Goals

The student or graduate PA will:

Test-Taking Tips
1. Identify proven techniques from the psychology of
learning and educational measurement which will
enhance test performance.
2. Identify information from testing theory which will help
avoid careless errors.

Jim Van Rhee, M.S., PA-C 3. Practice using clues to help identify correct and
incorrect responses to exam questions.
Program Director; Associate Professor
Yale School of Medicine, PA-Online

Test-Taking… To achieve our goals, we will discuss:

• Measures two things: • How to prepare
– 1) Knowledge
– 2) Test-taking skills • How to do your best during the exam

• The mechanics of test-taking

• Is a skill, like any clinical skill
– …but good clinical skills do not always translate directly into • Managing stress and anxiety
good test-taking skills!
• Some test question examples
• Has evidence-based, scientific foundations
• Some DOs and DON Ts for test-taking

Before the Test Standardized Testing

• Preparation • Norm-Referenced
– Know what to expect on the exam – All raw scores converted to a standard (norm) score
• Prepare mentally based on a reference group
– Stop worrying about how or what other students are
doing
• Average PANCE score is 500
• Know the testing site • SD is 100
– Allow time to drive to the site • Criteria-Referenced
– Dress accordingly – Standard for passing set by a group prior to the
• Supplies exam being given
– None allowed – PANCE is about 350
It s 3 A.M. but I
still have 2 more
chapters to get
through.

1
The Test: PANCE
• Pearson VUE testing centers
• 300 total questions
– ~20% surgical issues
• Five 60-question blocks each lasting 60 minutes
• No time stopping breaks after starting block
– Total break time 45 minutes
– Total exam time 5 hours 45 minutes
• Can register 90 days before graduation
– Take exam 7–90 days after graduation
The Test: PANRE
• Pearson VUE testing centers
• Must take exam every 10 years
• 4 hours plus breaks to complete
• 240 questions- multiple choice
– Four 60-question blocks each lasting 60 minutes
• Exam window period year around
• Exam Options
– 60% will be generalist exam
– 40% can be directed in one of 3 areas: adult medicine,
surgery, and primary care

Scoring PANCE Results- First Time Pass Rate

• One point for each correct answer • 2017
• NO penalty for incorrect answers – Pass rate 97%
• Tests then evaluated and questions removed if needed • 2016
and test re-scored – Pass rate 96%
• Passing score is predetermined • 2015
– Pass rate 96%
• 2014
Remember: Don t leave any answer blank. – Pass rate 95%
• 2013
• Pass rate 94%

Testing Center Identification

• Arrive 30 minutes early to Pearson VUE testing center. Acceptable forms of ID:
• Computer clock • Primary ID must contain a • Secondary ID must
permanently-affixed contain the candidate s
• No supplies allowed
photo, along with name:
– Marker board or scrap paper is supplied. candidate's pre-printed
name and signature:
• No personal belongings allowed – Driver s License – Employee ID
– You will be assigned a locker – Passport – Social Security Card
– Military ID – Credit Card
• Once you begin a block, no clock-stopping breaks are – Student ID – Birth Certificate
permitted. – Naturalization Papers
• Do not forget 2 forms of ID (at least one with a – Government-issued
International Driver s
photo). License

2
 Exam Content General Test Strategies
• Dump Information
% of Exam Diseases/Disorders/Organ System These five areas make up – Calculations, formulas, flow charts
13 Cardiovascular System 50% of the exam.
• Develop a plan
10 Pulmonary System
% of Tasks and Objectives – Budget your time
9 Gastrointestinal System/Nutrition Exam
• If taking more than 2 minutes, answer and move on
8 Musculoskeletal System 18% Formulating most likely diagnosis
– Plan to use the entire exam time
7 Eyes, Ears, Nose & Throat 17% History taking and physical exam

7 Reproductive System
• Make educated guesses
14% Clinical therapeutics
7 Endocrine System – Go back later to questions you don t know
14% Clinical intervention
6 Neurologic System – Don t waste time
12% Using lab and diagnostic studies
6 Psychiatry/Behavioral Science – Guess if you have to; don t leave it blank
10% Applying scientific concepts
5 Genitourinary System
10% Health maintenance
5 Renal System Note: Drug names: generic names for common names and
5% Professional Practice
5 Dermatologic System generic and trade for others; never just trade name
5 Hematologic System

6 Infectious Diseases

Question Options Multiple-Choice Tests

Multiple-Choice Formats • Work quickly.
• A-type Questions • Try to answer the question before looking at the
– Multiple-choice question: stem with 5 options choices.
– Negative ( All of the following EXCEPT ) questions • Pick the BEST answer.
are rare
– If it appears that there are 2 correct answers, select
– May have a scenario
the most specific one.
• B-type Questions
– Matching questions • Eliminate unlikely answers.
– Very few questions in this format • Look for clue words and numbers.
– Typically organized around a theme (anemia, IBD) • Avoid reading into the question (assume nothing).
• No K-type questions
• When in doubt, guess.

Normal Ranges Sample Question

A 29-year-old female complains to her health care provider of headaches,
fatigue, and weakness over the past several months. Physical exam is
significant for pallor, tachycardia, dizziness on standing, and spooning of the
nails. Laboratory studies reveals the following:
Hemoglobin 10.2 g/dL (normal 12-16 g/dL)
Hematocrit 31% (normal 35-45%)
Serum iron 24 mg/dL (normal 50-170 mg/dL)
Serum ferritin 30 ng/mL (normal 10-120 ng/mL)
TIBC 30 ng/ml (normal 250-450 mg/dL)
A peripheral blood smear would likely show which of the following?

A) Macrocytosis with hypersegmented neutrophils

B) Microcytosis with basophilic stippling
C) Microcytosis with hypochromia
D) Numerous schistocytes

3
Answer for Choosing
• Decide what the answer is to a question before looking
at the answer choices.
• Then pick the answer choice that most closely matches
your answer.
• Choose simple answers even if they seem obvious.
• Never pick an answer without first reading all the
choices.
Look for Clue Words and Numbers
• If 2 answers are opposites, one of them is probably
correct.
• Answers with the following words are usually
incorrect: always, never, all, none.
• Answers with the following words are usually correct:
seldom, generally, most, tend to, probably, usually.
• Look for grammatical clues.

Guess Three Phases of Question-Answering

• Even if you are randomly guessing, you • Phase 1
should get about 25% right. – Go through the exam and answer those items about
which you are confident.
• With educated guessing, that jumps up
• Saves time and builds confidence
to 75%.
– Don t leave any questions blank.
• Random guessing tips • Phase 2
– The longest response is often correct. – Go back and focus on marked/skipped questions.
– Answer C is a good choice. – Eliminate incorrect answers.
• Phase 3
– If there is a range in numbers, choose
– Take your best guess.
one in the middle.
– Watch random guessing on
standardized tests.

Test Anxiety Mechanics of Test-Taking

• Keep a positive attitude. • Time allowance
• Concentrate on the test. • Maintain a positive attitude
– Be prepared for a long (but not
– Don t worry about the person next to you.
unbearable) day
• Pay close attention to one question at a time. • Answering by elimination
• Relax. • Always triage first
• Medications • Should you change your answer?
– Yes, if a good reason to change
– Not the time to start something new
– But don’t stop regular medications

4
How to Pass the Exam… Types of Questions You Will Encounter and
Three conditions are generally necessary: Strategies for Dealing with Them
1. Know about or recognize medical information. 1. The Oversimplification
2. The Oversimplification that is Dangerous by Omission
• The best way to pass any exam is to know the
material. However, there are times when you will 3. Clues from Logic
need to guess between 2 or more choices. Don t 4. Clues from Related Areas
guess randomly, however; use educated guesses 5. Qualifying Words
involving known test-taking skills and strategies.
6. The Overqualified Choice
2. Use appropriate test-taking skills. 7. Strange Terms
3. Avoid situations leading to mistakes or impeding 8. Apple Pie Choices
performance. 9. Hints from Inconsistencies in Terminology
10. Rank Orders

Types of Questions You Will Encounter and The Oversimplification

Strategies for Dealing with Them Some questions appear tricky because you think, No question
could be this simple! If you really know the answer to a question,
Regardless of the question type, always triage first. Ask answer it without belaboring or looking for booby traps that are not
yourself the following: there.
A 24-year-old female presents with lower abdominal pain and
•Is this a friendly question? fever of 48 hours duration. During the pelvic exam, she
– Simply asks for information experiences exquisite pain when the cervix is moved. Which
of the following is the most likely diagnosis?
•Is this a trap?
A. Cervical carcinoma
– Attractive choices that can catch you off guard
B. Bacterial vaginitis
•Are choices potentially harmful? C. Leiomyoma
– Important pitfalls which must not be missed—probably D. Peritonitis
just the ones you would consider clinically important E. Cystitis

The Oversimplification The Oversimplification that is

A 24-year-old female presents with lower abdominal pain and fever of
48 hours duration. During the pelvic exam, she experiences exquisite
Dangerous by Omission
pain when the cervix is moved. Which of the following is the most
likely diagnosis? As always, triage questions for traps. Here, the correct choice
is an oversimplification that is dangerous by omission.
A. Cervical carcinoma
B. Bacterial vaginitis A 19-year-old male presents with a painless testicular
C. Leiomyoma mass. Which of the following diagnoses should be
D. Peritonitis pursued?
E. Cystitis
A. Strangulation
The item least likely to cause pain, (A), is eliminated.
Any of the remaining 4 are possibilities, but peritonitis B. Carcinoma
(D) of any etiology is usually a safe diagnostic C. Varicocele
consideration. D. Carbuncle
Do not get bogged down considering the unlikely E. Torsion
diagnostic possibilities when an obvious choice is
present.

5
The Oversimplification that is Dangerous Clues from Logic
by Omission Sometimes a logical (and correct) answer is contained in
A 19-year-old male presents with a painless testicular mass. Which of the following the stem.
diagnoses should be pursued?

(A)Strangulation At what time is the diagnosis of congenital hip

(B)Carcinoma dislocation made?
(C)Varicocele
(D)Carbuncle
(E)Torsion A. In utero
(A), (D), and (E) are incorrect because they are usually painful. (B) and
B. At birth
(C) are usually painless. Because of its prognosis if left untreated, a C. At 6 weeks of age
testicular mass should be considered cancer until proven otherwise.
Not to do so would be considered a life-threatening omission. (B) is D. At 6 months of age
correct. E. At 1 year of age
Screen questions for dangerous or critical choices whether harmful by
omission or commission. A potentially harmful choice may present itself
as an oversimplification.

Clues from Logic Clues from Related Areas

At what time is the diagnosis of congenital hip dislocation Similar to clues from logic, knowledge about related
made? disciplines can provide additional hints.

A. In utero An obese 50-year-old woman presents with acute groin

pain. Upon examination a 2–3 cm soft mass is noted in the
B. At birth right labia majora. Which of the following is the most likely
C. At 6 weeks of age diagnosis?
D. At 6 months of age
E. At 1 year of age A. Lymphadenopathy
B. Inguinal hernia
The term congenital means present at birth. This is when C. Uterine prolapse
the diagnosis of congenital hip dislocation is made. The
correct choice is (B). D. Femoral aneurysm
E. Neurofibroma

Clues from Related Areas Qualifying Words

An obese 50-year-old woman presents with acute groin pain. Test-item stems which contain qualifying words such as
Upon examination a 2–3 cm soft mass is noted in the right labia most, more, usually, often, less, seldom, or few can lead
majora. Which of the following is the most likely diagnosis? you to the correct answer.
A. Lymphadenopathy
B. Inguinal hernia A 30-year-old presents to the clinic with what is
C. Uterine prolapse suspected to be alcohol withdrawal. Which of the
D. Femoral aneurysm following would be the most likely finding?
E. Neurofibroma
A. Visual hallucinations
You would probably not miss the common diagnosis of B. Auditory hallucinations
inguinal hernia in a male patient. Remembering from
developmental anatomy that the labia majora and scrotum C. Fine motor tremors
are corresponding tissues, (B) would be selected as D. Motor seizures
correct, even if you had minimal knowledge about surgical E. Autonomic hyperactivity
emergencies.

6
Qualifying Words The Overqualified Choice
A 30-year-old presents to the clinic with what is suspected to be To make an answer acceptable, test-item writers
alcohol withdrawal. Which of the following would be the most
likely finding? sometimes must qualify a choice to the point at which the
savvy test-taker recognizes the ploy.
A. Visual hallucinations
B. Auditory hallucinations In the smoking patient, which of the following most
C. Fine motor tremors appropriately describes clubbing?
D. Motor seizures
E. Autonomic hyperactivity A. Discoloration of the nail bed
B. Flattened angle between the dorsal surface of the
Any of the above may be seen with alcohol distal phalanx and the proximal nail
withdrawal. However, fine motor tremors are by far the
most common. The stem contains qualifying words C. Abnormal, outwardly curved nail
( most likely ), suggesting (C) as the correct choice. D. Decreased eponychium

The Overqualified Choice Strange Terms

In the smoking patient, which of the following most Choices which contain completely unfamiliar words are likely to
appropriately describes clubbing? be distracters. If the choice appears completely bizarre, the
test-item writer was probably scraping the barrel for a
A.Discoloration of the nail bed distracter.
B.Flattened angle between the dorsal surface of the distal
phalanx and the proximal nail On a routine peripheral blood smear, a nucleated cell filled
C.Abnormal, outwardly curved nail with bright red granules and approximately 3x the diameter
D.Decreased eponychium of a typical red blood cell is noted. What is this cell called?

A. Reed-Sternberg cell
The overqualified (lengthy) choice, (B), is likely to be B. Myeloblast
correct, as we see here. However, recall the odd C. Eosinophil
choice described earlier. Sometimes, the short odd D. Lacunar cell
choice is correct. You will recognize this variation E. Kupffer cell
because it will be attractively precise and succinct.

Strange Terms Apple Pie Choices

On a routine peripheral blood smear, a nucleated cell filled with bright red
granules and approximately 3x the diameter of a typical red blood cell is
noted. What is this cell called?

A. Reed-Sternberg cell There are some responses to which no one would object.
B. Myeloblast
C. Eosinophil When evaluating a 23-year-old woman with vaginal
D. Lacunar cell bleeding, the most important clinical information is
E. Kupffer cell
gained from which of the following?
(A), (D), and (E), while real cell types, are not typically A. Complete blood count
noted in primary care. (B) is familiar—remember basic
B. Prothrombin time
hematology. However, identifying a myeloblast on the
peripheral smear is not basic primary care, which the C. Bleeding time
PANCE/PANRE exams cover. Physician assistants should D. Physical exam
recognize the morphology and significance of an E. History
eosinophil; thus, the correct response is (C).

7
 Apple Pie Choices Apple Pie Choices—Watch Out for
When evaluating a 23-year-old woman with vaginal bleeding, the most Seductive Traps!
important clinical information is gained from which of the following?
An unconscious patient presents to the emergency
A.Complete blood count room. Which of the following is the most important
B.Prothrombin time physical exam component to perform?
C.Bleeding time
D.Physical exam
E.History A. General inspection
B. Neurologic exam
A patient s history provides a clinician s best information and is C. Pulmonary exam
almost never incorrect. (E) is an apple pie choice.
D. Vital signs
The apple pie choice, however, can also be used by test-item E. Brain MRI
writers to set traps!

Apple Pie Choices Hints from Inconsistencies in Terminology

Watch out for seductive traps! Grammar inconsistencies between the stem and a choice (e.g., tense,
number, gender) are usually recognized by expert educational
An unconscious patient presents to the emergency room. Which of the evaluators who screen Board exam test questions. You will seldom
following is the most important physical exam component to perform? encounter this type of hint on Board exams.
A.General inspection A 19-year-old motorcycle accident victim with suspected multiple
B.Neurologic exam trauma is brought unconscious to the emergency room. The
C.Pulmonary exam
most significant physical findings will usually result from which
D.Vital signs
of the following?
E.Brain MRI

The initial triage here would identify this as a trap question A.Undressing the patient
B.Prompt neurologic exam
because the critical nature of the scenario is combined with an
C.Interviewing the family
incorrect apple pie choice. Brain MRI (E) is promptly dismissed
because it is not a physical exam component. (B) appears D.Interviewing a witness to the accident
attractive because of its apple pie component. But recall the E.All the above
ABCs of emergency care. (D) is correct.

Hints from Inconsistencies in Terminology Rank Orders

A 19-year-old motorcycle accident victim with suspected multiple trauma is When given a list of numbers or other rank orders, the
brought unconscious to the emergency room. The most significant physical
findings will usually result from which of the following? correct response most often occurs somewhere between
the extremes.
A.Undressing the patient
B.Prompt neurologic exam
In the patient with chronic schizophrenia, how long must
C.Interviewing the family the disease be present to be termed chronic?
D.Interviewing a witness to the accident
E.All the above
A. ½ year
(C) and (D) refer to historical findings, not physical. This also B. 1 year
excludes foil (E). Although indicated, at this point of presentation
the neurologic exam is too focused. A more general, overall
C. 2 years
assessment provides the best clinical information; thus, critical, D. 3 years
life-saving information across organ systems may be gained
from observing the patient. (A) is correct.
E. 4 years

8
Rank Orders
Most test-item writers try to bury the correct answer
somewhere in the middle. (C) is the correct answer
in each example.
As with hints from inconsistencies in terminology,
this clue does not often work on Board exams.
Educational evaluators try to randomize the position
of correct responses as much as possible. However,
when in doubt, it is better to avoid the extremes.
DOs and DON Ts
DOs
• DO reread instructions provided by the testing agency the
night before, to ensure you arrive on time, at the right
place, and with the right materials.
• DO review in detail the information on the PANCE or
PANRE content, instructions and format found at
www.nccpa.net.
• DO remember to bring admissions materials (such as your
government-issued identification).
• DO examine the computer station you are assigned. Be
alert for glare or other lighting problems, and potential
traffic flow as others arrive and leave throughout the day.
• DO consider the proctor is there to support you. Ask for
any reasonable support or change of computer location
that will help you do your best.
Q-Bank
DOs
• DO practice what you will be doing during the exam; that
is, answering multiple-choice questions on a computer.
This is imperative for the clinician who has not taken a
written or computer-based exam recently.
• DO direct your studying to the primary care areas with
which you are least familiar.
• DO get adequate sleep and rest before the exam.
• DO dress comfortably in layers that prepare you for
temperature extremes. Coats or jackets will not be
allowed.
• DO arrive alert, calm, and well-rested.
• DO bring beverages, food for lunch, and between-test-block
snacks.
DOs
• DO pace yourself, allowing a calculated amount of time per
question. Allow for some extra time at the end to return to
items you have marked as unsure.
• DO avoid situations that might put you in an unfavorable
mindset before the exam. Let nothing interfere with your best
possible performance.
• DO relate test questions to your own practice and
experience. Test-item writers are people who have derived
many of the test questions from their own clinical
experience. What would you expect a primary care
physician assistant to know?
• DO change your answer if you have a good reason to do so.
You are twice as likely to change from an incorrect response
to a correct one.
9
DOs
• DO triage each and every question before selecting your
answer. Evaluate it as a question designed to
– test knowledge in a friendly way
– trap by including common pitfalls
– evaluate your knowledge about potentially dangerous choices
• DO use the process of elimination. As with a patient s
differential diagnosis, this usually is done by elimination.
Avoid choosing an answer until after you have considered all
of the choices.
• DO eliminate choices containing completely unfamiliar words
as distracters. If the choice appears completely unfamiliar, it
is probably incorrect.
DOs
• DO mark items if you are not sure of the answer. Return to
these items when you finish the question block (but don t
leave them blank the first time through the exam).
• DO consider apple pie choices as probably correct.
However, beware that they may also be used to trap.
• DO consider choices that are different from the others—the
odd choice. These may include a choice having an odd
meaning or odd length—long or short. The overqualified
choice often is correct.
• DO select choice (C) when purely guessing; it is most
frequently the correct response on many one-choice-only
multiple-choice questions. If you eliminate (C) as a
possibility, (B) is the next most likely choice. This is a last-
ditch strategy that works more often on classroom tests
than on Board exams.

DON Ts
• DON T cram at the last minute; the exam covers mostly primary care
breadth rather than depth.
• DON T eat a large meal within 2 hours of the exam.
• DON T leave any items blank. Unanswered items will be counted as
wrong.
• DON T discuss the exam with others during the test administration, Sample Questions
breaks or even afterward; this adds to anxiety and may result in
disqualification or revocation of your certification.
• DON T become irate over seemingly absurd questions.
Answer them to the best of your ability, realizing that they
are probably experimental questions that will not affect your
score.
• DON T guess randomly. Even if you are completely unsure of an
answer, use the hints suggested today to increase the probability of
guessing the correct response. Make educated, not random, guesses.
• DON T think of anything except the exam in front of you.

A 15-year-old male presents to the office with jaundice. Vital

Which of the following is the most common cause of signs are normal except for a low-grade fever. A CBC is
non-gonococcal urethritis in men under the age of 35? performed and results noted below:
Hematocrit 46% Hemoglobin 15.4 g/dl MCV 86 fL
Platelets 150,000/mm3 WBC 14,500/mm
A. Pseudomonas aeruginosa
Diff: Neutrophils 20%, Bands 2%, Lymphocytes 70% (22% atypical with
B. Escherichia coli vacuoles), Monocytes 6%, Eosinophils 2%
C. Chlamydia trachomatis Which of the following is the most likely diagnosis?
D. Trichomonas vaginalis
A. Viral hepatitis
E. Ureaplasma urealyticum B. Pertussis infection
C. Infectious mononucleosis
D. Acetaminophen overdose
E. Acute lymphocytic leukemia

10
After This Program Ends
• Rank-order NCCPA organ systems from weakest to
strongest based on recent testing, and study them in
that order.
• During the remaining study time, devote more time to
weaker subjects and less time to stronger ones.
– This will help even out your knowledge base so that on the
actual exam, you won t lose a lot of points in any one area.
The End
• Don t worry.
• You will receive your scores in 10-14 days.
• Don t discuss the exam with others; it will just create
more anxiety plus it is unethical.
• Check policies and procedures at:
– http://www.nccpa.net/PoliciesProcedures?mID=101
• GOOD LUCK!
Effective Reviewing
• Make a plan and stick to it.
• Transform, apply, and extract key aspects into briefer
form.
• Practice testing should be cumulative, not single
subject.
• Analyze patterns in your test errors and adjust study to
strengthen habitual problem areas.
• Reward yourself for goals achieved.
• Gradually switch focus from reviewing to performing.
• Simulate exam-pacing plus item mix before test day.
• Let self-testing results dictate when you are test ready.
Questions
11
 The Cardiovascular System
Lecture 1 Cardiomyopathy
Congestive Heart Failure

The Cardiovascular System Lecture 2 Hypertension

Hypotension

Lecture 3 Ischemic Heart Disease

Other Forms of Heart Disease
Jim Van Rhee, MS, PA-C
Program Director; Associate Professor Lecture 4 Vascular Disease
Endocarditis
Yale School of Medicine, PA-Online
Lecture 5 Valvular Disease
Congenital Heart Disease

Cardiomyopathy
• Three Major Types
– Dilated
– Hypertrophic
Heart Failure
– Restrictive
Cardiomyopathy
Congestive Heart Failure

Dilated Cardiomyopathy Dilated Cardiomyopathy

• Due to malfunction of myocardium • Clinical manifestations
• Etiologies – Exertional intolerance
– Idiopathic (#1 etiology) – Atypical chest pain
– Alcohol – Signs of CHF
– Hypertension, myocarditis, ischemic heart disease, • Dyspnea, orthopnea, edema in LE
valvular disease • Physical examination
– Infectious, drugs (doxorubicin), peripartum – Crackles on pulmonary exam
– Thiamine deficiency (beriberi) – Mitral regurgitation and S3 on cardiac exam
• Pathophysiology
– Dilatation leads to right and left systolic dysfunction, and
then CHF
Dilated Cardiomyopathy Hypertrophic Cardiomyopathy
• Diagnosis • Common cause of sudden death in young athletes
– EKG: nonspecific ST-T – Inherited disorder (autosomal dominant) - 60% of
changes, possible LBBB
cases
– CXR: cardiomegaly and
pulmonary congestion – Hypertension, aortic stenosis
– Echo: dilated, thin left • Pathogenesis
ventricle, low EF (key
– Unexplained hypertrophy leads to LV outflow
diagnostic study)
obstruction and impaired diastolic filling
• Treatment
– Stop offending agent – Impaired diastolic filling leads to pulmonary congestion
– Treat CHF • Clinical
• ACE inhibitors, diuretics, – Most cases asymptomatic
sodium restriction
– Possible DOE, syncope, exertional chest pain,
– Most common cause of palpitations
heart transplant

Hypertrophic Cardiomyopathy Restrictive Cardiomyopathy

• Physical examination
– Mitral regurgitation
• Murmur increases with Valsalva and exercise; decreases with
handgrip and leg elevation
– S4 and prominent left ventricular impulse
• Diagnosis
– EKG: left axis deviation, abnormal Q waves, ST-T wave changes
– Echo: septal wall thickness and EF 80-90%
• Treatment
– No competitive sports or strenuous exercise
– Beta-blockers (decrease HR and improve diastolic filling time)
– Calcium-channel blockers (improve ventricular compliance)
– Diuretics for fluid overload
• Caused by an infiltrative process
– Amyloidosis, sarcoidosis, hemochromatosis
• Pathogenesis
– Damage leads to diastolic noncompliance with elevated
filling pressure and impaired filling
– Elevated filling pressure leads to pulmonary congestion
• Clinical
– Exertion intolerance and fluid retention
– Right heart failure with elevated JVD
– S3, S4 and mitral and tricuspid regurgitation

Restrictive Cardiomyopathy Cardiomyopathy Summary

• Diagnosis Hypertrophic Dilated Restrictive

– Echo: decrease in EF (25–50%), normal LV thickness, Etiologies Genetic Genetic Infiltrative

Hypertension Myocarditis
increased atrial size Aortic stenosis Chronic
• Treatment
EF (%) >60 <30 25–50
– Treat underlying cause LV wall size Increased Decreased Normal or
– Diuretics for CHF increased
Murmur Mitral regurgitation Mitral then tricuspid Mitral and tricuspid
– ACEI and beta-blockers regurgitation regurgitation
– Transplant First Exertional Exertional Exertional
symptoms intolerance intolerance intolerance
Chest pain Fluid retention
Congestive Heart Failure (CHF) New York Heart Association
• Pathophysiologic state in which abnormal cardiac Functional
Class Classification
Description
function renders the heart unable to pump blood at a I Patients with no limitations of activities; suffer no symptoms from
rate to meet the requirements of the metabolizing ordinary activities
tissue
II Patients with slight, mild limitations of activity; comfortable with
• Etiologies rest or mild exertion
– Valvular heart disease
– Ischemic heart disease III Patients with marked limitations of activity; comfortable only at rest
– Arrhythmias
– Hypertension
IV Patients confined to bed or chair; any physical activity brings on
– Cardiomyopathy discomfort and symptoms occur at rest

Congestive Heart Failure Congestive Heart Failure

• Clinical • EKG • CXR
– Dyspnea, orthopnea, – LVH, check for – Cardiomegaly
PND, fatigue, edema, myocardial infarction
(MI) – Increased pulmonary
exercise intolerance
• Labs vasculature
• Physical examination
– BNP: elevated – Pleural effusions
– JVD (>8 cm)
– Rales – Cardiac enzymes – Kerley B lines
– Tachycardia – CBC, electrolytes, renal • Echo
function
– Displaced PMI – Systolic or diastolic
– S3 (LV dysfunction) dysfunction
– Edema, ascites Right side failure, think systemic – Decreased EF
Source: David Matthew DeLonga

Left side failure, think pulmonary – LV/RV hypertrophy 16

– Regional wall motion

Kerley B lines CHF: Treatment

• Low sodium diet
• Diuretics (enhance sodium and water excretion)
– Loop diuretics - diuretics of choice
– Thiazide diuretics - use in mild heart failure
• ACE inhibitors: use early; reduce hypertrophy, ­ survival
• Angiotensin receptor blocker: no cough like ACEI
• Beta blockers - reduce vasoconstriction [preload &
afterload] and sodium retention
• Hydralazine - vasodilator
• Avoid corticosteroids, NSAIDs, calcium-channel blockers

Source: Mustafa Mohamed Alikhan

 The Cardiovascular System
Lecture 1 Cardiomyopathy
Congestive Heart Failure Blood Pressure
Lecture 2 Hypertension Hypertension
Hypotension
Hypotension
Lecture 3 Ischemic Heart Disease
Other Forms of Heart Disease

Lecture 4 Vascular Disease

Endocarditis

Lecture 5 Valvular Disease

Congenital Heart Disease

Hypertension (HTN) Defining HTN: Guidelines/Goals

• Incidence in adults 25-33%
• JNC 8 Guidelines • ACC/AHA Guidelines
• End-organ damage is common
– Adults >60 years old – Normal: Less than 120/80 mm Hg;
– Cardiac
treat when SBP≥150 – Elevated: Systolic between 120-
• LVH, angina/ prior MI, heart failure, aortic aneurysm 129 and diastolic less than 80;
or DBP≥90.
– Cerebrovascular – Stage 1: Systolic between 130-
• Goal is <150/90
• CVA/TIA 139 or diastolic between 80-89;
– Peripheral arterial disease
– Adults <60 years old – Stage 2: Systolic at least

– Renal proteinuria (Chronic kidney disease)

treat when SBP≥140
or DBP≥90.
– Retinopathy
• Goal is <140/90
– Adults ≥18 years old
with CKD or diabetes
treat when SBP≥140
or DBP≥90.
• Goal is <140/90
140 or diastolic at least 90 mm
Hg;
– Hypertensive crisis: Systolic over
180 and/or diastolic over 120
• With patients needing prompt changes
in medication if there are no other
indications of problems, or immediate
hospitalization if there are signs of
organ damage.
– Goal <130/80 mm Hg

Accurate BP Measurement: Technique Workup of Hypertension

• No recent coffee or smoking • History
• Patient seated comfortably, back and feet supported – Duration of hypertension
– Family and medical histories
• Arm at heart level
– Review of systems
• Correct size cuff – Social history
• Always inflate cuff with finger – NSAIDs
on brachial or radial pulse • Physical examination
– Optic fundi, carotids, heart, renal masses, renal artery bruit,
• Deflate at 2-4 mm Hg per second
pulses, skin
• Initially, take BP in both arms • Basic labs
• Always take a standing BP – UA, GFR, glucose, cholesterol, potassium, ECG
• Other special exams only if indicated
IMC, © 2010 DxR Development Group, Inc.
All Rights Reserved.
JNC 8 Treatment Algorithm for HTN ACC/AHA Treatment Guidelines
Lifestyle Modifications

General Population Diabetes CKD

(No diabetes or CKD) (no CKD) (With or without diabetes

BP Goal BP Goal CKD

Age <60: 140/90 <140/90 (with or without diabetes)
Age ≥60: <150/90 All Ages

Non-black Black All races

Thiazide, ACE inhibitor, or ARB Thiazide or calcium channel ACE inhibitor or ARB alone or
or calcium channel blocker blocker alone or in in combination with other
alone or in combination combination drug classes

Lifestyle Modifications Medication Notes

• Should be included in every antihypertensive regimen • Diuretics
– Chlorthalidone is the preferred thiazide, but requires closer
• May last from 6–12 months (unspecified in JNC 7) monitoring of electrolytes and renal function
• Lifestyle modifications – Furosemide is not considered a preferred initial diuretic
• ACEI/ARB
– Weight loss: ¯ BP 5-20 mm Hg/10 kg weight loss – Use in patients with protein in their urine
– Moderate dietary sodium reduction: ¯ BP 2-8 mm Hg – Contraindicated in pregnancy
– Discontinue smoking: ¯ BP 10-15 mm Hg • Beta-blockers
– No longer recommended as 1st or 2nd line agents unless
– Moderate alcohol intake: ¯ BP 2-4 mm Hg compelling indication (CAD or Atrial fibrillation)
– Exercise: ¯ BP 4-9 mm Hg – Combined alpha-beta blockers (Carvedilol, labetalol) are more
effective and less metabolic disturbances
• Caffeine consumption does not need to be eliminated – May worsen insulin resistance and dyslipidemia
– Caution in DM type 1, may mask hypoglycemia
• Calcium channel blockers
– May cause cause lower extremity edema
– Do not use short-acting nifedipine

Compelling Indications Major Contraindications

Indication Recommendation
Heart failure Thiazide, BB, ACEI, ARB, Aldosterone antagonist Drug Contraindications
Post-MI BB, ACEI, Aldosterone antagonist
Thiazides Gout
High CVD risk Thiazide, BB, ACEI, Ca++ channel blocker
Potassium-sparing Hyperkalemia
Diabetes Thiazide, BB, ACEI, ARB, Ca++ channel blocker diuretics
Renal disease ACEI, ARB ACEIs/ARBs Pregnancy, renal artery stenosis, hyperkalemia
Recurrent stroke Thiazide, ACEI Nondihydropyridine Heart block, systolic heart failure
prevention CCBs
Beta Blockers Heart block. Asthma, depression, cocaine abuse
Key: Alpha blockers Orthostatic hypotension, systolic heart failure
BB: beta blocker
ACEI: angiotensin converting enzyme inhibitor Direct vasodilators Orthostatic hypotension
ARB: angiotensin receptor blocker
Secondary Hypertension Secondary Hypertension
• Due to an identified cause Etiology Clinical Findings Evaluation
Renovascular disease Serum creatinine Ultrasound
– Obstructive sleep apnea – Cushing s syndrome Renal artery bruit MRA: renal arteries
– Drug-induced or – Pheochromocytoma Captopril renogram
related causes Coarctation of the aorta Unequal pulses MRI/CT
– Coarctation of the aorta Rib notching
– Chronic kidney disease Claudication
– Thyroid or parathyroid disease
– Primary aldosteronism Primary aldosteronism Hypokalemia Plasma renin/aldosterone
Cushing s syndrome Truncal obesity Plasma cortisol
– Renovascular disease Buffalo hump Dexamethasone
Hyperglycemia suppression
• Treatment
Pheochromocytoma Tachycardia Plasma metanephrine and
– Treat underlying cause Headache normetanephrine
Diaphoresis
Sleep apnea: obstructive Snoring Sleep study
Obesity

When to Suspect 2 HTN Hypertensive Emergencies

• Onset ages <30 or >50
• Sudden worsening of previously controlled HTN
• Failure to respond to therapy
• Hypokalemia (w/o diuretics): primary aldosteronism
• Labile HTN
• H/A, palpitations, diaphoresis: pheochromocytoma
• Renal failure after ACE-inhibitor
• Severe hypertension with severe and rapidly worsening
symptoms of end-organ damage
• Clinical signs
– Neurologic - encephalopathy, HA, confusion, seizures
– Cardiac - CP, MI, palpitations, dyspnea, JVD
– Nephropathy - hematuria, proteinuria, renal dysfunction
– Retinopathy - papilledema, hemorrhages, blurred vision
• Diagnosis
– CT brain, EKG, electrolytes, renal function
• Treatment
– IV nitroprusside, labetalol, enalapril

Hypotension: Cardiogenic Shock Cardiogenic Shock

• Tissue hypoperfusion due to acute MI or end-stage • Clinical
heart failure – SBP <90 mm Hg or decrease from baseline of 30 mm
Hg
– Overall prognosis poor
– Symptoms: altered mental status, cyanosis, oliguria
• Etiologies • Physical examination
– Acute MI – Cool, clammy extremities; signs of hypovolemia
– Tachyarrhythmia – PE findings of underlying condition

– Valvular heart disease

• Diagnosis
– Echo: decreased left ventricular function
– Traumatic cardiac injury
• Treatment
– Myocarditis
– Improve pressure with IVF or vasopressor agents
• Dopamine: increases cardiac output and BP
• Dobutamine: increases cardiac output but not BP
Hypotension: Orthostatic Hypotension: Vasovagal
• Decrease in SBP of 20 mm Hg or DBP of 10 mm Hg when • Vasovagal syncope (common faint) is most common
moving from recumbent to standing position cause of syncope.
• May result in syncope – Considered a benign condition,
• Symptoms
– Change in mental status; confusion
• Triggers- prolonged standing, emotional stress, pain
– Weak pulse • Symptoms
– Tachypnea – Lightheadedness, nausea, ringing in the ears, extreme hot or
• Treat Underlying Cause, Support BP cold feeling
• Etiologies
– Drugs (antipsychotic drugs, diuretics, alpha blockers, ACE
• Diagnosis
inhibitors, alcohol, tranquilizers, vasodilators) – Head Up tilt table test
– Polyneuropathies • Treatment
– Parkinson s disease – Treat underlying etiology
– Avoid blood pressure lowering medications

The Cardiovascular System

Lecture 1 Cardiomyopathy
Heart Failure Coronary Disorders
Lecture 2 Hypertension Chest Pain
Hypotension
Myocardial Infarction
Lecture 3 Ischemic Heart Disease Angina
Other Forms of Heart Disease
Other Heart Diseases
Lecture 4 Vascular Disease
Endocarditis

Lecture 5 Valvular Disease

Congenital Heart Disease

Chest Pain Ischemic Heart Disease (IHD): MI

Cardiac Features Pulmonary Features • Predisposing factors
Myocardial infarction Severe pain, >20 Pulmonary Tachypnea, dyspnea,
minutes duration embolism- infarction pleuritic pain – 50% of patients have identifiable factor
Aortic stenosis Typical systolic Pulmonary Signs of RV failure • Very heavy exercise
ejection murmur hypertension
Myocarditis Mild, vague pain Pneumothorax Sudden pain, dyspnea
• Severe mental stress: anger
Pericarditis Sharp pain, worse GI Features – Often preceded by periods of unstable angina
lying down, better
sitting up
– Circadian periodicity: 6 AM to 11 AM
Dissecting aortic Tearing pain, radiate Hiatal hernia Reflux of food, relief • Most deaths occur within 1 hour of onset
aneurysm to the back with antacids
– Due to ventricular fibrillation
MVP Midsystolic click, GERD Acid reflux, relief with
young woman antacids
Musculoskeletal Features Gallbladder disease RUQ pain, tenderness

Costochondritis Pain worse with PUD Epigastric pain, worse

inspiration, pain with 3 hours after eating
chest wall palpitation
Ischemic Heart Disease Major Cardiovascular Risk Factors
Modifiable Uncontrollable
• Dyslipidemia • Age
– Higher risk ­ LDL, ¯ HDL, ­ – Women age >65
cholesterol, ­ triglycerides, ­
lipoprotein A – Men age >55
• Smoking • Gender
– Double the risk, return to • Men greater risk
normal after 2 years post • Family history
smoking
• Hypertension – Women age <65
• Physical inactivity – Men age <55

• Obesity (BMI ≥30)

• Diabetes mellitus

Clinical Features of Myocardial Infarction (MI) Lab Studies

• Pain
– Usually severe & intolerable; retrosternal (may radiate to arm,
neck, jaw) • Leukocytosis
– Prolonged: 20 minutes to hours – 12,000 to 15,000/µL
– Quality: crushing, constricting, compressing, oppressing • Lipid profile
– Caused by ischemia, not infarction
• Serum cardiac markers
• Other symptoms
– Nausea/vomiting in 50% (usually inferior MI)
– Weakness
– Dizziness, palpitations
– Cold sweat, sense of impending doom
• Physical examination
– Typically no findings
– May have: Elevated BP, Tachycardia, Presence of S4

Cardiac Markers - Creatinine Kinase Cardiac Markers

• Exceeds normal range within 3–6 hours Troponin Myoglobin
• Normalizes in 2–4 days
• Troponin (I or T) has nearly • Non-specific
• Peaks at 24 hours (earlier if reperfusion)
absolute myocardial tissue • Detectable in 1–2 hours after
• Check serially every 8 hours for 24 hours specificity and sensitivity acute MI
• May elevate 10–20 times normal limit in AMI – T increased in renal disease,
– Lasts less than 1 day
polymyositis, dermatomyositis
• Isoenzymes • May elevate >20 times normal • Found in skeletal and cardiac
– MM: skeletal muscle muscle
range
– BB: brain; kidney • Begins to rise 2–4 hours post-
– MB: myocardium, small intestine, tongue, diaphragm, uterus, AMI
prostate – Peaks at 10–24 hours and may
persist for 5–12 days
– Ratio of CPK-MB to total CPK >4% is diagnostic
• Aids in picking-up acute MI in
patients who present late
Cardiac Markers Cardiac Enzymes: Summary

Marker Appearance Duration

Troponin I 2-4 hr 5-10 days

CK-MB 3-6 hr 2-4 days

Myoglobin 1-2 hr <1 day

Braunwald Heart Disease 5 th edition

EKG Findings EKG Findings

• ST elevation and Q waves are the 2 most characteristic • ST depression
features of AMI – Occurs with subendocardial ischemia
– Seen in only 50% of patients at presentation – More often seen in NQMI
• ST elevation – Differential diagnosis
– Injury pattern • Hypertrophy
– Occurs with transmural ischemia • Conduction abnormality
– Differential diagnosis • Electrolyte abnormality
• Drug effects
• Pericarditis
• Aneurysm
• LVH
• Early repolarization

If EKG normal then <10% chance

of patient having an MI

EKG Findings EKG Evolution

EKG Abnormality Onset Disappearance
Affected Cardiac EKG Leads Artery Involved
Wall Hyperacute T waves Immediately 6-24 hours

Inferior II, III, aVF RCA ST-segment elevation Immediately 1-6 weeks
Lateral I, aVL, V5, V6 Circumflex
Q waves One to several days Years to never
Anterior V2-V4 LCA
Posterior V1, V2 RCA T wave inversion 6-24 hours Months to years
(ST depression) Circumflex
Apical V3-V6 LAD
RCA
Anterolateral I, aVL, V4-V6 LAD
Circumflex
Anteroseptal V1-V3 LAD
Treatment of AMI: Medications General Treatment Measures
• Antiplatelets • Mnemonic • Control of pain
– ASA, thienopyridine, – M Morphine – Analgesics (morphine)
GP IIb/IIIa antagonists – O Oxygen • Pain control and BP control
• Anticoagulants – N Nitrates – Nitrates
– Heparin, LMWH – A Aspirin • Coronary artery dilatation reducing preload and
• Beta blockers afterload
• ACE-inhibitors – Hep Heparin • Beta blockers (to control BP & reduce risk of sudden
• Nitrates death)
• Statins – Contraindicated in presence of second- or third-degree
– B Beta blocker
heart block or heart failure
• Oxygen
• Oxygen (to avoid hypoxia)

Antiplatelet Therapy Other Medications

• Aspirin • ACE inhibitors
– Given to all patients unless contraindicated – Start in all patients with AMI; continue if LV dysfunction or CHF
– Inhibits platelet aggregation & development of coronary develops
thrombi – Cardioprotective effects
• Thienopyridine (ASA-allergic patients) [blocks platelet ADP • Improve endothelial function
receptor] • Regress LVH/ventricular remodeling
• Clopidogrel • Promote collateral vessel development
– Rapid onset of action • Improve outcomes in PTCA/CABG
– Better safety profile (avoid if emergent CABG needed) • Calcium channel blockers
• Glycoprotein IIb/IIIa inhibitors (inhibit platelet aggregation) – Immediate-acting nifedipine increases in-hospital mortality
• Side effect - bleeding and thrombocytopenia – Diltiazem and verapamil may prevent reinfarction in non-Q MI
– Abciximab (ReoPro)
– Not recommended in acute MI, especially if signs or symptoms of
– Eptifibatide (Integrilin) CHF
– Tirofiban (Aggrastat)

Antithrombin Therapy Recanalization Therapy

• Heparin • Surgical
– Inactivates thrombin and factor X – Primary percutaneous coronary intervention (PCI)
– Reduces morbidity and mortality from other – Percutaneous transluminal coronary angioplasty (PTCA)
complications related to MI • Fibrinolytic
– Indications: – Treatment needed within 12 hours
• Those not receiving thrombolytics – Side effects: bleeding and intracerebral hemorrhagic
• Those with ST depression
bleed
• Those getting TPA – Options
• Streptokinase
• Alteplase
• Reteplase
Thrombolysis
• Absolute Contraindications
– Active internal bleeding
– Suspected aortic dissection
– Recent head trauma or known
intracranial neoplasm
– History of CVA known to be
hemorrhagic
– Major surgery or trauma
<2 wks
Angina Pectoris: Stable
• Labs
– Enzymes negative
– EKG
• May show ST depression and T wave changes during
episode of pain
• Otherwise normal or reveal arrhythmia
– Diagnosis
• Positive stress test
• Perfusion scintigraphy testing
– Exercise, adenosine, dipyridamole
Angina Pectoris: Stable
• Treatment
– DC smoking
– Control hypertension
– Control diabetes
– Exercise plan
– Reduce progression:
• Manage lipids
• Anti-platelet meds
• Beta-blockers
• ACE inhibitors
– Control symptoms (beta blockers, nitrates, calcium channel
blockers)
– Revascularization: PTCA, CABG
• Relative Contraindications
– BP>180 mmHg on at least 2
recordings
– History of chronic, severe HTN
with or without Rx
– Active PUD
– History of CVA
– Known bleeding diathesis or
current use of anticoagulants
– Prolonged or traumatic CPR
– Diabetic hemorrhagic
retinopathy or other ophthalmic
hemorrhagic condition
– Pregnancy
– Prior exposure to SK or APSAC
(Eminase) esp. within 6-9 months
of exposure (does not apply to t-PA
/urokinase)
Angina Pectoris: Stable
• Symptom- pain that builds up rapidly in 30 seconds and
disappears within 5 -15 minutes
• Precipitated by activity and relieved by rest
• Related to a fixed stenosis of coronary artery
• Clinical
– Aching or dull midsternal discomfort with radiation to the neck,
left shoulder, or arm
– Profound weakness and breathlessness may be an angina
equivalent
• Physical examination
– May be normal or note S4 (stiff ventricle due to ischemia)
Stress Tests
• Exercise treadmill test
– May not detect low grade stenosis (<50%)
– Positive if >2mm ST depression and/or hypotension
• Effected by baseline EKG changes
– Contraindicated in unstable angina, MI, aortic dissection, aortic
stenosis, uncontrolled hypertension, ventricular arrhythmias
• Nuclear stress test
– Used in presence of baseline EKG changes (i.e. LBBB) or
certain medications (beta blockers, digoxin)
• Dobutamine or Adenosine stress test
– Used in people unable to exercise
• Stress echocardiogram
– Note wall motion abnormalities
Revascularization
• Coronary bypass graft
– Useful in those with left main coronary disease or 3 vessel
disease and LV dysfunction
– Used in those with symptoms despite medical therapy or
severe side effects
– More efficacious in patients with diabetes
– More beneficial in patients with low EF
• Percutaneous coronary intervention (PCI)
– Stent placement now standard
Angina Pectoris: Unstable Angina Pectoris: Unstable
• Diagnosed clinically • Physical examination
– New-onset angina – Normal exam or S4 may be present
– Increasing angina
• Labs
– EKG normal or non-specific changes
– Angina occurring at rest
– Cardiac enzymes normal
• Clinical • Treatment
– Dyspnea, palpitations, fatigue – Reduce progression to AMI
– Pain is retrosternal or epigastric (described as • Anti-platelets (aspirin)
pressure, burning, or squeezing) • Beta-blockers
– Possible nausea, SOB, diaphoresis • ACE inhibitors
– Revascularization

Angina: Prinzmetal’s variant

• Also called variant angina or vasospastic angina
• Chest pain at rest caused by vasospasm
• Signs and symptoms
– Young patients, present with chest pain, light-headedness not Other Heart Diseases
due to exercise; may have pain during sleep
– Triggered by nicotine, alcohol, cocaine, triptans
Pericarditis
• Diagnosis Cardiac Tamponade
– Angiography with vasospasm with ergonovine Pericardial Effusion
• Treatment
Lipid Disorders
– Prevention
– Acute- nitroglycerin
– Maintenance- Nitro long acting, Calcium channel blockers
(Nifedipine, Verapamil)

Acute Pericarditis Pericarditis

• Due to inflammation of the pericardial lining of the • Clinical presentation
heart – Chest pain most common
• Typically retrosternal, radiation to left side of neck/back,
• Characterized by chest pain, a pericardial friction trapezius, or scapula
rub, and serial electrocardiographic abnormalities • Coughing or deep breathing increases pain; leaning forward
may give relief
• Etiologies • SOB/DOE
– Idiopathic • Fever
– Viral pericarditis: Coxsackie B virus • Cough, weight loss
– Malignancy: lung, breast CA, and lymphoma are most common • Physical examination
– Metabolic: uremia – Friction rub (due to inflamed pericardial surfaces rubbing
– Infection: TB, SBE, fungal together; pathognomonic for acute pericarditis)
– Drug-induced: procainamide, hydralazine – Relative tachycardia
– Idiopathic inflammatory disease: SLE, RA – Hypotension (late)
– Post-myocardial injury s/p AMI (1-3 weeks post) • Labs: CBC, electrolytes, BUN/Cr, possible ANA, RF, PPD
r/o TB
Pericarditis: EKG Pericarditis: Treatment
• Diffuse ST • NSAIDs, ASA (for pain)
segment
elevation
• Steroids (if no response 48 hours)
with upright – Some patients can develop recurrent pericarditis and
T wave may need longer steroid therapy
• PR interval
• The following are self-limiting within 2–6 weeks:
depression
– Viral pericarditis
• Low voltage
– Idiopathic pericarditis
• A-fib/flutter
– Post-myocardial infarction pericarditis
– Post-pericardiotomy syndrome

Cardiac Tamponade Pulsus Paradoxus

• Pathophysiology • Exaggerated response from the normal physiologic
– Accumulation of fluid in pericardial sac and inability to drop in BP with inspiration
fill cardiac chambers in diastole lead to reduction of
stroke volume and cardiac output • Up to 10 mm Hg drop in systolic BP occurs normally
with inspiration
– Leads to hypotension
• Clinical – Tamponade >10 mm Hg drop
– Dyspnea on exertion, orthopnea, hepatic engorgement • Total paradox complete disappearance of palpable
– Hypotension pulse (severe)
– JVD (elevation in systemic venous pressure)
– Muffled heart sounds
– Pulsus paradoxus

Cardiac Tamponade Pericardial Effusion

• Echocardiogram • Prolonged and severe inflammation leading to fluid
– RA and ventricular collapse during diastole accumulation around the heart
– As little as 15 cc on fluid can be detected by 2D echo • Clinical
– Differentiate from other causes: tumor compression or – Small effusions
hematoma, RV infarct • No symptoms

• Treatment – Large effusions

– Drain the fluid: cath- or echo-guided • Signs of tamponade

– Treat symptoms as for pericarditis • Physical examination

– Pericardiotomy or window placement may be required – Diminished heart sounds
– Possible friction rub (if pericarditis present)
Pericardial Effusion Lipid Disorders
• Diagnosis • Linked to CAD and CVA • LDL
– Associated with increased
– CXR – 20% of American adults risk of atherosclerotic
– EKG have hyperlipidemia heart disease
• Low-voltage QRS • Major lipids: cholesterol, • HDL
– Echo triglycerides, and – Associated with
decreased risk of
• Fluid between phospholipids
pericardium layers atherosclerotic heart
• Causes disease
• Treatment
– Primary: familial • Triglycerides
– Pericardiocentesis – Associated with increased
hyperlipoproteinemia
– Maintain BP risk of atherosclerotic
– Secondary: DM, heart disease in women
hypothyroidism, hepatic and diabetics
NNMC
disease, obesity, drugs – Increased levels may lead
to pancreatitis

Lipid Disorders Risk Factors

• Clinical: no symptoms • Major risk factors which modify LDL goals
until signs of ASVD
• Exam – Cigarette smoking
– Xanthomas – Hypertension: BP ≥140/90 or on antihypertensive
– Lipemic blood sample meds
– Abdominal pain – Low HDL cholesterol (<40 mg/dL)
– Hepatomegaly – Family history of premature CHD
– Arcus senilis
• Men: first-degree relative age <55
• Women: first-degree relative age <65
– Age
• Men age ≥45
• Women age ≥55
© Richard Usatine, M.D. Used with permission.

Lipid Disorders ATP IV Guidelines

• Treatment The guidelines contain the following:
•All patients ( ≥ 21 years of age) with any form of CVD (not only
– Risk factor modification CHD), or LDL-C ≥ 190 mg/dl:
• Smoking cessation – Treat with high dose statins if <75 yo, moderate intensity of >75 yo
• Weight loss – e.g.: Atorvastatin 40-80 mg or Rosuvastatin 20-40 mg with the aim to
reduce LDL-C by >50 %
• Exercise
•All patients with diabetes (age 40-75 years) with LDL-C 70-189
– Diet mg/dl, without any evidence of CVD should receive statin therapy
• Cholesterol intake <200 mg/dL as follows:
– Moderate dose statin
• Carbohydrates 50–60% of total calories – e.g. Atorvastatin 10-20mg, Rosuvastatin 5-10 mg, Pravastatin 40-80 mg,
• Fiber 20–30 g/day Simvastatin 20-40 mg, with the aim to reduce LDL-C by 30-50 %.
• Total dietary fat to 30%; saturated fat <7% of total calories – However, consider high dose statin as above if 10-yr risk by new risk
calculator >7.5 %.
– Take aspirin daily unless contraindicated • This will translate to many patients with diabetes + additional risk
factors
•If using high dose and moderate dose statins as described
above, a specific target of LDL-C goal (< 70 or <100) is not
recommended.
•All patients must receive intensive lifestyle management.
 Lipid Disorders Lipid Lowering Agents Summary
• Treatment
– Medications Drug Class Lipid Effects Side Effects Contra-
• Bile acid-binding resins: form compounds with bile acids indications
in intestine
Statins LDL ¯ Rhabdomyolysis Acute liver dz
– Side effects: GI distress, constipation Myolysis Chronic liver dz
HDL ­
– Contraindication: bowel obstruction TG ¯ ­ LTFs
• HMG-CoA reductase inhibitors: limit cholesterol synthesis Bile acids binding LDL ¯ GI distress TG >400 mg/dl
– Side effects: myositis, elevated LFTs resins HDL ­ Constipation
– Contraindications: pregnancy, active liver disease TG ­ ¯ Drug absorption
• Fibric acid derivatives: reduce hepatic trig production and increase Niacin and LDL ¯ Flushing Chronic liver dz
HDL synthesis nicotinic acids HDL ­ Hyperglycemia Severe gout
– Side effects: cholelithiasis, dyspepsia TG ¯ ­ Uric acid levels
– Contraindications: severe hepatic or renal disease Liver damage
• Nicotinic acids: VLDL secretion inhibitors Fibric acids LDL ¯ Gallstones Severe renal dz
HDL ­ Myopathy Severe liver dz
– Side effects: flushing, hepatotoxicity, hyperglycemia TG ¯
– Contraindications- severe PUD, chronic liver disease, severe
gout

Cardiovascular System
Lecture 1 Cardiomyopathy
Vascular Disease
Heart Failure Aortic Aneurysm
Lecture 2 Hypertension Aortic Dissection
Hypotension Arterial Embolism
Lecture 3 Coronary Heart Disease Arterial Occlusion
Other Forms of Heart Disease Giant Cell Arteritis
Lecture 4 Vascular Disease Vasculitis Syndromes
Endocarditis
Thrombophlebitis
Lecture 5 Valvular Disease Venous Thrombosis
Congenital Heart Disease
Varicose Veins

Aortic Aneurysm Aortic Aneurysm

• Pathologic dilatation of the aorta • Diagnosis
• Abdominal aorta most common site – Ultrasound
• Atherosclerosis is most common underlying cause • Excellent screening tool
• Risk factors: smoking, – CT scan
hypertension, age,
• Monitors progression
hyperlipidemia
– CXR: thoracic aneurysm
• Clinical
reveals widened mediastinum
– Most cases asymptomatic
and enlarged aortic knob
• May have hypogastric
or low back pain • Treatment
• Steady gnawing pain – Screen every 6 months
– With rupture, decreased BP (aneurysms >4 cm)
and increased pain
– PE: pulsatile – Surgery (aneurysms >5 cm)
abdominal mass Source: Jeffrey D. Hirsch

Source: Rob Parker

USPSTF AAA Screening Recommendation Aortic Dissection
• The USPSTF recommends one-time screening for • Tear in intimal layer with blood entering the media
abdominal aortic aneurysm (AAA) by ultrasonography • Etiology
in men aged 65 to 75 who have ever smoked. – Peak incidence 6th–7th decades
• The USPSTF makes no recommendation for or against – Men > women 2:1
screening for AAA in men aged 65 to 75 who have – H/O HTN 80% of cases
never smoked.
– Bicuspid aortic valve
• The USPSTF recommends against routine screening
– Marfan's syndrome
for AAA in women.
– Arteritis
– Pregnancy 50% of dissection in women ages <40
– Trauma

Aortic Dissections Aortic Dissection: Classifications

• Majority occur in ascending aorta within several • DeBakey
centimeters of the valve (65%) – Type I originates in the ascending aorta and propagates to
the arch or beyond
• Descending aortic: distal to the left subclavian artery – Type II originates and is limited to the ascending aorta
(20%) – Type III originates in the descending aorta and goes distal or
rarely retrograde
• Aortic arch (10%)
• Stanford
• Abdominal aorta (5%) – Type A: all involving ascending aorta
– Type B: all others
• Descriptive
– Proximal /distal

Aortic Dissection: Symptoms Aortic Dissection: Diagnostic Findings

• Clinical • CXR: widened
– Severe chest pain 75–90% of cases mediastinum or
• Sudden onset, severe at inception; ripping/tearing/stabbing pain
silhouette 80-90%
– Migration of the pain 70% of cases
– Location • Contrast-enhanced CT
• Anterior pain more common ascending involvement
• Posterior pain more common descending involvement • MRI: current gold
• PE standard
– HTN • TEE/TTE
• Difference of >20 mm Hg in blood pressure between arms
– Pulse deficits
– Murmur of aortic regurgitation
– Neurological: CVA, altered consciousness or coma
– Widened pulse pressure

NNMC
Aortic Dissection: Management Arterial Embolism
• Untreated mortality about 1% per hour • Cause of arterial insufficiency
• Monitor BP, rhythm, and urine output • Secondary to:
– A-fib/flutter
– Start 2 large-bore IVs
– Mitral stenosis
• Central venous line (patients with hypotension or
– Transmural infarct
CHF)
– Trauma
• Reduce systolic blood pressure to 100-120 mm Hg
– Hypercoagulable states
• Beta blockers (to reduce contractility) – Post-arterial procedures
• Morphine (to treat CP)
• Surgical consultation

Arterial Embolism Chronic/Acute Arterial Occlusion

• Clinical • Decreased lumen by 50% will produce symptoms
– Severe pain – Cold limbs – More common in lower extremities
– Diminished pulses – Cyanosis • Most common cause is atherosclerosis
• PE (5 Ps) • Risk factors
– Pain – Smoking, hypercholesterolemia, diabetes, HTN
– Paresthesia
– Pallor
– Paralysis • Clinical
– Pulseless
– May be asymptomatic due to collateral circulation
• Diagnosis: echo, arteriogram
– Major symptom pain and then claudication
• Treatment: heparin, embolectomy
• Complications: limb loss, compartment syndrome With foot claudication, think thromboangiitis obliterans
– Compartment syndrome is treated with fasciotomy (Buerger s Disease).

Chronic/Acute Arterial Occlusion Chronic/Acute Arterial Occlusion

• Physical examination • Treatment
– Decreased pulses – Discontinue smoking
– Bruits – Lower cholesterol
– Ischemic skin changes and ulcers – Antiplatelet therapy
• Diagnosis • Clopidogrel
– Ankle/brachial index • Cilostazol (Pletal) [do not use in patients with heart
• 0.40 - 0.90 mild–moderate PAD failure]

• <0.40 severe PAD – Antiplatelet and vasodilating

• Aspirin
– Doppler ultrasound
– Arteriography – Angioplasty
– Thromboendarterectomy
Giant Cell Arteritis
• Granulomatous vasculitis of the temporal artery
• Etiology unknown
• Typically ages >50
– May coexist with polymyalgia rheumatica
• Clinical
– Headache, jaw claudication, vision loss
– Fever, fatigue, weight loss
Vasculitis Syndromes
Polyarteritis Nodosa
• Multisystem disease
– Skin, kidney, nerves, GI
tract
– Medium–sized arteries
• Fever, malaise, weight loss,
anorexia, abdominal pain
• Diagnosis by biopsy of
vessel
• Treatment
– High dose steroids
– Cyclophosphamide
Superficial Thrombophlebitis
• Diagnosis
– Rule out DVT
– Diagnosis based on clinical findings
• Treatment
– Warm, moist compresses
– NSAIDs for pain
– Low molecular weight heparin
– Antibiotics (if septic thrombophlebitis)
• Cover for Staphylococci
Giant Cell Arteritis
• Physical examination
– Temporal artery tender, enlarged, and erythema
• Labs
– Elevated sedimentation rate, anemia, leukocytosis
• Sedimentation rate >50 mm/hr
• Diagnosis
– Artery biopsy
• Treatment
– Corticosteroids
Inflammatory process involving the
blood vessels
Superficial Thrombophlebitis
Churg-Strauss Syndrome • Inflammatory thrombosis involving superficial veins of
the lower extremities
• Multisystem disorder
– Associated with varicose veins, pregnancy, catheter
– Medium-sized arteries placement
• Asthma, eosinophilia, – Septic thrombophlebitis seen in IV drug abusers
lung involvement
• Clinical
• Typical presentation -
– Vein is palpable and tender
middle aged patient with
• Induration, redness, and tenderness along course of
new onset asthma vein
• Diagnosis by biopsy – Cord is palpable
• Treatment
– Steroids
– Cyclophosphamide
Venous Thrombosis
• Development of clot in deep veins of the extremities or pelvis
• Predisposing factors
– Virchow s triad
• Venous stasis
• Vascular damage
• Activation of coagulation system
• Risk factors
– Prolonged immobilization – Hypercoagulable state
– Pregnancy
– Postoperative
– Obesity
– Pelvic/extremity trauma
– Smoking
– BCP
– Cancer
Venous Thrombosis Venous Thrombosis
• Clinical • Prophylaxis
– Pain swelling at site and distal to site – Needed for all high-risk patients
• Physical examination • LMWH
– May be normal • Elastic stockings
– Palpable cord, skin discoloration • Intermittent pneumatic leg compression
– Positive Homans sign • Acute
• Diagnosis – Unfractionated or low molecular weight heparin
– Ultrasound and venogram – Warfarin
– Positive D-dimer • Treat 3-6 months
• Complications – Vena cava filter to prevent PE
– Watch for PE

Varicose Veins Varicose Veins

• Clinical
• Due to incompetence of
– Asymptomatic
saphenous vein
– From increased • May have local aching and fatigue
intravascular pressure • Physical examination
or defective valves
– Tortuous veins easily compressed
• Primarily in superficial
veins of thigh, calf, and • Diagnosis
ankle – Based on clinical findings
• Factors: • Treatment
– Prolonged standing
– Conservative management
– Pregnancy
– Vein stripping or sclerosing agent
– Obesity
nhlbi.nih.gov

Bacterial Endocarditis Endocarditis

• Infection which produces vegetations on the valve • Most commonly involved heart valves
leaflet or endocardium – Mitral
– Native valve (NVE) – Aortic
– Prosthetic valve (PVE) • Acute endocarditis
• Predisposing conditions
– Most commonly associated with Staph aureus; rapidly
– MVP destructive; can be fatal <6 weeks if untreated
– Degenerative valvular disease • Subacute endocarditis
– IV drug abuse: 30 times increased risk
– Most commonly associated with Viridans Streptococci;
– Prosthetic valve takes from >6 weeks to 1 year to become fatal
– Congenital abnormalities
Endocarditis: Microorganisms Prosthetic Valve Endocarditis
• Community • Early onset
– S. aureus – Onset of symptoms <60 days post-operative
– Viridans strep
– Enterococci – Valve contamination during the procedure or bacteremia
post-operative
• Nosocomial
– S. aureus – Staphylococci most common type of organism
– S. epidermidis – Valve dysfunction/dehiscences: fulminant course
– Enterococci
• Late onset
– Fungal: Aspergillus, Candida
– Onset of symptoms >60 days post-operative
• Prosthetic Valve
– S. epidermidis – Streptococci most common type of organism
– S. aureus – Course similar to that of NVE
– Enterococci

Endocarditis: Clinical Features Endocarditis: Clinical Features

• Fever 80–85% • Janeway lesions Splinter hemorrhage
– Small erythematous or
• Chills, weakness 45–75% hemorrhagic macular lesions
Janeway lesions
on palms/soles 6-10%
• Anorexia/weight loss 25–40%
• Osler nodes
• Myalgia/arthralgia 15–30% – Small, tender subcutaneous
nodules on pulp of digits 7-
• Cardiac murmur (80–85%) 10%
• Changing murmur or new murmur • Finger clubbing 10-20%
Roth spots
• Splinter/subungual
• Splenomegaly 15–50% hemorrhages 5-15%
• Embolic phenomena
• Petechiae 10–40% – Large arteries (femoral), lungs
(IV abusers), brain(stroke,
brain abscess, purulent
© Richard Usatine, M.D. Used
meningitis) with permission.

20-40%
• Roth spots <5%

Endocarditis: Diagnosis Endocarditis: Diagnosis

• Based on • Transthoracic Echo
– Clinical suspicion – Rapid, non-invasive, and specificity for vegetations is 98%
– Labs – Sensitivity is <60%
– Echocardiographic data • Transesophageal Echo
• Labs – Procedure of choice with high index of clinical suspicion
– Bacteremia or fungemia – Increases sensitivity for vegetations to 75–95% yet maintains
• Blood cultures positive in +95% of cases specificity 85–98%
• Subacute cases: 3 sets of cultures over 3-6 hours – Negative transesophageal echocardiogram has negative
• Acute cases: do not delay treatment for 3 hours
predictive value of over 92%
• Negative cultures, consider: H. parainfluenza, Candida,
Aspergillus, Coxiella, Histoplasma – Particularly useful in prosthetic valves and for the evaluation of
myocardial invasion
– Anemia, leukocytosis, elevated sedimentation rate and CRP
 Endocarditis: Therapy
• Requires rapid eradication of all microorganisms from the
vegetations
• Use bactericidal vs. static agent
• Treat for minimum 4-6 weeks
Organism
Viridans streptococci
Enterococci
Staphylococcus aureus
MRSA
Staphylococcus epidermidis
SBE Prophylaxis
• New guidelines in 2007
• Required for certain high-risk patients and certain
invasive procedures
• Potential adverse reactions of antimicrobial agent
Treatment
– Allergic reactions complicate between 0.7–4.0% of all
Penicillin G or ampicillin plus gentamicin or
Ceftriaxone plus gentamicin or treatment courses
Vancomycin
– Anaphylactic reactions occur between 0.004-0.04%
Ampicillin or penicillin G plus gentamicin
– Death occurs 0.001%, approximately 300 deaths per
Nafcillin or oxacillin plus gentamicin
year
Vancomycin
Vancomycin plus gentamicin plus rifampin

High Risk Invasive Procedures

• History of prosthetic valve • Dental procedures
• Previous endocarditis • Tonsillectomy and adenoidectomy
• Unrepaired congenital heart disease
• Surgery involving intestinal or respiratory mucosa
• Repaired congenital heart defect with prosthetic
material or device • Surgery on infected soft tissue
– But only during first 6 months after the procedure • Established GU or other intra-abdominal infections
• Repaired congenital heart defect with residual
defects
• Cardiac transplantation recipients who develop
cardiac valvulopathy

Prophylactic Regimens

Route and Situation Agent Cardiovascular System

Lecture 1 Cardiomyopathy
Oral Amoxicillin Heart Failure

Lecture 2 Hypertension
NPO Ampicillin or cefazolin or ceftriaxone Hypotension

Allergic to penicillin: oral Cephalexin or clindamycin or azithromycin or Lecture 3 Ischemic Heart Disease
clarithromycin Other Forms of Heart Disease

Lecture 4 Vascular Disorders

Endocarditis
Allergic to penicillin: NPO Cefazolin or ceftriaxone or clindamycin
Lecture 5 Valvular Disease
Congenital Heart Disease
 Valvular Disease Principles
• Stenosis
– Obstruction to forward flow
– Leads to pressure overload in right and left ventricles
Valvular Disease • Regurgitation
Aortic Stenosis – Backward flow
– Leads to volume overload in the heart
Aortic Insufficiency/Regurgitation
Mitral Stenosis
Mitral Insufficiency/Regurgitation
Mitral Valve Prolapse
Tricuspid Insufficiency
Pulmonary Stenosis

Aortic Stenosis Aortic Stenosis

• Symptoms due to left ventricular outflow obstruction, • Etiologies
leading to increased left ventricular pressure, – Congenital
hypertrophy, and decreased ejection fraction • Bicuspid aortic valve (2% of population)
• Typically ages 60s-80s – Non-congenital
• As the disease progresses, calcification and fibrosis • Degenerative calcification
lead to leaflet stiffness and reduced systolic opening – Most common acquired valvular stenosis

– Area must be reduced to 1/4 its original size before – Mostly men (80%)
clinically significant obstruction occurs • Rheumatic heart disease (uncommon cause in the U.S.)
• Hallmark symptoms
– Angina, syncope, & symptoms of heart failure
(exertional dyspnea)

Aortic Stenosis Aortic Stenosis: Treatment

• Physical Examination • No standard medical therapy proven to improve outcome
– Systolic ejection murmur radiating to the neck • Aortic valve replacement is only effective treatment
• As severity increases, murmur peaks later in systole and can
• Activity levels vary with severity
become softer as CO decreases
– Mild: encourage patient to live a normal life
• Diminished carotid upstroke
• Loss of A2 component of second heart sound – Moderate: advise patient to avoid moderate and severe
exertion and competitive sports
• Diagnosis
– Severe: advise patient to use diuretics and nitrates with
– EKG: LVH
caution; do not want to reduce high ventricular filling
– CXR: dilatation of ascending aorta and pulmonary pressure which is needed to maintain cardiac output
congestion
– ECHO: thick left ventricular wall and valvular calcifications • Diuretics and sodium restriction (if CHF)
– Avoid ACE-inhibitors
– Stress testing is contraindicated in symptomatic patients
and should be used with caution in asymptomatic patients
Aortic Insufficiency Aortic Insufficiency: Signs & Symptoms
• Due to abnormal leaflets or proximal aortic root • Acute
– No time to mount adaptive response to larger end diastolic
• Results in increased end-diastolic volume and volumes
ventricular dilatation, leading to regurgitation – Increased end diastolic pressures cause inadequate
• Etiologies contractile response, causing decreased stroke volume
– Usually symptomatic
– Acute: infectious endocarditis, dissection, valve rupture
• Chronic
– Chronic: Hypertension, idiopathic dilation, bicuspid valve, – LV dilation (produces a larger stroke volume)
rheumatic heart disease, Marfan syndrome • Increased pulse pressure, causing systolic HTN
– Usually asymptomatic
• When adaptive response exhausts, ejection fraction begins
to fall
– CHF symptoms may develop
• Dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and
fatigue

Aortic Insufficiency Aortic Insufficiency

• Physical examination • Treatment
– Widening pulse pressure – Diuretics, digoxin, ACEI, salt restriction (if CHF)
– Bounding water hammer peripheral pulses – Surgery (symptomatic patients [more than mild], EF <55% ,
– Hyperdynamic apical pulse displaced to the left or end diastolic dimension >55 mm)
– Diastolic blowing murmur best heard along LSB • Mild disease
– Systolic and/or diastolic thrill or murmur heard over the femoral – No therapy; no restriction in activity
arteries (Duroziez sign)
• Moderate disease
• EKG: LVH
– No therapy; avoid heavy physical exertion
• CXR: LVH with or without CHF, enlargement of aortic knob
– Vasodilator therapy may be helpful by reducing symptoms
• Echo and ventricular function
– Determines severity of regurgitation

Mitral Stenosis Mitral Stenosis

• Leads to increased atrial pressure and atrial enlargement, • Physical exam
pulmonary congestion, pulmonary hypertension, and right side
– Opening snap with low-pitched diastolic rumble
heart failure
• Most cases secondary to rheumatic heart disease or rare – Murmur louder with isometric handgrips
congenital defect – Loud S1 and Loud P2
• Women > men, ages 40-50 – JVD
• Symptoms • Prominent jugular A wave
– Typical for those of left-sided heart failure
– Progression of symptoms is often subtle and gradual
– Palpable RV heave
– As severity increases: • CXR: LAH, congestion
• Fatigue, dyspnea
• RUQ pain 2 venous congestion • EKG: LAH, A-fib
• Hemoptysis • Palpitations/A-Fib (>50% of patients
• PND with severe MS have A-fib) • Echo: diagnostic
Mitral Stenosis Mitral Regurgitation
• Treatment • Most frequently related to ischemic or degenerative
– HR control mainstay of therapy process
• Acute or chronic
• Beta blockers
• Classified as functional or organic
• Calcium channel blockers
• Causes
• Digitalis (if LV/RV dysfunction)
– Acute – Chronic
– Diuretics (if pulmonary congestion) • Ruptured chordae tendineae • MVP most common cause
– Warfarin (if in atrial fibrillation) • Papillary muscle rupture • Ischemic heart disease
• Endocarditis • Cardiomyopathy
• Surgery • Trauma • RHD
– Closed or open commissurotomy • Infective endocarditis
– Percutaneous mitral balloon valvotomy • Myocardial disease or tumors
• Connective tissue disorders
(SLE)
• Congenital defect

Mitral Regurgitation Mitral Regurgitation

• Acute
– Typically symptomatic
– Left heart failure
• Dyspnea on exertion
• PND
• Pulmonary congestion
• Cardiogenic shock
• Chronic • ECG usually normal or LVH
– Even severe chronic
MR is more often • CXR may be normal or demonstrate LA enlargement
diagnosed by murmur • Echocardiogram (diagnostic)
• Holosystolic – Determine LV hypertrophy and left atrial abnormality
murmur at apex
with radiation to – Also determine presence of pulmonary hypertension
base or left axilla
• Treatment
– Fatigue and mild DOE
the most common – Medical therapy
presentation • ACE inhibitors (may provide clinical benefit by
– As disease reducing afterload)
progresses, more
severe DOE, PND, – Surgery (definitive therapy)
pulmonary edema, or
hemoptysis may
present

Mitral Valve Prolapse Mitral Valve Prolapse

• Most common form of valvular heart disease • Clinical syndrome
– Most cases asymptomatic
• Primary valve disorder
– Symptoms include:
– Idiopathic
• Palpitations • Dyspnea
• Redundant mitral apparatus • Syncope/lightheadedness
• Non-exertional CP
• Myxomatous degeneration of the valve • Fatigue • Anxiety
• Secondary • Physical examination
– Marfan syndrome – Midsystolic click
– Rheumatic heart disease – Late systolic murmur
– Ischemic heart disease • Diagnosis: echocardiogram
– Ruptured chordae tendineae • Treatment: typically not needed
– Papillary muscle rupture
Tricuspid Regurgitation Pulmonary Stenosis
• Most common cause is RV dilatation • Congenital etiology is most common cause
– Pulmonary hypertension from COPD – Rheumatic cause uncommon
– Infectious endocarditis
• Symptoms
– Thyrotoxicosis
– Angina, syncope
– Congenital
• Symptoms • Physical exam
– Signs of right-sided heart failure – Early systolic ejection click followed by systolic ejection
murmur with radiation to base of the heart
• Ascites, edema, RUQ pain
• Physical examination • Diagnosis
– JVD (+), pansystolic murmur at left sternal border – Echocardiogram

• Diagnosis: echocardiogram • Treatment

• Treatment: treat underlying cause – Balloon commissurotomy if increased gradient across valve

Artificial Heart Valves Summary

Valve Advantages Disadvantages

Bioprosthesis • Avoids anticoagulation in • Durability limited to 10–15 Aortic Stenosis Mitral Aortic Mitral Regurgitation
(Carpentier-Edwards) patients with sinus rhythm years Stenosis Regurgitation
• Durable • Relatively stenotic Etiology • Rheumatic Rheumatic • Endocarditis • Mitral prolapse
Mechanical valves • Good flow characteristics • Relatively stenotic • Congenital • Marfan syndrome • Endocarditis
(St. Jude, Starr-Edwards) in small sizes • Require anticoagulation Symptoms • Angina • Dyspnea • Dyspnea • Dyspnea
• Durable • Syncope • Orthopnea • Orthopnea • Orthopnea
• Heart failure • PND • Angina • PND
• Hemoptysis
Homografts/autografts • Anticoagulation not • Surgical implantation Cardiac • Systolic • Diastolic Diastolic blowing Holosystolic apical
required technically demanding Signs ejection murmur rumble murmur murmur
• Durability increased over • Delayed • Opening
bioprosthesis carotid upstroke snap
EKG LVH/LAA RVH/LAA LVH/LAA LVH/LAA

CXR Boot-shaped Straight left Cardiac Cardiac enlargement

heart heart border enlargement

Effect of Maneuvers on Systolic Murmurs

Valsalva Handgrip Squatting Amyl Leg
Nitrite Raising

¯ ¯ ­ or ¯ ­ ­
Aortic stenosis
Congenital Heart Disease
Hypertrophic ­ ¯ ¯ ­ ¯
obstructive Atrial Septal Defects
cardiomyopathy
Coarctation of Aorta
VSD ¯ ­ No change ¯ ­
Patent Ductus Arteriosus
Mitral regurgitation ¯ ­ No change ¯ ­ Tetralogy of Fallot
Ventricular Septal Defects
Transposition of Great Arteries
Atrial Septal Defects Atrial Septal Defects
• Defect in atrial septum (in region of fossa ovalis) • CXR
– Shunting of blood – Cardiomegaly
• Clinical • EKG
– Typically no symptoms; if severe, possible DOE – Right ventricular hypertrophy, RAD, RBBB
• PE • Echo (TEE is best for shunt determination)
– Right ventricular heave – Enlarged right ventricle and flow across defect
– Loud S1, fixed wide split S2 • Treatment
– Murmur – Spontaneous closure likely in first year of life
• Systolic ejection in pulmonic region – Surgery (to close defect)
• Done between ages 2-4

Coarctation of Aorta Coarctation of Aorta

• Narrowing in descending aorta • CXR
– Most at site of ductus arterious – Enlarged aortic knob
• Men > women – Rib notching
• EKG
– If patient is a woman, think Turner s syndrome
– RVH in neonate and LVH in older children
• Physical examination
• Echo
– Weak or absent femoral pulses – Aortic obstruction
– Femoral pulse delayed when compared to radial pulse • Treatment
– Systolic pressure higher in UEs (diastolic pressure the – Prostaglandin E1
same) – Balloon angioplasty or surgery

Patent Ductus Arteriosus Patent Ductus Arteriosus

• Ductus arteriosus remains open • CXR
– Connects aorta to left pulmonary artery
– Typically closes spontaneously by 4 days of age – Large shunt: cardiomegaly, LAH, LVH
– With drop in pulmonary resistance, left to right shunting of • EKG
blood occurs
– Presence of LVH
• Increased risk in premature infants
• Clinical • Echo
– Symptoms vary with degree of shunting – Presence of PDA
• Small shunts (no symptoms); large shunts (signs of CHF, slow
growth) • Treatment
– Continuous, machine-like murmur in left infraclavicular area – Indomethacin: decrease prostaglandin E1 levels
(radiates to left back)
– Wide pulse pressure • Works best in preterm infants
– Bounding arterial pulses – Surgery
Tetralogy of Fallot Tetralogy of Fallot
• Most common cyanotic congenital heart disease • Clinical
– Degree of cyanosis is based on
– Due to right-to-left shunting and decreased pulmonary degree of obstruction
flow • Other cyanotic disorder is
Transposition of Great
• Four defects Vessels
– Ventricular septal defect – Neonates: cyanosis & agitation
• Physical examination
– Right ventricular outflow obstruction
– RV heave
– Right ventricular hypertrophy – Loud systolic ejection murmur
LSB
– Overriding large ascending aorta • CXR
– Boot-shaped heart
• Due to hypertrophy of right Source: Jason T. Scism
ventricle

Tetralogy of Fallot Ventricular Septal Defects

• Diagnosis • Most common congenital defect
– EKG: right axis deviation, right ventricular hypertrophy • Communication between right and left ventricles
– Echo • May develop pulmonary hypertension
• Thick right ventricular wall • No symptoms until weeks 6–8 of life
• Overriding of the aorta – Due to decreased pulmonary vascular resistance
• VSD • Clinical
• Treatment – Symptoms vary with the size of defect and severity of
– Surgical repair at age 3-12 months pulmonary vascular resistance
• Tachypnea, tachycardia, poor weight gain, trouble feeding
– PGE1 infusion to prevent ductal closure (if cyanotic at
birth)

Ventricular Septal Defects Transposition of Great Arteries

• Physical examination • Aorta arises from the right ventricle and pulmonary
– Harsh pansystolic murmur LLSB, grade 2-4/6; systolic artery arises from the left ventricle
thrill – Have 2 parallel circuits- need open foramen ovale and PDA for
• Louder with smaller defects (diamond-shaped murmur) some mixture of desaturated and oxygenated blood
• Diagnosis • Clinical
– Echo: presence of defect – Cyanosis immediately after birth
– Cath: only way to measure pulmonary vascular – Tachypnea
resistance – Single and loud S 2
• If VSD present have harsh murmur at LLSB
• Treatment
– Small defects (shunts): defer until late childhood since
many will spontaneously close
– Large defects (shunts) require surgery
– Antibiotic prophylaxis (mandatory)
Transposition of Great Arteries
• Diagnosis
– Chest x-ray
• Egg on a string appearance - narrow heart base plus absence of
main segment pulmonary artery
– Echocardiogram
• Treatment
– PGE 1 to keep PDA patent
– Balloon atrial septostomy
– Arterial switch surgery in first 2 weeks
 209

JNC 7 Treatment Algorithm for HTN

Lifestyle Modifications

Not at Goal Blood Pressure (<140/90 mmHg)

(<130/80 mm Hg for those with diabetes, chronic kidney disease, CAD)

Initial Drug Choices

Without Compelling With Compelling

Indications Indications

Stage 1 Hypertension Stage 2 Hypertension Drug(s) for the Compelling

(SBP 140–159 or DBP 90–99 (SBP >160 or DBP >100 mmHg) Indications
mmHg). Thiazide-type 2-drug combination for most Other antihypertensive drugs
diuretics for most. May (usually thiazide-type diuretic and (diuretics, ACEI, ARB, BB,
consider ACEI, ARB, BB, ACEI, or ARB, or BB, or CCB) CCB) as needed.
CCB, or combination.
Not at Goal
Blood Pressure
Optimize dosages or add additional drugs
until goal blood pressure is achieved.
Consider consultation with hypertension specialist.

Van Rhee 2e: 8,9 • AAPA 4e: 35-37 P-CAm023

 210

JNC 8 Treatment Algorithm for HTN

Lifestyle Modifications

General Population Diabetes CKD

(No diabetes or CKD) (no CKD) (With or without diabetes

BP Goal BP Goal CKD

Age <60: 140/90 <140/90 (with or without diabetes)
Age 60: <150/90 All Ages

Non-black Black All races

Thiazide, ACE inhibitor, or ARB Thiazide or calcium channel ACE inhibitor or ARB alone or
or calcium channel blocker blocker alone or in in combination with other
alone or in combination combination drug classes

P-CAm023a
 211

Chest Pain
Cardiac Features Pulmonary Features
Myocardial infarction Severe pain, >20 Pulmonary Tachypnea, dyspnea,
minutes duration embolism- infarction pleuritic pain
Aortic stenosis Typical systolic Pulmonary Signs of RV failure
ejection murmur hypertension
Myocarditis Mild, vague pain Pneumothorax Sudden pain, dyspnea
Pericarditis Sharp pain, worse GI Features
lying down, better
sitting up
Dissecting aortic Tearing pain, radiate Hiatal hernia Reflux of food, relief
aneurysm to the back with antacids
MVP Midsystolic click, GERD Acid reflux, relief with
young woman antacids
Musculoskeletal Features Gallbladder disease RUQ pain, tenderness
Costochondritis Pain worse with PUD Epigastric pain, worse
inspiration, pain with 3 hours after eating
chest wall palpitation

Van Rhee 2e: 14 P-CA0e34

 212

Ischemic Heart Disease

Van Rhee 2e: 12 • AAPA 4e: 38 P-CA0k36

 213

P-CA0b61
 214

Pericarditis: EKG
• Diffuse ST
segment
elevation
with upright
T wave
• PR interval
depression
• Low voltage
• A-fib/flutter

Van Rhee 2e: 22-23 • AAPA 4e: 54-55 P-CAu128

 Chest Pain
215

Cardiac Features Pulmonary Features

Myocardial infarction Severe pain, >20 minutes Pulmonary embolism- Tachypnea, dyspnea,
duration infarction pleuritic pain
Aortic stenosis Typical systolic ejection Pulmonary Signs of RV failure
murmur hypertension
Myocarditis Mild, vague pain Pneumothorax Sudden pain, dyspnea

Pericarditis Sharp pain, worse lying GI Features

down, better sitting up

Dissecting aortic Tearing pain, radiate to Hiatal hernia Reflux of food, relief with
aneurysm the back antacids
MVP Midsystolic click, young GERD Acid reflux, relief with
woman antacids
Musculoskeletal Features Gallbladder disease RUQ pain, tenderness

Costochondritis Pain worse with PUD Epigastric pain, worse 3

inspiration, pain with hours after eating
chest wall palpitation
 Acyanotic Congenital Heart Diseases
216

Ventricular Septal Defect Atrial Septal Defects Patent Ductus Arteriosus Pulmonary Stenosis Coarctation of the Aorta
Rate of Congenital 25% ≈10% 5-10% 10% 10%
Disease

Clinical Small- asymptomatic Rarely symptomatic Small- asymptomatic Mild- asymptomatic Poor feeding
Manifestations Large- CHF, fatigue, poor Large- CHF Moderate- exertional Respiratory distress
growth dyspnea, easy Shock
fatigability

Murmur Pansystolic at LLSB Soft, systolic ejection Wide pulse pressure Systolic ejection at Weak and delayed
Fixed, split S2 Continuous machine-like 2nd left intercostal femoral pulses
Left infraclavicular space Systolic ejection click
Radiate over left back Radiates to the back

EKG Small- Normal RAD Small- normal RAD RVH

Large- LAH, LVH RVH Large- LVH, RVH RVH LVH

Chest X-ray Small- normal Cardiomegaly Small- normal Heart size normal Rib notching
Large- cardiomegaly, LVH Right atrial enlargement Large- increase RVH
Prominent pulmonary artery pulmonary vascularity LVH

Treatment 35% close spontaneously If present >3 yo surgery Diuretic, digoxin early Balloon valvuloplasty Prostaglandin E1
Surgery Surgery Surgery Balloon angioplasty
Diuretic, digoxin early Surgery
 Cyanotic Congenital Heart Diseases
217

Tetralogy of Fallot Transposition of the Tricuspid Atresia Hypoplastic Left Heart

Great Arteries Syndrome
Rate of Congenital ≈10% ≈5% ≈2% <1%
Disease (Most common cyanotic)

Clinical Hypoxic “Tet” spells Quiet tachypnea PDA or VSD required Signs of CHF
Manifestations Unconsciousness for survival Weak/absent pulses

Murmur Systolic ejection at 2nd left Single S2 Diastolic murmur at Single, loud S2
intercostal space Pansystolic at LLSB (if VSD mitral valve location No murmur
Radiates to the back present) Single S2 Cool, mottled skin
Single S2

EKG RAD RAD LVH RVH

RVH RVH

Chest X-ray Boot-shaped heart Increased pulmonary Cardiomegaly Cardiomegaly

vascularity Pulmonary edema
Cardiac shadow- egg on a
string

Treatment Oxygen Prostaglandin E1 Surgery Prostaglandin E1

Knee-chest position Balloon atrial septostomy Surgery
α-adrenergic agonist
β-adrenergic antagonists
Surgery
 Cardiac Murmurs
Maneuver Blood Flow Effect Murmur Effect
Inspiration venous flow to right heart right heart sounds
venous flow to left heart left heart sounds
Valsalva venous right and then left heart HOCM, MVP, MS
AS, MR, tricuspid stenosis
Amyl nitrite Venodilation, venous return right heart HOCM, MVP, AS
MR, VSD
Leg elevation AS
HOCM
Squatting venous right heart and afterload and MR, AS, MS
peripheral artery resistance HOCM
Handgrip afterload and peripheral artery resistance MR, AR, MS
AS, HOCM, MVP

Helpful Hints

Four systolic murmurs to think about- MR, VSD, AS, HOCM

Five maneuvers VALSH (Valsalva, Amyl nitrite, Leg raising, Squatting, Handgrip)
Remember the response to the maneuvers for HOCH. VA increase the murmur, LSH decreases
the murmur.
Except for L, S and V all the response of AS are the same as HOCM.
For MR and VSD the response is totally the opposite of HOCM except for squatting amd leg
elevation which have no effect on MR or VSD.

