Cardio-Vascular

Saturday, January 12, 2013 4:49 PM

Anatomy Page 1

CV Anatomy
Thursday, January 10, 2013 12:58 PM

Location and Orientation Mediastinum Middle region of the thorax This is where the heart is located Bottom border Diaphragm Pericardium attaches the heart to the diaphragm When you breathing and the diaphragm is moving up and down, the heart is going to have movement in your thorax area cause the PC is attached to the diaphgragm Borders Base (top) Right border Left border Apex (bottom) Inferior surface Down the diaphragm Surface Projection General Sits to the right side and is rotated to the left when we look at the heart from the front view, we see more of the right side Terms Costal cartilage (rib) Intercostal space Orientation Superior left Inferior right
Inferior left

Inferior border of second costal Sixth cartilage

Intercostal space between fifth and sixth

Superior right Third costal cartilage

Side view of Mediastinum (left) Sternal angle followed down by the four sternabrae Regions

Middle region

Heart, ascending aorta, pulmonary trunk

Anterior portion Lymph node, thymus gland (note in infants this is large, as large as a lung as you age it shrinks)

Posterior region Descending aorta, esophagus, lymph nodes, vagus nerve, thoracic duct
Superior region Aortic arch, esophagus, trachea

Anterior Surface Features Right atrium Right ventricle Left auricle Little flap like thing Left ventricle Dont see it full on just see it peeking through Note Dont see the right ventricle I believe Posterior Surface Features General Can see more of the left of the heart Aorta Superior vena cava Left atrium Left ventricle Right ventricle (some of it) Right atrium Inferior vena cava Groovy Heart (Sulci) General Have vessels sitting within the grooves. Dont want vessels moving when the heart moves, so the coronary vessels lie in them they are tracks Coronary Sulcus Lies between atria and ventricles Interventricular Sulcus Lies between left and right ventricles Vessels Big Vessels Off the Heart Aorta It comes off the LV, arches up and then descends behind the heart Pulmonary trunk Comes off RV and takes blood to the lungs To the Heart Superior Vena Cava Returning blood from upper body to the heart
Anatomy Page 2

 Returning blood from upper body to the heart Inferior Vena Cava Returning blood from lower body to the heart Anterior Coronary Arteries General Supplies blood to the heart muscle Right coronary Comes off arch of aorta Wraps all the way to the back of the heart, but before that it branches to the marginal artery, and then in the back it will branch into the posterior ventricular artery Comes off arch of aorta Branches very quickly, into the circumflex and the LAD Comes from right coronary Goes down the front of the heart
Comes from left coronary Goes to the back of the heart Is in the coronary sulcus Comes from left coronary Is in the interventricular sulcus

Left coronary Marginal artery

Circumflex artery

Left Anterior Descending (LAD)

Coronary Veins Small cardiac vein Anterior cardiac vein Middle cardiac vein (on the back side) Great cardiac vein (wraps to the back) Runs in the interventricular sulci up the heart, in the same groove as the LAD It will curve into the coronary sulcus (where the circumflex is) and will go to the back of the heart Coronary sinus (on the back side) This is where the coronary veins comes together and this is where the blood gathers before it is returned to the right atrium Posterior Coronary Vessels Great cardiac vein Coronary sinus Right coronary arteries Posterior interventricular artery Comes off the right coronary at the back of the heart in the interventricular sulci Obstructed Arteries Lumen is the inside of the artery, and in partially obstructed arteries there is atherosclerotic plaque, which narrows the artery This obstruction starts right after birth to everyone If the LAD is obstructed, will get an MI cause there is no anastomosis protecting it Pericardium and Heart Wall Pericardium General There to protect the heart Fibrous pericardium Dense irregular connective tissue Protects and anchors the heart Prevents overstretching Serous Pericardium Secretes serous fluid Parietal layer Serous fluid in between Reduces friction Visceral later (epicardium) Heart Wall Layers Epicardium Myocardium Where the specialized cardiac muscles are Endocardium Similar lining to what is in your blood vessels (endothelium) These are non-thrombogenic surfaces -- wont get clumping of components of the blood, like platelets and plaque formation Thickness The left side of the heart is much thicker than that of the right side this is cause the left side of the heart has to work much harder in order to deliver its flow Thickness is depending on the function of the chamber Inflammation Pericarditis Fluid, pus Myocarditis Can be caused by viral function and rheumatic fever Endocarditis Potentially fatal if not treated Chambers Chambers Right Atrium Right Ventricle Left Atrium
Anatomy Page 3

Left Atrium Left Ventricle Flow Blood goes from the body into the right atrium and then flows into the right ventricle. It will go from there through the pulmonary trunk to the lungs. Then oxygenated blood comes from the lungs into the left atrium, down to the left ventricle, and then out through the aorta to the body tissues. Body Right Atrium Right Ventricle Pulmonary trunk Lungs Left Atrium Left Ventricle Aorta Trabeculae Carnae = fleshy logs When you look at the inside of the heart, you notice a buumpy surface inside i.e. raised cardiac muscle Valves Help blood to travel in a specific path Tricupsid Right side of the heart Three leaflets (cusps) from these come out chordae tendineae (like parachute strings) to this is attached is the papillary muscle Bicupsid (mitral) Left side of the heart Two leaflets How So when the blood enters the ventricles, they need to contract to let the blood through the aorta or pumonary trunk. That pressure is huge and you dont want blood to back-flow to the atria. The pressure makes the chordae tendieae muscles to go taut, the papillary muscle contracts and these things prevents the cusps everting or opening up back into the atria Disorders Stenosis Congenital, Scarring Mitral Aortic Prolapse When you have the eversion of the cusps going back into the atria Mitral valve prolapse (MVP) Fibrous Skeleton General Helps maintain the diameter of the valves Attachment side for muscle fibers Electrically separates the atria from the ventricles Orientation Wraps around the heart Like a wet towel and how you wring it, the fibrous skeleton is similar in how the muscle squeezes the heart Operation of the AV Valves . Didnt copy this Des scribed above I think Operation of the Semilunar Valves General Between the ventricles and the aorta/pulmonary trunk Dont have the chordae tendenae and papillary muscle How When the pressure in the ventricle is higher than that in the vessel, the valves open When the pressure is less, the valves close Heart Sounds General Closure of the cusps (this as well?) and the turbulence of the blood going up against the cusps is whats causing the heart sounds Heart sound is not listened to right at the spot of the valve, but a different spot is the echo is what is heard best All Pig Eat Too Much Aortic valve Heard at the right sternal border at the second intercostal space Pulmonary Valve Best heard on the left side in the second intercostal space close to the sternal border Erb's Point (LLSB) Point in the third intercostal space where you can hear both the aortic and pulmonary valve sounds Tricuspid valve Heard to the left hand side even though this is at the right Best heard around the 4th or 5th intercostal space Mitral (bicuspid) valve Heard to the left hand side Best heard in 5th intercostal space at the midclavicular line Summary Heart location Heart orientation Heart surface features Coronary vessels Main arteries and veins Chamber and valves of the heart Heart sounds When the heart is contracting, coronary blood supply Decreases. When the heart contracts, the surface coronary vessels stay open, but the ones that are feeding the myocardium act ually get compressed. So during ventricular contraction, there is little blood supply going directly to the heart tissue. What might be the consequence of a heart attack that injured a segment of the papillary muscle. How would the flow of blood b e altered? If this happens, remembering that the papillary is the anchor for the chordae tendianae, the cusps dont have tension and the refore you have back-flow
Anatomy Page 4

 If this happens, remembering that the papillary is the anchor for the chordae tendianae, the cusps dont have tension and the refore you have back-flow into the atria. One condition associated with this is mitral valve regurgitation

Anatomy Page 5

CV Development
Saturday, January 12, 2013 3:22 PM

Function drives Development All about oxygen delivery Embryo Start with two tubes that eventually start forming into a heart like shape Fetal Heart looks similar to post-natal heart, except there are differences in features Postnatal/Adult Birth is a transition point Right is deoxygenated blood and left is oxygenated Adult Heart Four chambers RA RV Lungs LA LV Body Circulatory System Pulmonary side This is concerned with removal of CO2 and waste products from blood goal is to remove waste and get blood oxygenated This is the right side of the heart Systemic side Left side Delivery system Transport waste to the right side of the heart Post Natal Circulation

Arteries Blood away from the heart

Veins Blood towards the heart

Characteristics Two Closed Circuits Closed left side and closed right side Dont have mixing unless there is a defect Arranged in Series Pumping through the pulmonary circulation and then the systemic circulation Pressure Pressure on the left side of the heart is higher because of the vascular (?) resistance than on the right side of the heart Left side is supplying whole body right side to the pulmonary vasculature Fetus Fetal Circulation Characteristics Open circuits (left and right sides are not seperated oxygen-medium blood is an indicator of this) Circulation operates in parallel right and left occurs at the same time Pressure Right side has higher pressure due to the pressure associated with the vasculature of the pulmonary system Left side has a lower pressure because it has a low systemic resistance due to the placenta being there Oxygen exchange Oxygen exchange occurs at the placenta, not at the lungs Through diffusion no mixing between the two blood systems (of the mother and fetus I think) Blood flow Flows from the placenta through the umbilical cord and umbilicus then at the liver point ish there is mixing of the blood c ause there is blood coming from the fetus from the inferior vena cava that is deoxygenated I think this is through the ductus venosus (?) In the right atrium, there is an opening to the left side through the foramen ovalae this lets the blood go to the aorta qu ickly Some blood makes it to the pulmonary trunk through and therefore there is the ductus arteriosus to let the blood go from th e pulmonary trunk to the aorta 5-7% of the blood still goes to the pulmonary trunk to the lungs During the later stages of fetal development, this is important cause you're trying to get the lungs to work at birth so wa nt to start to get that system primed and ready Blood returns from the fetus through the umbilical arteries

Shunts Ductus venosus Allows the mothers blood to bypass for the most part the liver the maternal circulation is already filtering the blood so t he fetal liver doesnt need to do this Foramen ovalae Ductus arteriosus
Birth

Anatomy Page 6

 Birth What happens Events Placenta is lost This causes an increase in the pressure in the left hand side First breath Lungs open and the pressure associated with the right side will drop Shunts are closed All of them? Closures in postnatal circulation Shunts and Ligaments Umbilical vein Ligamentum teres Umbilical artery Medial Umbilical ligaments Ductus venosus Ligamentum venosus Ductus arteriosus Ligamentum arteriosum Foramen ovalae Fossa ovalis The FO is a depression in the atrial septum this can be seen in specimens Tubular Heart 2 Weeks Two thin tubes of cardio tissue two start to expand and fuse 4 Weeks Fused to one tube Starts to get sacculations is like a wavy tube Features
TA - Truncus Arteriosus Becomes the pulmonary trunk and the aorta

BC - Bulbus Cordis V - Ventricle A - Atrium SV - Sinus venosus

RV
LV

RA, LA, R+L Auricles RA, Coronary sinus, SA node

Heart starts to elongate and then fold into an S-shaped configuration Note that valves are in alignment Truncus Arteriosus (Division) Aorticopulmonary (spinal) Septum Separation of tubes Looking at it from top-down, there are from the sides ridges forming which grow towards each other and form a septum and that splits the tube into the two great vessels This develops in a spiral formation there is a 180 0 rotation occurring with the spiraling See pic So I'm thinking that its not the tube that is twisting, but the septum or divider inside of it that is twisting Locations PT sits in front of the aorta and the aorta curves behind the PT Arch of the aorta goes over the pulmonary arteries Formation of Valves This septum does this these are the semilunar valves

Truncus Arteriosus 1 vessel and 4 cusps Aorta + PT Now there are 2wo vessels with 3 cusps each

Problems Persistent Truncus No Separation of Aorta and PT Blood mixes from the left and right sides of the heart oxygenated and deoxygenated In the fetus its no problem but after birth the baby can become cyanotic Transposition of Great Vessels Septum fails to spiral In this case, Aorta comes of right side and PT from the left side There you have one circuit cycling oxygenated and one deoxygenated the deoxy is never getting reoxyed Not an issue in the fetus cause there are bypasses and shunts but in post -natal life this is fatal unless there are other defects such that the circuit becomes open Fatal in life without PDA, ASD and VSD Patent ductus arteriosus Atrial septal defect Opening between the atria Ventricular septal defect Opening between the ventricles Stenosis Septum has divided the right and half part unequally one side is expanded and the other is stenosed Factor-Effect Factor Effect

Obstruction or shunt

Obstruction

Blood flow Reduced blood flow to pulmonary artery Right ventricle Pressure and size increases natural response of body is to maintain what it sees in normal and therefore if pressure and size there is an increase in pressure, the tissue response is to increase in size this is so the pressure is distributed over more tissue, decreasing pressure on each individual piece of tissue Acyanotic or cyanotic Acyanotic its a moderate obstruction in the case study so its acyanotic if it was a full obstruction then it would be cyanotic possibly

Patent Ductus Arteriosus Normally in birth there is an immediate closure of DA and over time there is tissue accumulation to fully close it
Anatomy Page 7

 Normally in birth there is an immediate closure of DA and over time there is tissue accumulation to fully close it Here there will be an opening between the aorta and PT blood will go from aorta to PT cause pressure is higher in the left hand side Partitioning of Chambers Formation of Interatrial Septum The IAS begins with the formation of a septum that comes down from the roof of the aorta and downwards towards the endocardial cushion (midpoint between the atria and the ventricles) this first septum = septum primum it will continue to grow to the cushions but there will still be an opening called the foramen primum, which allows the open circuit in the fetal heart Get holes within the septum primum to keep the open circulation, and these are perfurations called the foramen secundem (?) Then get a second septum that is much thicker called the septum secundem come down beside the septum primum, and the hole that remain here is the foramen ovalae The remaining tissue that is left from the septum primum is called the valve of the foramen ovalae Foramen ovalae Before birth Pressure is higher on the right hand side, so blood will move from right to left Blood will cause the septum primum to open (or in other word the valve of the foramen ovalae) when the pressure build up on the left hand side, the valve will close After birth Pressure is higher on the right side, the valve of the foramen ovalae closes and unless there is problems it will be closed ASD (Atrial septal defect) This is an opening in the heart The foramen ovalae fails to close From next lecture If Baby Noah had a patent ventricular septum, what would be the effect It would be the same as the patent atrial septum (on the slides), which is that blood flow will be pushed from the left ventricle to the right ventricle. Baby Noah is going to be acyanotic so oxygenated blood is being pushed to the right side the blood that is still on the left side is not getting mixed with deoxygenated blood and therefore Noah will be acyanotic (will still get enough oxygen) Interventricular Septum Starts growing from the bottom of the ventricle and grows to the endocardial cushion the last bit of it that attaches to the cushion is the membranous portion, which is important cause formation of this membranous component is associated with the separation of the truncus arteriorsis into the aorta and the pulmonary trunk If there is problem with the formation of the membranous portion, there may also be a problems with the formations of the great vessels Membranous portion Formed from the endocardial cushions and the bulbar ridges The ridges are similar to the ones seen which played a role in the formation of the spinal septum Associated with the partitioning of truncus arteriosus Tetralogy of Fallot Defect involving the membranous portion of the interventricular septum There is some debate as to what causes the malformation Combination of four different defects that are occurring (numbering below is not necessarily #'s of occurrence or importance) Tetrology 1) Larger than normal aorta (overriding aorta cause it overrides both ventricles) picks up blood from both the left and right ventricles so it is picking up deoxygenated and oxygenated blood 2) Stenosed pulmonary trunk 3) Interventricular septal defect In the membranous portion 4) Enlarged (hypertrophied) right ventricle Thickness of a tissue responds to changes in pressure so in response to the higher pressure in the RV (cause there is blood flowing from the LV to RV) + increased pressure due to the resistance caused by the stenosed pulmonary valve/trunk therefore it grows in size Baby Can be cyanotic cause we have mixing deoxygenated and oxygenated blood Formation of the Atrioventricular Valves Tricuspid Bicuspid Formation From subendocardial mesenchymal tissue that proliferates and develops outgrows Note The way this valve is formed is that you have outgrowth of tissue but the shape of the valves is specific so it is sculpted by programmed cell death (apoptosis) this is similar to what we see in our fingers

