Aherrera Notes

Dr. Jaime Aherrera’s Internal Medicine Notes 2009

 Aherrera Notes
Dr. Jaime Aherrera’s Internal Medicine Notes 2009

I. Basic Information
II. Cardiology
III. Endocrinology
IV. Gastroenterology
V. Hematology
VI. Infectious Disease
VII. Nephrology
VIII. Neurology
IX. Pulmonology
X. Rheumatology
Aherrera Notes | TAABLE OF CONTENTS
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GENERAL NOTES
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Jaime Alfonso Manalo Aherrera, M.D.
Internal Medicine Notes 2009

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 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 . Dose (mcg/kg/min) = . (ugtt/min) x 13.3 .

13.3 body weight

 Dopamine Doses (from Harrisons p1453)

DOSE MECHANISM OF ACTION EFFECT
< 2 mcg/kg per min Stimulate DA1 and DA2 Receptors Vasodilation of Splanchnic and Renal
Vasculature
2-4 mcg/kg per minute Stimulate B1-Receptors Increase in Cardiac Output with little or no
change in Heart Rate or SVR
> 5 mcg/kg per minute Effects on A1-Receptors overwhelm the Vasoconstricion, leading to Increase in SVE,
Dopaminergic Receptors 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 It is an Endogenous Catecholamine that stimulates B1, A1 Receptors, and Dopaminergic Receptors (DA1, DA2) in
the heart and circulation
o Dopamine also releases Norepinephrine from nerve terminals, which itself stimulates A1 and B1 Receptors, thus
raising Blood Pressure
o 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
 In 1 Ampule of Dobutamine = 250mg/amp Strength Factors:
 1 amp of Dopamine = 13.3
NOTE: 19ugtts/min = 19cc/hr  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 = 11.23 mcg/kg/min
45 kg 45 kg
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 Recall the Action of Dopamine at Different Doses (Dr. Magno Notes):
Effect. This is what we want for a patient with Septic Shock. We 1. At 1-5mcg = RENAL VASODILATOR
can increase the ugtts/min if patient is still Hypotensive up to  Exerts selective Renal and Mesenteric Vasodilation
34ugtt/min (20mcg/kg/min) for a 45kg patient (Dopa Max). If still  Acts on Dopamine Receptors
No Response with Dopa Max, we can give LEVOPHED  Improve Renal Blood Flow and Urine Output
(Norepinephrine).
2. At 6-10mcg = INOTROPIC
In the computation, we used 26.6 because 2 ampules of dopamine  Positive Inotropic Effect
were used for the patient.  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

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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 mcg/kg/min = . (ugtt/min) x 16.6 .

16.6 body weight

C. Action of Dobutamine at Different Doses:

o 0 – 10 mcg/kg/min = INOTROPIC EFFECT Notes from Harrisons:
o 10 – 20 mcg/kg/min = VASOCONSTRICTION 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 **NOTE: cc/hr is equal to uggts/min
8mcg/cc
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

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III. COMMON FORMULAS USED
A. General Formulas

BMI = kg / m2 Ideal Body Weight:

Females: 100 pounds + (5 pounds per inch over 5 feet)
Males: 106 pounds + (6 pounds per inch over 5 feet)
Underweight < 18.5
Normal Weight 18.5 – 22.9 **NOTE: Divide 2.2 to convert to kilograms
Overweight 23 – 24.9
Obese I 25 – 29.9
Obese II > 30

B. Cardiac Output, Mean Arterial Pressure (MAP), Anion Gap, Osmolality, Etc.

Cardiac Output Heart Rate x Stroke Volume

Mean Arterial Pressure Systolic BP + (2 x Diastolic BP)

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Normal Value: 70 – 100 mmHg

Urine Anion Gap ( Na + K ) – Cl

Serum Anion Gap Na – ( HCO3 + Cl )

Urine Osmolality ( SG – 1 ) x 40,000

Plasma Osmolality [2 (Na + K)] + RBS (mmol/L) + BUN (mmol/L)

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 2 Na + RBS in mmol/L

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

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IV. BUN / CREATININE RATIO; CREATININE CLEARANCE
A. BUN / Crea Ratio (SI Units)

Interpretation:
BUN:Crea Ratio = BUN x 247
 If < 10: Intrinsic Renal Cause
Crea
 If 10-20: Doubtful Cause
Conversion Factor for Serum BUN: 1 mmol/L = 2.8 mg/dL  If > 20: Pre-Renal Cause

B. Fractionated Urine Na (Best test to Diagnose if Renal or Prerenal)

Interpretation:
FENa = [ UNA x PCR ] x 100 <1 Pre-Renal
[ PNA x UCR ] >1 Renal (Oliguric ATN)

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

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

72 x Serum Crea in mg/dL 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 GFR mL/min / 1.73m2
I Kidney damage with normal / increased GFT 90
II Kidney damage with mildly decreased GFR 60 – 89
III Moderately decreased GFR 30 – 50
IV Severely decreased GFR 15 – 29
V Renal Failure < 15 (for dialysis)

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

[ (40 – Albumin in g/L) x 0.02 ] + Measured Ca2 in mmol/L A Fall in Serum Albumin of
1gm/dL is associated with a Fall
OR of 0.8mg/dL in Total Calcium
( 4 – Albumin in g/dL x 0.08 ) + Measured Ca2+ in mg/dL

 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)

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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 x 0.6 x BW (kg)

140
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
hours. Safest route of administration of water is by mouth
160 – 140 x 0.4 x 50 kg = 2.9 L or via a nasogastric tube. Alternatively, 5% Dextrose in
140 Water of Half-Isotonic Saline can be given IV

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 4. Water Excess

Water Excess = Normal Na+ x TBW - TBW

Actual Na+

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
Oral Kcl:
(Desired K+ - Measured K+) x 100
 15cc: 10 mEqs
0.27
 30cc: 20 mEqs

 Desired K is 3.5 Kalium Durule:

 Target K is 3.5 – 4.9 mEq/L  1 tab = 10 mEqs
 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: 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
 Administer as 10% Solution, 15cc + 20mEqs KCl; 1/2 of the dose given within 24 hours,
then the excess within the next 3 days
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

8
 2. Hyperkalemia
Mild (K <5.5) Restrict Potassium Intake
Moderate (K = 5.5-6.5) 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
Severe (K > 6.5) 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: Multiply by 18

BUN: Multiply by 2.8
Crea: Divide by 88.4
Ca2+: Divide by 0.25
Bilirubin: Divide by 17.10

Equivalents 1cc Oral KCl: 1.33 mEqs K

15cc Oral KCl: 20 mEqs K Regular requirement for NaHCO3 is 21mEq/day,
1 K Durule (750mg): 10 mEqs K so we usually give NaHCO3 GrX TID
NaHCO3 50mL: 45 mEqs Na
NaHCO3 Gr X Tab: 7 mEqs Na

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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 GLUCOSE Na+ Cl- K+ Ca2+ HCO3
D5W 50 gm/L
D10W 100 gm/L
0.9 NSS 154 154
D5LR 130 109 4 3 28
NM 40 40 13
NR 140 98 5
D50.9 NaCl 50 gm/L 154 154
D5NMK 50 gm/L 40 40 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

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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 . x 100
713

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 . x 100 = 36% - therefore, we can decrease FiO2 to 36%
713

**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

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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 4‟u‟SC

If CBG >250: give HR 6‟u‟SC
CBG Monitoring pre-meals and at bedtime

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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 B. Atropine Toxicity
Dry Mucosa T > 390C
HR > 60 Flushing
Hypoactive BS (-) Sweating
Pupils > 4mm 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) Bolus Stop Rate Change Rpt aPTT
(H) (min) (cc/hr) (hrs) aPTT CHANGE
< 40 s 3000 0 22 6 < 1.25 times 80 Units/kg/Bolus; then
Increase by 4 units/kg/hr
40 – 49 0 0 1 6
1.25 – 1.5 times 40 Units/kg/Bolus; then
50 – 75 0 0 No Change Next am Increase by 2 units/kg/hr
76 – 85 0 0 -1 Next am
1.5 – 2.5 times NO Change!
86 – 100 0 30 -2 6
101 – 150 0 60 -3 6 2.5 – 3.0 times Decrease by 3 Units/kg/hr

> 150 0 60 -4 6 > 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 TARGET PTT LMWH DOSE AND SCHEDULE

Venous Thrombosis Pulmonary Embolism

Treatment 5000 U IV Bolus; 2-2.5x 100 U/kg SC BID
1000-1500 U/h
Prophylaxis 5000 U SC q8-12h < 1.5x 100 U/kg SC BID

Acute Myocardial Infarction

With Thrombolytic Tx
With Mural Thrombus
Unstable Angina
5000 U IV Bolus; 1.5-2.5x 100 U/kg SC BID
1000 U/hr
8000 U SC q8 + Warfarin 1.5-2.0x 100 U/kg SC BID
5000 U IV Bolus; 1.5-2.5x 100 U/kg SC BID
1000 U/hr

Prophylaxis
General Surgery 5000 U SC BID < 1.5x 100 U/kg SC BID before & BID
Orthopedic Surgery 10,000 U SC BID 1.5x 100 U/kg SC BID before & BID
Px with CHF, MI 10,000 U SC BID 1.5x 100 U/kg SC BID

PTT at RECHECK INTERVENTION

Normal (27-35s) 5000 U Bolus; 1300 U/h Infusion
< 50s Rebolus with 5000 U and Increase Infusion by 100 U/h
50 – 60s Increase Infusion Rate by 100 U/h
60 – 85s No Change
85 – 100s Decrease Infusion Rate by 100 U/h
100 – 120s Stop Infusion for 30 minutes and Decrease Rate by 100 U/h at Restart
> 120s Stop Infusion for 60 minutes and Decrease Rate by 200 U/h at Restart

**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 Formulation: Dilute 20 Units of Insulin in 100cc PNSS to concentration of 0.2 Unit/cc
o 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 ACTION
< 70 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
70 – 120 Decrease Rate by 0.3 unit/hr
121 – 180 No Change in Rate
181 – 240 Increase Rate by 0.3 unit/hr
241 – 300 Increase Rate by 0.6 unit/hr
> 300 Increase Rate by 1.0 unit/hr
b. Subcutaneous (SC)
CBG ACTION
< 80 Discontinue for 30 minutes, give 15-20mL of D50-50, re-measure in 30 minutes
80 – 180 No Change in Rate
181 – 200 Humulin-R 6 Units SC
201 – 300 Humulin-R 8 Units SC
> 300 Humulin-R 10 Units SC
K. Dopamine, Dobutamine, Heparin
o See above discussion
VI. VIRCHOW‟S 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:
o Central Obesity NCEP:ATPIII 2001 CRITERIA for Metabolic Syndrome: Three or More of the following:
o Hypertriglyceridemia  Central Obesity: Waist Circumference > 102cm (M), > 88cm (F)
o Low HDL Cholesterol  Hypertryglyceridemia: TG > 150mg/dL or specific medication
o Hyperglycemia  Low HDL Cholesterol: < 40 mg/dL and 50 mg/dL, respectively, or specific medication
o Hypertension  Hypertension: BO > 130 systolic or > 85 Diastolic or specific medication
 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 PRIMARY COMPENSATORY RESPONSE
DISTURBANCE
Metabolic Acidosis Decrease in HCO3 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 Increase in pCO2 Acute:
 Acute < 2 weeks 1 mEq/L INCREASE in HCO3 for every 10mmHg RISE in pCO2
 Subacute 2-6 weeks Chronic
 Chronic > 6 weeks 3-5 mEq/L INCREASE in HCO3 for every 10mmHg RISE in pCO2
Respiratory Alkalosis Decrease in pCO2 Acute:
 Acute 2 mEq/L DECREASE in HCO3 for every 10mmHg FALL in pCO2
 Chronic Chronic:
5 mEq/L DECREASE in HCO3 for every 10mmHg FALL in pCO2
 Normal Values:
pH 7.4 + 0.3
pCO2 (mmHg) 40 + 4
HCO3 (mEq/L) 24 + 2
Anion Gap 12 + 2
Cl (mEq/L) 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) *NOTE: 24 is the desired HCO3; 7 is the actual HCO3
= 18.75
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 . If: = 1  Pure HAGMA Diseases with HAGMA:
∆ HCO3 < 1  HAGMA + NAGMA -Lactic Acidosis
-Ketoacidosis
> 1  HAGMA + Metabolic Alkalosis  Diabetic
B. Normal Anion Gap Metabolic Acidosis  Alcoholic
 Starvation
. ∆ Cl . If: = 1  NAGMA -Toxins
∆ HCO3 < 1  NAGMA + HAGMA  Ethylene Glycol
> 1  NAGMA + Metabolic Alkalosis  Methanol
VI. ANION GAP  Salicylates
A. High-Anion Gap Metabolic Acidosis (HAGMA)  Propylene Glycol
 Pyroglutamic Acid
o Methanol -Renal Failure (Acute and Chronic)
o Uremia
o DKA MUDPILES Diseases with NAGMA
-Renal HCO3 Loss (Proximal RTA Type 2)
o Paraldehyde -Enhanced NH4 Excretion
o Isoniazid -Ingestion of HCl, NH, Cl, Lysine, Arginine
o Lactic Acidosis -GI HCO3 Loss (Diarrhea) or Acid Gain
o Ethanol -Impaired NH4 Excretion
-Distal RTA (Type 1)
o Salicylates -Diarrhea
B. Normal-Anion Gap Metabolic Acidosis (NAGMA) -Urinary Tract Obstruction
o Renal
o GI Losses
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 INTERPRETATION:
 Prevailing PCO2 is ABOVE Predicted Value Severe Pneumonia, Pulmonary Edema
 Example: Na 14, K 4.0, Cl 102; HCO3 18; AG 20
PCO2 38, pH 7.3
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
PCO2 38, pH 7.55 INTERPRETATION:
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
P-Wave < 0.12 sec
< 0.25 Mv in Limb Leads
< 0.1 Mv Terminal Negative Deflection in V1
PR Interval 0.12 – 0.20 sec (up to 5 small boxes)
QRS Duration < 0.11 – 0.12 sec
T Wave 5 – 10 mm (0.5 – 1.0 Mv)
QTc < 0.44 (females)
< 0.48 (males)
 Formula of Corrected QT-Interval (QTc)

Corrected QT Interval = . QT Actual .

√ R-R Interval

 Computation of Heart Rate

Rate = . 300 . = . 1500 .