Key:
AR- aortic regurgitation
AS- aortic stenosis
HOCM- hypertrophic obstructive cardiomyopathy
MR- mitral regurgitation
MS- mitral stenosis
MVP- mitral valve prolapse
VSD- ventricular septal defect
V- valsalva
A- amyl nitrate
L- leg raising
S- squatting
H- hand grip

218
 Anti-Arrhythmic Agents
219

Class Mnemonic Mechanism Mnemonic Agents EKG Effect Indications

I Some Sodium channel blockers
IA Intermediate kinetics Double Disopyramide, QRS and QT Atrial fibrillation and flutter
Quarter Quinidine, intervals Ventricular tachycardia
Pounder Procainamide
IB Rapid kinetics Lettuce Lidocaine, QT interval Ventricular tachycardia
Tomato Tocainide,
Mayo Mexiletine,
Pickles Phenytoin
IC Slow kinetics More Moricizine, QRS Atrial fibrillation and flutter
Fries Flecainide, interval Ventricular tachycardia
Please Propafenone AV Nodal reentrant tachycardia
II Block Beta blockers Propranolol heart rate Sinus tachycardia
Esmolol PR interval SA and AV nodal reentrant tachycardia
Timolol
Metoprolol
Atenolol
III Potassium Potassium channel blockers A Amiodarone QT interval Ventricular tachycardia
Big Bretylium Atrial fibrillation and flutter
Dog Dofetilide AV Nodal reentrant tachycardia
Is Ibutilide
Scary Sotalol
IV Channels Calcium channel blockers Verapamil heart rate SA and AV Nodal reentrant tachycardia
Diltiazem PR interval
 Electrical Conduction of the Heart

EKG/Rhythm Basics

Jim Van Rhee, MS, PA-C

Program Director; Associate Professor
Yale School of Medicine, PA-Online
nih.gov

Normal EKG Cycle (Lead II) EKG Basics

• Baseline Heart Rate Calculations Axis Calculations
• Waves Number Large Squares HR Lead I Lead aVF Axis
between QRS Complexes (bpm)
• Intervals
• Segments 5 60 ­ ­ Normal

4 75 ­ ¯ LAD

3 100 ¯ ­ RAD

2 150 ¯ ¯ RAD

IMC, © 2010 DxR Development Group, Inc. All Rights Reserved

Normal Sinus Rhythm (NSR) Sinus Arrhythmia

• Rhythm Regular
Rate: 85 • All components of NSR the same except regularity
• Rate 60 to 100 bpm
• Complete P before every Q; T after QRS • May coincide with respirations
• PR Interval 0.12 to 0.20 s • Considered a normal variant
• QRS < 0.12 s
Sinus Bradycardia Rate: 52
• All components of NSR the same except rate
• Rate <60 bpm
• Etiology: acute MI, carotid massage, vomiting, Valsalva, β-
blocker, Ca++-channel blocker, hypothyroidism, normal
• Treatment - atropine if symptoms, pacemaker if persists
Sick Sinus Syndrome
• Also called sinus node dysfunction
• Is a relatively uncommon syndrome
– Can result in sinus arrest, sinus node exit block, sinus bradycardia
– Also be associated with tachycardias, such as PSVT and atrial
fibrillation
• Tachycardia characterized by a long pause after the tachycardia
• Often caused or worsened by medications
– Digitalis, Ca++ channel blockers, beta blockers, sympatholytic
medications, and anti-arrhythmics
– Other etiologies include sarcoidosis, amyloidosis, Chagas disease
• Symptoms
– Stokes-Adams attacks, dizziness, palpitations, chest pain, SOB
• Diagnosis
– EKG with a variety of results
• Treatment
– Pacemakers for bradycardia and medications for tachycardias

Sinus Tachycardia Premature Ventricular Contraction

Rate: 130

• All components of NSR the same except rate

• PVC – early ventricular contraction
• Rate >100 bpm and <180 bpm
• NSR with wide, bizarre QRS periodically appearing in
• Etiology - response to fever, dehydration, hypotension, the pattern
anxiety, pain
– Other causes include thyrotoxicosis and anemia
• Loss of P wave in PVC

Atrial Flutter Atrial Flutter

• General • Treatment
– Symptoms include: – Cardioversion - if
• Dizziness unstable
• Palpitations – Rate control
• Chest pain • Acute
• Dyspnea – Beta-blockers
– Calcium-channel
• Associated with blockers
– COPD (common) • Chronic • Rapid atrial rate (250-300 beats/min)
– PE – Amiodarone
• Baseline between QRS contains jagged waves
– Thyrotoxicosis – Sotalol
– Quinidine (sawtooth pattern)
– Mitral valve disease – Procainamide
– Alcohol – Ablation of foci
Atrial Fibrillation Atrial Fibrillation
• General • Treatment
– Common sustained – Rate control
arrhythmia in adults • Beta-blockers
– Increased risk with • Calcium-channel
increased age blockers
– Increased risk of – Rhythm control
intra-atrial clot formation • Amiodarone,
flecainide • No defined P waves
• CHADS score • Coarse baseline
– Increased side
– CHF, HTN, Age >75, effects • Irregularly irregular ventricular rhythm
Diabetes, Prior stroke • Cardioversion – R-R interval irregular
• Score 0- aspirin – Atrial rate over 400 beats/minute
– As long as no clots
• Score 1- aspirin or warfarin – Ventricular rate 100–200 beats/minute
– Anticoagulation
• Score ≥2- warfarin
– Catheter ablation

Multifocal Atrial Tachycardia Paroxysmal Supraventricular Tachycardia

(PSVT)
• Reentry AV tachycardia
• Common in the elderly
with underlying heart
• Common in patients with COPD and the elderly disease
• EKG • Symptoms: palpitations,
– Differing PR intervals, rate 100-200 beats/min anxiety
– Presence of multiple-shaped P waves
• Treatment
• At least 3 different P wave forms
– Vagal maneuver
• Treatment
– Drugs
– Treat underlying cause nih.gov

– Calcium-channel blockers • Adenosine (drug of Regular rate 130–220 beats/minute

choice) or verapamil
– Avoid beta blockers because of lung disease etiology Atrial activity typically not noted
• Beta-blockers

Ventricular Tachycardia Ventricular Tachycardia

• Originates from below the bundle of His
• Precipitating causes:
– Electrolyte imbalance
– Acid-base changes
– Hypoxemia
– MI
• Symptoms
– Stable: none with short runs of VT
• QRS complex loses sharp peak and becomes wide
– Unstable: long runs present with syncope, CP, dyspnea
and bizarre in appearance, though somewhat uniform
• Treatment: amiodarone, lidocaine, procainamide if • All other waves absent
unstable
– Cardioversion may be required
Ventricular Tachycardia Ventricular Fibrillation

• Torsades de pointes
• Uncoordinated electrical activity
– Polymorphic VT
– Long QT interval • Disorganized electrical activity
– Etiology: antiarrhythmic drugs (quinidine, procainamide), – Noted in patients with ischemic heart disease & ventricular dysfunction
psychotropic drugs (phenothiazines, TCA, lithium), electrolyte • Treatment: defibrillation
imbalance, subarachnoid hemorrhage
• Life-threatening
– Treatment- lidocaine, phenytoin, correct underlying cause

First-Degree Heart Block Mobitz I / Wenckebach

• Second-degree block (block is usually AV nodal)

• PR interval >0.20 s and constant
• Progressive lengthening of the PR interval until a QRS complex
• Etiology - aging, digitalis, ischemia, inflammation, fails to appear after a P wave
cardiomyopathies • Repetitive
PR Interval: 0.28 seconds • Carotid sinus pressure may increase degree of block
• Atropine may shorten PR interval and increase AV
conduction
• Think acute inferior wall infarction

Mobitz II Third-Degree Heart Block

• Complete absence of conduction of the electrical

• Second-degree heart block (Block is infranodal) impulses through the AV node, Bundle of His, or
• An AV block with failed conduction of a beat with bundle branches
constant PR intervals • Characterized by independent beating of the atria
and ventricles
• Think acute anterior or anteroseptal MI • Etiology: aging, inferior or posterior infarction,
• Atropine and carotid sinus pressure have no effect digitalis, Ankylosing spondylitis
• Treatment - pacemaker
 Asystole Wolff-Parkinson-White Syndrome

• Due to an AV
bypass tract
• Wide QRS >0.12 s
• Short PR interval
<0.12 s
• Presence of delta
waves
• No complexes • Treatment -
cardioversion,
• Cardiac standstill or flat line amiodarone,
sotalol, ablation
• Avoid digoxin,
beta blocker,
and calcium
channel
blockers

Hyper/Hypokalemia Right Bundle Branch Block

Hyperkalemia
• Hyperkalemia
– Peaked T waves • QRS > 0.12 s
– QRS widening with • QRS
marked predominantly
hyperkalemia
positive in V1
• Hypokalemia • rSR or rsR in
– Flattening of T lead V1
waves • Wide S in lead
– Presence of U I and V6
waves
– Prolonged QT
interval with severe
hypokalemia
Source www.nih.gov

Left Bundle Branch Block Right Ventricular Hypertrophy

• QRS >0.12 s • Right axis deviation
• QRS – +90 degrees or greater
predominantly • Tall R wave in lead V1
negative in V 1
or
• Upright QRS
in leads I and • R in V1 plus S in V6 ≥11
V6 • Persistent precordial S
– QRS may waves
be notched
• Repolarization changes
– ST depression and
T inversion in right heart
leads

nih.gov
 Left Ventricular Hypertrophy Infarct Patterns
Affected Area EKG Leads Artery Involved EKG Reciprocal
• Deepest S (in V 1,V 2)
Changes
plus tallest R (in Inferior II, III aVF RCA I, aVL
V 5,V 6) ≥35 Lateral I, aVL, V5, V6 Circumflex V1, V2
– In a patient > age Anterior I, aVL, V1–V4, LCA II, III, aVF
35
Posterior V1, V2 RCA
• R in aVL >13
Circumflex
• Repolarization
changes Apical V3-V6 LAD None
RCA
– ST depression and
T inversion in left Anterolateral I, aVL, V4–V6 LAD II, III, aVF
heart leads Circumflex
www.nih.gov Anteroseptal V1-V3 LAD None

QRS Complex
Wide QRS (≥ 0.12 seconds) Narrow QRS (≤0.12 seconds)

Regular Irregular Regular Irregular

VT AF (rarely) ST AF

SVT PSVT MAT

WPW A. Flutter
 The Dermatologic System
Lecture 1 Eczematous Eruptions
Papulosquamous Diseases

The Dermatologic System Lecture 2

Desquamation

Vesicular Bullae
Acneiform Lesions
Viral Infections
Bacterial Infections
Isaak Yakubov, MS, PA-C Fungal Infections

Lecture 3 Verrucous Lesions

Neoplasms

Lecture 4 Insects/Parasites
Hair And Nails
Other

The Skin

Eczematous Eruptions
Eczema
Dyshidrosis
Lichen Simplex Chronicus

Eczematous Eczematous
• Atopic eczema • Diagnosis
– Probable immune dysregulation
– Positive family history
– Clinical; KOH to rule out fungal; family history
– History of other allergies or • Treatment
asthma
– Clinical – Moisturize with bland emollients and mild cleansers
• Red, scaling patchy rash with – Topical corticosteroids and antipruritics
lichenification, very itchy
– Distribution © Richard Usatine, M.D. Used with permission. – Sedating antihistamines
• Infants/younger kids: scalp, face,
extensor surfaces • Keys to effective treatment
• Older kids: flexural surfaces
– Patient education
• Nummular eczema
– No central clearing, sharply defined – Follow-up
– Coin-shaped plaques, very pruritic
– Itch control
– Dorsal hand, feet, extensor
surfaces

© Richard Usatine, M.D. Used with permission.

Eczematous Contact Dermatitis
• Dyshidrotic eczema • Irritant (80%); allergic (20%)
– Hands/feet
• Presentation
– Difficult to manage
– Papules/vesicles (acute)
– Tense pruritic vesicles, especially
lateral digits – Scaly, lichenified (chronic)
– Cracking/fissuring, erythema, scale • Diagnosis
© Richard Usatine, M.D. Used with permission.
– Associated with stress/metals – Clinical based on history,
– Differential diagnosis © Richard Usatine, M.D. Used with permission. exposure to metals, etc.,
• Tinea, pustular psoriasis, contact distribution, and pattern
dermatitis • Treatment
– Treatment
– Avoidance, bland emollients,
• Superpotent corticosteroids, tar topical or systemic
soaks, oral erythromycin, derm
corticosteroids, sedating
referral
antihistamines © Richard Usatine, M.D. Used with permission.

Perioral Dermatitis Perioral Dermatitis

• Eczema or acne-like perioral rash • Clinical
– Often resembles rosacea; patient may have both – Irregularly grouped,
conditions discrete red
• Women > men; ages 16–45 papulopustules on a
• Cause unknown red base
– Fluorinated-corticosteroid use on face, fluorinated – Perioral, but spare
toothpaste, mint/cinnamon products the vermilion border
• Treatment:
– Antibiotics:
metronidazole and
erythromycin
© Richard Usatine, M.D. Used with permission.

Stasis Dermatitis Seborrheic Dermatitis

• Eczema-like eruption on lower legs, secondary to • Oversecretion of sebaceous material and
PVD hypersensitivity to Pityrosporum ovale
• Mechanism • Dry (dandruff) to inflammatory, scaly plaques
• Distribution
– Venous incompetence > increased hydrostatic pressure and – Scalp, ears, face (nasolabial folds), chest, groin
capillary damage > leaking with extravasation of RBCs into
– Greasy scale: cradle cap
skin
• Clinical
• Diagnosis – Moist papules, transparent to pink-red patches that are
– Clinical (skin changes, varicosities often seen, swelling with macerated
pitting edema) • Treatment
– OTC dandruff shampoo; OTC/Rx ketoconazole shampoo;
• Treatment corticosteroid shampoo; ketoconazole cream; hydrocortisone
– Support stockings, elevation, ankle/calf exercises, weight cream (flares)
loss, topical corticosteroids/bland emollients
Lichen Simplex Chronicus
• Itch-scratch-itch
cycle
• Solitary patch
usually >1cm Papulosquamous
• Lichenification
Lichen Planus
• Scale +/-
• Treatment Pityriasis Rosea
– Avoid itching Psoriasis
– Steroids

© Richard Usatine, M.D. Used with permission.

Lichen Planus Pityriasis Rosea

• Etiology unknown • Etiology unknown
• 5 Ps: purple, planar, polygonal, pruritic, papules – Can mimic secondary
• Clinical syphilis (do an RPR in
sexually active patient)
– 2-10 mm lesions,
flat-topped, violaceous, • Clinical: herald patch
papule with irregular precedes breakout of
angulated border smaller lesions (Christmas
• Diagnosis tree pattern)
– Punch biopsy
– Typical lesion is round or
• Treatment oval following skin lines with
– Corticosteroids (topical light erythema; salmon-
or oral) are mainstay of colored
treatment © Richard Usatine, M.D. Used with permission.

© Richard Usatine, M.D. Used with permission.

Pityriasis Rosea Psoriasis

• Diagnosis • Etiology is unknown
– T-cell mediated Disease
– Usually confined to trunk and proximal extremities
– Genetic susceptibility
– Variable itching
• Various types
– Can last weeks to several months
– Palmar pustular psoriasis
• Treatment – Guttate psoriasis post streptococcal infection
– Topical mid-potency corticosteroids and/or antipruritics – Inverse psoriasis
(if needed) – Erythrodermic psoriasis
– UVB (may hasten resolution) • Primary lesion is the erythematous plaque or papule
with development of silvery, plate-like scale
– Extensor surfaces
Psoriasis
• Treatment
– Topical: corticosteroids,
retinoids, calcipotriene,
tars, salicylic acid, bland
emollients, shampoo for
scalp psoriasis
– Systemic: UV light,
methotrexate
– Biologicals- alefacept,
etanercept, infliximab
– Avoid systemic
corticosteroids
– If extensive disease, refer
Erythema Multiforme (EM)
• Immunologic reaction in skin
to antigen stimulus
– Multiple agents implicated
– Etiologies: medications, HSV or
mycoplasma
• Lesions
– Plaques, blisters, targetoid
• Extensor surface of arms
– Mucous membrane involvement
in severe form of EM → SJS
• Treatment
– Treat the infectious cause;
discontinue responsible med,
antihistamines
Drugs: NSAIDS, Sulfa, Quinolones, ASA,
Allopurinol, Colchicine
Toxic Epidermal Necrolysis
• Severe form of SJS
– >30% epidermal detachment
• Usually high fever; mortality rate 30% due to sepsis,
GI hemorrhage, fluid/electrolyte imbalance
• In SJS/TEN, early diagnosis and discontinuation of
medications is crucial
• Reexposure to causative agent results in a more rapid
& severe reaction than initial episode → medical alert
bracelet
Desquamation
Erythema Multiforme
Stevens-Johnson Syndrome
Toxic Epidermal Necrolysis
Pemphigus Vulgaris
© Richard Usatine, M.D. Used with permission.
Stevens-Johnson Syndrome (SJS)
• Severe form of EM
• Often starts with targetoid lesions
• Mucocutaneous drug-induced or idiopathic reaction
• <10% epidermal detachment
• Painful, tender oral & skin lesions
• Treatment
– Systemic steroids: value controversial; supportive care
(hydration, prevent secondary infection, pain relief)
[viscous lidocaine for oral lesions]
– Mortality rates 0-15%
© Richard Usatine., M.D. Used with permission.
Pemphigus vulgaris
• Autoimmune disease
– Idiopathic
– ACEI occasionally cause it
• Occurs in young
patients (30s-40s)
• Occurs primarily in the
mouth as erosions
– Then bullae on the skin
phil.cdc.gov
– Very painful
• Slightest pressure cause skin to pull off in sheets
• Diagnosis by biopsy
• Treatment systemic glucocorticoids
– Topical steroids are not useful
 The Dermatologic System
Lecture 1 Eczematous Eruptions
Papulosquamous Diseases Vesicular Bullae
Desquamation
Bullous pemphigoid
Lecture 2 Vesicular Bullae
Acneiform Lesions
Viral Infections
Bacterial Infections
Fungal Infections

Lecture 3 Verrucous Lesions

Neoplasms

Lecture 4 Insects/Parasites
Hair And Nails
Other

Bullous Pemphigoid
• Autoimmune attack on basement membrane causing
subepidermal blistering
• The elderly with
predilection for Acneiform Lesions
groin, axillae, and
flexural areas; itching Acne Vulgaris
• Diagnosis Rosacea
– Punch biopsy © Richard Usatine, M.D.

• Treatment Used with permission.

– Topical (if no oral

lesions) or oral
corticosteroids;
methotrexate

© Richard Usatine, M.D.

Used with permission.

Acne Vulgaris Acne Vulgaris

• One of the most common skin disorders • Inflammatory
• Common between ages 10–15 – Consists of papules,
– More common in women, but more severe in men pustules, and
• Lasts 5–10 years nodules/cysts
• Mechanism • Non-inflammatory
– Increased sebum production – Consists of
– Growth of sebaceous glands open (blackheads) and
– Increased Propionibacterium acnes closed (whiteheads)
comedones
Severity Papules/pustules Nodules
Mild Few to several None
Moderate Several to many Few to
several
© Richard Usatine, M.D. Used with permission.
Severe Many and/or Many
extensive
Acne Vulgaris Rosacea
• Treatment • Adult acne
– Comedones • Diagnosis
• Benzoyl peroxide
– No comedones; blushing
• Retinoids (Tretinoin)
history
– Papules/pustules
• Above plus antibiotics – Erythematous/ telangiectases
– Nodules/cysts • Treatment © Richard Usatine, M.D. Used with. permission

• Isotretinoin (Accutane) – Avoid triggers: hot beverages,

– Teratogenic, weather changes, spicy food
elevated lipids
• Steroids: triamcinolone
– Topical antibiotics:
or prednisone metronidazole, sulfacetamide,
– Hormonal therapy clindamycin
• BCP, spironolactone • Can progress to rhinophyma
© Richard Usatine, M.D. Used with permission. © Richard Usatine, M.D. Used with. permission

Warts/Condyloma Acuminatum
• Common, flat, plantar, digitate,
genital, or anal
• Etiology: HPV
Viral Infections • Diagnosis
– Pale white to pink, rough,
Warts/Condyloma barely raised papules

Molluscum Contagiosum – Smooth, velvety, and moist

• Treatment
Herpes Simplex
– Podofilox
Herpes Zoster – Liquid nitrogen
© Richard Usatine, M.D. Used with permission.

Viral Exanthems – Imiquimod (FDA-approved

for genital warts)

Molluscum Contagiosum HSV/HZV

• Poxvirus • Vesicles grouped on an
• Spread via skin-to-skin erythematous base
contact • Dermatomal pattern
• Clinical – HSV 1: >80% above waist
– Pearly umbilicated
– HSV 2: >80% below waist
papules (1-5 mm)
– Most common on face, – HZV: unilateral
neck, axillae, thighs • Diagnosis
– May itch and vary in – Clinical appearance
number – Confirmed with Tzanck or
• Increase in number with
immunocompromise viral culture © Richard Usatine, M.D. Used with permission.

patients • Treatment (HZV)

• Treatment
© Richard Usatine, M.D. Used with permission.

– Acyclovir, valacyclovir,
– May resolve spontaneously famciclovir
– Cryosurgery, curettage
Erythema Infectiosum (Fifth Disease) Rubeola (Measles)
• Most common under age 10 • Transmitted by infected droplets
• Due to parvovirus B19 – Very contagious

– Spread by respiratory droplets • Incubation period 10–12 days

• Malaise, headache, and pruritus • Prodrome
– Fever (40–41 C), coryza, cough, conjunctivitis, photophobia
– Little or no fever
• Rash: fiery red slapped cheek , circumoral pallor • Rash
and a subsequent lacy, maculopapular truncal rash © Richard Usatine, M.D. Used with permission. – Brick-red, irregular maculopapular rash
– No rash on palms or soles – 2–4 days after prodrome

• Complications: Miscarriage, aplastic crisis – Head to trunk to extremities

• Fever concurrent with rash
• Treatment: Supportive, NSAIDS

© Richard Usatine, M.D. Used with permission.

Rubeola Hand-foot-and-mouth disease

• PE • MC in children under the age of 5
– Koplik s spots (buccal mucosa): white or blue gray • Fecal-oral transmission
lesions on a red base opposite upper molar – Coxsackie virus
• Treatment • 3 days after exposure
– Primary immunization after – Low-grade fever with runny nose, sore throat, and decreased
age 15 months; second dose appetite
at age 4–6 • Vesicular lesions with red halos in mouth
– Isolate for 1 week after rash – 1 day later develop maculopapular rash on palms, soles, and
• Complications extremities

– Secondary bacterial infection (OM) • Treatment

– Encephalitis – Supportive therapy
– Lidocaine

© Richard Usatine, M.D. Used with permission

Impetigo
• Superficial bacterial
infection of epidermis
– Usually S. aureus

Bacterial Infections • Rare Group A strep

– Transmitted via skin-to-skin
Impetigo contact

Cellulitis • Clinical
– Honey-colored crusting,
Erysipelas inflammation; sometimes
vesicular
• Treatment © Richard Usatine, M.D. Used with permission.

– Mupirocin 2% tid x 7–10

days
– Dicloxacillin, Macrolide (if
PCN allergic)
Cellulitis Cellulitis
• Deep dermis and • Treatment
subcutaneous tissue – Oral antibiotics with
infection staphylococcus or
• Risk factors:
streptococcus coverage
– Diabetes
– Cirrhosis, renal failure
– Dicloxacillin,
amoxicillin/clavulanate,
– Malnutrition
oxacillin, first-generation
– Cancer
• Typically Staphylococcus
cephalosporins
or Group A Streptococcus
• Diagnosis
© Richard Usatine, M.D. Used with permission.

– Clinical: fever, chills,

malaise, pain
– Skin: erythema, edema,
typically no crusting,
weeping, or drainage

Erysipelas Folliculitis Folliculitis

• Infection of the epidermis and dermis
• Streptococcus pyogenes infection (group A beta strep)
– With facial cellulitis in infants/toddlers, consider H.
influenzae
• Diagnosis
– Malaise, fever, chills, nausea, adenopathy
– Elevated, sharply demarcated borders
• Treatment
– Penicillin, azithromycin, 1st generation cephalosporin
• Inflammation of follicular unit
– Hair follicle at the center of each lesion Furuncle
• May be due to persistent trauma or bacterial
– S. aureus or Pseudomonas (hot tub) Carbuncle
• Diagnosis
– Dome-shaped pustules with erythematous halos
– May be tender and itch
• Treatment: topical or oral antibiotics
– Mupirocin (Bactroban)
– Oral: oxacillin, dicloxacillin, and cefuroxime
– Ciprofloxacin (for hot tub folliculitis)

Tinea Infections
• Types
– T. capitis: scalp – T. pedis: feet
– T. faciei: face
(athlete s foot)
– T. corporis: body
– T. cruris: groin (jock itch)
Fungal Infections (ringworm)
– T. manuum: palms – T. unguium: nails
• Diagnosis
Tinea Infection – Clinical, but KOH or culture to confirm
– Many small, circular, white, scaling
Candida papules with raised border
• Treatment
– Antifungals - ketoconazole, clotrimazole
– Oral agents: griseofulvin DOC for capitis
• Griseofulvin not effective for nail
disease
– Terbinafine (Lamisil) or Itraconazole
(Sporanox) for hair and nail infections © Richard Usatine, M.D. Used with permission.
Tinea Versicolor Candida
• Scaly patches & plaques of • Risk factors
various colors – Moist areas, antibiotics/corticosteroid use, DM, HIV, poor
• Fine scale mostly truncal hygiene
– Due to Malassezia furfur – ~ 80% of diaper dermatitis
– Usually the organism in chronic paronychia
• Diagnosis
– Clinical; KOH to confirm © Richard Usatine, M.D. Used with permission. • Diagnosis
(short hyphae & spores) – Clinical; beefy red with satellite papules/pustules; KOH
• Treatment • Treatment
– Various regimens of – Topical nystatin or azoles
selenium sulfide
– Oral fluconazole or ketoconazole (widespread or recalcitrant
– Oral itraconazole or infection)
fluconazole – Dry environment and repair skin barrier

© Richard Usatine, M.D. Used with permission.

The Dermatologic System

Lecture 1 Eczematous Eruptions
Papulosquamous Diseases Verrucous Lesions
Desquamation
Actinic keratosis
Lecture 2 Vesicular Bullae
Acneiform Lesions Seborrheic keratosis
Viral Infections
Bacterial Infections
Fungal Infections

Lecture 3 Verrucous Lesions

Neoplasms

Lecture 4 Insects/Parasites
Hair And Nails
Other

Actinic Keratosis Seborrheic Keratosis

• Noted on chronic sun-exposed • Benign, epidermal neoplasm
areas • Usually noted after age 30
• Physical exam
– Rough, sandpapery patch • Diagnosis
of scaly papules to – 0.2–0.3 cm in diameter, flat
hypertrophic crusted lesions; or raised, smooth or velvety
pigmented variety – Stuck-on appearance
© Richard Usatine, M.D.,Used with permission.
• Diagnosis – Noted on face, shoulders,
– If lesion is thick or recurrent, chest, and back
shave biopsy to rule out SCC – Can resemble malignant © Richard Usatine, M.D. Used with permission.

• Treatment melanoma
– Liquid nitrogen
– Topical 5-FU • Treatment
– Regular follow-up – Liquid nitrogen, curettage,
– Sun protection & avoidance shave removal

© Richard Usatine, M.D. Used with permission.

© Richard Usatine, M.D. Used with permission.

 Basal Cell Carcinoma
• Most common skin cancer
– Common after age 40
• Risk factors
Neoplasms – UV exposure, ionizing
radiation
Basal Cell Carcinoma
• Physical exam
Squamous Cell Carcinoma – Common on face, scalp,
Melanoma ears, and neck (90%)
– Pearly-white, translucent,
Kaposi sarcoma rolled border
– Can ulcerate and bleed
– Variety of colors
© Richard Usatine, M.D. Used with permission

Basal Cell Carcinoma Squamous Cell Carcinoma

• Diagnosis • Second most common
– Shave or punch biopsy skin cancer
• Treatment • Chronic sun exposure,
– Surgical removal arsenic, radiation, HPV
– 5-FU • Physical exam:
• Follow-up – Most common on lips,
– Frequent clinician skin hands, neck, head
exam – Red, scaly papule or plaque
– Self skin exam every – Nodular (lips)
month
© Richard Usatine, M.D. Used with permission.
– Hyperkeratotic
– Sun protection/avoidance
– Localized eczematous
area that does not itch

© Richard Usatine, M.D. Used with permission.

Squamous Cell Carcinoma Melanoma

• Diagnosis • Rates increasing faster than any
– Clinical other cancer
– Skin biopsy to confirm – Most common cancer in women
before treatment ages 25-30
• Treatment • Know ABCDs but remember E
– Wide local excision (evolution)
• MOHS if very large or in
• Increased risk
cosmetically sensitive
areas – History severe blistering sunburns
– Radiation therapy – Intermittent intense sun exposure
• Follow-up – Fair skin
– Frequent clinical skin © Richard Usatine, M.D. Used with permission..
exam – Family history © Richard Usatine, M.D. Used with permission.

– Sun protection/avoidance – Dysplastic nevus syndrome

Melanoma Kaposi Sarcoma
• Diagnosis • Tumor cause by Human herpesvirus 8.
– Clinical – Transmitted through salvia
• Itching, tenderness • Skin lesions that are nodules/papules that are red,
• Bleeding, ulceration purple, brown, or black.
– Patient history
– May also be found in the mouth, GI tract, and respiratory tract
– Biopsy: excisional or punch
• Is an AIDS defining illness
• Treatment: excision with
• Diagnosis
adequate margins,
– Biopsy (presence of spindle cells) and physical examination
interferon reduces © Richard Usatine, M.D. Used with permission.
• Treatment
recurrence – Is not curable but lesions will shrink with antiretroviral therapy
• Follow-up – Alpha interferon
– Depends on size and stage of
lesion

The Dermatologic System

Lecture 1 Eczematous Eruptions
Papulosquamous Diseases Insects/Parasites
Desquamation
Lice
Lecture 2 Vesicular Bullae
Acneiform Lesions Scabies
Viral Infections
Bacterial Infections Spider Bites
Fungal Infections

Lecture 3 Verrucous Lesions

Neoplasms

Lecture 4 Insects/Parasites
Hair And Nails
Other

Lice Lice
• Head, body, & pubic lice • Treatment
– Close personal contact, contact with personal articles – Permethrin (Nix)
– Obligate human parasite; cannot survive longer than 10 days – Lindane (Kwell):
(adult) to 3 wks (eggs) without host neuro toxic
– Life cycle from egg to egg approximately 1 month; eggs
– Pyrethrins (RID)
incubate and hatch 8-10 days, thus need to retreat
– Other treatment:
• Diagnosis
• Ovide (Malathion)-
– Clinical: requires close, not cursory, inspection of individual flammable
hairs
• TMP/SMX bid x 3 d;
– Microscopic exam; crawling sensation repeat in 7-10 d
– Nit cemented to hair shaft, unlike hair casts © Richard Usatine. M.D. Used with permission.

– Blue-gray macules (pubic)

Scabies Scabies
• Due to Sarcoptes scabei • Diagnosis
• Consider with any – Often clinical, but do scabies prep: scrape multiple
generalized itchy rash lesions, especially burrows
• Exam • Treatment
– Web spaces, flexor surfaces © Richard Usatine. M.D. Used with permission.
– Permethrin 5%
or wrist, nipples, anterior – Ivermectin (resistant cases)
axillary, genitals – 6–10% sulfur in petrolatum (infants, pregnancy)
– Itchy papules/nodules on – Treat close contacts; launder bedding, clothes, etc.
scrotum are scabies until – Avoid lindane (Kwell) due to toxicity
proven otherwise • Seizures, headache
– Infants (palms & soles)
– Worse in
immunocompromised

© Richard Usatine, M.D. Used with permission.

Spider Bites: Black Widow Spider Bites: Brown Recluse

• Women: red hourglass marking • Small; violin marking on back; lives in dark, undisturbed
– Webs close to ground in sheltered places areas
• Immediate sharp pain to painless; look for small red fang • Symptoms
marks – Bite: minor stinging or burning
• Symptoms • Most bites are mild w/ minimal swelling/redness
– Initial swelling → generalized abdominal, back & leg pain → – Fatty areas show more reactions & may become necrotic within
15 minutes to 2 hours after bite 4 hours
– Dizziness, headache • Blue-gray, cyanotic pustule or vesicle/bulla
– Sweating – Severe pain within 4 hours
– Nausea, vomiting • Tissue damage can be severe & take months to heal with scarring
– Complications
• Symptoms gradually decrease over several days; possible
residual symptoms for weeks to months • Hemolytic anemia, DIC, renal failure, death

• Treatment: antivenin, calcium gluconate (muscle relaxant), • Treatment

analgesics – Ice, elevation, avoid strenuous activity, antibiotics, ASA

Alopecia Areata
• Autoimmune attack on hair
matrix is probable; acute
onset
Hair/Nails • Diagnosis
– No scarring; well
Alopecia Areata circumscribed areas;
Androgenetic Alopecia exclamation point hairs ;
check nails for pitting
Onychomycosis • Treatment: corticosteroids;
minoxidil
Paronychia © Richard Usatine,M.D. Used with permission.

• Alopecia totalis & universalis

– Course variable; relapses
Telogen effluvium- loss of hair in response to stress
Androgenetic Alopecia Onychomycosis
• Typically starts after puberty and ends by age 40 • Fungal infection of nail plate
• Patterns in men • Clinical
– Frontotemporal (does not respond to topical or finasteride) – Distal plate is yellow or
white
– Crown (does respond to treatment, response variable): wigs,
hair transplantation
• Diagnosis
– KOH prep
• Finasteride side effects
• Treatment
– Sexual dysfunction
– Lamisil 6 wks (fingernails),
– PSA-reading 12 wks (toenails)
– Finasteride should not be handled by women – Sporanox
– Diflucan
• Treatment: minoxidil, hair weaves, wigs, transplants © Richard Usatine, M.D. Used with permission.

Other
Paronychia Cherry Angioma
• Acute Telangiectasia
– Rapid onset, bright red,
swelling, pus; usual cause
Lacerations
is trauma or manipulation of Burns
cuticle; usually S. aureus
– Treatment Hidradenitis Suppurative
• Quick incision to drain abscess
• Topical or oral antibiotics Pilonidal Disease
• Chronic Acanthosis Nigricans
– Tenderness, mild swelling &
erythema, eczematous Melasma
changes, nail dystrophy, Vitiligo
absence of cuticle; usually
Candida, but multiple © Richard Usatine. M.D. Used with permission. Urticaria
organisms possible
• Treatment topical or oral Vasculitis
antibiotics
Decubitus Ulcers/Leg Ulcers
– Keep area dry
Lipomas
Epithelial Inclusion Cysts

Cherry Angioma Telangiectasia

• Dilated blood vessel usually small in size
• May be seen on any portion of the body but most
commonly on lower extremities or face
• Diagnosed clinically
• Treatment:
– Usually none needed
– May do sclerotherapy for cosmetic appearance
Lacerations Burns: Classification
• Wound that may involve opening of epidermis, dermis, • First-degree
subcutaneous tissue and deep fascia – Minor epithelial damage of epidermis
• MC due to injury – Redness, tenderness and pain are present, no blistering
• Wound must be assessed: – Most common causes are flash burns and sunburn
• Mechanism, age, foreign body, tetanus status, and • Second-degree
immunocompromised – Superficial partial-thickness burn
• Treatment: • Involves epidermis and superficial dermis layers
– Closure with sutures indicated only if wound closure will • Skin appears pink, moist, and soft, and thin-walled blisters are
prevent excess scarring present, very tender
– Wound irrigation before closure – Deep partial-thickness burn
– Antibiotics if immunocompromised • Involves epidermis and extends into the lower dermis layer
– Tetanus update • Skin appears red and blanched white with thick-walled blisters

Burns: Classification Burns

• Third-degree • Rule of nines
– Full-thickness burn that destroys epidermis and dermis – Adults BSA
• 9% head and neck
– Skin is white or leathery with underlying clotted vessels and is
• 9% each upper extremity
numb
• 18% anterior portion of trunk
– Skin grafting needed unless burn is small (<1 cm in diameter) • 18% posterior portion of trunk
– Caused by immersion scalds, flame burns, chemical and high- • 18% each lower extremity
voltage electrical injuries • 1% to perineum and genitalia
• Fourth-degree – Children BSA
• 18% head and neck
– Full-thickness destruction of skin, subcutaneous tissue, fascia, • 9% each upper extremity
muscle, bone, and other structures • 18% anterior portion of trunk
– Treatment requires debridement and reconstruction of tissues • 18% posterior portion of trunk
– Due to prolonged exposure to causes of third-degree burns • 13% each lower extremity
• 1% to perineum and genitalia
nih.gov

Burns: Treatment Burns: Treatment

• Pre-hospital care • Hospital care
– Fluid resuscitation
– Evaluate for signs of inhalation injury
• Parkland formula for fluid resuscitation
• Includes dyspnea, burns on mouth and nose, singed nasal
– Uses lactated ringers
hairs, sooty sputum, and cough
– Total volume given is 4 mL/kg/% body surface area burned
• Treat with humidified oxygen, non-rebreathing mask at
10-12 L/min in first 24 hrs (half is given in first 8 hrs; rest given over
next 16 hrs)
» Percent body surface area burned includes only
second- and third-degree burns
– Pain management
• Requirement for pain meds is inversely related to depth of
burn injury
– Full thickness burns are painless, due to sensory nerve
damage
• Morphine medication of choice
Hidradenitis Suppurative Pilonidal Disease
• Inflammatory disorder of the apocrine glands • Epithelial tissues trapped in the natal cleft
• Women > men 3:1; noted after puberty – Caused by infection of hair follicle
• Predisposing factors:
– Obesity
• Increased incidence in young adults
– Acne history – Men > women
– Apocrine gland occlusion
– Patients with hirsutism predisposed to disease, obese
• Diagnosis
– Double open-comedones pathognomonic • Clinical
– Boil-like lesions, scarring – Pain in area
• Treatment:
– Drainage
– Weight loss, avoid friction, antibacterial cleansers, antibiotics
(clindamycin), corticosteroids (flares), surgery

Pilonidal Disease Acanthosis Nigricans

• Exam • Causes
– Hereditary; obesity; endocrine disorders
– Multiple midline sinuses (diabetes); meds (OCPs, nicotinic acid)
– Abscess, tenderness • Localized hyperpigmentation
– Thick, velvety plaques: neck, axillae,
• Treatment inframammary folds, inner thighs/inguinal
– Good hygiene • Diagnosis: clinical
© Richard Usatine, M.D. Used with permission.
• Treatment
– Surgery: excision of sinus
– 12% lactic acid lotion/cream; check blood
• Complications sugar & insulin levels periodically; weight
loss; treat assoc disorders
– Abscess formation
• Sudden onset and/or in non-obese patient
suspicious for internal malignancy
(lymphoma, adenocarcinoma)

© Richard Usatine, M.D. Used with permission.

Melasma Vitiligo
• Acquired brown • Autoimmune attack on
pigmentation of the face melanocytes
and neck • Wood s lamp exam will
– Mask of pregnancy accentuate hypopigmentation
– Usually women • If no accentuation, probably
pityriasis alba or post-
• Increased melanin inflammatory
production by melanocytes hypopigmentation
– From extensive sun • Treatment
exposure – Topical corticosteroids;
• Treatment phototherapy
© Richard Usatine, M.D. Used with permission.
– Discontinue meds or end • Best chance for
of pregnancy repigmentation is in hair-
– Sun protection/avoidance bearing areas
© Richard Usatine, M.D. Used with permission.
Urticaria (Hives) Vasculitis
• Hypersensitivity reaction mediated by IgE & mast cells • Palpable purpura
• Individual lesions last <24 hours • Biopsy mandatory
– If >24 hrs, biopsy is mandatory to rule out vasculitis,
– Punch biopsy
connective tissue disease, drug eruption
• Acute: less than 6 wks; – Idiopathic >50%

• Chronic: greater than 6 wks – Lower legs most common area

– Chronic: 90% of the time, cause not found • Diagnosis
– Leading causes: meds, infection, foods – Palpable, non-blanching lesions confirmed by biopsy
• Treatment
– H1 blockers (start w/ non-sedating); add another as
needed; H2 blockers, tricyclic antidepressants (doxepin)

Vasculitis Drug Eruptions

• Treatment • Always consider for any generalized rash
– Rule out infection or systemic disease before treating • Usually morbilliform; urticarial, sudden, symmetric,
with oral corticosteroids bright red
– Search for underlying cause • Occur within 1-4 weeks
– ROS to rule out systemic involvement of vasculitis • Differential diagnosis
– Labs: UA, stool guaiac, CBC/diff, ANA, SR/CR, SPEP,
– Viral exanthem, contact dermatitis
RF, cryoglobulins, hepatitis panel, CXR
• Clinical
– Underlying cause if one is found; d/c med drug reaction is
suspected – Drug history crucial; may present with fever
• Dapsone, colchicine, immunosuppressants (chronic • Treatment
cutaneous vasculitis) – Discontinue medication; oral antihistamines; antipruritics;
topical or oral corticosteroids

Drug eruptions - Common Drugs Decubitus Ulcers

• Allopurinol • The elderly, bedridden
• Beta-lactam antibiotics • External compression on skin leads to ischemic tissue damage &
necrosis over bony prominences
• Sulfa medications
• Risk of bacterial infection & osteomyelitis/septicemia
• Anti-convulsants • Diagnosis
• ACE inhibitors – Always consider biopsy of any recalcitrant ulcer to rule out SCC
• NSAIDS • Treatment
– Constant repositioning
• Oral hypoglycemic agents
– Air mattress
• Thiazide – Keep clean
– Vit C/zinc supplements
– Topical abx
– Duoderm pads
– Surgical management
Lipomas Epithelial Inclusion Cyst
• Subcutaneous tumors of adipose tissue • Benign cyst found on the skin
– Refers to the implantation of epidermal elements into the
• Clinical
dermis
– Located on trunk, neck, and proximal limbs – Also called epidermoid cyst
– Soft, symmetric, and easily movable • Result from trauma, surgery, body piercing
– Not malignant but malignant tumors can arise from a cyst
– May be single or multiple
• May be asymptomatic or painful with touch
• Diagnosis
• Diagnosis
– Clinical findings – By microscopic evaluation after biopsy
• Treatment • Treatment
– None or surgical removal – Excision

© James Van Rhee.

Topical Steroids Topical Steroids

• Weak Steroids • Side Effects
– Used on thin-skinned and sensitive areas – Diabetes mellitus
• Face, eyelids, diaper area, perianal, intertrigo of groin and body – Osteoporosis
folds – Skin atrophy
• Moderate Steroids – Perioral dermatitis
– Use in wider non-occluded parts of the body- trunk, arms, and – Increase intra-ocular pressure
legs
• Groups
– Used for atopic dermatitis, nummular eczema, severe
dermatitis – See handout

• Strong Steroids
– Use in limited skin areas to minimize systemic side effects, use
on palms, soles, and limbs
– Used for psoriasis, lichen planus, discoid lupus, lichen simplex
chronicus, severe poison ivy
 The Endocrine System
Lecture 1 Endocrine Review

The Endocrine System Lecture 2 Diseases of the Parathyroid Glands

Diseases of the Thyroid Gland

Lecture 3 Diseases of the Adrenal Glands

Diseases of the Pituitary Gland

Stephanie Neary, MPA, MMS, PA-C Lecture 4 Diabetes Mellitus

Course Director, Preventative Medicine Lipid Disorders

Yale School of Medicine, PA-Online

Endocrine Review Hypothalamic Function

• If you think excess hormone, order a suppression • Releasing Factors
test. – GnRH (gonadotropin-releasing hormone)
• If you think decrease hormone, order a stimulation • FSH (follicle-stimulating hormone)
test. • LH (luteinizing hormone)

• Primary disease – TRH (thyrotropin-releasing hormone)

– Malfunction of the target organ • TSH (thyroid-stimulating hormone)
– GHRH (growth hormone-releasing hormone)
• Secondary disease
• GH (growth hormone)
– Malfunction of hypothalamus or pituitary gland
– CRH (corticotropin-releasing hormone)
• ACTH (adrenocorticotropic hormone)

The Pituitary Gland Anterior Pituitary Function

• TSH
– stimulates synthesis and secretion of thyroid hormones;
inhibited by T3/T4
• PRL
– prepares women breast for breast feeding; inhibited by
dopamine

• FSH
– Women: stimulates growth of ovarian follicle and ovulation
– Men: stimulates sperm production
– Inhibited by inhibin
Anterior Pituitary Function Posterior Pituitary Function
• LH • ADH
– Women: development of corpus luteum; release of oocyte;
– increases water reabsorption by the kidney
production of estrogen and progesterone
– Men: secretion of testosterone; development of interstitial • Oxytocin
tissue of testes
– stimulates contraction of pregnant uterus and milk ejection from
• GH
breasts after childbirth
– Stimulates bone and muscle growth; promotes protein
synthesis and fat metabolism; decreases carbohydrate
metabolism
– Inhibited by somatostatin
• ACTH
– Synthesis and secretion of adrenal cortical hormones

– Inhibited by cortisol

Feedback
Loops
The Endocrine System
Lecture 1 Endocrine Review
+ Lecture 2 Diseases of the Parathyroid Glands
Diseases of the Thyroid Gland

Lecture 3 Diseases of the Adrenal Glands

Diseases of the Pituitary Gland
– Lecture 4 Diabetes Mellitus
Lipid Disorders
+
+
nih.gov

Hyperparathyroidism
• Excess secretion of PTH
– ↑ absorption of calcium from bones, kidneys, and GI
systems
Diseases of the Parathyroid Glands • Primary
– Middle-aged to older adults, women > men
Diseases of the Thyroid Gland – Etiology: hyperfunctioning benign parathyroid adenoma
(80–85%); multiple endocrine neoplasia (MEN) 1 and 2a
Hyperparathyroidism • Secondary
Hypoparathyroidism – Due to chronic renal MEN 1 MEN 2a MEN 2b
disease Parathyroid Parathyroid Marfanoid
Hyperthyroidism – Metastatic bone body habitus
disease Pituitary Pheo Pheo
Hypothyroidism – Osteomalacia Pancreas Thyroid Thyroid
– Multiple myeloma
Thyroid cancer
Hyperparathyroidism Hyperparathyroidism
• Clinical • Labs
– Symptoms vary with calcium level – ↑ serum calcium (>10.5), ↑ PTH, ↓ serum phosphate
(<2.5), ↓ urine calcium, and ↑ urine phosphate
– Asymptomatic to anorexia, vomiting, nausea, – ↑ phosphate in secondary causes due to renal disease
constipation, fatigue, weakness, confusion – ↑ PTH (essential for diagnosis)
– Polyuria, polydipsia, bone pain, kidney stones • X-ray
• Work-up – Demineralization
– Cysts
– Must rule out other causes of hypercalcemia
• Malignancy (paraneoplastic syndrome)
• Multiple myeloma
• Sarcoidosis

Hyperparathyroidism Hypoparathyroidism
• Treatment • Etiologies
– Surgical removal of gland – Follows parathyroid or thyroid surgery
– Medical treatment of hypercalcemia – Autoimmune, congenital
– Complications • Clinical
• Pathologic fractures – Acute: circumoral tingling, tetany,
muscle cramps, irritability
• UTI
• Renal failure
– Chronic: lethargy, personality changes,
blurry vision, mental retardation
• Remember: Bones, stones, abdominal groans, psychic – Exam
moans with fatigue overtones • Positive Chvostek s sign (facial muscle
spasm)
• Trousseau s test (carpal spasm) nih.gov

• Hyperactive DTRs

Hypoparathyroidism Thyroid Disease

• Primary hyperthyroidism
– Thyroiditis
• Labs – Grave s disease
– ↓ calcium
– ↓ PTH • Primary hypothyroidism
nih.gov
– ↓ magnesium – Thyroiditis
– ↑ phosphate – Hashimoto s
– Normal renal function
• Secondary
– EKG: prolonged QT interval, T wave changes
• Treatment – Very rare
– Maintenance therapy: calcium, vitamin D – Pituitary dysfunction
• Monitor serum calcium levels
– Tetany: IV calcium gluconate
Thyroid Labs Classification of Thyroid Dysfunction
• Hypothyroidism TSH Level Thyroid Hormone
– ↑ TSH, ↓ T4 Level
• Hyperthyroidism Overt Low or Elevated FT4 or
– ↓ TSH, ↑ T4 hyperthyroidism undetectable FT3
• Other Subclinical Low or Normal FT4 or FT3
– T3 (will be ↑ in pregnant patients or patients on BCP) hyperthyroidism undetectable
– TSH most sensitive test Overt >5 mIU/L Low FT4
Hypothyroidism
Subclinical >5 mIU/L Normal FT4
hypothyroidism

Hyperthyroidism: Causes Hyperthyroidism: PE Findings

• Graves Disease (90% of cases) Exophthalmos Pretibial Myxedema
– Women > men, ages 30–60
– Autoimmune disease (may have positive ANA), familial
tendency
• Increased incidence of other autoimmune diseases (PA, DM)
– Exam: exophthalmos, pretibial myxedema, goiter (with a bruit),
lid lag
– Labs: ↑ T4, ↓ TSH
– Positive thyroid-stimulating immunoglobin (TSI)
• Toxic nodular goiter
– Elderly, no eye or skin changes
• Thyroiditis (more later)
• Drugs
– Amiodarone (hypothyroidism more common)

© Richard Usatine, M.D. Used with permission. © Richard Usatine, M.D. Used with permission.

Hyperthyroidism: Signs and Symptoms Hyperthyroidism

• Appetite change • Nervousness • Treatment
• Exertional SOB • Palpitations – Antithyroid drugs (methimazole, propylthiouracil)
• Diarrhea • Sleep disturbances • Inhibit hormone synthesis
• Fatigue • Sweating • Watch for low WBC with treatment

• Headache • Tremor • Propylthiouracil preferred in pregnancy

• Heat intolerance • Weakness – Radioactive iodine

• Hyperactivity • Weight loss • Decreases thyroid activity
– Monitor for hypothyroidism
• Irritability
• Avoid in pregnancy
• Menstrual disturbances – Beta blockers (propranolol)
• Relief of symptoms (tachycardia, tremor, diaphoresis,
anxiety, and palpitations)
Thyrotoxic Crisis (Thyroid Storm) Thyrotoxic Crisis: Treatment
• Life-threatening • Treat underlying cause
• Clinical • Thiourea drug - stop 1-2 weeks before radioactive
iodine
– High fever, tachycardia, vomiting, diarrhea, dehydration,
delirium, congestive heart failure – Propylthiouracil
• Iodide (Lugol s solution) - inhibit hormone release
• Mortality is high
• Propranolol
• Precipitated by stress, infection, surgery, or trauma
– Avoid in heart failure
• Labs • Hydrocortisone - inhibit hormone release, impair
– ↑ Free T4 and ↓TSH hormone production
• Aspirin
– Avoid due to displacing T4 and ↑ T4 level
• Radioactive iodide (delay until patient euthyroid)

Hypothyroidism Hypothyroidism
• Etiologies • Arthralgias • Fatigue
– Autoimmune thyroiditis (Hashimoto s) • Cold intolerance • Lethargy
• Most common cause of hypothyroidism • Constipation • Menstrual disturbances
• Women > men, middle aged • Decreased appetite • Muscle cramps
• Painless goiter • Decreased memory • Paresthesias
• Positive thyroid peroxidase/antimicrosomal/
• Decreased perspiration • Sleepiness
antithyroglobulin antibodies • Depression • Weight gain
– Post-ablative hypothyroidism • Dry skin
– Drug-induced: lithium, sulfonamides, amiodarone
– Iodine deficiency

Hypothyroidism Thyroiditis
• Physical Examination • Subacute
– Dry, coarse skin – Most common in women- 4th - 5th decade
– Thinning lateral half of eyebrows – Question viral infection as etiology
– Slow, prolonged relaxation phase of DTRs
– Bradycardia • Suppurative (acute)
– Thin, brittle nails – Rare, caused by pyogenic bacteria
– Thinning hair
• Treatment
– Thyroid replacement: synthroid
• Start low dose with the elderly or patients with CAD
– Monitor TSH level: check every 6 weeks until stable
Thyroiditis: Clinical Thyroiditis: Treatment
• Subacute • Subacute
– Acute, painful glandular enlargement with dysphagia
– Treat with aspirin for pain and inflammation
– Gland is woody, hard, and tender
– Beta blockers for thyroid symptoms
• Suppurative
– Very painful, tender, red asymmetrical swelling of the • Suppurative thyroiditis
thyroid gland
– Antibiotics and surgical drainage

Thyroid Cancer
• Present with painless single, hard, mass
– History of RT to the neck (papillary or follicular) The Endocrine System
– Link to MEN IIa and IIb (medullary) Lecture 1 Endocrine Review
• Thyroid function usually normal Lecture 2 Diseases of the Parathyroid Glands
• Women 2–3 times more common than men Diseases of the Thyroid Gland

• Diagnosis Lecture 3 Diseases of the Adrenal Glands

– Thyroid scan: cold nodule (non-functioning nodules) Diseases of the Pituitary Gland

– FNA is diagnostic Lecture 4 Diabetes Mellitus

Lipid Disorders
• Treatment: surgery, radioiodine ablation (not effective
in medullary)

Adrenal Gland Cortex

Location Hormone Function Controlling
Factor
Zona glomerulosa Aldosterone Control sodium Renin
balance
Diseases of the Adrenal Glands
Zona fasciculata Cortisol Maintain ACTH
physiologic integrity
Cushing s Syndrome
Zona reticularis Dihydroepi- Produce Androgen-
Corticoadrenal Insufficiency androsterone androgen/estrogen stimulating
(DHEA) hormone
Pheochromocytoma
Primary Hyperaldosteronism
Adrenocortical Function Tests Cushing s Syndrome
• Urine-free cortisol: used in adrenal • Exogenous or
hyperfunctioning endogenous
• Plasma cortisol: caution diurnal
variation – Exogenous:
• Excess steroid
• Plasma ACTH level
medications
• Provocative tests
– ACTH stimulation test – Endogenous:
• Adrenal hyperplasia
• Screening test for adrenal
hypofunction – Pituitary-
hypothalamus
– Corticotropin-releasing hormone
dysfunction
• Test to separate ACTH-
– Adenomas (Cushing
dependent from ACTH- disease)
independent hypercortisolism
– Dexamethasone suppression test • Nonendocrine tumors
• Test for adrenal hyperfunction • Adrenal neoplasia
nih.gov nih.gov

Cushing s Syndrome Cushing s Syndrome: Treatment

• Clinical
– Obesity (centripetal), extremities appear wasted, buffalo hump
– Thin skin, acne, hirsutism, amenorrhea
– Fatigue, proximal muscle weakness, pigmented striae
– Decreased libido
– Hypertension
• Labs
– Dexamethasone suppression test (plasma cortisol >10 µg/dL)
– Increase free cortisol in urine (>125 µg/dL in 24 hr)
– ACTH level- elevated in pituitary source of disease and
decreased in adrenal source
– Hyperglycemia and hypokalemia
• Treatment
– Transsphenoidal resection and replacement therapy
– Radiation therapy
– Adrenal inhibitors (this therapy alone not appropriate)
• Metyrapone
– Inhibits 11β-hydroxylase to reduce cortisol; may also cause
hypertension and hypokalemia and hirsutism
• Aminoglutethimide
– Often used together with metyrapone to reduce side effects.
– May cause hypothyroidism by interfering with iodine
incorporation into thyroid hormone
• Ketoconazole (antifungal agent)
– Blocks cholesterol side-chain cleavage to reduce cortisol

– MRI for pituitary tumor

Primary Corticoadrenal Insufficiency Addison s Disease

(Addison s Disease) • Labs
– Hyperkalemia (primary
• Causes disease), hyponatremia,
hypoglycemia
– Autoimmune inflammation of adrenal cortex (most
– ACTH (cosyntropin)
common) stimulation test
– TB/fungal infection, hemorrhage, trauma, metastatic • Cortisol <20 μg/dL in
Addison s
disease
– Increased ACTH >200
• Women > men mg/dL (primary disease)
– Low AM plasma cortisol
• Clinical (<3 mg/dL)
– Weakness, easy fatigability, orthostatic hypotension, • Treatment
anorexia, nausea/vomiting, diarrhea, weight loss, – Oral cortisone and
mineralocorticoid
hyperpigmentation (only in primary disease)
– IV saline, glucose,
– Exam: delayed DTRs glucocorticoids (if in
crisis)
Pheochromocytoma Pheochromocytoma
• Rare tumor arising from chromaffin cells of sympathetic • Treatment
nervous system – Surgery
• Cause of secondary hypertension – α-blockage followed by β-blockage (pre-surgery)
• Presentation
• α-blockage with phenoxybenzamine for 7–14 days
– Headache (80%), sweating (70%), palpitations (60%),
anxiety, tremor, abdominal pain • If no α before β, the hypertension will worsen
• Labs
– Hypermetabolism
– ↑ urine catecholamines (metanephrine & VMA)
– ↑ plasma catecholamines (epinephrine and
norepinephrine) (>2000 pg/mL)
– MRI/CT scan for adrenal tumor

Primary Hyperaldosteronism Primary Hyperaldosteronism

• Cause of secondary hypertension • Labs
– Aldosterone causes reabsorption of sodium – Stop all hypertensive medications first
– ↑ plasma/urine aldosterone level
• More common in women
– Low plasma renin
• Etiology • ↑ aldosterone and renin in 2º hyperaldosteronism
– Unilateral adrenocortical adenoma (Conn s syndrome) – Hypokalemia, metabolic alkalosis
– Bilateral cortical hyperplasia • Treatment
• Presentation – Conn s syndrome: adrenalectomy, spironolactone
– Hyperplasia: spironolactone
– Hypertension, polyuria, polydipsia, muscle weakness,
• Spironolactone blocks aldosterone
fatigue
• No edema

Acromegaly
• Excess of growth hormone from anterior pituitary
– Acromegaly in adults
– Gigantism in children
Diseases of the Pituitary Gland
• Due to a GH-secreting pituitary macroadenoma (90%)
Acromegaly/Gigantism
– Ectopic production with pancreatic, breast, or lung tumors
Short Stature is rare.

Diabetes Insipidus • Effects bone growth and metabolism

• Men > women, 3rd-5th decade of life
Syndrome of Inappropriate Secretion
of ADH (SIADH)
Hyperprolactinemia
Hypopituitarism
Acromegaly Acromegaly
• Clinical • Treatment
– Enlargement of hands, feet, skull
– Surgical removal of tumor is primary treatment
• Increase in glove and shoe size
– Space between teeth – Dopamine agonists: cabergoline, bromocriptine
– Metabolic: DM, weight gain – Somatostatin analogues
– Kidney stones • Octreotide: inhibits GH secretion
– HA, visual field defects
– Side effects: diarrhea and cholecystitis
• Labs © Richard Usatine, M.D. Used with permission.

– ↑ insulin-like growth factor I (IGF-I)- – GH analogue: pegvisomant

screening test • Blocks GH binding to its receptor
– Confirm with oral glucose
suppression test: if GH level high
confirms acromegaly
– MRI for pituitary tumor
© Richard Usatine, M.D. Used with permission.

Short Stature Short Stature: Etiologies

Normal Causes Pathologic Pathologic Proportionate • Familial short stature
Disproportionate
Familial Achondroplasia Prenatal – Establish growth curves at or below 5th percentile by
IGR age 2
Placental dysfunction
Intrauterine infection – Healthy, normal PE
Teratogens
Turner syndrome – Normal bone age and puberty at expected time
Trisomy 21
• Constitutional delay
Genetic Rickets Postnatal
Malnutrition – At or below 5th percentile at normal growth velocity
Chronic disease
Drugs – Delay in puberty and skeletal maturation
GH deficiency
Glucocorticoid excess – Will likely mature to expected height

Short Stature: Etiologies Dwarfism

• Growth hormone deficiency: growth at diminished • Prototype is achondroplasia
velocity • Clinical features
• Primary hypothyroidism
– Short limbs; long, narrow trunk; large head with
• Chronic disease midface hypoplasia; prominent brows
– Due to lack of caloric intake or absorption
– Delayed motor milestones
• Seen in cystic fibrosis, DM, CRF, IBD, celiac sprue
– Normal intelligence
• Turner s syndrome
– Only one X chromosome – Neurologic complications; bowing of legs; obesity;
dental problems; frequent ear infections
– Web neck, low hairline, multiple pigmented nevi, gonadal
dysgenesis, renal anomalies
• Medications: steroids, dextroamphetamine,
methylphenidate
Achondroplasia Diabetes Insipidus
• Labs • Causes (↓ ADH)
– Mutation in the FGFR3 gene – Central: ↓ production vasopressin from posterior pituitary

• Treatment • Due to tumor, pituitary surgery, sarcoid granulomas,

trauma (basilar skull fracture)
– Surgical correction of orthopedic problems
– Nephrogenic: ↓ renal response to vasopressin
– GH controversial
• Due to chronic renal disease, sickle cell, lithium,
colchicine
• Polyuria (20L/day)
• Polydipsia, low urine-specific gravity (<1.005)
• Dehydration, hypotension

Diabetes Insipidus Syndrome of inappropriate secretion of

• Labs ADH (SIADH)
– Hypernatremia • Caused by inability to suppress ADH à impaired water
– Hyperosmolality excretion
– Vasopressin challenge test for central DI (will reduce – CNS disturbances, malignancies (small cell lung CA), drugs
thirst and polyuria) (carbamazepine, desmopressin)
• Treatment • Presentation: hyponatremia, hypoosmolality, increased
– Treat underlying disease urine osmolality, euvolemic
– Central: desmopressin (DDAVP) intranasal or oral – Reduced urine output, fluid retention, hyponatremia
(a vasopressin agonist) – Small amount of highly concentrated urine
– Nephrogenic: treat underlying process, give thiazide
diuretics, limit renal water loss
– Monitor sodium levels

Syndrome of inappropriate secretion of

ADH (SIADH)
• Diagnostics: Diabetes Insipidus SIADH
– Low serum sodium and osmolality High urine output Low urine output
– High urine sodium and osmolality
Low ADH High ADH
– Must exclude hypothyroidism and Addison’s disease (possible
causes of euvolemic hyponatremia), paraneoplastic syndrome Hypernatremia Hyponatremia

• Treatment: focused on underlying disease Low urine sodium High urine sodium
– Fluid restriction (<800mL/day) – caution if cause is SAH Hypovolemic Euvolemic
– Oral vasopressin receptor antagonists (Tolvaptan) Thirsty! Thirsty!
• Selective water diuresis without electrolyte loss
– Possible IV sodium chloride + furosemide
Hyperprolactinemia Hyperprolactinemia
• Etiologies • Diagnosis
– Physiologic – MRI of pituitary
• Exercise, pregnancy, stress, suckling, seizure, chronic renal – Prolactin level (>100ng/mL think pituitary adenoma)
failure – Rule out other causes: LFTs, beta HCG, TSH, renal
– Pharmacologic function, drug history
• Phenothiazines, metoclopramide, methyldopa, reserpine,
• Treatment
TCAs, narcotics, cocaine, risperidone, SSRIs
– Stop medications if possible
– Pathologic
– Surgery; radiation therapy
• Pituitary adenomas, tumors, cirrhosis, hypothyroidism, SLE
– Dopamine agonists
• Clinical
• Bromocriptine and cabergoline
– Men: erectile dysfunction, gynecomastia, decreased libido
• Will return normal sexual function and fertility
– Women: oligomenorrhea, amenorrhea, galactorrhea, infertility • Side effects: fatigue, nausea, dizziness, orthostatic
– Large tumors: headaches, visual symptoms (visual field hypotension
deficits)

Hypopituitarism Hypopituitarism
• Partial or complete loss of anterior pituitary function • Clinical findings vary depending on hormone
– GH, FSH, and LH are typically lost early. – FSH/LH decrease
• Etiology • Women: amenorrhea, genital atrophy, infertility, loss of
axillary/pubic hair
– Pituitary tumors
• Men: impotence, testicular atrophy, infertility, loss of
• Pituitary adenomas axillary/pubic hair
– Pituitary apoplexy- acute hemorrhagic infarction of – GH decrease - not often clinically detectable- fine wrinkles,
pituitary adenoma hypoglycemia
• Severe headache, nausea, vomiting, decreased – TSH decrease - signs of hypothyroidism
consciousness – ACTH decrease - fatigue, decreased appetite, hyperkalemia
– Inflammatory diseases- sarcoidosis, TB, syphilis
– Vascular diseases
• Sheehan postpartum necrosis
• Stroke

Hypopituitarism Hypogonadism
• Diagnosis • General term referring to decrease in sperm production
– Measure GH, TSH, LH and IGFI and/or decreased in testosterone production from
– Insulin sensitivity test - in a positive test GH will not increase testes
(>10 mg/L) in response to hypoglycemia. • Primary hypogonadism: disease of testes
– Arginine infusion test - decrease GH is positive
– Damage to seminiferous tubules therefore cannot increase
– Metyrapone test- ACTH will not increase in a positive test spermatogenesis
• Treatment • Secondary hypogonadism: disease of
– Treat underlying cause hypothalamus/pituitary
– Hormone replacement – Typically restore spermatogenesis with GnRH therapy
Hypogonadism Hypogonadism
• Presentation: highly varied based on age of onset and underlying • Treatment:
condition – Aimed at underlying cause
– Adolescents: small genitalia, decreased muscle mass, lack of facial
hair, failure of voice change à delayed puberty – Typically includes testosterone replacement
– Adults:
• initial decreased libido, depression
• Chronic/severe: decreased muscle mass, hot flashes,
gynecomastia (> in primary)
• Diagnostics: must measure serum testosterone 2 x 8-10am,
consider semen analysis for fertility
– Primary:
• Low serum testosterone and sperm count
• High serum LH and/or FSH
– Secondary:
• Low serum testosterone and sperm count
• Low serum LH and/or FSH

The Endocrine System

Lecture 1 Endocrine Review
Diabetes Mellitus
Lecture 2 Diseases of the Thyroid Gland
Type I
Lecture 3 Diseases of the Adrenal Glands
Diseases of the Pituitary Gland Type II
Lecture 4 Diabetes Mellitus
Lipid Disorders
Hypoglycemia

Diabetes Mellitus Type I

• Insulin-dependent, autoimmune disease
• Occurs in young people (age <30)
extracellular
intracellular
hypoglycemia
hyperglycemia • Little or no endogenous insulin
• Clinical
– Polyuria, polydipsia, polyphagia
– Blurry vision, fatigue, weight loss
• Labs
– Fasting blood glucose >126 mg/dL; random blood
glucose >200 mg/dL
– Glycosylated hemoglobin ↑
Treatment Insulin Effects
• Diet
– Balance caloric intake with energy expenditure
– Match carbohydrate intake with insulin-dosing
– Limit cholesterol to 300 mg per day (<200 mg if LDL
reduction desired)
– Restrict daily protein intake to 10–20% of total calories
– Restrict saturated fats to 10% of total calories
– Restrict sodium to <2.4 g per day

nih.gov

Insulin Diabetes Mellitus Type I

• Complications
Type Onset (hr) Peak (hr) Duration (hr) – Diabetic ketoacidosis
Aspart Rapid-acting 0.2–0.5 0.5–2 3–4 • Ketones a result of fat metabolism
Glulisine • Precipitating factors:
Lispro
– Infection
Regular Short-acting 0.5–1 2–3 6–8
– Inadequate insulin treatment
NPH Intermediate 1.5 4–10 16–24
– MI (may be silent)
Lente Intermediate 1.5–3 7–15 16–24
– Other: trauma, stress, PE, drugs, alcohol
Ultralente Long-acting 3–4 9–15 22–28
• Clinical: abdominal pain, N/V, anorexia, thirst,
Glargine Long-acting No peak 24–36 tachycardia, fruity odor breath

DKA: Pathophysiology Diabetic Ketoacidosis

• Labs
– ↑ glucose and ketones
– Metabolic acidosis: ↓ pH, ↓ HCO3-
– Electrolyte abnormalities
• Potassium, sodium
• Treatment
– Insulin (regular)
– IVF
– Potassium supplement
– Treat underlying cause

nih.gov
Diabetes Mellitus Type II Diabetes Mellitus Type II
• Tissue resistant to insulin • Complications
• Middle-aged and older patients; overweight – Hyperosmolar hyperglycemic state
• Clinical • Used to be called hyperosmolar non-ketotic
hyperglycemia
– Polyuria, polydipsia, polyphagia
• Common in the elderly
– Fatigue, blurry vision
• Glucose markedly elevated (>600 mg/dL)
• Labs • Ketone negative (maybe a trace)
– Fasting blood glucose >126 mg/dL • Non-acidotic (pH rarely <7.30)
– Random blood glucose >200 mg/dL – HCO3- rarely <18 mEq/L
– Elevated hemoglobin A1c • Signs of dehydration (osmolarity >320)
• Treatment: fluids, insulin

Diabetes Mellitus Type II Diabetes Mellitus Type II

• Treatment
– Sulfonylureas (glyburide (Micronase), glipizide
(Glucotrol))
• ↑ pancreas insulin secretion
• Side effects: weight gain, hypoglycemia
– Biguanides (metformin (Glucophage))
• Initial pharmacologic treatment after lifestyle modifications
• ↓ hepatic glucose production, ¯ body weight, improve lipids
• Treatment, cont d
– Thiazolidinediones (rosiglitazone (Avandia))
• ↓ peripheral insulin resistance
• Side effects: cardiovascular risk
– Glucagon-like peptide-1 receptor agonist (exenatide
(Byetta))
• Enhances glucose-dependent insulin secretion by the
pancreatic beta-cells

• Side effects: lactic acidosis, diarrhea, nausea • Side effects: thyroid cancer, pancreatitis, renal impairment

– a-glucosidase inhibitors (acarbose (Precose)) – Insulin

• Delays postprandial digestion of sugars – Diet
• Side effects: nausea and diarrhea • Same as in type I

Diabetic Monitoring Diabetes: Complications

• Hgb A1c: target <7% • Ocular: cataracts, retinopathy, glaucoma
• Estimated average glucose (eAG) • Diabetic nephropathy
– Hgb A1c = 135 mg/dL – Pathologic albuminuria or microalbuminuria

– Add 35 mg/dL for every 1% change in A1c • Diabetic neuropathy

– Peripheral: stocking glove distribution
– eAG = 28.7 x A1c – 46.7
– Autonomic: gastroparesis, impotence
• Proteinuria: microalbuminuria
• Gangrene of the feet
• Blood pressure control: target <140/90 mm Hg • Pregnancy: avoid oral agents
• Lifestyle modification: diet and exercise (aerobic and
resistance training)
 Summary
Diabetes Concepts
Feature Insulin Shock DKA Hyperosmolar
• Honeymoon period shock
– Seen in IDDM patients Insulin Excessive Insufficient Normal or
– Ketoacidosis followed by symptom-free period, no treatment increased
required Onset Rapid Gradual Gradual
• Somogyi effect Skin Cold sweat, pale Dry, flushed Dry, flushed
– Rebound hyperglycemia in AM in response to
counterregulatory hormone release after episode of Respirations Normal or Slow and deep Usually normal
hypoglycemia in middle of the night shallow
• Dawn phenomenon Heart rate Rapid Rapid Usually normal
– Early morning rise in plasma glucose requiring increased
amounts of insulin to maintain euglycemia Blood pressure Normal Low Normal

Blood glucose Very low High Very high

pH Normal Low Normal
Acetone Absent Present Absent

Hypoglycemia Hypoglycemia: Etiology

• Blood sugar decreased • Fasting hypoglycemia
• Clinical – Endocrine disorders
– Sweating, palpitations, hunger, tremor, weakness – Liver / renal failure
– Lightheadedness, headache, confusion, seizures,
coma, dizziness
– Pancreatic tumors- insulinoma
• Labs – Insulin and sulfonylureas
– Glucose <55 mg/dL (prolonged fasting in hospital) • Postprandial hypoglycemia
– Insulin level • Postgastrectomy
– Peptide C • Functional
• Treatment: dextrose
• Alcohol-related
• Drugs

Lipid Disorders
• Linked to CAD and CVA
– 20% of American adults have hyperlipidemia
• Major lipids: cholesterol, triglycerides, and
Lipid Disorders phospholipids
Hyperlipidemia • Causes
Metabolic Syndrome – Primary: familial hyperlipoproteinemia
– Secondary: DM, hypothyroidism, hepatic disease,
obesity, drugs
Lipid Disorders Lipid Disorders
• LDL • Clinical: no symptoms
– Associated with increased risk of atherosclerotic heart until signs of ASVD
disease • Exam
• HDL – Xanthomas
– Lipemic blood sample
– Associated with decreased risk of atherosclerotic heart
disease – Abdominal pain
– Hepatomegaly
• Triglycerides – Arcus senilis
– Associated with increased risk of atherosclerotic heart • Labs (Fasting normal)
disease in women and diabetics
– TC: <200 mg/dL
– Increased levels may lead to pancreatitis – HDL: >60 mg/dL
– LDL: <100 mg/dL
– TG: <200 mg/dL © Richard Usatine, M.D. Used with permission.

Risk Factors Lipid Disorders

• Major risk factors which modify LDL goals • Treatment
– Risk factor modification
– Cigarette smoking • Smoking cessation
– Hypertension: BP ≥140/90 or on antihypertensive • Weight loss
meds • Exercise

– Low HDL cholesterol (<40 mg/dL) – Diet

• Cholesterol intake <200 mg/dL
– Family history of premature CHD • Carbohydrates 50–60% of total calories
• Men: first-degree relative age <55 • Fiber 20–30 g/day
• Women: first-degree relative age <65 • Total dietary fat to 30%; saturated fat <7% of total calories

– Age – Take aspirin daily unless contraindicated

• Men age ≥45

• Women age ≥55

ATP IV Guidelines Lipid Disorders

The guidelines contain the following:
•All patients ( ≥ 21 years of age) with any form of CVD (not only
CHD), or LDL-C ≥ 190 mg/dl:
– Treat with high dose statins if <75 yo, moderate intensity if >75 yo
– e.g.: Atorvastatin 40-80 mg or Rosuvastatin 20-40 mg with the aim to
reduce LDL-C by >50 %
•All patients with diabetes (age 40-75 years) with LDL-C 70-189
mg/dl, without any evidence of CVD should receive statin therapy
as follows:
– Moderate dose statin
– e.g. Atorvastatin 10-20mg, Rosuvastatin 5-10 mg, Pravastatin 40-80 mg,
Simvastatin 20-40 mg, with the aim to reduce LDL-C by 30-50 %.
– However, consider high dose statin as above if 10-yr risk by new risk
calculator >7.5 %.
• This will translate to many patients with diabetes + additional risk
factors
•If using high dose and moderate dose statins as described
above, a specific target of LDL-C goal (< 70 or <100) is not
recommended.
•All patients must receive intensive lifestyle management.
• Treatment
– Medications
• Bile acid-binding resins: form compounds with bile acids
in intestine
– Side effects: GI distress, constipation
– Contraindication: bowel obstruction
• HMG-CoA reductase inhibitors: limit cholesterol synthesis
– Side effects: myositis, elevated LFTs
– Contraindications: pregnancy, active liver disease
• Fibric acid derivatives: reduce hepatic trig production and increase
HDL synthesis
– Side effects: cholelithiasis, dyspepsia
– Contraindications: severe hepatic or renal disease
• Nicotinic acids: VLDL secretion inhibitors
– Side effects: flushing, hepatotoxicity, hyperglycemia
– Contraindications- severe PUD, chronic liver disease, severe
gout
Lipid Lowering Agents Summary Metabolic Syndrome
• Linked to insulin resistance
Drug Class Lipid Effects Side Effects Contra-
indications • A constellation of lipid and nonlipid risk factors of
Statins LDL ¯ Rhabdomyolysis Acute liver dz
metabolic origin
HDL ­ Myolysis Chronic liver dz • Clinical identification
TG ¯ ­ LTFs
Bile acids binding LDL ¯ GI distress TG >400 mg/dl – Must have 3 or more of the risk determinants noted on
resins HDL ­ Constipation the next slide
TG ­ ¯ Drug absorption
• Treatment
Niacin and LDL ¯ Flushing Chronic liver dz
nicotinic acids HDL ­ Hyperglycemia Severe gout – Reduce underlying causes (obesity and physical
TG ¯ ­ Uric acid levels inactivity)
Liver damage
– Treat associated nonlipid and lipid risk factors
Fibric acids LDL ¯ Gallstones Severe renal dz
HDL ­ Myopathy Severe liver dz
TG ¯

Metabolic Syndrome
Risk Factor Defining Level
Abdominal Obesity Waist circumference
Men
Women >102 cm (>40 in)
>88 cm (>35 in)
Triglycerides ≥ 150 mg/dL
HDL cholesterol
Men <40 mg/dL
Women <50 mg/dL
Blood pressure ≥130/≥85 mm Hg
Fasting glucose ≥110 mg/dL
 Eyes, Ear, Nose, & Throat
Lecture 1 Eye Disorders

Eyes, Ear, Nose, & Throat Lecture 2

Lecture 3
Ear Disorders

Nose/Sinus Disorders

Lecture 4 Mouth/Throat Disorders

Isaak Yakubov, MS, PA-C

Amaurosis Fugax
Eye Disorders
Amaurosis fugax Hordeolum • Transient loss of vision in one or both eyes
Amblyopia Hyphema
• Etiology
Blepharitis Iritis
Blowout fractures Keratitis – Transient Ischemic Attack
Chalazion Macular degeneration
Conjunctivitis Nystagmus – Giant cell arteritis
Cataracts Orbital cellulitis – Central retinal artery occlusion
Corneal abrasion Optic neuritis
Corneal Ulcer Papilledema
Dacryocystitis Pterygium/Pinguecula
Ectropion Retinal detachment
Entropion Retinal vascular occlusion
Foreign bodies Retinopathy
Glaucoma Scleritis
Globe rupture Strabismus

Amaurosis Fugax Amblyopia

• Clinical Features • A functional decrease in visual acuity due to
– Loss of vision in one/both eyes abnormal development of vision in childhood
• Etiology
• Treatment
– Treat the underlying issue – Strabismus
– Patients will need extensive workup – Refraction errors
– Congenital cataracts
• Treatment
– Refer to ophthalmology
Blepharitis Blepharitis
• Inflammation of the eyelids • Clinical Features
– Burning and itching of the eyes
• Etiology – Eye maybe red
– No change in vision
– Anterior: Staphylococcus, viral, or seborrheic – Eyelids show scaling and
crusting
infection
• Seborrheic blepharitis
scales are greasy
– Posterior: dysfunction of meibomian glands
• Treatment
– Supportive
• Lid scrubs (baby shampoo)
• Warm compresses
– Antibiotics
• Oral (tetracycline) © David C Cogan Ophthalmic Pathology Collection

• Topical (erythromycin,
bacitracin)

Blowout Fracture Blowout Fracture

• Direct trauma to zygomatic prominence or soft tissue of the • Diagnosis
orbit
– Plain films and CT scan
– Pressure blows out weak orbital floor
• Symptoms
• Treatment
– Double vision, due to – Surgery may be required
entrapment of inferior rectus
– Anesthesia anteromedial cheek
and upper lip, due to stretch
on infraorbital nerve
• Physical examination
– Double vision
– Limited upward gaze Source: Steve Ferrara
Source: James Smiriniotopulos, M.D.

Chalazion Bacterial Conjunctivitis

• Granulomatous inflammation of • Adults > children
and blockage of meibomian • Etiology
gland
– S. pneumoniae, S. aureus, H.
• Chronic disease influenzae, Moraxella
• Physical examination • Transmitted via direct contact,
– Painless, red, hard, non- autoinoculation
tender swelling of upper or – Chlamydia, N. gonorrhoeae
lower lid (ocular emergency)
– Can distort vision • Contact with infected genital
secretions (neonate)
• Treatment
• Clinical
– Warm compresses © Richard Usatine, M.D. Used with permission.
– Purulent discharge, pink-red eye
– Topical antibiotics – Foreign body sensation, eye phil.cdc.gov
(erythromycin)
crusting
– Incision and drainage – No photophobia or visual loss
Bacterial Conjunctivitis Viral Conjunctivitis
• Labs • Children > adults; midsummer to early fall
• Virus: adenovirus type 3
– Culture and gram-stain of eye
• Highly contagious, transmitted by direct
• Treatment contact
– Warm compresses • Clinical
– Antibiotics – URI, sore throat, fever, malaise (early)
• Flouroquinolones are first line – Starts unilateral but becomes
bilateral in 3–5 days
• Trimethoprim and polymyxin – Copious watery discharge, erythema,
• GC: IV ceftriaxone, topical erythromycin periauricular lymphadenopathy
• Chlamydia: oral tetracycline, doxycycline, • Treatment
azithromycin – Cool compresses, artificial tears
– Avoid neomycin and corticosteroids – Vasoconstrictor; antihistamine
(if severe itching) © David C Cogan Ophthalmic Pathology Collection

Allergic Conjunctivitis Herpes Zoster Ophthalmicus

• Seasonal • Due to infection with varicella-zoster

– Patients with atopy (asthma, eczema) • Infects ophthalmic branch of the trigeminal nerve
– For shingles noted on tip of nose, think eye involvement
– Hay fever
• Symptoms
• Symptoms: pruritus (severe); bilateral symptoms – Begins with prodrome: fatigue, malaise, mild fever
• PE – Pain & skin hyperesthesia prior to rash
– Injected, mucoid discharge • Physical examination
• Treatment – Rash is erythematous or maculopapular
following dermatomal pattern
– Topical vasoconstrictors or antihistamines
• Evolves into vesicles and pustules
– Topical mast cell stabilizer and then crusting
– Cool compresses • Treatment
– Immediate ophthalmology consult
© David C Cogan Ophthalmic Pathology Collection

Herpes Simplex Infection Conjunctivitis

• Due to primary or reactivation of pre-existing disease
• Symptoms
Bacterial Viral Allergic
– Pain, foreign body sensation, tearing, photophobia, clear
drainage, decreased visual acuity Itching Minimal Minimal Severe
• Physical examination Hyperemia Generalized: bright Generalized Generalized: milky
red
– Red eye
– Fluorescein stain (look for dendritic ulcers [branching]) Tearing Moderate Profuse Moderate
• Treatment Discharge Perfuse Minimal Minimal
– Oral acyclovir, famciclovir, valacyclovir Adenopathy Rare Common None
– Topical antivirals (trifluridine) (periauricular)

– Ophthalmology consult Sore throat and Occasionally Occasionally None

– No steroids fever
Cataracts Corneal Abrasion
• Lens opacity, usually bilateral • Superficial irregularities of the cornea
• Etiology • Caused by foreign bodies
– Congenital (rubella, CMV) – Injury, welder s arc, contact lens

– Traumatic • Symptoms
– Systemic disease (diabetes) – Foreign body sensation, pain, photophobia, redness, blurry
– Medications (corticosteroids) vision, small pupil

– Senile (most common ages >60) • Physical examination

• Clinical © nih.gov – Check visual acuity first

– Slow visual loss, contrast sensitivity, glare – Red eye, fluorescein stain

– Halo around lights

• Treatment: surgery

Corneal Abrasion Corneal Ulcer

• Treatment • Localized infection to the cornea
– Cycloplegics (dilate pupil and relieve pain) • Caused by Untreated infections
– Topical antibiotics – Injury, contact lens, and abrasions
• Erythromycin
• Symptoms
• Cover for pseudomonas in soft contact lens wearers
– Tobramycin or fluoroquinolone – Foreign body sensation, pain, photophobia, redness, blurry
vision, and tearing
– Pressure patch
• Physical examination
• Avoid if secondary to organic material or soft contact
lens – Check visual acuity first!
– Follow-up 24 hours & avoid contacts for 1 week after – Red eye, fluorescein stain
healing – White spot on eye seen with light
– Avoid topical anesthetics

Corneal Ulcer Dacryocystitis

• Treatment • Infection of lacrimal sac
– Cycloplegics (dilate pupil and relieve pain) – Obstruction of nasolacrimal system
– Topical antibiotics – Acute: S. aureus, beta-hemolytic strep, H. influenzae
• Erythromycin
• Infants and adults ages >40
• Cover for pseudomonas in soft contact lens wearers
– Tobramycin or fluoroquinolone • Symptoms
– Ophthalmology referral (same day or next day) – Pain, swelling, tenderness, redness in tear sac area
(usually unilateral)
– May have purulent discharge
Dacryocystitis Ectropion
• Physical examination • Outward turning of the lower lid (Basset-hound look)
– Acute: inflammation of the lid with: – Chronic: inflammation results in:
• Erythema • Madarosis (lash loss) • Elderly
• Edema • Trichiasis (misdirection of lashes)
• Tylosis (thickening & distortion of
• Lower lid margin droops outward, away from the
• Thickening
• Hyperkeratinization the lid margin) globe
• Poliosis (loss of lash pigmentation)
• Notching • May be excessive tearing but eyes are typically dry
• Irregularities of the lid margin • Punctal misdirection
• Scarring
• Treatment • Treatment: surgery
– Lid hygiene
– Antibiotics: topical (bacitracin and erythromycin) or systemic
(tetracycline)

Entropion Foreign Body

• Inward turning of the lower lid toward the eye • Test visual acuity first
• Elderly • May be on cornea or
under upper lid
• Eyelashes seen against the eyeball
– Pain and irritation noted with
eye movement
– Foreign body insult, can cause scarring
• Symptoms
• Redness and tearing
– Pain, foreign body
• Treatment: surgery sensation, red eye, tearing,
and blepharospasm

• Evaluation
– Topic anesthetic © David C Cogan Ophthalmic Pathology Collection

(proparacaine 0.5%)

– Fluorescein

Foreign Body Glaucoma

• Removal • Due to an increased intraocular pressure, which
– Use sterile saline irrigation first results in optic nerve damage and loss of vision
– Remove with fine-gauge needle
• Types
• Avoid wet cotton-tip applicator
– Primary angle-closure
• Treatment
• Has a narrow anterior chamber angle
– Polymyxin-bacitracin or erythromycin ointment – Primary open-angle
• Avoid steroids • Has a normal anterior chamber angle
– Steel foreign bodies, look for rust ring
• Remove rust ring at 24 hours
– Close follow-up; referral for intraocular foreign body
Acute Glaucoma Acute Glaucoma
• Occurs only with closure of preexisting narrow • Clinical

anterior chamber angle – Extreme pain, blurred vision (halos around lights), N/V, headache
• Physical examination
• Elderly – Eye is red, cornea steamy, pupils moderately dilated, nonreactive to
light.
• Triggers: – Narrow anterior chamber, globe is hard.
– Check visual fields
– Pupillary dilation
– Tonometry: elevated intraocular pressure (normal 10–22 mm Hg)
– Pharmacologic mydriasis • Treatment (refer to ophthalmologist)
– Primary: IV acetazolamide (Diamox) to lower pressure; once pressure
– Anticholinergic medications drops, start topical pilocarpine 2%
– Secondary: systemic acetazolamide
– Laser trabeculoplasty
• Prognosis: untreated, there is visual loss in 2-5 days

Primary Open-Angle Glaucoma Primary Open-Angle Glaucoma

• Due to abnormal drainage of aqueous through • Clinical
trabecular meshwork – Chronic, asymptomatic (no halos around lights)

• Commonly seen in ages >40, African Americans, those – Slight cupping of optic disc
with positive family history – Elevated intraocular pressure
• Schiotz tonometer or pneumotonometer
• Symptoms
– None (early stages) • Treatment
– Beta-adrenergic blocking agents (timolol or betaxolol)
– Gradual loss of peripheral vision (over a period of years)
• Respiratory or cardiac side effects
• Results in tunnel vision – Prostaglandin analogs
• No systemic side effects, lower pressure the greatest
– Carbonic anhydrase inhibitors (acetazolamide)
– Laser trabeculoplasty surgery

Glaucoma Screening Globe Rupture

Age Frequency

20–29 At least once during this period

Those with risk factors, every 3-5 years

30–39 At least twice during this period

Those with risk factors, every 2-4 years.

