < 80% Personal Best or Predicted (if available)

INITIAL TREATMENT:
Inhaled Short-Acting Beta-2 Agonist up to 3 Treatments in 1 Hour
Alternative: Oral Short-Acting Beta-2 Agonist and/or Theophylline

GOOD RESPONSE
(Mild Exacerbation)
No symptoms within 1 hr
PEF > 80% predicted
Sustained response for 4 hrs

INCOMPLETE RESPONSE
(Moderate Exacerbation)

POOR RESPONSE
(Severe Exacerbation)

PEF 60-80% Predicted

PEF < 60% Predicted

Continue regular bronchodilator for

24-48 hrs

Add Oral Steroid (1mg/kg/day)

Add Oral Steroid (1mg/kg/day)

Inhaled Short Acting B2-Agonist 2

puffs q3-4hr

Continue Beta-2 Agonist and/or

Theophylline regularly

Repeat inhaled Beta-2 Agonist if available

Alternative: Oral Short-Acting B2Agonist or Theophylline TID

Consult Clinician Urgently for Instructions
Contact clinician within 48hrs for follow up

Immediate Transport to Hospital (ER)

VIII. MANAGEMENT OF ACUTE EXACERBATION OF ASTHMA: HOSPITAL CARE

Oxygen at 2-6 lpm via Nasal Canula
Avoid or Control Trigger Factors
Mneumonic: N-A-S-A
A. Nebulization
o Salbutamol (Ventolin) Neb/Inhaler q3-6 hours (1 Nebule / 2-4 puffs); or
o Ipratropium Bromide + Salbutamol (Combuvent) Nebulization 1 vial q6 hours; or
o Ipratropium Bromide (Atrovent) 1 Unit Dose vial TID-QID (less tachycardia); or
o MDI plus Large Volume Spacer at 2-4 puffs q 20 minutes (cheaper and faster)
B. Antibiotics
o ONLY if with probable bacterial infection (fever, persistent purulence, crackles)
C. Steroids
o Acute Attack: Hydrocortisone (Solucortef) 250mg IV stat, then 100mg IV q4-6h x 4 doses or continuous if the
condition warrants
o More Stable: Start on Oral Steroids as soon as patients can safely swallow and taper off in 10-14 days
D. Aminophyline
o Only as Add-On Medication (if asthma still not controlled)
o Acute Attack: Not controlled by N, A and S, give Aminophylline Bolus at 5-6 mg/kg BW (if not maintained on
Theophyllines) then Aminophylline Drip
o More Stable: Shift to Long-Acting Theophylline
If NOT controlled by N-A-S-A, consider INTUBATION before Respiratory Fatigue sets in

11

3) CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

Syndrome of Chronic Dyspnea with Expiratory Airflow Limitation that, unlike asthma, does NOT fluctuate markedly

COPD includes Chronic Bronchitis and Emphysema

I. CLINICAL PRESENTATION

Chronic productive cough for many years, followed by slowly progressive Breathlessness brought on with Decreasing amounts of Exertion
Unusual in the absence of smoking
Nocturnal Symptoms are UNUSUAL in COPD unless associated with comorbidities (cardiac disease, obstructive sleep apnea,
gastroesophageal reflux, or marked reactive airway component)
Tachypnea, pursed-lip breathing, and use of accessory muscles
On PE: Hyperresonant chest, decreased breath sounds, adventitious sounds
Signs of Cor Pulmonale may be seen in severe or long-standing disease

II. SOME DIAGNOSTICS:

A. Chest Radiographs
o
o

Low, Flattened Diaphragms

Hyperlucent Lungfields with Bullae and diminished Vascular Markings (in Severe Emphysema)
Often, disease is prominent in Upper Long Zones (except in A1-Antitrypsin Deficiency: basilar predominance)

o
B. Pulmonary Function Testing
o
o

FEV1 and all other measurements of Expiratory airflow are Reduced

FEV1 = Standard Way of objectively assessing the clinical course and response to therapy
Total Lung Capacity, Functional Residual Capacity, & Residual Volume may be Increased, indicating Air-Trapping

o
C. Arterial Blood Gases
o

Perfusion of Poorly Ventilated Areas of the Lungs (ie. Areas with Low V/Q) results in an Increased Alveolar-Arterial Oxygen
Tension (P(A-a)O2) Gradient and Hypoxemia
A subpopulation of patients with Severe Airway Obstruction have chronically Increased Arterial PaCO 2, but Metabolic
Compensation (increased HCO3) maintains Arterial pH near normal
During Acute Exacerbation of COPD

Worsening Airway Obstruction

Increased Dead Space Ventilation & Respiratory Fatigue

Rapid Rise in PaCO2

Acute Respiratory Acidosis

III. CLINICAL SYNDROMES: Two Classic Types of COPD (from NMS)

Pink Puffers: Patients with EMPHYSEMATOUS, Dyspneic, or Type-A COPD
Blue Bloaters: Patients with BRONCHITIC, Tussive, or Type-B COPD
TYPE
Pink Puffers

PREDOMINANCE
Emphysema

AGE OF (+)
SYMPTOMS
Advanced Age
(>60)

SYMPTOMS
Progressive exertional dyspnea
Weight Loss
Little / No Cough & Expectoration

PULMONARY FUNCTION
TESTING
Mild Hypoxia, Hypocapnia
Decreased DLCO
Mild Increase in Raw
Little Improvement in Airflow after
Treatment with Bronchodilators

Blue Bloaters

Chronic Bronchitis

Young Age

Chronic Cough & Expectoration

Episodic Dyspnea
Weight Gain
Wheezing, Rhonchi
Cor Pulmonale often develops
(Edema, Cyanosis)

Severe Hypoxia, Hypercapnia

Polycythemia
Increased Raw
Improved Airflow after treatment
with Bronchodilators
Relatively preserved Lung Volumes
and DLCO

Emphysema: Proportional and Matched Losses of Ventilation and Perfusion hence, they are Spared Severe Hypoxemia
Chronic Bronchitis: Marked V/Q Mismatch, resulting in Severe Hypoxemia (which is worsened by Hypercapnia)

12

IV. CLASSIFICATION AND TREATMENT OF COPD (from Blue Book)

STAGE / SYMPTOMS & SIGNS
0: At Risk

Cough
Sputum

I: Mild COPD

> 80%

Cough, Sputum
Little or NO Dyspnea
Mild Symptoms
NO Abnormal Signs

II: Moderate COPD

FEV1 as %
PREDICTED
NORMAL

TREATMENT
Smoking Cessation for everyone
Reduce indoor pollution
Reduce occupational exposure
Flu vaccinations yearly
As needed B2-Agonists

Eg. Terbutaline Sulfate (Bricanyl Turbuhaler) 250mcg/dose: 1 inh prn q2-6h

Pulmonary Rehabilitation

50 79%

Cough, Sputum
Dyspnea on moderate exertion
Continuous or intermittent Sx

For intermittent Sx:

As needed B2 Agonists
For Continuous Symptoms:

Maintain on Tiotropium (Spiriva HandiHaler) inhalation of 1 Cap daily

If response is Unsatisfactory, add Long-Acting B2 Agonist or Oral Theophylline
Consider Mycokinetic Agent
Pulmonary Rehabilitation

III: Severe COPD

30 49%

Cough, Sputum
Dyspnea on Mild Exertion
Lung Hyperinflation
Wheezing

As needed B2 Agonists
For Continuous Symptoms:

Maintain on Tiotropium (Spiriva HandiHaler) Inhalation of 1 capsule daily

For frequent exacerbations (>4x/yr):

Add inhaled Steroids of Long Acting B-Agonists

Eg. Formoterol & Budesonide (Symbicort Turbuhaler) 1-2 inhalations BID

Pulmonary Rehabilitation

IV: Very Severe COPD

< 30%

Dyspnea even at rest

Chronic Respiratory Failure

In addition to the above treatments:

Add long-term O2 Therapy at home

Consider surgical treatments like Lung Reduction Surgery and Bullectomy

(removal of Bulla)

V. COPD VS ASTHMA (Med School Notes)

Smoker or Ex-Smoker
Symptoms under age 35
Chronic Productive Cough
Breathlessness
Night Time Awakening
Significant Diurnal or Day to Day Variability

COPD
Nearly All
Rare
Common
Persistent and Progressive
Uncommon
Uncommon

ASTHMA
Possible
Often
Uncommon
Variable
Common
Common

VI. THERAPY:
A. Pharmacotherapy
o Smoking Cessation: Bupropion, Nicotine Replacement Therapy
o Bronchodilators (Symptomatic Benefit)
o Anticholinergic Agens
o Beta Agonists (Symptomatic Benefit)
o Inhaled Glucocorticoids
o Oral Glucocorticoids
o Theophylline
o Oxygen
B. Non-Pharmacologic Therapies
o Pulmonary Rehabilitation
o Lung Volume Reduction Surgery (LVRS)
o Lung Transplantation (COPD is the single leading indication for
lung transplantation)

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Only 3 Interventions have been demonstrated to influence natural hx of COPD:

1) Smoking Cessation
2) Oxygen Therapy in Chronically Hypoxemic Patients
3) Lung Volume Reduction Surgery

13

VII. MANAGEMENT OF ACUTE EXACERBATIONS

A. Maintenance of Adequate Gas Exchange:
o Oxygen to achieve & maintain PaO2 55-60mmHg (88-90% Oxyhemoglobin Saturation)
o Mechanical Ventilation in patients with Acute Ventilatory Failure
B. Inhaled B2-Adrenergic Agonists
o First Line Therapy for Rapid Symptomatic Improvement in patients with Acute Bronchoconstriction
o Inhaled = most effective and safe
o Ex) Metaproterenol, Terbutaline, Albuterol (q30-60 min, as tolerated)
C. Anticholinergic Agents (Ipratropium Bromide)
o Have equivalent efficacy to B2-Adrenergic Agonists in treatment of Acute Exacerbations of COPD, but NO consistent
Synergistic Bronchodilation is obtained with combination therapy
o Combination of B2-Adrenergic Agonist and Anticholinergic Agent = provides Rapid Onset of the former PLUS the more
prolonged Action of the latter
D. Glucocorticoids (Methylprednisolone 125mg IV q6h for 3 days)
o Moderate improvement in clinical outcomes have been demonstrated
o Use in hospitalized patients (role of glucocorticoids for Acute Exacerbations in outpatients is controversial)
E. Theophylline
o Controversial
F. Antimicrobial Therapy
o Benefit of Antibiotic Therapy is seen in patients who have more severe underlying lung disease and in those who
experience more severe exacerbations
G. Chest Physiotherapy
o May improve clearance of secretions (>50mL/day)
VIII. LONG TERM MANAGEMENT
1) Relief of Symptoms and Managing Acute Exacerbations
2) SLOWING Progression of Airflow Obstruction and Loss of Vital Capacity
Includes the Following:
o
o
o
o
o
o
o
o