# of Big Sq # of Small Sq

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

II. AXIS
 Computation of Frontal Axis:

Axis = . 90 x aVF .
|I| + |aVF|
 Where:
o Avf and I are integers derived by subtracting the Positive Deflection from the Negative Deflection
o The Avf in the numerator is an Integer, while the I and Avf in the Denominator are absolute values of integers
o If I is a Negative Integer, then adjust the Axis by adding | 90 |

 Interpretation:
Right Axis Deviation (RAD) > 1000
Left Axis Deviation (LAD) < -300
Normal Axis -300 to 1000
Extreme Axis Deviation -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 P-Wave with 2.5mm Amplitude (0.25Mv) in any of Lead II, III or Avf

Left Atrial Enlargement 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 P-
Wave, 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 RAD is a Prerequisite Criterion for RVH

o 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 > 25% of the QRS Complex; or
> 0.04 sec
C. Walls of Involvement
LEADS MYOCARDIAL WALL INVOLVED
V1 Posterior
V1-V2 Septal
V1-V3 or V1-V4 Anteroseptal
V3-V4 Anterior
V5-V6 Lateral
V3-V6 Anterolateral
V1-V6 Massive Anterolateral
II, III, Avf 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 T-Piece and CPAP Weaning are best tolerated by patients who have undergone MV for brief periods and require little respiratory
muscle reconditioning
o 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
 PaO2 < 60 NOTES on FiO2:
 TV < 3.5mL/kg  FiO2 at Room Air = 21%
 VC < 10-15mL/kg  O2 via Nasal Prong = # lpm x 0.4 + 20
 Inspiratory Force < 25cmH2O
 FEV < 10mL/kg The primary indication for initiation of mechanical ventilation is
 VQ/VT > 0.6 Respiratory Failure, of which there are 2 basic types:
 To deliver High FiO2  Hypoxemic Respiratory Failure
 Absent Gag  Hypercarbic Respiratory Failure
 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 General: 8-10 mL/kg
o 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 (doesn‟t 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 patient‟s 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 Patient‟s 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 USUAL VALUE
1) Tidal Volume (VT) 8-10 mL/kg of Ideal Body Weight
 How much volume will the Machine Deliver? 6mL/kg for ALI/ARDS
10-15mL/kg for Neuromuscular Dse

2) Back-Up Rate: Number of Tidal Breaths Delivered per Min 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) 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) 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) 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 -2.0cm or 2L
 Ranges anywhere from –5 to –0.5cmH2O (Pressure Sensitivity) or
1 to 5 Liters (Flow Sensitivity) Different for PGH Vents
 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

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 patient‟s 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 Patient‟s 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 Patient‟s 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:

A/C MODE SIMV MODE
Assist Total Partial
Work of Breathing Almost NONE Variable
Can be Used for Weaning NO 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) At Sea Level:

FiO2 = 0.21 PaCO2 = Measured by Labs
PH2O = 47 R = 0.8
Normal PAO2-PaO2 Gradient = 10 PBREATH = 760
Increases by 5-6 per decade over 50

B. Desired FiO2
Example:
Desired FiO2 = (PaO2 Desired x FiO2 Known)
Desired FiO2 = 80 x 21%
PaO2 Known 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 patient‟s 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 patient‟s 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 patient‟s 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 4-11x109/L 4-11 x 103/mm3
RBC 4-6 x 1012/L 4-6 x 106/mm3 BLOOD CHEM
Hgb 120-180 g/L 12.0-18.0g/dL
Glucose 3.9-6.1 mmol/L 75-110 mg/dL
Hct 0.370-0.540 %
BUN 2.6-6.4 mmol/L 7-20 mg/dL
MCV 80-100 fL
Creatinine 53-115 umol/L 0.6 – 1.3 ng/mL
MCH 27-31 pg
Sodium 140-148 mmol/L 140-148 mEq/L
MCHC 320-360 g/L
Potassium 3.6-5.2 mmol/L 3.6-5.2 mEq/L
RDW-CV 11-16%
Chloride 100-108 mmol/L 100-108 mEq/L
Platelets 150-450 x 109/L 150-450 x 103/mm3
Calcium 2.12-2.52 mmol/L 8.7-10.2 mg/dL
Neut% 0.5-0.7 Magnesium 0.70-1.00 mmol/L 1.5-2.3 mg/dL
Lymph% 0.2-0.5 Phosphates 0.9-1.55/0.42-1.97
Mono% 0.02-0.09 Total protein 64-83 g/L 6.4-8.3 g/dL
Eo% 0.0-0.06 Albumin 34-50 g/L 3.4-5.0 g/dL
Baso% 0.0-0.02 Globulin 23-35 g/L
Pro/Mye/Jv 0 AST (SGOT) 15-37 U/L
Stabs 0.02-0.04 ALT (SGPT) 30-65 U/L
Blasts 0 Alk phos 36-92 umol/L
Reticulocytes 0.005-0.015 Total bilirubin 0-17.1 umol/L 0.3-1.3 mg/dL
Dir bilirubin 0 - 5.00 umol/L 0.1-0.4 mg/dL
Thyroid Hormones Ind bilirubin 3.4-13.7 umol/L 0.2-0.9 mg/dL
Free T4 0.8-2.0 ng/dL Urate 0.13-0.44 mmol/L
Free T3 2.3-4.2 pg/dL Amylase 30-110 U/L
TSH 0.25-4.30 microunits/mL Lipase 23-300 U/L
Serum T3 70-200 ng//dL LDH 100-190 U/L
Serum T4 4.0-11.0 ug/dL ESR M: 0-15 mm/h F: 0-20 mm/h
CRP 0.2-3.0 mg/L
Ammonia 19-60 ug/dL 11-35 umol/L
ABG
RF < 20 IU/mL
pH 7.35-7.45
PCO2 35-45 mmHg
PO2 90-100 mmHg Cardiac Enzymes
HCO3 22-28 mEq/L CK-total 55-170 U/L
CK-MB 0-16 U/L
Urinalysis CK-MM 8-97 U/L
Color Yellow Troponin I 0-0.09 ng/mL 0-0.09 ug/L
Transparency Clear/hazy Cut Off for MI > 0.4 ng/mL > 0.4 ug/L
SG 1.016-1.022
PH 4.6-6.5 Lipid Profile
Sugar, Albumin (-) HDL 0.91-1.56 mmol/L 35-60 mg/dL
RBC 0/0-2/hpf LDL 1.1-3.8 mmol/L 40-145 mg/dL
WBC 0-2/0-5/hpf Cholesterol 4.2-5.2 mmol/L 160-200 mg/dL
Casts hyaline, coarse, fine, granular, waxy
Triglycerides 0.41-2.37 mmol/L < 180 mg/dL
Crystals Small amounts
 HDL or LDL divided by 0.0259  to convert to mg/dL
Epith cells Small amounts
 TAG divided by 0.0113  to convert to mg/dL
Bacteria (-)
Mucus thr Small amounts
24 Urine Chemistry
Total volume 500-2000 cc
Creatinine 0.65-0.70 g/L 8.8-14 mmol/d
Cancer Markers
Total protein 0-0.1 g/24hour < 100mg/d
AFP 0-8.5 ng/L Na+ 80-216 mmol/L Varies with intake
PSA 0-4 ng/mL K+ 25-100 mmol/L
CA 125 0-35 U/mL Cl- 80-340 mmol/L
CA 19-9 0-37 U/mL Uric acid 4.42-5.9 mmol/24hr
CEA (-)Smoker: 0-3 ug/L (+)Smoker: 0-5 ug/L Ca++ 2.5-7.5 mmol/24hr

36
Phosphorus 22.4-33.6 mmol/24hr
Amylase 64.75-490.25 U/L
Microalbumin 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 REMARKS
Penicillins
Penicillin +++ - ++ Narrow spectrum penicillins
Oxacillin PO/IV ++ - + Specifically used for Staphylococcus aureus
Flucloxacillin ++ -
Amoxicillin PO, Ampicillin IV ++ ++ - Broad spectrum penicillin
Co-Amoxiclav ++ 1/2 ++ 1/2 ++ 1/2 Good anaerobic coverage
Ampi-Sulbactam ++ ++ ++ 1/2 Good anaerobic coverage
Piperacillin / Tazobactam ++ ++ 1/2 + Use as reserve drug for Pseudomonas
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 +++ +++ +++ Use as reserve drug
Meropenem Gm (+) activity as good as Penicillin
For Gm (-): may add Amikacin for Synergism
Anaerobic activity as good as Metronidazole
Ertapenem ++ +++ + Very little activity against pseudomonas
Macrolides
Erythromycin ++ 1/2 + 1/2 + May cause GI upset
Azithromycin ++ 1/2 ++ + 1/2
Clarithromycin
Dirithromycin
Tetracycline
Doxycycline ++ ++ + For patients > 8 years old
Tetracycline Tetracycline is cheaper, but given QID
Aminoglycosides
Amikacin + +++ - With Anti-Pseudomonas activity
Gentamicin Amikacin with Anti-TB action
Tobramycin
Netilmicin
First Generation Cephalosporins
Cephalexin PO +++ + -
Cefazolin IV
Second Generation Cephalosporins
Cefuroxime IV ++ 1/2 ++ + IV drug
Cefuroxime Axetil PO ++ 1/2 ++ + Oral drug
Cefoxitin ++ ++ ++ 1/2 Cephalosporin with best Anaerobic coverage
Third Generation Cephalosporins
Ceftriaxone ++ +++ ++ For multidrug resistant Typhoid
Ceftazidime ++ +++ ++ Ceftazidime is best for Pseudomonas
Cefotaxime ++ +++ ++ Cefotaxime is best for Meningitis
Fourth Generation Cephalosporins
Cefepime +++ +++ ++ These should be reserved for the very resistant
Cefpirome strains

Quinolones
38
Ciprofloxacin + +++ - Used for multidrug resistant Typhoid Fever
Norfloxacin Ciprofloxacin is best for Pseudomonas
Ofloxacin Norfloxacin is good for Severe UTI
Fleroxacin
Levofloxacin ++ +++ + Moxifloxacin with better Anaerobic activity
Moxifloxacin
Others
Co-Trimoxazole ++ 1/2 ++ 1/2 -
Co-Trimazine
Chloramphenicol ++ 1/2 ++ 1/2 ++ 1/2 Drug of choice for Uncomplicated Typhoid
Clindamycin ++ - +++ “Above diaphragm” Anaerobes
Good Gm(+) Activity
Metronidazole - - ++ 1/2 “Below diaphragm” Anaerobes
Rifampicin ++ ++ + 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  Cefoxitin  Amoxycillin-Clavulanic Acid
o Metronidazole  Meropenem  High Dose Penicillin
o Chloramphenicol  Ampicillin-Sulbactam
 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 **NOTE: Use Penicillins, Ampicillin
 Listeria monocytogenes
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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Jaime Alfonso Manalo Aherrera, M.D.

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Internal Medicine Notes 2009

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 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 Myocyte Hypertrophy
o Alterations in the Contractile Properties of the Myocyte
o Progressive Loss of Myocytes through Necrosis, Apoptosis, and Autophagic Cell Death
o B-Adrenergic Desensitization
o Abnormal Myocardial Energetics and Metabolism
o 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
o S3 Gallop 1 Major + 2 Minor Criteria
o Increased Venous Pressure (>16cmH2O)
o Positive Hepatojugular Reflux

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 DESCRIPTION GENERAL GUIDE
CLASS
I Dyspnea occurs with Greater than Ordinary Physical Activity Climbs > 2 flights of stairs with Ease
II Dyspnea occurs with Ordinary Physical Activity Can climb 2 flights of stairs but with difficulty
III Dyspnea occurs with Less than Ordinary Physical Activity Can climb < 1 flight of stairs
IV Dyspnea may be present even at Rest Dyspnea at rest

2
III. CANADIAN CARDIOVASCULAR SOCIETY CLASSIFICATION OF ANGINA
FUNCTIONAL DESCRIPTION
CLASS
I Angina occurs with Greater than Ordinary Physical Activity
II Angina occurs with Ordinary Physical Activity
III Angina occurs with LESS than ordinary Physical Activity
IV Angina may be present even at REST

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: Digitalis preparations have a narrow therapeutic range, so maintaining
o Potentially Life-Threatening Dysrhythmias the desirable serum level of the drug is difficult. HYPOKALEMIA,
o Heart Blocks a common side effect of diuretic therapy, POTENTIATES the Toxic
o Etc 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 Depressed ST-Segments in leads where the main QRS Deflection is Positive (eg. In the inferior and lateral leads); the ST-
Segments gradually slope downward and look “scooped out”
o Elevated ST-Segments in leads where the main QRS Deflection is Negative (eg. Lead V1)
o Flattened or Inverted T-Waves
o Shortened QT Interval
o 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
 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
o Ventricular Dysrhythmias
 Ventricular Premature Complexes (VPCs) Bidirectional VT (alternating Polarity of the QRS
 Ventricular Bigeminy Complex) is associated with Poor Prognosis
 Ventricular Tachycardia (VT)
 Ventricular Fibrillation
o Atrioventricular (AV) Block
 Atrial Tachycardia with AV Block
 Second Degree AV Block Type I
 Third Degree AV Block

E. Treatment of Digitalis TOXICITY

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

3
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 examiner‟s 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
Kussmaul’s 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

4
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

5
HYPERTENSION (from Harrisons)
CLASSIFICATION SYSTOLIC (mmHg) DIASTOLIC (mmHg)
Normal < 120 And < 80
Pre-Hypertension 120 – 139 Or 80 – 89
Stage 1 Hypertension 140 – 159 Or 90 – 99
Stage 2 Hypertension > 160 Or > 100
Isolated Systolic Hypertension > 140 And < 90

 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 B. Hypertensive Emergency

o Use ORAL Drugs first o Use IV Medications, stat
o ALA Hypertensive Crisis o AKA Malignant Hypertension
o Uncontrolled HPN with NO End-Organ Damage o WITH End Organ Damage (Papilledema,
o Lower BP within 24 hours Encephalopathy, Eclampsia, etc)
o Lower BP within 1 Hour

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

1. Oral / Sublingual
Nifedipine 5-10 mg SL q30 mins, then 5-10mg PO or SL q6-8hours; OR
30mg/tab PO OD-BID (max 90mg/day)
Captopril 25 mg/tab 1/2-1 tab SL q30 mins
Clonidine 75 mcg/tab SL q1 (max 700mcg)
2. IV
Nicardipine IV Initial 5mg/h; titrate by 2.5 mg/h at 5-15 min intervals
Max: 15mg/h
Hydralazine 5-10mg IV q3-6 hours (0.1-0.5mg/kg/dose, max 20mg/dose)
Duration: 3-6 hours
ISDN IV Especially for patients with concomitant CAD

Clonidine 1 amp (150mcg/amp) SC, IM or IV with patient supine

Nitroprusside IV Initial 0.3 ug/kg/min; usual 2-4 ug/kg/min;
Max 10 ug/kg/min for 10mins

6
Stages in the Evolution of Heart Failure (Recommended Therapy by Stage):
STAGE A STAGE B STAGE C STAGE D
At risk for heart Structural Heart Structural Heart Refractory HF requiring
failure, but without Disease but without Disease with Prior Specialized Interventions
structural heart disease Symptoms of HF Current Symptoms Patients who have marked
or symptoms of HF of HF Symptoms at rest despite
Patients with HPN, Patients with previous maximal therapy (eg. Those
CAD, DM MI, LV Systolic Patients with known who are recurrently
Dysfunction, Structural Heart hospitalized or cannot be
Or
Asymptomatic Disease, Shortness safely discharged from the
Patients using Valvular Disease of Breath and hospital without specialized
Cardiotoxins with FHx Fatigue, Reduced interventions)
CM Exercise Tolerance

Structural Heart Disease Symptoms of HF Develop Refractory Symptoms of HF at Rest

Therapy: Therapy: Therapy: Therapy:

Treat HPN All measures under All Measures under All measures under Stage
Encourage smoking Stage-A Stage-A A, B, and C
cessation Mechanical assist devices
ACE Inhibitors in Drugs (Routine Use):
Treat Lipid D/O appropriate patients -Diuretics Heart Transplant
Encourage regular -ACE Inhibitors Continuous (not
exercise Beta-Blockers -Beta-Blockers intermittent) IV Inotropic
Discourage Alcohol -Digitalis Infusions for Palliation
Intake, Illicit Drug use -Dietary Salt Hospice Care
Restriction
ACE Inhibition

7
 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
 Levine‟s 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

8
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
Long Acting Nitrates
B-Adrenergic Blockers
Ca+ Channel Blockers
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
None of the Long Acting Nitrates is as effective as Sublingual Nitroglycerin for the Acute
Relief of Angina
Reduce Myocardial O2 Demand by inhibiting the increases in HR, arterial pressure, and
myocardial contractility caused by Adrenergic Activation
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
 Prinzmetal‟s 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