40–64 Every 2-4 years

65 and older Every 1-2 years

Risk Factors: African descent, positive family history

Hordeolum Hyphema
• Staph infection of the • Hemorrhage into the anterior chamber
meibomian gland (internal) • Clinical
or glands of Zeis or Moll
(external) – Pain, photophobia,
decreased visual acuity
– A stye (external)
• Treatment
• Red, swollen, tender area on
– Fox shield, place patient at
upper or lower lid
45 (keeps red cells from
• Treatment: staining cornea)
– Warm compresses – Avoid aspirin and NSAIDs
– Antibiotic ointment (E- • Increased risk in sickle cell
mycin, bacitracin) © David C. Cogan Ophthalmic Pathology Collection

Rakesh Ahuja, M.D.

– If no improvement in 2 Source:

days, may have to I & D

Acute Iritis Infectious Keratitis

• Inflammation of the iris
• Etiology
– Trauma, infection, autoimmune
• Unilateral, painful red eye without discharge,
photophobia, blurry vision
• Physical examination
– Peri-limbal flushing (dilatation of radial vessels),
reduced vision, constricted pupil
• Treatment: topical steroids, analgesics, refer to
ophthalmology

Macular Degeneration Macular Degeneration

• Age-related, etiology unknown • Results in central vision loss only
• Leading cause of permanent
vision loss in the elderly – Test with Amsler grid chart
• Two groups • Treatment
– Atrophic (dry)
• Gradual progressive vision
– Laser photocoagulation
loss of moderate severity,
retinal pigment atrophy,
yellow deposits (drusen)
nih.gov
– Exudative (wet)
• More rapid onset and greater
severity of vision loss,
hemorrhages,
neovascularization,
Nystagmus Orbital cellulitis
• Rhythmic movement of the eyes Periorbital (Preseptal) Orbital (Postseptal)
• May be continuous or paroxysmal and can also be transient
• Infection of the eyelids • Infection of the orbital soft
• Symptoms
and periocular tissues tissue
– Vertigo MC symptom – Anterior to orbital septum – Posterior to orbital septum

– Blurred vision • Associated with URI • Spread from paranasal

– Abnormal head position • Organisms are S. aureus, sinusitis
S. epidermis, and Strep • Organisms are S. aureus,
– Room spinning sensation
sp. S. pneumoniae, and
• Treatment • Symptoms anaerobes
– Symptomatic therapy
– Tearing, fever, erythema, • Symptoms
warmth, tenderness – Tearing, fever, erythema,
warmth, tenderness

Orbital cellulitis Optic Neuritis

Periorbital (Preseptal)
• Visual acuity, pupillary
reaction, and EOM are
normal
• CT scan needed to
diagnosis
• Treatment
– Amoxicillin/clavulanic acid
– 1st generation
cephalosporin
Orbital (Postseptal) • Inflammation of the optic nerve
• Most common etiology is multiple sclerosis
• Pain with eye movement,
– Half of patients with MS will develop
decreased visual acuity,
– Other etiologies include infection, autoimmune disorders, IBD,
proptosis
and drug induced (chloramphenicol, ethambutol)
• CT scan needed to • Present with sudden loss of vision or blurry vision, pain
diagnosis with eye movement
• Treatment
• Funduscopic exam may be normal or show swelling
– Hospitalization, IV
antibiotics • Treatment
– 2nd or 3rd generation – Corticosteroids
cephalosporins, ampicillin-
sulbactam, carbapenems,
clindamycin

Papilledema Pterygium/Pinguecula
• Swelling of the optic disc • Pterygium
© Richard Usatine, M.D. Used with permission.
• Most common etiology is elevated intracranial pressure – Fleshy, triangular encroachment
of the conjunctiva onto the
– Mass, pseudotumor cerebri, cerebral edema
nasal side of the cornea
• Present with brief visual obscurations worse with head – Tropical climates
movements – Excision is indicated if
• Funduscopic exam will show swelling of the optic disc vision threatened

• Treatment • Pinguecula
– Treat the underlying problem, refer to specialist – Yellow, elongated conjunctival
nodule, commonly on the nasal
side in area of palpebral fissure
– Common over age 35, History
of exposure to wind, sun, sand,
and dust
– No treatment typically indicated
 Retinal Detachment Retinal Detachment
• Tear of the retina that is usually spontaneous • Treatment
– Most common location is superior temporal area – Refer to ophthalmology
• Mainly ages >50 – Supine and position head so retina falls back with the
• Predisposing conditions: cataract extraction, myopia help of gravity
• Clinical – Surgery
– Blurred vision in one eye becoming progressively worse • Photocoagulation
( curtain came down over my eye )
• Cryosurgery
– Flashes and floaters
– No pain or redness
– Exam: retina seen hanging in the vitreous, asymmetric red
reflex

Retinal Artery Occlusion Retinopathy

• Sudden, painless, profound visual loss (central artery) and marked • Diabetic • Hypertensive
decrease in visual fields (branch artery)
– Non-proliferative (early) – Affects both retinal &
• Typical onset ages 50-70
choroidal circulation
– Many have history of carotid • Dilation of veins,
artery disease – Retinal arterioles become
microaneurysms,
– Not related to hypertension retinal hemorrhage, tortuous and narrow,
abnormal light reflexes
• Physical examination hard exudates (silver-wiring, copper-
– Swelling of the retina, arteries – Proliferative (late) wiring)
are attenuated, box-car arteries,
pale retina with cherry red spot • Neovascularization, – AV nicking
• Treatment vitreous hemorrhage, – Flame-shaped
– Digital global massage © David C Cogan Ophthalmic Pathology Collection
cotton-wool spots hemorrhages in the
– Lower IOP – Treatment: yearly eye nerve layer of the retina
– Immediate referral exams and control blood – Treatment: control HTN
Retinal hemorrhages in retinal vein occlusion, none in retinal artery occlusion. sugar

Diabetic Retinopathy Strabismus (Non-Paralytic)

• Misalignment of visual axes of the 2 eyes
– Ocular muscle weakness or imbalance
– Should be well-aligned by age 2-3 months
• Leading cause of • May occur in one eye or both
blindness in the – May present with diplopia, scotoma, or amblyopia
U.S. • Prevalence in childhood 2-3%
• Exam: corneal light reflex and cover/uncover test
• Treatment: exercise, surgery

nih.gov
Retinoblastoma Retinitis Pigmentosa
• Inherited or sporadic • Inherited autosomal
dominant, recessive or X-
• Congenital malignancy: linked
lack of tumor suppressor
gene • Presents with night
blindness in childhood
• Absent red reflex
• Pigmentation on retina
• White pupil • Progressive visual loss
• Life-threatening; refer to begins in second decade
ophthalmology (tunnel vision)
• Blindness often by age 40-
50
© David C Cogan Ophthalmic Pathology Collection
© David C Cogan Ophthalmic Pathology Collection

• Vitamin A may be helpful

Scleritis Scleritis
• Diagnosis
– Slit lamp exam
– Look for underlying autoimmune or inflammatory condition
• Treatment
– Refer to Ophthalmology

Ear Disorders
Acute/Chronic Otitis Media

Eyes, Ear, Nose, & Throat Barotrauma

Lecture 1 Eye Disorders Foreign bodies

Mastoiditis
Lecture 2 Ear Disorders
Otitis Externa
Lecture 3 Nose/Sinus Disorders
Meniere's Disease
Lecture 4 Mouth/Throat Disorders Labyrinthitis
Hearing Loss
Tympanic Membrane Perforation
Cerumen Impaction

Acoustic Neuroma
Eustachian tube dysfunction

Cholesteatoma
Acute Otitis Media Acute Otitis Media (AOM)
• Infection of the middle ear between eustachian tube • More common in infants and children
and tympanic membrane – Peak age 6–18 months
– Usually precipitated by a viral upper respiratory infection – Risk factors
(URI) • Daycare attendance
• Pathogens • Sibling with AOM
• Parental smoking
– S. pneumoniae
• Bottle drinking
– H. influenzae Same as for bronchitis and sinusitis
• Prevention
– M. catarrhalis – Breast feeding, pneumococcal vaccine
– Viral

Acute Otitis Media Acute Otitis Media

• Clinical • Treatment (acute)
– Symptoms – First-line
• Ear pain, fever, URI symptoms, irritability, tugging at • Amoxicillin (if PCN-allergic, use azithromycin)
ears – Second-line
– TM erythema, decreased mobility of TM, fever, • Amoxicillin/clavulanate, cefaclor, cefixime, erythromycin
decreased hearing • TMP/sulfa (poor activity against S. pneumoniae)
• If drainage, think TM rupture. – Pain control
– TM bullae: think Mycoplasma pneumoniae
• Treatment (chronic)
• Lab
• Sulfamethoxazole
– Tympanocentesis (rarely performed) • Amoxicillin

Chronic Otitis Media Mastoiditis

• Due to recurrent acute otitis media • Follows inadequately treated AOM (most common
• Perforation of TM is usually present complication of AOM)
• Pathogens • Postauricular pain and erythema, fever, bulging TM
– P. aeruginosa, S. aureus • X-ray: coalescence of mastoid air cells due to destruction
• Clinical of bony septa
– Purulent aural discharge • Treatment:
– Conductive hearing loss – IV antibiotics (ampicillin, cefuroxime, ceftriaxone)
• Treatment – Myringotomy
– Remove debris, avoid water, use antibiotic drops (Cipro); – Possible surgical drainage (mastoidectomy)
possible surgery
– Complications: hearing loss (monitor hearing),
labyrinthitis, vertigo, facial nerve paralysis
Otitis Externa Otitis Externa
• Infection of external auditory canal • Treatment
– History of water exposure (swimmer s ear) or mechanical
– Otic aminoglycosides
trauma
• Neomycin sulfate
• Common in diabetes (malignant)
• Polymyxin B sulfate
• Pathogens
– Pseudomonas, staph, proteus, fungi (aspergillus) – Corticosteroids
• Clinical – Ear wick
– Otalgia, pruritus, purulent drainage
– Oral or otic quinolones
• If brown/yellow discharge with strong odor think
cholesteatoma – Fungal: amphotericin B
– Erythema, edema of ear canal skin, pain with movement of
auricle
– Periauricular lymphadenopathy

Cholesteatoma Barotrauma
• Eustachian tube unable to equalize pressure
– History of rapid changes in pressure (Airplane descent, Deep
sea diving)
• Clinical
– Ear pain with fullness usually present with hearing loss
– If TM perforated may present with discharge from
canal/bleeding
– On physical exam will see a perforated TM or petechiae
• Treatment: Swallowing or yawning
– Decongestants will help decrease edema around ET
• Sudafed
• Oxymetazoline

Eustachian Tube Dysfunction Foreign body

• Swelling of the ET leads to inability of tube to auto insufflate • Usually seen in children between 2-5 years old
– MC after URI or rhinitis • Clinical
• Clinical – Drainage from ear with ear pain
– Ear pain with fullness ”underwater feeling” – Conductive hearing loss
– Tinnitus – May be asymptomatic
– Conductive hearing loss • Treatment:
• Treatment: Swallowing or yawning – Foreign body removal
– Decongestants will help decrease edema • Alligator Forceps
• Pseudoephedrine • Pressure wash
• Oxymetazoline • Don’t miss TM rupture!!
Ménière s Syndrome Ménière's Syndrome
• Due to distention of the endolymphatic compartment of • Exam
inner ear
– Caloric testing: loss or impairment of thermally induced
– Cause unknown nystagmus on the involved side
• Peak onset ages 40–60 • Horizontal nystagmus
• Clinical – Audiometry: low-frequency sensorineural loss
– Episodic vertigo lasting 1–8 hours, rarely longer than 24 hours – Otoscopy normal
(horizontal rotational)
– Low-frequency sensorineural hearing loss
– Tinnitus > blowing quality
• These 3 above are classic triad
– Sensation of aural pressure

Ménière's Syndrome Labyrinthitis

• Treatment • Inflammation of the vestibular labyrinth
– Low-salt diet • Acute onset of continuous, usually severe, vertigo
– Anti-vertigo medications
• Accompanied by hearing loss and tinnitus
• Dimenhydrinate (Dramamine)
• Meclizine (Antivert)
• May take weeks to recover
• Diazepam (Valium) • Cause is unknown
• Scopolamine patch • Frequently follows a URI
– Diuretics (hydrochlorothiazide) • Treatment
– Surgical decompression of endolymphatic sac
– Typically self-limiting but may require diazepam, meclizine, or
• Watch out for acoustic neuroma (has same clinical dimenhydrinate
picture)
– Is a benign tumor of the myelin-forming cells of the
vestibulocochlear nerve (CN VIII).

Benign Paroxysmal Positional Vertigo Benign Paroxysmal Positional Vertigo

• Very common cause of dizziness • Diagnosis
– Makes up 20% of all cases
– Dix-Hallpike test positive
– More common in older patients • Move patient from sitting to supine with head turned 45
• Over age 50, common cause is head trauma degrees to one side and 20 degrees backward
• Due to debris in inner ear • Positive is burst of nystagmus
• Symptoms: dizziness, vertigo, lightheadedness, • Treatment
imbalance, nausea – Wait and see (may last up to 2 months)
– Symptoms brought on by change in position of the head – Epley maneuver
(tipping head back)
• Called particle repositioning
– Episodes last less than 1 minute • Involves moving the head into 4 positions and staying at
– Dizziness triggered by lying down or rolling over
each for 30 seconds
• May cause weakness, numbness, and visual changes
Vertigo Summary Cerumen Impaction
• Wax impaction in ear canal
Sign/Symptom Central Peripheral – History of Q-tip use or being in a pool for long periods of time
Severity Mild, gradual Marked, sudden • Clinical
Tinnitus/deafness Absent Present – Ear fullness usually present with hearing loss
Nystagmus – Conductive hearing loss
Vertical Occasional Never – On physical exam usually unable to see TM due to cerumen in
Horizontal Common Uncommon ear canal
Duration Variable/chronic Finite/intermittent
• Treatment: Irrigation of ear if > 75% of TM not visible
CNS Signs Common None
Etiologies Vascular Infection – Cerumen softening agents
Neoplasm Ménière's
• Debrox
Multiple sclerosis Trauma
Toxin • Hydrogen peroxide
BPPV

Hearing Loss Hearing Loss: Tests

• Conductive (middle ear)
– Problem with mechanical reception or amplification Weber Test Rinne Test
of sound
– Disease in the auditory canal, TM, or ossicles
• Sensorineural (inner ear)
– Degeneration/destruction of hair cells or CN VIII
– Disease in the cochlea, semicircular canal, neuron
– Loss clarity of hearing

IMC ©2010 DxR Development Group, Inc. All Rights Reserved.

Hearing Loss Hearing Loss

• Conductive • Conductive Etiologies • Sensorineural
– Decreased perception of sound – Otosclerosis Etiologies
• Fixed stapes – Presbycusis
– Low frequency tones
• Women > men • Aging, hair cell loss
– Weber: sound heard in ear with loss – Noise-induced
– Cerumen impaction
– Rinne: BC > AC • Chronic exposure
– Middle ear fluid
• Sensorineural – Drug-induced
• Aminoglycosides,
– Difficulty deciphering words Lasix, Cisplatin
– Tinnitus common – Acoustic tumor
– Rinne: AC > BC – Ménière disease
– Viral
Tympanic Membrane Perforation Acoustic Neuroma
• Occurs secondary to middle ear infections, barotrauma,
or trauma
– Barotrauma- due to pressure increase in middle ear
• Presentation
– Acute onset pain and hearing loss
– Bloody otorrhea possible
– Vertigo or tinnitus also possible but transient
– Physical exam reveals a perforated TM
• Treatment
– Most heal spontaneously (80%)
– Antibiotics not needed

Eyes, Ear, Nose, & Throat

Lecture 1 Eye Disorders Nose/Sinus Disorders
Lecture 2 Ear Disorders Acute/Chronic sinusitis
Lecture 3 Nose/Sinus Disorders Allergic rhinitis
Lecture 4 Mouth/Throat Disorders
Epistaxis
Nasal polyps

Acute Sinusitis Acute Sinusitis

• General • Clinical
– Due to impaired mucociliary clearance and obstruction of the – Symptoms >10 days
ostiomeatal complex – Pain and pressure over sinus
– Accumulation of mucous secretions and edema – Discolored, purulent nasal discharge
– Symptoms for less than 4 weeks – Fever, malaise, headache, tooth pain
– Maxillary most common, followed by ethmoid, frontal, and
• Physical examination
sphenoid
• Frontal develops as young child and sphenoid early 20s – Tender to palpation over sinus; opacification of the sinus
with transillumination
• Pathogens
– Viral: rhinovirus, parainfluenzae, influenzae, RSV
– Bacterial: S. pneumoniae, H. influenzae, and M. catarrhalis
– Fungal: Rhizopus, Mucor, Aspergillus (immunocompromised)
Acute Sinusitis Acute Sinusitis
• Labs • Treatment
– X-ray: opacification, – Oral decongestants (pseudoephedrine)
air-fluid levels, thick – Nasal decongestants (oxymetazoline)
mucosa
– Antibiotics
• Not routinely
• First-line: amoxicillin-clavulanate, doxycycline
indicated
• Second-line: Levofloxacin, cefpodoxime or cefuroxime plus
– CT scan: bone
clindamycin
destruction, air-fluid
levels, thick mucosa – Macrolides and TMP/sulfa not indicated as empirical
therapy due to increasing antimicrobial resistance
• Test of choice
• Treat for at least 10–14 days
– Analgesics
IMC ©2010 DxR Development Group, Inc. All Rights Reserved. – Drain sinus
• Complications
– Osteomyelitis, cavernous sinus thrombosis, orbital cellulitis

Chronic Sinusitis Allergic Rhinitis

• Chronic nasal congestion, cough, postnasal drip; • Due to airborne allergenic particles which initiate an
fever is rare IgE-mediated response
– Lasts >12 weeks • Seasonal or perennial
– Seasonal = hayfever
• Bacteria: S. aureus, anaerobes, H. influenzae, fungi
• Ragweed, grass, tree pollen
• Clinical: same as acute sinusitis – Perennial: house dust mites, animal dander, mold
• Labs: CT scan preferred over x-ray • Clinical
• Treatment: same as acute sinusitis; treat 2-3 weeks – Sneezing, nasal secretions, nasal congestion
– Itching eyes, postnasal drip, cough
• Remember to think about foreign body
– Worse in AM

Allergic Rhinitis Allergic Rhinitis: Treatment

• Exam • Allergen avoidance • Sympathomimetics
– Edematous mucosa that is pale or violaceous • Immunotherapy – Marked nasal congestion
• Ephedrine
– Clear nasal secretions • Antihistamines
• Pseudoephedrine
– Nasal polyps – First-generation H1
blockers (sedating)
• Topical steroids
– Watery eyes – Persistent symptoms
• Diphenhydramine
– Allergic shiners • Hydroxyzine • Mast cell stabilizer
– Allergic salute – Second-generation H1 – Cromolyn sodium
blockers (non-sedating) • Moderately effective
• Labs • Late & immediate
• Loratadine (Claritin)
– Eosinophils in nasal smear • Fexofenadine (Allegra) response
• Cetirizine (Zyrtec)
© Richard Usatine, M.D. Used with permission.
Epistaxis Epistaxis
• Causes • Anterior
– Trauma – Arises from anterior nasal septum (venous blood)
– Dry nasal mucosa – Site of bleeding easily seen
– Rhinitis – Unilateral, continuous, recurrent
– Medications (cocaine) • Posterior
– Allergic conditions – Intermittent, very brisk
• Signs and symptoms – Requires endoscopic instruments for localization
– Trauma, bleeding disorder, nasal discharge – Bleeding occurs from both nares (lateral wall)
– Bleeding seen in posterior pharynx

Epistaxis Nasal Polyps

• Management • Polypoidal masses from mucous membranes of nose
– Direct pressure/ice packs and paranasal sinuses
– Sitting and leaning forward • Frequently accompany allergic rhinitis
– Nasal decongestants for vasoconstriction
• Freely movable, non-tender
– Cauterization: silver nitrate or electrocautery
• Symptoms
– Nasal packing (24 hours)
• Anterior: petroleum packing – Nasal block, sinusitis, loss of smell

• Posterior: sponge pack, balloon tamponade

• Antibiotic prophylaxis: cephalexin, Augmentin, clindamycin,
Bactrim

Nasal Polyps
• Conditions associated with polyps
– Chronic rhinosinusitis Eyes, Ear, Nose, & Throat
– Asthma Lecture 1 Eye Disorders
– Aspirin intolerance
Lecture 2 Ear Disorders
– Cystic fibrosis
– Kartagener's syndrome Lecture 3 Nose/Sinus Disorders

• Treatment Lecture 4 Mouth/Throat Disorders

– Intranasal steroids
– Surgery
 Acute Pharyngitis
Mouth/Throat Disorders
• Types of pharyngitis
Acute pharyngitis
– Group A beta hemolytic strep (Streptococcus pyogenes)
Oral candidiasis
– Viral
Oral herpes • Herpes simplex
Oral leukoplakia • Coxsackie A
Peritonsillar abscess – Epstein-Barr virus
– Corynebacterium diphtheriae
Sialadenitis
– N. gonorrhoeae
Aphthous ulcers
– Mycoplasma
Deep neck infection
Epiglottitis
Laryngitis
Parotitis

Streptococcal Pharyngitis Viral Pharyngitis

• Most commonly ages 5–18 • Clinical
• Clinical – More insidious onset,
– Acute onset, fever, coryza, no exudate,
exudates posterior low-grade fever
pharynx, odynophagia,
rhinitis, cervical
• Labs
adenopathy – R/O strep
• Labs • Treatment
– Throat culture – Supportive
– Rapid strep screen phil.cdc.gov

• Treatment
– Penicillin, erythromycin, © Richard Usatine, M.D.. Used with permission.

cephalexin, azithromycin,
clarithromycin

Epstein-Barr Pharyngitis Laryngitis

• Clinical
– Malaise, tender
adenopathy, enlarged
spleen, jaundice,
exudative pharyngitis
(possible)
• Labs
– Monospot, reactive
lymphs
• Treatment
IMC © 2010 DxR Development Group, Inc. All Rights Reserved.
– Supportive
– Limit contact sports
– Avoid ampicillin
Oral Candidiasis Oral Candidiasis
• Also called thrush • Labs
• Etiology: Candida albicans – Wet prep
– KOH prep
• Seen in infants, denture wearers, those with diabetes
and HIV, and those taking chemotherapy or antibiotics • Treatment
• Clinical • Nystatin
– Painless or painful, white curd-like patches overlying • Clotrimazole troches
erythematous mucosa
– Easily rubbed off

Epiglottitis Epiglottitis
• General • Findings
– Life threatening supraglottitis/epiglottic infection – Tongue depressor or
• May result in acute airway obstruction
– Caused by Streptococcus pyogenes, or Staphylococcus aureus examination of oropharynx
or Mycoplasma may cause acute airway
• H. influenzae type b is uncommon in North America as a result obstruction
of immunization – Cherry-red epiglottis on
• Clinical findings laryngoscopy
– Fever
– Dysphagia
– Respiratory distress/stridor – Lateral neck x-ray
– Symptoms may overlap croup but toxicity suggests epiglottitis • Thumb sign - enlarged
• Severe sore throat
• Drooling epiglottis
• Absence of hoarseness – Once airway secure obtain
• Child s insistence on sitting forward with neck hyperextended
• Blood cultures, CBC,
Source: David Matthew DeLonga
culture of epiglottis

Epiglottitis Parotitis
• Treatment
– Secure airway
• Child should not be disturbed until personnel is
present and ready to perform intubation or
tracheotomy
– Antibiotic therapy
• IV ceftriaxone or cefotaxime for 7 to 10 days
• Prevention
– Vaccination for H. influenzae type b
– Rifampin to eliminate carriers and treat close contacts
Parotitis Deep neck infection
• Treatment
– Hydration with admission
• Outpatient therapy not recommended due to risk of
spread to deep tissues of neck.
– Antibiotic therapy
• IV Nafcillin plus Vancomycin or Metronidazole for 7 to
10 days
• If no response within 48 hours surgical I&D should be
done

Oral Herpes Simplex Oral Herpes

• Transmitted by direct contact • Clinical
• Etiology: herpes simplex types 1 and 2 – Painful eruption on
mucosa, most
– Type 1 most common
commonly at vermilion
• Incubation 2–20 days (usually 2 weeks) border
• Possible burning pain
• After infection, the virus migrates to the sensory or prior to vesicle formation
autonomic ganglia and becomes dormant
– Exam
• Reactive with stress, UV radiation, foods • Group of vesicles on an
erythematous base
which becomes phil.cdc.gov

pustules that rupture

Oral Herpes Oral Leukoplakia

• Labs • White striated or corrugated mouth lesion
– Viral culture • Most commonly ages >40
– Tzanck smear
• Caused by EBV or human papillomavirus
• Treatment
• Risk factors: tobacco, alcohol, oral infection
– Medications
• Clinical
• Oral route
– Asymptomatic
– Acyclovir
– Valacyclovir – Exam: white corrugated lesion on tongue
– Sides of tongue, soft palate, floor of mouth
– Famciclovir
– Suppression therapy – Not able to be scraped away (bleeds)

– Avoid contact
• Labs
© Katsumi M. Miyai, M.D., Ph.D., Regents of the – Biopsy
University of California. Used with permission.
Oral Leukoplakia Peritonsillar Abscess
• Treatment • Abscess formation between anterior and posterior
– Hairy leukoplakia tonsillar pillars and the superior pharyngeal constrictor
• Acyclovir muscle
– Leukoplakia – Complication of tonsillitis, peritonsillar cellulitis, and
• Isotretinoin mononucleosis
(Accutane) – Infection extends into tonsil through capsule
• Note
• Average ages <30
– Check HIV status
and rule out • Etiology: polymicrobial (anaerobic)
malignancy © Richard Usatine,M.D. Used with permission.

Peritonsillar Abscess Sialadenitis

• Clinical • Infection of salivary gland
– Severe sore throat, fever, odynophagia – Parotid, submandibular
– Exam: anterior chain adenopathy, drooling, trismus, hot • Acute swelling & pain with meals, tender and erythema at
potato voice, asymmetry of oropharynx with uvula deviation duct opening
• Labs • Usually due to mucus plug with secondary infection
– Leukocytosis
– Viral (mumps), S. aureus
– CT scan: abscess and edema
– Post 131 I therapy for thyroid cancer
– Fluid for aspiration, culture, and Gram stain
• Treatment
• Treatment
– Biopsy
– Surgical drainage/tonsillectomy
– Antibiotics: – IV antibiotics (nafcillin)
• Penicillin (PCN-allergic: erythromycin, cephalexin) – Increased salivary flow (sialogogues [lemon drops])
• Metronidazole, clindamycin – Massage of the gland

Aphthous Ulcers
• Canker sore
• Cause unknown but trauma
most common trigger
– Autoimmune association (IBD, celiac
disease, etc.)
• Clinical
– Initial tingling or burning sensation
at site © Richard Usatine, M.D. Used with permission.
– Progresses to form red spot or
bump, followed by an open ulcer
– Appears as white or yellow oval
with inflamed red border
• Treatment
– Analgesic, anesthetic agents,
antiseptics, anti-inflammatory
agents, sucralfate, silver nitrate
 Gastrointestinal System/Nutrition
Lecture 1 Esophagus
Stomach

Gastrointestinal System/Nutrition Lecture 2 Gallbladder

Liver
Pancreas

Lecture 3 Small Intestine/Colon

Dwayne Williams, PA-C Rectum
Author, The Ultimate Medical Mnemonic Comic Book
Lecture 4 Hernia
Director of Didactic Education, Infectious Diarrhea
Nutritional Deficiencies
PA Program, Long Island University Metabolic Disorders

Esophagitis
• Infectious esophagitis usually seen in immunocompromised patients
• Causes: candida, herpes, cytomegalovirus
• Clinical: Progressive odynophagia, dysphagia
Esophagus • Labs
Esophagitis – EGD, barium swallow, biopsy
Motor Disorders – Candida – linear lesions on EGD
Mallory-Weiss Tear – CMV – large, shallow ulcers on EGD
Neoplasms – HSV – small, deep ulcers on EGD

Strictures • Treatment
Varices – Fluconazole (Candida)
– Acyclovir (hsv)
– Ganciclovir (CMV) Source: Aaron Cho

Esophagitis Motor Disorders

• Other etiologies • Arise from diseases of smooth muscle or intrinsic
– Pill-induced nervous system
• Common in the elderly • Three common causes
– Achalasia (most common)
• Drugs include: alendronate, quinine, risedronate,
vitamin C, KCl, doxycycline, NSAIDS, iron sulfate – Diffuse esophageal spasm (uncommon)
• Chest pain and dysphagia
• Treatment: sucralfate
– Scleroderma
– Radiation
• Achalasia etiology
• With chest radiation over 3000 rad
– Loss of ganglion cells in Auerbach's plexus leads
– Caustic to increased tone and impaired relaxation of the LES
• Ingestion of drain cleaners, bleach, etc. (decreased nitric oxide) & absent peristalsis
 Achalasia
• Clinical Mallory-Weiss Tear
– Dysphagia: liquids and solids
• Non-penetrating mucosal tear at the GE junction
– Regurgitation hours after eating
of non-acidic material – Due to rise in transabdominal pressure
• Labs – Alcoholism strong predisposing factor
– Manometry: incomplete
– Prior history of vomiting, retching
relaxation of LES
– Esophagram: dilated, fluid-
filled esophagus, bird beak • Painless hematemesis: typically self-limiting
stricture
• Treatment
– Muscle relaxant (nifedipine), • Diagnosis: endoscopy
MC © 2010 DxR Development

– Nitroglycerin Group, Inc. All Rights Reserved.

Bird-beak
– Pneumatic Dilatation
• Treatment: often stops spontaneously,
– Botulinum toxin injection
epinephrine, cauterization

Esophageal Neoplasms Esophageal Neoplasm

• Due to chronic irritation and inflammation • Labs
Esophageal
• Both squamous cell carcinoma and adenocarcinoma dilatation
– Barium swallow
– Adenocarcinoma linked to Barrett s esophagus
(a complication of GERD) – EGD with biopsy
Neoplasm
• Risk factors: smoking, alcohol, achalasia, RT • Treatment
• Clinical – Esophagectomy
– Presents as a mechanical obstruction
– Progressive dysphagia with solids first, then liquids.
– RT/chemotherapy
– Odynophagia
(5-FU)
– Anemia, weight loss, enlarged lymph nodes

IMC © 2010 DxR Development Group, Inc. All Rights Reserved.

Esophageal Stricture
Lower esophageal ring
(Schatzki ring)
• Circumferential, lower
esophageal ring
• Clinical: intermittent solid
dysphagia
• Diagnosis: barium
swallow
• Treatment: bougie
dilators
Esophageal Stricture
• Esophageal web
Zenker's diverticulum – Non-circumferential, thin, squamous, mucosal
membrane in mid or upper portion of esophagus
• Protrusion of pharyngeal
mucosa at proximal – Clinical
esophagus
• Typically asymptomatic
• Clinical: dysphagia, • May cause dysphagia to solids only
halitosis, regurgitation – Associated with severe iron deficiency and dysphagia
• Diagnosis: barium • Plummer-Vinson syndrome
swallow
• Treatment: surgery – Treatment of Strictures:
• Dilation combined with acid-suppressive therapy
Mechanical (push-type or Bougie) or balloon dilators
Esophageal Varices
• Dilated submucosal veins
• Secondary to portal hypertension
– Portal hypertension due to cirrhosis
© Richard Usatine, M.D. Used with permission
Stomach
• Signs and symptoms of acute
upper GI bleed GERD
• Treatment Gastritis
– Endoscopy – rubber band ligation Neoplasms
– Octreotide
Peptic Ulcer Disease
– Balloon tamponade
– TIPS

© Katsumi M. Miyai, M.D., Ph.D.

Gastroesophageal Reflux Disease (GERD) GERD

• Chronic and reoccurring • Examination: Normal
• Etiology • Labs
– Loss or lack of resting LES tone, allows reflux of gastric – 24 hr pH monitoring, esophagogastroduodenoscopy (EGD)
contents into the esophagus – X-ray: barium swallow: injury, ulcer, stricture, hernia
• Persistent irritation of squamous epithelium leads to
metaplastic columnar epithelium (Barrett s esophagus)
• Diagnosis: recurrent heartburn with response to
• Precipitating factors: nicotine, alcohol, caffeine, peppermint, medication
chocolate, and anticholinergics • Treatment: lifestyle modification
• Clinical – Elevate head of bed 6 inches
– Recurrent heartburn (worse with bending over or lying down), – Stop smoking and alcohol intake
belching, regurgitation, sore throat – Reduce dietary fat and meal size, avoid bedtime snacks
– Red flags: progressive dysphagia, recurrent pneumonia, – Lose weight (if overweight)
persistent cough, bleeding® endoscopic exam required – Avoid chocolate, coffee, tea, cola, juice

GERD Gastritis
• Treatment, con t • Inflammation, erosion, or damage of the gastric mucosa
– H2 blockers • Common causes
– Proton pump inhibitors (block H+, K+-ATPase or proton – Stress
pump)
• CNS injury, burns, sepsis, surgery
– Surgery to tighten sphincter – Helicobacter pylori
• Indications • Gram-negative flagellated rod
– Refractory side effects with PPIs- headache, diarrhea
– NSAIDs
– Alternative to long-term/lifelong PPIs
• Cause injury by decreasing local prostaglandin production
– Complications in the stomach or cause direct injury to the cells by the pill

• Esophageal stricture and Barrett s esophagus

Gastritis Gastric Neoplasm
• Clinical • Types
– Due to underlying cause – Adenocarcinoma (95%)
• Men > women 2:1; never younger than age 40
– Bleeding and abdominal pain
– Lymphoma
• Labs • Stomach is common site for non-Hodgkin s lymphoma
– EGD with biopsy • Risk factors
– Tests for H. pylori (urea breath test) – H. pylori infection, dietary (excess salt and nitrates/nitrites),
smoking, pernicious anemia, chronic peptic ulcer, gastritis
• Treatment
• Clinical
– Treat underlying cause or remove causative agent
– Dyspepsia, weight loss, occult bleeding, progressive
dysphagia, postprandial vomiting, early satiety

Gastric Neoplasm Zollinger-Ellison Syndrome

• Gastrin-producing endocrine tumor (duodenal or
• Labs
– Anemia
pancreatic) leading to gastric acid hypersecretion
– LFT s increased with – Ages 35–65, Men > women 3:2
metastases • Clinical
– Low albumin with – Abdominal pain, diarrhea, heartburn
malnourishment
• Labs
– EGD with biopsy
– Barium swallow – Elevated gastrin level (off PPI and H blockers),
– Abdominal CT gastric pH <2.0
• Treatment – Secretin test: increased gastrin with secretin
– Chemotherapy administration
– Surgery (only chance for cure) IMC© 2010 DxR Development Group, Inc. All Rights Reserved. – EGD: multiple ulcers or ulcers refractory to treatment
– Radiation therapy (for • Treatment
lymphoma with chemo)
– Proton pump inhibitors
– Surgical resection

Peptic Ulcer Disease Peptic Ulcer Disease

• Imbalance between aggressive and defensive factors in • Exam
the gastroduodenal mucosa
– Physical examination typically unrevealing
– Mucosal defect at least 0.5 cm in diameter penetrates the
muscularis mucosae – Tenderness in RUQ/epigastrium is unusual
• Factors: H. pylori, NSAIDs, acid secretory abnormalities, – Possible peritoneal signs if rupture
stress (medical conditions)
– Increase risk of H. pylori with use of PPI and H2 blockers • Labs
• Clinical – H. pylori testing: biopsy, serology, stool antigen test,
– Recurrent episodes of deep, gnawing, or burning pain in breath test
midepigastric region
• Breath test or stool antigen helpful with follow-up
– Pain with eating (gastric ulcer), awakening at night
– Relief with food (duodenal ulcers) – EGD with biopsy – definitive diagnosis
– Nausea with or without vomiting
 Peptic Ulcer Disease H. Pylori Treatment
• Treatment Drug Class Drug Triple Therapy Quadruple
Therapy
– Lifestyle changes Acid suppression Proton pump 20-40 mg bid 20-40 mg bid
– Stop offending agents if possible inhibitor
Standard Bismuth compound 2 tablets bid 2 tablets bid
– H. pylori therapy antimicrobials
Amoxicillin 1 g bid
– Proton pump inhibitors Metronidazole 500 mg bid 500 mg tid
– H2 blockers Clarithromycin 500 mg bid
– Misoprostol (drug-induced ulcers) Tetracycline 500 mg qid
Salvage Levofloxacin 300 mg bid
– Surgery - indications include UGI bleeding, perforation, antimicrobials
Rifabutin 150 mg bid
refractory ulcers, and gastric outlet obstruction
Furazolidone 100 mg bid

• Triple therapy: PPI or bismuth with 2 of the above antibiotics for 7–14 days
• Quadruple therapy: PPI plus bismuth with 2 of the above antibiotics for 4–10 days

Gastrointestinal System/Nutrition
Lecture 1 Esophagus
Stomach Liver/Biliary System
Lecture 2 Gallbladder Liver Function Tests
Liver
Pancreas Cholecystitis
Lecture 3 Small Intestine/Colon Cholangitis
Rectum
Hepatitis
Lecture 4 Hernia
Diarrhea
Cirrhosis
Nutritional Deficiencies
Metabolic Disorders

Liver Function Tests Aminotransferases

• Hepatocellular damage • Cholestasis • AST (SGOT)/ALT (SGPT)
– AST/ALT – Alkaline phosphatase – Released with hepatocellular damage
– LDH – GGT • Also found in skeletal muscle
– Urobilinogen – Bilirubin – ALT more liver-specific
– Urobilinogen
– Increased in hepatitis, toxic injury, ischemic injury,
• Liver synthesis cirrhosis
– Albumin (decreased) • False elevations seen in medications such as erythromycin
– Prothrombin time (increased) – Very high levels rare in alcoholic liver disease
– Cholesterol (AST <300 IU/L)
– AST/ALT ratio >2:1 helpful in alcoholic hepatitis or
cirrhosis
Alkaline Phosphatase
• Found in bone, liver, intestine, kidney and placenta
• Elevations seen in acute biliary obstruction
– Obstruction due to gallstones can take several hours
until elevation of alkaline phosphatase.
– Also elevated in:
• Chronic inflammation of bile ducts (primary biliary
cirrhosis)
• Infiltrative process (neoplasm or TB)
• Cholestatic disease (drug toxicity)
• Biliary obstruction (neoplasm or cholelithiasis)
Increased Alkaline phosphatase with increased GGT think cholestasis
GGT
• Gamma-glutamyl transpeptidase
• Increased in cholestasis
– Sensitive marker for biliary tract disease but lacks
specificity
• Alcohol use may also increase GGT levels
– Maybe useful in screening for alcohol abuse
• Use means 3 or more drinks (>45 g) per day
– Also increased in phenobarbital and phenytoin use

Increased Alkaline phosphatase with normal GGT may be indicative of bone disorders

Bilirubin Lipids and Proteins

• Breakdown product of heme metabolism • Total and free cholesterol increased in cholestatic
• Jaundice does not occur until level >2.5 mg/dL disease

• Can be elevated in both hepatocellular & cholestatic • Increased triglycerides seen in liver parenchymal
disease injury
• Isolated elevations without increase in LFTs may be • Albumin decrease reflects severe, chronic
familial or hemolysis hepatocellular injury
– Gilbert s syndrome (unconjugated or indirect) – Due to decreased synthesis
– Dubin-Johnson syndrome (conjugated or direct) • Isolated low albumin due to renal loss or malnutrition,
or an inflammatory state
– Rotor syndrome

Others Cholecystitis
• Ceruloplasmin • Inflammation of the gallbladder
– Decreased in Wilson s disease • Etiology: obstruction by a stone in cystic duct; distention
• Ammonia and inflammation; infection by bowel flora
• Risk factors
– Hepatic encephalopathy
– Age 40s, women, obesity, parity, elevated triglycerides,
• Prothrombin time medications (estrogen, clofibrate, ceftriaxone,
– Factors II, V, VII, IX, and X produced in the liver Sandostatin)
• Clinical
– Elevated PT is evidence of severe liver dysfunction/failure
– RUQ pain, fever, leukocytosis
– ↑ when more than ¾ of liver s synthetic capacity is lost – Pain is steady, unremitting, may radiate to right scapula
• 15–30 min after a meal
– Nausea and vomiting; dehydration
 Cholecystitis Cholecystitis
• Exam • Radiology
– RUQ tenderness, decreased bowel sounds, guarding, – Ultrasound: look for
tachycardia thick gallbladder wall,
sludge, and stones
– Positive Murphy s sign
– HIDA scan: gallbladder
• Labs fails to fill
– Increased WBC with a left shift • Treatment
– Increased bilirubin and alkaline phosphatase – Antibiotics: ampicillin
plus an aminoglycoside
– Surgery
(cholecystectomy)

Cholangitis Hepatitis
• Infection of the bile duct • Inflammation of the hepatocytes
– Caused by bacteria (E. coli, Klebsiella, Enterococcus) • Caused by toxins and viruses
ascending from the duodenum – Five hepatitis viruses: A, B, C, D, E
– Due to gall stones, strictures, tumors – Toxins/drugs include alcohol, acetaminophen, isoniazid, lovastatin
– Autoimmune (women, positive ANA, treatment: steroids)
• Symptoms: jaundice, fever, abdominal pain in RUQ, • Clinical
malaise, and hypotension – Fatigue, malaise, nausea, anorexia
• Physical exam: include jaundice, RUQ tenderness – Skin and scleral icterus
– Charcot s triad- abdominal pain, jaundice, fever – Hepatomegaly
– Dark urine and light stools
• Labs: Increased WBC count and LFTs
• Labs
• Diagnosis: ultrasound, ERCP – Elevated AST and ALT (10–20x normal)
• Treatment: IV antibiotics (PCN and aminoglycosides), – Prothrombin time
ERCP – Serology testing © Richard Usatine, M.D. Used with permission

Hepatitis A Hepatitis B
• Transmitted by • Transmitted by direct contact with blood or body fluids,
fecal-oral route, sexual contact
shellfish
• Acute and chronic disease
• No chronic
hepatitis • Incubation 60-100 days
• Incubation 20-40 • Treatment
days
– Lamivudine (Epivir-HBV) (nucleoside reverse
• Serology transcriptase inhibitor)
• Treatment • Interferon not helpful
– Vaccine – Prophylaxis: hepatitis B immunoglobulin used in
– Post-exposure newborns of infected mothers, percutaneous, or sexual
immunoglobulin exposure
to contacts
cdc.gov – Vaccine at 0, 1, and 6 months
Hepatitis B Hepatitis B Serology
Anti-HBeAb

Anti-HBcAb
HBsAg

HBeAg

Anti-HBsAb

cdc.gov cdc.gov

Hepatitis B Hepatitis C
• Transmitted by blood and body fluids
• Time to seroconversion: 6 weeks
• 50–80% develop chronic hepatitis
– Link between hepatitis C and hepatocellular cancer
• Serology
– Hepatitis C antibody
• Treatment
– Peginterferon alfa and ribavirin (chronic)
– New options
cdc.gov • Simeprevir (Olysio)- protease inhibitor
• Sofosbuvir (Sovaldi)- polymerase inhibitor

Hepatitis C Hepatitis D
• Delta hepatitis
• Transmitted parenterally
• Seen only in conjunction with hepatitis B
• Serology
– Hepatitis delta antibody
• Treatment
– Hepatitis B vaccine

cdc.gov
 Hepatitis E Hepatitis Summary
• Transmitted by
fecal-oral route
Virus Spread Incubation Chronic Diagnosis Antibodies
• Incubation 15- Period Disease
60 days A Fecal-oral 15–45 days No IgM anti-HAV Anti-HAV
• Contaminated B Parenteral 30–180 5% HBsAg Anti-HBs
Sexual days Anti-HBc
food and water Anti-HBe
• No chronic C Parenteral 15–150 50-80% HCV RNA Anti-HCV
days
disease
D Parenteral 30–150 5% Presence of Anti-HDV
• Treatment: Sexual days hepatitis B
none E Fecal-oral 30–60 days No IgM anti-HEV Anti-HEV
cdc.gov

Cirrhosis Cirrhosis Spider angiomas Palmar erythema

• End-stage of chronic liver Causes of Cirrhosis • Physical exam

disease Alcohol abuse – Jaundice
– Involves fibrosis and is Viral hepatitis: B, D, C – Edema
irreversible
Metabolic disorders – Spider angiomas
• Clinical
Autoimmune hepatitis – Telangiectasis
– Weakness/fatigue © Richard Usatine,M.D. Used with permission

Biliary disorders – Palmar erythema Gynecomastia

– Anorexia
Drugs and toxins – Purpura
– Weight loss
Nonalcoholic fatty liver – Signs of
– Abdominal pain
feminization
– Muscle atrophy
– Small right liver
lobe
© Richard Usatine,M.D. Used with permission

Cirrhosis Treatment of Complications

• Diagnosis
– Determine underlying cause
– Abdominal ultrasound
– CT scan with liver biopsy
• Treatment
– Avoid alcohol
– Treat underlying cause,
symptoms, complications
– Liver transplant
• Complications
– Portal hypertension
– Varices and hemorrhage
– Ascites
– Hepatorenal syndrome
• Varices
– Beta blockers (to decrease portal pressure)
• Ascites
– Salt restriction (2 g/day) and spironolactone
– Paracentesis
• Hepatorenal syndrome
– Transplant
• Spontaneous bacterial peritonitis
– Cefotaxime, ceftriaxone, amoxicillin-clavulanic acid
– Spontaneous bacterial peritonitis • Hepatic encephalopathy
– Encephalopathy – Lactulose
– Jaundice
Metabolic Diseases of the Liver Portal Hypertension
• Due to arteriovenous shunting and/or mechanical
Disease Genetics Clinical Labs Treatment
a-1-antitrypsin Recessive • COPD ¯ a-1-antitrypsin Transplant
obstruction
• Cirrhosis Phenotyping • Clinical
Wilson s disease Autosomal • Kayser-Fleischer ­ Copper level Chelation
recessive rings ¯ Ceruloplasmin – Caput medusae
• Cirrhosis
– Marked ascites
Hemochromatosis Autosomal • Abdominal pain ­Ferritin Phlebotomy
recessive • Hepatomegaly ­Hepatic iron – Hypersplenism
• Cirrhosis Index
– Liver failure
• Complications
– Esophageal varices
– Hemorrhoids

Primary Biliary Cirrhosis

• Idiopathic autoimmune disorder noted in middle-aged
women
• Presents with fatigue and pruritus
• Elevated alkaline phosphatase and GGT Pancreas
• Diagnosis by biopsy and positive antimitochondrial Acute/Chronic Pancreatitis
antibody
Pancreatic Cancer
• Treatment
– Ursodeoxycholic acid or cholestyramine
– Steroids are of no benefit
– Ultraviolet light for the pruritus

Acute Pancreatitis Acute Pancreatitis

• Inflammatory disease of the pancreas • Clinical
– Constant mid-epigastric/
– Results in edema, vascular injury, tissue loss, and LUQ deep, boring pain
necrosis
– Radiation to the back
– Pancreas returns to normal after the episode – Severe nausea and
• Etiology vomiting
– Gallstones, alcohol, medications, trauma, • Exam
hyperlipidemia – Patient should avoid lying
• Medications include immunosuppressants, supine
trimethoprim-sulfamethoxazole (TMP/SXT), – Decreased bowel sounds
pentamidine, didanosine, furosemide, thiazide – Grey-Turner s sign: flank
diuretics, ACE-inhibitors, and estrogens ecchymosis
• Hypertriglyceridemia levels typically >1,000 mg/dL – Cullen s sign:
periumbilical ecchymosis
– Pleural effusion
 Acute Pancreatitis Acute Pancreatitis
• Labs • Treatment
– ↑ Amylase and lipase – Alcohol abstinence Ranson s Criteria
• Amylase increase in 2-12 hours, – Pain control On Admission Within 48 hours
decrease over 3-5 days Age >55 years Hct ¯ by >10%
– NPO
• Lipase best test & elevated WBC >16,000/µL BUN ­ by >5 mg/dL
– IV fluids
longer AST >250 U/L Ca++ <8 mg/dL
– ↑ AST/ALT & alkaline • Complications LDH >350 U/L Art. pO2 <60 mm Hg
phosphatase – Ranson s criteria Glucose >200 mg/dL Base deficit >4 mEq/L
– ↑ Glucose & decreased calcium – Infection,
– Leukocytosis
IMC, © 2010 DxR Development Group, Inc. All Rights
Reserved. pseudocysts, Fluid sequestration >6L
renal/respiratory
– Ultrasound to rule out
failure
gallbladder disease
– CT scan to evaluate for
complications

Chronic Pancreatitis Chronic Pancreatitis

• Inflammatory disease with progressive and permanent • Labs
damage to the pancreas – Amylase and lipase: normal to mild elevation
– Alcohol abuse (90% of cases) – Bilirubin increased, hyperglycemia
– Gallstones do not cause chronic pancreatitis – 72-hr fecal fat (measures pancreatic exocrine function)
• Clinical • X-ray
– Intermittent or chronic abdominal pain – Pancreatic calcifications on abdominal x-ray
– Diarrhea and steatorrhea – Ultrasound
– Weight loss, jaundice – ERCP (best test)

• Exam • Treatment
– Thin patient, mild jaundice – Abstinence from alcohol – Enzyme replacement for malabsorption

– Diffuse abdominal tenderness – Pain control – Surgery

Pancreatic Cancer Pancreatic Cancer

• Ductal adenocarcinoma most common • Exam
– 5-year survival rate of <5% – Large, non-tender, palpable gallbladder
• Risk factors (Courvoisier's sign)
– Smoking, history of chronic pancreatitis, obesity, high-fat – Jaundice
diet • Labs
• Clinical – Anemia, elevated alkaline phosphatase, bilirubin,
– Early AST/ALT
• Nonspecific abdominal pain, nausea/vomiting, anorexia, – ERCP with biopsy
malaise – Tumor marker CA-19-9 positive
– Late – CT scan
• Weight loss, obstructive jaundice • Treatment
– Classic painless jaundice is not very common – Palliative care
– Surgery: RT and chemotherapy (5-FU or gemcitabine)
 Gastrointestinal System/Nutrition
Lecture 1 Esophagus
Stomach Small Intestine/Colon
Lecture 2 Gallbladder Appendicitis
Liver
Pancreas Diverticular Disease
Inflammatory Bowel Disease
Lecture 3 Small Intestine/Colon
Rectum Irritable Bowel Disease
Ischemic Bowel Disease
Lecture 4 Hernia
Diarrhea Neoplasms
Nutritional Deficiencies Obstruction
Metabolic Disorders
Toxic Megacolon

Appendicitis Appendicitis
• Due to obstruction of appendiceal lumen by a fecalith • Exam
– Leads to inflammation and infection – Guarding RLQ, cutaneous hypersensitivity
– Positive Rovsing s sign
– Ages 10–30
– Positive psoas/obturator sign with peritonitis
• Clinical
• Labs
– Initial: intermittent periumbilical pain – Increased WBC with left shift
– 12 hrs later: pain RLQ (McBurney s point), worse with – Ultrasound, CT scan
movement • Treatment
– Nausea, low-grade fever, decreased appetite – Appendectomy

Abdominal Pain: Differential Diverticular Disease

Right Upper Quadrant Epigastric Left Upper Quadrant
• Onset >40 years
• Cholecystis • Gastric ulcer • Gastritis • Diverticulosis: presence of diverticula
• Choledocholithiasis • Gastritis • Peptic ulcer disease
• Duodenal ulcer • Pancreatitis • Splenic infarct • Diverticulitis: inflammation & infection of diverticulum
• Pneumonia • Esophagitis • Colonic ischemia
• Pulmonary embolus • Myocardial infarct • Pneumonia
• Fitz-Hugh-Curtis • Cholecystitis • Myocardial infract • Clinical
Right Lower Quadrant Periumbilical Left Lower Quadrant – Diverticulosis: 80% asymptomatic. Painless rectal
• Appendicitis • Early appendicitis • Diverticulitis bleeding (Most common cause of lower GI bleed).
• Crohn s disease • SBO • IBD crampy LLQ pain (rare).
• Ileitis • Pancreatitis • Colonic ischemia
• Ovarian cyst • Gastroenteritis • Ovarian cyst
• Tubal pregnancy • AAA • Tubal pregnancy – Diverticulitis: acute LLQ pain, anorexia, fever, chills,
nausea/vomiting, positive peritoneal signs
• Rectal bleeding is rare
 Diverticular Disease Diverticular Disease
• Exam • Treatment
– Diverticulosis: firm, tender
mass LLQ, rectal bleeding – Diverticulosis
– Diverticulitis: ↓ bowel sounds,
distention, rebound • High fiber diet
tenderness
and guarding, fever
• Labs
– Diverticulosis: normal labs – Diverticulitis
– Diverticulitis:
• Antibiotics
↑ WBC with left shift
– Broad spectrum:
• Radiology
– Air-fluid levels
e.g. Metronidazole + either Ciprofloxacin or TMP-SMX
– BE: lesions, appendages
IMC © 2010 DxR Development Group, Inc. All Rights Reserved.
• Clear liquid diet and IVF
– CT scan: abscess,
perforations, colonic wall • Surgery (young patients, ages <40)
thickening

Ulcerative Colitis Ulcerative Colitis

• Men = women, ages 15–25 and 55–65 • Exam
• Complications: 1/3 develop colon cancer – Pale, tachycardia, fever
• Involves only mucosa and submucosa of the colon – Distention, decreased
– Starts in rectum and is continuous bowel sounds,
tenderness LLQ
– Fistulas and fissures are rare
– Heme (+) stools
• Clinical
• Labs
– Pain LLQ
– CBC: anemia,
– Fever, weight loss, fecal urgency, and incontinence leukocytosis
– Bloody/mucous-containing diarrhea – Elevated sedimentation
– Systemic signs: arthritis rate IMC © 2010 DxR Development Group, Inc. All Rights Reserved.

– BE: loss of haustral

markings, luminal
narrowing

Ulcerative Colitis Crohn's Disease

• Sigmoidoscopy/Colonoscopy • Peak ages 15–25 and 55–65
– Edema, pus, easy friability
• Can affect any GI mucosa
• Treatment
• Is transmural
– 5-aminosalicylic acid
– Steroids – Fistulas and fissures are common
– Anti-tumor necrosis factor – Skip lesion, cobblestone
antibody appearance
• Infliximab • Clinical
– Immunomodulators – Diarrhea, abdominal pain, weight loss
• Azathioprine and 6- – Low-grade fever
mercaptopurine
– Relief of pain with defecation
– Surgery: colectomy © Katsumi M. Miyai, M.D., Ph.D.

• Complications
– Toxic megacolon
© Katsumi M. Miyai, M.D., Ph.D.
Crohn's Disease Crohn's Disease
• Exam • Treatment
– Thin, undernourished – 5-aminosalicylic acid (mainstay of therapy)
– Aphthous ulcers: lips, buccal mucosa – Steroids
– Tender RLQ
– Anti-tumor necrosis factor antibody (infliximab)
• Location varies depending on location of disease
– Rectal: fistula, fissures – Immunomodulators (azathioprine and 6-
mercaptopurine)
• Labs
– Slight increase in WBC and anemia – Surgery: colon resection
– UGI series • Complications
– BE: rectal sparing, edema, ulcerations – Abscess, fistula, obstruction, perianal disease
– Sigmoidoscopy/colonoscopy: cobblestoning, skip
lesions

Ulcerative Colitis vs. Crohn s Celiac Disease

• Inflammatory reaction in upper small intestine
Ulcerative Colitis Crohn s Disease • Present with iron deficiency anemia
Pathologic • Autoimmune disorder
• Rectal involvement • Always • Common
• Fissures/fistulas • Never • Common – 1% of population
• Skip lesions • Never • Always
• Perianal disease • Never • Common – Women > men

Clinical – Breastfeeding may be protective

• Rectal bleeding • Always • Occasional
• Malaise, fever • Occasional • Common – European ancestry, Middle Eastern, Asian, North
• Abdominal pain • Occasional • Common African
• Abdominal mass • Never • Common
• Precipitated by ingestion of gluten
Endoscopic
• Cobblestoning • Rare • Common – Found in wheat, barley, rye

Celiac Disease Irritable Bowel Syndrome (IBS)

• Clinical • Due to abnormal motor function of the GI tract and
– Watery diarrhea, abdominal pain increased gut visceral sensitivity
– Malabsorption symptoms • Women > men; onset age 30–50
– Dermatitis herpetiformis- vesicular rash
• Signs and symptoms
on extensor surfaces
– Crampy, lower abdominal pain that is relieved by
• Diagnosis defecation
– IgA tissue transglutaminase (tTG) antibody – Irregular disturbances in defecation (constipation &
(screening test)
diarrhea)
– Endomysial antibodies
– Small bowel biopsy – definitive diagnosis
– Abdominal bloating
– Response to gluten-free diet • Physical exam
• Treatment: gluten-free diet – Abdominal tenderness
© Katsumi M. Miyai, M.D., Ph.D.

• Complications: osteoporosis
Irritable Bowel Syndrome Chronic Mesenteric Ischemia
• Diagnosis Episodic intestinal hypoperfusion related to eating
– Rome criteria (2 or more) • Etiology
• Pain or discomfort relieved by defecation – History of atherosclerotic disease most common.
• Pain associated with increased or decreased stool – Rare: vasculitis, fibromuscular dysplasia
frequency • Clinical
• Pain associated with harder or looser stools – Chronic dull abdominal pain worse after meals intestinal
– Watch for red flags of cancer (weight loss, bleeding, etc.) angina
• Treatment – Anorexia & weight loss (aversion to eating due to pain)

– Increase fiber, avoid milk products and high-fat diet • Exam

– Diarrhea: Antispasmodics: Dicyclomine, Hyoscyamine. – Minimal exam findings

Loperamide • Labs
– Angiogram – definitive diagnostic test
– Constipation: prokinetics, bulk forming laxatives.
Lubiprostone • Treatment:
– Surgical revascularization definitive

Acute Mesenteric Ischemia Colorectal Cancer

Acute arterial occlusion • Typically adenocarcinoma

• Etiology • Peak incidence ages 60–80

– <10% before age 50
– Embolism most common (A fib, MI, valvular disease).
• Risk factors
– Thrombosis (atherosclerosis), non-occlusive arterial disease,
venous thrombosis – High fat/low fiber diet,
smoking, ulcerative colitis,
• Clinical familial polyposis, alcohol
– Acute severe abdominal pain out of proportion to intake
physical exam findings, melena.
• Clinical
• Exam – Asymptomatic for years
– Minimal exam findings. Peritonitis & shock if advanced disease. – Weight loss, anemia
• Labs – R-sided: rectal bleeding,
– Elevated WBC, amylase, CPK diarrhea
– Angiogram – definitive diagnosis – L-sided: bowel obstruction,
change in stool diameter,
• Treatment:
hematochezia
– Surgical revascularization. Systemic anticoagulation. © Katsumi M. Miyai, M.D., Ph.D.

Colorectal Cancer Screening for Colorectal Cancer:

Clinical Summary of a U.S. Preventive Services Task Force
• Exam
Recommendation (Adults)
– Occult bleeding on DRE
Population Ages 50-75 Ages 76-85 Older than age 85
• Labs
Recommendation Screen with high- Do not screen Do not screen
– Fe deficiency anemia sensitivity FOBT, routinely
sigmoidoscopy, or
– Increased CEA colonoscopy
– Colonoscopy with biopsy Screening Test High-sensitivity FOBT, sigmoidoscopy with FOBT, and colonoscopy
are effective
– BE: mass - “apple core” lesion
Screening Test Annual screening with high-sensitivity FOBT
• Treatment Intervals Sigmoidoscopy every 5 years, with high sensitivity FOBT every 3 years
Screening colonoscopy every 10 years
– Tumor resection: colectomy
Other USPSTF does not recommend the use of aspirin or NSAIDs for the
– Chemotherapy: 5-FU primary prevention of colorectal cancer
uspreventiveservicetask.com November 2008
– Radiation (for rectal cancer with
chemo)
– Monitor response with CEA
IMC © 2010 DxR Development Group, Inc. All Rights Reserved.
 Colon Cancer Syndromes: Inherited Small Intestine Obstruction
• Familial polyposis • Adhesions are the most common cause
– Young age (35 yo), numerous polyps – Also due to hernia, neoplasms, intussusception, volvulus

• Hereditary nonpolyposis colorectal cancer • Types

– Lynch s syndrome – Mechanical- due to a physical barrier
– Most common, autosomal dominant – Paralytic ileus- neurogenic failure of peristalsis

– Onset age 40, no polyps – Simple- occludes the lumen only

– Strangulation- impairs the blood flow and leads to necrosis
• Gardner s syndrome
– Numerous polyps but also extraintestinal • Presentation
– Vomiting, crampy abdominal pain
manifestations
– Increased bowel sounds, abdominal distention
• Peutz-Jeghers syndrome
– Autosomal dominant, age 20s
– Polyps, mucocutaneous pigmentation

Small Intestine Obstruction Large Intestine Obstruction

• X-ray • Secondary to carcinoma, volvulus, diverticular disease,
– Abdominal x-rays inflammatory disorders, fecal impaction
reveal ladderlike
• Presentation
pattern of dilated
– Deep, visceral, cramping pain referred to the hypogastrium
small bowel loops
with air-fluid levels – High pitched bowel sounds
• Colon is devoid – Constipation or obstipation
of gas – Abdominal tenderness
• Treatment • X-ray
– Decompression with – CT scan with rectal contrast is test of choice
nasogastric tube – Abdominal x-ray reveals a distended colon in a picture-frame
– Surgery outline of the abdominal cavity

© James Van Rhee

• Treatment- surgery

Toxic Megacolon
• Nonobstructive extreme colon dilation >6cm + toxicity
• Can be seen with ulcerative colitis & CMV colitis.
• Presentation
– Profound bloody diarrhea
– Abdominal pain, nausea, vomiting, tenesmus Rectal Disorders
– PE: lower abdominal tenderness & abdominal distention
Anal Fissures
– Signs of toxicity: AMS, fever, tachycardia, hypotension,
dehydration. Perianal Abscess
– Peritoneal signs – rigidity, guarding or rebound tenderness.
Hemorrhoids
Pilonidal Disease
• Diagnosis colonic diameter >6 cm on plain films
• Treatment
– Supportive mainstay – bowel rest, NG suction, antibiotics & fluids
– If patient worsens or fails to improve then surgery to prevent
perforation
Anal Fissure Perianal Abscess
• Linear shaped ulcers , typically <5 mm in length • Infected anal glands at base of anal crypts at the
– Most commonly in the posterior midline dentate line
– If off midline think Crohn s disease • Presentation
– Chronic fissures result in skin tags at outermost edge (sentinel pile) – Throbbing, continuous perianal pain
• Typically arise from trauma – Erythema, fluctuance, and swelling
• Presentation • Treatment
– Severe, tearing pain during defecation followed by throbbing pain – Local incision and drainage
– Hematochezia
• Treatment
– Supportive mainstay – Fiber supplements, sitz baths, increased
water intake, stool softeners
– Topical anesthetics

Hemorrhoid Pilonidal Disease

• Symptomatic as a result of activities that increase • Epithelial tissues trapped in the natal cleft
venous pressure – Caused by infection of hair follicle
– Straining, constipation, prolonged sitting, pregnancy, obesity
• Presentation • Increased incidence in young adults
– Rectal bleeding – Men > women
– May enlarge and protrude from anal opening – Patients with hirsutism predisposed to disease, obese
– Pain noted with external hemorrhoids, rare with internal
– External hemorrhoids are noted on perianal inspection
• Clinical
• Treatment – Pain in area
– High-fiber diet, increase fluid intake, stool softeners – Drainage
– Sclerotherapy, rubber band ligation, electrocoagulation
– Surgical excision (hemorrhoidectomy)

Pilonidal Disease
• Exam
– Multiple midline sinuses Gastrointestinal System/Nutrition
– Abscess, tenderness Lecture 1 Esophagus
Stomach
• Treatment
Lecture 2 Gallbladder
– Good hygiene Liver
Pancreas
– Surgery: excision of sinus
Lecture 3 Small Intestine/Colon
• Complications Rectum
– Abscess formation
Lecture 4 Hernia
Diarrhea
Nutritional Deficiencies
Metabolic Disorders
 Hernia
• Indirect
– Passes from internal inguinal ring obliquely toward the external
inguinal ring and into scrotum

Hernia • Direct
– Protrudes outward and forward and is medial to the internal
inguinal ring
• Diagnosis
– Bulge in the inguinal region
– Pain or vague discomfort in the region
• Extreme pain with strangulation

Hernia
• Physical exam
– Bulge in inguinal region
– Cough or Valsalva maneuver can facilitate identification
– Exam results Diarrhea
• Bulge moving lateral to medial suggests indirect
• Bulge progresses from deep to superficial through inguinal
floor suggests direct
• Bulge identified below the inguinal ligament suggests
femoral hernia
• Ultrasound may assist in diagnosis
• Treatment- surgery

Diarrhea Osmotic vs. Secretory Diarrhea

• Increased volume and liquidity of stool Feature Osmotic Secretory
• Acute vs. chronic Effect of fasting Diarrhea stops Diarrhea usually
– Acute: duration 2–3 weeks continues
– Chronic: greater than 4 weeks Fecal pH Frequently Normal
• Types of diarrhea decreased
– Secretory: E. coli toxin, Salmonella, Clostridium perfringens toxin
Fecal osmolality 330 290
– Osmotic: lactose deficiency, laxatives
Fecal electrolytes
– Inflammatory: IBD, radiation colitis, ischemic colitis,
Sodium (Na) 30 100
pseudomembranous Potassium (K) 30 40
• Must separate infectious from non-infectious (Na + K) x 2 120 280
Osmotic gap 210 10
 Diarrhea Etiology: Infectious Diarrhea
• Infectious • Non-infectious Viral Bacterial Protozoal

– 80% of acute diarrheas – 20% of acute diarrheas Rotavirus Shigella Giardia lamblia

– Clinical – Clinical Norovirus Salmonella Entamoeba

Norovirus-like agent Campylobacter Cryptosporidium
• Bloody diarrhea, • Watery diarrhea,
abdominal pain, crampy abdominal Enteric adenovirus Escherichia coli
dysentery, fecal WBC pain, no fecal WBC Calicivirus Yersinia
– Epidemiology – Epidemiology Astrovirus Clostridium difficile
• Food, antibiotics, • Medications, Small round viruses Clostridium perfringens
sexual activity, ingestion of osmotic Coronavirus Staphylococcus aureus
daycare, outbreaks, particles, fecal Herpes simplex virus Bacillus cereus
hospitalization impaction Cytomegalovirus Vibrio
Chlamydia
Neisseria gonorrhoeae

Infectious Diarrhea Pseudomembranous Colitis

• Etiology
Organism Spread Comments Treatment – Post antibiotics or chemotherapy
E. coli Fecal Traveler s diarrhea TMP-SMX • Clinical signs
(Not 0157:H7) contamination of Secretory Fluoroquinolone
food and water – Inflammatory diarrhea
Campylobacter Contaminated Self-limited Fluoroquinolone • Lab evaluation
water or milk Short duration Azithromycin
– Many fecal WBC
Salmonella Contamination of Acute, self-limited None
eggs and milk – Positive C. difficile toxins
Crampy abd pain
Shigella Fecal/oral Daycares Ampicillin or • Treatment
Bloody diarrhea TMP-SMX – Oral Vancomycin, Fidaxomicin
Giardia Fecal Water-borne Metronidazole – Metronidazole
contamination of infection
water
Norovirus/ Person-to-person Self-limited disease None
Rotavirus

Diarrhea- Other
• Ciguatera toxin
– Found in barracuda, red snapper, grouper
– Symptoms within 2-6 hours of ingestion
• Paresthesias, numbness, nausea, vomiting, abdominal cramps Nutritional Deficiencies
– No specific treatment
• Scombroid Niacin
– Ingestion of scombroid fish (tuna, mackerel, mahi mahi) Thiamine
– Contain large amount of histamine and cause:
• Rash, diarrhea, vomiting, wheezing, dizziness Vitamin A
– Treatment Riboflavin
• Antihistamines
Vitamin C
Vitamin D
Vitamin K
Nutritional Deficiencies Nutritional Deficiencies
• Niacin (B3) • Vitamin A
– Pellagra – Night blindness, xerosis, poor wound healing
– Due to diets high in corn and which lack tryptophan – Treatment: vitamin A
– 3 Ds: Dermatitis, Dementia, Diarrhea • Riboflavin
– Neovascularization of cornea, dermatitis
• Thiamine (vitamin B1)
– Glossitis, cheilosis, angular stomatitis
– Anorexia, muscle cramps, paresthesias, loss of reflexes
• Vitamin C (scurvy)
– High output heart failure, dilated cardiomyopathy
– Bleeding perifollicular and bruising upper thighs
– Wernicke’s encephalopathy: triad of ataxia, global – Bleeding gums: secondary to gingivitis
confusion and ophthalmoplegia.
– Due to poor diet, smoking
– Korsakoff dementia: memory loss, confabulation
– Treatment: thiamine injections

Nutritional Deficiencies
• Vitamin D
– Rickets, osteomalacia, osteoporosis, muscle weakness
– Treatment: vitamin D
Metabolic Disorders
• Vitamin K
Lactose Intolerance
– Bruising and bleeding
Phenylketonuria
– Treatment: SQ vitamin K

Lactose Intolerance Phenylketonuria

• Lactase is a brush border enzyme that hydrolyzes • Hereditary (recessive) familial disease
lactose into glucose and galactose
• Deficiency of phenylalanine hydroxylase
• Presentation
– Diarrhea, bloating, flatulence, and abdominal pain after • Children often blonde and blue-eyed
ingestion of milk products • After birth, develop vomiting, irritability, convulsions,
• Diagnosis mental retardation
– Improvement on lactose-free diet
– Hydrogen breath test • Urine has musty odor
• Treatment • Screen 24 hours after birth
– Lactase enzyme replacement
• Treatment: diet low in phenylalanine
Toxicology
• Physical findings See handout for poisoning antidotes
– Miosis
• Clonidine, barbiturates, opiates, cholinergic
– Mydriasis Other
• Sympathomimetics, anticholinergics
– Dry skin
Nut Allergies
• Anticholinergics Fecal Impaction
– Wet skin Obesity
• Cholinergics, sympathomimetic
– Blisters
• Barbiturates, carbon monoxide poisoning

Peanut, Tree Nut and Seed Allergies
• Among one of the most common food allergies
• Pathophysiology
– Most are IgE mediated but can be non-IgE mediated or mixed
• Risk Factors
– Genetics - siblings of children with peanut allergy are at
increased risk of developing a peanut allergy.
– Family history of personal history of atopic disease
– Family history of peanut allergy
– Timing of exposure – delayed introduction of nuts until > 3
years of age associated with increased risk
Peanut, Tree Nut and Seed Allergies
• Clinical Manifestations
– Skin: pruritus, flushing, diaphoresis, urticaria & angioedema,
contact urticaria
– Oropharyngeal: sneezing, nasal congestion, oral pruritus,
rhinorrhea
– Respiratory: wheezing, dyspnea, cough
– Cardiovascular: arrhythmias
– Eyes: conjunctival injection, lacrimation, pruritus & periorbital
edema
– GI: nausea, vomiting, abdominal pain, diarrhea
– Neurologic: dizziness, syncope, sense of doom

Peanut, Tree Nut and Seed Allergies

• Management
– Patient education on avoiding products containing or cooked
with the associated foods
– Complete avoidance of foods and similar foods
Other
– Epinephrine autoinjectors should be prescribed in case of
accidental exposure and reaction. Nut Allergies
– Acute attack – Antihistamines if mild.
• Epinephrine if severe
Fecal Impaction
Obesity
Fecal Impaction
• Fecal impaction occurs from the decreased ability to
sense and respond to the presence of stool in the
rectum.
• Risk Factors
– Age, physical inactivity
– Medications: opiates, tricyclic antidepressants,
antihypertensive agents, iron, anti-Parkinsonian agents
– Endocrine: hypothyroidism, hypocalcemia, diabetes mellitus
– Neurological: Parkinson disease, autonomic neuropathy,
Parkinson disease, multiple sclerosis
– Other: low fiber diet, dehydration, inactive lifestyle, colorectal
cancer
Fecal Impaction
• Diagnosis
– Digital rectal examination – copious amounts of stool in the
rectum.
– Abdominal radiograph can confirm the diagnosis in certain
cases.
• Management
– Disempaction and colon evacuation – digital (manual)
disempaction, warm water enema with mineral oil. This can be
followed by polyethylene glycol orally or via NG tube.
– Colonscope evacuation may be needed in severe cases.
– Maintenance of bowel regimen to prevent recurrent episodes.

Obesity
• Body mass index (BMI) ≥30 kg/m2 or body weight
≥20% over their ideal weight.

Other • Obesity associated with increased risk for coronary

disease, diabetes mellitus II, breast & colon cancers.
Nut Allergies
Fecal Impaction
• About 50% of patients experience binge eating
Obesity episodes.

Obesity
• Management
– Behavior modification: exercise & dietary changes, group therapy.

– Medical therapy: antidepressants if there is underlying depression. Gastroenterology

Treat any complications.
Duodenal Atresia
– Anti-obesity medications:
Intussusception
• Orlistat (decreases GI fat digestion)
• Lorcaserin (serotonin agonist)
Pyloric Stenosis

– Surgical options: include gastric bypass, gastric sleeve, gastric

banding, bariatric surgery.
Duodenal Atresia Intussusception
• Arises from failure to recanalize • Telescoping of proximal portion of intestine into a distal
lumen after solid phase of portion
intestinal development
– Mostly ileal-colic
• 50% of patients born premature
– Down syndrome and other • Can lead to necrosis
congenital anomalies
• Cause is unknown
common
• Clinical – Frequently a history of adenovirus or rotavirus infection, URI, or
– Bilious vomiting, peristaltic OM
waves, jaundice • Common ages 5 months to 2 years
– X-ray: double-bubble sign
with no distal bowel gas
• Clinical
• Treatment – Sudden onset, recurrent, paroxysmal, sharp abdominal
– Decompression, fluids, pain
surgery
– Vomiting
• Duodenoduodenostomy
Source: James C. Pascual

Intussusception Pyloric Stenosis

• Exam • Diffuse hypertrophy & hyperplasia of pyloric sphincter
– Lethargy muscle
– Sausage-like mass in upper
mid-abdomen • Males > females; onset ages 2–4 weeks
– Heme-positive stool – Northern European ancestry
– Currant jelly stool – First born males
• Labs • Clinical
– Ultrasound: bowel within
bowel – Projectile, non-bilious vomiting; child still hungry
– X-ray: loss of bowel gas – Movable olive-size (2cm) mass in midepigastrium
– Barium or air enema: – Dehydration
meniscus & coiled spring
signs Source: James C. Pascual
• Treatment
– Reduction by BE
– IV fluids

Pyloric Stenosis
• Labs
– Hypochloremic hypokalemic metabolic alkalosis
• Diagnosis
– Barium swallow: delayed gastric emptying, string sign
– Ultrasound: elongation and thickening of pylorus
• Treatment
– Rehydration
– Surgery (pylorotomy)
 The Genitourinary/Renal Systems
Lecture 1 Renal Review
Benign Conditions of the GU tract

The Genitourinary/Renal Systems Lecture 2 Infectious/Inflammatory Conditions

Neoplastic Diseases

Lecture 3 Bladder Disorders

Congenital Disorders
Stephanie Neary, MPA, MMS, PA-C Urethral Disorders
Course Director, Preventative Medicine
Lecture 4 Renal Diseases
Yale School of Medicine, PA-Online Electrolytes and Acid-Base Disorders
Urinalysis

Renal Review Nephron

• Basic unit is the nephron
– Glomerular filtration
• Controlled neurally and hormonally
– Tubular transport
• Filtration modified by:
– Active and passive reabsorption
– Secretion (active)
– Creatinine clearance (x 0.85 if female)

CrCl =
(140 - age )(weight kg)
72(serum creatinine )

Benign Prostatic Hypertrophy (BPH)

• Noncancerous abnormal
hyperplasia of the prostate gland
– Onset fourth decade of life
• Symptoms can start around age
Benign Conditions of the GU Tract 50; significant problems onset age
60
Benign Prostatic Hypertrophy • Etiology
Erectile Dysfunction – Related to testosterone
conversion to dihydrotestosterone
Hydrocele/Varicocele by 5-a-reductase
Testicular Torsion • Rapid onset, manifestations
Nephro/Urolithiasis before age 50, and filling
symptoms without voiding
Paraphimosis/Phimosis/Priapism symptoms are red flags and
Hypospadias/Epispadias suggest other diagnoses IMC, © 2010 DxR Development Group, Inc. All Rights Reserved.
BPH
• Clinical
– Blockage in passage of urine, increased frequency, urgency,
nocturia, hesitancy, hematuria, dripping or dribbling, weak
stream
– Exam: rubbery, enlarged, firm prostate
• Labs
– Cystoscopy, pressure-flow studies
• Treatment
– 5-α-reductase inhibitors (finasteride)
• Side effects: sexual or ejaculatory dysfunction
– α-1-adrenergic inhibitors (doxazosin, terazosin)
• Side effects: orthostatic hypotension, dizziness, retrograde
ejaculation
– Surgery: transurethral prostatectomy (TURP)
Erectile Dysfunction
• The consistent inability to attain or maintain a
sufficiently rigid penile erection for sexual performance.
• Typically due to organic causes- cardiovascular
disease, diabetes, androgen deficiency or secondary to
medications.
– Medications- HCTZ, nifedipine, propranolol, fluoxetine,
amoxapine, clorazepate, phenytoin, dimenhydrinate, flutamide,
alcohol, marijuana, and cocaine
• Treatment
– Hormone replacement- testosterone
– Vasoactive therapy- sildenafil (inhibits phosphodiesterase-5
and increases nitric oxide levels)
– Injectable agents- papaverine or phentolamine
– Vacuum erection device
– Penile prostheses

Hydrocele Varicocele
• Fluid between 2 layers of • Engorgement of internal spermatic veins above the
tunica vaginalis testis
• Diagnosis by – Abnormal dilatation of the pampiniform plexus
transillumination, smooth,
non-tender • Bag of worms
• Must rule out testicular • Exam: non-tender, non-transilluminable mass, usually
tumor on left side
• Labs: ultrasound to rule out
malignancy
• Should diminish or disappear when patient is supine
• Treatment: surgery if • Common cause of subfertility in men
present past age 18 months

Varicocele Testicular Torsion

• For ages <10 years or sudden-onset right-side • Testis twisted on spermatic cord, interferes with blood
varicocele, think retroperitoneal malignancy supply (urologic emergency)
• For sudden-onset left side-varicocele, think renal cell • Seen in ages 10–20 (rare under age 10)
carcinoma • Clinical
• Treatment: surgery (varicocelectomy) – Acute onset, pain, and swelling
– Elevation of testicle may exacerbate pain
– Non-transilluminable lesion
– Absent cremasteric reflex
– If >4–6 hours, possible ischemia of testicle
Testicular Torsion Nephro/Urolithiasis
• Labs • Peak incidence ages 30–50; men > women
– Doppler • Formed from calcium oxalate, calcium phosphate,
ultrasound/nuclear scan uric acid and cystine
shows decreased blood
flow • Size
• Treatment – <5 mm: pass without difficulty

– Surgical emergency – 5–10 mm: pass 50% of time

(scrotal orchiopexy) – >10 mm: obstruction
– Manual detorsion

IMC, © 2010 DxR Development Group, Inc. All Rights Reserved.

Nephro/Urolithiasis Nephro/Urolithiasis
• Risk • Clinical • Labs
– Calcium intake, purine- – Sudden onset flank pain, – Hematuria, pyuria
containing foods, oxalate,
UTI, gout, fluid status awakens patient at night, – X-ray: KUB (stone), helical
– Calcium oxalate (most pain waxes and wanes, CT (test of choice)
common) radiation to groin,
• Cysteine and uric acid
• Hypercalcemia, scrotum, vulva
sarcoidosis, stones not visible on
hyperparathyroidism – Stone in bladder KUB
• Hypercalcuria develops frequency,
• Idiopathic urgency, dysuria • Treatment
– Struvite – Pain control: narcotics
• UTI (Proteus) – Hematuria,
• Alkaline urine
nausea/vomiting – Hydration
– Uric acid • Exam – Diet: decrease protein and
• Gout, high purine diets sodium intake
– CVA tenderness,
– Cystine – Metabolic evaluation
• Genetic afebrile, soft abdomen
© Richard Usatine, M.D. Used with permission..

