Physiology Test 2

Front 1

Skeletal Muscle Overview

Back 1

1) Structure - A muscle is surrounded by epimysium. Within the muscle are bundles of muscle fibers (fascicles) surrounded by perimysium. Just outside the perimysium are the nerves and blood vessels. Within the perimysium are individual multinucleated muscle fibers covered by the endomysium and basal lamina. Within the muscle fiber are muscle fibrils

2) Fibers - Less than 200 microns wide and many cm across. They are multinucleated and post-mitotic

Front 2

Motor Units

Back 2

-A motor unit is all the muscle fibers innervated by a single somatic motor neurons
-As the neuron approaches the neuromuscular junction is loses myelination and begins to branch
-For muscle of fine control the motor units are small (5 fibers),and for powerful movements they are large (100 fibers)
-To test for motor units they use a glycogen stain. After neuron stimulation, the fibers depleted of glycogen are in the same motor unit
-a motor neuron cell body is in the ventral horn of the spinal cord. 1 motor neuron can only innervate 1 muscle, but muscle fibers within that muscle. Additionally, multiple motor neurons CAN innervate the same muscle

Front 3

Subcellular Muscle Organization

Back 3

-muscle fibers are made of many myofibrils
-myofibrils are bundles of contractile filament that are striated into dark/light bands

Front 4

Sarcomere

Back 4

-individual muscle unit, many of these make up a myofibril contractile fiber
-Composed of 2 primary filaments, a thick myosin and a thin actin
1) Myosin - Made up of a tail and head. The tail is 2 heavy chains and the head is 4 light chains. ATP hydrolysis occurs at the head and this interacts with actin. The tail helps form the M-line where the myosin filaments unit
2) Actin -

Front 5

Sarcomere Organization

Back 5

Thin Filament - A helical actin dimer bound by tropomyosin (covers active site where myosin binds) and troponin. Troponin is consisted of 3 subunits: Ti, Tc, and Tt
Myosin: 6 polypeptide subunits. 2 of them make the heavy chain tail, and 4 make the light chain head. The crossbridge is the myosin part with the hinge and globular head. It has a actin binding site and ATPase hydrolyzing site. Thick filament consists of many myosin filaments together in end to end fashion with over 300 crossbridges
Z line: Where thin filaments are anchored
I Band: Space between sarcomeres where only thin filament is located. Shrinks during contraction
A Band - Thick filament location, does not change during contraction
M Line - Where myosin units in end to end fashion. Only myosin tail

Front 6

Crossbridge Cycle

Back 6

-main focus is the myosin hinge, arm, and globular heads consisting of light chains
-the cycle is not synchronized between filaments but they do work together to pull Z-line towards one another
1) Once sarcoplasm Ca++ is released it binds Tc and induces a conf-c in Ti which moves tropomyosin to reveal the actin binding site
2) The Actin and Myosin + ATP are separate at first (A + M-ATP). However, once the active site is revealed the ATP is hydrolyzed (A + M-ADP-Pi) and the actin/myosin unite (A-M-ADP-Pi)
3. To generate force the inorganic phosphate is released (A-M-ADP) and the myosin head changes from 90 degrees to 45 degrees while the hinge region stretches
4. For the final pull ADP is released (A-M), the hinge retracts and pulls actin towards the M line
5. Finally new ATP will bind to myosin (A-M-ATP) and dissociate the complex (A + M-ATP)
-because there is no ATP around after death, muscle rigor mortis is associated with A-M stage

Front 7

Excitation-Contraction Coupling

Back 7

0) At rest the muscle fiber has a negative membrane potential (-75mV). The SR is filled with Ca++, the calcium channel on the SR is closed, the tropomyosin is covering the actin binding site
1) When depolarized signal reaches the NMJ it allows Ca++ to enter the presynaptic terminus. This allows the release of acetylcholine
2) As acetylcholine binds the ligand-gated nicotinic M receptors they allow Na+ to rush in and depolarize the cell
3) This depolarization wave continues along the cell due to voltage-gated Na channel until it reaches the T-tubules which transmit the action potential inside the fiber to the SR
4) This triggers voltage-sensitive protein coupled to Ca++ channels which release Ca++ to the sarcoplasm
5) Ca++ binds troponin in a 1:1 ratio, tropomyosin moves, and the crossbridge cycle occurs
6) After the cell repolarizes the calcium-ATPase pump (CIRA) on the SR pumps calcium back in. When calcium levels are low it is released from troponin C and tropomyosin covers the binding site

Front 8

Tetanus

Back 8

-a muscle action potential leads to a single twitch
-in tetanus we have a temporal summation of frequent stimulation. Since we have twitches because the previous action potential can get back to normal, the strength of the contraction increases
-Eventually at tetanization we get a frequency fusion (twitches coming so fast the muscle cannot relax)
-Because the depolarization events overlap the Ca__ sarcoplasm levels remain high, crossbridge continues, and contraction summates
-Only occurs in skeletal muscle

Front 9

Motor Unit Size

Back 9

-within muscle there are different motor unit sizes distributed at random
-a big motor unit (type IIb) controls several muscles and has a high threshold. Used for powerful movements
- a small motor unit has a few fibers and has a low threshold
-in a single muscle, the more stimulation we add the more of the motor units we excite, starting from small and ending on large motor units. This is called recruitment
-Each muscle usually has many small motor untis that contribute a little bit of force, and many large motor units that contribute a lot of force

Front 10

Control of Contraction

Back 10

-different muscle need to work at different rates. Ocular muscle needs to contract quickly for its many small movements with the soleus leg muscle needs to be on for a while to maintain posture
-The type of fiber (fast vs. slow) fits the function
-muscle will contain a mixture but a motor unit is one or the other

Front 11

Fiber Types - Slow

Back 11

-These are on all the time so they need a oxidative metabolism and have lots of mitochonrdira to make ATP
-To maintain the oxidative metabolism they need to catch lots of oxygen so they have plenty of myoglobin which makes them red
-By using oxidative metabolism they don't rely as much on a high glycolytic capacity (moderate)
-Their crossbridge is generally slower and thus their myosin isoform has a slower ATPase rate
-Don't need to generate a quick large force so their diameter is moderate
-These fibers are good for longer more continued activities like posture and marathon running

Front 12

Fiber Types - Fast

Back 12

-They need to receive ATP quickly so they have a high glycosyltic capacity and a myosin isoform with a fast ATPase rate
-At the same time their large diamter makes them rely on glycolysis more than oxidative capacity so they have less mitochondria and a lower myoglobin content
-Large fibers, less mitochondria and harder diffusion of oxygen let these muscle do high powered events for a shorter amount of time like sprinting and jumping

Front 13

Phosphocreatine

Back 13

-While the mitochondria makes ATP, this source alone would not be enough for muscle contraction
-Our muscles store liver made creatine
-Using creatine kinase, phosphocreatine donates a phosphate group to ADP to make ATP
-During rest this can go in reverse and ATP is converted to ADP
-Cell usually has more phosphocreatine than ATP
-in a cell there are 5 phosphate NMR peaks - organic Pi, phosphocreatine, and the 3 phosphate groups on ATP
-During twitch the phosphocreatine is converted to creatine, the phosphate is donated to ATP which becomes ADP and there is more free Pi. So the NMR shows a decrease in the PCr peak and a increase in the Pi peak

Front 14

Length-Tension Relationship

Back 14

-passive force is the force on a muscle before contraction (pulling a slinky)
-active force is the strength of the contraction
-A certain amount of passive force and optimal sarcomere length (2.6um) (filament overlap) leads to a massive active force. Once the passive force increases too much (Z-line further apart) or decreases too much, the active force decreases
-the relationship between preload (passive force) and force generated (active force) is the length-tension or force-length relationship

Front 15

Load-Velocity Relationship

Back 15

-determines weight a muscle can lift and how fast
-Uses isotonic recording where mscle attached on one end to a frame and the other other a muscle. Weights are varied and velocity of muscle shortening then measured
-In the velocity-load relationship, the smaller load leads to faster contraction, while the opposite is true for a larger load
-To get maximum power you need both load and velocity, so it would be in the middle of the load/velocity curve. This is because at maximum velocity you get no power (no load) and at maximum load there is no velocity because it is isometric force (muscle cannot contract). Since power equals force x velocity, the middle ground makes the more power
-fast fibers generate more force and quicker speeds

Front 16

Muscle Stem Cell

Back 16

-Outside of fiber (sarcolemma) but inside basal lamina
-Satellite cells are the source of muscle repair (myogenic precursor) and comprise 1-5% of muscle nuclear content
-Found in all skeletal muscles

Front 17

Steps in Regeneration

Back 17

1) Express receptor for GF
2) Express receptor for IGF
3) Proliferate
4) Differentiate into myoblast and unit to form muscle fiber
5) Satellite cell is regenerated

-in resistance training and overloading (working out) you damage muscle to activate SC. Their proliferation and fusion to existing muscle produces muscle hypertrophy
-With little use (immobilized/aged) the nuclei undergo apoptosis and you get muscle atrophy. With atrophy comes a smaller muscle diameter and change in fiber type

Front 18

Types of Atrophy

Back 18

1) Acute Model (Disuse - Immobilized)
-Lose 30-50% of muscle. The diameter decreases. You lose a little specific force (force per cross-sectional area) and the fibers shift towards fast (white)
-All muscles (white/red) will show decrease in force overtime if not used.