9
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 Prinzmetal‟s 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 In patients with clinical features of UA, the presence of New ST-Segment
o Transient ST-Segment Elevation Deviation, even of only 0.05 mV, is an important predictor of adverse outcome.
o T-Wave Inversion 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 CLINICAL CONDITION WHEN TO AVOID
Nitrates Administer IV when symptoms are not fully relieved with Hypotension
three sublingual nitroglycerin tablets and initiation of beta Patient receiving Sildenafil or other
blocker therapy 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 Pulmonary Edema
doses of nitrates and Beta Blockers or in patients unable to Evidence of LV Dysfunction (for
tolerate adequate doses of one or both of these agents or in Diltiazem or Verapamil)
patients with variant angina
Morphine Sulfate Patients whose symptoms are not relieved after three serial Hypotension
sublingual nitroglycerin tablets or whose symptoms recur Respiratory Depression
with adequate anti ischemic therapy Confusion
Obtundation

B. Anti-Ischemic Treatment  Aspirin

o Bed Rest  Clopidogrel
o Nitrates
o Beta Blockers 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. PRINZMETAL‟S 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 Q WAVE ST ELEVATION T WAVE TIMING
Hyperacute (-) (-/+) Peaked 0 – 6 hours
Acute MI (-/+) (++) (-/+) 6 – 24 hours
Recent MI (++) (++) Inverted 24 – 72 hours
Undetermined (++) (-) Inverted 72 hrs – 6 wks
Old MI (++) (-) Upright > 6 wks
B. Molecular Markers in the Diagnosis of AMI (Blue Book)
TESTS TIME TO PEAK DURATION MOST COMMON SAMPLING SCHEDULE
DETECTION
Troponin-T 3-12 hrs 24 hours 5-14 days Once at least 12 hrs after chest pain
Troponin-I 3-12 hrs 24 hours 5-10 days Once at least 12 hrs after chest pain
CK-MB 3-12 hrs 24 hours 2-3 days Every 12 hrs x 3; Start at 6 hrs after chest pain

Cardiac-Specific Troponin T and Troponin I:

Creatine Phosphokinase (CK)
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
 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
 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. KILLIP‟s CLASSIFICATION OF AMI

CLASS DESCRIPTION RISK OF MORTALITY
(Blue Book)
Class I No Signs of Pulmonary or Venous Congestion (0-5% Mortality Rate) 0-5% Risk Mortality
No Rales
Normal Blood Pressure
Class II Moderate Heart Failure 10-20% Mortality Rate
(+) Rales at the Lung Bases
Normal Blood Pressure with Basal Congestion
S3-Gallop
Tachypnea or Signs of Right-Sided Heart Failure (Venous & Hepatic Congestion)
Class III Severe Heart Failure 35-45% Mortality Rate
(+) Midbasal Rales
(+) S3 and S4
Normal Blood Pressure
Pulmonary Edema
Class IV Shock with Systolic Pressure < 90mmHg & evidence of Peripheral Vasoconstriction 85-95% Mortality Rate
Peripheral Cyanosis
Mental Confusion and Oliguria
Pulmonary Congestion
Hypotension; Cardiogenic Shock

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
 Relief of Chest Pain When ST-Segment Elevation of at least 2mm in 2
contiguous precordial leads and 1 mm in two adjacent
 Anti-Platelets / Anti-Coagulants limb leads is present, a patient should be considered a
A. Primary Goal in Management in STEMI = REPERFUSION candidate for reperfusion therapy
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 Avoid giving NSAIDS in the ACUTE Setting of Myocardial Infarction (AMI)
o B-Blockers

Sublingual Can be given up to 3 doses of 0.4mg at 5 min intervals. In addition to diminishing or abolishing chest
Nitroglycerin 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 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
Diet Nothing or only clear fluids (due to risk of emesis and aspiration) for the first 4-12 hours
Bowels Use of stool softener.
Sedation 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 patient‟s functional capacity and ability to perform test at home or work
 Evaluate efficacy of patient‟s 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
o 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 (JONE‟S 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%)
Syndenham’s 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) 2 Major Criteria
 Fever OR
2. Laboratory Findings of: 1 Major and 2 Minor Criteria
 Elevated Acute Phase Reactants (ESR / CRP)
 Prolonged PR interval PLUS
PLUS Supporting Evidence of Antecedent Group-A Strep Infection
o (+) Throat Culture or Rapid Strep-Antigen Test Evidence of Preceding Infection
o And/or Elevated or Rising Strep-Antibody Test
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
o Malar flush with pinched and blue facies
o 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
o RV Tap (due to enlarged RV) NOTE: JVP vs CVP
 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
o Low pitched rumbling Diastolic Murmur  Normal CVP = 8cm

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 SUBACUTE BACTERIAL IE
Pathogenic Organism Staph. Aureus (Virulent) Strep. Viridans, Enterococci (Less Virulent)
Clinical Presentation High Fever, Acute Course Low Grade Fever, Subacute Course
Cardiac Pathology Normal cardiac valves, No Murmurs Damaged Valves, (+) Murmurs
Prognosis Fatal in 6 weeks if Untreated Better Prognosis
II. DUKE‟S 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 3) Vascular Phenomena: Arterial embolism, CNS hemorrhage, conjunctival hemorrhage, Janeway lesions
o 4) Immunologic Phenomena: Immune-complex Glomerulonephritis, rheumatoid factor, false-positive
VDRL test, Osler‟s nodes, or Roth spots
o 5) Microbiologic Evidence: Positive Blood Culture results, but NOT Positive for Major Criterion
o 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 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
Subacute IE 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 BECK’S TRIAD:
Electrical Alterans  Hypotension
CXR Cardiomegaly  Engorgement of Neck Veins
No Pulmonary Venous Congestion  Muffled Heart Sounds
2D Echo (Diagnostic) RV Collapse with significant Pericardial Effusion
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
 Ewart’s 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

 Neck Vein Engorgement Diagnosis of SVC Syndrome is CLINICAL. Tracheal Obstruction
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)
 Laplace’s 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 Is the disease congenital, hypertensive, ischemic, or inflammatory in origin?
2) Anatomic Abnormalities 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?
3) Physiologic Disturbances Is an arrhythmia present? Is there evidence of congestive heart failure or of myocardial ischemia?
4) Functional Disability How strenuous is the physical activity 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
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vasoconstrictor that increases
permeability of renal collecting
ducts, leading to reabsorption
of free H2O. These afferent
signals to CNS also activate
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innervate the heart, kidney,
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Typical Clinical Features of Major Causes of Acute Chest Discomfort
CONDITION DURATION QUALITY LOCATION ASSOCIATED FEATURES
Angina More than 2 and less Pressure, tightness, Retrosternal, often with radiation to or Precipitated by exertion, exposure to cold,
than 10 mins squeezing, heaviness, isolated discomfort in neck, jaw, psychologic stress
burning shoulders, or arms – frequently on left S4 Gallop or MR murmur during pain
Unstable Angina 10-20 mins Similar to angina but Similar to angina Similar to angina but occurs with low levels of
often more severe exertion or even at rest
Acute MI Variable (often > Similar to angina but Similar to angina Unrelieved by nitroglycerin
30mins) often more severe May be associated with evidence of heart failure or
arrhythmia
Aortic Stenosis Recurrent episodes as As described for angina As described for angina Late-Peaking Systolic Murmur radiating to Carotids
described for angina
Pericarditis Hours to Days; may be Sharp Retrosternal or toward Apex May be relieved by sitting up and leaning forward
episodic May radiate to left shoulder (+) Pericardial Friction Rub
Aortic Dissection Abrupt Onset of Tearing or Ripping Anterior Chest, often radiating to the Associated with HPN and/or underlying CT D/O (eg.
unrelenting pain Sensation; back, between shoulder blades Marfan Syndrome)
Knifelike Murmur of Aortic Insufficiency, Pericardial Rub,
Pericardial Tamponade, or Loss of Peripheral Pulses
Pulmonary Abrupt Onset; Several Pleuritc Often lateral, on the side of Embolism Dyspnea, Tachypnea, Tachycardia, Hypotension
Embolism Minutes to a Few Hrs
Pulmonary Variable Pressure Substernal Dyspnea, signs of increased venous pressure
Hypertension including edema and JVP distention
Pneumonia or Variable Pleuritic Unilateral, often localized Dyspnea, cough, fever, rales, occasional rub
Pleuritis
Spontaneous Sudden Onset; Several Pleuritic Lateral to Side of Pneumothorax Dyspnea, Decreased Breath Sounds on side of
Pneumothorax Hours 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 Variable Aching Variable Aggravated by movement
Disease May be reproduced by localized pressure on exam
Herpes Zoster Variable Sharp or Burning Dermatomal Distribution Vesicular Rash
Emotional / Variable, may be Variable Variable; may be retrosternal Situational factors may precipitate symptoms
Psychiatric fleeting Often with anxiety / depression in Hx

25
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ENDOCRINOLOGY
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Jaime Alfonso Manalo Aherrera, M.D.
Internal Medicine Notes 2009

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

I. BURCH AND WARTOFSKY‟S DIAGNOSTIC CRITERIA FOR THYROID STORM

A. Thermoregulatory Dysfunction (Temperature)
37.2 – 37.7 0C 5 Scoring:
37.8 – 38.2 0C 10 < 25 Unlikely Storm
38.3 – 38.8 0C 15
38.9 – 39.3 0C 20 25 – 44 Impending Storm
39.4 – 39.9 0C 25 > 45 Highly Suggestive of
> 40.0 0C 30 Thyroid Storm
B. Central Nervous System Effects
Absent 0
Mild (Agitation) 10
Moderate (Delirium, Psychosis, Extreme Lethargy) 20
Severe (Seizure, Coma) 30
C. Gastrointestinal-Hepatic Dysfunction
Absent 0
Moderate (Diarrhea, Nausea/Vomiting, Abdominal Pain) 10
Severe (Unexplained Jaundice) 20
D. Cardiovascular Dysfunction
1. Tachycardia (Beats Per Minute)
99 – 109 5
110 – 119 10
120 – 129 15
130 – 139 20
> 140 25
2. Congestive Heart Failure
Absent 0
Mild (Pedal Edema) 5
Moderate (Bibasilar Rales) 10
Severe (Pulmonary Edema) 15
Atrial Fibrillation 10
3. Precipitant History
Negative 0
Positive 10

2
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 SECONDARY THYROTOXICOSIS THYROTOXICOSIS WITHOUT
HYPERTHYROIDISM
Graves Disease TSH Secreting Pituitary Adenoma Leakage
Toxic Multinodular Goiter Thyroid Hormone Resistance Syndrome  Subacute Thyroiditis
Toxic Adenoma H-Mole  Painless Thyroiditis
Thyroid CA / Mets  Suppurative Thyroiditis
Struma Ovarii 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 Grave‟s 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 Grave‟s 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

3
  Key to Management = EARLY Recognition
4. Some Laboratory Findings: Grave’s Ophthalmopathy
 Increased FT4, Increased FT3  90% will NOT go back to Normal
 Decreased TSH  RAI  can Worsen Ophthalmopathy if still in
 12 L ECG the Active Phase (wait until Ophthalmopathy is
 Leukocytosis, shift to the Left if (+) Infection more stable before giving RAI)
 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 LFT‟s 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 T4T3 (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

4
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:
 Lugol‟s 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 T4T3 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
o Potassium Perchlorate 1g PO QID  Inhibits release of Thyroid Hormones
o Cholestyramine 4g PO QID  Inhibit conversion of T4 to T3 by decreasing Type-1
Deiodinase Activity
F. Removal of T4 and T3 from the Serum:
o Cholestyramine
o Plasmapheresis
o Hemodialysis
o Hemoperfusion

5
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 Grave‟s Disease, Toxic MNG, and Toxic Adenomas
 Causes:
o Toxic Diffuse Goiter (Grave‟s Disease)
o Toxic Adenoma
o Toxic Multinodular Goiter (Plummer‟s Disease)
o Painful Subacute Thyroiditis
o Silent Thyroiditis, including Lymphocytic and Postpartum variations
o Iodine Induced Hyperthyroidism
o Excessive Pituitary TSH or Trophoblastic Disease
o Excessive Ingestion of Thyroid Hormone
A. Clinical Manifestations (Attributable to the effects of EXCESS Thyroid Hormones in the circulation)
SYMPTOMS SIGNS
Hyperactivity, Irritability, Dysphoria Tachycardia; Atrial Fibrillation in the elderly
Heat Intolerance and Sweating Tremor
Palpitations Goiter
Fatigue and Weakness Warm, Moist Skin
Weight Loss with Increased Appetite Muscle Weakness, Proximal Myopathy
Diarrhea Lid Retraction or Lag
Polyuria Gynecomastia
Oligomenorrhea, Loss of Libido
B. Laboratory Examinations
o Sensitive TSH Analysis: single best screening test for Hyperthyroidism TSH level is suppressed and total
and unbound Thyroid Hormone
o T4 or Free T4
Levels are increased. In 2-5% of
o Triiodothyronine T3 Radioimmunoassay (RIA) or Free T3 patients, only T3 is increased (T3
o Thyroid Autoantibodies – not routinely necessary Toxicosis). The converse state of
o Radioactive Iodine Uptake T4 Toxicosis, with elevated Total
o Thyroid Scan – done to help determine the cause of Hyperthyroidism and Unbound T4 and Normal T3
Levels, is occasionally seen when
Hyperthyroidism is induced by
Excess Iodine, providing surplus
substrate for Thyroid Hormone
Synthesis.

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6
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!!!