Anatomy Page 8

CV Physiology
Tuesday, January 15, 2013 1:34 PM

Myocardium General 95% of the heart Responsible for pumping action Striated, involuntary muscle Fibers swirl diagonally around heart in bundles This is kind of like the fibrous skeleton that we talked about earlier Cardiac Muscle Tissue Sacolemma = cell membrane Functional syncytium AP is started, then travels through the atria and then the ventricles (entire myocardium) Intercalated discs Desmosomes (cell junctions) Gap junctions (allow AP's to move from one cardiac muscle cell to another) Conduction System SAN Heart's pacemaker Sets the rhythm spontaneously depolarizes and keeps doing so until it reaches the threshold AP's that come from the SAN travel to the AV Node AV Node This is a spot between the atrium and the ventricles When we looked at the fibrous covering (skeleton?), that was preventing electrical connections between the atria and the ventricles, we said that this was so that there wasnt signals going between atria and the ventricles This is one exception to this When the AP hits the AV Node, there will be a pause which is important cause you want the atria and the ventricles to contract at different times During this time, the ventricles will be able to fill before they start their contraction From the the AV node, the signal goes to the AV bundles AV Bundles This is going down the interventricular septum Also referred to as the bundle of Hiss Signal continues to the right and left bundle branches and continues down to the purknije fibers which are modified cardiomyocytes At the Purkinje fibers, the signal is starting at the apex of the heart and will travel through these fibers up the walls of the ventricles and eventually depolarizing the entire ventricle Summary SA node anterior, middle, and posterior internodal tracts transitional fibers AV node penetrating fibers distal fibers Bundle of His (AV bundle) right and left bundle branches Purkinje fibers myocardium AP in a Ventricular Contractile Fiber Steps 1) Rapid depolarization Due to Na+ inflow when voltage-gated fast Na+ channels open This will stop with inactivation of the fast channels and Na+ influx will drop Note that contraction will not occur right at the depolarization, it will occur a little bit after 2) Plateau Due to Ca2+ inflow when voltage-gated slow Ca2+ channels open and K+ outflow when some K+ channels open Note: Strength of heart contractions influenced by substances that alter movement of Ca 2+ through the channels E.g. epinephrine when you have an increase, it increases the contraction force by increasing the amount of Ca 2+ that can increase the cytosol 3) Repolarization Due to closure of Ca2+ channels and K+ outflow when additional voltage-gated K+ channels open Contraction Note that the depolarization comes first, then the contraction Electrical activity (AP) Mechanical response (contraction) Similar to both cardiac and skeletal muscle Refractory period Time interval during which a second AP/contraction cannot be triggered Refractory period lasts longer than the period of contraction Tetanus Can occur in skeletal muscle, but not in cardiac muscle This is b/c the refractory period is longer than the period of contraction cant have a contraction after another after anot her Important Because the pumping action of the heart depends on the ventricles being able to alternate between relaxation and contraction Electrocardiogram ECG or EKG Composite record of AP produced by all the heart muscle fibers Note that this is composite of all fiber's AP in previous slides, we saw the AP of a single cardiac myocyte Detected at surface of the body

Anatomy Page 9

3 recognizable waves P Associated with a period of atrial contraction (when atria are in systole) Note that you can't detect when the atria are relaxing dont see this wave b/c the electrical activity level is so low that it is swamped out by depolarization activity QRS Associated with a period of ventricular contraction (ventricular systole) T Represents when the ventricles are starting to repolarize and relax ECG Waves, Systole and Diastole Note Systole = contraction Diasatole = relaxation Left to Right 1) AP potential in the SAN Depolarization of atrial contractile fibers and this produces the P wave AP starts first and then contraction of the atria afterwards 2) Atrial systole contraction After the P wave spike type of thing, this is the part of atrial contraction Also at this time we get that pause in the AV node, giving the ventricles time to fill up 3) Depolarization of ventricular contractile fibers produces QRS complex This produces the QRS thing 4) After the depolarization of the contractile fibers and the whole QRS spikes thing is done, we get the actual ventricular systole (contraction) Referred to the ST segment -- the space between the drop in the S and the start of the T wave 5) Repolarization of ventricular contractile fibers Produces T wave This is just before the ventricle will relax 6) Ventricular diastole After the T wave bump, we see the actual ventricular contraction Cardiac Cycle: ECG and Pressure Waves General Can connect the ECG with pressure Pressure is being generated cause you have blood in your heart contraction of muscles and blood pushing against the chamber s Pressure is measured in mmHg Note: Diagrams are showing the left side of the heart cause the pressures are much higher Steps Atrial Systole When the atria is finishing its contraction, the bicuspid is closed and we have a moment in time when all four valves are clo sed this is an isovolumetric contraction everything is staying the same (nothing is lengthening or shortening As pressure is rising in the left ventricles cause they are filling with blood, the blood closes the valves and you get rising pressure in the left ventricle Ventricular Systole Pressure in LV keeps rising as the fibers continue to contract then the pressure will rise above the pressure in the aorta, which normally is 80 mmHg once its passes this it opens the aortic valves blood will go into the aorta Note that the pressure in the aorta will be increasing but the pressure in the LV will also be increasing Then the pressure of both will start to fall and the aortic valve will close when the LV pressure drops below that in the aor ta at this point there is the dicrotic wave which is a slight bump/increase in pressure in the aorta due to the blood this is caused by the turbulence of the blood falling against the semilunar valves pressure in aorta will stabilize at 80 mmHg Relaxation Period Pressure in LV will continue to drop as it goes to the relaxation phase the bicuspid valves will open and the cycle will st art again Heart Sounds S1 Closure of AV valves (distinct) [right before isovolumetric contraction?]

S2
S3

Closure of SL valves (distinct)

Blood turbulence during filling of ventricles phase (quieter)

S4

Contraction of the atria (quieter)

Note: If blood is flowing smoothly (laminar flow), this will not generate sound. It is when its moving against something causing turbulence is what causes sound

Anatomy Page 10

After the ventricles relax such that they can be filled with blood, initially we get this kind of passive filling, but then there is a boost where the atria actually contract to push blood to the ventricles Stroke Volume EDV (End-Diastolic Volume) During the beginning of ventricular contraction, we have in the ventricles EDV before they are gonna contract at the end of relaxation phase, the volume of blood is referred to EDV ESV (End-Systolic Volume) At the end of contraction phase (after the ventricles have expelled the blood), whatever blood that is left over after contraction is referred to as ESV Stroke Volume = EDV - ESV Each ventricle expels the same amount of blood per beat (left will do the same as right) Remember that the LV is pushing against a greater pressure than RV its able to expel the same amount of blood cause of that thicker heart wall From next class
Heart Rate # of heart beats per minute Pacemaker cells in SA node Autorhythmic rate of 100 beats per minute (bpm) Native HR = 70 bpm Slowed down by parasympathetic stimulation In athletes this might be lower like 40 bpm Cardiac Output (CO) Volume of blood ejected from the left ventricle (or right ventricle) into the aorta (or PT) each minute CO = HR x SV When is increase needed? E.g. when you are running Example CO (ml/min) = HR (75 bpm) x SV (70 ml/beat) = 5250 ml/min Cardiac Reserve CR = CO (max) - CO (rest)

Anatomy Page 11

 CR = CO (max) - CO (rest) Have a reserve -- ability to put out more cardiac output How does CR change with training or heart failure? Stroke Volume Factors that regulate stroke volume Preload Degree of stretch on the heart before it contracts Frank-Starling Law of the heart The more you stretch the heart, the more blood you will be able to push out heart muscle is stretched (during diastolic filling) force of contraction volume of blood ejected into the aorta Ejection volume = Stroke Volume = CO

Factor

Increase

Decrease
Extremely rapid HR

Duration of ventricular diastole Slow HR more chance to (time when ventricles fill with blood) fill ventricle with blood so slow HR = increase in duration Venous return

Increase in venous return (e.g. exercise) Low venous return (e.g. severe blood loss)

Contractility Forcefulness of contraction of individual ventricular muscle fibers Strength of contraction at any given preload Due to changed in influx of Ca2+ From ECF and sarcoplasmic reticulum Type of Agent
Changes in contractility

Positive inotropic
Increase

Negative inotropic

Decrease Examples of inotropic substances Symp stimulation (e.g. adrenaline) Increase K+ Hormones (e.g. glucagon) Acidosis (excess H+) Drugs (digitalis) Calcium channel blockers

Inotropic = affects force of muscle contraction Many drugs are considered inotropic either positive or negative so either increasing or decreasing contractility of fiber s Afterload Is that point where ventricular pressure has to get to the point of the pressure of the aorta this was normally 80mmHg Formal definition: Pressure ventricles must overcome before the semilunar valves open Normal afterload Pressure in the aorta approx 80 mmHg Increase in afterload leads to a decrease in SV More blood will remain in the ventricles therefore ESV will be higher Changes in Afterload Factor
Blood Pressure Regulation of Heart Rate Factor Chemical Regulation Increase Hormones (e.g. E, NE, thyroid) Cations (e.g. Ca2+) Decrease

Increase
Elevated arterial BP (hypertension)

Decrease
Blood loss (hemorrhage)

Vessel Structure Narrowing of arteries by atherosclerosis Widespread vasodilatation (sepsis, anaphalaxsis)

Autonomic Regulation Symp (e.g. NE)

Parasymp (e.g. ACh)

Hypoxia ( O2) Acidosis ( H ) Alkalosis ( pH) Cations (e.g. Na+, K+)

Other factors

Age (have resting HR) with age body temp (e.g. fever, excersise) Decreased body temp

Nervous System Control of the Heart Input to CV Center From higher brain centers Cerebral cortex Limbic centers Hypothalamus From sensory receptors Proprioceptors Chemoreceptors (monitors blood chemistry) Baroreceptors (monitors BP) Cardiovascular Center In the medulla oblongata Output to Heart Affects the ability of the heart to contract and how much SV comes out what rate of repolarization will be

Anatomy Page 12

 Affects the ability of the heart to contract and how much SV comes out what rate of repolarization will be Cardiac Accelerator nerves (symp) Increased rate of spontaneous depolarization in SA/AV nodes Increased contractility of atria and ventricles to increase SV Vagus nerves (CN10, parasymp) Decreased rate of depolarization in SA/AV nodes which decreases HR Neural Regulation: Example Note the our slide is WRONG

Anatomy Page 13

Vascular System
Tuesday, January 15, 2013 5:32 PM

Aorta: 4 Principle Divisions Ascending Aorta R & L Coronary Arteries Arch of the aorta Brachiocephalic trunk Right Common carotid Right Subclavian Left Subclavian Left Carotid Thoracic aorta Pericardium, esophagus, bronchi, diaphragm, intercostal and chest muscles, mammary gland, skin, vertebrae and spinal cord Note: I think the diaphragm signals the change between thoracic and abdominal aorta Abdominal aorta Abdominal and pelvic viscera and lower extremities Branches Celiac trunk Same as celiac artery? Supplies panrcreas, duodenum and spleen Superior Mesenteric Inferior Mesentaric From this comes the common iliac artery 3 Paired Glands Suprarenal Renal Gonadal Lumbar Arteries There are 4 Note: There are reference slides that show all these parts and what comes off of them look at the slides Veins Superior Vena Cava Head, neck, chest and upper limbs Coronary Sinus Great cardiac vein, middle cardiac vein, small cardiac vein Inferior Vena Cava Abdomen, pelvis and lower limbs Hepatic Portal System Venous blood from GI organs and spleen go to the liver before going to the inferior vena cava (and then back to the heart) you need to filter that blood Superior and inferior mesenteric drain into hepatic portal vein which is going to go to the liver Blood Vessels Arteries Carry blood from the heart Artery Arterioles Capillaries Capillaries Site of gas and nutrient exchange Waste removal Veins Return blood to the heart Capillaries Venules Veins Arteries Pressure vessels Structure Tunica Intima Endothelium Smooth layer that blood is going be flowing up against Endocardium in the heart is a continuum of the endothelium in the aorta and PT Basement membrane Internal elastic lamina Is a giant sheet of elastic ____ with holes punched in with this elastic lamina and the holes it allows the artery to be st retched easily Tunica Media Smooth muscle cells Cells responsible for contraction Elastic fibers External elastic lamina Also fenestrated (has holes) Tunica Externa (Adventita) Elastic and collagen fibers Vasa vasorum Arteries that supply other arteries

Anatomy Page 14

 Arteries that supply other arteries Great vessels want to supply tissue with nutrients problem is the great vessels are large enough that the O 2 and nutrients cant reach the outer wall and therefore have these vaso vasorum Tiny vessels that supply O2 and nutrients to the outer walls of the great vessels Elastic and Muscular Arteries Elastic Largest of the arteries (e.g. aorta) D = 15mm T = 1mm Characteristics Pressure reservoir Conducting arteries Tissue makeup

More of a propelling vessel In depth Help to conduct blood to the muscular arteries Must resist pressure from the contractions of the heart (systole) and provide pressure between heart beats (diastole) What we want is whether the heart is relaxing or contracting, we want blood flow either way. Dont want blood flow to stop the aorta expands and it contracts, and when it does that it is still pushing blood to the systemic circulation regardless of whether we are in relaxation or contraction Tunica media is full of elastic fibers of connective tissue Elastic arteries expand when the blood pressure increases and contract when the blood pressure decreases evening out the pulse pressure Muscular Dimensions D = 6mm T = 1mm Tissue Makeup

Have a lot more smooth muscle tissue core difference is really in the amount of elastic tissue (EL) and smooth muscle (SL) they have More of a contraction vessel In depth Medium-sized arteries with more muscle than elastic fibers in tunica media Capable of greater vasoconstriction and vasodilation to adjust rate of flow Walls are relatively thick Distributing arteries direct blood flow Examples: Brachial artery in the arm radial artery in the forearm Arterioles and Capillaries Arterioles Referred to as resistance arteries D: 37 um T: 6um Tissue make-up

