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Course Instructors: Dr. Francis, Dr. Wolf and Dr.

Bautista
PASS PROGRAM
USMLE REVIEW STEPS 1, 2 AND 3

Course Instructors: Dr. Francis, Dr. Wolfe & Dr. Bautista

Lecture Page

Note Pages 5
Welcome to the Program 45
Low Energy State 53
Vitamins, Minerals, Trace Elements 55
Cellular Physiology 64
Membrane Physiology 71
Inflamation 76
Electrolyte Physiology 80
Pulmonary Physiology 87
Neuromuscular Physiology 105
Vascular Physiology 116
Cardiac Physiology 125
Gastrointestinal Physiology (GI) 135
Endocrinology 159
Rheumatology 171
Reproductive Endocrinology 184
Renal Physiology 192
Nephritic-Nephrotic 218
Neurophysiology 220
Hematology 238
Hemostasis 244
Lymphoma & Leukemia 248
Biochemistry 251
Amino Acids 254

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Protein Structure and Function 262
Enzymes 277
Anabolic Pathways 282
Catabolic Pathways 292
Cancers 303
Immunology 329
Immunodeficiencies 335
Leukocytes 344
Lymphocytes 351
Granulocytes 358
The Four Hypersensitivities 366
Antibiotics 369
Microbiology 371
Viruses 408
Note Pages 413
Obstectrics and Gynecology 453
Surgery & Trauma (Dr. Cordova) 477
Antibiotics (Dr. Cordova) 497
Biochemistry, Glycolysis,
Gluconeogenesis & TCA 515

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PASS PROGRAM
USMLE REVIEW STEPS 1, 2 and 3
Week 1 Monday Tuesday Wednesday Thursday Friday
Introduction Behavioral science Test taking/Time mgt. Membrane Phys Cardio Pathology
7:15-9:00
7:15 9:00 am Low Energy State EKG Phys Cardiac Phys
1 hr break Vitamins Psychiatry Arrhythmias Murmurs
10:00-12:00 Minerals Endocrine Phys
Trace elements Endo Path
LUNCH
1:30-4:00pm Cellular Phys Psych Endo Neuromuscular Cardio
Vascular Phys

Week 2 Monday Tuesday Wednesday Thursday Friday


Gastrointestinal Surgery Principals Pulmonary phys Renal Phys Neuro Phys
7:15-9:00 Physiology
1 hr break Trauma Pulm Path Renal Path Neuro Path
10:00-12:00 GI Path
LUNCH
1:30-4:00pm
GI Ansthesia Pulm Renal Neurology

Week 3 Monday Tuesday Wednesday Thursday Friday


Amino Acids OB Glycolysis Ketogenesis Nucleotides
7:15-9:00
7:15 9:00 Protein structure Gluconeogenesis Glycogen
1 hr break Protein function GYN Fructose/Galactose Pentose Pathway
10:00-12:00 OB/GYN Pharm Pyruvate metab.
LUNCH
1:30-4:00 pm Quaternary protein Reproductive TCA cycle Amino acids DNA
Repro Pharm Lipolysis Fatty acid synth.

Week 4 Monday Tuesday Wednesday Thursday Friday


Oncology Pediatricts Leukocytosis Rheumatology Myobacteria, Spiro.
7:15-9:00 Development Leukemia's Rickettsia
1 hr break Myelodysplasia Normal Flora Virus
10:00-12:00 Pediatricts Pharm Gram+/-
LUNCH
O l
Oncology I
Immunology
l Granulocytes
G l t FFungus
1:30-4:00pm Imm. Deficiency Hypersensitivities Parasites Closing remarks!!!
Transplantation Protozoa

Dr. Francis Dr. Wolf Teaching Associates


•Cellular physiology •Time management •Antibiotics-
Antibiotics Dr Cordova (date TBA)
•Behavioral •Endocrine •Surgery/Ansthesia- Dr Cordova
•Cardiology •Rheumatology
•Hematology- Dr Qi (date TBA)
•Pulmonary •Gastrointestinal
•Statistics- Dr Qi (date TBA)
•Biochemistry •Renal
•Reproductive •Neurology •DNA/RNA- Dr Bautista
•Immunology • Microbiology/Antibiotics
•Pediatricts •OB/GYN •Biochem pathways- Dr Lee
•Oncology

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4/30/2008

Making the most


out of your time
here at the PASS
program !!!

Study smart
not hard

NBME- National Board


Power is in of Medical Examiners
g !
knowledge For
profit
company
NBME- National Board
of Medical Examiners

• Shortage of family What do you want to do when


doctors throughout you finish medical school?
US
• You’re the next cutting edge
physician
• Shortage of OB/GYN • 20,000 new residents
physicians
p y in Fl, • Your p
pay?
y
Texas, California, and • Radiology, Dermatology,
Michigan Ortho.

• Cutoff for USMLE • Those making decisions,


control how many come
Step’s were raised across the bridge
from 182 to 185?

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4/30/2008

How do they comprise a test


Why do so many fail the that is written for you to fail?
test? • A physician sits and writes a question based
off of the discipline they want to test you on
ZOO
THEORY • A psychologists
h l i t rewordsd th
the question
ti ththe way
your mind thinks…
– This is why the wrong answers always look
good

55 PASS
PASS rules
rules in
in answering
answering A 38 y/o woman has congestive heart failure,
question
question premature ventricular contractions and
repeated episodes of ventricular tachycardia.
•• 1.
1. Cover
Coverthe
theanswers
answers
• 2. Read the last sentence and decide if it is
Her blood pressure is normal and there are no
• 2. Read the last sentence and decide if murmurs. Her heart is markedly enlarged.
a clue or concept question
it is a clue or concept
• 3. Read the vignette, and isolate the facts Coronary angiography shows no abnormalities.
question
of the vignette
•• 4.
3. Comprise
Read the vignette,
a thought and isolate the
process Which of the following is the
facts
• 5. Lookof the click vignette
down, and move !!!!!!! most likely diagnosis ?
• 4. Comprise a thought process
• 5. Look down, click and move !!!!!!!

A.Acute rheumatic fever A.Acute rheumatic fever


B.Congenital fibroelastosis B.Congenital fibroelastosis
C.Constrictive pericarditis C.Constrictive pericarditis
D.Myocardial infarction D.Myocardial infarction
E.Primary cardiomyopathy E.Primary cardiomyopathy

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4/30/2008

A 23 y/o man who is HIV positive has a 2 week


USMLE Step 2 and Step 3 approach history of midsternal chest pain that is aggravated
What is the next best step in management? by eating spicy foods; the pain is unrelated to
Is the patient stable? (based on hemodynamics) exertion or position and he reports no dysphagia.
- Unstable: ABC’s Treatment with H2 receptor blocking agents has
- Stable: read the vignette provided no relief. He takes clotrimazole for
thrush and zidovudine ((AZT).
) He has a CD4+ T
Do you have enough information to make a lymphocyte count of 220/mm3 (N>500).
definitive diagnosis?
- Yes- treat Which of the following is the most
- No- order a test (BLIS) appropriate next step in
blood/labs/image/surgery management?

A.Therapeutic trial of acyclovir A.Therapeutic trial of acyclovir


B.24 Hour pH probe B.24 Hour pH probe
C.Acid perfusion test C.Acid perfusion test
D.Esophageal manometry D.Esophageal manometry
E.Esophagoscopy E.Esophagoscopy

Procrastination in doing Procrastination in doing questions


questions • How many read all the choices
• How many read before doing in the explanation?
questions?
Wh t are you ttesting
What ti ? – Prior exposure to future
f
2 weeks later, what questions
happens?
– I have a lot of
details in my head

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4/30/2008

Procrastination in doing It’s ok to be wrong !!!!


questions • Block of 50 question and get
45/50 correct, are you any more
• How many do the questions prepared for the boards from the
moment you started that test?
in tutor mode?
• If you get 30 /50 wrong, you will
not be very happy
–Driving a car • Found a hole, that can be fixed
and lost
• Remember every time you fall

Why do we not listen to our first


My friends told me to do as
thought?
many questions as I can
before I take the test…
• We are scared of being wrong
• 6000 questions
• We do not want our over all • Multiple banks
average to be lower than the mean • You are doing questions to learn
from them
• Do we order test to learn about a
pathology
(i.e. Hypothyroidism – TSH panel)

3 steps to studying:
1. Obtain the information What bank to use?
2. Questions Q-Bank USMLE Rx. USMLEworld
3. Results of the bank
• Questions: Organ system based
– 50 question

– Do they ask you 50 new things?

– Pathological presentation does not


Do you see a pattern?
change, just the story line (clues are
so important)
At the end of your first week,
– Will you see the pattern in mixed
you will be evaluated by several
blocks? tutors to determine which is the
best test bank for you to use.

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4/30/2008

What should I do, with the What do most students do…


results of my question bank?
• Vignette….. Downs syndrome
• 50 questions completed – Answer: Endocardial cushion defect
(what is right or wrong)
• Read about it from the author
Example: Polyhydramnios: Down syndrome • Transcribe to note cards on ECD
What is the most common cardiac • Read the notes about ECD
abnormality? • Read the CMDT about ECD
• “Harrisons” and read about ECD
• Write the subject matter
• Look for patterns in the question Are you any more prepared for
• This is what you will read about Downs syndrome on the boards?

NBME practice exam…


Not enough time in the day !!!!!!!
• On line at http://www.NBME.org
- Exercise
– Step 1 – 5 forms (do not take form 3)
– Step 2 – 3 forms
- 210 score
– Step 3 – 1 form
- Proper sleep hygiene
-Take time out to
reward yourself
• When should I take
may NBME ?

PASS program clues vs. class notes Tutoring:


• This is your time to ask questions that
• You should drill the PP-clues with a you may have with the material
partner for at least 1 hour a night.
( ½ hour new, ½ hour random review)
• Do questions with your tutor (remember
its ok to be wrong)
• Caution in drilling class notes:
– Teacher vs. Student
• Your tutor is there to help
you find and fix your weakness

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4/30/2008

Tutoring cont.
• Try several tutors to find the chemistry that
works for you

• If you can not make it to your secession, please


inform your tutor, so they can fill the spot with
another student

• Once you are comfortable with a


couple of tutors, there is a request
book in the back.

(The key word, just a “request book”)

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Physiology:
Weeks One & Two

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WHO USES ENERGY?
• BRAIN • RAPIDLY DIVIDING CELLS
• MUSCLES – SKIN
INTRODUCTION: THE MOST •

PRIMARY ACTIVE TRANSPORT
HEART


HAIR
GI

POWERFUL CONCEPT IN • MEMBRANE MOVEMENT





RESPIRATORY
RENAL(PCT)
BLADDER
MEDICINE –

ENDOMETRIUM
ENDOTHELIUM
– BREASTS

THE LOW ENERGY STATE –




SPERM
GERM CELLS
CUTICLES
– BONE MARROW
• RED BLOOD CELLS
• WHITE BLOOD CELLS
• PLATELETS

SIGNS OF DISEASE: WHAT YOU


PRESENTATION OF A DISEASE CAN SEE
• When it bothers the patient enough, he or • TACHYPNEA and DYSPNEA
she will see the doctor as soon as possible
– Weakness so that the patient can not go to
work
– Shortness of breath scares people; they think
they might die

SYMPTOMS: THE PATIENT’S


COMPLAINTS MOST COMMON INFECTIONS
• WEAKNESS • PULMONARY INFECTIONS
• SHORTNESS OF BREATH • URINARY TRACT INFECTIONS

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OTHER COMPLICATIONS COMPLICATIONS, cont
• Dry skin • Endothelium – atrophic • Bladder – atrophic;
• Endometrium – leads to UTIs
• Hair dry and brittle atrophic • Respiratory – weak
• Nails brittle • Breasts – atrophic cough > infections
• Bone marrow suppressed • Sperm count – low • Germ cells – unable to
replicate > leads to
– Anemia • GI – nausea, vomiting
and diarrhea skin and GI cancers
– Leukopenia • CNS: MR (children)
• Renal- PCT shuts
– Thrombocytopenia down and dementia (adults)
• CV – heart failure

ANYTIME YOU CAN CONNECT TO THE LOW


ENERGY STATE …
• APPLY THE ENTIRE CONCEPT
• THIS ACCOUNTS FOR
MOST COMMON CAUSE OF DEATH? APPROXIMATELY 98% OF ILLNESSES
• WHENEVER IN DOUBT > ASSUME IT IS
A LOW ENERGY STATE
HEART FAILURE!!!
STOP GUESSING!!!

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Vitamin A
• A cofactor for PTH
VITAMINS, MINERALS and • Necessary for CSF production
TRACE ELEMENTS • Used for epithelial maturation, especially
hair, skin, and eyes
• Most unique function is night vision
THE BEGINNING
• A mild antioxidant
PTH & Ca2+ = same
calcium & Phosphorus Always opposite
(vs. VitD-> same direction)
PTH stim osteoclasts
vs. Vit D > osteoblasts

Vitamin A deficiency Vitamin A excess


• Poor night vision • Pseudotumor cerebri: excess CSF
• Decreased CSF production: asymptomatic production
• Hypoparathyroidism • Hyperparathyroidism: moans, groans,bones
• Epithelial cells fail to mature and stones

Pseudotumor Cerebri Vitamin B1: Thiamine


• Sign: papilledema • Necessary for four important enzymes:
• Symptom: headache – Pyruvate dehydrogenase
• Evaluation: CT scan ( shows enlarged – Alpha-ketogluterate dehydrogenase
ventricles) – Branched chain amino acid dehydrogenase
• Treatment: d/c vitamin A; serial LPs (30cc at a – Transketolase
time)
• Main complication: blindness
• This is the only cause of increased ICP where
you don’t have to worry about herniation

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Thiamine Deficiency Vitamin B2: Riboflavin
• Beriberi • Used in cofactors ( FAD)
– Dry beriberi
– Wet beriberi • Best source is milk
• Wernicke’s Encephalopathy • Sunlight breaks riboflavin down
– Receptive aphasia
• Wernicke-Korsakoff syndrome
– Mamillary bodies now also involved
– Confabulation
– Inability to move short-term memory to long-term
memory

Riboflavin deficiency Vitamin B3: Niacin


• Angular Cheilosis • Necessary for cofactors ( NAD, NADH,
NADP, NADPH)
• Needed by pyruvate dehydrogenase,
alpha-ketogluterate dehydrogenase, and
branched chain amino acid
dehydrogenase

Niacin deficiency Vitamin B4: Lipoic acid


• Pallegra : 4 D’s diarrhea, dermatitis, • Needed by pyruvate dehydrogenase,
dimentia and death alpha-ketogluterate dehydrogenase, and
• Hatnup’s disease: presents just like pallegra branched chain amino acid
– Defective renal transport of tryptophan dehydrogenase

• No deficiency state

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Vitamin B5: Panthotenic Acid Vitamin B6: Pyridoxine
• Needed by pyruvate dehydrogenase, • Needed by all transaminases
dehydrogenase, alpha-ketogluterate • INH pulls pyridoxine out of the body
dehydrogenase, and branched chain • Forms the cofactor pyridoxalphosphate
amino acid dehydrogenase
needed to make heme

• No deficiency state

Pyridoxine deficiency Vitamin B9: Folate


• neuropathy • The first vitamin to run out whenever you
have rapidly dividing cells
chronic neuropathy > no shooting/stabbing
amitryptaline • Used to make tetrahydrofolate (THF) from
which you make nucleotides
shooting neuropathy >
1st line carbamapine
2nd line gabapentin

Folate deficiency Vitamin B12: Cyanocobalamin


• Megaloblastic anemia • Needed by two enzymes:
• Hypersegmented neutrophils – Homocysteine methyltransferase
• Neural tube defects in fetuses – Methylmalonyl-CoA mutase

• Mcc: overcooked vegetables


• Used to make tetrahydrofolate
• Used to recycle odd-numbered carbon
fatty acids myelin

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Vitamin B12 deficiency Vitamin C
• Megaloblastic anemia • Used for hydroxylation
• Hypersegmented neutrophils • Hydroxylates proline and lysine in collagen
• Neuropathy, especially involving the dorsal and elastin
column pathways and corticospinal tracts • Main antioxidant in the GI system
• Mcc: pernicious anemia (type A gastritis)

Vitamin C deficiency Vitamin D


• Scurvy • Necessary for bone and teeth formation
• Bleeding from hair follicles and gums • Stimulates osteoblastic activity
• Stimulates calcium AND phosphorous
absorption and reabsorption
• Mineralizes bones and teeth

Vitamin D deficiency Vitamin E


• Rickets: in children • The main antioxidant in your blood
• Lateral bowing of the legs • Absorbs free radicals
• Osteomalacia: in adults
means soft bones

• Vitamin D resistant rickets


– Defective renal reabsorption of phosphorous
– As phosphorous leaks out, it pulls calcium
with it
X-linked Dominant
- also pyruvate DH deficiency

- dad gives it to all his daughters

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Diseases involving oxidation Antioxidants
• Cancer • Vitamin E: in blood
• Alzheimer’s disease • Vitamin C: in GI tract
• Coronary artery disease • Vitamin A
• Hemolytic anemia ( esp. G6PD) • Beta-Carotene
and trace elements

Biotin Biotin deficiency


• Necessary for carboxylation • Many carboxylases would lose their
function

Vitamin K Warfarin
• Needed for gamma-carboxylation • Competitive inhibitor of vitamin K
• Adds a third (gamma) carboxyl group to • Given orally
the vitamin k dependent clotting factors • Always give heparin first
– Clotting factors II, VII, IX, X, Protein C & • Crosses the placenta
Protein S 6 hr half life
– Protein C has shortest half life, followed by
• Teratogenic
factor VII • Follow PT ( prothrombin time )
VII half life of 2 days • INR 2 to 3x normal
> monitor w/ heparin in hospital for 10 days 2-3x more likely to not clot
or 2-3x longer to clot

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Heparin What are germs good for?
• Acts as a cofactor for antithrombin III
• Blocks thrombin, as well as clotting factors
IX, X, XI, and XII
– Follow by measuring PTT ( INR 2 – 3X NL)
– To reverse the action: protamine sulphate
– If patient acutely bleeding: give FFP to
reverse immediately
PE > give heparin > have another PE > put in IVC filter
>> warfarin for 6 mths
MC clot former > Factor V Lieden (90%)
comp: bleeding, hyperlipidemia (act HSL[hormone-sens lipase]; same
enzyme glucagon activates), HIT (can attach/act as hapten to platelet >
make it appear foreign)
> use LMWH
> pt w/ previous Hx HIT only > no heparin at all
> use agatroban (blocks thrombin)

Vitamins related to gut flora MINERALS


• They make: 90% of vitamin K
– Biotin carboxylation
– Folate B9
– Panthotenic acid B5
• They help absorb
– Vitamin B12

reason why broad spec antibiotics > 2 days > bleeding


- in babies > hemorrhagic dx of newborn
(4 cephalosporins)

Minerals Calcium
• Calcium • Intracellular calcium needed for all muscle
• Magnesium contraction
• Smooth muscle uses extracellular calcium
• Zinc for second messenger systems
• Copper • Atrium is ONLY membrane that uses
• Iron calcium to depolarize
• Cardiac ventricle depends on extracellular
calcium to trigger off its intracellular
calcium release

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Calcium, cont Magnesium
• Used for axonal transport • A cofactor for ALL kinases 90% ATP prod stops
• Presynaptic influx of calcium necessary for • A cofactor for PTH
release of ALL neurotransmitters • Interacts with potassium as well, but
• Needed for normal bone and teeth location currently
somewhere unknown
in the early distal convoluted tubules
development
Calcium and magnesium same direction (by way of PTH)
- both low or both high
- same role because distal convoluted tubules protein

Zinc Copper
lysyl
• Needed by hair, skin, sperm and taste • Needed by lysine hydroxylase in the
buds formation of collagen
• Also needed by complex IV of electron
• Zinc deficiency: dysguisia transport system

Movement disorder in a middle-


Copper excess
aged person
• Wilson’s disease • HUNTINGTON’S • WILSON’S DISEASE
– Autosomal recessive DISEASE (90%) – Autosomal recessive
– Autosomal dominant – Ceruloplasmin def
– Ceruloplasmin deficiency
– Trinucleotide repeats – Copper deposition in
– Copper deposition in lenticular nucleus (basal – Involves caudate lenticular nucleus, liver
ganglia), iris (Kayser-Fleischer rings) and in nucleus and iris
the liver (causing cirrhosis) – Has anticipation – Treat: penicillamine
– Tx: penicillamine – Treat with
Copper deficiency antipsychotics
- Menke's Kinky hair syndrome – Mcc of death: suicide
> orange colored hair - AD w/o dx > decreased penetrence
> Hair feels like copper wire - AD with diff pheno/pres > variable expression

> MC of death HF

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Trinucleotide repeats Iron
• Huntington’s disease • Needed for formation of heme and
• Fragile X hemoglobin
• Fredrieck’s ataxia • Ferrous iron binds oxygen
• Prader Willi syndrome uniparental disomy: chr15 • Needed by complex III and IV of electron
• Myotonic dystrophy
(dad both mutations) transport system
- "Proud dad" & "Moms angel)

And finally… the trace elements Trace Elements


• Chromium
• Selenium
• Molebdenum
• Manganese
• Tin
• Flouride

Chromium Selenium
• Enhances insulin action • Needed primarily by the heart
• Def: causes diabetes • Excess: breath smells like garlic ( arsenic
as well)
• Def: dilated cardiomyopathy

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Molebdenum and Manganese Tin
• Needed by many enzymes in glycolysis • Needed for hair growth
• Xanthine oxidase: needs both elements

Flouride
• Needed for teeth and bone growth
• Excess: blocks enolase of glycolysis
THE END
BUT, it is really the beginning…

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CELLULAR PHYSIOLOGY
• CELL ORGANELLS

IRREVERSIBLE CELLULAR INJURY NECROSIS


• APOPTOSIS • NECROSIS • ISCHEMIC(COAGULATIVE)
– CELL MEMBRANE – NUCLEUS • PURULENT pick bacterial every time
DISSOLVES FIRST DISSOLVES FIRST
– PROGRAMMED CELL – UNEXPECTED
• GRANULOMATOUS non-bacterial > macro + T cells
DEATH – INVOLVES • FIBRINOUS collagen vasc dx > uremia (RF) > TB (3rd mc)
– NONINFLAMMATORY INFLAMMATION • CASEOUS
chronic panc (retroperitoneal), breast (blunt trauma; shy little aches and pains, little eye
• FAT contact [hidden second diagnosis] > battered women)
– PYKNOSIS – PYKNOSIS
– KARYORHEXXIS – KARYORHEXXIS
• HEMORRHAGIC any organ w/ 2 or more Blood supplies
free radicals
– KARYOLYSIS – KARYOLYSIS • LIQUEFACTIVE 1/2 liquid & 1/2 solid show up at 3 hrs
= same as abscess
> which is anaerobic in nature > have 3 hrs to use tPA
cause of atresia's & mult digits -- If >3hrs > arterial > aspirin
(venous > heparin)
leuko-encephalo-mallesia elderly missing tissue
on the medial wall of the lateral ventricles- MC cause = ischemia
-MC for: small kidney, cerebral atrophy, dry skin
so if they ask you why cells died > dont know > pick ischemia

NECROSIS NECROSIS
• ISCHEMIC(COAGULATIVE) • ISCHEMIC(COAGULATIVE)
• PURULENT • PURULENT
• GRANULOMATOUS • GRANULOMATOUS
• FIBRINOUS • FIBRINOUS
• CASEOUS • CASEOUS
• FAT • FAT
• HEMORRHAGIC • HEMORRHAGIC
• LIQUEFACTIVE • LIQUEFACTIVE

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NECROSIS NECROSIS
• ISCHEMIC(COAGULATIVE) • ISCHEMIC(COAGULATIVE)
• PURULENT • PURULENT
• GRANULOMATOUS • GRANULOMATOUS
• FIBRINOUS • FIBRINOUS
• CASEOUS • CASEOUS
• FAT • FAT
• HEMORRHAGIC • HEMORRHAGIC
• LIQUEFACTIVE • LIQUEFACTIVE

NECROSIS NECROSIS
• ISCHEMIC(COAGULATIVE) • ISCHEMIC(COAGULATIVE)
• PURULENT • PURULENT
• GRANULOMATOUS • GRANULOMATOUS
• FIBRINOUS • FIBRINOUS
• CASEOUS • CASEOUS
• FAT • FAT
• HEMORRHAGIC • HEMORRHAGIC
• LIQUEFACTIVE • LIQUEFACTIVE

MESS WITH THE


NECROSIS CHROMOSOMES
• ISCHEMIC(COAGULATIVE) • MONOSOMIES: DIE! DIE! DIE!
• PURULENT – MCC: NONDISJUNCTION > in all of mono/trisomies
• GRANULOMATOUS • 90% IN DAD, USUALLY IN MEIOSIS 1; BUT
SPERM DIE ON A DAILY BASIS
• FIBRINOUS
• FEWER OCCUR IN MOM; BUT MOM KEEPS
• CASEOUS HER EGGS FOR LIFE AND IS THEREFORE
• FAT MORE LIKELY TO TRANSMIT HERS
• IF ONE WERE TO SURVIVE TO BE BORN, IN
• HEMORRHAGIC THE LEAST, THINGS WILL NOT GROW
• LIQUEFACTIVE

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TURNER SYNDROME
neck didnt dev. > brachial pouches didnt develop
• WEBBED NECK > so all the skin from neck fell on the shoulder
• CYSTIC HYGROMA brachial pouches didnt dev > cysts along neck
> lymphedema
• GONADAL STREAKS gonads didnt develop
• SHIELD-SHAPED CHEST shoulders fine but hips didnt develop
so goes to a point like a triangle
• COARCTATION OF AORTA so arch of aorta didnt finish
developing
MCC: nondisjunction in Dad
> if questions says transmission* > Mom

TRISOMIES extra-tissue
TRISOMIES
• DIE! DIE! • TRISOMIE 18: EDWARDS SYNDROME
both die
• FEW LIVE w/in 3mts
– ROCKERBOTTOM FEET (IN 95%)
• TRISOMIE 13: PATAU SYNDROME
– POLYDACTYLY
– PALATE IS HIGH-ARCHED
– PEE-ING SYSTEM ABNORMALITY
Protruding abdomen > omphalocele
(high incidence)

chance of anything abn happening >


1-3% gen pop
1 Risk factor > 10%

TRISOMIES
*
DOWN’S SYNDROME
• TRISOMIE 21: DOWNS SYNDROME • MENTAL RETARDATION – 100%
– MCC: NONDISJUNCTION – IQ: AVERAGE IS 85 TO 100 WITH A STANDARD
DEVIATION OF 15
– ROBERTSONIAN TRANSLOCATION: – SUPERIOR INTELLIGENCE: IQ > 130
HIGHEST INCIDENCE (33% OF – MILD MR: IQ < 70
OFFSPRING) if mult siblings have pick this
– MODERATE MR: IQ < 55
– HAS MANY THINGS TO CONSIDER – SEVERE MR: IQ < 40
– PROFOUND MR: IQ < 25 – NEEDS 24HR CARE
– MILD TO MODERATE MR CAN BE TAUGHT BASIC
ADLS

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DOWN’S SYNDROME
• EARLY-ONSET ALZHEIMER DISEASE
• HIGHER FREQUENCY OF AML;BUT ALL IS THE
MOST COMMON LEUKEMIA
• 20 TO 40% HAVE congenital heart
DISEASE
• -ENDOCARDIAL CUSHION DEFECTS
– VSD and ASD
– VSD
– ASD

DOWN’S SYNDROME DOWN’S SYNDROME


• CYANOTIC CONGENITAL HEART • 50% HAVE HYPOTHYROIDISM
DISEASE • WIDELY-PACED CRANIAL SUTURES
– TRANSPOSITION OF GREAT ARTERIES • MACROGLOSSIA
– TETROLOGY OF FALOT • DUODENAL ATRESIA
• HIRSCHSPRUNG’S DISEASE
• CLUES:
– MONGLIAN SLANT TO EYES
– WIDELY SPACED FIRST AND SECOND TOES
– SIMIAN CREASE

TRISOMIES Chemotherapy
• XXX: Normal female; has two barr bodies
• XXY: Klinefelter’s syndrome. Tall male
with gynecomastia, small penis and
testicles
• X- Fragile X syndrome
– Mcc of chromosomal induced MR
– Short stature; macrochordism
– Collagen disorder (increased risk of MVP)
– Isolated using the drug METHOTREXATE

67 67
CHEMOTHERAPY ANTIMETABOLITES
• Stops rapidly dividing cells • ARA-A
• ARA-C
• Attacks the nucleus in some way • 5-FU: blocks thymidylate synthetase
• Causes irreversible cellular death • 6-MERCAPTOPURINE: promotes gout; recognized by
xanthine oxidase
• WILL kill some patients • THIOGUANINE
• No such thing as safe chemo • METHOTREXATE: inhibits dihydrofolate reductase(as
does TRIMETHOPRIM and PYREMETHAMINE)
– Most commonly used antimetabolite
– Used to treat molar pregnancies
– Used to treat STEROID RESISTANT disease( followed by
AZOTHIOPRINE and CYCLOSPORINE)

ANTIMETABOLITES ANTIMETABOLITES
• METHOTREXATE • AZOTHIOPRINE
– Causes folate deficiency and megaloblastic – Used for steroid resistant diseases( behind
anemia METHOTREXATE and before
– Give LEUCOVORIN > FOLINIC ACID to CYCLOSPORINE)
prevent the anemia

ALKYLATING AGENTS ALKYLATING AGENTS


• Bind to double stranded DNA • Bleomycin • Hydroxyurea
• Busulphan • Melphalan
• Used primarily for slow growing cancers • Adriamycin • Mechlorethamine
• Cause the most nausea and vomiting • Cisplatnin • Procarbazine
– ONDANSETRON: serotonin blocker used to treat • Cyclophosphamide • Dacarbazine
nausea and vomiting in chemotherapy • Isophosphamide • Chlorambucil
• Mitomycin
• Antimycin • FOR RESCUES
• Acridine dyes • Desroxzasane
• Mesna

68 68
MICROTUBULE INHIBITORS NUTRIENT DEPLETION
• Vinblastine • L-ASPARAGINASE
• Vincristine
• Paclitaxel

IMMUNEMODULATORS
• LEVAMISOLE

IRREVERSIBLE CELLULAR
DEATH
• NUCLEAR DAMAGE
• LYSOSOMAL DAMAGE
• MITOCHONDRIAL DAMAGE

• OCCURS IN 6 HOURS in all tissues

69 69
IRREVERSIBLE CELLULAR IRREVERSIBLE CELLULAR
DEATH DEATH
• NUCLEAR DAMAGE • OCCURS IN 20 MINUTES IN THE BRAIN
• LYSOSOMAL DAMAGE
• MITOCHONDRIAL DAMAGE

• OCCURS IN 6 HOURS in all tissues


except the brain

The End?
To Be Continued…

70 70
WHAT A MEMBRANE DOES
• PROVIDE SHAPE
• AMPHIPATHIC
MEMBRANE PHYSIOLOGY – HYDROPHILIC and HYDROPHOBIC
– WATER SOLUBLE and FAT SOLUBLE
A MEMBRANE’S JOB IS NEVER – HYDROPHOBIC wants to be INSIDE away from
water
DONE
– HYDROPHILIC wants to be OUTSIDE in contact
with water

FAT SOLUBLE COMPOUNDS STEROID HORMONES


• DO NOT interact with the outer cell • MADE FROM CHOLESTEROL
membrane. They go right through and • FAT SOLUBLE( hydrophobic)
head for the nucleus • Do NOT interact with cell membrane
• HAVE NUCLEAR MEMBRANE • ALL have a nuclear membrane receptor
RECEPTORS except CORTISOL
• Concentration gradient is only limiting • CORTISOL has a cytoplasmic receptor;
factor but it still translocates to the nuclear
membrane

71 71
WATER SOLUBLE COMPOUNDS
WATER SOLUBLE HORMONES Factors affecting diffusion
• HYDROPHILIC • CONCENTRATION GRADIENT
• SIZE of molecule
• CAN NOT simply go through a fat soluble
• Net charge on molecule
membrane
• pH (affects the net charge of a molecule)
• Must bind to the outside membrane to a • THICKNESS of membrane
receptor • SURFACE AREA of membrane
• Requires a SECOND MESSENGER • FLUX (dx/dt)
• But first, what about ANY water soluble • REFLECTION COEFFICIENT
– NUMBER OF PARTICLES RETURNED / NUMBER
compound? OF PARTICLES SENT TO MEMBRANE

OTHER FUNCTIONS OF A
FICK’S EQUATION MEMBRANE
• Factors that FAVOR diffusion go in the • CREATE and MAINTAIN concentration
NUMERATOR gradients
• Factors that NEGATIVELY affect diffusion • SELECTIVE permeability
go in the DENOMINATOR • Has SATURATED fats( no double bonds)
• Has UNSATURATED fats( double bonds)
– Easier to break down
– Better temperature regulation
– More fluidity of movement, especially lateral

ESSENTIAL FATS OTHER MEMBRANE FUNCTIONS


• Can get them ONLY through the diet • PHAGOCYTOSIS: requires energy
• LINOLENIC – ENDOCYTOSIS: primarily for nutrition
• LINOLEIC – EXOCYTOSIS: primarily for getting rid of
waste products ( i.e. lipofuscin )
– Used to make ARACHADONIC ACID
– PINOCYTOSIS: for movement of fluids and
– Arachadonic acid becomes essential if linoleic
electrolytes
acid is missing from the diet
• SKIN is only organ that does this process

72 72
OTHER MEMBRANE FUNCTIONS OTHER MEMBRANE FUNCTIONS
• TEMPERATURE REGULATION • ALL membranes can depolarize
– RADIATION > concentration gradient • Resting membrane potentials
– CONDUCTION > requires contact
– CONVECTION > movement of environment
drags heat out of the body

ELECTROLYTE MOVEMENT
• CONCENTRATION GRADIENT
• ELECTRICAL GRADIENT
• DRIVING FORCE
• NERNST NUMBER (E-ion)
• CONDUCTANCE (G-ion)
• PERMEABILITY
– CHANNELS: small ions
– PORES: medium-sized molecules (sweat)
– TRANSPORT PROTEINS

TRANSPORT PROTEINS SECOND MESSENGERS


• PRIMARY ACTIVE TRANSPORT • C-amp > most common second messenger
>requires an ATPase. Going against a
gradient
• SECONDARY ACTIVE TRANSPORT
– Requires sodium’s gradient
– SYNPORT or COTRANSPORT >moving in
the same direction as sodium
– ANTIPORT > movement in opposite direction
as sodium

73 73
PHOSPHODIESTERASE INHIBITORS SECOND MESSENGERS, cont
• CAFFIENE • IP3 -DAG
• THEOPHYLLINE

• SILDENAFIL
• VARDENAFIL
• TADALAFIL

IP3-DAG SYSTEM CALCIUM –CALMODULIN SYSTEM


• All HYPOTHALAMIC HORMONES, except • 4 calcium molecules: 1 calmodulin
CRH • All SMOOTH MUSCLE CONTRACTION
• All SMOOOTH MUSCLE CONTRACTION by DISTENTION
by hormone or neurotransmitter

CALCIUM TYROSINE KINASE


• Used as a second messenger by • INSULIN and all GROWTH FACTORS
GASTRIN only

74 74
NITRIC OXIDE NITRATES
• NITRIC OXIDE > GUANYLATE CYCLASE • VASODILATORS
> elevates c-GMP • TACHYPHYLAXIS; rapid tolerance

• NITRATES • Nitroglycerin
• ENDOTOXIN • Dinilatrate
• ANP • Sodium Nitroprusside

The End
Insane in the membrane

75 75
INFLAMMATION SHUTTING DOWN THE Na-K ATPase
• Potassium still leaks out
• Cell becomes more negative > less likely
to depolarize

SHUTTING DOWN THE Na-K ATPase, cont EKG CHANGES


• With Na trapped within the cell, calcium • Na-K ATPase shuts down when a vessel
also gets trapped within the cell is 70% stenosed
– This increases contractility • Potassium leaks out, making cells more
• DIGITALIS negative
• DIGITOXIN
• OUBAIN
• This is why you get ST-wave
DEPRESSION

ST-WAVE DEPRESSION FOLLOW-UP FOR ANGINA


• Early ischemia • PAIN GOES AWAY
• 70% stenosis – Hospitalize for 24hours
• SYMPTOMS BEGIN – Do serial EKGs and CIEs (Q6h x 24h)
• Subendocardial ischemia – If negative workup, then discharge home
• STABLE ANGINA – Do a regular STRESS TEST in 6 weeks
– Comes on with exertion; goes away with rest – Do STRESS THALLIUM test in 6 weeks
– 30% flow is enough at rest, but not on exertion • Thallium flows through the coronary arteries
– TX: VASODILATORS > increase radius increases – Look for COLD AREAS: NO FLOW( ISCHEMIC)
flow

76 76
FOLLOW-UP FOR ANGINA, cont FOLLOW-UP FOR ANGINA, cont
• If you think they might have had an MI, • IF PATIENT UNABLE TO PERFORM THE
then do a Ca-PYROPHOSPHATE scan STRESS TEST:
– Cells that die calcify – DOBUTAMINE STRESS TEST
– Dead cells will take up the Ca- – DIPYRIDAMOLE STRESS TEST
PYROPHOSPHATE
• Look for a HOT SPOT

EKG CHANGES UNSTABLE ANGINA


• Na gets trapped within a cell when there is • 90% stenosis
at least 90% stenosis • EVENTS OCCUR
• Cells become more POSITIVE • PLAQUE RUPTURED, and platelets are
closing off the rest of the lumen
• TX: Aspirin > Nitrates> Oxygen > Heparin
> tPa > Morphine > B-blockers > Take to
CATH LAB for angiogram

ANGIOGRAM FINDINGS ANGIOGRAM FINDINGS, cont


• LEFT MAIN CORONARY ARTERY • ANY SINGLE OR DOUBLE VESSELL
OCCLUSION ( 70% stenosis or more) DISEASE
• THREE OR MORE VESSELL DISEASE
• TX: PTCA with STENT placement coated
• TX: GO STRAIGHT TO SURGERY with CLOPIDOGREL

77 77
CELLS ARE MORE LIKELY TO WITH Na and Ca trapped within the
DEPOLARIZE WHEN ISCHEMIC cell
• After a stroke: SEIZURES • Since atria use Ca to depolarize, the
• After an MI: ARRYTHMIAS trapped Ca may cause atrial arrythmias
• After ischemic bowel: BLOODY DIARREA • Contractility of muscles increases
• After a DVT: CRAMPS

WITH CELL DYING, SWELLING


• Sodium continues to accumulate inside • Cerebral edema
cell • Papilledema
• Chloride will follow • Hydropic changes
• WATER will follow next • Dilated lymphatics
• SWELLING is therefore the FIRST visible • Third spacing
change of cellular injury

WHEN TOO MUCH SODIUM


INFLAMMATION TIME LINE INSIDE CELL….
• < 24 hours: SWELLING • Sodium begins to leak OUT of the cell now
• AT 24 hours: NEUTROPHILS show up that concentration gradient is reversed
and peak at 3 days • The only way for sodium to get out is to
• T-cells and MACROPHAGES: show up at use the Na-Ca exchange protein which is
day 4 and peak at day 7 concentration driven
• FIBROBLASTS: show up at day 7, peak at
day 30, and take 3 to 6 months to
complete their work ( chronic
inflammation)

78 78
IF BLOOD SUPPLY NEVER WHEN ALL CALCIUM NOW
RETURNS TO THE CELL TRAPPED WITHIN THE CELL
• The sodium can pull ALL the calcium into • Cells that depend on EXTRACELLULAR
the cell calcium will lose function
• WHILE calcium is moving into cell, more – SMOOTH MUSCLE
atrial arrythmias may develop – ATRIUM
– VENTRICLE

SIGN OF CHRONIC DISEASE


• ON BIOPSY: you see evidence of fibrosis
• ON X-RAY: you see calcifications
ALL inflammatory processes…

DONE!!!

79 79
Electrolyte Movement
Electrolyte Physiology
• CONCENTRATION GRADIENT
• ELECTRICAL GRADIENT
• DRIVING FORCE
• NERNST NUMBER (E-ion)
• CONDUCTANCE (G-ion)
Something in the way she moves
• PERMEABILITY
me… – CHANNELS: small ions
– PORES: medium-sized molecules (sweat)
– TRANSPORT PROTEINS

Electrolyte Movement Electrolyte Movement


• CONCENTRATION GRADIENT • CONCENTRATION GRADIENT
• ELECTRICAL GRADIENT • ELECTRICAL GRADIENT
• DRIVING FORCE • DRIVING FORCE
• NERNST NUMBER (E-ion) • NERNST NUMBER (E-ion)
• CONDUCTANCE (G-ion) • CONDUCTANCE (G-ion)
• PERMEABILITY • PERMEABILITY
– CHANNELS: small ions – CHANNELS: small ions
– PORES: medium-sized molecules (sweat) – PORES: medium-sized molecules (sweat)
– TRANSPORT PROTEINS – TRANSPORT PROTEINS

Electrolyte Movement Electrolyte Movement


• CONCENTRATION GRADIENT • CONCENTRATION GRADIENT
• ELECTRICAL GRADIENT • ELECTRICAL GRADIENT
• DRIVING FORCE • DRIVING FORCE
• NERNST NUMBER (E-ion) • NERNST NUMBER (E-ion)
• CONDUCTANCE (G-ion) • CONDUCTANCE (G-ion)
• PERMEABILITY • PERMEABILITY
– CHANNELS: small ions – CHANNELS: small ions
– PORES: medium-sized molecules (sweat) – PORES: medium-sized molecules (sweat)
– TRANSPORT PROTEINS – TRANSPORT PROTEINS

80 80
Electrolyte Movement Electrolyte Movement
• CONCENTRATION GRADIENT • Depolarize: to become positive from
• ELECTRICAL GRADIENT baseline
• DRIVING FORCE • Overshoot: more positive than the
• NERNST NUMBER (E-ion) threshold potential
• CONDUCTANCE (G-ion) • Repolarization: to become negative from a
• PERMEABILITY
positive potential
– CHANNELS: small ions • Hyperpolarization ( or undershoot): to
– PORES: medium-sized molecules (sweat) become more negative than baseline
– TRANSPORT PROTEINS potential

Sodium Channels

81 81
HEART BLOCKS
• NORMAL PR-interval : <0.2sec
• FIRST DEGREE HEART BLOCK: fixed
and prolonged PR-interval
– Problem is AT the SA node or BETWEEN the
SA node and the AV node
– NO treatment necessary
– Speeding up the heart rate( exercise) will
make the block disappear

HEART BLOCKS, cont HEART BLOCKS, cont


• SECOND DEGREE HEART BLOCK • MOBITZ II: PR-interval is normal; QRS
• MOBITZ 1: progressive lengthening of PR- complexes are dropped erratically
interval until QRS is dropped – Late ischemia at the AV node
– Early ischemia at the AV node – Some cells are negative; some cells are
– Also called WENCKEBACK’S positive
– Put in pacemaker if symptomatic; do nothing if – ALL must have a pacemaker
asymptomatic

82 82
HEART BLOCKS, cont QRS COMPLEXES
• THIRD DEGREE HEART BLOCK • Premature ventricular complex (PVC)
– COMPLETE AV DISSOCIATION – No P- wave; wide QRS complex; a pause
following the QRS complex
– AV-node has INFARCTED
– BIGEMINY: A PVC every other beat
– P-waves and QRS complexes have NO
– TRIGEMINY: A PVC every third beat
relationship
– VENTRICULAR TACHYCARDIA: three or
– ALL must have a pacemaker more consecutive PVCs with a minimum heart
rate of 150
– VENTRICULAR FIBRILLATION: NO
recognizable QRS complexes

VENTRICULAR TACHYCARDIA VENTRICULAR FIBRILLATION


• IF PATIENT STABLE: treat with • EPINEPHRINE
medication • TREAT LIKE VENTRICULAR
• IF PATIENT UNSTABLE: TACHYCARDIA
– SHOCK with 200joules
– SHOCK with 300joules
– SHOCK with 360(max)joules
– LIDOCAINE
– SHOCK
– BRETYLIUM or AMIODORONE

ELECTROLYTES AFFECT
ATRIAL ARRHYTHMIAS DEPOLARIZATIONS
• Premature atrial contraction (PAC) • FOUR SPECIALIZED MEMBRANES
• Multifocal atrial tachycardia
• Paroxysmal supraventricular tachcardia – NEURONS
• Atrial flutter – SKELETAL MUSCLES
• Atrial fibrillation – SMOOTH MUSCLES
– If ACUTE and STABLE: treat with medication
– If ACUTE and UNSTABLE: DEFIBRILLATE – CARDIAC MUSCLE
– If CHRONIC: treat medically; put on coumadin • ATRIUM: uses calcium to depolarize
– May defibrillate after minimum 2 weeks on coumadin
• VENTRICLE: uses sodium to depolarize; uses
intracellular calcium to contract; depends on
extracellular calcium to trigger off intracellular
• TX: use synchronized button calcium release

83 83
HYPERMAGNESEMIA HYPOMAGNESEMIA
• LESS LIKELY TO DEPOLARIZE • MORE LIKELY TO DEPOLARIZE
• AFFECTS CALCIUM AND POTASSIUM • AFFECTS CALCIUM and POTASSIUM
• GETS IN THE WAY OF SODIUM • AFFECTS all KINASES
• TX: IV normal saline; loop diuretic • TX: magnesium sulphate

HYPERCALCEMIA HYPOCALCEMIA
• LESS LIKELY TO DEPOLARIZE • MORE LIKELY TO DEPOLARIZE
everywhere except the atrium( more likely) everywhere except the atrium( less likely)
• SMOOTH MUSCLE: initially less likely • WILL AFFECT SECOND MESSENGER
(blocks nerve) to depolarize, then more SYSTEMS
likely to CONTRACT (due to second • SMOOTH MUSCLE: initially more likely to
messenger systems) depolarize( nerve fires more) followed by
• TX: IV normal saline; loop diuretics less likely to CONTRACT (affects second
messenger systems)

HYPERKALEMIA HYPOKALEMIA
• Initially MORE LIKELY TO DEPOLARIZE • LESS LIKELY TO DEPOLARIZE
• Potassium will flow into the cell, taking the • Potassium will rush out of the cells,
membrane potential closer to threshold
making them more negative
• Potassium gets trapped INSIDE the cell during
– Cells repolarize even faster
repolarization; repolarization therefore takes
longer > LESS LIKELY TO DEPOLARIZE – Cells repolarize too much
– Peaked T waves • Narrow T waves
– Widened T waves • Flat T waves
– Prolonged QT interval • Flipped and inverted T wave
• Predisposes to arrythmias • The U wave( exaggerated flipped T wave)

84 84
HYPERNATREMIA HYPONATREMIA
• MORE LIKELY TO DEPOLARIZE • MORE LIKELY TO DEPOLARIZE
• SODIUM rushes into the cells, making • SODIUM will now leak out of a cell by Na-K
exchange
them more positive
• When calcium leaks INTO cell in exchange for
• After sometime, the NA-K ATP-ase kicks sodium leaking OUT, cells become more
Into high gear, making the cells more positive
negative( less likely to depolarize) • TX: IV normal saline; correct slowly
• TX: IV normal saline; correct slowly – Use 3% saline if sodium under 120 with symptoms
– Use fluid restriction if hyponatremia due to SIADH

Hyponatremia The End: Turn off the lytes

Antiarrhythmics Class 1: Na channel blockers


• 1a
– Quinidine
– Procainamide
– Disepyramide
• 1b
– Lidocaine
– Tocainide
– Mixelitine
– Phenytoin
• 1c
– Encainide
– Flecainide
– propofenone

85 85
Class II: Beta Blockers Class II: Beta Blockers
• All end in –lol • Propanolol Acebutalol
• Specific beta 1: begins with A thru M, but • Esmalol Atenalol
NOT L or C • Sotalol Pindalol
• Nonspecific: begins with N thru Z, • Timalol
including L and C • Butexalol
• Labetalol
• Carvedilol

Class III: K Channel blockers Class IV: Ca Channel blocker


• Napa ( from procainamide) • Verapamil Quinidine
• Sotalol • Diltiazem Procainamide
• Bretylium • Nifedipine Phenytoin
• Amiodorone • Nicardipine
• Nimodipine
• Femlodipine
• Amlodipine

IF YOU PLAY WITH LYTES… You may go down IN FLAMES

86 86
PULMONARY PHYSIOLOGY

PULMONARY PHYSIOLOGY
TAKING A DEEP BREATH

Foregut Endoderm Neural Crest


• Respiratory Tract • Tracheal cartilage
• GI Tract > from the mouth to the second • Laryngeal cartilage
part of the duodenum

Embryogenesis Surfactant
• Develops in the first trimester like every • Decreases atmospheric pressure’s effect
other organ on the alveoli > PREVENTS
• Surfactant production is NOT complete ATELECTASIS
until approximately 32 to 34 weeks • Increases compliance of alveoli
• Brain develops first in embryo: notochord
visible by 3 weeks; brain formed by 8 • Compliance = change in volume / change
weeks in pressure

87 87
You know surfactant production is
complete when…
• Lecithin / sphyngomyelin ratio is 2:1 or
greater or…
• You detect phosphatidylglycerol, a
breakdown product of surfactant

If mom comes in with preterm labor… When there was NO surfactant


• Check L / S ratio • Alveoli would collapse: Atelectasis
• Check for phosphatidylglycerol • > leads to very poor compliance
• > increases work of breathing
• > weakness and shortness of breath
• If both of the above are negative
• > oxygen is given
– Beclamethasone
• > oxygen has difficult time diffusing across
– Betamethasone
• > oxygen builds up, causing free radical
– If baby still born early, then there is synthetic formation > alveoli develop hyaline membrane in
surfactant that can be applied order to protect themselves

Restrictive Lung Disease


• Have poor • Develop a secondary
compliance perfusion problem
• Have trouble
breathing in
• LOW ENERGY state
• LOW VOLUME state
Hyaline Membrane Disease
• Have poor diffusion • ALL die from heart
• Have increased A-a failure known as COR
gradient PULMONALE = right
THE FIRST RESTRICTIVE LUNG
• pO2 =low pCO2 =low sided heart failure DISEASE
pH =high due to pulmonary
HTN (severe RVH)

88 88
COMPLICATIONS of HMD ( or RLD) Complications, cont
• As compliance drops, the need for • More pressure support can lead to a
pressure support increases PNEUMOTHORAX
• As diffusion decreases, the need for – Kussmaul sign: increased JVD on inspiration
oxygen increases – Pulsus paradoxicus: exaggerated drop in BP
( more than 10mm) or in pulse rate ( more
• More oxygen means more free radicals,
than 10 bpm)
which means more hyaline membrane
– Loss of pulse and BP
• Bring in the JET VENTILATOR – Cyanosis
– Hamman’s sign: subcutaneous emphysema

As free radicals traumatize the


Pneumothorax AIRWAY…
• Spontaneous • Airway produces mucus to protect itself
• Traumatic • Airway thickens
• Goblet cell hyperplasia
• Asymptomatic • Airway lumen narrows
• symptomatic • Increased REID index
• BRONCHOPULMONARY DYSPLASIA
– The first obstructive lung disease

EVERY lung disease presents with


Obstructive Lung Disease the SAME signs and symptoms!!!
• Difficulty breathing OUT
• Problem with VENTILATION
• ABG: pO2 = nl or low pCO2 = high pH=low
• Too much airway mucus
• Airway thickening
• Goblet cell hyperplasia
• Increased Reid Index
• Mcc of death is BRONCHIECTASIS

89 89
Can it really be this easy???