2) Chronic Model (Aging) - Lose 30% muscle mass. The diameter decreases. This time the specific force is significantly impaired and you lose the fast most powerful (IIB) fibers

Front 19

Enhanced Muscle Repair

Back 19

-Myostatin is a secreted protein that binds a receptor that inhibits muscle growth. Blocks that stimulatory effects on IGF
-In animals without functional myostatin they have muscle hypertrophy and hyperplasia
-People with this disorder have good looking muscles but they are not stronger

Front 20

Problems in Muscle Repair

Back 20

-After trauma SC can make bone instead of muscle leading to ectoptic bone formation in muscle
-An example of this is Fibrodysplasia Ossificans Progressiva (FOP). In this condition a BMP receptor is mutated so it's always on. This leads to SC driving bone formation instead of other tissues in nonskeletal areas.

Front 21

Problem in Muscle 2

Back 21

-You can also get fat between muscles (SC problem) or within muscle (metabolic disorder)
-Can be caused by insulin resistance or problem with oxidative capacity

Front 22

Stem Cell Wrap Up

Back 22

-Satellite cells are equivalemtn to MSC in that depending on the physical/chemical environment we can shift them towards other cell types like fat or bone
-For example, depending on the stiffness (substrate elasticity) we can shift them from muscle formation (low stiffness seeding) to bone (high stiffness seeding)

Front 23

Smooth vs. Skeletal Muscle

Back 23

Striations: Skeletal has, smooth doesn't
Nucleation: Skeletal is multinucleated and smooth is single
Connection: While skeletal has no connections, smooth is connection mechanically my desmosomes and also by gap junctions
Type of Myosin: Skeletal has 2 types of myosin for 2 types of muscles, smooth only has slow myosin
Energy Produced: Skeletal has inefficient glycolytic and oxidative metabolism while smooth has efficient oxidative
Control/Innervation: Skeletal is voluntary controlled by somatic NS, smooth is involuntary by autonomic NS
Tone: Skeletal has no tone while smooth does
Stimulation: While smooth can contract and relax, skeletal only contracts

Front 24

Types of Smooth Muscle

Back 24

Unitary: Lots of muscle cells connected as a single functional unit by desmosomes and gap junctions. Gap junction allows AP and ions to flow through so stimulation of one contracts them all. Found at the gut, uterus, and BV.

Multiunit: Do not have gap junctions, they function independently and innervated by single nerve ending or hormone in blood stream. Has no gap junctions. Example is iris, ciliary, and piloerector

Front 25

Connection Between Cells

Back 25

Gap Junction: 2 hexamers connected that allow ions and AP to go across, not large molecules.

Front 26

Structure

Back 26

-small cells with longer but unorganized thick and thin filaments
-Thin filaments have no troponin
-smooth muscle can shorten much more than skeletal
-Instead of Z-lines, thin filaments are connected to dense bodies on one end and the cell membrane or cytoplasm on the other. When contraction occurs thin filaments pull the sarcolemma into prominent folds creating tone
-Instead of t-tubules they have receptor rich caveolae which is immediately next to multiple SR with pockets of calcium
-Smooth muscle can be arranged in sheets, bundles, or rings

Front 27

Smooth Muscle Contraction

Back 27

-shortening occurs between dense bodies with one usually in the cytoplasm and one at the sarcolemma. Don't pull against each other, just against sarcolemma to ballon out the cell between the dense bodies
1) As sarcoplasm Ca increases (due to Ca from SR and EC) the 4 Ca++/calmodulin complex activates myosin light chain kinase (MLCK)
2) Originally the myosin (same 6 polypeptide as skeletal) has the tail folded on itself
3) Activated MLCK will phosphorylate the light chains causing the tails to be released and assemble with other tails to form a thick filament
4) Phorphorylation also activates the myosin ATPase activity. Myosin then uses ATP for crossbridge cycle, sliding of filament, and contraction (slow but can generate high stress and contract more)
5) The final step of the smooth muscle crossbridge is unique and allows smooth muscle to use less energy than skeletal but maintain the same contraction. It is called latch bridge
6) Once smooth muscle has reached full contraction the myosin becomes dephosphorylated by myosin phosphatase. Even though it's dephosphorylated it stays with actin for a protracted period of time to maintain tone and utilize minimal energy (similar to rigor where actin-myosin attached without any phosphate)

Front 28

Regulation of Light Chain Activation

Back 28

1) Neurotransmitter (Ach, Epi, Nor) binds GPCR on sarcolemma (muscarinic, alpha/beta) leading to PLC activation. PIP2 is cleaved to IP3 which binds SR Ca++ channel to release calcium
2) Depolarization wave can reach Ca++ on sarcolemma and cause EC calcium to come in
3) Binding of a receptor-activated Ca channel on the sarcolemma by its ligand.
4) Calcium is pumped outside by a Na/Ca exchange (repolarizes the cell since Ca more positive) or back into the SR by a Ca-ATPase pump

Front 29

Deregulation of Light Chain Activation

Back 29

1) Beta-2 receptor can activate adenylate cyclase which turns ATP to cAMP, which activates PKA which phosphorylates MLCK to inactivate (this can be blocked by phosphodiesterase turning cAMP to AMP)
2) Nitric Oxide from blood vessel can activate guanylate cyclase which activates cGMP leading to PKG which activates a myosin phosphatase through phosphorylation. This will dephosphorylate the myosin light chain leading to a relaxed state. Thus cGMP is a powerful muscle relaxer. It can help repolarize the cell by preventing calcium influx and promoting K efflux

Front 30

Control of Contraction Summary

Back 30

1) Autonomic nerves can use neurotransmitters or hormones (circulating/local) to start 2nd messenger cascade (IP3 or cAMP) or trigger a ligand gated calcium channel on the sarcolemma
2) Can get a electrical signal which depolarized voltage-gated calcium channel
3) Ions and metabolites from other cells (NO from endothelial cells)
4) Ion exchanges and pumps
5) Stretching leads to active force recoil

Front 31

Coordinating Smooth Muscle Contraction/Relation

Back 31

-the NT Ach and Nor will innervate the same smooth muscle but lead to contrasting results. And their results can be flip flopped depending on where the muscle is
1) Gut
-parasympathetic ACh-Muscarinic leads to peristalsis whereas sympathetic NE-alpha 1 leads to vasoconstriction., In this scenario the effects are still opposite but they innervate different part
2) In bronchiol muscles - Ach-MAchR leads to constriction whereas NE-B2 leads to relaxation. In this example they innervate the same part (muscle) with opposite results

Front 32

Smooth Muscle Action Potential

Back 32

-resting membrane potential -50. Calcium dominates change in Vm. 3 types
1) Spike Potential - LIke skeletal muscle. Stimulated by nerve stimulation, stretch, or hormones
2) Slow waves plus AP - Found in intestinal walls. The waves aren't AP but help make AP occur. The waves are fluctuations of Na/K pump and spikes are openeing of sarcolemma Ca channels
3) Plateau - Found in the uterus. Following the rapid depolarization the repolarization is delayed for a plateau

Front 33

Smooth Muscle Length-Tension Relationship

Back 33

-similar to skeletal muscle and due to degree of overlap between filaments. Smooth muscle has more CT and more passive force to begin with
-difference is that smooth muscle length-tension is much broader due to CT component and the longer filaments which have more overlap. So the curve is broader and smooth muscle operates over a wider range of resting lengths

Front 34

Smooth Muscle Velocity-Load Relationship

Back 34

-Similar to skeletal muscle. The velocy dependent on load. 3 differences
1) Speed of contraction MUCH lower due to slow ATPase of smooth muscle myosin
2) The force-velocity relationship heavily depends on the number of myosins that are phosphorylated by MLCK. If they are all phosphorylated it looks just like the skeletal muscle curve. The fewer phosphorylations there is less shortening, slower contractions, and less ability to load (curve ends at 40 pounds for example instead of 100 like all phosphorylation can pull) (the curve bends more inward)
3. Maximal load reached when 30% of myosin phosphorylated. Explained by latch bridge mechanism. Even though only 30% phosphorylated, the other 70% are still found to thin filament in unphosphorylated state

Front 35

Cardiovascular Overview

Back 35

-The cross-sectional area is related to the diameter of the vessel and the number. Since we branch as we get closer to the tissue, capillaries have the largest XS area while the aorta and vena cava have the smallest
Velocity: Flow is quickest with a lower XS area so it is inversely proportional to the XS area (highest in aorta, lowest in capillaries)
Pressure: Average heart rate is 120 (active) over 80 (resting) mmHg. Pressure drops from aorta to vena cava (0 mmHg)
Volume: Most of the blood is on the venous side (takes longer to return, thus a blood reservoir). Avg person has 5L

Front 36

Vasculature Details

Back 36

1) Smooth muscle regulate blood flow by changing vessel size. Not in capillaries or venules so no regulation here
2) More elastic tissue in artery
3) Internal diameter usually similar or large for the veins. Wall thickness is larger for the artery
4) Elastic and fibrous tissue gives vessel stretching and stiffness which prevent distension

Front 37

Resistance and Flow of Vasculature

Back 37

Ohm's Law: Change in blood pressure = flow x resistance. Therefore flow is directly proportional to the pressure (higher pressure = higher flow) and inversely proportional to the resistance (higher resistance = less flow)
-Conductance is the inverse of resistance, so higher conductance is a higher flow and pressure
Poiseullie's Law - Resistance only depends on the dimension of the tube (length/radius) and the characteristics of the fluid (viscosity). Resistance is proportional to the length and viscosity and inversely proportional to the radius to the 4th power. Thus, radius is the biggest factor in resistance. The larger the wall thickness, the lower the resistance, and the lower the resistance, the higher the flow and blood pressure (hence why aorta has a higher pressure than vena cava)
LaPlace's Law - Tension across the wall (to tear a longitudinal slit in it) is equal to the pressure x resistance