7
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 (Hashimoto‟s Thyroiditis) and Iatrogenic Causes are most
common (treatment of Hyperthyroidism)
 Secondary Causes: Pituitary Disease, Hypothalamic Disease

A. Clinical Features (Descending Order of Frequency)

SYMPTOMS SIGNS
Tiredness, Weakness Dry coarse skin; Cool Peripheral Extremities
Dry Skin Puffy Face, hands, and feet (Myxedema)
Feeling Cold Diffuse Alopecia
Hair Loss Bradycardia
Difficulty Concentrating and Poor Memory Peripheral Edema
Constipation Delayed Tendon Reflex Relaxation
Weight Gain with Poor Appetite Carpal Tunnel Syndrome
Dyspnea Serous Cavity Effusions
Hoarse Voice
Menorrhagia (later Oligomenorrhagia or Amenorrhea)
Paresthesia
Impaired Hearing

B. Laboratory Examinations
o TSH immunoassay In Hypothyroid: Increased TSH IRMA; Decreased FT4
o Free T4 A normal TSH Level Excludes Primary (but NOT Secondary) Hypothyroidism. If the TSH is
o Thyroid Autoantibodies 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
o Thyroid Scan Hypothyroidism. Circulating Unbound T3 Levels are NORMAL in 25% of patients. T3
o UTZ measurements are therefore, NOT indicated

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8
 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 Pemberton’s 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

9
3) DIABETES MELLITUS
I. CLINICAL FEATURES (Notes from Rounds)
A. Symptoms of DM
o Polyuria **NOTE: Polyphagia was removed
o Polydypsia  Target BP if (+) DM: < 130/80
o Unexplained Weight Loss

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 30‟u‟ 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 = 5.6–6.9 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 ONSET OF ACTION PEAK DURATION
Lispro (Rapid) 5-15 mins 30-90 mins 4-6 hours
Aspart (Rapid) 5-15 mins 30-90 mins 4-6 hours
Regular (Short) 30-60 mins 2-3 hours 6-10 hours
Isophane (Intermediate) 2-4 hours 4-10 hours 10-20 hours
Glargine (Long) 2-4 hours Peakless 24 hours
Detemir (Long) 3-8 hours Peakless

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 <7
Fasting / Preprandial Plasma Glucose 70-130mg/dL (3.9-7.2mmol/L)
Postprandial Plasma Glucose <180mg/dL (<10mmol/L)
Bedtime Plasma Glucose 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 DRUGS USED
Islet Cell Dysfunction (A and B) Sulfonylureas
 A: Increased Glucagon Meglitinides
 B: Decreased Insulin Insulin
DPP-IV Inhibitors
GLP-1 Analogues
Non-Suppressable Hepatic Glucose Output Metformin
(responsible for Fasting Hyperglycemia) Thiazolidinediones
Incretin Agents
Insulin Resistance Metformin
Thiazolidinediones
High Carbohydrate Diet A-Glucosidase Inhibitors
Decreased Incretin Levels / Activity DDP-IV Inhibitor
 GLT GLP-1 Analogues
 GIP Metformin

12
2. Consider Side Effects (Two Most Common Side Effects = Hypoglycemia and Weight Gain)
a. Common Side Effects
Insulin  Hypoglycemia
Weight Gain
Sulfonylureas  Hypoglycemia
Weight Gain
Metiglinides Few Hypoglycemia
Weight Gain
Thiazolidinediones No Hypoglycemia if MonoTx
Weight Gain
Edema, CHF, Osteoporosis, Anemia
Metformin No Hypoglycemia if MonoTx
Weight Loss
Lactic Acidosis (especially if with CKD, Heart Problem, Hypoxia)
Acarbose No Hypoglycemia if MonoTx
Weight Loss
Diarrhea, Flatulence, Abdominal Pain
GLP-1 Agonist No Hypoglycemia if MonoTx
Weight Loss
DP-IV Inhibitors 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 MANAGEMENT
6 – 7% Oral Monotherapy
7 – 10% Combination Therapy
 Oral + Oral
 Oral + Basal Insulin
 Biphasic Insulin
> 10% 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 PRIMARY CONTROL
Sulfonylureas Fasting Plasma Glucose
Meglitinides Postprandial Plasma Glucose
Metformin Fasting Plasma Glucose
Thiazolidinediones Fasting Plasma Glucose
Incretin Postprandial Plasma Glucose
Acarbose Postprandial Plasma Glucose
DDP-IV Inhibitor Postprandial Plasma Glucose

b. Combination Therapy
Sulfonylureas + Metformin
Sulfonylureas + Rosiglitazone
Sulfonylureas + Acarbose
Repaglinide + Metformin
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 PRIMARY CONTROL
Lispro (Rapid) Postprandial Plasma Glucose
Aspart (Rapid) Postprandial Plasma Glucose
Regular (Short) Postprandial Plasma Glucose
Isophane (Intermediate) Fasting Plasma Glucose
Glargine (Long) Fasting Plasma Glucose
Detemir (Long) Fasting Plasma Glucose

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

DRUG STARTED WHEN WILL DRUG TAKE WHEN TO MONITOR RESPONSE?
EFFECT? (Clinical Monitoring)
Sulfonylureas 1-2 Weeks 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 I
Stage A Pre or Postulcerative
Lesion, completely
epithelialized
Stage B Pre or Postulcerative
Lesion, completely
epithelialized with
Infection
Stage C Pre or Postulcerative
Lesion, completely
epithelialized with
Ischemia
Stage D Pre or Postulcerative
Lesion, completely
epithelialized with
Infection and Ischemia
Superficial Wound, not
involving Tendon Capsule
or Bone
Superficial Wound, not
involving Tendon Capsule
or Bone with Infection
Superficial Wound, not
involving Tendon Capsule
or Bone with Ischemia
Superficial Wound, not
involving Tendon Capsule
or Bone with Infection and
Ischemia
II
Wound Penetrating to
Tendon or Capsule
Wound Penetrating to
Tendon or Capsule with
Infection
Wound Penetrating to
Tendon or Capsule with
Ischemia
Wound Penetrating to
Tendon or Capsule with
Infection and Ischemia
III
Wound Penetrating to
Bone or Joint
Wound Penetrating to
Bone or Joint with
Infection
Wound Penetrating to
Bone or Joint with
Ischemia
Wound Penetrating to
Bone or Joint with
Infection and Ischemia

I: Change in color; Pre-ulcerative; Post-ulcer A: Non-infected; Non-ischemic

II: Dermal involvement B: Infected; Non-ischemic
III: Deep tissues (Muscle and bone) C: Non-infected; Ischemic
D: Infected; Ischemic

B. Wagner
0 No Open Lesion but may have deformity or cellulites
I 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)
V 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
DKA HHS
Glucose mmol/L (mg/dL) 13.9 – 33.3 (250 – 600) 33.3 – 66.6 (600 – 1200)
Na+ mEq/L 125 – 135 135 – 145
K+ Normal to Increased Normal
Mg2+ Normal Normal
Cl- Normal Normal
P Decreased Normal
Creatinine Slightly Increased Moderately Increased
Osmolality (mOsm/mL) 300 – 320 330 – 380
Plasma Ketones ++++ +/-
Serum Bicarbonate mEq/L < 15 mEq/L Normal to Slightly Decreased
Arterial pH 6.8 – 7.3 > 7.3
Arterial PCO2 mmHg 20 – 30 Normal
Anion Gap [Na-(Cl+HCO3)] High Normal to Slightly High

B. Clinical Features of DKA

SYMPTOMS PRECIPITATING EVENTS PHYSICAL FINDINGS
Nausea / Vomiting Inadequate Insulin Administration Tachycardia
Thirst / Polyuria Infection (PNA / UTI / Gastroenteritis / Sepsis) Dehydration / Hypotension
Abdominal Pain Infarction (Cerebral, Coronary, Mesenteric, Peripheral) Tachypnea / Kussmaul Respirations
Shortness of Breath Drugs (Cocaine) Respiratory Distress
Pregnancy Abdominal Tenderness (may resemble
Acute Pancreatitis / Surgical Abdomen)
Lethargy / Obtundation / Cerebral Edema
Possibly Coma
o Symptoms / Signs of DKA usually develop over 24 hours
o Hyperglycemia  Glucosuria, Volume Depletion, Tachycardia
o Classic Signs: Kussmaul Respiration and a Fruity Odor of patient‟s 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
o Alcoholic ketoacidosis Urine Ketone reaction correlates poorly with Ketonemia, but is usually
Positive in DKA
o Other Increased Anion Gap Acidosis
E. Complications of DKA Hyponatremia, Hyperkalemia, Azotemia, and Hyperosmolality are other
o Lactic Acidosis findings. Serum Amylase and Transaminases may be elevated, again
raising suspicion for Intra-Abdominal Pathology.
o Arterial Thrombosis
o Cerebral Edema

16
F. Management of DKA
o 1) Confirm diagnosis (High Plasma Glucose, (+) Serum Ketones, Metabolic Acidosis)
o 2) Admit to Hospital; Intensive Care Setting may be necessary for frequent monitoring or if pH < 7.00 or
Unconscious
o 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 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)
o 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)
o 6) Assess patient: What precipitated episode (noncompliance, infection, trauma, infarction, cocaine)? Initiate
appropriate workup for precipitating event (cultures, CXR, ECG)
o 7) Measure capillary glucose every 1-2 h; measure electrolytes (especially K+, bicarbonate, phosphate) and Anion
Gap every 4 h for first 24 hours
o 8) Monitor BP, pulse, respirations, mental status, fluid intake and output every 1-4 hours
o 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
o 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
o 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 . X = 45 cc / hour or 45 ugtts/min (which is equivalent to 9 U/hour)

100cc X
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 Decrease by HALF Ex) If we are giving 9 U/hr, give 4.5 U/hr
50-75 MAINTAIN Dose
< 50 Double Insulin Dose
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.
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Internal Medicine Notes 2009

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 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 The Most Common Upper GI Causes of Bleeding are Ulcer

 Hematemesis Disease, Gastroduodenitis, and Esophagitis.
 Melena
 Hematochezia Other etiologies include Portal HPN, Malignancy, Tears across the
Gastroesophageal Junction, and Vascular Lesions
 Occult GI Bleeding
 Symptoms of Blood Loss or Anemia

II. SOURCES OF BLEEDING III. MANAGEMENT

 PUD (Duodenal and Gastric)  Antacids
 Gastritis (Stress, Alcohol, Drugs)  H2 Blockers / PPI
 Esophagitis, Duodenitis  AntBx: Metronidazole, Amoxicillin, Tetracycline,
 Esophageal Varices, Gastroduodenal Varices Clarithromycin
 Mallory-Weiss Tears  Anticholinergics
 Angiodysplasia or Telengiectasia  Sucralfate
 Gastro-Esophageal Carcinoma  Bismuth
 Hemophilia  PGE2
 Gastroduodenal Fistula
 Bleeding Disorders (Leukemia, Aplastic Anemia)

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 patient’s bleeding is massive, ongoing, or severe enough that Colloid Infusion alone is NOT
adequate for Tissue Oxygenation
 Packed RBC Transfusion: should be continued until patient’s 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
2
VI. APPROACH TO PATIENT
A. History & PE
Degree of Volume Loss Patients with Lower GI Bleed have less hemodynamic compromise than those with Upper GI Bleed
Level of Bleeding Hematemesis or Coffee-Ground Emesis, Melena, Hematochezia
Etiology of Bleeding 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-willebrand’s 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) Preferred method of investigation and therapy of upper GI bleed
Colonoscopy All patients with acute Lower GI bleed from unknown source should undergo endoscopic
evaluation of colon
Tagged RBC Scanning RBCs labeled with technetium 99m remain in circulation for as long as 48 hours and
extravasate into the bowel lumen with active bleeding
Arteriography Allows rapid localization and potential therapy of GI bleeding when bleeding rates exceed
0.5mL/min
Surgery 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 High Dose-Proton Pump Inhibitors (Omeprazole 40mg PO BID) reduces rate of recurrent bleeding & need for
(PUD) 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 Coagulopathy
 More than one comorbid illness Large (>2cm) Ulcers
 Blood Loss > 5 units Recurrent Hemorrhage (within 72 hours)
 Shock on Admission Requirement for Emergency Surgery
 Bright-Red Hematemesis with Hypotension
Variceal Hemorrhage 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

3
 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, PPI’s
2) PANCREATITIS
 Pathologic Spectrum varies from Edematous Pancreatitis (Mild & Self-Limited) to Necrotizing Pancreatitis (correlates
with the Severity of the attack)

I. RANSON’S 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 AFTER 48 HOURS OF ADMISSION

Patients age > 55 y/o Fall in Hematocrit by > 10%
Leukocytosis or WBC > 16,000 mm3 Fluid Deficit of > 4000 mL
Hyperglycemia or FBS > 200 mg/dL Hypocalcemia (<8mg/dL)
Serum LDH > 400 units/mL Hypoxemia (PO2 < 60mmHg)
Serum AST or SGOT > 250 units/mL 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 1) Associated with Organ Failure and/or Local Complications such as Necrosis
o 2) Clinical Manifestations
 Obesity BMI > 30
 Hemoconcentration (Hct > 44%)
 Age > 70
o 3) Organ Failure
 Shock
 Pulmonary Insufficiecny (PO2 < 60)
 Renal Failure (CR > 2.0mg%)
 GI Bleeding
o 4) > 3 Ransom Criteria (not fully utilizable until 48 hours)
o 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 4

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:
 Cullen’s Sign = Faint blue discoloration around umbilicus which occurs as the result of Hemoperitoneum
 Turner’s 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.

5
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 Necrosis, Abscess, Pseudocyst, Ascites, Obstructive Jaundice
Systemic 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

6
H. Indicators of Organ Failure
Cardiovascular Hypotension (BP < 90mmHg) or Tachycardia ( > 130 beats/min)
Pulmonary PO2 < 60mmHg
Renal Oliguria (<50ml/h) or Increasing BUN, Creatinine
GIT 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

Meperidine Most Commonly used agent because it has the least effect on the Sphincter of Oddi
It is the DOC because it does NOT cause Spasm of the Sphincter of Oddi)
However, it is Contraindicated in Renal Failure.
Morphine & Pantazocine 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)

7
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)
Signs of Malabsorption are Common in
o PAIN = may be Continuous, Intermittent or Absent
Chronic Pancreatitis
o WEIGHT LOSS
o Abnormal Stools, MALABSORPTION
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 DON’T respond
satisfactorily to Pancreatic Enzyme

8
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 Alarming Symptoms: Weight Loss, Early Satiety, Bleeding, Anemia,
 Bloatedness, Nausea, Vomiting, Insomnia and lack of appropriate response to Acid Suppression
 UGIB

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 /
Hampton’s 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 DOSE
Triple Therapy
1. Bismuth Subsalicylate PLUS 2 tablets QID
Metronidazole PLUS 250mg QID
Tetracycline 500mg QID

2. Ranitidine Bismuth Citrate PLUS 400mg BID

Tetracycline PLUS 500mg BID
Clarithromycin or Metronidazole 500mg BID

3. Omeprazole (Lansoprazole) PLUS 20mg BID (30mg BID)

Clarithromycin PLUS 250 or 500mg BID
Metronidazole OR 500mg BID
Amoxicillin 1g BID

Quadruple Therapy
Omeprazole (Lansoprazole) 20mg (30mg) daily
Bismuth Subsalicylate 2 tablets QID
Metronidazole 250mg QID
Tetracycline 500mg QID

9
4) ACUTE CHOLANGITIS
I. CHARCOT’S TRIAD AND REYNOLD’S PENTAD
A. Charcot’s Triad
o Right Upper Quadrant Pain
o Jaundice
o Fever

**NOTE: Seen in 70% of patients with Bacterial Cholangitis

B. Reynold’s Pentad
o Right Upper Quadrant Pain
o Jaundice
o Fever
o Altered Mental Status
o Shock

II. TREATMENT OF ACUTE CHOLANGITIS

Mild (Grade I) Observation
(Antibiotic, Analgesia, prevention of organ damage)
Moderate (Grade II) Early Biliary Drainage
Non responsive to medical management

Severe (Grade III) Urgent Biliary Drainage

Patients with acute cholangitis and organ failure

**NOTE: Treatment for all = Treatment of ETIOLOGY

10
5) COMMON CAUSES OF GI SYMPTOMS
ABDOMINAL PAIN NAUSEA & VOMITING DIARRHEA GI-BLEEDING OBSTRUCTIVE
JAUNDICE
Appendicitis Medications Infection Ulcer Disease Bile Duct Stones
Gallstone Disease GI Obstruction Poorly Absorbed Sugars Esophagitis Cholangiocarcinoma
Pancreatitis Motor Disorders Inflammatory Bowel Dse Varices Cholangitis
Diverticulitis Functional Bowel D/O Microscopic Colitis Vascular Lesions Sclerosing Cholangitis
Ulcer Disease Enteric Infection Functional Bowel D/O Neoplasm Ampullary Stenosis
Esophagitis Pregnancy Celiac Disease Diverticula Ampullary Carcinoma
GI Obstruction Endocrine Disease Pancreatic Insufficiency Hemorrhoids Pancreatitis
Inflammatory Bowel Dse Motion Sickness Hyperthyroidism Fissures Pancreatic Tumor
Functional Bowel D/O CNS Disease Ischemia Inflammatory Bowel Dse
Vascular Disease Endocrine Tumor Infectious Colitis
Gynecologic
Renal Stone

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 **NOTE: More than 90% of Acute Diarrhea are caused by INFECTIOUS AGENTS
o Acute: < 2 Weeks  Remaining 10% are caused by Medications, Toxic Ingestions, Ischemia, etc
o Persistent: 2-4 Weeks
o Chronic: > 4 Weeks