Paraphimosis/Phimosis/Priapism
• Phimosis- fibrous constriction of the foreskin preventing
retraction. Treatment is circumcision.
• Paraphimosis- retracted foreskin develops a fixed
constriction proximal to the glans. Penis distal to
constricting foreskin may become swollen and painful.
Treatment is manual reduction and circumcision.
• Priapism- persistent, involuntary, painful erection.
Maybe secondary to sickle cell disease, leukemia,
alcohol, marijuana, and ecstasy.
Hypospadias/Epispadias
• Hypospadias
– Urethral opening appears on underside of penile shaft or on the
perineum.
– Occurs in 1/300 live male birth.
– Locations of meatus: distal to glans (71%); corona (43%); distal
shaft (34%), midpenis (16%), and proximal (13%)
– Associated abnormalities: cryptorchidism and inguinal hernia.
• Epispadias
– Congenital absence of upper wall of urethra that results in a
urethral meatus on the dorsum of the penis
– Occurs in 1/117,000 male births.
– There are 3 main types: penopubic, penile, and glandular.
– Associated abnormalities: diastasis of the symphysis pubis,
bladder exstrophy, renal agenesis, and ectopic pelvic kidneys.
 The Genitourinary/Renal Systems
Lecture 1 Renal Review
Benign Conditions of the GU tract Infectious/Inflammatory Conditions
Lecture 2 Infectious/Inflammatory Conditions Urinary Tract Infection
Neoplastic Diseases
Orchitis
Lecture 3 Bladder Disorders Epididymitis
Congenital Disorders
Urethral Disorders Prostatitis
Lecture 4 Renal Diseases Pyelonephritis
Electrolytes and Acid-Base Disorders
Urinalysis

Urinary Tract Infection Urinary Tract Infection

• Women > men • Clinical
• Incidence increases with increased sexual activity, DM, – Dysuria, frequency, urgency, suprapubic discomfort,
self-catheterization foul-smelling, cloudy urine, hematuria
• Fever and chills more common in pyelonephritis
• Cystitis: infection of the bladder
• Maybe asymptomatic in DM and the elderly
• Etiology
• Labs
– E. coli (>80% of cases)
– Enterobacter – Positive nitrites, leukocyte esterase
– Klebsiella – Positive bacteria, WBC (>5/HPF), RBCs
– Proteus – Culture
– Pseudomonas
– Staphylococcus

Urinary Tract Infection Orchitis

• Treatment • Inflammation of the testicle
– 7-day plan for pregnant patients, DM, the elderly, those • Viral etiology most common- mumps
with recurrent infections – Presents about 5 days after the parotitis
– Fluoroquinolones • May result in atrophy
– Trimethoprim/sulfamethoxazole (resistance-increasing) • Treatment
– Nitrofurantoin: safe in pregnancy – Symptomatic relief with recumbency and analgesics

– Cephalexin
• Urinary tract analgesic
– Phenazopyridine (Pyridium): orange urine
Epididymitis
• Inflammation of epididymis
• Seen typically in sexual active adults
• Due to retrograde infection from urethra
• Etiology
– Young boys: anatomic abnormalities, H. influenzae type
B
– Males <35 years: chlamydia
>35 years: Gram negative rods (E coli)
Prostatitis
• Acute bacterial prostatitis (type I)
– Etiology: E. coli, Pseudomonas, Serratia, Klebsiella,
Proteus
– Fever, dysuria, suprapubic or perineal pain, malaise
– Exam: febrile, prostate tenderness, enlarged
– Labs: UA–pyuria, positive culture, prostate massage not
recommended
• PSA increased but returns to normal post-treatment
– Treatment:
• Fluoroquinolones, ampicillin/gentamicin, TMP/sulfa
• Antibiotics for 1 month to avoid chronic disease
Prostatitis
• Chronic prostatitis- inflammatory/Chronic pelvic pain
syndrome (type IIIa)
– Autoimmune disease or viral cause (chlamydia or
Ureaplasma)
– Pelvic pain, urinary symptoms, pain during or after
ejaculation
– Physical exam: prostate findings vary
– Labs: UA negative, prostate secretions positive WBC but
culture is negative
– Treatment:
• Doxycycline or erythromycin?
• Alpha-blocker therapy
Epididymitis
• Clinical
– Dull, aching pain and swelling of epididymis
– Pain improved with testicular elevation
– Radiates to lower abdomen and flank
– Slow onset with gradual increase in pain
– Exam: epididymis is firm, swollen, and tender
• Labs: urethral smear, urinalysis/culture
• Treatment: antibiotics
• Chlamydia/GC: doxycycline, ceftriaxone
• TMP/sulfa
• Fluoroquinolones
Prostatitis
• Chronic bacterial prostatitis (type II)
– The elderly and those with recurrent UTI
– Chronic inflammation secondary to bacteria
– Dysuria, irritative voiding discomfort, not as much pain
– Etiology: enterococcus, gram-negative rods (E. coli)
– Exam: prostate findings will vary
– Labs: UA negative, prostate massage with secretions
showing increased WBC, and culture positive
– Treatment: TMP/sulfa, fluoroquinolones
• Treat for 6–12 weeks
Prostatitis
• Chronic prostatitis- non-inflammatory/Chronic pelvic
pain syndrome (type IIIb)
– Chronic prostatitis symptoms without signs of prostatic
inflammation
– Peaks the 5th decade of life
– Labs: prostatic secretion and urine no WBC, cultures is
negative
– Treatment
• Pain control
• No antibiotics
Prostatitis Pyelonephritis
• Asymptomatic inflammatory (type IV) • Infection of the parenchyma of the kidney; often follows
– Chronic prostatitis symptoms with mild signs of prostatic UTI
inflammation • Etiology
– Typically an incidental finding on biopsy – E. coli, Proteus, Klebsiella, Enterobacter, Pseudomonas
– Labs: prostatic secretion rare WBC, urine no WBCs, • Clinical
cultures is negative – Fever, chills, flank/back pain, nausea and vomiting,
– Treatment anorexia, dysuria, urgency
• Pain control – Exam: CVA tenderness, fever, toxic-appearing

• No antibiotics

Pyelonephritis
• Labs
– Urinalysis with culture
– WBC casts
– Proteinuria
– Positive LE/nitrite
Neoplastic Diseases
– Blood culture Bladder Cancer
– CBC with differential
Prostate Cancer
• Treatment
– Inpatient: children,
Testicular Cancer
pregnant women, septic © Richard Usatine, M.D. Used with permission.. Renal Cell Carcinoma
patients Wilms Tumor
– Antibiotics:
fluoroquinolones, Penile Cancer
ceftriaxone

Bladder Carcinoma Prostate Carcinoma

• Men > women 3:1 • Most commonly ages ≥65
– Mean age 70 years (rare before age 40) • Mets are common to the bone
• Risk factors: smoking, occupational exposure (rubber), • Histology: adenocarcinoma
chronic infections
• Risk factors: advancing age, positive FH, African American
• Clinical: hematuria (80–90%), irritative voiding symptoms
– Vasectomy and BPH do not increase risk
• Physical examination normal
• Clinical
• Labs: cystoscopy with biopsy
– Urinary obstruction
• Treatment: depends on staging
– Bone pain and LE edema in advanced disease
– Radical cystectomy with pelvic lymphadenectomy
– Impotence, hematuria, nocturia
• Chemotherapy combined with surgery
– RT in early-stage disease • Physical examination: DRE prostate enlarged, nodules hard
Prostate Carcinoma Renal Cell Carcinoma
• Labs • Men > women 3:1, increased incidence African
– PSA elevated (>4 ng/ml) Americans
– CT/MRI for staging – Mean ages 50–70
– Transrectal ultrasound with biopsy for diagnosis
• Risk factors: obesity, hypertension, smoking, diuretic
• Treatment
use
– Transurethral resection
– Radical prostatectomy • Clinical manifestations
– RT – Flank pain, abdominal mass, hematuria (classic triad)
– Hormone therapy (androgen deprivation)
– Weight loss, fatigue, anorexia
• Flutamide (Eulexin)
• Complications: pathologic fractures & spinal cord • Associated paraneoplastic syndrome is common
compression – Hypercalcemia, hypertension

Renal Cell Carcinoma Testicular Carcinoma

• Diagnosis • Young men ages 20–40
– Ultrasound, CT scan • Risk factors: cryptorchidism
• Treatment • The U.S. Preventive Services Task Force (USPSTF)
– Surgery recommends against screening for testicular cancer in
adolescent or adult males.
– Immunomodulatory with
interleukin-2 in • Clinical
metastatic disease – Painless, solid testicular swelling
– Resistant to radiation – Asymptomatic
and chemotherapy
– Associated with hydrocele (10%)

© Richard Usatine, M.D. Used with permission..

Testicular Carcinoma Wilms Tumor (Nephroblastoma)

• Labs • Malignant tumor kidney occurring in children
– Testicular ultrasound: hypoechogenic mass • Also known as nephroblastoma
– Elevated beta-HCG • Peak age 2–5
– Elevated alpha fetoprotein • May be associated with cryptorchidism
• Treatment • History
– Asymptomatic abdominal mass
– Orchectomy (treatment of choice)
– Hematuria 20-30%
– Radiation therapy
– Hypertension: due to obstruction of renal artery
– Chemotherapy
– Fever
Wilms Tumor Penile Cancer
• Physical examination • Squamous cell carcinoma
– Asymptomatic abdominal mass extending from flank – Most common malignant tumor of the penis.
toward midline (most common presentation) – Predisposing factors: lack of circumcision, poor hygiene,
phimosis, smoking and HPV infection.
– Anemia (due to hemorrhage in tumor)
– More frequent in men >50 years old.
– Hypertension – 30-40% of all SCC are HPV-related (High-risk genotypes are
• Diagnosis: Abdominal CT scan 16 and 18).
– Treatment- surgery, radiation therapy
• Treatment – Verrucous carcinoma:
– Nephrectomy (with preop chemotherapy in cases with • This is an uncommon form of squamous cell cancer that
large tumors) can start in the skin in many areas.
– Radiation (for pulmonary metastases) • Resembles a large genital wart.
• Tend to grow slowly but can sometimes get very large.

The Genitourinary/Renal Systems

Lecture 1 Renal Review
Benign Conditions of the GU tract Bladder Disorders
Lecture 2 Infectious/Inflammatory Conditions Incontinence
Neoplastic Diseases
Overactive Bladder
Lecture 3 Bladder Disorders
Congenital Disorders
Urethral Disorders

Lecture 4 Renal Diseases

Electrolytes and Acid-Base Disorders
Urinalysis

Urinary Incontinence Overactive Bladder

Stress Urge Overflow • Syndrome characterized by urinary urgency, frequency,
Amount of loss Small Large Small and nocturia with or without incontinence.
Duration of loss Brief Moderate Continuous • Symptoms attributed to detrusor overactivity,
Associated • Cough None None characterized by involuntary detrusor contractions during
event • Laugh Change in position
• Sneeze
bladder filling.
– Classified as neurogenic or non-neurogenic
Associated • None Urgency • Fullness
symptoms • No urine loss at Nocturia • Pressure • Uninhibited detrusor contractions can be detected on the
night • Frequency cystometrogram portion of urodynamic testing.
Cause • Cystocele Loss of bladder • Obstruction • Treatment
• Urethrocele inhibition • Loss of
neurologic control – Antimuscarinic agents (Oxybutynin, Tolterodine)
• Increase bladder capacity and decrease urgency by blocking
Treatment • Kegel exercises Anticholinergic • Self-
• Estrogen catheterization muscarinic receptor stimulation
replacement • Cholinergic meds • Anticholinergic side effects
• Surgery • Α-blockers – Beta-adrenergic therapy (Mirabegron)
• Promotes selective beta receptor stimulation of the detrusor
muscle to enhance smooth muscle relaxation
 Cryptorchidism
• Undescended testis
• A testis which does not remain at the bottom of
scrotum after cremasteric muscle has been fatigued
Congenital Disorders • Endocrinologic abnormalities
Cryptorchidism – Infertility

Peyronie’s Disease • Thermal effects

Trauma – Risk of testicular cancer

Vesicoureteral Reflux • Mechanical

– Risk of testicular torsion

Cryptorchidism Cryptorchidism
• Epidemiology • History
– Maternal drug use (steroids)
– Percentage of undescended testes increases with
– Family history
prematurity
• Therapy
– Majority of testes will descend by age 3 months – Hormonal therapy (GnRH and hCG)
• Associated with gonadotropin surge responsible for germ cell • Success rate 30-50%
maturation • Most helpful in low undescended testes
• If undescended testes continue, refer for surgical evaluation • 25% relapse rate
• Surgery
• Evaluation – Orchidopexy
– Ultrasound, CT, & MRI can detect testes in inguinal region – Goals
(50% accurate in demonstrating intra-abdominal testes) • Repair associated inguinal hernia
– Usually unnecessary in pre-op evaluation • Prevent testicular torsion/injury
• Cosmetic
• Decrease risks of malignancy/allow for self-testicular exam

Peyronie’s Disease Trauma

• Clinical • Traumatic injury is uncommon (incidence <1%)
– Affects men between 20-80 years old – Associated with pelvic injuries/fractures
– Presents with painful erection accompanied by distortion, • Overall, for the lower GU tract, blunt mechanisms
bending, or constriction of the erect penis predominate.
– Usually have palpable nodules or plaques on the dorsal surface
of the erect penis.
• Clinical
– Bladder- gross hematuria, suprapubic tenderness, trouble
• Pathology:
voiding
– Fibrosis of the tunica albuginea which does not affect the – Urethral- blood at the meatus, difficulty voiding, ecchymosis,
corpora cavernosa.
high riding prostate in men
– Fibrous tissue may look like simple fibrosis or may resemble
fibromatosis • Diagnosis with ultrasound and CT abdomen/pelvis
• Prognosis and treatment: • Treatment- surgery
– 30% resolve spontaneously; 40% progress; 30% remain stable.
– Treatment with surgical excision of plaques, radiotherapy, and
steroid injections.
Vesicoureteral Reflux Vesicoureteral Reflux
• Retrograde passage of urine from the bladder into the • Diagnosis
upper urinary tract. – Hydronephrosis on ultrasound
– May predispose to acute pyelonephritis, which may lead to – Demonstration of reflux of urine from the bladder to the upper
renal scarring, hypertension, and end-stage renal disease urinary tract by either contrast voiding cystourethrogram or
– More common in male children/infants radionuclide cystogram

• Types • Treatment
– Primary, most common form of reflux, is due to incompetent or – Depends on grading
inadequate closure of the ureterovesical junction – Watchful waiting
– Secondary VUR is a result of abnormally high voiding pressure – Antibiotic prophylaxis (TMP/Sulfa or Nitrofurantoin- avoid if <2
in the bladder that results in failure of the closure of the UVJ months of age)
during bladder contraction. – Surgical correction
• Secondary is often associated with anatomic or functional
bladder obstruction.

Urethral Stricture
• Common in men due to trauma or idiopathic
• Present with obstructive voiding symptoms
– Decreased stream, incomplete bladder emptying
Urethral Disorders • Diagnosis
– Uroflowmetry shows poor bladder emptying and low peak rate
Stricture of urine flow
• Treatment
– Urethral dilation and urethrotomy

The Genitourinary/Renal Systems

Lecture 1 Renal Review
Benign Conditions of the GU tract Renal Diseases
Lecture 2 Infectious/Inflammatory Conditions Acute Renal Failure
Neoplastic Diseases
Chronic Kidney Disease
Lecture 3 Bladder Disorders Glomerulonephritis
Congenital Disorders
Urethral Disorders Nephrotic Syndrome
Lecture 4 Renal Diseases Polycystic Kidney Disease
Electrolytes and Acid-Base Disorders
Urinalysis
Acute Renal Failure (Acute Renal Injury) Acute Renal Failure
• Abrupt increase in creatinine • Prerenal: think perfusion • Renal: think glomerular,
– Increase by 0.3 mg/dl or 50% problem (most common) tubular, or interstitial
• Three major classes – Shock problem
– Dehydration – Ischemic/inflammation
– Prerenal
– Decreased cardiac output – Nephritis
– Renal
– Renal arterial obstruction – Vasculitis
– Postrenal – HUS (E. coli)
• Postrenal: think
• Clinical obstruction – Toxins/drugs
– Based on severity of disease – Neoplasms • Aminoglycosides
– Fatigue, dizziness, swelling, decreased urine output – Stones • NSAIDs
– Prostate disease • Amphotericin B
• Contrast material

Acute Renal Failure Prerenal vs. Renal

• Exam Index Prerenal Renal
– Orthostatic hypotension, tachycardia, rales, Urine specific gravity >1.020 <1.010
JVD, edema, bladder distention
– Anuria (<100 mL) sign of obstruction Plasma BUN / plasma >20 <10–15
• Labs creatinine
– BUN, creatinine elevated, urine sediment Urine osmolality >500 <350
– Renal ultrasound Sodium fraction <1% >2%
– BUN/Cr ratio
• Prerenal and postrenal >20; renal <10 Urine sediment Scant Full (muddy
• Treatment brown)
– Treat cause, remove toxic drugs, fluid balance
– Low sodium, low potassium diet FENa = (UNa/PNa )/ (UCr/PCr )X 100
– Dialysis

Chronic Renal Failure Chronic Renal Failure: Multiple System Failure

• Etiologies • Metabolic • Hematology
– Diabetes (#1) – Hyperkalemia – Anemia
– HTN (#2) – Hyperphosphatemia • Dermatology
• Stages of Chronic Renal Failure – Hyperuricemia – Pruritus
– Hyperglycemia • Gastrointestinal
– Anorexia, N/V, diarrhea
Stage Reduction GFR – Hypocalcemia
– Metabolic acidosis • Neurologic
1 Slight >90 mL/min but presence of markers of kidney disease
– Encephalopathy
2 Mild 60–89 mL/min with presence of markers of kidney damage • Cardiovascular
– Neuropathy
– Hypertension
3 Moderate 30–59 mL/min • Skeletal
– CHF
– Osteomalacia
4 Severe 15–29 mL/min – Pericarditis – Osteoporosis
5 Established <15 mL/min or permanent replacement therapy
Chronic Renal Failure Glomerulonephritis
• Treatment: depends on stage; goal is to prevent • Damage of the renal glomeruli
further damage – Due to deposits of inflammatory proteins; secondary to an
– Blood pressure control autoimmune event, circulating antibodies, or vasculitis
• ACE inhibitors (monitor potassium level) • Clinical
• Lower salt intake, monitor weight
– Hematuria, tea-colored urine
– Treat anemia with erythropoietin
– Low protein diet – Oliguria or anuria
– Calcium, vitamin D, bicarbonate to avoid bone disease – Edema
– Dialysis – Hypertension
– Transplant

Glomerulonephritis: Etiologies Glomerulonephritis

Vascular Disease Glomerular Disease • Labs
Wegener granulomatosis Goodpasture syndrome
– ASO titer increased
Churg-Strauss syndrome Postinfectious glomerulonephritis
– RBC casts, dysmorphic
Henoch-Schönlein purpura IgA nephropathy
RBCs, WBCs, proteinuria
Polyarteritis nodosa SLE
– Serum complement (c3)
Thrombotic thrombocytopenia purpura Idiopathic rapidly progressive
glomerulonephritis ↓
Hemolytic uremic syndrome Alport syndrome – Renal biopsy for
Cryoglobulinemia Diabetes and hypertension diagnosis
Amyloid • Treatment
– Dietary management:
salt and fluids
– Dialysis © Richard Usatine, M.D. Used with permission..

– Treat underlying cause

Glomerulonephritis Nephrotic Syndrome

Disease S&S Serology Treatment Notes • Comprised of glomerular proteinuria (>3.5 g/day),
Poststreptococcal Children ASO titer positive Symptomatic Occurs after
Oliguric ¯ complement pharyngitis and hypoalbuminemia, hyperlipidemia, and edema
Edema impetigo
• Clinical
IgA nephropathy Microscopic or IgA levels elevated Corticosteroids Associated with
gross hematuria NL complement URI or flu-like
illness
– Abdominal distention, anorexia, oliguria, puffy eyes,
SOB, weight gain
Wegener s Fever ANCA positive Corticosteroids Respiratory tract
granulomatosis Malaise
Weight loss
NL complement Cyclophosphamide symptoms
common
– Ascites, edema, HTN, hematuria
Goodpasture s Hemoptysis Anti-GMB positive Plasma exchange
syndrome Corticosteroids

Lupus nephritis ANA positive Corticosteroids

¯ complement Cyclophosphamide
 Causes of Nephrotic Syndrome
Primary Renal Disease
Focal glomerulonephritis
Focal glomerulosclerosis
IgA nephropathy
Membranoproliferative
glomerulonephritis
Membranous glomerulopathy
Congenital nephrotic syndrome
Polycystic Kidney Disease
• Autosomal dominant
– Positive family history
• Age at onset 20s to 30s
• Cysts form in multiple organs
– Kidney, liver, cerebral aneurysms
• Can lead to ESRD
• Symptoms
– Abdominal or flank pain
– Hematuria
– Frequent UTIs
– Hypertension
Electrolyte Disorders and Acid-Base Disorders
Nephrotic Syndrome
• Labs
Secondary Renal Disease – UA: protein, oval fat
Post-strep glomerulonephritis bodies, hematuria
SLE • Oval fat bodies:
Malignancy maltese cross
Toxemia of pregnancy appearance in
polarized light
Drugs and nephrotoxins – RBC casts, fatty casts
Lymphoma/leukemia – Serum: decreased
albumin, azotemia
• Treatment
– Steroids,
cyclophosphamide
– Dietary management
– Avoid nephrotoxic drugs
Polycystic Kidney Disease
• PE:
– Large palpable kidney
– Renal insufficiency
– Diagnosis: ultrasound/CT
• Treatment:
– Treat hypertension
– Increase fluid intake
– Transplant
© Katsumi M. Miyai, M.D., Ph.D., Regents of the University of
California. Used with permission.
Hyponatremia
• Sodium less than 135 mEq/L
– Due to increased free water retention or urinary sodium loss
• Signs/symptoms
– Nausea, headache, weakness, mental confusion
– Seizures, lethargy, coma, death
Hypo/Hypernatremia
• Labs
Hypo/Hyperkalemia
– Serum sodium low
Hypo/Hypercalcemia
– Serum osmolality <270
Metabolic Acidosis/Alkalosis – Urine sodium varies with etiology
Respiratory Acidosis/Alkalosis
Serum osmolality = 2(Na) + BUN/2.8 + Glucose/18
Hyponatremia: Differential Diagnosis Hyponatremia
• Hypovolemic (edema, total body water ¯) • Treat underlying cause
– Renal losses: diuretic excess, mineralocorticoid deficiency • Correction
(urine sodium >20)
– Hypertonic saline with furosemide
– Extrarenal losses: vomiting, diarrhea, dehydration, sweating
(urine sodium <20) – Water restriction
• Hypervolemic (edema, total body water ­) – Do not increase sodium by more than 12–24 mEq/L
over 24 hours
– Urine sodium >20: acute and chronic renal failure
– Urine sodium <20: CHF, cirrhosis, nephrotic syndrome
• Euvolemic (no edema, total body water ­)
– Hypothyroidism, SIADH, Addison s, stress
• Pseudohyponatremia
– Increase trigs, proteins, glucose

SIADH SIADH
• Due to excessive release of ADH from posterior • Clinical
pituitary – No edema or hypertension
• Causes – Hyponatremia, urine osmolarity elevated (>300 mOsm),
urine sodium >20 mEq/L
– Small cell lung cancer, pancreatic cancer
– Elevated ADH level
– Pneumonia • Treatment
– Brain tumors – Treat underlying cause
– Head trauma – Fluid restriction (800–1,000 mL/day)
– Drugs: chlorpropamide, SSRIs, ecstasy, vincristine, – IV saline
cyclophosphamide, TCAs – Drugs
• Demeclocycline (chronic disease)

Hypernatremia Hypernatremia
• Usually severe thirst unless mental confusion • Labs
– Sodium >145 mEq/L
– Seen in the elderly, very young, or neuro-impaired
– Serum osmolality >300 (free water loss)
• Etiologies
– Normovolemia (diabetes insipidus) • Treatment
– Hypovolemia – Treat hypovolemia with isotonic saline, then replace
water
• Dehydration (GI or skin loss)
– Replace water deficit
• Osmotic diuresis
Water deficit = 0.6 x premorbid weight x (1 – ([Na+/140])
• Loop diuretics
• Clinical: decreased skin turgor, tachycardia, – Replace water gradually and watch for cerebral edema
hypotension, mental status changes
Hyperkalemia Hyperkalemia
• Serum potassium >5.5 • Differential diagnosis
mEq/L – Renal failure
– Hypoaldosteronism
• Signs and symptoms
• K-sparing diuretics, ACE-inhibitors, adrenal disease
– Weakness, paralysis, – Acidosis
abdominal distension, – Burns, hemolysis
diarrhea
– Spurious: increased platelets or WBC
• EKG • Treatment
– Peaked T waves, loss of – IV bicarbonate, calcium gluconate, glucose, insulin
P wave, QRS widened, (emergent)
arrest – Potassium restriction, sodium polystyrene sulfonate,
diuretics (non-emergent)
– Dialysis

Hypokalemia Hypokalemia
• Usually asymptomatic • Differential diagnosis
• May have muscle – Diuretic use
weakness, lethargy, – Alkalosis
paresthesias, polyuria, – Hyperaldosteronism
constipation – Magnesium depletion
• If severe, will cause ileus, – Hyperthyroidism
muscle necrosis, and – Diarrhea/vomiting
ascending flaccid – Renal tubular acidosis types I and II
paralysis
• Treatment
• EKG – Treat underlying cause; potassium supplement
– T wave flattening, ST
depression,
U waves, AV blocks

Hypocalcemia Hypocalcemia
• Signs and symptoms • Differential diagnosis
– Abdominal and muscle cramps, tetany, seizures – Vitamin D deficiency and osteomalacia
• PE – Malabsorption
– Positive Chvostek and Trousseau signs – Hypoparathyroidism
• Labs – Chronic renal failure
– Alcoholism
– Serum calcium <8.5 mg/dL (correct for albumin)
– Drugs: loop diuretics, phenytoin, foscarnet
• EKG
• Treatment
– Prolonged QT interval, ventricular arrhythmias (VT)
– Treat underlying disorder; calcium gluconate
 Hypercalcemia Hypercalcemia
• Signs/symptoms • Differential diagnosis
– Polyuria, constipation, abdominal pain – Primary hyperparathyroidism
– Thirst and dehydration, hypertension – Adrenal insufficiency
– Malignancy
– Altered mental status, hyporeflexia, coma
– Sarcoidosis
• Labs – Tuberculosis
– Serum calcium >10.5 mg/dL – Paget s disease

• EKG • Treatment
– Treat underlying cause
– Shortened QT interval
– Fluids first, then diuretics
– Bisphosphonates, calcitonin

Acid–Base Disorders Metabolic Acidosis

• Signs/symptoms
– Dyspnea, hyperventilation, fatigue, tachycardia,
Disorder pH pCO2 HCO3-
hypotension
Metabolic acidosis Low Low Low
Respiratory acidosis Low High High – Acetone breath
Methanol
Metabolic alkalosis High High High • Labs
Uremia
Respiratory alkalosis High Low Low
– pH <7.40 DKA
– Serum bicarb decreased Propylene glycol
Normal Ranges
Ingestion (Ecstasy, cocaine, etc)
pH 7.35–7.45 7.40 – Anion gap varies
Lactic Acid
pCO2 35–45 mm Hg
Ethylene glycol
HCO3- 24 mEq/L
Salicylates

Metabolic Acidosis: Increased Anion Gap Metabolic Acidosis: Normal Anion Gap
Disorder Urine pH UAG K+ BUN/Crt
Disorder Osmolar Glucose BUN/Crt Lactate Ketone Blood
Gap Level
Distal RTA type I >5.5 Positive Low Normal
Ethylene glycol Very High Normal Normal Low Neg Yes
ingestion Proximal RTA type II <5.5 Negative Low Normal
Methanol ingestion Very High Normal Normal Low Neg Yes Generalized RTA type IV <5.5 Positive High Normal
Alcoholic acidosis High Low-NL Normal Low Pos Yes Mild renal failure High
Diabetic acidosis High High Normal Low Pos GI loss of HCO3- <5.5 Negative Normal Normal
Severe renal failure High Normal High Low Neg Acid load <5.5 Negative Normal
Lactic acidosis Normal Normal Normal High Neg Yes Dilutional acidosis <5.5 Negative Normal

Toluene exposure Normal Normal Normal Low Neg

Salicylate toxicity Normal Normal Normal Low Neg Yes Low anion gap- myeloma, low albumin, and lithium.
Renal Tubular Acidosis Renal Tubular Acidosis
• Type I • Type III
– Distal H + secretion defect – Rare, associated with renal insufficiency
– Low serum K + , urine pH >5.5 – Normal serum K +, urine pH <5.5
– Sporadic, autoimmune disorders (Sjögren's), hypercalcemia,
drugs (lithium, ifosfamide, amphotericin B)
• Type IV
– Kidney stones develop – Hyporeninemic hypoaldosteronism

• Type II – High serum K +, urine pH <5.5

– Proximal HCO 3- reabsorption defect – Associated with diabetes mellitus, drugs (NSAIDs), sickle cell
– Low serum K +, urine pH <5.5 disease, Addison disease

– Associated with multiple myeloma, Fanconi syndrome, Wilson

disease

Metabolic Alkalosis Metabolic Alkalosis: Etiologies

• Signs/symptoms Chloride-Responsive Chloride-Resistant
– Weakness, malaise, lethargy
• Vomiting/ nasogastric • Severe Mg or K deficiency
– Hyporeflexia, tetany, muscle weakness drainage • Diuretics (thiazide, loop)
• Labs • Laxative abuse • Cushing s syndrome
• Diuretics • Primary aldosteronism
– pH >7.40
• Posthypercapnic states • Renal artery stenosis
– Serum bicarb increased
• Bartter syndrome
– PCO 2 up to 45 mm Hg

– Serum potassium and chloride usually low

Respiratory Acidosis Respiratory Alkalosis

• Signs/symptoms • Signs/symptoms
– Alveolar hypoventilation central to all – Lightheadedness, numbness and tingling, circumoral
– Confusion, altered mental status, somnolence paresthesias
– Dyspnea, respiratory distress • Labs: pH >7.40 and PCO2 decreased
• Labs: pH <7.40 and arterial PCO2 increased
• Differential diagnosis
• Differential diagnosis
– Restrictive lung disease/hypoxia
– COPD – CNS lesion
– Central nervous system depressants
– PE
– Structural disorders of the thorax – Salicylate toxicity
– Neurologic disorders (Guillain-Barré) – Anxiety
– Myxedema – Sepsis
– Pregnancy
Acid-Base Disorders Step 1: pH
• Look at pH.
Disorder pH pCO2 HCO3- • Whichever side of 7.40 the pH is on, the process that
Metabolic acidosis Low Low Low caused it to shift to that side is the primary
Respiratory acidosis Low High High abnormality.
Metabolic alkalosis High High High >7.40 is alkalosis
Respiratory alkalosis High Low Low
<7.40 is acidosis
Normal Ranges • Remember, the body does not fully compensate for
pH 7.40 primary acid-based disorders.
pCO2 35–45 mm Hg
HCO3- 24 mEq/L

pH Results Step 2: Anion Gap

• Calculate the anion gap (AG):
Variable Primary Normal Primary
Disorder Range Disorder AG = Na – (Cl + HCO3)
pH Acidemia <7.40> Alkalemia • If anion gap is ³20 mmol/L, there is a primary metabolic
acidosis regardless of the pH or serum bicarbonate.
pCO2 Respiratory <35–45> Respiratory • Remember, the body does not generate a large anion
(mm Hg) alkalosis acidosis gap to compensate for a primary disorder.

Bicarbonate Metabolic < 22–26> Metabolic

(mmol/L) acidosis alkalosis

Step 3: Excess Anion Gap Case #1

• Calculate the excess anion gap: • Labs • Step 1
– pH 7.50 • pH is high
Excess = total AG – normal AG of 12 + measured – pCO2 20 mm Hg – Alkalosis
bicarb
– Bicarb 15 mmol/L • Low bicarb and PCO2
• If > 30 mmol/L, there is an underlying metabolic – Sodium 140 mEq/L – Respiratory is primary
alkalosis. – Potassium 4.0 mEq/L
• If <23 mmol/L, there is an underlying non-anion gap – Chloride 103 mEq/L
metabolic acidosis.
• Normal bicarbonate: 23–30 mmol/L
Case #1 Case #1
• Labs • Step 2 • Labs • Step 3
– pH 7.50 • Anion gap – pH 7.50 • Excess anion gap
– pCO2 20 mm Hg AG = 140 – (103 + 15) – pCO2 20 mm Hg Excess = 22 – 12 + 15
– Bicarb 15 mmol/L Result = 22 – Bicarb 15 mmol/L Result = 25
– Sodium 140 mEq/L • Second disorder anion – Sodium 140 mEq/L • Normal result
– Potassium 4.0 mEq/L gap metabolic acidosis – Potassium 4.0 mEq/L • No further primary
– Chloride 103 mEq/L
– Chloride 103 mEq/L disorder

Case #1: Final Result Case #2

• Labs • Step 1
• Final results – pH 7.40 • pH is normal
– pCO2 40 mm Hg
– Respiratory alkalosis
– Bicarb 24 mmol/L
– Elevated anion gap metabolic acidosis – Sodium 145 mEq/L
– Potassium 4.0 mEq/L
– Chloride 100 mEq/L

Case #2 Case #2
• Labs • Step 2 • Labs • Step 3
– pH 7.40 • Anion gap – pH 7.40 • Excess anion gap
– pCO2 40 mm Hg AG = 145 – (100 + 24) – pCO2 40 mm Hg Excess = 21 – 12 + 24
– Bicarb 24 mmol/L Result = 21 – Bicarb 24 mmol/L Result = 33
– Sodium 145 mEq/L • Anion gap is elevated, – Sodium 145 mEq/L • Since excess anion gap
– Potassium 4.0 mEq/L so there is a metabolic – Potassium 4.0 mEq/L is >33, there is a
– Chloride 100 mEq/L acidosis (and you – Chloride 100 mEq/L metabolic alkalosis.
thought all the results
were normal)
Case #2: Final Result
• Final results
– Metabolic acidosis and metabolic alkalosis
– Patient had chronic renal failure leading to the
metabolic acidosis; he then began vomiting, which in
Urinalysis
turn caused the metabolic alkalosis Specific Gravity
– Result: a normal pH Protein
Ketones
Nitrite and Leukocyte Esterase
Microscopic Examination

Specific Gravity Protein

• Measure of kidneys ability to concentrate urine • Single most important indicator of renal disease
• Measured against density of distilled water – Protein filtered at the glomeruli
• Typically, SG varies inversely with amount of urine excreted,
• Can be seen in normal conditions such as exercise,
except in:
fever and CHF
– Diabetes: ↑ volume, ↑ SG
• Normal range: no protein or only a trace amount
– Hypertension: normal volume, ↓ SG
• Normal range 1.005–1.025 • Detects only albumin
– Low: diabetes insipidus, severe renal damage
– High: diabetes mellitus, dehydration, fever, vomiting, diarrhea,
CHF

Proteinuria Ketones
• Glomerular damage • Decreased tubular • A result of fatty acids and fat metabolism
– Glomerulonephritis reabsorption
• Three ketones:
– SLE – Renal tubular acidosis
– Acetone
– Malignant hypertension – Pyelonephritis
– b-hydroxybutyric acid
– Amyloidosis – Interstitial nephritis
– Acetoacetic acid
– Diabetes mellitus – Wilson s disease
• Form in liver and are completely metabolized
• Microalbumin
– Ketonuria noted in diabetes mellitus, starvation, high-
fat diets, prolonged vomiting, anorexia, low-
carbohydrate diet, fever, and hyperthyroidism
Nitrite and Leukocyte Esterase Red Blood Cells
• Nitrite • Seen in:
– Detects the presence of bacteria which convert nitrate to – Pyelonephritis
nitrite – Infections
– Most common in gram-negative bacteria that cause UTI, • Tuberculosis
e.g., E. coli
– SLE
• Leukocyte – Renal stones
– Detects the enzyme present in white blood cells – Prostatitis
– Indicates pyuria – Trauma
– Tumors

© Richard Usatine,M.D. Used with permission

WBC Hyaline Casts

• Seen in: • Clear, colorless casts made
when protein within the
– All renal disease
tubules precipitates
– UTI • Can indicate damage to the
– Strenuous exercise glomerular capillary
membrane
– Bladder tumors – Glomerulonephritis
– Glomerulonephritis – Pyelonephritis

– Interstitial nephritis – Diabetic nephropathy

– Can be temporary due to:
• Stress
© Richard Usatine,M.D. Used with permission
• Exercise
• Fever (dehydration)
© Richard Usatine,M.D. Used with permission

RBC Casts WBC Casts

• Indicate acute • Indicate renal
inflammatory or vascular parenchymal infection
disorders – Pyelonephritis
– Glomerulonephritis (most common)
– Renal infarction – Acute
– Goodpasture s syndrome glomerulonephritis
– Interstitial nephritis
– Lupus nephritis

© Richard Usatine,M.D. Used with permission

© Richard Usatine,M.D. Used with permission
Waxy Casts Crystals
• Formed under extreme • May be normal or
renal stasis associated with kidney
• Called renal failure stone formation
casts – Vary with pH of the
• Noted in: urine
• Acid urine
– Chronic renal failure
– Cystine, cholesterol,
– Nephrotic syndrome calcium oxalate
• Alkaline urine © James Van Rhee

– Calcium phosphate,
© James Van Rhee
ammonium biurate,
triple phosphate,
amorphous
phosphates
© James Van Rhee
 The Hematologic System
Lecture 1 Anemias and Other Disorders

The Hematologic System Lecture 2

Lecture 3
Coagulation Disorders

Malignancies

Jim Van Rhee, MS, PA-C

Program Director; Associate Professor
Yale School of Medicine, PA-Online

Hematopoiesis

Anemias
Iron Deficiency
Thalassemia
B12 Deficiency
Folate Deficiency
Hemolytic
Sickle Cell Disease
Aplastic Anemia

Anemia: Definition Clinical Findings

• Any condition resulting from a significant decrease in Clinical Symptoms Clinical Signs
the total body erythrocyte mass
• Dyspnea on exertion • Pallor
• Hemoglobin / hematocrit of less than:
• Easy fatigability • Tachycardia
– 12 g/dL or 37%
• Fainting • Systolic ejection flow
– Normal range murmur
• Lightheadedness
• Men 14–16 g/dL • Syncope
• Tinnitus
• Women 12–14 g/dL • Orthostatic hypotension
• Headache
Note:
RBC x 3 = Hgb
Hgb x 3 = Hct
 Normal Red Blood Cell Cytochromic Classification
• Biconcave disc • Microcytic, hypochromic
• Diameter – Iron deficiency anemia
– 7 microns – Thalassemias
• Volume – Anemia of chronic
– MCV 80 –100 fL disease
– Lead poisoning
– Sideroblastic anemia
• Normocytic,
normochromic
– Anemia of chronic
disease
– Hemolytic anemia
– Anemia of acute
hemorrhage
– Aplastic anemia
• Macrocytic anemia
– Vitamin B12 deficiency
– Folate deficiency

Normal Ranges
MCV 80-100 fL

Reticulocyte Count
MCH 26-34 pg Anemia
MCHC 31-36% Hgb Women <12 g/dL
Platelets 150,000-450,000/mm 3
Men <14 g/dL
WBC 5,000-10,000/mm 3
Neutrophils 50-65%
Bands 0-10% <2
Lymphocytes 25-35%
>2
Monocytes 5-10%
Eosinophils 1-5%
Basophils 0-1%
↓ production ↑ destruction
(History of anemia?)

No Yes

Congenital
MCV Acquired
Normal (80–100 fL)

Coombs
Membrane Hemoglobin Enzymes
•Hereditary •Sickle cell •G-6-PD
Microcytic Normocytic Macrocytic Negative Positive spherocytosis (+ Sickledex, •Pyruvate
(MCV <80 fL) (MCV 80- (MCV >100 •Hypersplenism •Drug-induced (+ osmotic confirm Hgb kinase
fragility) electrophore
•Iron Def. 100 fL) fL) •Microangiopathic (PCN,
(>80% sis)
(Ferritin <15) •Blood loss •B12 def. (Schistocytes) quinidine,
(↑ RDW) •Chronic (B12 (TTP, DIC, levodopa) spherocytes) •Hgb C
•Thalassemia disease <200) heart valve) •Warm •Hereditary disease

Corrected Retic Count

(Normal RDW) (Neuro on •Physical antibody elliptocytosis
•Sideroblastic PE) (Burns) (IgG type)

<2% = ¯ Production
(Ring sideroblasts) •Folate def. •Chemical (CLL,
•Chronic disease (Folate (Fresh water) lymphoma,
(ACD) <2.5) •Infectious SLE)

>2% = ­ Destruction
•Lead poisoning (No (Malaria, •Cold antibody
neuro) Clostridium) (IgM type)
(Mycoplasma,
EBV)

Fe Deficiency Anemia Causes Laboratory Features

• GI blood loss • Microcytic, hypochromic
• Vaginal blood loss – Elevated RDW

• Urinary blood loss • Decreased serum iron

• Malabsorption • Increased TIBC
• Increased demand • Decreased ferritin
• Poor dietary intake • Decreased free erythrocyte protoporphyrin
• Decreased iron stores in bone marrow
 Therapy
Microcytic, hypochromic cell
• Elemental iron 60 mg per day
• Response to therapy:
– Increased reticulocyte count in 7–10 days
– Increased hemoglobin in 2–3 weeks
– Normal hemoglobin in 2 months

Thalassemia Beta Thalassemia

• Defect in globin polypeptide chain • Two types
• Causes absent or decreased synthesis of the affected – Beta thalassemia minor
globin chain – Beta thalassemia major
• Two types • Beta thalassemia minor
– Alpha: defect in alpha chain – Patients asymptomatic
– Beta: defect in beta chain – Cells microcytic/hypochromic
– Increased level Hgb A2
– Target cells
– Treatment: genetic counseling, avoid iron

Beta Thalassemia
• Beta thalassemia major (Cooley s anemia)
– Severe anemia (Hgb about 6 g/dL), decreased MCV
– No symptoms until age 6 months
• Failure to thrive Target cell
• Hepatosplenomegaly
• Expansion of bone
– Increase levels of Hgb F
– Treatment
• Transfusions
• Splenectomy
• Iron chelation
Alpha Thalassemia: Clinical States Sideroblastic Anemia
• Silent carrier: 1 gene inactive • Mitochondrial defect
– No symptoms which prevents the
• Alpha thalassemia trait: 2 genes inactive incorporation of iron
– Mild anemia, very low MCV, no symptoms into hemoglobin
• Hemoglobin H disease: 3 genes inactive • Iron accumulates in
– Marked microcytic, hypochromic anemia mitochondria forming a
– Splenomegaly ringed sideroblast
– Hgb H 4–10% • Iron utilization defect
• Hydrops fetalis: 4 genes inactive – Ineffective
– No fetal or adult Hgb erythropoiesis
– Death in utero or neonatally

Sideroblastic Anemia Lead Poisoning

• Acquired or hereditary • Clinical
– Acquired - chloramphenicol, isoniazid, alcohol – Abdominal pain,
constipation, peripheral
• Labs neuropathy, neurologic
– Bone marrow: ringed sideroblasts changes
– Typically mild anemia (Hgb 8–10 g/dL) • Labs
– Elevated ferritin and iron, low TIBC – Anemia with basophilic
– MCV elevated in acquired; low in inherited stippling (denatured
RNA)
– Dimorphic cell population
– Elevated blood lead level
• Treatment
• Treatment
– Symptomatic – Remove from
– Pyridoxine (vitamin B6) in inherited form environment; chelation
• A cofactor in heme synthesis therapy (succimer or
dimercaprol and EDTA)

Macrocytic Anemia Vitamin B12/Folate

• MCV greater than 100 fL • Vitamin B12 • Folate
• Causes: – Essential for normal – Important in DNA
nuclear maturation synthesis
– Nutrition
– Diet is only source of – Found in green leafy
– Liver disease intake vegetables
– Preleukemia – Total body content 2–5 – Absorbed in proximal
mg jejunum
– Drugs - methotrexate, AZT, phenytoin
– Body stores last years – Body stores only 4
– Absorption in terminal months
ileum – Causes: inadequate
intake
Vitamin B12 Deficiency Macrocytic RBC
• Signs and symptoms
– Neurologic (tingling in feet,
gait abnormalities)
• Affects pyramidal tracts
and posterior column
– Glossitis
– Loss of vibratory sensation
• Diagnosis
– Hypersegmented neutrophils
– Serum Vitamin B12 level is IMC, © 2010 DxR
Development Group, Inc.
low 2 All Rights Reserved.
1
– Elevated methylmalonic acid 3
– Schilling s test
– Anti-IF antibody 4

• Treatment: IM injections 5
7 6

Folate Deficiency Anemia of Chronic Disease

ACD Fe def
• Signs and symptoms • Seen in:
Serum Fe ¯ ¯
– Glossitis, angular cheilosis – Infection
Transferrin NL/ ¯ ­
– No neurologic symptoms – Inflammatory disease % saturation ¯ ¯

• Diagnosis – Malignancy
Ferritin NL/ ­ ¯
– Serum and RBC folate – Renal disease
­ ¯
BM Fe
levels • Cells stores
– Normal methylmalonic acid – Microcytic/hypochromic or Normocytic/Normochromic
• Treatment normocytic/ normochromic
– Oral folate supplements • Labs
© Richard Usatine, M.D. Used with permission. – See table
• Treatment
– Treat underlying cause

Anemia
Hgb Women <12 g/dL

Hemolytic Anemia <2

Men <14 g/dL

>2
• Three elements of the red blood cell:
↓ production ↑ destruction
– Metabolic machinery (History of anemia?)

No Yes

– Hemoglobin
MCV Congenital

– Red cell membrane

Acquired
Normal (80–100 fL)

Coombs Membrane Hemoglobin Enzymes

Microcytic •Hereditary •Sickle cell •G-6-PD
(MCV <80 fL) spherocytosis (+ Sickledex, •Pyruvate
Normocytic Macrocytic
Negative Positive (+ osmotic confirm Hgb kinase
•Iron Def. (MCV 80- (MCV >100 fragility)
(Ferritin •Hypersplenism •Drug-induced electrophore
100 fL) fL) (>80%
<15) •Blood loss •B12 def. •Microangiopathic (PCN, sis)
(↑ RDW) spherocytes) •Hgb C
•Chronic (B12 (Schistocytes) quinidine,
•Thalassemia (TTP, DIC, levodopa) •Hereditary disease
disease <200)
heart valve) •Warm antibody elliptocytosis
(Normal (Neuro on
RDW) PE) •Physical (IgG type)
•Sideroblastic •Folate def. (Burns) (CLL, lymphoma,
(Ring (Folate •Chemical SLE)
sideroblasts) <2.5) (Fresh water) •Cold antibody
•Chronic (No •Infectious (IgM type)
disease neuro) (Malaria, (Mycoplasma,
(ACD) Clostridium) EBV)
•Lead
poisoning
Coombs Test (DAT) Coombs Negative
• Test for autoimmune hemolytic anemias • Hypersplenism
• Detects significant amounts of IgG and C3 on RBCs • Microangiopathic
• Chemical
• Physical
• Infection

Hypersplenism Microangiopathic
• Increased removal of cellular elements by the spleen • Mechanical disruption of
• Causes RBC
– Primary (idiopathic) • Schistocytes present
– Secondary • Etiology
• Acute and chronic infections – DIC
• Chronic inflammatory disease – TTP
• Congestive splenomegaly – HUS
• Myeloproliferative disorders – Prosthetic heart valves
• Leukemia/lymphoma

Coombs Negative Coombs Positive

• Chemical • Drug-induced
– Drugs (dapsone), fresh-water drowning – Hapten (penicillin)
• Physical – Immune complex (quinine)
– Burns, snake bites – Autoantibody (Aldomet)

• Infections • Warm antibodies (IgG)

– Malaria, Babesia, Clostridium perfringens, EBV • Cold antibodies (IgM)
Drug-Induced Hemolytic Anemia Summary of Drug-Induced
• Three types Mechanism Hapten Immune Complex Autoantibody
– Hapten-type (PCN)
Example Penicillin Quinidine Methyldopa
• Drug on RBC then Ab
DAT Positive Positive Positive
• IgG type Anti-IgG Positive Rarely positive Positive
– Innocent bystander-type (quinidine) Anti-C3d Rarely positive Positive Negative
• Ab binds to drug then RBC Indirect Coombs Negative Negative Either
(drug not in system)
• Anti-C3 type
– Autoantibody type (Aldomet) Indirect Coombs Positive Positive No change
• Autoantibodies against RBC by a drug (drug in system)

• Hemolysis even after drug discontinued

Examples Cephalothin HCTZ L-dopa
• Treatment: stop the drugs Ampicillin Antihistamines Ibuprofen
Methicillin Rifampin/INH Diclofenac
Sulfonamides a-interferon

Coombs + Hemolytic Anemia Coombs + Hemolytic Anemia

• Warm Antibody • Cold Antibody
– IgG type – Usually IgM
• Direct Coombs positive for IgG • Direct Coombs test positive for C3
• Decreased haptoglobin • IgM triggers complement

– Causes – Causes
• Viral (EBV) or mycoplasma infection
• Primary (Idiopathic)
• Lymphoproliferative diseases (lymphoma)
• Secondary
– Lymphoma, CLL – Treatment
– Autoimmune diseases (SLE, RA) • Keep patient warm; immunosuppression (chlorambucil)
• Drugs • Poor response to steroids
– May have Raynaud s phenomenon
– Treatment: steroids, IV gamma globulin,
splenectomy

Hereditary Spherocytosis
Congenital Hemolytic Anemia
• Membrane abnormalities • Autosomal dominant
– Hereditary spherocytosis trait
• Many spherocytes
– Hereditary elliptocytosis
seen on blood
• Enzyme deficiency smear
– G-6-PD deficiency • Most common in
– Pyruvate kinase deficiency people of northern
• Hemoglobinopathies European ancestry
• Defect is an
– Sickle cell anemia
abnormality of the
– Hemoglobin C and SC disease membrane protein
ankyrin
• Spectrin deficiency
seen in all patients
ccr.gov
 Hereditary Spherocytosis Hereditary Spherocytosis
• PE
– Splenomegaly
• Tests
– Elevated MCHC
– Osmotic fragility test
– >80% spherocytes on smear
• Treatment
– Splenectomy, folic acid

Hereditary Elliptocytosis G-6-PD Deficiency

• Autosomal dominant • Sex-linked
• Defect in horizontal • Populations include Mediterranean, West African,
junctions between a- Middle Eastern, and Southeast Asian
and b-spectrin dimers • Oxidant compounds (stress) lead to hemolysis
• Stressors of G-6-PD system
• Patients typically
– Antimalarials
asymptomatic
– Sulfonamides
• Smear – Nitrofurans
• Treatment: – Fava beans
splenectomy (stops – Infection
hemolysis but does – DKA
not correct defect)

G-6-PD Deficiency Pyruvate Kinase Deficiency

Burr cell
• Usually asymptomatic • Autosomal recessive
until times of stress • Reduced ATP formation causes RBC membrane
• Crisis rigidity, resulting in hemolysis
– Smear: spherocytes,
blister cells, burr • Seen usually in children
cells – Splenomegaly
– Lab evaluation – Cholelithiasis
• G-6-PD levels
– Jaundice
– Heinz bodies
• Composed of
denatured
hemoglobin
Sickle Cell Anemia Sickle Cell Anemia
• Clinical features • Treatment
• Frequency 1:400–500 African Americans – Bone, chest, and – Maintenance therapy
• Due to substitution of valine for glutamic acid at position abdominal pain in crisis • Hydroxyurea
6 on beta chain – Splenomegaly • Vaccines

– Leg ulcers • Antibiotics

– These abnormal beta chains combine with alpha chains
– Crisis therapy
to form abnormal Hgb S – Pulmonary infection and
infarctions • Analgesics
• At low oxygen tensions, Hgb S is poorly soluble and • Fluids
– Strokes
distorts the cell • Antibiotics
• Labs
• Oxygen
– CBC with diff
– Sickledex
– Hgb electrophoresis

Sickle cell
Sickle Cells Sickle Cell Trait
• Patients not anemic and rarely experience symptoms
• Electrophoresis
– 25–45% Hgb S
– Remainder Hgb A, F, and A2
• Complications
– Hematuria
– Splenic infarct
– Normal lifespan

Hemoglobin C Disease Aplastic Anemia

• Mild to moderate anemia • Decrease in production of all
cell lines
• Splenomegaly common Crystal
• Acquired or genetic
• Hemoglobin crystals – Toxin, radiation,
immunologic
• Target cells reason, NSAIDS,
• Diagnosis chemotherapy,
chloramphenicol, EBV,
– Electrophoresis CMV, Parvovirus B19
• Due to damage to the
stem cells
• Labs
– Pancytopenia
• Treatment
– Bone marrow transplant IMC, © 2010 DxR Development Group, Inc. All Rights Reserved.
Polycythemia Transfusion Reactions
• Excessive amounts of red blood cells in the absence of • Hemolytic Reactions
– Hemolytic reactions occur when the recipient's serum contains antibodies
hypoxia or elevated erythropoietin levels directed against the corresponding antigen found on donor red blood cells.
• Clinical – This can be an ABO incompatibility or an incompatibility related to a
different blood group antigen.
– Elevated hematocrit – Disseminated intravascular coagulation (DIC), renal failure, and death are
– Splenomegaly not uncommon following this type of reaction.
– The most common cause for a major hemolytic transfusion reaction is a
– Thrombosis clerical error
– Redness of the face (plethora) • Allergic Reactions
– Pruritis after exposure to warm water – Allergic reactions to plasma proteins
– Range from complaints of hives and itching to anaphylaxis.
• Diagnosis – Such reactions may occur in up to 1 in 200 transfusions of RBCs and 1 in
– Elevated hematocrit 30 transfusions of platelets.

• Treatment • Febrile Reactions

– White blood cell reactions (febrile reactions) are caused by patient
– Phlebotomy antibodies directed against antigens present on transfused lymphocytes or
granulocytes.
• Hydroxyurea
– The risk for febrile reaction is 1 in 1,000 to 10,000.
– Aspirin to prevent thrombosis – Symptoms usually consist of chills and a temperature rise > 1 degree C.

Transfusion Reactions
• Transfusion related acute lung injury (TRALI)
– TRALI is now the leading cause for transfusion-related The Hematologic System
mortality.
Lecture 1 Anemias and Other Disorders
– Caused most often when donor plasma contains HLA or
leukocyte (usually granulocyte) specific antibodies. Lecture 2 Coagulation Disorders
– Recipient leukocytes may be 'primed' by underlying illness to
become more adherent to pulmonary alveolar epithelium. Lecture 3 Malignancies
Introduction of the donor antibodies into the recipient causes
granulocyte enzymes to be released, increasing capillary
permeability and resulting in sudden respiratory distress from
pulmonary edema, typically within 6 hours of tranfusion.
Leukopenia may transiently occur.
– Most cases improve within 2 days.

Coagulation Cascade

Coagulation Disorders
Factor VIII deficiency
Factor IX deficiency
Factor XI deficiency
von Willebrand’s Disease
Thrombocytopenia
 Factor VIII Deficiency Factor VIII Deficiency
• Hemophilia A, X-linked disorder • Labs
• Categorized by factor activity level – Normal PT, ↑ PTT, normal thrombin time
• Bleeding into muscles, joints, and soft tissue; – Normal platelets
microscopic hematuria and cranial bleed – Reduced Factor VIII activity

• Seen primarily in men 1:10,000 • Treatment

– Factor concentrates (Factor VIII)
• Clinical
• Recombinant Factor VIII (Xyntha)
– Bleeding in joints and retroperitoneum
– FFP or cryoprecipitates
– e-aminocaproic acid (EACA) with or without DDAVP

Factor IX Deficiency Factor IX Deficiency

• Hemophilia B, X-linked disorder • Labs
• Bleeding into muscles, joints, and soft tissue; – Normal PT, ↑ PTT, normal thrombin time
microscopic hematuria and cranial bleed – Normal platelets
• Seen primarily in men – Reduced Factor IX activity
• 4–8x less common than hemophilia A • Treatment
• Clinical – Factor IX concentrate
– Bleeding in joints and retroperitoneum – FFP and cryoprecipitates

Prevalence & Severity of Hemophilia in the U.S. Factor XI Deficiency

Factor VIII or IX Incidence • Autosomal recessive
Level (U/dL) Clinical Picture Hemophilia A Hemophilia B • Ashkenazi Jews
<1 Severe, 70% 50% • Mild bleeding (post-op bleeding)
spontaneous • Labs
bleeding
– Prolonged PTT
1–5 Moderate 15% 30%
bleeding with – Reduced levels Factor XI
minimal trauma • Treatment
or surgery
– Fresh frozen plasma
5–30 Mild bleeding with 15% 20%
major trauma or
surgery
Von Willebrand's Disease Von Willebrand's Disease
• Most common severe congenital bleeding disorder • Three types
– Affects 1% of the population – Type 1 (1–2% of the population)
• 80% of all vWF cases
• Autosomal dominant pattern
• Partial deficiency
• Problem with platelet adhesion • Bleeding time may be normal
– Defect in vWF – Type 2
• Clinical • Multiple subtypes: 2A, 2B, 2N, and 2M
– Bleeding in nasal, sinus, vaginal, and GI mucous – Type 3 (1:250,000)
membranes • Severe deficiency
• Typically diagnosed in childhood

Von Willebrand's Disease Thrombocytopenia

• Labs • Thrombotic Thrombocytopenic Purpura
– Normal platelet count • Immune Thrombocytopenic Purpura
– Prolonged bleeding time • Heparin-induced
– Prolonged PTT due to decreased level Factor VIII • Splenomegaly
– Decreased vWF antigen – May hold 90% of platelets
• Treatment
– vWF concentrates: contain vWF and Factor VIII
– Cryoprecipitate: rich in vWF
– DDAVP: stimulates release of vWF

Immune Thrombocytopenic Purpura Adult vs. Childhood

• Most common consumptive thrombocytopenia in adults Characteristic Childhood (Acute) Adult (Chronic)
• Both adult and childhood ITP Age of onset Childhood Women ages 20–50
• More common in women (3:1) ages 20s to 30s
• Can be associated with other autoimmune diseases Previous infection Common Usually not
– Associated with recent viral infection in children
Platelet count <20,000 30,000–80,000
• Present with petechiae, purpura, gingival bleeding, and
menorrhagia Duration of Few weeks Months to years
thrombocytopenia
• No splenomegaly
Bleeding Abrupt Insidious
Spontaneous Occurs in most Rare
remission
ITP: Pathogenesis ITP: Diagnosis
• Results from platelet sensitization by auto-reactive • Thrombocytopenia
antibodies – May be <10,000 Megakaryocytes

– React to glycoprotein IIb/IIIa complex • Increased megakaryocytes

in bone marrow & large
• Increased amounts of platelet-associated IgG, leading platelets in peripheral blood
to shortened survival due to phagocytosis by splenic • Treatment
macrophages
– Prednisone
• Childhood version: viral antibody complex binds to – Splenectomy
platelet – Danazol
– High dose IV
immunoglobulin
• Will increase platelet
count in 1–5 days but
lasts only 1–2 wks

Thrombotic Thrombocytopenic Purpura (TTP) TTP

• Seen in previously healthy young women; often fatal • Labs
• A platelet consumption disorder – Schistocytes
• Clinical: classic five findings: – Thrombocytopenia
– Thrombocytopenia – Elevated LDH,
– Microangiopathic hemolytic anemia
Coombs negative
– Fever
– Neurologic signs • Treatment
– Renal involvement: mild insufficiency, hematuria – Plasma exchange with
• HUS identical to TTP but seen in children FFP
– No neurologic impairment, severe renal impairment – Steroids and aspirin
– Secondary to hemorrhagic colitis
• Enterotoxigenic E. coli (O157:H7) or Shigella dysenteriae

Disseminated Intravascular Coagulation (DIC) DIC: Etiology

• Acquired thrombohemorrhagic disorder • Infections • Obstetric
– Gram-negative sepsis – Abruptio placenta
• Results from excess formation of thrombin and
– Gram-positive sepsis – Eclampsia
plasmin in circulation
– RMSF – Retained placenta
– Thrombin to fibrin and clotting – Severe malaria
– Plasmin breaks down fibrin and bleeding • Other
• Malignancies
– Crush injury
• Always secondary to another condition – Acute promyelocytic
leukemia – Snake venoms
– Tumor lysis syndrome – Burns
– Lymphomas – ARDS
DIC: Signs and Symptoms DIC: Labs
• Signs of Thrombi • Signs of Bleeding Blood Test DIC Normal
– Blue toes/fingers – Petechiae Platelet count <150,000 µL 150,000–400,000/ µL
(ischemia) – Purpura
– Obtundation/coma – Hematomas
PT >15 sec 12–14 sec
– Respiratory failure – Intracranial bleeding
– GI stress ulcers – Massive bleeding
aPTT >37 sec 25–38 sec
– Intravascular hemolysis – Epistaxis Fibrinogen <150 mg/dL 150–350 mg/dL
– Oliguria – Hematuria
– Azotemia
FDP >20 µg/mL 2–10 µg/mL
– Fever (58%)
– Hypotension (50%)
D-dimer Positive Negative
Liver disease separated from DIC by finding normal levels of Factor VIII and D-dimer.

DIC: Treatment Heparin-Induced Thrombocytopenia (HIT)

• Treat the underlying cause
• Supportive measures to correct any
hypoxemia/hypovolemia
• Heparin therapy to stop blood activation
– If given heparin, must give antithrombin III (FFP) if low
• Replacement therapy with AT III, FFP, cryoprecipitate,
and platelets
– Platelets
• Transfuse if <20 or <50 with major bleeding
– FFP (contains all clotting factors) or cryoprecipitate
• Transfuse if fibrinogen <100 md/dL; goal is 150mg/dL
• Seen in 3% of patients receiving unfractionated heparin
and 1% receiving LMWH
• Patient produces antibodies (IgG) against the complex
formed by heparin and platelet Factor IV
• Platelet activation and thrombin generation occur
leading to a procoagulant state
– Patient develops thrombosis
– 50–66% of patients with HIT will have a thromboembolic
event

HIT: Thromboembolic Events HIT

• Venous
– Deep venous thrombosis
– Pulmonary embolus
– Cerebral vein thrombosis
– Adrenal insufficiency
– Central line thrombosis
• Arterial
– Cerebrovascular
infarction
– Myocardial infarction
– Splenic infarction
– Extremity arterial
thrombosis
– Aortic thrombosis
– Arterial line thrombosis
• Detection
– Scoring system
• Retrospective
– Rapid test for anti-heparin/PF4 antibody titers
• Treatment
– Stop the heparin
– Do not substitute LMWH
– Argatroban or hirudin (direct thrombin inhibitors)
Hypercoagulable States Prolonged PT and PTT
General Diagnosis
Prolonged Prolonged PTT Prolonged PT and
• Group of hereditary and • Testing is indicated in the PT PTT
acquired conditions that following groups:
• Inherited • Factor VII • Von Willebrand • Prothrombin, fibrinogen,
confer and increase risk to – Idiopathic or recurrent venous
deficiency disease Factor V, Factor X or
thromboembolism (VTE)
develop thrombi. • Factors VIII, IX, XI, combined factor
– VTE at age <40 years
• Disorders include the or XII deficiencies deficiencies
– VTE with strong family history
following: – VTE in unusual vascular sites • Acquired • Vitamin K • Heparin • Liver disease
– Antiphospholipid syndrome – Warfarin-induced skin necrosis deficiency • Antiphospholipid • DIC
– Factor V Leiden syndrome – Recurrent pregnancy loss • Liver disease antibody • Combined heparin and
• Warfarin use warfarin therapy
– Prothrombin gene G20210A • Initial screening tests
mutation • Inhibitor of prothrombin,
– PT/PTT/Fibrinogen
fibrinogen or Factor V or
– Elevated factor VIII – Anticardiolipin antibody assay
X
– Hyperhomocysteinemia – Protein C and S
– Deficiencies in antithrombin, – Antithrombin level
protein C, and protein S – C-reactive protein (CRP)
– Homocysteine

The Hematologic System

Lecture 1 Anemias and Other Disorders
Malignancies
Lecture 2 Coagulation Disorders
Acute/Chronic Lymphocytic Leukemia
Lecture 3 Malignancies
Acute/Chronic Myelogenous Leukemia
Lymphoma
Multiple Myeloma
Chemotherapy

Acute Lymphocytic Leukemia (ALL) Acute Lymphocytic Leukemia

• General • Labs
– Most common in children (peak age 4 years) – Blasts >30%
• Clinical characteristics • See photo cells #1-5
– Elevated WBC
– Anemia, bruising, infection
– Anemia
– CNS involvement – Bone marrow for diagnosis
– Lymphadenopathy, splenomegaly • Treatment
• Prognosis – Chemotherapy-
– Over 70% of cases are cured daunorubicin, vincristine,
prednisone
– CNS treatment-
methotrexate
– Transplant
Chronic Lymphocytic Leukemia (CLL) Chronic Lymphocytic Leukemia
• Cause unknown • Labs
• Increases with age (>50 years) – Lymphocytosis
• See photo cells
• Men > women #1-4
• Mainly B-cell lymphocytes – Smudge cells
• Increased risk of bacterial infections • See photo cell #5
• Treatment
• Clinical
– Chlorambucil to
– Usually asymptomatic reduce WBC count
– Splenomegaly, lymphadenopathy – Chemotherapy
– Slow, indolent course • Fludarabine

Acute Myelogenous Leukemia (AML) Acute Myelogenous Leukemia

Auer Rod
• More common in adults • Labs
– Blasts >30%
• Risk factors: radiation, chemicals, prior
– Auer rods
chemotherapy
– Elevated WBC
• Low survival rate even with treatment – Anemia
• Classification: FAB classes – Bone marrow for
diagnosis
• Clinical • Treatment
– Fatigue, anorexia, dyspnea – Chemotherapy-
cytosine arabinoside
– Exam: lymphadenopathy, splenomegaly and daunorubicin
– No CNS treatment

Chronic Myelogenous Leukemia (CML) Chronic Myelogenous Leukemia

• A myeloproliferative disorder • Labs
• Typical patient middle-aged – Philadelphia chromosome
positive
• Clinical
– Anemia, thrombocytosis,
– Fatigue, lethargy, SOB, weight-loss, easy bruising elevated LDH, low LAP
– Exam: splenomegaly score
– Differential reveals entire
• Phases
WBC cell line
– Chronic: lasts 3–5 years, elevated WBC, but few blasts • See photo cells #1-6
– Blastic: conversion to acute leukemia, blasts fill marrow • Treatment
– Imatinib
– Alpha interferon (rarely
used)
Hairy Cell Leukemia Myelodysplasia
• General • Considered pre-leukemia
– More common in men • Probable genetic defect
(4:1)
– Most common 5q deletion
– Peak age 55 years
– Infections frequent • Presentation
– Pancytopenia, elevated MCV
• Clinical presentation
– Fatigue, infections, bleeding
– Pancytopenia,
splenomegaly – Pelger-Huet cells

• Lab • Treatment
– Bone marrow: hairy cells – Transfusions as needed
• Treatment – Antibiotics for infection
– TNF inhibitors
– 2-chlorodeoxyadenosine
(2-CDA) • Lenalidomide or thalidomide
– Azacytidine or decitabine if 5q deletion present

Leukopenia Leukopenia
• Most cases result from absolute neutropenia (<2500 Neutropenia Lymphopenia
cells/mm3); rare cases are secondary to absolute
lymphopenia (<1000 cells/mm3) • Drugs • Most cases are
– Noncytotoxic drugs (e.g., secondary to:
• Patients with neutropenia usually have signs and quinidine, penicillins,
symptoms of infection that may be life threatening. sulfonamides, phenothiazines, – Drugs (e.g., steroids)
– Fever in the absence of localizing signs of infection is common. diuretics) – Radiation injury
After obtaining cultures, start broad-spectrum antibiotics – Alkylating agents, – Renal failure.
immediately. antimetabolites, and other
neoplastic agents – Some viral infections,
• Disorders leading to splenomegaly with splenic particularly HIV, can also
sequestration can cause neutropenia, but there usually • Infections
cause absolute
is associated thrombocytopenia. – Viruses (Epstein-Barr,
cytomegalovirus, HIV, lymphopenia.
– Differential diagnosis includes cirrhosis, sarcoidosis, glycogen hepatitis, measles)
storage diseases, and other uncommon conditions. – Bacteria (severe gram-
• Test of choice is a bone marrow biopsy and aspirate to negative and gram-positive
rule out a primary hematologic disorder organisms)
– Other: typhoid fever, malaria,
Mycobacterium, and fungi.

Hodgkin s Lymphoma Reed-Sternberg Cell

Hodgkin s Lymphoma
• Ages 15–35 and >50 • Clinical
years
– B symptoms: fever, night sweats, weight loss
– More common in men
(25–35 age group) • Labs (staging)
• Etiology: EBV? – CT chest, abdomen, pelvis
• Classic Reed-Sternberg
cells – Bone marrow
• Painless, enlarged lymph – Lymph node biopsy
nodes
• Clinical
– Lymphadenopathy
– Splenomegaly
– Hepatomegaly
Hodgkin s Lymphoma: Staging Hodgkin s Lymphoma
• Stage I • Treatment (depends on stage)
– Single lymph node region or structure – Chemotherapy
• Stage II
• Adriamycin, bleomycin, vincristine
– 2 or more lymph node regions on same side of
diaphragm – Radiation therapy
• Stage III
– Lymph node regions or structures on both sides of
diaphragm
• Stage IV
– Involvement of other organs (liver, bone marrow, CNS,
etc.)

Non-Hodgkin s Lymphoma Non-Hodgkin s Lymphoma

• Most commonly B lymphocytes • More common than Hodgkin s lymphoma
• Classification varies based on where they arise – Incidence is increasing
– Perifollicular B lymphocytes
• Incidence increases with age
• Small lymphocytic leukemia and chronic lymphocytic
leukemia • Moderate predominance in men
– Germinal center of lymphoid follicle • Present with lymphadenopathy
• Follicular lymphoma, large cell lymphoma, Burkitt s
lymphoma • Can involve the skin, GI tract, and CNS
– Mantle zone of lymphoid follicle
• Mantle cell lymphoma
– Marginal zone of lymphoid follicle
• Monocytoid lymphoma and mucosa-associated lymphoid
tissue (MALT) lymphoma

Non- Hodgkin s Lymphoma Non- Hodgkin s Lymphoma: Staging

• Clinical • Stage I
– Splenomegaly is common – Single lymph node region or structure
– B symptoms: fever, night sweats, weight loss • Stage II
– 2 or more lymph node regions on same side of
• Labs (staging)
diaphragm
– CT chest, abdomen, pelvis
• Stage III
– Bone marrow – Lymph node regions or structures on both sides of
– Lymph node biopsy diaphragm
• Stage IV
– Involvement of other organs (liver, bone marrow, CNS,
etc.)
Non-Hodgkin s Lymphoma Multiple Myeloma
• Chemotherapy • Plasma cell dyscrasia
– Respond very well but relapse is common
• Monoclonal production of IgG, IgA, IgD, IgE, or
• Radiation therapy
monoclonal light chains (Bence Jones proteins)
• Stem cell transplant
• Monoclonal antibodies • ↑ risk with age, African Americans
– Rituximab • Men = women
• Interferon
• Risk factors: radiation exposure and chemical
exposure (asbestos)

Multiple Myeloma Multiple Myeloma

• Clinical • Labs
– Anemia (Rouleaux on
– Early: fatigue, weakness, weight loss
smear)
– Later: bone pain, anemia, renal function changes, – ↑ sedimentation rate
neurologic abnormalities – ↑ plasma cells (>10% in
– Exam: skeletal pain on palpation, bruising, wasting, bone marrow)
neurologic deficits – ↑ serum total protein
• ↑ serum β2-
• Infection with encapsulated organisms is common microglobulin
– Pneumococcus, Haemophilus – Monoclonal spike on SPEP
– Bence Jones protein on
UPEP
– Renal insufficiency
– Calcium level elevated

Multiple Myeloma Monoclonal Gammopathy of Uncertain

• X-ray Significance (MGUS)
– Classic punched-out lesions • Overproduction of a particular immunoglobulin
– Skull, ribs, spine. and pelvis – Cause unknown
– Compression fractures develop • No systemic manifestations
later
• No symptoms
• Treatment
• Labs normal except elevated immunoglobulins
– Supportive: transfusions, pain
• No treatment
control
– Chemotherapy
• Melphalan and prednisone
• Complications nih.gov

– Increased risk of bacterial

infection (S. pneumoniae)
Chemotherapy Side Effects
• 6-thioguanine • Cisplatin
– Hepatotoxicity – Ototoxicity
• 6-mercaptopurine • Doxorubicin
– Hepatitis and biliary – Cardiomyopathy
stasis • Cyclophosphamide
• Bleomycin – Hemorrhagic cystitis
– Pulmonary fibrosis
• Vincristine
– Peripheral neuropathy
– Cranial nerve palsy
 Infectious Diseases
Lecture 1 Viral Diseases

Infectious Diseases Lecture 2 Fungal Diseases

Spirochetal Disease

Lecture 3 Mycobacterial Diseases

Parasitic Diseases

Jim Van Rhee, MS, PA-C Lecture 4 Bacterial Diseases

Program Director; Associate Professor HIV
Sepsis
Yale School of Medicine, PA-Online

Cytomegalovirus
• Member of the Herpes family
Viral Diseases • Neonatal infections
– Hepatosplenomegaly, purpura, CNS changes
CMV Infection • Immunocompetent patients
Epstein Barr Infection
– Mono-like illness with fever, myalgias,
Erythema Infectiosum hepatosplenomegaly, leukopenia with increase lymphs,
Herpes Simplex Virus no pharyngitis
Influenzae – IgM antibody is diagnostic
Mumps • Immunocompromised patients
Rabies – AIDS retinitis, pneumonia, meningoencephalitis,
Roseola chronic diarrhea
Rubella • Leading cause of blindness in AIDS patients
Rubeola
Varicella-Zoster Infection
Zika Virus

CMV Infection Epstein-Barr Infection

• Diagnosis Inclusion body • Member of Herpes family
– Cytopathology owl eye
– Cell culture • Causes infectious mononucleosis
– Antibody detection
• Treatment • Transmitted by salvia, incubation period 5–15 days
– Supportive care
• Prophylactic treatment in
• Peak age 14–18
HIV patients • Signs/Symptoms
– Ganciclovir
• Used in children & adults – Fever, pharyngitis, malaise, lymphadenopathy
• Side effect neutropenia
– Foscarnet
(posterior cervical), rash, splenomegaly
• Used in adults phil.cdc.gov

• Side effect renal toxicity

– Cidofovir
• 2nd or 3rd line due to
renal toxicity
Epstein-Barr Infection EBV-Specific Serology
• Labs
Atypical Lymphocyte
– Lymphocytosis with
atypical lymphocytes Antibody Time of Persistence % of IM Patients
Appearance with Ab
– Elevated liver function VCA-IgM At presentation 1–2 months 100%
tests
VCA-IgG At presentation Lifelong 100%
– Positive heterophile EBNA 3–6 weeks Lifelong 100%
antibody
VCA: viral capsid antigen
• Monospot EBNA: Epstein Barr nuclear antigen
– Positive EBV specific
serology VCA-IgM is the best indicator of primary infection.
Presence of VCA-IgG and EBNA indicates past infection.

Epstein-Barr Virus Erythema Infectiosum (Fifth Disease)

• Complications • Most common under age 10
– Splenic rupture • Due to parvovirus B19
– Hepatitis
– Spread by respiratory droplets
– Myocarditis
– Thrombocytopenia • Malaise, headache, and pruritus

– Encephalitis – Little or no fever

• Treatment • Rash: fiery red slapped cheek , circumoral pallor
– Supportive care and a subsequent lacy, maculopapular truncal rash
© Richard Usatine, M.D. Used with permission.

– No rash on palms or soles

– Ampicillin may cause a rash
• Complications: Miscarriage, aplastic crisis
• Treatment: Supportive, NSAIDS

© Richard Usatine, M.D. Used with permission.

Herpes Simplex Virus Herpes Simplex Virus

• Humans only natural reservoir • Type 1
• Transmission by direct contact with infected secretions – Any mucosal surface
• Recurrent grouped small vesicles on an erythematous – Painful and lasts 5–10
base days
• Perioral or perigenital – May be come latent in
• Primary Infection sensory nerve root
– Fever, regional lymphadenopathy, aseptic meningitis ganglion
– Recurrences: precipitated by stress, trauma, sun • Herpes whitlow: HSV of
finger or nail region
• Systemic Infection © Richard Usatine, M.D. Used with permission

– Immunosuppressed patients
– Proctitis, esophagitis, keratitis
Herpes Simplex Virus Herpes Simplex Virus
• Type 2 • Diagnosis
– Genital herpes – Tzanck smear
– Incubation period 5 days – Direct fluorescent
after sexual contact antibody
– Painful, multiple lesions – Culture
– May have systemic • Treatment
symptoms such as fever – Acyclovir
and myalgias
• IV for encephalitis
– Paresthesias may be – Famciclovir
noted 12–24 hours prior
to lesions – Valacyclovir © K atsum i M . M iyai, M .D ., P h.D .