Front 38

Resistance and Flow Part 2

Back 38

Series - In a series you add up the resistance and subtract it from the initial pressure to get the final pressure. The individual resistance work together to decrease pressure (P = F x R)
Parallel - There will not be a straight summation of the resistance, but rather 1/Rt will be equal to the sum of each 1/Ra + 1/Rb...This is because in a series the resistance in tube 1 affects the incoming pressure in tube 2. In parallel the incoming pressure is the same, they each have their effect, and join together for a outgoing pressure
Laminar flow - all elements move in streamlined parallel, use less E
Turbulent Flow - Elements move irregularly in lots of directions, less efficient. Occurs is there is an obstacle or branch point (normal)

Front 39

P/V changes with age

Back 39

-as we get older our compliance (V/P) decreases meaning that it takes a lot more pressure to move the same volume across the body than it does for a younger person
-As we get older if the heart can't get enough blood to the vasculature at 120, it increases leading to hypertension (as resistance increases flow does too)

Front 40

Viscosity

Back 40

Viscosity or hematocrit ratio is related to the number of RBC which increase viscosity and resistance
-normal number is around 40. People put on blood thinners if they have a high resistance (blood pressure) due to too many RBC and thicker blood

Front 41

Cardiac Anatomy

Back 41

-mitral valve is between the left ventricle and aorta and the tricuspid valve is between the right chambers. They are both AV valves
-The aortic and pulmonary valves regulate blow to the pulmonary and systemic circulation
-The left ventricle is thicker than the right because the systemic vasculature is greater than the pulmonary

Front 42

Electrical Activity of the Heart

Back 42

-Concentration of K+ is greater inside the heart while conc of Ca++ and Na+ is greater outside
-permeability of ions is greater for K+ so it controls the resting membrane potential (loudest at party)
-Resting membrane potential has little to do with sodium but the active potential does as it rushes into the cell

Front 43

Fast vs. Slow Response Fibers

Back 43

Fast Fibers - Resting membrane around -90 (K+ potential), has a quick AP and large plateus. The effective refractory period (no sodium channel open) goes from 0 (spike) until 3, and the RRP (a few sodium channels starting to open) goes from 3-4
-For slow response the resting membrane potential is -60, it has a slower de and repolarization, phase 1 is absent, and RRP extends into phase 4

Phases:
0 - Action potential depolarization dominated by sodium channel inflex
1 - small repolarization as k+ efflux open
2 - plateau due to slow calcium channels opening
3 - major repolarization - due to calcium channel becoming inactivated and K+ efflux taking over
4- resting potential. no hyperpolarization in cardiac cells
-during action potential the electrostatic direction goes from inside the cell (very negative) to outside the cell (very positive inside cell) back to inside the cell (very negative inside)

Front 44

Conduction and Excitability

Back 44

Effective Refractory Period - Sodium channels closed, calcium and potassium open, cell slowly becoming repolarized. No AP can be generated so no heart beat
Relative Refractory Period - We can generate an AP but they are not strong (Na+ channels have begun to open)

Front 45

Heart AP and Muscle Twitch

Back 45

-after the heart AP there is a short delay before the twitch, or contraction of the cardiomyocyte. This delay in twitch limits how fast the heart can beat making our max HR 180, or 3 times per second
-By using a calcium channel blocker (Diltiazem) we reduce the force of cardiomyocyte contraction. This reduces the plateau and isometric curve force. Therefore EC calcium is needed for heart contraction

Front 46

SA Node

Back 46

-SA node has no baseline resting membrane
-instead of usual potential channel you have iFunny (permeable to sodium and potassium) leads to a slow depolarization (phase 4)
-At -50mV the transient T-type Ca open to depolarize further
-At -40mV the L-type Calcium channel open to drive it to threshold and action potential (phase 0)
-K-channels open and cell is repolarizied (phase 3). Remember as Ca close the only other option is iFunny so the cell isn't completely repolarizing because Na is also rushing in. Kind of a slow repolarization, a tug-of-war
-the cell is continually depolarizing, NO steady state
-if you block the calcium channel with nifedipine the depolarization height decreases and the time between depolarization (beats) decreases which slows the heart down

Front 47

Autonomic Effect on the SA/AV Node

Back 47

1) Sympathetic - Speeds up AP (contraction) but creating a less polarized state between waves
2) Parasympathetic - Slows down the heart by allowing for K+ efflux which hyperpolarizes the Vm further so it takes longer to reach threshold

Front 48

Heart AP Conduction System

Back 48

-SA drives atrial contraction first and it is faster than AV contraction
-Because cardiomyoctes are connected to pass ions, an AP of one SA node cell will travel to other and can even cause AV node to fire, although AV node has their own system
-AV node fires second to drive ventricle contraction. This AP travels along short bundle of His and then purkinjge fibers, through the septum, and then ventricle tissue
-Septum depolarizes from left to right and inside (endocardium) to outside (epicardium)

Front 49

More Heart

Back 49

1) Tricuspid Valve - R A/V
2) Pulmonary Valve - Semilunar
3) Bicuspid (Mitral) Valve- L A/V
4) Aortic Valve - Semilunar
-valves open in 1 direction and blood flows in one direction
-Valves only open when the atrial pressure is greater than the ventricular

Front 50

Heart Sounds

Back 50

S1 - During systole the ventricles will contract and the AV valves (tricuspid/mitral) will close forming a Lubb sound. This is the loudest and longest
S2: During diastole the pulmonary and aortic valves close producing a Dub sound with aortic usually clothing a bit earlier. This is of a higher frequency and lower intensive as the AV valves
S3 - In children or if cardiomyopathy in adults you can hear a ventricular gallop in the middle 1/3 of disastole caused by turbulent filling of the ventricle. It is dull and low pitched
S4 - If someone has a hypertrophied (stiff) ventricle then ther atrium is forced to push harder and this causes a atrial gallop sound

Front 51

Cardiac Cycle

Back 51

1) In diastole the AV valves are open and the ventricles are filling with blood
2) At the beginning of systole the left ventricular pressure (LVP) increases without a change in blood, this is isovolumic contraction (IVC -in IVC ALL valves closed)
3) Once pressure reaches a pinnacle the aorta opens and blood rushes out in the ejection phase of systole
4) At the end of systole when the ventricle blood drops the aortic valve closes and we enter isovolumic relaxation (IVR) of diatole
5) When the pressure of the ventricle drops below the atrium then the mitral valve opens and the ventricle fills with blood to initiate diastole again

Front 52

Systole: Ejection

Back 52

-first 2/3 is a rapid ejection with high force and contraction. The final 1/3 is reduced in volume, force, and contraction. This is where pressure is maxed during heart beat
Stroke Volume - Amount of blood heart pumps out each beach. It is the EDV (heart when fille) - ESV (heart when empty). Tells how well the heart is working
Ejection Fraction (EF) - Tells how efficient we are getting blood out of the heart. It is the SV/EDV
-the maximal aorta blood flow coincides with the maximum pressure in ventricle and aorta

Front 53

Diastole

Back 53

-only the AV valves are open
-In S3 there is passive filling of ventricles where 80% of the blood goes in
-In S4 there is forceful flowing to the ventricles, mediated by atrial contraction

Front 54

Cardiac Cycle Summary

Back 54

Pair the following 4 with mitral valve (MV) and aortic valve (AV) state, the left ventriclular pressure (LVP), the aortic pressure (AP), and the left ventricular volume (LVV)
1) Isovolumic Contraction - MV and AV closed. LVP increasing while AP decreasing. The LVP is consistent
2) Ejection - The MV is closed while the AV is open. The LVP is increasing and then decreasing with the AP doing the same. The LVV is decreasing
3) Isovolumic Relaxation - The MV and AV are closed. The LVP is decreasing while the AP is increasing and then decreasing. Finally the LV volume has no change
4) Filling - The MV is open while the AV is closed. The LVP is increasing while the AP is decreasing and the LVV is increasing

Front 55

Cardiac Output

Back 55

-the amount of blood delivered by the heart per minuite (5L)
-combined heart rate (70bmp) and stroke volume (70mL/beat)
...affected by
1) Heart Rate - increased by the sympathetic NS
2) Preload - The amont of blood in the heart after diastole. This stretches the cardiac sarcomeres and the more thin/thick overlap the more force in the cardiac muscle and higher SV
Afterload - Presusre against which the stroke volume is ejected, closely related to aortic pressure
Contractility - Ability of the heart to generate pressure independent of preload or afterload. Determined by amount of calcium for the troponin molecule. It is regulated by the sympathetic nervous system
...the SNS regulates contractility (calcium to heart) and HR because heart can't do it itself

Front 56

Heart Compliance

Back 56

-pressure is required to change volume of LV during diastole
-the diastolic pressure-volume relationship shows that as we increase volume in the LV, the pressure to do so increases
-Compliance meausres the change in volume to the change in pressure
-Based off the previous sentences we can see that in a disease state where the ventrile compliance is decreased (V/P) the pressure is increased

Front 57

Isovolumic Pressure-Volume Relationship

Back 57

1) Isovolumic Contraction is made experimentally where you fill up the LV to a end-diastolic value (right before ejection), stimulate it, and measure the pressure created
2) As the LV end-diastolic volume increases, the pressure upon stimulation increases, this is the isovolumic pressure-volume relationship, an example of the starling mechanism

Front 58

The Pressure-Volume Loop

Back 58

-the volume and pressure is related to the left ventricle. Keep in mind the end-diastolic pressure-volume relationship (more blood in ventircle, the higher the pressure) and the end-systolic pressure-volume relationship (when the aorta blood flow cannot match the pressure of the aortic valve closing, the aortic pressure forces the valve closed)
1) D-A this is diastole where the volume of LV is increasing (50mL to 100mL) without much of a increase in pressure. At a certain end-diastolic pressure the MV closes
2) From A-B the pressure increases but not the volume, this is isovolumic change
3) From B-C the LV pressure is enough to open the aorta, systole begins, and ejection phase occurs (50mL). During this phase the pressure increases and then decreases. At point C there is the end-systolic pressure volume part where the blood flow force cannot overcome the aorta pressure and the aorta closes
4) C-D: The atrium will begin to fill with blood and in the LV the volume remains but the pressure decreases, another isovolumic change
-in this normal scenario the stroke volume is difference between A (EDV - 100mL) and D (ESV-50mL) to be 50mL
-the ejection fraction is the stroke volume 50mL/EDV (100mL) to be 50%

