Decreases atmospheric pressures effect

on the alveoli > PREVENTS

ATELECTASIS
Increases compliance of alveoli
Compliance = change in volume / change
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
Check L / S ratio
Check for phosphatidylglycerol
If both of the above are negative
Beclamethasone
Betamethasone
If baby still born early, then there is synthetic
surfactant that can be applied
When there was NO surfactant
Alveoli would collapse: Atelectasis
> leads to very poor compliance
> increases work of breathing
> weakness and shortness of breath
> oxygen is given
> oxygen has difficult time diffusing across
> oxygen builds up, causing free radical
formation > alveoli develop hyaline membrane in
order to protect themselves
Restrictive Lung Disease
Have poor
compliance
Have trouble
breathing in
Have poor diffusion
Have increased A-a
gradient
pO2 =low pCO2 =low
pH =high
Develop a secondary
perfusion problem
LOW ENERGY state
LOW VOLUME state
ALL die from heart
failure known as COR
PULMONALE = right
sided heart failure

due to pulmonary
HTN (severe RVH)
Hyaline Membrane Disease
THE FIRST RESTRICTIVE LUNG
DISEASE
88 88
COMPLICATIONS of HMD ( or RLD)
As compliance drops, the need for
pressure support increases
As diffusion decreases, the need for
oxygen increases
More oxygen means more free radicals,
which means more hyaline membrane
Bring in the JET VENTILATOR
Complications, cont
More pressure support can lead to a
PNEUMOTHORAX
Kussmaul sign: increased JVD on inspiration
Pulsus paradoxicus: exaggerated drop in BP
( more than 10mm) or in pulse rate ( more
than 10 bpm)
Loss of pulse and BP
Cyanosis
Hammans sign: subcutaneous emphysema
Pneumothorax
Spontaneous
Traumatic
Asymptomatic
symptomatic
As free radicals traumatize the
AIRWAY
Airway produces mucus to protect itself
Airway thickens
Goblet cell hyperplasia
Airway lumen narrows
Increased REID index
BRONCHOPULMONARY DYSPLASIA
The first obstructive lung disease
Obstructive Lung Disease

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

EVERY lung disease presents with

the SAME signs and symptoms!!!
89 89
Can it really be this easy???
Amniotic Fluid Production
80% is a filtrate of moms plasma
To SUBTRACT:
Swallow ( a reflex)
Digest ( need patent UGI)
20% comes directly from the fetus
To ADD:
Process the swallowed fluid, then add 20%
more than was swallowed, then URINATE
Role of Amniotic Fluid
Main function is shock absorption
Secondary action is to prevent
atmospheric pressure from affecting the
fetus, especially the lungs
Problem with amniotic fluid
POLYHYRAMNIOS
Autonomic dysfunction
( Riley-Day syndrome)
Neuromuscular
disease ( WerdnigHoffman syndrome)
UGI atresia
Esophageal atresia
Duodenal atresia
OLIGOHYDRAMNIOS
RENAL agenesis or
obstruction
Potters Syndrome
When OLIGOHYDRAMNIOS leads to
pressure effects on the fetus ( everything
is flattened)
Will lead to pulmonary aplasia or
hypoplasia due to the positive pressure
90 90
Prune Belly Syndrome
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
It is important to have negative
pressure in the thoracic cavity!
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
From the lips to the glottis
Narrows on inspiration; expands on
expiration
NOT protected by the thoracic cage
Intrathoracic Airway
From the glottis to the alveoli
Expands on inspiration; narrows on
expiration
Protected by the thoracic cage
Has a vacuum surrounding it
91 91
Trachea
Has 16 to 20 C-shaped cartilage rings,
with the opening to the C facing posteriorly
This allows partial collapse of the airway
during swallowing to prevent aspiration
Has three anatomic narrowings
The glottis
Midway: due to anterior compression by aorta
Carina: located at T4 (level of nipple)
Aspiration
If patient is unable to speak, then the
object is lodged in the trachea
LARGE OBJECTS tend to lodge at the
glottis 90% of time
Perform the Heimlick Maneuver
Perform Back Thrusts if less than 2 y/o
If still unable to dislodge the object
Perform emergency cricothyroidotomy
Aspiration, cont
Small objects tend to lodge in the right
lower lobe

 Recurrent RLL pneumonia: R/O FB aspiration

Do inspiratory-expiratory films
Right mainstem bronchus is larger and
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
Evaluation for aspiration
Inspiratory film: all lobes are inflated
Expiratory film: the lobe with the aspirated
object does NOT collapse
Tx: bronchoscopy
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
Upper 1/3 of trachea has squamous cells
Mid 1/3 of trachea is a combination
Main respiratory epithelium is tall columnar
ciliated epithelium
The more you smoke, the longer the zone
of squamous cells
Cilia
Line the entire airway
Beat in one direction > orad
Has the 9 + 2 configuration (9
microtubules surrounding 2 actin proteins)
Need a Dynein arm to have flexibility
Kartageners Syndrome
Dynein arm is defective
An obstructive lung disease