Amniotic Fluid Production Role of Amniotic Fluid


• 80% is a filtrate of mom’s plasma • Main function is shock absorption
• To SUBTRACT: • Secondary action is to prevent
– Swallow ( a reflex) atmospheric pressure from affecting the
– Digest ( need patent UGI) fetus, especially the lungs
• 20% comes directly from the fetus
• To ADD:
– Process the swallowed fluid, then add 20%
more than was swallowed, then URINATE

Problem with amniotic fluid Potter’s Syndrome


• POLYHYRAMNIOS OLIGOHYDRAMNIOS • When OLIGOHYDRAMNIOS leads to
– Autonomic dysfunction RENAL agenesis or pressure effects on the fetus ( everything
( Riley-Day syndrome) obstruction is flattened)
– Neuromuscular
disease ( Werdnig- • Will lead to pulmonary aplasia or
Hoffman syndrome) hypoplasia due to the positive pressure
– UGI atresia
• Esophageal atresia
• Duodenal atresia

90 90
It is important to have negative
Prune Belly Syndrome pressure in the thoracic cavity!
• Absence of abdominal wall musculature
• Fetus is unable to urinate in utero
• Fetus is unable to bear down and raise
abdominal pressure for urination
• OLIGOHYDRAMNIOS

• Unable to urinate due to neuromuscular


weakness?
– Teach to (self) catheterize

Diaphragmatic Hernias
• The diaphragm forms from Ventral to
Dorsal

• Bochtalek defect: rear defect


• Morgagni defect: anterior, midline defect
– Visible by sonography in utero
– Bowel sounds in chest exam
• Must repair surgically immediately after birth

Extrathoracic Airway Intrathoracic Airway


• From the lips to the glottis • From the glottis to the alveoli
• Narrows on inspiration; expands on • Expands on inspiration; narrows on
expiration expiration
• NOT protected by the thoracic cage • Protected by the thoracic cage
• Has a vacuum surrounding it

91 91
Trachea Aspiration
• Has 16 to 20 C-shaped cartilage rings, • If patient is unable to speak, then the
with the opening to the C facing posteriorly object is lodged in the trachea
– This allows partial collapse of the airway • LARGE OBJECTS tend to lodge at the
during swallowing to prevent aspiration glottis 90% of time
• Has three anatomic narrowings • Perform the Heimlick Maneuver
– The glottis
• Perform Back Thrusts if less than 2 y/o
– Midway: due to anterior compression by aorta
• If still unable to dislodge the object…
– Carina: located at T4 (level of nipple)
– Perform emergency cricothyroidotomy

Aspiration, cont Evaluation for aspiration


• Small objects tend to lodge in the right • Inspiratory film: all lobes are inflated
lower lobe • Expiratory film: the lobe with the aspirated
– Recurrent RLL pneumonia: R/O FB aspiration
object does NOT collapse
• Do inspiratory-expiratory films
– Right mainstem bronchus is larger and • Tx: bronchoscopy
straighter than the left
• If person is sitting or standing UP, the object will
lodge in the superior segment
• If patient is lying DOWN, the object will lodge in the
posterior segment

Airway Anatomical Divisions


• Dead space
• Respiratory unit

• Dead space ventilation


• Alveolar ventilation
• Total ventilation

92 92
Histology
• Pneumocytes
– Type 1: macrophages
– Type 2: produce surfactant
• Goblet cells: produce mucus to trap debris
– Mucus moves 1 inch per cough
• Smooth muscle
• Clara “dust” cells
• cartilage

Epithelium Cilia
• Upper 1/3 of trachea has squamous cells • Line the entire airway
• Mid 1/3 of trachea is a combination • Beat in one direction > orad
• Main respiratory epithelium is tall columnar • Has the 9 + 2 configuration (9
ciliated epithelium microtubules surrounding 2 actin proteins)
• The more you smoke, the longer the zone • Need a Dynein arm to have flexibility
of squamous cells

Kartagener’s Syndrome Lung Sounds


• Dynein arm is defective • Stridor: narrowing in extrathoracic airway
• An obstructive lung disease • Wheeze: narrowing in intrathoracic airway
• Rhonchi: air moving over mucus
• Bronchiectasis • Crackles: collapsed airways “popping”
• Infertility open
• Situs Inversus – Surfactant is missing
– Alveoli have been scarred down

93 93
Lung Sounds, cont Lung Sounds, cont
• Decreased breath sounds: space between • Tracheal deviation: towards atelectasis
alveolus and chest wall is occupied and away from a pneumothorax
• Dullness to percussion: as above • Hyperresonance: pneumothorax on same
• Increased fremitus: consolidation on same side or atelectasis on opposite side
side or atelectasis on opposite side
• Bronchophony, egophony, or e to a
changes: as above

Lung Infections Airway Infections


• Croup • Epiglotitis: H. Influenza B
• Bronchiolitis • Tracheitis: C. Diptheria
• Bronchitis • Pneumonia
– Acute – Rusty colored sputum: Strep Pneumonia
– chronic – Curant jelly sputum: Klebsiella Pneumonia
• Pneumonia – Sulphur granules: Actinomyces Israelii
– Airway – Frequent after the flu: Staph Aureus
– interstitial – Malodorous smell or gas formation:
• tracheitis Anaerobes

Interstitial Pneumonias Interstitial pneumonias


• Atypicals • Fungus, cont
– Chlamydia: from 0 to 2 mo – Paracoccidiomycosis: South America
– Mycoplasma: from 10 to 30 y/o – Aspergillus: moldy hay or moldy basement
– Legionella: over 40 y/o – Sporothrix: rose thorn
• Pneumoconioses
• Fungus
– Asbestosis
– Histoplasmosis: midwest
– Silicosis
– Blastomycosis: northeast – Bissinosis
– Coccidiomycosis: southwest – berrylliosis

94 94
Interstitial pneumonias, cont Lung Masses
• Nocardia: the only G+ that is partially acid • Most common MASS in children:
fast hamartoma
• Sarcoidosis: noncaseating granulomas; • Most common MASS in adults:
large hilar adenopathy; high ACE levels granulomas
• Most common TUMOR: adenoma

Central Cancers Peripheral Cancers


• Squamous Cell Carcinoma: produces PTH • Bronchogenic adenocarcinoma
• Small Cell Carcinoma • Bronchioalveolar adenocarcinoma
– Anaplastic
– Located at the carina • Carcinoid syndrome
– Produces 4 hormones: – flushing, wheezing and diarrhea
• ACTH: 90%
– Too much serotonin
• ADH: 5%
• PTH: 3%
– Measure 5-HIAA in the urine
• TSH: 2% • Large cell adenocarcinoma

Risk factors for lung cancer Time for the PHYSIOLOGY of the lung!!
• Primary smoking
– Risk increases with amount AND duration
– If you STOP smoking: 5 yrs > reversal of
damage visible; 15 yrs > risk back to baseline
• Radon
• Second hand smoke
– (1) sidestream smoke (2) mainstream smoke
• Pneumoconioses

95 95
Three PHYSIOLOGIC parts to the lung
• Intrathoracic space
– Chest wall
– Pleural space
• Pulmonary vasculature
• Pulmonary airway

Lung Volumes Lung Volumes, cont


• RV: the amount of air left in the lungs AFTER • TV: the amount of air you take IN during a
forced expiration NORMAL inhalation effort
– Can not be physiologically forced out
– Maintains some compliance in the airway
• IRV: the amount of air you can FORCE
INSPIRE after a normal inhalation effort
• ERV: the amount of air that can still be FORCED • TLC: ALL the air in your lungs at the END of a
out AFTER a normal exhalation
– Fills up the dead space; decreases the tidal volume
deep breath ( RV + ERV +TV + IRV)
that you would have to take in
• VC: all the air you can breathe in AFTER forced
• FRC: a combination of RV and ERV exhalation ( ERV + TV + IRV)

96 96
Compliance and Air Flow Inspiration
• Beginning: expansile forces of the CHEST
WALL is greater ( 0 to 49%)
• Middle: expansile forces of the LUNG is
greater ( 50 to 99%)
• End: recoil force of the chest wall
EQUALS the expansile force of the lung

Expiration Breathing in…


• Beginning: recoil forces of the CHEST • FRC: baseline > intrathoraxic pressure is
WALL are greater ( 0 to 49%) negative ( - 3 to – 5)
• Middle: recoil forces of the LUNG are • TV: intrathoraxic pressure gets more
greater ( 50 to 99%) negative ( -10 to -12)
• End: the recoil force of the lung EQUALS • TLC: intrathoraxic pressure most negative
the expansile force of the chest wall (-20 to -25)
• Intrathoraxic Pressure should always be
NEGATIVE

Intrathoracic Pressure Intrathoraxic Pressure


• Should ALWAYS remain negative
• Should decrease with inspiration
• If it gets positive, then it will resist any
blood or air from entering the thorax
• If you do not breathe in, there will be NO
pressure gradient for blood to enter the
thorax

97 97
Positive Intrathoracic Pressure Pericardial Tamponade
• Kussmaul sign: increased JVD with • Mcc: trauma or cancer
inspiration • CXR: enlarged cardiac shadow
• Pulsus paradoxicus: exaggerated drop in • ECHO: compressed small heart
BP( more than 10mmHg) or pulse ( more • Tx: pericardiocentesis
than 10bpm) on inspiration
• If recurrent: put in a pericardial window

• Mcc: pericardial tamponade or


pneumothorax

Pneumothorax
• Traumatic
• Spontaneous
– Associated with estrogen use or collagen
disease
– Less than 25% occupation & asymptomatic
– More than 25% occupation or symptomatic
• Tx: chest tube placement

Pulmonary Vasculature Flow ( Q )


• As you breathe in, the lung Inflates, pulling
on traction fibers attached to vessels
• As vessels DILATE, flow increases
• As flow increases, oxygen dilates the
vessels, significantly increasing Q
• The increased Q keeps the pulmonary
valve open longer, INCREASING S-2
splitting

98 98
Flow ( Q ) is greater to the bottom of
the lungs because… S-2 Splitting
• (1) gravity • Increases on inspiration due to Increased
• (2) less resistance pulmonary blood flow
• (3) more oxygen goes to the bottom of the • Decreases on expiration due to decreased
lungs with each breath pulmonary blood flow
• Normal RR = 12 to 16 breaths/min • This is why RIGHT sided heart sounds
increase on INSPIRATION
• Q increases on inspiration and decreases • This is why LEFT sided heart sounds
on expiration. increase on EXPIRATION

Oxygenation Ventilation (V)


• Directly related to DIFFUSION and • Inversely related to pCO-2
PERFUSION • Definition: patent airway
• More oxygenation is accomplished at the • Measurement: pCO-2 ( on ABG’s)
bottom of the lungs only on inspiration
• Most of oxygenation is accomplished at • More V to the bottom of the lungs only on
the top of the lungs > ALWAYS OPEN! inspiration
• Most V at the top of the lungs because it is
ALWAYS PATENT

The Law of V / Q Pulmonary Airway


• V /Q is greatest at the top of the lungs,
equally matched in the middle, least at the
bottom
• If you change one, you MUST change the
other in the SAME direction
• ANY V / Q mismatch will lead to hypoxia

99 99
Pulmonary Airway Pressure

The Only Pressure That Gets


Positive With Each Breath

How The Brain Monitors Pulmonary


Signals from the lungs and chest wall
Physiology
• J-receptors: found in the interstitium of
lungs
– Senses interstitial particles
– Increases respiratory rate
• Slow adapting receptors: found in the ribs,
especially the sternocostal junctions
– Senses stretch and inflation
– Causes exhalation

100100
SINUSES BODIES
• Maxillary • AORTIC BODY: found in the arch of the
• Ethmoid aorta
• Sphenoidal – Measures pCO-2, pH, and H+ ions

• Frontal • CAROTID BODY: located at the


bifurcation of the internal and external
carotids
– Measures PO2, PCO2, pH, and H+ ions

BRAIN
• More sensitive to elevated pCO-2
• Hypoxia and Hypercarbia are synergistic
• Forms of pCO-2:
– 90% in the form of HCO-3
– 7% as carbaminohemoglobin and
carboxyhemoglobin
– 3% is dissolved ( .03pCO2 )

Medulla
• Responsible for BASIC functions; has a
RR of 8 to 10

• BRAIN DEAD: no function above the


medulla
• COMATOSE: cerebral cortex is still alive,
but patient unable to respond

101101
Pons
• RESPONDS to the environment
• Locked-In syndrome: damage to pons; patient
only able to blink as response
• Most sensitive to osmotic shifts > Central Pontine
Demylinolysis

• Apneustic center: senses hypoxia; causes


inspiration
• Pneumotactic center: senses hypercarbia;
causes exhalation

Kussmaul Breathing
• RAPID, DEEP breathing
• Means METABOLIC ACIDOSIS

Apneustic Breathing
• Pneumotactic center is desensitized, as in
COPD
• A lesion below the pneumotactic center
but above the apneustic center

102102
Apnea
• Central Apnea: NO inspiratory effort, with or
without bradycardia, in 20 seconds or more
– Apnea monitor
– Tx: Caffiene; theophylline
• Obstructive Apnea: occlusion of airway during
sleep, usually caused by obesity
– Weight loss
– Progesterone
– CPAP
– Surgery: Uvulopalatoplasty

Lesions to MEDULLA

Lesions to MEDULLA THE END


• Hypoglycemia
• Ischemia
– Thoracic outlet syndrome
– Subclavian steal syndrome

103103
And now for a few good CLUES Obstructive Lung Diseases
• Bronchitis • Emphysema
– Acute – Panacinar
– chronic – Centroacinar
• Bronchiolitis – Distoacinar
• Asthma – Bullous
• Staph aureus
– Intrinsic
• Pseudomonas
– extrinsic
• Cystic fibrosis
• Bronchiectasis

Really! The End!!

104104
NEUROLOGICAL CONTROL

NEUROMUSCULAR
PHYSIOLOGY
“I WANT A CONTRACT”

Central Nervous System Inhibitory Neurotransmitters


• Involves the BRAIN and SPINAL CORD • GABA: brain; causes an influx of chloride

• PARASYMPATHETIC system • GLYCINE: spinal cord; causes an influx of


– Controls the craniosacral divisions chloride

• SYMPATHETIC system
– Controls the thoracolumbar divisions

PARASYMPATHETIC SYSTEM SYMPATHETIC SYSTEM


• Uses acetylcholine for preganglionic fibers • Uses acetylcholine for preganglionic
and postganglionic fibers fibers; uses primarily NE for postganglionic
fibers
• DEPOLARIZES the head and neck as well
as below the belt • Some pathways use DA or SEROTONIN
• DEPOLARIZES the brain and the
• HYPERPOLARIZES the thoracolumbar thoracolumbar areas
areas
• HYPERPOLARIZES the sacral area
• Has long preganglionic fibers, short • Has short preganglionic fibers, long
postganglionic fibers postganglionic fibers

105105
Second Messengers
• PARASYMPATHETIC: c-GMP
• SYMPATHETIC: c-AMP

• Smooth muscle contraction by


neurotransmitter or hormone: IP3/DAG
• Smooth muscle contraction by distention:
calcium-calmodulin

Parasympathetic Receptors Sympathetic Receptors


• Most are MUSCARINIC except at ganglia • Many are NICOTINIC, except for sweat
or neuromuscular junctions which are glands which are muscarinic or…
NICOTINIC

Alpha 1 Receptors Alpha 2 Receptors


• Arteries: vasoconstriction • All presynaptic sympathetic fibers: inhibit
• Sphincters: tighten NE release
• Radial muscles of the eyes: mydriasis w/o • Islet cells of pancreas: inhibit insulin
cycloplegia secretion

106106
Beta 1 Receptors Beta 2 Receptors
• CNS: increased activity • CNS: increased activity
• SA NODE: increase heart rate and • Ventricles: increased contractility but NOT
contractility rate
• JG Apparatus: increased renin release • Lungs: bronchodilation
• Alpha cells of pancreas: increased • Arterioles: vasodilation
glucagon release • Islet cells of pancreas: increased insulin
• Uterus and Bladder: relaxation

If you want to stimulate… If you want to inhibit…


• You want to depolarize • CNS: make CL move into cell
• Make the cell more positive • PNS: make K move out of cells
• Make Na move INTO the cell
• Make Ca move into SA node • In either case, cells become more
NEGATIVE and are less likely to
depolarize

NOW FOR THE MUSCLES! TYPES of MUSCLES


• CARDIAC muscle
• SKELETAL muscle
• SMOOTH muscle

107107
STRIATED MUSCLES Smooth Muscle
• Cardiac muscle • Appear smooth due to lack of striations
• Skeletal muscle

• Striations due to sarcomeres

Skeletal Muscle Cardiac Muscle


• Use intracellular calcium for contraction • Uses intracellular calcium for contraction
• 100% electrochemically coupled • Needs extracellular calcium to trigger off
• Function as motor units( one nerve fiber intracellular calcium release
and all the muscle fibers it innervates • Complete SYNCYTIAL activity
• Demonstrate RECRUITMENT • The most gap junctions
• NO AUTONOMICS • Complete AUTONOMICS
• NO SYNCYTIAL activity • Can function without innervation,
neurotransmitters or hormones

Smooth Muscle NEUROMUSCULAR TRANSMISSION


• Uses intracellular calcium for contraction
• Needs extracellular calcium for its second
messenger system ( when it flows inside
the cell)
• Has AUTONOMICS
• Has partial SYNCYTIAL activity
• Can function without innervation,
neurotransmitters or hormones

108108
MUSCLE CONTRACTION
• Calcium binds trop-C • Myosin heads release
• Trop-C releases trop-I ADP from previous rd
• Trop-I releases • Myosin heads bind
tropomyosin new ATP
• Tropomyosin releases • Myosin heads
actin binding sites hydrolyze ATP
• RELEASE occurs
• Myosin heads bind actin • Myosin heads return
• CONTRACTION occurs to start position

MUSCLE CONTRACTION, cont Clinical Application


• Tropomyosin binds actin
• Trop-I binds tropomyosin
• Trop-C binds trop-I
• Ca-ATPase pumps Ca back into SR
• Phospholambin inhibits Ca-ATPase when
it is done pumping

Diagnosis of a Myocardial
Infarction Management of an MI
• EKG: Na-K pump stops > peaked T-wave > ST- • 24 hour hospitalization
wave depression > ST-wave elevation > T-wave
• Check EKG Q6
depression, then inversion > Q-wave
• Troponin I: rises at 2 hours > peaks in 2days > • Check CIE’s Q6
positive up to 7 days • Monitor for arrythmias
• CK-mb: rises in 6 hours > peaks in 12 hours > • Discharge after 24 hours IF asymptomatic
gone in 24 to 36 hours
• Re-evaluate in 6 weeks
• LDH 1: rises in 24 hours > peaks in 48hours >
gone in 72 hours

109109
In 6 Weeks…
• Exercise stress test
– Positive IF: chest pain is reproduced; ST-wave
changes; drop in BP
• Stress Thallium test
– A perfusion test; looking for a COLD spot
The Functional Unit of Muscles
• Dobutamine or Dipyridamole stress test
– Use when patient unable to exercise
THE SARCOMERE
• Calcium Pyrophosphate scan
– Taken up by DEAD tissue; looking for HOT spot
• 2-D echo
– Evaluates anatomy of heart; measures SV and CO

MUSCLE DIFFERENCES

CARDIAC MUSCLE Smooth Muscle


• In addition to wave of depolarization, • Has NO sarcomeres
calcium MUST flow into the T-tubules • Contains NO troponin > actin and myosin
during phase 2 for contraction to occur are always bound ( LATCHING)
• Ventricle depends on EXTRACELLULAR • Contains BASAL BODIES
calcium to trigger its contraction • Has NO myosin ATPase activity
– Has MLCK and MLCP working together

110110
As Muscle Contracts… Length/Tension Curve
• LENGTH decreases
• FORCE and TENSION increase
• A band stays the same
• Amount of OVERLAP increases
• The H band and I band therefore shrink

Golgi Tendon Organs Muscle Strain


• Located at muscle insertions • Overstretching or tearing a muscle
• Monitor the force of muscle contractions • When a muscle is torn, it goes into spasm
• Allows muscle to hold MAXIMUM muscle to keep the fibers together for proper
contraction force for only one second healing
• Once it fires, muscle fibers MUST relax – Tx: rest it > apply heat > NSAIDS > muscle
relaxants
• Prevents destruction of sarcomeres

JOINT SPRAIN Frank-Starling Curve


• TORN tendon or ligament

• Tx: Rest it > Ice Compression > Elevate


the extremity

111111
Congestive Heart Failure after a
Congestive Heart Failure myocardial infarction
• Over 50% mortality in 5 years • AT LEAST 40% of myocardium lost
• Most common medicare diagnosis • EJECTION FRACTION is less than 45%
• Muscle fibers are overstretched • Due to left coronary artery infarcts 90% of
• Dilated ventricle time
• Increased EDV and ESV
• Decreased contractility > decreased CO
and EF

Treating CHF: Applying


Frank-Starling Curve NEUROMUSCULAR PROFILE
• Decrease volume
– Restrict sodium intake
– Restrict volume intake
• Increase contractility
– Digitalis
– Dobutamine
– Dopamine
• Decrease TPR
– Ace inhibitors

ALL YOU NEED NOW IS THE


CLUE…
Inflammatory Myopathies
• Myositis • ALL HAVE:
• Polymyositis – High ESR
• Dermatomyositis – High WBC count
– Myoglobinemia
• Fibrositis
– High AST, ALT and
• Fibromyalgia Aldolase
• Polymyalgia
rheumatica
• Temporal Arteritis

112112
Muscular Dystrophies Neuropathies
• Duchenne’s • Guillian Barre
– Gower’s sign • Diabetes mellitus
– Waddling gait
• Syphilis
– Pseudohypertrophy of the calf
– Dystrophin protein • Myesthenia Gravis / Myesthenic or “Eaton
– X-linked recessive; onset BEFORE age 5 Lambert” syndrome
• Becker’s
– Onset AFTER age 5
• Myotonic

Acetylcholinesterase inhibitors: Acetylcholinesterase inhibitors:


reversible irreversible
• Edrephonium • AKA Organophosphates
• Neostigmine – End in ….phate ( diflorophate; echothiophate)
• Pyridostigmine – End in ….thion ( malathion; nalathion;
parathion)
• Physostigmine

If they come back complaining


about more weakness… Anticholinergic Drugs
• Myesthenia Gravis has gotten worse or… • Side effects are sympathetic except for…
• Cholinergic crisis • HOT, DRY SKIN!

• Atropine
• REPEAT EDREPHONIUM TEST!!
• Glycopyrollate
– IF patient gets better > disease is worse
• Pilocarpine
• Increase neostigmine
• Benztropine
– IF patient gets worse > cholinergic crisis
• Hold neostigmine > give atropine > decrease • Trihexyphenidyl
neostigmine • ipratropium

113113
Neoplastic Associations Neuropathies, cont
• Myesthenia Gravis: THYMOMA • Multiple sclerosis
• Metachromatic leukodystrophy
• Myesthenic syndrome: SMALL CELL
CARCINOMA; a paraneoplastic syndrome
– Sarcoplasmic reticulum is slow to sequester
calcium; cancer blocks some calcium
channels

Treatment of MS Lower Motor Neuron Disease


• STEROIDS • Amyotrophic lateral sclerosis
• IV GAMMGLOBULINS • Werdnig-Hoffman Disease
• PLASMAPHARESIS • Polio

Cerebellar Disease in 5 to 10 Y/O


children Cerebral Palsy
• Ataxia Telangiectasia • Any permanent neurological damage suffered
PRIOR to age 21 years
• Fredrick’s Ataxia
• Adrenoleukodystrophy • Spastic Diplegia
– Midline cortical problem
• Spastic Hemiplegia
– Cortical problem on ONE SIDE of the brain
• Choreoathetosis
– BASAL GANGLIA is involved: kernicterus
• Atonic
– FRONTAL CORTEX: involves the CST

114114
THE END

115115
I’m Talking About
VASCULAR PHYSIOLOGY SMOOTH…
YOU GOTTA HAVE SOME FLOW SMOOTH MUSCLE, that is

Smooth Muscle Arterioles


• THICKEST layer of smooth muscle is • Considered the STOPCOCKS of the
found in the aorta vascular tree
• MOST smooth muscle by surface area • MOST smooth muscle by surface area
found in the arterioles allows most vasodilatation and
• LEAST smooth muscle found In the veins vasoconstriction
and veinules • Maintain AUTOREGULATION
• Do the MOST to regulate BP, up or down

AUTOREGULATION Veins and Veinules


• Between BP 60 to 160 systolic : cerebral, • Have the most CAPACITANCE
coronary, and renal perfusion remains • Have the least smooth muscle
constant • 60% of blood ( the most) is pooled here
• Depend on skeletal muscle contractions to
• ISCHEMIC infarct: BP went below 60 squeeze blood upward
systolic • Have one-way valves which move blood
• HEMORRHAGIC infarct: BP went above from superficial to deep veins
160 systolic

116116
CONTROL of vessels If Hypovolemia Develops…
• VEINS: under parasympathetic control • VENOCONSTRICTION is first response to
• This is why veins are usually dilated loss of volume > gets volume back into
• Blood flow rate is quite slow circulation
• example: subdural hematomas • Venoconstriction is most significant in skin
and GI
– Poor skin turgor
– Loss of bowel sounds and ileus

A-V Anastamoses CONTROL of vessels, cont


• Shunt blood away from nonessential • ARTERIES: under sympathetic control
organs • This is why arteries are usually constricted
• More concentrated in fingertips, tips of • Reactive hyperemia: cutting an artery or
toes, tip of nose, lips and earlobes the nerve to that artery causes immediate
– Severe vasoconstriction vasodilatation
– hypothermia • i.e. epidural hematoma

Receptors Capillaries
• ARTERIES: alpha one ( IP3/DAG) • Have the thinnest membranes
– vasoconstriction • Made for diffusion
• ARTERIOLES: beta 2 ( c-AMP) • Have the greatest surface area
– vasodilatation
• VEINS: alpha 1 ( IP3/DAG)
– venoconstriction

117117
As Blood Flows Through the
Capillaries… In the Veins and Venules…
• Fluid diffuses out; large proteins (albumin) • Osmotic pressure is now high enough to
stay in PULL waste products into vessels
• Osmotic pressure rises in the capillaries • Blood PULLS waste products back into
• Concentration gradient pushes particles circulation
out of capillaries

Total Pressure in a vessel As a Vessel Narrows…


• Velocity increases
• Flow decreases
• Resistance increases
• Blood Pressure rises

Resistance in Series

118118
Resistance in Parallel During Diastole…
• Ventricles are relaxing
• Very LOW RESISTANCE in coronaries
• Aortic valve is closed
• Aorta has MORE TRANSMURAL
PRESSURE

• MORE CORONARY BLOOD FLOW

During Systole… In Summary…


• Ventricles are CONTRACTING • LESS blood flow through coronary arteries
• There is HIGH RESISTANCE in coronary during SYSTOLE
vessels • MORE blood flow through coronary
• Velocity in aorta is too high arteries during DIASTOLE
• Aortic valve is open • Most work is done in systole!
• LOW TRANSMURAL PRESSURE • A-V O2 difference created during systole
• Therefore: MOST O2 EXTRACTION
• LESS CORONARY BLOOD FLOW occurs in systole

A-V O2 Difference Let’s Look at FLOW


• At REST: the heart extracts 97% of O2
• With EXERCISE: skeletal muscle
• After EATING: GI system
• During INTENSE CONCENTRATION: the
brain

• LOWEST A-V O2 difference: the kidneys,


at all times

119119
POISSOILE’ LAW

NEUROLOGICAL control of blood


Regulation of Radius pressure
• CNS: pCO2 pO2
• LUNGS: pO2
• MUSCLES: pCO2 pH
• CV: adenosine
• SKIN: temp pCO2
• GI: food, especially fats
• RENAL: PGE2; dopamine; ANP

Carotid Sinus REMEMBER!


• Located at the bifurcation of the common • Stroke volume, carotid sinus stretch, CN
carotid IX firing and CN X firing ALWAYS go in
• Responds to FLOW or STROKE VOLUME the same direction
• Increased STRETCH means increased • CN IX and CN X are ALWAYS firing
FLOW – Amount of firing varies always in SAME
DIRECTION as the stroke volume
• Sensory nerve : CN IX
• Efferent nerve : CN X

120120
Autonomic Dysfunction
• Mcc: DIABETES MELLITUS
• In Newborns: Riley-Day syndrome
• In Parkinsonism: Shy-Dragger syndrome
• In elderly: Sick Sinus syndrome

Low Volume State Low Volume State


• Low stroke volume > • > increased renin, • Decreased serum Na( dilutional)
low carotid stretch > angiotensinogen,
low CN IX firing > aldosterone secretion • Decreased serum Cl ( dilutional)
decreased CN X firing > increased Na • Decreased serum K (real and dilutional)
>increased heart rate reabsorption >
> increased NE from increased total body • Decreased urine pH ( aldosterone
NTS in medulla > Na > decreased excretes H)
increased TPR > urinary Na >
decreased RBF > decreased FENa > • Increased serum Ph (metabolic alkalosis)
decreased GFR > increased urinary K > • Increased TPR
>>>

Most common cause of Most common cause of


hyponatremia? hypokalemia?
• LOW VOLUME STATE • LOW VOLUME STATE

121121
Most common cause of
Most common cause of high TPR ?
hypochloremia?
• LOW VOLUME STATE • LOW VOLUME STATE

Most common cause of metabolic


alkalosis? Ace Inhibitors
• LOW VOLUME STATE • Stop conversion of AT-1 to AT-II
• Increased bradykinin
• ALKALOSIS favors calcium precipitation • VASODILATION and VENODILATION
with phosphate • Decreased preload and afterload
– KIDNEY STONES !!!! • BALANCED dilation
• Contain sulphur
• Decrease mortality in CHF; decreases
proteinuria in diabetic nephropathy

Ace Inhibitors Angiotensin Receptor Blockers


• Captopril • Losartan
• Lisenopril • Vosartan
• Enalopril
• rinilopril • Do not contain sulphur
• NO elevation in bradykinin

122122
What is a VASCULITIS? Vasculitis
• Schistocytes ( Burr cells; helmet cells)
• Petechiae, purpura and ecchymoses
• LOW ENERGY STATE
• LOW VOLUME STATE
• Restrictive lung disease profile
• CELL MEDIATED inflammation

All You Need Now is the Clue!!! Ig-A nephropathies


• Berger’s
• Henoch-Schonlein Purpura
• Alport’s

More vasculitides More vasculitides


• Buerger’s • Temporal arteritis
• DIC • Ankylosing Spondylitis
• HUS • PAN
• TTP • Wegener’s
• DM
• Goodpasture’s
• Syphilis
• Leukocytoclastic
• Takayasu
• kawasaki • Churg-Strauss

123123
Collagen Vascular Diseases with
Collagen Vascular Diseases LOW COMPLEMENT
• CREST syndrome • PSGN
• Scleroderma • Serum Sickness
• Progresive Systemic Sclerosis • SBE
• MCTD • SLE
• RA / JRA (Still’s disease) • MPGN : type l, ll
– Felty’s: RA & leukopenia and splenomegaly • Cryoglobulinemia
– Becet’s : RA & GI ulcerations
– Sjogren’s : RA & xeropthalmia, xerostomia

THIS IS THE END

124124
CARDIAC PHYSIOLOGY
THE HEART OF THE MATTER

PRESSURE is the GRADIENT of the


organs! OPENING SNAP
• A valve is popping open during diastole
– TRICUSPID STENOSIS
– MITRAL STENOSIS

EJECTION CLICK MIDSYSTOLIC CLICK


• A valve is popping open during systole • Blood is coming at high velocity, slapping
– AORTIC STENOSIS the mitral valve on the way out
– PULMONARY STENOSIS • Occurs closer to S-1 with standing and
closer to S-2 with lying down
– MITRAL VALVE PROLAPSE
• Occurs in 7% of normal women (estrogen
connection)

125125
SOFT S-1 LOUD S-1
• One of the two valves that contribute to • Either you have a stiff valve that bangs
this sound is NOT closing shut: TRICUSPID or MITRAL STENOSIS
• Or the ventricle is contracting harder
– TRICUSPID REGURGITATION
– MITRAL REGURGITATION
– VALVE IS NOT THERE!
• Tricuspid atresia
• Mitral atresia
– BOTH ARE CYANOTIC

SOFT S-2 LOUD S-2


• One of the two valves that contribute to • Either one of the valves is stiff and
this sound is NOT closing BANGS shut when it tries to open
– AORTIC REGUGITATION
– PULMONARY REGURGITATION • AORTIC STENOSIS
– OR the valve is not present
• PULMONARY STENOSIS
• AORTIC ATRESIA
• PULMONARY ATRESIA • Or there is HIGH pressure in front of the
– BOTH ARE CYANOTIC valves (systemic or pulmonary
hypertension)

S-3 S-3
• Sound made by a noncompliant ventricle • VOLUME overload
• ???????????????? • DILATED ventricle
• DECOMPENSATION

• S-3 said to be normal ONLY in an


adolescent female

126126
ESTROGEN CONNECTION S-4
• Estrogen is a muscle relaxant • Sound made by an atrial kick
• Causes liver to produce many proteins
– High ESR or CRP • PRESSURE overload
– Lipoproteins • HYPERTROPHY
– TBG
• COMPENSATION
– Angiotensinogen
– Clotting factors
• Especially fibrinogen, but not factor 11 • Most common gallop (atherosclerosis)

MURMURS! MURMURS! MURMURS! MURMURS CAUSED BY…


• TERBULENCE
• Reynold’s number > 2500
– Murmur: if it is in the heart
– Bruit: if it is in a vessel
• Occurs when you have 70% stenosis

127127
MURMUR GRADES A SYSTOLIC MURMUR
• Grade 1: barely audible • Valves that are supposed to be open are
• Grade 2: easily audible stenotic ( PULMONARY or AORTIC
• Grade 3: pretty loud STENOSIS)
• Grade 4: palpable thrill • OR valves that should be closed are not
closing ( MITRAL REGURGITATION or
• Grade 5: able to hear with stethoscope off TRICUSPID REGURGITATION)
the chest
• Grade 6: able to hear across the room
without stethoscope

HOLOSYSTOLIC ( PANSYSTOLIC)
SYSTOLIC MURMURS MURMURS
• Aortic stenosis • Tricuspid regurgitation
• Pulmonary stenosis • Mitral regurgitation
• Mitral regurgitation • VSD
• Tricuspid regurgitation
• Ventricular septal defect

PANSYSTOLIC – increases on PANSYSTOLIC – increases on


INSPIRATION EXPIRATION
• Tricuspid regurgitation • Mitral regurgitation
• VSD

• Radiates into the axilla: MITRAL

128128
SYSTOLIC EJECTION MURMURS AORTIC STENOSIS
• Aortic stenosis • Radiates to the carotids( neck)
• Pulmonary stenosis • LOUDER with leaning forward, making a
fist, blowing up a blood pressure cuff, or
squatting

• Crescendo – decrescendo or diamond


shaped murmur
• PULSUS TARDUS
• DELAYED CAROTID UPSTROKE

IHSS IHSS, cont


• Autosomal dominant • Excessive hypertrophy compresses the
• Muscle fibers are hypertrophied but coronary arteries
disorganized • Excessive hypertrophy obliterates the
• Any young athlete who dies suddenly, ventricular space
especially during peak exercise
• Septum is asymmetrically thick, especially • Murmur is LOUDER with standing or with
the top > causes SUBAORTIC stenosis Valsalva; decreased with increased TPR
• PULSUS BISFERIENS

IHSS, cont DIASTOLIC MURMURS


• Tx: need to decrease contractility; allow • Either the valves that should be open are
time for adequate ventricular filling stenotic (MITRAL STENOSIS or
– Beta – blockers TRICUSPID STENOSIS)
– Adequate fluid intake • Or the valves that should be closed are
– Bar from organized sports regurgitant ( AORTIC REGURGITATION
– Do an ECHO on entire family or PULMONARY REGURGITATION)

129129
DIASTOLIC BLOWINNG or
DECRESCENDO MURMUR Aortic Regurgitation
• AORTIC REGURGITATION Radiates to carotids; LOUDER with leaning
forward, making a fist, blowing up a blood
• PULMONARY REGURGITATION
pressure cuff, or squatting
Austin-Flint murmur: mitral regurgitation
• Increases on inspiration: Pulmonary Widens the pulse pressure
regurgitation bounding pulses
• Increases on expiration: Aortic waterhammer pulse
regurgitation head-bobbing
Quincke’s pulses

Pulmonary Regurgitation Diastolic Rumbles


• Radiates to the back • TRICUSPID STENOSIS
• Louder on inspiration • MITRAL STENOSIS
• Graham-Steele murmur: tricuspid
regurgitation • Increases on inspiration: tricuspid
regurgitation
• Increases on expiration: mitral
regurgitation

CARDIAC PATHOLOGY CARDIOMYOPATHIES


• DILATED
• HYPERTROPHIC
• RESTRICTIVE
– CVD
– Amyloidosis
– Hemochromatosis
• CONSTRICTIVE
– Tamponade ( Kussmaul sign; Pulsus Parodoxicus)
• Trauma
• cancer

130130
EFFUSIONS
• Transudate: mostly water
• Exudate: mostly protein

• Transudate: sp. G < 1.012


– Protein < 2grams
• Exudate: sp. G > 1.012
– Protein > 2grams

Congenital Heart Diseases Cyanotic Congenital Heart Disease


• VSD • Transposition of Great Arteries
• Tetrology of Falot
• ASD
• Tricuspid Atresia
• PDA • Total Anomalous Pulmonary Venous Return
• Coarctation • Truncus arteriosus
• Pulmonary Atresia
• Aortic Atresia
• Hypoplastic Left Heart
• Ebstien’s Anomaly

VALVULAR DISEASES: most common


causes
Pulmonary Disease
• Aortic stenosis: aging • Most common cause is ALWAYS
• Aortic regurgitation: aging congenital
• Mitral stenosis: Rheumatic fever • Pulmonary valve is protected on BOTH
• Mitral regurgitation: MVP, SBE, collagen sides
diseases
• Tricuspid stenosis: Rheumatic fever,
carcinoid syndrome
• Tricuspid regurgitation: acute endocarditis

131131
Flow – Volume Loops

Antiarrhythmics

132132
Na – Channel Blockers Wolf-Parkinson-White Syndrome
• Class Ia • Class Ic
– Quinidine – Encainide
– Procainamide – Flecainide
– Disepyramide – Propofenone

• Class Ib
– Lidocaine
– Tocainide
– Mixeletine
– Phenytoin

Class IV – Ca Channel Blockers Class II – Beta Blockers


• Verapamil • End in – lol
• Diltiazem • Specific B-1: begin with A thru M (not L,C)
• Nefedipine • Specific B-2: begin with N thru Z (incl L,C)
• Nicardipine
• Nimodipine
• Amlodipine
• Femlodipine

133133
Class II – Beta Blockers Class III: K – channel Blockers
• Propanolol Acebutalol • Napa
• Esmalol Atenalol • Sotalol
• Timolol Pindalol • Bretylium
• Butexalol • Amiodorone
• Sotalol
• Labetalol
• Carvidalol

THE END

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Foregut (rotation 90°)


Parasympathetic: Sympathetic:splanchnic
Celiac artery
Vagus nerves T5-T9

Midgut (rotation 270°)


Parasympathetic: Sympathetic: splanchnic

PHYSIOLOGY
Superior mesenteric
Vagus nerves T9-T12

Hindgut ( Septation)
Parasympathetic: pelvic Sympathetic: lumbar
Inferior mesenteric
splanchnic nerves splanchnic nerves: L1-L2

` Extends from the second part of duodenum


` Gives rise to the GI, from mouth to second to the spleenic flexure
part of duodenum, including the respiratory
tract ` Develops in the YOLK SAC

` Must go through a 270 degree rotation as it


` Lungs and upper GI have many congenital
migrates from yolk sac into abdominal cavity
connections
` MIDGUT ROTATION requires ciliary action
◦ KARTAGENER’S: SITUS INVERSUS

` CNS
` FROM splenic flexure to the anus
` ORAL
WATERSHED AREA: the spleenic flexure
` PHARYNGEAL
`
◦ H
Has th l t bl
the least d supply
blood l
◦ Most susceptible to ischemic infarcts
` ESOPHAGEAL
` UGI
` LGI

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` SENSORY INFORMATION
◦ THINKING about food ` Cortex can over ride any basic urge:


HEARING about food
SMELLING food (outer layer of the cerebrum-forgut)
◦ TOUCHING food
◦ TASTING food

◦ ALL sensory information must reach the cortex;


◦ Response is via the CORTOCOBULBAR pathway via the vagus ` LIMBIC SYSTEM- responsible for basic urges
◦ No longer do a vagotomy for peptic ulcer disease (can’t enjoy ◦ Hippocampus – long term memory
food) ◦ Amygdala- reward and fear, mating
◦ Highly selective parietal cell vagotomy now

Responsible for setting time: Circadian rhythms


Melatonin – from tryptophan- milk and turkey
` Neurotransmitter: melatonin
Light outside- melatonin low- DAYTIME - Bright lights in companies, casinos
Dark outside-
outside melatonin high-
high NIGHT
- 1st, 2nd, 3rd shift workers/ workers comp
Morning- catabolic processes are in their highest
function- working out in the morning is the best

Feeding Center Satiety Center ANOREXIA NERVOSA Bulimia


(HUNGER) ` Starvation ` Enjoys eating
` Location: Desentasize your
◦ Vento-medial nucleus of
`
` Chunky female
Location: hunger center
` the hypothalamus ` Trying to please her
◦ Lateral hypothalamus Body
ody dys
dysmorphic
o p c
b f i d
boyfriend
`

Stimulus: disorder
`
Small body frame and
` Purging
Stimulus: ◦ Stop feeding: ↑Glucose `
Abrasion on knuckles
`
◦ Feeding (hunger) ↓ Glucose thinks they are over `

Stomach stretch will weight ` Tooth enamel erosion


If sugar remains normal the stimulate satiety center ` Young female trying to ` Laxative abuse
Can override- Cortex
center will not fire please her mother ` BMI > 25
Destruction: ` BMI < 17
Destruction: Anorexia Hypothalamic obesity syndrome

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` Lesion of the satiety center (Ventormedial) ` Men: 5 feet = 106 lbs


` Women: 5 feet= 100 lbs
` Uniparental disomy- one parent carrying lesion
` Paternal in origin ` Add 5 lbs for each inch past that…
` T i
Trinucletide
l id repeats
` Chromosome 15 ` Small frame: add 15 lbs
` Large frame: add 30 lbs
` Very aggressive appetite
` Die due to over eating ` (i.e. male 5’10”: 106 + 50 +30 = 186 lbs)

` Norepinephrine or Serotonin (more important), ` They are taken up presynaptically, causing release
so many people use Amphetamines for weight of all catecholamines
loss…
◦ Increase DA, NE and Serotonin

` 80% of time > stimulates satiety center ◦ Nausea/ vomiting -(DA)


(DA) stimulates

◦ Neuromuscular- basal ganglia- tics (DA)


` 20% of time > stimulates hunger center
` Amphetamine tox. clue – vertical nystagmus

◦ Methylphenidate- ritilan (1st line) [drug dependence]


x Narcolepsey – (hipnogogic)hallucinations as you fall asleep ` Controls MENSES- progesterone stimulates
hunger system
◦ Pemoline-
x hepatic necrosis (hepatitis)- off the market 2005
` Pregnancy- due to corpus luetum
◦ Dexadrine-
D d i d
dexatrim
t i - weight
i ht loss
l OTC

FOOD craving…….
◦ LSD- hallucinations from Seratonin (slow, lazy)

◦ PCP- hallucinations from Seratonin (violent, aggressive)

◦ ECSTACY- hallucinations from Seratonin (stimulate thirst)

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STRESS RESPONSE:
` Controls TEMPERATURE:
◦ ANTERIOR Hypothalamus: cools (inhibits NE) x Parasympathetic first (HR dec.) increased
x Lesion anterior- die from: hyperthermia gastric motility, increase acid production

◦ POSTERIOR Hypothalamus: warms x Sympathetic second (B/P inc) constipation,


x Lesion posterior- die from hypothermia pulls blood from GI, so you can not buffer acid

◦ Acetametaphen: for use with fever Stress from burn- Curlings ulcer
(stimulate anterior hypothalamus- cools), then it ICP- Cushing's ulcer
blocks posterior so you do not go back up again
Seizure- foam at the mouth, defecate, urinate
◦ Toxicity- microsteatosis, Reye syndrome in children (all parasympathetic)
◦ Tx: N-acetylcystine-reducing agent
◦ - 4 hour level will determine if you use it Hollywood and sphincter control

` Put food into mouth- salivary glands respond

` SALIVARY GLANDS
◦ Parotid [ in front of ear ](serous)-water - CN 9
◦ Lingual [ on tongue ] (most serous) CN 7
◦ Sublingual [under tongue] (most mucus) CN 7
◦ Submandibular [jaw] (mucus) CN 7

◦ Saliva in your mouth has to be HYPOTONIC (cracker)


◦ Food on your cheek- food will get stuck (gummy bear)

` Acetylcholine- CNS: excitatory, PNS: activates


muscles ` Norepinephrine- α and β1
` Epinephrine- has methyl group (hormone)
` Methacholine- dx asthma (old), beta 2 agonist to ` Ephedrine- OTC med
bring you out ` Pseudoephedrine – stress incont.
` Phenylephrine- neurogenic shock Tx (constrict)
` Pilocarpine- sweat test ( > 60), open angle
glaucoma (chronic) ` RESULT: remove the blood supply to the GI causing
a decreased saliva that has increased osmolarity
` Carbachol- post op urinary retention (stimulate (less saliva- more salt)
bladder emptying)
` Bethanecol- post op urinary retention ` Exercise- mouth dry, white film in corner

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MCC: of malabsorption in children ` Meconium ileus: first presentation in neonate

` CFTR gene on chromosome 7 ` Malabsorption develops as pancreatic ducts


become clogged
` Defective CHLORIDE transport
` Infertility in men develops as epididymus is
clogged (unable to ejaculate)
` Chloride traps sodium, increasing the salt
content and thickness of secretions ` Obstructive lung disease develops over the
years (unable to cough up thick mucus)
` Affects GI tract, lungs, pancreatic duct, sweat
glands and epididymus

` Worst bacterial enemies: ` IgA


◦ Staph Aureus and Pseudomonas Auregenosa ` Lipase- little fat break down
` Amylase: breaks alpha 1,4 bonds
◦ MUST cover Staph Aureus with one ` Lysozyme: a detergent
antibiotic and Pseudomonas Auregenosa ` HCO3:
HCO3 three
h sources off acid
id
with two antibiotics ◦ From food- drinks
◦ Produced by bacteria ( strep mutans)
◦ Reflux
◦ Dx: Pilocarpine: Cl sweat test
< 40 Normal
40 – 60 Heterozygous
> 60 CF

` A normal phenomenon: GERD

` INCISORS: cut 10 – 15 months


` ESOPHAGITIS- tissue inflammation (T-cell/Mac)
` BICUSPIDS: chop 15- 18 months
` MOLARS: grind 18 – 24 months
` BARRETT’S ESOPHAGUS- short to long
columnar
` P i
Primary h fall
teeth f ll out by
b age 8 and
d are
replaced by permanent teeth
` MALORY WEIS SYNDROME- tears in submucosa
(ETOH, vomiting)

` BOORHAAVE’S SYNDROME- Rupture of


esophagus

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` Masseter- closes Tip of tongue rises >


` Temporalis- (closes) moves jaw forward and back ‰ Sides of tongue rise and fold medially >

` Medial Pterygoids (closes) ‰ Tip of tongue rises to hard palate >


‰ Gravity begins bolus rolling >
` Lateral Pterygoids- (opens) lowers jaw
‰ When bolus approaches trachea
trachea, epiglottis
‰ Closes off glottis >
` Innervated by cranial nerve 5 (Trigeminal)-
‰ Bolus rolls over epiglottis/touches the pharynx>
mandibular V3
‰ CN 9, 10 sense the bolus >
‰ UES opens relaxes >
` Develop from first branchial arch ‰ Bolus drops into esophagus

` Nucleus Ambiguus: innervates the UES-


` UPPER ESOPHAGEAL SPHINCTER efferent vagus (motor CN 10)
◦ Voluntary
◦ Skeletal muscle in upper 1/3 of esophagus
` Dorsal motor nucleus: innervates the rest
◦ Constrictors of the pharynx
of GI – efferent vagus (motor CN 10)
y p y g
◦ Stylopharyngeus
◦ Develops from 4th pharyngeal arch ` Primary peristalsis: requires vagus nerve
and Auerbach’s plexus; begins just distal
◦ Innervated by to the UES only
x CN 9(stylopharyngeus)
x CN10(all others) ` Secondary peristalsis: intrinsic to smooth
muscle; can begin anywhere in GI

Nucleus 1° Peristalsis
Ambiguous - Vagus CN 10
UES - Auerbauch (VIP)

2º Peristalsis
- Stretch from food

Dorsal motor nucleus No receptive


of CN 10 (Vagus)
LES
relaxation:
Receptive Achalasia
relaxation

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4/29/2008

Esophageal Pathology
` Choanal atresia: lack apoptosis /blue-
feeding
` Esophageal atresia w/ distal TE fistula
◦ Vomit on first feeding

` Zencker’s: congenital
UES
` Traction diverticula: occurs due to large bolus
Plummer Zencker’s
Vinson Diverticulium -
C
Congenital
it l
Schatzki rings: Syndrome UES
-Intermittent
dysphagia
Iron deficiency
Traction
- Around LES Diverticulium

LES Strips of mucosal tissue- lack apoptosis LES


Risk of esophageal cancer
Young woman
Microcytic anemia

Patients with a history of GERD > 5 years ` Abnormal esophageal acid exposure
(Screening for Barrette’s esoph.-sq. to columnar)
Tx: PPI’s, upper endoscopy every 2-3 years ` > 4 week trial of PPI’s still having symptoms

` E l d GERD iin patients


Exclude i i h unexplained
with l i d
Patient’s with long standing cirrhosis: screening for chest pain
varices
Tx: Propranolol- decreases risk of bleeding ` GERD symptoms with a negative upper
endoscopy

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` Best initial test for dysphagia ` Diagnosis:


Dysphagia
` Not the best test if the problem is due to an Unexplained chest pain w/o mechanical obst.
obvious obstruction, then the best test is
upper endoscopy ` Transducer
T d placed
l d iin esophagous
h to record
d
pressure
` Achalasia- bird beak
` Most accurate test for Achalasia, Esophageal spasm
` Diffuse esophageal spasm- cork screw

` Diagnosis: GERD

` NGT placed at the esophageal junction

` Dilute
Dil hydrochloric
h d hl i acid
id iis iinjected
j d through
h h
the NGT to reproduce the symptoms of GERD

` OLD TEST..PPI’s and 24 hour pH monitor

` ALWAYS THE WRONG ANSWER !!!!!!!!!