Capillaries Exchange vessels D: 9um T: 0.5um Tissue make-up

Structure Have endothelial cells forming a ring In the middle have a red blood cell Nucleus of endothelial cell
Anatomy Page 15

 Nucleus of endothelial cell Intercellular clefts Spaces between the endothelial cells Pericyte Cell that forms around the endothelial cells of the capillaries Tight junctions Types Continuous Brain, lungs, muscle Have: Basement membrane Nucleus of endothelial cell Lumen Intercellular cleft Fenestrated Kidney Need lots of perfusion Fenestrations (pores) Sinusoid Red bone marrow, liver Need bigger things moving out of the capillaries Have: Large intercellular cleft Incomplete basement membrane Microvascular (Capillary) Bed At the capillary level At the terminal end of the arteriole have something called a metarteriole At the metarteriole end have precapillary spincters When open Allow blood flow into the capillary bed and blood to perfuse the tissues If we follow the blood we have the postcapillary venule, which is then going to go into the venous circulation When closed The blood will bypass the capillary bed and go right from the arteriole end to the venous end through something called the thoroughfare channel This is to control the rate of blood flow and where blood is going to Vasomotion Ability of the sphincters to open and close Veins Volume reservoirs (2/3 of blood volume) Valves Helps assist blood returning to the heart and fight gravity can't have the blood fall back down Structure Tunica Intima Endothelium Basement membrane Tunica Media Smooth muscle cells Tunica Externa (Adventita) Elastic and collagen fibers Vasa vasorum Particularly in the larger veins Veins and Venules (from next lecture) Venule Size D: 20um T: 1um Tissue-make up Almost no elastic tissue Vein Size D: 5mm T: 0.5mm Tissue-make up Has some elastic tissue (little) Venous Return (from next slide) Skeletal muscle pump Contraction of muscle Compressed veins Milks blood to heart Respiratory pump Inhale diaphragm moves down pressure in abdomen Compresses abdominal vessels Also milks the blood Arteries vs. Veins Anatomically Veins have a much thinner muscular layer and tunica externa Veins have no elastic layers but they do have valves
Anatomy Page 16

 Veins have no elastic layers but they do have valves Physiologically Veins have almost no blood pressure to resist which means the vessel wall can be much thinner and weaker The valves are necessary to prevent back flow and assist in venous blood return From next lecture
Dynamics of Capillary Exchange Background (of the pic) Interstitial fluid that is surrounding the capillary and the cells Two ends Arterial end On this side, there is net filtration Venous end On this side, there is net reabsorption Starling's Law of the Capillaries 85-90% reabsorption Note: Fluids and proteins that escape get pulled into the lymphatic system Pressure Interstitial fluid The pressures associated with that are minimal so we will forget about them HP Blood hydrostatic pressure Result of water in the blood pressing against the blood vessel wall Higher at the arterial end than at the venous end OP Blood colloid osmotic pressure Associated with proteins present in the blood not all can enter interstitial space and these therefore cause this pressure Stays approx the same at both ends Causes stuff to go into the capillary HP and OP When HP > OP, there is net out flow of fluid out of capillary (filtration?) When OP > HP, there is net flow of fluid into the capillary (reabsorption) Molecule movement All small molecules can pass into the interstitial space but large molecules (> albumin size) cannot and stay in the blood Role of Lymphatic System Fluid and proteins escape from vascular capillaries Excess interstitial fluid collected by lymphatic capillaries Fluid = lymph (not interstitial fluid anymore) Returned to the blood This is for maintaining fluid levels and homeostasis Blood Distribution

60% of blood volume at rest is in systemic veins and venules Function as blood reservoir Blood is diverted from it in times of need E.g. you need to start running, this is possible 15% of blood volume in arteries and arterioles Blood Flow and Cardiac Output CO = Volume of blood flowing through a tissue/organ/vessel in a given time mL/min Flow to individual organs varies continually Sometimes the stomach gets more blood and sometimes gets less Total blood flow is cardiac output CO = HR x SV Blood Pressure General Pressure (force) exerted by the blood on the walls of a vessel Generated by contraction of the ventricles Water in the blood exerts the pressure on the walls of the vessels and this is known as blood pressure Slide 13 Pressure falls steadily in systemic circulation with distance from left ventricle

Anatomy Page 17

Mean Arterial BP Farther we get away from the heart and the LV and aorta, our pressure drops. By the time we get to the capillaries its 35 and by the RA its 0. Systolic/Diastolic BP This is the tracing of the blood pressure Difference in the peaks and troughs decreases as we get farther away from the LV, and by the time we get to the capillaries there are no peaks/troughs anymore the wave is non-existent anymore If decrease in blood volume is over 10%, BP drops Water retention increases blood pressure Blood Pressures - Terminology

Pulse pressure = Systolic (ventricular contraction) - Diastolic (ventricular relaxation) Mean pressure = Average pressure in the system MAP Is this the same as mean pressure and mean arterial blood pressure = MAP = diastolic BP + 1/3 (systolic BP diastolic BP) E.g. MAP = 80 + 1/3(120 80) = 93 mmHg MABP Average pressure during entire cardiac cycle Significance - system is designed to maintain mean ABP Mean ABP = CO x Total peripheral resistance (TPR) Any changes in SV and HR therefore can change MABP Pulse Pressure Difference in systolic and diastolic 120-80 = 40 mmHg If a person has hypertension, they have increase in systolic pressure which can change pulse pressure See what happens is that a small change in systolic/diastolic pressure creates a large change in the pulse pressure This is what we are measuring at different pulse points Pulse and Pulse Points Give indication on heart rate, strength and perfusion Common carotid artery Roughly equivalent to heart rate Radial artery Used for patients with peripheral arterial disease Dorsalis pedis artery Factors Affecting BP Heart rate Peripheral resistance Blood volume Equations Pressure = flow x resistance Remember CO is equal to total blood flow Flow = pressure / resistance Vascular Resistance Blood is fluid going through vessels in body resistance in the inside wall of the vessel it will be a type of drag force friction is greatest in inner SA? Friction between blood and the vessel's walls Blood vessel radius Smaller radius = more friction = more resistance Blood viscosity (thickness) Thicker blood = more resistance (dependent on the # of blood cells and water content ratio when youre dehydrated you have m ore viscous blood) Blood vessel length Longer the blood vessel = more resistance Arterioles control BP by changing diameter These vessels after changing their diameter if they become smaller, they make the resistance greater Systemic vascular resistance
Anatomy Page 18

 Systemic vascular resistance Same as TPR

Constriction of veins leads to increase in venous return Regulation of Blood Pressure Neural Types Baroreceptor reflexes Monitor pressure changes Chemoreceptor relfexes Monitor changes in chem composition in the blood Hormonal Short-term Types Epinephrine and NE Explanation symp stimuation Long-term RAA system

ADH Released from the posterior pituitary In response to dehydration / in blood volume (e.g. hemorrhage) Causes vasoconstriction BP ANP Released by cells in atria Cases vasodilation Promotes loss of salt/water BP Receptor Reflexes In carotid sinus area and aorta, there are these baro and chemo receptors. Signal sent to medulla oblongata Message goes down spinal cord and then out where they act on SAN and AVN to alter contraction of the heart, heart rate and so on to regulate change in BP Parasymp and symp mechanisms in place Example

Anatomy Page 19

Example

Effects of Shock Car accident - Michael Rapid resting heart rate Weak, rapid pulse Clammy, cool skin Sweating Diagnosis: hypovolemic shock Definition Shock is failure of cardiovascular system to deliver enough O2 and nutrients Inadequate perfusion Cells forced to switch to anaerobic respiration Lactic acid builds up Cells and tissues become damaged & die Shock and Homeostasis Remember the goal: Maintain MABP Compensation Mechanisms Activate RAA system Secrete antidiuretic hormone Activate sympathetic nervous system Release of local vasodilators

Anatomy Page 20

Blood
Tuesday, January 22, 2013 2:08 PM

Functions of Blood Transportation O2, CO2, nutrients, hormones, heat & waste products Regulation pH through the use of buffers Body temp Heart-absorbing/coolant properties of water in blood plasma Variable rate of flow through the skin Water content of cells influenced by blood osmotic pressure Protection Blood loss clotting Disease phagocytic white blood cells, antibodies etc. Components of Blood Plasma Plasma Liquid ECM 55% of whole blood Water, proteins, glucose, hormones, ions, metabolites, etc. Proteins: Albumin Fibrinogen Globulins Other (e.g. coagulation factors) Formed Elements Leukocytes (WBC) and platelets <1% Buffy coat Erythrocytes (RBC) 45% of whole blood Key points Blood is connective tissue Plasma is similar to interstitial fluid but has more protein Haematology Blood Tests Complete Blood Count (CBC) Hemoglobin Red cell count Hematocrit (packed cell volume without plasma) Morphology (shape of cells) White cell count Increase is indicative of infection Differential % of dif WBC's Platelets Erythrocytes (RBC's) Dimensions Diameter : 7.5um Thickness: 2 um Characteristics Biconcave disc Greatest surface area to volume ratio of a simple shape Strong, flexible membrane It has to travel through vessels without being damaged has to manipulate itself to travel through capillaries which sometim es allow only one cell at a time No nucleus If the RBC gets damaged, it can't repair itself Lack mitochondria; generate ATP anaerobically If the RBC gets damaged, it can't repair itself Hemoglobin Allows it to bind O2 and CO2 and NO Structure 2 beta chans and 2 alpha chains -globin is the protein compartment Hemo- is ring like structure that contains iron One oxygen molecule binds to one iron group we have 4 iron groups each hemoglobin molecule can bind to 4 O 2 molecules Characteristics Hemoglobin-O2 saturation: 97% - lungs, 75% - tissue Excess carrying capacity reserve Never give off all the O 2 from the blood cells Causes O2 release more readily temperature, CO2, pH (i.e., acidity) Tissue oxygen buffer system Helps to maintain P0 2 in tissues Production Hemopoiesis Process by which formed elements of blood develop Erythropoesis
Anatomy Page 21

 Erythropoesis Steps Pluripotent stem cell Myeloid stem cell Proerythroblast (nucleus ejected): Reticulocyte (leaves red bone marrow and enters blood stream): RBC (erythrocyte) Life-Span 120 days Steps Production (in red bone marrow) E.g. axial skeleton, ribs, pelvis in infants is mainly in long bones Destruction RBC death Phagocytosis Recycling of breakdown products RBC Production

Change in O2 levels if there is hypoxic situation where there isnt enough O2 , kidney's kick in Giving blood or high altitudes causes hypoxia Kidney's release erythropoietin Its release also depends on the health of the kidney diseased kidneys make not be able to produce enough of it Atherosclerosis If it's in vessels that is going to the kidneys, there will be less sensing of the low O2 levels This causes red bone marrow to release more RBC's Results in increase O2 carrying capacity Case Question Lisa is tired and cold. CBC (complete blood cell count) was ordered Decreased red blood cells Cause: Anemia decrease in O2 supply O2 is needed for ATP and heat production this naturally makes her tired and cold WBC Production Characteristics Nucleus No hemoglobin Most live a few hours to days to even years Steps

Streams 1) Pluripotent stem cell Myeloid stem cell [Eosinophilic meyoblast Eosinophil] + [Basophilic meyoblast Basophil] + [Neutrophilic meyoblast Neutrophil] + [Monoblast Monocyte] 2) Pluripotent stem cell Lymphoid stem cell Lymphoblast Lypmphocyte] Granular Contain granules in their cytoplasm
Eosinophil React with acidic dyes

Basophil

React with basic dyes

Neutrophil Mixture Agranular Monocyte Doesnt have granules in its cytoplasm Lymphocyte Doesnt have granules in its cytoplasm Functions
Type Neutrophil Percentage Function 60-70% Phagocytize bacteria

Anatomy Page 22

Neutrophil

60-70%

Phagocytize bacteria

Eosinophil

2-4%

Kill parasitic worms Destroy antigen-antibody complexes Inactivate some inflammatory chemicals of allergy Releases heparin (anti-coagulant) Releases histamine and other mediators of inflammation Mount immune response by direct cell attack or via antibodies Phagocytosis (pacman) Develop into macrophages (large eaters) in tissue

Basophil

0.5-1%

Lymphocyte 20-25% Monocyte 3-8%

Platelet (thrombocyte) Production Characteristics Disc-shaped 2-4 microns in size No nucleus Short life span (5-9) days

Pluripotent stem cell Myeloid stem cell Megakaryoblast Megakaryocyte Platelets Function Stop blood loss from damaged blood vessels Form a platelet plug Release chemicals that promote Blood clotting Vascular spasm Hemostasis General Sequence of responses that stops bleeding Quick, localized and controlled Prevents hemorrhage (loss of large amount of blood) from smaller blood vessels Medial intervention usually required for hemorrhage from larger blood vessels Mechanisms to Reduce Blood Loss (Steps) 1) Vascular spasm Vasoconstriction of the vessels Smooth muscle cells can contract, decreasing lumen diameter and we decrease the amount of blood flowing though idea is to slow the flow of blood as its moving part the area of injury want a chance for the hemostasis mechanism to kick in 2) Platelet plug formation Adhesion Endothelial layer is generally non-thrombogenic, but if its damaged the underlying layer is exposed to the blood Platelets are attracted to the collagen Release reaction Initial platelets release ADP, serotonin, and thromboxane A2 (ex.s) Help formation of the platelet plug Serotonin and TA2 help the smooth muscle cells constrict ADP and TA2 help activate other platelets Platelets at the site start to elongate and have extensions and grab onto other platelets that come into contact with them Aggregation Platelet plug A # platelets at the site of injury. ADP also helps platelets to become stick makes the platelets adherent so that the plug is solid 3) Blood clotting Positive feedback cycle Coagulation = formation of fibrin threads Blood Clot Contains Platelets Fibrin Usually red blood cells Formation of Fibrin Cascade of reactions in which each clotting factor activates the next one in a fixed sequence Note: Thrombus Clot in an unbroken vessel If a thrombus breaks off it is known as an embolus Clotting Pathways Extrinsic Characteristics Rapid occurs within seconds

Anatomy Page 23

 Rapid occurs within seconds Happens in the small vessels Named cause have substances that are outside the blood vessel and the cell In intrinsic, the activators are in direct contact with the blood, in extrinsic they are not initially in direct contact with the blood Steps

Tissue trauma (Tissue factor) ______ (Ca2+) Activates F10 (in presence of F5 and Ca 2+) Prothrombinase Intrinsic Characteristics In intrinsic, the activators are in direct contact with the blood, in extrinsic they are not initially in direct contact with the blood Occurs within minutes Steps

Blood trauma (to the blood vessel e.g. endothelial layer Activates platelets Platelet phospholipids released Activates F12 (in presence of platelet phospholipids + Ca2+) Activates F10 (in presence of F5 and Ca2+ and platelet phospholipids) Prothrombinase Common Pathway Prothrombinase (Ca2+) Makes prothrombin get cleaved into Thrombin Fibrinogen (soluble) Loose fibrin threads (insoluble) Activates F13 works with the loose fibrin threads and strengthens them, making them stronger