Smoking Cessation
Optimal Bronchodilator Regimen (not established)
Glucocorticoids
Oxygen Therapy
Pulmonary Hypertension and Cor Pulmonale
Comprehensive Pulmonary Rehabilitation Program
Influenza Vaccine and Pneumococcal Vaccine
Psychoactive Drugs
A1-Protease Inhibitor Augmentation Therapy

o
IX. SURGICAL CONSIDERATIONS

Non-Thoracic Surgery
Lung Resection, Lung Volume Reduction Surgery
Lung Transplantation
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X. NOTES FOR COPD (GOLD)

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XI. MECHANICAL VENTILATION FOR OBSTRUCTUVE AIRWAY DISEASES (ASTHMA & COPD) Lecture
A. Non-Invasive Positive Pressure Ventilation (NIPPV) for ARF due to COPD
o Patient receives air or air-O2 from a Flow Generator through a Full Facial or Nasal Mask
o Enhance Ventilation by Unloading the Fatigued Ventilatory Muscles
o Improve Gas Exchange by Increasing Alveolar Ventilation
1. At Least TWO of:
General Criteria for Acute Ventilatory Failure:
Moderate to Severe Dyspnea
Patient is Acutely Dyspneic, Altered Mental Status
pH < 7.35 or PaCO2 > 45
PaO2 < 50mmHg at Room Air
RR > 25

PaCO2 > 50mmHg

2. Best Modes:
Arterial pH: significant Respiratory Acidemia
PSV
BiPAP
CPAP
3. Contraindications to NIPPV in COPD
Frank Respiratory Arrest
Hemodynamic Instability
Inability to clear secretions or protect airways
Agitation or Uncooperativeness
Conditions that preclude placement of a Mask or achievement of a Proper Fit
B. Potential Deleterious Consequences of Severe OAD + MV:
o Post-Hypercapnic Metabolic Alkalosis
o Hypotension Secondary to Acute Hyperinflation
o Alveolar Overdistention
o Oxygen Toxicity Acute Lung Injury
o Cardiovascular
o Ventilator Associated Pneumonia (VAP)
C. Goals of MV in Severe OAD
o Restore Gas Exchange to stable baseline
o Rest Ventilator Muscles / Reduce Work of Breathing until Primary Disease Process reverses or improves
D. Monitoring Patients with Severe OAD on Mechanical Ventilation:
1. Peak Airway Pressure
PAP > 50cmH2O associated with Barotrauma
If HIGH, suspect:
AF Obstruction (PEEPi, Bronchospasm, Secretions, Mucus Plug)
Concomitant problems (Pneumonia, CHF, Pulmonary Embolism)
Complications (Pneumothorax, Atelectasis)
Patient-Ventilator Dyssynchrony
High Inspiratory Flow Rates
Small Size of ET
Kinks / Blocks along tubings, Right Mainstem Intubation
2. Plateau or Static Pressure
PPLAT > 30cmH2O predicted of Barotrauma
Estimate of average End-Inspiratory Alveolar Pressure
3. Auto-PEEP (PEEPi) / Dynamic Hyperinflation
Airflow obstruction prevents Complete Emptying of Alveolar Gas End Expiratory PALV remains Positive
Consequences:
Decreased Venous Return
Promotes Barotrauma
Increased Work of Breathing
4. PaO2, SaO2
Lowest possible FiO2 to maintain SaO2 > 92% or PaO2 > 60mmHg
Any further Increase in FiO2 will have little effect on SaO2 and Increases Risk of O2 Toxicity
5. pH, PaCO2
COPD patients are Chronically Hypercapneic
Maneuvers that attempt to PaCO2 also Worsen Dynamic Hyperinflation & promote Barotrauma & Hypotension
Permissive Hypercapnea: Ignore PaCO2 as long as pH is acceptable

16

E. Modes of MV of Patients with Severe OAD:

1. Assist Control Ventilation
Deliver breath with Preset Volume and Flow, either when Trigerred by patients Inspiratory Effort or to a
Preset Backup Respiratory Rate
Excessive Patient Work occurs if Peak Flow Insufficient to meet Patients Ventilatory Demands, especially
if Respiratory Drive is heightened or when Trigger Setting is NOT sufficiently sensitive
Risk for Hyperinflation
2. Synchronized Intermittent Mandatory Ventilation (SIMV)
Deliver Periodic Positive Pressure Breaths from the Ventilator at Preset Volume and Rate and also allow
Spontaneous Breathing
As Ventilator Rate is Decreased, Inspiratory Work and the Pressure-Time Product INCREASE
progressively, NOT only for the Spontaneous Breaths but also for the Assisted breaths largely due to
Inability of the Respiratory Centers to adapt to Intermittent Unloading
3. Pressure Support Ventilation
Set a Level of Pressure (rather than Volume) to Augment each Spontaneous breath
Each breath is Patient-Triggered, Inspiratory Assistance continues until Inspiratory Flow Decreases
Tidal Volume is determined by Set Pressure Level, Patients Effort, and pulmonary mechanics
F. Ventilator Setting Strategies and Targets in Patients with Severe OAD:
1. FiO2
Achieve PaO2 > 60mmHg, SpO2 > 92%
Lowest possible FiO2 to keep SpO2 > 92%
2. Trigger Sensitivity
Set the Level of Sensitivity (usually 1 to 2) which will keep patients Inspiratory Effort to a Minimum,
but NOT too sensitive that the MV Cycles inappropriately and results in Severe Respiratory Alkalosis
Consider the Effect of Auto-PEEP on Triggering: patients need to generate a negative pressure equal in
magnitude to the Level of Intrinsic PEEP (Auto-PEEP) in addition to the Sensitivity Setting
Flow Triggering (instead of Airway Pressure Change Triggering), is available on Newer Ventilators, can
Decrease Inspiratory Effort by 30-40% during Triggering
3. Inspiratory Flow Rate (IFR)
Should be HIGH (60-100 L/min) however High IFR can cause Peak Airway Pressure Barotrauma
If on A/C Mode at Low Flow Rates = the patient will NEED to Generate Inspiratory Effort against his own
Pulmonary Impedance + that of the Ventilator, resulting in Increased Work of Breathing
High Inspiratory Flow Rate:
Helps satisfy the demands of Most Patients
Decreases the likelihood of DHI by Increasing Expiratory Time allow more complete emptying
of regions with Gas Trapping
4. Tidal Volume
Avoid Alveolar Overdistention
Set at 5-7 cc/kg
Provide enough pressure to ensure Inhaled Medication Delivery
NOT set in PSV
5. Ventilator Rate
A/C Mode

IMV
PSV

Back up Rate of 4 Breaths per minute LESS than the Patients Spontaneous Rate to
ensure that the MV will continue to supply adequate Volume in case of Sudden Decrease in
Respiratory Center Output
If with High Spontaneous RR, Expiratory Time will Decrease and can become Shorter than
T1 and can result in Inverse Ratio Ventilation
Titrating the Level of Mandatory Breaths: consider NOT only the ABG but also the
Patients work of breathing and comfort
NOT set

17

4) PULMONARY EDEMA
I. CARDIOGENIC PULMONARY EDEMA
A. Pathophysiology
Increased Pulmonary Venous Pressure

Engorgement of Pulmonary Vasculature

CHF

Lungs become Less Compliant

Increased Resistance in Small Airways

Increased Lymphatic Flow and Intravascular Pressure

Interstitial Edema (net gain of fluid in the Extravascular Space)

Alveolar Edema
(Outpouring of liquid that contracts both RBC and Macromolecules)

Progressive Acidemia, Hypercapnea

Respiratory Arrest
o Manifested by Bilateral Wet Rales and Rhonchi
o CXR: Diffuse Haziness of the lung fields with greater density in the Proximal Hilar Regions
B. Treatment
1. Supportive:
O2 Support Raise the Arterial O2 Tension > 60mmHg
2. Pharmacologic
Morphine Sulfate
Furosemide
Nitroglycerin
Inotropes

Dilates pulmonary and systemic veins

2-5mg IV can be repeated 10-25min until effect is seen
Potent Venodilators
Initial Dose of 20-40mg IV, Max dose of 200mg
Venodilator
Can potentiate the effect of Furosemide
Dobutamine or Phosphatiesterase Inhibitors
In patients with concomitant hypotension and shock

3. Acute Hemodialysis and Ultrafiltration

4. Right Heart Catheterization
Differentiates between Cardiogenic and Noncardiogenic causes of Pulmonary Edema
5. Precipitating Factors should be corrected
II. NON-CARDIOGENIC PULMONARY EDEMA
Severe Liver Disease
Nephritic Syndrome
Other Forms of Pulmonary Edema:

Narcotic Overdose parenteral Heroin, Morphine, Methadone, Dextropropoxyphene

Protein Losing Enteropathy

Exposure to high altitudes due to pulmonary venous constriction or pulmonary

Lymphatic Carcinomatosis
arteriolar construction
Diffuse Pulmonary Infections

Neurogenic Pulmonary Edema in patients with CNS disorders without preexisting LV

Aspiration
dysfunction
Shock

18

5) INVESTIGATING AN SPN

SPN: Solitary Pulmonary Nodule

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CAUSES OF CHRONIC COUGH:

Intrathoracic: COPD, Bronchial Asthma, Central Bronchial

Carcinoma, Endobronchial TB, Bronchiectasis, Left Heart
Failure, Interstitial Lung Disease, Cystic Fibrosis