Front 59

Heart Load-Velocity Relationship

Back 59

-similar to skeletal muscle
-we increase load on heart by adding blood and stretching the muscle more so more filament overlap (preload)

Front 60

Increased Preload - Frank-Starling Effect

Back 60

-If we increase preload (end-diastolic volume) then A is moved to the right (125mL)
-This increases stroke volume without changing anything else, stretches out the loop
-It also increases the aortic volume due to increase blood flow and the afterload
-By increasing SV to 75mL and EDV to 125mL we get a EJ of 60%
-Can be done by adding saline or blood to a patient

Front 61

Increased Afterload

Back 61

-in patients who are hypertensive their aortic pressure is greater so it takes more pressure (between A-B) to open the aorta
-The problem with this is that the aortic valve will close sooner and the stroke volume will decrease from 50mL to 40mL and so the EJ will decrease to 40%

Front 62

Altering Ventricular Contracility

Back 62

-the sympathetic nervous system can increase the contractile state of the LV which increases the pressure the LV can generate
-This allows the heart to eject more blood (stroke volume) before the aortic valve closes
-EF increases to 75%
-Increase in contractility increases the slope of the end-systolic pressure-volume relationship (pressure and volume at which the aortic valve closes)

Front 63

Sympathetics and Contractility

Back 63

-sympathetic release of NE creates a positive inotrophic effect where we increase stroke work at any pressure
-So basically with more contractility more LV stroke work can be done at a similar pressure

Front 64

Heart Failure Model

Back 64

-in heart failure you can't pump enough blood due to a decrease in the inotrophic (contractile) state of the heart
-To compensate the heart enlarges, allows more pre-load which increases end-diastolic pressure and the loop is moved to the heart
-This causes pulmonary capillary fluid accumulation in the lungs while the heart uses a large amount of oxygen inefficiently
-Basically by moving the loop to the right our EF is reduced and it takes more work to get the same volume of blood out (volume at which pressure high enough to open aortic valve decreases so the volume must increase and now pressure at dangerous level for lungs)

Front 65

Staircase Phenomenon

Back 65

-As the HR increases the amount of force increases
-This is because additional calcium builds up slowly which makes the filaments overlap more (and a greater percentage do) leading to greater force production

Front 66

Sympathetic vs. Vagus

Back 66

-sympathetic drives the heart faster and parasympathetic through the vagus puts on the breaks
-If a normal heart rate is 80, then sympathetic stimulation increases the heart rate curve
-Increasing amount of vagal stimulation will decrease the heart rate
Atropine vs. Propranol test shows that parasympathetic vagal system contributes more to our average daily heart rate
1. Add atropine (turn off parasympathetic) and HR shoots up a lot. Once at max add propranolol (turn off sympathetic) and HR will drop slightly to intrinsic HR of 100
2. Add prop. first and the HR drops slightly. When it's done dropping add atropine and it will jump up to 100

Front 67

Baroreceptor

Back 67

-the carotid sinus at the bifurcation is a baroreceptor that senses a increased cardiac output and changes it
-As BP increase the firing frequency sensed by the wall tension (LaPlace's principle T = P x r) causes the heart rate to decrease and vasoconstriction to be blocked

Front 68

Bainbridge Reflex

Back 68

-in the heart the right atria bainbridge reflex sensor detects volume, lets us know how much blood is returning
-As the heart undergoes systole the ventricular volume decreases as the right atrial volume increases (and the pressure increases).
-When the ventricle volume is at a certain level the pressure will begin to decrease, and when the atrial pressure is high the reflex will open MV to allow bloody to flow into the ventricle
-This increases ventricle volume/pressure and decreases atrial volume/pressure

Front 69

Combining Bainbridge and Baroreceptors

Back 69

-Both deal with increases atrial volume
-With a intravenous infusion there are multiple effects on the heart
1) Increased right atrial pressure due to increase volume will stimulate bainbridge reflex and increase HR
2) At the same time increased cardiac output (more HR at SV) leads to increased arterial pressure and the baroreceptor reflex triggers the heart to slow down

Front 70

Effects of Volume Change

Back 70

Situation 1: Blood Transfusion - The bainbridge reflex is triggered due to increase in atrial pressure. This leads to a greater HR , stroke volume (minimal), and cardiac output. Actually focuses on increase HR, doesn't alter SV too much

Situation 2: Gun Shot - During a gun shot you will lose blood and the baroreceptors will have the heart rate increase. As you bleed out you will have a lower stroke volume and lower cardiac output while maintaining the large heart rate

Front 71

Respiratory Sinus Arrhythmia

Back 71

-heart and lungs in same space so with every breath we change environmental pressure around the heart
-during expiration we creates a positive pressure in the lungs which decreases the HR while increasing the HR cycle length
-During inhalation we create a negative pressure which increase the HR and shortens the HR cycle
-changes in venous return (bainbridge reflex), changes in arterial pressure (baroreceptors), and changes in lung volume (stretch receptors) trigger the cardiac vagal center in the medulla. This leads to HR change. By turning vagal center on or off you can increase/decrease CO

Front 72

Chemoreceptors

Back 72

-the carotid body responds to blood oxygen levels and responds to the lungs and heart
-Chemoreceptors at the carotid body respond to high carbon dioxide levels and low pH
1) Turn off the vagus to allow heart to beat fast and deliver more blood to body including lungs
2) Tells the lungs to have more respiratory activity to release carbon dioxide
-in the curve when HR fast the oxygen level is high. As oxygen level decreases the HR will decrease with it. Eventually the chemoreceptors will be triggered and a increase in HR will then again increase the oxygen level

Front 73

Extra

Back 73

-Atrial pressure change experiment: change atrial pressure and look at aortic pressure.
1) Add more blood to increase right atrial pressure. The SV increases to get this blood out.
2) As right atrial pressure returns to normal the SV
-throughout this change in atrial pressure and stroke volume the aortic pressure does not fluctuate much. Heart wants to maintain a normal aortic pressure. Shows that increasing atrial pressure we activate atrial stretch receptrs (bainbridge reflex) and heart rate increases to get rid of it
-bainbridge and baroreceptor reflex can act in opposite manner (bainbridge increase HR while baroreceptor in same circumstance decrease it)

Front 74

Heart Overview

Back 74

-if you take away the myocardium (heart tissue) only BV of the coronary artery and veins remain
Potential Problems
1) No blood to coronary arteries takes away energy from the heart (pump)
2) Valve problems like valvular regurgitation or stenosis leads to backflow
3) Timing problems, or arrhythmias lead to brady (slow) and tachy (fast)
4) Weakening of the pump due to myopathy (muscle trouble) or heart failure
-test heart condition with angiography using a contrast dye
-in coronary artery disease fat/cholesterol build on wall and compress lumen (> 70% and blood flow compromised). Rupture can lead to thrombosis which closes of artery leading to a myocardial infarction - if heart doesn't get enough blood you get chest pain called angina

Front 75

Coronary Artery Disease

Back 75

Risk Factors: Hypertension, hypercholesterolemia, Diabetes (cause problem with vessels), Cig smoking (allow cholesterol plaque to form), genetic
Symptoms:
1) Asymptomatic - block not big enough to hinder blood flow to notice point
2) Angina
a) Stable - only show symptoms when doing exercise
b) Unstable - Always have chest pain. Due to a blood clot occluding the vessels
3) Myocardial Infarction
4) Congestive Heart Failure
5) Cardiac Shock - Occurs after a MI where the weakened heart cannot function properly
6) Cardiac Death - Heart weakened so much that it cannot function at al

Front 76

Stable Angina

Back 76

Stable: A supply and demand problem. Relief at rest but chest pain with exertion. Improves with beta blockers (lower HR), calcium channel blockers (same), and nitrates (dilate BV)
At Dentist: Patient anxiety can cause a catecholamine surge which raises the BP/HR leading to angina. Also, massive blood loss during a procedure will lead to ao increase in HR - treat by taking breaks or stopping and talking to their cardiologist

Front 77

Unstable Angina

Back 77

-similar to a MI in that a unstable or recently ruptured plauqe is the cause. Difference is that damage to myocardium hasn't occured yet
-Patient will display chest pain or pressure
-treatment includes aspirin (325mg) which thins the blood so less of a clot, sublingual nitroglycerine, oxygen, and an AED
-hospital could give beta-blocker, anticoagulants, do

Front 78

Heart Problem Treatments

Back 78

1) Angioplastic - Thin wire put across vessel and a balloon is inflated to increase lumen size
2) Stent - A metal stent over the balloon which remains to keep lumen open
3) Coronary Artery Bypass - Use a leg vein to create new blood supply to the heart from the aorta to the distal artery after the block. Using a vein (saphenous) only last 10-15 yrs, using a artery like the internal mammary artery (runs down cheek wall) makes it last forever
4) Post Op Care -lifelong aspirin, platelet inhibitors (life long aspirin and coated stents, beta blockers, and sometimes anticoagulants like warfarin

Front 79

Heart Disease

Back 79

1. Ischemia - Blood clot weakens the heart
2. Dilated Cariomyopathy - Non-ischemic heart disease (alcoholic, post-partum hormone problem, virus). Causes heart to enlarge and only squeeze 20^
3. Hypertrophic
4. Congestive Heart Failure - Get blue around lip (hypoxia), edema (venous blood build up), and liver enlargement. Get pulmonary edema where increase heart pressure pushes blood into the lungs and this hinders the lungs ability to oxygenate the blood