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
**REITER’s SYNDROME = Arthritis, Urethritis, Conjunctivitis
 Salmonella
 Campylobacter Reiter’s 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) HAV
Antibodies Anti-HAV Some Points:
Features Early Fecal Shedding There is NO Progression to
Diagnosis Acute Infection = IgM and Anti-HAV Chronicity!
Previous Infection = IgG Anti-HAV
Age Preference Children, Young Adults No Carrier State!
Transmission
 Fecal-Oral +++ No Predisposition to
 Percutaneous Unusual Development of
 Perinatal - Hepatocellular Cancer
 Sexual +/-
Clinical
 Severity Mild
 Fulminant 0.1%
 Progress to Chronicity None
 Carrier None
 Cancer None
 Prognosis Excellent
Prophylaxis Immunoglobulin
Inactivated Vaccine
Therapy NONE (No Specific Treatment – it is just Supportive)
B. Hepatitis-B Virus
Features Blood-Borne Virus, Carrier State Some Points:
Age Preference Young Adults (Sexual and Percutaneous)
It CAN Progress to
Babies, Toddlers
CHRONICITY (especially if it
Transmission
 Fecal-Oral - is Transmitted Perinatally –
 Percutaneous +++ from mother to neonate)
 Perinatal +++ There is a Recombinant
 Sexual ++
Vaccine!
Clinical
 Severity Occasionally Severe Prognosis is WORSE with Age
 Fulminant 0.1-1%
It is a DNA Virus (unlike
 Progress to Chronicity Occasional (1-10%) – 90% of Neonates
0.1 – 30% Hepatitis-A)
 Carrier
 Cancer (+) Neonatal Infection If we are Vaccinated = we will
 Prognosis Worse with Age, Debility be (+) Anti-HBs
Prophylaxis Recombinant Vaccine
Therapy Interferon (Immunomodulator); Lamivudine (Antiviral)
C. Hepatitis-C Virus
Antigen (s) HCV, C100-3, C33c, C22-3, NS5
Antibodies Anti-HCV
Features Blood-Borne Agent
Some Points:
(formerly labeled as Non-A, Non-B Hepatitis)
Diagnosis Acute Diagnosis = Anti-HCV
Chronic Diagnosis = Anti-HCV and HCV RNA NO Vaccine Yet (because of the
Age Preference Any Age, but More Common in Adults Several Subtypes!)
Transmission
 Fecal-Oral - Formerly labeled as Non-A Non-
 Percutaneous +++ B Hepatitis
 Perinatal +/-
 Sexual +/- Most Common: Blood
Clinical Transfusion Infection
 Severity Moderate
 Fulminant 0.1% Complications and Sequalae
 Progress to Chronicity Common: 50-70% chronic hepatitis; 80-90% chronic infection
1.5-3.2%  RARELY = Fulminant
 Carrier
+ Hepatitis-C
 Cancer
 Prognosis Moderate  Chronic Hepatitis-C
Prophylaxis NONE
Therapy Interferon + Ribavirin

14
 D. Hepatitis-D Virus
Antigen (s) HBsAg, HDV Antigen
Antibodies Anti-HBs, Anti-HDV Complications and Sequelae
Features Defective RNA-Virus – requires Helper Function of HBV  Fulminant Hepatitis
(Hepadnaviruses)  Mild Disease
 Asymptomatic Carriers
HDV Antigen present in Hepatocyte Nucleus
Diagnosis Anti-HDV, HDV-RNA
HBV/HDV Coinfection:
-IgM Anti-HBc and Anti-HDV
HDV Superinfection:
-IgG Anti-HBc and Anti-HDV
Age Preference Any Age (Similar to HBV)
Transmission
 Fecal-Oral -
 Percutaneous +++
 Perinatal +
 Sexual ++
Clinical
 Severity Occasionally Severe
 Fulminant 5-20%
 Progress to Chronicity Common
 Carrier Variable
 Cancer +/-
 Prognosis Acute = Good
Chronic = Poor
Prophylaxis HBV-Vaccine (None for HBV Carriers)
Therapy Interferon +/-

E. Hepatitis-E Virus
Antigen (s) HEV Antigen
Antibodies Anti-HEV
Features Agent of Enterically Transmitted Hepatitis
Diagnosis IgM/IgG Anti-HEV (assays being developed)
Virus in Stool, Hepatocyte, Cytoplasm, Bile
Age Preference Young Adults (20-40 years)
Transmission
 Fecal-Oral +++
 Percutaneous -
 Perinatal -
 Sexual -
Clinical
 Severity Mild
 Fulminant 1-2%
 Progress to Chronicity None
 Carrier None
 Cancer None
 Prognosis Good
Prophylaxis Unknown
Therapy None

 Summary of Some Differences:

A B C D E
Incubation 15-45 30-180 15-160 30-180 14-16
Onset Acute Insidious or Acute Insidious Insidious or Acute Acute
Vaccination IG, Inactivated Recombinant NONE HBV Vaccine Unknown
Transmission Feco-Oral Percutaneous (+++) Percutaneous (+++) Percutaneous (+++) Feco-Oral
Perinatal (+++) Sexual (+/-) Perinatal (+)
Sexual (++) Sexual (++)
Therapy None Interferon Interferon Interferon None
Lamivudine Ribavirin

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

INTERPRETATION HBsAg Anti-HBs Anti-HBc HBeAg Anti-HBe
Acute HBV Infection
(High Infectivity) + - IgM + -
Chronic HBV Infection + - IgG + -
(High Infectivity)
1) Late-Acute or Chronic HBV Infection + - IgG - +
(Low Infectivity)
2) HBeAg-Negative (“Precore-Mutant) Hepatitis B
(Chronic or, rarely, Acute)
1) HBsAg of one Subtype and Heterotypic Anti-HBs
(Common)
2) Process of Seroconversion from HBsAg to Anti- + + + +/- +/-
HBs (RARE)
1) Acute HBV Infection - - IgM +/- +/-
2) Anti-HBc Window
1) Low Level Hepatitis B Carrier - - IgG - +/-
2) Hep B in Remote Past Infection
Recovery from HBV Infection - + IgG - +/-
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

If after 6 months, the HBsAg is still present,

QuickTime™ and a
then the Patient already has CHRONIC
TIFF (Uncompressed) decompressor
are needed to see this picture.
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 ALT may be Fluctuating – if it is Elevated,
are needed to see this picture.
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 DON’T 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, 5’Nucleotidase, 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 With the EXCEPTION of Factor-VIII, the blood clotting factors are made exclusively in HEPATOCYTES
o Useful for this purpose is the Serum Prothrombin Time (Factors II, V, VII, X)
o 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)
Allows calculation of Liver Volume
MRI 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
B. Amebic Liver Abscess inhomogenous fluid characteristics. CT findings will include a
o Should be considered in patients from endemic areas complex hypodense mass with peripheral enhancement. In patients
with a solitary dominant abscess, percutaneous aspiration with
o Diagnosis requires high index of clinical suspicion
evaluation by GS/CS is essential to direct further antimicrobial &
o Tx: Metronidazole, Chloroquine
drainage therapy
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
 80% Elevated Alkaline Phosphatase  Viscous Abscess contents that tend to plug the catheter
 33% Jaundice = Increased Bilirubin  Associated Disease requiring surgery
 40% = (+) Blood Culture  Lack of a clinical response to percutaneous drainage in 4-7 days
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 Aspiration & Drainage is rarely indicated. It is indicated only if there is
(+) Secondary Pyogenic Infection
B. Therapy = AMOEBICIDES:
o METRONIDAZOLE 750mg PO or IV 5-10 days More than 90% respond to Metronidazole Tx, with Decrease in Pain and
o Choloroquine Fever within 72 hours

C. Complications = CYST RUPTURE into the following: Indications for Aspiration of Liver Abscess:
o Pleural Space  Need to rule out Pyogenic Abscess
o Lungs  No Clinical Response in 3-5 days
o Bowel  Threat of Imminent Rupture
o Retroperitoneum  Need to prevent Rupture of Left Lobe Abscess into
Pericardium
VI. HEPATOBILIARY TUBERCULOSIS
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%)
o Treatment: STOP Pill; Surgery Biopsy is not Suggested due to Hypervascularity
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)
Wilson’s 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:
o Anemic from either Chronic GI Blood Loss LIVER ENZYMES:
o Nutritional Deficiencies AST / ALT >2 Alcoholic Liver Disease
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 Coagulopathy (Factor Deficiency, Fibrinoysis, Thrombocytopenia)
Gastropathy, Splenomegaly, Hypersplenism, Ascites / SBP Bone Disease (Osteopenia, Osteoporosis, Osteomalacia)
Hepatorenal Syndrome (Type 1, Type 2) Hematologic Abnormalities (Anemia, Hemolysis, Neutropenia, Thrombocytopenia)
Hepatic Encephalopathy Malnutrition
Portopulmonary Hypertension Hepatopulmonary Syndrome
CAUSES OF CIRRHOSIS
Alcoholism Cardiac Cirrhosis
Chronic Viral Hepatitis (Hep-B, Hep-C) Inherited metabolic Liver Disease
Autoimmune Hepatitis - Hemochromatosis
Non-Alcoholic Steatohepatitis - Wilson’s Disease
Biliary Cirrhosis - A1-Antitrypsin Deficiency
 Primary Biliary Cirrhosis - Cystic Fibrosis
 Primary Sclerosing Cholangitis Cryptogenic Cirrhosis
 Autoimmune Cholangiopathy

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 B C
Serum Bilirubin (mg/dL) < 2.0 2.0-3.0 > 3.0
(umol/L) < 34 34-51 > 51
Serum Albumin (g/dL) > 3.5 3.0-3.5 < 3.0
(g/L) > 35 30-35 < 30
Prothrombin Time Seconds Prolonged 0-4 4-6 >6
INR < 1.7 1.7 – 2.3 > 2.3
Ascites None Easily controlled Poorly controlled
Neurologic Disorder None Minimal 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 SAAG CELL COUNT OTHER TESTS
(g/L) (g/dL) RBC, WBC, per uL
>10,000u/L
Cirrhosis Straw colored or bile stained < 25 (95%) > 1.1 1% < 250 (90%)
Predominantly
Mesothelial
Neoplasm Straw colored, hemorrhagic, > 25 (75%) < 1.1 20% > 1000 (50%) Cytology, cell block,
mucinous, or chylous Variable Cell types peritoneal biopsy
TB Peritonitis Clear, Turbid, Hemorrhagic, > 25 (50%) < 1.1 7% > 1000 (70%) Peritoneal Biopsy, Stain
Chylous Usually > 70% L and Culture for AFB
Pyogenic Turbid or purulent If purulent, < 1.1 Unusual Predominantly PMN Positive Gram Stain,
Peritonitis > 25 Leukocytes Culture

CHF Straw-colored Variable > 1.1 10% < 1000 (90%)

(15-53) Usually Mesothelial,
Mononuclear

Nephrosis Straw-colored or chylous < 25 (100%) < 1.1 Unusual < 250 If chylous, ether
Mesothelial, extraction, sudan staining
Mononuclear

Pancreatic Turbid, Hemorrhagic, or Variable, Variable, may Variable  Amylase in Ascitic

Ascites Chylous often >25 be blood stained Fluid & Serum

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
 Portal Vein Thrombosis Management of Ascites:
 Veno-Occlusive Disease  Dietary Salt Restriction (2g Salt/day)
 Diuretic Therapy
 Fatty Liver of Pregnancy
 Paracntesis
2. If SAAG is < 1.1g/dL (or 11 g/L)  TIPS
 Peritoneal Carcinomatosis
 Infection (Peritonitis, TB) Spontaneous Bacterial Peritonitis:
 Nephrotic Syndrome  Infectious complication of Portal HPN-Related
 Pancreatic or Biliary Ascites Ascites
 Abdominal Pain & Distention, Fever,
B. Absolute WBC Count (PMN) > 250/mm3 Decreased Bowel Sounds, Worsening of
o Infection Hepatic Encephalopathy
o When Mononuclear Cells are predominant: TB, Fungal  Diagnosis is likely when Ascitic Fluid has >
3
C. RBC Count > 50,000/mm = Hemorrhagic Ascites 250 neutrophils/u/L
o Malignancy
o TB
o Trauma
D. Others:
Amylase Increased in Pancreatic Ascites
TAG Increased in Chylous Ascites
Cytology Positive in Malignancy
Gram Stain or Culture Bacterial Infections
pH < 7 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 PERSONALITY AND NEUROLOGIC EEG ABNORMALITIES
CONSCIOUSNESS INTELLECT ABNORMALITIES
0 Normal Normal Normal Normal
1 Inverted Sleep Forgetful, Mild Confusion, Tremor, Apraxia, Incoordination, Slowing Triphasic Waves
Pattern, Restless Agitation, Irritable Impaired handwriting
2 Lethargic, Slow Disorientation from time, amnesia, Asterixis, Dysarthria, Hypoactive Slowing Triphasic Waves
Responses decreased inhibitions, Reflexes
inappropriate behavior
3 Somnolent but can be Disorientation for place, aggressive Asterixis, Hyperactive Reflexes, Slowing Triphasic Waves
aroused, confused Babinski’s Sign. Muscle Rigidity
4 Coma Nil Decrebrate Slowing Delta Waves

Portosystemic Encephalopathy is a serious

**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.
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 Varices increase progressively by 7-8% per year

o Determinant of Severity of Varices = Severity of Liver Disease
o Everyone with Cirrhosis should be Endoscoped!
o 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 Primary Prophylaxis: Prevention of First Variceal Hemorrhage

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 Treatment of Acute Variceal Hemorrhage:

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 Secondary Prophylaxis: Prevent Recurrent Hemorrhage

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 Peritoneum

SAAG > 1.1 SAAG < 1.1

Capillarized Sinusoid Normal Leaky Sinusoid Peritoneal Lymph

Ascites Protein < 2.5 Ascites Protein > 2.5 Ascites Protein > 2.5
Sinusoidal HPN: Post-Sinusoidal HPN Malignancy
-Cirrhosis -Cardiac Ascites TB
-Late Budd-Chiari -Early Budd-Chiari
-Venoocclusive

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 +

 Note:  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

 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.
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Internal Medicine Notes 2009

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 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)

2
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 MANAGEMENT
< 7 g/dL PRBC is Justified

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 cross-
matching 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

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

o 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

CLASS I CLASS II CLASS III CLASS IV
Blood Loss (mL) Up to 750 mL 750 – 1500 mL 1500 – 2000 mL > 2000 mL
Blood Loss (% BV) Up to 15 % 15 – 30 % 30 – 40 % > 40 %
Pulse Rate < 100 > 100 > 120 > 140
Blood Pressure Normal Normal Decreased Normal
Pulse Pressure Normal or Decreased Decreased Decreased Decreased
Respiratory Rate 14 – 20 20 – 30 30 – 40 > 35
Urine Output (cc/h) > 30 20 – 30 5 – 15 Negligible
CNS / Mental Status Slightly anxious Mildly anxious Anxious and confused Confused, Lethargic

3
 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 SINGLE DONOR / APHERESIS PLATELETS
Dose 1 Unit / 10kg BW 1 Pack (equivalent to 4-8 Units of RDP)
Advantage: may reduce Infectious Disease
Transmission by reducing the number of Donor
Exposures
Response 1 Unit increases PC by 5,000 – 10,000 cells/uL 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

4
  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

5
 BASIC HEMATOLOGY NOTES

INTRODUCTION
I. SOME FORMULAS
Hemoglobin: M: 16 + 2 F: 13 + 2
Hematocrit: M: 47 + 6 F: 40 + 6
Serum Fe: 50 – 150 mg/dL
TIBC: 54 – 64 mmol/dL
Serum Ferritin 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:
 Patient’s Reticulocyte Count x Patient’s 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 = Patient’s Reticulocyte x Patient’s Reticulocyte

45

Corrected Reticulocyte Count = Absolute Reticulocyte Count

Maturation Time (MT)

Interpretation:
MT is 1 when Hct is 45%
1.5 35% CRC < 1% Hypoproliferative BM
2.0 25% > 2% Hemolysis or
2.5 15% 100,000mm2 Blood Loss

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B. Hematology Formulas
o MCH = Hgb/RBC N: 27 – 31 Chromic
o MCV = Hct (100)/RBC N: 76 – 100 Cytic
o MCHC = Hgb/Hct N: 330 – 390

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 Macrocytosis

Thalassemia Reticulocytosis
Lead Poisoning Liver Disease
Chronic Infection Down’s Syndrome
Megaloblastic
 Folic Acid Deficiency
 B12 Deficiency
C. Absolute Neutrophil Count (ANC)

(Neutrophils + Stabs) x WBC x 1,000 < 500 = NEUTROPENIC!