© Richard Usatine, M.D. Used with permission

Influenza Influenza
• RNA virus (Orthomyxoviridae) • Clinical
• Influenza A and B – Abrupt onset fever (101–106 F)
– Myalgias, headache, nonproductive cough
– Influenzae A highly infectious; institutional settings
– Coryza and sore throat
– Influenzae B noted in schools and military – Exam usually normal
• Spread by respiratory droplets • Labs
• Incubation 1–3 days – Leukopenia or normal WBC
– CXR normal
• Outbreaks every winter
– Viral culture
• Community outbreaks

Influenza Mumps
• Treatment • Painful, swollen salivary glands (parotid)
– Symptomatic – Fever, headache, malaise
– Influenza A > amantadine, rimantadine no longer indicated • Spread via respiratory droplets
– Influenza A or B > oseltamivir, zanamivir – Incubation period is 12–24 days
• Antivirals reduce duration of symptoms if given within 48 hours • May have orchitis, oophoritis, meningoencephalitis, or
pancreatitis
phil.cdc.gov
– Antibiotics if secondary bacterial infection
– Immunization: elderly, respiratory disease, pregnant women, • Diagnosis
cardiac disease, health care workers, immunosuppressed – Viral culture in salvia
• Complications – Antibodies after week 2
– Reye s syndrome (aspirin); secondary bacterial infections: • Treatment
pneumonia – Immunization
• Vaccine at 12–15 months,
then at age 4–5
– Supportive
Rabies Rabies Treatment
• Rhabdovirus (bullet-shaped) • Wash and clean the wound
• Transmitted by infected saliva – Observe the animal
• History of animal bites
• Post-exposure immunization
– Bats, bears, skunks, foxes,
– Rabies immune globulin (RIG)
raccoons
• Full dose around wound
– Dogs and cats in
developing countries • Do not give if previously immunized
• Signs/Symptoms – Vaccine
– Paresthesias, hydrophobia, • Dose on days 0, 3, 7, and 14 and 28
rage cdc.gov • If previously immunized, on days 0 and 3
– Convulsions, paralysis, • Treatment
thick saliva, muscle spasms – Supportive

Roseola Rubella
• Roseola infantum (sixth disease) • Systemic illness, transmitted by
infected droplets
• Etiology is human herpes virus 6 and 7
• Incubation period 14–21 days
– Incubation 10 days • Cervical, suboccipital, posterior
• Typically under age 5 (typically age 6-15 months) auricular lymphadenopathy 5-
10 days before rash
• Symptoms • Fever, malaise, and coryza and
– High fever (41 C) for 3 days, resolves, then rash appears then 2–3 days later,
– Faintly erythematous, macular, and diffusely disseminated maculopapular rash develops
(starts on trunk) – Forchheimer spots: petechial
lesions soft palate
• Complications – Rash to face, trunk, then
– Febrile seizures, encephalitis extremities (rapidly fades,
lasts 3 days)
• Treatment
• Joint pain common (young
– Supportive, fever control
women) phil.cdc.gov

Rubella Rubeola (Measles)

• Complications • Transmitted by infected droplets
– Thrombocytopenia – Very contagious
– Postinfectious
• Incubation period 10–12 days
encephalopathy
– Congenital rubella • Prodrome
• Growth retardation, – Fever (40–41 C), coryza, cough, conjunctivitis, photophobia
cataracts, deafness, • Rash
PDA
– Brick-red, irregular maculopapular rash
• Check immune status in
– 2–4 days after prodrome
pregnant patients
• Treatment – Head to trunk to extremities

– Active immunization after • Fever concurrent with rash

age 15 months; second
dose at age 4–6
 Rubeola Varicella-Zoster Infection
• PE • Acute Varicella (Chicken Pox)
– Koplik s spots (buccal mucosa): white or blue gray – Fever, malaise
lesions on a red base opposite upper molar – Rash
• Treatment • Pruritic, centripetal, papular rash, vesicular and pustular
before crusting
– Primary immunization after • First lesion is drop on rose petal
age 15 months; second dose • Lesions in all stages at any given time
at age 4–6 – Macules, papules, vesicle, pustules
– Isolate for 1 week after rash – Incubation period 10–21 days
• Complications • Reactivation (zoster/shingles)
– Secondary bacterial infection (OM) – Dermatomal distribution
– Vesicular rash with preceding pain
– Encephalitis
© Richard Usatine, M.D. Used with permission

© Richard Usatine, M.D. Used with permission

Varicella-Zoster Varicella-Zoster Infection

• Complications
– Bacterial infection (most common)
– Pneumonia
– Encephalitis, Guillain-Barré syndrome
– Post-herpetic neuralgia
• Treatment
– Supportive: lotions, antihistamines
© Richard Usatine, M.D. Used with permission – Antivirals: acyclovir, valacyclovir, famciclovir
– Immune globulin: pregnancy, immunosuppressed

© Richard Usatine, M.D. Used with permission

Varicella-Zoster Vaccination Zika Virus

• Shingrix (recombinant zoster vaccine) as preferred over • A single-stranded RNA virus of the Flaviviridae family,
Zostavax (zoster vaccine live) for the prevention of herpes genus Flavivirus.
– Transmitted primarily through the bite of an infected Aedes mosquito.
zoster (shingles) and related complications. • Perinatal, in utero, and possible sexual and transfusion transmission
– CDC recommends two doses of Shingrix separated by 2 to 6 months events have also been reported.
for immunocompetent adults age 50 years and older: • Clinical Signs & Symptoms
• Whether or not they report a prior episode of herpes zoster – Many people infected are asymptomatic.
– Characteristic clinical findings include fever with maculopapular rash,
• Whether or not they report a prior dose of Zostavax
arthralgia, or conjunctivitis, other symptoms include myalgia and headache.
• Who have chronic medical conditions (e.g., chronic renal failure, – Clinical illness is usually mild with symptoms lasting for several days to a
diabetes mellitus, rheumatoid arthritis, chronic pulmonary week
disease), unless a contraindication or precaution exists. Similar – Infection during pregnancy is a cause of microcephaly and other severe fetal
to Zostavax, Shingrix may be used for adults who are: brain defects.
– are taking low-dose immunosuppressive therapy • Diagnosis & Reporting
– Detect virus, viral nucleic acid, or virus-specific immunoglobulin M and
– are anticipating immunosuppression
neutralizing Ab.
– have recovered from an immunocompromising illness • Treatment
– It is not necessary to screen for evidence of prior varicella infection. – No specific antiviral treatment is available.
– Treatment is generally supportive
– Zostavax may still be used to prevent shingles in healthy adults 60 – Consider possible dengue or chikungunya virus infection in differential
years and older.
 Infectious Diseases
Lecture 1 Viral Diseases
Fungal Diseases
Lecture 2 Fungal Diseases
Spirochetal Diseases Candida albicans
Lecture 3 Mycobacterial Diseases Cryptococcosis
Parasitic Diseases
Histoplasmosis
Lecture 4 Bacterial Diseases
HIV Coccidioidomycosis
Sepsis
Pneumocystis

Candida Infection Candida Infection

• General • Oropharyngeal (Thrush)
– Most common opportunistic – White plaques on buccal mucosa
fungal infection – Erythematous base
– Normal flora in GI and GU tract • Vulvovaginitis
– Due to Candida albicans – Women child-bearing years
– Pruritus, curd-like discharge
• Clinical
phil.cdc.gov • Cutaneous
– Oropharyngeal – Intertriginous areas
– Vulvovaginitis – Erythematous lesions with distinct borders and
– Cutaneous satellite lesions
– Disseminated • Disseminated
• Endocarditis – Hepatosplenic infection in leukemic patients
• Candidemia
© Richard Usatine, M.D. Used with permission

Candida Albicans Cryptococcosis

• Diagnosis • Most common cause of fungal meningitis
– KOH prep
– Organism: Cryptococcus neoformans
– Culture
• Treatment • Predisposing factors
– Mucocutaneous – Hodgkin s, steroid therapy, HIV
• Clotrimazole
• Fluconazole in AIDS
• Symptoms
– Vulvovaginitis – Headache
• Miconazole, clotrimazole – Mental status changes
– Disseminated © R ichard U satine, M .D . U sed w ith perm ission
– Meningismus
• Fluconazole,
amphotericin B
– Visual abnormalities
 Cryptococcosis Histoplasmosis
• Labs • Histoplasma capsulatum
– CSF (dimorphic fungi)
– Endemic to Mississippi
• ¯ glucose and Ohio river valleys,
• ­ protein eastern Canada, Mexico &
• ­ WBC (lymphs) C. America
– India ink prep • Related to bird droppings phil.cdc.gov

– Latex agglutination titer and bat exposure

phil.cdc.gov – Inhale spores
• Treatment
• Most patients
– Amphotericin B plus flucytosine for CNS infection asymptomatic
– Fluconazole (PO) for pulmonary disease – Respiratory illness
• May disseminate in
immunocompromised
– Leukemia, steroids, HIV phil.cdc.gov

Histoplasmosis Coccidioidomycosis
• Labs • Caused by Coccidioides
– Bone marrow positive immitis
– Dimorphic organism
– Urine antigen test
• Exposure usually in
– Skin test
Southern California to
– CXR: pneumonia, Texas
miliary pattern • Present with pulmonary
• Treatment symptoms, arthralgias
– Itraconazole (mild to • Diagnosis:
moderate disease) – Culture
– Amphotericin B (severe – Serology
• Treatment
phil.cdc.gov
disease)
– Fluconazole, itraconazole
– Amphotericin B
© Richard Usatine, M.D. Used with permission

Systemic Fungal Organisms

Histoplasmosis Blastomycosis Coccidioido- Candidiasis Cryptococcu Aspergillosis
Pneumocystis Jirovecii
mycosis s
• A protozoan
Type Dimorphic Dimorphic Dimorphic Yeast Yeast Fungus
– Noted in AIDS patients with CD4 <200
Epidemio- Mississippi and North central Southwest Normal flora Western US Ubiquitous • Symptoms
logy Ohio river and south US GI, GU and
central US skin – Fever, chills, sweats, fatigue, dyspnea, nonproductive
Soil, caves soil, decaying Pigeon Water/soil
wood excreta cough
Soil
Route of Inhalation Inhalation Inhalation Direct or Inhalation Inhalation
• CXR
infection blood
– Bilateral diffuse interstitial disease without hilar
Disease Pulmonary Pulmonary Pulmonary Vagina, Pulmonary Pulmonary
Disseminated Disseminated Disseminated esophagus, CNS adenopathy
skin
Diagnosis Culture Culture Culture Gran stain Culture Culture
– Apices are typically spared
stains stains stains KOH prep
Culture • Exam
Treatment Itraconazole Itraconazole Ketoconazole Clotrimazole Amphotericin Amphotericin
– Bibasilar crackles or normal
Amphotericin B Amphotericin Fluconazole Miconazole B B
B Amphotericin Fluconazole Flucytosine Itraconazole
B
Pneumocystis Jirovecii
• Labs
– ↓ partial pressure of oxygen
– ↑ LDH
– Diagnosis made with bronchoalveolar lavage and special Spirochetal Diseases
lung tissue stains
Lyme Borreliosis
• Treatment
Rocky Mountain Spotted
– Trimethoprim-sulfamethoxazole
Fever
– Pentamidine
– Prednisone if PaO2 <70 mm Hg Syphilis
– Clindamycin plus primaquine in mild cases

Lyme Disease Lyme Disease

Lyme Disease Incidence 1993-2012
• General • Location
– Massachusetts to
– Most common vector- Maryland
borne infection in the
• Animal hosts
U.S,
– White-footed
• Vector Ixodid tick mouse

– Agent: Borrelia – White tail deer

burgdorferi • Settings
– Summer months
• Fastidious,
– Camping, hunting
microaerophilic © Richard Usatine, M.D. Used with permission

spirochete cdc.gov

Lyme Borreliosis Lyme Disease: Treatment

• Three stages
– Stage 1: 3-30 days after tick Age Category Drug Dosage Maximum Duration, Days
bite, flu-like symptoms, Adults Doxycycline 100 mg, twice per N/A 10-21*
day orally
headache, fever/chills, and
Cefuroxime axetil 500 mg, twice per N/A 14-21
skin rash (erythema day orally
migrans) Amoxicillin 500 mg, three times N/A 14-21
per day orally
– Stage 2: weeks to months
Children Amoxicillin 50 mg/kg per day 500 mg per dose 14-21
later: Bell s palsy, AV block, orally, divided into 3
doses
meningitis
Doxycycline 4 mg/kg per day 100 mg per dose 10-21*
– Stage 3: months to years orally, divided into 2
doses
later: migratory polyarthritis Cefuroxime axetil 30 mg/kg per day 500 mg per dose 14-21
• Lab orally, divided into 2
doses
– Antibody testing (ELISA) © Richard Usatine, M.D. Used with permission
Rocky Mountain Spotted Fever Rocky Mountain Spotted Fever
• Due to tick bite exposure in endemic area • Labs
– Tick from Dermacentor family – Leukocytosis, proteinuria,
hematuria,
• Etiology: Rickettsia rickettsii
thrombocytopenia
• Incubation 2–14 days
• Diagnosis
• Influenzal prodrome followed by chills, fever, severe – Serologic tests
headache, myalgias
• Acute and
– Classic triad: abrupt onset headache, fever, and rash
convalescent
• Red, macular rash with onset between days 2–6 of • Treatment
fever – Doxycycline drug of
phil.cdc.gov

– Rash on hands: petechial or purpuric choice

– Then moves to the center – Chloramphenicol

Syphilis Syphilis
• Primary • Primary
– Caused by Treponema – Labs
pallidum • Dark field examination
– History of sexual contact • RPR
– Painless ulcer on • VDRL
genitalia, perianal area,
• TP-EIA
rectum, pharynx
• Chancre resolves in 3–6 • FTA–ABS
weeks © Richard Usatine, M.D. Used with permission – Treatment
– Enlarged regional lymph • Benzathine penicillin phil.cdc.gov

nodes • Doxycycline or
tetracycline if PCN
allergic

Syphilis Syphilis
• Secondary
– Noted 4–8 wks after • Late (Tertiary)
chancre – Infiltrative tumors of skin, bones, liver
– Generalized maculopapular – Aortitis, aneurysms, aortic regurgitation
rash – CNS disorders
– Fever, meningitis, hepatitis, – Labs
arthritis, iritis • VRDL (75%)
• Labs • FTA–ABS (98%)
– TP-EIA – Treatment
– VDRL • Penicillin
– FTA–ABS
• Treatment
– Same as primary
© Richard Usatine, M.D. Used with permission
– CNS or ocular: PCN only
Syphilis
• Neurosyphilis
– Can be noted at any time during course of disease Infectious Diseases
– Meningitis may present with HA, nausea, vomiting, Lecture 1 Viral Diseases
stiff neck, cranial nerve palsies, hearing loss
– Meningovascular meningitis can lead to hemiparesis, Lecture 2 Fungal Diseases
hemiplegia, aphasia, and seizures Spirochetal Diseases

– Argyll Robertson pupils: small irregular pupils that react Lecture 3 Mycobacterial Diseases
normally to accommodation but not to light Parasitic Diseases
• Labs Lecture 4 Bacterial Diseases
• Positive CSF- VDRL, TP-EIA HIV
Sepsis
• Treatment
• PCN

Tuberculosis
• Etiology
– Mycobacterium tuberculosis
• Acid fast bacilli
Mycobacterial Diseases – Transmitted by respiratory droplets

Tuberculosis – Most exposed patients do not progress to clinical illness

• Clinical Features
Atypical Mycobacterial – Fever, chills, night sweats, anorexia, weight loss, fatigue,
Disease chronic non-productive cough, and hemoptysis
• Labs
– Positive PPD
– AFB cultures (gold standard) and smears

Tuberculosis Treatment
Acid-fast bacilli
• Latent TB
– INH 5mg/kg (300mg max) 2 X week for 9 months
– Rifampin 10 mg/kg (600mg max) every day for 4 months
(6 months in children)
• Culture Positive TB
– Initial: INH, rifampin, pyrazinamide, ethambutol - 7 days a
week for 8 weeks
• Continuation
– INH/rifampin - 7 days per week for 18 weeks

phil.cdc.gov
 Atypical Mycobacterial Disease
• Mycobacterium avium complex
– Disseminated disease, pulmonary disease
• Fever, weight loss, anorexia, diarrhea
– Seen in HIV patients Parasitic Diseases
– Diagnosis: blood cultures, bone marrow, DNA probes
– Treatment: multiple drugs (rifabutin [mycobutin], Amebiasis
azithromycin, clarithromycin, ethambutol) Hookworms
• Leprosy
– Mycobacterium leprae
Malaria
– Skin lesions and peripheral nerve involvement Pinworms
– Treatment: months or years (dapsone, rifampin, Toxoplasmosis
clofazimine)
Trichomoniasis

Amebiasis (Amebic Dysentery) Giardiasis

• Entamoeba histolytica • Organism: Giardia duodenalis
• Contaminated water
• Fecal–oral transmission
• Fecal–oral transmission
– Areas of poor sanitation
• Symptoms
• Causes colitis: abdominal pain, bloody diarrhea – Foul-smelling, non-bloody
• Hepatic infection/abscess: fever, hepatomegaly, pain, diarrhea, abdominal pain,
localized tenderness malabsorption
• Diagnosis
• Labs – O&P, serology
– Antigen testing and PCR – Normal WBC, negative fecal
– O&P WBC
• Treatment • Treatment
– Metronidazole, tinidazole
– Metronidazole, Iodoquinol
cdc.gov

cdc.gov

Hookworms Hookworms
• Necator • Symptoms
americanus
– A nematode – Skin penetration:
• Moist tropics ground itch
and – Lungs: dry cough,
southeastern
U.S. blood-tinged sputum
• Life cycle – GI: anorexia, diarrhea,
– Penetrate skin vague abdominal pain
– Migrate to lung; phil.cdc.gov
ciliary action
brings organism
to mouth;
swallowed
– Move to upper
cdc.gov
bowel; mature
and release
eggs
Hookworms Ascaris lumbricoides
• Labs • Roundworm
– 2–3 cm long
– Iron deficiency anemia
– Reside in small intestine
– Stool-positive blood • Oral egg ingestion
– O&P for diagnosis – Contaminated soil
• Asymptomatic
• Treatment cdc.gov

– Fever, cough, GI distention

– Albendazole (drug of • Labs
choice) – O&P, eosinophil
• Treatment
– Albendazole

Source: www.cdc.gov

cdc.gov

Malaria
• History of travel to endemic area
• Transmitted by anopheles mosquito
• Episodes of fever, chills, and sweating
• Headache, myalgias, splenomegaly, anemia, and
leukopenia
• Diagnosis: parasite in the blood
– Thin and thick smear

cdc.gov

P-IDg061

Malaria Malaria Treatment

• Plasmodium
– Vivax: fever every 48
hours
– Malariae: every 72 hours
– Ovale: every 48 hours
– Falciparum: continuous
• Complications
– Hemolytic anemia
– Cerebral malaria
• P. falciparum
– Blackwater fever
cdc.gov
• P. falciparum

cdc.gov
 Pinworms Pinworms
• Enterobius vermicularis • Labs
• Humans are the only host; found worldwide – Scotch tape test
• Treatment
• Life cycle
– Patient plus family
– Adult worms inhabit the cecum
– Albendazole single
– Females migrate to anus to lay eggs dose
– Patient then auto-infects • Repeat in 2 weeks

– Eggs hatch in duodenum, larva migrate to cecum

• Signs/symptoms
– Perianal pruritus (night), restless sleep
cdc.gov
– No eosinophilia

Tapeworms
Taenia solium Taenia saginata Diphyllobothrium Toxoplasmosis
latum
• Caused by Toxoplasma gondii (a protozoan)
Disease Pork tapeworm Beef tapeworm Fish tapeworm
• Cats are the host
Location Mexico, S.and C. Worldwide Europe, Canada,
America, Africa, Alaska, and Japan • Infection results from ingestion of:
Southeast Asia, India
– Cysts in raw or undercooked meat (pork/lamb)
Intermediate Pig Cow Freshwater fish
host – Cat feces (cat litter)
Signs/ Asymptomatic Asymptomatic Bloating, abdominal
symptoms pain, diarrhea • Congenital transmission can lead to infection in the
Labs Eosinophilia Eosinophilia Eosinophilia and
fetus
vitamin B12
deficiency
• Signs/symptoms
Diagnosis Stool O&P Stool O&P Stool O&P – Asymptomatic in immunocompetent patients
Treatment Praziquantel or Praziquantel or Praziquantel or
niclosamide niclosamide niclosamide
Prevention Adequate cooking Adequate cooking Adequate cooking

Toxoplasmosis Trichomoniasis
• Primary infection in immunocompromised patients • Flagellated, pear-shaped protozoan
– Typically due to reactivation of latent disease • Spread via sexual contact
– Fever, malaise, headache, lymphadenopathy (cervical), • Rancid odor, vulvar pruritus, dysuria, dyspareunia
myalgia, arthralgia, stiff neck, sore throat • Physical exam
• Labs – Discharge (yellow-green, frothy, increased amount, vaginal
– Detection of organism in body fluids pH >5)
– Serology: IgM antibodies – Strawberry cervix
– CT scan: ring-enhanced lesions with contrast • Diagnosis
• Treatment – Motile protozoan
– Pyrimethamine + folinic acid + sulfadiazine or clindamycin • Treatment
– Proper cooking – Metronidazole (Flagyl)
– Avoid cat litter – Tinidazole (Tindamax)
• Must treat partner; this is an STD

CDC
 Infectious Diseases
Lecture 1 Viral Diseases
Gram - Negative Bacteria
Lecture 2 Fungal Diseases
Spirochetal Diseases Cholera
Lecture 3 Mycobacterial Diseases Gonococcal Infections
Parasitic Diseases
Salmonellosis
Lecture 4 Gram-Negative Bacteria
Gram-Positive Bacteria Shigellosis
HIV
Sepsis
E coli O157:H7
Campylobacter

Cholera Cholera
• Caused by Vibrio cholerae • Treatment
• Acute diarrheal illness leading to profound hypovolemia – Fluids and
and death electrolytes
– Water and food
• Epidemics: crowding and famine safety
• Acquired from contaminated water and food – Vaccination if travel
to endemic areas
• Stool: liquid and grey in color (rice water) (not usually
• Diagnosis indicated)
– Antibiotics
– Dark field microscopy • Tetracycline/doxycycline
– Stool culture or macrolides may phil.cdc.gov

shorten duration of vibrio

excretion

Gonococcal Infection Gonococcal Infection

• Venereal disease • Evaluation
– Neisseria gonorrhoeae
• G(-) diplococci, intracellular
– Gram stain/culture
• Incubation period is 2–8 d – HIV, RPR
• Purulent, profuse urethral/ • Treatment
cervical discharge
• Disseminated disease – Ceftriaxone/cefixime/cefpodoxime
© Richard Usatine, M.D. Used with permission
– Fever, skin lesions, – Treat also for chlamydia
tenosynovitis, monoarticular
arthritis (knee, ankle, wrist) (doxycycline/azithromycin)
• Other sites of infection • Complications
– Conjunctivitis, pharyngitis,
proctitis, endocarditis, – Epididymitis/salpingitis/PID
meningitis – Disseminated

phil.cdc.gov
Salmonellosis
• Caused by Salmonella typhi and typhimurium
• Transmitted by ingestion of contaminated foods (eggs,
milk) or contact with reptiles
• Signs/symptoms
– Nausea, headache, fever
– High-volume diarrhea (pea soup), no blood in stool
– Cramping, abdominal pain 12–48 hrs after ingestion
– Rash: rose spots (2–3 mm salmon-colored maculopapule
on trunk)
Salmonellosis
• Diagnosis
– Normal or low WBC count
– Stool culture, positive for fecal WBCs
– Blood cultures: bacteremia rare
• Treatment
– Fluids and electrolyte replacement
– Antibiotics
• Fluoroquinolones and ceftriaxone in sickle cell,
immunosuppression, and bacteremia
– Chloramphenicol useful except for side effects
• In other patients, will reduce symptoms by 1–2 days

Shigellosis Shigellosis
• Caused by Shigella sonnei, flexneri, and dysenteriae • Labs
– Leukocytosis and positive fecal WBC
• Bacillary dysentery
– Stool culture
– Infectious colitis, mainly rectosigmoid colon – Blood cultures often positive
• Fecal oral transmission (day care) • Treatment
– Raw vegetables or cold salads – Supportive care
• Signs/symptoms – Antibiotics
• Based on sensitivity patterns
– Fever, malaise, toxic-appearing (decreased BP) – Ciprofloxacin: drug of choice if sensitivity unknown
– LLQ cramping, abdominal pain with bloody diarrhea – Trimethoprim sulfa
– Tenesmus and rectal prolapse – Ampicillin

E. Coli O157:H7 Campylobacter

• Produces shigella-like toxins • Gram-negative
• Related to undercooked hamburger, unpasteurized – Incubation 2-4 days
milk, raw fruits and vegetables • Clinical Presentations
– Diarrhea (bloody), abdominal pain, fever, N/V
• Incubation period 1–8 days
– Can mimic appendicitis or ulcerative colitis
• May be asymptomatic (afebrile) or include bloody
• Transmitted in raw/undercooked poultry, unpasteurized
diarrhea and HUS
dairy products, contaminated water
– HUS is ARF with thrombocytopenia and hemolytic
anemia
• Treatment
– Fluids
• Treatment
– Antibiotics- azithromycin, ciprofloxacin
– No antibiotics (will increase HUS)
• Outcomes
– Arthritis, irritable bowel syndrome, Guillain-Barre syndrome
 Botulism
• Caused by Clostridium botulinum neurotoxin
• Ingestion of home-canned, smoked, or vacuum-packed
foods; raw honey
Gram-Positive Bacteria • Signs/symptoms
Botulism – Sudden onset of cranial nerve paralysis, (CN III, IV, VI,
VII, IX)
Diphtheria
– Diplopia, dysarthria, dysphagia, dysphonia (4 Ds)
Tetanus
– Descending symmetrical paralysis with eventual loss of
Rheumatic Fever deep tendon reflexes (Classic)
MRSA – Progressive muscle weakness (floppy baby syndrome)
– Fixed and dilated pupils in 50%
– Children: irritability, weakness, and hypotonicity

Botulism Diphtheria
• Diagnosis • Due to Corynebacterium diphtheriae
– ID toxin in serum or food – Gram-positive bacillus
• Treatment • Humans are only known reservoir
– Removal of toxin from gut: lavage or cathartics • Incubation 1–7 days
– Trivalent antitoxin or specific antitoxin (toxins A, B, or E) – Spread via respiratory droplets
– Support • Primarily infects the respiratory tract
• Complications – May develop myocarditis, conduction disturbances,
– Respiratory failure neurologic impairment

Diphtheria Tetanus
• Sore throat, fever, discrete white exudate (bleeds when • Caused by Clostridium tetani
removed) – Found in the soil
• Marked cervical adenopathy (bull-neck appearance) – Incubation 5 days to 15 weeks
• Treatment • History of wound and possible contamination
– Antitoxin (equine diphtheria antitoxin) – Due to a neurotoxin
– Penicillin or erythromycin – Affects neurotransmitter
– Prevention • Symptoms
• Immunization (2, 4, 6, 15–18 months, with a preschool – Stiffness of neck and other muscles (trismus), dysphagia,
booster at age 4–6) irritability, hyperreflexia
Tetanus Tetanus Wound Management
• Treatment Clean, minor All other
wounds wounds
– Supportive care and wound cleaning
– Immunization Vaccination History Td* TIG Td* TIG
• See next slide
– Antibiotics: penicillin, metronidazole Unknown or <3 doses Yes No Yes Yes
– Benzodiazepines for muscle spasm
– Booster every 10 years at mid-decade ages (15, 25, 35, ≥3 doses No+ No No** No
etc.)
• Complications *Tdap may be substituted for Td if the person has not previously received Tdap
and is 10 years or older
– Airway obstruction
+Yes, if more than 10 years since last dose
– Cardiac failure **Yes, if more than 5 years since last dose

Acute Rheumatic Fever Acute Rheumatic Fever: Clinical Manifestations

• Inflammatory disease in response to group A strep • Major (Jones) Criteria
infection – Carditis
• Murmur apical systolic
• Causes inflammatory lesions on connective tissue – Polyarthritis
(heart, joints, subcutaneous tissue) • Swollen, warm, red, tender
• Migratory, large joints (knees, ankles, wrists, elbows)
• Mechanism unknown – Chorea
• Time from infection to onset of symptoms is 1-5 • Rapid, purposeless movements
weeks – Erythema marginatum
• Macule or papule with central clearing
• Peak incidence ages 5-15 – Subcutaneous nodules
• Firm, painless
• On bony surface and tendons

Acute Rheumatic Fever: Clinical

Manifestations MRSA
• Gram positive cocci
• Minor Criteria • Treatment • Infections
– Clinical – Prevention – Cellulitis
• Arthralgia • Treat strep throat infection – Toxic shock syndrome
• Fever – Antibiotics do not • Toxin mediated
– Labs modify course of – Staphylococcal Scaled Skin Syndrome
• Elevated sedimentation disease • Toxin mediated- no signs of shock
rate – Anti-inflammatory • Nikolsky sign
• Increase CRP
drugs suppress the • Treatment
• EKG - prolonged PR
interval
signs and symptoms – Vancomycin, Linezolid, TMP/Sulfa, Daptomycin, Ceftaroline
• Supporting
– Positive strep screen Diagnostic Criteria:
– Elevated or increasing 2 major or
ASO titer 1 major and 2 minor
 HIV
• Epidemiology
– Risk factors: sex, IV drug abuse, transfusions
• Etiology
HIV
– Retrovirus
Sepsis
– Changes viral RNA to viral DNA with the aid of reverse
transcriptase
• Acute infection
– Viral-like illness

nih.gov

HIV Life Cycle HIV- Diagnosis

HIV: Opportunistic Infections HIV: Opportunistic Infections

• Opportunistic Infections (CD4 count/µL)
– 700-1,500: Normal Bacterial Protozoan Fungal Viruses Malignancy
Mycobacterium Toxoplasma Candida species Varicella zoster Kaposi s
– >500: Lymphadenopathy tuberculosis gondii sarcoma
Mycobacterium Cryptosporidium Cryptococcus Human Non-Hodgkin s
– 200–500: TB, thrush, zoster, lymphoma, avium- parvum neoformans papilloma virus lymphoma
intracellulare
Kaposi Isospora belli Pneumocystis
Microspora
– 100–200: PCP, histoplasmosis
– 50–100: Toxoplasmosis, cryptococcus
– <50: MAC, PML, CMV retinitis
 Prophylaxis Treatment: HIV: Treatment
Opportunistic Infections • Antiretroviral therapy (ART) is recommended for all
individuals with HIV, regardless of CD4 T lymphocyte
Pathogen Primary Prophylaxis Secondary Prophylaxis
cell count, to reduce the morbidity and mortality
Pneumocystis TMP/SMX Dapsone
associated with HIV infection.
Toxoplasmosis TMP/SMX Pyrimethamine +
sulfadiazine + folinic acid • ART is also recommended for individuals with HIV to
TB (INH-sensitive) INH Rifampin prevent HIV transmission.
TB (NIH-resistant) Rifampin + pyrazinamide • When initiating ART, important to educate patients
MAC Azithromycin/ Rifabutin regarding the benefits and considerations of ART.
clarithromycin
– On a case-by-case basis, ART may be deferred because of
CMV retinitis Valganciclovir Ganciclovir + foscarnet
clinical and/or psychosocial factors, but therapy should be
Cryptococcal Fluconazole Amphotericin B initiated as soon as possible.
Histoplasmosis Itraconazole Amphotericin B

HIV: Treatment HIV: Treatment Side Effects

• Recommended Initial Regimens for Most People with
HIV
• Integrase Strand Transfer Inhibitor + 2 Nucleoside
Reverse Transcriptase Inhibitors:
– Bictegravir-tenofovir alafenamide-emtricitabine—only in adults
≥18 years of age
– Dolutegravir-abacavir-lamivudine—only if HLA-B*5701 negative
– Dolutegravir plus tenofovir alafenamide-emtricitabine
– Dolutegravir plus tenofovir DF-emtricitabine
– Elvitegravir-cobicistat-tenofovir alafenamide-emtricitabine
– Elvitegravir-cobicistat-tenofovir DF-emtricitabine
– Raltegravir plus tenofovir DF-emtricitabine
– Raltegravir plus tenofovir alafenamide-emtricitabine
• Older nucleoside reverse transcriptase inhibitors
(NRTIs) were associated with mitochondrial toxicity.
– Lactic acidosis, hepatic steatosis, myopathy, cardiomyopathy,
peripheral neuropathy, pancreatitis, and lipoatrophy, but these
adverse effects are rare with newer, recommended NRTIs.
• Abacavir can cause a hypersensitivity syndrome in
persons who are HLA-B*5701 positive.
– Abacavir may increase the risk of myocardial infarction
compared with other NRTIs.
• Tenofovir DF can cause nephrotoxicity, including
progressive chronic kidney disease and Fanconi
syndrome.
• Tenofovir DF has also been linked to decreased bone
density.

HIV: Treatment Side Effects Sepsis- Definitions

• Efavirenz may cause significant neuropsychiatric side effect
profile, and may cause neural tube defects if used by
pregnant women in the initial 6 weeks of pregnancy.
• Protease inhibitors have been traditionally linked to higher
rates of gastrointestinal effects, though newer PIs with
lower ritonavir boosting doses are generally better tolerated.
• Atazanavir associated with nephrolithiasis and cholelithiasis.
• The most common side effects of darunavir include
gastrointestinal symptoms (diarrhea, abdominal pain,
vomiting) and rash; the rash usually self-resolves and
requires discontinuation of the drug in less than 1% of cases.
• Medications in the integrase strand transfer inhibitor class
are generally well tolerated and moderate to severe side
effects are uncommon.
• Enfuvirtide, the only drug in the fusion inhibitor class, causes
injection site reactions (both acute inflammatory responses
and persistent sclerotic lesions) in most patients who take it.
• Sepsis
– Defined as life-threatening organ dysfunction caused by a
dysregulated host response to infection
• Organ Dysfunction
– Can be identified as an acute change in total SOFA score by 2
points consequent to the infection.
• Septic shock
– A subset of sepsis in which underlying circulatory and
cellular/metabolic abnormalities are profound enough to
substantially increase mortality.
– Patients with septic shock by persisting hypotension requiring
vasopressors to maintain MAP > 65mmHg and having a serum
lactate level >2 mmol/L (18mg/dL) despite adequate volume
resuscitation.
• With these criteria, hospital mortality is in excess of 40%.
 Organ Dysfunction
Laboratory Evaluation
• CNS
• Appropriate routine microbiology cultures including
– Associated encephalopathy
blood cultures
• Pulmonary
– At least two sets of blood cultures, aerobic and anaerobic
– ARDS
• Obtain before starting antibiotics
• Cardiovascular
– As long as it does not results in a substantial delay in the the
– Ventricular dysfunction start of antibiotics
• Renal • CBC
– Insufficiency
• Lactate
• Hematopoietic
– Leukocytosis or leukopenia, DIC
• Endocrine
– Glucose intolerance, adrenal insufficiency

Initial Resuscitation Gram Stain

• Gram-Positive Cocci • Gram-Positive Rods
– Staphylococci – Corynebacterium
• Airway
– Streptococcus – Listeria
– Intubate early
– Peptostreptococcus – Anthrax
– Protect from respiratory arrest and aspiration
– Lactobacillus
• Breathing
– Bacillus
– Conventional mode of ventilation
– Propionibacterium
– Provide a high degree of ventilatory support
• IV Fluids
– Establish adequate IV access
– Appropriate fluid therapy
• Antibiotics
– Empiric broad-spectrum therapy
phil.cdc.gov phil.cdc.gov

Gram Stain
• Gram-Negative Cocci • Gram-Negative Rods
– Neisseria – Escherichia
– Klebsiella
– Enterobacter
– Serratia
– Pseudomonas
– Proteus
– Salmonella phil.cdc.gov

– Shigella
phil.cdc.gov
– Moraxella
– Haemophilus
 The Musculoskeletal System
Lecture 1 Strains/Sprains
Disorders of the Upper Extremity

The Musculoskeletal System Lecture 2 Disorders of the Back/Spine

Disorders of the Lower Extremity

Lecture 3 Infectious and Benign Conditions

Osteoarthritis
Stephanie Neary, MPA, MMS, PA-C
Course Director, Preventative Medicine Lecture 4 Rheumatologic Conditions
Neoplasms
Yale School of Medicine, PA-Online

Sprains
• Disruption of ligament connective tissue by sudden
twisting of a joint
• Degrees
– First: minimal swelling and tenderness; normal joint
motion; no disability
– Second: partial tear; variable swelling; tenderness, and
ecchymosis; normal joint motion; variable disability
– Third: complete disruption, severe pain, swelling, and
ecchymosis; abnormal joint motion; significant disability
• Treatment
– Protection, rest, ice, compression, elevation (PRICE)
Strains
• Overstretching or disruption of muscle or muscle-
tendon unit; may be acute or due to overuse
• Degrees
– First: localized pain; minimal loss of function
– Second: variable fiber disruption; local pain and swelling;
variable ecchymosis and hematoma; variable loss of
function; may have palpable defect
– Third: complete muscle tear, severe pain, swelling,
ecchymosis, and hematoma; anatomic deformity;
significant disability; possible avulsion fracture
• Treatment
– Protection, rest, ice, compression, elevation (PRICE)

Salter-Harris Classification:
Epiphyseal Fractures

Disorders of the Shoulder

Rotator cuff disorders
Separations
Dislocations
Clavicle fracture
Rotator Cuff Disorders Rotator Cuff Disorders
• Muscles include: • Clinical
– Supraspinatus – Dull aching in shoulder; difficulty reaching overhead
– Infraspinatus – Weakness on external rotation and abduction
– Teres minor – Passive range of motion (ROM) normal; active range
limited
– Subscapularis – Positive drop test in severe tears
• Mechanism of Injury • Labs
– Loss of normal integrity of the tendons due to overuse or – MRI or arthrography
trauma
• Treatment
– Cuff impinges on the acromion and coracoacromial – Avoid aggravating factors/rest
ligament
– NSAIDs, steroid injection, PT, surgical repair

Shoulder Separation Shoulder Separation

• Degrees • Labs
– 1st degree: stretching of the ligaments – X-ray: >5 mm of separation between clavicle and
– 2nd degree: partial tearing of superior/inferior AC acromial process
ligament
• Treatment
– 3rd degree: complete tearing of superior/inferior AC and
coracoclavicular ligament – Limit ROM of the shoulder
– 4th and 5th degree: significant displacement with • Sling for 1st and 2nd degree
penetration through overlying muscle
• 3rd degree may require surgery
• Clinical
– Result from fall on tip of shoulder • 4th and 5th degree will require surgery
– Pain with ROM and point tenderness to palpation, – Rest and ice first 48–72 hours
swelling
– Presents with arm held close to the side

Shoulder Dislocation Dislocation: Anterior

• Anterior
– 90% of all dislocations
– Fall on abducted/externally rotated arm or forceful throwing
motion
• Posterior
– Direct blow to anterior shoulder when arm is in adduction and
internal rotation
– Status post seizure
• Presentation
– Squared-off appearance of shoulder
– Acromion is more prominent
– Anterior: arm held externally rotated and internal rotation
painful
– Posterior: arm held internal rotation and external rotation
painful
Source: Daniel Patrick Moloney
Shoulder Dislocation Clavicle Fracture
• Exam • Very common in
– Check for possible axillary nerve injury pediatrics
• Numbness in middle of deltoid muscle • Due to fall on
– X-ray: pre- and post-reduction outstretched arm
• Treatment • Exam
– Reduction – Holds ipsilateral arm
close to trunk
• Straight traction or Stimson s method
– X-ray
– Immobilize
– Check neurovascular
– Follow up 2–3 weeks and begin PT
status
– Surgery (recurrent dislocations)
• Treatment
Source: Mark D. Travis
– Figure 8 or cradle sling

Boxer s Fracture
• Fracture at distal end of 5th metacarpal
Disorders of the Forearm/Wrist/Hand • Result from direct blow of closed fist against another
object
Fractures/Dislocations Tenosynovitis
Boxer s fracture Carpal tunnel syndrome • Increased angulation (>25–30%) may result in
Radial fracture De Quervain s malunion
Ulnar shaft fracture Epicondylitis – Malunion leads to permanent hyperextension deformity
Colles fracture Olecranon bursitis • Physical exam
Smith s fracture
Hutchinson s fracture – Swelling over fracture site and depression of knuckle
Monteggia fracture • Treatment
Galeazzi fracture – Gutter splint, surgery (pinning)
Gamekeeper s thumb
Scaphoid fracture

Boxer s Fracture Radial Fracture

• Due to fall on outstretched
hand with elbow extended
• PE
– Tenderness over radial
head or pain with passive
rotation or flexion of
forearm
• X-ray
– Positive fat pad: anterior
or posterior
• Treatment
– Sling support
– Surgery

Source: William Coy, M.D.

Source: Mark M. Morton
P-MU0j18
Ulnar Shaft Fracture Colles Fracture
• Nightstick fracture • Most common injury of the wrist
• Due to direct blow to ulna • Fracture of the distal radius
• Exam – Due to fall on outstretched arm with wrist in extension
– Point tenderness – Transverse fracture of the distal radial metaphysis with
dorsal displacement of the distal fragment
• Diagnosis
• Typically also an injury to the ulnar styloid or ulnar
– X-ray
collateral ligament
• Treatment • Check for fractures of the elbow
– Long arm cast or
posterior splint

Colles Fracture Smith s Fracture

• X-ray • Fracture of distal radius with volar displacement of
– Fracture through radial distal fragments
metaphysis
• Due to fall on outstretched hand or direct blow to back
• Exam: dinner fork of wrist
deformity of the wrist
• Reverse Colles fracture
• Treatment: reduction and
• Treatment
immobilization with short-
arm cast – Casting in supination

– Cast for 6 weeks – May require open reduction with internal fixation

Source: Gloria Jicha

Hutchinson s Fracture Monteggia Fracture

• Radial styloid fracture • Ulnar fracture usually in the
proximal third, and radial
– Chauffeur s fracture head dislocation
• Due to fall on outstretched hand or high-energy impact • Due to forced pronation of
injury the forearm or direct blow
over the posterior aspect of
• Difficult to see on lateral view, need AP the ulna
– Look for associated scaphoid fracture • X-ray
• Can occur with radiocarpal dislocations – Ulnar fracture with
dislocation of the radial
• Treatment head, in the direction of
angulation of the ulnar
– Thumb spica or double sugar-tong splint fracture
– Internal fixation • Treatment
– Closed treatment or open
reduction with internal
fixation Source: Laurence Brett Herzog
Galeazzi Fracture Gamekeeper s Thumb
• Radial fracture usually located • Due to forced radial
at the junction of the middle abduction at the MCP, with
and distal thirds, and injury to ulnar collateral
dislocation of the distal ligament of the thumb
radioulnar joint • Affects pincer function
• Pain over MCP of the thumb
• Due to direct blow on
dorsolateral wrist or from a fall • Tear diagnosed by
measuring angle of joint
• Treatment opening with abduction
– Surgery stress
>20% means complete tear
Source: TAMC
• Treatment: thumb spica Right thumb has a small displaced
avulsion fracture at the inner (ulnar)
(partial disruption) and aspect of the proximal phalangeal
surgery (complete disruption) base

Source: Cory Zachary Trivax, M.D.

Scaphoid Fracture Scaphoid Fracture

• Most common carpal bone Anatomical snuffbox
• X-ray
tenderness
fracture; seen in young
adults – May need to repeat in
2 weeks to detect
– Think of a patient with a
sprained wrist, with • Treatment
persistent pain and
swelling – Short-arm thumb spica
cast for 8–12 weeks
• Mechanism
– Fall on outstretched hand
• Physical exam
– Point tender anatomical
snuffbox IMC© 2010 DxR Development Group, Inc. , All
Rights Reserved.

– Pain with hand grip

– Limited ROM of wrist and
thumb Source: Andrew Sellers

Carpal Tunnel Syndrome

Fracture Diagnosis Immobilization Treatment Red Flags • Compression of the medial nerve under the transverse
Duration
carpal ligament
Clavicle Point tenderness Figure 8 or cradle 4-6 weeks Nonunion
Clavicle x-ray sling • Etiology
Radial head Elbow x-ray Variable Variable Displaced or – Repetitive overuse, pregnancy, DM, hypothyroidism, RA,
Fat pad large fracture
scleroderma, SLE
Ulnar shaft Forearm x-ray Long-arm cast 4-6 weeks Comminuted or
(nightstick) Long-arm splint displaced • Clinical
Colles Wrist x-ray Short-arm cast 6-8 weeks Articular or – Dull ache in wrist, then burning pain, numbness, and
comminuted
tingling in thumb and digits 2, 3, half of 4
Scaphoid Scaphoid x-ray Short-arm thumb 8-12 weeks Displaced,
spica nonunion • Relief with shaking of wrist
Boxers Hand x-ray Ulnar gutter splint 2-3 weeks >15 angulated • Weakness, dropping items
Metacarpal Hand x-ray Radial or ulnar 4 weeks >10 angulated • Pain which awakens at night
shaft gutter splint
Phalangeal Hand x-ray Cast, splint, tape 3 weeks Displaced
Carpal Tunnel Syndrome
• Exam
– Thenar muscle atrophy,
decreased sensory in
distribution of median nerve
– Positive Phalen s test and
Tinel s sign
• Labs
– Nerve conduction studies/EMG
• Treatment
– Eliminate the cause
– Splint in neutral position: cock
up splint
– Anti-inflammatory
agents/Steroids
– Surgery: nerve release
Epicondylitis
Lateral
• Due to manual labor, sports,
or spontaneous event
• Tennis elbow
– Caused by racquet sports
– Pain at insertion site on
lateral epicondyle
• Increase on pronation of
the forearm and
dorsiflexion of the wrist
– Palm down-lifting is painful
• Treatment: rest, NSAIDs,
elbow brace, gradual
resumption of sports
The Musculoskeletal System
Lecture 1
Lecture 2
Lecture 3
Lecture 4
De Quervain's Tenosynovitis
• Inflammation of the sheath around extensor pollicis
brevis and abductor pollicis longus of the thumb
• Etiology: overuse/repetitive gripping
• Clinical
Phalen – Pain (sharp or aching) radiates into hand or forearm; inability to
grip
– Point tenderness over radial styloid process
– Positive Finkelstein test (passive stretching of affected tendons)
• Labs: X-ray normal
• Treatment: RICE, NSAIDs, steroids, thumb spica splint
Tinel
IMC© 2010 DxR Development Group, Inc. All Rights Reserved.
Olecranon Bursitis
Medial • If acute, there is painful swelling over the olecranon
– Chronic disease is typically not painful
• Golfer s elbow
• Due to trauma and repeated irritation (bar stool elbow)
– Due to repetitive motions
in golfing, pitching, • If fever, think septic bursa
racquet sports
• Exam
– Pain at insertion site on
– Physical exam is normal except for pain and swelling
medial epicondyle
(ROM normal)
• Increase on – X-ray to rule out fracture
supination and wrist
flexion against • Treatment: steroid injection, RICE, and NSAIDs
resistance
• Treatment:
– Rest, NSAIDs, gradual
resumption of sports
Strains/Sprains
Disorders of the Upper Extremity Disorders of the Back/Spine
Disorders of the Back/Spine Ankylosing Spondylitis
Disorders of the Lower Extremity
Back Strain/Sprain
Infectious and Benign Conditions Kyphosis/Scoliosis
Osteoarthritis
Spinal Stenosis
Rheumatologic Conditions
Neoplasms Cauda Equina Syndrome
Rib/Cervical Fractures
Spondylolisthesis
Ankylosing Spondylitis Ankylosing Spondylitis
• Inflammation and progressive fusion of the vertebrae • Clinical
– Affects sacroiliac joint (required for diagnosis), spine, and hips – Low aching back pain (Improves with bend forward)
(axial skeleton)
– Morning stiffness (>1 hour) and stiffness after inactivity
• A seronegative spondyloarthropathy
• Improves with exercise
• Possible immune-mediated disease – Extraarticular manifestations: Anterior uveitis, aortic
• Onset ages 15–30 insufficiency, 3rd degree heart block
– Very rare after age 40
– Exam: limited spinal motion, loss of chest expansion,
• Men > women 3:1 (+) Schober s test (measures spine flexion)
– Different than other autoimmune diseases

Ankylosing Spondylitis Seronegative Arthropathies

• Labs
– ­ sedimentation rate; Diseases Characteristics
negative RF/ANA
Ankylosing spondylitis Seronegative (ANA and RF negative)
– (+) HLA-B27
Reactive arthritis Involves lower back and SI joint
– X-ray: bamboo
appearance, squaring of Psoriatic arthritis HLA-B27
the vertebral bodies, Enteropathic arthropathy Extraarticular manifestations
bilateral sacroiliitis
• Treatment
Untreatable diseases except for reactive arthritis
– NSAIDs: indomethacin
(drug of choice)
– Exercise and physical
therapy
– TNF-blockers (infliximab,
adalimumab, etanercept)

Source: Kevin Banks

Back Strain/Sprain Lumbar Radiculopathy

• Most common cause of lower back pain is prolapsed
disk or low back strain (mechanical)
• Clinical Lumbar Pain Sensory Motor DTR
Root Altered
– Pain in low back with radiation down leg; suggests nerve
root irritation L3 Medial Medial thigh Hip None
thigh Flexors
– Area of point tenderness suggests musculoskeletal cause
L4 Medial calf Medial calf Quads Knee
– Sciatica pain in buttocks, posterior thigh, and
posterolateral aspect of the leg around lateral malleolus L5 Lateral calf, Lateral calf, Tibialis anterior, None
dorsum foot Dorsum foot Extensor
hallicis longus
S1 Posterior Lateral foot Plantar flexors Achilles
calf, heel and ankle
Back Strain/Sprain Kyphosis
• Labs • Increased convex curvature of thoracic spine
– X-rays not required when exam is normal • Clinical
– Round back appearance when several vertebrae involved
– MRI/CT scan
• Labs
– EMG
– X-ray
– Myelogram • Treatment
• Treatment – Curves 45-60 : observe
– Curves >60 : use Milwaukee brace
– Short-term bed rest (2 days); NSAIDs
– Surgery if no improvement
– Ice vs. heat
– Fitness program

Scheuermann s Disease Scoliosis

• Fixed kyphosis which • Lateral curvature of the spine
develops at the time of • Causes
puberty
– Secondary to underlying causes (motor neuron disease,
• Cause unknown myopathies)
• X-ray – Idiopathic most common
– Vertebrae wedging
• Greatest risk in women between puberty growth spurt
– End plate irregularity and cessation of spinal growth
– Schmorl s nodules – Ages 10-13
between T2 and T12
• Right thoracic curve most common
• Treatment
– Brace, postural exercise

Source: Jeremiah R Long

Scoliosis Spinal Stenosis

• Clinical • Nerve compression due to narrowing of the spinal canal
– Asymmetry in shoulders, iliac height, scapular prominence or neural foramina
– Flank crease with forward bending
– Gait and neurologic exams are normal
• Most cases result from degenerative changes (OA)
– Screen with Adams test (forward bending) • Age 60 is average age
• Labs
– X-rays
• Clinical
– Vertebral levels: measure greatest tilt anterior by – Low back pain and bilateral extremity pain in buttocks,
Cobb method legs, and thighs
• Treatment: based on curvature
– Walking makes pain worse
– 10–15 : observe and follow with forward bending test
– 15–20 : follow with AP x-rays – Neurogenic claudication pain relieved by 15-30 minutes
– 20–45 : brace in supine position with pillow between knees
– >40 : refer to surgeon for internal fixation rods
Claudication Spinal Stenosis
• Clinical
Feature Neurogenic Vascular – Relief of symptoms when leaning forward while standing or
sitting
Claudication distance Varies Fixed
– Exam: may be normal; increased pain with spinal extension
Relief of pain Sitting Standing
suggests stenosis
Walking up hill No discomfort Discomfort
• Labs
Type of pain Numbness, ache Tightness
– X-rays reveal extensive vertebral osteophytes and
Pulses Present Absent
degenerative disk disease
Skin Normal Loss of hair
– CT/MRI
Weakness Occasional Rare
Back pain Common Uncommon
• Treatment: NSAIDs; epidural steroid injections; surgical
decompression
– Avoid aggravating activities

Cauda Equina Syndrome Rib Fracture

• Secondary to spinal trauma or disc protrusion • Most common thoracic cage injury
– Motor vehicle accident most
• Clinical common etiology
– Bilateral sciatica – Watch for underlying
liver/spleen injury
– Saddle anesthesia • Presentation: localized tenderness,
– Disturbance in bowel and/or bladder function pleuritic chest pain, splinting,
crepitus, ecchymosis
• PE – Increased risk of
– Saddle anesthesia developing pneumonia and
inhibiting ventilation
– Bilateral root dysfunction • Diagnosis
– Decreased anal sphincter tone – Rib series x-ray
• Treatment
• Radiology: MRI
– Pain control, incentive
• Treatment: surgery, steroids spirometry
– Binders/belts not indicated

Cervical Fractures Cervical Fractures

• Jefferson
– C1 fracture • Clay-Shoveler s
– Seen best on odontoid – Avulsion of C6 or C7
view spinous process
• Hangman s – Mechanism is heavy
lifting
– Bilateral C2 pedicle
fracture
– Secondary to
hyperextension of the
neck

Source: Brent Adler

Source: William Schaff
Spondylolisthesis Spondylolisthesis
• Anterior slippage of vertebral body on inferior • Radiology
counterpart – Bilateral defect in the
• Etiology pars interarticularis
– Pars interarticularis defect (Spondylolysis) – Forward slippage of the
– Stress fracture vertebrae
• Treatment
• Location: L4/L5 or L5/S1
– Exercise program
• Clinical
– Rest
– Asymptomatic, low back pain with activity, and relief with
rest – Weight loss
• Exam – NSAIDs
– May note a step off in spinous processes
– Neurological deficits are rare Source: Alice Boyd Smith

Thoracic Outlet Syndrome

• Compression of neurovascular bundle in thoracic outlet
(superior to 1st rib, posterior to sternum, anterolateral to
spinal column)
– Scalene space most commonly involved à brachial plexus Disorders of the Hip/Knee
compression
• Pathogenesis: developmental, injury, predisposing Hip Fracture
activities Hip Dislocation
• Clinical presentation and evaluation dependent on Hip Dysplasia
involved structures: neurogenic, venous, arterial Knee Bursitis
• Diagnostics: Meniscal/Ligament Injuries
– X-ray, duplex US
Osgood-Schlatter Disease
• Treatment:
Slipped Capital Femoral Epiphysis
– Varied by cause; PT, corticosteroids, direct catheter
thrombolysis, thoracic outlet decompression

Hip Fracture Hip Fracture

• Common in elderly with osteoporosis • Labs
• Types – Hip x-ray: PA, lateral,
– Intracapsular: femoral head and neck: may damage
frog leg view
blood supply
– Extracapsular: inter or subtrochanteric • Treatment
• Risk factors – Immobilization
– Osteoporosis – Surgical
– Falls
• Intracapsular: prosthetic replacement Source: Kenneth Terhaar

• Clinical
– Pain in hip that radiates to groin and inner thigh • Intertrochanteric: open reduction and
internal fixation
– Leg is short and held in external rotation
– Watch for avascular necrosis
– Mortality high due to DVT and PE
Hip Dislocation Hip Dysplasia
• Due to high impact trauma • Congenital or acquired deformation or misalignment of the
– Knee is struck with hip and knee flexed hip joint.
– Femoral head displaced from acetabulum – Ranges from barely detectable to severely dislocated
• PE: • Physical exam
– Posterior (90%): limb short, adducted and internally – Click or clunk noted with Ortolani or Barlow maneuver
rotated • Diagnosis
– Anterior: flexion, abduction, and external rotation – Confirmed by ultrasound or x-ray

• Diagnosis: x-ray, CT • Treatment

– Early dysplasia often treated with Pavlik harness
• Treatment – Surgery
– Prompt reduction; watch for sciatic nerve injury with
posterior and avascular necrosis

Slipped Capital Femoral Epiphysis (SCFE)
• Anterolateral and superior displacement of capital
femoral epiphysis from the femoral neck (proximal
femur distal to physis)
• Presentation:
– Obese adolescents, ~12-13 yo
– Hip pain, Trendelenburg gait
– Additional risk factors: hx of radiation therapy, hypothyroidism,
growth hormone deficiency (atypical SCFE)
Slipped Capital Femoral Epiphysis (SCFE)
• Diagnosis:
– Preslip, Acute, Acute-on-chronic, Chronic
– Stable vs unstable
– Severity (mild, moderate, severe)
– Hip x-ray (AP and lateral/frog-leg) and pelvic x-ray
• Appears posterior displacement of femoral epiphysis; “ice-
cream slipping off cone”
• Treatment:
– Prompt referral to ortho, possible best rest, surgical stabilization
– Complication: avascular necrosis of femoral head

Knee Bursitis Baker s Cyst

• Inflammatory periarticular disorder of the bursa • Fluid-filled semimembranous bursa behind the knee.
– Anserine bursa: located medially – Located medial aspect in popliteal space
• Tenderness noted below the joint line
• Recurrent bursitis here is noted with OA of the knee
• Develops at any age
– Prepatellar bursa: noted between skin and patella • Etiology: in adults, due to pathology in knee i.e., medial
– Semimembranosus bursa: noted posterior knee meniscus, RA, or OA
• Site of Baker s cysts • Diagnosis
• Caused by repetitive friction, trauma, or systemic disease
(RA, gout, infection) – Bulge behind knee
– Prepatellar (housemaid s knee) • Lateral to medial hamstrings in popliteal fossa
• Pain and tenderness, swelling, increase in fluid – US/MRI
• Treatment: prevention, rest, NSAIDs, steroid injections • Treatment: drainage, surgical removal
Meniscal/Ligament Injuries Meniscal/Ligament Injuries
• Due to trauma
• Ligament involved depends on mechanism of injury
Meniscus/Ligament Mechanism of Injury
• Injuries present with pain and effusion Meniscus Twisting or hyperflexion
• Hemarthroses are common Medial collateral ligament Blow to lateral aspect of leg or lower thigh
Lateral collateral ligament Blow to medial aspect of leg or lower thigh
• Meniscal injuries commonly associated with ligament
Anterior cruciate ligament Sudden deceleration or rotation
injuries
Posterior cruciate ligament External force on anterior aspect with knee
– Meniscal injury will see joint line pain, effusion, and flexed
or
locking
Forced hyperflexion or hyperextension with a
varus/valgus force

Meniscal/Ligament Injuries Meniscal/Ligament Injuries

• Exam • McMurray s
– Symptoms
– Patient supine, knee flexed and externally (medial
• Meniscus: locking and popping of knees, giving out of knee,
meniscus) and internally (lateral meniscus) rotated, then
pain at joint line, joint effusion
extended; pain equals tear
• Ligament: popping of knee, inability to bear weight, swelling
– Lateral/medial force for laxity • Apley s
– Drawer test (cruciate ligaments) – Patient prone, knee to 90 , axial loading with rotation
– Lachman and pivot-shift test (ACL)\bulge test for effusion causes pain with meniscal disease
IMC © 2010 DxR
Anterior Drawer test Development Group,
Inc. All Rights Reserved

Lachman test

Meniscal/Ligament Injuries Tibial Plateau Fracture

• Diagnosis • Make up 33% of all knee fractures
– MRI • Etiology
– Due to valgus force with axial load on leg (car bumper)
– Physical exam
• Presentation
• Treatment – Not able to ambulate
– Knee immobilization, crutches, analgesics, ortho consult • Diagnosis
– X-ray
• Treatment
– Immobilize and refer to ortho
Osgood-Schlatter Disease
• Osteochondritis of the tibial tubercle
• Traction apophysitis of the proximal tibial tubercle at the
patellar tendon’s insertion point (overuse injury)
• Presentation: Diseases of the Ankle/Foot
– 9-14 yo athlete after rapid growth spurt, males>females
Ankle Sprain
– Gradually increasing knee pain, relieved with rest, worse with
jumping, squatting or climbing stairs Ankle Fracture
• Diagnostics: Plantar Fasciitis
– Clinical evaluation; pain with palpation of tibial tubercle Foot Fracture
– Reproduction of pain with knee extension against restriction
• Treatment:
– Non-surgical interventions, continue sport as tolerated,
NSAIDs, ice after sport, physical therapy
– can take 6-18 months to heal

Ankle Sprain Ankle Fracture

• Typically inversion with plantar flexion • Mechanism
• Types – Eversion or lateral rotation forces on the talus
– 1st degree: mild, stretch, no tear • Clinical
– 2nd degree: moderate, some tearing, moderate swelling,
– Pain, tenderness, swelling, bruising
pain
– 3rd degree: severe, complete tear • Types: unimalleolar, bimalleolar, trimalleolar
• Clinical • Treatment
– Swelling, bruising, unable to bear weight – Depends on severity
– Ankle x-ray – If talus displaced, refer to orthopedics
• Treatment – Casting 4-8 weeks
– RICE, splinting, casting, PT

Ottawa Ankle Rules Plantar Fasciitis

Ankle X-ray
Required if pain in the malleolar zone
and:
1 Bone tenderness at posterior edge or tip
of lateral malleolus or
2 Bone tenderness at posterior edge or tip
of medial malleolus or
3 Inability to bear weight at time of injury
and in ER
Foot X-ray
Required if pain in midfoot and:
Bone tenderness base of 5th metatarsal
or
Bone tenderness at navicular or
Inability to bear weight at time of injury
and in ER
• Etiology
– Overuse with degeneration and micro tears
– Inflammation in the fascial band
• Clinical
– Pain under the calcaneus and medial arch
– Worse in the AM or after prolonged sitting
• Exam
– Point tenderness and with dorsiflexion of toes and ankle
– X-ray to rule out spur
• Treatment: heel cups, therapy, steroid injection,
NSAIDs
Foot Fracture Jones Fracture
• Stress • Fracture at base of 5th
– Due to walking/marching metatarsal
– Typically midshaft of 3rd – Heal slowly
metatarsal
– Short leg cast for
• Calcaneus 6–8 weeks
– Due to falling from a
height – Surgery may be required
– Presents with pain and
severe swelling
– Typically have lumbar
compression fracture

Source: John Yasmer

Source: Jeremy C. Mauldin

The Musculoskeletal System

Lecture 1 Strains/Sprains
Disorders of the Upper Extremity Infectious Conditions
Lecture 2 Disorders of the Back/Spine Acute/Chronic Osteomyelitis
Disorders of the Lower Extremity
Septic Arthritis
Lecture 3 Infectious and Benign Conditions
Osteoarthritis

Lecture 4 Rheumatologic Conditions

Neoplasms

Osteomyelitis Osteomyelitis
• Inflammatory/infectious process of the bone Risk Factor Organism

– Acute: develops over 4-6 weeks IV drug abuse S. aureus

Pseudomonas
– Chronic: develops over months to years IV catheters S. aureus and S. epidermidis
• Etiology Candida species
URI Enterobacteriaceae
– S. aureus, E. coli, Pseudomonas, Salmonella, anaerobes
Sickle cell Salmonella
• Two pathway of infection Diabetes S. aureus and S. epidermidis
– Hematogenous: spread from distant infectious foci Corynebacterium species
Anaerobes
– Contiguous: secondary to infection close to bone
• Diabetes a risk factor for chronic disease
Osteomyelitis Osteomyelitis: Films
• Clinical
– Fever, chills, malaise, anorexia, night sweats
– Erythema, drainage, swelling, pain at site of infection,
warmth
• Labs
– ­ WBC, sedimentation rate (if normal not osteomyelitis)
– Blood cultures
– X-ray: soft tissue swelling, periosteal reaction, cortical
irregularities
• May not be noted for 10-14 days
– MRI, white blood cell scan (indium 111 white cell scan)

Source: Eva M. Smietana

Osteomyelitis: Treatment Septic Arthritis

• Treatment: IV antibiotics for 4-6 weeks; surgery • Underlying joint disease predisposes to septic arthritis
Organism First Choice Second Choice • History of joint trauma and/or hematogenous spread
S. aureus Nafcillin 2nd generation cephalosporin – May be secondary to UTI, IV drug abuse, IV lines
(methicillin-sensitive) Oxacillin
S. aureus Vancomycin Gentamicin or TMP/SXT plus • Microbiology: S. aureus is most common
(methicillin-resistant) rifampin, linezolid
– IV drug abuse, think pseudomonas
Enterococcus Ampicillin Vancomycin
E. coli Ciprofloxacin 3rd generation cephalosporin – Young adults, think N. gonorrhoeae
Pseudomonas Ciprofloxacin Piperacillin and gentamicin – Chronic: TB, fungi, Lyme disease
Anaerobes Clindamycin Ampicillin, metronidazole
Mixed Ampicillin-sulbactam Imipenem

Septic Arthritis
• Clinical
– Fever, shaking chills
– Swollen, tender, erythematous joint; limitation of motion
• Labs
– Synovial fluid: increased WBC with neutrophils (positive gram
Benign Conditions
stain and cultures)
Ganglion Cysts
• Treatment
– Drainage and antibiotics Osteoporosis
• Staphylococcus: nafcillin, vancomycin, 1st generation
cephalosporin
• GC: Ceftriaxone
• Pseudomonas: ceftazidime, aminoglycoside
 Ganglion Cyst Osteoporosis
• A cystic collection of synovial fluid within a joint or • Metabolic disease of bone
tendon sheath • Decreased bone mass; increased susceptibility to
– Arise from herniation of synovial tissue from a joint capsule or fracture
tendon sheath
• Primary
• Presents with tender cystic swelling over or near a
tendon sheath – Type I: loss of estrogens, seen in postmenopausal
– Common locations include dorsal or volar wrist, flexor surface
women only; Fx: wrist and vertebrae
of MCP joint, or base of nail – Type II: age-related, both men and women; Fx: hip
• Treatment • Secondary
– Pain control and NSAIDS – Due to Cushing s, steroids, thyrotoxicosis, multiple
– Cyst aspiration, steroid injection, surgical excision myeloma, hyperparathyroidism, anticonvulsants, alcohol
– Many resolve spontaneously

Osteoporosis Osteoporosis
• Clinical Classification Density Results • Treatment
– Asymptomatic; Normal <-1 SD below
normal – Prevention
pain with fracture • Activity, calcium, vitamin D, estrogen-progesterone therapy
Osteopenia >-1 SD but <-2.5
– Labs: normal SD below normal – Estrogen therapy contraindicated in patients at high-risk
– Bone density Osteoporosis >-2.5 SD below of endometrial or breast cancer
normal
• Dual energy x-ray – Anti-resorptive
absorptiometry Severe >-2.5 SD below
osteoporosis normal and • Bisphosphonates: slows resorption and increases density
– X-ray presence of – Side effects: frozen bones, jaw osteonecrosis
• Decreased bone fracture
• Calcitonin: inhibits bone resorption
density
– Side effects: nasal stuffiness, flushing

Osteoporosis- USPSTF
Population Women age ≥65 years
without previous known
Women age <65 years whose 10-
year fracture risk is equal to or
Men without previous
known fractures or
Osteoporosis Summary: USPSTF
fractures or secondary
causes of osteoporosis
greater than that of a 65-year-old
white woman without additional
secondary causes of
osteoporosis • Recommendations for bone-mineral density testing in
Recommendation Screen
risk factors
No recommendation women:
Grade: B Grade: I
(insufficient evidence)
– Screen all women age 65+
Risk Assessment As many as 1 in 2 postmenopausal women and 1 in 5 older men are at risk for an osteoporosis-related fracture.
Osteoporosis is common in all racial groups but is most common in white persons. Rates of osteoporosis increase – Screen women younger than age 65 if their 10-year fracture
with age. Elderly people are particularly susceptible to fractures. According to the FRAX fracture risk assessment
tool, available at http://www.shef.ac.uk/FRAX/, the 10-year fracture risk in a 65-year-old white woman without risk is similar to or greater than that of a 65-year-old white
additional risk factors is 9.3%.
Current diagnostic and treatment criteria rely on dual-energy x-ray absorptiometry of the hip and lumbar spine.
woman without additional risk factors — roughly 9%
Screening Tests
Timing of Screening Evidence is lacking about optimal intervals for repeated screening.

Intervention
Suggestions for Practice
Regarding the I Statement for
In addition to adequate calcium and vitamin D intake and weight-bearing exercise, multiple U.S. Food and Drug
– Use WHO's FRAX tool to estimate fracture risk of patient
Administration–approved therapies reduce fracture risk in women with low bone mineral density and no previous
fractures, including bisphosphonates, parathyroid hormone, raloxifene, and estrogen. The choice of treatment
should take into account the patient's clinical situation and the tradeoff between benefits and harms. Clinicians
• There is not enough evidence to determine whether
should provide education about how to minimize drug side effects.
Clinicians should consider:
screening is beneficial or harmful in men.
•potential preventable burden: increasing because of the aging of the U.S. population

Men •potential harms: likely to be small, mostly opportunity costs

•current practice: routine screening of men not widespread

•costs: additional scanners required to screen sizeable populations

Men most likely to benefit from screening have a 10-year risk for osteoporotic fracture equal to or greater than that
of a 65-year-old white woman without risk factors. However, current evidence is insufficient to assess the balance of
benefits and harms of screening for osteoporosis in men.
 Osteoarthritis: PE
Osteoarthritis
Heberden s nodes (DIP joint)
• Most common form of joint disease
– Increased incidence with age, obesity, and joint
wear and tear Bouchard s nodes
– Non-inflammatory (PIP joint)
• Primary and secondary causes
– Idiopathic: no underlying factor
– Secondary: have underlying factor (trauma, avascular necrosis,
hip dysplasia, metabolic disorders, gout)
• Clinical
– Decreased ROM, deep achy pain, crepitus, tenderness
– Pain in A.M. <60 minutes, relieved by rest (early in disease)
– Heberden s nodes (DIP)
– Bouchard s nodes (PIP)
© Richard Usatine, M.D. Used with permission

Osteoarthritis
• Labs
– X-ray: asymmetric The Musculoskeletal System
narrowing of joint space,
Lecture 1 Strains/Sprains
osteophytes, subchondral
Disorders of the Upper Extremity
sclerosing, and bone cysts
– ESR normal Lecture 2 Disorders of the Back/Spine
Disorders of the Lower Extremity
– Synovial fluid: mild
inflammation, no crystals
Lecture 3 Infectious and Benign Conditions
• Treatment Osteoarthritis
– Acetaminophen, NSAIDs, Lecture 4 Rheumatologic Conditions
steroid injections, exercise Source: Russell A. Patterson Neoplasms
– Capsaicin cream
– Joint replacement, PT

Approach to Arthritis
• Distribution and number joints involved?
Rheumatologic Conditions – Polyarticular: RA, SLE, parvovirus B19, hepatitis B
Fibromyalgia – Monoarticular: OA, gout, pseudogout, septic, trauma
Juvenile Rheumatoid Arthritis • Acute or chronic?
Gout – Chronic: OA
Pseudogout – Acute: Septic, gout, pseudogout
Polyarteritis Nodosa (PAN) • Systemic symptoms?
Polymyositis/Dermatomyositis – SLE, Sjögren s, scleroderma, Wegener granulomatosis
Polymyalgia Rheumatica
• Joint inflammation?
Reiter s Syndrome
– Yes: RA, gout, SLE
Rheumatoid arthritis (RA)
– No: OA
Systemic Lupus Erythematosus (SLE)
Scleroderma
Sjögren's Disease
Synovial Fluid Analysis Fibromyalgia
• Tests: cell count, crystals, cultures (3C’s) plus gram stain • Etiology unknown: women > men
• Clinical
Disease WBCs Crystals/Polarization
– Non-articular musculoskeletal aches; chronic pain and
DJD <2,000 Negative stiffness; fatigue; poor sleep
Traumatic
– Exam: multiple tender points (≥11 of 18 tender points
Inflammatory 5,000-50,000 Gout: needle-shaped, negative
birefringent positive)
Pseudogout: rhomboid-shaped, • Labs: no lab markers
positive birefringent
• Treatment
Septic >50,000 Negative (positive culture)
– Tricyclic antidepressants
– Physical activity: exercise program
– Patient education

Juvenile Idiopathic Arthritis Juvenile Idiopathic Arthritis

• Chronic arthritis in one or more joints for at least 6-12 • Laboratory findings
weeks – No diagnostic tests
– Cause unknown, possible autoimmune – Elevated ESR, CRP, WBC, and platelet count
• Symptoms include pain, swelling, warmth, tenderness, – Positive anti-cyclic citrullinated peptide (CCP)
morning stiffness, and decreased range of motion • Treatment
• Four main subtypes – NSAIDS- first line therapy
– Oligoarticular, polyarticular, systemic, and enthesitis-associated – Methotrexate- second line therapy
– Oligoarticular- most common, medium to large joints, leg length – Leflunomide- antipyrimidine medication
discrepancy – TNF medications- etanercept, infliximab
– Polyarticular- large and small joints, symmetrical – Corticosteroids
– Systemic- known as Still disease, high fever – Rehabilitation

Gout Gout
• Due to altered purine metabolism • Labs
• Sodium urate crystals in synovial fluid – Increased serum uric acid (>6.0 mg/dl)
– Uric acid in the urine (kidney stones) – Monosodium urate crystals in synovial fluid
• Abrupt onset, throbbing pain, • Needle-shaped, negatively birefringent
single joint (great toe) • Treatment
– First attack at night
– High-dose NSAIDs, colchicine, steroids (acute)
• Men, peak age 45
– Allopurinol (overproducers, or under secretors)
• Clinical – Probenecid (under secretors)
– Pain, redness, swelling of joint
• Note
• Mimics cellulitis
– Avoid thiazides, furosemide, cyclosporine, aspirin, alcohol
© Richard Usatine, M.D. Used with permission. (will elevate uric acid levels)
 Pseudogout: Chondrocalcinosis
Calcium Pyrophosphate Dihydrate Deposition Disease
(CPPD)
• Etiology
– Calcium-containing deposits in pericellular matrix of cartilage
• Affects large joints in lower extremities
– Knee, wrist, shoulder, ankle
– Asymptomatic or arthritis-like pain
• Labs:
– Calcium pyrophosphate crystals in synovial fluid
• Rhomboid, positive birefringent
– X-ray: chondrocalcinosis
• Treatment:
– NSAIDs, intraarticular steroids
– No role for uric-acid lowering drugs

Source: Boma O. Afiesimama

Polyarteritis Nodosa (PAN) Polyarteritis Nodosa (PAN)

• Vasculitic disease involving medium-sized arteries • Diagnosis
– Positive anti-neutrophilic cytoplasmic antibody (P-ANCA)
• Mainly middle-aged men
– Elevated ESR
• Affects the skin, kidneys, peripheral nerves, and GI – Anemia, leukocytosis
tract – UA: positive protein and blood
– Diagnose by tissue biopsy
• Clinical manifestations
– Angiogram reveals micro-aneurysms
– Fever, malaise, weight loss
• Treatment
– Renal involvement, peripheral neuropathy (70%) – Steroids

– Skin: palpable purpura – Immunosuppressive therapy

– Watch for occlusion and aneurysms
– Post-prandial abdominal pain

Polymyositis Dermatomyositis
• An idiopathic inflammatory myopathies • An idiopathic inflammatory
myopathy
• Women> men, age 40-50 years • Women> men, age 40-50
• Present with gradual, progressive bilateral proximal years
muscle weakness • Present with bilateral proximal
muscle weakness
– Leg weakness presents first- difficulty in rising from a chair
• Physical exam
– No facial or ocular muscle weakness – Rash- dusky rash in a
• Laboratory malar distribution or noted
on neck, shoulders, upper © Richard Usatine, M.D. Used with permission.

– Elevated CK and aldolase chest, and back

• ESR and CRP are often normal – Periorbital edema and
– Diagnosis by muscle biopsy purple rash over the upper
eyelids
• Treatment – Gottron sign- scaly, pink
– Corticosteroids patches over the dorsum of
the PIP and MCP joints
Dermatomyositis Polymyalgia Rheumatica
• Aching/stiffness in proximal muscles and inflammation of
• Occult malignancy are common synovial joints shoulder/hip
– Symptoms occur for greater than 1 month
– Ovarian, lung, pancreatic, stomach, colorectal, and non-
Hodgkin s lymphoma – Tends to be self-limited
• Laboratory • Linked to giant cell arteritis
– Elevated CK and aldolase • Age >50; women > men 2:1
• ESR and CRP are often normal • Clinical
– Diagnosis by muscle biopsy – Abrupt or gradual, aching, stiffness
• Treatment – Occurs in the A.M.; lasts at least 1 hour or after inactivity
– Corticosteroids – Fatigue, weight loss, fever (low-grade)
• IVIG used if corticosteroids are not effective

Polymyalgia Rheumatica Polymyalgia Rheumatica

• Diagnosis • Exam
– Age >50 years – Muscle tenderness, no loss of muscle strength
– Aching and stiffness for >1 month • Labs
– Negative ANA, RF
– Affects at least 2 of 3 areas: shoulders, neck, pelvic girdle
– Increased sedimentation rate (>50)
– Morning stiffness >1 hour
– Normocytic, normochromic anemia
– ESR >50 mm/hr • Treatment
– Exclude other diseases – Corticosteroids (relief in 24-48 hours)
– Rapid response to steroids – NSAIDs

Reiter s Syndrome Reiter s Syndrome

• Reactive arthritis in response to an infectious process • Exam
elsewhere in the body – Sausage toes or fingers
– Chlamydia, gastroenteritis (Yersinia, Campylobacter, – Mucocutaneous lesions
Shigella, Salmonella) • Small, shallow, painless ulcers on glans penis (circinate
balanitis)
• Associated with HLA B-27
– Painless, papulosquamous eruptions on palms and soles
• Peak age 20s; men > women • Keratoderma blennorrhagicum
• Clinical • Labs
– Asymmetrical oligoarthritis which favors the lower – Increased sedimentation rate
extremities; conjunctivitis; urethritis • Treatment
– Antibiotics (to treat infection that triggered disease)
– NSAIDs: indomethacin
– Steroids (to manage skin and eye disease)
Rheumatoid Arthritis Rheumatoid Arthritis
• Etiology • Diagnosis Criteria
– Chronic, systemic disease – Morning stiffness (≥1 hr) for 6 weeks
• Immune complex formation leading to immune reaction and
pannus formation; thickening of the synovium
– Swelling (soft tissue) of 3+ joints
– Symmetric synovial inflammation of peripheral joints • DIP and lower back never involved
• PIP, MCP, wrists, elbows, knees, ankles – Swelling (soft tissue) of hand joints (PIP, MCP, or wrist)
• Epidemiology – Symmetrical swelling (soft tissue)
– Women > men 3:1
– Subcutaneous rheumatoid nodules
– Peak onset ages 35–50
– Serum rheumatoid factor positive
– Genetic link
• Greatest risk: HLA-DR4- and HLA-DR1-positive individuals – Radiograph: erosions and/or periarticular osteopenia
seen in hand or wrist joints

Rheumatoid Arthritis: Exam Rheumatoid Arthritis

• Joints swollen and tender,
decreased ROM, warmth, • Labs:
no erythema – RF positive in 80%
– Z deformity: radial deviation – Anti-CCP (cyclic citrullinated peptide) positive
of wrist with ulnar deviation
of fingers – Elevated ESR
– Boutonnière deformity: – N/N anemia
© Richard Usatine, M.D. Used with permission.
flexion deformity of PIP & • X-rays:
extension DIP
– Erosions
– Swan-neck deformity:
hyperextension PIP & – Bony decalcifications
flexion of DIP
– Osteopenia

Rheumatoid Arthritis SLE

• Treatment • Chronic, multisystem inflammatory disease
– NSAIDs, aspirin, PT, rest (first line) (autoimmune)
– Disease-modifying anti-rheumatic drugs (DMARDs) – Linked to HLA-DR2 and HLA-DR3
• Hydroxychloroquine: monitor retinas – Active disease interspersed with remissions
• Methotrexate: monitor CBC, LFTs • Mainly women (90%), ages 15–40
– Corticosteroids: oral or intra-articular • Etiology unknown
• Long-term use: cataracts, osteoporosis
• Drug-induced lupus
– Anti-TNF drugs (etanercept, adalimumab, infliximab)
– Procainamide
• Increase risk of infection, cancer, and heart failure
– Hydralazine
– Rheumatology consult
– Isoniazid
– Quinidine
SLE SLE
In pregnancy anti-Ro can cross the
• Clinical • Labs
placenta, causing neonatal lupus and heart
– Fever block. – Positive ANA
– Malar/discoid rash – Positive anti-ds DNA and anti-Sm antibodies
– Arthritic pain • Positive anti-histone in drug-induced SLE
– Photosensitivity – Elevated ESR
– Oral ulcers – Antiphospholipid antibodies (hypercoagulable states)
– Pericarditis
• Treatment
– Proteinuria
– Corticosteroids
– Seizure/psychosis
– Chloroquine
– Anemia
– Hydroxychloroquine
– Leukopenia
– Methotrexate
– NSAIDs

© Richard Usatine, M.D. Used with permission.

Scleroderma (Systemic Sclerosis) Scleroderma (Systemic Sclerosis)

• Disorder of connective tissue • Clinical
– Joint stiffness, arthralgia, myalgia
– Fibrosis/thickening of skin, blood vessels, visceral organs
– Skin thickening, hide-bound
– Overproduction and accumulation of collagen – Raynaud phenomenon
• Two subtypes – Systemic: carpal tunnel,
pulmonary fibrosis, dysphagia,
– Diffuse pericarditis, renal failure
• Changes on extremities, face, trunk • Labs
• Risk of visceral disease early in disease – Positive ANA (positive anti-Scl-70
– Limited cutaneous (CREST) in diffuse; anti-centromere in limited)
• Treatment
• Changes to distal extremities and face
– Symptomatic: ACEI for renal insuff, CCB for Raynaud,
• Women > men, ages 20–40 D-penicillamine for skin changes
– Immunosuppressive therapy (cyclophosphamide, methotrexate)

Sjögren's Syndrome Sjögren's Syndrome

• Chronic, immune-mediated inflammatory disease
– Lymphocytic invasion of exocrine glands
(lacrimal/salivary glands)
– Mainly women (90%); average ages 30–50
• Linked to increased incidence of B-cell lymphoma
• Clinical
– Dry eyes, dry mouth, oral sores, dry skin
– Polyarthralgia, polyarthritis, dysphagia
– Low-grade fever, malaise
• Labs
– Schirmer's test (measures the wetting of standardized
tear test strips, which are applied between the eyeball
and lateral inferior lid)
– Autoantibodies: ANA, RF, anti-Ro, anti-La
– Salivary gland biopsy: lymphocyte infiltration
• Treatment
– Artificial tears and saliva
– NSAIDs, chloroquine, glucocorticoids (to treat
extraglandular manifestations)
Rheumatology Testing:
Antinuclear Antibody
Positive Test Disorders
ANA RA, SLE, scleroderma, polymyositis, dermatomyositis
Anti-ds DNA SLE Neoplasms
Rheumatoid factor RA
Anti-Sm SLE Osteosarcoma
Anti- Ro, Anti-LA Sjögren's (anti-Ro neonatal lupus) Ewing’s Sarcoma
Anti-SCL 70 Scleroderma Osteochondroma
Anti-centromere Limited scleroderma (CREST)
ANCA Wegener s (now granulomatosis with polyangiitis - GPA)
Anti-histone Drug-induced lupus
Anti-RNP Mixed connective tissue disease

Osteosarcoma Ewing’s Sarcoma

• Malignant neoplasm • Malignant neoplasm
• Presentation: • Presentation:
– 10-14yo, night-time bone pain – <25yo
• Diagnostics: – Long bones (femur), pelvis
– X-ray shows ‘starburst’ or ‘sunray’ pattern – Localized pain and swelling, possible palpable fixed soft tissue
mass
– Visualize radiodense and radiolucent areas
– Frequent metastasis to lungs and bones
• Diagnostics: average delay of 9 months before diagnosis
– Xray shows ‘moth-eaten’ destructive lesion with associated soft
• Treatment:
tissue mass
– Surgical resection, radiation
– Frequent metastasis to lungs and bones
• Treatment:
– Surgical resection, radiation

Osteochondroma
• Benign neoplasm
• Cartilage-capped bony spur, typically spontaneously
occurring
• Presentation:
– Adolescents, M>F
– Painless mass near joint, painful if discovered as result of trauma
– Can effect growth plate leading to angular deformities
• Diagnostics:
– X-ray: osseous spur pointing away from joint
• Sessile: large base
• Pedunculated: large cap
• Treatment:
– Observation, annual x-rays
 The Neurologic System
Lecture 1 Alzheimer’s Disease
Cerebral Palsy

The Neurologic System Lecture 2

Diseases of the Peripheral Nerves

Headaches
Infectious Disorders
Vascular Diseases

Jim Van Rhee, M.S., PA-C Lecture 3 Movement Disorders

Program Director; Associate Professor Multiple Sclerosis
Seizure Disorder
Yale School of Medicine, PA-Online Head Injuries/Other

Alzheimer s Disease
• Very common cause of dementia
– 60–80% of all dementia cases
– Women > men
Dementia/Cerebral Palsy • Anterograde amnesia is dominant symptom
Alzheimer s Disease • Probable Alzheimer s
Delirium – Clinical evidence of progressive dementia
Cerebral Palsy – No disturbance of consciousness
– Absence of systemic or another brain disease which
causes dementia
• Definite Alzheimer s
– Requires neuropathologic conformation of clinical
diagnosis

Alzheimer s Disease Alzheimer s Disease: Stages

• Pathology • Early
– Cortical atrophy and ventricular enlargement – Loss of recent memory
– Microscopic • Inability to learn and retain new information
• Neurofibrillary tangles: occupy neuronal cell body – Language problems (word finding)
• Senile plaques: amyloid in microglia, astrocytes – Mood swings
• Genetics – Personality changes
– Autosomal dominant in some families – Diminished ability to perform activities of daily living
(ADLs)
– Loci on chromosomes 1, 14, 19, 21
• Drawing and driving
Alzheimer s Disease: Stages Alzheimer s Disease: Stages
• Intermediate • Severe
– Inability to learn and recall new information – Inability to walk or perform ADLs
– Diminished memory of remote events
– Total incontinence
– Behavioral changes
– Complete loss of recent and remote memory
• Agitation, hostility, aggressiveness; may wander
– Loss of all sense of time and place – Possible inability to swallow and eat
• Gets lost and increased risk of falls – End stage: coma, death
– Aphasia, apraxia
– Requires assistance to perform ADLs

Functional Assessment Staging Tool Alzheimer s Disease

• Stage1: No difficulties • Diagnosis
• Stage 2: Subjective complaints of forgetting – Exclude other causes of dementia

• Stage 3: Decreased job functioning noted by coworkers, difficulty
traveling to new locations
• Stage 4: Decreased ability to perform complex tasks (finances)
• Stage 5: Requires assistance in choosing proper clothes for day or
season
• Stage 6: Cannot dress, bathe, or perform mechanics of toileting without
assistance, maybe incontinent of urine and bowel
• Check CMP, B12, TSH, CSF studies
– Watch for depression (can mimic early Alzheimer s)
– Definitive diagnosis only at autopsy
• Prognosis
– Life expectancy 3–12 years, median survival 1.3 years

• Stage 7: Limited speech, unable to ambulate independently, cannot sit

up independently

Alzheimer s Disease Degenerative Dementias

• Treatment • Neurodegenerative • Traumatic dementia
– Caregiver support/Hospice disorders – Punch drunk
– Acetylcholinesterase inhibitors (enhance cholinergic – Alzheimer s disease • Infectious dementia
neurotransmission)
– Lewy body disease – AIDS encephalopathy
• Donepezil, rivastigmine, galantamine to improve cognition,
– Huntington s disease
ADLs, apathy – Creutzfeldt-Jakob disease
– Memantine (Namenda)- acts on glutamatergic system by – Parkinson s disease
– Progressive multifocal
blocking NMDA receptors – Pick s disease leukoencephalopathy
– Delusions
• Risperidone, olanzapine (avoid haloperidol)
– Agitation
• Trazodone, divalproex, carbamazepine (avoid
anticholinergic drugs which worsen dementia)
Delirium Delirium
• Delirium is a transient, reversible cerebral dysfunction • Etiology
that has an acute or subacute onset and is manifest – Infection
clinically by a wide range of fluctuating mental status – Medications
abnormalities. – Organ failure
– Occurs in 10-30% of hospitalized medical/surgical patients • Treatment
• Mental status abnormalities in delirium – Discontinue meds
– Global cognitive impairment in: – Treat underlying etiology
• Thinking
• Memory
• Perception
– Decreased attention
– Change in level of consciousness
– Agitation or decreased motor activity
– Disturbances in sleep-awake cycle

Cerebral Palsy Cerebral Palsy: Clinical

• Group of motor syndromes resulting from disorders of • Spastic diplegia
early brain development – Spasticity in both legs with relative sparing of arms

– Delay in normal motor milestones – Related to bilateral hypoxic-ischemic lesion

• Spastic hemiplegia
• Secondary to brain lesion acquired pre- or perinatally
– Unilateral cerebral hemispheric damage related to trauma or
– Usually due to hypoxic-ischemic insult, infection, vascular event
hemorrhage, or brain maldevelopment – Spasticity in arm and leg on same side with undergrowth of
• Intellectual ability may be spared limbs and abnormal posturing
• Choreoathetosis
– Initial hypotonia evolving into choreoathetosis and dystonia
• Uncontrolled jerking, writhing, and posterior movements

Cerebral Palsy
• Treatment
– Maximize mobility

– Provide team of various specialties Diseases of Peripheral Nerves

• Physical therapy, occupational therapy, speech
Bell s palsy
– Spasticity treated with oral dantrolene sodium,
benzodiazepines, and baclofen Guillain-Barré syndrome
Myasthenia gravis
Complex Regional Pain Syndrome
Bell s Palsy Bell s Palsy
• Idiopathic facial paresis of lower motor neuron type • PE
– May be link to recent viral infection: herpes simplex or – Seventh nerve palsy
varicella-zoster virus – Taste loss anterior 2/3 of tongue
• Inflammatory reaction involving facial nerve (CN VII) – Hyperacusis
near stylomastoid foramen
• Management
• Clinical
– 70% resolve without treatment
– Hemifacial weakness
– Corticosteroids should be considered in
– Difficulty closing eye
in new-onset Bell s palsy
– Ipsilateral ear pain

© Richard Usatine, M.D. Used with permission.

Guillain-Barré Syndrome Guillain-Barré Syndrome

• Demyelinating injury • Labs
– Associated with viral infection, stress, Campylobacter – Spinal tap: ↑ total protein, normal cell count
jejuni enteritis
– EMG: consistent with demyelination
• Progressive, ascending, symmetric weakness with
• Treatment
variable paresthesia or dysesthesia
– Watch for involvement of respiratory muscles
• Physical exam
– IV immunoglobulin
– ↓ DTRs, weakness in ascending pattern
– Plasma exchange
– Loss of proprioception
– Steroids are not effective

Myasthenia Gravis Myasthenia Gravis

• Due to block of neuromuscular transmission
– Acetylcholine receptors
– Antibody-mediated autoimmune
• Fluctuating weakness/fatigue of voluntary muscles
– Proximal muscles affected more than distal
• Diplopia, dysphagia, ptosis, facial weakness, difficulty
swallowing
– Early stage affects the eye muscles; activity increases
weakness
• All ages affected; mainly young women
• Diagnosis
– Acetylcholine-receptor antibodies (80–90%)
– Short-acting anticholinesterase (Tensilon test: edrophonium)
• Improvement in weakness
• Cholinergic side effects: nausea, diarrhea, bradycardia
– EMG
• Treatment
– Anticholinesterase drugs (pyridostigmine or neostigmine)
– Thymectomy
– Plasmapheresis to relieve symptoms
– Corticosteroids (long-term treatment)
– Aminoglycosides worsen disease so should be avoided
Complex Regional Pain Syndrome
• Also known as Reflex Sympathetic Dystrophy (RSD)
• Typically develops after an injury, surgery, heart attack, or
stroke.
The Neurologic System
– The pain is out of proportion to the initial event. Lecture 1 Alzheimer s Disease
Cerebral Palsy
• Disorder of a portion of the body, usually starting in a limb,
Diseases of the Peripheral Nerves
which manifests as extreme pain, swelling, limited range of
motion, and changes to the skin and bones. Lecture 2 Headaches
• It may initially affect one limb and then spread throughout Infectious Disorders
the body Vascular Diseases
– 35% of affected people report symptoms throughout their whole
bodies. Lecture 3 Movement Disorders
Multiple Sclerosis
• Uncommon and its cause not clearly understood. Seizure Disorder
• Treatment is most effective when started early. Head Injuries/Other
– Involves medications, physical therapy and occupational therapy,
psychological treatments, and neuromodulation.

Cluster Headache
• ≥5 attacks that are: • ≥1 of the following on
– Severe, unilateral, the side of pain:
supraorbital, and/or – Conjunctival injection
Headaches temporal – Lacrimation

– 15–180 minutes in length – Nasal congestion

Cluster
– 1 qod to 8/day – Rhinorrhea
Migraine – Facial sweating
• Men > women 6:1
– Miosis
Tension • Predominantly middle-
– Ptosis
aged
– Eyelid edema
• Treatment
– Oxygen
– Ergotamine

Migraine Migraine: Common Triggers

• ≥5 attacks with 2 of the • Aura (may or may not • Stress • Lack of sleep
following: be present) • Menses • Glare
– Unilateral – Scotoma • Oral contraceptives • Changes in weather
– Pulsating – Numbness • Alcohol • Physical exertion
– Moderate to severe – Paresthesias • Food • Fatigue
– Aggravated by activity – Paralysis – Cheese • Head trauma
• 4–72 hours in length if • Epidemiology – Chocolate
untreated
– Women > men; ages
• 1 of the following: 15–45
– Nausea/vomiting – Genetic
– Photo/phonophobia predisposition
Migraine: Treatment Tension Headache
• Prophylactic (recommended if headache limits normal • On average >15/month for • At least 2 of the following:
activity >3 days/month, is severe, or has 6 months – Pressing/tightening
complications) • No vomiting – Band-like pain
– Aspirin – Mild or moderate severity
– Propranolol
• ≤1 of the following:
– Phonophobia – Bilateral pain
– Amitriptyline
– Photophobia – No aggravation by physical
– Clonidine
exertion
– Verapamil – Nausea
• Abortive
– Cafergot
– Sumatriptan (5-HT receptor agonist) (avoid in HTN or CAD)
– Analgesics: NSAIDs (avoid opiates)

Tension Headache Pseudotumor Cerebri

• Most common cause of headache • Idiopathic increase intracranial pressure
– Increased by stress, fatigue, noise, glare • Women > men
• Associated with obesity, chronic lung disease, Addison
• Not common in the elderly disease, BCP, and tetracycline
– Women > men; onset in second decade of life • Symptoms: headache, visual disturbances, CN VI palsy
• CT and MRI normal
• Treatment
• Treatment
– Simple analgesics: acetaminophen, NSAIDs – Weight loss
– Prophylactic treatment – Remove offending agent
– Diuretics (acetazolamide/furosemide)
• Tricyclic antidepressants (amitriptyline)
– Shunt placement

Encephalitis
• Infection of the brain parenchyma
• Causes include herpes (#1), enterovirus, EBV, CMV,
measles, Eastern and Western equine, St. Louis,
varicella, West Nile
Infectious Diseases • Physical exam
– Fever, malaise, stiff neck, nausea, altered mentation
Encephalitis – Signs of upper motor neuron lesion (exaggerated DTRs, spastic
paralysis)
Meningitis • Labs
– CSF: ↑ lymphocytes; glucose normal or decreased; ↑ protein
– Polymerase chain reaction
• Treatment
– Supportive (acetaminophen)
– Acyclovir: Herpes simplex, varicella-zoster
– Ganciclovir or foscarnet: CMV
– Avoid steroids
Meningitis Meningitis Lab Results
• Inflammation or infection of the meninges
Agent Pressure WBC PMN Lymphs Protein Glucose
• Bacterial (g/dl) (mg/dl)
– Signs and symptoms
• Headache, nuchal rigidity, fever, change in mental status,
seizures Bacterial High >100 >80% <20% >100 <30
• Brudzinski or Kernig sign
Viral High >50 <50% >50% >50 >50
• Rash: petechial, think Neisseria
• Labs Fungal High >50 <50% >50% >50 <30
– CSF
• See next page Normal <5 None 100% <50 >50

• Rapid antigen tests

Bacterial Etiologies Meningitis: Treatment

Neonates Children (<15 yo) Adults (>15 yo) Organism First Choice Second Choice
Streptococcus Penicillin G or ampicillin or Vancomycin or
Gram-negative H. influenzae (type b) S. pneumoniae pneumoniae ceftriaxone chloramphenicol

bacilli Neisseria meningitidis Penicillin G or ampicillin Ceftriaxone

Haemophilus influenzae Ampicillin or ceftriaxone 3rd generation

Streptococci N. meningitidis N. meningitidis cephalosporin or
chloramphenicol
Listeria S. pneumoniae Gram-negative Listeria monocytogenes Ampicillin or penicillin G TMP/sulfa

bacilli Staphylococcus aureus Nafcillin Vancomycin

Gram negative bacilli Cefotaxime or ceftazidime Meropenem +

Listeria plus aminoglycoside aminoglycoside

(age >60) Pseudomonas aeruginosa Cefepime plus tobramycin Meropenem +

aminoglycoside

• Viral meningitis: symptomatic treatment but treat herpes with acyclovir

• Treat contacts of those with Neisseria with rifampin, ciprofloxacin, or azithromycin

Meningitis: Empiric Treatment

Age Group First Choice Second Choice
Neonates Ampicillin + cefotaxime Ampicillin + gentamicin
Children Cefotaxime or ceftriaxone + Ampicillin + meropenem
vancomycin Vascular Diseases
Adults Cefotaxime or ceftriaxone + Meropenem
vancomycin Cerebral aneurysm
Cerebral vascular accident
Elderly Cefotaxime or ceftriaxone + Cefotaxime + vancomycin +
ampicillin + vancomycin TMP/sulfa Transient cerebral ischemia
Arteriovenous Malformation

Dexamethasone day 1 in all patients and for 4

days in confirmed case of bacterial meningitis.
Cerebral Aneurysm
• Asymptomatic until expansion or
rupture
– Symptoms vary depending on
site
• Rupture characterized by
sudden, severe headache,
altered mental status,
photophobia, vomiting
• Focal neuro signs (unusual)
• CT, MRA, or angiography
• Treatment
– Nimodipine
– Surgery
Etiology CVA
• Principal mechanisms
– Large artery thrombosis
– Small artery thrombosis
(lacunar)
– Embolic (cardiogenic or
artery-to-artery)
– Vascular dissection
– Systemic hypertension
– Bleeding
Lacunar Disease
• Follows occlusion of the penetrating branches of:
– Circle of Willis
– Middle cerebral artery stem
– Vertebral and basilar arteries
• Pathophysiology
– History of hypertension
• Clinical manifestations
– Hemiparesis of arm, leg, foot, toes, face
– Dysarthria
Cerebral Vascular Accident (CVA)
• History of atherosclerotic heart disease, hypertension,
diabetes, atrial fibrillation
• Sudden onset neurologic complaint
– Focal weakness, sensory abnormalities, visual changes,
language defect, altered mentation
• Deficits >24 hours
– Transient ischemic attack (TIA)
• Brief episode of neurologic dysfunction caused by
focal brain ischemia with symptoms typically lasting <1
hour without evidence of acute infarction
Source: Charles F. Gould • Obtain MRI within 24 hours of presentation
Blood Supply/Symptoms
• Risk factors Anterior (carotid) Posterior (vertebrobasilar)
– Age
– Family history • Anterior cerebral (ACA) • Posterior cerebral (PCA)
– Diabetes – Contralateral weakness arm – Contralateral homonymous
hemianopia
– Hypertension – Sensory loss leg – Visual hallucinations
– Smoking – Urinary incontinence – Agnosias
– Hypercholesterolemia – Confusion • Basilar artery (BA)
– Bilateral sensory/weakness
– Atrial fibrillation • Middle cerebral (MCA)
– Cerebellar dysfunction
– Contralateral hemiplegia – Cranial nerve dysfunction
– Hemisensory loss • Vertebral
– Homonymous hemianopia – Vertigo
– If dominant side: aphasia – Vomiting
– Ataxia
Laboratory Evaluation
• Physical exam
– Neuro exam
– Cardiac/carotids
• Labs
– Non-contrast CT scan
– CBC, sedimentation rate, electrolytes, glucose
– VDRL, lipid profile, coagulation panel, thyroid function
CT/MRI Changes Treatment
Basal Hemorrhage Brain Tumor • Modify risk factors
• Anti-platelet agents
– Aspirin is first-line therapy; add dipyridamole or clopidogrel
• Anticoagulation therapy
– Heparin for those with risk for recurrent stroke (A fib,
stroke in evolution)
– Warfarin
• Direct-acting oral anticoagulation
• Surgical therapy
– Carotid endarterectomy
• Thrombolysis
– Tissue plasminogen activator within 3 hours

Source: James M. Grimson Source:Steven J. Goldstein

• Rehabilitation

Stroke Complications Arteriovenous Malformation

Complication Cause • Abnormal connection between arteries and veins,
Pneumonia Aspiration and hypoventilation bypassing the capillaries
Hypovolemia Lack of fluid intake, often because of dysphagia – Usually congenital
Hyponatremia Inappropriate ADH, diuretics, poor intake • Occurs commonly in the CNS
Seizures Excitable partially injured cerebral tissue – But can occur elsewhere
Depression Organic mental changes, discouragement • Many AVMs are asymptomatic
Shoulder dislocation Lack of proper care of paralyzed limbs – Symptoms of AVM vary according to the location of the
Peripheral nerve injury Improper positioning of paretic limbs malformation.
Decubitus ulcer Immobility, lack of turning and movement – Commonly symptoms include headache and seizures.
• Can cause intense pain or bleeding or lead to other serious
UTI Indwelling cather, bladder distention
medical problems.
Bleeding, brain or systemic Excessive anticoagulation
• Diagnosis
Congestive heart failure Fluid overload
– CT or MRI
Hypotension Excessive use of antihypertensives
• Treatment
– Endovascular embolization, neurosurgery or radiosurgery.