Extrathoracic: Postnasal Drip, Gastroesophageal Reflux, Drug

Therapy (eg. ACE Inhibitors)

19

6) CASE ON PULMONARY DISEASE

I. CASE: 71/F With Chief Complaint of DOB
Hypertensive, Dyslipidemia, Congestive Heart Failure FC II, history of PTB
Admitted due to Pleural Effusion prob 20 to Left Pleural Mass S/P Thoracentesis (no malignant cells)
Symptoms: Dyspnea, back pain, undocumented fever, weight loss, anorexia, easy fatigability, no cough
II. OTHER SYMPTOMS (ROS):
A. Blurring of Vision
o Flame Shaped Hemorrhages = consistent with HYPERTENSION
o Diplopia = nagdadalawa ang paningin
B. Polyuria
o In patients presenting with Pulmonary Mass, significance of Polyuria = Paraneoplastic Syndrome
o Patient may also be diabetic, as a part of the Metabolic Syndrome
C. Screen for other Organ Systems, as a site of Possible Metastasis
o Breasts (Most Common CA for age group)
o GI System (changes in stools, abdominal pain)
o Liver (history of jaundice)
1. Colon Carcinoma (2nd most common CA):
Right Side = sometimes ASYMPTOMATIC
Left Side = decreased caliber of stools
2. Gynecologic Carcinomas (3rd most common CA)
Ask for gynecologic complaints
III. PHYSICAL EXAMINATION
Decreased breath sounds, increased tactile fremitus on Left
Crackles, wheezes on Right
A. Shifting Dullness
o Can also be done in the chest / lungs
o To differentiate fluid from solid
B. No Clubbing in Extremities
o Elicit because Pulmonary Mass
IV. DIAGNOSTICS
A. Chest X-Ray (AP/L)
o Findings: the mass is causing an Obstructive Atelectasis to the LEFT, there is shifting of trachea to right
o On Lateral: there is NO effusion in the POSTERIOR GUTTER (most dependent portion)
B. Bronchoscopy
C. Notes on PT / PTT
1. Prothrombin Time (PT)
Tests the Extrinsic and Common Coagulation Pathways
Prolonged Time = deficiency / dysfunction in Factor V, VII, X, Prothrombin, Fibrinogen
2. Partial Thromboplastin Time (PTT)
Tests the Intrinsic and Common Coagulation Pathways
Prolongation = deficiency / dysfunction of factor V. VIII. IX. X. XI. XII. Prothrombin, Fibrinogen

20

7) COMMUNITY ACQUIRED PNEUMONIA

Pneumonia is an infection of the Pulmonary Parenchuma

Results from the Proliferation of microbial pathogens at the alveolar level & hosts response to those pathogens

I. CLASSIFICATION (2004): Management-Oriented Risk Stratification of CAP in Immunocompetent Adults

CAP

Any of the following:

1. RR > 30 / min
2. PR > 125 / min
3. Temp > 400C or < 350C
4. Extrapulmonary evidence of
sepsis
5. Suspected aspiration
6. Unstable comorbid conditions*
7. CXR: Multilobar, pleural
effusion, abscess, progression of
lesion to > 50% of initial within
24 hours

YES

Any of the following:

1. Shock or signs of Hypoperfusion
-Hypotension
-Altered mental status
-Urine output < 30mL/hr

2.

NO

LOW RISK CAP

MODERATE RISK CAP

LOW RISK CAP

Stable Vital Signs

RR < 30/min

PR < 125bpm

SBP > 90mmHg

DBP > 60mmHg

In Patient
MODERATE RISK CAP
Unstable Vital Signs:

RR > 30/min

PR > 125bpm

Temp > 400C or < 350C

Unstable Comorbid Condition

No evidence of Extrapulmonary Sepsis

Uncontrolled DM, Active Malignancies, Progressing

Neurologic Disease, CHF Class II-IV, Unstable CAD,
Renal Failure on Dialysis, Uncompensated COPD,
Decompensated Liver Disease

No evidence of Aspiration

Evidence of Extrapulmonary Sepsis

Hepatic, Hematologic, GI, Endocrine

No or Stable Comorbid Conditions

Chest X-Ray:

Localized infiltrates

No evidence of Pleural Effusion nor

abscess

NOT progressive within 24 hours

HIGH RISK CAP

PaO2 < 60mmHg or Acute

hypercapnea (PaCO2 >
50mmHg)

NO

Outpatient

YES

Suspected Aspiration
Chest X-Ray:

Multilobar Infiltrates

Pleural Effusion or Abscess

Progression of findings to >50% in 24h

Intensive Care
HIGH RISK CAP
Any of the clinical features of Moderate
Risk CAP plus any of the following:
1) Shock or Signs of Hypoperfusion

Hypotension

Altered Mental State

Urine Output < 30mL/hr

2) Hypoxia (PaO2 < 60mmHg) or Acute
Hypercapnea (PaCO2 > 50mmHg)
Chest X-Ray:
* As in Moderate Risk CAP

21

II. MANAGEMENT OF CAP (from 2004 guidelines) see updated 2010 guidelines when available
POTENTIAL PATHOGENS
EMPIRIC THERAPY
Low Risk CAP
S. pneumoniae
Previously Healthy:
H. influenzae
Amoxicillin
C. pneumoniae
OR
M. pneumoniae
Extended Macrolides
M. catarrhalis
Alternative: CoTrimoxazole
Gram (-) Enteric Bacilli
With Stable Comorbid Illness:
Co-Amoxiclav or Sultamicillin
OR
2nd Generation Cephalosporins
OR
Extended Macrolides
Moderate Risk
CAP

High Risk CAP

S. pneumoniae
H. influenzae
C. pneumoniae
M. pneumoniae
M. catarrhalis
Gram (-) Enteric Bacilli
Legionella pneumophilia
Anaerobes (with risk of aspiration)
S. pneumoniae
H. influenzae
C. pneumoniae
M. pneumoniae
M. catarrhalis
Gram (-) Enteric Bacilli
Legionella pneumophilia
Anaerobes (with risk of aspiration)
S. aureus
P. aeruginosa

IV Non-Pseudomonal B-Lactam
With or Without B-Lactamase Inhibitor
PLUS Macrolide
OR
Antipneumococcal Fluoroquinolones (FQ)
No Risk for P. aeruginosa:
a. IV Non-Pseudomonal B-Lactam with or without BLactamase Inhibitor + IV Macrolide
b. IV Antipneumonococcal FQ
With Risk for P. aeruginosa
IV Pseudomonal B-Lactam with or without B-Lactamase Inhibitor
PLUS
IV Macrolide or IV Antipneumococcal FQ
With or Without
Aminoglycoside or IV Ciprofloxacin

**NOTE: Respiratory Quinolones (because they cover Pneumococcus)

o Levofloxacin
o Gatifloxacin
o Moxifloxacin

III. DIAGNOSIS
A. Differential Diagnosis of Pneumonia
o Infectious
o Non-Infectious (Acute Bronchitis, Acute Exacerbations of Chronic Bronchitis, Heart Failure, Pulmonary Embolism,
Radiation Pneumonitis)
B. Diagnostics
o Gram Stain and Culture of Sputum
o Blood Cultures
o Antigen Tests, PCR, Serology
IV. CRITERIA IN HARRISONS 17TH EDITION: CURB-65 CRITERIA
C: Confusion
Scoring System:
U: Urea >7mmol/L

0: Outpatient
R: Respiratory Rate >30/min

2: In-Patient
B: Blood Pressure (Systolic <90 or Diastolic <60)

>3: In-Patient ICU

65: Age >65years old

22

8) HOSPITAL ACQUIRED PNEUMONIA

I. EARLY VS LATE ONSET HAP
EARLY ONSET
( 5 days in Hospital)
S. pneumoniae
H. influenzae
M. catarrhalis
S. aureus
Enteric Gram (-) Bacteria

LATE-ONSET
(> 5 days)
P. aeruginosa
Enterobacter spp
Acinetobacter spp
K. pneumoniae
S. marcescens
E. coli
Other Enteric Gram (-) Bacteria
S. aureus

OTHERS
Anaerobic Bacteria
Legionella
Candida spp
Influenza A and B
RSV

**NOTE: Organisms we deal with in Asia are DIFFERENT from the US / Europe
II. EMPIRICAL ANTIBIOTIC TREATMENT OF HEALTH CARE ASSOCIATED PNEUMONIA (Harrisons)
A. Patients without Risk Factors for MDR Pathogens:
o Ceftriaxone (2g IV q24h); or
o Moxifloxacin (400mg IV q24h), Ciprofloxacin (400mg IV q8h), or Levofloxacin (750mg IV q24h); or
o Ampicillin / Sulbactam (3g IV q6h); or
o Ertapenem (1g IV q24h)
B. Patients with Risk Factors for MDR Pathogens
1. A Beta-Lactam:
Ceftazidime (2g IV q8h) or Cefepime (2g IV q8-12h); or
Piperacillin / Tazobactam (4.5g IV q6h), Imipenem (500mg IV q6h or 1g IV q8h), or Meropenem
(1g IV q8h); PLUS
2. A Second Agent Active Against Gram-Negative Bacterial Pathogens:
Gentamicin or Tobramycin (7mg/kg IV q24h) or Amikacin (20mg/kg IV q24h); or
Ciprofloxacin (400mg IV q8h) or Levofloxacin (750mg IV q24h); PLUS
3. An Agent Active Against Gram-Positive Bacterial Pathogens:
Linezolid (600mg IV q12h) or
Vancomycin (15mg/kg, up to 1g IV q12h)

23

9) PLEURAL EFFUSION AND PNEUMOTHORAX

I. PLEURAL EFFUSION
Excess quantity of fluid in the pleural space
Decreased pleural fluid removal by the lymphatics
Excess pleural formation from the interstitial spaces of the lung, parietal pleura, or peritoneal cavity
A. Transudative and Exudative Pleural Effusion
1. Transudative VS Exudative
a. Transudative
Systemic factors that influence the formation and absorption of pleural fluid is altered
Ex) LV Failure, Pulmonary Embolus, Cirrhosis
b. Exudative
Local factors are altered
Ex) Bacterial Pneumonia, Malignancy, Viral Infection, Pulmonary Embolus
2. Lights Criteria (Exudative Effusions meet at least ONE, Transudative Effusions meet NONE)
Pleural Fluid Protein / Serum Protein > 0.5
Pleural Fluid LDH / Serum LDH > 0.6
Pleural Fluid LDH > 2/3 Normal upper limit for Serum LDH
If one or more of the Exudative Criteria are met and the patient is clinically thought to have a condition
producing a Transudative Effusion, the difference between the Albumin Levels in the Serum and the Pleural
Fluid should be measured
If > 12g/L (1.2g/dL) = TRANSUDATIVE!