Bronchiectasis
Infertility
Situs Inversus
Lung Sounds
Stridor: narrowing in extrathoracic airway
Wheeze: narrowing in intrathoracic airway
Rhonchi: air moving over mucus
Crackles: collapsed airways popping
open
Surfactant is missing
Alveoli have been scarred down
93 93
Lung Sounds, cont
Decreased breath sounds: space between
alveolus and chest wall is occupied
Dullness to percussion: as above
Increased fremitus: consolidation on same
side or atelectasis on opposite side
Bronchophony, egophony, or e to a
changes: as above
Lung Sounds, cont
Tracheal deviation: towards atelectasis
and away from a pneumothorax
Hyperresonance: pneumothorax on same
side or atelectasis on opposite side
Lung Infections
Croup
Bronchiolitis
Bronchitis
Acute
chronic
Pneumonia
Airway
interstitial
tracheitis
Airway Infections
Epiglotitis: H. Influenza B
Tracheitis: C. Diptheria
Pneumonia
Rusty colored sputum: Strep Pneumonia
Curant jelly sputum: Klebsiella Pneumonia
Sulphur granules: Actinomyces Israelii
Frequent after the flu: Staph Aureus
Malodorous smell or gas formation:
Anaerobes
Interstitial Pneumonias
Atypicals
Chlamydia: from 0 to 2 mo

Mycoplasma: from 10 to 30 y/o

Legionella: over 40 y/o
Fungus
Histoplasmosis: midwest
Blastomycosis: northeast
Coccidiomycosis: southwest

Interstitial pneumonias
Fungus, cont
Paracoccidiomycosis: South America
Aspergillus: moldy hay or moldy basement
Sporothrix: rose thorn
Pneumoconioses
Asbestosis
Silicosis
Bissinosis
berrylliosis
94 94
Interstitial pneumonias, cont
Nocardia: the only G+ that is partially acid
fast
Sarcoidosis: noncaseating granulomas;
large hilar adenopathy; high ACE levels
Lung Masses
Most common MASS in children:
hamartoma
Most common MASS in adults:
granulomas
Most common TUMOR: adenoma
Central Cancers
Squamous Cell Carcinoma: produces PTH
Small Cell Carcinoma
Anaplastic
Located at the carina
Produces 4 hormones:
ACTH: 90%
ADH: 5%
PTH: 3%
TSH: 2%
Peripheral Cancers
Bronchogenic adenocarcinoma
Bronchioalveolar adenocarcinoma

Carcinoid syndrome
flushing, wheezing and diarrhea
Too much serotonin
Measure 5-HIAA in the urine
Large cell adenocarcinoma

Risk factors for lung cancer

 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
Time for the PHYSIOLOGY of the lung!!
95 95
Three PHYSIOLOGIC parts to the lung

Intrathoracic space
Chest wall
Pleural space
Pulmonary vasculature
Pulmonary airway

Lung Volumes
RV: the amount of air left in the lungs AFTER
forced expiration
Can not be physiologically forced out
Maintains some compliance in the airway
ERV: the amount of air that can still be FORCED
out AFTER a normal exhalation
Fills up the dead space; decreases the tidal volume
that you would have to take in
FRC: a combination of RV and ERV
Lung Volumes, cont
TV: the amount of air you take IN during a
NORMAL inhalation effort
IRV: the amount of air you can FORCE
INSPIRE after a normal inhalation effort
TLC: ALL the air in your lungs at the END of a
deep breath ( RV + ERV +TV + IRV)
VC: all the air you can breathe in AFTER forced
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
Beginning: recoil forces of the CHEST
WALL are greater ( 0 to 49%)

 Middle: recoil forces of the LUNG are

greater ( 50 to 99%)
End: the recoil force of the lung EQUALS
the expansile force of the chest wall
Breathing in
FRC: baseline > intrathoraxic pressure is
negative ( - 3 to 5)
TV: intrathoraxic pressure gets more
negative ( -10 to -12)
TLC: intrathoraxic pressure most negative
(-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
Kussmaul sign: increased JVD with
inspiration
Pulsus paradoxicus: exaggerated drop in
BP( more than 10mmHg) or pulse ( more
than 10bpm) on inspiration
Mcc: pericardial tamponade or
pneumothorax
Pericardial Tamponade

Mcc: trauma or cancer

CXR: enlarged cardiac shadow
ECHO: compressed small heart
Tx: pericardiocentesis
If recurrent: put in a pericardial window

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
(1) gravity
(2) less resistance
(3) more oxygen goes to the bottom of the
lungs with each breath
Normal RR = 12 to 16 breaths/min
Q increases on inspiration and decreases
on expiration.
S-2 Splitting
Increases on inspiration due to Increased
pulmonary blood flow
Decreases on expiration due to decreased
pulmonary blood flow
This is why RIGHT sided heart sounds
increase on INSPIRATION
This is why LEFT sided heart sounds
increase on EXPIRATION
Oxygenation
Directly related to DIFFUSION and
PERFUSION
More oxygenation is accomplished at the
bottom of the lungs only on inspiration
Most of oxygenation is accomplished at
the top of the lungs > ALWAYS OPEN!
Ventilation (V)
Inversely related to pCO-2
Definition: patent airway
Measurement: pCO-2 ( on ABGs)
More V to the bottom of the lungs only on
inspiration
Most V at the top of the lungs because it is
ALWAYS PATENT
The Law of V / Q
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

