Physiology for Medical Students

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PHYSIOLOGY

• IMEC Inc.

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OSMOSIS

• Osmosis Net diffusion of H20

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Osmolarity

• Osmolarity? Osmoles/ per liter of solution
• Osmoles (moles X species)

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OSMOLARITY AND SODIUM CONCENTRATION Water
Conservation and Excretion obligatory urine
volume Antidiuretic hormone Countercurrent
Mechanism Loop of Henle countercurrent
multiplier distal tubule and collecting ducts
urea vasa recta Quantifying Urine
Concentration and Dilution )smolar clearance
free water clearance Control of Extracellular
Fluid Osmolarity estimation from plasma sodium
osmoreceptors and ADH feedback sequence ADH
synthesis and release neuroanatomy
cardiovascular reflexes Thirst thirst center
stimuli for thirst integration of osmoreceptors
and thirst
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Facilitated diffusion

• Occurs down an electro-chemical gradient
  (DOWNHILL)
• Does not require energy
• Therefor PASSIVE

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Primary Active Transport

• DIRECT INPUT OF ENERGY
• Carrier mediated so it is STEREOSPECIFIC
• Na-K Pump (note digitalis/oubian)
• Ca Pump (SR Cells)
• Proton Pump (Parietal Cells)

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Secondary ctive Transpoty

• Na-glucose Co transport (Kidney)
• DOWNHILL
• Na-Ca Co Transport (antiport)
• Uphill and downhill

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Normal Body fluids

• 5 Dextrose
• 0.9 NaCl

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Voltage Gated channels

• These are channels that are egulated by Na
  (Sodium). During the upstroke of nerve action
  potentia

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Ligand gated channels

• These are channels opened or close by hormones,
  second messenger (IP3, DAG), or neurotransmitters

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Analogy of systems

• Q P1-P2
• R

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Capillary Fluid Exchange
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Regulation
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Starlings Forces
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Starling Hypothesis

• (Pc - Pi) s (Pp - Pi)
• Driving Forces.
• a. Capillary hydrostatic pressure, Pc.  20-27
  mmHg
• (Guyton Says 17 mmHg ) b.
  Interstitial hydrostatic pressure, Pi. -7 to -1 
  mmHg
• (Guyton Says -3 mmHg) c. Plasma solute
  osmotic pressure, P. 25 mmHg 
• (Guyton Says 28 mmHg) d. Interstitial
  solute osmotic pressure, Pi. 1 to 3 mmHg.
• (Guyton 8 mmHg)

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Starling Forces
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Starling Equation
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Total Blood Volume

• TBVPlasma Volume
• 1-HCT

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Mean Arterial Pressure

• (2 X Diastolic) Systolic
• 3

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Normal Parameters

• MAP - 70-110 mmHg
• CO - 4-7 L/min

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Resistance Pressures

• SVR ( MAP - RAP/ CO ) x 80 - systemic vascular
  resistance
• SVR - 900-1200 dynes/cm square
• PVR ( PAP - PAOP/ CO ) x 80 - pulmonary
  vascular resistance

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Normal Cardiac Pressures

• RA - 0-7 mmHg
• RV - 15-30 / 0-7 mmHg
• ( systolic / diastolic )
• PA - 15-30 / 8-15 / 10-17 mmHg
• ( systolic / diastolic / mean )
• PAOP mean - 6-12 mmHg

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OHMs LAW

• It is written as V/I R
• V is the voltage of a device,
• I is the current, and
• R is the resulting resistance.

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Depolarization

• Following a stimulus there is a sudden change in
  permeability to (Na)
• Note-remember that sodium is not normally
  permeable
• Opening of channels causes a rapid alteration in
  the voltage of the membrane from 70 mv to 35 mv

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Repolarization

• After about 0.8 miiliseconds, the Na Channels
  close, and and increased number of potassium (K)
  escape to the outside of the cell that drive the
  potential back to 70mv
• There is a brief period of overshoot or
  hyperpolarization

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Restorative process

• There is a restorative process that pumps these
  to electrolytes back to there normal state,
  against there gradients
• This can be done using metabolic energy and
  enzyme operated pumps until stable

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ACTIVE TRANSPORT

• Primary ATPase (ADPP)
• Can be GTP/NADPH
• Does not waste energy
• More efficient
• Na? K Pump
• Ca Pump
• Glucose Transport

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Passive transport

• Relys many on gradient
• Faster at first then slows down

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Myocardial Sarcomere
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SARCOMERE
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Sarcomere (Band, Lines, Zones)
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Relaxation and Contraction
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Myosin-Troponin Crossbridge
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THE HEART
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The Frank-Starling relationship

• In general muscle fiber length-force
  relationship (force developed vs initial fiber
  length) At very short muscle length, thin actin
  filaments overlap, interfere, not optimal, force
  therefore not maximal At optimal muscle lengths,
  optimal actin-myosin interactions (sarcomere
  around 2.0 to 2.4 mm),
• maximal force generated
• At overly stretched muscle lengths, too few
  points of actin-myosin overlap, too few myosin
  heads engaged, force sub-maximal
• In cardiac muscle, translates to a
  pressure-volume relationship (pressure developed
  vs initial volume)

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Preload

• Preload Is a case, where something determined
  the initial fiber length. In the heart, this was
  the amount of blood in the ventricle, I.e. the
  end-diastolic volume.
• This is called the PRELOAD.