Front 80

Acute Decompensation

Back 80

-chronic stable heart failure may easily decompensate to produce respiratory distress, it is caused by
Caused by:
1) Dietary problems (too much salt can increase BP)
2. Not following medication
3. Myocardial infarction
4. Valvular regurgitation
5. Disease progression

Front 81

More Chronic Heart Failure

Back 81

Symptoms: Fatigue, shortness of breath, edema, ab distention/pain, decrease urine
Signs: quick breathing or heart rate, fluid-filled alveoli crackling sound,
S3 ventricular gallop when listening, edema, enlarge liver, jugular distension
Treatment: Diuretics so you pee more and reduce extra fluid (lessen edema, pulmonary problems), oxygen therapy, afterload reduction
Dental Issues: is acute you need to stop the procedure and give oxygen/diuretics. If chronic be careful about the fluids you give them

Front 82

Hypertrophic Cardiomyopathy/Valvular Heart Disease

Back 82

-genetic disorder where ventricle gets too large so blood being pumped decreases
-Give drugs to relax the heart

-aoritc and mitral are most at risk because they are pumping against the aorta which has a higher resistance than the pulmonary artery
-mitral problem is ususllay genetic and has trouble opening or becomes scarred. A ventricle blood blockage can weaken the papillary muscles so they can't pull on the chordae enough to open the mitral. Also a heart attack can weaken the heart so it enlarges leading to a leaky mitral valve. If mitral leaky then left atria leaky and so is the lung capillary pressure so pulmonary edema develops in which liquid is in the lungs and patient has trouble breathing
-aortic valve can become calcified leading to stenosis where it cannot open fully or pump blood effectively

Front 83

Listening for Heart Problems in Valve Disease

Back 83

-heart problems lead to turbulent flow so you hear the problem as a murmur
-fix temporarily with diuretics/aferload reduction and more permanently with surgery
-you can fix with a prosthetic heart valve
-example is ball and strut (ball opens and closes with heart pumps) or tilting disk valve
-you can also use a bio-prosthetic valve from an animal. Benefit is usually immunosafe and unlike other pros you don't need to be on anticoagulants (warfarin) fo ryour life. Downside is that they become stenotic within 10 yrs, so this is mainly for older people who won't need a replacement
...as a dentist know that antibiotic prophylaxis (given to prevent) to decrease bacterial endocarditis

Front 84

Arrhythmias

Back 84

-organized and synchronized
-SA node, intra-atrial (Bachmann's bundle), AV node, His bundle, purkinje fibers
-failure leads to beating problems (arrhythmias)

Front 85

Conduction System Anatomy

Back 85

P-Wave - First small bump, signifies atrial contraction
PR Segment: AV node, His bundle
QRS Complex- Large bump, signifies ventricular contraction
T-wave - ventricular depolarization that occurs slower so it's to the right of QRS. Phase 3 (RRP)

Front 86

Sinus Node/AV Node

Back 86

Sinus:
-pacemaker of the heart that beats on its own and rate is affected by drugs (beta/calcium blockers) that affect autonomic NS
-It is calcium-dependent AP with iFunny

AV Node: Calcium dependent AP that is innervated by autonomic system and affected by autonomic drugs (calcium channel blocker, beta blocker).
-The signal is delayed from atria so atria and ventricle contraction is delayed. Protects ventricle and allows heart to beat properly

Front 87

His Bundle

Back 87

-fast fibers whcih are sodium-dependent. Not affected by drugs as much except Na+ channel drugs. Usually fail by myocardial infarction

Front 88

EKG Introduction

Back 88

-looks at the whole conduction system as the same time. Sum up the many AP in the heart
-bradycardia only cause by SA "pacemaker" dysfunction or heart block where impulse reach SA but can't make it to the ventricle (if the cardiomyocytes in the ventricle don't take over on their own you can die)
-on the EKG you'll see too many boxes between heart beats knowing that the pacemaker is not working properly

Front 89

AV Conduction Block

Back 89

1st Degree - delay between P and QRS where the PR interval> 200ms

Second Degree - not all P waves give a QRS. Space between the two may increase until it skips a beat
a. Mobitz 1 (Wenchebach Block) - P and QRS distance increases before a drop in QRS, and P-QRS distance shortens after a drop
b. Mobitz 2 - PR interval same and then a drop

Third Degree - complete block, atrium and ventricle not in sync so they beat at their own rate

Front 90

The Arrhythmias

Back 90

-treat bradyarrhythmia with atropine (block para to speed up heart) or pacemaker (battery that sparks heart) - can see a line before QRS to indicate pacemaker electricity

Tachyarrththmia
-measure it by regular/irregular (time between QRS) and narrow/wide (width of QRS)
1. Irregular and Narrow - QRS narrow and space between not consistent. Almost no P-wave
2. Regular and Narrow - Very minimal P-wave
3. Regular and Wide - caused by ventricular tachycardia where one ventricle activated before the other

Front 91

Reading EKG

Back 91

5 big boxes (200ms/each) = 1 second
25 small boxes (40ms/each) = 1 second

Brady < 60 bpm
Tachy > 100 bmp
..heart block leads to P and QRS not equal, or P and QRS delayed

Normal: p before every qrs. 3.5 boxes between QRS. QRS less than .12 seconds
Brady: 8 boxes between QRS. Can happen during sleep naturally
Tachy: 2 boxes between QRS. Occur naturally by running on a treadmill

Front 92

EKG and Leads

Back 92

-leads form a triangle cause on both arms and left leg (grounding)
-lead 1 goes from right to left and lead 2 goes from right to leg, and lead 3 goes from left to leg
normal...QRS in lead I and II are upright
Right Axis Deviation - Lead I QRS negative
Left Axis Deviation - Negative QRS in 3

Front 93

EKG Continued

Back 93

-you break up the EKG into anatomical regions to look at different heart walls and see where the problem is
Lateral - I, AVL, V5, V6
Inferior: II, III, AVF
Septal: V1, V2
Anterior: V3, V4

Front 94

Translating EKG

Back 94

12 total leads
Q problem - old infarction
ST elevated - acute infarction
ST depression - ischemia
T wave inversion - symmetric means ischemia or old infarction.
Ex: Inferior Wall Infarction (heart attack on bottom) - At V2, V3, and AVF we see only 3 boxes between, so 300/3 = HR of 100. After a heart attack we'll get a negative QRS
-depending on the R or S in different leads you can also see a hypertrophic heart
Low Voltage - (height for AP). Can get if something is between the EKG and heart like fatness, fluid, or air (COPD/emphesema)

Front 95

Wrap Up

Back 95

Problems occur with
1) Pump energy supply - CAD
2) Pump Material - Cardiomyopathy
3) Valves
4. Timing

Front 96

Respiration Overview

Back 96

-transfer of oxygen for CO2 brings oxygen to tissues and helps balance the pH
-The conducting passages (to the primary bronchi) do not allow for gas exchange. Covered in mucus and cilia to remove damage agents. Has cartilage to keep tubes open during negative pressure
-Exchange of gas occur as terminal bronchiole gives way to respiratory bronchiole. These have alveoli duct and alveoli sacs which maximize surface area for gas exchange and are heavily vascularized. Bronchioles have smooth muscle to control the diameter

Front 97

Intro to Breathing

Back 97

1) Pleural Cavity - Encompasses the lungs. Outer layer of lung is viscera pleura, next is the interpleural space with pleural fluid, and then the parietal pleura. Pleural fluid constantly drained by lymphatics to allow negative pressure needed to breath
Inspiration: Diaphragm contraction pulls lungs down and negative pressure allows air to enter.
Expiration: No contraction, just elastic recoil of lungs as air leaves
Passive vs. Active Breathing - Passive involves mainly the diaphragm. For morer active breathing you can use diaphgragm to push air out like in yoga/singing or the ribs

Front 98

Intro to Breathing 2

Back 98

-for heavy breathing the rib cage is moved upward and outward
Muscle of Inspiration: External intercostal (raise rib cage), SCM (pulls up on sternum), scalleni (lift 1-2 ribs), anterior serratus (helps lift other ribs)
Expiration: Relaxation of the ones mentioned. Internal intercostal and abdominalis contract only for active expiration

Front 99

Pressure

Back 99

-Pressure is the amount of Force/Area
-According to Boyle's Law pressure and volume are inversely related. As volume increase, pressure decrease, and this theory allows atmospheric air to rush into lungs upon inspiration
Alveoli - During inspiration pressure in alveoli goes to -1 cm H2O allowing .5L to rush in under 2 seconds. For expiration it changes to +1 cm H20

Front 100

Pulmonary Pressure

Back 100

-pleural pressure is that of the pleural fluid. Constant drain keeps it negative so lungs in place
-alveolar pressure is pressure in alveoli
-transpulmonary pressure is the alveolar pressure through pleural pressure
-as we inhale the alveoli/pleural pressure becomes slightly negative and then less negative, expiration the opposite. As we breath our lungs fill so it creates pressure. Changes in pleural pressure is larger
-when the alveolar pressure is less than atmospheric, air rushes in

Front 101

Compliance

Back 101

-think of it as volume/pressure as related to stretchability (balloon more compliant than soccer ball)
-2 forces determine compliance in lungs, elastic forces (collagen/elastin), and surface tension
-Due to this it takes 3X as much pressure to fill lungs with air than water. Surface tension of water/air interface takes more pressure to overcome
Less Compliances - In asthma or fibrosis the lungs are less compliant and it takes more work to fill them with air, usually leads to less volume
More Compliants - in emphysema the lungs are more compliant and air rushes in easier, get a bigger volume