3. Symptoms / Signs of Pleural Effusion

Intercostal Pain (Inflammation of Parietal Pleura)

Cough, Dyspnea
Dullness on Percussion
Decreased or Absent Tactile Fremitus
Decreased Breath Sounds
Tracheal Deviation
Pleural Rub

B. Parapneumonic Effusion
o Associated with bacterial pneumonia, lung abscess, bronchiectasis
o Empyema = Grossly purulent effusion
o If free fluid separates the lung from the chest wall by > 10mm THORACENTESIS!
o Factors indicating need for procedure more invasive than Thoracentesis (increasing order of importance)

Loculated Pleural Fluid

Pleural Fluid pH < 7.2
Pleural Fluid Glucose < 3.3mmol/L (<60mg/dL)
Positive Gram Stain or Culture of Pleural Fluid
Presence of Gross Pus in the pleural space

C. Thoracentesis
o
o
o

Usual Site: 8th ICS L PAL

Maximum Drainage = 1.5 L every 24 hours
Send Specimen:

Bottle 1: Cell Count, Differential Count, Total Protein, LDH (5-10mL EDTA)

Bottle 2: AFB, Gram Stain, C&S

Bottle 3: Cytology and Cell Block (obtain 200cc of Fluid or more to increase yield)

D. Indications for Chest Tube Insertion

o
o
o

1) Gross Pus on Thoracentesis

2) Presence of Organisms on Gram Stain of the Pleural Fluid
3) Pleural Fluid Glucose < 50mg/dL
4) Pleural Fluid pH below 7.00 and 0.15 units lower than Arterial pH

24

E. Indications for Chemical Pleurodesis: Talc or Tetracycline Pleurodesis

o
o
o

1) Recurrent Pleural Effusion

2) Malignant Pleural Effusions
3) Secondary Pneumothorax including Iatrogenic Pneumothoraces
4) Patients with Poor Surgical Risk
Differential Diagnoses of Pleural Effusions:
1. Transudative Pleural Effusion

Congestive Heart Failure

Cirrhosis

Pulmonary Embolization

Nephrotic Syndrome

Peritoneal Dialysis

Superior Vena Cava Obstruction

Myxedema

Urinothorax

QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

2. Exudative Pleural Effusions

Neoplastic Diseases

Infectious Diseases (Bacterial, TB, Fungal, Viral)

Pulmonary Embolization

GI Diseases (Esophageal Perforation, Pancreatic, etc)

Collagen Vascular Diseases (SLE, Rheumatoid Pleuritis, etc)

Post-Coronary Artery Bypass Surgery

Asbestos Exposure

Sarcoidosis

Uremia

Meigs Syndrome

Yellow Nail Syndrome

Drug-Induced Pleural Disease

Trapped Lung

Radiation Therapy

Post-Cardiac Injury Syndrome

Hemothorax

Iatrogenic Injury

Ovarian Hyperstimulation Syndrome

Pericardial Disease

Chylothorax

25

II. PNEUMOTHORAX

Presence of Gas in the Pleural Space

Spontaneous Pneumothorax: Occurs WITHOUT antecedent Trauma to the Thorax
A. Primary Spontaneous Pneumothorax
o Occurs in the absence of Underlying Lung Disease
o Usually due to Rupture of Apical Pleural Blebs, Small Cystic Spaces that lie within or immediately under the visceral pleura
o Occur almost exclusively in Smokers, which suggests that these patients have subclinical lung disease
o Initial Recommended Treatment: Simple Aspiration
o Thoracoscopy and Thoracotomy with Pleural Abrasion is almost 100% successful in preventing recurrences
B. Secondary Pneumothorax
o Most are due to Chronic Obstructive Pulmonary Disease, but Pneumothoraces have been reported with every lung disease
(pneumothorax with lung disease is more life-threatening)
o Nearly all should be treated with Tube Thoracostomy
o Most should also be treated with Thoracoscopy or Thoracotomy with Stapling of Blebs & Pleural Abrasion
C. Traumatic Pneumothorax
o Can result from both Penetrating and Non-Penetrating Chest Trauma
o Should be treated with Tube Thoracostomy, unless they are very small
o Iatrogenic Pneumothorax: due to Transthoracic Needle Aspiration, Thoracentesis, Insertion of Central IV Catheters
D. Tension Pneumothorax
o Occurs during Mechanical Ventilation or Resuscative Efforts
o The positive Pleural Pressure is life-threatening both because Ventilation is severely compromised and because the Positive
Pressure is transmitted to the Mediastinum, which results in Decreased Venous Return to the heart and reduced Cardiac Output
o Diagnosis is made by Physical Examination:

Enlarged Hemithorax with NO Breath Sounds

Hyperresonance to Percussion

Shift of Mediastinum to the Contralateral Side

o Must be treated as a Medical Emergency
o A large bore needle should be inserted into the Pleural Space through the 2 nd Anterior Intercostal Space if large amounts of gas
escape from the needle after insertion, the diagnosis is confirmed

26

10) PULMONARY EMBOLISM

When Venous Thrombi dislodge, they embolize to the Pulmonary Arterial Circulation or, paradoxically, to the
Arterial Circulation through a patent foramen ovale or ASD
Most Common Gas Exchange Abnormalities:
o Hypoxemia (Decreased Arterial PO2)
o Increased Alveolar-Arterial O2 Tension Gradient (represents inefficiency of O2 Transfer across lungs)

I. PATHOPHYSIOLOGY:
Anatomic Dead Space INCREASES because breather gas does NOT enter gas exchange units of the lung
Physiologic Dead Space INCREASES because ventilation to gas exchange units exceeds Venous Blood Flow
through the pulmonary capillaries
Other Pathophysiological Abnormalities:
o Increased Pulmonary Vascular Resistance (due to vascular obstruction)
o Impaired Gas Exchange
o Alveolar Hyperventilation
o Increased Airway Resistance
o Decreased Pulmonary Compliance
II. CLINICAL PRESENTATION
A. High Index of Suspicion
o Presence of DVT
o Hypercoaguable State
o Pathologic Fractures
o Long Bone Fractures
o Post-Partum Period
B. Symptoms:
o Unexplained Breathlessness
o Cough, Dyspnea
o Pleuritic Chest Pain, Syncope

Differentials:
Dissecting Aortic Aneurysm
Acute Bronchitis
Bronchogenic CA
Pericarditis, Pericardial or Pleural Disease
Acute Coronary Syndrome / Myocardial Ischemia
Congestive Heart Failure
Axiety
Pneumonia, Asthma, COPD
Pleurisy: Viral Syndrome, Costochondritis, Musculoskeletal
Rib Fracture, Pneumothorax

C. Physical Examination
o Tachypnea, Tachycardia
o Increased P2
o Inspiratory Crackles / Rales
NOTES from BLUE BOOK:
1. Diagnosis of Pulmonary Embolism:
Clinical setting & high index of suspicion
On PE: Increase JVP but Clear Lungs, Load P 2
ABG may show Respiratory Alkalosis, Hypoxemia
ECG: Transient RAD, RBBB, S-Waves at precordial leads
V/Q Scan: Interpreted as Normal, Low, Intermediate or High Probability of PE
Pulmonary Angiography: Gold Standard for Diagnosis
2. Diagnosis of Deep Vein Thrombosis (as source of Emboli)
Duplex Ultrasound of the Lower Extremities (Non-Invasive)
Ascending Venography: Gold Standard

27

III. DIAGNOSTICS
A. Non-Imaging Diagnostic Modalities:
1. Expected ABG
Mild Respiratory Alkalosis
Hypoxemia
The most common gas exchange abnormalities are Hypoxemia (Decreased Arterial PO2) and an Increased AlveolarArterial O2 Tension Gradient, which represents the inefficiency of O2 Transfer across the lung. Anatomic dead space
increases because breathed gas does not enter gas exchange units of the lung. Physiologic dead space increases because
ventilation to gas exchange units exceeds venous blood flow through the pulmonary capillaries.
Arterial Blood Gases LACK diagnostic utility for Pulmonary Embolism, even though both the PO 2 and PCO2 often
decrease. Among patients suspected of PE, neither the room air Arterial PO2 nor calculation of the Alveolar-Arterial O2
Gradient can reliably differentiate or triage patients who actually have PE at angiography.