Pulmonary Airway
99 99
Pulmonary Airway Pressure
The Only Pressure That Gets
Positive With Each Breath
How The Brain Monitors Pulmonary
Physiology
Signals from the lungs and chest wall
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
100 100
SINUSES
Maxillary
Ethmoid
Sphenoidal
Frontal
BODIES
AORTIC BODY: found in the arch of the
aorta
Measures pCO-2, pH, and H+ ions
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

101 101
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
102 102
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

Hypoglycemia
Ischemia
Thoracic outlet syndrome
Subclavian steal syndrome

THE END
103 103
And now for a few good CLUES Obstructive Lung Diseases
Bronchitis

Acute
chronic
Bronchiolitis
Asthma
Intrinsic
extrinsic
Cystic fibrosis
Bronchiectasis

Emphysema
Panacinar
Centroacinar
Distoacinar
Bullous
Staph aureus
Pseudomonas

Really! The End!!

104 104
NEUROMUSCULAR
PHYSIOLOGY
I WANT A CONTRACT
NEUROLOGICAL CONTROL
Central Nervous System
Involves the BRAIN and SPINAL CORD
PARASYMPATHETIC system
Controls the craniosacral divisions
SYMPATHETIC system
Controls the thoracolumbar divisions
Inhibitory Neurotransmitters
GABA: brain; causes an influx of chloride
GLYCINE: spinal cord; causes an influx of
chloride
PARASYMPATHETIC SYSTEM
Uses acetylcholine for preganglionic fibers
and postganglionic fibers
DEPOLARIZES the head and neck as well
as below the belt
HYPERPOLARIZES the thoracolumbar
areas
Has long preganglionic fibers, short
postganglionic fibers
SYMPATHETIC SYSTEM
Uses acetylcholine for preganglionic
fibers; uses primarily NE for postganglionic
fibers

 Some pathways use DA or SEROTONIN

DEPOLARIZES the brain and the
thoracolumbar areas
HYPERPOLARIZES the sacral area
Has short preganglionic fibers, long
postganglionic fibers
105 105
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
Most are MUSCARINIC except at ganglia
or neuromuscular junctions which are
NICOTINIC
Sympathetic Receptors
Many are NICOTINIC, except for sweat
glands which are muscarinic or
Alpha 1 Receptors
Arteries: vasoconstriction
Sphincters: tighten
Radial muscles of the eyes: mydriasis w/o
cycloplegia
Alpha 2 Receptors
All presynaptic sympathetic fibers: inhibit
NE release
Islet cells of pancreas: inhibit insulin
secretion
106 106
Beta 1 Receptors
CNS: increased activity
SA NODE: increase heart rate and
contractility
JG Apparatus: increased renin release
Alpha cells of pancreas: increased
glucagon release
Beta 2 Receptors
CNS: increased activity
Ventricles: increased contractility but NOT
rate

Lungs: bronchodilation
Arterioles: vasodilation
Islet cells of pancreas: increased insulin
Uterus and Bladder: relaxation

If you want to stimulate

You want to depolarize

Make the cell more positive
Make Na move INTO the cell
Make Ca move into SA node

If you want to inhibit

CNS: make CL move into cell
PNS: make K move out of cells
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
107 107
STRIATED MUSCLES
Cardiac muscle
Skeletal muscle
Striations due to sarcomeres
Smooth Muscle
Appear smooth due to lack of striations
Skeletal Muscle
Use intracellular calcium for contraction
100% electrochemically coupled
Function as motor units( one nerve fiber
and all the muscle fibers it innervates
Demonstrate RECRUITMENT
NO AUTONOMICS
NO SYNCYTIAL activity
Cardiac Muscle
Uses intracellular calcium for contraction
Needs extracellular calcium to trigger off
intracellular calcium release
Complete SYNCYTIAL activity
The most gap junctions
Complete AUTONOMICS
Can function without innervation,
neurotransmitters or hormones

Smooth Muscle
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
NEUROMUSCULAR TRANSMISSION
108 108
MUSCLE CONTRACTION
Calcium binds trop-C
Trop-C releases trop-I
Trop-I releases
tropomyosin
Tropomyosin releases
actin binding sites
Myosin heads bind actin
CONTRACTION occurs
Myosin heads release
ADP from previous rd
Myosin heads bind
new ATP
Myosin heads
hydrolyze ATP
RELEASE occurs
Myosin heads return
to start position
MUSCLE CONTRACTION, cont
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
Clinical Application
Diagnosis of a Myocardial
Infarction
EKG: Na-K pump stops > peaked T-wave > STwave depression > ST-wave elevation > T-wave
depression, then inversion > Q-wave
Troponin I: rises at 2 hours > peaks in 2days >
positive up to 7 days
CK-mb: rises in 6 hours > peaks in 12 hours >
gone in 24 to 36 hours
LDH 1: rises in 24 hours > peaks in 48hours >
gone in 72 hours

Management of an MI

24 hour hospitalization
Check EKG Q6
Check CIEs Q6
Monitor for arrythmias
Discharge after 24 hours IF asymptomatic
Re-evaluate in 6 weeks