Orad Fundus
Region
LES
` Orad region- fundus and proximal portion of
Caudad Cardia FOOD the body
Region ◦ Thin muscle wall

` Caudad region - distal portion of the body


Body and the antrum
Pyloris ◦ Thicker muscle wall
◦ Region responsible for mixing the food

Antrum –
G cells
Duod

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` Mechanoreceptors detect distension of


the stomach and relay this information
to the CNS via sensory neurons
` Receptive relaxation: relaxation of the lower
esophagous sphinctor and the orad region to ` CNS then sends efferent information to
the smooth muscle wall of the orad
accept food into the stomach.
stomach, causing it to relax

` Vagovagal reflex
reflex- both afferent and efferent ` Neurotransmitter released from
f the
limbs of the reflex are carried in the vagus postganglionic vagal nerve fibers is VIP
nerve VIP
Afferent
Vagotomy eliminates receptive
Vagus `
relaxation
Efferent

` During fasting- periodic gastric contrations


occur MMC ` Takes approximately 3 hours to empty
“ migrating myoelectric complexes”

Rate must be regulated to provide adequate time to


` Mediated
d d my Motilin
l `
◦ neutralize the gastric H+ in the duodenum
◦ adequate time for absorption of nutrients
` Occur ever 90 minutes

` Function to clear the stomach of any


residue remaining from a previous meal

Four major components:

` Two factors slow or inhibit gastric emptying: ` Hydrochloric acid (HCL)- function is to reduce pH for
◦ Fat and H+ in the duodenum the conversion of pepsinogen to pepsin
◦ Fat- mediated by CCK (secreted by duodenum)
` Pepsinogen (inactive) Low pH converts it to the active
◦ H+- mediated by reflexes of the enteric nerves (myenteric form- pepsin for protein digestion
plexus) ensures content is delivered to the duodenum
slowly
` Intrinsic factor-for the absorption of Vit. B12 in the
ileum (essential)

` Mucus- protects the gastric mucosa from HCL

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Glands of the Body of the Stomach Glands of the Antrum of the Stomach
` Empty their secretory products via ducts
` Opening of the glands are called pits ` Contain 2 cell type:
` Lined with epithelial cells ◦ Mucus cells- mucus and HCO3 are
protective
Gastric
Lumen ◦ G-cells (secrete gastrin into circulation)
Epithelial cells Gastric
Lumen Epithelial cells

Mucous cells
Mucous cells Mucus, Pepsinogen, and HCO3-

Parietal cells HCL & Intrinsic factor


G - cell Gastrin
Chief cells Pepsinogen

` Mucus from goblet cells


` Prostaglandins (PGE2)
` HCO3: alkaline tide

` Aspirin-
A i i irreversible
i block
ibl bl kCCox 1 & 2
` NSAIDs - reversible inhibit COX
` Steroids

` COX 1 – GI COX 2- Joints

` Misoprostyl- replace PGE ` Gastric ulcers due to lack of blood supply;


(Vasocon/Vasodilation- alprostadil) sympathetic output causes vasoconstriction

` CUSHING’S ULCER
` Cox 2 inhibitors
◦ Celecoxib- only one left ` CURLING’S ULCER
◦ Rofecoxib- off the market
◦ Valdecoxib – off the market ` STRESS ULCER
◦ (problem if on > 18 mo)- block
prostacyclins- inhibit platelet agg.

10

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4/29/2008

Regulation of H+ Secretion

` Is the most common cause of upper GI ` Type B gastritis (located in antrum)


bleeding in older children and adults
◦ Due to a breakdown in barrier protection
` Superficial erosions

◦ “NOT TOO MUCH ACID!”


` Type A Gastritis (located in body)
◦ Autoimmune etiology
◦ Antiparietal cell antibody ◦ Associated with Helicobacter Pylori
◦ Atrophic gastritis
Body
◦ Adenocarcinoma risk

` Gastric Ulcer ` Duodenal Ulcers

◦ Pain is worse during the meal ◦ Pain is worse 30 to 40 minutes after a meal and
also at night
◦ Located in the antrum
◦ Located in the second part of the duodenum
◦ Associated with H. Pylori 70% of time
◦ Associated with H. Pylori 95% of time
◦ Associated with CANCER 20% of time
◦ Cancer risk < 1%
◦ Endoscopy on ALL patients
◦ Treat empirically with medication

11

145
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` Surgical indications: ` Definition: a mass made of


undigestible materials
◦Intractable pain- meds fail
Hemorrhage massive UGB
◦Hemorrhage- ◦ Most common type:
yp Hair

◦Obstruction- Scarring ◦ Causes a gastric outlet obstruction


◦Perforation- Retroperitoneal
R/O- CT ◦ TX: endoscopy and removal

` SLIDING TYPE: 90% ` ROLLING TYPE:

◦ Involve sliding of the fundus into the esophageal ◦ Due to a defect in the diaphragm
hiatus
q
◦ Requires g y
surgery
◦ MCC: obesity; restrictive lung disease
◦ Risk of strangulation and infarction
◦ TX: conservative measures; medications;
x surgery( Nissan fundoplication)- no belch

◦ High incidence of GERD

` Hypertrophy of the pyloric muscle


` Rare
` Presents at 3 to 4 weeks of life
` Large RUGAL FOLDS on biopsy
` PROJECTILE
J vomiting
g
` H l i off goblet
Hyperplasia bl cells
ll
` Olive sign; string sign on Barrium;
` Cells ooze out proteins
◦ Like nephrotic syndrome
◦ Low albumin ` DX: ultrasound
` TX: correct fluids and electrolytes
pyloromyotomy

12

146
4/29/2008

` PROTEIN: no protein digestion in the mouth;


significant digestion in the stomach;
completed in the small bowel

` SUGARS: significant
g digestion
g in the mouth;; it
stalls in the stomach; completed in the small
bowel Now we call it CHYME
` FATS: negligible digestion in the mouth; it
stalls in the stomach; completes in the small
bowel

` Secretin ` Zymogens: inactive enzymes


` CCK
` Motilin ` First
trypsin activated by
` GIP enterokinase
` VIP
` Somatostatin ` Trypsin
then activates all other
` Enterokinase
enzymes

` Lactase
` Breaks alpha 1,4 glycosidic bonds ` Sucrase
◦ Lactose ` Maltase
◦ Sucrose ` Alpha-dextrinase
◦ Maltose
◦ Alpha-dextrins
p ` Sucrase def is most common primary
disacharidase deficiency
◦ Fructose is only sugar with its own transport system
` Lactase def is most common secondary
disacharidase deficiency

◦ First enzyme to disappear in gastroenteritis; last


one to return( in about 48 hours)

13

147
4/29/2008

` Phlegmon: inflamed pancreas with the


` The most common severe abdominal pain intestines wrapped around it

` Causes a severe ileus


` Pain is mid-epigastric, boring through to the
back
` Severe dehydration
` Children: MCC is (1)abdominal trauma
(2) infections ` Ransons criteria:
x Cocksackie B, Mumps virus x Age > 55 years
x Blood sugar rises above 200
x WBC > 16,000
` Adults: MCC is (1) alcohol x LDH > 350
(2) gallstones x AST > 250

` Poor prognosis in first 24 hours if… ` MANAGEMENT: (for ANY abdominal pain)
◦ NPO
◦ Patient needs more than 6 liters of fluid ◦ NG tube
◦ IV normal saline
◦ pO2 < 55 (ARDS)
◦ Meperidine
◦ Hemoglobin drops by 2 or more grams
◦ Abdominal x-ray

◦ Calcium drops to below 8

` Hemorrhagic pancreatitis: ` Pseudocyst: has no epithelial lining


◦ Bleeding into the retroperitoneal
◦ Grey-Turner sign ◦ Can become infected ( abscess)
◦ Cullen sign
◦ Tx: connect it to skin or small bowel

◦ TX: subtotal pancreatectomy ◦ Characterized by persistent high amylase

14

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` RUQ colic (stone): pain comes in waves


` Virchow’s triangle
` Murphy’s sign: cessation of inspiratory
effort with RUQ palpation
Bile Lecithin
` 80% are made of cholesterol (not seen on x-ray)
Salts
` 20% are made of calcium bilirubinate (hemolytic
anemia) excess biliruben

` 90% get lodged in cystic duct (Alk phos normal)


Cholesterol
` 10% get lodged in the common bile duct
` (Inc. Alk phos)

` 3 clues for common bile duct stone: ` Dx: Ultrasound;


` HIDA scan (most specific)- injectable radioactive
◦ Pancreatitis - if an obstruction- non visualization of gall bladder

◦ High alkaline phosphatase-


phosphatase common bile duct ` Management: like ALL abdominal pains
◦ NPO
◦ High WBC count and fever- pus backs up ◦ NGT
◦ IV
◦ Opiates- meperadine (always start with)
◦ ABD xray

` Stone in common bile duct…

◦ Surgery: ERCP (endoscopic retrograde


choleangopancreotophagraphy-pull it out by mouth;

◦ Laporoscopic cholecystectomy- 90% of cases

◦ Asymptomatic gallstones-ursodeoxycolic acid


◦ (DM, OCP, pregnancy) and schedule for surgery (60 % will
progress)

15

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4/29/2008

` Helps EMULSIFY fats


` Bile acids:
` Comes from Phosphatidylcholine Cholesterol go to the liver and forms
Cholic and Chenodeoxycholic acids
which are conjugated to Glycine and
` Modified to make surfactant
Taurine to form bile salts

` Help EMULSIFY fats

` Cholestyramine ` Micelle
` Colestipol ` Short chain fatty acids
` Medium chain fatty acids
` Side effects: need cholesterol to make ` Long chain fatty acids
Estrogen ` Chilomicrons
Chil i
Steroids ` VLDL
Malabsorption (diarrhea) ` IDL
Fat for energy ` LDL
Fat soluble vitamins ` HDL
Cause gall stone

Atherosclerosis
LDL and B100 Clathrin Pits
` Metabolism of the lipoprotein is
Symptoms:
70% Stenosis
defective
FOAM CELL
Events: ` Triglycerides, cholesterol or both can
90% Stenosis be elevated
Atheroma Cholesterol

16

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4/29/2008

` Predisposes to xanthelesma and ` Predisposes to early coronary artery


pancreatitis disease and xanthomas

` Defective metabolism of VLDL, IDL ` Defective metabolism of LDL


or Chilomicrons

` TYPE 1: elevated chilomicrons


` STATINS: block HMG-CoA reductase
` TYPE 2A: elevated LDL ` Main side effects: myositis; hepatitis

` TYPE 2B: elevated LDL & VLDL ◦ Lovastatin


◦ Provostatin
` TYPE 3: elevated IDL ◦ Simvastatin Works best after 8pm
◦ Atorvastatin
` TYPE 4: elevated VLDL ◦ Cirivastatin
◦ Valdestatin
` TYPE 5: elevated VLDL & CHILOMICRONS ◦ Reduvastatin

` Cholestyramine- binds bile and blocks ` Gemfibrozil : increases LPL


reabsorption ` Clofibrate
` Colestipol

` Niacin
` Probucol
` Niacin :
(-) VLDL
` Probucol

17

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` Intravascular hemolysis ` Extravascular hemolysis


◦ Vasculitis ◦ Splenomegaly
◦ Schistocytes ◦ Something is wrong
◦ Low haptoglobin with RBC membrane
◦ Fibrin deposition in vessels x Mcc: autoimmune
tear RBCs and platelets hemolytic anemia

` Direct hyperbilirubinemia: conjugated ` DIRECT


◦ Criggler-Najjar syndrome, type 2
` Indirect hyperbilirubinemia: unconjugated
◦ Rotors syndrome
` INDIRECT ◦ Dubin Johnson syndrome
Dubin-Johnson
◦ Low albumin
◦ Gilbert syndrome
◦ Criggler-Najjar syndrome
x Type 1

` Newborns: choledochal cyst; biliary atresia ` The Ileum: in children


` The Sigmoid: in adults
` Children and adults: pancreatitis; gallstones;
sclerosing cholangitis; primary biliary
cirrhosis ` Diverticulosis
` Diverticulitis
` After age 40: pancreatic cancer ` Volvulus
` Intussusception

18

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` The last part of the small bowel ` Begins with pain around umbilicus
(visceral pain)

` An organ with NO known function ` Pain settles into RLQ ( McBurney’s point)
–somatic
somatic pain

` Caused by a fecolith

` Management: like ALL abdominal pains


◦ 30% perforate in 24 hours
◦ Incidental appendectomies can be done

` The first part of the colon


` LAST chance to REABSORB fluids and
electrolytes
` The largest part of the colon

` Many Na-K pumps controlled by


` Cecal cancer has poor prognosis
aldosterone

` Haustration ` Haustration

` Mass movement
` Mass movement
` Watershed area: spleenic flexure

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` Relax pubococcygeus muscle


` Rectum falls in line with sigmoid colon
` Sits at a 90 degree angle with the ` Gravity and distention start moving stool
descending colon AND rectum down
` Once stool touches internal anal sphincter,
f
first urge to d f
defecate occurs
` Pubococcygeus muscle forms the
` Once stool touches external anal sphincter,
sling that holds the rectum at 90 last urge to defecate occurs
degree angle ` Relaxation of pelvic floor muscles relaxes
both sphincters
` NO sympathetic input to defecation

Duodenum Jejunum Ileum

Amino 90 ` Ca-carbonate ` PPI


Acids
` Aluminum hydroxide ◦ Omeprazole
Mg-hydroxide ◦ Esomeprazole
FATS 80 `
◦ Pantaprazole
` Gaviscon ◦ Robeprazole
Sugars 90 ` Sucralfate ◦ lomeprazole
` Bismuthh
Iron ` H-2 Blockers
90 ◦ Cimetidine
◦ Ranitidine
A,D,E,K,
100 ◦ Famotidine
B12
◦ Nizatidine

All else 90

` Simethicone ` Mineral oil ` Abetalipoproteinemia

` Loperamide ` Cisapride ` Ataxia telangiectasia


` Diphenoxylate ` Metachlopramide ` Selective Ig-A def

` Psillium ` Sulfasalazine
H
` Heavy h i disease
chain di
` Sorbitol ` Sulfapyrazone ` Celiac Sprue
Mg-citrate
` Tropical Sprue
`
` Phenophthalien
` Docussate sodium ` Necrotizing enterocolitis

20

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` Irritablebowel syndrome ` Crohn’s disease


◦ Women
` Ulcerative Colitis
◦ Men
` Spastic colon
◦ Transmural ◦ Hematochezia
◦ Melena ◦ Mucosal
` Whipple’s disease
◦ Granulomatous ◦ Starts in rectum > prox
◦ Creeping fat ◦ Pseudopolyps
` Toxic megacolon
◦ Cobblestoning ◦ Continuous
◦ Skip lesions ◦ HLA B-27
` Ischemic bowel
◦ From mouth to anus ◦ Sclerosing choolangitis
◦ Starts in ileum ◦ Toxic megacolon
◦ Fistulas ◦ Lead pipe colon
◦ Colon cancer risk: 10%
at 10 years
x Begin annual colonoscopy
at 7 years

` Newborns: swallowed maternal blood

` Children: epistaxis

` Adults:
Ad l gastritis
ii

` Massive UGI bleeding


◦ Children: meckels diverticulum
◦ Adults: Peptic ulcer disease

` Newborns: swallowed maternal blood ` Newborns:


◦ Choanal atresia
` Infants: anal fissure
◦ C-type esophageal atresia
` Child
Children: l
polyps
◦ Duodenal atresia
` Adults: IBD

` Elderly: Angiodysplasia
x Diverticulosis
x Cancer

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`3 to 4 weeks old `4 to 6 months old


y
◦Pyloric stenosis ◦achalasia

`2 years to 40 years
`6 months to 2 years of age
◦intussusception
◦Adhesions

◦Internal hernias

` FIRST year of life `1 year to 40 years

Hirschsprung s disease
◦Hirschsprung’s Adhesions
◦Adhesions

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` After age 40
◦Adhesions GI
Obstipation
◦Obstipation
◦Diverticulitis Management
◦Cancer

` Measurement of radiolabeled carbon dioxide after


the oral ingestion of labeled urea ` Detect steatorrhea as a sign of fat
malabsorption
` H. pylori splits urea with urease
` Pick Sudan black stain when you see a patient
` Confirm eradication of H
H. pylori with chronic pale
pale, greasy
greasy, malodorous
diarrhea and no evidence of infection
` If ulcer is found on endoscopy, the test of choice
will be biopsy, not urea breath test

` Suspect chronic pancreatitis in pt’s w/steatorrhea


` Wheat or gluten (gliadin) antigens
` Trypsinogen levels are low from a burned out
pancreas
` DX of celiac disease

` Pick trypsinogen level only after Sudan black stain has


` Small bowel biopsy is the most accurate test for
confirmed a fat malabsorption
celiac disease

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` Differentiate between intestinal malabsorption and


chronic pancreatitis ` Best initial test for Wilson’s disease

` D-xylose is a sugar that should be absorbed if the small ` Unexplained hepatic and psychiatric abnormalities
bowel is intact with movement disorder

` Low urine levels of D-xylose- defective intestinal mucosa ` Low ceruloplasmin levels = Wilson’s disease
( Celiac, tropical sprue and Whipple’s disease)
` Most accurate test is a liver biopsy

` Best initial test in the diagnosis of acute pancreatitis


` Best initial test for autoimmune hepatitis
` Lipase is more specific to the pancreas
` Young female with liver disease
` y
Amylase g to the salivary
can be elevated from damage y
glands, esophagus or small bowel
` Liver biopsy – most accurate test
` Most accurate test for acute pancreatitis is abdominal
CT- indicator of the need for a pancreatic biopsy

` Best initital test for primary biliary cirrhosis


(PBC)

` Middle aged female with itching (pruritus) and


an elevated alkaline phosphatase with normal

24

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Endocrinology, cont
ENDOCRINOLOGY
Exocrine: secreted into a cavity (pancreas)

Paracrine: secreted, then works only in the vicinity


(somatostatin)

Autocrine: secreted by the cell it works on


(granulosa cells)

Apocrine ( merocrine) tip of cell is secreted with the


substance (sweat glands)

Holocrine: entire cell is secreted with the substance


(sweat glands of the arm pit and groin)

HORMONE HORMONES
Name and where it comes from
Main stimulus STEROID HORMONES PROTEIN HORMONES
Main inhibitor Fat soluble Water soluble
Nuclear membrane Cell membrane
Where does it go?
g receptors
receptor
What is the main action? Affect DNA replication, Work via second
messengers
What is second messenger? transcription and
translation
Miscellaneous syndromes Work via proteins
NO second messengers

ERYTHROPOETIN
Made by: renal parenchymal cells

Signal: hypoxia ( NOT anemia)

Inhibitor: increased oxygen

Where it goes: bone marrow

What it does: erythropoiesis

Second messenger: tyrosine kinase

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POLYCYTHEMIA POLYCYTHEMIA
First….check erythropoietin
Increased erythropoietin: due to hypoxia
Normal erythropoietin: Acute hypoxia: tachypnea and dyspnea
Gaisbock syndrome; Chronic hypoxia: clubbing
(angiogenen new vessels)
(angiogenen-new
Stress polycythemia; Restrictive LD; COPD;
Spurious (not real) ; RENAL CELL CARCINOMA- adults
Due to loss of plasma volume Wilms tumor- children

POLYCYTHEMIA
Decreased erythropoietin:
You have a cancer !!!!!!!!
Angiotensin II
g on its own
Bone marrow is acting

ACTH
POLYCYTHEMIA RUBRA VERA

Essential thrombocythemia
(platelets>600000) ACTH

ADRENAL CORTEX ALDOSTERONE, cont


Miscellaneous syndromes: (tumor)
Zona Glomerulosa: ALDOSTERONE
Stimulus: hypovolemia; hyponatremia; hyperkalemia
Too much: CONN’S SYNDROME
Inhibition: hypervolemia Hypernatremia
Hypokalemia (K freely filters out)
Where it goes: late DCT
Alkalosis (K/H exchange)
What it does: stimulate synthesis of Na-K pumps Hypertension (3 H2O for every Na+)

Second messenger: none

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ALDOSTERONE, cont 21 β Hydroxylase deficiency:


Too little: ADRENAL INSUFFICIENCY Decreased Aldosterone [mineral corticoid]
(Na+ wasting)- hypotension
21 hydroxylase def
11 hydroxylase def
Lo cortisol
Low co tisol [Gl
[Glucocorticoid]
coco ticoid]
no feedback by ACTH
In adults:
Abrupt withdrawal of steroids
Autoimmune adrenalitis Increased Androgens-
virilization

11 β Hydroxylase deficiency: Zona Fasciculata


Excess 11-Deoxycorticosterone-
retain salt – HTN CORTISOL
Stimulus: stress; hypoglycemia
Aldosterone decreased – desmolase rate limiting
step
t iin th
the pathway-
th allosteric
ll t i activator-
ti t AT II
AT-II Inhibitor: hyperglycemia
(down regulated due to the HTN)
Where it goes: everywhere >PERMISSIVE
Low cortisol- no ACTH feedback
What it does: up regulates ALL receptors during stress

Increased Androgen production- virilization


Second messenger: none

CORTISOL Cortisol, cont


Too little: Adrenal insufficiency ( Addisons )

Physiologic affects Anti-inflammatory Too much: CUSHING’S SYNDROME


Pituitary adenoma: Cushing’s disease (to much ACTH)
Proteolysis Kills T-cells and
Small cell carcinoma: Cushing’s disease
Gluconeogenesis eosinophil Adrenal adenoma: Cushing’s syndrome
(break down protein Inhibit macrophage
to make glucose) migration
Disease affects one organ
Stabilizes endothelium
Stabilizes mast cells
Syndrome affects many organs
Inhibits phospholipase-A

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Dexamethasone suppression test Dexamethasone suppression test


Hi dose: 1 mg IV Q6 x 4
Lo-dose: 0.5mg IV Q6 x 4 If suppression occurs
If suppression occurs Pituitary adenoma
Obesity If suppression does NOT occur
Depression Check ACTH levels:
Normal variant
High ACTH: SMALL CELL CARCINOMA

Low ACTH: ADRENAL ADENOMA

ZONA RETICULARIS TESTOSTERONE


Testosterone DHT: made in testes by 5 alpha reductase

Stimulus: Leads to secondary male characteristics at


Controls male external genitalia in utero puberty.
Increase in appetite Responsible for hair growth
Aggression and violence Too much leads to hair loss, especially in the
middle and front of scalp
Increases libido and RBC count
Stimulated by ACTH
Male patterned baldness
FENESTERIDE blocks 5 alpha reductase
Second messenger: none
FLUTAMIDE blocks DHT receptors

ADRENAL MEDULLA Pheochromocytoma or Neuroblastoma


Epinephrine: An excess of NE and Epi
Intermittent palpitations, HTN, diaphoresis and headache
Stimulus: stress/hypoglycemia
Inhibition: hyperglycemia Neuroblastoma:
hypsarrythmia (dancing eyes)
Where it goes: liver and adrenal cortex opsoclonus (dancing feet)

What it does: gluconeogenesis; Dx: measure urinary VMA and metanephrines


glycogenolysis ( dopamine > HVA)
Phentolamine- short acting alpha blocker for diagnosis
Second messenger: c-AMP Tx: phenoxybenzamine (longer acting, not specific)
Misc. syndromes…

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Pheochromocytoma or Neuroblastoma
Pheochromocytoma
Difficult to differentiate benign from malignant
on biopsy; they look alike
24 hr urine collection
Metanephrine
Neuroblastoma is MOST common abdominal
Vanillyl mandelic Acid (VMA)
mass in children Catecholamines

Pheochromocytoma If elevated… CT or MRI


10% are malignant
10% are bilateral
10% are in children If CT or MRI find nothing:
10% are familial meta-iodo-benzyl-guanidine (MIBG) scinigraphy
(NE analogue that concentrates in the adrenals)
10% are metastatic at diagnosis

Stress Hormones Pancreatic Hormones


Epinephrine: Insulin: within 30 min
immediately ADH: within 30 min Glucagon: from ALPHA cells
Glucagon: within 20
minutes Insulin pushes the Insulin: from BETA cells
Cortisol: within 2 to 4 sugar into
i t cells
ll and
d
hours ADH normalizes the
GH: after 24 hours osmolarity Somatostatin: from DELTA cells

THESE PRODUCE THE Pancreatic Polypeptide: from ‘F’ cells


SUGAR

Glucagon Glucagonoma
From: pancreatic alpha cells (β1 receptors) Pancreatic tumor
Stimulus: hypoglycemia and stress
Inhibition: hyperglycemia High glucose; high lipids; and high
Where it goes: adrenal cortex, liver, and ketones
adipose
di tissue
ti
What it does: gluconeogenesis (raises
sugar), glycogenolysis (glycogen), lipolysis Related to MEN I ( Wermer’s)
(fat), and ketogenesis
Second messenger: c-AMP Hormone responsible for KETOACIDOSIS
Misc. syndromes… in type 1 diabetes

163
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β cells of the pancreas lnsulin


From: pancreatic islet cells β cells
(β2 and α2 receptors)
Stimulus: hyperglycemia
Inhibition: hypoglycemia
Wh
Where it goes: everywhere
h exceptt BRICKLE
What it does: increase all anabolic
processes
Second messenger: tyrosine kinase
Misc syndromes…

Insulinoma vs Nessidioblastosis Somatostatin


INSULINOMA NESSIDIOBLASTOSIS
From: pancreatic DELTA cells
Seen primarily in seen primarily in
adults infants Stimulus: insulin and glucagon
Causes hypoglycemia causes Inhibition: low insulin and glucagon
M
Measure hi
highh iinsulin
li hypoglycemia Where it goes: paracrine
Wh
and high C-peptide measure high insulin
and high C-peptide
What it does: inhibits insulin and glucagon
Dx: cat scan
Tx: remove surgically Tx: subtotal Second messenger: c-AMP
pancreatectomy Misc. syndromes…

Somatostatinoma Pancreatic Polypeptide


Usually a pancreatic tumor NO KNOWN FUNCTION!
Severe constipation
Dx: cat scan
Whatt iis the
Wh th only
l know
k organ with
ith no
Tx: surgery
known function?

164
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GI Hormones
Stomach Duodenum

GI Gastrin Secretin
CCK
Motilin

HORMONES GIP
VIP
Somatostatin

Secretin CCK
From: duodenum From: duodenum
Stimulus: low pH Stimulus: food, especially fats
Inhibition: high pH Inhibition: high pH
Where it goes: paracrine (pancreas & Where it goes: pancreas (digestive enzymes)
gallbladder) and gallbladder (bile)
What it does: stimulates production and
What it does: primarily fat and protein
secretion of bicarbonate ions from pancreas
& GB digestion
Second messenger: c-AMP Second messenger: IP3/DAG
Misc. syndromes: none Misc. syndromes: none

GIP GIP Syndromes


From: duodenum Dumping Syndrome: seen after Bilroth ll
procedure
Stimulus: glucose
Increased osmotic load dumped Into duodenum
Inhibition: high pH Causes osmotic diarrhea
Wh
Where it goes: pancreatic
ti iislet
l t cells
ll Can also cause postprandial (reactive)
hypoglycemia
What it does: enhances insulin secretion
Second messenger: c-GMP
Misc. syndromes… Causes insulin resistance over time (type 2
diabetes)

165
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Somatostatin VIP
From: duodenum From: duodenum (from Auerbachs
plexus)
Stimulus: duodenal hormones
Stimulus: duodenal hormones
Inhibition: high pH Inhibition: high pH
Where it goes: paracrine Where it goes: paracrine
What it does: purely inhibitory What it does: purely Inhibitory to all
Second messenger: c-AMP duodenal hormones
Misc. syndromes: somatostatinoma Second messenger: c-AMP
Misc. syndromes…

Vipoma Gastrin
From: antrum of stomach
Usually a pancreatic tumor Stimulus: high pH
WATERY or secretory diarrhea Inhibition: low pH
Dx: cat scan Where it goes: parietal cells of the
stomach (mostly in the body of stomach)
Tx: surgery
What it does: production of HCL and
intrinsic factor (for absorbing VIT B12)
Second messenger: calcium
Misc. syndromes…

Gastrinoma ANP ( B-type natriuretic peptide )


From: right atrium
Usually a pancreatic tumor
Stimulus: high volume (stretch of right Atrium)
Zollinger-Ellison syndrome Inhibition: low volume
Gastrin levels are high all the time Where it goes: kidney
What it does: dilates the afferent renal artery;
Can be part of MEN-1 syndrome inhibits aldosterone
Second messenger: nitric oxide
Misc. syndrome…leads to polyuria, nocturia and
hyponatremia in right atrial distention

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PTH PTH
Superior parathyroids: 4th pharyngeal pouch
VITAMIN D Inferior parathyroids: 3rd pharyngeal arch
CALCITONIN Stimulus: low calcium; high phosphorus
Inhibition: high calcium; low phosphorus
Where it goes: (1) osteoclasts of bone (2)late

CALCIUM DCT
What it does:

METABOLISM (1) stimulate osteoclastic activity


(2) increases secretion of phosphorus
(3) activates 1-alpha hydroxylase

PTH, cont PTH Syndromes


HYPO-PARATHYROIDISM
Second messenger: c-AMP
Primary: due to thyroidectomy
Misc. syndromes…
Pseudo:
P d receptor
t nott working;
ki short
h t 3rd
and 5 digit
th

Pseudopseudo
HYPOPARATHYROIDISM : only
difference is that calcium is normal

PTH Syndromes Vitamin D


HYPER-PARATHYROIDISM
From: skin > liver > renal
Primary: due to parathyroid adenoma;
MCC of isolated hypercalcemia in adults Stimulus: low calcium; low phosphorus
Inhibition: high calcium; high phosphorus
Secondary: due to renal failure Where it goes: (1) kidney and (2) GI
Renal Osteodystrophy What it does: (1) production of Ca-ATPase and
Osteitis Fibrosa Cystica- fibrous tissue (2) production of CBP ;(3) stimulates
Osteopenia- low density osteoblastic activity
Osteomalacia- nutrition Second messenger: none
Osteosclerosis- trauma Misc. syndromes…

167
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Vitamin D syndromes Calcitonin


From: parafollicular cells
Deficiency: Osteomalacia in adults; Rickets in
children Stimulus: high calcium

Excess: high
g calcium; high
g pphosphorus
p Inhibition: low calcium

Where it goes: bone

What it does: inhibit osteoclastic activity

Second messenger: c-AMP

Misc. syndromes

MEN Syndromes Bisphosphonates


Inhibit osteoclastic activity like calcitonin
MEN 1: pituitary adenomas, parathyroid
adenomas, and pancreatic adenomas
(Wermer syndrome) Second line drugs for osteoporosis

MEN 2: medullary carcinoma of thyroid (high Very corrosive in the GI


calcitonin), pheochromocytoma, plus or minus
parathyroid adenoma( Sipple syndrome) Causes osteonecrosis (if received via IV)

MEN 3: men 2 with neuroma/ganglioneuroma but Stored in bone for up to 20 years


minus parathyroid adenoma
i.e. etidranate; elandronate; ibondranate,
residronate

Prolactin:
Hypothalamic Hormones Stimulate PRL release- nipple
stimulation

Inhibit PRL release- DA

Pituitary Hormones

10

168
4/29/2008

Dopamine Agonists Dopamine Blockers (D-2)


L-Dopa/Carbidopa Phenothiazines
Bromocriptine- old (stop lactation) Chlorpromazine
Prochlorperazine (Compazine): anti-N/V
Selegyline- MAO type B, increases extracellular
Promethazine
dopamine
Fluphenazine
Amantadine- antiviral (influenza A) Thioridazine- pigment retinopathy

(-) prolactin- can’t lactate Thioxanthenes


N/V CTZ Thiothixene- long acting (>30 days)
Movement disorders- gross motor

Dopamine Blockers (D-2) Pituitary Tumors


Butyrephenones
Nonfunctional (chromophobic) adenomas: most
Haloperidol- antipsychotic- schizophrenia, psychosis
common pituitary tumor
Droperidol - antimetic

Prolactinoma: most common functional pituitary


At i l block
Atypicals: bl k D
D-4
4 receptors
t tumor
Used for negative symptoms
Used when pt has had extrapyramidal side effects ALL pituitary tumors associated with high prolactin
Clozapine- agranulocytosis levels
Onlazapine- wt. gain
Resperidone- neuroleptic anesth. High PRL > galactorrhea and amenorrhea
(fever, muscle stiffness)

Hypothyroidism Hypothyroidism:
Cretinism- Mom and fetus- hypo
3º T4 TSH TRH
Iodine deficiency

Hashimoto’s disease

DeQuarvain’s disease- Virus (painful)-self limiting 2º T4 TSH TRH

Lymphocytic thyroiditis (postpartum )

Riedel’s Struma- capsule cancer (woody)


1º T4 TSH TRH
Tx: Thyroxine(T-4) or L-Thyronine (T-3)

11

169
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Hyperthyroidism
Grave’s Disease ( autoimmune) < 50 y/o TSH
antibody
Plummer’s Syndrome: toxic multinodular goiter
> 50 y/o – one area hot (iodine takeup)
THE
END
Tx: propanolol
Propylthiouracil- blocks peroxidation
Methimazole- block peroxidation
I-131- destroy the tissue
Thyroxine- replacement

12

170
6/25/2008

First Step: Distribution


• Polyarticular symmetric-

Rheumatology
gy • Monoarticular arthritis –

Steps to evaluate a patient • Oligoarticular asymmetric-

• Migratory arthropathy-

Polyarticular symmetric First Step: Distribution


• Rheumatoid arthritis (RA) • Polyarticular symmetric:

• SLE (spares joint destruction)


• Monoarticular arthritis
• Viral (Hep
(Hep. B,
B EBV,
EBV CMV
CMV, B19)
• Oligoarticular asymmetric

• Migratory arthropathy

Monoarticular arthritis First Step: Distribution


• OA • Polyarticular symmetric:
• Gout
• Septic arthritis • Monoarticular arthritis:

• Oligoarticular asymmetric:

• Migratory arthropathy:

1
171
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Oligoarticular asymmetric joint First Step: Distribution


• Spondyloarthropathies • Polyarticular symmetric:

• Monoarticular arthritis:

• Oligoarticular asymmetric:

• Migratory arthropathy:

Migratory arthropathy Second step:


• Rheumatic fever Acute or Chronic…
• Gonococcal arthritis (disseminated)
• Lyme disease • Osteoarthritis

Pain move around the body • Septic arthritis

• Crystal induced

Third step: Fourth step:


• Is there any evidence of systemic • Any evidence of inflammation?
symptoms?
• OA:
Lungs:
Kidney: • RA:
CNS:
Skin:
Hemotologic:

2
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6/25/2008

Inflammation association CASE 1


• Morning stiffness > 1hr
•72 y/o woman
• Red,, warm,, tender presents with left
• Erythematous joint knee pain.
• Increased ESR and CRP

CASE 2

• Monoarticular •30 y/o female


–OA (chronic)
presents with wrist
wrist,
–Septic (acute)
–Crystal induced (acute) MCP and PIP
swelling and pain.

CASE 3

•Polyarticular • 32 y/o male presents with


–SLE knee swelling after you had
seen him for left wrist pain
–Viral
the day before which has
–RA now resolved.

3
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6/25/2008

Case 4

•Migratory arthropathy •25 y/o female presents


–GC
GC complaining of right
knee pain and swelling
–Rheumatic fever
and left hip pain.
–Lyme disease

• Oligo-arthropathy
–Spondyloarthropathy (Reiters)
Test in
Rheumatologic
diseases

Test: Test:

• Joint Aspiration: whenever there • Joint Aspiration: whenever there is fluid


in a joint, you need to aspirate it
is fluid in a joint, you need to
aspirate it • Exception: “ Contraindication”
–Bleeding disorders
• Exception: “ Contraindication” –Anticoagulants with bleeding diathasis
–Cellulitis overlying

4
174
6/25/2008

Test: WBC ranges

Always order the 3 C’s and a • OA / Traumatic arthritis

gram stain
1. • Inflammatory (RA, Gout)
2.
3. • Septic arthritis

Crystals: Anti-Nuclear Antibodies (ANA)


• OA / Traumatic arthritis • Antibodies against part of the
• RA nucleus
• SLE
• Gout • 10% of normal people have + ANA
• Pseudo gout
• Septic • High AB titer

Anti-Nuclear Antibodies (ANA) • If you think the patient may have


SLE, what is your first step in
• 97% of SLE patients have a + ANA
management?

• So
S if the
h test results
l come bbackk
negative, assume they don’t have
SLE • If positive, order…

5
175
6/25/2008

Ab association Rheumatoid Factor (RF)


• SLE (60%), lupus nephritis
• Antibodies against antibodies
• SLE (30%)
• Drug induced lupus
• Neonatal lupus, Sjogrens • Fc portion of IgG
• Sjogrens
• CREST • Increase with age
• Mixed connective tissue dz.

Anti-Neutrophilic Cytoplasmic
Diseases:
Antibodies (ANCA)
• Antibodies against certain • Rheumatoid Arthritis
proteins in the cytoplasm of
neutrophils. • Systemic Lupus Erythematosus
• Scleroderma (SSc)
• (c) ANCA:
• Sjogren Syndrome
• (p) ANCA:

Rheumatoid Arthritis Rules of 6:


• Chronic inflammatory disease • Morning stiffness > 1 hr - for at least 6 weeks

• Target- Synovium • Swelling of wrist, MCP, PIP – 6 weeks

• Symmetric distribution • Swelling of at least 3 joints- 6 weeks

• Potential to destroy cartilage and bone • Symmetric joint swelling – 6 weeks


erosion

6
176
6/25/2008

Extra-articular manifestations Labs for RA


• Damage to tendon and ligaments
• RF
• Anemia
• Boutinniere deformity- PIP flexion, DIP extension
• ESR

• Swan neck deformity- PIP extension, DIP flexion


• X-ray:

• Rheumatoid nodules- vasculitis


• Synovial fluid analysis

• Caplan syndrome- rheumatoid nodules in lungs

Mgt. for RA CASE 5


Old Tx:
NSAIDS > Steroids > Methotrexate (2yrs later)
• Patient with RA presents
with a swollen painful calf.
NEW TX: Start with MTX
after 1 week add prednisone for 1 week • Diagnosis?
only use for flare-ups

Antimalarial- hydroxychloroquine- MTX backup

Alentoaxial Subluxation in RA Systemic Lupus Erythematosus (SLE)

• C1, C2 • Systemic disease


• Tissue and multiple organ damage by
antibodies and immune complexes
• Dx: X-ray
X ray / CT
• Remember: you can have all the criteria for
SLE, but if the ANA is negative, the patient
• Must rule out before surgery does not have lupus

7
177
6/25/2008

Organs involved with SLE Diagnosis of SLE


• CNS: confusion, personality change • Best screening test ANA
• Skin:
• Kidney: • Specific Ab’s associated
• Lungs:
• Complement levels (C3,C4,CH50)
• Hematologic:
• Immune:
• Active lupus
• Bone:
• Lupus nephritis

Case 6 Pregnancy and SLE


• Fertility rates:
• 26 y/o female, admitted for
confusion. Hx. SLE and was recently • Spontaneous abortions and still births
pp
tappered off p
prednisone ((10
• DOC Mgt.:
mg/day). Pt was fine a couple of days
ago. PE- no focal deficits. • Exacerbation (flare up) DOC:
• DDx?
• All pregnant women with SLE need to be
screened:

Mgt. SLE Drug induced lupus


• NSAID’s for arthritis • Limited form of lupus due to a drug

• Antimalarials: Chloroquine • No major organ involvement

• Dx: rash + anti-histone antibodies


• Steroids: for major organ involvement (complement normal)

• Cytotoxins: Azathioprine • Mgt: Discontinue offending drug


Cyclophosphamide

8
178
6/25/2008

Scleroderma (SSc) CREST syndrome


• Chronic multisystem disease
• Limited form of scleroderma
• Thickening of the skin
• Symmetrical skin thickening
• Raunaud phenomenon
C
• g involvement
Visceral organ
R
– GI: esophageal dysmotility, hypomotility of small
intestine E
S
– Pulmonary T

– Renal • Anti-centromere antibodies

Sjogren Syndrome Spondyloarthropathies


• Chronic auto-immune disease • Ankylosisng spondylitis
• Xerostomia and dry eyes
• Reactive Arthritis
• Lymphoproliferative disease- Malignant lymphoma
• Psoriatic Arthritis
• Bilateral parotid enlargement

• Itchy eyes, sand under their eyes • Enteropathic arthropathy

• Keratoconjunctivitis sicca

Ankylosing spondylitis Extra-articular manifestations AS


• Inflammatory disorder of axial skeleton and peripheral
joints • Cardiac:

• Rare after age 40 • Spine:


• 90% of patients + HLA-B27
• Eyes:
• Young male 20’s, chronic lower back pain, morning
stiffness > 1hr, get better with exercise • Skin:
• Cervical spine involvement- late stage of the disease
• Mgt: NSAID’s, Physical therapy, Exercise

9
179
6/25/2008

Reactive Arthritis: Reactive Arthritis Mgt.


• Complication of an infection somewhere in • NSAID’s
the body.
• Non-Gonococcal urethritis:
1. • Antibiotics (prompt)
2.

• Infectious diarrhea:
1.
2.
3.

Psoriatic Arthritis Enteropathic Arthropathy

• DIP joint • Ulcerative colitis


• Crohn’s disease
• Nail pitting
• Sausage shaped digits • Skin lesions:
– Pyoderma gangrenosium
– Erythema Nodosum

Osteoarthritis (OA) Osteoarthritis (OA)


• Target- articular cartilage • Target- articular cartilage
• Hypertrophy of bone • Hypertrophy of bone
• NOT an inflammatory disease • NOT an inflammatory disease

• MC joint affected? • MC joint affected? Knee


• 2nd most common joint affected? • 2nd most common joint affected?
• Joint involved with the greatest disability? • Joint involved with the greatest disability?

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180
6/25/2008

Two forms of OA: Association with OA


• Idiopathic • Joint pain with exercise

• Secondary (cause) • Relieved by rest


– Arthropathies - gout
– Endocrine dz • Morning stiffness (< 20- 30 min)
– Desosition dz
– Mechanical factors • Slow, progressive, irreversible

• NO systemic manifestations

Labs with OA Mgt. with OA


• CRP and ESR : Normal • Non- pharmacological
– Correct poor posture
• X-ray: Osteophytes – Weight reduction
– Physical therapy
Unequal joint space
Bouchard’s nodules (PIP)
• Drug therapy
Heberden’s nodules (DIP)
– First drug- Acetaminophen (contra: use ibuprofen)
– Add Capsaicin

Orthopedic surgery and joint


Crystal Induced Arthropathies
arthroplasty
• Unsatisfactory medical Tx • Monosodium urate (MSU)

• Calcium phrophosphate (CPPD)


• Quality of life decreased
• Calcium oxylate (CaOx)

• Calcium hydroxyapatite (CaHA)

11
181
6/25/2008

Gout: Predispose to Gout:


• Acute Monoarthritis
• Excess ETOH
• Trauma
• Tophi: • Infection

• Metaatarsophalangeal joint (first toe): • Diuretics: Hydrochlorthiazide, Furosemide

• First episode: • Anti-TB meds: Pyrazinamide


Ethambutol
• Red, tender, warm

Diagnosis of Gout: Mgt. Acute Gouty Arthritis


• It is made with fluid analysis of synovial fluid • NSAID’s
– Indomethacin – 50 mg 3 x day
– MSU crystals
– Negative
N i Birefringent
Bi f i • Colchicine: 0.6 mg every hr until symptoms
– Needle shape crystals resolve
– WBC 5,000-50,000
• Steroids: intraarticular or oral (elderly)

Chronic Hypouricemic Therapy Pseuod-gout:


• Low urine levels of uric acid • CPPD crystal formation
• Usually life long therapy
• Follow uric acid levels here !!! • Elderly and pre-existing joint damage

• Probenecid- under secretors • May present acute like gout

• Allopurinol- over producers • Knee most common joint affected

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182
6/25/2008

Diagnosis of pseudo-gout Septic Arthritis


• Arthrocentesis: • MCC gonorrhea
– Rhomboid crystals
– + Birefrengent • 70% of cases > age 40

• X-ray: linear radiodense deposits in joint • Elderly- “Staph aureus” (pre-existing joint
menisci “ Condro- calcinosis” destruction)

• Mgt: same as acute gout

Mgt. Septic Arthritis


• Non-GC: (older) – Staph aureus

• GC (younger) sexually active

• Both WBC > 50,000 and negative crystals


THE END
• Staph aureus- IV Vancomycin
• GC- IV Ceftriaxone

• Therapeudic arthrocentesis

13
183
REPRODUCTIVE
Menstrual irregularities
ENDOCRINOLOGY
• The number one reason an adult woman
goes to see a doctor
• The number one reason a teenage female
misses work or school (dysmenorrhea)

Dr. Naegle Naegle’s Rule


• Assumed that a woman’s menstrual cycle
lasts 28 days long
• Allows us to calculate the EDC
– Begin with the last first day of menses, go
forward 9 months or go backward 3 months,
then add one week
– If the woman’s menstrual cycle varies from 28
days, then you add/subtract the difference at
the end

Some Rules Naegle’s rule also allows us to…


• Term pregnancy: 37 to 42 weeks
• Average birth weight: 2500gms to
3500gms (5 to 7 pounds)
• Preterm: birth prior to 37 weeks
• Postterm: birth after 42 weeks
• SGA: small for gestational age
• LGA: large for gestational age

184185
Oogenesis Oogenesis: The Steps
• Begins in-utero at about 5mo gestation • One round of mitosis first: 2n to 4n (occurs in
utero)
• At birth, a female ovary contains about – Primary oocyte
400k eggs • Enters meiosis 1 and arrests in Prophase (cells
• Beginning at puberty, 8 to 10 follicles still at 4n)
begin development; but, only ONE egg will • Eggs remain arrested in meiosis 1 in prophase
until ovulation occurs
ovulate
• If egg ovulates, it will complete meiosis 1, give
– The eggs that do not finish development will off first Polar Body, and enter meiosis 2,
turn into small white nodules (corpus arresting again in Metaphase(4n to 2n)
albicans) – Secondary oocyte

Oogenesis: The Steps


• If fertilization occurs, egg will complete
meiosis 2, give off the second Polar Body,
and form a zygote (2n to 1n)
Because mom’s eggs remain
– Tertiary oocyte arrested for SO long…
You can trace 80% of
chromosomal mutations to MOM

185186
OCP’s HRT
• Norethindrone • Decreases symptoms
• Mestranol • Decreases osteoporosis ( decreases
• Depo-provera osteoclastic activity)
• Estrone • Decreases risk of CAD ( increase HDL;
• Estradiol vasodilator)
• Estriol
• Controversy!!

Other Hormonal Drugs Now, introducing…TYRONE!


• Clomiphene
• Leuprolide
• RU-486 (mifeprostone)

Spermatogenesis Sertoli Cells


• Begins at puberty • Produce inhibin
• First sign of puberty in a male is testicular • Maintain the blood-testes barrier
enlargement • Protect and nourish the sperm to maturity
• Controlled by testosterone
• LH > testosterone > spermatogenesis
• FSH > Sertoli cells > produce inhibin

186187
Spermatogenesis Spermatogenesis, cont
• One round of mitosis: 2n to 4n • Each day 20 to 40 million sperm mature
– Primary spermatogonium
• Meiosis 1: 4n to 2n • Complete spermatogenesis takes 41 to 72
– Secondary spermatocyte days
• Meiosis 2: 2n to 1n
– Tertiary spermatid • Sperm can live for 5 days in fallopian tube
while an egg can live for only 3 days
• One spermatogonium gives rise to 64 spermatids
• As spermatogonia mature, they move from the basal
layer into the epididymus to finish maturing

Virility Infertility
• 20 to 40 million sperm per cc of semen • 50% male factor
• 4 to 5cc of semen per ejaculate – Always do sperm analysis first
• No more than 40% abnormal forms • 30% female factor
• 30 to 60% of sperm must still be motile – Mcc is PID
after 5 minutes on a glass slide • 20% miscellaneous
• The pH is basic

Before Sperm Can Leave…


• Seminal vesicles: semen; fructose
• Bulbourethral ( Cowper’s ) gland: HCO3
• Prostate: Zn ; acid phosphatase;
hyaluronidase

187188
Sexual Response

Sexual Dysfunction The Difference Between the Sexes


• In young men: premature ejaculation • Men have a longer refractory phase; short
• In older men: stress induced impotence excitement phase
• In the elderly: vascular impotence • Women have a longer excitement phase;
– Atherosclerosis decreases blood flow short refractory phase
– Takes longer to establish an erection
– Harder to maintain an erection
– Need for more direct stimulation
– Longer refractory phase

To Address Premature
Ejaculation…
• Apply the SQUEEZE TECHNIQUE
– Gently squeeze the head of the penis; it starts
retrograde peristalsis in the ejaculatory duct
and epididymus

188189
Once the sperm are deposited in Once the sperm are deposited in
the vagina… the vagina…
• Sperm hide under the semen • Sperm enter the uterus
• HCO3 is released to neutralize lactic acid • They swim through the fallopian tubes
• Zn is used for the Capacitation Reaction • By the time the sperm approach the egg,
• Fructose is used for energy only a few thousand sperm remain
• 70% of sperm are dead before reaching • Sperm surround the egg
the cervix • They dart in and out, opening their heads
• Acid phosphatase is used to eat through to release enzymes ( Acrosomal Reaction)
cervical mucus

Once the sperm are deposited in


Stages to Know
the vagina…
• Once one sperm head fuses with egg, a • Zygote: 2 cell stage
wall forms behind the sperm ( – 90% fertilizations occur in the ampulla
Crystallization Reaction) – It must now migrate into the fallopian tubes
– This prevents Polyspermy – Ectopic pregnancy: mcc is PID (forms scars)
– A ZYGOTE is formed when egg (1n) and the • Morula: 16 cell stage
sperm head (1n) fuse
– This stage enters the uterus
• Blastula: 256 to 512 cell stage
– This is the stage that implants

Formation of the Placenta Placental Hormones


• HCG
• PROGESTERONE
• ESTRIOL
• HUMAN PLACENTAL LACTOGEN
• INHIBIN
• RELAXIN

189190
HCG HCG, cont
• Detectable in BLOOD one week after • Maintains corpus luteum production of
fertilization; in the URINE two weeks after progesterone
• Has the same alpha subunit as FSH. LH, • Can lead to Hyperemesis Gravidarum
and TSH ( check the beta-HCG) – DES
• Cervical incompetence
• Adenomyosis
• Maintains the corpus luteum • Clear cell carcinoma of the vagina
• Increases GI motility and absorption • Increases BMR
• Sensitizes the TSH receptor

HCG, cont How to Follow the First Trimester


• Doubles every 2 days until week 12 • Fundal height rises 1cm per week
• HCG of 600: viable fetus – Pubic symphasis = 12 weeks
• HCG of 2000: fetus visible on abdominal – Umbilicus = 20 weeks
ultrasound • HCG doubles every 2days
• Estriol level rises linearly

• If fetus dies: estriol level falls first

Think of Molar Pregnancy if… Progesterone


• Fundus growing higher than predicted • Increase RR from pons
• HCG rising faster than predicted • Increase appetite
• HTN in first trimester • Pica
• Increase RBC mass by 30%
• Causes acne
• Complete mole
• Hyperpigmentation
• Incomplete mole
• Cloasma or malasma
• Helps increase plasma volume by 50%

190191
Estrogen Inhibin
• Smooth muscle relaxation • Inhibits FSH
• Stimulates protein synthesis in the liver • Prevents another menstrual cycle from
– High ESR beginning
– Hyperlipidemia
– Increased TBG
– Increased angiotensinogen
– Increased clotting factors

Human Placental Lactogen Relaxin


• BLOCKS mom’s Insulin receptors • Relaxes tendons and ligaments
• Creates insulin resistance • Stretches the pelvis
• Gestational diabetes

The END

191192
4/29/2008

Renal Embryology:
At different points of gestation, various
organs are embryologically developed.