The Neurologic System

Lecture 1 Alzheimer s Disease
Cerebral Palsy Movement Disorders
Diseases of the Peripheral Nerves
Essential tremor
Lecture 2 Headaches
Infectious Disorders Huntington s chorea
Vascular Diseases Parkinson s disease
Lecture 3 Movement Disorders Amyotrophic Lateral Sclerosis (ALS)
Multiple Sclerosis
Seizure Disorder Tourette Disorder
Head Injuries/Other
Essential Tremor Huntington s Chorea
• Cause is uncertain • Autosomal dominant
• Onset ages 30–55, with gradual chorea and dementia
– Sometimes inherited autosomal dominant
– Personality changes, impulsiveness, aggressive behavior,
• Begins at any age; typical onset age 60s depression, and paranoid psychosis are noted (may precede
the motor manifestations)
• Involves hands and/or head • Motor manifestations
– Lacks hypokinetic features and rigidity of Parkinson s – Flicking movements of the extremities
disease – Lilting gait
– Inability to sustain a motor act
• Alcohol improves tremor – Facial grimacing
• Treatment – Ataxia
– Dystonia
– Propranolol

Huntington s Chorea Parkinson s Disease

• Progressive • Idiopathic, slowly progressive, degenerative CNS disorder
• Labs due to dopamine depletion in basal ganglia
– CSF normal • Insidious onset in older patient
– CT scan: cerebral atrophy – Men > women
– Diagnosis by genetic testing • Clinical
• Treatment – Pill-rolling tremor, rigidity, bradykinesia, postural instability,
– Supportive only micrographia
– Genetic counseling • Physical exam
– Anti-dopaminergic agents (haloperidol) may work early – Mask-like facies, cog wheeling of extremities, DTR normal,
– Fatal 15–20 years after diagnosis shuffling gait, may have intellectual deterioration
– Dementia (50%) and depression common

Parkinson s Disease: Treatment Amyotrophic Lateral Sclerosis (ALS)

• Levodopa
– Side effects: nausea, vomiting, hypotension
• Dopamine agonists
– Bromocriptine, ropinirole, pramipexole
• Side effects: orthostatic hypotension
• Monoamine oxidase type B inhibitors (↑ intracellular
• Presents with spasticity, hyperreflexia, and Babinski
sign (upper motor neuron signs) in the setting of
progressive muscle wasting and weakness (lower
motor neuron signs)
– Progressive degeneration of corticospinal tracts, anterior horn
cells, and/or bulbar motor nuclei

dopamine) • Men > women; median age 55 years

– Selegiline, rasagiline • First signs: muscular weakness and atrophy in the
• Side effects: orthostasis, confusion, headache hands
• Catechol-O-methyltransferase (COMT) inhibitors prevent
– Fasciculations of tongue, spasticity, dysarthria, & dysphagia
breakdown of dopamine
– Entacapone
• Side effects: GI upset, brown urine discoloration
 Upper/Lower Motor Neuron Disorders ALS
• Signs/symptoms
Upper Motor Neuron Lower Motor Neuron – Fasciculations, spasticity, hyperactive DTRs, extensor plantar
reflexes, dysarthria, and dysphagia

Spasticity Flaccid paralysis • Several aspects of neurologic function are usually

Hyperreflexia
No fasciculations
Upward Babinski reflex
Little or no muscle atrophy
spared, including mentation, extraocular movements,
Areflexia or hyporeflexia bowel/bladder function, and sensation
• Rare long-term survival
Fasciculations
– Typical survival 3–5 years
Downward Babinski reflex – Riluzole may reduce progression by 3-6 months (blocks
release of glutamic acid and disrupts glutamate-mediated
Loss of muscle tone and atrophy neurotoxicity)

Tourette Syndrome
• Inherited disorder with onset in childhood, ages 3-8
– Cause is unknown

• Present with multiple physical tics and at least one

vocal tic Multiple Sclerosis
– Physical tics include eye blinking, facial movements, sniffing
and throat clearing

• Treatment
– Therapy

– Medications include atypical neuroleptics (risperidone,

ziprasidone, haloperidol, or the antihypertensive clonidine

Multiple Sclerosis Laboratory Diagnosis

• Slowly progressive CNS disease with disseminated • CSF studies
patches of demyelination in brain and spinal cord – Mononuclear cell
– Probably autoimmune in nature pleocytosis
• Women > men; onset age <50; Northern European – Elevated levels of
descent total Ig
• Episodic symptoms – Presence of oligoclonal
– Sensory abnormalities, blurred vision (optic neuritis), sphincter Ig
disturbances, weakness (heat may worsen symptoms)
– Lhermitte s sign positive (sensation of electricity down back
• MRI
with passive flexion of the neck) – Abnormal hyperintense
– Fatigue, depression, bladder urgency, weakness, impaired areas in white matter, Source: Steven J. Goldstein
balance, and impaired coordination found in brainstem,
cerebellum, spinal cord
Multiple Sclerosis: Treatment
• Relieve symptoms
• Modify disease course
– Corticosteroids
– Interferon-β1b (Betaseron), IFN-β1a (Avonex), IFN-β1a (Rebif) Seizure Disorders
– Glatiramer acetate (Copaxone)
– Natalizumab (Tysabri)
• Note: All of the above for relapsing, remitting MS
– Mitoxantrone (Novantrone) (for worsening forms of MS and
secondary progressive MS)
• IV gamma globulins

Seizure Disorder Seizure Disorder: Classification

• Sudden, excessive, and • Etiologies • Partial seizures
disorderly discharge of – Vascular – Simple
cerebral neurons which – Infection • Single locus in the brain
causes abnormal – Trauma
• Focal motor or somatosensory symptoms
movements or perceptions – Autoimmune
• Consciousness is preserved
• Peak incidence in – Metabolic
• May be followed by transient neuro deficit (Todd s paralysis)
childhood – Idiopathic
– Neoplasm – Complex partial
– pSychiatric • Impaired consciousness may be preceded, accompanied, or
followed by aura symptoms
• Motor dysfunction: chewing movements, lip smacking

Seizure Disorder: Classification Seizure Disorder

Type Preferred
• Generalized seizures • Labs
Partial
– Absence (petit mal) – EEG: most important Simplex Phenytoin
• Impaired consciousness Carbamazepine
• Mild clonic, tonic, or atonic components – MRI: rules out other causes
Complex Phenytoin
• Onset and termination abrupt, no post ictal period • Treatment Carbamazepine
– Myoclonic Lamotrigine
• No loss of consciousness Generalized
• Single or multiple myoclonic jerks Tonic-clonic Phenytoin
– Tonic-clonic Carbamazepine
• Sudden loss of consciousness Lamotrigine
• Rigid, fall to ground Absence Ethosuximide
Lamotrigine
• Urinary incontinence (common)
• Post ictal Myoclonic Valproic acid
Clonazepam
Febrile Phenobarbital
 Status Epilepticus
• Single seizure lasting 5 minutes or multiple seizures
without regaining consciousness
• Clinical
– Presents typically with tonic-clonic seizures
Head Injuries/Other
• Diagnosis
– Rule out other causes: drug screen, CMP, LP, CT/MRI Simple concussion and brain contusion
– EEG Epidural hematoma
• Treatment Subdural hematoma
– Immediately give thiamine and glucose
– Lorazepam or diazepam Subarachnoid hemorrhage
– Phenytoin or fosphenytoin Intracranial mass lesion
– May need to intubate

Simple Concussion Concussion Grading Systems

• Transient loss of consciousness followed by complete recovery Grade I Grade II Grade III
– Implies an injury which resolves 7–10 days without complications Colorado Medical Confusion, no Confusion, post Any loss of
• Clinical Society Guidelines loss of traumatic consciousness
consciousness amnesia, no loss
– Headache, dizziness, nausea/vomiting, sleepiness of consciousness
– Short period of amnesia is often related
– No focal neurologic findings American Academy Confusion, Symptoms last Loss of
of Neurology symptoms last >15 min, no loss consciousness
• Brain contusion
Guidelines <15 min, no loss of consciousness IIIa lasts seconds
– Brain damage with prolonged coma, amnesia, & focal signs of IIIb lasts minutes
– May suffer from chronic impairment consciousness
• Treatment: monitor for return to activity
• Complications- Post-concussion syndrome Return to activity when symptom-free during rest and
– Presents immediately or months after injury with headache, exertion and neuropsychological tests are normal.
dizziness, sensitivity to light or noise, blurred vision, irritability,
anxiety, depression, or change in personality

Epidural Hematoma Subdural Hematoma

• Rupture of middle meningeal • Accumulation of blood in
artery subdural space caused by
• Due to skull fracture or tearing venous bleeding
of dural veins to sagittal sinus • CT scan: crescent-shaped
• May have rhinorrhea of spinal hematoma
fluid • Due to head injury with latency
• CT reveals lens-shaped between the event and
hematoma symptoms
– Headache
• Brief period of
– Confusion
unconsciousness that may
– Stupor
appear resolved, and then a
– Coma
sudden loss of consciousness
– Delirium
Source: Andrew Mullins Source: Brendan T. Doherty
– Hemiparesis
Subarachnoid Hemorrhage Summary
• Spontaneous arterial bleeding
into subarachnoid space
Hematoma Mechanism Clinical
• May result from an aneurysm
– Associated with connective Epidural Skull fracture • Spinal fluid rhinorrhea
tissue disease • Unconsciousness followed by resolution and
– Head trauma as a cause is then later unconsciousness
rare
• Abrupt onset
– Worsens over 30–90 min Subdural Head injury • Symptoms develop later after injury with
headache, confusion, coma, and hemiparesis
• Causes headache, stiff neck,
photophobia, and papilledema
• Blood in spinal tap
• Treatment Subarachnoid Aneurysm • Worst headache of life
– Nimodipine reduces risk of • Stiff neck and delirium
Source: Charles F. Gould
stroke
– Surgical clipping

Intracranial Mass Lesion Syncope

• Brain neoplasms are a diverse group of primary tumors • Transient (< ~1 minute) loss of consciousness
• Glioblastoma • Results from global cerebral hypoperfusion
– Is most common primary in adults
• Types
– Neurocardiogenic
– Symptoms and signs depend on size, growth and location of
• Most common type, diagnosed clinically
tumor
• Vasovagal (faint)
• Most frequent are headache, seizure, and signs of
• Carotid sinus
increased intracranial pressure (mental status change,
• Orthostatic hypotension
vomiting, papilledema)
– Cardiac syncope
– Diagnose with CT/MRI and biopsy • Arrhythmias- most common of this type
• PET scan may be helpful • Structural heart problems- inadequate output
– Treatment • Diagnosis
• Surgery, RT, chemotherapy – ECG, Holter monitoring, Echocardiogram, Electrophysiological
study
• Treatment
– Underlying etiology
 Pharmacology
Lecture 1 Analgesics
Migraine Medications

Pharmacology Lecture 2 Antibiotics

Lecture 3 Cardiac Medications

Lecture 4 Endocrine/GI Medications

Jim Van Rhee, M.S., PA-C
Program Director; Associate Professor Lecture 5 Psychiatric Medications

Yale School of Medicine, PA-Online Lecture 6 Other

Acute Pain Management

Analgesics
Acetaminophen
NSAIDS
Opiates
Migraine Treatment

Pharmacologic Options Acetaminophen

• Non-opioids • Opioids • Inhibits synthesis of prostaglandins in CNS and peripherally
– APAP (Acetaminophen) – Moderate pain blocks brain impulse generation
– NSAIDs • Codeine combination – Onset of action 30–60 minutes
products – Duration of action 4 hours
• ASA
• Hydrocodone • Analgesic and antipyretic effects
• COX-II inhibitors
combination products • No anti-inflammatory or anti-platelet effects
• Diclofenac • Maximum dose 4 grams/day (3 grams/day for chronic use)
• Oxycodone
• Ibuprofen
combination products • Metabolized in liver, excreted in urine
• Naproxen
– Severe pain – Hepatic impairment limit to 2 grams/day
• Ketorolac • Morphine – Severe renal insufficiency (CrCl <10ml/min) decrease frequency
• Oxycodone • Well-tolerated without common toxicities expected with
• Hydromorphone NSAIDs
• Fentanyl – Hepatotoxicity when combined with carbamazepine, ethanol,
• Oxymorphone INH
– Preferred analgesic during pregnancy and breastfeeding
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Medications
• Analgesic, antipyretic, and anti-inflammatory effects • Aspirin
– Low dose: analgesic (Used for mild-moderate pain) – Risk of Reyes syndrome in patients with viral infection
– High dose: anti-inflammatory – Contraindicated in pregnancy
• MOA – Stop drug one week prior to surgery
– Inhibit cyclooxygenase COX (enzyme which releases PG • Diclofenac (Voltaren)
known to sensitize or activate peripheral nociceptors in • Ibuprofen (Motrin)
producing pain)
• Naproxen (Anaprox, Naprosyn)
• Produces synergy with opioids
• Indomethacin (Indocin)
• May increase risk of thrombosis, stroke and MI
– Used in treatment of patent ductus arteriosus
• Increase risk of hypersensitivity in patients with aspirin • Ketoralac (Toradol): IV/IM
receptors
– Can be as effective as morphine, no euphoria
– Bronchial asthma, aspirin intolerance, rhinitis
– Limit duration of use to 5 days (Increase risk of ulcers)

Limitations of NSAIDs COX-2s

• NSAID-induced gastropathy • MOA
– Inhibit cyclooxygenase-2 (COX-2) which inhibits prostaglandin
• Anti-platelet effect synthesis which results in decreased formation of prostaglandin
precursors.
• Renal toxicity – Does not appear to block COX-1, decreasing GI toxicity
– Can compromise existing renal function • Used in patients where an NSAID is indicated with
• Drug interactions – History of GI ulcers
– Elderly
– Enhances effect of heparin, warfarin, digoxin, and lithium
– Low platelet count (< 50K) because it does not inhibit
– Decreases effects of ACE/ARBs, beta blockers, and diuretics platelet aggregation
– Receiving anticoagulation
– Receiving corticosteroids
– Coagulopathy
– Prior intolerance to non-selective NSAID

Celecoxib (Celebrex) Tramadol (Ultram)

• Used for acute and chronic pain
– OA, RA, dysmenorrhea
• Familial adenomatous polyposis (FAP)
• Many drug interactions that should be watched
(warfarin, CYP450)
• Caution in patients with sulfonamide allergy
• Binds to mu-opiate receptors but also binds to
norepinephrine (modifies the ascending pain pathway).
• Needs to be adjusted in renal dysfunction
(CrCl <30 mL/min) and hepatic dysfunction
• Limited by N/V, constipation, and dizziness
– May lower seizure threshold

• Caution in patients with CHF, fluid retention, • Concurrent use of quinidine will increase drug level
hypertension • Risk of serotonin syndrome when used with MAOIs,
TCAs, and SSRIs.
• Avoid in renal insufficiency, severe heart disease,
dehydration, liver failure
– Can increase cardiovascular risk (thrombosis, Stroke, MI)
Opioids Morphine/Hydroprophone
• Major class of analgesics in the management of Morphine Hydroporphone
moderate to severe pain
• Gold standard for cancer • Multiple dosage forms
• Act as a mu-opioid receptor agonist, altering the pain management • Used in moderate to
perception and response to pain centrally and
• Active metabolite: severe pain
peripherally
morphine-6-glucuronide • Multiple drug interactions
• Well-established efficacy • Well-tolerated: release of • Side effects
• Common toxicities are generally easily managed or histamine – Hallucinations, respiratory
prevented • Inexpensive and CNS depression,
sedation
• Doses are easily titrated • Multiple formulations
• May increase intracranial
pressure in head trauma
patients

Oxycodone Fentanyl
• Slightly more potent than morphine • 100 times as potent as morphine
• Fewer dosage forms – 1 mg IV morphine = 10 mcg fentanyl
– PO (IR and SR)
• Unique dosage forms
– Multiple combination products with acetaminophen and
ibuprofen – IV, transdermal, lozenge
• Milder side-effect profile relative to morphine • Least likely to induce histamine release
• May be less sedating in the elderly • Not known whether dose requires adjustment for renal
or hepatic failure
– Renally eliminated and hepatically metabolized

Meperidine Methadone
• Only recommended for pain management unless no • Opioid agonist & NMDA antagonist
other options – Used in detoxification of opiate addiction
• Short duration of action • Long half-life can lead to accumulation and toxicity
• Toxic metabolite • Very large inter-patient variability in PK
– Normeperidine – 80% oral bioavailability
– CNS toxic: seizures – t½ = 15–60 hours (up to 130 hours)
• Used for post-anesthesia and amphotericin B-related – Metabolized by CYP 3A4 (minimal renal excretion)
rigors • Watch drug interactions
– Increased toxicity (sedation and respiratory depression)
with CYP 3A 4 inhibitors (fluvoxamine and other
antidepressants)
– May prolong QT interval (Torsade de pointes)
Major Adverse Effects of Opioids
• CNS
– Mood changes
– Somnolence/CNS excitation
– Meiosis Migraine Abortive Therapy
• Respiratory system
• Urinary effects
• CV effects
• Constipation

Migraine Abortive Therapy Migraine Abortive Therapy

• Aspirin
– Appropriate, if tolerated, due to potent anti-inflammatory effect
– Combination products with caffeine and butalbital (Fiorinal) not
much more effective than aspirin alone
– Excedrin Migraine: aspirin + acetaminophen + caffeine
• NSAIDs
– MOA: anti-inflammatory activity
– Recommend short-acting NSAIDS (ibuprofen, naproxen
sodium) for faster onset
• Acetaminophen if ASA or NSAIDs not tolerated
• Midrin: combination product
– Not much more effective than simple analgesics
– Contains isometheptene (vasoconstrictor), dichloralphenazone
(anti-nausea properties), and acetaminophen (analgesic)
• Ergotamine alkaloids
– Direct vasoconstrictor of smooth muscle in cranial vessels/non-
selective 5HT agonist
– Dosage forms
• Tablets/suppositories: Cafergot in combination with caffeine
• Nasal spray: Migranal (D.H.E. dihydroergotamine)
• Injectable: D.H.E. for IM or IV use
– Adverse effects (mainly from vasoconstrictor effects):
• More common: N/V, abdominal pain (can be prevented by
concomitant antiemetics)
• Ergotism : abdominal cramps, nausea/vomiting, diarrhea,
vertigo, distal paresthesias
• Large doses potential for angina / MI
– Contraindications: angina/history of MI, peripheral arterial
disease, pregnancy, uncontrolled hypertension

Migraine Abortive Therapy Migraine Abortive Therapy

• 5HT1B/1D agonists ( triptans ) • 5HT1B/1D agonists
– 5HT 1B receptors in meningeal arteries: stimulation – Adverse reactions (due to vasoconstriction properties)
produces vasoconstriction
• Cardiovascular: arrhythmias, chest pain/angina,
– 5HT 1D receptors in trigeminal nerves: stimulation MI (patients with a history of CAD)
interrupts nociceptive transmission and neuropeptide
• Other: tingling, flushing, nausea, dizziness
release therefore decreasing transmission
– Dosage forms • Injection (Imitrex): associated with warm/tingling sensation,
• Tablets: sumatriptan (Imitrex); naratriptan (Amerge); rizatriptan feeling of chest heaviness, irritated injection site
(Maxalt, Maxalt XLT); zolmitriptan (Zomig, Zomig ZMT);
frovatriptan (Frova); eletriptan (Relpax); almotriptan (Axert)
• Injectable: sumatriptan (Imitrex)
• Nasal spray: sumatriptan (Imitrex); zolmitriptan (Zomig)
Migraine Abortive Therapy
• 5HT1B/1D agonists
– Drug interactions Pharmacology
• Ergotamine derivatives: additive vasoconstriction
• SSRIs: may increase risk of serotonin syndrome Lecture 1 Analgesics
(myoclonus, hyperreflexia, tremors): rarely reported Migraine Medications
problems when combined
Lecture 2 Antibiotics
• MAOIs: inhibit metabolism of triptans: markedly increased
levels and dangerous vasoconstrictor effects (except Lecture 3 Cardiac Medications
naratriptan)
– Contraindications Lecture 4 Endocrine/GI Medications
• Coronary artery disease
• Uncontrolled hypertension Lecture 5 Psychiatric Medications
• Ischemic heart disease
Lecture 6 Other
• Concurrent MAOI therapy or within 2 weeks of d/c MAOI
• Use of ergotamine within previous 24 hours

Cell Wall Synthesis Inhibitors

• Penicillin
– Natural
– Antistaphylococcal
Antibiotics – Extended spectrum
Beta-Lactams – Antipseudomonal
Protein Synthesis Inhibitors – Monobactams
Fluoroquinolones • Cephalosporins
Anti-Folate – 1st to 4th generation
Anti-Tuberculosis • Vancomycin
Anti-Virals

Beta-Lactam Antibiotics Natural Penicillins

• MOA
– Inhibit the transpeptidase enzyme (penicillin-binding
proteins) and prevents cross-linking of peptidoglycan
chains, inhibiting bacterial cell wall
• Resistance
– By production of beta-lactamase that cleaves the beta-
lactam ring to inactive the metabolite
– Alteration in penicillin-binding proteins
– Decrease penetrability of the cell wall
• Side effects
– Type 1 hypersensitivity reaction
– Nausea, vomiting, diarrhea, rash
• Penicillin G (IM) and V (oral, because acid stable)
– Renally excreted; add probenecid (decreases renal
secretion) to ­ blood levels
– Crosses blood brain barrier with inflammation
• Spectrum of activity
– Gram-positive
• Non-resistant Staphylococcus and Streptococcus, anthrax
• With aminoglycoside for enterococcus
– Gram-negative: Neisseria meningitidis
– Anaerobes: Clostridium (not B. fragilis)
– Spirochetes: Treponema
Anti-Staphylococcal Penicillinase Resistant Extended-Spectrum Penicillins
• Methicillin (IV), nafcillin (IV), oxacillin (IV), dicloxacillin • Ampicillin (PO, IV), amoxicillin (PO)
(PO) • Spectrum of activity
– Resistant to breakdown by beta-lactamase – Cover Streptococcus
• Spectrum of activity – Have some gram-negative coverage
• Haemophilus influenzae
– Beta-lactamase-producing staphylococcus • E. coli
– Not effective against gram-negative organisms • Listeria monocytogenes

– MRSA treat with vancomycin • Proteus mirabilis

• Salmonella
• Side effects • Neisseria
– Methicillin: interstitial nephritis (not used clinically)

Extended-Spectrum Penicillins Antipseudomonal Penicillin

• Beta-lactam inhibitors: extend the spectrum of activity • Carbenicillin (PO), ticarcillin (IV), piperacillin (IV)
– Clavulanate • Spectrum of activity
• Plus amoxicillin is Augmentin – Cover Pseudomonas and some aerobic and anaerobic
gram-negative rods
– Sulbactam
• E. coli, Proteus, Enterobacter, Citrobacter, Serratia,
• Plus ampicillin is Unasyn Klebsiella
• Side effects • Side effects
– Ampicillin: diarrhea, pseudomembranous colitis – GI disturbances
– Ampicillin rash: infectious mono – Prolonged bleeding time (platelet dysfunction)
• Beta-lactamase inhibitors: addition adds staph
coverage
– Clavulanate
• Plus ticarcillin is Timentin
– Tazobactam
• Plus piperacillin is Zosyn

Monobactams Cephalosporins: First Generation

• Aztreonam (IV) • Cefazolin (Ancef) (IV), cephalexin (Keflex) (PO),
cephalothin (Keflin) (IV), cefadroxil (Duricef) (PO)
• Spectrum of activity
• Spectrum of activity
– Active against gram-negative rods, including – Oral cavity anaerobes except B. fragilis
Pseudomonas – Cover some gram-negatives (use in UTI)
– No activity against gram-positive rods or anaerobes • E. coli
– Cover S. pneumoniae and H. influenzae but not as well as
• Side effects later generations
– While is a beta-lactam, it is not contraindicated in patients • Avoid in treating URI
allergic to penicillin or cephalosporins – Cover staphylococcus (not MRSA)
• Used in surgical prophylaxis
– GI upset, vertigo, headache
Skin Coverage
Cephalosporins: First Generation
• Side effects
– Diarrhea
– Hypersensitivity reactions
– Fever
– Increased liver function tests (uncommon)
– Neutropenia, thrombocytopenia (uncommon)
Cephalosporins: Third Generation
• Ceftriaxone (Rocephin) (IV), cefixime (Suprax) (PO),
ceftizoxime (Cefizox) (IV), ceftazidime (Fortaz) (IV),
cefpodoxime (Vantin) (PO)
• Spectrum of activity
– Activity against S. pneumoniae and H. influenzae
• Good penetration of CNS (meningitis)
– Used to treat N. gonorrhoeae
– Covers pseudomonas (ceftazidime, cefepime)
– Poor activity against S. aureus
• Side effects Pneumonia and CNS
– Same as first and second generations
– Increased risk of enterococcal superinfection
– Ceftriaxone can lead to gall stones with long-term use
Carbapenems
• Imipenem plus cilastatin (IV), meropenem (IV)
– Cilastatin inhibits breakdown of imipenem in the kidney
• Spectrum of activity
– Broad spectrum- gram positive, gram negative,
anaerobes
• Covers 90% of clinically important bacteria
– Meropenem has ­ activity against Pseudomonas
• Side effects
– Can cause seizures
– GI upset
Cephalosporins: Second Generation
• Cefaclor (Ceclor) (PO), loracarbef (Lorabid) (PO), cefoxitin
(Mefoxin) (IV), cefuroxime (Zinacef, IV) (Ceftin, PO),
cefotetan (Cefotan) (IV), cefprozil (Cefzil) (PO)
• Spectrum of activity
– Increased activity against S. pneumonia and H. influenzae
(cefuroxime is the best for URI/sinusitis)
– Active against anaerobic infection (including B. fragilis)
(cefoxitin and cefotetan)
• Use in PID
– Covers same gram-negatives as first-generation plus H.
influenzae, Enterobacter, Klebsiella, Proteus, and Neisseria
species
• Side effects: same as first-generation
Respiratory and PID
Cephalosporins: Fourth Generation
• Cefepime (Maxipime) (IV)
• Spectrum of activity
– Gram-negative bacilli including Pseudomonas
– MRSA
– S. pneumoniae
• Side effects
– Same as other groups
• Ceftaroline (Teflaro) (IV)
– Active against MRSA
– A fifth generation cephalosporin
Vancomycin
• A glycopeptide
• Action
– Binds to portion of cell wall precursors (D-alanyl-D-alanine)
preventing elongation of peptidoglycan strands and halting cell
wall synthesis
– Bactericidal against most bacteria (except Enterococcus)
• Spectrum of activity
– S. aureus (including MRSA), S. epidermidis, Streptococcus,
Corynebacterium diphtheriae, and Clostridium species
• Use in endocarditis, osteomyelitis, necrotizing fasciitis
• Pseudomembranous colitis (oral vancomycin)
– No coverage against gram-negative organisms
Vancomycin Protein Synthesis Inhibitors
• Side effects • Chloramphenicol
– Red man syndrome • Tetracycline
• Rash, flushing, tachycardia, hypotension • Macrolides
• Due to histamine release
• Aminoglycosides
• No problem if drug given slowly
– Ototoxicity (can be permanent) • Clindamycin
– Nephrotoxicity (increased with other nephrotoxic drugs) • Linezolid
– Bone marrow suppression (rare)

Chloramphenicol Tetracycline
• Bacteriostatic; binds to 50S ribosomal subunit • Short- versus long-acting
• Metabolized in the liver and enters CNS – Tetracycline: t ½ 6-12 hours
– Good choice for brain abscess – Doxycycline/minocycline: t ½ 16-18 hours
• Spectrum of action • MOA
– Kills most gram-positive, gram-negative, and anaerobes – Bacteriostatic, reversibly binds to 30S ribosomal subunit
– Effective against Rickettsial infections (RMSF)
– Crosses the placenta and is in breast milk
• Side effects
– Binds to calcium and antacids
– Bone marrow suppression/aplastic anemia
• Inhibits absorption
– Gray baby syndrome
• Due to inability to metabolize drug to inactive metabolite – Renal excretion
• Present with shock, abdominal distention, cyanosis • Doxycycline eliminated non-renal, so safe in renal failure

• Decrease use due to severe side effects

Tetracycline Macrolides
• Spectrum of activity • Erythromycin (E-mycin)
– Cover gram-positive and gram-negative but not drug of choice
due to increased resistance • Clarithromycin (Biaxin)
– Covers: • Azithromycin (Zithromax)
• Rickettsial infections
• Spirochete infections (Lyme disease) • Fidaxomicin (Dificid)
• Mycoplasma pneumoniae
• Chlamydial infection • MOA
• Minocycline for acne – Bacteriostatic, bind to 50S ribosomal subunit
• Side effects – Hepatic metabolism
– Hepatotoxicity
– Azithromycin concentrates in tissue and releases slowly
– GI upset: diarrhea, nausea, vomiting
– Phototoxic dermatitis
over prolonged period (t ½ ~72 hours)
– Discolored teeth/ decreased bone growth (do not give to
children age <8 or pregnant women)
– Use of outdated drug can lead to Fanconi syndrome
• Disease of the proximal renal tubules in which substances are
passed in the urine instead of being reabsorbed.
Macrolides Aminoglycosides
• Spectrum of action • Gentamicin, tobramycin, amikacin, streptomycin
– Group A streptococcus, Strep. pneumoniae, chlamydia, – Neomycin combined with polymyxin for topical use in
mycoplasma, haemophilus, and legionella (URI) superficial infections
– MAI can use clarithromycin or azithromycin
• MOA
– Fidaxomicin used in treatment of C. difficile
– Bactericidal
• Side effects
– GI upset- nausea, diarrhea – Poor oral absorption
– Cholestatic hepatitis – Eliminated by the kidneys
– Inhibits cytochrome P-450 (erythromycin, clarithromycin) – Bactericidal; bind to 30S ribosomal subunit and inhibit
• Can lead to an increase in other drug levels if metabolized in bacterial protein synthesis resulting in cell death
liver (theophylline, warfarin, digoxin)
– Antibiotic enters bacteria by oxygen-dependent active
– Acute ergot toxicity when combined with ergot derivatives transport
– Prolong QTc interval
• Not effective against anaerobes

Aminoglycosides Clindamycin
• Spectrum of action • Can be given PO, IV, topically
– Aerobic gram-negative • MOA
– Tobramycin more active against pseudomonas – Bacteriostatic, binds to 50S ribosomal subunit to inhibit
• Used as inhaled drug in cystic fibrosis bacterial protein synthesis
– Amikacin reserved for the most serious infections • Spectrum of action
– Endocarditis due to enterococcus – Gram-positive and anaerobic bacteria
• Must combine with cell wall inhibitor to be effective against • Anaerobes above the diaphragm
gram positives
• MRSA (most strains)
• Side effects • Will cover Streptococcus pyogenes
– Ototoxicity • Treatment of PCP and toxoplasmosis
• Hearing loss (usually irreversible), tinnitus, vertigo, ataxia • Alternative agent to PCN and cephalosporin in allergic
– Nephrotoxicity patients
• Acute tubular necrosis • Side effects
• Monitor serum creatinine – Abdominal pain, nausea, vomiting, rash, pruritus
– Pseudomembranous colitis

Linezolid Fluoroquinolones
• MOA • Ciprofloxacin (Cipro), ofloxacin (Floxin), norfloxacin
– Inhibits protein synthesis; binds to 50S subunit (Noroxin), levofloxacin (Levaquin), moxifloxacin
(Avelox)
• Spectrum of activity
• MOA
– MRSA, VRE, Corynebacterium, Listeria
– Bactericidal; bind to and inhibit bacterial enzyme DNA gyrase
• Side effects (topoisomerase II) resulting in inability of bacterial DNA to
supercoil and inhibits DNA replication and RNA transcription
– GI upset, diarrhea, headache, rash, thrombocytopenia
– Undergo hepatic biotransformation and are excreted
unchanged in the urine

• Moxifloxacin not eliminated by the kidneys

– Decreased oral absorption with ingestion of dairy products and
antacids
 Fluoroquinolones Antifolate Drugs
• Spectrum of action • Sulfonamides
– Broad spectrum: aerobic gram-positive and gram-negative bacteria – Sulfacetamide (Sulamyd) (topical)
• UTI/Prostatitis: due to gram-negative rods plus Pseudomonas – Sulfadiazine (PO or topical)
• Anaerobic infections (moxifloxacin) – Sulfamethoxazole (PO)
• Traveler s diarrhea: due to Shigella, Salmonella, E. coli, Campylobacter • Folate reductase inhibitors
• URI: due to Pneumococci, Chlamydia, Mycoplasma, Haemophilus,
Legionella – Trimethoprim (PO)
• Some coverage of Mycobacterium, treatment of anthrax – Trimethoprim-sulfamethoxazole (Bactrim) (PO, IV)
• Side effects • MOA
– Nausea, headache, dizziness, hepatitis – Decreased production of essential cofactors for the synthesis
of DNA, RNA, and proteins through the blockage of
– Photosensitivity, prolong QTc interval (lead to V tach) tetrahydrofolic acid production
– Due to damage to growing cartilage, contraindicated in children • Folate reductase inhibitors- inhibit dihydrofolate reductase
(<18yo) and during pregnancy
• Sulfonamides- compete with para-aminobenzoic acid in
• Except for ciprofloxacin used to treat anthrax and in kids with CF folate synthesis
– Multiple drug interactions (Theophylline, phenytoin, warfarin)

Antifolate Drugs Metronidazole

• Spectrum of action • MOA
– Gram positive- S. pneumoniae – Bactericidal, drug reduced to toxic agents that bind intracellular
macromolecules
– Gram negative- H. influenzae, E. coli, Shigella, Salmonella
– Metabolized in the liver
– Other- Pneumocystis, Toxoplasmosis
• Spectrum of action
• Side effects
– Active against nearly all anaerobic and microaerophilic
– Allergic skin rash: Stevens-Johnson syndrome bacteria, including B. fragilis
– Kernicterus: displacement of bilirubin which penetrates the – C. difficile colitis
CNS – Anti-parasitic
– Bactrim: nausea, vomiting, GI upset, bone marrow suppression • Side effects
– Avoid during pregnancy (fetotoxic) – Disulfiram reaction
– Drug interactions – Carcinogenic potential
– Metallic taste
• Thiazides- thrombocytopenia and bruising
– Pancreatitis
• Oral hypoglycemic agents- potentiated hypoglycemia

Nitrofurantoin Antituberculosis Drugs

• Macrobid or Macrodantin (PO) • Isoniazid (INH)
• MOA – Mechanism of action
– Inhibits several bacterial enzyme systems interfering with • Bactericidal, inhibits synthesis of mycolic acid in
metabolism and possibly cell wall synthesis mycobacterial cell wall
– Rapidly excreted in the urine – Side effects

• Spectrum of action • Hepatic impairment

– Treat UTI due to E. coli, Enterococcus, S. saprophyticus – Hepatitis: monitor AST/ALT

– Safe in pregnancy except at term, may cause hemolytic • Peripheral neuropathy: rare at standard doses
disease of the newborn – Minimize with administration of pyridoxine (B6)

• Side effects • Abdominal pain, nausea, vomiting

– Nausea and vomiting, hemolytic anemia (G-6-PD), • Drug induced lupus

pulmonary and hepatic toxicity, lupus-like syndrome • Increases toxicity from phenytoin and theophylline
Antituberculosis Drugs Antituberculosis Drugs
• Rifampin • Pyrazinamide
– Mechanism of action – Mechanism of action

• Bactericidal, inhibits DNA-dependent RNA polymerase • Bactericidal, Unknown mechanism.

– Also used to treat carriers of N. meningitides
– Side effects
• Nausea, vomiting, elevated liver function tests
• Ethambutol
– Increase risk when combined with INH
• Induces cytochrome P-450 and increases metabolism of
many drugs
– Coumadin, BCP, phenytoin, beta blockers, digoxin
• Orange discoloration of body fluids
• Pseudomembranous colitis
• Works best in the acid environment
– Side effects: liver toxic; hyperuricemia
• Along with streptomycin, not used in pregnancy
– Mechanism of action
• Bacteriostatic, inhibits the enzyme involved in synthesis of
cell wall
• Eliminated mainly by the kidneys
– Side effects
• Optic neuropathy (diminished visual acuity, loss of color
vision)

Anti-Viral Respiratory Agents

• Amantadine (Symmetrel)
– Influenzae A treatment- not recommended
– Inhibits viral un-coating
– CNS side effects including seizure

Anti-Viral • Rimantadine (Flumadine)

– Influenzae A treatment- not recommended
– Fewer CNS effects
• Zanamivir (Relenza)
– Influenzae A and B treatment
– Competes with viral enzyme neuraminidase, needed to release
virus
– No major side effects: bronchospasm

Anti-Viral Respiratory Agents HIV Drugs MOA

• Oseltamivir (Tamiflu)
– Similar to zanamivir
– Side effects: mild nausea and vomiting
• Ribavirin (Virazole)
– Inhibits viral messenger RNA formation
– Influenzae A & B; RSV; hepatitis A, B, & C treatment
– Side effects
• Hemolytic anemia, headache, nausea
• Teratogenetic, mutagenetic
– Contraindicated in pregnancy
HIV: Treatment HIV: Treatment
• Antiretroviral therapy (ART) is recommended for all • Recommended Initial Regimens for Most People with
individuals with HIV, regardless of CD4 T lymphocyte HIV
cell count, to reduce the morbidity and mortality • Integrase Strand Transfer Inhibitor + 2 Nucleoside
associated with HIV infection. Reverse Transcriptase Inhibitors:
• ART is also recommended for individuals with HIV to – Bictegravir-tenofovir alafenamide-emtricitabine—only in adults
prevent HIV transmission. ≥18 years of age

• When initiating ART, important to educate patients – Dolutegravir-abacavir-lamivudine—only if HLA-B*5701 negative

regarding the benefits and considerations of ART.
– On a case-by-case basis, ART may be deferred because of
clinical and/or psychosocial factors, but therapy should be
initiated as soon as possible.
– Dolutegravir plus tenofovir alafenamide-emtricitabine
– Dolutegravir plus tenofovir DF-emtricitabine
– Elvitegravir-cobicistat-tenofovir alafenamide-emtricitabine
– Elvitegravir-cobicistat-tenofovir DF-emtricitabine
– Raltegravir plus tenofovir DF-emtricitabine
– Raltegravir plus tenofovir alafenamide-emtricitabine

HIV: Treatment Side Effects HIV: Treatment Side Effects

• Older nucleoside reverse transcriptase inhibitors
(NRTIs) were associated with mitochondrial toxicity.
– Lactic acidosis, hepatic steatosis, myopathy, cardiomyopathy,
peripheral neuropathy, pancreatitis, and lipoatrophy, but these
adverse effects are rare with newer, recommended NRTIs.
• Abacavir can cause a hypersensitivity syndrome in
persons who are HLA-B*5701 positive.
– Abacavir may increase the risk of myocardial infarction
compared with other NRTIs.
• Tenofovir DF can cause nephrotoxicity, including
progressive chronic kidney disease and Fanconi
syndrome.
• Tenofovir DF has also been linked to decreased bone
density.
• Efavirenz may cause significant neuropsychiatric side effect
profile, and may cause neural tube defects if used by
pregnant women in the initial 6 weeks of pregnancy.
• Protease inhibitors have been traditionally linked to higher
rates of gastrointestinal effects, though newer PIs with
lower ritonavir boosting doses are generally better tolerated.
• Atazanavir associated with nephrolithiasis and cholelithiasis.
• The most common side effects of darunavir include
gastrointestinal symptoms (diarrhea, abdominal pain,
vomiting) and rash; the rash usually self-resolves and
requires discontinuation of the drug in less than 1% of cases.
• Medications in the integrase strand transfer inhibitor class
are generally well tolerated and moderate to severe side
effects are uncommon.
• Enfuvirtide, the only drug in the fusion inhibitor class, causes
injection site reactions (both acute inflammatory responses
and persistent sclerotic lesions) in most patients who take it.

Pharmacology
Lecture 1 Analgesics
Migraine Medications Cardiac Medications
Lecture 2 Antibiotics Diuretics
Lecture 3 Cardiac Medications ACE Inhibitors
Beta Blockers
Lecture 4 Endocrine/GI Medications
Alpha Blockers
Lecture 5 Psychiatric Medications
Calcium Channel Blockers
Lecture 6 Other Vasodilators
Anti-Arrhythmics
Diuretics Site of Action Diuretics
• Lower blood pressure primarily by depleting body of
sodium and reducing blood volume
– 10–15 mm Hg reduction in most patients
• Most effective in low renin or volume-expanded forms
of HTN (blacks/elderly vs. whites)
• Classes
– Thiazides
– Loops
– Potassium-sparing/aldosterone antagonists

Thiazide Diuretics Thiazide Diuretics

• MOA • Chlorothiazide (Diuril) • Adverse effects
– Bind to Na+/Cl- cotransporter in distal tubules and inhibit • Chlorthalidone – Electrolyte
the reabsorption of Na+ and Cl- disturbances
• Hydrochlorothiazide
– Result in increased urinary excretion of Na+,Cl- and H2O • ¯ K, Na, Mg
• Indapamide (Lozol)
– Have direct arteriolar vasodilatory effect • ­ Ca, uric acid (Gout)
• Metolazone (Zaroxolyn) – Dehydration
• Not effective in renal dysfunction (CrCl <30ml/min)
– Except in combination with loop diuretics – Sexual dysfunction
• Benefits: diuresis generally within 1 hour – Induction of new-onset
diabetes with long-
• Uses term use
– Hypertension, mild heart failure, lithium-induced diabetes – Hyperlipidemia
insipidus

Loop Diuretics Loop Diuretics

• MOA • Bumetanide (Bumex) • Adverse effects
– Inhibit apical Na+-K +-Cl- cotransporter in thick ascending loop of • Furosemide (Lasix) – Hypokalemia
Henle, thereby increasing their excretion; results in loss of
• Torsemide (Demadex) – Hypomagnesemia
concentrating ability of the kidneys
– Loss of electrostatic driving force also increases excretion of • Ethacrynic acid (Edecrin) – Chronic dilutional
Ca2+, Mg2+, and NH 4+ hyponatremia
• Powerful with rapid onset – Metabolic alkalosis
– Hyperuricemia
• Use in hypertension only as adjunct agent in Note: Furosemide 40 mg PO
combination with vasodilators – Ototoxicity
is equal to Bumetanide 1 mg
– Generally used only in severe HTN, when multiple drugs with PO. With IV the ratio is 20:1.
sodium retaining properties are used, in renal insufficiency
(GFR <30–40), and/or CHF exacerbations
Potassium Sparing Diuretics Potassium-Sparing Diuretics
• MOA • Potassium-sparing • Adverse effects
– Potassium-sparing diuretics block apical Na + channel in • Amiloride (Midamor) – Hyperkalemia
principal cells of the cortical collecting duct • Triamterene (Dyrenium) – Anti-androgen-like
• Blockade of Na+ entry causes drop in apical membrane potential effects/gynecomastia
(less negative), which is driving force for K+ secretion • Aldosterone antagonists (Spironolactone)
– Aldosterone antagonists prevent conversion of the receptor to • Eplerenone (Inspra) – GI
the active form, thereby preventing the action of aldosterone disturbances/diarrhea
• Spironolactone
• Can be used in combination with other diuretics to – Leg cramps
(Aldactone)
prevent K+ loss
• Do not use together (i.e., triamterene + spironolactone);
use with caution with ACEIs/ARBs
• AAs are good choice for patients with CHF and post-MI

ACE Inhibitors
• MOA
– Inhibition of ATII formation from ATI, thereby reducing
vasoconstriction, sodium retention, and cell proliferation and
remodeling
• Most effective in high renin HTN (white vs. black patients)
– Efficacy similar in white and black patients when used in combo
with a diuretic
• Drugs of choice in patients with HTN and DM
– Also used in CHF, arrhythmias, post-MI, CKD
• Blood pressure effect not that great
– Most lower BP <10 mm Hg; however these drugs do have
important long-term benefits in preventing or reducing renal
disease in patients w/ DM and reduction of HF

ACE Inhibitors Angiotensin II Receptor Antagonists

• Benazepril (Lotensin)
• Captopril (Capoten)
• Enalapril (Vasotec)
• Fosinopril (Monopril)
• Lisinopril (Prinivil, Zestril)
• Moexipril (Univasc)
• Perindopril (Aceon)
• Quinapril (Accupril)
• Ramipril (Altace)
• Trandolapril (Mavik)
• Adverse effects • MOA
– Cough
– Competitive inhibition of ATII receptors, thereby reducing
– Renal insufficiency in vasoconstriction and aldosterone effects
RAS
– Lack bradykinin effects
– Hyperkalemia
– Taste alterations, • Similar place in therapy to ACEIs
angioedema, rash
– Benefit in CHF and CKD
• Contraindicated in
pregnancy • Used in patients who cannot tolerate ACEI due to
• Eliminated by kidneys cough
(except fosinopril and • Teratogenic
moexipril)
• Reduce dose with renal
insufficiency
Angiotensin II Receptor Antagonists Beta Blockers
• Candesartan (Atacand) • Adverse effects • MOA
• Eprosartan (Teveten) – Dizziness – Beta-adrenoceptor antagonism
– GI effects • β1: heart, kidneys
• Irbesartan (Avapro)
– Blockade decreases force, rate, conduction, and
• Losartan (Cozaar) – Congestion automaticity of heart and renin release from
– Hyperkalemia juxtaglomerular cells of kidneys
• Olmesartan (Benicar)
– Angioedema • β2: lung, liver, GI tract, smooth muscle
• Telmisartan (Micardis) – Blockade enhances bronchoconstriction and decreases
• Valsartan (Diovan) glycogenolysis and gluconeogenesis
• Use
– Most effective in high renin HTN
– Indicated in patients with CHF and post-MI
– Arrhythmias
– Also used in the treatment of migraine, essential tremor,
and anxiety.

Beta Blockers Beta Blockers

• Propranolol (Inderal) • Adverse effects • Non-selective (β1 and β2)
• Atenolol (Tenormin) – Bronchospasm – Propranolol, nadolol, carteolol, timolol
• Carvedilol (Coreg) – Hypotension – Avoid in patients with asthma, diabetes, or peripheral vascular
• Esmolol (Brevibloc) – Heart block disease

• Labetalol (Normodyne) – Hypoglycemia • Cardioselective (β1)

– Lipid abnormalities – Metoprolol, atenolol, nebivolol, betaxolol, bisoprolol, esmolol
• Metoprolol (Lopressor,
– Fatigue • Atenolol is hydrophilic so may produce fewer CNS effects
Toprol)
– Sexual dysfunction • Drugs with intrinsic sympathomimetic activity (ISA)
• Nadolol (Corgard)
– Insomnia – Pindolol, acebutolol, penbutolol
• Pindolol (Visken) – Depression
– Have low-level agonist activity at β-adrenergic receptor
• Timolol (Blocadren)
– May be useful in patients with excessive bradyarrhythmias or
PVD

Beta Blockers Alpha Blockers

• Drugs with vasodilating effects • MOA
– Labetalol, carvedilol, nebivolol
• Labetalol and carvedilol due to α 1 effects; nebivolol due to – Blockade of vascular α-adrenoceptor
effects on nitric oxide release – Prevent sympathetic vasoconstriction and lead to dilation
• Parenterally available of both peripheral arterioles and veins and also relax
– Labetalol, esmolol, atenolol, metoprolol, propranolol smooth muscles in the prostate and bladder neck.
• Labetalol given PRN IV boluses to treat hypertensive
emergencies • α1: blood vessels, GI sphincters, male sex organs
• Esmolol has short half-life so given via continuous infusion
for peri-operative hypertension and hypertensive • α2: blood vessels, GI smooth muscle, adrenergic nerve
emergencies terminals
• Metoprolol has long half-life so not generally given IV to
treat HTN but rather for heart rate control
• Mortality benefit in CHF
– Metoprolol succinate, carvedilol, bisoprolol, nebivolol
Alpha Blockers Calcium Channel Blockers
• Selective α1 blockers • MOA
– Prazosin (Minipress) • Block L type calcium channels located in cardiac and
– Terazosin (Hytrin)
smooth muscle
– Doxazosin (Cardura)
– Monotherapy or adjunctive therapy in HTN • Effects on vascular smooth muscle à coronary and
– More commonly used to treat BPH peripheral vascular relaxation à decreased BP and
– Adverse effects: first dose hypotension and syncope, reduced cardiac afterload
tachycardia, dizziness, dry mouth, salt, & water retention when • Effects on cardiac muscle cells à decreased
used w/o diuretic contractility
• Non-selective α-blockers • Certain CCBs also decrease heart rate (non-DHPs)
– Phentolamine, phenoxybenzamine
– Used to treat hypertensive crises in pheochromocytoma • Most effective in low renin hypertension (black and
– Adverse effects: postural hypotension, reflex tachycardia, fluid elderly)
retention, diarrhea
– Contraindicated in patients with decreased coronary perfusion

Calcium Channel Blockers Dihydropyridine CCBs

• Non-dihydropyridine • Amlodipine (Norvasc) • More selective vasodilators
– Vasodilatory, negative chronotropic (heart rate) and negative • Felodipine (Plendil) – Decrease afterload and
inotropic (contractility) effects increase reflex in
– Often used to treat angina and arrhythmias
• Isradipine (DynaCirc) sympathetic stimulation of
• Avoid their use in AMI and heart failure • Nicardipine (Cardene) heart
– Increase contractility and
– Adverse effects: constipation, flushing, AV block, may worsen • Nifedipine (Adalat,
heart failure, hypotension, and bradycardia with IV formulations heart rate, increasing
Procardia) cardiac output
• Verapamil (Calan, Isoptin, Verelan) • Nisoldipine (Sular) – Adverse effects: peripheral
• Least selective CCB edema, flushing, headache,
• Clevidipine (Cleviprex)
• Avoid use with beta-blockers nausea, reflex tachycardia,
• Diltiazem (Cardizem) dizziness, constipation
• Less pronounced negative inotropic effect than verapamil
• More favorable side-effect profile

Calcium Channel Blockers- Side Effects Direct Vasodilators

Verapamil Diltiazem Nifedipine • Hydralazine
AV Block +++ ++ – MOA- release of nitric oxide from endothelial cells
• Dilation of arteries and arterioles; leads to ¯ PVR
Decreased cardiac ++ + + – Use in combination with other agents (BBs, diuretics, nitrates in
contractility
HF)
Increased coronary blood + ++ +++ – Adverse effects: tachycardia with palpitations, hypotension, dry
flow mouth, headache, nausea, edema, lupus-like syndrome with
Hypotension ++ + +++ prolonged use/high doses
Ankle edema ++ +/- +++ • Minoxidil
– MOA
Headache + 0 +++ • Opening of K+ channels in smooth muscle stabilizes membrane,
Contraindications Sick sinus, AV Aortic stenosis, making contraction less likely; affects arterioles
node disease, Unstable – Used in severe hypertension as add-on agent
EF <35% angina – Adverse effects: tachycardia, angina, edema, headache,
swelling, hypertrichosis
Direct Vasodilators Centrally-Acting Agents
• Sodium nitroprusside • α-methyldopa (Aldomet)
– IV only; short acting; used in hypertensive emergencies and – MOA
severe heart failure
– MOA • Prodrug taken up by central adrenergic neurons; converted
to α 2 adrenoceptor agonist, α-methylnorepinephrine
• Dilation of arterial and venous vessels due to activation of
guanylyl cyclase via nitric oxide release • Reduced adrenergic outflow from CNS leads to reduction in
• Increased intracellular cGMP, causing vascular relaxation PVR
– Adverse effects: tachycardia, sweating, nausea, psychosis, – Major use: hypertension during pregnancy
cyanide toxicity from metabolite (prolonged, high doses)
• Also for patients with renal insufficiency (does not reduce
• Diazoxide blood flow to kidneys)
– IV only
– MOA – Adverse effects: sedation, depression, lactation
• Similar to minoxidil (increases prolactin), positive direct coombs test
– Adverse reactions: excessive hypotension and reflex
sympathetic response; avoid in ischemic heart disease

Centrally-Acting Agents Nitroglycerin/Nitrates

• Clonidine (Catapres)
– MOA
• Central α 2 agonist
• α 2 stimulation in brainstem reduces sympathetic tone,
causing centrally-mediated vasodilatation, reduction in heart
rate, and blood pressure.
– Adjunctive agent; good in patients with renal insufficiency
– Also available as weekly patch (Catapres-TTS)
– Adverse effects: dry mouth, sedation, depression, vivid
dreams, withdrawal (hypertensive crisis: must taper), skin
reactions (patch)
– Also used in opioid withdrawal, decreases sympathetic
tone; migraine prophylaxis; restless leg syndrome
• MOA
– Formation of nitric oxide ® activation of guanylyl cyclase
® ­ in cGMP ® ¯ cystolic free Ca++ ® vascular smooth
muscle relaxation
– Reduce preload and afterload, dilate coronary arteries
• Absorption
– Orally: undergo first-pass effect so bioavailability is low
(<10–20%)
– Sublingual: avoid first-pass effect, short duration of action
(15–30 minutes)

Nitroglycerin/Nitrates Antiarrhythmics
• Contraindicated in patients with previous • Class 1
hypersensitivity – Fast sodium channel blockers
• Side effects – Increase action potential duration and effective refractory
– Headache, flushing period
– Hypotension (do not use if SBP <80) – Drugs
– Reflex tachycardia • Quinidine (Class1A)
– Increases heart rate and AV conduction
– Reflex increase in contractility
– Used in A fib
• Pregnancy: Class C
– Side effects- hypotension, increase QT interval,
• Drug interaction with phosphodiesterase inhibitors cinchonism
– Result in severe hypotension and death • Procainamide (Class 1A)
– Side effects- SLE-like syndrome, torsades, decrease
platelets and WBCs
Antiarrhythmics Antiarrhythmics
• Class 1 • Class 2
– Drugs – Beta blockers
• Lidocaine (Class 1B)- decrease action potential duration • Decrease HR and slow phase 4 depolarization
– Used post-MI, digoxin toxicity – Decrease SA and AV nodal activity
– Side effects- CNS toxicity (seizures)
• Good for atrial arrhythmias and tachycardias
– IV use because of first pass effect
• Drugs
• Mexiletine (Class 1B)
– Propranolol- post Mis and SVTs
– Same as lidocaine
– Oral – Acebutolol
• Flecainide (Class 1C) – Esmolol- used to treat SVTs
– Use effect on action potential duration
– Limited use

Antiarrhythmics Antiarrhythmics
• Class 3 • Class 4
– Potassium channel blockers
– Calcium channel blockers
• Prolong phase 3 repolarization and may have some beta
blocking effects • Decrease SA and AV nodal activity
– Increase action potential duration and effective – Drugs
refractory period • Verapamil and Diltiazem
• Drugs
– Amiodarone – Used in supraventricular tachycardias
» Use in any arrhythmias, long half-life – Side effects- constipation, dizziness, flushing,
» Side effects- pulmonary fibrosis, Blue skin hypotension
pigmentation, phototoxicity, hepatic necrosis
– Drug interactions
– Sotalol
» Avoid with beta-blockers and digoxin- block AV
» Use in life-threatening ventricular arrhythmias node
» Side effect- torsades

Antiarrhythmics Digitalis (Digoxin)

• Others
– Adenosine
• Activates adenosine receptors and decrease in cAMP
– Decrease SA and AV nodal activity
• Used in PSVT and AV nodal arrhythmias
• Very short half life (seconds)
• Side effects- flushing, sedation, dyspnea
– Magnesium
• Used in torsades
• MOA
– Influence Na and Ca ion flow in cardiac muscle,
increasing contraction of atrial and ventricular
myocardium and EF (+ inotropic effect)
• Used in treatment of left-sided heart failure
– Not indicated in right-sided HF
– Used in patients with HF and A fib
• Side effects: arrhythmia (slowing AV conduction), anorexia,
N/V, headache, alteration in color perception
• Increased toxicity noted with hypokalemia, quinidine,
verapamil, amiodarone, hypothyroidism, and renal
failure
 Pharmacology
Lecture 1 Analgesics
Migraine Medications Endocrine Medications
Lecture 2 Antibiotics Insulin
Lecture 3 Cardiac Medications Biguanides
Lecture 4 Endocrine/GI Medications
Sulfonylureas
Lecture 5 Psychiatrric Medications
Thiazolidinediones
Lecture 6 Other
Lipid Lower Agents

Insulin Effects Insulin

• Released from the beta cells of the pancreas
• Lowers glucose by stimulating peripheral glucose
uptake in the skeletal muscle and fat, and by inhibiting
hepatic glucose production
• Used in the treatment of diabetes mellitus type I and II
and diabetic ketoacidosis
• Side effects include hypoglycemia, edema, lipoatrophy.

nih.gov

Insulin Biguanides
• Decrease hepatic glucose • Products available
Type Onset (hr) Peak (hr) Duration (hr) production and intestinal – Glucophage
absorption of glucose and
Aspart Rapid-acting 0.25–0.5 0.5–2 3–4
improve insulin sensitivity (Metformin)
Glulisine
Lispro • Drug of choice for initial
Regular Short-acting 0.5–1 2–3 3-6
therapy
• Side effects include
NPH Intermediate 2-4 6–10 10-16
diarrhea, vomiting, and
Lente Intermediate 1.5–3 7–15 16–24 weight loss
• Hold in patients
Ultralente Long-acting 3–4 9–15 22–28 • Contraindicated in renal
disease (Crt >1.5 mg/dl), undergoing a radiologic
Glargine Long-acting 4 No peak 24–36
active liver disease, procedure involving
decompensated heart contrast media
failure, metabolic acidosis
 Sulfonylureas
• Lowers glucose by • Products available
stimulating insulin release – Glimepiride (Amaryl)
from the beta cells of the – Glipizide (Glucotrol)
islet cells of the pancreas. – Glyburide (Micronase)
• Use cautiously in patients • Can be used in
with renal and hepatic pregnancy
impairment – Chlorpropamide
(Diabinese)
• Start with low doses and
• Has a very long half-
titrate upward according life
to patient response
– Tolazamide (Tolinase)
• Lowers HbA1c by 1-2%
– Tolbutamide (Orinase)
• Safe in renal
dysfunction
Thiazolidinediones
• Decrease insulin • Products available
resistance by enhancing – Pioglitazone (Actos)
insulin receptor sensitivity
– Rosiglitazone
• Typically used in (Avandia)
combination therapy
• Reduces HbA1c by 1-
1.5%
• Use increases risk of
• Side effects
myocardial infarction,
– Hypoglycemia, weight so use with caution in
gain, edema patients with previous
– Contraindicated in MI
heart failure, liver
failure

Others Lipid Lowering Agents

• a-glucosidase inhibitors (acarbose (Precose))
– Delays postprandial digestion of sugars
– Side effects: nausea and diarrhea

• Glucagon-like peptide-1 receptor agonist

(exenatide (Byetta))
– Enhances glucose-dependent insulin secretion by the
pancreatic beta-cell
– Side effects: thyroid cancer, pancreatitis, renal impairment

Lipid Disorders Lipid Lowering Agents Summary

• Medications
– Bile acid-binding resins: form compounds with bile acids
in intestine Drug Class Lipid Effects Side Effects Contra-
indications
• Side effects: GI distress, constipation
• Contraindication: bowel obstruction Statins LDL ¯ Rhabdomyolysis Acute liver dz
HDL ­ Myolysis Chronic liver dz
– HMG-CoA reductase inhibitors: limit cholesterol synthesis
TG ¯ ­ LTFs
• Side effects: myositis, elevated LFTs
Bile acids binding LDL ¯ GI distress TG >400 mg/dl
• Contraindications: pregnancy, active liver disease resins HDL ­ Constipation
– Fibric acid derivatives: reduce hepatic trig production and increase HDL TG ­ ¯ Drug absorption
synthesis
Niacin and LDL ¯ Flushing Chronic liver dz
• Side effects: cholelithiasis, dyspepsia nicotinic acids HDL ­ Hyperglycemia Severe gout
• Contraindications: severe hepatic or renal disease TG ¯ ­ Uric acid levels
– Nicotinic acids: VLDL secretion inhibitors Liver damage
• Side effects: flushing, hepatotoxicity, hyperglycemia Fibric acids LDL ¯ Gallstones Severe renal dz
HDL ­ Myopathy Severe liver dz
• Contraindications- severe PUD, chronic liver disease, severe gout
TG ¯
 GI Medications Anti-Ulcer
Anti-Ulcer
Anti-Diarrheals
Laxatives
Anti-Emetics

Antacids PUD Drugs MOA

• MOA
– Neutralize acid secretions
(raise gastric pH >4)
– Inactivate pepsin and bile
salts
– Increase LES tone
• High and frequent dosing for
maximal effectiveness of
drug interaction
– Tetracyclines,
fluoroquinolone antibiotics,
keto- and itraconazole,
warfarin
• Products available
– Aluminum-containing
(Amphojel, AlternaGEL)
– Magnesium-containing
(Milk of Magnesia)
– Aluminum/magnesium
combo (Maalox)
– Calcium-containing
(Tums, Rolaids)
• Antiflatulent
– Simethicone-containing
(Mylanta, Gelusil)

Histamine2 Receptor Antagonists Histamine2 Receptor Antagonists

• MOA
– Competitively and reversibly
bind to H 2 receptor on
parietal cell, decreasing
histamine-stimulated gastric
acid 90-95%
• Well-absorbed orally
• Dose adjustment for renal
impairment
• Drug interactions can occur
via hepatic enzyme inhibition
(CYP 450 3A4)
– With Cimetidine
• Products available
– Cimetidine (Tagamet)
– Ranitidine (Zantac)
– Famotidine (Pepcid)
– Nizatidine (Axid)
Therapeutic uses
– Healing and maintenance of
duodenal and gastric ulcers
– GERD/erosive esophagitis
– Prevention of stress ulcer
– Hypersecretory conditions
Adverse effects
– CNS disturbances
• Dizziness, headache,
confusion, hallucinations
– Hematologic effects
• Thrombocytopenia,
leukopenia, anemia
– Gynecomastia
• Cimetidine
Proton-Pump Inhibitors
• MOA
– Bind irreversibly to H +— K +
ATPase enzyme needed to
pump H + ions and acid
secretions
– Inhibit basal and stimulated
gastric acid secretion
almost completely (99%)
Proton-Pump Inhibitors
• Products available • Indications • Adverse Effects
– Omeprazole (Prilosec) – Healing of duodenal and – Nausea
– Lansoprazole (Prevacid) gastric ulcers
– Diarrhea
– Rabeprazole (AcipHex)
– GERD/erosive – Headache
– Pantoprazole (Protonix) esophagitis
– Long term use leads
– Esomeprazole (Nexium) – Prevention/treatment of
to:
NSAID-induced ulcers
• Osteoporosis
– H. pylori eradication
• Vitamin B12 deficiency
– Hypersecretory
conditions

Sucralfate (Carafate) Bismuth Preparations

• MOA
– Aluminum hydroxide
and sucrose sulfate
dissolve in stomach
acid and release
aluminum, forming a
viscous gel
– Gel binds to ulcers,
creating a barrier to
irritants
• Indications
– Maintenance and
healing of GU and DU
• Take on empty stomach • Bismuth subsalicylate (BSS) (Pepto-Bismol)
• Take multiple daily – MOA
doses • In presence of pH <3.5, reacts with acid to form
bismuth oxide and salicylic acid
• Administer separately
• Disrupts H. pylori integrity and ability to adhere to
from meals &
interacting medications epithelial surface
(similar to antacids) • Salicylate provides antisecretory effects
• Adverse effects • Adverse effects
– Constipation – Black stools, tongue
– Nausea
– Metallic taste

Metoclopramide
• A prokinetic agent
• Blocks dopamine receptors in the chemoreceptor zone
and enhances response to acetylcholine in the upper GI
tract, causing increased motility and accelerating Anti-Diarrheal
gastric emptying
• Used to treat diabetes gastroparesis, nausea and
vomiting, GERD, and post-pyloric placement of enteral
feeding tube
• Side effects include- extrapyramidal reactions,
dizziness, headache, and fatigue.
• Patients can develop neuroleptic malignant syndrome
and tardive dyskinesia
 Antidiarrheal Brand Mechanism Comments

Antimotility
Diphenoxylate/ Lomotil ¯ GI motility and For short-term use
atropine propulsion Other: paregoric, opium
Loperamide Imodium AD tincture (historical; rare
use today)

Adsorbent Laxatives
Polycarbophil FiberCon Adsorb water & ¯ Nonspecific in action;
stool liquidity possible adsorption of
nutrients, drugs, etc.
Antisecretory
Bismuth PeptoBismol Block secretory flow High doses ® salicylism
subsalicylate Kaopectate
Enzymes
Lactase LactAid Hydrolyze lactose For lactose intolerance
into digestible sugars
Bacterial Replacement
Lactobacillus Lactinex Replace colonic Somewhat controversial
acidophilus bacterial microflora

Laxative Brand Comments

Agents resulting in soft or semifluid stool in 6-12 hours (acute use only)
Agents that cause softening of feces in 1-3 days
Bulk-forming Stimulant
Polycarbophil FiberCon Work by adsorbing water, Bisacodyl (oral) Dulcolax MOA unknown; may
expanding the stool increase peristalsis by
Psyllium Metamucil Senna Senokot
content, leading to direct irritant effect on
Methylcellulose Citrucel intestinal distention & Cascara sagrada intestinal smooth muscle
peristalsis Agents that cause watery evacuation in 1-6 hours (acute use only)
Emollients Saline laxatives
Docusate sodium Colace Stool softeners; promote Magnesium citrate Citroma Highly osmotic ions draw
water permeation of stool, water into the gut, leading
Docusate calcium Kaopectate Stool Softener Sodium phosphates Fleet Phospho-Soda
usually for prevention to increase intestinal
Polyethylene glycol- GoLYTELY, Colyte motility; usually reserved
Hyperosmotic electrolyte preps for complete bowel
Lactulose Cephulac Attract water into the evacuation
intestines, leading to fluid
Sorbitol Stimulant
accumulation, peristalsis,
Polyethylene glycol MiraLAX & bowel evacuation Bisacodyl (rectal) Dulcolax
136
Lubricant 135 Hyperosmotic laxative
Mineral oil Coat stool surface, retain Glycerin Used in pediatrics
water

Antihistamine Antiemetics
• MOA Drugs
– Antihistamine, Dimenhydrinate
anticholinergic effect (Dramamine)
Anti-Emetics on vestibular apparatus Diphenhydramine
• Use (Benadryl)
– Treatment of simple Hydroxyzine (Vistaril)
N/V Meclizine (Antivert)
– Adjunctive treatment in
complex N/V
• Adverse effects
– Sedation
– Dry mouth
– Urinary retention
 Phenothiazine Antiemetics
• MOA
– Block dopamine receptors
– Primarily in CTZ
• Use
Prochlorperazine (Compazine)
– Treatment of simple N/V
– Treatment and prevention
of mildly emetogenic
chemo-induced N/V
• Adverse effects
– Drowsiness
– Extrapyramidal reactions
– Sedation
– Bone marrow suppression
(rare)
Serotonin (5HT3) Antagonists
• MOA
– Block serotonin in the CTZ
and possibly GI tract
• Use
– Prevention/treatment of
chemo-induced N/V
– Also for post-operative
N/V
• Adverse effects
– Constipation
– Drowsiness
– Headache
– Prolong QT interval
Psychiatric Medications
Drugs
Chlorpromazine (Thorazine)
Perphenazine (Trilafon)
Promethazine (Phenergan)
Drug
Dolasetron (Anzemet)
Granisetron (Kytril)
Ondansetron (Zofran)
Palonosetron (Aloxi)
Benzodiazepines
Anti-Depressants
Anti-Psychotics
Stimulants
Butyrophenone Antiemetics
• MOA Drug
– Block dopamine Droperidol (Inapsine)
receptors in CTZ
• Use
Note: has black box
– Post-operative N/V warning for arrhythmias
(PONV)
• Adverse effects
– Sedation
– Dystonic reactions
– Prolong QT interval
Pharmacology
Lecture 1 Analgesics
Migraine Medications
Lecture 2 Antibiotics
Lecture 3 Cardiac Medications
Lecture 4 Endocrine/GI Medications
Lecture 5 Psychiatric Medications
Lecture 6 Other
Benzodiazepines
• Used in anxiety, agitation, anticonvulsant, and insomnia
– Do not reduce depressive symptoms
• Work by augmenting GABA function in the limbic system
– Rapid onset of action
• Safety: ability to overdose, abuse potential
– Dependence can occur even in the absence of abuse
– If used long term must taper the dose gradually to avoid
rebound, relapse, or withdrawal symptoms.
• Side effects
– Drowsiness
– Respiratory depression
– Memory impairment
 Benzodiazepines Benzodiazepines
Drug Onset Half-life
(hours) Drug Indications
Alprazolam Xanax Intermediate 6-20 Alprazolam Anxiety, panic, phobias
Chlordiazepoxide Librium Intermediate 30-100 Diazepam Anxiety, pre-op sedation, muscle relaxation
Lorazepam Anxiety, pre-op sedation, status epilepticus
Clonazepam Klonopin Intermediate 18-50 Midazolam Pre-op sedation, IV anesthesia
Temazepam Sleep disorder
Diazepam Valium Fast 30-100
Oxazepam Sleep disorders, anxiety
Flurazepam Dalmane Fast 50-160
Lorazepam Ativan Intermediate 10-20
Oxazepam Serax Slow 8-12
Temazepam Restoril Intermediate 8-20
Triazolam Halcion Fast 1.5-5

Anti-Depressants: SSRIs Anti-Depressants: SNRIs

• Bind to presynaptic serotonin reuptake proteins, • Inhibit reuptake of serotonin and norepinephrine
inhibiting reuptake • Used in treatment of major depression, mood disorders,
• Onset of effect in about 6 weeks ADHD, OCD
• Use with caution in HTN
• Used in depression and anxiety disorders
• Side effects
• Side effects
– Loss of appetite, weight, sleep, diminished libido, SIADH
– Nausea Fluoxetine (Prozac)
– Increase suicide risk
– Headache Sertraline (Zoloft)
– Discontinuation syndrome
– Insomnia/sedation Paroxetine (Paxil)
• With abrupt withdrawal- anxiety Avoid with St. John s wort due
– Sexual dysfunction Fluvoxamine (Luvox) • Venlafaxine (Effexor) to possible serotonin syndrome.

– Withdrawal delirium Citalopram (Celexa) • Desvenlafaxine (Pristiq)

– Increase suicide risk Escitalopram (Lexapro) • Duloxetine (Cymbalta)
– Risk of serotonin syndrome – Can lead to hepatic failure

Anti-Depressants: TCAs Anti-Depressants: TCA Side Effects

• MOA: block uptake of serotonin and norepinephrine Name Anti- Arrhythmia Sedation Weight gain
cholinergic
• High relapse rates
• Potentially fatal in high doses Nortriptyline ++ ++ ++ +++
(Pamelor)
• Onset of action: 1-6 weeks Imipramine +++ +++ +++ ++++
• Side effects: (Tofranil)
– Weight gain Desipramine ++ ++ ++ ++
– Dry mouth
(Norpramin)
– Blurred vision – Tremor
– Dizziness
– Drowsiness Amitriptyline ++++ +++ ++++ ++++
– Arrhythmia – Sexual dysfunction (Elavil)

– Hypotension Doxepin ++++ ++ ++ +++

(Sinequan)
Anti-Depressants: MAOIs Bupropion (Wellbutrin, Zyban)
• Inhibit presynaptic monoamine oxidase, which • Inhibits uptake of dopamine and norepinephrine
catabolizes norepinephrine, dopamine, and serotonin • Effective in depression and smoking cessation
• Foods high in tyramine (aged cheese, beer, red wine)
• Side effects
should be avoided
– Headache, insomnia, weight loss
– Can lead to hypertensive crisis
– Seizures
• Side effects MAOIs
• Contraindicated in patients with seizure risk
– Insomnia, agitation, sedation Isocarboxazid
– Sexual dysfunction – Low incidence of sexual side effects or sedation
Phenelzine
– Orthostatic hypotension Tranylcypromine

Mirtazapine (Remeron) Buspirone (BuSpar)

• Central presynaptic alpha-2 adrenergic antagonist, leads • Agonist of serotonin receptors and antagonist of
to increase release of serotonin and norepinephrine dopamine receptors

• Used in depression • A non-benzodiazepine anti-anxiety agent

• Side effects • Used in the treatment of generalized anxiety disorder
– Sedation – Takes several weeks to note improvement in symptoms
– Weight gain
• Side effects
– Sexual side effects (few) – Dizziness
• No cytochrome P450 inhibition – Nervousness
– Nausea
– Restless leg syndrome
– Extrapyramidal symptoms

Lithium (Eskalith) Antipsychotics

• Mood stabilizer, mainstay in treatment of bipolar • MOA: block dopamine receptors (first- and second-
disease/mania generation) and block serotonin (second-generation)
• MOA: not well-determined, possibly alter reuptake of • Effective in treating positive psychotic symptoms
serotonin and/or norepinephrine by altering cation transport • Side effects
across cell membrane – Restlessness, neuroleptic malignant syndrome, extrapyramidal
symptoms, weight gain
• Must monitor lithium levels on a regular basis – Anti-cholinergic (dry mouth, constipation, urinary retention)
– Reduced seizure threshold
– Contraindicated in severe renal function decline, cardiac
– Hypotension (Risperidone)
disease, and pregnancy
– Agranulocytosis (Clozapine)
• Side effects – Increase
– QT prolongation
– Minor: tremor, weight gain, polyuria, GI distress, acne
– Elevated prolactin
– Major: ataxia, confusion, course tremor, coma, sinus
arrhythmia, teratogenicity, death
Antipsychotics Stimulants
• MOA- mediate CNS stimulation through the release of norepinephrine and
Drug EPS M Sedation Alpha Other
dopamine and by blocking their uptake
Block Block
Typicals • Used in the treatment of ADHD, narcolepsy, and excessive daytime
sleepiness
Chlorpromazine ++ ++ +++ +++
• Have black box warning for abuse/addiction potential and serious cardiac
Thioridazine + +++ +++ +++ Cardiotoxicity- Torsades events
Fluphenazine +++ + + + • Side effects
Haloperidol +++ + + + Most likely to cause NMS and TD – Insomnia, headache, weight loss, loss of appetite

Atypicals – Long term use can suppress growth in children

Clozapine • Products available

+/- ++ + +++ Agranulocytosis, seizures.
Increased salivation – Amphetamine/Dextroamphetamine (Adderall)
– Methylphenidate (Ritalin, Concerta)
Olanzapine +/- + + ++ Improves negative symptoms – Lisdexamfetamine (Vyvanse)
Risperidone + +/- ++ ++ Improves negative symptoms – Modafinil (Provigil)
Aripiprazole + +/- +/- +/-
M block- M uscarinic blockage
N M S - N euroleptic m alignant syndrom e
Td- Tardive dyskinesia

Pharmacology
Lecture 1 Analgesics
Other
Migraine Medications Cholinesterase Inhibitors
Lecture 2 Antibiotics Anti-Coagulants
Lecture 3 Cardiac Medications Anti-Gout
Lecture 4 Endocrine/GI Medications
Anti-Convulsants
Lecture 5 Psychiatric Medications
TNF Inhibitors
Lecture 6 Other
Chemotherapy
Anti-Parkinson

Cholinesterase Inhibitors Anticoagulants

• MOA- inhibit acetylcholinesterase and increase the amount of • Heparin
acetylcholine at the synapse – MOA- binds to antithrombin and increases inhibition of factors IXa,
• Used in the treatment of Alzheimer’s dementia, dementia Xa, XIa, XIIa, and IIa.
associated with Parkinson’s disease, and Lewy body dementia – Used in the treatment of DVT, PE, peripheral arterial embolism,
DIC and DVT prophylaxis.
• Are not a cure, but may reduce symptoms – Side effects include:
• Side effects • Bleeding, thrombocytopenia, osteoporosis (long term use)
– Nausea and vomiting, diarrhea, bradycardia, hypertension, insomnia – Multiple drug interactions
– Concurrent use of ginko biloba may worsen side effects with donepezil
– Monitor levels with aPTT
– Overdose
• Products available • Very short half-life (1 hour) so holding drug will decrease levels
– Donepezil (Aricept) quickly
– Rivastigmine (Exelon) • Protamine sulfate is antidote
– LMWH- inhibit factors Xa and IIa
• Dalteprin (Fragmin)
• Enoxaparin (Lovenox)
• Anti-Xa levels can be used to monitor LMWH levels
Direct Acting Oral Anticoagulants Drug Effects with Warfarin
• Used to prevent stroke, systemic embolism, and • Increase INR • Decrease INR
venous thromboembolism
– Amiodarone – Carbamazepine
• No blood monitoring of levels needed
• Three agents – Fluconazole – Rifampin
– Dabigatran (Pradaxa) – Metronidazole – Alcohol (Chronic)
• Thrombin inhibitor
• May have some risk of major bleeding – Ciprofloxacin – Propylthiouracil
– Apixaban (Eliquis) – Erythromycin
• Facto Xa inhibitor
– Rivaroxaban (Xarelto)
– Prednisone
• Factor Xa inhibitor – TMP/Sulfa
– Cimetidine
– Alcohol (Acute)

Anti-Gout
• Colchicine
– MOA- unknown, possibly preventing activation and migration of
neutrophils associated with mediating some gout symptoms.
– Used in the treatment and prophylaxis of acute gout, also used
in pericarditis and primary biliary cirrhosis
– Side effects
• Diarrhea, nausea and vomiting, myelosuppression, aplastic
anemia, and hepatotoxicity
– Does adjustment in hepatic and renal failure
Anti-Gout
• Allopurinol
– MOA- decreases production of uric acid by blocking xanthine
oxidase.
• Xanthine oxidase converts hypoxanthine to xanthine and
then to uric acid
– Used to prevent gout attacks, treatment/prevent tumor lysis
syndrome, and prevent recurrent calcium oxalate calculi
– Side effects include maculopapular rash and pruritus
• Rare side effect include Stevens-Johnson syndrome and
toxic epidermal necrolysis
• Reduce dose in renal failure

Anti-convulsants-MOA Anti-convulsants- Uses

Seizure Type Effective Drugs
Medication MOA Partial- simple or Valproic acid
Carbamazepine Decrease axonal conduction by preventing Na+ influx complex Phenytoin
Phenytoin through fast Na channels Carbamazepine
Lamotrigine
Barbiturates Increase inhibitory tone by facilitation of GABA-mediated
Benzodiazepines hyperpolarization General- tonic Valproic acid
clonic Phenytoin
Lamotrigine Decrease excitatory effects of glutamic acid
Topiramate Carbamazepine
Felbamate Lamotrigine

Ethosuximide Decrease presynaptic Ca2+ influx through type-T channels General- absence Ethosuximide
Valproic acid in thalamic neurons Valproic acid
Status epilepticus Lorazepam
Diazepam
Phenytoin/Fosphenytoin
 Anti-convulsants- Side Effects Chemotherapy
Drug Class MOA
Medication Side effects Alkylating agent Form strong covalent bonds with DNA inhibiting replication and
causing bond breaks and cell death
Phenytoin Gingival hyperplasia, CNS depression, Hirsutism, aplastic
anemia, Osteomalacia Anthracyclines Inhibition of DNA and RNA synthesis by intercalation of DNA
base pairs and inhibition of DNA repair by topoisomers
Carbamazepine CNS depression, aplastic anemia, Osteomalacia, exfoliative
dermatitis, increased ADH secretion Antimetabolites Inhibit DNA synthesis or incorporate themselves into DNA
causing apoptosis.
Valproic acid Hepatotoxicity, thrombocytopenia, pancreatitis, alopecia
Aromatase Inhibit aromatase that converts androgens to estrogens
Ethosuximide Drowsiness, headache, GI complaints, pancytopenia inhibitors
Lamotrigine Stevens-Johnson syndrome Monoclonal Bind to receptors on tumor cells stopped cell growth and spread
Felbamate Hepatotoxicity, aplastic anemia antibodies
Platinum Form covalent bonds with DNA inhibiting replication and causing
compounds cell death
Vinca alkaloids Prevent microtubules assembly preventing cell mitosis
Tyrosine kinase Block signaling pathway and slowing or stopping cell
inhibitors proliferation

Chemotherapy Chemotherapy
Drug Class Examples Drugs Side Effects
Alkylating agent Cyclophosphamide (Cytoxan) Cyclophosphamide (Cytoxan) BMS, hemorrhagic cystitis
Anthracyclines Doxorubicin (Adriamycin) Doxorubicin (Adriamycin) BMS, cardiomyopathy
Antimetabolites Cytarabine (ARA-C) Bleomycin Pneumonitis, pulmonary fibrosis
5-fluorouracil (5-FU) Cytarabine (ARA-C) BMS, mucositis, diarrhea, N/V
Methotrexate (Rheumatrex) 5-fluorouracil (5-FU) BMS, mucositis, palmar erythema
Aromatase Letrozole (Femara) Methotrexate (Rheumatrex) BMS, hepatotoxicity, N/V
inhibitors Letrozole (Femara) Hot flashes, night sweats, edema
Monoclonal Rituximab (Rituxan) Rituximab (Rituxan) Lymphopenia, tumor lysis syndrome, rash
antibodies Trastuzumab (Herceptin) Trastuzumab (Herceptin) Rash, nausea, cardiotoxicity, pulmonary toxicity
Platinum Carboplatin (Paraplatin-AQ) Carboplatin (Paraplatin-AQ) BMS, ototoxicity, peripheral neuropathy
compounds Cisplatin (Platinol) Cisplatin (Platinol) N/V, peripheral neuropathy, nephrotoxicity
Vinca alkaloids Vincristine (Oncovin) Vincristine (Oncovin) Peripheral neuropathy, constipation, depression
Tyrosine kinase Imatinib (Gleevec) Imatinib (Gleevec) BMS, fluid retention, rash, hepatotoxicity
inhibitors
BMS- Bone marrow suppression
N/V- nausea and vomiting

Psychiatry/Behavioral Science
Isaak Yakubov, MS, PA-C
DSM-5
Diagnostic and Statistical Manual of
Mental Disorders
• The goal in revising DSM-5 was to account for the
last 20 years of scientific and clinical advancement.
• The changes aligned DSM-5 to the World Health
Organization’s International Classification of
Diseases (ICD).
The Anxiety Disorders
Separation Anxiety
Specific Phobia
Social Anxiety Disorder
Panic Disorder
Agoraphobia
Generalized Anxiety Disorder
Post Traumatic Stress Disorder
Obsessive-Compulsive Disorder
Psychiatry/Behavioral Science
Lecture 1 Anxiety Disorders
Mood Disorders
Lecture 2 Personality Disorders
Sleep-Wake Disorders
Psychoses
Lecture 3 Somatoform Disorders
Substance Abuse
Eating Disorders
Dissociative Disorders
Childhood Disorders
Medications
DSM-5
• Section 1 – Introduction
• Section 2 – Outline of Categorical diagnoses
• Section 3 – Emerging Measures and Models
– Conditions that require further research prior to consideration to
be a formal diagnosis, cultural formulation, glossary
• No longer using a Multi-Axial System
– “General medical condition” has been replaced by “another
medical condition” across all disorders
Separation Anxiety Disorder
• The presence of excessive fear or anxiety
regarding separation from attachment figures.
• Must interfere with ability to leave the home, travel
or work outside the home.
• Prevalence generally decreases across the
lifespan, 4% in childhood to 2% of adults.
• In childhood, may see fear of leaving the home or
refusal of attending school.
• In adults, may see dependency and overprotective
behavior along with CV symptoms.
• Must be present for 4 weeks in children, 6 months
in adults
1
Separation Anxiety Disorder
• Diagnostic Criteria (3 of the following)
– Recurrent excessive distress when anticipating or experiencing
separation from home or attachment figures
– Persistent and excessive worry about losing major attachment
figures (by death, harm, illness, disaster)
– Persistent and excessive worry about experiencing an
untoward event that causes separation (an accident, getting
lost, being kidnapped)
– Persistent reluctance to go to school, work, or away due to fear
of separation.
– Persistent fear of being alone without major attachments
– Persistent fear of sleeping away from home or being able to fall
asleep with attachments near
– Repeated nightmares involving separation
– Complaints of physical symptoms when experiencing or
anticipating separation.
Specific Phobia
• Anxiety disorder characterized by intense fear of a
particular object or situation, 6 months duration
• Women > men; typical onset in childhood
• Must experience a marked, persistent fear that is
recognized by the patient to be excessive or
unreasonable
• Management
– Childhood phobias may remit spontaneously with age and often
present with tantrums, clinging, freezing behaviors.
– Rarely cause disability
– Treatment of choice is exposure therapy
– Medications not indicated

Social Anxiety Disorder Social Anxiety Disorder

(previously social phobia) • The avoidance interferes significantly with person s
• Marked or persistent fear of social or performance routine
situations in which person is exposed to scrutiny by • Exposure to the social situation provokes anxiety
others
• If a general medical condition or another mental
• Person fears that he/she will act in a way which will be disorder is present, the fear is unrelated
embarrassing
– e.g., the fear is not of stuttering or trembling in
• Social situations are either avoided or endured with Parkinson s disease
intense anxiety or distress
• Lifetime reported rate of up to 13%
• Women>men. Peak onset in teens.
• Often associated with a depressive disorder

Panic Attack Panic Disorder

• Discrete fear in which in which 4 of the following • Recurrent unexpected panic attacks.
symptoms develop abruptly, peak within 10 minutes,
• Can be “unexpected” – occur out of the blue
and resolve within about 30 minutes.
• A panic attack is not a disorder itself but is a specifier to • Can be “expected”: - recurring due to specific triggers
another dx.
• 4 or more panic attack symptoms, recurring, followed
– Palpitations
– Sweating by at least one month of worry or concern about more
– Trembling attacks or a significant maladaptive change in behavior
– Dyspnea
related to the attacks
– Choking Feeling
– Nausea
– Dizziness
– Chills/hot flashes
– Fear of dying
– Paresthesia

2
Agoraphobia
• Marked fear and anxiety about 2 or more of the
following:
– Public transportation (bus, train, auto, plane)
– Being in open spaces (parking lot, shopping mall)
– Being in enclosed spaces (cinema, stores)
– Standing in line or within a crowd
– Being outside of the home.
Generalized Anxiety Disorder
• Excessive anxiety or worry occurs in majority of days in
6-month period (about a number of events or activities)
• Patient finds it difficult to control the worry
• The worry is associated with 3 or more of the following:
– Restlessness
– Fatigue
– Difficulty concentrating
– Irritability
– Muscle tension
– Sleep disturbance
Trichotillomania
• Recurrent pulling out of hair, resulting in hair loss
• Repeated attempts to stop or decrease pulling out hair
• Must cause significant distress in the social or
occupational functioning.
• New in DSM V
Agoraphobia
• Fear must be persistent for 6 months or more
• Must be out of proportion to any real danger
• The fear is that escape may be difficult, help may not
be available, or an embarrassing event may occur (
incontinence, falling)
• These situations are avoided, require the presence of a
companion, or are endured with intense fear and
anxiety
• Cannot be accounted for by another medical or
psychological disorder
• Agoraphobia is diagnosed irrespective of the presence
of panic disorder.
• If criteria for both panic and agoraphobia are met, both
dx should be used
Anxiety Disorder Treatment
• Medication
– SSRIs
– SNRIs: venlafaxine (FDA-approved for long-term treatment of
GAD)
– Tricyclic antidepressants
– Buspirone for GAD
– Benzodiazepines – watch for abuse potential, Rapid onset of
action
– Beta-blockers – for performance and social anxiety. Not first
line.
• Psychotherapy
Selective Mutism
• Consistent failure to speak in specific social settings
where there is an expectation of speaking, despite
being able to speak in other situations.
• The disturbance must interfere with educational or
occupational achievement, or with social
communication.
• The disturbance is of at least one month duration (not
limited to the first month of school)
• The failure to speak is not due to lack of knowledge or
language,
• The disturbance is not better explained by a
communication disorder.
• New to DSM V
3
Post-Traumatic Stress Disorder (PTSD)
• Person has been exposed to a traumatic event in
which there is:
– Actual or threatened death, serious injury or sexual
violation to self or others in one or more of the following
ways:
Post-Traumatic Stress Disorder (PTSD)
• Prevalence 8–9% of population
– Less than 10% of people exposed to a traumatic event
will develop PTSD
– Recovery most pronounced in first year following the
trauma

– Direct experience
• Most common group is young adults
– Trauma for men is often combat experience; can be life
– Directly witnessing the event happening to another threat by violence in other (non-military) high-risk groups
– Learning that the event happened to close family/friend (urban violence)
– Trauma for women is usually assault or rape
– Experiencing repeated exposure to aversive details of
traumatic events (ie first responders, police involved in – Adult survivors of childhood sexual abuse
child abuse) This does not apply to TV, media
exposure.