Front 102

More Surface Tension

Back 102

-because water wants to interact with itself at water-air interface, it takes extra pressure at alveoli to have air interact with water
-If surface tension of alveoli increases (pulmonary edema) it would take more pressure to get air in.
-Alveoli coated with only water would close them shut due to surface tension. To counter this type II cells release lamellar bodies with pulmonary surfactant (DPPC), a detergent that breaks up water bonds and reduces surface tension

Front 103

Pulmonary Volumes

Back 103

Total Lung Capacity TLC) - About 6L
Tidal Volume (TV) - Usually you have 2.5 liters in your lungs and on an average breath it will fluctuate .5L
Inspiratory Reserve Volume (IRC)- The amount you can add on a full breath from the tidal - 3L
Expiratory Reserve Volume -(ERV) The amount you can forcefully expire from tidal volume, about 1L
Residual Volume (RV)- The amount that you cannot get out of your lungs - 1L
Functional Residual Capacity (FRC)- Bottom of tidal volume to empty lungs. ERV + RV (2.3l)
Inspiratory Capacity (IC)- Bottom of tidal volume to max you can bring in. Tv + IRV (3.5l)
Vital Capacity (VC) - Amount of oxygen you can bring in and out. IC + ERV, IRV + Tv + ERV (4.6l)
TLC = VC + RV, or IC + FRC
--the minute respiratory volume is amount of air you bring in per minute. It is tidal volume times breaths per minute

Front 104

Types of Breathing Work

Back 104

1. Compliance Work - Needed to overcome elastic forces
2. Tissue Resistance Work - Needed to overcome viscosity of lung and chest walls
3. Airway Resistance - Needed to overcome airways (greater in asthma)
-all these higher in inspiration but can be higher in expiration during exercise or pathology

Front 105

Dead Space

Back 105

-space where oxygen is not exchanged with carbon dioxide
1) Anatomical - Where no alveoli are present (conducting passages)
2) Alveolar - Pathological where no BV pass by alveoli
-when you breath in, the first air out will still be oxygen cause no dead space gas released first

Front 106

Pulmonary Circulation

Back 106

-blood passes through pulmonary capillaries in .8 sec
-pulmonary arteries carry venous blood and are thinner walled and more compliant to accomodate stroke volume of right ventricle
-Pulmonary system pressure (artery, vein, capillary) less than systemic

Front 107

Pulmonary vs. Systemic Constriction/Dilation

Back 107

Pulmonary: Low oxygen in alveoli constricts capillary in that area while high oxygen stretches alveoli, releasing NO and dilating the BV
Systemic: Low oxygen leads to artery dilation so more blood and thus oxygen can pass

Front 108

Effect of Vertical Lung

Back 108

-Gravity and hydrostatic forces push on vasculature so there is more blood at bottom of lung leading to the zones
-BV pressure needs to be higher than alveolar for there to be blood flow. Think of blood pressure as opening capillaries and alveolar as closing
Zone 1 (top) - Doesn't exist in healthy people, but in unhealthy the alveoli pressure is always higher so no blood flow
Zone 2 (middle) - At apex for healthy people. Alveolar pressure is greater than diastolic (venous flow back to heart) but less than systolic (arterial flow from heart). Therefore there is intermittment blood flow.
-Capillary pressure is 15 mm Hg below the heart
-If the right ventricle systolic pressure is 25 then capillary at this point is 10. During diastole when it drops to 8 then capillary is -7.
-Since alveolar pressure is 0 at peak of inspiration, in zone 2 only blood flow during systole
Zone 3 (Bottom) - Blood pressure always greater than alveolar so continuous blood flow

Front 109

Nervous System's Role

Back 109

-In pulmonary arteries sympathetic constriction leads to increase pressure and dilation to decrease pressure
-Sympathetics respond to alpha-adrenergic receptors, not beta. By stimulating alpha receptor you get constriction and increase in pressure, by blocking alpha you get dilation and pressure decrease

Front 110

Exercise

Back 110

-during exercise the HR and BP increase so the arterial pressure in more of the lung is greater than alveolar pressure, so more capillaries open and more blood flow. Looks like graph for zone 1-3 but shifted up
-at first exercise leads to modest increase in pressure without lung edema. If pressure passes 30 (of left atrium) then a backlog increases pulmonary pressure so there is pulmonary edema
-exercise increase blood flow through recruitment (open vessels) and dilation (increase their width)

Front 111

Fluid Dynamics in the Lungs

Back 111

-capillary goes through lung and passes alveoli to exchange gas. Separate by insterstitial space with fluid
Force on interstitial fluid:
1) Hydrostatic Pressure - High in capillary forces +7 fluid out. There is also -8 mm Hg pulling from the interstitial space
2) Osmotic Pressure - Solute concentration in capillary is higher due to proteins. So pulls 28 mm Hg fluid inside the capillary. In interstitial fluid a bit of protein so 14 mm Hg pulling the fluid in.
-if you add these numbers there is a net pressure pushing fluid out of the capillary to the interstitim, and to keep the alveoli fluid free there is a lymphatic system to drain the extra fluid
Hydrostatic pressure - Net pressure is +15 out (7 and 8 are individuals)
Osmotic Pressure - Net pressure of -14 in. Total is +1 out
Osmotic Pressure -

Front 112

Problems with Lungs

Back 112

1) In pulmonary edema the left atrial pressure increases beyond normal range. This is tied into pulmonary arterial pressure. High arterial pressure leads to edema
-The increase in capillary pressure leads to the interstitial space and alveoli filling with fluid
-This alveolar flood can also happen if capillaries are damaged
-Anytime the capillary pressure overwhelms the lymphatics draining you get edema
2) Pulmonary Arterial Hypertension - When the pulmonary BV are constricted the right ventricle works harder and swells. Treated with Viagra
-Viagra inhibits phosphodiesterase 5 (PDE5) which degrades cGMP. cGMP is naturally increased by NO and helps dilate pulmonary arteries. Since PDE5 is pretty specific for pulmonary vessel, if we inhibit it with Viagra then we can increase pulmonary dilation and decrease BP

Front 113

Gas Laws

Back 113

-gas moves from high to low partial pressure
-diffusion carries gas between blood and capillaries
-energy to move the gas comes from kinetic motion
Dalton's Law: In a mixture of gases, each gas behaves as if it were alone and has the same partial pressure. Therefore, the total pressure of a gaseous mixture is the sum of the partial pressures
-this theory applied shows that atmosphere is a mixture of gases, and each gas diffuses independently of the others until it reaches its own equilibrium. This allows for oxygen to come in as carbon dioxide goes out

Front 114

Henry's Law and Gas Solubility

Back 114

Partial pressure of gas in a liquid = the concentration of the gas/solubility coefficient
-the more soluble a gas is in a liquid, the more it dissolve in the liquid and the lower the partial pressure is
-important because CO2 and O2 will be dissolving from air to blood (liquid) and vice versa
(in other words, concentration of gas fluid proportional to the concentration of the gas and inversely related to the solubility coefficient)
-since carbon dioxides solubility is 20 times more than oxygen, if you had 1 mole of oxygen and carbon dioxide, the oxygen partial pressure would be 20 times higher because it didn't dissolve as well as CO2

Front 115

Gas Movement

Back 115

Movement into Fluid (diffusion rate) is directly proportional to the difference in pressure (between air and liquid), the area with which to work, and the solubility coefficient of the gas.
-Diffusion into another medium is hindered by the length of travel (1mm barrier vs. 10mm barrier) and the molecular weight (big clunky items that travel long distances take longer).
-Carbon dioxide will diffuse much quicker than oxygen
D= = delta P (S) (A)/ l (square root of weight)

Front 116

Diffusion Through Tissues

Back 116

-since gases are lipophilic, their diffusion from alveoli to blood is basically just like the diffusion to blood
-As atmospheric air reaches the alveoli the partial pressure of oxygen decreases (goes to blood) and carbon dioxide increases (comes from blood). Opposite true during exhalation when air reaches the outside
-With each breath (tital volume) there is still about 30% of functional residual capacity that remains. After a new breath it takes about a minute for all that air to be cleared. This helps buffer the pH and prevents sudden fluctuations
-the more you use up oxygen (exercise) the quicker you must take it in through increases ventilation or else partial pressure of carbon dioxide will build up. So with each breath oxygen PP increases and carbon dioxide's decreases

Front 117

Respiratory Unit

Back 117

-most gas exchange in alveoli, but also in respiratory bronchioles and elsewhere along the way
-When capillaries come across alveoli the blood is spread especially thin (increase area increase exchange)
-The capillary size as it passes the alveoli is very small so the blood cell must squeeze through, 1 at a time, and touch the walls allowing for optimal gas exchange
-For the gasses to get from the RBC to the alveoli they must pass
1) Fluid layer (water + DPPC)
2. Alveolar epithelium
3. Epithelial basement membrane
4) Interstitial Spae
5) Capillary basement membrane
6) Capillary endothelial membrane

Front 118

Gas Diffusion

Back 118

-remember earlier diffusion equation
1) Distance can be increased to decrease diffusion when liquid in alveoli, like edema
2) Area can be decreased during emphysema as the walls collapse
3) deltaP can be increased (amount of molecules striking the alveolar or capillary membrae)
-Diffusion capacity (DC) is a measurement of the volume of gas going through a membrane per minute. The DC of carbon dioxide is higher because of its increased solubility