Clot Retraction and Blood Vessel Repair Clot plugs ruptured area of blood vessels Platelets pull on fibrin thread causing clot retraction By retraction you are able to pull the places closer together this is pretty much the healing process Edges of the damaged blood vessel are pulled together Fibroblasts and endothelial cells repair the blood vessel wall Clot Lysis (Fibrinolysis) Activated F12 + Tissue plasminogen activator (tPA) Make inactive Plasminogen which is incorporated into the clot plasmin (active) which break down the fibrin and break the clot

Preventing/Breaking up Clots
Anatomy Page 24

 Preventing/Breaking up Clots Antiplatelet agents Asprin Anticoagulants suppresses or prevent blood clotting Heparin Vitamin K antagonists Thrombolytics break up clots Tissue plasminogen activator (tPA) In certain patients that have a certain type of stroke, if this is given within the first few hours it can reverse some of th e damage Antigens and Antibodies General Red blood cells have antigens on them Antigens can promote the production of antibodies seen as foreign substances In our plasma we have antibodies ABO Blood Group System Descriptions

Compatibility Ex. Donor 'A' to Recipient 'B' Problem A antigen is being introduced into blood with an Anti-A antibody. Result could be death RBC's could end up clumping RBC's can rupture Toxic reaction Rh Blood Groups General Based on an antigen discovered in the Rhesus monkey Rh antigen on RBC surface = Rh+ Rh+ is more common than Rh 85% of European population Normally plasma doesnt contain anti-Rh antibodies Antibodies develop only in Rh- blood type and only with exposure to the antigen Hemolytic Disease of Newborn Rh- mother First Pregnancy Fetus that is Rh+ At birth there can be leaking of fetal blood across placenta as such the Rh+ antigens can be introduced to the mum Between Pregnancies Produces anti-Rh antibodies Second Pregnancies Has Rh+ fetus Antibodies in the mum can go into the fetal blood and bind with the RBC's of the fetus Treatment Removes fetal blood from mother's system

Anatomy Page 25

Lymphatics
Thursday, January 24, 2013 1:11 PM

Lymphatic System Consists of Lymph (fluid) Lymphatic vessels Structures/organs containing lymphatic tissue Red bone marrow Functions Drain excess interstitial fluid from tissue spaces and return it to the blood Transportation of dietary lipids & lipid-soluble vitamins from GI tract Carry out immune responses Recognize microbes or abnormal cells Kill directly or secrete antibodies Dynamics of Capillary Exchange . Formation of Lymph Fluid and proteins escape from vascular capillaries Excess interstitial fluid collected by lymphatic capillaries Fluid = lymph (not interstitial fluid anymore) Returned to the blood This is for maintaining fluid levels and homeostasis Lymphatic Vessels and Circulation Lymphatic capillaries Closed at the end Opening between the cells have anchoring filaments that anchor the cells to the surrounding tissue Get stretching of the openings and we get fluid go into the lymphatic capillaries Merge to become larger vessels Flow of Lymph Skeletal muscle pump Respiratory pump Valves prevent back-flow More valves than veins Lymph Drainage Routes Cisterna chyli Thoracic (left lymphatic) duct CCC is the beginning of thoracic duct Picks up lymph fluid from all of the lower body + area behind the ribs + upper part of left body as well Right lymphatic duct Fluid from the upper right part of the body Enters the venous system at the junction between the subclavian and the left jugular vein it will then go into the heart Lymph Nodes Lymphatic fluid is filtered here Location (major) Cervical Axillary Inguinal Location (other) Tonsils Thymus Spleen Largest single lymphatic tissue White pulp Lymphatic area Red pulp Reservoir for the RBC's Peyer's patches In the intestinal region

Anatomy Page 26

Case Study - Blue Baby

Friday, January 11, 2013 8:58 PM

Dont need to send so much blood to lungs as there is no gas exchange there at this point only send blood there to develop lung What is doing the gas exchange is the placenta Bypasses/Shuts There are two of them to make sure that the blood bypasses the lungs One is between the atria and ventricles blood from the umbilical vein goes to right atria to right ventricle to normally the pulmonary trunk, but instead we have the foramen ovalae this is between the atria Second is between the pulmonary trunk and the aorta some of the blood from the placenta will be going to right ventricle and then P. trunk, but b/c the pressure there is higher in the P trunk than in the aorta, the blood will go right to the aorta to go right to systemic circuit ductus arteriosus ? Pulmonary Circuit There is large resistance, and therefore there is lots of pressure on the right hand side (of the body) cause the right ventricle is pumping against a closed door In adults, there is higher pressure in the left hand side Oxygenation Blood needs to travel through the ascending aorta, then the thoracic aorta, then the abdominal aorta, then the common iliac, and then the internal ilial, then the paired umbilical arteries When you do ultrasound, want to see 3 things one large umbilical vein and two smaller umbilical arteries Note: The liver is also bypassed through the ductus venousus, such that the oxygenated blood from the placenta gets to the ri ght atrium quickly through the inferior venca cava also this will now be mixed blood, partly oxygenated and partly deoxygenated

Pressure Need to have higher pressure on one end of a tube as compared to another to have blood flow in that tube Heart is there to make the pressure Resistance As the tube becomes smaller, resistance increases and therefore need the more and more amounts of pressure to get the same flow of blood through the tube Resistance is inversely proportional to radius Note Heart is most concerned with keeping flow

Anatomy Page 27

 During birth and the first breath, by opening and expanding the lungs you get a huge fall in the pulmonary vascular resistance, causing the pressure in the right side of the heart drops as compared to the left This has something to do with the pulmonary vasculature being stretched (later on in the lecture?) Also, the placenta is lost at birth it was a low resistance sponge, and therefore its loss results in higher pressures in the left side

Normal gestation should be 40 weeks Problems are ten days after birth Lots of breathing is happening indicates that the kid is having problems oxygenating the blood Legs being cool means legs are not getting enough blood and mottled means that it looks like mottled cheese

White marking in the black are the pulmonary arteries where blood is going for gas exchange in the lungs black = air in the lungs

Heart is bigger Apex of heart is lifted There is a lot of blood in the pulmonary circuit what happens is that the plasma goes into the airways problem with water in the airways is that oxygen doesnt diffuse well through a watery barrier

Anatomy Page 28

 Which shunt didnt close Lack of blood in lower limbs suggests that there is blood being diverted from the systemic circuit to the pulmonary circuit

Note that in the fetal state oxygenated blood comes from the umbilical veins, through the inferior vena cava, into the right atrium, bypass the lungs and the pulmonary trunk by going through the foramen ovalae to the left ventricle The little bit of blood that does make it to the pulmonary trunk is shunted as well to the aorta through the ductus arteriosus

Anatomy Page 29

 Echo is to confirm doctors suspicions that there is a patent (still open) ductus arteriosis Systole - ventricles are contracting, generating pressure in aorta Diastole - just back pressure in aorta Open ductus arteriosis Will cause heart murmur cause of blood turbulence Indomethesin Like giving ibuprofen gets rid of relaxant prostaglandins leaving contractatory PG's which will hopefully close the shunt didnt work in this case Surgical clip To close the shunt

PDA = open ductus arteriosis Murmur Start to hear in diatole as well cause over time, resistance in right side keeps dropping (starting from right after birth), and therefore at some point even in diastole the pressure in the aorta will be high enough to push blood to the pulmonary trunk

Anatomy Page 30

 As the oxygen tension increases in lungs, pulmonary resistance falls. As areas get well ventilated, you want blood to flow there and best way is to relax vessels going there Increasing lung volume = lower resistance Lower pH indicated high CO2 levels sign for vessels to constrict so blood doesnt go there cause there isn't a lot of O2

Well ventilating lungs didnt help get blood into bloodstream indication that there is not a lot of blood getting to the lungs

Look at the lack of blood in the pulmonary circuit well ventilated lungs but no blood flow to it Also see how the apex of the heart is higher the right side of the heart is getting larger casing this

Anatomy Page 31

 There is a stenosis to the opening to the pulmonary trunk

Pressure in the right side is going to be high after birth Pressure will be higher than the left side of the heart and therefore even after birth you will have right to left blood flow through the foramen ovalae

Note at the beginning the baby was fine cause it also had a patent ductus arteriosus, so blood would go back from left to right, from the aorta to the pulmonary trunk and then to the lungs allowing the blood to get loaded with oxygen Problem was, due to the influence of constricting prostaglandins, the ductus arteriosis started to close, and therefore the blood could not get to the pulmonary trunk

Anatomy Page 32

 Interm solution is to use E1 to keep the ductus arteriosus open

Use balloon to open pulmonary valve use it to rip it open (scar tissue will later form no problem) I think the picture above shows mitral valve but in this cause it was the pulmonary valve

Anatomy Page 33

Anatomy Page 34

Case Study - Shock

Thursday, January 17, 2013 12:30 PM

Definition "a momentary pause in the act of death" Its not just hypotension in fact shock can occur without hypotension, and hypotension can occur without shock It is when .. Either your not supplying enough oxygen to the tissues or the demand of the tissue is greater than the supply Key is getting enough oxygen to the tissues It is an imbalance in tissue perfusion (of O2) to tissue demand Supply (of O2) Blood pressure (need a certain amount of pressure to get O2 to tissue) = CO * [systemic vascular resistance] Systemic vascular resistance = [viscosity * length of radius]/[radius 4] Cardiac output = heart rate * stroke volume Stroke volume Determined by: preload, afterload and contractility Oxygen content Partial pressure oxygen and hemoglobin PPO: therefore different in Hamilton vs. Mt. Everest Hemoglobin: Note that ~ 97.3+% of O2 in blood is not free floating and rather on hemoglobin Demand (of O2) Metabolic rate Infection Fever Work of organs (heart and lungs) Agitation or Pain Classification of Shock Cardiogenic When? e.g. Cases of heart attack Causes Loss of muscle Muscle is damaged and therefore cant pump therefore delivery of O2 is reduced Infarct, inflammation Affects stroke volume Loss of conduction Heart block Atria and ventricle aren't talking to each other in terms of conduction Affects heart rate Obstructive General Something that blocks or obstructs blood flow Causes Tamponade Fluid in the pericardial sac Can cause pressure in the right atrium and if its high enough the right ventricle in either case there is block of blood entering the right side of the heart (I think this is an especial problem on the right side cause there are low pressures on the right side) Pulmonary Embolism Block in the arteries leading to the lungs (or going through the lungs?) So the blood from the right side of the heart cant reach the left side of the heart stuck in the lung segment of the flow Risk factor Tension Pneumothorax Lung is collapsed It is air now that fills the pleural space now the heart would get pushed to the side and this messes up blood flow Hypovolemic General Loss of blood Causes e.g. Diarrhea Distributive General This means blood vessels wide (?) open Most common cause is sepsis (response to infection that affects the whole body) Causes Sepsis Response to infection in the setting of genetics, host response and organism can lead to septic shock Necrotizing fascitis Pneumonia Anaphylaxis Response to allergen in the setting of genetics and host response can lead to anaphylactic shock
Anatomy Page 35

Response to allergen in the setting of genetics and host response can lead to anaphylactic shock Summary Cardiogenic Reduced stroke volume (or heart rate) Causes Heart attacks Viral heart infection Conduction abnormality Severe heart valve problems Cold/Cool Obstructive Impaired flow Causes Massive pulmonary embolism Significant cardial effusion (tamponade) Tension pnemothorax Cardiac tumour Blue Hypovolemic Reduced preload Causes Bleeding Trauma Ulcer Dehydration Heart shock Diuretics Diarrhea Peripheral Pulses not Palpable Blood is preferentially directed to the brain Distributive Reduced systemic vascular resistance Causes Sepsis Anaphalaxysis Adrenal insufficiency Acute hepatists Over active thyroid Acute spinal cord injury Warm Pink (or flushed) Bounding Peripheral pulses Reduced systemic vascular resistance Signs Mottled knees Need a breathing machine breathing tube Anuria (not enough urine) Kidneys are not work Delerium Consequences Start with any one of the causes of shock Lack of tissue perfusion which causes them to die (after they first become cold and clammy and stuff) Can get ARDS Can get bleeding from bowels Vicious Circle Start with cardiac failure and major trauma surgery Can't get blood to tissues and they fail in the GI tract, when it doesnt get enough blood flow (cause blood is directed to vital organs) all the bacteria there escape and you dont have the immune system to fight it Mortality Rates Septic shock Cardiogenic shock Hemorrhagic shock Treatment Fluid resuscitation Give liters and liters of fluid Septic shock Antibiotics Tension pneumothorax Relieve pressure big needle Hypovolemic shock (gun shot) Get to the OR and put a finger in the hole Support ventilation Breathing requires lots of energy so if you have another big metabolic demand, its good to help ventillation Problem is that the diaphragm forgets how to work

Anatomy Page 36

Case Study - Cardiac Arrest

Tuesday, January 22, 2013 5:31 PM

Michael Is overweight mainly due to stress Suffered emotional bullying as a child This discouraged him from sports He eats unhealthy at university He went to a resort got paired up with a trainer and nutritional adviser. Characteristics = 305lbs Height = 5'9 Blood work choloesterol BP blood glucose levels History Individual Occasional drinker Stressed Family Diabetes CVD Cancer Atherosclerosis Etymology Athero = gruel/paste Sclerosis = hardness Definition Plaque formation in the inner lining of the artery Can lead to Stenosis Wall of artery becomes thickened so that lumen narrows reducing blood flow Thrombosis Thrombi (blood clots) form on the wall of the vessel Extreme case - Embolization Thrombi can break off wall of artery and be carried by flowing blood to plug up other vessels CVD - Risk Factors Diabetes Smoking Hypercholesterolemia Hypertension Obesity Inactivity Synergism Total risk is greater than the sum of risks Ex. Risk of Heart Attack Exercise Stress Test Measures Electrical activity Blood pressure Heart rate Doctor -- Michael was ok to exercise but had to take it slowly Last Chance Workout Right before the weekly weigh-in Michael wanted to do one last work-out to lose a beast amount of weight Michael decided to not walk on the treadmill -- rather to run What happened to Michael -- can he lose consciousness as a result Yes Why Extremely rapid heart rate SV due to insufficient ventricular filling CO -- not enough blood reaching central nervous system Light-headed lose consciusness Cardiac Reserve = CO (max) - CO (rest) How does this change with training / heart failure? Will increase with training ~7-8x Heart failure may cause little to nocardiac reserve Hospital Michael went to the hospital ECG + Blood work + Angiogram Angiogram Use catheter to put dye in then get to get pictures of the vessels and such Michael did not have a heart attack he had angina Percutaneous Trasluminal Coronary Angioplasty Process that is used to open a vessel that is blocked by atherosclerosis Stick a tube with an uninflated baloon, and when it reaches the narrowing, it inflates, pushing that plaque (squashing it) to make the lumen wider Stent in an Artery
Anatomy Page 37