109 109
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
Dobutamine or Dipyridamole stress test
Use when patient unable to exercise
Calcium Pyrophosphate scan
Taken up by DEAD tissue; looking for HOT spot
2-D echo
Evaluates anatomy of heart; measures SV and CO
The Functional Unit of Muscles
THE SARCOMERE
MUSCLE DIFFERENCES
CARDIAC MUSCLE
In addition to wave of depolarization,
calcium MUST flow into the T-tubules
during phase 2 for contraction to occur
Ventricle depends on EXTRACELLULAR
calcium to trigger its contraction
Smooth Muscle
Has NO sarcomeres
Contains NO troponin > actin and myosin
are always bound ( LATCHING)
Contains BASAL BODIES
Has NO myosin ATPase activity
Has MLCK and MLCP working together
110 110
As Muscle Contracts

LENGTH decreases
FORCE and TENSION increase
A band stays the same
Amount of OVERLAP increases
The H band and I band therefore shrink

Length/Tension Curve

Golgi Tendon Organs

Located at muscle insertions
Monitor the force of muscle contractions
Allows muscle to hold MAXIMUM muscle
contraction force for only one second
Once it fires, muscle fibers MUST relax
Prevents destruction of sarcomeres
Muscle Strain
Overstretching or tearing a muscle
When a muscle is torn, it goes into spasm
to keep the fibers together for proper
healing
Tx: rest it > apply heat > NSAIDS > muscle
relaxants
JOINT SPRAIN
TORN tendon or ligament
Tx: Rest it > Ice Compression > Elevate
the extremity
Frank-Starling Curve
111 111
Congestive Heart Failure
Over 50% mortality in 5 years
Most common medicare diagnosis
Muscle fibers are overstretched
Dilated ventricle
Increased EDV and ESV
Decreased contractility > decreased CO
and EF
Congestive Heart Failure after a
myocardial infarction
AT LEAST 40% of myocardium lost
EJECTION FRACTION is less than 45%
Due to left coronary artery infarcts 90% of
time
Treating CHF: Applying
Frank-Starling Curve
Decrease volume
Restrict sodium intake
Restrict volume intake
Increase contractility
Digitalis
Dobutamine
Dopamine
Decrease TPR
Ace inhibitors
NEUROMUSCULAR PROFILE

ALL YOU NEED NOW IS THE

CLUE
Inflammatory Myopathies
Myositis
Polymyositis
Dermatomyositis
Fibrositis
Fibromyalgia
Polymyalgia
rheumatica
Temporal Arteritis
ALL HAVE:
High ESR
High WBC count
Myoglobinemia
High AST, ALT and
Aldolase
112 112
Muscular Dystrophies
Duchennes
Gowers sign
Waddling gait
Pseudohypertrophy of the calf
Dystrophin protein
X-linked recessive; onset BEFORE age 5
Beckers
Onset AFTER age 5
Myotonic
Neuropathies
Guillian Barre
Diabetes mellitus
Syphilis
Myesthenia Gravis / Myesthenic or Eaton
Lambert syndrome
Acetylcholinesterase inhibitors:
reversible
Edrephonium
Neostigmine
Pyridostigmine
Physostigmine
Acetylcholinesterase inhibitors:
irreversible
AKA Organophosphates
End in .phate ( diflorophate; echothiophate)
End in .thion ( malathion; nalathion;
parathion)
If they come back complaining
about more weakness
Myesthenia Gravis has gotten worse or
Cholinergic crisis

 REPEAT EDREPHONIUM TEST!!

IF patient gets better > disease is worse
Increase neostigmine
IF patient gets worse > cholinergic crisis
Hold neostigmine > give atropine > decrease
neostigmine
Anticholinergic Drugs
Side effects are sympathetic except for
HOT, DRY SKIN!
Atropine
Glycopyrollate
Pilocarpine
Benztropine
Trihexyphenidyl
ipratropium
113 113
Neoplastic Associations
Myesthenia Gravis: THYMOMA
Myesthenic syndrome: SMALL CELL
CARCINOMA; a paraneoplastic syndrome
Sarcoplasmic reticulum is slow to sequester
calcium; cancer blocks some calcium
channels
Neuropathies, cont
Multiple sclerosis
Metachromatic leukodystrophy
Treatment of MS
STEROIDS
IV GAMMGLOBULINS
PLASMAPHARESIS
Lower Motor Neuron Disease
Amyotrophic lateral sclerosis
Werdnig-Hoffman Disease
Polio
Cerebellar Disease in 5 to 10 Y/O
children
Ataxia Telangiectasia
Fredricks Ataxia
Adrenoleukodystrophy
Cerebral Palsy
Any permanent neurological damage suffered
PRIOR to age 21 years
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

114 114
THE END
115 115
VASCULAR PHYSIOLOGY
YOU GOTTA HAVE SOME FLOW
Im Talking About
SMOOTH
SMOOTH MUSCLE, that is
Smooth Muscle
THICKEST layer of smooth muscle is
found in the aorta
MOST smooth muscle by surface area
found in the arterioles
LEAST smooth muscle found In the veins
and veinules
Arterioles
Considered the STOPCOCKS of the
vascular tree
MOST smooth muscle by surface area
allows most vasodilatation and
vasoconstriction
Maintain AUTOREGULATION
Do the MOST to regulate BP, up or down
AUTOREGULATION
Between BP 60 to 160 systolic : cerebral,
coronary, and renal perfusion remains
constant
ISCHEMIC infarct: BP went below 60
systolic
HEMORRHAGIC infarct: BP went above
160 systolic
Veins and Veinules
Have the most CAPACITANCE
Have the least smooth muscle
60% of blood ( the most) is pooled here
Depend on skeletal muscle contractions to
squeeze blood upward
Have one-way valves which move blood
from superficial to deep veins