Front 119

Ventilation and Perfusion

Back 119

-important to remember for this one that the partial pressure of oxygen and carbon dioxide in the alveoli is a mixture of what's coming in from atmosphere (ventilation) and what's coming in from blood (perfusion)
-Ventilation is the air coming into the alveoli
-Perfusion is the air going from the alveoli to the blood
-Body prefers if these are equal so V/Q = 1
-If ventilation blocked then ratio approaches 0 and the concentration of oxygen in alveoli will approach venous blood
-If perfusion blocked then oxygen in alveoli reaches infinity meaning that it will come to equal the outside oxygen level, that of humified air (since no CO2 can leave blood, in this scenario the alveoli CO2 level will approach 0)
Scenario 1 Ventilation Blocked - The alveoli oxygen partial pressure will equal that coming out of the veins through perfusion (40) and carbon dioxide will be 45
Scenario 2: Normal - Alveoli oxygen partial pressure is a combination of humidified oxygen and venous oxygen so it is 104 while carbon dioxide is 40 cause less of it in atmosphere (but more solubility, is how it keeps up)
Scenario 3: When perfusion blocked then alveoli oxygen partial pressure is equal to outside air (149) and carbon dioxide equals 0

Front 120

Body Scenarios

Back 120

model: you have a alveoli from each lung and 1 pulmonary BV going to each to pick up oxygen, return carbon dioxide, and meet up at the left atrium
-since alveolar oxygen is higher than venous, oxygen moves to blood. Opposite true of carbon dioxide
1) Physiologic Shunt - One lung in this model, so all ventilation goes to the other lung, while shunted lung has a V/Q of 0. Shunted alveoli has a oxygen pressure equal to venous and the carbon dioxide pressure increase cause no removed as effectively. While the working lung has more oxygen and blood passing through it gains more oxygen, venous blood passes the shunted unit. The result is a left atrium with a mixture of venous blood and highly oxygenated blood, this creates blood less oxygenated than it should be
2. Dead Space - Air goes to both lungs, but only perfusion at one of them. Less carbon dioxide can be returned so carbon dioxide level increases. Once again a mixture of well ventilation and not ventilated blood equals less oxygen more carbon dioxide

Front 121

Body Scenario 2

Back 121

-top of lung is dead space, no blood flow all air so V/Q goes to infinity
-Bottom of lung is a physiologic shunt, all blood flow no air, V/Q goes to 0
1. Normal Lung - Ventilation is 2 and perfusion is 2.5 for a V/Q of .8. At alveoli oxygen comes in, both pulmonary veins have oxygen pressure of 100 so the left atrium has oxygen pressure of 100. The concentration of oxygen remains steady at 20
2. Physiologic Shunt on left - The V is increased to 2.5 cause more air in right so V/Q = 1. On left the V drops to 1.5 so V/Q = .6 (Q unchanged). On the right side the alveoli oxygen level is elevated (it is hyperventilated) and the vein oxygen level is 130. On the left side the alveoli oxygen level is low, at 50 so the pulmonary vein is 50. The atrium has mixed blood and at 70 (not saturated) while concentration of oxygen is decreased
3. Result of the Impaired Ventilation - On the right side the blood flow increase and on the left side it decrease. So on the right perfusion increase so V/Q = .8, normal. On the left side ventilation and perfusion decrease, V/Q = .8. Even though pulmonary veins on both sides has the same value, since flow faster on right side, it contributes more to the left atrial blood, whiches oxygen level approaches normal.
Quicky - when V/Q high you are at conductory passage, no perfusion, alveolar air = humidified, no blood circulation. When V/Q is low then no air getting through, alveolar air approaches venous gas levels

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Gas Exchange

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-oxygen diffuses quickly in capillaries to reach the maximum level and all it travels through the body it goes down to the lowest level as it's used up
-At the tissue the opposite happens, the blood oxygen level is higher than tissue (only needs to be 1-3 higher) so blood goes to the tissue. If the difference is lower than no diffusion and atrophy happens
-As blood flow changes the rate of oxygen delivery changes. When blood flow increase, tissue oxygen increase. When oxygen usage increase (or blood flow decrease) tissue oxygen decrease

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DIffusion of Carbon Dioxide

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-carbon dioxide follows a similar (but reverse) principal as oxygen, but the rapid diffusion isn't due to a a large difference in carbon dioxide levels, it's due to the high solubility of carbon dioxide
-even with a small difference, diffusion will happen quickly from tissue to blood and then alveoli
-Between the pulmonary artery and vein carbon dioxide level decrease a lot

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Hemoglobin

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-Most of blood oxygen carried by hemoglobin which has 4 subunits each with a heme
-Allosteric binding allows one heme bound to increase affinity of other bound
-Oxygen is loosely bound to heme so it can be released easily
-Hemoglobin saturation depends on level of oxygen in blood, less oxygen, less hemes bound to oxygen
-In lungs hemoglobin is 97% saturated, as it moves through the tissue is becomes less saturated.
-During exercise there is a step drop off in hemoglobin saturation (much like the more oxygen bound the easier it is to bind others)

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Bohr Effect

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-Carbon dioxide joins water and using carbonic anhydrase makes carbonic acid. Carbonic acid will release H+ and be left with HCO3
-So at the lungs when CO2 leaves the pH increases which favors oxygen binding to hemoglobin
-At the tissue as carbon dioxide builds the pH drops which favors removal of oxygen
-During exercise more CO2 (lower pH) and higher temperature helps release oxygen. Additionally, hypoxia releases BPG which helps release more oxygen. So when you need it the most, oxygen is there

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Transport of Carbon Dioxide

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-from ths tissue 7% of carbon dioxide diffuses into the plasma. This number increases with more carbon dioxide because part of diffusion equation is difference in gas levels
-In the RBC
1) Carbon dioxide binds Hb (23% stays in this state)
2) Carbonic anhydrase converts CO2 + H20 - carbonic acid which readily converts to HCO3 and H+
3) At this point HCO3 is released to the blood and H+ is bound to Hemoglobin to act as a buffer
4) During exercise level of CO2 too high, H+ released to blood and pH drops (acidosis)
5) An AE1 membrane antiport trades HCO3 for Cl- (Cl- in RBC always higher in venous blood, more HCO3 to trade). This is important for CO2 transport. If you block carbonic anhydrase with acetazolamide then blood CO2 levels skyrocket (would rather have HCO3)

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Transport of CO2

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-at alveoli the opposite of this process occurs
1) oxygenation of Hb causes H+ to leave Hb
2) HCO3 will come in the cell and Cl will leave
3) H and CO3 join, and using carbonic anhydrase H20 is released and CO2 is back
4) The increasing CO2 level will help it go to the alveoli.
This is the haldane effect. Basically under heavy oxygen conditions it removes carbon dioxide from the blood and into the lungs

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CO2 Summary

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At tissue Bohr Effect - CO2 kicks oxygen out (CO2 conc high, H+ increase, temp increase, BPG), converted to HCO3 and traded for Cl while H+ bound to Hb
At alveoli Haldane Effect - Oxygen kicks proton off (oxygen level higher) which binds HCO3 in for Cl-. You end up with water and CO2 which goes to the lungs

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Respiratory Control

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-controlled in the brainstem by the dorsal respiratory group (inspiration) and ventral respiratory group (inspiration and expiration)
-Pneumotaxic center inhibits rate/depth
Dorsal Respiratory Group: In charge of endogenous, rhythmic (unconscious) breathing. Gathers imput from chemoreceptors, baroreceptors, CN X and CN IX. Ramps up breathing instead of gasping. Controlled by the
Pneumotaxic Center - Localed in the pons nucleus parabrachialis it controls rhythm of the DRG. It turns off inspiration ramp and reduces duration and depth of inspiration (faster/shallower)
Ventral Respiratory Group - Located in the nucleus ambiguus it is inactive during quiet breathing, and during exercise it is activated to increase ventilation mainly through expiration, some inspiration

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Hering-Breuer Inflation Reflex

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1) Stretch receptors in bronchioles activated during deep breath
2) Vagus sends inhibitory signal to DRG to decrease duration of the tamp
3) Through the phrenic nerve the diaphragm is told to contract less and reduce lung volume and stretch (more shallow breaths = quicker rate)

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Chemical Control of Respiration

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CO2 Crossing Blood Brain Barrier
1) CO2 build up leads it to cross the blood-brain barrier. Body uses CO2 because it can cross barrier, H+ cannot
2) Converted to H+ and HCO3 by carbonic anhydrase
3) H+ binds receptor in ventral medulla
4) Signal to DRG to increase ventilation
-linear relationship, more CO2 rises, quicker your ventilation goes to rid your body of it

Chemoreceptors
1) Blood always flows over the carotid body which measures partial pressure of oxygen
2) When oxygen drops the nerves increase in firing
3) Firing signal CN IX to trigger DRG to increase breathing
...initiated by hypoxia induced release of ATP from glomus cells whcih leads to NT release down the line
v2
1) Carotid Body also triggered by CO2 and H+, but less than oxygen
2) CO2 crosses into glomus cells and conveted to HCO3 => AC => cAMP => PKA => Open L-type Ca++ channels which depolarize cell and send signal to DRG

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Interrelated Effects of CO2, O2, and pH

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-As partial pressure of CO2 increase the ventilation rate increase for a given oxygen. In other words, change in ventilation is based off how much CO2 increases and what oxygen is at the time
-Same thing with pH, as pH decrease, increased ventilation for given oxygen

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Exercise and Ventilation

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-during exercise the neural signal to increase ventilation comes from muscle contraction, not change in blood gases (too minor)
-Because of this there is a delay between CO2 elevated, so the corresponding increase in ventilation is always a undershoot of what is needed
-same for when you stop working out. Body catches up to increase CO2 after you're done, so for a few minutes there is a overshoot in ventilation even though it's not needed
-This is similar to the Cheyne-Stokes breathing. Any change in respiration comes gas levels in brain (CO2 in brain) which takes a while to get there so the response is always delayed

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Anesthesia

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-anesthesia acts on medulla respiratory center to reduce ventilation

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Respiration at High Altitude