PTSD PTSD
• The trauma is persistently re-experienced (>1 month) • Avoidance of stimuli:
as one or more of the following: – Thoughts, feelings, or conversations
– Recurring, involuntary, intrusive memories – Activities, places, or people
– Distressing dreams – Memory lapse about certain aspects of event
– Acting/feeling as if event were recurring (flashbacks) – Decreased interest in activities
– Physiological and psychological distress when exposed – Feelings of detachment
to cues that symbolize the trauma – Restricted range of affect
AND... – Sense of foreshortened future

PTSD Treatment
• Symptoms of increased arousal (2 or more of the • Refer to psychiatry
following): – Medications (antidepressants)
– Difficulty falling or staying asleep • SSRIs: paroxetine, sertraline (first-line DOC)
– Irritability • TCAs and MAOIs
– Difficulty concentrating – Cognitive-behavioral therapy
– Hypervigilance • Psychotherapy (individual or group)

– Exaggerated startle response • Counseling

– Combination of meds/treatment is more effective than
• The disturbance causes significant impairment either one alone
• Duration of disturbance (dreams, flashbacks, physical
disturbance) is greater than 1 month

4
Acute Stress Disorder
• Like PTSD
– Symptoms for a duration less than 1 month
• Other criteria less stringent than PTSD
– Treatment
• Initial counseling/psychotherapy
• If persistent, same medications as for PTSD
• Treatment may vary according to acuity of patient
Obsessive-Compulsive Disorder (OCD)
• Obsessions or compulsions (or both)
• Prevalence 2.5% lifetime
• Mean onset: age 20 (one-third of cases by age 15;
rare after age 50)
• Men = women but men present earlier
• Common to have other comorbid conditions
– Depression, panic disorder, phobia, tics

Obsessions/Compulsions
• Obsessions
– Recurrent or persistent thoughts; thoughts are NOT excessive
worries about real life problems
– Person attempts to ignore or suppress the thoughts
– Person realizes the thoughts are a product of his/her own mind
• Compulsions
– Repetitive behaviors the person is driven to perform
– Behaviors are aimed at preventing or reducing distress
(consciously or unconsciously)
OCD
• At some point in the disorder, the person realizes the
obsessions/compulsions are unreasonable.
• The obsessions or compulsions cause marked distress,
are time consuming, or significantly interfere with
person s life.
• The content of the obsessions/compulsions may not be
restricted to other co-existing diagnoses.
– In an eating disorder, for instance, person may have
preoccupation with cleanliness, in addition to food

OCD Treatment
• At least 75% of patients have both obsessions & • Medications
compulsions – SSRIs
• Patients frequently present to primary care • Fluvoxamine, sertraline, paroxetine
• Four major symptoms patterns of – Tricyclic antidepressant
obsessions/compulsions • Clomipramine
– Contamination • Therapy
– Doubt – Cognitive-behavioral therapy
– Symmetry/precision • Exposure and response prevention (ERP)
– Intrusive thoughts without compulsion: frequently a – Psychoeducation
sexual/aggressive act that is repulsive to the patient – Support groups

5
 Major Depressive Disorder
• One or more episodes of major depression
• Criteria
– Five or more of the following symptoms must be present
Mood Disorders during the same 2-week period, at least one of which is
Major Depressive Disorder depressed mood or loss of interest (core symptoms)

Disruptive Mood Dysregulation

Disorder
Premenstrual Dysphoric Disorder
Dysthymic Disorder
Bipolar Disorder

Major Depressive Disorder Major Depressive Disorder

• Symptoms in – Depressed mood (core symptom) • Symptoms do not meet the criteria for a mixed episode
depressed episode: – Diminished interest or pleasure (mania or hypomania + depressive symptoms)
(core symptom)
• Symptoms cause significant impairment
– Significant weight change (>5%)
– Insomnia or hypersomnia • Symptoms are not better accounted for by
– Psychomotor agitation or retardation bereavement
– Feelings of worthlessness/guilt
– ↓ concentration/indecisiveness
– Recurring thoughts of death or
suicide
– ↓ energy/fatigue

Major Depressive Disorder Treatment

• History: Somatic symptoms
– Headache
– Constipation
– Skin changes
– Chest pain
– Abdominal pain
– Cough
– Shortness of breath
• Incidence • Psychotherapy
– 5–10% of primary – Goal is to deal with stressors more adaptively
care patient – First-line therapy in mild to moderate depression that is
population nonpsychotic and not chronic/highly recurrent
– Women > men 3:1 • Electroconvulsive therapy (ECT)
• 1/4 of cancer patients
– Indicated in patients who are suicidal or worried about drug
• 1/4 women at some point side effects
have clinical depression
• Increased prevalence with
family history, substance
abuse, chronic pain,
chronic illness, and severe
or unanticipated stress

6
Treatment Treatment
• SSRIs • TCAs
– Fluoxetine (Prozac) – Elavil (amitriptyline)
– Paroxetine (Paxil) – Pamelor (nortriptyline = first metabolite of amitriptyline)
– Citalopram (Celexa) – Tofranil (imipramine)
• Aminoketones:
– Sertraline (Zoloft)
– Wellbutrin (bupropion) = atypical antidepressant
– Escitalopram (Lexapro)
(DA + NE + some 5-HT)
• Anti-OCD SSRIs: fluvoxamine (Luvox) • Atypical SSRIs:
• Anti-OCD (not SSRI): – Remeron (mirtazapine)
– Clomipramine (Anafranil) • More sedating at lower doses; activating at higher doses

Suicide Risk Factors Dysthymic Disorder

• Age • Impulsive • Mild, chronic form of major depression
– Peak attempts: men 25–30 and • Rigid in thinking
women 45–50 • Symptoms are less severe than major depression
• Ethnicity • Faces stressful events • Diagnosis
– Caucasians > others • Has made direct verbal – At least 2 years of chronically depressed mood most of
• Living alone warnings the time
• Bereaved • Has made plan – Symptoms: change in appetite and sleep, fatigue, decreased
• Unemployed • Has had past attempts concentration, hopelessness
• Poor health status • Treatment
• Feels hopeless
– Similar to major depression
• Has anxiety

Disruptive Mood Dysregulation Disorder Premenstrual Dysphoric Disorder

• Severe recurrent verbal or physical temper outbursts • In the majority of menstrual cycles, a total of five
that are out of proportion to the situation. symptoms must be present in the final week before the
• The outbursts are inconsistent with development level. onset of menses, improve within a few days onset of
• Outbursts occur three or more times weekly. menses, and become minimal or absent in the week
following menses.
• The mood between outbursts is angry most days, and
is observable by others. • One or more of the following:
– Marked affective lability (mood swings, sad, tearful)
• Sx must be present for at least twelve months to dx, – Marked irritability or anger
and have occurred in at least two different settings
– Marked depressed mood
• Dx should not be made initially before age 6 or after – Marked tension, anxiety
age 18 (median age at dx 10)
• AND……
• Dx cannot co-exist with ODD or bi-polar.

7
Premenstrual Dysphoric Disorder Bipolar Disorder
• One or more of the following (to reach total of five from • Has a variety of presentations which must incorporate
list on previous slide) a current or prior manic, hypomanic, mixed, or
– Decreased interest in usual activities depressive episode
– Subjective difficulty concentrating
• Manic episode: criteria
– Lethargy, easily fatigued
– Marked change in appetite, overeating, or food cravings
– A period of abnormally and persistently elevated,
expansive, or irritable mood, lasting at least 1 week
– Hypersomnia or insomnia
– Physical symptoms (breast tenderness, bloating, muscle
aches)
Symptoms must markedly interfere with work, school, social
events, or relationships.

Manic Episode Manic Episode

• During the disturbance, 3 or more of the following • Symptoms do not meet the criteria for a mixed
persist: episode
– Inflated self-esteem or grandiosity
• Mood disturbance causes marked impairment or
– Decreased need for sleep necessitates hospitalization to prevent harm to self or
– Increased talkativeness others, or there are psychotic features
– Flight of ideas
– Distractibility

– Increased goal-directed activity

– OR excessive involvement in pleasurable activities that have
high potential for painful consequences

Hypomanic Episode Hypomanic Episode

• Period of elevated, expansive, or irritable mood • Episode is associated with a definitive change in
lasting at least 4 days, that is clearly different from the functioning
usual nondepressed mood • The change is observable by others
• During the disturbance, 3 or more of the following
persist: • Episode is not severe enough to cause marked
– Inflated self esteem or grandiosity
impairment or psychotic features
– Decreased need for sleep
– Increased talkativeness
– Flight of ideas
– Distractibility
– Increased goal-directed activity
– Excessive involvement in pleasurable activities

8
Bipolar Disorder Bipolar Disorder: Treatment
• Incidence • Mania
– About 1% of the general population – Lithium, valproate, second-generation antipsychotics
– Men = women • Depression
– New onset rare after age 50 – Lithium, valproate, carbamazepine, second-generation
• Strongest risk factor: family history antipsychotics
• Treatment • Use may cause a switch to manic, hypomanic, or mixed
states
– Referral to psychiatry
• Avoid the treatment of just depression in bipolar disease
– Good sleep hygiene
– Mood stabilizers
• Mixed
– Atypical antipsychotics, valproate
– Therapy: cognitive behavioral & interpersonal/social rhythm

Psychiatry/Behavioral Science
Lecture 1 Anxiety Disorders
Mood Disorders Personality Disorders
Lecture 2 Personality Disorders Paranoid
Sleep-Wake Disorders
Psychoses
Schizoid
Schizotypal
Lecture 3 Somatoform Disorders Antisocial
Substance Abuse
Eating Disorders Borderline
Dissociative Disorders Histrionic
Childhood Disorders Narcissistic
Medications
Dependent
Avoidant
Obsessive-compulsive

Personality Disorders Paranoid Personality DO (Cluster A)

• 10–15% of the general population
• Onset teen years or early adulthood
• Organized into 3 clusters
– Cluster A: Social detachment with unusual behaviors
– Weird symptoms, odd, or eccentric
– Cluster B: Drama
– Wild symptoms, dramatic, emotional, erratic
– Emotional and impulsive
– Cluster C: Anxiety and fearful
– Whiny, anxious, fearful, dependent
• Signs and symptoms
– Distrust and suspiciousness
• Unforgiving of enemy or friend, fear confiding in others, perceive
threats; socially isolated; avoid intimacy
• Illness experience & illness behavior
– Highly defended against any challenge of the self-protective,
rigid way they approach social interactions
– Pride themselves as being rational and objective
• Appear to others as unemotional, affectively restricted, and
hypervigilant

9
Schizoid Personality Disorder (Cluster A)
• Signs and symptoms
– Detached with limited emotional expression
• Indifferent, work alone, no close friends
• May maintain an important bond with a family member
• Illness experience & illness behavior
– Strong emotions they can t deal with
– Enjoy solitary pursuits
Antisocial Personality Disorder (Cluster B)
• Signs and symptoms
– Disregard for others, behavior violates others
• Ignore obligations, lack remorse/empathy, underhanded,
have temper
• M>F 3:1
• Differential diagnosis
– Must be age 18 to make diagnosis; if younger, then diagnosis
of conduct disorder
– Overlaps with other personality DO traits
• Illness experience & illness behavior
– Excessively self-assured, entitled, hostile
– May appear charming and engaged
Histrionic Personality Disorder (Cluster B)
• Signs and symptoms
– Excessive attention-seeking & emotionalism
• Center of attention; influenced easily; exaggerated
emotions, provocative
• Illness experience & illness behavior
– Threatens sense of physical attractiveness
– Overly concerned with physical appearance
– Speech impressionistic and vague
– May be perceived as vain
Schizotypal Personality Disorder (Cluster A)
• Signs and symptoms
– Cognitive, perceptual, and behavioral eccentricities
– Pervasive discomfort with close relationships
– Embrace unusual beliefs to a degree that exceeds the norm
• Illness experience & illness behavior
– Inept and uncomfortable
– Speech is vague, may talk to self in public
Borderline Personality Disorder (Cluster B)
• Signs and symptoms
– Unstable self-image, relationships
• Despair, unstable affect, rage, relationship instability,
empty feeling
• Illness experience & illness behavior
– Have difficulty distinguishing reality from fantasy
– Substance abuse is a major co-morbidity
– Rapid mood swings, impulsivity, chronic boredom
Narcissistic Personality DO (Cluster B)
• Signs and symptoms
– Need for praise and admiration
• Entitled, conceited, arrogant, lack of empathy
• Extravagant sense of self-importance
• Illness experience & illness behavior
– Threatens their image of well-being
– Blindly ambitious, self-serving
– Hypersensitive to issues of self-esteem
10
Dependent Personality DO (Cluster C)
• Signs and symptoms
– Excessive need to be taken care of
• Reassurance required, reliance on others, will not initiate
• Illness experience & illness behavior
– Fear that illness leads to helplessness and abandonment
– Clingy, often demanding for care
– Submissive and passive toward others
– May volunteer for unpleasant tasks, agree with others who may
even be wrong
Obsessive-Compulsive Personality Disorder
(Cluster C)
• Signs and symptoms
– Perfectionists who require a great deal of order and control
• Attention to minutiae impairs ability to finish projects; cold
and rigid in relationships; make frequent moral judgments
• Illness experience & illness behavior
– Serious and plodding, sober with every task
– Want perfection, may not follow through
Personality Disorders: Treatment
• Medications may help alleviate related conditions but they
can't cure underlying disorder
• Antidepressants: SSRIs such as fluoxetine (Prozac),
sertraline (Zoloft), citalopram (Celexa), paroxetine (Paxil),
and escitalopram (Lexapro), or the related antidepressant
venlafaxine (Effexor)
• Anticonvulsants: may help suppress impulsive and
aggressive behavior
– Carbamazepine (Tegretol) or valproic acid (Depakote)
– Topiramate (Topamax) may aid in managing impulse-control
problems
Avoidant Personality Disorder (Cluster C)
• Signs and symptoms
– Desire relationships but avoid them
• Have intense feelings of inadequacy, very sensitive to
criticism, fear rejection and humiliation
• Illness experience & illness behavior
– Social inhibition
– Avoid relationships
Personality Disorders: Treatment
• Psychodynamic psychotherapy
– Goal is to help patients recognize how they're responsible for
the turmoil in their lives and learn healthier ways of reacting to
people and problems
• Individual, group, and family therapy can all be helpful
• Cognitive behavior therapy
– Goal is to actively retrain the way patients think about
problems, which in turn improves their emotions and behaviors
• Dialectical behavior therapy
• Goal is to focus on coping skills
• Most often used to treat borderline personality disorder
Personality Disorders: Treatment
• Antipsychotics: patients with borderline and
schizotypal personality disorders are at risk of losing
touch with reality
– Antipsychotic meds such as risperidone (Risperdal) and
olanzapine (Zyprexa) for distorted thinking
– Haloperidol (Haldol) for severe behavior problems
• Other medications
– Anti-anxiety meds such as alprazolam (Xanax) and
clonazepam (Klonopin)
– Mood stabilizers such as lithium (Eskalith, Lithobid) may
relieve symptoms associated with personality disorders
11
 Narcolepsy
• Daytime sleepiness with cataplexy and sleep paralysis
• Incidence
– About 1% of the general population
Sleep-Wake Disorders – Men = women
– MC affects young adults
Narcolepsy
Parasomnias • Strongest risk factor: family history
• Clinical
– Daytime sleepiness
– Cataplexy
– Hypnagogic hallucinations

Narcolepsy Parasomnias
• Diagnosis • Complex movements and behaviors during sleep
– Polysomnography • 3 major groups
– Multiple sleep latency test – Events that happen during NREM sleep
• Diagnostic criteria: – Events that happen during REM sleep
– Demonstration of irrepressible daytime sleep for at least 3 – Other parasomnias
months, plus one of the following: • Clinical: Depends on type
• Cataplexy, or
– Sleepwalking with eyes open
• CSF hypocretine-1 levels are low
– Sleep terrors
• Treatment – Eating raw foods or food that isn’t common to eat while
– Avoid meds that lead to sleepiness (alcohol) asleep
– Sleep hygiene – Nightmare
– Modafinil – Sleep talking with motor movements
– Methylphenidate

Parasomnias

Psychoses

12
 Psychoses
Psychosis • Schizophrenia
– Greater than 6 months duration
• Schizophreniform Disorder
– Meets criteria for schizophrenia but duration less than 6
Psychiatric Disorders Non-Psychiatric Conditions months
• Schizoaffective Disorder
Psychotic Disorders Other Disorders Illness (types) Substances
– Schizophrenia and major depression (unipolar or bipolar)
Schizophrenia MDD with PF Infectious Drugs of abuse
Schizoaffective d/o Bipolar with PF
? Acute stress d/o
Neoplastic Intoxication • Delusional Disorder
Schizophreniform d/o Metabolic Withdrawal
Delusional d/o ? Personality d/o Autoim m une Iatrogenic drugs – Paranoid disorder, non-bizarre delusions about things that
Brief psychotic d/o Endocrine
Traum a
Steroids could happen in real life (being followed, poisoned, etc.),
Shared psychotic d/o Opiates
onset later in life
• Brief Psychotic Disorder
– 1–30 days duration, onset in mid life. Usually follows
catastrophic event.

Schizophrenia Schizophrenia
• 1% population • 6 months of illness with 1 month of acute
• Most present between ages 15–45 symptoms
• Men > woman (slight increase) but men earlier onset • 2 or more of the following: at least one being
• Risk factors
the top three
– Delusions
Environmental Genetic
– Hallucinations
Prenatal infections and starvation Family history
– Disorganized speech
Obstetric complications Paternal age
– Disorganized or catatonic behavior
Born in winter or urban setting Genetic syndromes
– Negative symptoms: social withdrawal; lack of emotional
Head injury Specific susceptibility genes
expression, communication, and reactivity
Drug use
• Must also have functional decline

Schizophrenia Hallucinations and Delusions

• No major depressive, manic, or hypomanic episodes Hallucinations Description
have occurred Visual Can be simple (flashing light) or complex (face). More
common in deliria and dementias.
• If there is a diagnosis of autism, schizophrenia
Auditory (most Can be a sound or voice. Voice often in the third-person
diagnosis is made only if prominent delusions or common) talking about the patient ( He is such a loser. ) or can be
hallucinations are present for at least 1 month command hallucinations.
Olfactory Often have the character of stench. Also common in
temporal lobe epilepsy.
Tactile Sensation of being touched or insects on skin. Also seen
in cocaine and amphetamine use.
Somatic Sensation arising from within the body (noting movement
of the brain). Are common and obvious.
Gustatory Very rare. Can be part of persecutory delusions (tasting
poison in food).

13
Hallucinations and Delusions Schizophrenia: Treatment
Delusions Description • Psychosocial rehabilitation
Persecutory A person or force is interfering with, observing, and wishing to harm • Antipsychotics: DA receptor antagonists
the patient
Reference Random or innocuous events take on personal significance – First-generation: chlorpromazine or haloperidol
Control Some agency takes control of a patient's thoughts, feelings, and • Side effects: extrapyramidal symptoms like lip-
behaviors smacking
Somatic Part of the body is diseased or malfunctioning, or physically altered
– Second-generation: clozapine, risperidone, olanzapine
Grandeur Unrealistic belief in one s power and abilities; can be obvious or (first-line drugs of choice)
subtle
• Clozapine: possible agranulocytosis (second-line
Nihilism Exaggerated belief in the futility of everything
drug)
Delusion of love Feel loved by another, often higher status, but is merely an innocent
bystander • Risperidone: increased prolactin levels
Jealousy Somebody is suspected of being unfaithful; typical for alcoholics • Olanzapine: marked weight gain
Delusion of Believes a family member of close friend has been replaced by an
Doubles identical double

Neuroleptic Malignant Syndrome

• Rare, potentially lethal complication of neuroleptic
treatment (first-generation antipsychotic) Psychiatry/Behavioral Science
• Present with: Lecture 1 Anxiety Disorders
– Hyperthermia Mood Disorders

– Rigidity Lecture 2 Personality Disorders

– Confusion Sleep-Wake Disorders
Psychoses
– Diaphoresis
– Autonomic instability Lecture 3 Somatoform Disorders
Substance Abuse
– ↑ CPK and leukocytosis Eating Disorders
• Treatment: discontinue medication Dissociative Disorders
Childhood Disorders
Medications

Somatic Symptom Disorder

• Preoccupation with medical or surgical therapy
– Poly-surgery is a feature

• Woman > Men 10:1 ratio

Somatoform Disorders
Somatic Symptom Disorder
Conversion Disorder
Pain Disorder
Illness Anxiety Disorder
Factitious Disorder
• Diagnosis includes at least the following:
– 4 different pain symptoms
– 2 GI symptoms
– 1 sexual symptom
– 1 pseudoneurological symptom other than pain
– Symptoms must cause significant role impairment or result in
medical attention

14
Somatic Symptom Disorder Conversion Disorder
Mnemonic Symptom System • Loss or change in sensory or motor function suggestive of
Somatization Shortness of breath Respiratory a physical disorder but caused by psychological factors
Disorder Dysmenorrhea Female reproductive – Symptom is not intentionally produced or feigned
Besets Burning in sex organ Psychosexual • Common symptoms
Ladies Lump in throat (difficulty swallowing) Pseudoneurological – Paralysis, aphonia, seizures, gait issues, blindness,
anesthesia
And Amnesia Pseudoneurological
Vexes Vomiting Gastrointestinal • Patients commonly have depression, anxiety,
schizophrenia, and personality disorders
Physicians Painful extremities Skeletal muscle
• Extreme psychosocial stress may be the most important
precipitating factor
Two or more positive means a high likelihood of somatization disorder. • Treatment is behavioral therapy
Other, 1985

Pain Disorder Illness Anxiety Disorder

• Long history of severe pain not constant with anatomic • Preoccupation with the fear or belief that one has a
and clinical signs serious, undiagnosed disease
– Pain is source of all life troubles – Also absence of a physical disorder, persistence of fear
despite reassurance, significant distress or role
• Pain exists in 1 or more sites and leads to distress impairment, and duration at least 6 months
• Mainly women, ages 40–50 • Men = women, 5% of the population
• Typically long medical history • Ages 20–30
• Poor prognosis • Doctor shop; increase use of OTCs/herbals
• Treatment is behavioral therapy. SSRI may be helpful. • Treatment: group therapy. SSRI may be helpful if
Avoid pain medications, narcotics. anxiety or depression present.

Factitious Disorders
• Intentional symptoms
– Self-induced symptoms or false physical or lab findings
• May include self-mutilation, fever, hemorrhage,
hypoglycemia, seizures Substance Disorders
• Typically women with a medical background
• Munchausen
– Present in exaggerated or dramatic fashion
– Munchausen by proxy: parent creates illness in child to
maintain relationship with clinician

15
Substance Abuse/Addictive Disorders Substance Abuse
• Important clinical problem • A maladaptive pattern of use of a substance which has
– Persons adversely affected by substance use make up about abuse potential leading to significant functional
20% of PCP visits. impairment in at least 1 of the following areas over a
– Substance use disorders 12-month period:
• At-risk alcohol use
– Non-fulfillment of important responsibilities
• Problem alcohol use
– Recurrent use in physically dangerous situations
• Dependent alcohol use
• Tobacco use – Legal entanglements
• Caffeine, steroids, chemicals, adrenaline, ephedrine – Use in spite of social problems caused
• Illicit drug use
• Prescription drug abuse
• Gambling Disorder (new in DSM5)

Substance Dependency Substance Dependency

• A maladaptive pattern of substance use leading to • Signs of withdrawal
significant distress or impairment greater than – Anxiety, sweating, tachycardia, insomnia, hand tremor, nausea,
substance use; must be manifested by at least 3 of the vomiting, agitation, hallucination or seizures
following over a 12-month period: – Substance used to relieve symptoms

– Signs of tolerance • Signs of dependency

– Need for increasing amounts to achieve desired effect
– Diminished desired effect with continued use of the same
quantity of the substance
– Substance taken in larger amounts over longer periods of time
than intended
– Efforts to cut down or stop are unsuccessful
– Large amount of time spent seeking the substance or
recovering from its effects
– Disruption of work, social, or recreation activities
– Substance use continues despite realization that it impacts
health

Alcohol: Screening
• CAGE Test
• Have you felt you ought to Cut down on your drinking?

• Have people Annoyed you by criticizing your drinking? Eating Disorders

• Have you felt Guilty about your drinking?

• Have you ever needed an Eye opener in the morning to

steady your nerves?

• Positive test = 2 or more yes responses

16
Eating Disorders Eating Disorders
• Anorexia nervosa BMI Weight Category • Anorexia
and bulimia nervosa
<14 At risk for refeeding syndrome
– Distorted body image
• Severe
abnormalities in <17.5 Anorexic range – Refusal to maintain a minimally normal body weight
<18.5 Underweight
eating behavior • Loses weight, introverted, takes pride in weight control,
18.5–24.9 Normal weight less sexually active, feels in control with food; abuses
• Disturbance in >22 At increased risk for DM, HTN, laxatives
perception of body CHD
shape and weight 25–29.9 Overweight • Bulimia
>30 Obese
– Repeated binge eating, followed by behavior to
>40 Morbidly obese
prevent weight gain
• Has minor weight changes, extroverted, has shame,
sexually active, feels out of control with food

Eating Disorders
• Medical complications
– GI disturbances
– Electrolyte imbalance
– Cardiac abnormalities Dissociative Disorders
– Amenorrhea (with severe anorexia)
Dissociative Identity Disorder
• Treatment
– Medical treatment of complications Derealization Disorder
– Supportive psychotherapy or cognitive behavioral therapy Dissociative Amnesia
– Pharmacologic therapy (not effective in anorexia)
• Fluoxetine (bulimia)

Dissociation Dissociative Identity Disorder

• Loss of sense of self. Alteration in consciousness,
personality, memory, and/or behavior that is temporary.
• Having 2 or more identities/personalities that are
distinct from each other
• These identities change and control behavior
• Usually observed by others and may be self-reported
• Most commonly seen in women > men
• History of sexual abuse is strongest risk factor
• Usually cannot recall certain events

17
Depersonalization Disorder Dissociative Amnesia
• Constant feelings of being detached from oneself
and/or ones environment
• “Out of body experience”
• Reality testing is usually intact
• The symptoms must cause distress
• Men = Women
• Stories of experiences may make others think that they
are “crazy”

Autism Spectrum Disorder

• Pervasive developmental disorder
– Characterized by persistent deficits in social
communication and social interaction across multiple
Childhood Disorders contexts

Autism – Reciprocal social interaction skills

ADHD – Lack of or delayed communication skills

Oppositional Defiant Disorder – Presence of stereotyped behavior, interests, and
Conduct Disorder activities

Tourette Syndrome – May be associated with some mental retardation

Child/Elder Abuse

Autism Spectrum Disorder ADHD

• Presentation usually in context of school dysfunction • Distractibility, short attention span (sometimes with
or behavioral acting out hyper-focus), hyperactivity, impulsivity
– Present in more than one setting
• Referral for neuropsychologic testing as age,
– Emotional immaturity, disruptive
language skills allow
• Duration longer than 6 months (symptoms prior to age
• Possible referral to psychiatrist for medication for 12)
behavioral dyscontrol, mood disorders
– Males > females 4:1
• Treatment modalities emphasize behavioral strategies • No association with psychosis
• Treatment
– Behavior modification
– Stimulant drugs
• Methylphenidate (Ritalin) • Pemoline (Cylert)
• D-amphetamine (Adderall) • Strattera (Atomoxetine)

18
Oppositional Defiant Disorder Oppositional Defiant Disorder
• Persistent pattern of negative, hostile and defiant • Males = Females
behaviors lasting at least 6 months. Must exhibit 4 • History of family conflict and school failure, low self-
symptoms from below, and must direct actions toward esteem and mood lability
at least person who is not a sibling.
• Symptoms grouped into three types: • May develop into conduct disorder
– Angry/irritable • Treatment: behavioral therapy
• Losing temper, easily annoyed, resentful
– Argumentative/Defiant
• Argues with authority, defies or refusal to comply,
deliberately annoying, blames others
– Vindictive
• Spiteful or vindictive at least twice in 6 month period

Conduct Disorder Conduct Disorder

• Repetitive pattern of behavior in which the basic rights • Males > females 9:1; must be age <18
of others or societal norms are violated. Presence of at • Has social and academic difficulty
least three of the following in past 12 months, with at
least one present within 6 months. • Has lack of guilt or remorse
– Bullies, threatens others • Treatment: difficult
– Initiates physical fights
– Use of a weapon
• Prognosis: poor (often precedes antisocial PD)
– Physically cruel to people or animals
– Thievery
– Has forced someone into sexual activity
– Fire setting
– Deliberately destroyed others property
– Lying to obtain goods
– Truancy from school prior to 13 years of age
– Running away from home at least twice

Tourette Syndrome Child Abuse

• Inherited disorder with onset in childhood, ages 3-8 • Non-accidental physical abuse to a child, ranging from
– Cause is unknown bruises to fractures to death.
• Present with multiple physical tics and at least one • Occurs as a result of punching, beating, kicking,
shaking, throwing, stabbing, burning.
vocal tic
• Inflicted by parent, caregiver or other person who has
– Physical tics include eye blinking, facial movements, sniffing
responsibility for the child.
and throat clearing
• Spanking or paddling is not considered abuse as long
• Treatment
as it is reasonable and causes no bodily injury.
– Therapy

– Medications include atypical neuroleptics (risperidone,

ziprasidone, haloperidol, or the antihypertensive clonidine

19
Child Neglect Elder Abuse
• Any confirmed or suspected act or omission by a child’s • Maltreatment by a family member or caregiver
parent or caregiver that deprives the child of basic age • Non-accidental acts of physical, emotional or sexual
appropriate needs and ultimately results in physical or aggressions that result in or have the potential to result
psychological harm to the child. in harm or fear to the elder.
– Abandonment – Abandonment
– lack of supervision – Hitting
– Failure to attend to needs – Choking
– Failure to provide food, shelter, clothing, education, medical – Threatening
care
– Withholding nourishment
– Withholding medical treatment
– Neglect of hygiene assist
– Stealing, scamming for goods or money

Antipsychotics
• MOA: block dopamine receptors (first- and second-
generation) and block serotonin (second-generation)
• Effective in treating positive psychotic symptoms
Medications • Side effects
– Restlessness, neuroleptic malignant syndrome, extrapyramidal
symptoms, weight gain
– Anti-cholinergic (dry mouth, constipation, urinary retention)
– Reduced seizure threshold (all)
– Hypotension (risperidone)
– Agranulocytosis (Clozapine)
– QT prolongation (all)
– Elevated prolactin (risperidone)

Anti-Depressants: SSRIs Anti-Depressants: SNRIs

• Bind to presynaptic serotonin reuptake proteins,
inhibiting reuptake
• Onset of effect in about 6 wks
• Side effects
– Nausea
– Headache
– Insomnia/sedation
– Sexual dysfunction
– Withdrawal delirium
• Inhibit reuptake of serotonin and norepinephrine
• Used in treatment of major depression, mood disorders,
ADHD, OCD
Fluoxetine (Prozac) • Use with caution in HTN
• Side effects
Sertraline (Zoloft)
– Loss of appetite, weight, sleep
Paroxetine (Paxil)
– Diminished libido
Fluvoxamine (Luvox)
– Discontinuation syndrome
Citalopram (Celexa) • With abrupt withdrawal- anxiety Avoid with St. John s wort due
Escitalopram (Lexapro) • Venlafaxine (Effexor) to possible serotonin syndrome.

• Desvenlafaxine (Pristiq)
• Duloxetine (Cymbalta)
– Can lead to hepatic failure

20
Anti-Depressants: TCAs Anti-Depressants: MAOIs
• High relapse rates • Inhibit presynaptic monoamine oxidase, which
• Potentially fatal in high catabolizes norepinephrine, dopamine, and serotonin
doses • Foods high in tyramine (aged cheese, beer, red wine)
should be avoided with MAOIs
• Onset: 1-6 weeks
– Can lead to hypertensive crisis
• Side effects:
– Dry mouth – Weight gain • Side effects MAOIs
– Blurred vision – Tremor – Insomnia, agitation, sedation Isocarboxazid
– Drowsiness – Dizziness – Sexual dysfunction Phenelzine
– Arrhythmia – Sexual dysfunction – Orthostatic hypotension Tranylcypromine
– Hypotension

Bupropion (Wellbutrin, Zyban) Mirtazapine (Remeron)

• Inhibits uptake of dopamine and norepinephrine • Noradrenergic antagonist
• Effective in depression and smoking cessation • Used in depression
• Side effects • Side effects
– Seizures – Sedation
• Contraindicated in patients with seizure risk – Weight gain
– Low incidence of sexual side effects – Sexual side effects (few)
• No cytochrome P450 inhibition

Benzodiazepines Benzodiazepines
• Used in anxiety, agitation, and insomnia Drug Onset Half-life
(hours)
– Do not reduce depressive symptoms
Alprazolam Xanax Intermediate 6-20
• Work by augmenting GABA function in the limbic system
– Rapid onset of action Chlordiazepoxide Librium Intermediate 30-100
Clonazepam Klonopin Intermediate 18-50
• Safety: ability to overdose, abuse potential
– Dependence can occur even in the absence of abuse Diazepam Valium Fast 30-100

• Side effects Flurazepam Dalmane Fast 50-160

– Drowsiness Lorazepam Ativan Intermediate 10-20
– Respiratory depression Oxazepam Serax Slow 8-12
– Must be tapered after extended use as withdrawal can occur, agitation Temazepam Restoril Intermediate 8-20
– Caution with liver disease
Triazolam Halcion Fast 1.5-5

21
Buspirone (BuSpar) Lithium
• Agonist of serotonin receptors and antagonist of • Mood stabilizer
dopamine receptors
• MOA: not well-determined
• Used in the treatment of generalized anxiety disorder
• Must monitor lithium levels on a regular basis
– Takes several weeks to note improvement in symptoms
– Adjust dose with renal function decline
• Side effects
• Side effects
– Dizziness
– Minor: tremor, weight gain, polyuria, GI distress, acne
– Nervousness
– Nausea – Major: ataxia, confusion, course tremor, coma, sinus
arrhythmia, teratogenicity, death

22
 The Pulmonary System
Lecture 1 Infectious Diseases

The Pulmonary System Lecture 2 Obstructive Pulmonary Diseases

Pulmonary Circulation

Lecture 3 Neoplastic Disease

Pleural Disease

Jim Van Rhee, M.S., PA-C Lecture 4 Restrictive Pulmonary Disease

Program Director; Associate Professor Other Pulmonary Disease
Pulmonary Function Tests
Yale School of Medicine, PA-Online

Acute Bronchitis
• Inflammation of large airways of the tracheobronchial
tree due to an infectious agent
• Most prevalent in winter and early spring
Infectious Diseases
• Commonly caused by viruses
Bronchitis – Adenovirus, Influenzae, Parainfluenzae, Coxsackie
Bronchiolitis – Bacteria: Bordetella, Chlamydia, Mycoplasma
Epiglottitis
• Usually follows a URI
Croup
Influenza • Risk factor: smoking
Pneumonia
RSV
Tuberculosis

Acute Bronchitis Acute Bronchiolitis

• Clinical • Infection and inflammation of the smaller airways
– Cough preceded by URI symptoms (nasal congestion, – Most common cause is RSV
sore throat, sneezing)
– Children > adults
• No findings of pneumonia
– Dyspnea is rare • Clinical
– Symptoms >1 week – Diffuse wheezing, variable fever, cough, cyanosis, rhinorrhea
– Exam: findings of URI with possible rales, crackles, or • Physical exam
wheezing
– Hyperinflation, crackles, prolonged expiration, wheezing
• Lab
– CXR normal, WBC slight increase with no left shift – Nasal flaring, retractions

• Treatment
– D/C smoking, supportive, rest, hydration, antibiotics
(erythromycin, azithromycin for atypical organisms)
Acute Bronchiolitis Epiglottitis
• Diagnosis • General
– Life threatening supraglottitis/epiglottic infection
– Based on clinical findings and isolation of RSV
• May result in acute airway obstruction
– Chest x-ray: hyperinflated lungs with patchy atelectasis – Caused by Streptococcus pyogenes, or Staphylococcus aureus
or Mycoplasma
– CBC normal
• H. influenzae type b is uncommon in North America as a result
• Treatment of immunization
• Clinical findings
– Supportive – Fever
– Hospitalization – Dysphagia
– Respiratory distress/stridor
– Heated humidified high-flow nasal cannula (HFNC) – Symptoms may overlap croup but toxicity suggests epiglottitis
therapy and/or continuous positive airway pressure (CPAP) • Severe sore throat
– No use for bronchodilators or steroids • Drooling
• Absence of hoarseness
• Child s insistence on sitting forward with neck hyperextended

Epiglottitis Epiglottitis
• Findings • Treatment
– Tongue depressor or – Secure airway
examination of oropharynx
may cause acute airway – Antibiotic therapy
obstruction • IV ceftriaxone or cefotaxime plus Vancomycin for 7 to
– Cherry-red epiglottis on 10 days
laryngoscopy
• Prevention
– Lateral neck x-ray – Vaccination for H. influenzae type b
• Thumb sign - enlarged – Rifampin to eliminate carriers and treat close contacts
epiglottis
– Once airway secure obtain
• Blood cultures, CBC,
Source: David Matthew DeLonga
culture of epiglottis

Laryngotracheobronchitis (Croup) Laryngotracheobronchitis Source: Paul Cunningham

• General • Laboratory findings

– Viral infection of the glottic and subglottic region – Neck x-ray (typically not
• Epidemiology needed)
• Steeple sign
– Disease of childhood ages 7–36 months
• Differentiate from
• Very few cases over age 6
epiglottitis with lateral x-
• Etiology ray
– Commonly occurs as epidemic in fall or winter • Treatment
– Parainfluenza virus most common, also RSV and adenovirus – Goal is to reduce airway
• Clinical findings edema/obstructive
symptoms
– Inspiratory stridor (may be dramatic and alarming; usually follows
days of milder cold symptoms; worsens at night; and may be – Humidified air
accompanied by cough and hoarseness) – Nebulized epinephrine
– Barking cough • May have rebound
after several hours
– Retractions – Corticosteroids
– Antibiotics not needed
 Influenza Influenza
• Systemic viral illness due to influenza A and B • Labs

• Spread by respiratory droplets in an epidemic pattern – Leukopenia or normal WBC

– Rapid antigen detection of nasopharyngeal secretions
– Very contagious
– Viral culture
• Incubation 1–3 days • Treatment
• Clinical – Symptomatic (acetaminophen)
– Toxic appearance
• Avoid aspirin due to Reye s syndrome
– Abrupt onset fever (101–106⁰ F), chills, rigors, malaise
– Myalgias, headache, nonproductive cough – Oral oseltamivir (Tamiflu), inhaled zanamivir (Relenza)
(influenza A or B)
– Coryza and sore throat, clear nasal drainage
– Exam usually normal • Neuraminidase inhibitors
– Antibiotics (if secondary bacterial infection)

Influenza Vaccine Pneumonia

• Vaccinate everyone over 6 months of age • Infection of the lung parenchyma
• High-risk groups in need of vaccine • Community-acquired vs. hospital-acquired vs.
– Children, ages 6-60 months aspiration
– Elderly (≥50 years old)
– Or typical vs. atypical
– Those with chronic disease (COPD, Cardiac disease, DM, Renal
disease, hemoglobinopathies) • Caused by many different microorganisms
– Immunosuppressed
– Pregnant women • Predisposing conditions
– Nursing home residents
– Smoking, diabetes, alcoholism, malnutrition, cancer,
– Native Americans, Alaska Natives
immunosuppression
– Extremely obese (BMI >40)
– Groups in contact with high-risk patients

Avoid in patients with history of allergy to vaccine or

episode of Guillain-Barre Syndrome within 6 weeks of
previous dose

Etiology of Pneumonia Community-Acquired Pneumonia (CAP)

• Etiology
Factor Etiology Factor Etiology
– Streptococcus, Haemophilus, Staphylococcus, Klebsiella
Smoking, Streptococcus pneumoniae Recent history of Staphylococcus aureus
COPD Haemophilus influenzae influenzae Streptococcus pneumoniae • Presentation
Haemophilus influenzae
Nursing home Streptococcus pneumoniae – Productive cough for 1–10 days,
resident Gram-negative bacilli SOB, fever, tachycardia, pleuritic
Cystic fibrosis Pseudomonas aeruginosa
Haemophilus influenzae
Tuberculosis chest pain, tachypnea
IV drug abuse Staphylococcus aureus
Alcoholism Streptococcus pneumoniae Anaerobes • Clinical
Klebsiella pneumoniae Tuberculosis
– Rhonchi or rales, consolidation
Exposure to Histoplasma capsulatum Aspiration Anaerobes
bats • Labs
Exposure to Cryptococcus neoformans HIV/AIDS Pneumocystis jirovecii – Increased WBC with left shift
birds Chlamydia psittaci
– Sputum culture or gram stain
Young, healthy Mycoplasma Water source Legionella
adults • >25 WBC and <10 epithelial
– Chest x-ray
phil.cdc.gov
Streptococcus pneumoniae is #1 cause of CAP.
 Chest X-ray Chest X-ray

Lobar pneumonia Interstitial pneumonia

Nodular pneumonia

Source: Nicholas Lange

cdc.gov

phil.cdc.gov

Infiltrate vs. Pleural Effusion CAP: Treatment

• Infiltrate • Pleural Effusion
CAP diagnosis

Comorbidities present
Yes
No
Low-risk class Mod/high-risk class

Treat as OP Increased Severity

• Macrolides • ¯ pO2 or O2 sat Treat as IP
• Fluoroquinolones • RR >30/min IV beta-lactam plus a
• Doxycycline • MS changes macrolide or a
• Hypotension fluoroquinolone
Source: Ron Boucher Source: Adriane E. Bell

Atypical Pneumonia Aspiration Pneumonia

• Etiology • Noted in CVA and altered mental status (drugs,
– Mycoplasma, viruses, Chlamydia, Legionella alcohol)
– Make up 10% of CAP
• Presentation • Etiology
– Low fever, mild pulmonary symptoms – S. aureus, Gram-negative rods, anaerobes
– Typically young healthy adults • Clinical
• Clinical – Cough, fever, SOB
– Nonproductive cough, myalgia, fatigue
• Labs • Labs
– Increased WBC, no culture or gram stain – CXR: common side RLL
• Treatment • Treatment
– Antibiotics – Antibiotics (amoxicillin, clindamycin, fluoroquinolone)
• Macrolides (Mycoplasma)
• Tetracycline (Chlamydia)
• Oseltamivir (Tamiflu), zanamivir (Relenza)
– Supportive care
Hospital-Acquired Pneumonia Pneumococcal Vaccine
• Very common hospital infection • Recommend routine administration of pneumococcal
– Increased incidence with increase length of stay conjugate vaccine (PCV13) for all children younger than 2
years of age:
• Most commonly due to Gram- – Give PCV13 to infants as a series of 4 doses, one dose at each of
negative rods these ages: 2 months, 4 months, 6 months, and 12 through 15
• Signs and symptoms months.
– Children who miss their shots or start the series later should still
– Cough, purulent sputum, fever get the vaccine. The number of doses recommended and the
• Labs intervals between doses will depend on the child’s age when
– Leukocytosis, infiltrate on CXR vaccination begins
• Treatment • CDC recommends pneumococcal vaccination (PCV13 and
PPSV23) for all adults 65 years or older:
– Ampicillin-sulbactam, amoxicillin – Give a dose of PCV13 to adults 65 years or older who have not
plus metronidazole, imipenem or previously received a dose. Then administer a dose of PPSV23 at
Piperacillin-tazobactam least 1 year later.
• Complications: ARDS – If the patient already received one or more doses of PPSV23, give
the dose of PCV13 at least 1 year after they received the most
phil.cdc.gov
recent dose of PPSV23.

Respiratory Syncytial Virus (RSV) RSV

• Clinical
• Most important cause of lower respiratory tract infection – First rhinorrhea and pharyngitis, then cough, wheezing, and
in children fever

• Peak season: cold weather in temperate climates – Tachypnea, difficult feeding

• Epidemics in late fall and early spring – Exam: hyperinflation, crackles, wheezing, prolonged
expiration
• Leading cause of bronchiolitis
• Labs
– Positive RSV antigen nasal or pulmonary

• Imaging
– Diffuse hyperinflation and peribronchiolar thickening

RSV Tuberculosis
• If conjunctivitis present, think Chlamydia trachomatis • Etiology
– Also, no fever or wheezing – Mycobacterium tuberculosis
– Transmitted by respiratory
• Complications droplets
– Secondary bacterial infections of middle ear – Most exposed patients do
not progress to clinical
• Treatment illness
– Oxygen • Clinical
– Corticosteroids- avoid in children under 2 years of age – Cough, fever, chills, night
sweats, anorexia, weight
– Ribavirin loss, and fatigue
• Immunosuppressed patients only • Labs
– Positive PPD
– AFB cultures (gold phil.cdc.gov
standard)
and smears
 PPD Interpretation
≥5 mm induration
HIV-positive patients
Those who have had
contact with patients with
clinically active TB
Patients with findings of old, Work/resident of high-risk
healed TB
Organ transplant patients
Immunosuppressed
patients
≥10 mm induration
Recent arrivals from high
prevalence countries
IV drug abusers
setting:
• Prisons/jails
• Nursing
homes/hospitals
• Homeless shelters
Clinical condition that
places patient at high risk
Children age <4 or exposed
to adults in high-risk setting
≥15 mm induration
No know risk factors for TB
All positive PPDs
need CXR and if
abnormal, AFB
smears and culture
Chest Radiograph
• Abnormalities such as
cavitation often seen in
apical or posterior
segments of upper lobe
– Ghon s complex involves
calcified nodules
• May have unusual
appearance in HIV-
positive persons
• Cannot confirm diagnosis
of TB
Source: MS-4 USU Teaching File, Uniformed Services University

Latent TB
PPD (+) but no active The Pulmonary System
disease treat with:
Lecture 1 Infectious Diseases
9 months of INH plus
vitamin B6
Lecture 2 Obstructive Pulmonary Diseases
Pulmonary Circulation

Lecture 3 Neoplastic Disease

Pleural Disease

Lecture 4 Restrictive Pulmonary Disease

Other Pulmonary Disease
Pulmonary Function Tests

cdc.gov

Asthma
• Chronic inflammatory disorder of the airways
– Reversible
• Three major characteristics
Obstructive Pulmonary Disease – Obstruction of airflow

Asthma – Bronchial hyper-reactivity

– Inflammation of airways
Chronic bronchitis
• Clinical features
Emphysema – Persistent wheeze, chronic episodic dyspnea, chronic cough,
Bronchiectasis increased respiratory rate
– Asymptomatic periods

Asthma Classification
Step Classification
1 Mild intermittent <2 times per week
2 Mild persistent >2 times per week
3 Moderate persistent
4 Severe persistent
Asthma
• Laboratory findings
– Decreased FEV1, improved with bronchodilator (10% increase)
– Positive methacholine challenge
Frequency Nocturnal Symptoms
– Eosinophilia, increased IgE levels
– ABG: hypoxemia(<60) and hypocarbia (<40), oxygen saturation ~90%
<2 times per month
• Treatment
– Acute
>2 times per month • Corticosteroids
• Beta-adrenergic agonists: short-acting
Daily >6 times per mouth • Oxygen
– Chronic
Continuous Frequent • Corticosteroids
• Beta-adrenergic agonists: long-acting
• Leukotriene antagonists (zafirlukast, zileuton, montelukast)
• Mast cell stabilizers (cromolyn, nedocromil)
• Theophylline, vaccines

Managing Asthma
Status Asthmaticus
• Unremitting asthma with rapidly increasing severity
• Due to:
– Diffuse bronchial obstruction leading to hypoxia
– Respiratory muscle fatigue
• Clinical
– Acute onset chest tightness, SOB, cough
• Physical examination
– Tachycardia, tachypnea, cyanosis, accessory muscle use,
intercostal retractions, no wheezing

National Library of Medicine Guidelines and Diagnosis of

Asthma

Status Asthmaticus Chronic Bronchitis

• Diagnosis • Excessive sputum production with chronic or recurring
– Hypoxemia, hypercapnia cough on most days for a minimum of 3 months of the
– Decreased peak flow and FEV1 year, for at least 2 consecutive years
– CXR hyperinflation • Pathology
• Treatment – Smooth-muscle hypertrophy
– Inflammation
– Oxygen: maintain oxygen saturation at 92–94%
– Mucosal edema
– Bronchodilators every 2 hours
– Narrowing of airways
– Corticosteroids: high dose IV
– Mucus plugging
– Mechanical ventilation
– Peribronchial fibrosis
 Chronic Bronchitis Chronic Bronchitis
• Clinical • Labs
– Dyspnea on exertion – PFT: obstructive pattern (decreased FEV1)
– Thick, yellow, copious sputum – CXR: normal or signs of CHF
– Blue bloater – ABGs: hypoxemia
• Obese, cyanotic
• Treatment
– Smoking cessation (disease seen after >10 years of
• Tachypnea, tachycardia
smoking)
• JVD, right-sided heart failure
– Anticholinergic agents (ipratropium)
• Hepatomegaly, ascites – Beta agonist (albuterol)
• Physical examination – Methylxanthine (theophylline)
– Coarse rhonchi, wheeze, prolonged expiration, edema – Steroids
– Mucokinetic (guaifenesin)
– Oxygen
– Vaccines

Emphysema Emphysema
• Enlarged air spaces due to destruction of alveolar septa • Labs
– PFTs: obstructive pattern IMC © 2010 DxR Development Group, Inc. All Rights Reserved.
• Etiology unknown
(decreased FEV1)
– Possibly due to increased proteolytic enzymes – CXR: hyperinflation, flat
– Smoking diaphragm
– Alpha-1-antitrypsin • Treatment
• Clinical – Smoking cessation
– Vaccines
– Minimal cough, non-productive
– Beta agonist (albuterol)
– Dyspnea – Anticholinergic agents
– Weight loss (ipratropium)
– Pink puffer: thin, cachectic, pursed lip breathing; barrel chest; – Theophylline
tachypnea; decreased breath sounds, prolonged expiration – Steroids
– Oxygen: O 2 saturations
>90%

COPD Summary Table

Emphysema Chronic bronchitis
Description Pink puffer Blue bloater
Major complaint Dyspnea Chronic cough
Age at onset >50 30s to 40s
Pulmonary Circulation
Body habitus Thin Overweight Pulmonary Embolism
Lung exam No adventitious signs Rhonchi present
Peripheral edema Negative Positive Pulmonary Hypertension
Hemoglobin Normal Elevated Cor Pulmonale
Blood gases pO2 NL/¯ pO2 ¯
pCO2 NL/¯ pCO2 ­

Chest x-ray Hyperinflated, flat diaphragm Increased interstitial markings

and normal diaphragm
 Pulmonary Embolism Wells Probability System
• DVT symptoms/signs 3 points
• PE as or more likely 3 points
• Due to thrombi in the venous circulation or right side • HR >100 1.5 points
of heart • Immobilization/surgery 1.5 points
– 80–90% originate in deep veins of lower extremities • Previous DVT/PE 1.5 points
• Hemoptysis 1 point
• Risk factors • Malignancy 1 point

– Hypercoagulable states: malignancy, thrombophilia

Wells Total Pretest Likelihood of PE
– Pregnancy/BCP
Score Probability
– Surgical procedures: orthopedic surgery <2.0 Low 9%
– Atrial fibrillation 2.0–6.0 Moderate 30%
– Major trauma >6.0 High 68%

Pulmonary Embolism
• Clinical
– Pleuritic chest pain (74%)
– Dyspnea (85%), cough (53%), hemoptysis (30%)
• Physical examination
– Tachypnea (92%), tachycardia (45%), fever (45%), thrombophlebitis
• Labs
– ABG: hypoxemia, hypocapnia, wide A-a gradient Classic findings:
– EKG: sinus tachycardia (S1Q3T3) Classic S1Q3T3
• EKG changes (S1Q3T3) due to right heart strain (cor pulmonale) S wave in lead I
– CXR: normal Q wave in lead III
• Westermark sign (decreased vascularity) Inverted T waves in III
• Hampton hump (wedge-shaped infiltrate = pulmonary infarction)
– D-dimer (normal result = no PE in low-risk patients)
– Ultrasound LE

Pulmonary Embolism: Tests Pulmonary Embolism: Treatment

• V/Q scan
– Uses radioactive material to compare ventilation and perfusion
– Scoring system
• Normal <1% PE rate
• Low probability 14% PE rate
• Intermediate 30% PE rate
• High probability 87% PE rate
• Angiography (gold standard)
– Very invasive and not easily available.
• Spiral CT scan
– 95% sensitive for large PE
– 75% sensitive for subsegmental PE
Pulmonary Hypertension Pulmonary Hypertension
• Idiopathic pulmonary hypertension • Pathology: high blood flow, low pressure, and
– Idiopathic low resistance
– Young, middle-aged females – Present when pulmonary artery pressure rises to a high
– Progressive dyspnea, fatal level inappropriate for the level of cardiac output
• Secondary pulmonary hypertension • Dyspnea, fatigue, chest pain, and syncope on exertion
– Reduction in cross-sectional area of pulmonary arterial bed • Physical examination
– Increased pulmonary venous pressure – Narrow splitting of second heart sound with loud
– Increased pulmonary blood flow pulmonary component
– Increased blood viscosity • Right ventricular hypertrophy on CXR and EKG
– COPD most common cause

Pulmonary Hypertension Cor Pulmonale

• Diagnosis • Right ventricular hypertrophy and failure due to
– Cardiac echo pulmonary disease/hypoxia
– Pulmonary arteriogram • Clinical
• Treatment – Both from pulmonary disease and heart effects
– Oxygen – Chronic productive cough, exertional dyspnea, wheezing,
weakness
– Treat underlying disorder
– JVD, edema, hepatomegaly, ascites
– Lung transplant
• Etiology
– Calcium channel blockers (idiopathic)
– COPD (most common)
– Pneumoconiosis
– Pulmonary fibrosis

Cor Pulmonale
• Labs
– Polycythemia, decreased oxygen saturation The Pulmonary System
– EKG: right axis deviation, deep S waves in V6, prominent P Lecture 1 Infectious Diseases
waves in II, III, AVF (atrial enlargement)
– PFT: underlying lung disease Lecture 2 Obstructive Pulmonary Diseases
Pulmonary Circulation
– Echo: right ventricular dilation
• Treatment Lecture 3 Neoplastic Disease
– Treat the pulmonary problem Pleural Disease

– Oxygen, salt and fluid restriction; diuretics Lecture 4 Restrictive Pulmonary Disease
– No use for digoxin Other Pulmonary Diseases
Pulmonary Function Tests
• Prognosis: 2–5 years
 Lung Cancer
• Leading cause of cancer death
• Two groups
– Non-small cell (adenocarcinoma, squamous cell, large cell)
Neoplastic Disease – Small cell

Squamous Cell Carcinoma • Risk factors

– Cigarette smoking (10x greater risk than nonsmokers)
Adenocarcinoma – Asbestos exposure; radon exposure
Small Cell Carcinoma – Exposure to uranium, arsenic, chromium, nickel
– History of COPD
Pulmonary Nodules
– Idiopathic pulmonary fibrosis
Carcinoid Tumor

Squamous Cell Carcinoma Adenocarcinoma

• Starts in central bronchi and metastasizes to nodes • Most common histologic type
• Clinical features • Appears at periphery of lungs and metastasizes to
– Cough, chest pain, weight loss, dyspnea, hemoptysis distant organs
• Labs • Clinical features
– Chest x-ray, cytology, bronchoscopy – Lymphadenopathy, hepatomegaly, and clubbing
• CXR: hilar or peripheral masses, cavitation, effusions • Labs
– Hypercalcemia – CEA; bronchoscopy; chest x-ray (small peripheral masses)
• Treatment • Treatment
– Surgery, radiation, chemotherapy
– Surgery, radiation, chemotherapy

Small Cell Carcinoma Lung Cancer

• Most aggressive type
• Arises in peribronchial tissue, located centrally
• Clinical features
– Paraneoplastic syndromes (15–20%)
• SIADH, Cushing s syndrome, Lambert-Eaton syndrome
– No clubbing
• Labs
– Electrolytes; bronchoscopy; chest x-ray (hilar mass, wide
mediastinum)
• Treatment: chemotherapy

cancer.gov
Solitary Pulmonary Nodule Solitary Pulmonary Nodule
• 25% are primary bronchogenic cancer
• 10% are mets
• Clinical features
– Round, oval, sharp lesion up to 3 cm in diameter (>3 cm = a
mass )
– Central cavitation and calcification may occur
• Biopsy
– Benign: has not enlarged in >2 years, calcified, size <2cm
– Malignant: occasionally symptomatic, age >45, size >2 cm,
rarely calcified, indistinct margins
• Treatment: exploratory thoracotomy or thoracoscopy

Source: Zachary M Alexander

Carcinoid Tumor Pancoast Tumor

• Low-grade malignant neoplasms • Non-small cell lung cancer
– Slow growing and rarely metastasize • Mass in extreme apex of lungs
• Most patients under age 60
– Invades other tissues (lymph nodes, nerves, ribs),
• Presentations leading to other symptoms
– Hemoptysis, cough, focal wheezing, recurrent pneumonia
– Carcinoid symptoms (flushing, diarrhea, wheezing,
• Symptoms
hypotension) are rare – Severe pain in shoulder and along inner side of arm
• Diagnosis and hand; atrophy (due to invasion of brachial plexus)
– CT scan – Horner syndrome
– Octreotide scintigraphy for localization of tumor
• Treatment
– Surgery, resistant to chemotherapy and radiation therapy

Pancoast Tumor
• Horner syndrome
– Due to invasion of paravertebral sympathetic chain and
stellate ganglion
– Drooping eyelids Pleural Disease
– Decreased sweating (anhidrosis) Pleural Effusion
– Pupil contraction
Pneumothorax
• Evaluation: CXR, CT, MRI
• Treatment
– Surgery
– RT and chemotherapy before surgery because of
location
 Pleural Effusion Pleural Effusion
• Transudates (from vessel • Exudates (from an
Exudates Transudates
leakage into pleural inflammatory process)
space) – Infection* Protein > 3 g/dL <3 g/dL
– CHF* – Malignancy*
Pleural/serum protein >0.5 <0.5
– Nephrotic syndrome – Pulmonary embolism
– Malnutrition – Collagen vascular (RA, LDH >200 IU/L <200 IU/L
– Cirrhosis SLE)
Pleural/serum LDH >0.6 <0.6
– Ascites – Trauma
– Pulmonary embolism – Uremia Glucose <60 mg/dL >60 mg/dL
– Pancreatitis

* Three most common causes of pleural effusion

Pleural Effusion Infiltrate vs. Pleural Effusion

• Physical exam Infiltrate Pleural Effusion
– Dull to flat percussion
– Absent tactile fremitus
– Decreased breath sounds
• Labs
– CXR: blunting of costophrenic
angle, loss of landmarks
• Unilateral: think exudate
• Bilateral: think transudate
• Treatment: thoracentesis

Source: Nancy Miller Source: Ron Boucher

Source: Adriane E. Bell

Pneumothorax Pneumothorax
• Accumulation of air in pleural space • Clinical features
• Entry through opening in visceral or parietal pleura – Tall, thin men at greatest risk
– Acute onset ipsilateral chest pain and dyspnea
• Causes • Physical exam
– Spontaneous – Tympany on percussion, decreased breath sounds,
• Primary: thin males, smokers, those with no underlying lung hyperresonance
disease
• Labs
• Secondary: those with underlying lung disease
– CXR: presence of pleural air
– Traumatic (penetrating/nonpenetrating chest injury)
– Hypoxemia
– Tension (chest wound/pulmonary laceration) • Treatment
• Pressure positive in pleural space throughout respiratory cycle
– 20–30% resolve spontaneously (depends on size)
• Occurs during mechanical ventilation or resuscitation – Oxygen
– Chest tube with pleurodesis
Tension Pneumothorax Pneumothorax

Source: John Yasmer

Source: James G. Smirniotopoulos, M.D.

The Pulmonary System

Lecture 1 Infectious Disease Restrictive Lung Disease/Other
Idiopathic Pulmonary Fibrosis
Lecture 2 Obstructive Pulmonary Disease
Pulmonary Circulation Cystic Fibrosis
Lecture 3 Neoplastic Disease Pneumoconiosis
Pleural Disease Sarcoidosis
Lecture 4 Restrictive Pulmonary Disease ARDS
Other Pulmonary Diseases
Pulmonary Function Tests Hyaline Membrane Disease
Foreign Body Aspiration
Sleep Apnea
Pulmonary Function Tests

Idiopathic Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis

• Also called cryptogenic fibrosing alveolitis • Diagnosis
• Progressive parenchymal scarring and loss of – Lung biopsy
pulmonary function • Treatment
– Etiology unknown – Nintedanib a receptor blocker for multiple tyrosine kinases that
• Men > women, >50 years of age mediate elaboration of fibrogenic growth factors appears to
slow the rate of disease progression
• Presentation – Corticosteroids, azathioprine, N-acetylcysteine no longer
– Gradual onset exertional dyspnea, nonproductive cough recommended
– Fine bibasilar inspiratory crackles, clubbing – Lung transplant only known cure
• Cyanosis and cor pulmonale late features • Course is progressive, high mortality
• Labs
– Chest x-ray- bilateral reticular opacities in periphery and lower
lobes
– CT scan- subpleural honeycombing, ground-glass appearance
Cystic Fibrosis Cystic Fibrosis- Respiratory
• Etiology • Symptoms • Clinical findings
– Multiple complications – Chronic productive
– Progressive, multi-system disease
related to viscous cough
– Autosomal recessive mode of transmission mucus, malabsorption,
and infection – Wheezing
– Most common lethal recessive disease affecting
Caucasians (1:2500 live births) – Abnormally thick – Dyspnea
bronchial secretions – Nasal polyps
– CF gene leading to
• Chronic – Hemoptysis
• Located on long arm of chromosome 7
infection/recurrent – Pneumothorax
• Directs production of the cystic fibrosis transmembrane pneumonia
conductance regulator protein (CFTR) • Inflammation of the – Cor pulmonale
respiratory tract – Progressive
• Bronchiectasis
• Respiratory failure respiratory failure

Cystic Fibrosis Cystic Fibrosis: Additional Clinical Findings

• Clinical findings, pancreatic • Respiratory: allergic bronchopulmonary aspergillosis
– Insufficiency of exocrine pancreatic function (85-90% • Gastrointestinal: meconium ileus
of cases) • Hepatobiliary disease
• Causes malabsorption and failure to thrive – Prolonged neonatal jaundice
– Symptoms – Cholelithiasis
• Chronic diarrhea • Reproductive
• Abdominal bloating – Infertility in men
• Ravenous appetite – Reduced fertility in women
• Steatorrhea (fatty malodorous stools) • Sweat abnormalities
• Rectal prolapse – Dehydration with hypochloremic, hyponatremic
• Excessive flatulence metabolic alkalosis
• Secondary to vitamin deficiency (A,D, E, K)

Cystic Fibrosis: Additional Clinical Findings Cystic Fibrosis

• Skeletal • Laboratory findings
– Diagnostic tests
– Arthritis
• Sweat chloride test (elevated >60 mEq/L)
– Clubbing
• Genotype testing
• Hematologic – Offered for up to 62 of the most common mutations
– Anemia – Appropriate for screening in families of a patient with
CF
• Secondary to iron deficiency
– Diagnostic Criteria
– Easy bruising due to • One or more phenotypic feature of cystic fibrosis
vitamin K deficiency © Richard Usatine, M.D. Used with permission. • Sibling with cystic fibrosis or (+) newborn screening
• (+) sweat chloride test
• 2 mutations known to cause cystic fibrosis
Cystic Fibrosis Cystic Fibrosis
• Treatment • Treatment
– Acute exacerbations – Chest physiotherapy – form of percussion
• Antibiotic therapy – Mucous-thinning drugs
– Guided by results of ongoing sputum cultures • N-acetylcysteine

• Cover Pseudomonas and Burkholderia • Deoxyribonuclease (DNase)

• May reduce frequency of acute exacerbations
• Corticosteroids
– Lung transplantation (when forced expiratory volume is
– Used short-term or prolonged to treat airway
stable at 30–40% of predicted value)
inflammation
– Pancreatic insufficiency
• Nonsteroidal anti-inflammatory agents
• Pancreatic enzyme supplements (to enhance absorption)
– Ibuprofen
• Fat-soluble vitamins A, D, E, K
– May slow progression of inflammatory process

Pneumoconiosis Pneumoconiosis
• Chronic, fibrotic, occupational lung disease
Asbestosis Coal Worker s Lung Silicosis
• Caused by inhalation of foreign particle
Material Asbestos Coal dust Silica
• Examples Occupation Brake lining workers Coal miners Foundry workers
– Coal worker s lung Insulators Glass makers
Shipyard workers Sandblasters
– Farmer s lung Mining, milling Pottery workers
– Silicosis CXR Reticular, basilar Small nodules upper Nodular, upper
predominance lung field lobes
– Asbestosis PFT pattern Restrictive Obstructive Restrictive
• Appears 20-30 years after constant exposure Complication Mesotheliomas Caplan syndrome Lung cancer
Bronchogenic CA (RA) ­ risk TB
Treatment Supportive care Supportive care Supportive care
Steroids Steroids Steroids

Pneumoconiosis Sarcoidosis
• Clinical • Multi-systemic disease of unknown cause
– Usually asymptomatic • Noncaseating granulomatous inflammation in affected
– Dyspnea, inspiratory crackles, clubbing, cyanosis, cough organs (lung, nodes, eyes, skin, liver, spleen)
– Exam: unremarkable • Seen in North American blacks
• Occupational history • Adults ages 20–30
• Labs • Clinical: cough, dyspnea, fatigue, chest discomfort
– CXR: small, round parenchymal opacities • Labs
– Leukopenia, eosinophilia, elevated ESR, hypercalcemia
• Treatment
– Elevated ACE levels
– Beta agonist, steroids, anticholinergic agents, oxygen
• Diagnosis
– Biopsy
Sarcoidosis Acute Respiratory Distress Syndrome (ARDS)
• Chest x-ray • Acute onset of respiratory distress
– Symmetric bilateral – Increased permeability of alveolar-capillary membrane
hilar and right
and pulmonary edema
paratracheal – Follows systemic or pulmonary insult w/out evidence of
adenopathy; diffuse heart failure
reticular infiltrates – Etiologies: sepsis, aspiration, trauma, drugs, multiple
transfusions, pneumonia, burns, pancreatitis, DIC
• Biopsy
• Clinical
– Non-caseating
granulomas
– Rapid onset (12–48 hrs) after event
– Labored breathing, tachypnea, intercostal retractions,
• Treatment crackles
– Steroids – CXR: diffuse or patchy bilateral infiltrates
IMC © 2010 DxR Development Group, Inc. All Rights Reserved.
– Methotrexate • Spare costophrenic angle
• Air bronchograms

ARDS ARDS
• Labs
– Swan-Ganz catheter
• Normal cardiac output
• Normal capillary wedge pressure
• Increased pulmonary artery pressure
• Treatment
– Treat underlying cause
– Positive end-expiratory pressure [PEEP] (to stabilize the
lung)

© MS-4 USU Teaching File, Uniformed Services University

Hyaline Membrane Disease Foreign Body Aspiration

• Newborns • Accidental inhalation of foreign material into airway
– Predisposing factors: or esophagus
premature, mother with DM,
positive family history • Epidemiology
• Deficiency of surfactant – Highest incidence in children age <3
– Alveoli collapse
• Limited mastication skills
• Clinical • Commonly place objects in mouth in active exploration
– Dyspnea, tachypnea, nasal
flaring, retractions, grunting – Aspiration in older children
respirations, cyanosis
• Improperly chewed food
– CXR: diffuse
reticulogranular pattern and • Habitually chewed objects
air bronchograms – Pen tops, erasers, small toy parts
• Treatment IMC © 2010 DxR Development Group, Inc. All Rights Reserved.

– Corticosteroids, CPAP
Foreign Body Aspiration Foreign Body Aspiration
• Pathophysiology • Clinical findings
– Sites where foreign bodies lodge – Varies according to location, size and shape of object
• Respiratory tree • Occluded upper airway (sudden & severe respiratory
– Trachea distress)

– Major bronchus most common location • Peripheral airway (chronic cough)

– Smaller airways • Radiographic changes
• Gastrointestinal – Normal chest X-rays (80% of cases)
– Esophageal – Inspiratory/expiratory films may be helpful in cases of
• Common in younger children partial obstruction
• Can cause significant tracheal compression, stridor, – Right and left decubitus films (may demonstrate
or cough partial airway obstruction)
Coughing or choking episode followed by wheezing, think airway foreign body.

Foreign Body Aspiration Sleep Apnea

• Treatment • Cessation of airflow (>10 seconds) that occurs at least 10-15
times per hour during sleep
– Removal of foreign body • Oxygen saturations will decrease and pulmonary pressures
• Manual increase
– Can lead to cor pulmonale
• Rigid or flexible bronchoscopy
• Clinical
• Thoracotomy – Daytime somnolence, daytime headaches, fatigue
• Antibiotics – Secondary cause of hypertension
• Diagnosis
– When evidence of secondary infection
– Positive polysomnography
– May develop respiratory acidosis with elevated bicarbonate
• Treatment
– Obstructive: CPAP
– Central: Conservative measures (weight loss, avoid alcohol),
supplemental oxygen

Pulmonary Function Tests Pulmonary Function Tests

• FVC
– Forced vital capacity PFT Normal range
(% predicted)
– Measure of volume
TLC 80–120%
• FEV1 RV 75–120%
– Forced expiratory volume in 1 sec FEV1/FVC ratio 80%
– Measure of flow
FEV1 80–120%
• FEV1/FVC ratio
Values <80% are abnormal and
– Flow/volume relationship >120% indicates air trapping
• RV
– Residual volume of air that cannot be exhaled due to air
trapping
• Peak flow
IMC © 2010 DxR Development Group, Inc. All Rights Reserved.
– Maximum flow rate that can be maintained for 10 milliseconds
Pulmonary Function Tests Interpretation of Spirometry
• Obstructive (reduced air flow)
– Decreased FEV1, decreased FEV1/FVC ratio
Obstructive Restrictive
– Examples:
Forced vital capacity Normal or reduced Reduced
• Asthma • Cystic fibrosis (FVC)
• COPD • Emphysema: watch for ¯ DLco FEV1 Reduced Reduced
• Restrictive (reduced air volume) FEV1/FVC Reduced Normal
– Decreased FVC, increased FEV1/FVC ratio FEF25-75% Reduced Normal or reduced
– Examples: Peak flow Normal or reduced Normal or reduced
• Interstitial pneumonitis Total lung capacity Normal or reduced Reduced
• CHF (TLC)
• Pulmonary fibrosis: watch for ¯ DLco
• Thoracic deformities
• Sarcoidosis Residual volume (RV) Increased Reduced
RV/TLC Increased Unchanged
Functional residual Increased Reduced
capacity (FRC)
 2/1/19

The Reproductive System

Lecture 1 Uterine and Ovarian Disorders

The Reproductive System Lecture 2

Lecture 3
Cervical and Ovarian Disorders

Menstrual and Breast Disorders

Lecture 4 Contraceptive Methods

Infertility
Stephanie Neary, MPA, MMS, PA-C Uncomplicated Pregnancy
Course Director, Preventative Medicine
Lecture 5 Complicated Pregnancy
Yale School of Medicine, PA-Online

Menstrual Cycle

Uterine Disorders
Dysfunctional Uterine Bleeding
Endometrial Cancer
Endometriosis
Adenomyosis
Leiomyoma
Metritis
Prolapse
Incontinence

Menstrual Cycle Female Tanner Staging

Pubic Hair
• Phase 1: Menstrual
• Stage I: none
First day of menses is considered as day 1. Characterized by
sloughing of the endometrium. • Stage II: small amount,
long downy hair on labia
• Phase II: Proliferative
• Stage III: more coarse,
Estrogen stimulation leads to increase in LH, growth of the curly, extends laterally
uterine lining and ovulation occurs
• Stage IV: adult-like,
• Phase III: Luteal/Secretory extends across pubis but
not thighs
↑ progesterone leads to ↓ FSH/LH. Without fertilization,
progesterone falls, corpus luteum atrophy occurs and • Stage V: extends to
menstrual phase is triggered medial surface of thighs
Breast
• Stage I: papilla elevation
only
• Stage II: breast buds
palpable and areolae
enlarge
• Stage III: elevation of breast
contour; areolae enlarge
• Stage IV: areolae forms
secondary mound on the
breast
• Stage V: adult breast
contour, areola recesses to
general contour of breast

1
 2/1/19

Dysfunctional Uterine Bleeding Dysfunctional Uterine Bleeding

• Presenting complaint
– Infrequent & light to frequent & heavy menstrual bleeding
– DUB may evolve into amenorrhea
– Shortened menstrual cycle (luteal phase defect)
– Mid-cycle spotting
• Pathophysiology
– Most likely to occur with anovulation (PCOD, perimenopause,
exogenous obesity, adrenal hyperplasia)
– Constant, non-cyclic blood estrogen levels
• Stimulates growth & development of the endometrium
• Without ovulation & the influence of progesterone,
endometrium overgrows and sloughs at irregular times and
in unpredictable amounts
• Anatomic causes must be excluded
– Uterine leiomyomata
– Inflammation/infection of the genital traction
– Carcinoma of the cervix or endometrium
– Cervical erosions or polyps
– Lesions of the vagina
• Exam findings
– Signs of inflammation or infection of genital tract, visible
changes on cervix or walls of vagina
– Palpably abnormal size/shape to the uterus or ovaries
– Pap smear abnormalities
– Endometrial biopsy: proliferative or hyperplastic endometrium

Dysfunctional Uterine Bleeding Endometrial Carcinoma

• Treatment • Most common gynecologic malignancy in the U.S.
– Aim is to convert proliferative endometrium into secretory – Two times as common as cancer of cervix
endometrium
– Administer a progestational agent (medroxyprogesterone
– Mean age 60 years
acetate) for 10 days Q month • Fourth most common malignancy in American women,
– Oral contraceptives (OC) to establish regular, predictable after cancer of lung, breast, and colorectal
cycles
• Control acute bleeding episode with OCs, 3-4 pills daily • Estrogen-dependent
for 6-7 days • Often associated with prior endometrial hyperplasia
– If no response to medical therapy consider endometrial ablation
• Age at onset: postmenopausal (75%), perimenopausal
or hysterectomy
(15–20%), menstrual (5–10%)
– Treat any associated anemia

Endometrial Carcinoma Endometriosis

• Risk factors • Benign condition in which endometrial glands and
– Obesity, hypertension, diabetes, nulliparity stroma are present outside the endometrial cavity
• Presenting symptoms • Presenting complaints
– Dysmenorrhea
– Abnormal vaginal bleeding
– Dyspareunia
– Post-menopausal bleeding is always abnormal and must be
investigated – Dyschezia (painful bowel movement)
– Pre- and post-menstrual spotting
– Diagnosis: endometrial biopsy
– Ovulatory pain and mid-cycle vaginal bleeding
• Treatment: TAH-BSO and post-op radiation therapy – Pelvic pain
– Infertility

2
 2/1/19

Endometriosis Endometriosis: Treatment

• Exam findings
– Exam findings may be very subtle or non-existent
– Tender, fixed, retroverted uterus with bimanual exam
– Laparoscopic exam with biopsy: only definitive
diagnostic tool
• Pelvic transvaginal ultrasound: cannot make a definitive
diagnosis
– Surgical considerations
• Large lesions (endometriomas 6 cm or greater)
• Fertility desired: conservative laparoscopic treatment
• Severe disease: combine surgical and medical treatment
– Medical therapy treatment
• Combination of estrogen/progesterone OCs
(pseudopregnancy) plus NSAIDs
• Progesterone therapy (suppresses GnRH at hypothalamus)
• Danazol (testosterone): prevents LH and FSH increase mid-
cycle thereby inhibiting ovulation
– Masculinizing side effects
• Lupron (GnRH analogue) down-regulates the pituitary
through negative feedback to suppress LH and FSH

Adenomyosis Leiomyoma (Uterine Fibroids)

• Islands of endometrial tissue within the myometrium (muscular • Common occurrence (30% of women)
layer of uterus)
• Most common indication for hysterectomy
• Presenting complaints
– Seen mostly in women age 30s
– Dysmenorrhea
– Diagnosis supported by exclusion of other causes of secondary – Five times more prevalent in African Americans
dysmenorrhea • Presenting complaints
– Definitive diagnosis done with histological examination of uterus
– Menorrhagia
(post-TAH)
• Exam findings: tender, symmetrically enlarged, “boggy” uterus – Dysmenorrhea

• Treatment – Pressure symptoms related to size and number of tumors and location
– Total abdominal hysterectomy
– If fertility is to be preserved: symptomatic therapy in the form of
analgesics or modification of the menstrual cycle with low-dose OCs

Leiomyoma (Uterine Fibroids) Leiomyoma

• Exam findings • Treatment
– Bimanually or – Aim is to minimize uterine bleeding
abdominally palpable – Majority do not require surgical or medical treatment
mass
• Large, irregular • Myomectomy (fertility can be preserved)
contoured, hard, • Hysterectomy
enlarged pelvic • Pharmacologic inhibition of estrogen secretion by
mass
suppression of GnRH (Lupron) or medroxyprogesterone
– Irregularities of the (Provera)
uterine cavity found
during curettage
Leiomyoma Adenomyosis
– Pelvic ultrasound: will
reveal shadowing Asymmetric Symmetric
Firm Soft
Nontender Tender

3
 2/1/19

Metritis Prolapse
• Post-partum uterine infection (post-partum metritis) • Common etiology is childbirth and post menopausal
– Endometritis = decidua state
– Endomyometritis = decidua + myometrium
• Uterine: sagging of uterus into vagina
– Increase risk with cesarean section
• Provide single dose perioperative antimicrobial prophylaxis – Grading see next slide
– Ampicillin or 1st generation cephalosporin • Cystocele
• Organisms – Posterior bladder protrudes into anterior vagina
– Group A strep, S. aureus, anaerobes, and polymicrobial • Enterocele
• Presentation – Pouch of Douglas (containing small bowel) protrudes into
– Fever, abdominal pain upper vagina
• Treatment • Rectocele
– Clindamycin plus gentamicin following cesarean section
– Distal sigmoid colon (rectum) into posterior distal vagina
– Ampicillin plus gentamicin following vaginal delivery

Uterine Prolapse Prolapse

• 1st degree: descent • Presenting complaint
into upper 2/3 of the – Feeling of pelvic fullness or heaviness
vagina – May be described as something “falling out”
• 2nd degree: cervix – Backache: worse with prolonged standing
approaches the – Difficulty walking
introitus – Dyspareunia
– Purulent vaginal discharge, ulceration, or vaginal bleeding
• 3rd degree: – Urinary frequency, urgency, and incontinence
structure is outside
• Exam and findings
the introitus
– Vaginal speculum exam with and without Valsalva maneuver
• 4th degree or will demonstrate degree of prolapse
procidentia: entire – Rectal exam may demonstrate rectocele
uterine body is
outside the vagina

Prolapse Urinary Incontinence

• Treatment: Stress Urge Overflow
– Prophylactic Amount of loss Small Large Small
• Treatment of chronic respiratory disease and constipation Duration of loss Brief Moderate Continuous
Associated • Cough None None
• Weight control event • Laugh Change in position
• Pelvic muscle exercises (Kegel) • Sneeze
– Non-surgical treatment Associated • None Urgency • Fullness
symptoms • No urine loss at Nocturia • Pressure
• Pessaries
night • Frequency
• Estrogen therapy
Cause • Cystocele Loss of bladder • Obstruction
– Surgical treatment • Urethrocele inhibition • Loss of
• Hysterectomy neurologic control

• Uterosacral or sacrospinous ligament fixation “sling” Treatment • Kegel exercises Anticholinergic • Self-
• Estrogen catheterization
replacement • Cholinergic meds
• Surgery • Α-blockers

4
 2/1/19

Functional Ovarian Cysts

• Arise as a result of normal ovarian function
– When an ovarian follicle fails to rupture,
follicular cyst may develop (most
spontaneously resolve)
– When a follicular cyst ruptures, it may
Ovarian Disorders cause acute pelvic pain
• Presenting complaint
– Mild to moderate unilateral LLQ or RLQ
Functional Ovarian Cysts pain (dependent on size of cyst)
Benign Ovarian Neoplasms – May have alterations of menstrual interval
• Exam findings
Malignant Ovarian Neoplasms – Unilateral pelvic tenderness/pain on exam
– Palpable, mobile, cystic adnexal mass
Polycystic Ovarian Disease – Ultrasound may demonstrate cystic echo
on ovary
• Treatment
– Most spontaneously resolve within two
months
– OCs to suppress gonadotropin stimulation
of the cyst

Ovarian Torsion Benign Ovarian Neoplasms

• Twisting of ovary (and fallopian tube) → blocking sufficient blood flow
– Most commonly precipitated by presence of cyst or neoplasm
• Can occur at any age, most commonly occurs 20-40yo
• Presenting complaint
– Acute onset of abdominal/pelvic pain, nausea, and vomiting
• Exam findings
– Nonspecific: Unilateral adnexal tenderness, abdominal mass
– Transvaginal doppler US: enlarged ovary, absent blood flow
– Definitive diagnosis requires direct laparoscopic visualization
• Treatment
– Surgical emergency! Detorsion is preferred to preserve function,
removal of the ovary may be necessary
• In reproductive-age women, 90% of ovarian neoplasms
are benign
– 25% malignant if including postmenopausal women
– Risk for malignant transformation rises with increasing age
• Exam findings
– Usually an incidental finding on exam
– Ultrasound to differentiate
• Treatment
– Surgery (because of potential for malignancy or torsion)

Malignant Ovarian Neoplasms Malignant Ovarian Neoplasms

• Fifth most common of all cancers in women • Exam findings
– Mortality rate highest of all gynecologic cancers – Solid, irregular, fixed mass on ovaries
– Mainly ages 40–60 – May palpate upper abdominal mass or ascites
– Risk Factors – BRCA1, family hx, nulliparity – Possible detection of serum tumor marker CA-125
• Presentation
– Rarely symptomatic until extensive metastasis
– Possible irregular menses, menorrhagia, or post-
menopausal bleeding
• Symptoms
– Abdominal fullness or distension, nausea, abdominal or
back pain, decreased energy, urinary frequency

5
 2/1/19

Malignant Ovarian Neoplasms Polycystic Ovarian Syndrome

• Evaluative Procedures: • Chronic anovulation with infertility
– Laparoscopic exam • History of irregular bleeding
– CT • Examination: hirsutism, obesity, acne, acanthosis
– Pelvic ultrasound nigricans
– Endometrial biopsy and endocervical curettage with – Bilaterally, enlarged, smooth, mobile ovaries
abnormal bleeding • Labs: mild ↑ testosterone, LH:FSH ratio 3:1 (normal
– Upper GI or barium enema if GI complaints are present 1.5:1)
– Mammography for primary in breasts – Ultrasound: bilaterally enlarged ovaries with multiple
• Treatment: pearly white cysts
– Surgery (tumor-debulking) • Management: combination OCPs (normalize bleeding
– Chemotherapy: paclitaxel (Taxol), cisplatin and treat hirsutism), spironolactone (treat hirsutism),
clomiphene (infertility), metformin (increase ovulation)

The Reproductive System

Lecture 1 Uterine and Ovarian Disorders
Cervical Disorders
Lecture 2 Cervical and Vaginal Disorders
Cervical Carcinoma
Lecture 3 Menstrual and Breast Disorders
Cervical Dysplasia
Lecture 4 Contraceptive Methods Pap Smear Screening
Infertility
Uncomplicated Pregnancy Incompetent Cervix
Lecture 5 Complicated Pregnancy

Cervical Carcinoma Cervical Carcinoma

• Link to human papillomavirus • Diagnosis
• Average diagnosis age 45 – Pap smear
• Risk factors • Treatment
– Early onset sexual activity – Cone biopsy (microinvasion)
– Increased number sexual – Hysterectomy (invasive but no spread)
partners
– Radiation therapy (advanced disease)
– Sexually transmitted infections – Chemotherapy: cisplatin
– DES exposure
• Prevention
• Cell types
– HPV vaccine (Gardasil)
– Squamous – 90% © Katsumi M. Miyai, M.D., Ph.D., Regents of the
• If <15 yo: 2 doses over 6-12 months (0, 6-12 months)
– Adenocarcinoma (<10%) University of California. Used with permission.