For example:
- Notochord at 2 wks
- Brain at 4 wks
- Renal system is formed at 12 wks

ƒ METANEPHROS - give rise to the kidney Renal


Pelvis

ƒ URETERIC BUD - gives


i rise
i tot the
th entire
ti Calyx
collecting system
ƒ Collecting duct, major and minor calices, papillae,
hilum and ureters
URETERIC BUD
Ureteric bud must make contact with the Metanephros
metanephros or kidney will NOT develop

ƒ Gives rise to the GENITALIA in MALES


ƒ Gives rise to female genitalia

Paramesonephros
Has
H kidney
kid (never functional)
function prior as a kidney
to kidney
formation

ƒ Develops into the ovaries, fallopian tubes, uterus and


ƒ Develops into the testes, seminal vesicles, vas upper vagina
deferens and epididymus
ƒ A female can develop either by DESIGN or by DEFAULT
ƒ To develop, you need a Y chromosome and MIF

1
192
4/29/2008

Vitelline Duct: Allantois:


Omphalomesenteric duct

ƒ IN MALES: becomes the PENIS

ƒ IN FEMALES: becomes the CLITORIS


Urogenital Sinus

ƒ IN MALES: prostate, prostatic urethra and


bulbourethral ( Cowper’s) glands Urogenital
Tubercle

ƒ IN FEMALES: lower vagina, and labia minora

L1 and L2 levels: Cortex: outermost layer of the kidney.


right kidney is positioned ƒ It contains the nephrons, PCT, and DCT
slightly
li htl lower
l th
than the
th left
l ft
kidney ƒ Cortical nephrons are shorter in length
compared to the medullary nephrons

Why? ƒ Functions to maintain an isotonic urine

2
193
4/29/2008

Medulla: deeper layer of the kidney

Pyramids collect urine from the collecting


ducts that drain into each renal papilla
p p

From the papilla > calyces > ureters

Responsible for hypertonic urine

Why do we sweat in different regions? Renal Blood Supply


In hot places, we sweat and lose water.
ƒ Right renal artery
IIn cold areas, we do
d nott sweatt and
d thus
th dod
not need to preserve this water. ƒ Right renal vein
The nephrons elongate after 3-4 days

Allows for more water conservation


(hypertonic urine) and fluid replacement lost

Healthy Unhealthy
Kidney Kidney
Renal Blood Supply
Sodium and
Fluid
water
overload
ƒ Right gonadal vein removal

y drains into the


directly
Elevated
IVC. Right sided Waste waste- Urea,
infection or cancer has removal Creatinine,
Potassium
a worse prognosis
Hormone Changes in
ƒ Left gonadal vein production hormone levels
• Renin • Blood pressure
drains into the left • Erythropoietin's • Making red blood
cells
renal vein • Prostaglandins • Uptake of calcium

3
194
4/29/2008

ƒ Divide the kidney into 4 regions.

ƒ When one of the 4 are affected, ultimately it will affect the others Blood
Vessels

ƒ 20% off blood


bl d from
f the
th CO is
i going
i tot the
th kidneys
kid
Tubules Glomeruli
ƒ 90% of it, supply’s the cortex

ƒ Only blood supply for the medulla - vasa recta

Blood
Interstitium ƒ Medulla- first place to infarct in a low volume
vessels
state leading to medullary necrosis

Glomeruli Tubules
ƒ Consist of visceral epithelial cells
(foot processes-podocytes) ƒ Proximal convoluted tubule (80% of reabsorption)

ƒ Glomular basement membrane ƒ Loop of Henely (triple transport)


(electron dense-type 4 collagen)
ƒ Distal convoluted tubule
ƒ Parietal epithelium lines bowman's space ƒ Collecting tubule (for concentrating the urine).
ƒ Fenestrae (in the endothelium) ƒ Most tubular diseases are frequently
ƒ Most glomerular diseases are immunologically caused by toxic or infectious agents
mediated.

Interstitium

ƒ In the cortex, comprising mostly of fenestrating


capillaries (so any change in space, i.e. edema is
abnormal).

ƒ Most interstitial disorders are


frequently caused by toxic or infectious
agents.

4
195
4/29/2008

ƒ Patient presents with polyuria and


polydyspia……

ƒ You rule out diabetes based on glucose…

ƒ What next?

Diagnosis Cause Labs


Excessive fluid intake Uosm/Posm > 0.7

i.e. As much as 10-12 gallons


Psychogenic DI of H2O a day
Restrict H2O for 24 hours
Urine will concentrate

Posterior pituitary does not


Uosm/Posm < 0.7
release the stored ADH
Central DI ADH is
i nott present,
t but
b t
i.e. Infarction of the pituitary
gland when you give it, expect
the urine to concentrate

Renal kidneys are Uosm/Posm < 0.7


unresponsive to ADH
Nephrogenic DI ADH is present and wants
i.e. Renal failure, lithium,
to work, but it’s a receptor
low volume state infracting
problem
the medulla of the kidney
Urine will not concentrate

ƒ For burn patients: Parkland formula ƒ Head and neck: 9%


( to calculate fluid deficit only) ƒ Each arm: 9%
ƒ 4cc x Wt (Kg) x % burned areas ƒ Front of torso: 18%
ƒ Back of torso: 18%
ƒ Each lower extremity: 18%
ƒ Never calculate more than 50% of burned
ƒ Genitalia: 1%
body area
ƒ For newborns: subtract 9% from each lower
ƒ Replace fluids: extremity and add it to the head and neck
▪ ½ within the first 8 hrs ( from time of trauma) ƒ Head 27%, legs 9%
▪ Remainder over the next 16 hrs

5
196
4/29/2008

ƒ A 36 y/o fire fighter (70 kg),was trapped in a


burning building and suffered 2nd and 3rd degree ƒ Urine Output: 1cc/kg/hr (70 kg male)
burns to over 65% of his body. What will be the
fluid replacement management?
A. 15, 20, 15 ml/hr
ƒ Urine output : 1cc/kg/hr
B. 300, 250, 270 ml/hr
ƒ 70 kg x 50 % = 3500 x 4cc = 14,000 ml (14L)
C. Over 48 hrs, urine output has been
ƒ 7 L first 8 hrs : 7 L remaining 16 hrs
between 50-100 ml/hr. Now on day 3,
ƒ 2nd day ½ that, 3rd day nothing urine output 250, 300. Next step in mgt.?

Never give a hypertonic solution… this will pull fluids out of the
extracellular fluid to help fill the vascular space, which will be
replaced by the intracellular fluid.

H2O
Cell

Intracellular
H2O
Extracellular

Ok great job on getting patient X’s blood pressure back to the normal range, but
at what cost…. the tissue (oops!!!)

ƒ Body water is broken down into fluid compartments:


Exception to the rule:
ƒ Intracellular fluid (2/3 of Body Water)
Hyponatremic patient ( Na <120) patients: ƒ Extracellular fluid (1/3 of Body Water)
ƒ Interstitial fluid (ISF) 2/3 ECF
Use 3% (hypertonic) saline to get sodium ƒ Vascular fluid (VF) 1/3 ECF

above 120
ISF VF

ICF ECF

6
197
4/29/2008

Loss of isotonic fluid: Loss of hypotonic fluid:


Hemorrhage, Diarrhea, Vomiting Dehydration, Diabetes Insipidus, Alcoholism

Osm

ICF ECF ICF ECF

Gain of isotonic fluid: Gain of hypotonic fluid:


Isotonic saline Hypotonic saline, Water intoxication

ICF ECF ICF ECF

Gain of Hypertonic fluid:


Hypertonic saline, Mannitol

Renin –
Angiotensinogen
ICF ECF Pathway

7
198
4/29/2008

Bartter's syndrome:
Renin
(JG cells-afferent)
JG cell hyperplasia with renin excess
No increase in blood pressure due to insensitivity
of the presser effects of AT-II
AT-II (stimulates)
Defect in the kidney's ability to reabsorb
• alpha 1 vasoconstriction Liver p
potassium
• Adrenals
Ad l (Z
(Z. Gl
Glomerlus)-
l ) (Angiotensinogen)-
Aldosterone release release AT-I
• Posterior pituitary- ADH release Excessive amount of potassium is excreted from
• CNS- thirst center the body. This is also known as potassium wasting

Lungs
(AT-I is converted
to AT-II via ACE)

DKA – metabolic acidosis, which causes a Hypomagnesemia – due to decreased


switch in H+/K+ pumps leading to K+
leaving the cells and intering the serum. gastrointestinal (GI) absorption
(Diarrhea, malabsorption, diet)
Not a true hyperkalemia, just ions shifted in
the wrong place.
or increased renal loss(diuresis due to
Kidneys will
Kid ill recognize
i the
th high
hi h K+ and
d start
t t
to secrete it in the urine. alcohol, thiazides and loop diuretics)
(Hyperkalemia to Hypokalemia)

• Always look a pH first, then HCO3-

• You should be able to differentiate


based off of these two

8
199
4/29/2008

ACID / BASE Disorders:

HCO3- ↑
(compensations)
For example… Respiratory
PaCO2 ↑
HCO3- normal
ƒ If the patient’s pH is acidic, you should (non-compensation)

expect that patient’s HCO3- to be low Acidosis


A id i
PaCO2 ↓
(buffering) (compensation)
Metabolic
HCO3- ↓
ƒ If not, then the problem has to be PaCO2 normal

respiratory
(non-compensation)

ACID / BASE Disorders:

HCO3- ↓
Respiratory (compensating) Arterial pH 7.3
PaCO2 ↓ HCO3- normal
(non-compensation) pCO2 30 mm Hg
Alk l i
Alkalosis pO2 95 mm Hg
PaCO2 ↑ Serum HCO3- 14 mEq/L
Metabolic (compensating)
HCO3- ↑ PaCO2 normal
(non-compensation)
What is the diagnosis?

Metabolic acidosis

Arterial pH 7.3 (ACID) Check anion gap... Na+ - (Cl- + HCO3-)


pCO2 30 mm Hg (N: 8-12 mEq/L)
pO2 95 mm Hg
Serum HCO3- 14 mEq/L (low) Increased anion gap Normal anion gap
MUD PILES
•Diarrhea
•M- methanol
What is the diagnosis? •U- uremia
•Renal tubular acidosis
•D- DKA •Hyperchloremia
•P- paraldehyde or phenformin
Metabolic Acidosis •I- iron tablets or INH
•L- lactic acidosis
w/respiratory compensation •E- ethylene glycol
•S- salicylates

9
200
4/29/2008

PCT

Diuretics Acetazolamide, Dorzolamide:

Mannitol:

Ethacrynic Acid (no sulfa)


Furosemide (sulfa) Hydrochlorothiazide (sulfa)
Indapamine (no hyperlipidemia)

Intra- Renal

Pre- Renal Post-Renal

Spironolactone:

Amiloride:
Triamterene: (no anti-androgenic effects)

10
201
4/29/2008

• Volume depletion
• Dehydration (nausea, vomiting)
• Burns ( massive)
• Third spacing (i.e. liver chirossis)
Kidneys stop functioning properly: increase in… • Diarrhea
• Decrease in Aldosterone (Addisons)
Creatinine
BUN and/ or Pre- • Cardiovascular
Decreased urine output… • Hypotension (CHF)

Renal • Coarctation / tamponade

• Oli
Oliguria
i : decrease
d iin urine
i output ( < 400 cc/day)
/d ) • Decrease in Oncotic pressure
(inflow to • Low Albumin

• Anuria ( < 100 cc/day) the • Nephrotic syndrome


• Edematous states ( Cirrhosis)
kidneys) • Renal Artery Vasoconstriction
• Medications ( NSAID's- block PG's, ACE-I)
• Anatomical Renal Artery Stenosis

• Decreased Vascular Resistance


• Shock

• Intra-renal problems
Pre-Renal
• Drugs ( Gentamicin,
Amphoteracin B, Cisplatin) -
BUN/Cr > 20/1 takes 5 to 7 days to damage

Urine Na+ < 10 Renal • Crystals-


• Uric acid - tumor lysis
(Kidneys) • Oxilate stones- antifreeze
or malabsorption
FeNa+ < 1% • Crushing injuries-cell lysis
• dipstick positive (NO RBC's)
UOsm > 500 • Thromboembolism, ATN

Renal • Bladder obstruction


• Prostate enlargement
BUN/Cr < 20/1
Post- • Pelvic tumors
Renal • Urethral strictures
(foley,retroperitoneal
Urine Na+ > 20 ( out flow obstruction)
fibrosis)
Both kindeys need
to be affected to
FeNa+ > 2% see any deficit • Urethral obstruction
• Tumor
Low specific gravity • Stones
(can not concentrate urine)

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202
4/29/2008

Post- Renal
ƒ If you suspect a pre-renal problem-
the patients usually have
Obstruction ƒ
ƒ
positive orthostatics
dry
d mucous membranes b
(hydronephrosis) ƒ increase for thirst
ƒ rapid heart rate
ƒ skin tenting (turgor)
Increased post void Consider (co-morbid) conditions that could
residual volume lead to their pre-renal problem

ƒ For a renal problem (intra-renal)- ƒ Myoglobin is a normal intracellular proteins:


- toxic to the kidneys
consider drug history - intra-renal damage
ƒ Knowing the patients drugs could prevent ƒ If you suspect arteroemboli, look for…
unnecessary test for the patient and time ƒ subcutaneous nodules
wasted in determining the cause. ƒ digital ischemia or immobility

ƒ Any recent history of exposure to possible


ƒ With Glomerulonephritis:
ƒ red cast
toxins that could be nephro-toxic.
ƒ edema (protein loss)
ƒ hypertension (renin pathway)

Check the urine (RBC's, WBC's, cast,


ƒ If you suspect a post-renal problem, eosinophils), Electrolytes
check for…
FeNa+ can destinguish between pre-
renal and renal problems
ƒ prostate disease (Prostitis, BPH, Prostatic CA)
DRE, urinary cath as well as ultrsound
can rule out an obstruction
ƒ all can lead to an enlarged bladder with pain
radiating to the flanks Renal biopsy only when the cause of
intra-renal can not be determined

12
203
4/29/2008

Urinalysis CLUES
Attempt to balance fluids and Eosinophils
electrolytes Drug induced •

• (Most common cause-


hypersensitivity Cephlosporins)

Glomular • RBC cast


Dialysis if necessary-
necessary Hyperkalemia,
Hyperkalemia
nephritis
Metabolic acidosis, Fluid overload, Pericarditis,
Encephalopathy
• WBC's
Infection • Bacteria

Discontinue medications if they are the cause of the


renal disease
Uric Acid (Gout) • Crystals

Urinalysis CLUES Glomerular Disease:


Have you ever noticed, that when you
• Proteinuria (bence
Multiple jones)
wake up in the morning and urinate,
myeloma there is a soapy appearance to your
urine in the toilet bowl?
• Blood dipstick +, but
Myoglobinuria no red blood cells
Why is it, that when a nurse is going to
do a morning U/A on a patient, you ask
• Proteinuria > her to get a mid-steam catch?
Nephrotic 3.5gm/d
syndrome
• Fat cast

When we look at nephritic or nephrotic


syndromes, we need to decide what sets
them apart from each other.
Macroscopic /
Aside from a few details, it just comes down Microscopic
to protein loss and the magical number is Hypertension hematuria
(smokey brown
3 5g/day
3.5g/day. urine)

If less than 3.5 g/day then we name that


“Nephritic” and if greater than 3.5 g/day, we
call that “Nephrotic.” Oliguria Edema

Why 3.5 g/day?

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Treat any hypertension, fluid overload and


24 hour U/A ( best initial test) - look uremia with…
for hematuria, proteinuria
Salt and water restrictions, diuretics and if
needed, dialysis
If GFR is decrease…think auto immune
auto-immune
check complement, ANCA and anti-GBM

Renal biopsy (most definitive) - LM, IF, or If the underlying cause is inflammation of the
EM to help in the diagnosis glouerular, the give corticosteroids

1. Post Strep GN

2. Good Pasture GN

3. RPGN

4. IgA Nephropathy

5. Membranoproliferative GN
(can be both)

ƒ Proteinuria (> 3.5 g/day)


Generalized
ƒ Generalized edema Foamy urine
Edema
ƒ Hypoalbuminemia
ƒ Hyperlipidemia.

ƒ Approximately one-third of all cases are


the result of systemic diseases such as Hypercoagulable
Ascites
state
DM, SLE, or amyloidosis.

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U/A - proteinuria (>3.5 g/day), Diet restrictions of salt and protein


lipiduria

Blood chemistry- decreased albumin


(<3g/dL), hyperlipidemia Diuretics and antihyperlipidemics

Always look for secondary causes If the patient is a diabetic- put them on an ACE-I for it
decreases the prograssion of the disease

Renal biopsy (definitive): LM, IF, EM Vaccinate (PPV 23)- patients at risk of Streptococcus
pneumoniae infections

Nephrotic Syndrome

Mcc in children: minimal change disease 1.Membranous GN


2.Minimal change disease
Mcc in adults: membraneous nephropathy
3.Focal Segmental GN
Mcc in Blacks and Hispanics: FSGN 4. Amyloidosis
Fat cast
5.Nodular Glomular Sclerosis

ƒ Block aldosterone
ƒ Have sulfur in them- anaphylaxis, hapton to RBC’s
ƒ Angioedema- block C1 esterase inhibitor

ƒ Serum
S Na- dec. , K -inc.,
i pH –dec (hangs
( onto H+))
ƒ Captopril
ƒ Lisenopril
ƒ Enalopril

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Acute Renal Failure

FLOW Pa X Pb

If you increase resistance at X


• Pa pressure will increase
• Pb pressure will decrease
GFR- look at Cr clearance: Renal Plasma flow
Renal Blood Flow- assocated with Cr BUN Flow will decrease throughout
clearance (lab) use PAH
(Lab) use inulin

Glomerular Peritubular Renal


GC cap pressure cap pressure plasma flow

GFR Post- efferent Efferent

1. Constrict efferent

2. Dilate efferent

3. Constrict afferent

4. Dilate afferent

A E A E
GC GC

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A E A E
GC GC

Glomerula Filtration Rate (GFR)

ƒ Rate at which plasma is filtered into


∏ = Oncotic Decreased in
bowman’s capsule. pregnancy, liver
failure, over
hydration
y
ƒ Units of filtration:
(Volume filtered per unit of time) GFR = Kf [ (PGC-PBC)-(∏ GC-∏BC)]
e.g. ml/min, L/day
P= Hydrstatic
Inreased in Breakdown of
kidney stone, bowman’s
obstruction capsule

PGC is the main


factor that
determines GFR
(promotes filtration)

ƒ The negative charge of the filtering


∏ GC
membrane inhibits the filtering of
PGC proteins [anions ((-)]
)]

PBC opposes filtration


PBC
ƒ If the negative charge is not
Should not be a factor
Does not affect the
∏BC
present, significant protein
rate of filtration,
except in obstruction filtration takes place

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ƒ Filtration fraction (FF) – fraction of material that • Carriers are easily saturated
enters the kidney, that is filtered normally (.20 or 20%) • Carriers have high affinity for the substrate
• Low back leak

GFR 140 ml/min The entire filtered load is reabsorbed until the
RPF 400 ml/min
carriers are saturated, then the excess is excreted.
.35 or 35% FF

Constrict Efferents

Morning glucose is 600 mg/100ml, Tubular Secretion (PAH):


how much will leave the kidneys? (para-amino-hippurate)

120 (GFR) x 6 = 720mg Secreted from the peritubular


will be filtered capillaries into the PCT.

There are enough carrier to


secrete 4 times the amount
How much will leave filtered.
in the urine?
If you inject 100 mg of PAH into
(normal carrier Tm 375 mg/min) a patient, how much will be
So urine dipstick will measure excreted?
345 mg/min 100 mg
(20% filtered and 80% secreted)

Protein Inulin
Manitol Glucose
Lipid soluble
(filtered, not
secreted or
reabsorbed)

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Theoretical volume of plasma from which a substance is removed over a


period of time…

Calculate the clearance ?


V = 2ml/min
Px = 2mg/ ml
Ux = 2mg / ml
2 x 2 = 2 ml/ min
2

Kidney Pathology If the kidneys are too small…


ƒ Renal Artery Stenosis
ƒ Each kidney measures about 3 to 7 inches
ƒ atherosclerosis
ƒ If kidneys too small… ƒ fibromuscular dysplasia
ƒ Renal Artery Stenosis ƒ Unilateral
ƒ Abdominal bruit
ƒ If kidneys too large…
ƒ Low volume state
ƒ Polycystic kidney disease
ƒ Medullary sponge kidneys
ƒ Dx: ultrasound; renal vein renin elevated
ƒ Medullary cystic kidneys
( higher renin output indicates stenosis)

Treatment
Goldblat Kidney
Avoid ACE-inhibitors once HTN is severe
(AT-II Dependent)

Ipsilateral atherectomy
h (or stent if not a surgical
candidate) and contralateral nephrectomy

RAS: most common cause of secondary


hypertention

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If you have large kidneys… Polycystic Kidney Disease


ƒ ADULT TYPE
ƒ Polycystic kidney disease ƒ AD ƒ INFANTILE TYPE
ƒ Bilateral, HTN, RF ƒ AR

ƒ SAH - berry aneurysms ƒ Unilateral


ƒ Medullary sponge kidneys ▪ In posterior ƒ NO HTN
communicating artery ƒ NO RF
▪ CN 3- blown pupil
ƒ Medullary cystic kidneys ▪ Worst headache
▪ Tx: Transplant

Medullary Cystic Kidneys Medullary Sponge Kidneys

ƒ Multiple cysts destroy the medulla ƒ Many holes develop in the medulla

ƒ Polyuria ƒ Polyuria
ƒ Polydypsia ƒ Polydypsia
ƒ Low volume state ƒ Low volume state

ƒ Occasional kidney stone ƒ Multiple kidney stones

ƒ Dx: Sonogram (bubbles) ƒ Dx: Sonogram (holes)

Ureters: 3 anatomical narrowings Kidney stones


ƒ Hilum
ƒ Most common type: calcium

ƒ Mid ureter: caused by going ƒ MCC: hypercalciuria


over the iliac bones
ƒ Tx: Normal saline
Opiates for pain
ƒ Ureteropelvic junction Thiazides decrease hypercalciuria
( where it enters the bladder) by forcing the PCT and Loop to
increase Ca2+ absorption

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Kidney stones Urease Positive Bugs


ƒ Struvite stones (Staghorn calculus)
ƒ Proteus
ƒ Triple phosphate stones ƒ Pseudomonas
ƒ Ureoplasma
ƒ C M NH4 Ph
Ca-Mg-NH4-Phosphate
h t ƒ Nocardia
N di
ƒ Cryptococcus
ƒ MCC: urease positive UTIs ƒ Helicobacter Pylori
ƒ Staph Saprophyticus
ƒ Tx: normal saline; opiates for pain
ƒ Brucellosis

Kidney stones Kidney stones


Cystine stones
ƒ Uric acid stones
ƒ CYSTINURIA
ƒ Cysteine
ƒ The only stone NOT visible on xray
ƒ Ornithine
(radiolucent) ƒ Lysine
ƒ Arginine
ƒ Associated with rapid cellular death
(burn pt, CA, massive trauma) ƒ AD
ƒ Coffin lid, enveloped
ƒ Tx: normal saline ƒ Defective renal transport of amino acids
opiates for pain
ƒ Tx: normal saline; opiates for pain

Kidney stones Kidney Stones: management

Oxalate stones ƒ IV normal saline


ƒ Opiates for pain
ƒ Due to malabsorption in GI tract ƒ < 5mm (½ cm)
ƒ Let it pass
ƒ When you have malabsorption, calcium gets
trapped in the malabsorbed fat (saponification) and
do not therefore bind oxalates from proteins ƒ 5mm to 1cm
breakdown. Oxalate get absorbed in the GI ƒ Lithotripsy (whorl pool)

ƒ Can be hexagonal ƒ > 1cm


ƒ Open laparotomy (i.e. struvate)

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Kidney Stones: management


-Street- Heroin (short acting)
ƒ If pyelonephritis develops:
-For withdraws- Methadone (long acting) percutaneous nephrostomy stent placement
to drain the pus
-Kidney stones
stones- Morphine
ƒ Dx: KUB; spiral CT; IVP;
-Abdominal pain- Meperadine ƒ Sonogram (if with hydronephrosis)
(no contraction of sphincter of odi) ƒ Ureteroscopy- if stone is in the middle or
lower 1/3 of ureter

HYDRONEPHROSIS BPH
ƒ Newborns: ƒ Most common cause of urinary obstruction in
ƒ (1)malimplantation of the ureters (lack 2 90º) adult men
ƒ (2) posterior urethral valves

ƒ Children: UTIs
ƒ Obstruction is periurethral (central) : Dx DRE

ƒ Adolescents: urethral strictures ( from STDs) ƒ Tx: terazosin or doxazosin


(alpha 1 blockers) loosen sphinctor
ƒ Adult men: BPH ƒ Tamsulosin (Flomax)- least side effects
ƒ 2nd line - Fenesteride (block 5 alpha recductase)
ƒ Adult women: uterine prolapse and cystocele
ƒ Sx –TURP (transurethral resection of prostate)

HYDRONEPHROSIS Bladder
ƒ UNILATERAL ƒ BILATERAL Allantois develops into…
ƒ Kidney stones ƒ Retroperitoneal
fibrosis
▪ Methysergide
Urachus develops in the
(seretonin – Rx for abdomen and descends into the
migranes)
▪ Nitrofurantoins pelvis …

forming the Bladder

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Urachal Cyst Exotrophy of the Bladder


ƒ Urachus retains attachment to the ƒ Bladder was caught outside the abdominal
umbilicus cavity

ƒ Predisposes to bladder cancer (MC


ƒ Clue: urine drains from the umbilicus complication)

ƒ Tx: surgery ƒ Risk for bladder cancer persists even after


surgery (UA and CT every year)

ƒ Tx: surgery

MCC: Atherosclerosis < 4 cm diameter


- control HTN
Location: 90% occur below the renal arteries
- follow
Presentation:
1. Ripping, tearing pain down the lower back > 6 cm in diameter
2. Pulsating abdominal mass - control HTN
(can only feel if they are thin) - surgery

Dx: Sono, CT scan 4 – 6 cm (surgery is the doctors call)

Incontinence
MCC: 1# Trauma , 2# Collagen disease

Presentation:
1. Ripping, tearing pain between the shoulder blades

Diagnosis: Spiral CT

Treatment: Type A – control HTN, surgery


Type B- control HTN, pray
(not much connective tissue)

The involuntary loss of urine

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Urge Incontinence Urge Incontinence, cont


ƒ Detrusser muscle activity is increased. ƒ Tx: have patient urinate around the
ƒ A spastic bladder ( UMN lesion) clock beginning with…
ƒ Bladder capacity is low due to repetitive
bladder emptying - hourly for 2 to 3 days
days,
ƒ Sphincter pressure is normal
ƒ Gotta go…gotta go…gotta go - then every 2 hours for 2 to 3 days,
- then every 3 hours for 2 to 3 days,
ƒ Tx: - then every four hours (normal)
Imipramine (in children) TCA
Oxybutynin (in adults) Blocks Ach (M)
(to decrease bladder contractions)

Stress Incontinence Stress Incontinence, cont


ƒ Due to weak pelvic floor muscles
ƒ MCC: obesity; estrogen connection
ƒ Estrogen connection
ƒ Tx: weight loss; Kegle exercises to
ƒ Any increase in abdominal pressure tighten up pelvic floor muscles
( like from sitting down, laughing, coughing,
sneezing, etc) causes a sudden loss of urine
ƒ Use pseudoephedrine to tighten up the
ƒ Detrussor muscle function is normal sphincter (alpha adrenergic)
ƒ Bladder capacity is normal
ƒ Suggest diapers or panty liners in the
ƒ Sphincter pressure is decreased meantime

Overflow Incontinence Overflow Incontinence, cont


ƒ Due to an anatomical obstruction
ƒ Causes:
ƒ Detrussor muscle activity is decreased due to ƒ In newborns: posterior urethral valves
stretching

ƒ Bl dd capacity
Bladder it iis iincreased
d ƒ In children: strictures

ƒ Sphincter pressure is increased


ƒ In adult men: BPH
ƒ Sx: a weak urine stream; dribbling after urination;
urgency; frequency ƒ In adult women: uterine prolapse and
cystoceles
ƒ Tx: surgically remove the obstruction

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Urethra: Penis
ƒ Develops dorsal (top) to ventral
(bottom)

ƒ Fuses from the tip to the base of penis or Hypospadia


yp p
clitoris
The most common congenital genitourinary abnormality!

Hypospadia ( still zipping) Circumcision


ƒ Located at the base of the penis just next ƒ Done primarily for cosmetic reasons
to the anus
ƒ UTI argument
ƒ Predisposes to UTIs
ƒ Penile cancer argument
ƒ Tx: surgical correction immediately to
prevent UTIs ƒ Should be done in first 48 hours

ƒ Clean by pulling the foreskin up, then


clean; pull the foreskin back, then clean

Inflammatory Problems Infections


ƒ Phimosis: foreskin is scarred and ƒ Ballanitis ( head of the penis )
adherent to the head of the penis ƒ Staph Aureus

ƒ Paraphimosis: foreskin is scarred and ƒ Urethritis ( dysuria)-


dysuria) infection of urethra
adherent to the base of the penis ƒ Chlamydia Trachomatis # 1 (90% asymp.)
ƒ Nisseria Gonorrhea # 2 (90% symp. Men)
ƒ Tx: urology consult (50% symp. Women)
ƒ Actinomyces Israelii

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Infections, cont

ƒ Azythromycin 1gm or 2gm (Chlam + GC) ƒ Cystitis: ( urgency and frequency)

ƒ Ceftriaxone (250 IM) ƒ Pyelonephritis: ( WBC Casts)- only nephron


ƒ Cefixeme ( 400 PO) can form cast
ƒ Cefoxitin (250 IM)
ƒ Causes:
Quinolones (400 PO) ƒ E. Coli
ƒ Ciprofloxacin
ƒ Proteus
ƒ Ofloxacin
ƒ Gatifloxacin ƒ Klebsiella
ƒ Enterococcus: nitrite negative

Nephritis Casts
ƒ Pyelonephritis: WBC Casts; sepsis ƒ WBC casts: nephritis

ƒ RBC casts: glomerulonephritis


ƒ Interstitial nephritis: drug allergy; ƒ Eosinophil casts: interstitial nephritis
collagen vascular disease
ƒ Fat casts: nephrotic syndrome
ƒ Glomerulonephritis: RBC Casts; hematuria ƒ Waxy casts: chronic renal failure

ƒ Hyaline and epithelial casts: normal findings;


represent sloughed off cells, most from the PCT

ƒ Crescents: RPGN. Goodpasture’s or Wegener’s

RTAs
ƒ Type I: distal H/K exchange is defective
ƒ Urine pH is very high; renal stones; UTIs
ƒ Type II: proximal CA does not work
ƒ Urine pH is very high ( distal H/K exchange still

ƒ
works)
ƒ Can not reabsorb HCO3-
TYPE III: combines the above two
THE END !
ƒ Urine pH is normal
ƒ Type IV: hyporenin-hypoaldosterone syndrome
ƒ Seen in diabetics; JG apparatus is infarcted

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Embryology of the Brain


Primitive Streak
Making
M ki The Connections
Th C i
Notochord

Spinal cord

In the first trimester… Amniotic Fluid


y Notochord: visible by 3 weeks y 80% of amniotic fluid is filtrate from mom’s
plasma
y Brain: fully formed by 8 weeks
y Fetus SUBTRACTS by swallowing the
y Brain is active early with movements, fluid
especially reflexes y Fetus must absorb and digest the fluid

y 20% is added by the fetus


y Brain is active in formation of amniotic fluid
y Fetus then urinates the additional fluid into
the sac

Polyhydramnios Oligohydramnios
y AFI yRenal agenesis

y Neuromuscular
N l disease
di y Urinary outlet obstruction
y Autonomic dysfunction: dry eyes- Riely Day syndrome
y Muscle disease: in a newborn – fasciculation- Wernig
Hoffman syndrome

y GI obstruction

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Spinal Cord Vertebral Arches


y Develops from the notochord y Fuse ventral to dorsal
y Goes down as far as L-1 or L-2
y Begins
g at the cervical level
y End : Conus Medullaris
y Proceeds bi-directionally
y Nerves: Cauda equina
y If child born prematurely, a hole can
y Filum terminalis: anchors be still present at either end

Lower vertebral arch defects


Upper- vertebral arch defects y Spina Bifida Occulta
y Anencephaly – no contact to the brain
y Only has the medulla ySpina Bifida Aperta
y Breath 8-10 ipm
y Encephalocele 1. Meningocele
AFP

y Encephalo-meningocele 2. Meningomyelocele
y Arnold Chiari Malformation (Type I and II)
y Syringomyelia
y Encephalo-meningo-myelocele

Now you need some CSF How CSF differs from plasma
y A filtrate of plasma y Less HCO3-

y More CL-
y the Choroid
y Made by Plexus in each ventricle
y Lower pH 7.34 (acidic)
y Requires Vitamin A
y Up to 25 WBCs normal in first month of life normal
y Requires Carbonic Anhydrase
y >1 month, only up to 3 WBCs normal

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Lateral ventricles >

foramen of Munro >


Vomiting Centers
3rd ventricle >

aqueduct of Sylvius > y Chemotactic Trigger Zone: located on


4th ventricle > the floor of the 4th ventricle
foramina of Lushka & Magendie

subarachnoid layer > y Responds to any increase in ICP


spinal canal >

CSF Flow dural sinuses >


y Stimulated by dopamine
back into plasma

Vomiting Centers Hydrocephalus


y Area Postrema: located on the blood yNon-communicating:
side of the blood brain barrier (BBB)
y due to an obstruction

y Responds to offensive smells or


taste
yCommunicating:
y overproduction of CSF
y Stimulated by dopamine

Communicating Hydrocephalus Communicating Hydrocephalus


y Newborns: mainly premature newborns y Adults: over ingestion of vitamin A
y Intraventricular hemorrhage y Pseudotumor Cerebri

y Children: due to inflammation y Elderly: due to brain atrophy


y Meningitis (posterior fossa) CN 3, y Normal Pressure Hydrocephalus
9,10,11,12
y Ventricles enlarge

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Normal Pressure Hydrocephalus Noncommunicating Hydrocephalus


y Ventricles expands as the brain atrophies y Due to some form of obstruction
y In newborns:
y Enlarged ventricles then compress the long midline
fibers that go to the bladder and legs y MCC: Aqueductal stenosis
y Triad:
y 2nd Dandy-Walker cyst
y Dementia
y Incontinence y In children: meningitis, especially TB
y Ataxia
y In adults: cancer
y Tx: VP shunt y In elderly: cancer

The role of CSF Neurocutaneous Syndromes


y To add cushion for the brain Sturge Weber Syndrome:
y Shock absorption yBenign port wine stain- capillaries
yOpthalmic branch of CN V
y Head Injury
y Coup lesions yMental retardation
y Contracoup lesions – worst than the ySeizure
coup (brain makes CSF for repair)

Neurocutaneous Syndromes Neurocutaneous Syndromes


Osler-Weber Rendu Syndrome Tuberous sclerosis: benign tumors
ySmall aneurysmal telangiectasia on y AD
the
h skin
k and d mucus membrane
b y Mental
M l retardation
d i
yCauses GI bleeding y Seizure
y Retinal angiomyolipoma
yPulmonary AV fistula
y Cardiac rhabdomyoma
y Pancreatic cyst / Coloboma

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Embryology of the Brain


Neurocutaneous Syndromes
Prosencephalon Æ Telencephalon Æ cerebrum
Von-Hippel Lindau Diencephalon Æ thalami and BG
g
yCerebellar hemangioma
Mesencephalon Æ Mesencephalon Æ midbrain
yRetinal hemangioma
yRenal cell carcinoma Rhombencephalon Æ Metencephalon Æ pons & cerebellum
(increased EPO’s) Myelencephalon Æ medulla

Visual Cortex Abnormalities of the Eyes


y Anisocoria: unequal pupil size
y Light must hit the retina by 3 months of age
y MCC: Congenital (AD) – check parents
or the child is blind for life
y If it occurs in childhood- inc. ICP until proven
otherwise
h i – Dx:
D CT,
CT LP
y You must verify that a child has a RED reflex
on eye exam at birth (retinal arteries, and if y Amblyopia: difference in visual acuity
y Lazy eye
you can see them- nothing is in the way)
y Tx: Patch the eye up to age 5
y Weak muscles- CN: 3,4,6

Abnormalities of the Eyes Vision Correction:


y 20/20 – 20/100 (5 times the difference)
y Strabismus: misalignment of the eyes
y Isotropia
20 ft. – 4ft
y Exotropia
Weak muscles of the eye….. Tx. Patch good eye y 20/200 legally blind (no drivers license)
y can not see details
y Stigmatism: corneal defect
y Straight line card (pt will see a blip in the line)
y Convex or a concave defect in the cornea
y Laser keratotomy

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Abnormalities of the Eyes Myopia- can not see far away


y My-opia: near sightedness (can not see far)
y Focus of light is before the retina
y Tx: Concave lens- disperses light

y Hyperopia: far sightedness


y Focus of light is behind the retina
y Tx: Convex lens- focuses light earlier

y Presbyopia: loss of accommodation seen with aging


y Due to muscles weakening with age
y Ability to focus on objects coming close

White Reflex White Reflex


y Cataracts: opacification of the lens
y Does not allow light to hit the retina y Retinoblastoma (rare)
y Must be removed
y Increased
d incidence
d with
hhhigh
h glucose
l or
y Rb gene
galactose ( sorbitol or galactitol accumulates) y Cancer

y Idiopathic: 90%
y High association with Ewing’s
y Diabetes or galactosemia sarcoma
y Rubella

Optic Nerve

Visual field deficits Optic Tract

Meyer’s

Optic Chiasm

Optic Radiation
Calcarine
Fissure

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L R
Monocular Visual Loss
Optic Radiation Optic Nerve
L R

Meyer’s Loop

Monocular blindness

L R Bitemporal Hemanopsia
Monocular blindness
y Newborns: cataracts or retinoblastoma
y Children: optic nerve gliomas L R
y Neurofibromatosis
y MEN III
y Adults: embolic phenomena
y TIA (Amaurosis Fugax)
y Acute retinal artery occlusion
y (white retina, macula has its own blood supply)

y Acute retinal vein occlusion (bluish retina)


y Elderly: macular degeneration
y Receives the smallest arteries of the retina - atherosclerosis
Optic Chiasm Lesions

Contralateral
L R
Homonymous
Optic Chiasm Lesions Hemianopia

L R
y Pituitary tumors: 90%
y Pituitary sits just beneath the chiasm

y Pineal tumors
y Pineal gland sits just lateral to the
chiasm
y Circadian rhythm - Responds to light
Optic Tract Lesions

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L R
Optic Tract Lesions Contralateral Superior
Quadrantanopia
L R

yMcc:
M
cancers or tumors

Contralateral
L R L R
Homonymous
Contralateral Inferior Hemianopia with
Quadrantanopia Macula Sparing
L R L R

Quadranopsia Frontal Lobe ( Precentral Gyri)


y Can get such a lesion in y CST (corticospinal tract) motor fibers
the Optic radiation or originates from here
Meyer
Meyer’ss loop
y Unique information:
y Pie in the sky y Personality – is stored in the frontal lobe
y Abstract reasoning
y (don’t cry over spilled milk)

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Frontal Lobe Lesions Temporal Lobe


y Atonic seizures- generalized (knock out CST)
y Hearing
y Dementias y Balance
y Alzheimer's
Al h i ' y Hallucinations ( released by serotonin)
y Pick’s disease y PCP
y LSD
y Schizophrenia: loss of asymmetry
y Posterior temporal lobe: Wernicke’s area
y Frontal lobotomies

Amphetamines Amphetamines
y Used in ADD
y Methylphenidate (use in Narcolepsy)
y Taken up presynaptically; cause release y Pemoline -
y Adderal
of catecholamines y Dexadrine

y OTC for weight loss


y Dexatrim
y Clue: vertical nystagmus
y Cause hallucinations
y LSD
y PCP
y ECSTACY

SSRI’s Parietal Lobes


y Fluoxetine y Dominant lobe: long term memory; all the
things you learned since kindergarten
y Paroxetine
y left side is dominant in 90% of right
right-
y Luvoxetine Depression, eating disorders handed and left-handed people
y Sertraline (MAOI- wait a month)
y Nefazadone y Nondominant lobe: apraxia and hemineglect
y Trazadone y Right side is nondominant in 90% of right-
handed and left-handed people

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Anterior
Communicating Anterior Cerebral

Lateral Pontine Syndrome

Occlusion AICA (anterior


inferior cerebellar artery)
Posterior Cerebral

Superior Cerebellar
CN 7- ipsilateral facial
Anterior Inferior Cerebellar paralysis
Posterior Inferior Cerebellar

Vertebrals
CN 8- hearing loss

Lateral Medullary Syndrome


( Wallenberg) Medial Medullary
Syndrome
Occlusion of PICA (posterior inferior
cerebellar artery ) Occlusion of vertebral artery
Cerebellar peduncle- ipsilateral limb
ataxia Pyramid- contralateral spastic
hemiparesis
Descending hypothalamics-
ipsilateral horners CN 12- tongue deviates
toward the lesion
Nucleus ambiguus- dysphagia

Median Midbrain Syndrome


(Weber) Epidural Hematoma
y Middle meningeal
Occlusion of posterior cerebral artery
artery

CST- contralateral spastic y Fracture of


temporal bone
hemiparesis (upper limb)

Corticobulbar tract- lower face y Lucid interval


(contra)
y Lenticular shape
CN3- eye (down and out)

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Subdural Hematoma Subarachnoid Hemorrhage


y Bridging vein y Aneurysm rupture
y Venous bleed
y Worst headache of
y Delayed onset their life

y Shaken baby
y Elderly y Bloody spinal tap

y Crescent shape

THALAMI- SENSORY Epithalamus


yEpithalamus
y The ONLY nucleus with NO known
yThalamus function

yHypothalamus

ySubthalamic Nucleus

Thalamus Hypothalamus
y Controls hunger
y ALL SENSORY information in and out of y Hunger center: lateral
y Satiety center: medial- 80% NE and 5HT (+)
the brain MUST stop here
y You can override via cortex – stimulus “FOOD”
y Controls menstrual cycle
y ALL information about the ARMS stay
LATERAL y Controls temperature
y Anterior: cools
y Posterior: warms
y ALL information about the LEGS stay
MEDIAL y Controls stress response (NE release)

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Stress Response Acetomenophen


y Parasympathetic discharge always first y Works at the level of the hypothalamus
y Sympathetic discharge always second
y First, it cools the body (+ anterior hypothalamus)
y Stress ulcers
2nd it resists fever (blocks posterior hypothalamus)
h pothalamus)
y Curling’s ulcers
y Oxidizes the liver (toxicity) – by destroying bisulfur
y Cushing’s ulcers (triad: bradycardia, HTN, Inc. ICP) groups
y IBS y Treat with n-acetylcystiene ( reducing agent);
y the four hour level is the most important factor

Subthalamic Nucleus
y Final relay station for coordinating
fine motor movements

y Lesion: Ballismus and Hemiballismus

Substantia Nigra Parkinson’s Disease


y Responsible for INITIATING movements y Loss of DOPAMINE fibers from substantia nigra
to striatum (caudate and putamen)
y Uses DOPAMINE for neurotransmitter
y Unable to initiate activities

y Receives inhibitory signals from basal ganglia via ACH y Mask like facies
or GABA y Bradykinesia
y Shuffling gait
y Pill rolling tremor
y Autonomic dysfunction: Shy Dragger syndrome

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Movement disorder in middle-aged people


Parkinson’s Disease, cont
y Treatment: L-dopa/ carbidopa y Huntington’s disease y Wilson’s disease
y 90% y < 10%
y AD y AR
y 2nd line: Bromocryptine (dopamine agonist) y Trinucleotide repeats y Ceruloplasmin def
y Caudate nucleus involved y Copper excess
y Amantadine (Tx influenza A)- increase DA y Anticipation y Lenticular nucleus
release from nerve terminal y Decreased GABA fibers involved
y Treat with DA blockers y Kayser-Fleischer rings
(they have too much DA) y Liver involvement
y Selegyline (MAO-B inhibitor)- prevent DA y Treat with penicillamine
breakdown

Internal Capsule Reticular Activating System (RAS)


y ALL MOTOR fibers going in and out of the brain goes y Maintain FOCUS on one item at a time
through here

y Blood
Bl d supply l comes from
f the
h lenticulostriate
l i l i arteries
i y Requires NE and Serotonin
( smallest arteries in the brain)

y cAMP second messenger (sympathetic)


y Lacunar hemorrhages: due to HTN
y Causes significant MOTOR deficits
y Has a refractory period first thing in the
morning

Sleep cycles
Attention Deficit Disorder
y BAT D
y Beta waves – wide awake (eyes open)

y Alpha waves - Eyes close - awake – “not asleep”


y ADD or ADHD (Not focus).
y Theta waves y RAS not working
y light waves stage 1 and 2. (Stage 2: K complex and sleep spindles)

y Poor attention and focus


y Delta waves – Deep sleep big– stage 4 all motor activities (teeth
griding, sleepwalking, enuresis). y Restlessness
y Night terrors occur
y Benzos, imipramine inhibts this fase y Unable to sit long enough to complete a task
y Beta waves - Rem sleep. Every 90 min. (REM latency) 5-7 x night y Tx: methylphenidate (1st in children);
y Parasympathetic. Most of the rest.
y Dreams, penile/clitoral erection pemoline; dexadrine; adderal
y NE, EtOH, Barbs, Age inhibts this
y 5-HT, Ach increase

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Corticospinal Tract
y Responsible for fine motor activity
y Has to inhibit extension so that smooth flexion can
occur

Mid-brain
Mid brain y Spasticity- can not flex
y Babinski – extension of toes
y Hyperreflexia
y Clonus

Corticospinal Tract, cont CST Pathology


y Fibers originate from the frontal lobes, yAtonic seizures: depolarization
the precentral gyri goes across the frontal cortex

y Fibers descend through the internal


yB-12 deficiency
capsule and CROSS at the medullary
pyramids
yALS

Increased Intracranial Pressure


y First sign: papilledema (optic nerve)
y First symptom: headache

y Second sign: esotropia (CN VI paralysis)


abdusence
y Second symptom: diplopia or blurred vision

y Third sign: Sluggish pupils

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Decorticate Posturing
If Herniation Continues…
y Second sign of herniation:
DECORTICATE posturing
y Compression has occurred below CN
III but above the red nucleus
y Red nucleus still makes the upper
extremities flex while the legs extend
y UNTIL…

The Final Push DECEREBRATE posturing


y Herniation goes beyond the red nucleus
y CST and Corticorubral and rubrospinal
tracts are all lost
y All extremities will extend by default
y Medulla is pushed through the foramen
magnum.

y DECEREBRATE posturing

Dorsal Columns Dorsal Columns, cont


y Vibratory sensation
y Two-point discrimination y Gracilis: carries leg fibers; located
y Position sense MEDIALLY
y (toe m0vement)
y Conscious proprioception yCuneatus: carries arm fibers; located
y (eyes closed knowing what he is doing)
LATTERLY
y The only sensory pathway with four
synapses

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Dorsal Columns, cont Dorsal Column Pathology


y FIRST SYNAPSE: dorsal root ganglion
Fasciculus gracilis: ( lower extremities)
ySyphilis
Fasciculus cuneatus: ( upper extremities) yVitamin B-12 Def
y SECOND SYNAPSE: MEDULLA yBrown-Sequard
y THIRD SYNAPSE: THALAMUS

y FOURTH SYNAPSE: parietal lobes


y ( postcentral gyri)- ALL SENSORY

Spinothalamic Tract Spinothalamic Tract


y Pain and Temperature y FIRST SYNAPSE: dorsal root ganglion
y (opposite all other lesions)

y SECOND SYNAPSE: thalamus


y The only pathway that CROSSES in the
spinal cord (only one)
y THIRD SYNAPSE: parietal lobes
y Fibers enter the spinal cord, ascend two y ( postcentral gyri)- Sensory
levels, then cross to opposite side via the
anterior white commisure

Spinothalamic Tract Pathology Spinocerebellar Pathway


y Syringomyelia y The only pathway in the spinal cord that crosses
twice ( equivalent to ipsilateral)

y Responsible for depth perception


y Signs of damage:
y INTENTION TREMOR (during reach)
y DYSMETRIA (heal to shin) or PRONATOR DRIFT

P y DYSDIODOKINESIS (rapid movement)


y ROMBERG SIGN (loss of unconscious proprioception)

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Spinocerebellar Pathway Pathology


Spinocerebellar Pathway, cont
y This pathway does NOT reach the cortex y Alcohol attacks the vermis (midline) of the cerebellum
while other diseases attack the hemispheres
y Unconscious proprioception
y (don
(don’tt have to think about it)
y Fredrieck’s Ataxia-retinitis pigmentosa

y FIRST SYNAPSE: dorsal root ganglion


y Ataxia Telangiectasia- spider vein all over your body
y SECOND SYNAPSE: thalamus

y THIRD SYNAPSE: cerebellum y Adrenoleukodystrophy- defective long chain FA

PONS Pons – Pathology


y Responsible for responding to the environment y Locked-in Syndrome

y Contains the
y Central Pontine Demyelinolysis
y PNEUMOTACTIC (superior)inhibitory to the APNEUSTIC
(bottom) responds to pO2 dec., pCO2 inc.

y CNS area most sensitive to osmotic shifts

Medulla Make sure you know the cranial nerves !