116 116
CONTROL of vessels

VEINS: under parasympathetic control

This is why veins are usually dilated
Blood flow rate is quite slow
example: subdural hematomas

If Hypovolemia Develops
VENOCONSTRICTION is first response to
loss of volume > gets volume back into
circulation
Venoconstriction is most significant in skin
and GI
Poor skin turgor
Loss of bowel sounds and ileus
A-V Anastamoses
Shunt blood away from nonessential
organs
More concentrated in fingertips, tips of
toes, tip of nose, lips and earlobes
Severe vasoconstriction
hypothermia
CONTROL of vessels, cont
ARTERIES: under sympathetic control
This is why arteries are usually constricted
Reactive hyperemia: cutting an artery or
the nerve to that artery causes immediate
vasodilatation
i.e. epidural hematoma
Receptors
ARTERIES: alpha one ( IP3/DAG)
vasoconstriction
ARTERIOLES: beta 2 ( c-AMP)
vasodilatation
VEINS: alpha 1 ( IP3/DAG)
venoconstriction
Capillaries
Have the thinnest membranes
Made for diffusion
Have the greatest surface area
117 117
As Blood Flows Through the
Capillaries
Fluid diffuses out; large proteins (albumin)
stay in
Osmotic pressure rises in the capillaries

 Concentration gradient pushes particles

out of capillaries
In the Veins and Venules
Osmotic pressure is now high enough to
PULL waste products into vessels
Blood PULLS waste products back into
circulation
Total Pressure in a vessel As a Vessel Narrows

Velocity increases
Flow decreases
Resistance increases
Blood Pressure rises

Resistance in Series
118 118
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
Ventricles are CONTRACTING
There is HIGH RESISTANCE in coronary
vessels
Velocity in aorta is too high
Aortic valve is open
LOW TRANSMURAL PRESSURE
LESS CORONARY BLOOD FLOW
In Summary
LESS blood flow through coronary arteries
during SYSTOLE
MORE blood flow through coronary
arteries during DIASTOLE
Most work is done in systole!
A-V O2 difference created during systole
Therefore: MOST O2 EXTRACTION
occurs in systole
A-V O2 Difference
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
Lets Look at FLOW
119 119
POISSOILE LAW
Regulation of Radius
CNS: pCO2 pO2
LUNGS: pO2
MUSCLES: pCO2 pH
CV: adenosine
SKIN: temp pCO2
GI: food, especially fats
RENAL: PGE2; dopamine; ANP
NEUROLOGICAL control of blood
pressure
Carotid Sinus
Located at the bifurcation of the common
carotid
Responds to FLOW or STROKE VOLUME
Increased STRETCH means increased
FLOW
Sensory nerve : CN IX
Efferent nerve : CN X
REMEMBER!
Stroke volume, carotid sinus stretch, CN
IX firing and CN X firing ALWAYS go in
the same direction
CN IX and CN X are ALWAYS firing
Amount of firing varies always in SAME
DIRECTION as the stroke volume
120 120
Autonomic Dysfunction

Mcc: DIABETES MELLITUS

In Newborns: Riley-Day syndrome
In Parkinsonism: Shy-Dragger syndrome
In elderly: Sick Sinus syndrome

Low Volume State

Low stroke volume >
low carotid stretch >
low CN IX firing >
decreased CN X firing
>increased heart rate
> increased NE from
NTS in medulla >
increased TPR >
decreased RBF >

decreased GFR >

> increased renin,
angiotensinogen,
aldosterone secretion
> increased Na
reabsorption >
increased total body
Na > decreased
urinary Na >
decreased FENa >
increased urinary K >
> > >
Low Volume State
Decreased
Decreased
Decreased
Decreased
excretes H)
Increased
Increased

serum
serum
serum
urine

Na( dilutional)
Cl ( dilutional)
K (real and dilutional)
pH ( aldosterone

serum Ph (metabolic alkalosis)

TPR

Most common cause of

hyponatremia?
LOW VOLUME STATE
Most common cause of
hypokalemia?
LOW VOLUME STATE
121 121
Most common cause of
hypochloremia?
LOW VOLUME STATE
Most common cause of high TPR ?
LOW VOLUME STATE
Most common cause of metabolic
alkalosis?
LOW VOLUME STATE
ALKALOSIS favors calcium precipitation
with phosphate
KIDNEY STONES !!!!
Ace Inhibitors
Stop conversion of AT-1 to AT-II
Increased bradykinin
VASODILATION and VENODILATION
Decreased preload and afterload
BALANCED dilation
Contain sulphur
Decrease mortality in CHF; decreases
proteinuria in diabetic nephropathy

Ace Inhibitors

Captopril
Lisenopril
Enalopril
rinilopril

Angiotensin Receptor Blockers

Losartan
Vosartan
Do not contain sulphur
NO elevation in bradykinin
122 122
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

Bergers
Henoch-Schonlein Purpura
Alports
More vasculitides
Buergers
DIC
HUS
TTP
DM
Syphilis
Takayasu
kawasaki
More vasculitides