2. Plasma D-Dimer (ELISA)

Normal Value: < 500ng/mL
Useful RULE-OUT Test;
It is NORMAL in > 95% of patients WITHOUT Pulmonary Embolism (PE)
In patients with low clinical suspicion of DVT, it is NORMAL in > 90% WITHOUT DVT

QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

The
quantitative
plasma
D-Dimer
Enzyme-linked
Immunosorbent Assay (ELISA) rises in the presence of DVT
or PE because of plasmins breakdown of fibrin. Elevation of
D-Dimer indicates endogenous although often clinically
ineffective thrombolysis. The sensitivity of D-Dimer is > 80%
for DVT and > 95% for PE.
D-Dimer is NOT Specific. Levels increase in patients with:

Myocardial Infarction

Pneumonia

Sepsis

Cancer

Postoperative State

Second o Third Trimester Pregnancy

Troponin Levels increase in RV Microinfarction. Elevated
Cardiac Biomarkers predict increase in major complications
and mortality from PE

3. ECG in Pulmonary Embolism

Most Cited Abnormality (in addition to Sinus Tachycardia) = S1-Q3-T3
S-Wave in Lead I
Q-Wave in Lead III
This finding is relatively SPECIFIC, but INSENSITIVE
Inverted T-Wave in Lead III
Most Frequent Abnormality: T-Wave Inversion in Leads V1 to V4

28

B. Non-Invasive Imaging Modalities

1. Venous Ultrasonography
UTZ of DVT: relies upon loss of vein compressibility
A Normal Venous UTZ does NOT exclude Pulmonary Embolus (PE)
2. Chest X-Ray (Multidetector-Row Spiral CT)
May be NORMAL or Near Normal
Some Signs:
Westermarks Sign: Decreased Vascularity
Hamptons Hump: Wedge-Shaped Density above Diaphragm in outer 2/3 lung field
Pallas Sign: Enlarged Right Descending Pulmonary Artery
Knuckles Sign: Abrupt tapering / termination of Vessels
3. Chest CT Scan: 60% Sensitivity; 97% Specificity
Principal imaging Test for the Diagnosis of PE
CT Scanners can image small peripheral emboli
RV Enlargement on chest CT indicates a fivefold likelihood of death within the next 30 days compared with PE
patients with Normal RV size on chest CT
4. V/Q Lung Scan (Lung Scanning)
Segmental Perfusion defect with Normal Ventilation
Key Diagnostic Test second-line diagnostic test for PE
High Probability of PE: defined as 2 or more segmental perfusion defects in presence of Normal Ventilation
5. Magnetic Resonance (MR) Contrast Enhanced
MR Venography is an excellent imaging modality to diagnose DVT
6. Echocardiography
NOT a reliable diagnostic imaging tool for acute PE because most patients w/ PE have normal echocardiograms
McConnells Sign: Hypokinesis of the RV Free Wall with Normal Motion of the RV Apex (which is the BestKnown Indirect Sign of PE)
C. Invasive Diagnostic Modalities
1. Pulmonary Angiography: GOLD STANDARD
Can detect as small as 1-2mm Embolus
(+) Intraluminal Filling Defect in Pulmonary Circulation
2. Contrast Phelbography
Venous Ultrasonography has virtually replaced contrast phlebography as the Diagnostic Test for suspected DVT
IV. TREATMENT
Give O2 at 2-4 lpm via NC; consider Intubation
Embolectomy
Thrombolytics
A. Primary Therapy VS Secondary Prevention
o Primary Therapy: consists of Clot Dissolution with Thrombolysis or removal of PE by Embolectomy
o Secondary Prevention: Anticoagulation with Heparin & Warfarin or placement of an Inferior Vena Cava Filter
B. Risk Stratification
ANTICOAGULATION OF VTE:
1. Immediate Parenteral Anticoagulation

Unfractionated Heparin, Bolus and continuous infusion, to

achieve aPTT 2-3 times the upper limit of the laboratory normal,
or

Enoxaparin 1mg/kg BID with normal renal function

2. Warfarin Anticoagulation

Usual Start Dose is 5-10mg

Titrate to INR, target 2.0 3.0

Continue parenteral anticoagulation for a minimum of 5 days and

until 2 sequential INR values, at least 1 day apart, return in the
target range

29

C. Anticoagulation (Medicine Notes)

o Foundation for successful treatment of DVT and PE
o Immediately effective anticoagulation is initiated with a parenteral drug: UFH, LMWH, Fondaparinux
o Parenteral drugs are continued as a transition or bridge to stable, long term anticoagulation with Warfarin (Vitamin-K
Antagonist) Warfarin requires 5-7 days to achieve a therapeutic effect
Unfractionated Hepatin
(UFH)

Anticoagulates by binding to and accelerating the activity of Antithrombin III, thus preventing
additional thrombus formation and permitting endogenous fibrinolytic mechanisms to lyse clots
Achieve a Target aPTT 2-3 times the upper limit (~aPTT 60-80s)

5000-10,000 u IV bolus, then infusion of 1000-1500 u/h (maintain PTT 1.5-2.5x)

Low Molecular Weight
Heparin (LMWH)
Warfarin

Ex) Initial Bolus of 80 units/kg, followed by initial infusion rate of 18 units/kg per hour
Exhibit less binding to plasma proteins and endothelial cells
No monitoring or dose adjustment needed
Enoxaparin 1mg/kg BID and Tinzaparin 175 unigs/kg OD
Vitamin-K Antagonist prevents carboxylation activation of Factors II, VII, IX, X
Full effect requires 5 days, even if the Prothrombin Time becomes elevated more rapidly
Overlapping UFH, LMWH, or Fondaparinus with Warfarin for at least 5 days can counteract the early
procoagulant effect of unopposed warfarin
Initiated at a dose of 5mg. Prothrombin is standardized with INR. Target INR = 2.5 (2.0 3.0)
Warfarin 5-10mg PO 3 days before stopping heparin (maintain PT INR 2.0-3.0) continue for 3 months

**NOTE: Protamine Sulfate = Administer if there is Life-Threatening or Intracranial Hemorrhage due to UFH / LMWH
Duration of Hospital Stay:
Acute PE Patients, who traditionally have required 5-7 day hospital stays for IV heparin as a bridge to warfarin, can be considered
for abbreviated hospitalization if (+) excellent prognosis
Duration of Anticoagulation:
Patients with PE following surgery or trauma ordinarily have a low rate of recurrence after 3-6 months of anticoagulation.

D. Fibrinolysis
o Successful fibrinolytic therapy rapidly reverses right heart failure
o Thrombosis usually:
Dissolves much of the anatomically obstructing pulmonary artery thrombus
Prevents continued release of serotonin and other neurohormonal factors that exacerbate pulmonary hypertension
Dissolves much of the source of thrombus in the pelvic or deep leg veins, thereby decreasing the likelihood of
recurrent PE
**IMPORTANT Notes:
Preferred Fibrinolytic Regimen is 100mg of Recombinant Tissue Plasminogen Factor (tPA) on IV infusion
over 2 hours
E. Other Management:
o Inferior Vena Caval (IVC) Filters Indications:
1) Active Bleeding that precludes anticoagulation
2) Recurrent Venous Thrombosis despite Intensive Anticoagulation

o
o
o
o

Maintaining Adequate Circulation (for patients with Massive PE and Hypotension = 500-1,000mL normal saline)
Pulmonary Embolectomy
Pulmonary Thromboendarterectomy
Emotional Support
Prevention of Posphlebitic Synrdome (compression stockings)

V. PREVENTION (Medicine Notes)

Coumadine x 6 months
IVC Filter (for patients with Absolute Contraindications to Anticoagulants)
DVT Prophylaxis

VI. PREVENTION OF VENOUS THROMBOEMBOLISM

Compression Stockings and Pneumatic Compression Devices may complement mini-dose UFH, LMWH, a Pentasaccharide, or Warfarin
Administration

Prophylaxis for Medically Ill Patients: Mini-UFH or LMWH

o Mini-UFH: 5000 units SC twice or three times a day
o LMWH: Enoxaparin 40mg OD

30

11) ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)

I. DEFINITION
A. Clinical Syndrome of:
o Severe Dyspnea of rapid onset
o Hypoxemia
o Diffuse Pulmonary Infiltrates
B. Definition:
o Acute Onset
o Bilateral infiltrates on CXR
o PCWP < 18mmHf or Absence of LAH
II. CAUSES OF ARDS
DIRECT LUNG INJURY
Pneumonia
Aspiration of Gastric Contents
Pulmonary Contusion
Near-Drowning
Toxic Inhalation Injury

INDIRECT LUNG INJURY

Sepsis
Severe Trauma
Multiple Bone Fractures
Flail Chest
Head Trauma
Burns
Multiple Transfusions
Drug Overdose
Pancreatitis
Post-Cardiopulmonary Bypass

III. ACUTE LUNG INJURY (ALI) VS ACUTE RESPIRATORY DISTRESS SYNDROME

OXYGENATION
ALI
ARDS

PaO2 / FiO2 < 300mmHg

PaO2 / FiO2 < 200mmHg

IV. THREE PHASES OF ARDS

Exudative (Day 0-7)
Proliferative (Day 7-21)
Fibrotic
Three Compartments in ARDS Lung:
1) Normally Aerated / Hyperaerated
2) Poorly Aerated (Ground Glass)
3) Non-Aerated (+) Shunting

ONSET
Acute
Acute

CHEST XRAY
Bilateral alveolar or
interstitial infiltrates

ABSENCE OF LEFT ATRIAL

PRESURE
PCWP < 18mmHg or No clinical evidence
of Increased Left Atrial Pressure

Pathology:
Severe Injury to the Alveolocapillary Unit: Alveolocapillary Leak

Permeability Pulmonary Edema (Protein Rich Edema Fluid)

Surfactant Disruption
Hyaline Membrane Formation
Alveolar Collapse, Consolidation

Cellular Necrosis, Epithelial Hyperplasia, Inflammation

Fibrosis

31

V. MANAGEMENT OF ARDS
Some Notes:
Mortality: mostly due to Sepsis or Multiple Organ
Failure
Primary Pulmonary cause / AHRF Causes < 20%
of ARDS Mortality
Impaired Lung Compliance = Hallmark of
ARDS
QuickTime and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

Goals in ARDS: Protective Mechanical Ventilation:

To accomplish Effective Gas Exchange
To minimize further Lung Damage & facilitate
Healing
Aim to PROTECT the Lung:
Decrease Tidal Volume
Give PEEP

A. Lung Protective Ventilation (LPV)

1. Avoid Alveolar Overdistention
Low Tidal Volume (6-8mL/kg)
Control Plateau Pressure to be below UIP
2. Use Sufficient PEEP
To prevent significant Shearing or Cyclic Atelectasis to be above LIP
3. Permissive Hypercapnea
This is a consequence of Low Tidal Volume (but we allow this)
Beneficial effect of Permissive Hypercapnea is still controversial
Safety of a very High PaCO2 is NOT proven
Usually well-tolerated the ARDSNet used NaHCO3 when pH<7.3 aside from Increasing the Respiratory
Rate
Contraindications to Permissive Hypercapnea:
Increased ICP
Active Myocardial Ischemia
Hypotension and/or Severe LV Failure with Catecholamine Dependence
Pulmonary Hypertension with Acute RV Failure
Severe Metabolic Acidosis
B. Other Ventilatory Strategies:
o Prone Positioning
o Recruitment Maneuvers
o Pressure VS Volume Limited Mode
o High Frequency Ventilation
o Inverse Ratio Ventilation
o ECMO, Partial Liquid Ventilation
o Spontaneous Breathing Trial