 Stent in an Artery On the balloons, they put a chicken mesh wire and when the balloon is inflated, the wire is embedded on the wall of the vesse l. When the balloon deflates, the stent remains in place Purpose Maintains patency of blood vessel Myocardial Infarction Michael's uncle had a MI General When a coronary artery gets blocked Anastomosis At some point, the anastomosis will not be in a spot that will allow you to supply the tissue Some of the anastomoses are present, but how well they work in a time in need is not enough to get blood to that tissue Heart Attack -- Warning Signs Chest discomfort Discomfort in other areas of upper body (e.g. left arm) Shortness of breath Sweating Nausea Light headedness Following a massive MI, one may develop shock. Which type? Cardiogenic By-Pass Graft By-passing the block providing another route for the blood to flow through sometimes its the femoral vein put in, sometimes the mammary artery it depends on various things History of MI - Increased Risk of . Reinfarction Stroke Heart failure Heart Failure Loss of pumping efficiency of the heart Left-sided Blood backing up in the system left side is receiving from the pulmonary system and therefore you will have pulmonary edema and can suffocate Right-sided Blood backing up in the system left side is receiving from the periphery and therefore you will have edema seen in legs due to gravity and therefore will have swollen ankles Stroke Brain symptoms result on the opposite side of the body Peripheral Arterial Disease General Pain in legs Relieved with rest Exertional limb fatigue and pain = claudication Intermittent claudication as it happens intermittently it's not constant pain Physical Exam Findings Appears cold Skin is dry/thin Little hair No pulse Causes? - Or risk factors Stenosis Calcified Artery In the case on the slide, no PAD yet, but there was calcified arteries they showed up on normal x -rays

Anatomy Page 38

Immunology
Tuesday, January 29, 2013 1:30 PM

Anatomy Page 39

Immunity and Immuno I

Tuesday, January 29, 2013 1:30 PM

Immunity Definition Immune system is principally concerned with the maintenance of homeostasis Immunology Study of the multi-layered 'host defense' system that protects us against Pathogens Tumors Toxins Allergens Vaccination Introduces all or subunits of an 'attenuated' and/or 'inactivated' pathogen Attenuated = make it weaker Inactivated = like kill the virusq Protection From interior and exterior threats 4 Classes of Pathogens Extracellular bacteria, parasites, fungi = Extracellular pathogen Intracellular bacteria, parasites Leprosy Malaria TB Viruses (intracellular) Small pox Flu HIV Parasitic worms (extracellular worms) Schistosomiasis Protection

Intrinsic Barriers (Start lecture from here) General Stop an infection from even making its way into your body If this does its job, you dont need to mount the immune response This is why you dont die when you touch a door-knob Types Mechanical Expulsive force (coughing/sneezing/defecation/urination) Mechanical way to get for ex bacteria out Ciliary beating Inside of your respiratory system lined with cells that have cilia little fingers beat and push things up and up Called mucous ciliary escalator because there is mucous covering the cilia nad the cilia push the mucous up towards the top of the respiatory tree, after which you swallow it What would have went from the lungs to the blood stream now is in the stomach, which is killer for pathogens (acids, protease s etc) Tight junctions in the epithelium Proteins between skin cells that keep pathogens from sneaking in between two cells Chemical Low pH barriers (stomach/vagina/sebaceous fatty acids) Fats underneath the skin at low pH (like the stomach and vagina) and this puts a strain on the proteins that the pathogen is using denatures those proteins in order to prevent them from working Proteolytic enzymes Lysozymes and pepsin in tears and gut which digest whatever comes in Bactericidal peptides Defensins, cryptidins in skin and mucosa Kill invading bacteria Physiological Temperature regulation Body temp is 37oC plus minus 1 Some bacteria cant live at that temp Fever Raising ones temp by two degrees really harms the bacteria Microbiological

Anatomy Page 40

 Microbiological Commensal flora compete with pathogens Gut is lined with bacteria are there to outcompete pathogenic bacteria that you eat (Resident) Innate Immunity General The immunity is primed waiting for the bad guy Types Complement proteins Made in the liver and circulate throughout the body exist as inactive precursor (zymogen) proteins throughout the body When cleaved they become active Activated by: Antibody-pathogen binding If antibody binds onto a pathogen and that causes complement to start breaking apart Lectin-mannose binding Bacteria have specific sugars on their surface called mannose (we dont have it in the same geometry as the bacteria) Our immune system has evolved a mannose-binding lectin, which is a protein that will bind to those mannose residues and start complement to get cleaved Pathogens themselves Some unlucky pathogens have enzymes on them that when complement binds to them, it cleavess the complement When activated, cause (all three always): Inflammation Thee small fragment of the complement ('a' fragment) causes local blood vessels to dilate and become leaky allows cells, fl uid and protein out of the blood vessel and into the tissue where it can go fight the infection Membrane attack complex formation Complement proteins punch holes into bacterial cells this is a membrane attack complex Polymerize into these barrel shaped pores that provide an open communication between the bacterial cells inside and the outside world Bacteria leaks and dies Opsonization (Tagging) This means that your tagging or flagging something Here the big fragment of the complement protein ends up stuck to the bacterial surface and our immune cells have receptors th at look for those complement fragments . And if they see something with a big complement fragment on it . they will kill it This is to mark for phagocytosis? Phagocytes Macrophages Resident in the tissue Acidification Dendritic cells Resident in the tissue Neutrophils Recruited later What they do Acidification If a bacteria is opsonized, a passing macrophage can go and engulf it, bring it inside and then destroy it by mixing the phag osome with a lysozome that contains acids and enzymes and such If you acid digest a bacterium, its harmless and the macrophage can dump what's left Toxic oxygen-derived products NT's and macro's produce oxygen radicals that have free electrons on them and they dump those onto the invading organism to damage it Toxic nitrogen oxides Antimicrobial peptides Proteins that try to kill the invading organisms Enzymes Like lysozyme Inflammation Activation Patter-recognition receptors (PRRs) (are on the surface of our cells) such that the toll-like receptors (TPR's) (which according to wiki are a type of PPRs) recognize pathogen associated molecular patterns (PAMPs) (something only pathogens make) expressed by microbes. This will initiate inflammation. If all pathogens are wearing blue coats and our cells are red coats, then the PAMPs are the blue coats Toll-Like Receptor Ligand TLR-2 TLR-3 TL-4 Peptidoglycan binds to this TLR It is a mandatory component of every gram-positive bacteria We dont have dsRNA LPS (lipo-polsacharidde) is an obligatory component of gram negative bacteria

This is a perfect way to tell self from non-self Its also obligatory its not like gram negative bacteria can just not have LPS to be the bacteria, it has to have LPS LPS-Induced Cytokine/Chemokine Cascade If you hit a cell with LPS which binds to TLR-4, that cell will do a few cardinal things It will make IL-1 (a cytokine) This is the first of a # of interleukins This along with IL-6 and TNF-a cause fever and inflammation CCLD8 (IL-8) This is a chemokine that recruits other cells This acts to bring neutrophils in Tissue Inflammation If you activate the cells, it causes the release of cytokines and chemokines that causes vasodilation and permiabalization of the blood vessels Cytokine or chemokine ? Immune cells that is made to communicate with other immune cells over a great distance Viral-Induced Cytokine Cascade Produces interferon (IFN-a and IFN-b)
Anatomy Page 41

 Produces interferon (IFN-a and IFN-b) Dont produce the same as a LPS induced cascade Produce and anti-viral immune response Early Induced Innate Response Takes 4 hours to get underway Basically consists of inflammation Has to get moved into where the infected site is from the blood (this is why it takes long) If this deals with something well, the adaptive immune response doesnt need to get activated Inflammation Cardinal signs Rubor + tulor + calor + dolor + funcio laesa Redness Swelling Heat Pain Loss of function Inflammatory Cells Neutrophils Found in the blood Migrate to tissues during inflammation Recruited by chemokines including IL-8 (CXCL8) Contain toxic granules that can kill invaders MUST be regulated in order to prevent immunopathology Never see a healthy tissue with neutrophils Macrophages Sentinel cells Phagocytose pathogens and infected cells Produce cytokines and chemokines to orchestrate immune responses Resident in tissues, AND more recruited during inflammation You will find them in healthy tissue There to clean up the mess that neutrophils made Mast cells + Eosinophils + Basophils Implicated in allergy, and anti-parasite defense Functions still largely unknown Dumps stuff to make parasite angry and dumps things to make GI tract angry (causing diarheaa) Natural Killer Cells Detect virus-infected cells and tumor cells Produce cytokines and chemokines Produce granules that lyse tumor and infected cells Adaptive Immune Response Takes days

Anatomy Page 42

Immunity and Immuno II

Tuesday, January 29, 2013 5:31 PM

Innate vs. Adaptive Immunity If you had to choose one you would pick innate cause its better Mouse Take out the innate immune system Infection goes out of control almost immediately and dies E.g. get rid of neutrophils or macropahges Take out adaptive E.g. take out T/B cells Initially can keep the bacterial/viral burden under control but then it goes out of control This means that for the first part the innate immune system kept it under control but at some point it couldnt and since there is no adaptive the animal dies Normal After day 5, adaptive immunity comes on and wipes the pathogen

Bubble Boy Born without an adaptive immune system Therefore need both innate and adaptive Features Innate PPR's that look for broadly-conserved PAMPs Note: PAMPs are essential for pathogen survival PRRs encoded in germ line DNA Broad specificity Doesnt care if the gram-negative bacteria is e.coli or club pneumonia Limited repertoire of specificities List of toll-like receptors and a few other PPRs these are all the immune system needs to recognize all the pathogens Perfect self: non-self-discrimination No human has made LPS for ex Common to all metazoans Any multi-cellular organism has some sort of an innate immune system Immediate response No memory If you give e.coli once and then again in two years, your response will be the same each time based on the innate immune system Adaptive BCRs and TCRs recognize specific antigenic determinants Antigens can be any protein in a pathogen BCR and TCR generated by somatic recombination This is a mix and match with little gene segments make a composite receptor that is specifically tailored every time a b-cell or t-cell is born Each receptor has narrow specificity but overall there is obv a huge specificity repertoire Good, but imperfect self: non-self-discrimination Do get cases when it attacks our own cells Restricted to jawed vertebrates Slow (3-5 days to initiate) Memory If you get infection and then a year later and then 10 years later or whatever the same infection, you will mount a better response the second time Memory Hallmark of adaptive immunity

Give vaccine A to person Lag phase Adaptive immune system is ramping up and generating the antibodies to release Initial jump Get peak of antibody production and that clears the influenza from the body Over time, the antibodies begin to wane over months and years, the amount of antibody comes back down If you give the same vaccine again though, there is no 5-day waiting period Start off a bit higher and end way higher and get there in a short time
Anatomy Page 43

Start off a bit higher and end way higher and get there in a short time Faster + stronger response Secondary immune response (memory response) Faster and stronger response the second time Note: Its not a general state of immune activation If you give vaccine B, its not that you get a better response this also has to go through the primary and secondary respons e Reality Adaptive + Innate are blended together What mixes them are APC's Professional Antigen-Presenting Cells (APC's) Dendritic cells Have long dendrites that they project out to increase SA to make them a big target for pathogens Macrochemocytosis Take little drinks of the extra cellular environment constantly doing surveillance of whats in the tissue Responsible for viruses and small antigens Macrophages Do phagocytosis Take big chunks of things like bacterium and larger Responsible for looking at big things ex cells B cells Dont go about at random like the other two Only bind to the one thing in the universe that their antigen receptor is specific for so all b cells have antibody on their surface which is the b cell receptor that we take about if something will bind to that b cell receptor, it will take it in and have a look Both APC's and also effector cells dont get confused they have two different roles Note: T-cells Dont phagocytose and more importantly dont have MHC Class II therefore arent professional APC's Antigen Definition Any molecule to which an antibody can specifically bind generate antibodies Types Proteins Carbs Nucleic acids Process Antibody is made as a dimer two parts consisting of two heavy chains and two light chains They bind to their antigen each antibody can bind to at least two molecules of antigen They bind to non-processed, native antigen If you have influenza virus, that antibody for flu will bind right onto the influenza virus particle the particle doesnt n eed to be broken up, modified or whatever Antigen Presentation T-cells cant recognize native antigen - only processed fragments of antigen That's why you need the APC's APCs pick up antigen, process it and present it on Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA) pr oteins Are a billboard that APC's use to put on their surface and show a snap-shot of what they see in the environment MHC proteins were discovered tragically through failed tissue transplantation operations If you can match MHC from donor to host, you can do these type of skin grafts that initially failed Antigen Processing Intracellular pathogens Live in the cytoplasm -- e.g. virus Lives in cytoplasm, makes its proteins in cytoplasm and then these proteins then go and infect other cells MHC Class I takes a continuous sample of all the proteins in the cytoplasm, grinds them and then puts it up on the surface for all the cells (especially t cells) to see Anything thats in the cytoplasm goes on MHC1 and gets presented to CD8 (+) killer T-cells Note: Every nucleated cell in the body has MHCC1 Cell got infected by the intracellular pathogen therefore every cell is a target so every cell needs a way to tell the immune system that it got infected by the virus Extracellular pathogens In membrane bound vesicles As far that the cell is concerned, that is exterior environment When the bacteria is phagocytosed, it makes its way into the endosome the endosome is acidified by the cell to kill what's in it, protease grind up the proteins and those are loaded onto MHC Class II antigen is presented to CD4 helper T-cells Defining feature of professional APC's is that they have MHC Class II This is because pretty much only the professional APC's have phagocytic ability therefore they are the only ones that need MHC Class II Innate and Adaptive Immunity Meet Lymphoid Organs Primary Bone marrow Thymus This is where B and T cells mature Secondary Lymph nodes Spleen Mucous associated lymphoid tissue Bronchiole associated lymphoid tissue Gut associated lymphoid tissue This is where they go to find what they are going to attack Therefore the lymph nodes and the secondary lymphoid tissues are the nexus where the adaptive and innate immune system meet Process E.g. DC (could also be macrophage or b cell) picks up antigen and puts it on its surface in the context of MHC and that provides Activation signal to a T cell Also provides a second activation signal called co-stimulation
Anatomy Page 44