Midbrain 3,4
yControls ALL basic functions
y Respiration of 8-10 ipm
Pons 5,6,7,8
Medulla 9,10,11,12

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You know it’s a spinal cord


How Do I Figure lesion when…

Out Any Lesion? y Pain and temperature loss is opposite to


all other deficits

y Level of the lesion is two dermatomes above


where pain and temperature loss begins and on the
opposite side (Lesion L2- loss at L4)

You know it’s a CNS lesion


when…
y UMN signs on one side of the body
y ( upper and lower extremities)

y Then the lesion is on the opposite side of the brain


Too slow grasshopper !!!!
y Use the cranial nerves to locate the level of the
THE END !
lesion

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Red Blood Cell

Hematology
Hasenchecheg Qi MD
MD., Ph
Ph.D.
D

Hemoglobin
1. A Hb is composed of: Hemoglobin
1). four globins, proteins
1. Hb A α2β2 m.c.
pair of alpha (a2): located on chromosome 16
pair of beta (b2): located on chromosome 11.
2). four heme groups, with the iron compound which binds with the O2 2. Hb A2 α2δ2 2.5% δ chain synthesis begins late in the
third trimester and in adults
2. Hb has 2 forms:
T (taut) low affinity for O2 3. Hb F α2γ2 m.c. in the small amounts in an adult, may be
fetus abnormally elevated in certain forms
R (relaxed) high affinity for O2
of anemia
3. Function
4. Hb S sickle-cell
1). In the lungs, each iron on Hb combines O2 reversibly.
hemoglobin
2). Each Hb also has attached a single cysteine, which attracts nitric oxide (NO).
5. Hb H β4 An abnormal Hb is not effectively
3). The enriched Hb circulates to the tissues, where the NO dilates the small capillaries, transport O2, it is usually associated
allowing to deliver O2 to the tissues.
with a α-thalassemia syndrome.
4). Then the O2- and NO–free Hb picks up CO2 and free NO and transports both back to
the lungs, where they are exhaled as waste. 6. Barts γ4 An abnormal Hb that is not effective in
O2 transport, found in α-thalassemia.
5). When RBC are destroyed
the hema (iron) is stored in the liver for the manufacture of new red blood cells.
Globins is converted into bile and stored in the gall bladder

Anemia Heme Synthesis (mitochondria)


Sideroblastic
Rate limited Anemia
Hb <11 mg/dl Glycine + Succiny CoA
ALA Synthase + B6
MCV < 80 MCV (80—100) MCV > 100
δ-Aminolevulic acid Lead (Pb)
1. Thalassemia 1. B12 deficiency
Reticulocyte
2. AOC 2. Folate Deficiency ALA dehydrase
3. Iron deficiency < 2.0 %Low > 2.0% high Prophobilinogen
3. Alcoholic Liver
anemiai disease
1. Marrow failure Uroporphyrinogen-I
4. Lead Poisoning 4. Drug induce
2. Aplastic synthase
5. Sideroblastic Anemia Uroporphyrinogen-III
anemia Acute Intermittent
3. Myelofibrosis 1. All the 2. All the Porphyria
4. Ca matastasis hemolytic autoimmune
1. Sickle Cell Disease anemia anemia Protoporphyrin IX (protoheme)
2. Hemaglubin C 5. AOC
Disease
6. Renal failure
Fe2+ Ferrochelatase Lead (Pb)
3. G-6-P-D deficiency Intra- Extra- Hereditary
4. Thelassemia Major vascular vascular Spherocytosis Iron Deficiency Heme
5. PNH Anemia

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Microcytic Anemia Microcytic Anemia


Sideroblastic Anemia Lead Poisoning
cause Symptoms Acute Intermittent Porphyria Porphyria Cutanea Tarda
1. decrease Vit B6 (m.c.) 1. Lead Line: in gums Uroprophyrinogen-1 Synthase Uroprophyrinogen
2. isoniazid therapy 2. CNS : Encephapathy, deficiency decarboxylase deficiency
3. Abdominal pain (lead colic) Clinical Feature Clinical Feature
1. AD, variable expression 1. Photosensitivity
4. PNS: wrist and foot Drop
2. acute abdominal ppain 2. blistering
g of skin
Diagnosis: Diagnosis:
multiple laparoscopies (scars on
1. BM: ring sideroblast 1. blood lead level > 10 µg/dl abdomen)
(most specific test)
3.psychotic changes
An erythroblast containing 2. increase free erythrocyte
granules of ferritin protoporhyrin 4. increase ALA and PBG
(prophobilinogen)
2. Lab 3. basophilic stippling (remnants of
RNA) : 5. no photosensitivity
6. Contraindicate: barbiturate
Treatment Treatment
Pyridoxine succimer (PO), EDTA

Anemia of Chronic Disease (AOCD)


Anemia of Chronic Disease (AOCD)
Definition Lab Treatment reticuloendothelial
1. Iron being trapped in 1. serum ferritin system
bone marrow elevated
macrophages, causes 2. serum iron low
inability to use of iron in
3. reticulocyte count
stores.
low
lo
2. long term chronic 1. decrease protein
disease cause decreased synthesis
liver functions, 2. Transferrin low =
TIBC low
3. It can be microcytic or
normocytic

Iron deficiency Anemia Iron deficiency Anemia


Cause 1. decrease intake or elderly, children, pregnant women
Increase demand
2. decrease absorption: 1) decrease acid (Vc)
(malabsorption) 2) Dumping Syndrome: decrease
small intestine transit time
3) after gastrectomy
3. chronic blood loss 1) GI Ca (m.c. in USA)
((m.c.)) 2) GYN bleeding
3) Hookworm (m.c. rest of the world)
Sequence 1. decrease storage iron in Decrease ferritin
event due intestinal mucosa, spleen,
to iron and liver
deficiency: 2. decrease circulating iron Decrease serum iron
Increase TIBC
3. formation of Decrease RBC size
microcytic/hypochromic
anemia

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Iron deficiency Anemia Terminology


Symptoms 1. General Low energy state, pallor of skin and nails,
2. others 1. Koilonychia: spooning of the fingernails 1. Hb Hemoglobin F12-15 g/dl,
2. Pica M 13-16g/dl

Lab Hb, MCV, Ht Decrease 2. Ht (Hct) Hematocrit % of RBC in the blood 40 --50%

RDW decrease 3. MCV mean cell (corpuscular) volume 80—100

Serum iron decrease


4. MCH mean cell hemoglobin 25.4—35 pg/cell
Transferrin (TIBC) increase
5. MCHC mean cell hemoglobin concentration 31—36 g/dl
ferritin decrease
microscope microcyte 6. RDW red cell distribution width (A measure 6—12%)
anisocytosis abnormal size of the variation in size of red blood
cells)
poikilocytosis abnormal shape
Diagnosis 1. depend on lab 7. Reticulocyte immature RBC (1 day, normal 1.5%)

2. definitive Dx: bone marrow < 1%, poor bone marrow response

Treatment 1. diet > 1%, good bone marrow response


2. ferrous sulfate tablets Bluish color (polychromasia) due to
free ribosome RNA
3. parenteral iron
4. blood transfusion: most effective

Terminology Go Back
Microcytic Anemia
serum iron 100mg/dl Iron AOCD Thalassemia Sideroblastic
deficiency minor anemia
Ferritin 1. physiological storage iron form
2. intestinal mucosa, spleen, and liver serum decrease decrease normal increase
Hemosiderin 1. degraded ferritin + lysosomal debris Iron
2. Prussian blue positive
serum decrease increase normal increase
Transferrin A beta globulin in blood serum that combines with and
transports iron. ferritin
Total iron-binding 1. means transferrin level
capacity (TIBC):
TIBC increase decrease normal decrease
2. Transferrin = TIBC = 300 mg/dl

% saturation of serum iron/TIBC = 1/3


transferrin % decrease decrease normal increase
saturation

B12 Deficiency Anemia B12 Deficiency Anemia


Causes Diagnosis
1. Dietary 1. B12 in red meat and fished
1. peripheral smear Macroblastic anemia, hypersegmented
deficiency 2. B12 stores at body for more than 1 year supply. neutrophils
3. strict vegetarians, alcoholism 2. anti-IF: initial test sensitivity 50-80% , specificity 100%
2. Decrease 1. decrease IF, gastrectomy or pernicious anemia
3. serum homocysteine Due to folate or B12 deficiency
absorption 2. Pancreatic insufficiency increase
3. intestinal malabsorption 4. increase only due to B12 deficient
a. p
parasites: fish tapeworm
p diphyllobothrium
p y latum methylmalonic acid
b. bacteria: blind-loop syndrome
5. Schilling test: over the 24 hours, a normal result shows at least
c. Crohn’s disease 10% of the oral intake radioactive vitamin B12 will
Sign and symptom be in the urine.
1. beefy tongue due to generalized epithelial atrophy i. B12 injection + radiolabelled B12 orally
2. peripheral neuropathy ii. B12 injection + radiolabelled B12 orally + IF
3. SCDSD: (Subacute combined degeneration of the spinal cord)
Treatment Treatment
ii. demyelination of the posterior columns and lateral corticospinal tracts and
spinocerebellar tracts B12 oral After give B12, may develop hypokalemia in 48
iii. Urinary and fecal incontinence, impotence Or parenteral hrs, because potassium rapidly go into cells
iv. Dementia

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Go Back
Folate Deficiency Autoimmune Hemolytic Anemia (AIHA)
Warm AIHA Cold AIHA
Folate Deficiency
Mechanism The IgG attach to a RBC, antibodies initiate
1. contain in green leaves vegetable leaving their FC portion complement lysis of
2. 3 month supply sticking out. The FC is red blood cells
Cause by recognized and grabbed onto
by monocytes and
1. cause by “tea and toast” life-style
macrophages in the spleen.
2. Methotrexate
Antibody 1. IgG to Rh type 1. IgM
3 Ph
3. Phenytoin
t i 2. IgA
4. Pregnancy Cause 1. Methyldopa 1. Quinidine
Lab 2. Penicillin
1. serum homocysteine increase: due to both folate and B12 deficiency coomb’s test + IgG, or IgG + C3 C3
Treatment Cold agglutinin negative positive
Treatment 1. steroid 1. Cyclophosphamide
Folic acid
2. splenectomy 2. Chlorambucil
3. treat causes
4. Cyclophosphamide

Hereditary Spherocytosis
Normocytic Anemia Definition 1. AD,
Intravascular (SH GTP) Extravascular Microangiopathic 2. defect spectrin in RBC membrane
Hemolytic Anemia
Clinical 1. splenomegaly
increase methemoglobin no methemoglobin 1. increase shictocytes feature 2. increase risk for acute aplastic crisis with Parovirus
(oxidized hemoglubin) (fragmented RBC) B19 infection
Rx; methylene blue 2. Helmet cell Lab 1. increase spherocytes
markedly decrease decrease 2. normocytic hyperchronic
haptoglobin heptoglobin
3. increase MCHC
4. increase osmotic fragility
1. Sickle Cell Disease Hereditary 1. DIC
2. Hemaglubin C Disease spherocytosis 2. TTP Rx
3. G-6-P-D deficiency 3. HUS
4. Thelassemia Major 4. Prosthetic Heart Valve
5. PNH 5. HELLP

Sickle Cell Disease Sickle Cell Disease


Sickle Cell Diasese Hemoglobin C Disease
single nucleotide change in codon casues single nucleotide change in
valine (neutral) to replace normal glutamic codon causes lysine (basic) to Affecting factors 1. increase concentration (dehydration), make it
acid (acidic) at 6 position of the β-globin replace normal glutamic acid worse
chain (acidic) at 6 position of the β-
globin chain decrease concentration make it better
Hemoglobin S Sign: 2. Decrease pH decrease oxygen affinity: worse
1. become less soluble under decreasing 1. splenomegaly 3. increase HbF: better
oxygen concentrations Increase RBC 1 Erythroid hyperplasia
1.
2. The deoxygenated molecules form rigid 2. target cell destruction cause 2. increase bilirubin
rods called polymers into crystals that distort
the red blood cells into a sickle shape.
3. These abnormally sickle-shaped cells are 3. rod-shaped crystals in RBCs
both rigid and sticky.
Genitic types
1. heterozygous (AS): trait
blood urine and resistance to malaria
2. Homozygous (SS):Sickle cell disease

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Sickle Cell Disease


Vaso-occlusion
1. Hand-foot syndrome (dactylitis) 1st sign of SD, in children
2. Vaso-occusive (painful) crisis Rx: 1. Self –limiting, last 2-7 days
2. hydration: NS
3. Morphine for pain
4. keep warm
5. Oxygen
3. Autosplenoectomy 1. Howell-Jolly bodies in peripheral blood:
remnantt off nuclear
l chromatin
h ti
2. increase infection of encapsulated
organisms, Rx: vaccinations
4. Leg ulcers increase Salmonella osteomyelitis (leg pain)
5. Avascular necrosis of the joints M.c. hip, 2nd shoulder
6. Priapism Emergencies, Rx: transfusion
7. Acute chest syndrome Emergencies, Rx: transfusion
8. Aplastic crisis with infection of B19, Rx: folic acid
Treatment 1. Hydroxyurea; increase HbF
2. BM transplantation

G-6 PD Deficiency Thalassemia Syndrome


G-6 PD Deficiency
Definition: quantitative, not qualitative, abnormalities of hemoglobin
G-6 PD deficiency causes decrease glutathione peroxidase
1. α-thalassemia 2. β-thalassemia
(antioxidant)
1. decrease α-globin chains , 1. decrease β-globin chains,
Clinical Feature
excess β-chains excess α-chains
1. X-link R
i. African American type: 2. most commen in Asian population 2. most common in Mediterranean
ii. Mediterranean type 3. expression in prenatally and expressed postnatally only
postnatally
2 H
2. Heinz
i b bodies:
di oxidation
id ti off h
hemoglobin
l bi
3. Bite cell: to eat heinz bodies by splenic macrophages
Treatment

α-Thalassemia β-Thalassemia
Genetic 1. normal: 2 β chains,
2. point mutations,
Genetic 4 α-chain (αα/αα)
Normal 1. β-Thal minor asymptomatic, increased HbA2 or HbF

Silent carrier 1. deletion 1α-chain 2. β-Thal intermedia a severe anemia, but no transfusions needed
2. (-α/αα), 3. β-Thal major 1). normal at brith
(Cooley Syndrome) 2). develop at about 6 month as HbF decrease
α-Thal trait deletion 2 α-chain 1. Genotype: cis (--/αα) type
3). severe hemolytic anemia
(minor) in Asian
a. increase bilirubin, gallstones
2 G
2. Genotype:
t trans
t (-α/-α)
( / ) b. Congestion heart failure is most common cause of
type in African-American death
Hb H disease 1. deletion 3 α-chain 1. increase Hb H, 4). Erythroid hyperplasia in BM: x-ray: “crewcut” skull ,
“chipmunk” face
(major) 2. (--/-α) 2. forms Heinz bodies
5). Peripheral in the blood: Numerous target cells
Hydrops fetalis 1. deletion 4 α-chain, increase barts Hb Treatment 1. do not require specific treatment
2. lethal in utero (--/--) 2. β-major: blood transfusions 1 or 2 / month:
SE: Hemochromatosis, treat with deferoxamine
3. splenectomy eliminates severe hemolytic anemia:
4. Bone marrow transplantation

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PNH
Paroxysmal Nocturnal Hemoglubinuria Summery
decreased glycosyl phosphatidyl inositol (GPI) linked proteins, especially RBC shapes Diseases
decay accelerating factor (DAF)
Anisocytosis Iron deficiency anemia
Function of DAF:
Poikilocytosis Iron deficiency anemia
1. inhibit the activation of the complement cascade by breaking down C3
convertase Shperocytes 1. hereditary spherocytosis
2. decrease O2, trigger complement pathway Target cells Thalassemia, Hb C disease, Liver Disease
Symptoms and Complication Bite cell G6PD deficiency
aplastic anemia, leukemia, venous thrombosis Teardrop cells Myelofibrosis
Diagnosis Elliptocytes Hereditary elliptocytosis
1. Ham’s test (Acidosis in vitro) Acanthocytes abetalipoproteinemia
2. sucrose lysis test (sugar water test) Echinocytes (burr cells) uremia
Schistocytes (Helmet cells) HUS, DIC, TTP
3. flow cytometry: CD55, CD59, much more sensitive and specific
Rouleaux Multiple myeloma
Treatment
1. Glucocorticoids
2. BM transplantation

Summery Other types Anemia


RBC Diseases
inclusions 1. Diamond-Blackfan Syndrome:
Basophilic Cytoplasmic remnant Lead poisoning
stipling RNA congenital pure RBCs anemia
Howell-Jolly
Ho ell Joll Remnants of nuclear
n clear Iron deficienc
deficiency anemia 2. Fanconi anemia (Constitutional)
bodies chromatin
Ring Iron trapped Sideroblastic anemia pencytopenia with abnormal structures
sideroblasts abnormally in
mitrochondria forming
a ring around nucleus
Heinz-bodies G6PD

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Hemostasis 3:1 = M:E (myeloid to erythroid) ratio.

Bleeding
g Disorder
Hasenchecheg Qi MD., Ph.D.

Hemostasis
1. vascular wall 1. bleed
injury 2. transient changes blood flow cause
vasoconstriction turbulence and stasis

Bleeding Reynolds number = (diameter)


(velocity) (density)/viscosity
> 2000 = turbulent flow
< 2000 = laminar flow
3. thrombogenic factors 1. release tissue factor, activate
VII ((extrinsic)
ti i )
2. active factor XII (intrinsic)
due to expose subendothelial
collagen
3. release vWF
2. transient clotting platelet clotting bleeding time 2—7 min
Hemostasis 3. Secondary Extrinsic Coagulation PT: Prothrombin Time 12sec
clotting factor
Intrinsic Coagulation PTT: Partical Throboplastin
factor Time 30sec

Platelets
1. platelets
adhesion
1. vWF adheres
to subendothelial
Coagulation Factors
collagen
2. Platelets
adhere to vWF Adhesion
by glycoprotein Ib
2. platelets 1. platelets
activation changes shape
and
degranulation
Aggregation
2. synthesis of
TXA2
ADP
3. platelets 1. ADP
aggregation clopidogrel,
Ticlopidine
2. TXA2
Vitamin K
3. GpIIb/IIIa
Abciximab, ‫ ץ‬Glutamyl Carboxylase
Eptifibatide,
Tirofiban

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Bleeding Disorder
Thrombomodulin (transmembrane protein) Platelet 150,000—450,000/mm3 bleeding time: 2—7 min
1. Decrease Platelet
+
account
Thrombin
2. Abnormal Platelet
(60 hrs) function
Protein C 3. Von Willebrand AD/AR, vWF 1. bleeding time prolong
C-activated protein Disease (vWD) 2. ristocetin
(Half life 14 hrs) + attributed to Factor 8 3. PTT prolong
Wafarin: Protein S deficiency
Rx: Desmopressin
Transient deficiency
acetate (DDAVP)
of protein C
4. Bernard-Soulier Gp Ib deficient Rx: Platelet
Inactivates Syndrome
Factor V leiden: Factors Va and VIIIa 5.Glanzmann Gp IIb/IIIa deficient Rx:
variant of factor V Thrombasthenia

Thrombocytopenia Thrombocytosis
Immune Thrombotic Hemolytic Disseminated
Thrombocytopenia Thrombosytopenia Uremic Intravascular
Thrombocytosis (reactive) Essential Thrombocythemia (ET)
Purpura Purpura Syndrome Coagulation
1. anti-platelet Fever Diarrhea 1. D-dimers Cause Clinical Features
2. Increase BM Anemia Renal failure 2. Platelet count 1. Bleeding, hemolysis 1. Increased platelet count
megakaryocyte Thromcytopenia decrease
3. acute form: child Renal failure 3. Bleeding time increase
2. Inflammation 2. increased BT
after viral infection 3. Iron deficiency, Stress 3. increased BM megakaryocytes
4 chronic: adult
4. Neuropathy 4 PT and PTT increase
4.
4 postsplenectomy
4. t l t
women 20-40 yo
5. Malignancy
Treatment Treatment Treatment Treatment
1. child self limited in plasmapheresis 1. adult: 1. supportive
6mo, or prednisone plasmapheresis
2. adult 2. child: 2. FFP
a. prednisone self limited 3. Cryoprecipitate
b. IVIG, anti Rh (D): fast 4. treat causes
c. splenoectomy,
Vaccine
d. platelet transfusion

Disorder of Coagulation Hypercoagulation


von Willebrand’s Disease Hemophillia A Hemophillia B
vWF deficiency, VIII deficiency, IX deficiency, 1. XII deficiency Thrombosis, no bleeding PTT prolong,

AD/AR, XR, XR, 2. XIII deficiency Rare, Normal PT and PTT


May have VIII deficiency vWF normal newborn bleeding from cut Dx. Clot solubility test in 5M
umbilical cord urea, positive
Clinical Feature Clinical Feature
1. Cutaneous and mucosal bleeding 1. joint and soft tissue bleeding 3. Antithrombin (AT) Thrombosis PTT prolong

2. Menorrhagia, 2. Hemarthrosis: m.c. III deficiency


3. GI bleeding 3. Intracranial bleeding: 2nd m.c. 4. Antiphospholipid Thrombosis PTT prolong
antibody Syndrome Recurrent abortion
Di
Diagnosis
i Di
Diagnosis
i Di
Diagnosis
i
1. BT increase, may with increase PTT 1. PTT increase 1. PTT increase 5. Factor V leiden Leiden variant of factor V, recurrent DVT
(Activated protein C Rx: life-along anticoagulation
Treatment Treatment Treatment
resistance) (Warfarin)
Do not give Aspirin/NSAIDs
6. Protein C Active Factors Va and VIIIa 1. dermal vascular thrombosis
1. DDAVP (desmopressin) 1. factor VIII 1. factor IX
Deficiency 2. skin necrosis
2. Factor VIII concentrations, 2. FPP not recommended because virus infections
give all Pt with vWD after major trauma Treatment of Acute hemarthrosis 7. Protein S
or during surgery
1. Analgesia, (Codeine) Deficiency
2. Immobilization
(reduced ristocetin-induced platelet
aggregation) 3. Synovectomy (arthroscopic) or radiosynovectomy
for severe and recurrent hemarthrosis

245
10/13/2008

Streptokinase
+
Urokinase
Alteplase (tPA)
Reteplase (rPA)
Plasma: no cells from blood
Anistreplase
Serum: no coagulation factor from plasma.
include all the ion and antibodies, immunoglobulin.

Anticoagulation Medications
Heparin LMWH Warfarin
Thrombolytics Low-Molecular –Weight Heparin VIt K antagonist
Inhibit IIa and Xa Mostly inhibit Xa Inhibit II, VII, IX, X, and protein C and S
Half-lift time Half-lift time Half-lift time
1 hour 3-24 hours 4 days
Administration Administration Administration
1. therapeutic dose: 1. subcutaneously 1. orally: monitor PTT, Monitor INR (2-3)
IV heparin, monitor PTT PTT monitor not necessary
2. prophylactic dose:
SC low-dose
low dose heparin
heparin,
PTT monitor not necessary
SE and Advantage SE and Advantage SE and Advantage
1. Bleeding 1. easer use out Pt 1. Hemorrhage
2. Heparin-induced 2. no HIT or osteoporosis 2. skin necrosis ( decrease protein C)
thrombocytopenia (HIT)
3. Osteoporosis 4. no osteoporosis 3. Teratogenic during pregnacy
4. Transient alopecia 5. more expensive
5. rebound hypercoagulability
d/t depression of ATIII
SE Treatment SE Treatment
1. stop medication, 2. Give PPF, 3. Warferin over dose may also give Vit K

246
10/13/2008

247
10/13/2008

Lymphoma
&
3:1 = M:E (myeloid to erythroid) ratio.

L k i
Leukemia
Hasenchecheg Qi M.D.; PH.D.

Lymphoma Lymphoma
Non-Hodgkin Disease HD Non-Hodgkin Disease HD

If > 65 years old


Precursor Precursor Mature Plasma Cell Mature Not B-cell
1. CLL: m.c. Mature B cell
B-Cell T-Cell B cell Neoplasma T cell Not T-cell
chronic lymphocytic leukemia, or
1. Multiple myeloma small lymphocytic lymphoma
ALL T-ALL 1. not infections
2 MGUS (Monoclonal Gammopathy
2. 1. Follicular 1. m.c. non
non-HD
HD 18: bcl
bcl-2:
2: inhibits
< 15 year old Thymoma 2. “owl-eye” 2. Hairy cell leukkemia Lymphoma apoptosis by blocking the
2. t (14, 18)
undetermined significance) Dx: TRAP + bax channel
Positive TdT < 25 years old 3. R-S cell
3. Waldenstrom macroglobulinemia 2. Diffuse large B- 1. EBV
Rx: 2CDA cell lymphoma 2. HHV-8
Terminal Deoxynucleotide 1. ATLL
1. L1 Tartrate-resistant acid 3. Samll noncleaved 1. starry-sky 8: c-myc
transferase 2. MF and Sezary S. lymphoma (Burkitt
phosphatase 2. t (8, 14)
2. L2 1. NS: m.c. Lacunar cell
lymphoma)
Acute Lymphoblastic Leukemia
3. L3 4. Mantle Cell T (11, 14) 11: bcl-1 (cyclin D)
2. LP: popcorn cell 2- Lymphoma
chlorodeoxyadenosine
3. LD: most RS cell 5. MALToma Treat as H.pylori
(Marginal zone
4. Mixed: eosinophils, IL-5 Lymphoma)

Leukemia
AML MDS Myeloproliferative Syndrome

BM blast > 30% BM blast <30%


CML P. vera ET MF
1. M0—M4: myelo-, WBC
2 M3:
2. M3 t (15
(15, 17) 1 t (9
1. (9, 22) 1. Dry tap
15: PML 9: c-abl 2. Teardrop RBC
17: retinoic acid receptor α-gene 22: bcr
(RAR-α) 2. LAP low
3. M5: monoblasts
4. M6: erythroblasts
5. M7: megakaryocytes

248
Biochemistry:
Week Three

249261
250262
Three sources of energy
• Proteins

BIOCHEMISTRY
• Fats
• Sugars

AMINO ACIDS

AMINO ACIDS

Proteins
The main intracellular buffers

An Acid A Base
Pka is less than 7 Pka is greater than 7

251263
An Acid A Base
• Dissociates early • Dissociates later
• Likes to give up hydrogen ions (protons) • Likes to accept hydrogen ions (protons)
• Pka is less than 7 • Pka greater than 7
• Strong acid: Pka 1 to 3 • Weak base: Pka 7 to 9
• Weak acid: Pka 4 to 7 • Strong base: Pka greater than 9

Three Easy Words That are Hard


To Understand
• Dissociate: to lose a hydrogen (proton)
• Soluble: charged or polar
Pka 4 to 9… • Bioavailable: neutral

Can be a weak acid or a weak


base

Dissociation Dissociation
To Lose A Hydrogen

252264
Soluble Soluble
Charged Or Polar

Soluble Bioavailable
Water Soluble

Bioavailable Bioavailable
Neutral Fat Soluble

253265
AMINO ACIDS As an acid dissociates…
• It gains a negative charge
• It gains solubility
• It loses bioavailability

As a base dissociates… Henderson-Hasselback Equation


• It loses its positive charge
• It loses solubility
• It gains bioavailability

Henderson-Hasselback Equation ACIDS


• IF you want to absorb more…
– Add more Acid
• IF you don’t want to absorb it…
– Add base

254266
Base Acids you need to know
• IF you want to absorb more… • Aspirin
– Add more base • Barbiturates
• IF you don’t want to absorb it… • Myoglobin
– Add acid • TCAs

Bases you need to know


• Amphetamines
The main acid used in
medicine
NH4CL

Now we look at the ISOELECTRIC


POINT

The main base used in


medicine
HCO3

255267
Isoelectric Point
• NO NET charge on the molecule
• Also called a zwitterion
• Will NOT migrate towards anode or
cathode

Cathode Anode
Where CATIONS go: the Where ANIONS go: the positive
negative electrode electrode

256268
To further categorize the
amino acids…

Glycine PHE, TRP, TYR


• Smallest amino acid • Aromatic amino acids
• NO chiral carbon • Recognized by chymotrypsin
• Inhibitory neurotransmitter for the spinal
cord

LYS, ARG Asp, Glu


• Basic amino acids • Acidic amino acids
• Have a positive charge
• Recognized by trypsin

257269
Asp Cys, Met
• The only excitatory amino acid in the brain • Contain sulphur
( NMDA pathway) • Make disulphide bonds

Asparagine, Glutamine Serine, Threonine, Tyrosine

Involved in N- bonds Involved in O- bonds

Leu, Iso, Val Tyr


• Branched chain amino acids • Used to make catecholamines
• Used to make melanin

258270
Trp Ketogenic Amino Acids
• Used to make serotonin • Lysine
• Arginine

Both glucogenic and ketogenic Glucogenic Amino Acids


• PHE • ALL OTHERS
• ISO
• THR
• TRP

Essential Amino Acids Essential Amino Acids


• You get them ONLY from the diet
• NO cycle in YOUR body can make these
• A deficiency will ALWAYS lead to a
disease
• Deficiencies put the body into a starvation
state

259271
How does the body utilize energy
during starvation? Energy Utilization
• (1) plasma glucose: lasts 2 to 4 hours
• (2) liver glycogen: lasts 24 to 28 hours
• (3) proteolysis for gluconeogenesis
• (4) lipolysis
• (5) ketogenesis

Notables Phenylketonuria
• PHE used to make TYR • Phenylalanine hydroxylase is deficient
– TYR becomes essential if PHE is deficient • Unable to make tyrosine
– Unable to make DA and NE and EPI
• MET used to make CYS • Unable to make melanin without tyrosine
– CYS becomes essential if MET is deficient – Blonde hair; blue eyes; fair skin
• Phenylacetate and phenylpyruvate build
up
– Musty odor

PKU Newborn Screening


• Must screen all newborns at 48 hours • PKU ( Guthrie test)
• Must avoid aspartame (nutrisweet) • Hypothyroidism (TSH)
• Pregnant mother must be on restricted diet • CAH
especially during first 8 weeks while brain • Biotinidase def
is developing • Galactosemia
• Rainbow colored wheel on food products
would warn these patients against
aspartame

10

260272
Albinism Vitiligo
• Tyrosinase deficiency • Autoimmune antibodies against
• Predisposed to skin cancer melanocytes
• Loss of pigmentation
• Predisposed to skin cancer

Alcaptonuria (ochronosis) Maple Syrup Urine Disease


• Homogentisic acid oxidase deficiency • Involves branched chain amino acids
• Tyrosine builds up • Defective renal transport of these amino
• Urine turns black when exposed to air acids
• LEUCINE
• ISOLEUCINE
• VALINE

Cystinuria
• Defective renal transport of amino acids

THE END
• Hexagonal, envelope shaped, or coffin lid
shaped crystals in the urine
• CYSTIENE
• ORNITHINE TO BE CONTINUED…
• LYSINE
• ARGININE

11

261273
Protein Structure
• Primary
Protein Structure • Secondary
• Tertiary
and Function • Quarternary
Putting the Amino Acids
Together

Protein Structure Primary Structure


• Primary • The amino acid sequence
• Secondary • Involves peptide bonds
• Tertiary • Restriction enzymes are used to sequence
• Quarternary proteins

Peptide Bond Peptide Bond


• Planar
• Restricted mobility
• R-groups are in trans-configuration

262274
Sequencing

Before we understand the


present…
We need first visit the past!

The history of sequencing Acid Hydrolysis


• Acid hydrolysis • Denatures the protein
• Gel electrophoresis
• Ninhydrin reaction • Does NOT actually sequence the protein
• Edman’s degredation • Turns asparagine into aspartate (acidic
• Restriction peptidases form) and glutamine into glutamate (acidic
form)

Gel electrophoresis Gel Electrophoresis


• Uses agarose gel to separate proteins by
size first, charge second
• Smaller proteins migrate further
• Larger proteins stay closer to the start site

• Does NOT sequence the proteins

263275
Ninhydrin Reaction Edman’s degredation
• Reacts with all amino acids creating a • Uses phenylIsoThioCyanate (PITC)
purple color • Reacts with ANY amino acid starting on
• Proline reaction creates a yellow color the amino terminal
• Amino acids are identified by
• Good ONLY for counting prolines spectrophotometry (light transmission)

• Procedure is accurate ONLY up to 100


amino acids

Restriction Peptidases Restriction Peptidases


• Restricted by what amino acids they can • Trypsin: cuts to the right of LYS and ARG
recognize • Chymotrypsin: cuts to the right of the
• Used to actually sequence proteins aromatic amino acids, PHE, TRP, TYR
• Elastase: cuts to the right of GLY, ALA,
SER
• CNBr: cuts to the right of MET
• Aminopeptidase: cuts to the right of the
amino terminal amino acid

Restriction Peptidases, cont An Example


• Carboxypeptidase: cuts to the left of any
amino acid on the carboxyl terminal
• Mercaptoethanol: breaks up disulfide bonds

264276
Secondary structure Alpha helix
• Alpha helix
• Beta pleated sheet

Beta pleated sheet Serum proteins


• Functional
• Acute phase reactants

Too many proteins in your plasma


• Elevated ESR or CRP
– Indicates nonspecific inflammation TOO many acute phase
• Falsely high ESR: anemia
proteins…
• Falsely low ESR: sickle cell anemia;
polycythemia Leads to AMYLOIDOSIS
• Acute phase reactants caused by IL-6

265277
AMYLOIDOSIS Secondary Amyloidosis
• Primary: autosomal dominant • AA: chronic inflammatory disease
– Massive intracerebral hemorrhage in a young • AB: Alzhiemer’s disease
person with no prior h/o HTN
• AB-2: Chronic renal failure
• Secondary: due to any chronic
• AE and AF: MEN-II
inflammatory disease
• AL: Multiple myeloma

• Congo red stain


• Apple green birefringence

Tertiary Structure Quarternary Structure


• 3-D structure • Two or more proteins are interacting
• Most important factor is hydrophobic and • Cooperativity
hydrophilic interactions • Allosterism: refers to enzymes
• Covalent bonds now form – Allosteric enzyme means the slowest enzyme;
means rate-limiting enzyme; means the
kinetic curve is sigmoidally shaped

Hemoglobin
• Type A: 2 alpha – 2 beta chains

Hemoglobin • Type A-2: 2 alpha – 2 delta chains

The first quarternary protein • Type F: 2 alpha – 2 gamma chains


discovered

266278
Hemoglobin F Hemoglobin F
• Found in the fetus
• Disappears by 6 months of age
• Has a low affinity for 2,3, DPG
• Has a high affinity for oxygen

Erythropoiesis Heme Synthesis


• Begins: in yolk sac at 4 months gestation
• 6 mo gestation: moves into the liver,
spleen, and flat bones
• 8 mo gestation: moves into the long bones
• 1 year of age: liver, spleen, and flat bones
close
• If you lose the long bones after 1 year, the
spleen can reopen causing massive
splenomegaly

Iron deficiency anemia Lead Poisoning


• Most common cause of microcytic • Lead inhibits delta ALA dehydratase as
hypochromic anemia well as ferrochetolase
• In children: Mcc is inadequate intake • Mcc: eating peeling paint from old
• In young adults: Mcc is still inadequate buildings
intake • Classic clue: basophilic stippling; elevated
• 20 to 40: IBD FEP (free erythrocyte protoporphrins)
• > age 40: mucasal bleeding
• Tx: ferrous sulphate

267279
Heme Synthesis Lead levels to know
• Normal: < 10
• If above 10: notify PHD; treat with succimer
• If above 30: notify PHD; hospitalize; do a
Ca-EDTA challenge; treat with
penicillamine and dimercaprol (BAL) if
urinary lead is high
• If above 50: do as above; skip EDTA
challenge

Drug induced lupus


• Antihistone antibodies
Lead used to be the most
• Hydralazine common cause of mental
• INH retardation…
• Procainamide But NOT ANY MORE!
• Penicillamine
• Phenytoin
• Ethusuximide

Mental retardation Porphyrias


• Fetal alcohol syndrome • A group of enzyme deficiencies
• Fragile X syndrome • Synthesize too many porphyrin rings or
• Down’s syndrome inadequate metabolism are the problems
• Porphyrin rings in the urine make it red
• Two types are most important…

268280
Erythrocytic Protoporphyria and
Acute Intermittent Porphyria Porphyria Cutanea Tarda
• Enzyme dificiency • Enzyme dificiency
• A build up of porhyrin rings • Porphyrin rings are deposited underneath
• Porphyrin rings are deposited in visceral the skin
organs and around nerves • Light reacts with the rings causing a
• Recurrent severe abdominal pain and release of heat which leads to burns
neuropathy • Mcc of death: skin infections
• Tx: • Tx: protect them from light

Opiates Opiates
• CNS depressants • Heroin • Loperimide
• Muscle relaxants • Methadone • Diphenoxylate
• Morphine • Fentanyl
• Analgesics
• Meperidine • Pentazocine
• Codone
• Receptors: • Oxycodone
– Mu ( CNS) • Codiene
– Kappa: Spinal cord • Dextromethorphan

Hemoglobinopathies Hemoglobin S disease


• Hemoglobin S disease • Autosomal recessive
• Hemoglobin C disease • High prevalence in Africa ( natural
selection)
• Substitution of valine for glutamate at
position 6 of beta chain
• Hypoxia causes cells to sickle leading to
vaso-occlusion

269281
Vaso-occlusive crises Aplastic crisis
• CVA • Complete bone marrow suppression
• PULMONARY INFARCTION • Always check the reticulocyte count
• SPLENIC SEQUESTRATION • Mcc: parvovirus B-19
• PRIAPISM

• Tx: exchange transfusion; oxygen

A Few Points to Remember… Hemoglobin C disease


• Functional asplenia by age 6 due to • Autosomal recessive
infarcts • Substitution of LYS for GLU at position 6
– Susceptible to encapsulated organisms
of beta chain
– Give pneumovax anytime after age 2
• NO sickling occurs since both amino acids
• Infections are mcc reason for crises
are hydrophilic
• Hydroxyurea increases HgF, decreasing
chance for hypoxia
• Use opiates for pain
• Transfuse when anemic and symptomatic

Thallesemias Hemoglobins
• Represent gene deletions
• Autosomal recessive
• Common in Mediterainian people
• Minor: at least one gene remaining
• Major: no genes remaining

270282
Alpha Thalessemia Baseline labs
• RBC Mass: 3.5 to 4.5 million
• Hemoglobin/Hematocrit: 15/45%

Alpha Minor Alpha Thalessemia Major


• One gene missing • NO genes remaining
– Asymptomatic – ( HG 12) 75% • Unable to make any hemoglobin at all
• Two genes missing • Hydrops Fetalis
– IF sedentary: asymptomatic • Hemoglobin Bart ( 4 gamma chains)
– IF active: symptomatic (HG 7.5) 50%
• Hemoglobin H ( 4 beta chains)
• Three genes missing
– Symptomatic in ALL (HG 4 to 5)

Beta Thalessemia: 2 genes Blood Transfusions


• Beta minor (Hg 7.5) • Beta major • Done ONLY when patient is symptomatic
– One gene missing – Both genes missing
• One unit of PRBCs
– If sedentary: – Able to make only Hg
asymptomatic A-2 and Hg F – Raises Hg by 1 to 2 grams ( 3 to 6 HCT)
– If active: symptomatic – Asymptomatic until 6 – Delivers 3.4 grams of iron
– Increased Hg A-2 and months of age
Hg F – Transfusion dependent
– Ineffective
erythropoiesis

10

271283
Iron Overload Hemochromatosis
• Hemosiderosis: bone marrow is • Primary • Secondary
overwhelmed by iron – Autosomal recessive – Too many transfusions
– Too much iron – Mcc of death in first 10
• Hemochromatosis: iron overload has absorption from years: transfusion
involved other organs duodenum related infections
– Skin: bronze pigmentation – HLA A3 on – Mcc of death after 10
chromosome 6 years: CHF
– Liver: bronze cirrhosis
– Pancreas: bronze diabetes
– Heart: restrictive cardiomyopathy

Transfusion Related INFECTIONS Transfusion related infections


• HIV Bacterial infections
• Hepatitis B Malaria
• Hepaitis C Babesiosis
• Hepatitis D Syphilis
• EBV
• CMV
• Hemorrhagic viruses

Hemoglobin Saturation Curve COLLAGEN

11

272284
4 Types of collagen
• Type 1: Skin
More than a quarternary • Type 2: Connective tissue
structure… • Type 3: Arteries
• Type 4: Basement membrane
It’s a TRIPLE HELIX

To synthesize collagen Protein synthesis for packaging…


• Glycine: every third amino acid
• Lysine
• Proline
• OH-Proline
• OH-Lysine

Protein synthesis for packaging… Protein synthesis for packaging…

12

273285
Protein synthesis for packaging… Who makes collagen?
• Fibroblasts: simple scarring
• Myofibroblasts: if you need wound
contraction

When collagen synthesis goes


wrong…

DESMOPLASIA

COLLAGENOUS REACTION
SURROUNDING A TUMOR

COLLAGEN PROFILE

KELOID

TOO MUCH COLLAGEN


DEPOSITION

13

274286
ALL YOU NEED NOW IS A CLUE Collagen diseases
• Ehlers Danlos
• Marfan’s
• homocystienuria
• Scurvy
• Osteogenesis imperfecta
• Minky’s kinky hair syndrome

Secondary collagen diseases Collagen Vascular Diseases


• Ankylosing spondylitis • CREST • SLE
• Fragile X syndrome • Scleroderma • MCTD
• Progressive systemic
• Syphilis
sclerosis
• Takayasu’s disease • Rheumatoid arthritis
– Felty’s syndrome
– Becet’s syndrome
– Sjogrens syndrome

ELASTIN Elastin
• Has many GLYCINES
• Has PROLINES
• Has LYSINES
• Has OH-PROLINES
• NO hydroxylysines

14

275287
Elastin Elastase
• Provides COMPLIANCE • Destroys elastin
• Provides ELASTICITY • Cuts to the right of GLY, ALA, and SER
• Has DESMOSINE • Alpha-one antitrypsin inhibits elastase
• Found in neutrophils and bacteria
• Smoke inhibits alpha-one antitrypsin
• Decreased alpha-one antitrypsin with
aging

Who’s afraid of staph aureus and


Emphysema pseudomonas?
• Destruction of elastin • Neutropenic
• Loss of recoil • Burn patients
• Cystic fibrosis
• Panacinar: alpha-one antitrypsin deficiency • Diabetics
• Centroacinar: smoking
• Disto-acinar: aging • If any fever, cover staph aureus with one
• Bullous: staph aureus and pseudomonas antibiotic and cover pseudomonas with
two antibiotics

Keratin
• Made for tensile strength

THE END…
• Contains a lot of CYSTEINES

…ONLY FOR NOW

15

276288
IF asked whether a reaction is
ENZYMES possible…
THE MOST IMPORTANT THE answer is always YES!
PROTEINS IN YOUR BODY

A Reaction

ANYTHING, as we know…

IS POSSIBLE!!

An Enzyme… An ENZYME has…


• Brings substrates together in space and
time
• Lowers the free Energy of activation
• Stabilizes the hi energy intermediate

• Is not consumed in the reaction

277289
Competitive inhibition Noncompetitive inhibition
• Inhibitor is similar to the substrate • NOT similar to the substrate
• The inhibitor is competing for the active • Does NOT bind active site
site • Binds to regulatory site
• Affinity I decreased • Turns off the enzyme
• Km increases • Km remains the same
• Vmax remains the same ( just add more • Vmax decreases
substrate) • irreversible
• reversible

What makes a reaction favorable Effects of temperature on a


and spontaneous reaction

E
• You want it to be negative
E • When negative: has electrons
to give
REDOX POTENTIAL • When positive: wants to accept
electrons

278290
Reducing agent Oxidizing agent
• Has a negative delta E • Has a positive delta E
• Wants to give away electrons • Wants to accept electrons
• Gets oxidized after the reaction • Gets reduced after the reaction

Electron Transport System

Inhibitors and Uncouplers

279291
Inhibitors Uncouplers
• DNP
• ASPIRIN
• FREE FATTY ACIDS

How to name enzymes

FIRST NAME of an enzyme

IS the name of the SUBSTRATE

LAST NAMES of enzymes


• Kinase • Synthase
• Phosphorylase • Synthetase
LAST NAME of an enzyme • Isomerase • Dehydrogenase
• Epimerase • Hydrolase
• Mutase
Is what you did to the substrate
• Transferase
• Lyase
• Carboxylase

280292
Coming to a screen near
you…

THE PATHWAYS

281293
Anabolic Pathways: As soon as you eat…
Putting it all back together You replenish your plasma glucose

After glucose returns to After you turn off


the liver… gluconeogenesis…
You turn off gluconeogenesis You turn on glycogen synthesis

Glycogen Synthesis

282294
Pentose Pathway

NADPH is used for… X-linked Recessive Enzymes


• Fatty acid synthesis • G6PD
• DNA synthesis • Fabry’s ( alpha galactosidase)
• RBC repair ( used by glutathione) • Hunter’s ( Iduronidase)
• CGD ( NADPH Oxidase)
• Lesch-Nyhan ( HGPRT)
• Pyruvate Dehydrogenase
• Adrenoleukodystrophy ( CAT-1)

G6PD
• More common in Meditteranians ( protects
them from malaria)
• Mcc of hemolytic crisis: ( 1) infection (2)
drugs
• Drugs that oxidize RBC’s: sulfa drugs;
antimalarials; metronidazole; INH

283295
Amino Acid Synthesis Fatty Acid Synthesis

Palmitic Acid
• The main fatty acid that we make every
day
• Saturated FA: NO double bonds
• Unsaturated FA: has double bonds
• Omega FA: counting carbons from the right
side
– Omega 3 FA: Lowers serum cholesterol
– Pocosanol

Rules for Fatty Acids Essential Fatty Acids


• We do NOT go beyond C-16 • Linolinic
• Double bonds have to be at least 3 • Linoleic ( used to make arachadonic acid)
carbons apart • Come ONLY from the diet
• NO double bonds after C-10 • Your body can not make these

284296
Irreversible Cyclo-Oxygenase
Arachadonic Acid Inhibitor
• Aspirin

Reversible Cyclo-Oxygenase
inhibitors Steroids
• NSAIDs • Antiinflammatory • Physiologic actions
– Indomethacin actions – Proteolysis
– Inhibit PLP-A – gluconeogenesis
– Phenylbutazone
– Kills T-cells and
– Ibuprofen eosinophils
– Naproxen – Inhibits macrophage
– Baclofen migration
– Stabilizes mast cells
– Ketorelac
– Stabilizes endothelium
– cyclobenzaprine

Steroids Mast Cell Stabilizers


• Prednisone • Cypropterone • Cromolyn
• Methylprednisalone • Megestrol • Nedacromyl
• Triamcinalone • Fluticasone
• Beclamethasone • Mometasone
• Betamethasone • Danazol
• Hydrocortisone
• Dexamethasone
• fludrocortisone

285297
LRBs Triglyceride Synthesis
• Zifurlekast
• Montelekast
• Zileutin

Triglyceride Transport Sphyngolipids


• Chilomicrons
• VLDL
• IDL

• Signs:
– Xanthelesma
– Pancreatitis

Lysosomal Storage Diseases


• Gaucher: glucocerebrosidase
• Fabry’s: alpha galactosidase


Krabbe’s: beta galactocerebrosidase
Tay Sacks: hexoseaminidase A And Now…
• Sandhoff’s: hexoseaminidase A & B
• Nieman Pick: sphyngomylinase The final anabolic
• Metachromatic leukodystrophy: arylsulphatase
• Hurler’s: iduronidase process
• Hunter’s: iduronidase sulphatase

286298
Cholesterol Synthesis NUCLEOTIDES

NUCLEOTIDES PURINES
• RNA • Adenine
• DNA • Guanine
• ENERGY
• CARRIERS ( UDP & CDP)
• METHYL GROUP CARRIER ( S-AM)
• SECOND MESSENGERS

PYRIMIDINES NUCLEOTIDES
• Thymidine
• Cytidine
• Uracil

287299
THE BLOTS
• Southern blot: DNA
• Northern blot: RNA
• Western blot: PROTEIN EUCHROMATIN
• PCR: amplifies DNA or RNA
• ELIZA Loose DNA; has more A and T

PURINES
HETEROCHROMATIN
Tight DNA; has more G and C

PYRIMIDINES RIBONUCLEOTIDE REDUCTASE

288300
SCID The DNA Helix
• Adenosine deaminase def
• Unable to make DNA
• Affects all rapidly dividing cells, especially
bone marrow
• Bone marrow transplant is now current
therapy

HISTONES Anti-Histone Antibody


• Help bind DNA helix • Hydralazine
• H-1 • INH
• H-2a • Procainamide
• H-2b • Penicillamine
• H-3 • Phenytoin
• H-4 • Ethusuximide
• Basic

CELLULAR CYCLE DNA REPLICATION

289301
TRANSCRIPTION TRANSLATION

DIFFERENCES MUTATIONS
• DNA Replication • Translation • Frameshift mutations
– DNA POL alpha – Fmet vs met
– DNA POL beta • Point mutations
– DNA POL gamma – Transition mutations
– DNA POL delta – Transversion mutations
– DNA POL epsilon • Silent mutations
– Replication forks
• Missence mutations
• Transcription • Nonsence mutations
– Monocistronic
– polycistronic

IT IS THE END…

CAN IT BE ?
YES, IT IS!!!