7
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

8
IV. SCREENING ASSAYS (from Harrisons) Interpreting PT
 Commonly used Screening Tests are: 1. INR
o PT  If > 1: means that blood is LESS Coaguable, prone to bleeding, ideal for ACS px
o aPTT  If < 1: coaguable blood
o Platelet Count 2. Activity

A. Prothrombin Time (PT)

 > 70% = needed if you will do Invasive Procedures / Surgeries
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: Prolonged aPTT:

 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
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

9
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 To Avoid further HEMOLYSIS
Corticosteroids 15-30mg EOD To Control the Hemolysis
Iron Replacement for IDA Questionable – because if we give more Iron, we can promote Hemolysis
Heparin / Warfarin If with History of Thrombosis
ATG 150mg/kg (Total) over 4-10 days For Marrow Hypoplasia
Hematopoietic Stem Cell Transplant (HSCT) 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

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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 Reticulocyte Index > 2.5

Red Cell Morphology Hemolysis / Hemorrhage

Blood Loss
Normocytic Micro or Macrocytic
Intravascular Hemolysis
Normochromic
Metabolic Defect
Membrane Abnormality
Hypoproliferative Maturation Disorder Hemoglobinopathy
Immune Destruction
Marrow Damage Cytoplasmic Defects
*Infiltration / Fibrosis *Iron Deficiency Fragmentation Hemolysis
*Aplasia *Thalassemia
*Sideroblastic Anemia
Iron Deficiency
Nuclear Defects
Decreased Stimulation *Folate Deficiency
*Inflammation *Vitamin B12 Deficiency
*Metabolic Defect *Drug Toxicity
*Renal Disease *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

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D. Laboratory Examinations:
1. CBC
 Hemoglobin, Hematocrit
 Red Cell Indices Microcytosis: MCV < 80
Macrocytosis: MCV > 100
 MCV (N: 90 + 8)
MCV and MCH reflect defects in Hemoglobin Synthesis
 MCH (N: 30 + 3)

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 patient’s 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

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F. Bone Marrow Examination
RETICULOCYTE PRODUCTION INDEX E/G RATIO
Hypoproliferative Anemia <2 1:2 or 1:3
Hemolytic Disease >3 At least 1:1
Maturation Disorder Decreased 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  Serum Iron  % Transferrin Saturation N or  TIBC  Ferritin
In Mild to Moderate Deficiency  Serum Iron  % Transferrin Saturation  TIBC  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

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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 Etiology: Hereditary, radiation, chemical and other occupational exposures, drugs
o 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 Common in children – ALL is NOT a common Leukemia in Adults
o ALL cell origin is in the Lymphoid Line
o Most Common ALL Variant (75%) = B-Cell Lineage

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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 Diagnosis is established by identifying a Clonal Expansion of a Hematopoietic Stem Cell possessing a reciprocal
translocation between Chromosomes 9 and 22
o 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. Hodgkin’s VS Non-Hodgkin’s Lymphoma:
HODGKIN’S LYMPHOMA NON-HODGKIN’S LYMPHOMA
Spread Orderly Spread by Contiguity Random, Hematogenous Spread
Extranodal Site Involvement RARE In UNFAVORABLE Types
Systemic Symptoms Of Prognostic Importance Less Common
Involvement Axial and Central Lymph Nodes Peripheral, Mesenteric Lymph Nodes
Blood; Waldermyer’s Ring
Cure POSSIBLE for All Types 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 Hodgkin’s Lymphoma
o Immunohistochemistry
D. Differential Diagnosis
o Reactive Lymph Node Hyperplasia (as in INFECTIONS)
o Undifferentiated Carcinoma
E. Prognosis
o Hodgkin’s Lymphoma is BETTER than Non-Hodgkin’s Lymphoma
o International Prognostic Index (IPI) for Non-Hodgkin’s 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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INFECTIOUS DISEASE
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Jaime Alfonso Manalo Aherrera, M.D.
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Internal Medicine Notes 2009

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 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:
o Retro-Orbital Pain  Inflate cuff midway between Systolic and
o Myalgia / Arthralgia Diastolic for 5 minutes
o Rash (Petechial)  (+) If > 20 Petechiae in a 1 square inch area
o Hemorrhagic Manifestations (Petechiae + Tourniquet Test) 1.5 inches from Volar Aspect of Antecubital
o Leukopenia Fossa

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 Virion’s 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)

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 C. Clinical Presentation of DHF
o Identified by detection of Bleeding Tendencies (Torniquet Test, Petechiae) or Overt Bleeding in Absence of underlying causes
o Dengue Shock Syndrome: accompanied by Hemorrhagic Signs & results from Increased Vascular Permeability leading to shock
Mild DHF / DSS 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
More Severe Cases 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 GRADE 2 GRADE 3 GRADE 4

Fever with Non-Specific Sx Grade 1 PLUS: Grade 1 + 2 PLUS: Grade 1 + 2 + 3 PLUS

Hemorrhagic Manifestations: Circulatory Failure Profound SHOCK
 (+) Torniquet Test  Rapid Weak Pulse Undetectable BP or Pulse
 Easy Bruisability  Narrowing Pulse Pressure
 Gum Bleeding  Hypotension
 Epistaxis, Rashes  Cold, Clammy Skin
 Petechiae on Palate  Restlessness
 Petechiae on Axillae
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 Monitor Platelet Count + Hematocrit Levels q12-24 hours
o Others: AST/ALT, urinalysis, CXR

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

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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 Persistent High Fever
Diaphoresis Relative Bradycardia
Anorexia Rose Spots (Rashes primarily trunk area)
Myalgia Abdominal Tenderness
Cough Hepatomegaly
Weakness / Malaise Splenomegaly
Sore Throat Thyroid Psychosis / Encephalitis
Dizziness Epistaxis
Constipation / Diarrhea
Abdominal Pain
Abdominal Distention
III. CRITERIA FOR ADMISSION (Medicine Notes)
All Patients Suspected of Having Typhoid Fever with All Patients suspected of having Complicated Typhoid Fever
ONE or More of the Following:
Persistent Vomiting or Unable to take Oral Fluids Intestinal Perforation
Severe Dehydration GI Hemorrhages
Spontaneous Bleeding Peritonitis
Persistent Abdominal Pain Pericarditis
Listlessness Hepatic and Splenic Abscesses
Changes in Mental Status DIC
Weak, Rapid Pulse Myocarditis
Cold, Clammy Skin Meningitis
Circumoral Cyanosis
Seizures
Hypotension or Narrowing Pulses

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%

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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

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3) LEPTOSPIROSIS
 MILD FORM = Leptospirosis may present as an Influenza-Like Illness with Headache and Myalgia
 SEVERE FORM (Weil’s 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)

6
B. Severe Leptospirosis (WEIL’S 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 Weil’s 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 Weil’s 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 Weil’s 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

7
III. LABORATORY DIAGNOSIS OF LEPTOSPIROSIS

Isolation of Leptospires in Culture CERTAIN Scoring System:

(+) Serology: Endemic  (+) = Isolation of Leptospires from Culture
Single (+), Low Titer 2  Presumptive:
Single (+), High Titer 10 o A or A + B = 26
Paired Sera, Rising Titer 25 o A + B + C = 25
 Suggestive
(+) Serology, NOT Endemic o A or A + B = 20 – 25
Single (+), Low Titer 5 o A + B + C = 20 – 25
Single (+), High Titer 15
Paired Sera, Rising Titer 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

8
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
9
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 Nausea, Vomiting, and Orthostatic Hypotension
o Classic Malarial Paroxysms
o Anemia
o Splenic Enlargement
o Slight Enlargement of the Liver
o 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
MALIGNANT VS BENIGN TERTIAN
 Malignant Tertian Malaria = severe w/ complications (Plasmodium falciparum)
 Benign Tertian Malaria = mild (Plasmodium ovale, vivax)
Quartan Periodicity 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)

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NEPHROLOGY
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Jaime Alfonso Manalo Aherrera, M.D.
Internal Medicine Notes 2009

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 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

2
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 ARF is often considered to be reversible, although a return to baseline serum
 First step in evaluating a patient with renal failure creatinine concentrations postinjury might not be sufficiently sensitive to detect
is to determine if the disease is Acute or Chronic clinically significant irreversible damage that may ultimately contribute to CKD.
 Findings Suggestive of Chronic Renal Failure:
o Anemia Kidney Size may be Normal or Increased in some CKD:
o Neuropathy  Diabetic Nephropathy
o Renal Osteodystrophy  Amyloidosis
o Small, Scarred Kidneys  Polycystic Kidney Disease
 HIV Associated Nephropathy
ACUTE KIDNEY DISEASE CHRONIC KIDNEY DISEASE
Kidney Size Normal Small
Carbamylated Hemoglobin Normal High
Broad Casts on Urinalysis Absent Present
History of Kidney Disease, HPN, Abnormal Urinalysis Absent Present
Anemia, Metabolic Acidosis, Hyperkalemia, Hyperphosphatemia Often Present Usually Present
Reversibility with Time Usually Complete 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 DESCRIPTION SOME EXAMPLES

Pre-Renal Most Common Form, which occurs in the setting of Renal Hypoperfusion Hypovolemia (GI losses, decreased intake, etc)
Prolonged Hypoperfusion  leads to Acute Tubular Necrosis (Ischemic) Low Cardiac Output
Systemic Vasodilation
Clinical Features: thirst, orthostatic dizziness, orthostatic hypotension, Selective Intrarenal Vasoconstriction
tachycardia, reduced jugular venous pressure, decreased skin turgor, dry Hepatorenal Syndrome
mucous membranes
Intrinsic Can be conceptually divided based on the Predominant Compartment: Ischemic Acute Tubular Necrosis
 1) Ischemic or Nephrotoxic Tubular Injury Nephrotoxic ARF
 2) Tubulointerstitial Diseases
 3) Diseases of the Renal Microcirculation & Glomeruli
 4) Diseases of Larger Renal Vessels
Post-Renal Urinary Tract Obstruction accounts for < 5% of hospital acquired ARF Bladder Neck Obstruction (Most Common)
Because one kidney has sufficient reserve to handle generated nitrogenous  Prostatic Disease
waste products, ARF from obstruction requires:  Neurogenic Bladder
 Obstruction to Urine Flow between external urethral meatus and  Therapy with Anticholinergics
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

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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

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 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:
QuickTime™ and a ARF impairs renal excretion of Na, K. and H2O
TIFF (Uncompressed) decompressor
are needed to see this picture. and perturbs divalent cation homeostasis and
urinary acidification mechanisms
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 THERAPY

Reversal of Renal Insult

Ischemic ATN Restore systemic hemodynamics and renal perfusion through volume resuscitation and use of vasopressors
Nephrotoxic ATN 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

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 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)

Interpretation:
BUN:Crea Ratio = BUN x 247
 If < 10: Intrinsic Renal Cause
Crea
 If 10-20: Doubtful Cause
Conversion Factor for Serum BUN: 1 mmol/L = 2.8 mg/dL  If > 20: Pre-Renal Cause

VIII. CREATININE CLEARANCE (mL/min): Cockroft and Gault Equation

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

72 x Serum Crea in mg/dL 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 DESCRIPTION GFR mL/min / 1.73m2 ACTION
I Kidney damage with normal / increased GFT 90 Diagnosis and Treatment, Tx of
comorbid conditions, slowing
progression, CVD risk reduction
II Kidney damage with mildly decreased GFR 60 – 89 Estimating progression
III Moderately decreased GFR 30 – 50 Evaluating and Treating
complications
IV Severely decreased GFR 15 – 29 Preparation for kidney
replacement therapy
V Renal Failure < 15 (for dialysis) Kidney Replacement (if uremia
is present)

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  NOTES from Harrisons:
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
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
o An Accurate 24-Hour Urine Collection is the Gold Standard for measurement of Albuminuria
o Microalbuminuria refers to the excretion of amounts of Albumin too small to detect by urinary dipstick
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 Chronic Renal Failure applies to the process of continuing significant irreversible
 Endocrine-Metabolic reduction in nephron number, and typically corresponds to CKD Stages 3-5.
 Neuromuscular Pathophysiology of CKD involves 2 Broad Sets of Mechanisms of Damage:
 Cardiovascular and Pulmonary  1) Initiating mechanisms specific to underlying etiology
 Dermatologic  2) Set of progressive mechanisms, involving hyperfiltration and
 Gastrointestinal hypertrophy of the remaining viable nephrons
 Hematologic and Immunologic

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: Osteitis Fibrosa (classic lesion of secondary hyperparathyroidism)
 HIGH Bone Turnover
 HIGH PTH Levels
Those Associated with: Osteomalacia
 LOW Bone Turnover Adynamic Bone Disease
 NORMAL PTH Levels

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)

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 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

8
  Other Contraindications to Renal Biopsy:
o Uncontrolled Hypertension **NOTE: Ultrasound-Guided Percutaneous Biopsy is favored
o Active Urinary Tract Infection
o Bleeding Diathesis
o Morbid Obesity

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 Nephrotic Syndrome classically presents with Heavy Proteinuria, Minimal Hematuria,
Hypoalbuminemia, Hypercholesterolemia, Edema, and Hypertension
 Hypoalbuminemia
 Hyperlipidemia
 Hypercoaguability
Most Common Cause in Adults = Membranous Glomerulonephritis
 Edema
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