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Afterload

• When a muscle contracts against an opposing
  force, we can call that force to be overcome the
  AFTERLOAD.
• AFTERLOAD. If you can generate 25 lbs of force,
  but you grab 40 lb weights, you will be unable to
  move the weights. Your biceps cannot overcome the
  afterload. Example When the left ventricle
  begins to contract, the valve between it and the
  aorta (the aortic valve) is closed and there is
  high pressure (maybe 70 mmHg) out there in the
  aorta.

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CONTRACTILITY

• The innate property of a muscle is to
  contract. This can be altered with a variety of
  inotropic agents, (such as, catecholes,
  digitalis, phosphodiesterase inhibitors).
• Why would you do this? Usually this is done
  because the contractility has been diminished by
  whatever disease process is going on.

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Pressure-Volume Curve
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ISOMETRIC CONTRACTION

• Isometric contraction occurs where the muscle is
  prevented from shortening. Examining such
  preparations we find that when we "preload" the
  muscle (stretch it by adding weight before
  stimulation) then there is an increase in the
  tension that the muscle develops when stimulated.
  The time to development of peak tension remains
  the same, implying that the rate of tension
  development also increases as does the preload.

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ISOTONIC CONTRACTION

• Isotonic contraction is slightly more complex -
  the muscle is preloaded, and then prevented from
  stretching any further. A further load is then
  added (the "afterload") and the muscle is allowed
  to shorten when stimulated. Because the
  stimulated muscle can shorten, lifting the load,
  the force that the muscle "isotonic" - that is,
  throughout contraction the force is constant.
  Here the physiologist can measure both change in
  length and change in force with respect to time.

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The effect of inotropy

• Inotropy is the term applied to changes in heart
  muscle performance independent of alterations in
  preload and afterload. This implies that any one
  of the active function curves that we plot will
  alter once the inotropic state of the myocardium
  changes. The curve commonly used to assess
  inotropy is the isometric length-tension curve -
  a positive inotropic stimulus shifts the curve up
  and to the left, and a negative stimulus down and
  right.
• Inotropy varies with a variety of factors,
  including increases associated with increased
  frequency of contraction and the effect of
  post-extrasystolic potentiation, as well as
  catecholamines, glucagon, and inotropic drugs
  and decreases with myocardial isch
• Inotropy decreases, heart failure, and depressant
  agents (including almost all anaesthetics).

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Dicrotic Notch
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Ejection Fraction

• Stroke Volume
• End Diastolic Volume

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EINTHOVENs LAW

• The electrical potential of any three bipolar
  leads can be determined mathematically from
  summing the values of the first two

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Hexial Reference System
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CHEST LEADS
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Precordial Chest Lead Positioning

• 1. V1 is placed in the fourth intercostal space
  to the right of the sternum.2. V2 is placed in
  the fourth intercostal space to the left of the
  sternum.3. V3 is placed in between V2 and V4.4.
  V4 is placed in the fifth intercostal space in
  the midclavicular line near the nipple.5. V5 is
  placed in between V4 and V6.6. V6 is placed in
  the fifth intercostal space in the midaxillary
  line.

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Lead-views
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Normal EKG
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P WAVE

• P Waves represents depolarization of the atrial
  myocardium. (Sinus node depolarization is too
  small in amplitude to be recorded from the body
  surface so it is not seen.)
• Not wider than 0.12-.2 sec (under 3 little boxes
  on the ECG paper).
• Not taller than 3 mm.

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Normal QRS Characteristics

• 0.07-0.11 sec in width. QRS widths often vary in
  different leads. The widest QRS measurement on
  the 12-lead ECG is the correct one. Best leads to
  look at are usually leads I and V1.
• Should not be smaller than 6 mm in leads I, II,
  and III and nor should it be taller than 25-30 mm
  in the precordial leads.

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Q-T Interval

• QT Interval measurement of the refractory
  period or the time during which the myocardium
  would not respond to a second impulse measured
  from the beginning of the QRS complex to the end
  of the T wave.
• If there is a U wave visible, the measurement
  is made to the end of the U wave and is called
  the Q-TU interval.
• Q-T interval should be roughly less than half
  the preceding R-R interval.