290302
OR IS IT.

291303
Sources of Energy
• Glucose ( 40% of diet)
• Proteins ( 30% of diet)
Catabolic Pathways • Fats ( 30% of diet)
• Ketones ( last resort)
Breaking it all down

Breaking Down Sugars First

Breaking Down Sugars…


Begins With Glycolysis

RBC Connection
• RBCs use ONLY glucose for energy
• Hypoglycemia will ALWAYS affect RBCs
first, causing a hemolytic anemia
• The only other pathway RBCs have is the
pentose pathway for making NADPH to
maintain the membrane

292304
Glycolysis Glycolysis
• The most active pathway in your body
• CATABOLIC in all cells except the liver
where it is ANABOLIC

CATABOLIC STATE How to use energy


• Is controlled by the sympathetic system
• Second messenger is C-amp
• Is controlled hormonally by epinephrine
and glucagon

293305
DHAP
• Used in the glycerol 3 phosphate shuttle
• Used in triglyceride synthesis

Glyceraldehyde 3 phosphate
dehydrogenase Mercury Toxicity
• Has sulphur in the active site • Mcc: (1) Tuna (2) a child biting into a
• Is blocked by mercury poisoning thermometer
• Blocks glyceraldehyde 3 phosphate
dehydrogenase
• LOW ENERGY STATE
• RBCs affected first
• Brain affected the most

Pallegra
• Niacin deficiency
• The 4 Ds
– Dermatitis
– Diarrhea
– Dimentia
– Death
• Hartnup’s: presents just like pallegra.
– Defective renal transport of tryptophan

294306
Flouride Poisoning
• Blocks the enzyme ENOLASE
• Caused in the past by eating rocks of
flouride
• Rare today since flouride added to water
and toothpaste
• Clue: extra white teeth and bones

Gluconeogenesis

Gluconeogenesis
• Controlled by epinephrine and glucagon
• Second messenger is C-amp
• Occurs only in the liver (90%) and the
adrenal cortex (10%)
• Occurs while other tissues are running
glycolysis
• Occurs in the mitochondria and cytoplasm

295307
To reverse glycolysis Galactose Metabolism
• Pyruvate carboxylase ( rate limiting)
• PEP Carboxykinase
• F16DPase
• G6Pase

Detecting Sugars
• In the urine: CLINITEST
• In the stool: positive REDUCING SUBSTANCES

Galactosuria
• Galactokinase deficiency
• Hexokinase fills in for galactokinase
• Galactose in the urine ( clinitest positive)
• Symptoms: polyuria; polydypsia; UTIs

296308
Galactosemia Fructose Metabolism
• Galactose 1 phosphate uridyltransferase
deficiency
• Galactose 1 phosphate builds up in the
cells
• RBCs affected first
• Brain affected the most
• LOW ENERGY STATE

Fructosuria
• Fructokinase is missing
• Hexokinase fills in
• Fructose in the urine ( clinitest positive)
• Polyuria
• Polydypsia
• UTIs

Fructosemia
• Aldolase B is missing
• Fructose 1 phosphate is trapped within the
cells and can not leave Before you enter the KREB CYCLE
• RBCs affected first
• Brain affected the most YOU NEED TO
• LOW ENERGY STATE
KNOW…

297309
THE FIVE FATES OF
PYRUVATE
5 FATES OF PYRUVATE

Pyruvate Dehydrogenase KREB CYCLE

Malate-Aspartate Shuttle Glycerol 3 Phosphate Shuttle

298310
Amino Acid Catabolism Fatty Acid Catabolism
• Palmitic acid: C-16 the main fatty acid we
make daily
• Three formulas to know:
– ( C/2 – 1) : the number of rounds it takes to
break down a fatty acid chain or the number
of rounds it took to make a fatty acid chain
– ( C/2 – 1) 2 : the number of NADPHs it cost to
make a fatty acid chain
– ( C - 1): the number of ATPs it cost to make it

Fatty Acid Catabolism Adrenoleukodystrophy


• Defective carnitine shuttle
• Long chain free fatty acids accumulate in
the cytoplasm, unable to enter
mitochondria
• X-linked recessive
• Adrenal gland failure
• Early white matter involvement

X-linked Recessive Enzymes Beta - Oxidation


• G6PD
• Pyruvate dehydrogenase
• NADPH-Oxidase
• HGPRT (Lesch-Nyhan)
• Alpha-Galactosidase ( Fabry’s)
• Iduronidase ( Hunter’s)
• CAT-1 (Adrenoleukodystrophy)

299311
Odd numbered carbon fatty acid
metabolism Ketogenesis

Reasons NEVER to give bicarbonate


IDDM ( TYPE 1 DIABETES) in treatment of DKA…
• Autoimmune • DKA • It merely corrects a number without
• 2 weeks after a viral – Hypovolemia
correcting the actual problem
(Cocksackie B) infection – Lack of insulin
• Anti-islet cell antibody – Low body potassium • Decreased cardiac output
– Hyperkalemia
• Sx begin after 90% of
– Hypophosphatemia • Causes hypokalemia
islet cells are destroyed
– Pseudohyponatremia
• Remaining 10% will • Shifts hemoglobin dissociation curve to the
– Correcting sodium
undergo hyperplasia – Visceral pain left
( honeymoon period) – False high creatinine • Bicarbonate ion does NOT cross the blood
• Signs and sx: LOW – Correcting glucose
ENERGY STATE – Correcting acidosis
brain barrier ( CSF pH falls paradoxically)

NIDDM ( Type II Diabetes) Sulfonylureas


• Genetic • Complications • Chlorpropamide
• Connected to obesity – Vasculitis
• Tolbutamide
• Downregulation of – Clots
– Bleeds • Tolezalide
insulin receptors
– Nephropathy
• Hyperinsulinemia
– Neuropathy
• Nonketotic • Glipizide
– IDM
• Hyperglycemic, – Tx: weight loss • Glyburide
nonketotic coma • Meds
• insulin

300312
Other Oral Hypoglycemics Insulins
• Ascarbose
• Miglitol

• Metformin

• Piaglitazone
• Rotiglitazone
• Repaglinide
• Troglitazone

Dawn effect Somoji effect


• Increase in blood sugar each morning • Actually caused by HYPOGLYCEMIA that
caused by the normal increase in occurred in the early morning ( 2 to 3 am)
epinephrine, glucagon and cortisol that leading to reactive HYPERGLYCEMIA in
occurs each morning the late morning ( 6 to 7 am)

• Tx: increase morning regular insulin • Tx: decrease evening NPH insulin

Glycogen: Synthesis / Catabolism Glycogen: Synthesis / Catabolism

301313
Glycogen: Synthesis / Catabolism Glycogen: Synthesis / Catabolism

Glycogen: Synthesis / Catabolism Glycogen Storage Diseases

Glycogen Storage Diseases


• Von Gierke’s: glucose 6 phosphatase
• Anderson’s: branching enzyme
• Cory’s: debranching enzyme The End of CATABOLISM
• Her’s: liver phosphorylase
• Mcardle’s: muscle phosphorylase The Beginning of ANABOLIC
• Pompe’s: cardiac alpha 1,4 glucosidase PATHWAYS

302314
Forgiveness
• Through God’s love, you always have
infinite forgiveness
• Unfortunately, you don’t always have The Physiology of CANCERS
infinite time
CELLS OUT OF CONTROL

Anaplasia Metaplasia
• Cells revert back to their mesenchymal • Replacement of one adult cell type for
origin another
• NO MATURATION TIME NEEDED • The new cell can better handle the stress
• The most aggressive type of cancer
• Divides rapidly
• Metastasizes early and aggressively
• SENSITIVE to radiation or chemo

303315
Desmoplasia
• A collagenous reaction surrounding a
tumor

Dysplasia
• Loss of cell to cell contact inhibition
• Cells begin to crawl on top of each other
• This is the FIRST STAGE OF CANCER
• Also known as carcinoma in situ ( CIN)
• Any cancer that is caught at this stage has
a good prognosis if removed ( 90% 5 year
survival)
• ALL screening is done to find cancer at
this stage

NEOPLASIA Malignant Neoplasia


• BENIGN • MALIGNANT • Angiogenin
– Well circumscribed – Not circumscribed
• Endostatin
– Freely mobile – Adherent
– Encapsulated – Not encapsulated
– Does not outgrow – Outgrows capsule
capsule – Outgrows blood supply
– Does not outgrow – METS
blood supply – Does NOT obey
– NO METS physio
– Obeys physio

304316
When you have one BILLION How long does it take for ONE
cells… BILLION cells to reassemble?
• You can SEE the cancer with the naked
eyes
• You can PALPATE it on exam
• Chemo must kill at least one billion cells to
be considered effective

If a cancer outgrows its blood


To Name a Tumor…
supply, go to the …
• BRAIN • First name: the most common cell type
• LUNGS • Last name: add - oma at the end
• BONE
• LIVER
• ADRENAL
• PERICARDIUM

To Name a Cancer… TRICKY - OMAs


• First name: most common cell type being • Hamartoma: abnormal growth of normal
stressed tissue
• Prefix for every glandular tissue is ADENO • Choristoma: abnormal location of normal
• Last name: carcinoma if it originates from tissue
epithelium
– Sarcoma if it originates from connective tissue

305317
Cancers that lost their proper Let us now begin…one organ at a
endings time
• Hepatoma
• Seminoma
• Lymphoma
• Teratoma
• Mesothelioma
• Retinoblastoma
• Neuroblastoma
• Nephroblastoma ( Wilm’s tumor)

BRAIN Psammoma Bodies


• Most common INTRACRANIAL tumor: • Papillary carcinoma of thyroid
MENINGIOMA • Serous
– Displaces the brain • Adenocarcinoma of the ovaries
– Psammoma bodies ( calcifications)
• Meningioma
• Mesothelioma

BRAIN, cont Neurocutaneous Syndromes


• Most common primary brain tumor: • ALL have mental retardation, seizures and
ASTROCYTOMA cerebral calcifications in common
– GLIOMA • All have tumors or cancers associated with
– OLIGODENDRIGLIOMA them
– EPENDYMOMA • All have different cutaneous findings

306318
Neurofibromatosis Sturge – Weber syndrome
• Café au lait spots ( hyperpigmented • Port wine stain on forehead
macules) • Angiomas of retina and brain
• Associated with chromosome 17/22
• Neuromas
– Peripheral neuromas: chromosome 17(type 1)
– Central neuromas: chromosome 22(type 2)
• fibromas

BRAIN, cont Pituitary


• Most common primary brain cancer: • Most common tumor: pituitary ADENOMA
astrocytoma grade IV or GLIOBLASTOMA – Cell types:
MULTIFORME • Chromophobes ( nonfunctional) 95%
• Acidophils (produce PRL and GH)
• Basophils ( produce ACTH, TSH, FSH and LH)
• Most common cancer: METASTASES • Most common FUNCTIONAL tumor:
– Usually found at the grey-white matter PROLACTINOMA
junction • Most common cancer:
ADENOCARCINOMA (rare)

Pineal Posterior Fossa Tumors


• Most common tumor: pineal adenoma • Present with early morning vomitting
( PINEALOMA) • Common in children
– CN VI palsy (esotropia)
• MEDULLOBLASTOMA
– Precocious puberty
– Cerebellar origin; it sits on top of the medulla
• Most common cancer: • CRANIOPHARYNGIOMA
ADENOCARCINOMA (rare) – Develops from Rathke’s pouch
– Has a motor oil appearance
– Has some calcifications
– May damage anterior or posterior pituitary

307319
Mediastinum Posterior Mediastinum
• Anterior • Mostly ganglia located there
• Middle • Most common tumor: NEUROMA
• Posterior • Most common cancer:
NEUROBLASTOMA

Neural Crest Cancers Neural Crest Cancers


• NEUROBLASTOMA • PHEOchromocytoma • Paroxysmal palpitations, HTN, headache
– Most common – Located in adrenal and diaphoresis
abdominal mass in medulla
children
• Unable to differentiate benign from
– 10% in children
– Hypsarrythmia
malignant histologically
– 10% bilateral
– Opsoclonus – 10% metastatic
• Must remove ALL of them
– Highest spontaneous – 10% familial • Dx: check urinary VMA, metanephrines, or
regression rate (2%) – 10% malignant HVA
– Phentolamine
– Phenoxybenzamine

Anterior Mediastinum Thymus


• Thymus • Most common tumor: THYMOMA
• Thyroid – Associated with ALL autoimmune diseases
except Grave’s disease
• T-cell leukemias/lymphomas
– These cells are pleuripotent;
• Teratomas
– Thymus is immunopreviledged
• Most common cancer:
ADENECARCINOMA (rare)

308320
Thyroid Thyroid Masses
• Most common mass: cyst( throglossal) • CYSTIC • SOLID
– Thyroglossal cyst is – First do a thyroid scan
• Most common tumor: follicular adenoma most common – cold nodule and h/o
• Most common cancer: papillary – Do ultrasound to verify previous irradiation to
– Do FNA: diagnostic the neck: lobectomy
carcinoma and therapeutic – If hot nodule: treat
– Local metastases only hyperthyroidism
– Cold nodule w/o h/o
– Psammoma bodies previous irradiation:
– Risk factor: previous irradiation to the neck biopsy
• Do lobectomy only if
malignant

Parathyroid MEN Syndromes


• Located behind the thyroid glands • MEN I: pituitary, pancreatic, and
• Most common tumor: parathyroid adenoma parathyroid tumors ( Wermer Syndrome)
– Most common cause of isolated • MEN II: medullary carcinoma of thyroid,
hypercalcemia in adults pheochromocytoma, plus or minus
• Most common cancer:adenocarcinoma parathyroid adenomas ( Sipple
Syndrome)
• Men Syndromes • MEN III: MEN II plus neuroma or
ganglioneuroma but w/o PTH adenomas

Parafollicular Gland Middle Mediastinum


• Also found behind the thyroid glands • Contains the heart
• Most common tumor: adenoma • Heart has three layers: endocardium,
• Most common cancer: medullary myocardium, and epicardium. Pericardium
carcinoma of thyroid (produces calcitonin) encases the heart

309321
Endocardium Myocardium
• Most common tumor: myxoma • Related to skeletal muscle
– Usually seen in left atrium • Most common tumor: rhabdomyoma
– Diastolic plop • Most common cancer: rhabdomyosarcoma
– Middle aged female who passes out, only to
recover a few seconds later
• Estrogen connection
• Most common cancer: angiosarcoma (rare)

Epicardium Pericardium
• Hardly ever involved in neoplasia • Most common tumor: fibroma
• Most common cancer: metastases

Lungs Lung Cancers


• Most common mass in children: • CENTRAL: squamous cell carcinoma
hamartoma ( produces PTH)
• Most common mass in adults: granulomas – Small cell carcinoma ( produces ACTH, ADH,
• Most common tumor: adenoma PTH and TSH)
• Most common cancer: metastases
• Most common intrathoracic cancer:
squamous cell carcinoma
• Most common primary cancer:
bronchogenic adenocarcinoma

310322
Lung Cancers, cont Lung Cancers, cont
• Peripheral: bronchogenic adenocarcinoma • RISK FACTORS: primary smoker – risk
and bronchoalveolar adenocarcinoma increases with amount and duration
– Radon
• Bronchoalveolar adenocarcinoma is the – Second hand smoke
• Sidestream smoke
only primary lung cancer NOT related to
• Mainstream smoke
smoking
– Pneumoconioses: all of them increase risk of
cancer except anthracosis

Pneumoconioses Treatment of Lung Cancer


• Anthracosis • Poor prognosis
• Asbestosis • Surgery done only if lesion smaller than
• Silicosis 2cm in size and localized, and if there is a
• Bissinosis V/Q mismatch
• berryliosis • Chemo or radiation is effective against
small cell carcinomas

Pleural Cavity Nasopharynx


• Most common tumor: mesothelioma • Most common mass: polyp
• Most common cancer: mesothelioma – Aspirin sensitive asthma: avoid aspirin or
– Ferrugenous bodies NSAIDS
– Psammoma bodies • Most common tumor: fibroma
– Pleural thickening • most common cancer: nasopharyngeal
carcinoma
– Commonly seen in Chinese women
– EBV association

311323
Oral Cavity Esophagus
• Most common tumor: fibroma • Most common tumor: leiomyoma
• Most common cancer: squamous cell • Most common cancer: squamous cell
carinoma carcinoma
– Floor of mouth • Most common cancer in lower 1/3rd of
– Lower lip
esophagus: adenocarcinoma
– Risk factor: Barrett’s esophagus
– Tip of tongue
– Almost always ulcerates
– Odynophagia
– Poor prognosis ( < 5% 5 year survival)

Stomach Risk Factors for UGI Cancers


• Most common tumor: leiomyoma • Smoking
• Most common cancer: adenocarcinoma • Alcohol
– Virchow’s nodes
• Nitrites
– Leather water bottle appearance
– Linnitis plastica • Japanese
– Signet ring cells
– Kruckenberg tumor
– Severe weight loss ( due to stomach
distention)

Small Intestine Appendix


• Most common tumor: leiomyoma • Most common tumor: leiomyoma
• Most common cancer: adenocarcinoma • Most common cancer: carcinoid
• Most common cancer of the ileum: – Does NOT metastasize
lymphoma – Carcinoid syndrome usually originates from
– Early UGI obstruction the (1) pancreas and (2) ileum
• Puts out large amounts of serotonin (check urinary
– Napkin ring lesion 5-HIAA
– 70% of lymphoid tissue is located in the ileum

10

312324
Colon Colon cancer risk factors
• Most common tumor: leiomyoma • Low fiber diet
• Most common cancer: adenocarcinoma • High fat diet
– Napkin ring lesion
• Polyps
– Eaten apple core lesion
– Pencil thin stool • Ulcerative colitis
– Melena
– Third most common cancer, and most
common cause of cancer deaths in both
sexes

Polyps Liver
• Most common mass: cyst
• Most common tumor: adenoma and AVMs
• Most common cancer: metastases
• Most common primary cancer:
hepatocellular adenocarcinoma

Hepatic Adenoma AVMs


• Associated with estrogen use or injected • Connect arteries to veins
steroids • Increased venous oxygen
• Tends to rupture if abdominal pressure • Decreased AVO2 difference
rises significantly • Risk:
• Rupture can lead to acute life threatening – Burst and bleed
hemorrhage – Sequester platelets and cause bleeding
– Sequester blood, leading to high output heart
failure

11

313325
Risk Factors for Hepatocellular
AVM Syndromes
Carcinoma
• Osler – Weber – Rondu: multiple AVMs in • Smoking
the pulmonary circulation • Alcohol
• Hepatitis B
• Von Hipple Landau: multiple AVMs in the
• Hepatitis C
abdomen and brain
• Shistosomiasis
– Has an increased incidence of renal cell
• Analene dyes
carcinoma
• Aflatoxin
– Associated with chromosome 3p
• Vinyl Chloride ( Angiosarcoma)
• Benzene

Gallbladder Biliary Tract


• Most common tumor: leiomyoma • Most common mass: choledochal cyst
• Most common cancer: adenocarcinoma • Most common tumor: cholangioma
• Most common cancer: cholangiosarcoma
• Poor prognosis because it’s hidden – Risk increase with chronic scarring
beneath the liver • PRIMARY BILIARY CIRRHOSIS
– Antimitochondrial antibodies
• Thickened calcified gallbladder • SCLEROSING CHOLANGITIS
– Seen in ulcerative colitis

Pancreas Pancreatic Adenomas


• Most common mass: cyst • Glucagonoma: elevated glucose, lipids,
• Most common tumor: adenoma and ketones
• Most common cancer: Adenocarcinoma • Insulinoma (or nessidioblastosis): high
– Cholestatic jaundice: blocks biliary tract insulin and high C-peptide
– High direct ( conjugated) bilirubin • Somatostatinoma: severe constipation
– Trousseau syndrome: migratory • Vipoma: watery diarrhea
thromphlebitis • Gastrinoma (Z-E syndrome) elevated
– Most common mucinous cancer gastrin levels all the time

12

314326
Ovary Other Ovarian Tumors
• Most common mass: follicular cyst • Fibroma: associated with pleural effusion or
ascites ( Meig’s syndrome)
• Most common tumor: serous cystadenoma
• Granulosa cell tumor: high estrogen
• Most common cancer: serous
• Yolk sack cancer: high AFP
cystadenocarcinoma
• Choriocarcinoma: high HCG
– Highly malignant
• Sertoli-Leydig cell tumor: masculinization
– Most mucinous cancer in women
• Mucinous cystadenocarcinoma: very mucinous
(pseudomyxoma peritonei)
• Teratoma: struma ovarii

Uterus Uterine Polyp


• Most common mass: polyp • Presents with passing of blood clots
• Most common tumor: leiyomyoma • Tx: surgery
• Most common concer: adenocarcinoma

Fibroids Endometrial adenocarcinoma


• Submucosal (90%): presents with • Dependent on estrogen
menorhagia • Presents with metrorrhagia
• Subserosal: presents with pelvic pain or • Metrorrhagia after age 35 requires
pressure endometrial biopsy
• Dependent on estrogen • Tx: surgery
• Focal thickening; firm mass
• Tx: OCPs; Leuprolide; surgery

13

315327
Cervix Warts
• Most common mass: warts • Condyloma lata: secondary to syphilis
• Most common tumor: fibromas – Fleshy appearance
• Most common cancer: squamous cell • Condyloma accuminatum: secondary to
carcinoma HPV
– Verrucous or mushroom like warts

– Tx: podophyllin drops; cryosurgery

Cervical cancer Vagina


• Squamous cell carcinoma • Most common mass: warts; Bartholin cyst
• Risk factors: HPV; other STDs • Most common tumor: fibroma
• Tx: hysterectomy • Most common cancer:
– Upper half: squamous cell carcinoma from the
cervix
– Lower half: skeletal muscle
• Tumor: rhabdomyoma
• Cancer: rhabdomyosarcoma (sarcoma botyroides)

Warts Bartholin cyst


• Condyloma lata: secondary to syphilis • Congenital
– Fleshy appearance • Fluctuant mass behind the labia majora
• Condyloma accuminatum: secondary to • Complication: infections/ abscess
HPV formation
– Verrucous or mushroom like warts • After first infection: treat with antibiotics
• After second infection: surgery
– Tx: podophyllin drops; cryosurgery
(marsupialization)

14

316328
Rhabdomyoma/
Kidney
Rhabdomyosarcoma
• 90% of rhabdomyosarcomas occur under • Most common mass: cyst
age 3 years • Most common tumor: adenoma
• Increased incidence in Tuberous Sclerosis • Most common cancer:
• Sarcoma botyroides: looks like a ball of – In children: Wilm’s tumor
grapes when removed – In adults: renal cell adenocarcinoma

Wilm’s tumor Renal Cancer


• Renal cancer in children • 90% occur on superior pole of kidney
• Classic clues: aniridia and • Presentation: painless hematuria; flank mass
hemihypertrophy • Most vascular cancer
• Produces erythropoietin
• Metastasizes via retroperitoneum
• Favorite metastatic site: lungs (cannon ball
metastases
• 20% contralateral recurrence

Renal Cancer, cont Adrenal Gland


• Risk factors: smoking; Von Hippel Landau; • Most common mass: cyst
Tuberous Sclerosis • Most common tumor: adenoma
• Evaluation: UA; sonogram;IVP; CT scan; • Most common cancer: adenocarcinoma
angiogram;
• Tx: surgery
• Annual CT scans after surgery to detect
contralateral recurrence

15

317329
Adrenal adenomas Bladder
• Glucagonoma • Most common mass: diverticulum
• Insulinoma • Most common tumor: leiomyoma
• Somatostatinoma • Most common cancer (including ureters):
• Pheochromocytoma transitional cell adenocarcinoma

Bladder diverticulum Bladder Cancer


• Complications: UTIs and kidney stones • Transitional cell adenocarcinoma
• Tx: surgery – Multiple primaries
– Presents with painless hematuria
– Tx: surgery; radiation
– Risk factors: smoking; anilene dyes; benzene;
aflatoxin; cyclophosphamide

• Squamous cell carcinoma


– Schistosoma hematobium

Prostate BPH
• Most common tumor: BPH • Presentation: strains to urinate; weak
• Most common cancer: adenocarcinoma stream; dribbling after urination; frequency
and urgency
• Tx: terazicin/doxazocin; tamsulocin;
fenesteride; TURP

16

318330
Prostate Cancer Prostate cancer screening
• Most common cancer in men • Age 35: baseline rectal/prostate exam
• Second to lung cancer for cancer deaths • After age 40: annual rectal/prostate exams
in men • Annual sigmoidoscopy begins after age 40
• Tx: surgery; hormonal therapy or radiation – After 2 normal annual sigmoidoscopies,
repeat in 3 to 5 years
after surgery
• Colonoscopy every 3 to 5 years begin at
age 50
– Full colonoscopy should follow any abnormal
sigmoidoscopy

Testicles Testicular exams


• Most common mass: • Begin in adolescence
– In newborns: hydrocele • ANY firm testicular mass: perform an
– In children and adults: hematoma orchiectomy
– In older adults: varicicele
• Most common tumor: adenoma
• Most common cancer:
– In first year of life: yolk sak cancer
– In teens to adults: seminoma

Skin Skin Tags


• Most common mass: • Very common
– Skin tag (acrochordon) • Tx: shave it off
– hemangioma
• Most common tumor: fibroma
• Most common cancer: basal cell
carcinoma
• Most common malignancy: squamous cell
carcinoma

17

319331
Hemangiomas fibromas
• Found anywhere on the body • Very common
• An enlarged flat blood vessel • Easy to remove if you need to do so
• Tx: observation for 18 months; inject with • Many of them seen in neurofibromatosis
steroids; laser surgery

All Neurocutaneous Diseases


Neurocutaneous Diseases
have…
• Neurofibromatosis • Mental retardation
• Sturge – Weber • Cerebral calcifications
• Tuberous Sclerosis • Seizures

Neurofibromatosis Sturge - Weber syndrome


• Café au lait spots (at least 3 with 1.5 cm • Port wine stain on face ( V-1)
diameter minimum); hyperpigmented • Angiomas of retina and brain associated
macules
• Neuromas
• Fibromas
• Chromosome 17/22 involved
– Type 1: chromosome 17; peripheral
neuromas
– Type 2: chromosome 22; central neuromas

18

320332
Tuberous Sclerosis Basal cell carcinoma
• Ashen leaf spots (hypopigmented • Most common skin cancer; but, it does
macules) NOT behave malignantly
• Tubors: primary brain tumors • Usually found on the face from sun
• Rhabdomyomas and rhabdomyosarcomas exposure
of the heart • Wide resection is curative
• Renal cell carcinoma

Squamous cell carcinoma melanoma


• Behaves malignantly • The MOST malignant skin cancer
• Ulcerates • Melanotic nevi are risk factors
• Main risk factor: sun exposure (use SPF • Malignant risk:
15 )
– Area
• Predisposing skin diseases: actinic
– Borders
keratosis; Bowen’s disease
– Color
• Diseases with increased risk: albinism;
vitiligo; porphyria cutanea tarda; PKU; – Depth of invasion (worst prognostic factor)
Wiscott-Aldridge; Job’s syndrome

Bone neoplasia Epiphysis


• Made of cartilage
• Most common tumor: chondroma
• Most common cancer:chondrosarcoma

19

321333
Diaphysis Metaphyseal osteosarcoma
• Made of osteocytes • Seen mainly in adults
• Most common tumor: osteoma • Codman’s triangle
• Most common cancer: metastases • Star burst effect on the cortex
• Most common primary cancer:
osteosarcoma

Diaphysis Ewing’s osteosarcoma


• Made of osteocytes • Primary bone cancer in children
• Most common tumor: osteoma • Onion skinning seen in bone
• Most common cancer: metastases • T(11/22)
• Most common primary cancer:
– In children: Ewing’s osteosarcoma
– In adults: plasmacytoma or multiple myeloma

Multiple myeloma Breasts


• Plasmacytoma: when single lesion • Most common mass: cyst
• Multiple myeloma: MULTIPLE osteolytic • Most common tumor:
lesions – < 25y/o: fibroadenoma
– IG-g: most common heavy chain – >25y/o: fibrocystic disease
– Kappa: most common light chain • Most common cancer: intraductal
– Hypercalcemia adenocarcinoma
– Ruleaux formation

20

322334
Fibroadenomas Fibrocystic disease
• Estrogen dependent • Progesterone dependent
• Enlarges in first two weeks of menstrual • Enlarges in the two weeks preceeding
cycle menses
• Has greenish fluid on aspiration

Intraductal adenocarcinoma Other breast neoplasms


• Estrogen dependent • Intraductal papilloma: nipple bleeding
• Lobular adenocarcinoma: contralateral primary;
• Top locations: upper outer quadrant; cells lined up in single file
nipple • Comedocarcinoma: focal areas of necrosis
• Usually presents with a dimple • Inflammatory adenocarcinoma: peau d’orange
• Metastases can be osteolytic or (infiltrates lymphatics); the most malignant
cancer
osteoblastic
• Cystsarcoma phylloides: a sarcoma; explodes out
of the breast, then stops growing; wide resection
is adequate

Breast cancer screening Cystic breast mass


• Baseline exam: age 35 • History
• Age 40 to 50: annual breast exam by • Physical
doctor; monthly SBE • Ultrasound
• Age 50 to 79: add annual mammogram • Fine needle aspiration: diagnostic and
• Family h/o breast cancer: begin therapeutic
mammography 5 years before the age of
the index case

21

323335
Firm breast mass Benign firm breast mass
• History • After lumpectomy, we are done
• Physical
• Mammogram
• Lumpectomy
• Send to pathologist for definitive
identificaton

Malignant firm breast mass Tamoxifin / Roloxifene


• After lumpectomy, perform a modified • Anti-estrogen at the breast and pituitary
radical mastectomy • Proestrogen at the bone, liver, and the
• Nodal dissection uterus (Tamoxifin only)
• Check for estrogen and progesterone
receptor positivity
• Tamoxifin or Roloxifene for estrogen
positive cases
• Chemotherapy for premenopausal women
and radiation for postmenopausal cases

Cancer Profile Cancer Antigens


• Signs and symptoms: low energy state • Prior to surgery: associated with…
• Cancer more common in males: under age • After surgery: if it rises again, there is a
30 and after age 50 95% chance you have recurrence or
• Cancer more common in women: age 30 metastases
to 50
• Most common cause of death: infections,
except for uterine and cervical cancers
(renal failure)

22

324336
Cancer Antigens Cancer Markers
• PSA • Desmin • T(9/22)
• CEA • Vimentin • T(8/14)
• S-100 • Ca-125 • T(14/18)
• AFP • Ca-19 • T(11/22)
• T(15/17)
• HCG • BCL-2
• ERB
• C-MYC • RET
• HER 2 NEU
• L-MYC • RB
• BRCA
• N-MYC • P53

THE END

23

325337
326338
Microbiology & Immunology:
Week Four

327339
328340
Immunology Immunology
LISCENCED TO KILL Study of the immune system

Antigen
• HAPTEN • IMMUNOGEN
– Less than 6000D – Greater than 6000D
– Too small to set off the – Large enough to set
immune system by off the immune system
itself by itself

The most important factor that


determines Immunogenicity is… Antigen
• HAPTEN • IMMUNOGEN
– Less than 6000D – Greater than 6000D
– Too small to set off the – Large enough to set
immune system by off the immune system
itself by itself

329341
Carrier Effect Making use of the carrier effect
• What macrophages do for a living

• Ingest
• Phagosome formation
• Digest
• Present
• MHC II complex
• V-beta region
• Invariant chain is displaced
• IL-1 is released

IL-1
• Fever
• Nonspecific symptoms of illness
• Recruits T-helper cells

Fever Infections that cause heart block


• Def: one degree above normal body temp • Legionella
• Raises heart rate 10bpm for each degree • Lyme disease
rise above normal • Chaga’s disease
• Allows immune cells to come around • Diptheria
faster • Typhoid fever
• Causes secretion of Ig-A

330342
Fever Antigen
• Means that IL-1 showed up • HAPTEN • IMMUNOGEN
• By itself can NOT tell you the cause – Less than 6000D – Greater than 6000D
– Too small to set off the – Large enough to set
• The pattern of fever can be diagnostic immune system by off the immune system
• Causes discomfort at about 101 degrees F itself by itself

How do you make an Immunogen


less immunogenic? Detergent
• Disrupts the ADHESION of pathogens by
disrupting membrane forces

Antiseptic/Disinfectant Sterilization
• Phenol is most common • For spores
• Iodine is most common in the hospital – A dormant form of a bacteria
• These chemicals DESTROY the – CAN NOT replicate in this form
membrane and INACTIVATE endotoxin – CAN still release toxin, especially when
exposed to heat
• These chemicals actually KILL 99% of
– Bacillus and Clostridium
germs
• Done at 121* C with VAPORIZED heat

331343
The two arms of the Immune
Most immunogenic bacteria system
• SHIGELLA • HUMORAL • CELL MEDIATED
• Only 8 to 10 microbes required to get a full – BLOOD – TISSUE
infection

The two arms of the Immune


system MACROPHAGES
• HUMORAL • CELL MEDIATED • Microglia: brain
• Type-1 pneumocytes: lungs
– BLOOD – TISSUE
• Kuffler cells: liver
– B-CELLS – T-CELLS
• RES cells: spleen
– NEUTROPHILS – MACROPHAGES • Dendritic cells: lymph nodes
• Osteoclasts: bone
• Mesangial cells: kidneys
• M cells: Peyer’s patches
• Langerhan’s cells: skin
• Monocytes: blood
• Connective tissue: epitheloid cells; giant cells; histiocytes

The two arms of the Immune


system All Else
• HUMORAL • CELL MEDIATED • Virus
– BLOOD – TISSUE • Fungus
– B-CELLS – T-CELLS
– NEUTROPHILS – MACROPHAGES
• Mycobacteria
– BACTERIA – ALL ELSE!!! • Protozoa
• Parasite
• Neoplasm

332344
Inflammation Acute Inflammation
• Look for SWELLING or NEUTROPHILS

Chronic Inflammation Can it really be this easy?


• Cellular infiltrate: T-cells and macrophages
• What you see on biopsy: fibrosis
• What you see on x-ray: calcifications

Can it really be this easy? THE END


•YES!

333345
Or Maybe Not…. Let The Leukocytes Loose!

334346
Humoral Immune Sytem
• Protect the blood

Immunodeficiencies
LACKING A LITTLE

Humoral Immune Sytem Humoral Immune Sytem


• Protect the blood • Protect the blood
• B cells • B cells
• Neutrophils

Humoral Immune Sytem Cell mediated Immune System


• Protect the blood • Protect the tissues
• B cells
• Neutrophils
• Bacterial infections

335347
Cell mediated Immune System Cell mediated Immune System
• Protect the tissues • Protect the tissues
• T-cells • T-cells
• Macrophages

Cell mediated Immune System Cell mediated Immune System


• Protect the tissues • Protect the tissues
• T-cells
• T-cells
• Macrophages
• Macrophages
• Nonbacterial infections
• Nonbacterial infections – Virus
– Fungus
– Mycobacterium
– Protozoa
– Parasite
– neoplasm

T-cell immunedeficiencies DiGeorge syndrome


• DiGeorge syndrome • Third pharyngeal pouch is missing
• Chronic mucocutaneous candidiasis • Inferior parathyroids glands are missing
• Steroids • The only immunodeficiency with
• Cyclosporine hypocalcemia
• Hairy cell leukemia
• SCID
• Wiscott-Aldridge syndrome
• HIV

336348
Chronic Mucocutaneous
Candidiasis Steroids
• A T-cell defect at a submolecular level • Anti-inflammatory actions
– Kills T-cells and eosinophils
• T-cells can fight everything else under “all – Inhibits macrophage migration
else” except candida – Stabilizes mast cell membranes
• Candida infections on skin and mucous – Stabilizes endothelium
– Inhibits phospholipase A
membranes
• Physiologic actions (catabolic)
• Causes chronic fatigue syndrome – Proteolysis
– Gluconeogenesis
– Upregulates all receptors during stress ( permissive)

Steroids Cyclosporine
• Prednisone • Fludrocortisone • Revolutionized transplantations in America
• Hydrocortisone • Danazole • Prolongs the longevity of transplanted
• Methylprednisalone • Cypropterone organs
• Triamcinalone • Megesterol • Inhibits calcineurin which is needed to
• Beclamethasone • Dexamethasone produce the interleukins
• Betamethasone
• Fluticasone
• Causes gingival hyperplasia and
• Mometasone
hirsutism

Tacrilimus Hairy Cell Leukemia


• Now used in place of cyclosporin due to • Most commonly a B-cell leukemia (75%)
much fewer side effects • More frequently a T-cell leukemia (25%)
• Has hairy cell membrane projections
• Tartrate Resistant Acid Phosphatase (TRAP)

337349
T-cell Lymphomas SCID
• Mycosis Fungoides ( cutaneous) • Involves adenosine deaminase deficiency
• Sezary syndrome ( present in the blood) • DNA synthesis is disrupted
• T-cells have characteristic indented cell • Affects all rapidly dividing cells
membrane • Affects T and B-cells
• Bone marrow transplant is now the
standard of care

Wiscott-Aldridge syndrome B-cell Immunodeficiencies


• Bruton’s agammaglobulinemia
• Involves T-cell interaction with B-cells
• CVID
• X-linked recessive • Leukemias
• Lymphomas
• Fair-skinned • Plasmacytoma
• Eczema • Multiple myeloma
• Heavy Chain disease
• Thrombocytopenia • Selective Ig-A def
• Selective Ig-G2 def
• Normal Ig-A and Ig-E levels
• Job’s syndrome
• Increased incidence of lymphoma • SCID
• Wiscott-Aldridge syndrome

Bruton’s Agammaglobulinemia CVID


• X-linked recessive • Late onset Bruton’s ( after first year of life)
• Cell signalling is defective • B-cell count is also normal; B-cell function
• B-cell count is normal; function is lacking is lacking
• Early onset • Cell signalling is defective

338350
Leukemias Lymphomas
• 98 B-cells for every T-cell in periphery • 98 B-cells for every T-cell in periphery

Plasma Cell Cancer Heavy Chain Disease


• Plasmacytoma: only ONE lesion • Ig-A Multiple Myeloma of the bowel wall
• Multiple Myeloma: MULTIPLE osteolytic • Ig-A plasma cells visible on biopsy
lesions • Causes malabsorption
– Ruleaux formation
– Hypercalcemia
– Ig-G is most common M-spike
– Kappa light chains are most common Bence
Jones protienuria

Selective Ig-A def Selective Ig-G2 def


• Many mucosal infections • Runs with selective Ig-A def
• Runs with selective Ig-G2 def 95% of time • Ig-G is main opsin ( coats encapsulated
• Anaphylaxis during a transfusion organisms)
– Must use a filter for all subsequent • Recurrent encapsulated organism
transfusions or use blood from another Ig-A infections
def patient

339351
Encapsulated Organisms Job’s syndrome
• Gram positive • Gram negatives • Cell signalling defect
– Streptococcus – Salmonella • Increased Ig-E
pneumonia – Klebsiella
– H. Influenza B
• Fair-skinned
– Pseudomonas • Red-haired female
– Nisseria
– citrobacter

The Final Two Neutrophil Defects


• SCID • Myeloperoxidase def
• WISCOTT-ALDRIDGE • NADPH-oxidase def (CGD)
• Absolute neutropenia

Chronic Granulomatous Disease


Myeloperoxidase def (CGD) NADPH-oxidase def
• Recurrent gram positive infections • X-linked recessive
• Negative NBT test ( detects nadph-oxidase)

340352
At Risk for Staph and Pseudomonas
Absolute Neutropenia Infections
• ANC = ( % Neutrophils + % bands) WBC • Absolute neutropenia
– < 2500 • Cystic Fibrosis
– <1500
• Burn patients
– <1000
• At risk for staph aureus and pseudomonas • Diabetics
infections
• If any fever: cover staph aureus with one
antibiotic and pseudomonas with two
antibiotics

Macrophage Defects Chediak-Higashi syndrome


• NADPH-Oxidase def ( CGD) • Lysosomes are slow in fusing with
• Chediak-Higashi ingested pathogen
• Lysosomal inclusions
• Albinism

HIV Where CD-4 receptors are found


• The two populations with the highest • Female cervix
incidence are heterosexual Black women • Blood vessels
and the elderly • Macrophages
• Lowest risk population: prepubertal female • T-helper cells
• HIV likes acidic medium, mucosae, and • CNS
CD-4 receptors • Testes
• HIV is only virus that does NOT penetrate
the cells; it injects its RNA into the cells

341353
Cancers Common in HIV HIV Infection
• Cervical cancer • Attaches to CD-4 receptor using GP120
• Kaposi sarcoma ( helped by Herpes 8) • GP 41 has no known function
• CNS and testicular lymphomas • Injects the RNA inside
• POLymerase protein is used to integrate
the RNA into host genome
• Reverse transcriptase is used for
transcription
• P17 and P24 used for assembly

To Prevent Attachment of HIV Screening for HIV


• CCR5 • ELIZA ( Ig-G antibody test)
• CCR4 • Western blot ( detects protein)
• Northern blot ( detects RNA)
• Southern blot ( detects DNA)
• PCR ( amplifies RNA or DNA)

Screening for HIV, cont PCR


• MORE sensitive than Southern blot or
Northern blot
• Used for screening only in the first 18
months of life ( mom’s Ig-G interferes with
ELIZA)

342354
T-helper cell Counts HIV Treatment
• Normal: 800 to 1200 • START with two nucleoside inhibitors and
normal in newborns: 1500
one protease inhibitor
• Begin treatment: CD4 counts < 500
– Pediatrics: < 50% ( 750) • AZT
• Begin PCP prophylaxis • 3TC
– CD4 count < 200
• 4DT
– Pediatrics: < 20%
• Begin MAI prophylaxis • DDI or DDC
– CD4 count < 100 • Rotenovir; Indinavir; Sequinavir
– Pediatrics: <10%

Mycobacterium Avium
PCP Prophylaxis Intracellulare ( MAI)
• Trimethoprim/Sulfamethoxazole • Clarithromycin
• Pentamidine aerosole • Azithromycin

HIV: THE END


• THE MOST COMMON CAUSE OF DEATH FROM AGE
19 TO 44 !!!

343355
Leukocytes
• NORMAL: 4 to 12K

LEUKOCYTES
• Leukopenia: < 4K
• Leukocytosis: > 12K
• Your leukocyte count accounts for only
Shoot when you see the WHITES of 10% of total leukocytes
their eyes • 90% of leukocytes are marginated

When Leukocytes are needed… Leukopenia


• Demargination: caused by epinephrine and • Most common causes: acute viral infection
cortisol and drugs
• Pavementing:
– Selectrins
– Integrins
• Margination
• Diapedesis
• Migration

Viruses that commonly suppress Drugs that suppress the


leukocytes bone marrow
• Any virus can do it; but, the most common • Vinblastine
are… • AZT
• Parvovirus B19 • Chloramphenicol
• Hepatitis E • benzene
• Hepatitis C

344356
Drugs that cause agranulocytosis… Leukocytosis
• Carbamezapine • Stress demargination
• Ticlopidine • Infections
• Clozapine • Leukemoid reaction
• Leukemia
• Myelodysplastic syndromes

Leukocytosis Leukemoid Reaction


• Extreme demargination
• Looks like leukemia because WBCs so
high
• Increased leukocyte alkaline phosphatase
( LAP)
• Extreme stress

Leukemia Lymphomas
• Too many white cells in the periphery • Cancer of the lymph nodes
• A cancer • Involves the lymphocytes
• Acute: cancer began in the bone marrow
• Chronic: cancer began in the periphery

345357
Myelodysplastic syndromes Leukemias
• Cancer that involves the ENTIRE bone
marrow
• All cell lines are involved

Lymphomas Lymphomas, cont


• Hodgkin’s lymphoma: 20 to 40 y/o • Nonhodgkin’s lymphoma
– Characterized by the Reed-Sternberg cells – Usually occurs in immunocompromised
which have the CD 30 marker persons
– Commonly begins as a swollen lymph node – Presents as an abdominal mass in America,
– Most malignant lymph nodes or a jaw mass in poor countries
• Supraclavicular – Most common type: follicular lymphoma
• Epitrochlear • BCL-2
• inguinal • T( 14/18)

Burkitt’s Lymphoma Lymphomas


• BCL-2
• C-myc
• T( 8/14)
• EBV
• Starry sky appearance

346358
Lymphomas Lymphoma: Staging
• Stage 1: one group of lymph nodes involved
• Stage 2: two groups of lymph nodes on
same side of diaphragm involved
• Stage 3: two or more groups of lymph
nodes on both sides of diaphragm
involved
• Stage 4: metastases

Lymphoma Treatment Lymphoma Treatment, cont

Nodular Sclerosis Lymphocyte Predominance


• More common in women • Best prognosis
• The fewest Reed-Sternberg cells
• Intermediate prognosis

347359
Lymphocyte Depleted Mixed Lymphocytic/Histiocytic
• Worst prognosis • Intermediate prognosis
• A paucity of lymphocytes • Has the most Reed-Sternberg cells
(lacunar cells)

Myelodysplastic Syndromes Myelodysplastic syndromes


• Hyperproliferative:
– Polycythemia Rubra Vera
– Essential thrombocythemia
• Hypoproliferative:
– Aplastic Anemia
– Myelophistic Anemia ( myelifibrosis;
agnogenic myeloid dysplasia)

Polycythemia Rubra Vera Essential Thrombocythemia


• ALL cell lines are elevated; RBCs elevated • ALL cell lines are increased; platelets are
the most increased the most
• HCT> 60% • Platelet count > 600K
• Itching after a hot bath
• Uric acid stones
• Increased gout
• Splenemegaly
• Increased LAP

348360
Aplastic Anemia Aplastic Anemia: Viruses
• ALL cell lines are depleted • Parvovirus B-19: 90%
• Bone marrow usually suppressed by virus • Hepatitis E : pregnant women
or drugs • Hepatitis C : occassional
• Bone marrow usually replaced by fatty
infiltration
• Low reticulocyte count

Aplastic Anemia: Drugs Myelofibrosis


• Chloramphenicol • Bone marrow is destroyed by cancer and
• AZT replaced by scarring
• Benzene • Tear drop cells
• Vinblastine • Low reticulocyte count

The End Or Is It…??

349361
Ain’t No Groove Like A Granulocyte
Groove

350362
Lymphocytes
The ultimate control

B-Lymphocytes B-Lymphocyte Differentiation


• Develop in the bone marrow • Macrophage ingests antigen
• Mature : Bursa of Fabricus equivalent ?? • Macrophage forms a phagosome
• Differentiate : germinal centers of lymphoid • Lysosome digests the antigen
tissue • Macrophage presents the antigen
• Antigen binds to MHC-II complex
• IL-1
• IL2
• IL-3

B-Lymphocyte Differentiation Stages of B cell development


• IL-4
• 1L-5
• IL-6
• IL-10
• IL-12
• T cells talk to B cells via the CD-40 ligand
• B cells display CD-19 and CD-20

351363
To stimulate B cells… Primary Response
• Endotoxin • IG-M:
• Pokeweed mitogen – Arrives in 3 days
– Peaks in 2 weeks
– Lasts for 2 months
• Then add labelled thymidine
• IG-G:
– Arrives in 2 weeks
– Peaks in 2 months
– Lasts for 1 year

Vaccines Schedule Memory

Memory Response Memory Response


(Anamnestic)
• Develops beginning at 12 months; fully
developed by 15 months
• Involves ONLY IG-G
• IG-G has highest affinity
– Arrives in 3 days
– Peaks at 5 years
– Lasts for 10 years

352364
Antibody Structure/Function Live Vaccines
• MMR
• BCG
• OPV ( Sabin)
• Varicella
• Rotavirus
• Smallpox
• Yellow fever

Vaccine changes at age 6


• Pertussis no longer needed
• HIB no longer needed
• Only half dose diptheria needed (D Isotype
becomes d)
Antibody Class: Gamma;
Alpha; Mu; Delta; Epsilon

Idiotype Allotype
The actual antigen binding Differences between two
site members of same species

353365
Applied to Transplants…

Xenotype or Heterotype
Differences between two
members of different
species

Isograft or Syngraft Allografts


Twin to Twin transplants Transplants between
members of same species

Autografts Xenograft or Heterograft


Self to Self transplants Transplant between
members of different
species

354366
T cell
maturation/differentiation

T cell differentiation T cell differentiation


• Macrophage ingests antigen • IL-4
• Macrophage forms a phagosome • 1L-5
• Lysosome digests the antigen • IL-6
• Macrophage presents the antigen • IL-10
• Antigen binds to MHC-II complex • IL-12
• IL-1 • T cells talk to B cells via the CD-40 ligand
• IL2 • T cells talk to macrophages via B-7 molecule (on
T cell) connecting with the CD-4 receptor
• IL-3 causing the formation of the CD-28 molecule

T Lymphocytes At the thymus…


• Develop in the bone marrow • T cells enter undifferentiated
• ALL T cells have CD3 • They must go through NEGATIVE
• ALL have CD4 and CD8 labels when they selection followed by POSITIVE selection
leave the bone marrow • Thymosin and Thymopoietin control clonal
• They have to go to the thymus to deletion
differentiate • Thymus is one of four immunopriviledged
• Express the MHC II complex sites in the body
• One T cell controls many B cells – Have no lymphatics; express NO antigens

355367
Immunopriviledged sites CD 8 CELLS
• Brain • First cells to make it through clonal
• Thymus deletion
• Cornea • Express MHC I complex; respond to MHC I
antigens (self antigens)
• Testicle
• T suppressors: keep infection from
spreading
• T cytotoxic: destroy infected cells

CD 4 CELLS T Helper cells


• The second set of lymphocytes to make it • T Helper 1: respond to cell mediated
through clonal deletion • T Helper 2: respond to humoral
• Express MHC II complex; responds to • Secrete every interleukin except IL-I
foreign antigens • Produce interferon gamma and TNF
• Speaks to B cells via CD 40 ligand; gamma
speaks to macrophages via B7 / CD28 • Control B cells and macrophages
molecule
• T Helper cells

NK Cells
• Develop WITH the T cells in the thymus
• Do NOT go through clonal deletion
• Express MHC I complex and actually Levamisole
COUNT MHC I antigens
• Express CD 16 and CD 56 Enhances NK cell’s ability
• Responsible for immunosurveillance
• Can detect cancer at the one cell stage

356368
Once a T cell processes
an antigen…
It is considered differentiated

GREED THE END…FOR NOW


A MAN SPENDS HIS HEALTH CHASING
GREAT WEALTH
THEN HE SPENDS HIS WEALTH TRYING
TO GET BACK HIS HEALTH

357369
Granulocytes

Granulocytes
What do they do for a living?

Granulocytes Granulocytes

Gram stain
• Step 1: add crystal violet ( binds to
exposed peptidoglycan)
• Step 2: add iodine ( seals blue color into
wall)
• Step 3: wash with alcohol ( washes off
excess crystal violet)
• Step 4: add saffrin ( colors outer
membranes)

358370
Acid fast stain Neutrophils
• Also called Ziel Neilson stain • The most abundant granulocytes
• The pathogen stains pink;ALL other cells • 60% of WBCs
stain blue • First line of defence
• Completely acid fast: mycobacterium • Show up at 24 hours; peak at day 3
• Partially acid fast: Nocardia ( gram • 10% are circulating; 90% are marginated
positive) and Cryptosporidium ( protozoa) • Contain myeloperoxidase and NADPH-
Oxidase

Catalase positive bacteria


• Staph Aureus
• Pseudomonas
• Nisseria

359371
Free Radicals Abscesses
• Begin coming into the area at 3 hours • Day 1 to 3: staph aureus
• Oxygen burst ( peak free radical formation) • Day 3 to 7: strep pyogenes
occurs at day 7 • After day 7: anaerobes
• Hi energy free radicals transfer their • Abscesses are anaerobic by nature
energy to anything in the way • Occurs most commonly in: the brain
• Area becomes anaerobic once oxygen ( liquefactive necrosis)
burst occurs • Occurs least commonly in: the lungs (most
– Now you have an abscess oxygen)

Clues to anaerobic infections


• Malodorous smells
• Gas formation

Absolute Neutropenia Neutropenia


• ANC = (% neutrophils + % bands) WBC • Most common causes: viral infection and
• < 2500 drugs
• < 1500
• < 1000
• ANY FEVER: cover staph aureus w/ one
antibiotic and cover pseudomonas with
two antibiotics; and if fever persists after 48
hours, then cover for fungus

360372
Monocytes Macrophages in the…
• A macrophage in circulation • Brain • Peyer’s patches
• They change names after they enter • Lungs • Connective tissue
tissues • Liver
• Interferon mediates their transformations • Kidneys
after they enter different tissues • Spleen
• Lymph nodes
• Contain ONLY nadph-oxidase for killing
• Skin
since free radicals can kill anything
• Bone

Monocytosis Granulocytes
• Mcc: viral infection ( cell mediated)
• Extreme monocytosis: monocytes > 15%
– Salmonella typhi
– Tuberculosis
– EBV
– Lysteria
– Syphilis

Understanding Allergies Primary response to allergens


• MAST CELLS • EOSINOPHILS • First contact: asymptomatic
– Allergen was ingested
– Phagasome formed
– Digested
– Presented to T-lymphocytes
– T-cells bind to B-cells by CD-40 ligand
– T-cells produced IL-4
– B-cells produced Ig-E

361373
Secondary response to allergens Understanding Allergies
• Symptomatic • MAST CELLS • EOSINOPHILS
– Histamine (immediate) – Histaminase
• When allergen re-enters the system, Ig-E
– SRS-A ( 4 to 8 hrs later) – Arylsulphatase
now binds the allergen
– ECF-A – heparin
• Ig-E buries the F-c portion into a mast cell
• Mast cell degranulates

Slow Reacting Substance of


Histamine Anaphylaxis (SRS-A)
• Responsible for all of the acute symptoms • The most potent bronchoconstricter that
of allergies we know
• Redness and flushing • This is responsible for late symptoms of
• Wheezing allergies
• Itching • Produced 4 to 8 hours after initial
• Warmth symptoms
• Swelling (nasal congestion; rhinitis; • Responsible for killing many asthmatics
conjunctivitis; wheal and flare; urticaria) before we understood it

Eosinophil Chemotactic Factor of


Anaphylaxis ( ECF-A) Eosinophils…
• Chemoattractant for eosinophils • Are counter-regulatory
• Responsible for the eosinophilia seen in • Make sure mast cells do NOT get out of
allergic reactions hand

• In other words…

362374
Eosinophils… Eosinophils…
• Histaminase: breaks down histamine • Histaminase: breaks down histamine
• Arylsulphatase: breaks down SRS-A

Eosinophils… Heparin
• Histaminase: breaks down histamine • Acts as a cofactor for antithrombin III
• Arylsulphatase: breaks down SRS-A • Blocks thrombin as well as clotting factors
• Heparin : breaks down any clots that might IX,X,XI and XII ( the intrinsic clotting
have formed cascade)
• Follow the PTT
• INR should be 2 to 3 times normal
• If INR too high, reverse it with protamine
sulphate

Heparin, cont Low Molecular Weight Heparins


• If patient acutely bleeding then give FFP to • Well standardized to minimize physician
correct immediately errors
• Side effects: • BENEFITS:
– Bleeding • NO need to do daily PTTs (saves on
– Hyperlipidemia ( activates hormone-sensitive nursing and hospital costs)
lipase)
• Fewer bleeding complications
– Heparin induced thrombocytopenia ( acts as a
hapten, inducing autoimmune antibodies) • Lower incidence of heparin induced
thrombocytopenia

363375
Eosinophilia Eosinophilia
• N • Neoplasia, especially lymphomas
• A • A
• A • A
• C • C
• P • P

Allergic Rashes: type 1


Eosinophilia hypersensitivity
• Neoplasia • Urticaria
• Allergies and Addison’s disease • Erythema multiforme
– Allergic rhinitis and conjunctivitis • Stevens-Johnson syndrome
• A • Toxic Epidermal Necrolysis
• C
• P

Allergic Rashes: type IV


hypersensitivity Eosinophilia, cont
• Atopic dermatitis • Neoplasia
• Contact dermatitis • Allergies and Addison’s disease
• Eczema • Asthma
– Spongiotic • C
– nummular • P

364376
Asthma Eosinophilia, cont
• Intrinsic asthma: you are born with it; colds • Neoplasia
and cold air set it off • Allergies and Addison’s disease
• Extrinsic asthma: caused by environmental • Asthma
factors • Collagen Vascular Disease
– Dust mites
• P
– Roach droppings
– Pet dander

Eosinophilia, cont Bands


• Neoplasia • Immature neutrophils with maximum germ
• Allergies and Addison’s disease fighting ability
• Asthma • Have myeloperoxidase and NADPH-
• Collagen Vascular disease Oxidase enzyme systems
• Parasites • Come straight out of the bone marrow
without margination
• Increased numbers = a left shift

Basophils To Be Continued…
• Said to be precursors to mast cells
• They have similar granules to mast cells

365377
TYPE I
• Immediate hypersensitivity
• Involves mast cells and eosinophils
THE FOUR HYPERSENSITIVITIES • NO COMPLEMENT involved

PUTTING IT ALL
TOGETHER

TYPE II TYPE III


• Cytotoxic • Immune complex deposition
• A deliberate attack on self • NOT a deliberate attack on the tissue
• Complement comes in after the attack • Tissue is damaged due to inflammation
• So much COMPLEMENT used that it
measures LOW

TYPE IV Complement System


• CELL MEDIATED
• T cells
• Macrophages

366378
Angioedema ACE Inhibitors and ARBs
• Due to C-1 esterase inhibitor deficiency • Captopril
• Too much C5-A produced • Enalopril
• Causes recurrent facial swelling and • Lisenpril
abdominal pains • Rinilopril
• Mcc of death: suffocation due to airway
swelling • Losartan
• Caused by ACE inhibitors and ARBs • Vosartan

ANTIBODIES Antibodies
• Antimicrosomal • Anti-rho, La, SSA • Anti-topoisomerase
• Antithyroglobulin • Anti-SM • P-anca
• Anti-TSH receptor • Anticardiolipin • C-anca
• Anti-ACH receptor • Anti-DS DNA • Anti-GBM
• Anti-myelin • Anticentromere
• Anti-anchoring
• Anti-parietal cell • Anti-smooth muscle proteins
• Anti-mitochondrial • Antihistone
• Antiplatelet
• Anti-melanocyte • Anti-Scl 70
• Anti-RBC
• Anti-IgG • Anti-RNP

TRANSPLANT IMMUNOLOGY ABO

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CROSSMATCH MIXED LYMPHOCYTE REACTION

HLA TYPING Rejection


• Hyperacute
• Acute
• Chronic
• Graft vs host

Just when you thought it was over… Now it is time for the BUGS !!!