32

12) RESPIRATORY FAILURE

A Condition in which the Respiratory System FAILS in one or both of its Gas Exchanging Functions
Ie. Oxygenation of, and CO2 Elimination from Mixed Venous (Pulmonary Arterial) Blood
Findings in Respiratory Failure:
o HYPOXEMIA = PO2 < 60mmHg at Sea Level (inadequate blood oxygenation)
o HYPERCARBIA = PCO2 > 45 mmHg (excess of circulating CO2)

I. ACUTE VS CHRONIC RESPIRATORY FAILURE

A. Acute Respiratory Failure
o SUDDEN
o Leads to Life-Threatening Respiratory Insufficiency
B. Chronic Respiratory Failure
o Gradual WORSENING of Respiratory Function leads to Progressive Impairment of Gas Exchange
o Metabolic Effects are PARTIALLY Compensated by Adaptations of other Systems
II. CLASSIFICATION BASED ON ONSET AND CATEGORY
A. Acute VS Chronic:
1. Hypercapneic Respiratory Failure = PaCO2 > 45mmHg (due to HYPOVENTILATION)
a. Acute
Develops in Minutes to Hours with ACIDEMIA (Ph < 7.3)
There is Acute Respiratory Acidosis (Ph is LOW, and PCO2 is HIGH!)
b. Chronic
Develops over Several Days or Longer
However, there may be Compensation in Chronic Respiratory Failure (Ph may even normalize)
2. Hypoxemia Respiratory Failure = PaO2 < 60mmHg when FiO2 > 0.60
a. Acute
Develops in Minutes to Hours
Ex) Severe Pneumonia
**NOTE: FiO2 = Fraction of Inspired Oxygen (Oxygen delivered to the Patient)
b. Chronic
Develops over Several Days or Longer
Ex) Milder Pneumonia
The Central & Peripheral Nervous Systems, Respiratory Muscles & Chest Wall and Airways constitute the RESPIRATORY PUMP:
HYPERCAPNEA = Hallmark of Respiratory Pump Failure

Hypoventilation Decreased VA Accumulation of CO2 & Respiratory Acidosis

Just in comparison, we see Respiratory Alkalosis in people who Hyperventilate

HYPOXEMIA constitutes the Primary Disturbances in ALVEOLAR Disturbances, producing Respiratory Failure

Pulmonary Edema

Pneumonia, etc

III. GENERAL CRITERIA FOR ACUTE RESPIRATORY FAILURE

Patient is Acutely Dyspneic

PaO2 < 60mmHg (Breathing Room Air)
PaCO2 > 45mmHg
Arterial Ph shows Significant Respiratory Acidemia (Acute)
**NOTE: Many Patients with ARF do NOT Fulfill all FOUR Components of this Definition
o MUST SHOW AT LEAST TWO OF THE FOUR CRITERIA
o ABG is very Important in the Diagnosis

33

IV. TYPES OF RESPIRATORY FAILURE

A. TYPE 1: Acute Hypoxemic Respiratory Failure
o Occurs when alveolar flooding and subsequent intrapulmonary shunt physiology occurs
o Hypoxemia = PO2 < 60mmHg
o Mechanism = Problem is in the Lungs itself
o Etiology = Air Space Flooding (consequence of Pulmonary Edema, Pneumonia, Alveolar Hemorrhage)
1. Pulmonary Edema
Cardiogenic (Increased Hydrostatic Pressure)
Non-Cardiogenic (ARDS Secondary to an Acute Lung Injury)
2. Pneumonia
In Pneumonia, there is Accumulation of Secretions in the Alveoli
This leads to V/Q Abnormalities (Ventilation-Perfusion Mismatch)
Decrease in Ventilation, therefore, there will be Hypoxemia
3. Lung Hemorrhage
Ex) In a Vehicular Accident, there may be Pulmonary Contusion & Decreased Perfusion
This leads to Hypoxemia and V/Q Mismatch
4. ARDS
Defined by Diffuse Bilateral Airspace Edema seen by CXR, the absence of Left Atrial HPN, and profound
shunt physiology
Occurs in sepsis, gastric aspiration, pneumonia, near drowning, multiple BT, pancreatitis
B. TYPE 2: Acute Hypoventilatory Respiratory Failure
o Due to alveolar hypoventilation and results in the inability to eliminate CO 2 effectively
o PCO2 > 45mmHg
o Hypoventilation leads to a Problem in CO2 Elimination (Hypercarbia and Respiratory Acidosis)
1. Mechanism = Decreased Alveolar Ventilation (VA) there is Hypoventilation (RR < 10/min)
Decrease in CNS Drive = Central Lesion
Decrease Neuromuscular Coupling: Ex) Respiratory Muscle Fatigue
Increased Load in Respiratory System: Ex) Bronchospasm in Asthma, COPD, Emphysema
2. Clinical Description
a. Diminished CNS Drive:
Drug Overdose, Brain Stem Injury
Sleep disordered breathing
Hypothyroidism
b. Reduced Strength
Impaired Neuromuscular Transmission (Myasthenia Gravis, GB Syndrome, Amyotrophic Lateral
Sclerosis, Phrenic Nerve Injury)
Respiratory Muscle Weakness (Myopathy, Electrolyte Derangements, Fatigue)
c. Increased Overall Load in the Respiratory System:
Increase in Resistive Loads

Bronchospasm

Loads due to Reduced Lung Compliance

Alveolar Edema
Atelectasis
Intrinsic Positive and Expiratory Pressure

Loads due to Reduced Chest Wall Compliance

Pneumothorax
Pleural Effusion
Abdominal Distention

Loads due to Increased Minute Ventilation Requirements

Pulmonary Embolus with Increased Dead

Space Fraction, Sepsis

34

C. TYPE 3: Perioperative Respiratory Failure

o Occurs as a result of Lung Atelectasis (occurs so commonly in the Perioperative Period)
o Mechanism = ATELECTASIS
o Etiology = Decreased Functional Residual Capacity (FRC) w/c lead to Collapse of Dependent Lung Units
o Clinical Description (they cause a Decreased FRC)
Supine Position / Obese
Ascites (Difficulty in Lung Expansion)
Upper Abdominal Incision
General Anesthesia
Airway Secretions
D. TYPE 4: Shock
o Mechanism = HYPOPERFUSION
o Etiology: Cardiogenic, Hypovolemic, Septic
o Clinical Description
Myocardial Infarction (Cardiogenic Shock)
Hemorrhage (Hypovolemic Shock)
Dehydration (Hypovolemic Shock)
Endotoxemia (Septic Shock)

12) COR PULMONALE

RV Enlargement 20 to a Disease process which Primarily involves the LUNGS, Pulmonary Vasculature, or
Respiratory Gas Exchange
o Acute: Pulmonary Thromboembolism
o Chronic: Severe COPD
o Acute on Chronic: COPD + Infection & Worsening Hypoxemia

I. SYMPTOMS / SIGNS
A. Clinical Manifestations:
o Acute (see Pulmonary Embolism)
o Chronic: Productive Cough, Exertional Dyspnea, Easy Fatigability, Weakness
B. Physical Examination: RV-Failure Signs
o Neck Vein Engorgement
o RV Heave
o Increased O2
o Systolic Murmur (TR)
o Hepatomegaly
o Dependent Edema
II. MANAGEMENT
A. Diagnostics
12-L ECG

Tall, Peaked P Waves

RAD with RVH

CXR

Cardiomegaly, RV Form
Enlarged Pulmonary Conus

2D Echo

Diagnostic
Allows measurement of RV Thickness VS LV

B. Management
o Oxygen (Vasodilates Pulmonary Arteries, decreasing Resistance and Pulmonary Pressure)
o Treat Infection, remove secretions
o Diuretics (Caution in Loop Diuretics it causes Metabolic Alkalosis and Decreases Pulmonary Drive)
o Bronchodilators (Theophylline)

35

13) TYPICAL CHEST EXAMINATION FINDINGS:

CONDITION

PERCUSSION

FREMITUS

Normal

Resonant

Normal

Consolidation or Atelectasis
(with Patent Airway)

Dull

Increased

BREATH
SOUNDS
Vesicular
(at lung bases)
Bronchial

VOICE TRANSMISSION

ADVENTITIOUS
SOUNDS
Absent

Consolidation or Atelectasis
(with Blocked Airway)

Dull

Decreased

Decreased

Decreased

Absent

Asthma

Resonant

Normal

Vesicular

Normal

Wheezing

Interstitial Lung Disease

Resonant

Normal

Vesicular

Normal

Crackles

Emphysema

Hyperresonant

Decreased

Decreased

Decreased

Absent or Wheezing

Pneumothorax

Hyperresonant

Decreased

Decreased

Decreased

Absent

Pleural Effusion

Dull

Decreased

Decreased

Decreased

Absent of Pleural
Friction Rub

Normal
Bronchophony, Whisphered
Pectoriloquy, Egophony

Crackles

36

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RHEUMATOLOGY
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Jaime Alfonso Manalo Aherrera, M.D.