Temporal arteritis
Ankylosing Spondylitis
PAN
Wegeners
Goodpastures
Leukocytoclastic
Churg-Strauss

123 123
Collagen Vascular Diseases
CREST syndrome
Scleroderma
Progresive Systemic Sclerosis
MCTD

RA / JRA (Stills disease)

Feltys: RA & leukopenia and splenomegaly
Becets : RA & GI ulcerations
Sjogrens : RA & xeropthalmia, xerostomia

Collagen Vascular Diseases with

LOW COMPLEMENT
PSGN
Serum Sickness
SBE
SLE
MPGN : type l, ll
Cryoglobulinemia
THIS IS THE END
124 124
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
A valve is popping open during systole
AORTIC STENOSIS
PULMONARY STENOSIS
MIDSYSTOLIC CLICK
Blood is coming at high velocity, slapping
the mitral valve on the way out
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)
125 125
SOFT S-1
One of the two valves that contribute to
this sound is NOT closing

TRICUSPID REGURGITATION
MITRAL REGURGITATION
VALVE IS NOT THERE!
Tricuspid atresia
Mitral atresia
BOTH ARE CYANOTIC

LOUD S-1
Either you have a stiff valve that bangs
shut: TRICUSPID or MITRAL STENOSIS
Or the ventricle is contracting harder
SOFT S-2
One of the two valves that contribute to
this sound is NOT closing
AORTIC REGUGITATION
PULMONARY REGURGITATION
OR the valve is not present
AORTIC ATRESIA
PULMONARY ATRESIA
BOTH ARE CYANOTIC
LOUD S-2
Either one of the valves is stiff and
BANGS shut when it tries to open
AORTIC STENOSIS
PULMONARY STENOSIS
Or there is HIGH pressure in front of the
valves (systemic or pulmonary
hypertension)
S-3
Sound made by a noncompliant ventricle
????????????????
S-3
VOLUME overload
DILATED ventricle
DECOMPENSATION
S-3 said to be normal ONLY in an
adolescent female
126 126
ESTROGEN CONNECTION
Estrogen is a muscle relaxant
Causes liver to produce many proteins
High ESR or CRP
Lipoproteins
TBG
Angiotensinogen
Clotting factors
Especially fibrinogen, but not factor 11
S-4
Sound made by an atrial kick
PRESSURE overload

 HYPERTROPHY
COMPENSATION
Most common gallop (atherosclerosis)
MURMURS! MURMURS! MURMURS! MURMURS CAUSED BY

TERBULENCE
Reynolds number > 2500
Murmur: if it is in the heart
Bruit: if it is in a vessel
Occurs when you have 70% stenosis

127 127
MURMUR GRADES
Grade 1: barely audible
Grade 2: easily audible
Grade 3: pretty loud
Grade 4: palpable thrill
Grade 5: able to hear with stethoscope off
the chest
Grade 6: able to hear across the room
without stethoscope
A SYSTOLIC MURMUR
Valves that are supposed to be open are
stenotic ( PULMONARY or AORTIC
STENOSIS)
OR valves that should be closed are not
closing ( MITRAL REGURGITATION or
TRICUSPID REGURGITATION)
SYSTOLIC MURMURS

Aortic stenosis
Pulmonary stenosis
Mitral regurgitation
Tricuspid regurgitation
Ventricular septal defect

HOLOSYSTOLIC ( PANSYSTOLIC)
MURMURS
Tricuspid regurgitation
Mitral regurgitation
VSD
PANSYSTOLIC increases on
INSPIRATION
Tricuspid regurgitation
PANSYSTOLIC increases on
EXPIRATION
Mitral regurgitation
VSD
Radiates into the axilla: MITRAL

128 128
SYSTOLIC EJECTION MURMURS
Aortic stenosis
Pulmonary stenosis
AORTIC STENOSIS
Radiates to the carotids( neck)
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
Autosomal dominant
Muscle fibers are hypertrophied but
disorganized
Any young athlete who dies suddenly,
especially during peak exercise
Septum is asymmetrically thick, especially
the top > causes SUBAORTIC stenosis
IHSS, cont
Excessive hypertrophy compresses the
coronary arteries
Excessive hypertrophy obliterates the
ventricular space
Murmur is LOUDER with standing or with
Valsalva; decreased with increased TPR
PULSUS BISFERIENS
IHSS, cont
Tx: need to decrease contractility; allow
time for adequate ventricular filling
Beta blockers
Adequate fluid intake
Bar from organized sports
Do an ECHO on entire family
DIASTOLIC MURMURS
Either the valves that should be open are
stenotic (MITRAL STENOSIS or
TRICUSPID STENOSIS)
Or the valves that should be closed are
regurgitant ( AORTIC REGURGITATION
or PULMONARY REGURGITATION)
129 129
DIASTOLIC BLOWINNG or