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4/29/2008

Gram + Cocci: Semisynthetic PCN’s

• Oxacillin
• Cloxacillin
• Dicloxacillin
• Nafcillin
More efficacious than Vancomycin

Antibiotics •

Beta-lactamase resistant PCN
MRSA tx- Vancomycin (linezoid)

Streptococci: pyogenes
Ampicillin + Amoxicillin:
viridans can be used for Strep infections
pneumonia when combined with beta-lactamase
inhibitor:
• Penicillin G - Sulbactam
• Penicillin
P i illi VK - Amoxacillin+clavulanate
A illi + l l t
• Ampicillin
• Amoxicillin
Effective against: Enterococci
Listeria

Cephalosporins:
1st Generation: Cefazolin 2nd Generation: Cefoxitin
Cephalosporins:
Cefadroxil Cefotetan
Cephalexin Cefuroxime 3rd Generation:Ceftazidime 4th Generation: Cefepime
Cefprozil Cefotaxime
Loracarbef Ceftraxone
Cefotaxime
1st g
generation: Staph
p and Strep
p
Some gram negatives (E. coli, Moraxella) O l C
Only Ceftazidime
ft idi &C
Cefepime
f i cover “P
“Pseudomonas”
d ”

2nd generation: Moraxella, E. coli, Haemophilus, 3rd Generation: not good for Staph (especially
Klebsiella, Citrobacter, Proteus Vulgaris Ceftazidine)

4th Generation: Cefipime (never pick Stap/Strep)

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Allergic cross reactivity with penicillins:


Allergic cross reactivity with penicillins:
•Genuine allergy to PCN has less than 5% cross
reactivity with Cephalosporins
•If anaphylaxis to PCN, never pick a Cephalosporin as
an answer
•Seldom anaphylactic reaction will occur
Minor infection-
infection Macrolide (Clarithromycin, Azithro)
New fluoroquinolones : (Levofloxacin, goti, moxi)
•Patients usually just get a rash, so you can still use
cephalosporins Serious infections: life threatening
- Vancomycin, Linezolid

Quinolones:
Ciprofloxacin Aminoglycosides:
Levofloxacin -Gentamicin
Gatifloxacin -Tobramycin
Moxifloxacin
-Amikacin
Ofloxacin

Monobactams:
Good for…. E. coli Moraxella -Aztreonam
Proteus Citrobacter
Enterobacter Serratia
Haemophilius Kelbsiella
For the test, think of these as exclusively
Gram negative agents
• Ciprofloxacin is good for pseudomonas
• New fluoroquinolones- first line in pneumonia’s Aminoglycosides have a synergistic effect
because it covers, Mycoplasma, Chlamydia, with PCN
Legionella

Carbapenems: Anaerobes:
- Imipenem Metronidazole (Flagyl)- most active against
- Meropenem anaerobes

Clindamycin- less active against anaerobic


g
Best use for Gram negative infections: gram negative bacteria in the bowel
- Pseudomonas (Bacteroides fragilis, Clostridium difficle)
- Enterobacteraceas
Carbapenems have the same efficacy as
Excellent staph and anarobic coverage Metronidazole

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• If a bacteria normally lives on


Microbiology: a part of your body, normally
Normal Flora exposed to OXYGEN
What is bugging you !!!

• Call it a GRAM POSITIVE

• If a bacteria lives on a part Skin flora


of your body NOT normally
• Staphylococcus aureus
exposed to oxygen….
• Staphylococcus pyogenes
• Staphylococcus epidermitis
Call it a GRAM NEGATIVE • Staphylococcus saprophyticus
• Propionobacterium acne

Strep pyogenes is # 1
• Lymphangitis
• Impetigo
Skin Infections
• Necrotizing fascitis
• Erysipelas
• Scarlet fever

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Skin Infections Skin Infections


• Cellulitis: flat, red, blanches • Mastitis: cellulitis around the breast

Skin Infections Skin Infections


• Balanitis: infection at the head of the penis • Panniculitis- cellulitis around abdomen

Skin Infections Skin Infections


Periorbital cellulitis: infants, trauma • Orbital cellulitis: proptosis, older patient
Staph aureus • Strep pneumonia

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Skin Infections Skin Infection


• Carbuncle: nodular induration w/ infection • Furuncle: hair follicle in middle of
carbuncle, No pus

Skin Infections Skin Infection


• Carbunculosis: deep skin infection • Furunculosis: many infections of hair shafts
• Staph aureus

Skin Infection Skin Infection


• Fasciitis: inflammation of fascia • Folliculitis: infection of hair shaft
• Plantar or Necrotizing

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4/29/2008

Skin Infection Mouth Flora


• Blepharitis: infection of eye lid • Strep pyogenes
• Strep pneumonia
• H. Influenza
• Nisseria catarrhalis
– N. gonorrhea
– N. meningitidis

Mouth Flora cont. Stomach Flora


• Peptococcus • Helicobacter pylori
• Peptostreptococcus
• Fusobacterium
• Actinomyces
• Strep viridans
– S. mutans
– S. sanguis
– S. salivarius

Urease Positive Bugs Curved Rods


• Proteus • Vibrio
• Pseudomonias
• Ureoplasma • Camphlobacter
• Nocardia
• Lysteria
• Cryptococcus
• H. Pylori • H. pylori
• Staph. Saprophyticus
• Brucellosis

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Small Intestinal Flora Small Intestinal Infections

•95% E. coli • Cholecystitis


• Ascending cholangitis
• Appendicitis
pp
• Spontaneous bacterial peritonitis
• Abdominal abscess

E. Coli makes… E. Coli helps you absorb..


• 90% of your vitamin K • Vitamin B12
• Biotin
• Folate
• Panthotenic acid

Distal ileum and colonic flora Big MaMa anerobes


• Proteus • Bacteroides fragilis
• Klebsiella • Strep bovis
• Serratia marscencens • Clostridium melanogosepticus
• Acenetobacter
• Clostridum difficile
• Citrobacter
• E. coli

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4/29/2008

Rectal flora •GET READY FOR THE


RIDE…..
• Group B Strep
• E. Coli
• Lysteria
L t i monocytogenes
t It allll buzz
Its b words
d from
f
here on !!!!

STAPHLOCOCCUS
Gram
Positives
GRAM POSITIVE
COCCI IN CLUSTERS

Staphylococcus aureus enzymes:


• Catalase + : breaks down H2O2

• β-lactamase : breaks through β lactam


containing drugs

• Coagulase & Staphlokinase- eats


through clots
– MCC of Acute Endocarditis- eats
through valves
– MCC of death in burn patients in the first week

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376
4/29/2008

Enzymes continued:: Staphylococcus aureus toxins:


• Lipase: breaks down fat
– Panniculitis
– Folliculitis • Staph Scalded Skin Syndrome:
– Mastitis – Exfoliating (Nikolski sign)
– Red rash all over the body
– Palms and Soles
• Elastase: breaks elastin
– Bullous
B ll Emphysema
E h (Pneumatocelle)
(P t ll )
• Toxic Shock Syndrome:
– Triad: high fever, hypotension (shock), rash (P & S)
• Collagenase: skin & bone (breaks peptide bonds)
– Retained tampon
– MCC of osteomyolitis (2nd Salmonella)
– Type IV (basement membrane)
– Type III (endothelium- arteries affected) • Erythrodermic Toxin:
– Type II (connective tissue) Scarlet fever [Strep]
– Sand paper rash, palms and soles, strawberry tongue

Staphylococcus aureus toxins: Staph epidermidis:


• Lecithinase: causes skin infections • Catalase +
– subcutaneous fat • White pigment
• Resides under the skin
• Enterotoxin:
i causes food
f d poisoning • MCC of shunt infections and central line
– dairy products- gastroenteritis infections
– Fast 2-6 hours
• Tx: Vancomycin
• Linezolid- for Vancomycin resistance
– Keep patient is a negative pressure room

Staph saphrophyticus:
• Catalase + STREPTOCOCCUS
• No Pigment

• Frequent cause of UTI’s:


– Age 5-10- play with themselves
– Age 18-24: post coital UTI, Gram positive
no circumcision
(E. coli- MCC of UTI’s) cocci in chains

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377
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Streptococcus
Streptococcus Streptokinase- responsible for
β hemolysis- clear zone
• Groups: A, B, C, D
• Breaks clots – converts plasminogen to
plasmin
• Types of hemolysis:
– α hemolysis
hemolysis- partial (green zone) • If recent Strep infection-
infection it will not
– β hemolysis- complete (clear zone) work, use tPA…
– γ hemolysis- no hemolysis (red zone)
- Converts plasminogen to plasmin-
breaks clots

- Binds fibrinogen- will not clot again

Strep pneumoniae
Thrombolytics
(Pneumococcus)
• Urokinase- opens fistulas and grafts
• Gram + diplococci
• Streptokinase- β hemolytic- acute MI • α hemolysis (green zone)
• 80 strains
• Tissue plasminogen activator (tPA)-
acute MI, acute stroke (within 3 hrs)
Pneumococcal vaccine (pneumovax)
– Covers 23 strains (98%) coverage
Antidote: aminocaproic acid
(for all three)

: on it…
Who should be Group A: Strep pyogenes
– > 65 y/0
• β-hemolytic (clear zone)
• 70 Strains
– > 2 y/o with Sickle cell (spleen- encapsulated
organisms)
• Most common cause for throat infections-
– End organ failure can lead to “Rheumatic fever”

– PSGN (skin and throat can cause this) • 2nd most common cause of skin
strain 12 infections

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378
4/29/2008

Group D: Strep viridians


Group B: Strep agalactaciae
(mutans, saguis, salivarius)
• Most common cause of Neonatal Sepsis • α hemolytic (green zone)

• β
β- hemolytic (clear zone) • # 1 cause of Subacute Bacterial
Endocarditis

• Previous damage to heart valve


predispose to SBE

Tx: Amoxicillin

Group D: Strep viridians Enterococcus


(mutans, saguis, salivarius) (Faecalis, Faeceum)
# 1 cause of Subacute Bacterial Endocarditis • Anaerobic
– Septic emboli to brain
• γ hemolytic (red zone)
– Roth spots- emboli to retina
• Likes immunocompromised patients
– Osler nodes- emboli to fingers (painful)
– Splinter hemorrhages- emboli to nail beds • Nitrite Negative UTI
– Janeway lesions- emboli to toes
Tx: Vancomycin

Vancomycin: Vancomycin treatment:

• MOA: cell wall inhibitor 1. MRSA


– Inhibits phospholipid carrier (irreversible)
– Tx for all gram +
2 Staph epidermidis
2.
Toxicity:
• Red man syndrome
• Intense histamine release (not allergic) 3. Enterococcus
• Ototoxicity
• Nephrotoxicity

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Meningitis Cornybacterium Diptheria


• 0 to 2 mo: • Chinese letters
– Group B strep: Strep agalactaciae
– E. Coli • Toxin that ADP-ribosylates EF-2
– Lysteria – (affects translocation of protein synthesis)
• 2 mo to 10 years:
– Strep pneumonia
– Nisseria M. • Intracellular pathogen
• 10 years to 21 years:
– Nisseria M. • Cells die, slough off, and mix with
– Strep pneumonia mucus, forming a grey membrane in
• > 21 years: posterior pharynx
– Strep pneumonia • Do NOT scrape: will hemorrhage profusely

Cornybacterium Diptheria,
ADP-Ribosylators
cont.
• Toxin may also cause heart block • Gs: Vibrio cholera, ETEC
• DPT: 2m, 4m, 6m, 18m, 5-6y
• Gi: Bordatella pertussus
p

• Tx: antitoxin first; antibiotic (toxin is


hurting the patient, not the bug) • EF2: C. diptheria, pseudomonas

Cause heart block :


• Lyme disease
• Legionella SPORE FORMERS
• Typhoid
yp fever
• Diptheria
• Chaga’s disease

BACILLUS &
CLOSTRIDIUM

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380
4/29/2008

A SPORE Bacillus
• Has poly D-Glutamate membrane
• Made of “Ca-dipocholinate”
(we have L-amino acids)

• Dormant form of the bacteria • B. Anthrax


– Has a toxin: (1) lethal factor – kills cell
• C
Can NOT replicate
li t but
b t CAN release
l toxin
t i (2) edema factor
especially when exposed to heat (3) protective factor- mediates entry

(MAD!!!) – Cutaneous Anthrax: malignant pustule


(skin necroses)
• Is destroyed ONLY by sterilization process
– Pulmonary Anthrax: wool sorter’s disease
– 121 degrees centigrade vaporized heat
(hot desert) mediastinal hemorrhagic
lymphadenitis

Bacillus Clostridium
• C. difficile: gastroenteritis associated with
antibiotic use
B. Cereus:
– Fried / Reheated rice (hot wok) – Antibiotics destroy E. coli

Two toxins: – Pseudomembranous colitis


colitis- gray membrane
with yellow plaques on colon
– Emetic toxin- (from the rice) fast (1-6 hrs) –
diarrhea, vomiting
– Most effective drug - vancomycin;

– Diarrheal toxin (meats, sauces): – Current treatment is metronidazole


18 hrs- increases cAMP- watery diarrhea (promotes production of free radical)

– Side effect: dysguzia, disulfiram reaction

Clostridium Clostridium
• C. perfringens:
C. perfringens: food poisoning
Gas gangrene
– Gastroenteriti
– Known to attack extremities in diabetics associated with holiday ham or turkey
• Dry gangrene- necrotic skin
• Enterotoxin
• Wet gangrene- blood to the area
(risk of gas emboli)
• Immediate symptoms- diarrhea
• Tx: Immediate amputation
(hyperbaric chamber) ?????

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4/29/2008

Clostridium Clostridium
• C. tetani
• C. melanogosepticus
– Associated with dirty wound

– Associated with colon cancer – Give anti-immunoglobulin


g to bind toxin
( along with strep bovis ) (into the wound)

– Produces a black pigment – Toxin:


• inhibits release of glycine (inhibitory)
in the spinal cord- increasing contraction-
respiratory failure
• Lock jaw

: Clostridium
C. botulinum: - botulism

• Toxin- inhibits presynaptic release of


Ach- flaccid p
paralysis
y (floppy
( ppy baby)y)

• Muscle won’t work- die of respiratory


failure

C. botulinum: - botulism Propionobacterium Acne


: • Progesterone stimulates propionic acid or
Children- honey, molasses
sebum
Do not give children honey until 6 mo of age
(normal flora will appear) • Acne more severe in women and adolescent
boys
Adults- ingest spores via canned foods
• Tx: antitoxin first, antibiotic second • Refer to a dermatologist when its nodular
or nodulocystic

• Gram positive anaerobe; hides in the


hair follicles

12
382
4/29/2008

Propionobacterium Acne,
Retinoic acid
cont.
• White comedones: clear vesicles • Pre vitamin A
• Black comedones: sebum has been
oxidized; turns black • Cause proliferation of skin cells, pushing the
pathogen to the surface (hypersensitivity)

• Tx: oxy-5 or oxy-10; benzoyl peroxide • Main side effects:


or abrasive pads; antibiotics – hyperlipidemia (fat soluble);
( minocycline, clindamycin, or – hyperparathyroidism;
erythromycin ); retinoic acid – pseudotumor cerebri;
– teratogenic (must do pregnancy test)

Lysteria monocytogenes Monocytosis


• The only gram positive with endotoxin • Syphilis
(kills quickly)
• Tuberculosis
• Causes monocytosis
monocytosis- granulomatous • EBV
inflammation
• Lysteria monocytogenes
• Attack placentas, causing abortions • Salmonella typhi

• Requires iron to grow; high incidence in


patients with hemochromatosis STELS

Lysteria monocytogenes
• Causes neonatal sepsis
Curved rods
• Vibrio
• Causes gastroenteritis associated with
migrant workers, raw cabbage, spoiled • Campylobacter
milk,
ilk hot
h t dogs
d
• Lysteria
• Curved rod, tumbling motility • H. Pylori
• Intracellular, Cold growth

• Tx: Ampicillin, Macrolide, Vancomycin

13
383
4/29/2008

Listeria cont.
Gram Negatives
• Listeria meningitis:

–Is
Is the most common cause of
meningitis in…
• Renal transplant patients
• Adults with cancer

Hemophilus Hemophilus
• Gram negative pleomorphic rod • 80% are not encapsulated and
therefore cause noninvasive
• Has IgA protease (cuts IgA) respiratory diseases
(
(non-typeable)
bl )
• Part of normal flora for the posterior
pharynx • 20% are encapsulated
( poly D-glutamic acid) causes
the systemic form (H. inf. B)

Hemophilus Hemophilus
Influenza: Influenza, type B: #1 ONLY for epiglottitis
• thumb print sign
2nd MCC of sinusitis,, otitis media,, • droolingg
bronchitis and pneumonia • fever
• stridor
Strep pneumoniae # 1
Tx: intubate immediately

14
384
4/29/2008

Thumb Print Sign


Hemophilus
• Aegyptus: Pink eye (not viral conjunuctivitis)

A B

Painful genital lesions


Hemophilus • Chancroid ( H. Ducreyi)- Most common ulceration
with central necrotic area. Tx: Ceftriaxone
• Ducreyi: MCC of chancroid, the most common
painful genital lesion (LN unilateral) • Herpes ( Herpes Simplex II)- small vesicular rash
– Acyclovir 5x day
– Pancyclovir 3x day
– Valcyclovir (Valtrex) 2x day- more compliant

Remember: does not cure- dec. symptomatic days


dec. viral shedding
dec. recurrence

Pregnancy- symptomatic within 2 weeks of


planned deliver- you must do a C-section

Painful genital lesions


HiB Vaccine
• Lymphogranuloma venereum (
• Has cut HiB infections down by 90%
Chlamydia trachomatis- ulcerative LN drain
(bilateral)
– Tx: Doxycycline
• Given at 2m, 4m, 6m, 18m;

• Last dose (at 5y) no longer needed


• Granuloma Inguinale
( Calymmatobacterium Donovini)
– Donovini bodies –macrophages with the
bug in it

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4/29/2008

Nisseria Nisseria
• The only gram negative diplococci • Meningitidis: ferments maltose + glucose
– Presents with DIC (uses up clotting factors)
• D-dimer and Fibrin split products
• Has IgA protease
– Waterhouse-Fredrickson syndrome-hemorrage into
adrenal gland
• Part of normal throat flora
– MCC of meningitis from 10 to 21y/o

• Encapsulated (Has the largest capsule)


– Give Dexamethasone BEFORE antibiotic
to prevent hearing loss from inflammatory
neurological damage
• The ONLY gram negative that releases
endotoxin during the log phase
– Give Rifampin to close contacts (>25 hrs wk)

Nisseria Nisseria
• Gonorrhea: ferments glucose
• Gonorrhea, cont
– Has pili that naturally transform each year
– Fitz-Hugh-Curtis syndrome: purulent
( phase variation)
abscess right underneath the liver

– #1 for causes of purulent STDs


– Gonococcal arthritis: it loves tendons and
– #2 for causes of STDs (1# Chylamidia) ligaments (i.e. tenosynovitis)
• In men: 90% of cases are symptomatic
• In women: 50% are symptomatic
– When cultures positive, cover for
chlamydia as well ( but not vice-versa)
– Uses the pili to walk up the uroepithelium
to gain access to the blood

One dose therapy for GC


and Chlamydia Nisseria
• Azythromycin: 1gm or 2gm • Catarrhalis : does not ferment sugar

• Ceftriaxone: 250mg I.M. – Most common strain in the back of the throat
• Cefixime: 400mg po
• Cefoxitin: 250mg I.M. – Loves mucus

• Ciprofloxacin: 500mg po – #3 for respiratory tract infections


( sinusitis; otitis media; bronchitis;
• Gatifloxacin: 400mg po
pneumonia)
• Ofloxacin: 400mg po

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4/29/2008

Helicobacter Pylori
• Curved rod, Urease positive
H. Pylori
• Silver stain – GI tissue • Treatment: Amoxicillin, Bismuth, H-2
• CLO test blocker or PPI
• Associated: duodenal ulcers (95%) and
gastric
t i ulcers
l (70%)
• Bismuth- suffocates
• Treat ALL positive gastric cultures
• 3 drugs for 2 weeks (98%
eradication)
• Hydrogen breath test is most • MCC- bad water (sewer system)
diagnostic if available for eradication

Urease positive bugs E. Coli


• Protease • Makes up 95% of small intestinal normal flora
• Pseudomonas
• Ureoplasma Urolyticum
• Small intestinal infections:
• Nocardia – Acute cholecystitis- + murphy sign, colic pain
• Cryptococcus – Ascending cholangitis- inc. alk phos
– Acute appendicitis
• H. Pylori
– Abdominal abscess
• Staph Saprophyticus – Acute spontaneous bacterial peritonitis
• Brucellosis

E. Coli
• Makes: ETEC (Enterotoxogenic E. coli)
– 90% of vitamin K
– Biotin • Major cause of diarrhea in
– Folate developing areas
– Panthotenic acid
• Traveler’s diarrhea (rice water)
• Helps absorb:
– Vitamin B-12
• Dorsal column • Severe watery diarrhea
• Cortical spinal tract ( > 20 L day)
• USA- pernicious anemia
• Antiparietal cell Ab

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4/29/2008

EPEC (Enteropathognic E. coli) EIEC (Enteroinvasive E. coli)


• Plasmid shared by Shigella
• Young children and infants
• Invades intestinal mucosa
• Causes loss of microvilli
• Produces shiga like toxin (verotoxin)
• Diarrhea from malabsorption
• Bloody, purulent diarrhea

EHEC (Enterohemorrhagic E. coli) Proteus Mirabilis


• O157:H7 (out break- epidemic) • #2 for UTIs (1# E. coli)

• Cattle, sheep, goats


• Urease positive
• Ingestion
I ti off contaminated
t i t d ffood
d
• Associated with high urine pH,
• Bloody diarrhea, endemic HUS struvite stones, staghorn calculus,
(renal failure) high ammonia in the urine

• Anemia, thrombocytopenia, renal failure Tx: Quinolones

Klebsiella Pneumonia Like Immunocompromised


• #3 for UTIs people

• Likes to attack alcoholics and homeless • Serratia Marscesens


people
• Citrobacter
• In lungs: curant ( blood mixed with • Pseudomonas auregenosa
mucus) jelly sputum; likes to attack
fissures

• Encapsulated

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388
4/29/2008

Serratia Marscesens Citrobacter


• Produces citric acid

• Produces a red pigment • Encapsulated

• Likes to attack 0 to 2m/o (babies)

• Causes multiple cerebral abscesses

Pseudomonas Auregenosa Pseudomonas Auregenosa


• Same enzymes as Staph aureus • Causes: whirlpool folliculitis:
– Tennis shoe folliculitis- nail through shoe
• Likes to attack diabetics, burn patients,
neutropenics, and cystic fibrosis
– Malignant otitis externa- mastoid (coagulase)
• Gold
G ld pigment
i l k staph
like h aureus
– Mcc of death in second week after a burn
• Also produces a green pigment
– Recurrent pulmonary infections in CF
• Has a fruity grape smell when plated
• Likes plastic ( endotracheal tubes; bladder
– ICHTHYMA GANGRENOSUM- blood form
catheters)
(black bulla on the skin)

Shigella
Salmonella
• Causes gastroenteritis associated with daycare
outbreaks • Encapsulated
• Loves to attack people with sickle cell
• Most immunogenic bacteria anemia ( causes osteomyelitis)
• Causes gastroenteritis associated with
• Has an exotoxin ( shigatoxin) which causes raw chicken or raw eggs
seizures • Runs and hides in the gallbladder if
you treat it with antibiotics
• S. Sonneii: common in the US – Can precipitate cholecystitis

• S. Dysentery: common outside the US

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4/29/2008

Salmonella, cont Salmonella Typhi


• The cause of typhoid fever
• Causes monocytosis
• Triad: (1) Fever (2) Rose spots (3)
Intestinal fire
• S. Enteritidis:
d most common strain
in US • Causes heart block

• S. Dysentery: common outside the • Associated with contaminated water


US
Treat with ciprofloxacin

Bordatella Pertussis Bordatella, cont


• Causes extreme lymphocytosis (? PMN’s)
• Causes “ whooping cough”
– Prodromal stage- fever, runny nose
– Catarrhal stage- increase mucus • Mcc of death was suffocation
– Paroxysmal stage- cough • Vaccination

• Has an exotoxin that ADP-ribosylates Gi • Diagnosis: do ELIZA on nasopharyngeal


subunit of the G-protein
washings

• Exotoxin is intracellular; kills cells


• Treatment: erythromycin; also treat
close contacts with erythromycin
• High cAMP increases mucus in the lungs

Pasturella Multocida Brucella


• Causes cellulitis associated with an • Causes undulating fever (5 to 7 fever
infected cat or dog bite. spikes per day)

• Found in the saliva of cats and dogs • Seen primarily in vetrinarians and
farmers who deliver animals
Tx: Amoxacillin
• Attaches to placenta

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390
4/29/2008

Bartonella Henselae Francisella Tularensis


• Silver stains • Causes tularemia or oculo-glandular
fever
• Causes cat scratch disease
• Transmitted by rabbits (90%) and
• Carried by kittens deer (10%)

• Treatment: Streptomycin

Miscellaneous Vibrio
Gram Negatives • CHOLERA
– Curved rod
– Has an exotoxin that ADP ribosylates Gs and elevates
cAMP
– Rice water diarrhea (also ETEC)

• PARAHEMOLYTICUS
– Diarrhea associated with raw fish

• VULNIFICUS
– Diarrhea associated with raw oysters

Campylobacter Jejunii Yersinia


• A curved rod
• Likes the Southwest

• Attacks the jejunum, causing a • PESTIS


p
copious bloodyy diarrhea – Bubonic plague
– Pneumonic plague

• Causes diarrhea associated with raw


chickens or raw eggs • Enterocolitica
– Likes to attack the ileum, causing ileitis
or mesenteric adenitis (mimic append)
Treat with erythromycin – Causes Reiter’s syndrome

21
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4/29/2008

HLA-B27 DISEASES

Atypicals
• Reiter’s Syndrome- any post infection
arthritis

• Ankylosing Spondilytis- Shoeberg


test, bamboo spine

• Psoriasis- silver plaque on extensor


surfaces

• Psoriasis w/o arthritis- HLA B13

Atypicals Chlamydia
• Have NO cell wall
• Parasites: depend on host for ATP

• Granulomatous inflammation
• Eosinophilia

• Covered by Quinalones, Macrolides and


• Has two forms:
Tetracyclines
– elementary body (infectious)
– reticulate body ( dormant form)
• Causes interstitial pneumonia
– Symptoms out of proportion to physical • Granulomatous inflammation
findings

Chlamydia Trachomatis Chlamydia Trachomatis


• Causes trachoma: Mcc of neonatal blindness • Do ELIZA with all pap smears
in the world
– Trachoma: destruction of cornea from scarring
– Prevention: apply erythromycin to eyes
• One-dose treatment: azithromycin
• Mcc of lymphogranuloma venereum 1gm

• Mcc of STDs ( 90% are asymptomatic)


• Old treatment: doxicycline
• Mcc of infertility in WOMEN for 7 days

• Mcc of ectopic pregnancy ( from scarring)

22
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4/29/2008

Chlamydia Pneumonia Chlamydia Psitacii


• Mcc of atypical pneumonia (0 to 2 mo)
• Associated with parrots and
• Eosinophilia parakeets
• Interstitial pneumonia
• Causes interstitial pneumonia or
• Symptoms out of proportion to physical findings
nonbacterial endocarditis
• Steccato coughing

• Found to be connected to alzheimer’s


disease and coronary artery disease

Mycoplasma Pneumonia
Mycoplasma
• NO cell wall • Mcc of atypical pneumonia from age
10 to 30

• NO epithelial lining
• Cold agglutinins
gg (cryoglobulinemia)
( y g )

• Look like jellyfish • Causes “ walking pneumonia”

• Interstitial pneumonia with symptoms


out of proportion to physical findings

Legionella Pneumophila
Mycoplasma Hominis
• Mcc of atypical pneumonia age 40yr
• Interstitial pneumonia
• An occassional cause of vaginitis
• silver stains
• Grows on CYAE
• Likes standing water on heating and air
conditioning systems

• Causes high rise building syndrome


or hotel/motel syndrome

23
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4/29/2008

Legionella Pneumophila Heart Blocks


• First degree: fixed prolonged PR
• Pontiac Fever: fever and nonspecific interval
symptoms
• Second degree:
• Legionnaire’s
g disease: full blown – Mobitz 1: progressively prolonged PR
pneumonia interval until a QRS complex is dropped
– Mobitz 2: normal PR interval; erratic
• Granulomatous inflammation dropping of QRS complexes

• Causes heart block • Third degree: NO relationship


between P waves and QRS complexes

Infections that cause heart


Ureoplasma Urolyticum
blocks
• An occasional cause of vaginitis
• Legionella
• Lyme • Has NO cell wall or epithelial lining
like mycoplasma
• Diptheria
• Chaga’s
• Urease positive
• Typhoid fever

Urease Positive
• Proteus
• Pseudomonas Fungi
• Ureoplasma
• Nocardia
• Cryptococcus
• H. Pylori
• Staph saprophyticus
• Brucellosis

24
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4/29/2008

FUNGI Antifungals
• Bind to ergestrol
• Like warmth and moisture – Amphotericin B- IV for systemic fungal infections
(skin folds, groin, axilla, vagina) • Gets confused with cholesterol
• Pokes holes in your cells- releasing K+

• Like to eat sugar- in diabetics – Nystatin


– Mycostatin
– Miconazole
• To prevent fungal infections, keep cool – Clotrimazole
and dry – Tolnaftate
– Terbenafine

• Have a unique lipid in their


– Flucytosine (5FC) – inhibits mitosis
membrane called ergesterol (acts like pyramadine)

Antifungals Superficial Fungi


• Inhibits ergesterol synthesis • Piedre – black balls on the hair
– Fluconazole- best CNS penetration
shaft
– Itraconazole
– Ketoconazole- inhibits P450’s, blocks 5α –Tx: cut hair
reductase

Inhibits microtubules
• Microsporum Beigeii- white
- Griseofulvin
balls on hair shaft
–Tx: cut hair

Cutaneous Fungi Cutaneous Fungi


• General (4 classes): • Tinea
– Capitus - scalp
– Versicolor- v on back
– Dermatophyton – skin
– Corporus- body ring worm
– Manis – between fingers
– Trichophyton- hair follicle – Nigra – palms – life lines get dark
– Intertrigo- skin to skin
– Epidermaphyton- epidermis – Cruris- jock itch - groin
– Pedis – between the toes
– Unguum – under nail beds (one nail
– Microsporum- (Wood lamp +)
affected)

25
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4/29/2008

Vaginitis
Deep Fungi • Candida: curdy white discharge; pruritic
– Candida part of normal flora and lactobacili keep
• Onychomycosis- fungus of nails it in check (antibiotics will destroy lactobacilli)
– Tx: Fluconazle

• Candidiasis – most common ll fishy


• Gardnerella:
G d fi h odor;
d “ clue
l cells”
ll ”
cause of vaginitis – Tx: Metronidazole

• Trichamonas : frothy green discharge


– Protozoa: flagella
– Tx: Metronidazole and remember to treat
partner (STD)

Systemic Fungi Systemic Fungi


• Histoplasmosis (Midwest) pigions, bats • Sporothrix- rose gardner, skin-potassium
iodine; Amph B and Fluconazole if systemic
• Blastomycosis (North east) pigon,
broad base budding • Cryptococcus- AIDS patient with
meningitis indian ink stain
meningitis,
• Coccidiomycosis ( South west) Broad
base budding • Aspergillus-Moldy hay or moldy
basement (mimics asthma)
• Paracoccidiomycosis (South America)
shipwheel • Rhizor/ Mucor – nose of diabetic
patients

Symptoms from the Pulmonary Infiltrate with


Southwest Eosinophilia
• Coccidiomycosis- fungus • Allergic Bronchopulmonary Dysplasia

• Loeffler’s Syndrome
• Hantavirus-
H t i virus
i (hemorrhagic)
(h h i ) – Necator Americanus
– Anclystoma Duodenale
– Strongyloides
• Yersinia Pestis- bacteria – Shistosomiasis
– Ascaria Lumbricoides

• Churg-Strauss

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4/29/2008

PARASITES
PARASITES • Cause gastroenteritis

• T-cells, Macrophages, Eosinophils

• LOW VOLUME STATE

FARTENPOOPIN • Chronic infections lead to iron


deficiency anemia

Liver Flukes
Liver Flukes • Toxacara : cat or dog poop
• Schistosomiasis : walking barefoot thru a – Carti- cat larvae
swamp – Cani- dog larvae
– S mansoni: liver cancer – Cutaneus larva migrans- burrowing under
– S. hematobium: causes squamous cell carcinoma skin
of the bladder (chronic irritation)

• Ecchnococcus : messing with sheep; raw


lamb; dog food
– Causes solitary ( hydatid) cyst of the liver

Liver Flukes Hookworms


• Clinorchis ( or opthorchis) • Hooks into the intestinal/bowel wall
• Severe cramps and diarrhea
• Sinensis: seen in Chinese; likes the
biliaryy tract ((Alkaline Phosphatase)
p ) • “NEAT
NEAT AS
AS”
– Necator americanus
TX for all liver flukes: – Enterobius Vermiculris- pin worm
Parziquantel • Pruritis ani (eggs)
• Scotch tape test- female comes out at night
• Worm lives in the cecum

27
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4/29/2008

Hookworms Hookworms
“NEAT AS” • Treatment:
• Anclystoma Duodenale – Mobendazole- paralyzes microtubules
– Duodenal obstruction (can’t hook on to tissue)

• Trichuris Trichurium
Trichurium- Whip worm
– Pyrantel pamaoate- specific treatment
– Anchors into rectum
for pin worm
– Rectal prolapse
• Ascaris lumbricoides – Thiobendazole- tx for Strongyloides
• Strongyloides

NASSA Flat Worms


• NASSA- parasites associated with • Will curl around the intestine:
loffler syndrome (endocarditis – D. Latum- like to eat B12
and pneumonitis) – Tanea Saginatum- raw beef
– Tanea Solium- raw pork, swims in
aqueous
q humor of the eye
y
• Necator americanus – Trichinella Spiralis- raw bear meat,
• Anclystoma duodenale tunnel under skin causing myoisitis

• Schistosomiasis
Tx: Hyclosamine
• Strongyloides Niclosamine
• Ascaris lumbricoides Inhibit oxidative phosphorylation – decreasing ATP

Protozoa
Brain:

Protozoa – Naeglaria Fowleri


• Swimming through swamp- cribiform plate
• Fulminant meningo encephalitis

– Toxoplasmosis
• Cat litter (feces)
• Parietal lobe ring enhanced lesion
• Tx: Pyremethamine/ Sulfadiazine

– Trypanosoma Rhodienses
• Carried by Tsetse fly
• African sleeping disease

28
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4/29/2008

Protozoa Protozoa
Cornea: • Erlichiosis
• Acanthomoeba – Dog licking face (in saliva)
– Contact lenses – Penetrates side of eye
– Will eat through cornea

Protozoa Protozoa
Heart Lung:
• Trypanasoma Cruzi • Pneumocystic Corinii
– Chagas disease – Silver stain (also Legionella)
– Eats g
ganglia
g and causes heart block – CD4 count < 200
– South America – Tx: Bactrim (SMX-TMP)
– Reduuvid bug

Protozoa
Protozoa
GI
• Giardia- gastroenteritis
GI
– Loves fresh water/well water • Microsporidium
– Hiking in the mountains – MCC of diarrhea in AIDS patients
– Tx: IV Metronidazole
• Cryptosporidium
• E. histolyticum – Watery diarrhea
– Multiple liver abscesses – Partially acid fast
(never do surgery) – Tx: Ciprofloxacin
– Tx: Metronidazole (8 weeks)

29
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4/29/2008

Protozoa Protozoa
GU Skin
• Leschmaniasis (RASH)
• Trichimonas
– Gulf War syndrome
– 3rd MCC of Vaginitis – Sand fly
– Tx: Metronidazole 2gmg x1
– Also treat partner • Leschmania Donivini (face eaten away)
– Attacks skin and nostrils

• Leschmania Rhodiensis (organ)


– Systemic (attacks organs)-Kala Azar
– Tx: Stibogluconate

Protozoa
Lymphatics Protozoa
• Wucheria Bacrofti Blood
– Elephantitis
– No treatment • Babesiosis
– East coast
– Looks different on a smear
– Tx: anti-malarial
– Ixodes tick
(same for Lyme disease)

Protozoa Protozoa
Blood Blood- Plasmodium
• Plasmodium Malaria • Symptoms
- MC strain world wide (fever every 3rd – Malaria- fever every 3rd day
day) – Falciparum, vivax, ovale- fever every 2
• Falciparum
Falciparum- most fatal (hemolize days
RBC’s)
– Black water fever- urine turn black • Treatment:
• Vivax- go to the liver (chronic malaria) – Quinine
– Likes reticulocytes (young RBC’s) – Chloraquine- mostly RBC’s
– Mefloquine- good liver penetration
• Ovale- go to the liver (chronic malaria) – Primaquine- best liver penetration
– Likes mature RBC’s (vivax and ovale)

30
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4/29/2008

Mycobacterium, Mycobacterium
• NOT a true bacterium
Spirochetes , • Has bacterium in its name because
Rickettsia it has a peptidoglycan wall
• Atypical due to MYCOLIC ACID in
its membrane
• Cell mediated inflammation
• If you destroy mycolic acid, you
destroy mycobacterium

Mycolic Acid Isoniazid ( INH)


• A special lipid found in the wall of • Inhibits the synthesis of mycolic acid
mycobacterium • Fat soluble
• Pulls vitamin B6 out of the system
• INH works by inhibiting mycolic acid • Must give vitamin B6 with this drug to
prevent neuropathy
synthesis

• Side effects: myositis; hepatitis;


hepatic necrosis ( especially after
age 35 years); neuropathy;
oxidizes RBCs: blocks P450

Primary response to
Primary Tuberculosis
Mycobacterium
• Asymptomatic • Usually lands in the RLL in terminal
• Ghon focus: naked tubercle on bronchioles
respiratory epithelium
• Virulence
Vi l factor:
f CHORD FACTOR • Once GRANULOMA is formed:
• Ghon complex: tubercle ingested by – Interferon
macrophages and taken to the – Tumor Necrosis Factor
lymph nodes – 1 hydroxylase
• Granuloma: macrophages now
surrounded by T cells

31
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4/29/2008

Infliximab
• As long as your T cells and
• An antibody against TNF macrophages stay healthy…

• Useful in patients with RA


• You have nothing
g to worryy
about.
• Decreases joint destruction
.

But if cell mediated immunity is


Secondary Tuberculosis
ever impaired…
• Fever, night sweats, weight loss,
• Mycobacterium is still alive within
and hemoptysis
macrophages
• Mycobacterium explodes out of the • RLD profile
macrophages
h and
d into
i t the
th airways
i • Cavitary lesion visible in upper
• Hemoptisis occurs lobes on the Xray
• Mycobacterium works its way to
the upper lobe and sets up a Tx: first isolate patient when
cavitary lesion
TB is suspected; get sputum
• Patient now very symptomatic
sample for culture

Disseminated Tuberculosis
• After TB replicates inside of the cavity, • In GI: causes ileum obstruction
it then disseminates • Bone: Pott’s Disease
• Lymph Nodes: diffuse lymphadenopathy
• Skin: Erythema Nodosum
• Mycobacterium now has full access • Along Psoas Muscle: cold abscess
to the entire body. • CNS: posterior fossa
– Neuropathies
– Hydrocephalus
– Meningitis

32
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4/29/2008

Disseminated Tuberculosis
• Renal: sterile pyuria
• Adrenal gland: insufficiency
• In pregnant woman: treat as in
anyone else

• Most people don’t know they


have ever come in contact
with TB unless…

TB Treatment
• Four drugs for 4 months for everyone TB Treatment
• At the end of twelve months of treatment, then
culture the sputum again
• If strain of TB is sensitive to both INH
and RIFAMPIN, then finish 8 more
months with just these two drugs • Sputum cultures are repeated monthly

• If strain of TB is NOT sensitive to both • Stop treatment when there are three
of these drugs, complete 8 more consecutive negative sputum samples
months with four drugs
• Patient may take drugs every day; or he
• Substitute other drugs if any bad may opt to take it every other day but
witnessed by a healthcare professional
side effects

TB Prophylaxis
• INH plus vitamin B6 for 9 to 12
Mycobacterium Family
months • M. TB
• M. Leprae ( Hanson’s Disease)
• In pregnant women, you must still • M. Avium Intracellulare
give
i prophylaxis
h l i • M. Scrofulaceum
f l
• M. Marinum
• In patients with history of BCG • M. Ulcerans
vaccine, ignore the history, and • M. Kansasii
merely follow the algorhythm

33
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4/29/2008

Dapsone
• Indicated for the treatment of dermatitis
Spirochetes
herpetiformis, Pneumocystis carinii in HIV • So named due to their spiral shape
patients, and for leprosy

• For leprosy: use with clofazimine and • Have axial filaments at their two
p for 6 to 24 months
rifampin
ends
• Mimics PABA like sulfa drugs
• Use a lateral tumbling motion
• Side effects: megaloblastic anemia;
oxidizes RBCs; coombs positive hemolytic
anemia; inhibits P450 system
• Cell mediated response

Treponema Pallidum Tertiary Syphilis


• Causes syphilis
• Tabes Dorsales
• The most common cause of painless
genital ulcer
• Shooting, lancinating, stabbing neuropathy

• Primary syphilis- non tender chancre


• Syphilitic aortitis
( contagious )

• Argyle Robertson pupil


• Secondary syphilis- 1 to 3 mo
( rash P & S )
• Syphilis loves to attack bones
( saber shins)
• Tertiary syphilis *

Toxoplasmosis
TORCH infections • Multiple ring enhancing lesions in the parietal
• They attack in the first trimester lobes
( except herpes) • Caused by cat urine
• Asymptomatic in healthy people (walled off
• They cause severe neurological in a granuloma)
damage • Symptomatic
S t ti iin pregnantt women d
due tto
• All cause IUGR, microcephaly, suppressed immune system
• Pregnant women should NOT change a litter
hypotonia and developmental
box
impairment • Treat with pyremethamine/sulfadiazine
combo
• How do you separate them ?

34
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4/29/2008

Syphilis Rubella
• Loves to attack bones • Blueberry muffin rash
– Flat forehead
• Cataracts
– Saddle nose
– Sniffles
• PDA
– Micrognathia • Hearing loss
l
– Rhagades • Autism
– Hutchinson’s teeth
– Sabre shins

Autism Autistic
• Four features: • AUTISM- below normal intelligence, difficulty
– Inability to bond forming relationships
– Impaired language development
– Automatism- no control of there actions • Asperger syndrome: milder form, normal
intelligence and lack social skills
– Overreacts to small disturbances

• Pervasive developmental disorder of childhood


• Brain is found on autopsy to be
arrested in development • Rett’s syndrome- girls only, starts by
age 4, hand wringing
• MMR controversy

Herpesvirus
Cytomegalovirus • Attacks newborn on the way through the
vagina
• Loves to attack the retina
• Loves to attack the temporal lobe, causing
temporal lobe hemorrhagic encephalitis
• Mcc of Congenital blindness
• If pregnant mother has an outbreak of
lesions within two weeks of delivery, do a
• Causes central calcifications C-section

• Give pregnant mother acyclovir in last


• Attacks the midline month to prevent outbreaks

35
405
4/29/2008

Syphilis Treponema Family


• Treatment: • Treponema Pallidum
– Primary syphilis: 1.2 million units of long
acting penicillin (Procaine or Benzathine)
– Secondary syphilis: 2.4 million units, half in • Treponema Pallidum variant: Bijel
eachh buttock
b tt k
– Tertiary syphilis: 2.4 million units once • Treponema Pertenue: Yaws-
weekly for 3 weeks tropical form
– Neonatal syphilis: 50,000 units per
Kg per day in divided doses
• Treponema Carateum: Pinta

Borellia Borgdorferi Borellia Borgdorferi


Lyme Disease • Treatment:
• Primary stage- bull’s eye rash (resolve – Penicillin
in 1 month) – Doxycycline
• Secondaryy stage-
g flu like symptoms
y p ,
organ involvement – If a pregnant woman is bitten by a tick,
treat with IV ceftriaxone
• Tertiary stage- arthritis
– Any patient with heart block,
• Dx: history of Erythema Chronicum hospitalize and treat with
Migrans; IV ceftriaxone
– Do IgM and IgG titers

Leptospira Interrogans
Borellia Recurrentis • Causes leptospirosis
• Causes Relapsing Fever

• Seen primarily in sewage workers


• Fever occurs once weekly

• Transmitted by rat urine


• Organism hides in lymph nodes and
mutates slightly each week
• Weil’s Disease: attacks the liver
(hepatitis) and the kidney (nephritis)
• Treat with penicillin or doxicycline

• Causes Fort Braggs Fever

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4/29/2008

Rickettsia Rickettsia
• Rickettsia Rickettsia: RMSF: tick borne

• Treatment: Doxicycline or
• Rickettsia Typhi: endemic typhus: flea borne
Chloramphenicol
• Rickettsia Prowzekii: epidemic typhus: louse
borne

• Rickettsia Akari: rickettsial pox: mite borne

• Rickettsia Tsutsugamushi- scrub typhus;


chiggers

We both wish you the best


of luck on your exam !!!!