• Clear cell: linked to • If >15 yo: 3 doses over 6 months (0, 1-2, 6 months)
diethylstilbestrol (DES) • Routine ages 11–12 (9-26yo)
• Clinical • Not recommended in pregnant, lactating, or
– Post-coital bleeding, watery immunocompromised patients
discharge, pelvic pain

6
 2/1/19

Cervical Dysplasia Cervical Dysplasia

• Caused by HPV
• Precursor to cervical cancer Biopsy Followup Options Biopsy
– Cervical intraepithelial neoplasia I: cancer 7 years Observation
– Cervical intraepithelial neoplasia II: cancer 4 years Repeat Pap, colposcopy
and Pap, HPV-DNA
• No clinical signs or symptoms
• Diagnosis by Pap smear and colposcopy with biopsy Ablative Therapy
CIN 1 Cryotherapy, laser, electrofulguration
– Pap smear classification by Bethesda system CIN 2
CIN 3
• Treatment Excisional Procedure
– Next slide LEEP, cold-knife cone

• Follow-up Hysterectomy
– Pap smear every 6 months for 2 years Only recurrent CIN 2 or CIN 3

Pap Smear Screening Pap Smear Guidelines

• Per U.S. Preventive Services Task Force (USPSTF) and
American Cancer Society
– Women between ages 21 and 65 without risk factors (DES exposure
or immunodeficiency) should undergo cytologic screening every 3
years
– Those aged 30-65 (one of the following):
• Screening with both cytologic exam and HPV testing every 5 years
• Cytology alone every 3 years
• HPV alone every 5 years
– Women younger than 21 should not be screened
– Women older than 65 who have been adequately screened previously
and have no history of should not be screened
• Patients with history of total hysterectomy (for reasons other
than cervical cancer) need no further screening
• ACOG
– Age 21 regardless of age of onset of sexual activity
– Every 3 years from age 21–29 with cytology alone,
every 5 years age ≥30 with cytology and HPV testing
– Discontinue age 65:
• No history of moderate or high-grade
precancerous lesion
• 3 negative cytology screenings in a row OR
• 2 negative co-tests in a row (last within 5 years)
– No screening after hysterectomy with removal of the
cervix (unless history of cervical cancer → continue
screening for 20 years after hysterectomy)

Incompetent Cervix
• Fetal membranes are exposed to vaginal flora
• May lead to:
– Infection
– Vaginal discharge Vaginal/Vulvar Disorders
– Premature rupture of membranes
• Symptoms Vaginal/Vulvar Cancer
– Painless dilation and effacement of cervix Infections of the Genital Tract
– Bleeding, vaginal discharge Pelvic Inflammatory Disease
– Noted during second trimester Human Papillomavirus
• Diagnosis based on PE
• Treatment: typically poor prognosis; bed rest, vaginal
rest, routine US, cerclage
– Future pregnancies: prophylactic cerclage,
hydroxyprogesterone caproate IM

7
 2/1/19

Vaginal/Vulvar Cancer Infections of the Genital Tract

• Vaginal • Vulvar • Vaginitis: inflammation of the vaginal vault or tissue
– Rare, usually secondary – Peak age 70s – Infectious
to other cancers – 90% squamous cell • Bacterial vaginosis, Candida, Trichomonas
– Peak age 50s (linked to • Symptoms – Non-infectious
DES exposure) – Pruritus, red/white • Non-specific vaginitis
ulcerative lesions – Atrophic vaginitis most common cause in post-
– 80–90% squamous cell
• Symptoms • Diagnosis menopausal women due to estrogen-deficient mucosa;
– Biopsy presents with vaginal dryness, discharge, itching, burning,
– Asymptomatic • Treatment and dyspareunia
• Diagnosis – Surgery, radiation – Treatment: oral estrogen/progesterone or estrogen cream
– Pap smear, biopsy therapy, chemotherapy • Foreign body
• Treatment – Usually a forgotten tampon, diaphragm or condoms
– Treatment: removal of object and antibacterial vaginal
– Radiation therapy
cream
– Toxic shock caused by staphylococci

Bacterial Vaginosis Trichomonas

• Due to lack of Lactobacillus and overgrowth of G. vaginalis • Flagellated, pear-shaped protozoan
• Discharge, bad odor (possibly worse after intercourse) • Spread via sexual contact
• Discharge • Rancid odor, vulvar pruritus, dysuria, dyspareunia
– Thin, homogeneous, white to gray, adherent, often increased • Physical exam
amounts – Discharge (yellow-green, frothy, increased amount, vaginal pH
– Vaginal pH >5 (normal 3.8–4.2) >5)
– Positive clue cells, positive whiff test – Strawberry cervix
• Treatment • Diagnosis
– Metronidazole (Flagyl) – Motile protozoan
• Used in pregnancy • Treatment
– Clindamycin (Cleocin) – Metronidazole (Flagyl)
– Tinidazole (Tindamax)
• Must treat partner; this is an STD

phil.cdc.gov

Candida Infection Infections of the Genital Tract

• Due to Candida albicans
• Itching, burning, discharge Bacterial Candidiasis Trichomoniasis
• Physical exam Vaginosis
– Discharge Symptoms • Discharge • Itching • Discharge
• White, curdy, “cottage- • Odor worse after • Burning • Bad odor
cheese like,” sometimes sex • Discharge • Dysuria
• Itching/burning
increased amounts
• Vaginal pH <4.5 © Richard Usatine, M.D. Used with permission Discharge amount Often increased Sometimes Increased
increased
• Labs
– Budding yeast and Discharge Thin, gray-green White, curdy Frothy, gray-green
appearance
pseudohyphae
Vaginal pH >4.5 Normal >4.5
• Treatment
– Fluconazole Whiff test Present Absent Possible present
– Miconazole, clotrimazole Microscopic Clue cells Hyphae, yeast Trichomonads
• Intravaginal creams,
Treatment Metronidazole Fluconazole Metronidazole or
suppositories
Clindamycin Tinidazole
phil.cdc.gov

8
 2/1/19

Pelvic Inflammatory Disease (PID) Pelvic Inflammatory Disease

• Any infection, including an STD, can cause PID • Clinical criteria
– Spontaneous, ascending reproductive-tract infection – All 3 of the following:
– May lead to infertility or ectopic pregnancy • Abdominal tenderness with or without rebound
• Risk factors • Adnexal tenderness
– Prior PID, multiple sex partners, not using condoms, sexual
• Cervical motion tenderness
assault
– Always ask about sex with men and/or women, current and
– Plus 1 or more of the following:
past • Gram-stain positive for gram-negative intracellular
• Presenting complaints diplococci
– Pelvic pain, dyspareunia, vaginal discharge, dysuria, nausea, • Temperature >38° C
vomiting • WBC >10,000
• Exam findings • Pus on culdocentesis or laparoscopy
– Lower abdominal tenderness • Pelvic abscess on bimanual exam or ultrasound
– Uterine/cervix/adnexal tenderness to palpation & motion
“Chandelier sign”
– Purulent cervical discharge
– Fever

Pelvic Inflammatory Disease Summary

• Treatment
– Inpatient: cefoxitin or cefotetan plus doxycycline Signs and Symptoms Diagnostic Adjuncts
– Outpatient: single-dose ceftriaxone plus doxycycline Genital • Flu-like symptoms • Serologies to detect
herpes • +/- genital itching, pain, or antibodies against HSV-1 &
• Complications paresthesias HSV-2
• Painful lesions on an • HSV cell culture
– Fitz-Hugh-Curtis syndrome (perihepatitis) erythematous base
• Due to peritoneal involvement Cervicitis • Abnormal vaginal discharge • Wet-mount microscopy
• Irregular vaginal bleeding (may • Culture for C. trachomatis
• May see “violin string” adhesions from parietal be associated with intercourse) and N. gonorrhoeae
peritoneum to liver
PID • Lower abdominal or pelvic pain • Wet mount microscopy or
• Treat underlying infection • Cervical motion, adnexal, or culture
uterine tenderness • Laboratory tests (elevated
• Fever ESR, CRP, WBC count) may
• Abnormal vaginal discharge support diagnosis

Human Papillomavirus (HPV) Infection HPV

• Genital Warts (condyloma acuminatum) • Physical examination Syphilis chancre Genital W arts

– More than 30 types of HPV can infect the genital tract – Fleshy growths on vulva,
• Most are asymptomatic or subclinical vagina, cervix, urethral
meatus, perineum, and anus
– Types 16, 18, 31, 33, and 35
– Spread by direct skin-to-skin
• Strongly associated with cervical neoplasia (vaccine)
contact
• Associated with squamous intraepithelial neoplasia
• Genital warts
– Visible genital warts usually HPV types 6 or 11
– Types 16, 18, 31, 33, and 35
– May be infected simultaneously with multiple types • Strongly associated with
– Usually present with <10 visible genital warts cervical neoplasia (vaccine)
• Associated with squamous
intraepithelial neoplasia
phil.cdc.gov

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HPV
• Diagnosis
– PE The Reproductive System
– Biopsy (only under certain circumstances) Lecture 1 Uterine and Ovarian Disorders
– Diagnosis uncertain
Lecture 2 Cervical and Vaginal Disorders
– Lesions do not respond to standard therapy
– Disease worsens during therapy Lecture 3 Menstrual and Breast Disorders

– Patient is immunocompromised Lecture 4 Contraceptive Methods

• Treatment Infertility
Uncomplicated Pregnancy
– Chemical (trichloroacetic acid, podophyllin, imiquimod)
Lecture 5 Complicated Pregnancy
– Cryosurgery, excision, intralesion injection

Amenorrhea
• Primary: never menstruated at age 14 without secondary
sexual characteristics or age 16 with secondary sexual
characteristics
Menstrual Disorders • Secondary : previously menstruated but has not had menses
for the past 6 months
Amenorrhea – Oligomenorrhea: ↓ frequency with cycle length >35 days but <6
months
Dysmenorrhea
• Most common cause: pregnancy
Premenstrual Syndrome
– If history suggests pregnancy, confirm with serum/urine hCG
Menopause
• Other causes are divided into 3 areas:
– Hypothalamic-pituitary dysfunction
– Ovarian dysfunction
– Alterations of the genital outflow tract

Primary Amenorrhea Amenorrhea

• Are breasts present? • Hypothalamic-pituitary dysfunction
– Presence of breasts = adequate estrogen – When secretion of GnRH is disrupted or altered in the
• Is a uterus present? hypothalamus, the anterior pituitary does not secrete FSH or
LH.
– Other
Uterus Present Uterus Absent
• Functional causes: weight loss, excessive exercise, obesity
Breasts present • Imperforate hymen • Müllerian agenesis
• Vaginal septum • Androgen insensitivity • Drug-induced causes: marijuana, tranquilizers
• Anorexia
• Pregnancy

Breasts absent • Gonadal dysgenesis Rare: not clinically relevant

• H-P failure

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Amenorrhea Amenorrhea
• Other causes • Treatment of hypothalamic-pituitary dysfunction
– Neoplastic causes
– Modify functional causal behaviors
• Prolactin-secreting pituitary adenoma
– Also may present with galactorrhea – Stimulate gonadotropin secretion
• Craniopharyngioma • Clomiphene citrate (Clomid)
• Hypothalamic hamartoma
• Menotropins (Pergonal)
– Psychogenic causes: chronic anxiety, pseudocyesis, anorexia
nervosa – Treat underlying psychogenic, medical (hypothyroidism),
– Other causes: head injury, chronic medical illness or drug-induced causes
• Definitive diagnosis of hypothalamic-pituitary dysfunction
– Surgery (tumors)
– Serum measurement of FSH, LH, and prolactin
• FSH and LH decreased
• Prolactin normal in most conditions but elevated in prolactin-
secreting pituitary adenomas

Amenorrhea Amenorrhea
• Ovarian Failure • Treatment
– Follicles are either exhausted or resistant to stimulation by FSH
– If progesterone challenge causes “withdrawal bleeding,”
and LH, resulting in increase serum FSH and LH levels
the patient is anovulatory or oligo-ovulatory.
– Symptoms of estrogen deficiency are present:
• Hot flashes, mood changes, sleep disturbance, vaginal dryness, • Use exogenous hormone replacement therapy
dyspareunia
– If “withdrawal bleeding” does not occur, the patient is
– Exam findings
hypoestrogenic or has an anatomic condition such as
• Signs of estrogen-deficiency: vaginal dryness, thin vaginal
epithelium, thinning and/or flushing of the skin Asherman’s syndrome or outflow tract obstruction.
– Diagnosis
• Progesterone challenge test (PCT)
– 100 mg progesterone IM or 10 mg oral medroxy-progesterone
acetate (Provera) QD for 10 days

Amenorrhea Dysmenorrhea
• Obstruction of the genital outflow tract • Painful menstruation which prevents performing normal
– Congenital abnormalities in development of Müllerian activities
ducts – Primary
• Imperforate hymen • Due to increased prostaglandins, leading to painful uterine
muscle-wall activity
• Transverse vaginal septum • Common in women in teens and 20s; declines with age
• Scarring of the uterine cavity (Asherman’s syndrome) – Secondary
• Due to clinically identifiable cause: endometriosis, adenomyosis,
– Hysteroscopy (to diagnose and treat adhesions)
adhesions, PID, or leiomyomata
– Estrogen therapy (to stimulate endometrial regeneration • More common as a woman ages
of denuded areas) • Symptoms
– Diffuse pain in lower abdomen and suprapubic
– Pain comes and goes, associated with N/V, diarrhea,
headache, and backache

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Dysmenorrhea Premenstrual Syndrome (PMS)

• Physical examination • Group of physical, mood and behavioral changes which
occur in a regular, cyclic relationship to the luteal phase of
– Primary: normal physical examination
the menstrual cycle
– Secondary: varies with etiology • Symptoms occur in most cycles, resolving near the end of
• Treatment menses with a symptom-free interval of at least 1 week
– NSAIDs (primary) • Symptoms in 75–85% of women; significant disruption in 5–
10%
– OCP
• Premenstrual dysphoric disorder (PMDD)
– Vitamin B
– PMS with more severe emotional symptoms; may require more
– Treat underlying cause (secondary) intensive therapy
– 3–5% of women

Premenstrual Syndrome (PMS) PMS: Treatment

• Signs and Symptoms • Multidisciplinary
– Common somatic complaints: breast swelling & pain, bloating, – Education
headache, constipation and/or diarrhea, fatigue, muscle/joint
aches – Chart system
– Common emotional complaints: irritability, depression, anxiety, – Diet, exercise, and medication to induce ovulation
hostility , libido changes
– Progesterone
– Common behavioral complaints: food cravings, poor
concentration, sensitivity to noise, loss of motor skills – NSAIDs
• No definitive physical or laboratory findings to aid – Diuretics
diagnosis – Anxiolytics and antidepressants
• Documentation of the relationship of symptoms to luteal – Vitamin therapy
phase of menstrual cycle – SSRIs
– Menstrual diary
– To confirm diagnosis, must have a symptom-free follicular phase
(approximately 1 week) in contrast to the problems during luteal
phase

Menopause Menopause
• Cessation of menses for 1 year with elevated FSH/LH • Exam findings
– Average ages 50–52 – Skin: becomes thin and dry with decreased elasticity
– Climacteric (perimenopause) 5–10 years prior
– Vaginal mucosa
• Presenting complaints:
• Thin, dry epithelium
– Menstrual cycle alterations
• pH increased to 7
– Hot flushes and vasomotor instability (hallmark signs of
perimenopause) • Cervical os is stenosed and transformation zone
– Sleep disturbances and mood changes is inverted
– Vaginal dryness and genital atrophy (dyspareunia) – Musculoskeletal changes
– Skin, hair, and nail changes
• Decreased bone density
– Cardiovascular lipid changes (increased TC and LDL; decreased HDL)
– Osteoporosis

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Menopause: Treatment Hormone Replacement Therapy

• Exogenous estrogen + progestin
Estrogen + Progestin Estrogen Only
– Use estrogen vaginal cream for vaginal complaints
Vaginal dryness Benefit Benefit
– May use estrogen alone if uterus has been removed
• Use of unopposed estrogen increases the risk of Hot flashes Benefit Benefit
endometrial cancer Vasomotor symptoms Benefit Benefit
• Collagen and bone loss Osteoporosis Benefit Benefit
– Bone mineral analysis (densitometry) Breast cancer Risk No Change
– Calcium with vitamin D Heart disease Risk No Change
– Bisphosphonates or calcitriol Stroke Risk Risk
– Weight-bearing exercises
– Smoking cessation

Benign Breast Disorders

• Fibrocystic Disorder
– Most common of benign breast conditions
– Seen mostly in women 30 -40s

Breast Disorders
Benign Breast Disorders
Breast Abscess
• Fibroadenoma
Breast Cancer
– Usually multiple, well-demarcated, “mirror images,” and can present
as “sheets” of dense tissue
– Mobile, moveable with no axillary involvement or nipple discharge
– Can be tender in premenstrual period
– Second most common of benign breast diseases (10–20% of women)
– Usually 1 or 2 smooth, well-circumscribed, rubbery lumps. Unilateral,
painless.
– Mobile, moveable with no axillary involvement or nipple discharge
– Mostly women late teens and early 20s
– Can enlarge in pregnancy and cause discomfort

Gynecomastia Benign Breast Disorders

• Proliferation of glandular male breast tissue • Mastitis
– Noncancerous – Infection of breast duct
– Due to an imbalance of estrogen and androgens • Mostly lactating women
– Often physiologic in newborns and adolescent males
• Sudden onset of fever, chills, malaise, & general body
– Pathologic causes: Klinefelter’s syndrome, medication use (GnRH
aches
analogues, 5a reductase inhibitors, hcg), primary hypogonadism
– Diagnosis: history and physical exam • Erythema and tenderness
• Skin dimpling and nipple discharge are not normal with • Brawny, indurated area to palpation
gynecomastia (unless prolactin secreting pituitary tumor is • Almost always unilateral
present) → must always rule out breast cancer
• Many proceed to generalized sepsis quickly
– Treatment:
• Spontaneously resolves in most patients – Antibiotic treatment with dicloxacillin recommended
• Selective estrogen receptor modulators (SERMs) • May continue to breastfeed or pump breast

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Breast Abscess Breast Cancer

• Presents with localized • Second most common • Risk factors
pain, swelling, and fever malignancy in women – Inherited genetic mutations
• BRCA 1 and BRCA 2
• Physical examination • Those with increased risk
– Fluctuant mass – First-degree relative with
factors for breast cancer breast cancer
• Treatment make up only 25% of breast
– Older than age 65
– Stop breast feeding cancer patients – Never breast fed a child
– Surgical drainage – No full-term pregnancies or
– Antibiotic therapy first full-term pregnancy
after age 35
• Nafcillin
– Early (<12) onset menarche
• Vancomycin
– Late menopause
• Clindamycin
– Hormone therapy
© Richard Usatine,M.D. Used with permission • HRT or OCs
– Alcohol consumption

Breast Cancer Breast Cancer

• Presenting complaint • Mammogram
– Usually painless and may feel mobile early – Screening may demonstrate a non-palpable lump 2–3 years before it
– With progression, borders become less distinct would be found manually
and fixation to surrounding tissue occurs – Ultrasound recommended for women age <35 due to high density
– Nipple discharge and peau d’orange are late breast tissue
changes and associated with poor prognosis © Richard Usatine, M.D. Used with permission – Microcalcifications and other changes suspect for malignancy
– 80% of cancers present as a mass
• Ultrasound
– 90% of breast cancers are found by the patient
– Can differentiate fluid-filled or solid mass
• Exam findings
– May be used to guide needle for aspiration
– Asymmetry, distortion, discoloration, or skin/nipple changes
– Recommended initial modality to evaluate a breast mass in women
– Describe size, shape, consistency and mobility, as well as position of
age <40
any palpable lesions
– Axillary or clavicular nodes

Breast Cancer: Treatment

• Most breast cancer treated by local excision & adjunctive
therapy The Reproductive System
– Breast cancer spreads by both vascular and lymphatic routes with
some direct infiltration Lecture 1 Uterine and Ovarian Disorders
• Surgical resection of malignancy
Lecture 2 Cervical and Vaginal Disorders
– Lumpectomy removes cancerous and surrounding-normal tissue
(common) Lecture 3 Menstrual and Breast Disorders
– Mastectomy removes entire breast
– Removal of regional (axillary) lymph nodes (to determine metastases) Lecture 4 Contraceptive Methods
• Non-surgical Infertility
Uncomplicated Pregnancy
– Radiation therapy/chemotherapy
– Hormonal manipulations Lecture 5 Complicated Pregnancy
• Anti-estrogen (tamoxifen)
• Monoclonal antibody therapy

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Contraception

Contraception

© Kaplan

Birth Control Birth Control

• Barrier-spermicidal methods • Steroid contraception
– Prevent entry of sperm through the cervix – Inhibit midcycle LH surge preventing ovulation, thicken cervical
– Do protect against some STIs mucosa, alter endometrium
– No systemic side effects – Side effects: fluid retention, ↑ gall stones, mood changes,
– Failure rate approaches 20% depression, may worsen migraine

– Examples: condoms, vaginal diaphragm, spermicides
• Intrauterine contraception
– Inhibit sperm transport, cause failure of implantation
– Contraindications: pregnancy, pelvic malignancy, undiagnosed
vaginal bleeding
– Contraindications: pregnancy, liver disease, vascular disease,
smoker over age 35, uncontrolled hypertension, thrombophilia
– Examples: combination OCPs, combination vaginal ring,
transdermal skin patch, progestin-only OCPs, progestin-only
injectable, progestin-only subcutaneous implant

Infertility
• Failure to conceive following 1 year of regular,
unprotected intercourse
– Primary: never conceived
Infertility – Secondary: conceived in the past but unable in the
present
• Causes: female
– Anovulation or ovulatory dysfunction (30%)
– Anatomic defects
• Causes: male
– Abnormal spermatogenesis (40%)

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Infertility
• Evaluation
– Anovulation or ovulatory dysfunction
• Basal body temperature chart
– Temperature-rise with ovulation Uncomplicated Pregnancy
– Serum progesterone measure mid-luteal phase
Pregnancy
– Anatomic defect: hysterosalpingogram, diagnostic laparoscopy,
or hysteroscopy
Prenatal Care
– Abnormal spermatogenesis: semen analysis for volume, Intrapartum Care
concentration, motility, viscosity, morphology, pH, WBCs Postpartum
– Further evaluation should be referred

Pregnancy “Signs” of Pregnancy

• History of 1 or more missed periods • Chadwick’s sign: cervix (also vulva and vagina) with bluish
• Associated fatigue, nausea/vomiting, breast swelling/tenderness color, occurs at 8–12 weeks gestation
• Diagnostic tests of pregnancy
– Increased urine hCG: test (+) 4 weeks after conception • Goodell’s sign: softening of cervix, occurs at 4–5 weeks
– Increased serum hCG: quantitative hCG
gestation
– Increased serum progesterone • Hegar’s sign: softening of the uterine isthmus, occurs at 6–
• Exam findings 8 weeks gestation
– Uterus changes
– Cervix: Chadwick’s and Hegar's (softening of cervix) signs
• McDonald’s sign: fundus flexes easily on the cervix, occurs
– Ultrasound (detects fetus at 5–6 weeks) at 7–8 weeks gestation
– Fetal heart tones: Doppler at 10–12 weeks
• Ladin’s sign: softening of the uterus after 6 weeks
– Palpable fetal parts
– Appreciable fetal movements at 16–20 weeks (quickening)

Prenatal Care Prenatal Care

• Initial screening • Subsequent pre-natal
– Risk assessment and maternal history visits
– Estimated date of delivery (EDD) – BP, weight, and check
• First day of LMP plus 7 days minus 3 months and/or for edema
ultrasound for gestational age (Nägele's rule) – Routine laboratory
– Complete physical examination screening
– Pelvic exam for uterine size • Urine for glucose and
protein
– CBC, UA, blood group/RH, antibody screen, serologic
tests for syphilis (RPR, VDRL), HIV, hepatitis B, rubella – Fundal height
titer, Pap smear, tests for chlamydia and gonorrhea measurements
– Glucose tolerance test
(24–28 weeks)

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MS α-Fetoprotein Prenatal Care

• Measured at 15–20 weeks • Subsequent prenatal visits
– Increased in open neural tube defects (ONTD)
– Rh immune globulin (RhoGAM at 28 weeks and within
– Decreased in Down’s syndrome (Trisomy 21) 72 hours of childbirth)
– Fetal heart tones (120–160 bpm)
– Group B strep (32 weeks)
• Treat with IV penicillin G (or ampicillin) intrapartum for
>4 hours
– Determination of presentation or “lie”
• Leopold’s maneuvers

• Breech presentation → consider c-section

Prenatal Care Intrapartum Care

• Fetal monitoring • Braxton-Hicks contractions (false labor)
– Quantification of fetal activity – Spontaneous uterine contractions occurring late in pregnancy
– Electronic fetal monitoring
– Not associated with dilation of the cervix
– Ultrasonography
– Non-stress test (NST) • Lightening
• Measures fetal heart rate for 20 min; also monitors fetal – Fetal head descending into pelvis results in change in shape of
movement abdomen and sensation that baby has become less heavy
• A reactive (normal) test shows fetal heart rate acceleration
• Bloody show
– Contraction stress test (CST)
• Measures response of fetal heart rate to the stress of a – Passage of blood-tinged mucus late in pregnancy
uterine contraction – Occurs as cervix begins thinning out (effacement) with
• A negative (normal) test shows no fetal heart rate associated extrusion of mucous from endocervical glands
deceleration

Intrapartum Care Intrapartum Care: Stages of Labor

• Ruptured membranes • Stage 1: onset of labor to full dilation of cervix (10 cm),
– May present with sudden gush of liquid or constant leakage of divided into 2 phases:
fluid
– Latent phase: cervical effacement and early dilation
• True labor
– Active phase: more rapid cervical dilation, usually
– Contractions that are felt over the uterine fundus with radiation
of discomfort to the lower back and lower abdomen
beginning at 3–4 cm
• Vaginal examination • Stage 2: complete dilation of cervix through delivery of infant
– Not in the presence of significant bleeding • Stage 3: begins after delivery of infant and ends with delivery
– Determine effacement of cervix (%) of placenta
• Shortening of the cervical canal • Stage 4: immediate postpartum period of ~2 hours after
– Determine relative position of cervix (anterior, mid-position,
delivery of placenta
posterior)
– Dilation of cervix (0–10)
– Fetal station and presentation

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Postpartum: Puerperium Postpartum Mood Disorders

• Uterus Postpartum Blues Postpartum Depression

– ~12 week size Incidence 70-80% ≥10%

– Barely palpable above symphysis pubis Average Time 2–4 days postpartum 2 weeks–2 months
postpartum
– Normal size 6 weeks postpartum Average 2–3 days, resolve within 3-14 months
• Lochia serosa (pinkish-brown vaginal bleeding) Duration 10 days
Symptoms Mild insomnia, tearfulness, Irritability, labile mood,
– Postpartum days 4–10 fatigue, irritability, difficulty falling asleep,
– Resolves by 3 weeks depressed affect phobias, anxiety, worse in
the evening
• Breasts
Mother cares Yes May have thoughts about
– Breast milk on postpartum days 3–5, bluish white about baby hurting baby
Treatment None, self-limited Antidepressants

DSM V does not recognize postpartum depression as separate diagnosis, patients must
meet criteria for MDD with specifier of peripartum-onset

The Reproductive System

Lecture 1 Uterine and Ovarian Disorders
Complicated Pregnancy
Lecture 2 Cervical and Vaginal Disorders
Multiple Gestation
Lecture 3 Menstrual and Breast Disorders
Abortion
Lecture 4 Contraceptive Methods Ectopic Pregnancy
Infertility Hypertension in Pregnancy
Uncomplicated Pregnancy
Isoimmunization
Lecture 5 Complicated Pregnancy Gestational Trophoblastic Disease
Third Trimester Bleeding
Dystocia
Gestational Diabetes
Premature Rupture Membranes

Multiple Gestation Complications of Pregnancy

• Suspect if: elevated serum hcg (30-50%
higher than single gestation), fundal height
inconsistent with weeks gestation, family
history, history of fertility treatment
• Risks:
– Premature labor
• Abortion
– Termination of pregnancy before 20 weeks
– Estimated at about 50% of all pregnancies
– Symptoms
• Vaginal bleeding
– Bright red bleeding is usually significant
– Saturation of 1 sanitary pad an hour is significant

– Low birth weight • Low back pain

• Abdominal cramping
– Intrauterine growth restriction
• Passage of products of conception
• All are considered high risk
• Higher rates of cesarean

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Complications of Pregnancy Complications of Pregnancy

• Threatened abortion • Inevitable abortion
– Possible pregnancy loss – Pregnancy cannot be salvaged
– Pregnancy may continue without further problems – Moderate bleeding
– Slight bleeding before 20 weeks – Moderate to severe uterine cramping
– Abdominal cramping – Cervical os is dilated
– Uterine size compatible with dates – Uterine size is compatible with dates
– Cervical os is closed – Products of conception are not passed
– No products of conception are passed – Prognosis is poor
– Prognosis is unpredictable

Complications of Pregnancy Complications of Pregnancy

• Incomplete abortion • Complete abortion
– Some products of conception are passed before 20 – All products of conception are expelled before 20 weeks
weeks – Bleeding may be minimal
– Moderate to severe uterine cramping – Uterine contractions have subsided
– Heavy bleeding – Uterus is normal prepregnancy size
– Uterine size is compatible with dates – Cervical os may be opened or closed
– Cervical os is dilated
– Prognosis is poor

Complications of Pregnancy Complications of Pregnancy

• Missed abortion
– Embryo is not viable but is retained in utero for at least
6-8 weeks
– Uterine contractions are absent
– Bleeding may initially be absent, but spotting begins and
later becomes heavier
• Recurrent pregnancy loss
– 3 or more consecutive spontaneous abortions
– Etiologies: genetic, autoimmune, anatomic
• Elective Abortion
– Most start at 6 weeks (missed second period)
– Medical abortion (using oral medication) can be done
up to 7 weeks gestation
• Mifepristone (RU-486): anti-progestin
• Methotrexate: anti-metabolite
• Misoprostol: prostaglandin
– Surgery should be done before 24 weeks from LMP,
22 weeks gestationally (vacuum extraction most
common)

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Ectopic Pregnancy Ectopic Pregnancy

• Presentation: • Implantation of fertilized ovum outside the uterine cavity
– 1–2 months of amenorrhea • Risk factors
– Unilateral abdominal pain
– History of infertility
– Possible mild vaginal bleeding
– History of prior ectopic pregnancy
– Malaise and syncope
– History of tubal ligation or reconstruction
– Referral of pain to shoulder (blood irritates diaphragm)
– History of PID
– Atypical presentations
– History of IUD use
• Vague or subacute symptoms
• Menstrual irregularity – Endometriosis

Ectopic Pregnancy Ectopic Pregnancy

• Treatment
• Exam findings:
– Laparoscopic repair/removal may be necessary to save
– Signs of shock the reproductive area
– Unilateral abdominal tenderness
– Methotrexate (to clear remaining trophoblastic tissue)
– Pelvic exam: vagina, cervix, bimanual exam
– Follow-up with RhoGAM if needed
• Laboratory tests
– Assess serum beta-hCG levels • Use contraception for at least 2 months following

• Should double every 24–48 during first trimester

– Ultrasound (to determine presence of intrauterine
pregnancy)
– Definitive diagnosis with laparoscopy

Diseases of Pregnancy HTN in Pregnancy: Treatment

• Hypertension (HTN) in pregnancy • Chronic hypertension
– Defined as sustained systolic blood pressure ≥140 mm/Hg or – Not indicated unless SBP >150 or DBP >100
– Options include methyldopa (DOC), labetalol (α/β blocker),
diastolic blood pressure ≥90 mm/Hg
nifedipine (calcium channel blocker)
– Pathophysiology: maternal vasospasm • β blocker linked to intrauterine growth retardation
– HTN with no other symptoms (late) is called transient or • Avoid ACEI and diuretics
gestational HTN • Preeclampsia
– Rest and frequent monitoring
– Preeclampsia is the development of HTN with proteinuria or
edema, or both (second half of pregnancy). – Magnesium sulfate (to prevent seizures)
– Hydralazine and/or labetalol (for hypertension)
– Eclampsia is the presence of convulsions in a woman who has • Eclampsia
met the criteria for preeclampsia. – Life-threatening
– Chronic HTN is hypertension present before the 20th week or – Magnesium sulfate
after 6 weeks postpartum. – Hydralazine and/or labetalol (for hypertension)
– Delivery

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HELLP Syndrome Diseases of Pregnancy

• Noted in 5-10% of patients with severe preeclampsia • Isoimmunization
• Includes: – Several hundred blood group systems
– Hemolytic Anemia – ABO and Rh most common
– Elevated Liver Enzymes • Mother lacks the Rh antigen (Rh-) and father has the
Rh antigen (Rh+)
– Low Platelets (thrombocytopenia)
– If any mixing of maternal/fetal blood (and fetus is Rh+),
• Treatment there is potential for Rh isoimmunization
– Prompt delivery • Prophylaxis: Rh antigen is determined during initial
– Transfer to high-risk OB assessment
– If not present in mother, RhoGAM (pooled anti-D IgG) is
administered 28 weeks and within 72 hours of birth

Diseases of Pregnancy Placenta Previa

• Gestational Trophoblastic Disease • Third-trimester bleeding
– Hydatidiform mole (molar pregnancy) • Abnormal placement of placenta over—or in close proximity to—the
cervical os
• Neoplasm derived almost entirely from abnormal placental
(trophoblastic) proliferation • Sudden onset of
– Characteristic features painless bleeding
• Potential for malignant transformation at 29–30 wks
• Clinical presentation as a pregnancy – Spontaneously
• Uterine size/date discrepancies resolves
• Bleeding (<16 wks gestation) suggestive of spontaneous
• Ultrasound to
abortion
• Profound hormonal changes localize placenta
– No digital © Kaplan
– Ultrasound: “snowstorm” appearance & absence of fetal
parts vaginal exam
– Treatment: removal of intrauterine contents • Treatment: hospitalization, bed rest, and C-section when fetal maturity
is attained

Abruptio Placenta Vasa Previa

• Third-trimester bleeding
• Premature separation of the placenta from uterine wall
• Shares some characteristics with placenta previa (vaginal bleeding)
• Severe abdominal discomfort and painful uterine contractions
• Fetal vessels traverse the fetal membranes over the
internal cervical os.
– If fetal vessels rupture fetal exsanguination can occur
© Kaplan

• Interferes with
• Clinical
oxygenation of the – Rupture of membranes, painless vaginal bleeding followed by
fetal bradycardia
fetus
• Treatment: • Diagnosis
hemodynamic – On ultrasound, vessels seen crossing cervical os
stabilization and • Treatment
delivery
– Immediate Cesarean section

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Placenta Previa vs Abruptio Placenta Fetal Distress

• Non-specific term referring to insufficient
Placenta Previa Abruptio Placenta
oxygen to fetus
Magnitude of Variable Variable
• Fetal heart tracings used to monitor fetal
blood loss heart rate and uterine activity
Duration Often stops within 1–2 hrs Usually continuous • Accelerations = normal
Abdominal None Can be severe
• Decelerations = not normal
discomfort – Early
FHR pattern Normal Tachycardia, then brady – Late
Decelerations present
Associated None • Cocaine use
– Variable
history • Abdominal trauma
• Maternal hypertension
• Multiple gestation

Dystocia Gestational Diabetes

• Abnormal progression of labor • Glucose intolerance identified during pregnancy
• Three categories of abnormality – Typically subsides postpartum

– Power: uterine contractions • Identified during prenatal screening

– Passenger: position, size, or presentation of the fetus – Screen at 24–28 wks
– Passage: pelvis/soft tissues – Positive if blood sugar >140 mg/dL with 1-hour glucose
challenge
• Treatment
• Risk factors
– Stage 1 of labor: if labor >14–20 hours, amniotomy or oxytocin
– History of gestational diabetes
– Stage 2 of labor: if stage >2 hours, increased risk of fetal
morbidity and mortality – Repeated spontaneous abortions

• Options include oxytocin or C-section – (+) family history

– History of infant weighing >4,000 g at birth

Gestational Diabetes: Treatment Premature Rupture of Membranes (PROM)

• Patient education • Rupture of chorioamniotic membrane before onset
• Diet of labor
• Insulin (if not well-controlled) • Associated with preterm labor, cord prolapse and
– Does not cross the placenta increased neonatal morbidity and mortality
• Oral hypoglycemic agents contraindicated except • Risk factors
glyburide – Sexually transmitted infections
– Glyburide does not cross the placenta – Smoking
• Goal is fasting blood sugar <95 mg/dL – Prior PROM
• Possible complications: – Prior preterm delivery
– Macrosomia, shoulder dystocia, neonatal hypoglycemia – Multiple gestations

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Premature Rupture of Membranes (PROM) Preterm Labor

• Diagnosis • Delivery which occurs prior to 37 weeks gestation
– Sterile speculum exam (test
– Most common cause of perinatal morbidity and mortality
for infection)
– Nitrazine test (amniotic fluid • Risk factors
pH >7.1)
– Prior history of preterm birth
– Fern test (amniotic fluid, fine
fern pattern) – PROM
• Treatment – African American
– Hospital admission
– Cervical insufficiency
– Await spontaneous labor
– Monitor for infection – Infection
• Chorioamnionitis: infection
of fetal membranes and – Placental abnormalities
© Jim Van Rhee
amniotic fluid – Smoking
– Treat with antibiotics
and delivery – Uterine enlargement or distortion

Preterm Labor Postpartum Hemorrhage

• Clinical • Common cause of maternal death within 24 hours of
– Signs and symptoms delivery
• Menstrual-like cramps; low, dull backache; abdominal – Sequelae include RDS, DIC, pituitary necrosis
pelvic pressure; abdominal cramping; uterine • Most common cause is uterine atony
contractions (often painless) • Risk factors
• Evaluation
– Prolonged labor
– Fetal monitoring
– Rapid labor
– Check status of cervix
– History of postpartum hemorrhage
– Rule out infection: UTI, group B strep
– Overdistended uterus
• Treatment
– Operative delivery
– Tocolytics: magnesium sulfate
– Beta adrenergic receptor agonists - terbutaline
– Corticosteroids: enhance fetal lung maturity

Uterine Atony Fetal Assessment: APGAR Score

• Due to failure of uterine corpus to contract Score of 0 Score of 1 Score of 2 Component of
Acronym
• Physical exam
Skin Blue or pale all • Blue at extremities• No cyanosis Appearance
– Uterus is soft and boggy; cervix is open color/Complexion over • Body pink • Body and
• Treatment (acrocyanosis) extremities pink

– Monitor for signs of shock (tachycardia, orthostatic, Pulse Rate 0 <100 ≥100 Pulse
narrow pulse pressure, decreased capillary refill) Reflex Irritability No response to Grimace/feeble cy Cry or pull away Grimace
stimulation when stimulated when stimulated
• Maintain blood pressure
– Transfuse blood, platelets, and FFP Muscle Tone None Some flexion Flexed arms and Activity
legs that resist
– Bimanual uterine massage extension
– Uterotonic agents: oxytocin, misoprostol
Breathing Absent Weak, irregular, Strong, lusty cry Respiration
gasping

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Professional Practice
Lecture 1 Legal/Medical Ethics

Professional Practice Lecture 2 Medical Informatics

Lecture 3 Patient Care/Communication

Lecture 4 Physician/PA Relationship

Jim Van Rhee, M.S., PA-C Lecture 5 Professional Development

Program Director; Associate Professor Lecture 6 Public Health
Yale School of Medicine, PA-Online
Lecture 7 Risk Management

Ethics- Four Basic Principles

• Autonomy
• Beneficence
• Non-maleficence
Legal/Medical Ethics • Justice

Autonomy
• Patient has freedom of thought, intention and
action when making decisions regarding
health care procedures
– For a patient to make a fully informed decision,
she/he must understand all risks and benefits of
the procedure and the likelihood of success
• A person should be free to perform whatever
action he/she wishes, regardless of risks or
foolishness as perceived by others, provided
it does not impinge on the autonomy of others
Autonomy
• Always respect the autonomy of the patient -
then the particular patient is free to choose
• Such respect is not simply a matter of
attitude, but a way of acting so as to
recognize and even promote the autonomous
actions of the patient
• The autonomous person may freely choose
loyalties or systems of religious belief that
may adversely affect him

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 2/1/19

Autonomy Autonomy
• The patient must be informed clearly of the • In the case of a child, the principle of avoiding the
consequences of his action that may affect him harm of death, and the principle of providing a
adversely. medical benefit that can restore the child to health
• Desiring to "benefit" the patient, the physician may and life, would be given precedence over the
strongly want to intervene believing it to be a clear autonomy of the child's parents as surrogate decision
"medical benefit." The physician has a duty to respect makers.
the autonomous choice of the patient, as well as a
duty to avoid harm and to provide a medical benefit.
• But the physician should give greater priority to the
respect for patient autonomy than to the other duties.
• However, at times this can be difficult because it can
conflict with the paternalistic attitude of many health
care professionals.

The Patient Self-Determination Act

Adjustments to Autonomy
Institutions Receiving Medicare And Medicaid
Autonomy is not Absolute
• All adult patients must be notified in writing at the
• Contextual — depending on values, priorities, needs, time of admission
social configurations – Right to refuse treatment
– Rights under state laws regarding advance directives
• Limits on choices
– Summaries of institution’s policies regarding withholding and
– Unacceptable medical practice
withdrawing of life-sustaining treatments
– Non-beneficial treatment
• Institutions may not discriminate about advance
• Uncertainties and probabilities
directives
– Violates deeply held beliefs of caregiver
– Limited resources • Notification must be documented
– No decisional capacity • Advance directive information must be documented
• On-going staff and community education programs
on advance directives

Beneficence Adjustments To Beneficence

• The practitioner should act in “the best interest” of the • Patient’s values and priorities
patient - the procedure be provided with the intent of • Patient’s exercise of autonomy
doing good to the patient
• No benefit from intervention
• One should render positive assistance to others and • Disproportional burdens
abstain from harm (minimalist principle of non-
maleficence) by helping them to achieve benefits • Lack of costworthiness
which will further their important and legitimate • Limitations on resources
interests
• Harm principle as a form of beneficence
– Prevent an individual from harming another
• This needs health care provider to:
– Develop and maintain skills and knowledge by continually
updating training
– Consider individual circumstances of all patients

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 2/1/19

Non-Maleficence Non-Maleficence
• “Above all, do no harm,“ – Make sure that the • Physicians are obligated to not prescribe medications
procedure does not harm the patient or others in they know to be harmful.
society • Some interpret this value to exclude the practice of
• When interventions undertaken by physicians create euthanasia
a positive outcome while also potentially doing harm • Violation of non-maleficence is the subject of medical
it is known as the "double effect." malpractice litigation

• E.g., the use of morphine in the dying patient eases

pain and suffering while hastening the demise
through suppression of the respiratory drive

Medical Malpractice Justice

• An act or omission by a health care provider that
deviates from accepted standards of practice in the
medical community which causes injury to the
patient.
• The distribution of scarce health resources, and the
decision of who gets what treatment “fairness and
equality”
• The burdens and benefits of new or experimental
treatments must be distributed equally among all
groups in society
• The four main areas that Health care provider must
consider when evaluating justice
– Fair distribution of scarce resources
– Competing needs
– Rights and obligations
– Potential conflicts with established legislations

Morally Relevant Differences Adjustments To Justice

• A feature which is • Possible Morally Relevant • Compassion
considered so significant Differences In Healthcare • Medical uncertainties/probabilities
that it separates – Disease — reversible vs.
• High tolerance for risks
individuals into groups Chronic vs. Terminal
which are then treated in – Age • Borderline morally relevant differences
notably distinct ways – Need • Institutional mission considerations
• What counts as a morally – Merit

relevant difference is – Ability to contribute to

society
determined in an ongoing
– Ability to pay
dialogue in society which
– Documented wishes
continually reassesses the (advance directives)
significance of the
characteristic

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Professional Practice
Lecture 1 Legal/Medical Ethics

Lecture 2 Medical Informatics

Lecture 3 Patient Care/Communication

Lecture 4 Physician/PA Relationship

Lecture 5 Professional Development

Lecture 6 Public Health

Lecture 7 Risk Management

PAs Can Perform Services Traditionally Difference Between PAs and NPs:
Reserved for Physicians Direct Billing/Payment
PAs NPs
• 190 Physician Assistant Services • Medicare does allow PAs to • NPs may direct bill under their
– “PAs may furnish services billed under all levels of submit claims under their own NPI and receive direct
CPT evaluation and management codes, and NPI payment from Medicare.
diagnostic tests if furnished under the general • Medicare does not allow PAs • NPs may reassign reassign
to direct bill/receive direct their payment to their
supervision of a physician.” payment; while the claim is employer.
submitted under the PA’s NP, • However, most NPs reassign
the payment field is to the PA’s as a condition of their
employer. employment.
• Payment is not associated with
supervision/collaboration,
although
supervision/collaboration is
required by Medicare.

Summary Medicare Language for PA Services

• PAs and NPs are recognized as enrolled “non- Medicare benefit policy states:
physician providers”, “ordering/referring” providers, • “The physician supervisor (or physician designee) need
and “eligible providers” in the Medicare program. not be physically present with the PA when a service is
• Covered services are those that a physician would being furnished to a patient and may be contacted by
otherwise have to provide. telephone, if necessary, unless State law or regulations
• Must be enrolled in Medicare if ordering, referring require otherwise.”
and/or billing.
• Reimbursement for the services by PAs and NPs are
reimbursed at 85% of the physician fee schedule.
• There are provisions for 100%, such as incident-to in
the office and shared visits in the hospital setting;
specific rules apply.

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Summary: Collaboration Guidelines

• At the highest level, supervision/collaboration is
defined by state law

• Policy for supervision/collaboration is essentially

same for PAs and NPs

• Medicare Conditions of Payment and Medicare

Medicare Billing and
Conditions of Participation require that PAs/NPs are
supervised by an MD/DO.
Reimbursement

Medicare Topics Why only 85%?

• Incident to billing
– Physician must personally perform the initial visit • This still generates profit because:
– Never applies in a facility/provider-based setting – PAs are paid approximately one-half to one-third the salary
– Must be employed by the same entity of the physician counterpart
• Shared Visit – The profit/contribution margin is greater when PA provides
the services, even at the 85% reimbursement rate.
– Physician must have face-to-face visit with patient
• Co-signature is not sufficient
– There are specific physician documentation requirements Physician PA
– Must be employed by the same entity Annual Salary $114/hour $48/hour
Admission H&P (99221) is 100% for $102 85% for $87
• New Patients/New Problems reimbursed
– PAs may provide evaluation and management services to Profit Minus $12 Plus $39
new patients and established patients with new problems in
the Medicare program
– When they do, the encounter should be billed under the PAs
NPI for Medicare
– Reimbursement will be at 85% of the physician rate

Medicare
• PAs are recognized as enrolled “non-physician
providers”, “ordering/referring” providers, and “eligible
providers” in the Medicare program
• PA covered services are those that a physician would
otherwise have to provide, covered under Part B
• Must be enrolled in Medicare (PECOS) if ordering,
referring and/or billing. Need an NPI and must have
an employer first
Payer Enrollment • Reimbursement for services provided by PAs are
reimbursed at 85% of the physician fee schedule

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Medicaid Commercial Payers

• Medicaid programs in all states and DC pay for • Private payers may have their own rules
services provided by PAs • Many choose not to enroll PAs
– Reimbursement ranges from 70-100% of the physician rate – They do however pay for services provided by PAs

• Medicaid enrolls or identifies the PA on the claim as • If not enrolled the claim is submitted under the
the billing provider in 40 states physician's number
• 10 states and DC do not recognize PAs as billing • Many do not discount; payment is at the physician
rate
providers
– Claims are submitted under the physician
• The organization billing must ascertain claims
methodology and payment rate for each payer with
– But the PAs must be enrolled
whom they contract
• Some states Medicaid programs do not cover
services provided in hospitals and/or first assist
services

Part B: Incident-to
• Incident to is a Medicare office billing provision that
allows reimbursement for services delivered by PAs
at 100% of the physician fee schedule, provided that
all incident to criteria are met.
– Incident to billing only applies to the office
– Does not apply in a facility (hospital) setting.
• Incident to does not apply to commercial payers unless
specified in policy.
Medicare: Incident-to

Incident-to Rules
Incident-to Rules for the Office Setting
• The physician must have some ongoing participation
• Initial visit • Follow up Visit in the patient’s care.
– The physician must have – A physician, does not
personally treated the need to be the same • This must be reflected in the medical records
patient on his or her physician, is within the somewhere
initial visit for the same suite of offices – In the event of an audit
particular medical when the PA renders the
problem and established service upon the patient’s • If all requirements are met, encounter can be billed
the diagnosis and return for follow-up for under the physician’s NPI for 100% reimbursement
treatment plan. the same problem.
– This cannot be a shared – Following the treatment • If all are not met, bill under the PA’s NPI
visit. plan established by the – Reimbursement will be at 85%
physician.

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Documentation Required
• A clearly stated reason for visit
• Date of the service provided
Professional Practice
Lecture 1 Legal/Medical Ethics
• Signature of the person providing the service
• The patient's progress. Response to, and Lecture 2 Medical Informatics

changes/revision in the plan of care. Lecture 3 Patient Care/Communication

Lecture 4 Physician/PA Relationship

• While a co-signature of the supervising physician is not
required, evidence of that the supervising physician was Lecture 5 Professional Development
involved in the care of the patient and was present and Lecture 6 Public Health
available during the visit.
Lecture 7 Risk Management

The BASICS of Informed Consent The BASICS of Informed Consent

1. Provider decides management needed
2. Capacity: Patient or surrogate (agent)
3. Competence of MD, Resident, Physician
Assistant
4. Patient understands the illness
5. Goal or nature of Proposed Treatment
6. All reasonable treatment options
7. Include the option not to undergo treatment
8. The most likely benefits and burdens for
each of the reasonable options
9. Your recommendation, and reasons
10. Did the patient understand what you said?

The BASICS of Informed Consent When to Get Signed Informed Consent

11. Providers financial and research interests 1. Prior to all invasive or operative procedures
12. Possible presence of Industry 2. For administration of blood
manufacture s representative being present. 3. For use of investigational drugs or treatment
13. Both provider and patient sign and date - Research
14. Witness needed ONLY if signed with X or - Unapproved use
obtained telephonically 4. When patient seems reluctant?
15. Good for 90 days, or until situation changes 5. Before examining

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AMA- 1995 Guidelines

Professional Practice
Lecture 1 Legal/Medical Ethics “The role of the physician assistant(s)
Lecture 2 Medical Informatics
in the delivery of care should be
defined through mutually agreed upon
Lecture 3 Patient Care/Communication
guidelines that are developed by the
Lecture 4 Physician/PA Relationship
physician and the physician assistant
Lecture 5 Professional Development and based on the physician’s
Lecture 6 Public Health delegatory style.”
Lecture 7 Risk Management

PAs and Physicians: Clinical Colleagues Why does this relationship work?
• Shared knowledge base
While many laws and regulations use the term – Trained in medical model
“supervision,” the professional relationship between PAs • Communication, Coordination, and Continuity of Care
and physicians is collaborative and collegial. The regulatory – Clear lines of communication
term “supervision” does not mean that the physician must • Autonomous medical decision-making
be physically present or direct every aspect of PA practice. – Autonomy is delegated by the physician
Far from it— many PAs practice with a high degree of
• Agency relationship
autonomy, with a physician available by phone or other
– PAs are agents of the supervising physician
electronic means. PAs become more autonomous over
– 3 factors
time, as they grow in skill and experience.
• Physician consents to the relationship
• Physician accrues some degree of benefits from the acts
of the PA
C aw ley JF , B ush E . Levels of supervision am ong practicing
physician assistants. JA A P A . 2015;28(1):61-2. • Physician has some degree of control of, or right to
control, the PA

Six Key Elements of Modern PA Practice Act Key Points

• Licensure as the regulatory term • Physician-PA team is a proven model for high-quality,
• Full prescriptive authority cost effective care
• Scope of practice determined at the practice level • Encouraged training programs to promote and
• Adaptable collaboration requirements support opportunities to precept students and
participate in the education
• Co-signature requirements determined at the practice
• Encourage interdisciplinary education
level
• Physician representation on accrediting and
• Number of PAs a physician may collaborate with
certification bodies
determined at the practice level
• Investigate workforce issues
• Encourage flexibility in federal and state regulation so
• https://www.aapa.org/wp-
content/uploads/2017/01/Issue-brief_Six-key- that each medical practice determines appropriate
clinical roles within the medical team
elements_0117-1.pdf

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Common Types of Malpractice Malpractice Lawsuit Timeline

• Failure to diagnose a medical condition } Act or omission
• Prescription errors
} Summons and complaint is issued
• Failure to perform surgery or other medical procedure
properly } Pretrial alternatives/motions—
• Delay in treatment interrogations and depositions
• Failure to fully explain a medical procedure or
} Trial—typically 2-5 years after
potential side effects issuance of complaint
• Improper treatment
} Verdict

} Payment or appeal

Statute of Limitations Elements of Medical Negligence

• Why have a statute of limitations? • 4 elements must be present and proven:
– Duty
• Statute of limitations sets time limits within which – Breach of duty
suits may be initiated – Injury or damages
– Varies from state to state – Causation
– Generally 2 years • Burden of proving the negligence is on the
plaintiff and the jury must be convinced of the
plaintiff's proof by a “preponderance of the
evidence”

Duty Standard of Care

• Owing a duty to another implies that a
relationship exists between the parties
• The plaintiff must prove a patient-clinician
relationship existed
• May be expressed or implied
• A patient-clinician relationship has certain
obligations associated with it for both parties
• Standard of care defines the scope of these
obligations

• A reasonably prudent PA has the knowledge

and skills possessed normally and ordinarily
in the PA profession

9

Standard of Care
• Standard of care varies from case to case
• The manner in which a particular patient
should have been treated with a particular
condition can be established by various
means:
– Both plaintiff and defendant will produce evidence
of what they believe to be the standard of care
– The jury will determine, based on the
preponderance of evidence, which standard
should be applied
Breach of Duty
• The jury has to be convinced that the clinician
did not meet the standard of care
• Can either be an act of omission or an act of
commission
• Evidence can come from different sources:
• Medical record, depositions, etc.
Causation
• Many factors can contribute to the injury
– Vicarious liability
– Noncompliance by the patient
• Contributory negligence
• Comparative negligence
• Informed consent and the principle of autonomy and
self-determination
– May be implied or expressed
– May also be substituted
• Children and incompetent adults
• What constitutes proper informed consent?
– More in ethics course
2/1/19
Standard of Care
• Most states have a national standard of care, which
implies that the quality of care should be the same
regardless of geographic location
– Is this true?
• If the national standard of care is accepted, experts
from anywhere in the nation can testify
• Some states have a local standard or locality rule
– This holds a clinician to a standard of reasonable prudence
as practiced in the same or similar location
– Expert witnesses must be from the same community or a
community with similar size and resources
Causation
• The plaintiff must prove the breach of duty
caused the bad outcome in the patient
• Usually, the most difficult part of the case to
prove
• Plaintiff must show “proximate” cause of the
bad outcome
– The acts of the defendant were a substantial factor
in producing the injury to the patient
Sufficiency
• Sufficiency of information is determined by the
jurisdiction, with 3 different standards
– What would a reasonable clinician reveal under similar
circumstances?
– Ask the injured party if the information was sufficient for
them to make an informed decision
– The jury is asked to determine what information a
reasonable person would have required under the
circumstances to make an informed decision
• At a minimum, sufficient information should include:
– Risks, both inherent and potential
– Benefits, including the likely outcome
– All available alternative treatments, including no treatment
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Injury/Damage
• Injuries can be physical, mental, or financial
• Includes pain and suffering, past and future medical expenses, Professional Practice
and financial losses Lecture 1 Legal/Medical Ethics
– Some of these are easily calculated; others not so easy
– Plaintiff’s attorney must provide evidence that the nature and Lecture 2 Medical Informatics
duration of the pain and suffering is sufficient to deserve
compensation Lecture 3 Patient Care/Communication
– Intangible injuries
Lecture 4 Physician/PA Relationship
– Some states have laws limiting the amount of damages
• Damage caps sets upper limits on the amount a defendant Lecture 5 Professional Development
must pay
• Can prevent the plaintiff from being fully compensated for their Lecture 6 Public Health
injuries
– Loss of consortium can be claimed by spouse and/or family of an Lecture 7 Risk Management
injured or dead patient
• Punitive damages are awarded to punish the defendant, not to
compensate the plaintiff

Definition of EBM Why?

• Evidence-based medicine (EBM) has been defined • Most physicians pay attention to changing knowledge
as "the conscientious, explicit, and judicious use of in their field and specialty, spending approximately
current best evidence in making decisions about the two hours per month in self-education, but still fall
care of individual patients. The practice of evidence behind in staying abreast.
based medicine means integrating individual clinical • Good clinicians use both individual clinical expertise
expertise with the best available external clinical and the best available external evidence, and neither
evidence from systematic research."(1) alone is enough.
• More recently it has been described as the
"integration of best research evidence with clinical
expertise and patient values."(2)
• David Sackett, et al. "Evidence Based Medicine: W hat It Is and W hat It Isn't," BMJ 312,
no.7023,71-72 (1996).
• David Sackett, et al. Evidence-Based Medicine: How to Practice and Teach EBM (New
York: Churchill Livingstone, 2000), 1.

WHY? Life Long Learning

• EBM is not cookbook medicine.
– Requires a bottom up approach that integrates the best
external evidence with clinical expertise and patients’ choice.
– Question you have focus on the individual patient and
problem, not a group.
• The practice of evidence-based medicine is a process of
lifelong, self-directed, problem-based learning in which caring
for one's own patients creates the need for clinically important
information about diagnosis, prognosis, therapy and other
clinical and health care issues.
• Instead of routinely reviewing the contents of dozens of journals
for interesting articles, EBM suggests that you target your
reading to issues related to specific patient problems.
Developing clinical questions and then searching current
databases may be a more productive way of keeping current
with the literature.
• Evidence-based medicine "converts the abstract exercise of
reading and appraising the literature into the pragmatic process
of using the literature to benefit individual patients while
simultaneously expanding the clinician's knowledge base."
(Bordley DR, 1997)

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Components of EMB Ask the Clinical Question

• Ask the clinical question • Patient
– Three elements: patient, intervention, expected outcome – Describe the patient in terms of age, sex, ethnic group
• Find the best evidence – Describe the clinical problem in terms of the patient’s
disease or general health condition
– Usable search strategy
– Databases • Intervention
– Browse – Clinical examination, prevention, prognosis, etiology,
differential diagnosis, diagnosis tests, self-improvement
• Critique the evidence
– Is the evidence valid and important?
• Expected outcome
• Apply the evidence
• Evaluate the performance

Find the Best Evidence Critique the Evidence

• Translate the clinical question into a useable search
strategy
• Select appropriate database resource
• Enter your search strategy
• Browse the records located to identify those that are
the best
• Is the evidence valid? Is it true, accurate, correct?
• Is the evidence important?
• Is it useful in clinical practice?
• Uses a variety of different strategies to evaluate
evidence.

Apply the Evidence Remember not all Stats are Great

• Integrate the evidence into clinical practice

USA Today has come out with a new
survey - apparently, three out of every
four people make up 75% of the
Evaluate the performance population.

- David Letterman

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Certification Maintenance CME: Defining the Terminology

• 10-year certification maintenance cycle comprised of • Category I CME –The activity or provider is
5 two-year blocks preapproved by the AAPA, ACCME, AAFP, AMA or
– Log 100 hours of CME every two years AOACCME.
• At least 50 Category I (Preapproved) hours • Minimum requirement: 50 hours per two-year cycle
• How do you know it’s Category I? Some clues:
– Pass the Physician Assistant National Recertifying
– Certificate upon completion that makes reference to one of
Exam (PANRE) in year 9 or
the sponsors.
year 10 of your ten-year cycle.
– Someone paid for you to participate.
– Any doubt? Contact the provider.

CME: Defining the Terminology

• Category II (Elective) CME – Any other practice-
related educational activity pursued outside of your
Professional Practice
employment. No minimum requirement. Lecture 1 Legal/Medical Ethics

• Category II hours should be logged hour-per-hour. Lecture 2 Medical Informatics

• Some examples:
Lecture 3 Patient Care/Communication
– reading medical journals
– postgraduate coursework Lecture 4 Physician/PA Relationship
– precepting
Lecture 5 Professional Development
– even time spent studying for PANRE
Lecture 6 Public Health

Lecture 7 Risk Management

Ten Great Public Health Ten Great Public Health Achievements—

Achievements—U.S. 1900-1999 U.S. 2001-2010
• Vaccine-Preventable Diseases
• Prevention and Control of Infectious Diseases
• Tobacco Control
• Maternal and Infant Health
• Motor Vehicle Safety
• Cardiovascular Disease Prevention
• Occupational Safety
• Cancer Prevention
• Childhood Lead Poisoning Prevention
Image Source: www.whatispublichealth.org ; CDC. Ten great public health achievements – United States, 1900-1999. MMWR. 1999; 48(12):241-3.
• Public Health Preparedness and Response

- T en G reat P ublic H ealth A chievem ents--U nited S tates, 2001— 2010. M M W R . 2011; 60(19);619-623.

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10 Essential Public Health Services The Disciplines of Public Health*

Environmental Health

• Monitor health status to identify community health problems. • A ir quality; food protection; radiation protection; solid w aste m anagem ent; hazardous w aste m anagem ent; w ater quality;
noise control; environm ental control of recreational areas, housing quality, vector control

• Diagnose and investigate health problems and health hazards in Epidemiology

• The study of the occurrence and distribution of health-related states or events in specified populations, including the study
the community. of the determ inants influencing such states, and the application of this know ledge to control the health problem s. Ŧ
Health Services Administration/Management
• Inform, educate, and empower people about health issues.
• M anaging the database at a school clinic; developing budgets for a health departm ent; creating policies for health
• Mobilize community partnerships to identify and solve health insurance com panies; directing hospital services
International/Global Health
problems.
• A ddressing health concerns from a global perspective, am ong different cultures in countries w orldw ide
• Develop policies and plans that support individual and community Maternal Child Health
health efforts. • P roviding inform ation and access to birth control; prom oting the health of a pregnant w om an and an unborn child;
dispensing vaccinations to children
• Enforce laws and regulations that protect health and ensure safety. Nutrition
• Link people to needed personal health services and assure the • P rom oting healthy eating and exercise; researching the effect of diet on the elderly; teaching the dangers of overeating
and over dieting
provision of health care when otherwise unavailable. Public Health Laboratory Practice

• Assure a competent public health and personal healthcare • D iagnosing, preventing, treating, and controlling infectious and chronic diseases in com m unities, as w ell as environm ental
health and new born screening.
workforce. Public Health Policy

• Evaluate effectiveness, accessibility, and quality of personal and • A nalyzing the im pact of seat belt law s on traffic deaths; m onitoring legislative activity on a bill that lim its m alpractice
settlem ents; advocating for funding for a teen anti-sm oking cam paign

population-based health services. Public Health Practice

• A n interdisciplinary field that requires nurses, physicians, veterinarians, dentists and pharm acists; a degree in public health
• Research for new insights and innovative solutions to health practice enables clinicians to apply public health principles to im prove their practice

problems. *Adapted from: http://www.whatispublichealth.org/what/index.html#Practice

ŦPorta M, ed. A Dictionary of Epidemiology. 5th ed. New York, NY: Oxford University Press; 2008.

Perspectives of
Healthy People 2020: Goals
Public Health and Medicine
Public Health Medicine
• Attain high-quality, longer lives free of preventable
Primary focus on population Primary focus on individual
1 disease, disability, injury, and premature death

Public service ethic, tempered by Personal service ethic, conditioned by

concerns for the individual awareness of social responsibilities
• Achieve health equity, eliminate disparities and
2 improve health for all groups
Emphasis on prevention, health Emphasis on diagnosis and treatment,
promotion for the whole community care for the whole patient

• Create social and physical environments that

Public health paradigm employs a Medical paradigm places predominant promote good for all
spectrum of interventions aimed at the emphasis on medical care 3
environment, human behavior and
lifestyle, and medical care
• Promote quality of life, healthy development, and
Multiple professional identities with Well-established profession with sharp 4 healthy behaviors across life stages
diffuse public image public image
w w w .healthypeople.gov
Table 1. Perspectives of medicine and public health from: Fineberg HV. Public health and medicine: where the twain shall meet.
Am J of Prev Med. 2011;41(4S3):S141-S143.
Harvey Fineberg, M.D., Ph.D. 1990

Factors That Affect Health

What are Determinants of Health?
Examples
Smallest
• Policymaking Impact Condoms, eat healthy,
be physically active
• Social factors Counseling
& Education
– Social Determinants
Rx for high blood
– Physical Determinants pressure, high
Clinical
cholesterol
• Health services Interventions

• Individual behavior Immunizations, brief

intervention, cessation
Long-lasting
• Biology and genetics Protective Interventions
treatment, colonoscopy

Fluoridation, 0g trans
fat, iodization, smoke-
Changing the Context
to Make Individuals’ Default free laws, tobacco tax
Decisions Healthy
Largest
Impact Poverty, education,
housing, inequality
Socioeconomic Factors

Frieden TR. A framework for public health action. Am J Public Health. 2010;100(4):590–595.

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Clinical Prevention and Public Health: Burden of Disease

Actual Causes of Death
• Is the impact of a health problem as measured by
financial cost, mortality, morbidity, or other indicators.
• Quantified in terms of quality-adjusted life years
(QALYs) or disability-adjusted life years (DALYs),
both of which quantify the number of years lost due to
disease (YLDs)

Definition Four A’s of Public Health

• One DALY can be thought of as one lost year of • Affordability
"healthy" life. The sum of these DALYs across the
population, or the burden of disease, can be thought
• Acceptability
of as a measurement of the gap between current • Accessibility
health status and an ideal health situation where the • Appropriateness
entire population lives to an advanced age, free of
disease and disability.

• DALYs for a disease or health condition are

calculated as the sum of the Years of Life Lost (YLL)
due to premature mortality in the population and the
Years Lost due to Disability (YLD) for people living
with the health condition or its consequences.

Affordability
Questions of the costs to consumer and financial
viability of service provider
• Out of pocket expenses to consumer - pricing and pricing policy
[eg., sliding fee scale, co-payments, deductibles, exclusions
• Ability to acquire third party coverage – eligibility rules,
administrative process/requirements to document eligibility (e.g.,
Birth certificates with raised seal, rent receipt in own name) –
relationship between multiple funding streams
– Comparison of actual enrollment with estimated eligibles
• Level of adequacy of direct funding to service provider from
local, state, federal authorities to support adequate supply of
quality services (direct grants and contracts, fee scale, case
rate, capitation rate)
Acceptability
Questions of the degree to which the recipient of
services believes that the services are congruent
with cultural beliefs, values, world view
• Services offered within the context of the norms and values of
the cultural group – including who is to be included or not
included in decision making
• Use of persons that the cultural group deems as appropriate
service providers – by race/ethnicity, discipline/education,
western or nonwestern provider indigenous, sexual
orientation/gender identity
• Role of stigma within the cultural community
• Demonstration of respect and honor of norms and values
– Premature termination rates
– Utilization rates
– Participation rates
– Satisfaction rates

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Accessibility
Questions of ease and convenience to obtain and
use the services
• Referral process, wait time for appointment, wait time for
service, hours and days of operation, travel time, travel access-
by car, parking, public transportation – routes (any transfers?
How many?, costs, availability, schedule, cab – ease of getting,
costs, physical accessibility, child care, language, interpreters,
translation)
– Penetration rates
• Consider the system within which the services are made
available – private/public, health, mental health, criminal justice,
child welfare, school, employer (EAP), etc.
Availability
Questions of existence of the service
• Does the service exist where people live their lives
(live, work, study, play, shop, worship, etc.)
• If so, in adequate supply
Surveillance
• An ongoing, systematic collection, analysis and
interpretation of health-related data essential to the
planning, implementation, and evaluation of public
health practice
• Surveillance is undertaken to inform disease
prevention and control measures
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Appropriateness
Questions of correctness of service
offered/provided for prevention and treatment
• Screening and assessment tools and processes take cultural
issues into account in the construction, implementation and
analysis
• Diagnoses are accurate and appropriate for context of
population
• Interventions including medications are designed to achieve
optimal outcomes for the context of the recipient of services
(consider dosage, intensity of service, duration of services,
location of service (e.g., home, facility, school, church, etc.),
level of restrictiveness of care, etc.
• Communicated within the language that is meaningful to the
service recipient for the nature of the service
Public Health Tools
• Recognize public health tools to address the burden
of disease:
• Surveillance
• Reporting
• Intervention
Surveillance
Why is surveillance needed?
• Serve as an early warning system, identify public
health emergencies
• Guide public health policy and strategies
• Document impact of an intervention or progress
towards specified public health targets/goals
• Understand/monitor the epidemiology of a condition
to set priorities and guide public health policy and
strategies
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Surveillance
An effective surveillance system has the following
functions:
• Detection and notification of health events
• Collection and consolidation of pertinent data
• Investigation and confirmation (epidemiological,
clinical and/or laboratory) of cases or outbreaks
• Routine analysis and creation of reports
• Feedback of information to those providing the data
• Feed-forward (i.e. the forwarding of data to more
central levels)
• Reporting data to the next administrative level
Reporting
• Category 1 Diseases
– Report immediately by telephone on the day of
recognition
– Examples: anthrax, cholera, measles, TB
• Category 2 Diseases
– Report by mail within 12 hours
– Examples: gonorrhea, hepatitis, HIV
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Reporting
Persons Required to Report Reportable Diseases,
Emergency Illnesses and Health Conditions:
• Every health care provider who treats any person
who has or is suspected to have a reportable
disease, emergency illness or health condition shall
report the case to the public health department
• If the case or suspected case of reportable disease,
emergency illness or health condition is in a health
care facility, the person in charge shall ensure that
reports are made.
Intervention
• Activities taken on behalf of the public or an
individual
• Examples:
– Health teaching
– Outreach
– Screening
– Coalition building
– Advocacy
Epidemiology
• Epidemiology is the study of the distribution and determinants of
health-related states within a population. It refers to the patterns
of disease and the factors which influence those patterns
• Endemic: The usual, expected rate of disease over time; the
disease is maintained without much variation within a region
• Epidemic: Occurrence of disease in excess of the expected
rate; usually presents in a larger geographic span than
endemics (epidemiology is the study of epidemics )
– Pandemic: worldwide epidemic
– Epidemic curve: Visual description (commonly histogram) of an
epidemic curve is disease cases plotted against time; classic
signature of an epidemic is a “spike” in cases during a period of
time
• Incubation period is the period of time from the point of infection
to the onset of clinical illness
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Epidemiology
• Health service interventions are evaluated using the
following concepts/metrics:
– Efficacy: performance of an intervention under optimal
conditions, e.g., prophylactic medications in a clinical trial
– Effectiveness: actual results in the real world, e.g., treatment
outcomes in the community
– Efficiency: a ratio of the benefit compared to the cost
associated with an intervention (high efficiency would deliver a
greater benefit at minimal cost)
• Upper and lower bounds account for uncertainty of the
estimate (most commonly 95% confidence intervals)
Prevention
• The goals of prevention in medicine are to promote
health, preserve health, restore health when it is
impaired, and minimize suffering and distress.
• These goals aim to minimize both morbidity and
mortality.
– Primary prevention is the promotion of health at both
individual and community levels; this is done by facilitating
health-enhancing behaviors, preventing the onset of risk
behaviors, and diminishing exposure to environmental
hazards. Primary prevention efforts decrease disease
incidence.
– Secondary prevention is the screening for risk factors and
early detection of asymptomatic or mild disease, permitting
timely and effective intervention and curative treatment.
Secondary prevention efforts decrease disease prevalence.

Prevention
• The goals of prevention in medicine are to promote
health, preserve health, restore health when it is
Professional Practice
impaired, and minimize suffering and distress. Lecture 1 Legal/Medical Ethics

• These goals aim to minimize both morbidity and Lecture 2 Medical Informatics
mortality.
Lecture 3 Patient Care/Communication
– Tertiary prevention is the reduction of long-term impairments
and disabilities and prevention of repeated episodes of Lecture 4 Physician/PA Relationship
clinical illness. The goals of tertiary prevention are to prevent
recurrence and slow progression. Lecture 5 Professional Development
– Primordial prevention is a newer concept in disease
prevention. It targets the most distal determinants of health Lecture 6 Public Health
(social, economic, environmental, and cultural).
Lecture 7 Risk Management

Quality
Carrying out interventions correctly
according to pre-established standards and
procedures, with an aim of satisfying the
Quality Improvement customers of the health system and
maximizing results without generating
health risks or unnecessary costs.
Part 1

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Definitions Definitions
• The Merriam-Webster Dictionary (2017) defines • The National Association of Quality Assurance
quality as “degree of excellence” or a “superiority in Professionals describes quality as “the level of
kind.” excellence produced and documented in the process
of patient care, based on the best knowledge
• The Agency for Health Care Research and Quality available and achievable at a particular facility.”
defines quality as “the degree to which health care
services for individuals and populations increase the • The Community Health Accreditation Program
likelihood of desired health outcomes and are defines quality as “the degree to which consumers
consistent with current professional knowledge.” progress toward a desired outcome.”

You have to define it before you can Problems and Opportunities

measure it...
• Enormous, unexplained variations in practice
• “The degree to which health services for individuals patterns
and populations increase the likelihood of desired • Explosion in knowledge
health outcomes and are consistent with current
professional knowledge.” • Focus on quality and patient safety
– Institute of Medicine, 1990 • Democratization of medical knowledge
• “Doing the right thing at the right time in the right way
for the right person and having the best results
possible.”
– Agency for Healthcare Research and Quality

To Err is Human Crossing the Quality Chasm

• Serious and widespread quality problems exist • “Americans should be able to count on receiving care
throughout American medicine that uses the best scientific knowledge to meet their
• Very large numbers of Americans are harmed as a needs, but there is strong evidence that this is
direct result frequently not the case”
• Current efforts to improve will not succeed unless we – William C. Richardson, IOM Committee Chair and
President of the W.K. Kellogg Foundation
undertake a major, systematic effort to overhaul how
we deliver health care services, educate and train
clinicians, and assess and improve quality • Reorganization and reform are urgently needed to fix
a disjointed and inefficient system
– IOM, 2001

IOM, Consensus Statement, National Roundtable on Health Care Quality , JAMA, 16 Sep 98

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Quality Problems Equity is a key component of quality

• Under use of proven effective interventions • Disparities exist across several of the quality domains
– Beta blockers outlined in Crossing the Quality Chasm
– Failure to immunize – Effectiveness
– Prenatal care begun too late • Blacks are less likely to be screened for colorectal cancer than
whites and more likely to be diagnosed at advanced stages
• Overuse
– Safety
– Antibiotics for colds
• Hispanics have a higher rate of in-hospital death following
– Surgery performed for clearly inappropriate indications complications of care than non-Hispanic whites
• Misuse – Timeliness
– Prescribing errors • Asians 2x more likely than whites to report trouble receiving
care as soon as needed, blacks 1.5x more likely to leave the
ER without being seen
– Patient-centeredness
• Poor patients 2x more likely to report poor communication with
health care providers than high income patients

Select Indicators Barriers to Quality Improvement

• Only 55% of patients receive recommended care • Individuals are not usually the problem; systems are
• Medication-related errors for hospitalized patients • Explosion in knowledge
cost $2B/year • Information infrastructure
• Lag between discovery of more effective forms of • Culture
treatment and incorporation into practice averages 17
years
“Our present efforts resemble a team of engineers
trying to break the sound barrier by tinkering with a
Model T Ford.”
-IOM consensus statement

Bad Apples vs. Continuous Improvement Reliable, Honest and Patient Centered:
What About Physician Measures?
Volume data for selected NHC HEDIS Data, eg:
BAD APPLES CQI procedures, eg: • Breast & Cervical Cancer Screening

• Cardiac procedures • Chlamydia Screening

• Kill the messenger • Every defect is a • Total joint replacement
• Colorectal Screening

• Distort the data or treasure • Prostatectomy

• Childhood immunization status
• Flu shots, pediatric & adults
change the • Problems are built into • Heart transplant • Cholesterol management for patients
measurement processes • Solid organ transplant with CVD (LDL-C screening)
• Laminectomy • Comprehensive Diabetes Care
• Turn somebody else in • Understand and • Cholecystectomy Screening
improve the processes • Bariatric surgery: lap band and
– Eye Examination
– LDL-C Screening Performed
• Harness entire team in Roux-en-Y
– HbA1c testing
improvements • Minimally invasive procedures (all) – Nephropathy Monitoring
• Robotic procedures: gyne/onc, – Examination of feet (non-Hedis
urologic measure)
• Controlling high blood pressure
• Getting care quickly (emergent,
urgent, routine, preventive)

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Crossing the Quality Chasm: Simple Rules for Health Care

“STEEEP”
• Patients should not be harmed by the care that is
intended to help them (Safe)
Current Approach
• Unnecessary waits and harmful delays should be Do no harm is an individual responsibility.
reduced (Timely)
• Care should be based on sound scientific knowledge
(Effective) New Rule
• Care shouldn’t be wasteful (Efficient) Safety is a system property.
• Care shouldn’t vary in quality because of patient
characteristics (Equitable)
• Care should be responsive to individual preferences,
needs, and values (Patient-centered)
» IOM, 2001
IOM, Crossing the Quality Chasm

Simple Rules for Health Care Simple Rules for Health Care

Current Approach Current Approach

Professionals control care.
New Rule
The patient is the source of control.
Decision making is based on training and
experience.
New Rule
Decision making is evidence based.

IOM, Crossing the Quality Chasm IOM, Crossing the Quality Chasm

Simple Rules for Health Care Simple Rules for Health Care

Current Approach Current Approach

Information is a record. Secrecy is necessary.

New Rule New Rule

Knowledge is shared and information Transparency is necessary.
flows freely.

IOM, Crossing the Quality Chasm IOM, Crossing the Quality Chasm

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What is QI?
• Quality Improvement is a formal approach to the
analysis of performance and systematic efforts to
improve it. There are numerous models used. Some
commonly discussed include:

Quality Improvement – CQI: Continuous Quality Improvement

– TQM: Total Quality Management
• These are various models to get at the same thing:
Part 2 improvement. All of these are forms of ongoing effort to
make performance better.
• In industry, they talk about product failures or work-
related injuries. In administration, one can think of
increasing efficiency or reducing re-work. In medical
practice, the focus is on reducing medical errors and
needless morbidity and mortality.

What’s the difference between QI and QA? APPROACHES OF QUALITY

• Quality Assurance is an older term.
• Quality Control (QC)
– It was retrospective, policing, and in many ways
punitive. • Total Quality Management (TQM)
– Often involved determining who was at fault. • Quality Assurance (QA)
• Quality Improvement is a newer term. • Continuous Quality Improvement (CQI)
– QI involves both prospective and retrospective
reviews.
– Aimed at improvement -- measuring where you are,
and figuring out ways to make things better.
– Specifically attempts to avoid attributing blame, and
to create systems to prevent errors from happening.

Quality Control Quality Control Process

• Quality control in health care organization refers to • An eight-step process for monitoring and evaluating
activities that evaluate, monitor or regulate services performance. It must include the following steps:
rendered to consumers.
1. Establish control criteria.
• The process 2. Identify the information relevant to the criteria.
Observe
3. Determine ways to collect the information.
4. Collect and analyze the information.
• Variable characteristics
Identify 5. Compare collected information with the established
criteria.
Track
• Variables through statistical methods 6. Make a judgment about quality.
7. Provide information and if necessary, take corrective
action regarding finding to appropriate source.
8. Determine when there is a need for re-evaluation.

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Total Quality Management (TQM) Quality Assurance

• A way to continuously improve performance at every
level of operation in every functional area of on
organization using all available human and capital
resources.
• Aim to reduce the waste and cost of poor quality.
All of the activities that make it possible to
define standards, to measure and improve
the performance of services and health
providers so that care is as effective as
possible.

• The main elements of TQM are three:

– The customer, whose needs are paramount to
the determination of quality
– The teamwork as a mean of achieving quality
– The scientific approach to decision-making
based on data collection and analysis.

Quality Assurance Quality Assurance

• Defined as “the process for objectively and Define Standards, norms,
systematically monitoring and evaluating the quality guidelines)
and appropriateness of patient care, for pursuing
Quality One cannot measure that
which one has not defined
opportunities to improve patient care for resolving
identified problem”.
• The variation in standards
Measure One cannot improve that
• The focus of quality assurance is the discovery and Quality which one has not
correction of errors. These activities are carried out measured
by quality assurance personnel or department
personnel.
Improve • Comply with norms
Quality

Continuous Quality Improvement (CQI) Continuous Quality Improvement Cycle

• CQI is a cyclical process.
• It involves identifying an area where there is
an opportunity for improvement then outline
the sequence of activities that should occur in
order to solve that problem, and
implementing them.
• Once the cycle is completed it has to be
determined whether the problem has been
solved.
• If the problem continues, the cycle should be
repeated.
(CQIC)
There are seven steps involved in implementing CQI
cycle:
• Step 1 à identify an area where opportunities for
improvement exist.
• Step 2 à define a problem within that area, and
outline the sequence of activities (the process) that
should occur in that problem area.
• Step 3 à establish the desired outcomes of the
process and the requirements needed to achieve
them.

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Continuous Quality Improvement Cycle QI Opportunities and Benefits

(CQIC) cont.
QI can give you the opportunity to …..
• Step 4 à select specific steps in the process, and for
each step list the factors that prevent the
achievement of desired outcome. • Look at things differently
• Step 5 à collect and analyze data about the factors • Come up with new options and solutions
that are preventing the achievement of the desired • Eliminate things that make you crazy
outcomes of the desired steps.
• Step 6 à take corrective action to improve the
process.
• Step 7 à monitor the results of the action taken

Health Care: Cost and Access Perspectives on Quality

• Improvements in technology • Providers
• Higher prices • Payers
• Greater demand • Employers
• Integrated medical delivery systems • Consumers

QI is a “Hot Topic”

“…The quality of health care received by the

people of the United States falls short of what it
should be.”
Quality Improvement
» IOM, 2001 Part 3

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Medical Errors “Crossing the Quality Chasm”

IOM 2001
• How extensive is the problem of medical
errors? • Under use – helpful services not delivered
• Overuse – useless interventions
• More people die in a year from medical errors • Mistakes – inevitable human error
than from motor vehicle accidents, breast
cancer, or AIDS

Medical Errors QI in Health Care

• Not the fault of individuals • How can you measure quality in health care?
• Lessons from industry • What do you want to measure?
• How can you do it?
• What are the challenges?

Issues in Measurement Process vs. Outcome

• Structure • Process:
• Process – How health care is provided
• Outcome – How the system works
• Outcome:
– Health status
– Does it make a difference?

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Proxy Measures Information Systems

• Used when you can’t exactly measure what • Can be a valuable tool
you want or need • Can facilitate quality efforts
• Measure something that is close enough to • Examples:
reflect similarly – Databases
– Disease registries

Convenience Samples QI: Issues in Measurement

• Takes a limited number • Process vs. Outcome
• Extrapolates to the whole population • Proxy measures
• Not necessarily randomized • Information systems
• Convenience samples

Quality Improvement vs.

Performance Improvement
• Quality Improvement focuses on quality of
care
• Performance Improvement focuses on
administrative systems
• The goal is improvement in quality

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