 Also provides a second activation signal called co-stimulation T Cell Activation T cells are very specific -- each has only one specificty of t cell receptor (TCR) Each T cell will only react to one antigen A T cell for ex that recognizes influenza won't recognize HIV But there are 1012 different possible antigens But based on the human genome project we only have 20,000 genes Generation of Diversity Germline theory Separate gene for each T cell receptor Somatic Diversification This is the correct theory Play mix-and-match see next point VDJ Recombination in T Cells The way that we generate each T/B cell receptors Gene fragments V = variable segments J = joining segments D = diversity segments Play mix and match to create one final receptor expressed as a T cell receptor B and T cell Development All that diversity = 10 18 possible receptors Problem: some of them are things that we need (stuff we make ourselves) some will be auto reactive and target self -molecules Steps B/T Cells - Negative Selection Aka central tolerance Start with ex T cell Screen the T cell against every single protein in your body (through a TF) If something binds to a self-protein then it undergoes apoptosis If it doesnt bind to you, it is allowed to survive T cells also undergo positive selection Aka MHC restriction Steps Check to see if the T cell can bind to not just antigen, but antigen in the context of our MHC If it can't recognize an antigen in the context of its own host MHC it is a useless T cell it can't actually detect the target that it is looking for Only T cells that dont bind self but do bind antigen in the context of self MHC are allowed to survive Dumbed Down Version Happens in the thymus -- called the thymic university where T cells get educated See if T cell wants to attack me. So run it through a bunch of cells that have my own proteins in MHC (wait why MHC?). If it tries to kill one of my own cells, then its a threat so we make that T cell go through apoptosis If the T cell can at least recognize the MHC + protein, it means that it can recognize any protein in the context of our own MHC that means that the T cell can in theory do its job (cause T cell can only bind processed antigen) If it doesnt apoptosis time Self-protein vs. self MHC Protein is the message on the billboard the MHC is the billboard + protein Second Dumbed down Version Negative selection Run t cell against cells that have our own self protein on them if it reacts in a manner that it wants to kill it, the t ce ll is canned Positive selection Can it recognize the antigen in the context of MHC If it can't it gets canned From last lecture
T cell process Geography of Adaptive Immune Responses Antigen uptake by APCs in tissue APC's move to lymph node where they present antigen to T cells T cells get activated and provide help to b cells and those b cells become plasma cells and memory cells and make antibody T cell then go do their thing and B cell goes does its thing as well Effector function of T cell CD8 Killer t cells Go and find a virus infected t cell, recognize that it has MHC C1 with virus peptides on it (therefore is an infected cell) a nd thereafter kill the cell Dont kill neighboring cells CD4 Recognize the peptide in the context of MHC C2 TH1 (t helper 1) Recognize mostly macrophages that have engulfed pathogens TH1 dumps interferon gamma (a cytokine) onto the macrophage, activating it to kill whatever is inside of it TH2 Help B cells which proliferate and differentiate into: Memory cells Stay for a long time Plasma cells Professional antibody production factories Overall help B cells make antibodies Treg Downregulate immune responses Make cytokines that help turn off immune responses
Anatomy Page 45

 Make cytokines that help turn off immune responses Effector Function of Antibodies Neutralize Neutralize pathogens Coat a pathogen and makes it not able to infect us Opsonization Easy for other cells to phagocytose them and kill them (tagging) Activate complement Coating Coat a target cell (like a tumour cell) and then a natural killer cell (NK) cell comes by and does ADCC (antibody dependent cell cytotoxicity) they are there to flag NK to come and kill the cell Allergies Antibodies coat the mast cells if this happens this will be allergenic (almost always) Peanut specific antibodies floating in blood and go on mast cells when peanuts show up in the body the mast cell will see it dump histamine (causing allergic reactions) IGE is the specific antibody that causes allergies

Anatomy Page 46

Immunity and Immuno III

Thursday, January 31, 2013 12:21 PM

Influenza Virus General Infection RNA virus that infects the respiratory tract Symptoms Productive cough Mucous Cilia (beating) Expulsive reflexes Generalized aches Inflammatory mediators (PGEs) These mediators get perceived as aches and pains Fever Inflammatory mediators (IL-1) Innate Immune activation Resident defenses PRRs detect PAMPs Cells detect influenza with TLR3 (dsRNA) & other PRRs Epithelial cells and macrophages (and DCs) produce interferons (?) and cytokines/chemokines Dendritic cells mature, process and present influenza peptides in In particular DC's are responsible for activating adaptive immunity MHC I (if infected themselves) This is the main way MHC II (after phagocytosing infected material) Dendritic Cells Start as immature When they get activated, they change the expression of the things (proteins on their surface) and they get out of the tissue and into the lymphatics Arming a T cell In the lymph node, activated dendritic cells present influenza virus peptides in MHC to MANY naive T cells When T cell with a TCR thats specific for influenza virus finds that dendritic cell, they couple, and the T cell becomes act ivated Two signals One through the T cell receptors One through co-stimulation factors After getting turned on, T cell divides rapidly (to make many copies cause you want more flue specific t cells) and different iates to become effector T cells Arming a B cell An activated T cell runs into MANY B cells in the lymph node When an activated influenza-specific T cell runs into an influenza-specific B cell, it provides help and activates the B cell T cell arms the b cell The B cell enters a germinal center where it rapidly divides, and differentiates into memory B cells and plasma cells B cell then and goes and starts dividing (this is about the fastest mammalian cell division cycle) products are memory b ce lls (that live for a long time) and plasma cells (which produce boatloads of flue specific antibodies) Effector Function Note that these are T cells that have been activated in the lymph node those that have been turned into active t cells (fro m nave t cells) T cells CD4 Respond to MHC II + influenza peptide Produce cytokines (i.e. IFNg) to activate macrophages and other cells, promoting inflammation Activate B cells to produce antibody that can neutralize free influenza virus Activate even more B cells CD8 Respond to MHC I + influenza peptide Find influenza infected cells recognize them using the TCR bind to them (the MHC) and induce the infected cell to undergo apoptosis Note that for influenza and other viruses, for the purposes of this course we look at MHC C1 Secrete perforin and granzyme, Fas-ligand, and other molecules that influenza-infected cells to undergo apoptosis This is not just for influenza and viruses but also tumor cells One kill method Perforin = punches holes in the cell Granzyme = enters through the holes and turns on apoptosis Dont confuse this with the membrane attack complex! Second kill method Fas-lingand = Another way of killing cells make this protein and dump on the surface of the infected cell that this alone can turn on apoptosis This prevents infection from spreading B cells Antibodies can: Neutralize free influenza virus Activate complement to promote inflammation Arm NK cells to kill influenza-infected cells Antibodies are critical to influenza-specific immune memory Regulation of the Primary Immune Response Immune responses are self-limiting Negative feedback that kicks-off as soon as the immune response gets rolling When activated, T-cells automatically, but slowly begin expressing Cytotoxic T Lymphocyte Antigen 4 (CTLA -4) This is important as it binds to the co-stimulatiory molecules on APCs Normally when we activate T cells, APC provides Signal 1: Through t cell receptor and MHC

Anatomy Page 47

 Signal 1: Through t cell receptor and MHC Signal 2: Through a molecule called CD28 (another receptor on the surface of the t cell) and binds to b7 (on the APC which is a ligand) Over time T cells not only express CD28 but also CTLA4 (another receptor) which provides a strong negative signal and therefore as mo re and more CTLA4 is expressed, there is more and more negative signaling turning off the t cell This is over the course of a few days therefore viruses that can outlast this process can outlast the t-cells CTLA-4 binds to co-stimulatory molecules on APCs, but instead of turning the T-cell on (like CD28 does), it turns the cell off

Red dots = T cells specific to flue Phase one We have activation Phase 2 When you turn them on, you get expansion of T cells specific to flue (top left) Phase 3 T cells not only being turned off but dying Phase 4 Numbers decrease not to 0 (baseline) as there are still some rare but enriched memory t cells kicking around waiting for the next instance of the virus Secondary Immune Response Intro Immune memory: Protects against re-infection Controls persistent infections Protects immunologically immature offspring from primary infections Babies are protected through mothers antibodies: before parturition and breast-milk Pre-existing Abs at the mucosa prevent re-infection with the same influenza strain Lying there in the lungs waiting for the influenza Long-lived memory B- and T cells are waiting, and divide rapidly and provide additional protection if necessary Principally in the bone marrow Faster (no need to do all the lymph node stuff) More effective, more potent (high-quality memory B and T cells are already in place) More lethal t cells and higher quality antibodies EXTREMELY long-lived protection Double-edged sword We once thought the immune system was able to perfectly tell self from non -self, attacking non-self, while leaving self alone. But what about: Autoimmunity: Not all auto-reactive T- and B-cells are removed during negative selection, and can attack self Rheumatoid arthritis Type 1 diabetes Immunopathology: Some immune responses are inappropriately robust and can hurt us just by accident Immune response is too zealous Pneumonia is the classic example Limits of self-non-self-theory We are constantly exposed to non-self agents like pollution, but most of us dont respond Exception: allergy Not all auto-reactive T cells are caught by negative selection, yet most of us dont suffer ill effects Exception: autoimmunity Janeway postulated that the innate immune system was the gatekeeper to the immune response: PRRs and PAMPs APCs are gatekeepers which recognize something that has a PAMP on it as being foreign Immune system recognize PAMPS from non-PAMPS Matzinger went further and proposed danger associated molecular patterns (DAMPS) to explain why we sometimes attack ourselv es Broader category of things that the immune system sees as threatening e.g heat shock proteins, electrocution etc Anything that the immune system sees as dangers likely causes the IS to turn on doesnt have to be a pathogen, just something that annoys the innate immune system Reality: No grand theory APCs present lots of Ag (antigen) to T cells, (mostly innocuous self antigen.) Self-antigen = our own proteins on the MHC lets immune system see what's going on in our cells By default APCs are in an immature state and DONT prime T -cells. When danger signals are present, APCs mature, express co -stimulatory molecules, and can prime T cells Costimulatory molecules If you have a costimulatory molecule up on the surface of an APC, it can turn on a T cell (this is whats happening in autoimmunity especially) Whatever APCs are presenting at the time is a potential immunogen, whether self or non -self (bystander activation) A combination of mechanisms maintain self tolerance Positive and negative selection (central tolerance) T cells that react against self antigens are supposed to get canned its not a perfect process Regulatory T-cells There to deal with the one in a million leaker T cells that get through and are auto-reactive Anergization/clonal deletion

Anatomy Page 48

Anergization/clonal deletion If a T cell ever binds to a cell with antigen in MHC but without any costimulatory signals that would signal danger to the T cell, the immune system assumes this is because its a self antigen (otherwise, thered be a costimulatory signal along with it). The T cell is then anergized, so it wont respond in the future, even if it sees the same antigen with costimulation. Its better to have a useless T cell floating around the body than to risk having an autoreactive one. Autoimmunity Systemic Lupus Erythematosus Target: own nuclear antigens Multiple sclerosis Target: myelin proteins Rheumatoid arthritis Target: Collagen in joints Pemphigus vulgaris Target: Desmoglein The thing that anchors skin cells to each other Myasthenia gravis Target: acetylcholine receptors Insulin-dependent (Type I) diabetes mellitus Pancreatic b cells Type 1 diabetes - More depth Have beta cells in the pancreas and at some point during the childhood, T cell comes along and mistakes a beta cell as a thre at and kills it leaves the alpha cells and the delta cells behind Therefore there must be an antigen that the t cell recognizes on the beta cell Probably a virus that many of us get infected with that has an antigen on it that looks like the antigen on the beta cell Immune system tries to deal with that infection but attacks beta cells as well Immunopathology Autoimmunity leads to immunopathology, but immunopathology is not necessarily autoimmune An immunopathology generally results from the loss of a brake on the immune system, leading to an excessive immune response Severe immunopathologies Pneumonia Sepsis Anaphylaxis Less severe (can become severe in some cases) Allergy/asthma Contact dermatitis Allergy Breakdown in tolerance leads to immune responses against harmless environmental antigens Tolerance = either central tolerance, regulatory cells or anergization Eosinophils move to the site of allergy and make inflammatory mediators in response to cytokines Mediators call in more immune cells B-cells make IgE antibodies against the allergen, which coats mast cells, and when allergen is introduced, they respond predict ably

The next time we see the peanuts, the antigen hits the antibodies on the mast cells and causes the cell to release histamine On the rise Allergy has been increasing, especially in developed countries Enter the Hygiene hypothesis Reduced frequency of childhood infections may bias the immune system away from protective immunity and towards allergy Immune system if left alone will default to do something find something to attack and since there is no virus/bacteria it attacks the environment Sepsis General Is one of the leading causes of death in hospitals Infection If you get a local infection, you get a predictable inflammatory response If the bacteria makes its way to the blood, it goes to the liver which has kupfer cells (macrophages responsible for cleaning blood) and these do the same thing as the mast cells in the tissue: dump TNFa, IL-1 etc In a local environment it causes local dilation, in sepsis there is a massive vasaodilation Coagulation Now there isn't just local coagulation (ex in the hand) which would keep the bacteria in the hand, there is disseminated intervascular coagulation (random clots all over your body)
Summary

Anatomy Page 49

Anatomy Page 50

Case Study - HIV

Tuesday, February 5, 2013 5:33 PM

Case Study Children losing weight is a bad thing Thrush on buccal mucosa Low CD4 T cell count Serum contained antibodies against HIV This means youve seen HIV before The mom and dad have ant-HIV antibodies HIV came from a tainted blood transfusion with the mom HIV/AIDS HIV is the virus that causes AIDS, which is the human clinical condition Retrovirus Has RNA genome no DNA Generates DNA copy and integrates into the host genome where it persists for the life of the host Retroviruses can go from RNA to DNA (against the central dogma)

HIV particle binds to CD4 and co-receptor on T cell CD4 is on T cell therefore HIV is very specific to CD4 T cells Does it skip APCs and MHC? Virus dumps RNA genome into cell reverse transcriptase then makes the DNA (from the RNA) which is integrated into host geno me When the T cell is activated, it starts transcribing the good stuff that it ahs but also the virus thats within its genome New virus packages are created which go to other cells Course of Infection in Humans CD4 Count

Summary First flu-like symptoms, then asymptomatic phase and then symptomatic and then AIDS Flu This is when the virus is killing the CD4 T cells The CD4 count plummets Seroconversion (asymptomatic phase) = you make antibodies against something .. Therefore when you seroconvert against HIV, you make antibodies on it Abs deals with the HIV and CD4 T cells come back but you steadily lose CD4 over time Threshold #1 - 500 / um Become symptomatic When the antibody count falls below a set amount Suffer from infections which aren't normal for people .. But they can fight off Threshold #2 - 200/um AIDS Immune Response

Anatomy Page 51

Red = HIV = How much HIV you have in the blood Drops after the initial peak Blue = Antibodies Help control virus when out of the cell Yellow HIV specific cytotoxic t lymphocytes (CD8) Really helpful to control HIV Without CD4 Slowly the IS can't handle the HIV and you progress Opportunistic Pathogens and Cancer There are infections and cancers that you just dont see in normal people, and only see in people with immunosuppression Intracellular bacteria TB Is found in normal people, but not in the same amount Fungi Pneumocystis carinii A fungal oppurtunistic pathogen that causes PCP ( pneumonia) this is how we first detected pneumonia (or HIV?) Generate an ELISA Enzyme linked immunoabsorbent assay to detect the presence of Abs to HIV Steps Take proteins (HIV proteins) (in red dots) and stick them onto a plate Then take a blood sample from 2 people -- one with HIV and one without Put the samples into two different wells Non-infected individual Antibodies dont bind HIV-infected individual The Abs do bind Wash away the unbound antibody Knocks off anything that isn't bound but leaves the bound antibodies stuck to the plate Add an anti-human antibody (its an antibody that binds to only a human antibody) This tells you if there is any antibody in the well The point is that there will only be antibody in the one where there was an HIV (blood sample?) in the first place Wash away any unbound antibody Detection In the back end of this anti-human antibody, there is an enzyme which takes a colorless substrate and converts it into a colored product