DECRESCENDO MURMUR
AORTIC REGURGITATION
PULMONARY REGURGITATION
Increases on inspiration: Pulmonary
regurgitation
Increases on expiration: Aortic
regurgitation
Aortic Regurgitation
Radiates to carotids; LOUDER with leaning
forward, making a fist, blowing up a blood
pressure cuff, or squatting
Austin-Flint murmur: mitral regurgitation
Widens the pulse pressure
bounding pulses
waterhammer pulse
head-bobbing
Quinckes pulses
Pulmonary Regurgitation
Radiates to the back
Louder on inspiration
Graham-Steele murmur: tricuspid
regurgitation
Diastolic Rumbles
TRICUSPID STENOSIS
MITRAL STENOSIS
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
130 130
EFFUSIONS
Transudate: mostly water
Exudate: mostly protein
Transudate: sp. G < 1.012
Protein < 2grams
Exudate: sp. G > 1.012

 Protein > 2grams

Congenital Heart Diseases
VSD
ASD
PDA
Coarctation
Cyanotic Congenital Heart Disease

Transposition of Great Arteries

Tetrology of Falot
Tricuspid Atresia
Total Anomalous Pulmonary Venous Return
Truncus arteriosus
Pulmonary Atresia
Aortic Atresia
Hypoplastic Left Heart
Ebstiens Anomaly

VALVULAR DISEASES: most common

causes
Aortic stenosis: aging
Aortic regurgitation: aging
Mitral stenosis: Rheumatic fever
Mitral regurgitation: MVP, SBE, collagen
diseases
Tricuspid stenosis: Rheumatic fever,
carcinoid syndrome
Tricuspid regurgitation: acute endocarditis
Pulmonary Disease
Most common cause is ALWAYS
congenital
Pulmonary valve is protected on BOTH
sides
131 131
Flow Volume Loops
Antiarrhythmics
132 132
Na Channel Blockers

Class Ia
Quinidine
Procainamide
Disepyramide

Class Ib
Lidocaine
Tocainide
Mixeletine
Phenytoin

Class Ic
Encainide
Flecainide
Propofenone

Wolf-Parkinson-White Syndrome
Class IV Ca Channel Blockers

Verapamil
Diltiazem
Nefedipine
Nicardipine
Nimodipine
Amlodipine
Femlodipine

Class II Beta Blockers

End in lol
Specific B-1: begin with A thru M (not L,C)
Specific B-2: begin with N thru Z (incl L,C)
133 133
Class II Beta Blockers
Propanolol Acebutalol
Esmalol Atenalol
Timolol Pindalol
Butexalol
Sotalol
Labetalol
Carvidalol
Class III: K channel Blockers

Napa
Sotalol
Bretylium
Amiodorone

THE END
134 134
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1
PHYSIOLOGY
Midgut (rotation 270)
Foregut (rotation 90)
Celiac artery
Parasympathetic:
Vagus
Sympathetic:splanchnic

nerves T5-T9
Hindgut ( Septation)
Inferior mesenteric
Parasympathetic: pelvic
splanchnic nerves
Sympathetic: lumbar
splanchnic nerves: L1-L2
Superior mesenteric
Parasympathetic:
Vagus
Sympathetic: splanchnic
nerves T9-T12
` Gives rise to the GI, from mouth to second
part of duodenum, including the respiratory
tract
` Lungs and upper GI have many congenital
connections
` Extends from the second part of duodenum
to the spleenic flexure
` Develops in the YOLK SAC
` Must go through a 270 degree rotation as it
migrates from yolk sac into abdominal cavity
` MIDGUT ROTATION requires ciliary action
KARTAGENERS: SITUS INVERSUS
` FROM splenic flexure to the anus
` WATERSHED AREA: the spleenic flexure
Has the least t blood d ly H th l bl suppl
Most susceptible to ischemic infarcts
`
`
`
`
`
`

CNS
ORAL
PHARYNGEAL ` PHARYNGEAL
ESOPHAGEAL
UGI
LGI

135
4/29/2008
2
` SENSORY INFORMATION
THINKING about food
HEARING about food
SMELLING food

 TOUCHING food
TASTINGTING food TAS food
ALL sensory information must reach the cortex;
Response is via the CORTOCOBULBAR pathway via the vagus
No longer do a vagotomy for peptic ulcer disease (cant enjoy
food)
Highly selective parietal cell vagotomy now
` Cortex can over ride any basic urge:
(outer layer of the cerebrum-forgut)
` LIMBIC SYSTEM- responsible for basic urges
Hippocampus long term memory
Amygdala- reward and fear, mating
Responsible for setting time: Circadian rhythms
` Neurotransmitter: melatonin
Light outside- melatonin low-DAYTIME
Dark outside- melatonin high- NIGHT Dark outside melatonin high NIGHT
Morning- catabolic processes are in their highest
function- working out in the morning is the best
Melatonin from tryptophan- milk and turkey
- Bright lights in companies, casinos
-1st, 2nd, 3rd shift workers/ workers comp
Feeding Center
(HUNGER)
` Location:
Lateralal hypothalamus
Satiety Center
` Location:
Vento-medial nucleus of
the hypothalamus
Destruction: Anorexia
Destruction:
Hypothalamic obesity syndrome
Later hypothalamus
` Stimulus:
Feeding (hunger) Glucose
If sugar remains normal the
center will not fire
` Stimulus:
Stop feeding: Glucose

Stomach stretch will

stimulate satiety center
Can override- Cortex
ANOREXIA NERVOSA
` Starvation
` Desentasize your
hunger center
` Bodyody dysmorphicys
Bulimia
` Enjoys eating
` Chunky female
` Trying to please her
boyfriend f i d
d o p c
disorder
` Small body frame and
thinks they are over
weight
` Young female trying to
please her mother
` BMI < 17
b
`
`
`
`
`