Internal Medicine Notes 2009

COMMON RHEUMATOLOGIC CASES

1) SYSTEMIC LUPUS ERYTHEMATOSUS

Autoimmune Disease in which organs and cells undergo damage mediated by Tissue-Binding Autoantibodies and Immune
Complexes

I. ACR CRITERIA FOR SLE

Discoid Rash
We ONLY need FOUR out of the ELEVEN to make a
Oral Ulcers
Diagnosis of SLE
Photosensitivity
Arthritis
Malar Rash
Immunologic Disorder
Neurologic Disorder (Seizures, Headaches, Stroke, etc)
Renal Disorder (Albuminuria, Hematuria, Pyuria, etc)
Antinuclear Antibody
Serositis
Hematologic Disorder

CLASSIFICATION CRITERIA FOR THE DIAGNOSIS OF SLE (Harrisons):

CRITERIA
Malar Rash

REMARKS
Fixed Erythema, Flat or Raised, over the Malar Eminences

Discoid Rash

Erythematous Circular Raised Patches with Adherent Keratotic Scaling and Follicular
Plugging; Atrophic Scarring may occur

Photosensitivity

Exposure to Ultraviolet Light causes Rash

Oral Ulcers

Includes Oral and Nasopharyngeal Ulcers; observed by Physician

Arthritis

Non-Erosive Arthritis of 2 or more Peripheral Joints, with Tenderness, Swelling or Effusion

Serositis

Pleuritis or Pericarditis documented by ECG or Rub or Evidence of Effusion

Renal Disorder

Proteinuria > 0.5g/d or 3+, or Cellular Casts

Neurologic Disorder

Seizures or Psychosis without other causes

Hematologic Disorder

Hemolytic Anemia or Leukopenia; or Lymphopenia; or Thrombocytopenia in the absence of

offending drugs

Immunologic Disorder

Anti-ds DNA, Anti-Sm, and/or Anti-Phospholipid

Antinuclear
Antibodies

An Abnormal Titer of ANA by Immunofluorescence at any point in time in the absence of

drugs known to induce ANAs

If > 4 of these Criteria, well documented, are present at any time in a patients history, the diagnosis is likely to be SLE
(Specificity is ~95%; Sensitivity is ~75%)

II. CLINICAL FEATURES OF SLE

Constitutional
Fever, Fatigue, Weight Loss
Mucocutaneous

Discoid LE, Subacute Cutaneous LE, Panniculitis, Alopecia, Vasculitis

Musculoskeletal

Arthritis, Osteonecrosis, Inflammatory Myositis

Gastrointestinal

Pancreatitis, Bowel Vasculitis, Hepatitis

CNS

Seizures, Psychosis Stroke

Most Common Manifestations of Diffuse CNS Lupus = Cognitive Dysfunction

Cardiovascular

Inflammation of all the Linings of the Heart: Pericarditis, Myocardial, Endocardial (Libman-Sacks
Endocarditis), Accelerated Atherosclerosis, Raynauds Phenomenon
Most Frequent Cardiac Manifestation = PERICARDITIS

Pulmonary

Pleuritis, Pneumonitis, Pulmonary Hemorrhage, Pulmonary Embolism, Pulmonary Hypertension

Most Common Pulmonary Manifestation = PLEURITIS with or without Pleural Effusion
May respond to NSAIDs if MILD
Glucocorticoid Therapy if Severe

Hematologic

Hemolytic Anemia, Leukopenia, Lymphopenia, Thrombocytopenia, Prolonged PTT

Most Frequent Hematologic Manifestation = ANEMIA (Normochromic, Normocytic)

Eyes

Conjunctivitis, Uveitis, Scleritis, Retinitis

Laboratory
Abnormalities
Renal

Hypocomplementemia (Low C3 and C4 Levels), Elevated ESR and CRP

Azotemia, Renal Failure, Hematuria, Albuminuria, Persistent Pyuria (not infection related)
Nephritis = the Most SERIOUS manifestation of SLE
Nephritis is usually ASYMPTOMATIC in Most Lupus Patients

III. METHYLPREDNISOLONE (rounds)

MPPT: Methylprednisolone Pulse Therapy Drip
Usually, dose is 500-1000mg 4-6 hours given 1 dose/day for 3 days (check harrisons)
This therapy is given in patients with SLE in Activity:
o Carditis
o Nephritis
o Anemia, Etc
FROM HARRISONS:
Methylprednisolone Sodium Succinate IV (approved for Lupus Nephritis): Used for SEVERE Disease at a Dose of
1g IV qd for 3 days

IV. MANAGEMENT OF SLE (Harrisons)

A. Conservative Therapies for Management of Non-Life Threatening Disease
o Sx: Fatigue, Pain, (+) Autoantibodies of SLE, but WITHOUT Major Organ Involvement
o Management is directed to suppression of symptoms
o Mainstay: Analgesics and Antimalarials
1. NSAIDs
Useful analgesics / anti-inflammatories, particularly for arthritis / arthralgias
TWO Major Issues CAUTION with NSAIDS
SLE patients are at increased risk for NSAID-Induced Aseptic Meningitis, elevated serum
transaminases, HPN, and renal dysfunction
All NSAIDS (particularly COX-2 Inhibitors) may increase risk for MI
2. Antimalarials (Hydroxychloroquine, Chloroquine, Quinacrine)
Reduce dermatitis, arthritis, fatigue
Potential Retinal Toxicity
B. Life Threatening SLE: Proliferative Forms of Lupus Nephritis
o Mainstay for any Inflammatory Life-Threatening or Organ-Threatening Manifestations of SLE =
SYSTEMIC GLUCOCORTICOIDS (0.5-2mg/kg per day PO or 1000mg of Methylprednisolone Sodium
Succinate IV Daily for 3 days, followed by 0.5-1mg/kg of daily Prednisolone or equivalent
o Evidence that glucocorticoid therapy is life-saving comes from studies survival is better in people with DPGN
treated with high dose daily glucocorticoids (40-60mg Prednisone daily for 4-6 months)
o Currently, high doses are recommended for much shorter periods (recent trials of interventions for severe SLE
employ 4-6 weeks of these doses). Thereafter, doses are tapered as rapidly as the clinical situation permits (usually
to a maintenance dose of 5-10 mg Prednisone
V. MANAGEMENT OF SLE (from Medicine Notes)
For Arthritis

Diclofenac Na 50mg/tab BID

For Active SLE

(CNS, Renal, Hema)

Prednisone 5mg/tab PO 40-60mg/day, maintained on dose of 10-20mg

MPPT 500-1000mg/am in D5W 50cc x 6h X 3 doses in 3 days (Severe SLE with Organ Damage)
Cyclophosphamide 2-3mg/kg/day

For Photosensitivity

Cyclophosphamide IV Pulse Therapy 500-1000mg in D5W 500cc x 6h (give Metoclopromide 2 tabs before the
drip) for life threatening SLE
Sunscreens

For Skin Lesions

Hydrocortisone 200mg BID + Betamethasone 0.05% Ointment

For Thrombosis

Coumadine PO

2) RHEUMATOID ARTHRITIS

Chronic multisystem disease of unknown cause systemic disease of unknown etiology

Characteristic Features: Persistent Inflammatory Synovitis, usually involving Peripheral Joints in a Symmetric Distribution

I. CLINICAL MANIFESTATIONS
Onset: RA is a chronic polyarthritis which begins insidiously with fatigue, anorexia, generalized weakness, and vague
musculoskeletal symptoms until the appearance of Synovitis becomes apparent
Specific symptoms usually appear gradually as several joints, especially those of hands, wrists, knees, and feet, become
affected in a Symmetric Fashion
Signs and Symptoms: Pain, Swelling, and Tenderness
PAIN in affected joint, aggravated by movement, is the Most Common Manifestation of established RA
Generalized Stiffness, usually greatest after periods of Inactivity, Morning Stiffness of > 1 hour duration
II. LABORATORY FINDINGS
Rheumatoid Factors (RF): Autoantibodies Reactive with the Fc Portion of
IgG found in more than 2/3 of adults with the disease and have classically
been used to evaluate patients with RA
Normochromic, Normocytic Anemia is frequently present in Active RA
ESR is increased in nearly all patients with Active RA
Synovial Fluid Analysis: presence of Inflammatory Arthritis

Labs Requested for RA:

ERC / CRP

RF

CBC

Renal

ALT (for MTX Therapy)

Urinalysis

Synovial Fluid Analysis

III. CRITERIA FOR THE DIAGNOSIS

A. Guidelines for Classification:
o Four of Seven Criteria are required to classify a patient as having Rheumatoid Arthritis (RA)
o Patients with Two or More Clinical Diagnoses are NOT Excluded

B. Criteria
o a) Morning Stiffness: Stiffness in and around the joints lasting 1 hour before Maximal Improvement
o b) Arthritis of Three or More Joint Areas: At least 3 Joint Areas, observed by a physician simultaneously, have
Soft Tissue Swelling or Joint Effusions, not just bony overgrowth. The 14 possible joint areas involved are right or
left proximal interphalangeal, metacarpophalangeal, wrist, elbow, knee, ankle, and metatarsophalangeal joints
o c) Arthritis of Hand Joints: Arthritis of Wrist, Metacarpophalangeal Joint, or Proximal Interphalangeal Joint
o d) Symmetric Arthritis: Simultaneous involvement of the same joint areas on BOTH sides of the body
o e) Rheumatoid Nodules: Subcutaneous Nodules over bony prominences, extensor surfaces, or juxtaarticular
regions observed by a physician
o f) Serum Rheumatoid Factor: Demonstration of abnormal amounts of Serum Rheumatoid Factor by any method
for which the result has been positive in less than 5% of normal control subjects
o g) Radiographic changes: Typical changes of RA on Posteroanterior Hand and Wrist radiographs that must include
erosions or unequivocal bony decalcification localized in or most marked adjacent to the involved joints
Criteria a-d must be present for at least 6 weeks. Criteria b-e must be observed by a physician

IV. THERAPY GOALS

1) Relief of Pain
2) Reduction of Inflammation
3) Protection of Articular Structures
4) Maintenance of Function
5) Control of Systemic Involvement

Medical Management:

NSAIDs or Selective COX-2 Inhibitors

Glucocorticoids for:
o 1) Symptomatic relief while waiting for a response to a slow-acting
immunosuppressive or immunomodulatory agent
o 2) Persistent Synovitis despite adequate trials of NSAIDs and
immunosuppressive or immunomodulatory agents
o 3) Severe constitutional symptoms (fever, weight loss) or extraarticular disease (vasculitis, episcleritis, pleurisy)

Immunomodulatory and Immunosuppressive Agents

o Methotrexate (initial choice for moderate to severe RA)
o Hydroxychloroquine or Sulfasalazine