9
10
 FLUID & ELECTROLYTE / METABOLIC DERANGEMENTS
CAUSES OF HYPONATREMIA vs HYPERNATREMIA
HYPONATREMIA HYPERNATREMIA
I. Pseudohyponatremia I. Nonrenal Water Loss
A. Normal Plasma Osmolality  Evaporation from the skin and respiratory tract (insensible
 Hyperlipidemia losses)
 Hyperproteinemia  GI Losses: diarrhea (most common)
 Post-TURP  Increased Insensible Loss due to fever, exercise, heat
B. Increased Plasma Osmolality exposure, severe burns, mechanically ventilated patients
 Hyperglycemia
 Mannitol Na+ concentration of sweat decreases with profuse perspiration,
thereby increasing solute-free water loss
II. Hypoosmolal Hyponatremia
A. Primary Na+ Loss (20 H2O Gain) II. Renal Water Loss (Most Common Cause of Hypernatremia)
 Integumentary Loss: sweating, burns  Drug Induced Diuresis
 GI Loss: vomiting, tube drainage, fistula, obstruction, diarrhea  Osmotic Diuresis (Hyperglycemia, Glucosuria, IV Mannitol)
 Renal Loss: diuretics, osmotic diuresis, hypoaldosteronism, salt-wasting  Diabetes Insipidus
nephropathy, postobstructive diuresis, nonoliguric acute tubular necrosis
B. Primary H2O Gain (20 Na+ Loss) III. Primary Na+ Gain
 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
CAUSES OF HYPOKALEMIA VS. HYPERKALEMIA
HYPOKALEMIA HYPERKALEMIA
I. Decreased Intake I. Renal Failure
A. Starvation
B. Clay Ingestion II. Decreased Distal Flow
II. Redistribution into Cells (ie. Decreased Effective Circularing Arterial Volume)
A. Acid-Base: Metabolic Alkalosis
B. Hormonal III. Decreased K+ Secretion
 Insulin A. Impaired Na+ Reabsorption
 B2-Adrenergic Agonists (Endogenous or Exogenous)  Primary Hypoaldosteronism: Adrenal insufficiency,
 A-Adrenergic Antagonists Adrenal enzyme deficiency (21-Hydroxylase, 3B-
C. Anabolic State Hydroxysteroid Dehydrogenase, Corticosterone Methyl
 Vitamin B12 or Folic Acid (RBC production) Oxidase)
 Granulocyte-Macrophage Colony Stimulating Factor (WBC production)  Secondary Hypoaldosteronism: Hyporeninemia, Drugs
 Total Parenteral Nutrition
(ACE inhibitors, NSAIDs, Heparin)
D. Other
 Pseudohypokalemia  Resistance to Aldosterone: Pseudohypoaldosteronism,
 Hypothermia Tubulo-Interstitial Disease, Drugs (K+ Sparing
 Hypokalemic Periodic Paralysis Diuretics, Trimethroprim, Pentamidine)
 Barium Toxicity B. Enhanced Cl- Reabsorption (Chloride Shunt)
 Gordon’s Syndrome
II. Increased Loss  Cyclosporine
A. Non-Renal
 GI Loss (Diarrhea)
 Integumentary Loss (Sweat)
B. Renal
 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, Bartter’s 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, Liddle’s 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 Profound Weakness
o Absent P-Waves
o QRS Widening
o 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 Parathyroid Hormone (PTH)
o Active Vitamin-D Metabolite 1,25-Dihydroxyvitmin-D (1,25(OH)2D)

A decrease in ECF Ca2+ triggers an Increase in Parathyroid Hormone

QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
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 Life-
Threatening Complications
 Moderate to Severe Hypocalcemia: Paresthesias, usually of the fingers, toes, and circumoral regions, and is caused by
Increased Neuromuscular Irritability
 Chvostek’s Sign: Twitching of the Circumoral Muscles in response to gentle tapping of the facial nerve just anterior to the
ear may be elicited
 Trousseau’s Sign: Carpal Spasm may be induced by inflation of a BP cuff to 20mmHg above patient’s 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 Usually Asymptomatic and recognized only on routine Calcium Measurements
(up to 11 – 11.5 mg/dL Some may complain of vague Neuropsychiatric Symptoms
Trouble concentrating, personality changes, or depression
Peptic Ulcer Disease or Nephrolithiasis, Increased Fracture Risk
More Severe Hypercalcemia Lethargy, Stupor, Coma
(>12-13 mg/dL) GI Symptoms: nausea, anorexia, constipation, pancreatitis
Decreased Renal Concentrating Ability – Polyuria and Polydipsia
B. Hypercalcemia can present with ECG Changes:
o Bradycardia
o AV Block
o Short QT Interval
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
o 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. WHIPPLE’S 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
 2) NaHCO3  If > 70, we DON’T given CaCO3, because we run the risk of Metastatic Calcification
 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 Fluid and Electrolyte Disturbance
o Endocrine Metabolic Disturbances (Hyperuricemia, 2 0 Hyperparathyroidism, Osteomalacia)
o Neuromuscular Disturbances (fatigue, headache, sleep disorders, lethargy, etc)
o Cardiovascular & Pulmonary Disturbances (Pericarditis, CHF, Pulmonary Edema, etc)
o Dermatologic Disturbances (pallor, pruritus, ecchymoses, hyperpigmentation, uremic frost)
o Gastrointestinal Disturbances (anorexia, nausea, vomiting, uremic fetor, GI bleeding)
o Hematologic and Immunologic Disturbances (anemia, lymphocytopenia)

V. ALBUMIN (IN URINALYSIS) VI. SUGAR (IN URINALYSIS) Polyuria > 3L/d. A 24 hour urine collection is
 Trace = 0.05 – 0.2 g/L Trace = 5mmol/L needed for this evaluation. Results from either:
 +1 = 0.3 g/L +1 = 15  1) Excretion of nonabsorbable solutes (eg.
Glucose); or
 +2 = 1.0 g/L +2 = 30
 2) Excretion of water (usually from a
 +3 = 3.0 g/L +3 = 60 defect in ADH production or renal
 +4 = > 20 g/L +4 = 120 responsiveness)

16
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NEUROLOGY
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Jaime Alfonso Manalo Aherrera, M.D.
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Internal Medicine Notes 2009

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 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 Toxins
o Metabolic Conditions
o Infections
o Endocrinologic Conditions
o Cerebrovascular Disorders
o Autoimmune Disorders
o Seizure-Related Disorders
o Neoplastic Disorders
o Hospitalization
o 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 MYOPATHIC
Atrophy None Severe Mild
Fasciculations None Common None
Tone Spastic Decreased Normal / Decreased
Distribution of Weakness Pyramidal / Regional Distal / Segmental Proximal
Tendon Reflexes Hyperactive Hypoactive / Absent Normal / Hypoactive
Babinski’s Sign Present Absent Absent

2
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 Primary generalized, tonic-clonic seizures are the main seizure type in ~10% of all persons with
Clonic Seizures Epilepsy. Most common seizure type resulting from metabolic derangements. Begins abruptly
(Grand Mal) 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.

3
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PULMONOLOGY
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Jaime Alfonso Manalo Aherrera, M.D.
Internal Medicine Notes 2009

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 PULMONARY DISEASES
1) PULMONARY TUBERCULOSIS
I. CLASSIFICATION OF TB (ATS)
CLASS DESCRIPTION TREATMENT
ATS Class 0 No Exposure BCG in high prevalence area
(-) PPD
ATS Class 1 (+) Exposure If with recent exposure:
(-) PPD  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
ATS Class 2: (+) Exposure 70% of adult Filipinos are (+) for PPD, and are therefore naturally infected
TB Infection (+) PPD If with recent PPD Conversion, give Primary Prophylaxis HR for 4 months or
(-) Target Organ TB Lesion 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
ATS Class 3: See Table Below See Table Below
PTB Active ATC Class 3 patients are
further subdivided into
WHO Category I, II, III
ATS Class 4: Eg. CXR with Minimal
Previous PTB Infiltrates, but NO
Disease Symptoms of Active
Disease or Previously
treated PTB
ATS Class 5: Check previous CXR
PTB Suspect 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 2 HRZE 4 HR
New cases of Severe Forms of Extra-Pulmonary TB
II Sputum Smear-Positive: Relapse
Treatment Failure 2 HRZES and 1 HRZE 5 HRE
Treatment after Interruption
III ** New Smear-Negative PTB (other than in Category I)
New Less Severe Forms of Extra-Pulmonary TB 2 HRZE 4 HR

* 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

2
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 CHILDREN ADULTS
H: Isoniazid (INH) 5 mg/kg/day 300-400mg PO
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

3
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 All THREE (3) Smear Negative

Classify as Collect another 3 Sputum Specimens Refer to Physician (Symptomatic Tx for 2-3 wks)
SMEAR POSITIVE TB Immediately

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

Consistent with Active TB? on CXR

Yes No Consistent with Active TB

Observation / Further Exam,

If necessary

Yes No

Classify as Not Consistent with

SMEAR NEGATIVE TB 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

4
VI. NATIONAL TB CONTROL PROGRAM MANUAL OF PROCEDURES, 2005
A. Definition of Terms
TB Symptomatic 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
Active Case Finding A health worker‟s purposive effort to find TB cases who do not consult with personnel in a DOTS Facility
Passive Case Finding 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 DEFINITION OF TERMS
LESION EXAMINATION
Pulmonary TB (PTB) Smear Positive 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
Smear Negative 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. 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
2. 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 DEFINITION OF TERMS
New 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 A patient who returns to Treatment with Positive Bacteriology (Smear or Culture), following Interruption of
(RAD) 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”. Re-
Register as “Other” for the next treatment
 3) Chronic Case: a Patient who is Sputum Positive at the End of a Re-Treatment Regimen

5
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 Another 1 Month of HRZE

o If after 2 Months of HRZE you have Sputum Smear Negative, go directly to 4 Months of HR
o 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
o 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 Ethambutol Discontinue Ethambutol and refer to Ophthalmologist
Vision due to Optic Neuritis
Hearing Impairment, Ringing of Ear and Streptomycin Discontinue Streptomycin and refer to MHO / CHO
Dizziness due to Damage of CN-VIII
Oliguria or Albuminuria due to Renal Streptomycin Discontinue Anti-TB Drugs and refer to MHO / CHO
Disorder Rifampicin

Psychosis and Convulsion Isoniazid Discontinue Isoniazid and refer to MHO / CHO
Thrombocytopenia, Anemia, Shock Rifampicin Discontinue Anti-TB Drugs and refer to MHO / CHO

6
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 CHRONIC ASTHMA SEVERITY
Mild Intermittent 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 Occasional use of B2 Agonists Regular use of Inhaled Use of Combination of Inhaled
control Corticosteroid and Long-Acting Corticosteroids, Long-Acting B2
B2 Agonists 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 PARTLY CONTROLLED UNCONTROLLED
Daytime Symptoms None (twice or less/week) > 2x / week Three or more symptoms
Limitation of Activities None Any of Partly Controlled
Nocturnal Symptoms (Awakening) None Any Asthma in any week
Need for Reliever None (twice or less/week) More than twice/week
Lung Function Normal < 80% Predicted
Exacerbation None > 1x / year One in any week

7
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)
Long Acting Bronchodilators
Combined Corticosteroids and
Long Acting Bronchidilators
Leukotriene Receptor
Antagonists
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
Anti-Cholinergic Agents
Combined Anti-Cholinergics
and Short Acting B2 Agonists
Inhaled:
 Beclomethasone Dipropionate (Qvar Metered Dose Inhaler)
 Budesonide (Budecort Turbuhaler / Primavent Metered Dose Inhaler)
Oral / Systemic:
 Prednisone (Orasone)
 Methylprednisolone (Medrol)
Long Acting B2 Agonist
 Formoterol Fumarate (Inhaled)
 Salbutamol (Oral / Systemic)
 Bambuterol (Oral / Systemic)
Long Acting Theophylline (Sustained Release Formulation)
 Nuelin SR
Formoterol and Budenoside (Symbicort Turbuhaler)
Salmeterol and Fluticasone
Montelukast Na (Kastair, Singulair)
Zafirlukast (Accolate)
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
Ipratropuim Bromide (Atrovent)
Ipratropium Bromide + Salbutamol (Combivent Metered Dose Inhaler)
8
IV. MANAGEMENT OF CHRONIC ASTHMA: HOME TREATMENT
CLASSIFICATION
Step 1: Mild Intermittent NONE
Step 2: Mild-Moderate Persistent
Step 3: Severe, Persistent
CONTROLLER USED RELIEVER USED
Inhaled Short Acting B2 Agonist
PRN Only, NOT > 3x/week
Daily Medication: Inhaled Short Acting B2 Agonist, NOT to
Inhaled Corticosteroids PLUS Long Acting exceed 3-4x/day
B2 Agonists Consider Inhaled Ipratropium Bromide
(Seretide or Symbicort Inhaler)
Daily Medication: Inhaled Short-Acting B2 Agonist, NOT to
Inhaled Corticosteroids PLUS Long Acting exceed 3-4x/day
B2 Agonists (eg. Seretide or Symbicort Add inhaled Ipratropium Bromide
Inhaler)
Oral Steroid > 7.5mg daily or alternate days

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 **NOTE: Epinephrine & Isoproterenol are not commonly used
 Ephedrine because of their effect on the Heart (B1 Receptors)
2. B1, B2 Agonists
 Isoproterenol
3. Selective B2-Agonists
SHORT ACTING LONG ACTING
Terbutaline Salmeterol
Albuterol Bitolterol
Levalbuterol Formeterol
Mataproterenol
Pirbuterol

B. Methylxanthines o Zileuton
o Theophylline
o Aminophylline
o Anhydrous Theophylline
o Theobromine
o Caffeine

C. Anticholinergics
o Ipatropium Bromide
o Atropine Methylnitrate

D. Leukotriene Modifying Drugs

o Zafirlukast
o Montelukast

9
 E. Glucocorticoids
INHALED CORTICOSTEROIDS SYSTEMIC CORTICOSTEROIDS
Beclomethasone Dipropionate Prednisone
Triamcinolone Acetonide Hydrocortisone Sodium Succinate
Flunisolide
Budesonide
Fluticasone propionate
F. Cromolyn Sodium

VI. BASIC MECHANISMS OF SOME DRUGS IN ASTHMA

ATP

Adenylyl Cyclase Beta Agonists

Bronchodilation
(+)
cAMP

BRONCHIAL TONE Phosphodiesterase

Antimuscarinics Theophylline
Acetylcholine (+) 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 INCOMPLETE RESPONSE POOR RESPONSE

(Mild Exacerbation) (Moderate Exacerbation) (Severe Exacerbation)

No symptoms within 1 hr PEF 60-80% Predicted PEF < 60% Predicted

PEF > 80% predicted
Sustained response for 4 hrs

Continue regular bronchodilator for Add Oral Steroid (1mg/kg/day) Add Oral Steroid (1mg/kg/day)
24-48 hrs
Inhaled Short Acting B2-Agonist 2 Continue Beta-2 Agonist and/or Repeat inhaled Beta-2 Agonist if available
puffs q3-4hr Theophylline regularly
Alternative: Oral Short-Acting B2-
Agonist 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 Low, Flattened Diaphragms
o Hyperlucent Lungfields with Bullae and diminished Vascular Markings (in Severe Emphysema)
o Often, disease is prominent in Upper Long Zones (except in A1-Antitrypsin Deficiency: basilar predominance)
B. Pulmonary Function Testing
o FEV1 and all other measurements of Expiratory airflow are Reduced
o FEV1 = Standard Way of objectively assessing the clinical course and response to therapy
o Total Lung Capacity, Functional Residual Capacity, & Residual Volume may be Increased, indicating Air-Trapping
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
o 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 PREDOMINANCE AGE OF (+) SYMPTOMS PULMONARY FUNCTION
SYMPTOMS TESTING
Pink Puffers Emphysema Advanced Age Progressive exertional dyspnea Mild Hypoxia, Hypocapnia
(>60) Weight Loss Decreased DLCO
Little / No Cough & Expectoration
Mild Increase in Raw
Little Improvement in Airflow after
Treatment with Bronchodilators
Blue Bloaters Chronic Bronchitis Young Age Chronic Cough & Expectoration Severe Hypoxia, Hypercapnia
Episodic Dyspnea Polycythemia
Weight Gain Increased Raw
Wheezing, Rhonchi
Cor Pulmonale often develops Improved Airflow after treatment
(Edema, Cyanosis) 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 FEV1 as % TREATMENT
PREDICTED
0: At Risk NORMAL Smoking Cessation for everyone
 Cough Reduce indoor pollution
 Sputum Reduce occupational exposure
Flu vaccinations yearly

I: Mild COPD > 80% As needed B2-Agonists

 Cough, Sputum  Eg. Terbutaline Sulfate (Bricanyl Turbuhaler) 250mcg/dose: 1 inh prn q2-6h
 Little or NO Dyspnea Pulmonary Rehabilitation
 Mild Symptoms
 NO Abnormal Signs
II: Moderate COPD 50 – 79% For intermittent Sx:
 Cough, Sputum  As needed B2 Agonists
 Dyspnea on moderate exertion For Continuous Symptoms:
 Continuous or intermittent Sx  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% As needed B2 Agonists
 Cough, Sputum For Continuous Symptoms:
 Dyspnea on Mild Exertion  Maintain on Tiotropium (Spiriva HandiHaler) Inhalation of 1 capsule daily
 Lung Hyperinflation
For frequent exacerbations (>4x/yr):
 Wheezing
 Add inhaled Steroids of Long Acting B-Agonists
 Eg. Formoterol & Budesonide (Symbicort Turbuhaler) 1-2 inhalations BID
Pulmonary Rehabilitation
IV: Very Severe COPD < 30% In addition to the above treatments:
 Dyspnea even at rest  Add long-term O2 Therapy at home
 Chronic Respiratory Failure  Consider surgical treatments like Lung Reduction Surgery and Bullectomy
(removal of Bulla)
V. COPD VS ASTHMA (Med School Notes)
COPD ASTHMA
Smoker or Ex-Smoker Nearly All Possible
Symptoms under age 35 Rare Often
Chronic Productive Cough Common Uncommon
Breathlessness Persistent and Progressive Variable
Night Time Awakening Uncommon Common
Significant Diurnal or Day to Day Variability Uncommon 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 QuickTime™ and a
TIFF (LZW) decompressor
B. Non-Pharmacologic Therapies are needed to see this picture.
o Pulmonary Rehabilitation
o Lung Volume Reduction Surgery (LVRS)
o Lung Transplantation (COPD is the single leading indication for
lung transplantation)
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 Smoking Cessation
o Optimal Bronchodilator Regimen (not established)
o Glucocorticoids
o Oxygen Therapy
o Pulmonary Hypertension and Cor Pulmonale
o Comprehensive Pulmonary Rehabilitation Program
o Influenza Vaccine and Pneumococcal Vaccine
o Psychoactive Drugs
o A1-Protease Inhibitor Augmentation Therapy
IX. SURGICAL CONSIDERATIONS
 Non-Thoracic Surgery
 Lung Resection, Lung Volume Reduction Surgery
 Lung Transplantation
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.