37
407
6/25/2008

What all viruses do…


• Invasion
• Adhesion
And NOW…The final topic! • Penetration
• Uncoating
• Replication
VIRUSES • Assembly
• Lysogeny

To prevent uncoating To prevent replication


• Amantidine • Acyclovir
• Rimantidine • Pencyclovir
• Demcyclovir
• Valcyclovir
• Famcyclovir
• Gancyclovir
• Ribavarin

Detectives The 90%


• Southern blot • DNA Viruses • RNA Viruses
– Double stranded ( ex – Single stranded ( ex
• Northern blot parvovirus and orthomyxovirus and
hepadnovirus renovirus
• Western blot – Replicate
p in nucleus ( ex – Replicate
p in cytoplasm
y p
• Southwestern blot poxvirus) (ex retrovirus)
– Assemble on nuclear – Assemble on cell
• ELIZA membrane membrane
• PCR – Naked ( ex herpesvirus) – Enveloped (ex
cocksackievirus)
– +-strand vs -strand

408
6/25/2008

Encephalitis
• Presents with headache and ataxia
Most Common causes of
• Causes:
viral infections…
infections – Arbovirus
– Herpesvirus
From head to toe

Meningitis Common Cold


• AKA aseptic meningitis • Rhinovirus
• Presentation: mild headache; photophobia; • Coronavirus vs Adenovirus
Kernig’s and Brudzinski’s signs • Herpesvirus
• CSF
CS results
l • Influenzavirus
• Causes: enteroviruses • Parainfluenzavirus

Common Childhood infections Childhood Rashes


• Mumps • Hand-Foot-Mouth • Seborrheic dermatitis diaper dermatitis
• Rubeola disease
• Kawasaki disease • Erythema toxicum Pediculosis pubis
• Rubella
• Varicella • Molluscum • Milia
• Varicella-Zoster contagiosum
i • Mongolian spots
• Fifth’s disease • Nevus Flemmeus
• Roseola
• Café au lait spots
• Pityriasis Rosea
• Rosacea • Port wine stain

409
6/25/2008

The four itchiest rashes Croup


• Urticaria • Stridor and barking cough
• Scabies • Steeple sign on neck film
• Dermatitis herpetiformis • Cause:
• Lichen planus – Parainfluenzavirus 80% mild
– RSV 15% severe
– Adenovirus
– Influenzavirus

Bronchiolitis Myocarditis
• All the signs and symptoms of asthma • Leads to loss of contractility
• Under 2 years of age • Diffuse ST wave depression on EKG
• Caueses: • Cause:
– Parainfluenzavirus 80% mild – Cocksackie B Virus
– RSV 15% severe
– Adenovirus
– Influenzavirus

Pericarditis Gastroenteritis
• Causes a friction or tri-phasic rub • In adults: Adenovirus
• May lead to tamponade • In children: Rotavirus
• Diffuse ST wave elevation • Travel: Norwalk agent
• Cause:
– Cocksackie B Virus

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6/25/2008

Cystitis Hepatitis
• Urgency and frequency
• Cause: Adenovirus

Hepatitis Chronic Active Hepatitis


• Active inflammation on biopsy
• Fibrosis present
• May progress to liver cancer
• Will lead to cirrhosis
• Due to Hepatitis B: Tx with interferon and
lamuvidine
• Due to hepatitis C: Tx with interferon and
ribavarin

Chronic Persistent Hepatitis Chronic Carrier


• Elevated liver enzymes or persistent • Still has positive HbSag after 6 months
symptoms after 6 months • No active inflammation or fibrosis on biopsy
• No active inflammation or fibrosis on liver • Still pose a threat to others
biopsy • Can NOT be blood donors or organ donors

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6/25/2008

THE END

412
413448
414449
415450
416451
417452
418453
419454
420455
421456
422457
423458
424459
425460
426461
427462
428463
429464
430465
431466
432467
433468
434469
435470
436471
437472
438473
439474
440475
441476
442477
443478
444479
445480
446481
447482
448483
449484
450485
451486
452
4/29/2008

G5 P4 Ab1
G: Gravita: number of
pregnancies

P: Para: > 20 Weeks


Obstetrics and
Ab: Abortive: abortions
Gynecology
G6 P0 Ab5

Ultrasound (Utz.)
Prenatal Non-invasive imaging

Diagnostic
g No adverse effects on the fetus

18-20 weeks of gestational


Testing anatomical anomalies

Accuracy for gestational age:


At 12 weeks +/- 5 days
At 18 weeks +/- 7 days

Nucal Translucency Chorionic Villous Sampling


(CVS)
10- 14 weeks via Utz. Aspiration of placenta
tissue (9-12 wks)

Sono guided

Karyotyping
Thick area you should think of
cystic hydroma “Down’s Syndrome” Pregnancy loss rate 0.7%

1
453
4/29/2008

Percutaneous Umbilical Blood


Amniocentesis
Sampling (PUBS)
Transabdominal needle to withdraw
amniotic fluid under sono (15-20 wks) Fetal blood from umbilical vein
(> 20 weeks)
Looking at DNA from fetal cells
Fetal karyotyping
Not enough fluid prior to 15 weeks
IgM antibody
Pregnancy loss rate (0.5%)
Blood typing
24 weeks- Rh isoimmunization
(bilirubin levels) Intrauterine Blood Transfusion

34 weeks- Lecithin-sphingomyelin Pregnancy loss rate 1-2%

Fetoscopy Fetal Development


Experimental (18-20 weeks) 1 week for Implantation

Fetal tissue biopsy


Ichthyosis
y
Genetic skin condition
(fish scales) Folic acid
1mg
4mg
Coagulation in twin-twin
transfusion

Week 2-3 post conception Weeks 4-8 Post Conception


Bilaminar germ disk: Major organs forming
Teratogenic risk
- Epiblast
- Ectoderm
- Hypoblast
- Mesoderm
Cytotrophoblast
- Endoderm
Synchotrophoblast
Must have all 3 in order to a
Primitive streak teratogen to cause problems

2
454
4/29/2008

Female vs Male cells Teratogenesis Stages


Theca Conception to end of first week
Granulosa
Weeks 3-8

Leydig
L di Post week 9
Sertoli
5 alpha reductase – DHT (external
genitalia)

Teratogens Teratogenic Syndromes


Ionizing radiation Alcohol: fetal alcohol syndrome

Chemotherapy
Long philtrum
T b
Tobacco

ETOH Midfacial hypoplasia

Cocaine
Short palpebral fissure

Teratogenic Syndromes Teratogenic Syndromes


Diethylstilbestrol (DES) Isotretinoin (Accutane)

T-shaped uterus Congenital deafness


Congenital heart defects
Vaginal adenosis-
adenosis clear cell
carcinoma iPLEDGE

Incompetent cervix

3
455
4/29/2008

Teratogenic Syndromes Teratogenic Syndromes

Lithium: Streptomycin

Ebstein anomaly (R heart defect) CN 8 damage- hearing

Tricuspid lower

Very large right atrium

Teratogenic Syndromes Teratogenic Syndromes

Tetracycline Thalidomide: drug for N/V

Competes with Ca2+ Phocomelia (days 42-48)

Teeth discoloration after 4 months Pyloric and duodenal stenosis

Teratogenic Syndromes Teratogenic Syndromes


Warfarin (Coumadin)
Valproic acid (Depakote)

Chondrodysplasia: stippled
Neural tube defect
epiphysis
Mgt: Migrans and Bipolar

4
456
4/29/2008

Human Chorionic Gonadotropin

Pregnancy
Syncytrophoblast

In blood by day 10
Hormones
Alpha subunit

Beta subunit (specific)

High levels of hCG Human Placental Lactogen


(HPL)
Twins
Hydatiform moles Increased through pregnancy
Choriocarcinoma
Antagonizes
tago es insulin
su

LOW levels:
Ectopic
Threatened abortion
Missed abortion

Skin
Organ Line nigra

system Chloasma

changes in Chadwick sign

pregnancy Stria gravidarum

Spider angiomata/palmer erythema

5
457
4/29/2008

Heart Murmurs
Blood pressure Systolic murmur:

Plasma volume

Femoral venous pressure Diastolic murmur:

CO

Peripheral vascular resistance (PVR)

Blood GI
RBC’s Stomach:
Plasma volume
Large bowel
WBC’s

Platelets

Coagulation

Pulmonary Renal
Tidal Volume Increase in size:

Minute volume
Gl
Glucosuria:
i

Respiratory volume

Proteinuria:
Blood gases

6
458
4/29/2008

Endocrine Fetal Circulation


Pituitary 3 in utero shunts:

Ductus venosus

Thyroid
Foramen ovale

Ductus arteriosus

Fetal Hart Tone (FHT)

Fetal Doppler stethoscope: 10-12 wks

Testing Auscultation 18-20 wks

Quickening: 16-18 weeks


(primigravida 18-20)

Ultrasound Dating Pregnancy 1st trimester


1st trimester: < 13 weeks

N/V

2nd trimester and 3rd


S tti / bl
Spotting/ bleeding
di
Biparietal diameter
Head circumference
Wt gain 5-8 lbs
Abd. Circumference
Femur length
Complication: spontaneous
abortion

7
459
4/29/2008

Pregnancy 2nd trimester Pregnancy 3rd Trimester


13 – 26 weeks Decreased libido, back pain, urinary
frequency
Round ligament pain
Lightening
Braxton-Hicks contractions
Bloody show
Quickening
Wt gain 1 lb/week
Wt gain 1 lb/wk
Complication: PROM
Complication: incompetent cervix

Mean Corpuscular Volume

Prenatal Hb/Hct- low due to dilution

Lab MCV most reliable

Test
< 80
> 100

Rubella IgG antibody Hepatitis B Virus


Antibodies present HBV surface antibody: successful
vaccination

HBV surface antigen:


Absence puts patient at risk
E antigen:

Immunization:

8
460
4/29/2008

STD screening Urine Screening


Cervical cultures: Urinalysis:
Proteinuria
Ketones
Syphilis: Glucose
VDRL Bacteria
RPR
MHA-TP Culture: asymptomatic bacteruria
FTA (ASB)

Mgt. Penicillin

Tuberculosis Screening HIV screening


PPD or Tine test: Recommended for all pregnant
women
Positive skin test
Opt out: informed refusal
CXR negative
Opt in: informed consent
CXT positive

Elisa test Alpha Fetal Protein


Detectable HIV antibodies
True causes of increased AFP:

Babies born to an HIV + mothers

Western Blot MCC dating


MCC- d ti errors

Zidovudine

9
461
4/29/2008

Triple Marker Screening Triple marker screening


MS-AFP
hCG
Trisomy 21 Trisomy 18
Estriol
Downs Edward’s

Accurate dating is important MS-AFP

hCG

Estriol

Do karyotype for both

Third Trimester Lab Test

Antenatal
Diabetic Test:
1hr (50 gm) oral glucose

3hr (100 gm) oral glucose


Fetal
Normal: FBS: < 95, 1hr <180, 2hr < 155,
3hr < 140
Testing

Nonstress Test (NST) Fetal Monitor Tracing


Check frequency of fetal movement
External fetal HR monitor Base line FHR: 110-160
Accelerations
< 110 Bradycardia
Meds: beta adrenergic blockers, anesthetics
< 32 wks: > 10 or more BPM, Fetal arrhythmia-
arrhythmia congenital heart block (lupus)
lasting >10 sec
>160 Tachycardia
Meds: beat adrenergic agonist (terbutaline,
> 32 wks: > 15 or more BPM, ritodrine)
lasting > 15 sec Fever
Fetal repetive movements

10
462
4/29/2008

Early Deceleration: Variable Deceleration-


head compression cord compression

Late Decelerations- uteroplacental


Biophysical profile (BPP)
insufficiency ( fetal acidosis)
5 components of fetal well
being:
1. NST: scores 0-2 for each
2. Amniotic fluid volume
3. Fetal g
gross bodyy movement
4. Fetal extremity tone
5. Fetal breathing movements

2-5 assessed through Utz.

BPP scoring Contraction stress test (CTS)


Testing fetus response to tolerate
8-10 = reassuring (weekly BPP)
transitory decreases in blood flow

4-6 = worrisome
Presence or absence of late
> 36 wks- deliver
deceleration
< 36 wks-
k BPP every 12-24
12 24 h
hours

Induce with IV oxytocin


0-2 = fetal hypoxia (deliver ASAP)

Negative test is good- no late D-


cells

11
463
4/29/2008

Umbilical Artery Doppler


Measures ratio of Systolic and

Infections
Diastolic blood flow in umbilical
artery

Increased throughout
g pregnancy,
p g y,
since diastolic pressure falls more

Group B beta hemolytic Strep Treat for Group B Strep if…


Normal GI tract flora
Positive urine culture GBBS
30% of women are asymptomatic carriers
Previous baby had GBBS
Vertical transmission
Screening by vaginal cultures:
Early onset 3rd trimester
If + then prophylaxis IV PCN
Late onset
Preterm or Membrane rupture > 18hrs,
Mgt: IV penicillin: if allergic- Clindamycin or maternal fever…… Mgt.
and Erythromycin Prophylaxis IV PCN

Toxoplasma Gondii Varicella


Chicken Pox
Parasite associated with cat feces Herpes Zoster
Raw goat milk Spread via respiratory droplets
Under cooked infected meat ZIG ZAG skin lesion
Vertical transmission Maternal varicella pneumonia
Lethal if first trimester
Third trimester- asymptomatic Mgt: administer VZIG to suspected
Intracranial calcification gravid within 96 hrs of exposure

Mgt: Pyrimethamine Sulfadiazine

12
464
4/29/2008

Rubella Cytomegalovirus (CMV)


RNA virus spread through Spread via body secretions
respiratory droplets
Transmission only if primary
infection Life long latency, so fetus can get
Fetus= VSD it on reactivation
Neonate= congenital deafness
Prevention: rubella IgG antibody Periventricular calcification
screening
MCC of congenital deafness
Live attenuated virus- avoid
pregnancy for 1 month after
immunization Mgt: Ganciclovir

Herpes Simplex Virus (HSV) Human Immunodeficiency Virus


Multinucleated Giant Cells
Maternal genital lesion is MC route HIV + mothers take zidovudine
for fetal infection starting at 14 wks until delivery

Dx: + culture from ruptured vesicle C-section for delivery


Prevention: C-section
C section
Breast feeding contraindicated
If membrane already ruptured and it
has been >8-12 hours- too late to
do a C-section Neonate gets AZT for 6 wks, then
check again
Mgt: Acyclovir

Maternal Syphilis infection


Primary- painless ulcer with rolled up
edges (chancre)- gone in 2-3 wks Bleeding
g late
during
Secondary- 2-3 months after contact,
maculopapular skin rash and
condyloma lata

Tertiary- organs affected


Heart- aortitis
Dorsal column- tabes dorsalis
pregnancy
CSF +
Mgt: Vaginal delivery: Benzathine PCN and if allergic
desensitization to PCN

13
465
4/29/2008

Bleeding Abruptio Placenta


Initial evaluation: Painful bleeding
Maternal : check vitals
Fetus: FHT Overt (external) Concealed (internal)

Mgt: large bore IV NS


Foley- monitor output

If fetal jeopardy is present or +/- 36


wks- deliver

Types of Abruption Mgt. of Abruptio


Mild- no fetal abnormality
Emergency Cesarean if mother or
Moderate- 25 – 50% surface fetal jeopardy
separation
Monitor
o to for
o late
ate D-cells
ce s Vaginal delivery if bleeding is
controlled or > 36 wks
Severe- abrupt, knife like uterine
pain Conservative (in hospital)
> 50% placental separation Stable and remote from term
DIC may occur Confirm placental location on sono
Severe late D-cells Replace fluids

Placenta Previa Mgt. for Placenta Previa


Painless bleeding Emergency Cesarean if mother or
fetal jeopardy
Placenta is implanted in lower
uterine segment Vaginal delivery- lower placental
edge must be > 2cm of os
Common early in pregnancy
(migration) Scheduled C-section
Fetal lung maturity by amniocentesis
3 types:
Total, complete or central- covers os Conservative (in hospital)
Partial- partial cover of os Bed rest, preterm, confirm placental
Marginal, low lying- near os location

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Complications of Placenta Previa Vasa Previa


Fetal vessels transverse the internal OS
Villi may invade uterine tissue
Bleeding from fetoplacental circulation

Rapid fetal exsanguination


Endometrium
Placenta
accreta 75%
Due to amniotomy (AROM)

Myometrium Placenta Increta


20% Triad:
ROM
Painless vaginal bleeding
Placenta Fetal bradycardia
Serosa
percreta 5%
Mgt: immediate C-section
Bladder

Uterine Rupture
Triad:

Obstetrical
Painful bleed
Loss of FHT
Head floating

MCC- classical incision


MCC Complications
p
Myomectomy

Excessive oxytocin

Mgt: surgical

Abortion vs fetal demise Fetal demise (>20 wks)


Fetal death prior to 20 weeks: Most serious consequence…
Abortion
- Missed
DIC (disseminated intravascular
- Threatened coagulation)
- Inevitable
- Incomplete Usually takes 3-4 wks to occur
- Complete
Release of thromboplastin from
After 20 weeks: fetal demise deteriorating fetal organs
Must report to the state
Do not deliver until mom is ready as
long as there is no DIC

15
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4/29/2008

Twin Delivery Rho GAM


Pooled anti-D IgG
Vaginal C-section ?

Passive antibodies (IM)


B
B B IIgG
G antibodies
tib di attach
tt h to
t the
th
A A
A
foreign RBC and lysis occurs
before mom can produce an
immune response
Both A- breech A- cephalic
Cephalic B- cephalic B- breech

RhoGAM given at… Kleihauer Betke Test


Give to Rh(D) negative mothers at Quantitates fetal RBC’s in mom’s
28 weeks blood

Within 72 hours of Looks at a peripheral smear


Chorionic villus sampling
Amniocentesis
Rh+ delivery
Will access if more than one vial is
D&C
needed

Give 300 micrograms (1 vial)

Premature Rupture of Membrane


Diagnosis PROM
(PROM)
Sterile speculum
Risk of ascending infection
Pooling – clear fluid in posterior
vaginal fornix
History of sudden gush of copious
vaginal fluids
Nitrazine p
positive ((turns p
paper
p blue))

Oligohydramnios on Utz. Fern test- on microslide

Chorioamnionitis:
Maternal fever
Uterine tenderness
Confirmed PROM

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468
4/29/2008

Management PROM Preterm Labor


3 criteria:
Uterine contractions present Between 20 and 37 weeks
(don’t use tocolysis)
Uterine contractions (3 in 30 min.)

Chorioamnionitis IV antibiotics,
Chorioamnionitis-
Cervical changes
delivery (dilation changes > 2cm)

No infection
< 24 wks- dismal outcome
>24- bed rest, IM betamethasone, 7 day
prophylaxis of ampicillin and
erythromycin

Tocolytic Agents Types of Tocolytics


Prolong pregnancy for up to 72 hrs MgSO4- blocks Ca2+
Monitor: DTR
IM betamethasone to work Antidote: IV calcium gluconate
Contraindications: renal insufficiency, MG

Transport mother/fetus to neonatal


intensive care Beta adrenergic agonist- terbutaline,
ritodrine

Given parenteral
Ca2+ blockers- Nifedipine, Procardia

PG inhibitors- Indomethacin

Post Date Pregnancy


Worried about placental breakdown
HTN during
p g
pregnancyy
Fetus not getting the O2 it needs

Meconium risk

42 wks maximum time in uterus

Shoulder dystocia

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4/29/2008

Preeclampsia: Eclampsia

Mild Severe Unexplained grand mal seizures


with…
HTN
B/P
Proteinuria
> 20 wks gestation
Proteinuria
Severe diffuse cerebral
Gestation vasospasms

Mgt.

Mgt. of Eclampsia HELLP Syndrome


5-10% of preeclamptic patients
First protect the mothers airway H- hemolysis
EL- elevated liver enzymes
IV MgSO4, with IV bolus of 5g to stop LP- low platelets
seizure
Mgt. prompt delivery at any age
Maintenance dose 2g/hr

Deliver at any gestational age

Lower diastolic B/P to 90-100mmHg

Fetal Presentation Station in delivery


Cephalic- head presents first

Breech- feet or buttock first


Frank (vaginal delivery)- sucking on
toes
Complete
Footling

Compound- more than one body part


present

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4/29/2008

Overview of Labor Cardinal Movement in Labor

Uterine changes: Engagement


Contraction of upper uterine segment Descent
Exerting expelling forces Flexion
Internal rotation
Cervical effacement: Extension
Thinning due to oxytocin and PGE2 External rotation
breaking disulfide bonds in collagen
fibers
Expulsion

Normal cervix: 2cm long/ 2cm wide

Stages of Labor
Stage 1: onset of uterine contraction

Abnormal
and ends with complete dilation
Latent- cervical dilation up to 20 hrs (3-4 cm)
Active – rapid cervical dilation (1.2 cm/hr)

Stage 2: complete cervical dilation to

L b
Labor
delivery (2 hrs)

Stage 3: delivery to placental expulsion


(30 min)

Stage 4: observation of mother for


preeclampsia and post partum
hemorrhage

Prolonged Latent Phase Prolonged Active Phase or Arrest


Cervical dilation > 3cm…
Cervical dilation <3cm for…
Prolonged dilation < 1.2 cm for > 2h
> 20hrs primipara
> 14 hrs multipara
Passenger problem: size or
orientation
MCC iinjudicious
j di i analgesia
l i
Power problem: inadequate uterine
Mgt. Therapeutic rest contraction

Hypotonic muscle- IV oxytocin


Contraction normal- go to C-section

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471
4/29/2008

Prolonged 3rd stage Prolapsed Umbilical Cord


Placenta has not delivered within 30 Obstetric emergency
min
Cord gets compressed affecting
If it does not remove with IV fetal oxygenation
oxytocin,
y , then think accreta ((etc.)) Occult- head and uterine wall
Partial- head and cervical os
Complete- protruding into vagina
Mgt. manual removal or
Hysterectomy
Mgt. Knee-chest position
Elevate presenting part
Immediate C-section

Shoulder Dystocia Cesarean Section


Maternal mortality and morbidity is
Delivery of fetal shoulder is
higher than vaginal delivery
delayed after delivery of head

Hemorrhage : > 1000 ml


Impacted of pubic symphysis

Infection
Mgt. suprapubic pressure
McRoberts maneuver- thigh flexed
Woods corkscrew- internal rotation Visceral injury: bowel, bladder
Manual delivery of posterior arm
Thrombosis- DVT

Uterine Incisions Cervical Ceretage


Pt’s with incompetent cervix
Lower segment transverse
(pull bladder down) Shirodkar- beneath cervical
mucosa- left in place with deliver
of C-section
Fetus must be in longitudinal lie

McDonald- removed by 36 wks for


Cut non-contractile portion of uterus vaginal delivery

Can still have VBAC Placed at 14 wks, before cervical


(vaginal birth after c-section) dilation and effacement occur

20
472
4/29/2008

Post Partum Fever


PP day 0: Atelectasis
PP day 1-2: UTI Gynecologic
Neoplasia
PP day 2-3: Endometritis
PP day 4-5: Wound infection
(antibiotics and drain)
PP day 5-6: Septic thrombophlebitis
(IV heparin 7-10 days) and Cancer
PP day 7-21: Infectious mastitis
(oral cloxacillin and continue
breast feeding)

Human Papilloma Virus (HPV) PAP test


Screening for premalignant lesions
16, 18, 31, 33 and 35 Transformation zone (T-zone)
Premalignant squamous/columnar
Cancerous
3 years after onset of sexual
activity
act ty o
or 21 y/o
6,11
6 11
Benign condyloma acuminata
Discontinued >70 with 3 negative
pap’s

< 30 y/o annually (2 yrs liquid based)


> 30 every 2-3 yrs after 3 (-) pap’s

Bethesda System Diagnostic Approach


Negative- no malignancy Accelerated repeat PAP: ASC-US

ASC- atypical squamous cells HPV-DNA testing: ASC-US

LSIL low grade squamous intraepithelial


LSIL- Colposcopy abnormal pap
Colposcopy-
lesion (HPV or CIN I) (acetic acid)

HSIL – high grade squamous intraepithelial Endocervical curettage (ECC)- r/o


lesion ( CIN 2,3, moderate dysplasia) endocervical lesion [not in pregnancy]

Cancer- invasive Cone biopsy- PAP worse than histological

21
473
4/29/2008

Mgt. according to histology Invasive Cervical CA


Observation: CIN I, repeat pap 6-12 Penetrated through basement
months membrane

Ablative: CIN 1, 2, 3: Cryotherapy Postcoital vaginal bleeding

Excisional: CIN 1, 2, 3: LEEP (loop Dx. Cervical biopsy- sq. cell CA


electrosurgical excision), cold
knife
Mgt. Hysterectomy
Hysterectomy- recurrent CIN 1,2,3

Cervical Neoplasia in Post Menopausal Bleeding


Pregnancy
Menopause- after 3mo or cessation
Pregnancy does not change of menses
progression
Endometrial carcinoma (MCC)
p g
Test female same as non-pregnant
Skip ECC- cervix more vascular
Unopposed estrogen

Invasive CA:
Dx: Endometrial sampling
<24 wks: hysterectomy
> 24 wks: wait until 32-33 wks, then
C-section and hysterectomy Mgt: Positive histology: TAH & BSO

Enlarged Uterus Enlarged Uterus


Leiomyoma: Adenomyosis:
Benign smooth muscle of the Ectopic endometrial glands and stroma
myometrium located within the myometrium of the
uterine wall

More common in black females Tender uterus in absence of pregnancy


p g y

Mgt. Observation Dx. Utz or MRI


Presurgical shrinkage 3-6 mo GnRH analog
Myomectomy Mgt. Levonorgestrel intrauterine system
Embolization
Hysterectomy
Definitive : Hysterectomy

22
474
4/29/2008

Premenopausal Adnexal Mass

Ovarian
Simple Cyst- luteal or follicular
Complex cyst- dermoid (germ layers)

Neoplasia
Dx. hCG levels to rule out pregnancy:
Sonogram

Mgt.
Simple cyst- observation, OCP’s,
(>7cm laparoscopic)

Complex cyst- surgical removal

Adnexal Mass With Pain Prepubertal Adnexal Mass


Sudden onset of severe lower Functional ovarian cyst not
abdominal pain in presence of possible because ovarian
adnexal mass….”Ovarian torsion” follicles are not functioning

Mgt. untwist p
Suspicious of neoplasm
p
Observation to assure revitalization
Routine exam annually Dx. Tumor markers…
LDH- dysgerminoma
Beta HCG- Choriocarcinoma
Alpha fetal protein- endodermal sinus
tumor

Postmenopausal Adnexal Mass Classifications


Ovaries should be atrophic Epithelial tumor (80%)- post menopausal
MC serous
Any enlargement, should draw
suspicion of ovarian cancer Germ Cell tumor (15%)- teenagers
MC dysgerminoma

BRCA-1
Stromal tumor (5%)
Granulosa cell tumor- increased estrogen

Metastatic tumor- Krukenberg


stomach to ovary

23
475
4/29/2008

Vulvar Intraepithelial Neoplasia


Vulvar Neoplasia
(VIN)
Vulvar lesion with pruritus
Vulvar itching Squamous dysplasia

Squamous hyperplasia
((whitish focal area)) Mgt. surgical excision
Mgt. corticosteroids

Lichen Sclerosis
(bluish-white papule)
Parchment like
Mgt. testosterone cream

The
End

24
476
10/13/2008

 “Trauma" refers to a serious


or critical bodily injury,
wound, or shock, as from
violence or accident.

Immediately life- Potentially life-


threatening injuries threatening injuries
Simple
Airway obstruction
pneumo/haemothorax
Tension pneumothorax Aortic rupture
Open pneumothorax Blunt cardiac injury
Massive haemothorax Pulmonary contusion
Flail chest Tracheobronchial rupture
Cardiac tamponade Diaphragmatic rupture

477
1
10/13/2008

SIGNS & SYMPTOMS: (Your CLUES)


1. No, weak, noisy, labored or gurgled respiration
OBTAIN HISTORY OF:
2. Pale, cool, clammy skin; delayed capillary refill 1. PMH/Meds/Allergies
3. Irregular/unstable vital signs 2. Mechanism of injury/weapon description
4. Contusion, abrasion, laceration, hematoma 3. Use of protective devices: helmets, seatbelts,
5. Pain, tenderness, guarding, numbness/tingling airbags, padding
6. Bruising, swelling, deformity, false/limited motion 4. Substance abuse
7. Muscle weakness/paralysis, loss of sensation 5. Estimated blood loss at scene
8. Altered mental status 6. Time of injury
9. Asymmetric pupils, JVD, incontinence 7. Loss of consciousness

STABLE or UNSTABLE UNSTABLE

 The Famous “A B C’s”  The Famous “A B C’s”


- Airway In the vignette:
- Breathing
- Circulation - GET RID OF DISTRACTORS!
- Look for Pt. Stability and
decide:

478
2
10/13/2008

 The Famous “A B C’s”  Case:


 25 y/o man falls from a tree. At the moment
In the vignette: he is unconscious. His breathing is difficult
and his mouth is full of blood. His arm has an
unusual angle and there’s laceration in his
- GET RID OF DISTRACTORS! forehead and chest. What is the best next
step?
- Look for Pt. Stability and
decide:

 Case:  AIRWAY:
 25 y/o man falls from a tree. At the moment What to check?
he is unconscious. His breathing is difficult -No, weak, noisy, labored or gurgled respiration
and his mouth is full of blood. His arm has an -Abnormal, silent or low voice or uncompleted
unusual angle and there’s laceration in his sentences while talking
forehead and chest. What is the best next - Unconsciousness
step?

 AIRWAY:  AIRWAY:
Then: Administer air ANYHOW! Then: Administer air ANYHOW!

- Mask w/ 100% O2 - Mask w/ 100% O2


- Orotracheal intubation
- Cricothyroidotomy

479
3
10/13/2008

 AIRWAY:  AIRWAY:
Then: Administer air ANYHOW! Then: Administer air ANYHOW!

- Orotracheal intubation - Cricothyroidotomy

 AIRWAY:  AIRWAY:
Then: Administer air ANYHOW! Possible causes: (If diagnose is asked)
How to choose? - Foreign object
Rules: - Body fluids (blood, vomit)
- Swelling of trachea, epiglottis,
1.-Use less invasive first
tongue, uvula, etc
2.-Follow the order if the patient - Disruption of airway (direct trauma)
has been started but - Anesthesia, drugs
oxygenation didn’t succeed - Head trauma
(Check PULSE OX. <90)

 Case:  Case:
 25 y/o man falls from a tree. At the moment  25 y/o man falls from a tree. At the moment
he is unconscious. His breathing is difficult he is unconscious. His breathing is difficult
and his mouth is full of blood. His arm has an and his mouth is full of blood. His arm has an
unusual angle and there’s laceration in his unusual angle and there’s laceration in his
forehead and chest. In the ambulance the forehead and chest. In the ambulance the
patient is intubated successfully. Physical patient is intubated successfully. Physical
Examination: Loud blow sound in the left Examination: Loud blow sound in the left
when ambu is compressed. What is the best when ambu is compressed. What is the best
next step? next step?

480
4
10/13/2008

 BREATHING:  BREATHING:
What to check? Then: CORRECT (Depends in vignette)
-Symmetry of air flow - One side airflow - Re-direct tube
-Is air going to lungs actually? - Crepitus peri resp. - Other way of ventilat.
-Breath automatism - Pulse Ox. Low - Other way of ventilat.
-OVERVENTILATION - Air outside lungs - Re-diagnose
-Crepitus in peri respiratory system

 BREATHING:  Case:
Possible causes:  19 y/o unmarried, at term pregnant woman
- Bad technique has a MVA 30 minutes ago. She is able to
- Flail chest answer the anamnesis and is lucid. At the
- Cardiac tamponade moment she is crying, and seeks for
companion, she is very worried about the
- Rupture of airway, thorax, baby because she doesn’t feel movements
diaphragm or arthery (hemo, anymore and ask for the mother to be called.
pneumo thorax) Temperature is 37C, Pulse 102’m, BP 60 over
- Under ventilation 40. Fetal signs negative. What is the best next
step?

 Case:  CIRCULATION:
 19 y/o unmarried, at term pregnant woman  What to check?
has a MVA 30 minutes ago. She is able to -History of profuse bleeding
answer the anamnesis and is lucid. At the
moment she is crying, and seeks for -Hypotension
companion, she is very worried about the -Pale, cool, clammy skin
baby because she doesn’t feel movements -Delayed capillary refill
anymore and ask for the mother to be called.
Temperature is 37C, Pulse 102’m, BP 60 over
40. Fetal signs negative. What is the best next
step?

481
5
10/13/2008

CIRCULATION: CIRCULATION:
What to check? Then: Restore volume ASAP
-History of profuse bleeding 1.Two IV lines (16-Gauge)
-Hypotension 2. Plenty liquids:
-Pale, cool, clammy skin Ringer lactate
- Dry mucosas (Tounge, no tears) Normal saline
- Depresed fontanelles (children) Blood
-Delayed capillary refill 3. If not enough, third line in
saphenous vein
4. Children <4y/o Intraosseus in tibia
or frontal

CIRCULATION:  CIRCULATION:
Then: Control of hemorrhage Possible causes:
- Direct pressure - Trauma in abdomen or thorax (not in
cranium, not enough space to cause
- Clamping artery shock)
- Curettage if obstetric - Bleeding (obstetric, big wounds)
- Dehydration (deprivation)
- Hyper urination (DI, diuretic overuse)

 SHOCK GENERAL:
DUE TO SKIN CO SVO2 SVR PCWP
SEPTIC BACT. WARM HIGH HIGH LOW LOW 1) All Trauma Patients: CS, Chest, Pelvic XR
TOXIN
2) If unstable, proceed to laparotomy
VOLUME BLEEDING PALE LOW LOW HIGH LOW
LIQ. DEP COLD 3) If abdomen cannot be examined: CT scan
of abdomen and pelvis w/ oral and IV
CARDIO HYPO PALE LOW LOW HIGH HIGH
Contrast
MOTILITY COLD
4) Gunshot in abdomen: Laparotomy
NEURO VAGAL WARM LOW LOW LOW LOW
REFLEX

CO: Cardiac Output


SVR: Sistemic Vascular Resistance
SVO2: Systemic Venous Oxigen
PCWP: Pulmonary Capilary Wedge Pressure

482
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10/13/2008

BEST WAY ORGANIZATION:

From HEAD TO TOES

 EPIDURAL HEMATOMA:  EPIDURAL HEMATOMA:


- Bleeding between skull bone and - Anisocoria
dura mater - Bi-concave hematoma
- Rupture of Middle Meningeal Artery
- Tx:
- PROGRESSION:
1. After trauma, only image
- Unconciusness
w/o symptoms at all: OBSERVATION
- Lucid interval
- Coma 2. Symptoms & Immage:
EMERGENCY SURGERY

 EPIDURAL HEMATOMA:  SUBDURAL HEMATOMA:


-Bleeding between dura mater and
arachnoides
- Rupture of veins crossing subdural
space “Bridging veins”
- Image: Concave hematoma

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 SUBDURAL HEMATOMA:  SUBDURAL HEMATOMA:


- SEEN TYPICALLY IN:
Elderly, demented, alcoholics

- Tx: 1.If small and no symptoms:


OBSERVATION
2. Affect mental status:
SURGERY

 SUBARACHNOID HEMORRHAGE:  SUBARACHNOID HEMORRHAGE:


- Bleeding between arachnoides and - “MOST SEVERE EVER” headache.
pia mater. - Leaves sequelae like epilepsy,
- MCC: TRAUMA followed by Ruptured blindness
Berry Aneurism (HTN) - IF VIGNETTE LOOKS FOR Dg:
- Blood is seen in ventricles and NEVER USE CONTRAST
around brain (NOT IN BRAIN)

 SUBARACHNOID HEMORRHAGE:  SUBARACHNOID HEMORRHAGE:

Tx: If due to anaeurism or AV


malformation, SURGERY -No mases
Otherwise: Support, observation or -No ventricules
-Deviation
anti-convulsivats if needed.

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 INTRACEREBRAL HEMORRHAGE  INTRACEREBRAL HEMORRHAGE


-Bleeding into brain parenchima - Tx: Surgery is reserved for large
typically in basal ganglia. bleedings if they are accesible.
-Due to Trauma, HTN, tumor.
- IF VIGNETTE LOOKS FOR Dg:
NEVER USE CONTRAST

 INTRACEREBRAL HEMORRHAGE WHEN DO WE DECIDE FOR


SURGERY IN ANY CASE?

WHEN CT scan OR MRI SHOW


DEVIATION OF MIDDLE
LINE

DIRECT HEAD TRAUMA: CONSECUENCE:


CONSECUENCE:
1
- Open or close head injury
- Increased Intracranial Pressure
2 - Reversible or Irreversible neuronal
3
damage
- DEAD

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What to do next? What to do next?


- After ABC’s finish PE w/ Glasgow - Elevate head
scale - Intubate and hyperoxigenate
- Look for signs of Intracranial - Lower CO2
Hypertension: - Mannitol
- Decrease in the comma scale - Sedation
- Anisocoria
- Signs of decerebration

After stabilization: DIFUSE AXONAL INJURY


- High speed injury with stretching or
- CT scan shearing of brain tissue
- XR of skull (look for fractures) - Immage shows petechial hemorrhages in

- If Open Wound (clean and close) white matter tracts


- Associated with immediate deep coma,
cerebral edema and elevation of ICP
- High mortality

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DIVIDED IN TWO: WHAT TO DO IN BLUNT TRAUMA:

- BLUNT TRAUMA - If UNSTABLE: -EXPLORE


Respiratory compromise
- PENETRATING TRAUMA Hematoma
Shock

WHAT TO DO IN BLUNT TRAUMA: WHAT TO DO IN PENETRATING TRAUMA

- If STABLE: -Look for other symptoms


If patient OK then - Decide which ZONE is compromised
REASURANCE

IF ZONE I & III

UNSTABLE:
Neck’s base to mandible’s angle III
1)A, B, C always first!
2) Surgical exploration
Mandible’s angle to Cricoid II

Cricoid to Clavicle I

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IF ZONE I & III IF ZONE II

STABLE: UNSTABLE:
1) Endoscopy of: Respiratory tract 1)A, B, C always first!
Esophago/Gastro
2) Surgical exploration
Artheries
Always explore if
2) Reassurance if nothing found
musculocutaneus platysma is
affected

IF ZONE II IF ZONE I & III


UNSTABLE:
STABLE:
1) Endoscopy if hoarseness/hematoma:
Respiratory tract
Musculocutaneus Esophago/Gastro
Platysma Artheries
2) Reassurance if nothing found

PROBLEM MISCELANEUS SYMPTOM (CLUES) TEST TREATMENT

Rib Fracture MCC of injury History CXR Pain medication


Elderly Pain w/ resp.
Fall Hematoma/open
wound
Costochondral
junction middle
and lower ribs

Flail Chest 4 or more ribs Major trauma CXR Anesthesia and rib
fractured in 2 Caves during blockage, positive
places respiration and ventilation and high
bulges in oxygen (avoid
expiration barotrauma) surgical
stability not required

Cardiac Liquid between Trauma, URI Echocardiogram Pericardiocentesis,


tamponade heart and Tachycardia pericardial window
pericardium, CA Hypotension
Pulsus paradoxus
JVD

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PROBLEM MISCELANEUS SYMPTOM (CLUES) TEST TREATMENT PROBLEM MISCELANEUS SYMPTOM (CLUES) TEST TREATMENT

Aortic rupture Violent trauma, Look for wide If CRX not Surgery
Pericarditis Inflammation of URI CXR, Treat cause, NSAIDS,
deacceleration mediastinum in conclusive and
pericardium Friction rub echocardiogram, pericardiocentesis,
CRX suspicious is
EKG, CK MB (rule pericardiostomia
high, CT scan or
out MI), ESR very
transesophageal
high
echo
Pleuritis Inflammation of URI, CA, LES, RA, CBC, Treat cause, NSAIDS
Pulmonary Violent trauma With flail chest or CT scan, look for Fluid restriction and
(Pleuresy) pleura Irritants (asbestos), thoracocentesis,
contusion rib fracture, but atelectasia oxygen. Prolonged
Drugs CXR, Chest echo
crackles symptoms possible
Stabbing pain
ARDS
during inspiration
Cardiac Violent trauma, Abnormalities in EKG Supportive
contusion CPR ventricle to Echocardiogram EKG monitorization
Tracheal/ Violent trauma Trauma, gunshot, X-rays, CT scan Object: rigid fiber optic contract
Bronchial infection, object bronchoscopy to EKG right bundle
rupture Cough w/blood retrieve object branch block)
Gas under need Others: Surgery Sinus tachycardia
skin of neck, chest if big plus chest tube w/ Ventricular
suction dysrhythmia

PROBLEM MISCELANEUS SYMPTOM (CLUES) TEST TREATMENT

Trachea Expansion Breath Sounds Percussion

Hemothorax Trauma, CA, Respiratory failure CXR Treat the cause


thorax surgery TachycardiaAnxiet Thoracocentesis Stabilize, Stop bleeding, Decreased.
Tension Diminshed or
y Analysis of fluid Thoracic tube, Away Chest may be fixed Hyper-resonant
Pneumothorax in hyper-expansion
absent

May be hyper-
Simple
Pneumothorax Trauma Sudden sharp pain CXR, ABG Treat the cause, drain Midline Decreased May be diminished resonant. Usually
(spontaneus) on respiration, gas w/ needle if
Pneumothorax normal
Tachycardia, emergency and later w/
cianosis, nasal thoracic tube
flaring, no air Diminished if large. Dull, especially
Haemothorax Midline Decreased
movement Normal if small posteriorly

Pulmonary Normal. May have


Midline Normal Normal
Contusion crackles
Diaphragmatic Trauma, only in Sounds of bowel in CXR, Barium Surgery
rupture left side thorax (left) or no swallow
air in left lung Lung collapse Towards Decreased May be reduced Normal

CARDIAC TAMPONADE
PNEUMOTHORAX

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AORTIC DISECTION BRONCHIAL RUPTURE

INSPIRATION EXPIRATION

DIAPHRAGMATIC RUPTURE FLAIL CHEST

ACUTE ABDOMEN: Sudden, severe


abdominal pain that is less than 24
hours in duration

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IMPORTANT POINTS: ALWAYS LOOK FOR CLUES:

1) NPO to reduce risk of aspiration 1) How and why of pain, how often
2) NG tube to decompress abdomen 2) Time of iniciation (cronic or acute)
3) IV hydration/ secure via 3) Localization and Progresion
4) Analgesia (meperidine) 4) Irradiation
5) Abdominal X-RAY 5) Scale of pain and type
6) AGE, GENDER

PROBLEM MISCELANEUS SYMPTOM (CLUES) TEST TREATMENT


DIFFERENTIAL DIAGNOSIS
Appendiscitis Inflamation of First periumbilical CBC (infection) Laparoscopy, PROBLEM SYMPTOM (CLUE) TEST
apendix, young and then iliac Normally clinical, laparotomy
people. fossa (migration) and only atypical Biliary colic Cystic duct blocked. Sharp and constant pain LFT WNL. Ultrasound
Causes: Tender Mc. cases CT scan or without fever. Negative Murphy's sign.
Inflamation Burney’s point, ultrasound to rule
Fecalith Rovsing’s sign, out ectopic
Parasite Obturator sign, pregnancy or
Cholecystitis Cystic duct blocked with infection. Colicky Increased AST, ALT, AP,
Trauma Psoas sign, fever, pregnant ladies
brief pain at first, then constant pain in RUQ WBC.
Complication: anorexia and
with fever caused by E coli, klebsiella, Ultrasound
peritonitis vomit
pseudomonas, B fragilis, enterococcus.
Murphy's sign positive.

Choledocholithiasis Common bile duct blocked. Colicky pain. Increased bilirubin.


Cholecystitis Due lith in Famous FFF’s ALK Phos. If acute: surgery Jaundice. Cholangiogram, ERCP
cystic duct Pain after fatty Elevation, CBC, If septic shock:
leading to stasis meals radiate to Ultrasound. Best percutaneus
shoulder diagnosis is CT drainage
Cholangitis Infection of entire biliary tract. Charcot's triad. Increased AST, ALT, AP,
scan. HIDA if If not acute:
Jaundice and fever bilirubin. Cholangiogram
suspect and elective surgery
negative US

PROBLEM MISCELANEUS SYMPTOM TEST TREATMENT PROBLEM MISCELANEUS SYMPTOM (CLUES) TEST TREATMENT
(CLUES)

Pancreatitis Peptic ulcer perforation Epigastric pain High Sens: If cyst> 5Cm
Alcohol radiating to the Amylase Dranaige Diverticuliti Older people w/ Left Lowe Q pain, CT scan, No First episode: IV
Neoplasm back (belt) High Spec: If due to s diverticulosis becames leucocitosis, fever enemas or fluids and
Cholelithiasis, CF Cullen’s sign: Lipase obstruction: ERCP inflamed and contrast antibiotics
Renal Dz Periumbilical CT Scan Pancreatic CA: perforated(bulging of Subsequent:
ERCP Turner’s sign: Surgery bad prog colon walldue to Surgery
Anorexia Flanks weakness) low fiber diet,
Trauma family history.
Infection
Toxins: Prils, HIV, ASA
Incinerations
Scorpion bite Ectopic Prior PID Acute L R or L Q Positive pregnancy laparoscopy and
Pregnancy pain, acute, test, Ultrasound laparotomy
maybe shock for evidence
Intestinal Due to Shock, Atrial fib. Bowel Neutrophilic Surgery (rupture)
Ischemia Hypercoagulable state distention, and leucocitosis (left) localized in area.
Watershed area SMA and bloody diarrhea, increase amylase. Vaginal bleeding,
IMA pancreatic flexure bowel sounds CT scan Air in cullen sign
will be absent bowel and
inflamation of
watershed area

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PROBLEM MISCELANEUS SYMPTOM TEST TREATMENT


(CLUES)

Peritonitis Inflamation of peritoneum Pain, tenderness CBC leucocitosis Stabilization with


due to perforation and guarding, Plain AXR, IV liquids, correct
rebound edematous acidosis and
Complication of vicerae, air. Lavage electrolite
rupture of if doubt imbalance,
viscera Surgery,
antibiotics broad
spectrum

Volvulus Malrotation of midgut, Bowel Abdominal X-ray, Surgery, correct


obstruction and upper GI series rotation, if
distension and
vomitus. No
necrosis resection
of portion.
PANCREATITIS
passage of
gases, intestinal
silence.

APPENDISCITIS CHOLECYSTITIS

PELVIC FRACTURE:

PERITONITIS

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PELVIC FRACTURE:  HAND

1) Stabilize patient
2) Military Antishock Trousers
3) Fixate externally
4) If blood loss, Embolize

 HAND:  HAND:

Sacaphids: Avascular necrosis

Hamate: Rupture of hook, nerve damage


(Ulnar)
BOXER’S FRACTURE

Tx:
Mild: Immobilize
Severe: Surgery w/ pins

 ARM:  ARM:

◦ Tx:
- Alignement
- Analgesia
- Close reduction: No complication, no skin break
- Open reduction: Intra-articular fracture is displaced
ORIF Closed reduction was ineffective
Fracture traverses a cancerous lesion
When prolonged immobility
- Surgery: If artery damage is suspected

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- COMPARMENT SYNDROME: - COMPARMENT SYNDROME:

 Due to inflamation of tissues


underneed the skin or fascia
 Nerve and circulation compression

OPEN THE AREA!

- GANGRENE: - GANGRENE:
Infection due to deep entrance of
bacteria to body (diabetic foot, nail)

AMPUTATION!

- OPEN FRACTURES: - OPEN FRACTURES:


1) Clean the area w/ saline and
pressure
2) Verify if nerves or circulations are
intact
3) If < 6 hours, SUTURE AND REDUCT
IN OR

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- DISLOCATION OF HIP: Shorten leg, - DISLOCATION OF HIP:


un-anatomical position.

1) Correct position
2) Emergency Reduction

FEVER: NEUROLOGICAL:
-Hypoxia
DAYS Famous W LUIDA CAUSE
ARDS
DAY 1 WIND LUNGS Pneumonia, Post- anesthesia
Atelectasis
DAY 3 WATER URINE UTI
-Delirium Tremens
DAY 5 WOUND INFECTION S. Aureus -Water intoxication: HypoNA
DAY 7 WALK DVT
DAY 10 WONDER WHY Abscess
HyperNA

NEPHROGENIC: ABDOMINAL:
-Post Surgery Urinary Retention
-Hypovolemia - Paralysis of intestine (Ogilvie Synd)
-Clamping of ureter - Adhesions
- Paralytic Ileus due to Anesthesia

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INFECTION:  Do you understand that ABC’s always


is first?
1)Find the cause with multiple culture  Can you do differential diagnosis?

2) Antibiotic Therapy  Do you know what to do first?


 Do you have a sequence of thinking?
 Do you know basically the treatment?
 Are you consistent with your thought
process?

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ANTIBIOTICS
What is an antibiotic?
An agent that inhibits the growth or multiplication
of, or kills, a living organism; usually used in
reference to bacteria or other microorganisms.

Who invented them?


Alexander Fleming, in 1928 is the one who
purified PENICILLIN. THE CAT?
PURE LUCK?

Who is the genius?

Of course not…
OR

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BASIC PRINCIPLES TYPES OF


FOR ANTIBIOTICS
PHARMACOTHERAPIE
„ CellWall Inhibitors
„ Learn MOA
„ Protein
P i Synthesis
S h i IInhibitors
hibi
„ Learn SIDE EFFECTS
„ Metabolite Inhibitors
„“Don’t kill a mosquito with a gun”
„ Special Function Inhibitors
„ Cost – Benefit’s law

CELL WALL INHIBITORS Where do you get the molds?


1.-- Penicillin
1.
- Oxa
Oxa,, cloxa dicloxa,
dicloxa, nafi
nafi-- CILLIN
- Ticarcillin
- Aztreonam
2.-- Cephalosporins
2.
3.-- Carbipenems
3.
4.-- Vancomycin
4.

1.--PENICILLINE
1. 1.--PENICILLINE
1.

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1.--PENICILLIN
1. 1.--PENICILLINE
1.
1.
1.-- Binds to PBP 1.
1.-- Binds to PBP

2 - Disrupt cell wall


2.-
2.

3.
3.-- Provoke apoptosis

1.-- PENICILLIN
1. 1.--PENICILLIN
1.

2.
2.-- Disrupt cell wall

3.
3.-- Provoke apoptosis

1.--PENICILLINE
1. 1.--PENICILLIN
1.
What does it
kill?
Staph. Aureus Bacillus
Staph. Epidirmidis Clostridium
Staph. Saprophiticus Klebsiella
Strep. Pneumoniae Neisseria
Strep. Pyogenes Citrobacter
Strep. Sanguis P. Auroginosa
Strep. Mutans H. Influenza B
Strep. Agalactiae Actinomyces israelii

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1.--PENICILLIN
1. 1.-- PENICILLIN
1.
…Or, if you don’t remember: „ Side effects:
1.- Typical: Anemia, Vomiting,
1.-
¾ GRAM + Diarrhea Alopecia
Diarrhea, Alopecia, Photosensitivity
Photosensitivity.

¾ Capsulated bacteria
2.-- Special: Allergie
2.

1.-- PENICILLIN
1. 1.-- PENICILLIN
1.
Typical side effects: Resistance:
- Mutate PBP, so drug cannot bind

D to d
Due destruction
i off R
Rapidly
idl - Thicker
Thi k membranes,
b so ddrug
dividing cells cannot get in
- Mutate or destroy the drug with an
enzyme

1.-- PENICILLIN
1. 1.-- PENICILLIN
1.
Oxa, Cloxa,
Oxa, Cloxa, Dicloxa
Dicloxa,, Nafi –CILLIN
1.-- MOA Same as penicillin
1.
2.-- BULKIER - R - Ring
2.

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1.-- PENICILLIN
1. 1.-- PENICILLIN
1.
What does it mean? What do you kill with them?
- Penicillinase can’t bind to
the R group for being huge - Staph.
S h Aureus
A
so the antibiotic won’t get
deactivated and will attach
PBP

1.-- PENICILLIN
1. 1.-- PENICILLIN
1.
Can you kill OTHER gram WHY?
positives and capsulated You could use simple
bacteria? penicillin for that
that…
YES !
Do you kill them w/ Naficillin
Naficillin?? Don’t kill a Mosquito with a gun!
NO !

1.-- PENICILLIN
1. 1.-- PENICILLIN
1.
AMPICILLIN Vs. AMOXICILLIN AMPICILLIN Vs. AMOXICILLIN

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1.-- PENICILLIN
1. 1.-- PENICILLIN
1.
AMPICILLIN Vs. AMOXICILLIN AMPICILLIN Vs. AMOXICILLIN
Ampicillin - Ampicillin
Ampicillin:: Adults
- 80% off d
drug deactivated
d i d with
ihP P--450
Amoxicillin - Amoxicillin: Children
- Gets ACTIVATED with P- P-450 Liver failure

1.-- PENICILLIN
1. 1.-- PENICILLIN
1.
AMPICILLIN Vs. AMOXICILLIN AMPICILLIN Vs. AMOXICILLIN

A
Amoxicillin
i illi + Cl
Clavulanic
l i ac.: MOA SAME
MOA:
To inhibit B
B--Lactamase
SIDE EFFECTS: SAME

1.-- PENICILLIN
1. 1.-- PENICILLIN
1.
AMPICILLIN Vs. AMOXICILLIN Ticarcillin::
Ticarcillin
Bugs to kill:
¾ Gram
G + T kill PSEUDOMONA…
To PSEUDOMONA
¾ Capsulated bacteria

¾ E. Coli?

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1.-- PENICILLIN
1. 1.-- PENICILLIN
1.
Ticarcillin:
Ticarcillin: Ticarcillin:
Ticarcillin:
WHY? WHY?

1.-- PENICILLIN
1. 1.-- PENICILLIN
1.
Ticarcillin::
Ticarcillin AZTREONAM:
For GRAM –
“ Pseudomona
P d i li
is lion attacking,
ki S
Same principle:
i i l “If you wouldld kill
so you need a big riffle to kill it” a Gram+, then use a smaller
SIDE EFFECS: SAME weapon”
SIDE EFFECTS: SAME

2.-- CEPHALOSPORINS
2. 2.-- CEPHALOSPORINS
2.

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2.-- CEPHALOSPORINS
2. 2.-- CEPHALOSPORINS
2.
1st gen + - Cephalexin, cefazolin
MOA: SAME AS PNC
2de ggen + - Cefuroxime, cefotetan
SIDE EFFECTS
EFFECTS: SAME

3th gen + - Ceftriaxone, cefotaxime

4th gen + - Cefepime

2.-- CEPHALOSPORINS
2. 2.-- CEPHALOSPORINS
2.

3.-- CARBAPENEMS
3. 4.-- VANCOMYCIN
4.
“THIS IS A BAZOOKA FOR
TERRORISTS”
„ Inhibitscell wall of ALL GRAM+
IMIPENEM/CILASTATIN
„ MOA: Inhibit cell wall
- To inhibit renal dihidropeptidase mucopeptide formation gen
MOA: SAME D-ala – D-ala
SIDE EFFECTS: SAME „ Resistance: mut.
mut. D-
D-ala to D
D--lac
$ 450 a vial QUID X 10 days…

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PROTEIN SYNTHESIS
4.-- VANCOMYCIN
4.
INHIBITORS
RED MAN SYNDROME:
- Pretreat w/ antihistaminics A good business:
BUY C
-LOWER INFUSSION
A E
30s 50s
T L
L

PROTEIN SYNTHESIS PROTEIN SYNTHESIS


INHIBITORS INHIBITORS

PROTEIN SYNTHESIS PROTEIN SYNTHESIS


INHIBITORS INHIBITORS

OR…

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PROTEIN SYNTHESIS PROTEIN SYNTHESIS


INHIBITORS INHIBITORS
A good business: Chloramphenichol Aminoglucosides:
Aminoglucosides:
BUY Erithomycin -Gentamicin,
Gentamicin, amikacin,
amikacin, streptomycin
Aminoglucosides (Macrolides
Macrolides)) -MOA: Inhibit Initiation co