Purging
Abrasion on knuckles
Tooth enamel erosion
Laxative abuse
BMI > 25

136
4/29/2008
3
` Lesion of the satiety center (Ventormedial)
` Uniparental disomy- one parent carrying lesion
` Paternal in origin
Tirinucletide l id ` T repeats
` Chromosome 15
` Very aggressive appetite
` Die due to over eating
` Men: 5 feet = 106 lbs
` Women: 5 feet= 100 lbs
` Add 5 lbs for each inch past that
` Small frame: add 15 lbs
` Large frame: add 30 lbs

` (i.e. male 510: 106 + 50 +30 = 186 lbs)

` Norepinephrine or Serotonin (more important),
so many people use Amphetamines for weight
loss
` 80% of time > stimulates satiety center ` 80% of time > stimulates satiety cen
ter
` 20% of time > stimulates hunger center
` They are taken up presynaptically, causing release
of all catecholamines
Increase DA, NE and Serotonin
Nausea/ vomiting -(DA) stimulates Nausea/ vomiting (DA) stimulates
Neuromuscular- basal ganglia- tics (DA)
` Amphetamine tox. clue vertical nystagmus
Methylphenidate- ritilan (1st line) [drug dependence]
x Narcolepsey (hipnogogic)hallucinations as you fall asleep
Pemolinex hepatic necrosis (hepatitis)- off the market 2005
Dexadrine- d i dexatrim t i ihtght loss OTCC D d - wei l OT
LSD- hallucinations from Seratonin (slow, lazy)
PCP- hallucinations from Seratonin (violent, aggressive)
ECSTACY- hallucinations from Seratonin (stimulate thirst)
` Controls MENSES- progesterone stimulates
hunger system
` Pregnancy- due to corpus luetum
FOOD craving.
137
4/29/2008
4
` Controls TEMPERATURE:
ANTERIOR Hypothalamus: cools (inhibits NE)
x Lesion anterior- die from: hyperthermia
POSTERIOR Hypothalamus: warms
x Lesion posterior- die from hypothermia

 Acetametaphen: for use with fever

(stimulate anterior hypothalamus- cools), then it
blocks posterior so you do not go back up again
Toxicity- microsteatosis, Reye syndrome in children
Tx: N-acetylcystine-reducing agent
- 4 hour level will determine if you use it
STRESS RESPONSE:
x Parasympathetic first (HR dec.) increased
gastric motility, increase acid production
x Sympathetic second (B/P inc) constipation,
pulls blood from GI, so you can not buffer acid
Stress from burn- Curlings ulcer
ICP- Cushing s ulcer
Seizure- foam at the mouth, defecate, urinate
(all parasympathetic)
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 Lingual [ on tongue ] (most serous) CN
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
` Methacholine- dx asthma (old), beta 2 agonist to
bring you out
` Pilocarpine- sweat test ( > 60), open angle
glaucoma (chronic)
` Carbachol- post op urinary retention (stimulate
bladder emptying)
` Bethanecol- post op urinary retention
` Norepinephrine-
nd 1
` Epinephrine- h
s methyl group (hormone)
` Ephedrine- OTC med
` Pseudoephedrine stress incont.
` Phenylephrine- neurogenic shock Tx (constrict) ` Phenylephrine- neurogenic sho
ck Tx (constrict)
` RESULT: remove the lood supply to the GI c
using

decre
sed s
liv
th
t h
s incre
sed osmol
rity
(less s
liv
- more s
lt)

` Exercise- mouth dry, white film in corner

138
4/29/2008
5
MCC: of m
l
sorption in children
` CFTR gene on chromosome 7
` Defectiveive CHLORIDERIDE tr
nsport ` Defect CHLO tr
nsport
` Chloride tr
ps sodium, incre
sing the s
lt
content
nd thickness of secretions
` Affects GI tr
ct, lungs, p
ncre
tic duct, swe
t
gl
nds
nd epididymus
` Meconium ileus: first present
tion in neon
te
` M
l
sorption develops
s p
ncre
tic ducts
ecome clogged
` Infertility in men develops
s epididymus is
clogged (un
le to ej
cul
te)
` Ostructive lung dise
se develops over the
ye
rs (un
le to cough up thick mucus)
` Worst 
cteri
l enemies:
Staph Aureus and Pseudomonas Auregenosa
MUST cover Staph Aureus with one
antibiotic and Pseudomonas Auregenosa
with two antibiotics
Dx: Pilocarpine: Cl sweat test
< 40 Normal
40 60 Heterozygous
> 60 CF
`
`
`
`

IgA
Lipase- little fat break down
Amylase: breaks alpha 1,4 bonds
Lysozyme: a detergent

HCO3: hree f id ` HCO3 th sources of acid

From food- drinks
Produced by bacteria ( strep mutans)
Reflux
` A normal phenomenon: GERD
` ESOPHAGITIS- tissue inflammation (T-cell/Mac)
` BARRETTS ESOPHAGUS- short to long

columnar
` MALORY WEIS SYNDROME- tears in submucosa
(ETOH, vomiting)
` BOORHAAVES SYNDROME-Rupture of