QuickTim e™ and a
TIFF (LZW) decom pres s or
are needed to s ee this picture.

14
X. NOTES FOR COPD (GOLD)

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

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

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

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

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

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

15
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:
 Moderate to Severe Dyspnea General Criteria for Acute Ventilatory Failure:
 pH < 7.35 or PaCO2 > 45  Patient is Acutely Dyspneic, Altered Mental Status
 RR > 25  PaO2 < 50mmHg at Room Air
2. Best Modes:  PaCO2 > 50mmHg
 PSV  Arterial pH: significant Respiratory Acidemia
 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 patient‟s Inspiratory Effort or to a
Preset Backup Respiratory Rate
 Excessive Patient Work occurs if Peak Flow Insufficient to meet Patient‟s 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, Patient‟s 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 patient‟s 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 Back up Rate of 4 Breaths per minute LESS than the Patient‟s 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
IMV Titrating the Level of Mandatory Breaths: consider NOT only the ABG but also the
Patient‟s work of breathing and comfort
PSV 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 Dilates pulmonary and systemic veins
2-5mg IV can be repeated 10-25min until effect is seen
Furosemide Potent Venodilators
Initial Dose of 20-40mg IV, Max dose of 200mg
Nitroglycerin Venodilator
Can potentiate the effect of Furosemide
Inotropes 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
 Protein Losing Enteropathy
 Lymphatic Carcinomatosis
 Diffuse Pulmonary Infections
 Aspiration
 Shock
Other Forms of Pulmonary Edema:
 Narcotic Overdose – parenteral Heroin, Morphine, Methadone, Dextropropoxyphene
 Exposure to high altitudes – due to pulmonary venous constriction or pulmonary
arteriolar construction
 Neurogenic Pulmonary Edema – in patients with CNS disorders without preexisting LV
dysfunction

18
5) INVESTIGATING AN SPN
 SPN: Solitary Pulmonary Nodule

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

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

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 & host‟s response to those pathogens

I. CLASSIFICATION (2004): Management-Oriented Risk Stratification of CAP in Immunocompetent Adults

CAP

Any of the following: Any of the following:

1. RR > 30 / min 1. Shock or signs of Hypoperfusion
2. PR > 125 / min -Hypotension
3. Temp > 400C or < 350C -Altered mental status
4. Extrapulmonary evidence of YES -Urine output < 30mL/hr YES
HIGH RISK CAP
sepsis
5. Suspected aspiration 2. PaO2 < 60mmHg or Acute
6. Unstable comorbid conditions* hypercapnea (PaCO2 >
7. CXR: Multilobar, pleural 50mmHg)
effusion, abscess, progression of
lesion to > 50% of initial within
24 hours

NO NO

LOW RISK CAP MODERATE RISK CAP

Outpatient In Patient Intensive Care

LOW RISK CAP MODERATE RISK CAP HIGH RISK CAP

Stable Vital Signs Unstable Vital Signs: Any of the clinical features of Moderate
 RR < 30/min  RR > 30/min Risk CAP plus any of the following:
 PR < 125bpm  PR > 125bpm
 SBP > 90mmHg  Temp > 400C or < 350C 1) Shock or Signs of Hypoperfusion
 DBP > 60mmHg  Hypotension
Unstable Comorbid Condition
Uncontrolled DM, Active Malignancies, Progressing  Altered Mental State
No or Stable Comorbid Conditions Neurologic Disease, CHF Class II-IV, Unstable CAD,  Urine Output < 30mL/hr
Renal Failure on Dialysis, Uncompensated COPD,
No evidence of Extrapulmonary Sepsis Decompensated Liver Disease 2) Hypoxia (PaO2 < 60mmHg) or Acute
Evidence of Extrapulmonary Sepsis Hypercapnea (PaCO2 > 50mmHg)
No evidence of Aspiration Hepatic, Hematologic, GI, Endocrine
Chest X-Ray:
Suspected Aspiration * As in Moderate Risk CAP
Chest X-Ray:
 Localized infiltrates Chest X-Ray:
 No evidence of Pleural Effusion nor  Multilobar Infiltrates
abscess  Pleural Effusion or Abscess
 NOT progressive within 24 hours  Progression of findings to >50% in 24h

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 S. pneumoniae
CAP H. influenzae IV Non-Pseudomonal B-Lactam
C. pneumoniae With or Without B-Lactamase Inhibitor
M. pneumoniae PLUS Macrolide
M. catarrhalis
Gram (-) Enteric Bacilli OR
Legionella pneumophilia
Anaerobes (with risk of aspiration) Antipneumococcal Fluoroquinolones (FQ)
High Risk CAP S. pneumoniae No Risk for P. aeruginosa:
H. influenzae a. IV Non-Pseudomonal B-Lactam with or without B-
C. pneumoniae Lactamase Inhibitor + IV Macrolide
M. pneumoniae b. IV Antipneumonococcal FQ
M. catarrhalis
Gram (-) Enteric Bacilli With Risk for P. aeruginosa
Legionella pneumophilia IV Pseudomonal B-Lactam with or without B-Lactamase Inhibitor
Anaerobes (with risk of aspiration) PLUS
S. aureus IV Macrolide or IV Antipneumococcal FQ
P. aeruginosa 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 HARRISON‟S 17TH EDITION: CURB-65 CRITERIA
 C: Confusion
 U: Urea >7mmol/L Scoring System:
 R: Respiratory Rate >30/min  0: Outpatient
 B: Blood Pressure (Systolic <90 or Diastolic <60)  2: In-Patient
 >3: In-Patient ICU
 65: Age >65years old

22
8) HOSPITAL ACQUIRED PNEUMONIA
I. EARLY VS LATE ONSET HAP
EARLY ONSET LATE-ONSET OTHERS
(≤ 5 days in Hospital) (> 5 days)
S. pneumoniae P. aeruginosa Anaerobic Bacteria
H. influenzae Enterobacter spp Legionella
M. catarrhalis Acinetobacter spp Candida spp
S. aureus K. pneumoniae Influenza A and B
Enteric Gram (-) Bacteria S. marcescens RSV
E. coli
Other Enteric Gram (-) Bacteria
S. aureus

**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. Light‟s 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 Usual Site: 8th ICS L PAL
o Maximum Drainage = 1.5 L every 24 hours
o 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 1) Gross Pus on Thoracentesis
o 2) Presence of Organisms on Gram Stain of the Pleural Fluid
o 3) Pleural Fluid Glucose < 50mg/dL
o 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 1) Recurrent Pleural Effusion
o 2) Malignant Pleural Effusions
o 3) Secondary Pneumothorax including Iatrogenic Pneumothoraces
o 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
2. Exudative Pleural Effusions
 Neoplastic Diseases
 Infectious Diseases (Bacterial, TB, Fungal, Viral)
 Pulmonary Embolization
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
 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 Alveolar-
Arterial 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 plasmin‟s 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:
 Westermark’s Sign: Decreased Vascularity
 Hampton’s Hump: Wedge-Shaped Density above Diaphragm in outer 2/3 lung field
 Palla’s Sign: Enlarged Right Descending Pulmonary Artery
 Knuckle’s 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
 McConnell’s Sign: Hypokinesis of the RV Free Wall with Normal Motion of the RV Apex (which is the Best-
Known 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 Anticoagulates by binding to and accelerating the activity of Antithrombin III, thus preventing
(UFH) 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)
Ex) Initial Bolus of 80 units/kg, followed by initial infusion rate of 18 units/kg per hour
Low Molecular Weight Exhibit less binding to plasma proteins and endothelial cells
Heparin (LMWH) No monitoring or dose adjustment needed
Enoxaparin 1mg/kg BID and Tinzaparin 175 unigs/kg OD
Warfarin 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 Maintaining Adequate Circulation (for patients with Massive PE and Hypotension = 500-1,000mL normal saline)
o Pulmonary Embolectomy
o Pulmonary Thromboendarterectomy
o Emotional Support
o 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 INDIRECT LUNG INJURY
Pneumonia Sepsis
Aspiration of Gastric Contents Severe Trauma
Pulmonary Contusion  Multiple Bone Fractures
Near-Drowning  Flail Chest
Toxic Inhalation Injury  Head Trauma
 Burns
Multiple Transfusions
Drug Overdose
Pancreatitis
Post-Cardiopulmonary Bypass

III. ACUTE LUNG INJURY (ALI) VS ACUTE RESPIRATORY DISTRESS SYNDROME

OXYGENATION ONSET CHEST XRAY ABSENCE OF LEFT ATRIAL
PRESURE
ALI PaO2 / FiO2 < 300mmHg Acute Bilateral alveolar or PCWP < 18mmHg or No clinical evidence
ARDS PaO2 / FiO2 < 200mmHg Acute interstitial infiltrates of Increased Left Atrial Pressure

IV. THREE PHASES OF ARDS Pathology:

 Exudative (Day 0-7) Severe Injury to the Alveolocapillary Unit: Alveolocapillary Leak
 Proliferative (Day 7-21) 
Permeability Pulmonary Edema (Protein Rich Edema Fluid)
 Fibrotic Surfactant Disruption
Three Compartments in ARDS Lung: Hyaline Membrane Formation
1) Normally Aerated / Hyperaerated Alveolar Collapse, Consolidation
2) Poorly Aerated (Ground Glass) 
3) Non-Aerated  (+) Shunting 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 Goals in ARDS: Protective Mechanical Ventilation:

TIFF (Uncompressed) decompressor
are needed to see this picture.  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 BREATH VOICE TRANSMISSION ADVENTITIOUS
SOUNDS SOUNDS
Normal Resonant Normal Vesicular Normal Absent
(at lung bases)
Consolidation or Atelectasis Dull Increased Bronchial Bronchophony, Whisphered Crackles
(with Patent Airway) Pectoriloquy, Egophony
Consolidation or Atelectasis Dull Decreased Decreased Decreased Absent
(with Blocked Airway)
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

36
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RHEUMATOLOGY
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Jaime Alfonso Manalo Aherrera, M.D.
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Internal Medicine Notes 2009

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 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
 Oral Ulcers We ONLY need FOUR out of the ELEVEN to make a
 Photosensitivity Diagnosis of SLE
 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 REMARKS
Malar Rash 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 An Abnormal Titer of ANA by Immunofluorescence at any point in time in the absence of
Antibodies drugs known to induce ANAs
If > 4 of these Criteria, well documented, are present at any time in a patient’s history, the diagnosis is likely to be SLE
(Specificity is ~95%; Sensitivity is ~75%)

2
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, Raynaud’s 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 Hypocomplementemia (Low C3 and C4 Levels), Elevated ESR and CRP
Abnormalities
Renal 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

3
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 Prednisone 5mg/tab PO 40-60mg/day, maintained on dose of 10-20mg
(CNS, Renal, Hema) 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
Cyclophosphamide IV Pulse Therapy 500-1000mg in D5W 500cc x 6h (give Metoclopromide 2 tabs before the
drip) – for life threatening SLE
For Photosensitivity Sunscreens
For Skin Lesions Hydrocortisone 200mg BID + Betamethasone 0.05% Ointment
For Thrombosis Coumadine PO

4
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 Labs Requested for RA:
 ERC / CRP
IgG – found in more than 2/3 of adults with the disease and have classically
 RF
been used to evaluate patients with RA
 CBC
 Normochromic, Normocytic Anemia is frequently present in Active RA  Renal
 ESR is increased in nearly all patients with Active RA  ALT (for MTX Therapy)
 Synovial Fluid Analysis: presence of Inflammatory Arthritis  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

Medical Management:
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
 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 extra-
articular disease (vasculitis, episcleritis, pleurisy)
 Immunomodulatory and Immunosuppressive Agents
o Methotrexate (initial choice for moderate to severe RA)
o Hydroxychloroquine or Sulfasalazine

5
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 Contains < 180 Cells (predominantly Mononuclear Cells)
Acute Bacterial Infections Cell Counts averaging 100,000/uL (25,000-250,000/uL) with > 90% Neutrophils
Crystal Induced, Rheumatoid, and other Non < 30,000-50,000 cells/uL
Infectious Inflammatory Arthritides
Mycobacterial and Fungal 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

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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 (don’t 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

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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 DURATION
1. Gram (+) in Smear 1. Staphylococcus:
 Oxacillin or Nafcillin 2g q4h  4 Weeks
2. Penicillin Sensitive Pneumo / Strep:
2. Gram (-) in Smear  2 Weeks on Penicillin-G 2m u q4h
 Cefotaxime 1g q 8h
 Ceftriaxine 1-2g q 24h 3. Penicillin-Resistant
 Cefotaxime / Ceftriaxone for 2 Weeks
3. Suspect Pseudomonas 4. Enteric Gram (-)
 Add Aminoglycoside; or  3-4 Weeks 2nd /3rd Generation Cephalosporin IV; or
 3rd Generation Cephalosporin  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!

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More on Rheumatologic Diseases:
Algorithm for the Diagnosis of Musculoskeletal Complaints: Sites of Hand or Wrist Involvement & Diseases

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

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

Definition of Terms:
Crepitus A Palpable (less commonly audible) vibratory or
crackling sensation elicited with joint motion
Subluxation Alteration of joint alignment such that articulating QuickTime™ and a
TIFF (Uncompressed) decompressor
surfaces incompletely approximate each other are needed to see this picture.
Dislocation Abnormal displacement of articulating surfaces such that
the surfaces are not in contact
Range of For diarthrodial joints, the arc of measurable movement
Motion through which the joint moves in a single plane
Contracture Loss of full movement, resulting from a fixed resistance
caused either by tonic spasm of muscle (reversible) or to
fibrosis of periarticular structures (permanent)
Deformity Abnormal shape or size of a structure; may result from
bony hypertrophy, malalignment of articulating
structures, or damage to periarticular supportive
structures
Enthesitis Inflammation of the entheses (tendinous or ligamentous
insertions on bone)
Epicondilytis Infection or Inflammation involving an Epicondyle