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R-Wave Transition
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ST-DEPRESSION
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Digitalis effect Due to K Flux

• Shortened QT interval
• Characteristic down-sloping ST depression,
  reverse tick appearence, (shown here in leads V5
  and V6)
• Dysrhythmias
• Ventricular / atrial premature beats
• Paroxysmal atrial tachycardia with variable AV
  block
• Ventricular tachycardia and fibrillation
• many others

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1st Degree Heart Block
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2nd degree AV block
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Mobitz Type I (Wenckebach)
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2nd degree (MOBITZ II)
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3rd Degree Heart Block
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RBBB
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LBBB
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SA BLOCK
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Idioventricular Rhythm
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ESCAPE BEATS
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Ischemia
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Various PVCs
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V-TACH
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MEAN QRS AXIS DETERMINATION
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Tachycardias

• In adults and children over 15, resting heart
  rate faster than 100 beats/minute is labelled
  tachycardia. Tachycardia may result in
  palpitation however, tachycardia is not
  necessarily an arrhythmia. Increased heart rate
  is a normal response to physical exercise or
  emotional stress. This is mediated by the
  sympathetic nervous system on the sinus node and
  called sinus tachycardia. Other things that
  increase sympathetic nervous system activity in
  the heart include ingested or injected
  substances, such as caffeine or amphetamines, and
  an overactive thyroid gland (hyperthyroidism).

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INOTROPIC EFFECT
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MUSCLE-NERVOUS Conduction
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Saltatory Conduction

• Saltatory conduction is the process that allows
  for electrical conduction to bounce between the
  nodes of ranvier in the extracellular fluid.
• Remember that peripheral nerves are coated with a
  lipoprotein rich myelin sheeth.

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PROTON PUMP
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Muscle Contraction
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Characteristic of Potentials

• THRESHOLD
• ABSOLUTE REFRACTION
• RELATIVE REFRACTION
• STRENGTH OF POTENTIAL
• FREQUENCY

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Nerst Equation

• V R T
• 2 f

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Sodium Channels
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SMOOTH MUSCLE
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Potential ChannelsSodium/Calcium/Potassium
(ATPase used)
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POST SYNAPTIC MEMBRANE POTENTIAL

• EPSP- AchE/Glutamate (-) Na gated-
  (depolarizing)
• IPSP- Glycine/ Gaba ()
• Cl-/K (hyperpolarization)

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Muscle Action Potential
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Action Potential

• All or nothing- One value
• Depends on Voltage regulated Gates
• Threshold dependent
• Continuous or saltatory

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THE NERVE
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NERVES

• Typing
• A- most rapid
• B-non-mammalian
• Types I, II, III, and IV
• I is largest with greatest conduction
• IV is Unmyelinated
• Myelin lowers resistance somewhat, but greatest
  effect is increasing capacitance

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Neural Cleft
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Fast Sodium Channels
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Fast/Slow Channel
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Action Potential with Chemistry
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Excitation/Contraction Coupling
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Actin/Tropomyosin
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Muscle Contraction Steric Hinderance Model
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Power/ Workload Curve
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Acetylcholine Receptor
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Normal vs. Myastenia Gravis
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ADENYL CYCLASE
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KIDNEYS
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Renal Clearance

• Cx Ux V/Px
• This equals volume of plasma from which the
  substance is cleared completely/ per unit time

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Free Water Clearance

• CH20 V-Cosm
• V urine flow rate

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Filtration Fraction

• FF GFR/RPE
• GFR C insulin
• RPF C PAF

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THE LUNGS
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RENAL BLOOD FLOW
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BRONCHI
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ALVEOLI
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Laminar and Turbulent Flow
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Pouisselles Law

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DIFFUSION

• Directly related to (solubility and diffusion
  coefficient) and the
• Driving pressure (force)
• 760 mmHg is atmospheric
• 47 mmHg is water vapor pressure

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Henrys Law

• PressConcentration of dissolved gas
• Solubility coefficient

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Solubility coefficient

• Oxygen------------------.024
• Carbon dioxide---------.57
• Carbon monoxide------.018
• Nitrogen-----------------.012
• Helium-------------------.008

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RESPIRATORY MEMBRANE

• HAS 6 DIFFERENT LAYERS
• FLUID IN THE ALVEOLI
• TYPE I- SQUAMOUS/TYPE II EPITHELIUM
• BASEMENT MEMBRANE (ALVEOLAR)
• BASEMENT MEMBRANE OF CAPILLARY
• DISTANCE TO BLOOD VESSEL
• LIPID MEMBRANE OF RBC

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What factors effect diffusion

• THICKNESS
• SURFACE AREA
• DIFFUSION COEFFICIENT
• PARTIAL PRESSURE DIFFERENCES

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V/Q (VENTILATION/PERFUSION) RATIO