Anatomy Page 52

Case Study - Arthritis

Tuesday, February 5, 2013 6:01 PM

Case Study Endocarditis Inflammation of the endocardium the valves Has an anti-human immunoglobulin in his body This is the thing we were doing in the Elisa, but this is happening in his blood Something binding to the antibodies activates complement, so he always has inflammation Rheumatoid Arthritis General Chronic inflammatory disease Autoimmune in nature Therefore is an immunopathology autoimmune are an especially bad case of immunopathology Usually found in smaller joints (hands and feet). May also affects other tissues and organs (skin, blood vessels, heart, lung s, muscles) Characterized by inflammatory synovitis Process Have cells making their way into synovium (between joints) which make TNFa and other inflammatory cytokines and chemokines wh ich cause problems, including the destruction of the cartilage which makes your joints smooth Immunopathology Infiltration of inflammatory cells into the synovium High levels of cytokines in joints Rheumatoid factor (autoantibody) Metalloproteinases that degrade cartilage Monoclonal Antibodies We put on anti-TNFa to kind of fight the root of the disease i.e. We can stick in an antibody which will stop the TNF-a which is recruiting cells into the synovium This is through monoclonal antibodies Steps Take a mouse and take human TNF-a and inject it into the mouse. The animal will mount an immune response and make antibodies against human TNF-a (through the B cells) Take the spleen of the animal get splenocytes (some will be antibody producing cells (B cells)) but most wont be specific for TNF-a Also, another problem is that all B cells have a finite life-span and will die Genius moment: Therefore, take myeloma cells (cancer cells) and fuse them with the antibody-producing cells from the spleen Get a hybridoma Take hybridoma and put them into a HAT medium HAT ensures that: Any of the original B cells that didnt fuse with the myeloma die Any of the myeloma cells that didnt fuse die All that remains is the hybridomes (which are immortal) Take hybridomes and see what antibodies they are making To do this you observe manually or with fancy machines -- individually look till you find one that makes antibody to TNA-a Cell 2 in the pic in the slide do (cell 1 and 3 dont so they are useless) Note: These are immortal antibody producing cells The selected cell is a clone as its the exact same as the original (genetically identical) Then make boat-loads of the antibodies Dont give the cells to people, but just the antibodies Note: If you isolate one, it will proliferate Summary Splenocytes from immunized mouse are fused with immortal myeloma cells. Fused cells are cultured in special medium in which only hybridomas survive. Selection of hybridoma with desired specificity.

Anatomy Page 53

Respiration
Tuesday, February 5, 2013 1:30 PM

Anatomy Page 54

Upper Airways
Tuesday, February 5, 2013 1:30 PM

Structure of Thorax 12 thoracic vertebrae 12 pairs of ribs and costal cartilages Tips of the ribs are not completely ossified it is costal cartilage useful as it gives thoracic cage flexibility which is useful for CPR need the thoracic cage to compress so you can apply force to the underlying heart Heart is trapped between the sternum and the thoracic vertebrae behind by compressing the heart, we are relying on the valves between the four chambers of the heart to keep that blood flowing in one direction this is why CPR works Ribs articulate through their costal cartilages with the sternum Sternum Manubrium Body Xiphoid Is partly ossified till 40 years of age Need to be careful of this when doing compressions (CPR) dont want to place hand over it as it can pop off and you can lacerate the underlying viscera (like the liver) Landmarks Suprasternal notch Top of the manubrium Useful for tracheostamy (alternate path to get air into the trachea) Sternal angle Angle between the manubrium and the body is useful as a landmark for oscultion of heart vavles above it have the second intercostal space and below it the third intercostal space Heart is trapped between the sternum and thoracic vertebrae therefore ____ CPR Features of Thoracic Vertebrae Extra articular processes Articulate with the ribs. Ribs articulate via their head and tubercle (and then the ribs articulate with the sternum thorugh their costal cartilages) Prominent spinous processes Articulations One rib only T1, T10, T11, T12 Two rib T2-T9 Has dei-facets to articulate with multiple ribs Features of the Ribs 1-7 are true ribs Articulate directly with the sternum via costal cartilages 8-12 are false ribs Dont articulate directly with the sternum Costal cartilage articulates with costal cartilage of rib #7 Is this for rib 11 and 12 as well? 11&12 are floating Dont articulate directly with the sternum Inserted with the musculature of the posterior abdominal wall Quadratus lumborum runs on the anterior aspect of these two ribs All based on association with sternum Facets For articulation with vertebrae Lateral sides Ribs creates a large angle on the lateral margins of the thoracic cage this is where it has the most curvature in the rib therefore most likely to crack here Costal groove Found on the inferior surface of each rib Contains a VAN Costal means rib so here this has a vein, artery and nerve Intercostal Muscles and the Diaphragm General Alter size or volume of thoracic cage All skeletal muscle Voluntary control innervated by LMN External intercostals (inspiration) Superficial Fibers go 'hands in your pockets' Pull all the ribs upwards towards a fixed upper rib Ribs go up and out, increasing volume of thoracic cage Increases antero-posteral diameter of the thoracic cage so it protrudes out in front of you Internal intercostals (expiration) 90o to the external intercostals this helps to improve integrity of thoracic cage and the abdominal cavity Working on fixed lower rib They depress the thoracic cage (reduce volume -- expelling air) Innermost intercostals Ignore these Diaphragm Muscles of Breathing

Anatomy Page 55

 Muscles of Breathing

Quiet Breathing External intercostals Elevates ribs Diaphragm Pulls dome downwards to increase the superior-inferior dimensions of the lungs (increases lung volume) Forceful inspiration Need accessory muscles to help i.e. SCM + scalenes Further elevate the most superior portion of the thoracic cage so work with the external intercostal muscles Quiet breathing (expiration) Relies on the elastic recoil properties of the lung like letting a balloon to deflate Active breathing Internal intercostals Depress ribs Abdominal muscles Internal/External oblique + transverse/rectus abdominus Help compress the andomino-pelvic cavity which pushes the viscera up to the diaphragm, helping move it in a superior direction Intercostal VAN From in to out Parietal pleura Single layer of epithelial cells that secrete serous fluid which helps lubricate the pleural cavity Internal intercostals Ribs Costal groove In the inferior aspect of the rib In the groove is the VAN The nerve is the thoracic spinal nerve For each intercostal space, its a separate thoracic level of a spinal nerve its segmental innervation External intercostals Importance If you want to pull excess fluid off the heart (tamponade) or pneumothorax, want to get a needle in there to remove the excess fluid or air the safest way is the aim for the superior aspect of a rib avoid the intercostal VAN Thoracic Cage - Blood Supply Anastomoses

General There is anastomoses for both the arterial and venous blood circuits Arteries Anterior intercostal artery L/R thoracic arteries supply it branch off the subclavian (also known as the mammary artery and is good for CABG) Posterior intercostal artery Descending aorta supplies is Vein Anterior intercostal vein Posterior intercostal vein Venous drainage Front: Internal thoracic vein eventually dumps into the subclavian vein Back: Left side: Hemiazygous V Hemi cause its half the size as the vein on the right (azygous) Will drain into azygous (cross from left to right) which dumps into SVC Right side: Azygous vein Diaphragmatic Origin Schematic Central tendon Contains a central tendon

Anatomy Page 56

 Contains a central tendon Aponeurosis Skeletal muscles Anterior: Attach to the inferior margin of the ribcage out front Posterior: Runs along the inferior margin of the 12th thoracic rib Crosses T12 and goes to the other side Inspiration Diaphragm moves inferiorly helps bring air into lungs Pulls central tendon downwards Both active and passive Supplied by the phrenic nerve (C3,4,5) Travels through the fibrous pericardium to enter the diaphragm Many structures pass through the diaphragm Aorta Esophagus Inf. Vena Cava Pass through the openings in the diaphgragm Openings Aortic hiatus (hole in the muscle) This is where the diaphragm is said to have two legs through which the aorta comes Thoracic duct comes through Esophageal hiatus Vagus nerve follows esophagus Caval opening Doesnt go through muscle Tendon is dense connective tissue helps maintain patency of IVC that passes through it Upper Respiratory System Upper Airways: Nose Air enters through external nares (openings for your nasal cavity) Nasal cavity Lined by mucous membrane to trap particulate matter Surround the superior, middle and inferior nasal meatuses (openings) Warms the air Humidifies the air (mucous has water component which evaporates into the air) Nasal Chonche Bony protrusions Stets up turbulent air flow, forcing air to the sides of the nasal cavity, forcing it on the mucous Find pseudostratified, ciliated columnar Psuedostratified Cause it's hard to tell whether there are 1-2 layers cells constantly dividing Ciliated Have cilia to move mucous to the back of the mouth then you can swallow or spit the mucous Sinuses Pharynx Nasopharynx Upper most region Associated with the nasal cavity Oropharynx Behind the oral cavity represents a structure that is a conduit of both air and food Laryngopharynx A structure that is a conduit of air and food Found in the region of the larynx Note: Food Has to crisscross over the airways the epiglottis is there to prevent that Esophagus Trapped between the trachea and the vertebral column at the back When you swallow food, the esophagus will protrude into the trachea, which has smooth muscle at the back leaving it soft so food can push past Cells Pseudostratified, ciliated columnar in the nasal cavity Stratified squamous Rest of the places So you can stop the abrasive forces Larynx Larynx extends from C4-C6. Air leaves the pharynx and enters the larynx via the glottis. Glottis = is an inward folding of the edges of the larynx also known as the false vocal cord Three main cartilages form larynx (other smaller ones for a total of 9). Epiglottis Protects the lower airways from food entering Thyroid Sits above the thyroid gland so doesnt protect the thyroid gland Represents the fusion of two cartilages makes the Adam's apple due to the 900 angle in females the angle is larger so dont have an Adam's apple Cricoid Defines the inferior border of the larynx Ligaments (including vocal ligaments) found in this area Connective tissue from cartilage to cartilage Vibrate to make sound This represents the division of the upper airways from the lower airways Everything above the vocal cords is not sterile and below is clean Epiglottis serves to protect lower airways during deglutition (swallowing)
Anatomy Page 57

 Epiglottis serves to protect lower airways during deglutition (swallowing) Food stuff passing from the oral cavity at the front have to get behind into the esophagus Epigottis has to close down to prevent food from getting in there Closure is aided by the fact that the larynx during swallowing moves superiorly to help the epiglottis seal off the opening for the trachea Epiglottis Functions Close off trachea During swallowing, vomiting Generate Cough/sneeze During these maneouvers you generate a lot of pressure in the thoracic cavity and lungs the only way to do that is to close the glottis and then contract the muscles of expiration to generate the pressure in the lungs you then open the glottis to release the pressure Cough Send the air out through the lungs in high velocity usually through the oral cavity Have irritant receptors in the lower airways, in the primary bronchi to generate this Sneeze Trying to get rid of irritants that have stimulated irritant receptors in the upper airways (nasal cavity) so you direct your air through the nasal cavity Expulsive maneuvers Valsalva maneuver (defecation) Have to close the epiglottis so the thorax and diaphragm cant move up as your contracting the abdominal muscle Pressure goes onto the large colon Peeing Childbirth Structural support If your trying to lift something

Anatomy Page 58

Lower Airawys
Tuesday, February 5, 2013 2:02 PM

Upper airways Responsible for helping to condition the incoming air Warming it Making it moist Removing as much particulate matter as possible Lower airways also does many of the same thing Still filtering air Provides structural support to maintain patency of airways to let the air get in Air doesnt exert as much pressure on the walls of vessels like blood does, so unless you close your glottis to make pressure , you need something to keep the airways open Trachea Right below larrynx ~12cm long by ~2.5cm in diameter Contains 16-20 C-shaped cartilage structures This provides structural support Tracheal smooth muscle (trachealis muscles) (under autonomic control) finishes the circle Rigid structure divides into primary bronchi Direct air into left or right lung At this bifurcation, there is the carina Lining of epithelium provides same protection as nasal cavity and larynx Pseudostratified, ciliated columnar epithelium Help generate the mucociliary apparatus so mucous that traps stuff will be moved up the larynx can spit the stuff out then or digest it Successive Structure Trachea Bifurcation Carina Internal ridge at bronchial junction (assoc. cough reflex) Epithelial tissue has irritant receptors so particulates will generate a cough reflex Primary bronchi Primary bronchi Divide into right and left lung at the hilus (special names cause other cool stuff enters and exits the lungs at this point) Divide into right and left lung? Or divide at the right and left lung From slide: Primary bronchi enter each lung at the hilus then divide into secondary bronchi Right primary Shorter, more vertical Right bronchus almost goes straight down Therefore food will prob go this side more than the left side Left primary Longer, more angled This is because we have the heart sitting there Secondary bronchi Secondary (lobar) bronchi for each lobe (3 in Right, 2 in Left) Direct air into the separate lobes of the lung Lungs Lobes and Fissures Right Lobes Superior Middle Inferior Fissures Grooves that run into the lung tissue) Horizontal fissure Between superior and middle Oblique fissure Between middle and inferior Left Lobes Superior Lingula - end of the superior lobe Is its own bronchopulmonary segment Inferior (have heart occupying the space) Fissures Oblique fissure iClicker - Trachea (?)