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-at a steep climb (12K ft) the oxygen partial pressure drops to where Hb not well saturated. You get fatigues, headache, drowsy...trick, get acclimated
1) At high altitude the oxygen is released
2) Body reads the situation and increases respiration which decreases CO2
3) After CO2 released the body goes to normal breathing, thinks everything should be alright. But since atmosphere oxygen low, you now just have low level of both gases
4) After a few days kidneys notice CO2 decrease and secrete HCO3- which acidifies and a low pH triggers chemoreceptors to breath more and increase oxygen

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Exhalation

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Normal:
-You can inhale quicker than exhale
-You can exhale quicker when your lungs are full, then the rate decreases
-Elastic pull on bronchioles and muscle pull on alveoli decrease with lower volume
Constricted Lungs:
-in Tb your lungs cannot expand so you have reduced TLC and RV. You're expiratory rate is less because you can't get that expansion. Basically curve pushed to right, same rate for lung volume as expected

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Exhalation 2

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Obstructued Lung:
-usually you use force in inhale and exhale is automatic. In asthma or emphysema your lung bronchiole are collapse and there is great resistance so it is harder to breath out.
-Over time to compensate your TLC and RV will increase but the rate will never be that high
-treat asthma over-constricted muscle with a beta-adreneric agonist to relax the muscles and steroids to reduce inflammation
-A novel treatment uses bitter compounds to trigger TAS2R bitter receptor in the bronchiole smooth muscle cells. This leads to Ca++ release via IP3 which triggers K+ channel efflux, repolarization, and muscle relax

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Emphysema

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-The alveoli become stretched by air in mucus and epithelial edema
-This destroys alveolar walls and increases exhalation resistance
-The result is a mismatch in lungs with normal alveoli mixed with physiological shunt and dead space, as well as less surface area for gas exchange
-The result is less capillaries (no oxygen and cap shunt off) and same amount of blood so the BP increase and you get hypertension which drives more pulmonary edema in
-in emphysema there is collapse and breakdown of alveoli for less gas exchange
-The diffusion "l" and "a" increase and decrease respectively

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Pneumonia

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-bacterias or viral inflammation of alveoli makes them filled with fluid
-This reduces surface area for gas exchange and as ventilation decrease V/Q decrease
-This leads to hypoxemia (low blood o2) and hypercapnias (high blood co2)
-in pnemonia there is blood (from cap) and debris (from virus and infection) in alveoli and edema in interstititial tissue
-in diffusion the "l" and "a" change

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Pulmonary Fibrosis

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-called scarring of the lungs, the CT interstitial space between alveolar epithelial cells and capillaries (basement membranes) thickens
-This increase "l" in diffusion rate so it impairs oxygen diffusion from alveoli to blood
-the "l" in diffusion change big time here

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Coagulation and Dentistry

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-up to 10% of tooth extractions heal improperly
-complicated by vitamin K deficiency (poor health), patient on anti-coagulant, liver problems, or hemorragic disorder

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Intro to Terms

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Hemostasis - The collection of processes that prevent blood loss
Thrombus - Clot that develops in blood vessel (normal for injury, abnormal in plaque). Can be red if it occurs in vein where RBC trapped or white if it happens in artery where blood too fast to trap RBC
Emboli - A free flowing clot or platelet plug that breaks away from vessel. Cause of strokes, and fatal

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Clotting Overview

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-caused by vascular wall (endothelium), the ECM, and platelets
-initiated by damage to vascular wall (external trauma or internal trauma like plaque formation or virus) and blood problem (sickle cell)
Stages
1) Vascular Phase - Vasoconstriction upstream
2) Primary Hemostasis - platelet activation phase
3) Secondary Hemostasis - Platelet form active surface where thrombi cascade occurs
4) Plug formation and dissolution because leaving clot there too long bad

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Vascular Phase

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Contraction occurs from many sources
1) Pain leads to nerves stimulating it
2) Muscle contraction leading to BV contraction
3) Local Factors - platelets release TXA2 and endothelium release serotonin
-leads to blood flow upstream and collagen exposed at surface of injury

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Primary Hemostasis - Platelet Activation

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-inactive platelet is anuclear discard from megakaryocyte. Most platelets in blood for 8-12 days, others in spleen
1) adhesion - Upon binding to ECM (collagen, fibronectin, proteoglycans, and vWF) it is activated
2) activation - changes shape to get sticky fingers and secretes granules with pro-coagulants and serotonin (vasoconstrictor). In this way it is auto-catalytic and will recruit other platelets. Feedback loop also knows how to prevent excessive activation
3) Aggregation - form a plug and a catalytic surface for the coagulation cascade. Produce thrombin which cleaves fibronogen to fibrin

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Platelet More Details

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1) Platelet receptor GP1b binds endothelial cell vWF
2) This interaction acts as a catcher and thus allows platelet to bind collagen which leads to stimulation
3) Binding to collagen changes shape to stick-spine spheres (activated surface) and released granulues. Granulues have pro-coag ADP/TXA2, and constrictor serotonin
-ADP and TXA2 bring other platelets to the spot and at this point constriction disappear so protease cascade must occur quickly
4) During platelet aggregation the plug is formed before fibrin is processed. Platelet bring fibrinogen to the "party" by binding through GpIIb. It also cleaves prothrombin to thrombin

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Balance of Platelet Aggregation

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-endothelium (healthy) product anti-aggretory psotacyclin and ADpase while platelet product pro-aggregatory ADP and THXA2
-In this way healthy tissue doesn't have clot formation while unhealthy has only pro-coagulation molecules

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Coagulation Cascade

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-series of proteolytic reaction in which a inactive enzyme is cleaved and becomes active
-two pathways are intrinsic and extrinsic which converge at factor X production to form prothrombinase complex
-End result is production of thrombin which produces fibrin which forms the cage to protect site of injury

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Extrinsic and Intrinsic Pathways

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-calcium is required for both to promote or accelerate
-both lead to factor X and prothrombinase complex
Extrinsic - Begins with trauma to vascular wall and it's very quick

Intrinsic - Begins in blood after exposure of platelet to collagen. A bit slowerr

-at end is prothrombinase complex where thrombin made which feedbacks to activate some of the other and promote the cascade
-prothrombinase complex begins with factor X activation which puts prothrombin in position to be cleaved
-vitamin K so necessary because it ffects prothrombinase part

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Prothombinase Complex

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-the entire cascade happens on the activated platelet surface (after collagen bound). The factors are circulating blood and activated surface lets them bind
-Factor 5 binds surface and acts as scaffold. Held on negative phospholipid membrane by gla-domain interaction with calcium. gla-domain made possible by vitamin K
-Factor X binds membrane separately and then the two are joined
-Factor V binds Factor X and prothrombin
-Factor X cleaves prothrombin to thrombin
-thrombin cleaves fibrinogen (negatively charged and repel one another) to fibrin which forms a polymer with the help of factor 13 which requires vitamin K

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Clot Retraction

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-after fibrin clot is formed it begins to contract or tighten
-The fluid pushed out of the clot is serum and contains clotting factors and left over fibrinogen
-Platelets help by retracting their spicules touching fibrin thus pulling the edges of the broken bv together
-problem with retraction can lead to release of clot and a emboli

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Removal of Clot

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-thrombin produces clot by fibrin formation and tries to maintain clot by creating PAI which blocks tPA
1) During clot formation plasminogen incorporated into the plug
2) A day after the injury the endothelium (around clot) release tPA to activate plasminogen to plasmin
3) Plasmin degrades fibrin polymer into small pieces and removes clot
4) To slow the rate of plasmin it is bound to anti-plasmin (AP)
5) To slow down tPA thrombin (in addition to making fibrin) makes plasminogen-activator inhibitor which blocks tPA

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Clot Prevention

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1) Thrombomodulin - Make in endothelial cell, it slows down clot formation by binding and inactivating free thrombin. ALso activates protein C and S which inactivates factor V and VIII
2) Anti-thrombin III - binds and inactivates remaining thrombin. Also inhibits factor X
3) heparin - Binds anti-thrombin III and increases the affinity to thrombin
4) Prostacyclin
5) Plasmin

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Bleeding DIsorders

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-liver disease and vitamin-K deficiency
Liver Disease - less clotting factors made by the liver
Vitamin K - When oxidized it moves NADH to NAD and turns glutamate to y-carboxyglutamate and with double negative it can bind calcium
-needed to make factor 9, 10 (bind platelet surface), 12, and prothrombin. It is lipid soluble so bile issues or absorption problem will decrease it.
-Anti-coagulants like warfarin work blocking functional vitamin K

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Bleeding DIsorder

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1) Thrombocytopenia - low levels of platelets. Autoimmune, and seen as bruises
2) Hemophilia - Abnormal Factor 8 or 9 (rarely). X-linked. Can cure Factor 8 problem by injecting it into the body
30 vWF deficiency - most common inherited bleeding disorder. Similar clinically to hemophilia. Without vWF you cannot catch platelets so whole produce inadequate

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Lab Bleeding Test

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1) Prick Finger - If bleed more than 6 min you have a problem
2) Count platelets on a slide
3) Clotting Tube - Of blood in test tube
4) ELISA - measure coagulation cascade factors
5) Activated Partial Thromboplastin Time - Measures intrinsic pathway
6) Prothrombin Time - measures extrinsic pathway and effectiveness of oral anti-coagulants
...to suture wound use absorbable hemostats with collagen to help activate/recruit platelets and plug to form

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Summary

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Anti-Coag
1) Smooth surface
2) prostacyclin
3) Thromboodulin
4) t-PA => plasminogen => plasmin

Pro-Coag
1) collagen
2) vWF
3) thrombin - if too high then clot made and it can also help break down mesh
4) inhibitor of plasminogen activator