• THE IDEA IS TO MATCH VENTILATION AND PERFUSION AS
  WELL AS POSSIBLE IN THE VARIOUS LUNG ZONES
• Physiologic shunt
• Ventilation reduced relative to blood flow
• Perfusion without ventilation
• Physiologic dead space
• Ventilation occurring without perfusion

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Physiologic shuntEquation

• Qs CIO2 CaO2
• Qt CIO2 CvO2

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Physiologic dead spaceEquation

• Vd PaCO2 PeCO2
• VT PaCO2

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OXY-HEMOGLOBIN CURVE
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The Respiratory Center

• 3 major groups
• Dorsal respiratory group
• (inspiratory ramp)
• Ventral respiratory group
• (cuts off inspiratory ramp)
• Pneumotaxic center
• Other
• Hering Breuer reflex that can switch off the
  inspiratory ramp when Vt get to 1.5 L

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Chemical control of breathing

• Central Receptor (PONS)
• Special blood supply at glossophayrngeal nerve
• Carbon Dioxide (Primary)
• Increased CO2 as in emphysema
• Oxygen (Secondary)
• PaO2 fall below 60 mmhg
• J- Receptors do exist juxta positional in the
• ALVEOLAR WALL
• Pulmonary damming

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Types of Respiratory Patterns

• Periodic breathing
• Consider abnormal (10-20 second pauses)
• Cheyne-Stokes
• Cerebral brain damage (starts and stops)
• Apneustic
• Occurs at pons, shuts off insp ramp
• Apnea Pauses in breathing greater than 20 seconds
• Kussmaul
• AT MIDBRAIN, can be seen in keto-acidosis,
• Very fast, deep, regular breathing

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Medium Flow
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HIGH-FLOW
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Lung Zones
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Direct Fick Equation Gold Standard
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Lung Volumes
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Lung Volumes

• Tidal Volume (VT) - the difference in volume
  between peak inspiration and peak expiration
  during tidal breathing. Measured with spirometry.
  The volume of the VT for normal individuals at
  rest is approximately 0.5 liters. When
  exercising, the VT increases to 1.5 - 2 liters
• Vital Capacity (VC) - The difference in volume
  between the maximum possible exhaled and inhaled
  volumes. Measured with spirometry. A normal value
  for the VC is approximately 5 - 6.5 liters.
• Residual Volume (RV) - Volume of gas that
  remains in the lungs at the end of maximum
  expiration. Measured with a body plethysmograph

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Restrictive Lung Disease
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Lung Volumes

• Expiratory Reserve Volume (ERV) - The difference
  in volume between peak expiration during tidal
  breathing and maximum possible expiration.
  Measured by spirometry.
• Inspiratory Reserve Volume (IRV) - The
  difference in volume between peak inspiration
  during tidal breathing and maximum possible
  inspiration. Measured by spirometry.
• Functional Residual Capacity (FRC) - Volume of
  air remaining in the lungs after exhalation
  during tidal breathing. Measured by helium
  dilution technique.
• FRC ERV RV.
• Total Lung Capacity (TLC) - Maximum volume of
  gas that the lung can contain.
• TLC VC RV.

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Measurement of FRC

• Helium Dilution Method
• i. If we have a close system of known volume and
  concentration of helium, and then let the system
  equilibrate at some new volume and measure the
  resulting equilibrated helium concentration, we
  can determine the volume of the lung.
• ii. V2 in most measurements is the FRC.
• iii. In reality the measurement is complicated by
  the fact that oxygen is continuously absorbed
  into the blood, and CO2 is continuously released.
  This could cause a change in partial pressures of
  the system and therefore measurements of volume
  would be incorrect. This is remedied by supplying
  oxygen continuously and absorbing the CO2.
• iv. Helium is the tracer of choice since it is an
  inert gas and will not react with other metabolic
  components, and does not readily diffuse across
  the alveolar-pulmonary capillary barrier.

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COPD

• Chronic obstructive pulmonary disease (COPD) has
  historically included the spectrum of chronic
  bronchitis and emphysema, with overlaps the most
  common presentation of disease. More recently it
  has been recognized that an old designation,
  asthmatic bronchitis, should also be included in
  the COPD spectrum because there are often
  asthmatic features in COPD, including nonspecific
  bronchial hyper-reactivity and atopic features
  that are interrelated with smoking. Evidence of
  smoking-related airway inflammation has been
  identified by bronchoalveolar lavage in chronic
  bronchitis. Taken together, these findings and
  concepts suggest that reversible features of COPD
  are often present that may be amenable to
  therapeutic intervention. These interventions
  include smoking cessation and the use of
  anti-inflammatory drugs. A significant number of
  patients with COPD experience increased airflow
  with the use of inhaled bronchodilators.

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Bernoullis Principle
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Venturi Effect