3) INFECTIOUS ARTHRITIS

Staphylococcus aureus, Neisseria gonorrhoeae, and other bacteria are the MOST COMMON Causes of Infectious Arthritis (various
Mycobacteria, Spirochetes, Fungi, and Viruses also infect joints)
Acute Bacterial Infection typically involves a Single Joint or a Few Joints
Subacute or Chronic Monoarthritis or Oligoarthritis suggests Mycobacterial or Fungal Infection
Approach to Patients with Infectious Arthritis:
o ASPIRATION of SYNOVIAL FLUID an essential element in the evaluation of potentially infected joints
o Ultrasonography or Fluoroscopy may be used to guide aspiration of difficult to localize effusions
Normal Synovial Fluid
Acute Bacterial Infections
Crystal Induced, Rheumatoid, and other Non
Infectious Inflammatory Arthritides
Mycobacterial and Fungal

Contains < 180 Cells (predominantly Mononuclear Cells)

Cell Counts averaging 100,000/uL (25,000-250,000/uL) with > 90% Neutrophils
< 30,000-50,000 cells/uL
10,000-30,000/uL with 50-70% Neutrophils & the remainder Lymphocytes

**NOTE: Definitive Diagnosis of Infectious Process:

o Identification of Pathogen in Stained Smears of Synovial Fluid
o Isolation of Pathogen from Cultures of Synovial Fluid and Blood
o Detection of Microbial Nucleic Acids and Proteins by PCR-Based Assays and Immunologic Techniques
I. ACUTE BACTERIAL ARTHRITIS
A. Pathogenesis
o Bacteria enter the joint from the bloodstream; from a contiguous site of infection in bone or soft tissue; or by direct
inoculation during surgery, injection, animal or human bite, or trauma
o Hematogenous Route: Most Common Route in all age groups
B. Microbiology
o Infants: Group-B Strep, Gram (-) Enteric Bacilli, and S. aureus
o Young Adults & Adolescents: N. gonorrhea (most commonly implicated organism)
o S.aureus accounts for most Non-Gonococcal Isolates in Adults of all ages
Infectious Arthritis is generally categorized into Gonogoccal and Nongonococcal Disease. Usual presentation is with fever and an acute
monoarticular arthritis, although multiple joints may be affected by hematogenous spread of pathogens
Nongonococcal Infectious Arthritis in adults tends to occur in patients with previous joint damage or compromised host defenses. In contrast,
Gonococcal Arthritis causes one-half of all septic arthritis in otherwise healthy, sexually active young adults
General Principles of Treatment:
1. Joint Fluid Examination

Includes Gram Stain and Culture mandatory to make a diagnosis and to guide management

Joint Fluid Leukocyte Count: useful diagnostically and as a baseline

Cultures of Blood and other extra-articular sites of infection also should be obtained
2. Hospitalization

Indicated to ensure drug compliance and careful monitoring

3. IV Antimicrobials

Provide good serum and synovial fluid drug concentrations

Oral or Intra-Articular Antimicrobials are NOT appropriate as initial therapy

4. Repeated Arthrocenteses

Should be performed daily or as often as necessary to prevent reaccumulation of fluid

Arthrocentesis is indicated to:

o 1) Remove destructive inflammatory mediators
o 2) Reduce intra-articular pressure and promote antimicrobial penetration into the joint
o 3) Monitor response to therapy by documenting sterility of synovial fluid cultures & decreasing Leukocyte Count
5. Surgical Drainage or Arthroscopic Lavage & Drainage Indications:

1) Septic Hip

2) Joints in which either the anatomy, large amounts of tissue debris, or loculation of pus prevent adequate needle drainage

3) Septic Arthritis with coexistent Osteomyelitis

4) Joints that do not respond in 4-6 days to appropriate Tx and repeated arthrocenteses

5) Prosthetic joint infection

II. NON-GONOCOCCAL BACTERIAL ARTHRITIS

90% present with involvement of a Single Joint most commonly the KNEES (less frequently the hip)
(+) Moderate to Severe Pain that is uniform around the joint, effusion, muscle spasm, and decreased range of motion
(+) Fever 38.3 38.90C
Inflamed, Swollen Joint
Cellulitis, Bursitis, and Acute Osteomyelitis, which may produce a similar clinical picture, should be distinguished from
Septic Arthritis by their greater range of motion and less-than-circumferential swelling
Labs: (+) Blood Cultures in 50-70% of S.aureus infections, Synovial Fluid is turbid, serosanguinous, or frankly purulent,
Gram smears confirm presence of large numbers of Neutrophils
Total Protein and Lactate Dehydrogenase in synovial fluid are elevated; Glucose Level is Depressed
Synovial Fluid

Turbid
WBC Count > 100,000
1. On Gram Stain:

Gram (+) = we will see 65-75% Staph / Strep

In 30-50%, we will have NOTHING on Gram Stain (dont automatically rule this out)

Gram (-) Bacilli = 30-50%

2. Culture of Synovial Fluuid:

> 90% Culture (+) for Staphylococcus aureus

Culture other Fluids

Blood CS will be (+) 50% for Staph

Peripheral WBC

Elevated with a Leftward Shift

Acute Phase Reactants

ESR / CRP = HIGH

X-Ray of the Joint

1. Early Infection

Soft Tissue Swelling

Joint Space Widening

2. Late Infection

Bone Erosions

Joint Space Narrowing

III. GONOCOCCAL ARTHRITIS

Accounted for up to 70% of Infectious Arthritis
Consequence of Bacteremia arising from Gonococcal Infection or, more frequently, from asymptomatic gonococcal mucosal
colonization of the Urethra, Cervix, or Pharynx
A. Diffuse Gonococcal Infection (DGI)
o Most Common Manifestation: Fever, Chills, Rash, and Articular Symptoms. Small numbers of papules that
progress to hemorrhagic pustules develop on the trunk and the extensor surfaces of the distal extremities
o Migratory Arthritis and Tenosynovitis of the knees, hands, wrists, feet, and ankles are prominent
o Cutaneous Lesions and Articular Findings = due to immune reaction to circulating gonococci and immune complex
deposition in tissues
o Cultures of Synovial Fluid are consistently NEGATIVE, and Blood Cultures are Positive in < 45%
o Synovial Fluid may be difficult to obtain from inflamed joints, and usually contains only 10,000-20,000
leukocytes/uL
B. True Gonococcal Septic Arthritis
o True Gonococcal Septic Arthritis is LESS Common than the Diffuse Gonococcal Infection (DGI) Syndrome and
always follows DGI, which is unrecognized in 1/3 of patients
o A single joint (hip, knee, ankle, or wrist) is usually involved
o Synovial Fluid has > 50,000 leukocytes/uL and can be obtained with ease
o Gonococcus is only occasionally evident in Gram-Stained Smears
o Cultures of Synovial Fluid are Positive in < 40% of cases
o Blood Cultures are almost always Negative

IV. DIAGNOSIS
Difficulty in isolation of Gonococci from Synovial Fluid and Blood
Specimens for culture should be obtained from potentially infected mucosal sites
Cultures and Gram-Stained Smears of Skin Lesions are occasionally Positive
All specimens for culture should be plated onto Thayer-Martin Agar directly or in special transport media at the bedside
and transferred promptly to the microbiology laboratory in an atmosphere of 5% CO 2, as generated in a candle jar
V. TREATMENT
A. Non-Gonococcal Septic Arthritis

EMPIRICAL
1. Gram (+) in Smear

Oxacillin or Nafcillin 2g q4h

2. Gram (-) in Smear

Cefotaxime 1g q 8h

Ceftriaxine 1-2g q 24h

3. Suspect Pseudomonas

Add Aminoglycoside; or

3rd Generation Cephalosporin

DURATION
1. Staphylococcus:

4 Weeks
2. Penicillin Sensitive Pneumo / Strep:

2 Weeks on Penicillin-G 2m u q4h

3. Penicillin-Resistant

Cefotaxime / Ceftriaxone for 2 Weeks

4. Enteric Gram (-)

3-4 Weeks 2nd /3rd Generation Cephalosporin IV; or

Quinolone IV/PO
5. Pseudomonas

At Least 2 Weeks

B. Gonococcal Septic Arthritis

o CEFTRIAXONE 1g IV or IM q 24 h:
7 days If with Resolution and if Isolate Sensitive
7 day additional Ciprofloxacin 500mg bid po
Ceftriaxone (1g IV or IM every 24 hours) to cover possible Penicillin-Resistant Organisms. Once local and systemic signs are
resolving, the 7-day course of Tx can be completed with an oral agent such as Ciprofloxacin (500mg BID)

4) OSTEOARTHRITIS

OA or Degenerative Joint Disease characterized by deterioration of articular cartilage, with subsequent formation of
reactive new bone at the articular surface

I. MEDICAL MANAGEMENT: Objectives = Relief of Pain + Prevention of Disability

Acetaminophen (dose up to 1000mg up to QID) initial pharmacologic treatment
Low-Dose NSAIDs or Selective COX-2 Inhibitors
Glucosamine Sulfate 1500mg/day
Intra-Articular Glucocorticoid Injections
Tramadol
Topical Capsaicin
II. ADJUNCTIVE MEASURES: Non-Pharmacological Measures
Brief periods of rest for the involved joint relieve pain

5) GOUTY ARTHRITIS

90% due to Uric Acid UNDER Excretion

10% due to Uric Acid OVER Production
Ex) Beer BOTH Under and Over!

More on Rheumatologic Diseases:

Algorithm for the Diagnosis of Musculoskeletal Complaints:

Sites of Hand or Wrist Involvement & Diseases

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Definition of Terms:
A Palpable (less commonly audible) vibratory or
Crepitus
crackling sensation elicited with joint motion
Alteration of joint alignment such that articulating
Subluxation
surfaces incompletely approximate each other
Abnormal displacement of articulating surfaces such that
Dislocation
the surfaces are not in contact
For diarthrodial joints, the arc of measurable movement
Range of
through which the joint moves in a single plane
Motion
Loss of full movement, resulting from a fixed resistance
Contracture
caused either by tonic spasm of muscle (reversible) or to
fibrosis of periarticular structures (permanent)
Abnormal shape or size of a structure; may result from
Deformity
bony hypertrophy, malalignment of articulating
structures, or damage to periarticular supportive
structures
Inflammation of the entheses (tendinous or ligamentous
Enthesitis
insertions on bone)
Epicondilytis Infection or Inflammation involving an Epicondyle

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