Anatomy Page 59

 iClicker - Trachea (?) Is involved in conditioning incoming air Is not an upper airway structure Not supported by plates of cartilage (its rings) Its not posterior to the esophagus and is not supported by the pulmonary circuit Tertiary bronchi Secondary bronchi continue dividing to create tertiary (segmental) bronchi 10 right lung, 8* in left lung Bronchopulmonary segment. Area supplied by tertiary bronchi Subsections of each lobe of the lung Functionally and anatomically independant 10 on right side and 8 on the left If you have cancer, you can remove one segment of the lung and the others will be just fine Cartilage rings From the trachea, they gradually disappear and are replaced by cartilage plates. The plates are shields without the hole at the back Divide into bronchioles Bronchioles Eventually cartilage is replaced by smooth muscle only. Spiral smooth muscle bands regulated by the ANS. Bronchioles branch up to 14X to make terminal bronchioles. As you go down further, the cartilage disappears and gets replaced with elastic tissue also see smooth muscle At the terminal bronchiole, all you have is elastic fibers (no cartilage) This provides that elastic recoil property of the lung which aids in you doing passive expiration Important for asthma cause its not the trachea or primary bronchi its the airways at the level of the terminal bronchioles that get affected Smooth muscle component of the airways becomes a bigger factor in the distal airways parasymp innervation causes contractio n = increases resistance in the airways This is the smaller bronchioles all the way up to the terminal bronchioles that are affected Lobule (acinis) Each terminal bronchiole forms a lobule This represents the division between the conducting zone of the lungs (bringing air in, filtering and humidifying it) and t hen respiratory region where there is gas exchange Each lobule is composed of a: Terminal bronchiole Arteriole + Venule Apart of the pulmonary circuit comes off of RV and going back to LA respectively Lymphatic vessels All wrapped in elastic tissue Gives that recoil property Terminal bronchioles divide into respiratory bronchioles So thin that there can be gas exchange between blood and air Respiratory bronchioles connected to alveolar sacs by alveolar ducts Alv ducts conduct air to individual alveoli Circulations in the lung Trachea Terminal bronchioles Walls of the airways are so thick so just gas exchange will not work for those walls need a circuit that gives oxygenated b lood This is the bronchiole circuit Bronchial arteries service the conducting regions. Coming off the LV of the heart (descending aorta) Have to follow all the structures down (like trachea down to the terminal bronchiole) Pulmonary arteries service the gas exchange regions. Starts at the acinis At and after the lobules, no its the pulmonary circuit that is playing a role These come off the RV of the heart Goes to a capillary bed that surrounds each alveolus, participated in gas exchange and then the blood will go back to the LA Generations Each division represents a division At each level the division is mostly dichotomous (two by two by two) Trachea is generation 0 Primary bronchii are generation 1 Gas exchange Gen 15-23 Begins with respiratory bronchiole all the way to gen 23 = alveoli Summary so far Air has traveled through the external nares, nasal cavity, is funneled into the pharynx, through the glottis to the larynx (start of lower airways approx) and into the trachea Warming, humidifying and filtering The trachea splits into the primary bronchi which divide into the secondary bronchi. These further subdivide into tertiary bronchi Tertiary bronchi eventually split into terminal bronchioles which form lobules (acini). Terminal bronchioles split into respiratory bronchioles which end in clusters of alveoli called alveolar sacs. Conducting
Anatomy Page 60

 Conducting

Respiratory

Now the airways are microscopic cause you need a microscope to see them Gas Exchange Membrane Gas exchange occurs at alveolar-capillary membrane. This is at the acinis of the lung mostly at the the alveoli part of it Surface area in the other parts is not as much to make it that significant Interface of the capillaries of the pulmonary circuit and the alveoli 300 million alveoli with surface area totaling 750 sq ft (~70 m2) Alveolus Two types of alveolar cells: Type I alveolar cells (pneumocyte) Air cell Squamous in nature -- provide greatest SA and therefore is primary site of gas exchange. Continuous lining of alveolar wall. Type II alveolar cells Secrete a liquid called surfactant. Soap like liquid (detergent) which reduces the surface tension of the mucous that lines the alveoli See the mucous has water and water likes to attract each other (cohesion) (as well as adhesion) and the cohesion causes surface tension. This is always trying to collapse the alveolus down (thats why bubble making solution is soapy if it was just water, the bubble would collapse on itself too fast) Note: Elastic fibers also help to keep alveoli open. 1/3 of the recoil property of the lung comes from elastic tissue and 2/3 from the surface tension from the alveoli Gas Exchange Membrane Really thin only 0.5um thick Gas goes between alveoli (airway) and blood Diffuse O2 in and CO2 out Capillary endothelial cell and type 1 pneumocyte (alveolar cell) share the same basement membrane This glues the two together Pleura Lungs in the thoracic cavity are covered in a thin membrane (1 cell thick) called pleura The lungs and thoracic cavity are covered in pleura Parietal and Visceral Pleura Parietal lines the thoracic wall Visceral lines the lungs Pleural cavity Between the two layers Space between parietal and visceral pleura Serous membrane secretes pleural fluid and is found in the cavity Pleural fluid allows lung and thoracic wall to move with little friction AND creates a hydrostatic force (very important!) The water molecules within the serous fluid keeps the lungs plastered against the thoracic wall which is useful when breathing in. As you increase the size of the thoracic cage, you want the lung tissue to follow it -- therefore you rely upon the adhesive properties of the water (serous fluid) to bring the lungs along for a ride Negative pleural pressure (-2 to -6 mmHg) Negative is a slight vacuum Negative with respect to the outside atmosphere sub-atmospheric If you put air in the cavity, the lung wont follow the thoracic wall = pneumothorax Pleural Membranes

Anatomy Page 61

Parietal and visceral are actually one continuous membrane Formation When primary bronchii form, they develop lung buds at the tips (lung tissue growing into thoracic cavity. At the time the thoracic cavity is lined by parietal pleura. As the buds grow into the cavity, they pull the parietal pleura with them. But now that the parietal pleura is associated with the lung bud, we call it now the visceral pleura. The lung will continue to grow and occupy the thoracic space until you have just a small potential space between the two pleura which again is one continuous structure Impressions from the Lungs Left Lung Cardiac notch Space heart is occupying Arch of the aorta and descending aorta Makes like an arching impression and then a falling one Diaphragm Impression on the inferior surface of the lung Right Lung Azygous vein Dumps into the SVC Heart Very slight impression Diaphragm More elevated on the right hand side (you have the liver so it elevates the diaphragm) so the notch is slightly elevated Note: You can identify three lobes and two fissures (rather than two and one for the left side) Mechanisms of Ventilation Ventilation You getting air into and out of your lungs Leads to respiration which = doing gas exchange Ventilation works on Boyles Law PV=k Pressure x volume = constant Quite simply: volume = pressure Now atmospheric pressure is greater than that in the lungs so this will push air into the lungs Decrease volume = pressure Pressure inside lungs is higher than atmospheric pressure causes air to exit Compliance = Change is related to elastic nature of tissue Pretty much how easy it is to make your lungs larger Ex: balloons Party balloons easy to inflate by mouth so it is highly compliant Part animal balloons stiff plastic and cant do by mouth so it is non -compliant Decrease in Compliance In any fibrotic disease that causes scar tissue to go down (collagen) which doesnt stretch well which makes it difficult to inflate the lung Note: A decrease in elastic tissue causes compliance to increase Mechanisms of Respiration Ability to: Exchange gases between alveoli and blood Exchange gases between blood and tissues Daltons Law [pressure] x [gas %] = Partial pressure of gas (Pgas) Each gas in a mixture gives off its own partial pressure Most gas in atm is nitrogen so it gives off most pressure Oxygen is low and therefore exerts a small partial pressure PP is dependent on the percent that the gas occupies in the environment Why is this important? Direction of diffusion is determined by partial pressure of the gas. (gas movement from high to low pressure) Differences in the partial pressure causes the oxygen to move from one medium to another

Anatomy Page 62

Differences in the partial pressure causes the oxygen to move from one medium to another Example for PO2: Atmosphere: 160mmHg Alveolar: 105mmHg (104) Drops from the atm as there is CO2 mixing with it and cause we are humidifying the air with water, decreasing the pressure (as water gives off its own pressure) Arterial blood: 100mmHg (104) Tissue: 40mmHg Note: (104) cause in a healthy lung, the PP should equilibrate at the level of the alveoli Quiet Inspiration Increased thoracic capacity due to downward movement in diaphragm (1-2 cm) Diaphragm does much of the work Adult = 0.5L of air per inspiration (tidal volume) Pressure difference Atmospheric air pressure = 60 mmHg. Intrapulmonary air pressure = 758 mmHG This small difference drives the movement of air Note: Also use the external intercostals Forced Inspiration Diaphragm (8-10cm) External Intercostals Bring ribs up and out Muscles that fix upper ribs (Scalenes, Sternocleidomastoid) Help fix upper portion of the thoracic cage Works with the external intercostals Hydrostatic force created by the pleural fluid allows lungs to move with the thoracic wall and diaphragm. Remember its that hydrostatic force caused by the serous fluid Where does a stich originate from? Not the diaphragm as the innervation is C3,4,5 and therefore it would be referred pain to the neck (dermatomes of 3,4,5 corre spond to that) Its actually from the intercostal muscles which have segmental innervation Hard to Breathe When Pregnancy Diaphragm doesnt have much room to move that 1 -2cm is pretty max Eat lots Food is filling the stomach which sits under left border of diaphragm Corset Expiration Quiet Expiration Elastic recoil of lungs and musculature (relaxes) Forced Expiration Internal intercostal muscles (contract) Abdominal wall musculature (compress viscera) Muscles that fix inferior ribs (e.g. Quadratus lumborum)

Anatomy Page 63

Respiration 1+2
Tuesday, February 12, 2013 1:33 PM

Definitions Ventilation Movement of air into and out of lungs Anatomy Mechanics Respiration Exchange of gases (O2 and CO2) Happens at Tissue Between tissue and blood Between blood and lungs By definition includes ventilation Tissue Respiration Aerobic Refers to O2 utilization and CO2 production by metabolizing tissues Fuel + O2 H2O + CO2 In the process you do ADP ATP Energy (movement, protein synthesis, ion pumps etc.) Rates Oxygen utilization = VdotO2 = Vdot is rate of volume (dot is time) Resting = 3.5 ml/ kg body weight / min Exercise = 25-80 ml/ kg body weight / min (depends on fitness) CO2 Production = VdotCO2 = Rate depends on VO2, fuel source and metabolism Ex. Carbohydrates (CHO) as fuel source 1 O2 in puts 0.7CO2 out Therefore VdotCO2 = 0.7*VdotO2 Fats as a fuel source Most efficient fuel source 1 O2 in puts 1 CO2 out VdotCO2 = VdotO2 Anaerobic Refers to the production of ATP without the utilization of oxygen Occurs mainly when aerobic isn't enough Fuel Lactic acid It is an acid that will cause a decrease in pH in blood stream It consists of a Lactic anion and a proton that can dissociate from it This still contributes to the production of CO2 Carbs Lactic acid (La:H) La- + H+ Proton can accumulate in skeletal muscle that contributes to cramps MI - chest pain comes when you switch to anaerobic respiration making lactic acid which causes pain H+ + HCO3- H2O + CO2 Note: Metabolism should not be considered to be purely 'aerobic' or 'anaerobic' anaerobic processes are invoked to augment aerobic processes when the supply of oxygen cannot meet the energy utilization demands Ex intense exercises, myocardial infarction etc. Lung Volumes Spirograph When you inspire, the bell sinks and the pen rises (pen part ?) When you expire, the bell rises and the pen falls (pen part ?) The pen records the rise and sink and therefore the changes in volume of your lungs Spirographic record

On the left is the volumes of the lung (0-60L)

Anatomy Page 64

 On the left is the volumes of the lung (0-60L) Quiet breathing Creates the tidal volume Only bringing in approx 0.5 liters of air Total lung capacity Higher in males (approx 6L) Inspiratory Reserve Volume Additional volume you can bring into the lungs above the quiet breathing that you normally do (tidal) Expiratory Reserve Volume After doing the forced inspiration in the picture, this is what happens after you breathe out as much as possible Vital Capacity Volume of air that can move through your lungs that will be useful for gas exchange Most you can breathe in - how much you can breathe out Residual Volume Lungs still have air in even after you breathe out as much as possible Reasons If you completely empty the lungs each time, the alveoli would collapse on yourself the fluid would glue them shut As you breathe out, blood is still flowing out. As such, if you remove all air, you would only be doing gas exchange half the time Note: Getting hit or sacked in sports More air than normal comes out, and therefore its real hard to take the next breath some of the airways have collapsed on themselves need extra force to open them up Total lung capacity Vital capacity + residual volume Functional Residual Capacity If you paralyze all the muscles of respiration, you sit at the end tidal volume you breathe out air in tidal respiration (all based on the passive recoil) no muscles used at this time if you wanted to go below that you want have to use muscles of expiration
Ventilation Rates of Ventilation General Analogous to cardiac output Dependent on breathing frequency + how much air is moved per breath Minute ventilation Air moving past your mouth in one minute = VdotE = rate that air move in and out of mouth E cause you collect air expired in a bag when testing for this = breathing frequency (fb) x tidal volume (VT) At rest = 12 breaths/min x 500 ml/breath = 6l/min Maximum exercise 60 * 3000 = 180 L/min Alveolar Ventilation How much air goes down to the respiratory regions of the lungs to participate in gas exchange There is air trapped in the upper and lower airways that volume is approx 150mL so you have to subtract that from each breath = VA = rate that fresh air moves in and out of alveoli Less than VE due to dead space volume of lungs (VD) Dead space is the part of the airway closest to the mouth/nose that does not exchange gasses with blood (~150ml) the last 150 ml of each breath fills dead space and is then breathed out again without any gas exchange Anatomical dead space as its a fixed volume Calculation Summary So every new breath that you bring in, the last 150mL is not doing anything for you and when you breathe out, the last 150 mL is sitting there doing nothing for you Tidal volume Ex if you have chest pain, it may hurt to breathe in, so you might take shallower breaths. This decreases tidal volume. But your dead space doesnt change so your alveoli see less good air Same for pregnancy For both, you may have to increase breathing frequency to get the same amount of air Effects of Breathing Rate and Depth of Alveolar Ventilation

Anatomy Page 65

Deep and slow is energy intensive though cause you have to recruit muscles to move that much air across the mouth Ventilation - Mechanics of Breathing The forces (and their origins) that move air in and out of the lungs - and the impedances that these forces overcome Origins of Ventilatory Forces Inspiratory muscles Expiratory muscles Mainly for forced expiration Disorders of Force Generation Muscle weakness Muscular dystrophy MS Disuse atrophy Coma patients dont use their muscles so when they wake up they have to be weaned from the ventilator Abnormal/altered anatomy Scoliosis Pregnancy Lung volumes Muscle contraction causes movement of the chest wall and produces change in lung volume - see spirometry diagram Impedances Overcome During Ventilation Elastance General Measure of the elastic property of the lung Stiffness of the lung Related to forces needed to keep lung inflated Analogous to pressures needed to blow up a balloon (how hard it is) Equation = P/V Lungs with high elastance = stiff Fibrosis Low surfactant Compliance How easy it is to blow up a balloon 1/elastance High elastance = low compliance Surfactant Reduces lung elastance by reducing the surface tension of the water molecules sitting in the lung Elasticity of Lung Lung elastic tissue highly compliant The elastic tissue makes the lungs more compliant it decreases elastance Water Water increases the elastance (decreases the compliance) therefore need add surfactant to break up the surface tension of the water Most of the elastic recoil of the lung is from the surface tension of the water lining the alveoli Structure One side is hydrophilic and one is hydrophobic Philic - phosphate head Phobic - lipid tail Phosholipid released by type 2 pneumocytes throughout airways spread over surface and reduces surface tension of the water Reduces pressures needed to breathe Prevents fluid buildup in the lung Produced continuously after 27-28 weeks gestation Problem with pre-me babies cause they dont have enough surfactant yet Resistance General Property of any tube like structure

Anatomy Page 66

 Property of any tube like structure Greatest determinant is radius of the tube Related to pressures needed to generate air flow Need higher pressures in one end to get flow in the other end Pressure difference needed between the two sides to have flow from one end to the other Equation Need p1 to be higher for flow Increased resistance means that you need the pressure difference to be higher (ex asthma) Pathologies Asthma Radius of vessels become smaller need higher pressures to make the same volume of air to go by Chronic Obstructive Lung Disease Associated with chronic smoking and other exposures Causes remodeling of lung (hyperplasia of smooth muscle) making the airways smaller Reduction of diameter of tube that you can't reverse using drugs Pleural Pressure General Lungs have parietal and visceral pleura In the potential space, we have some serous fluid there is actually a measurable pressure in the cavity called the pleural pressure (Ppl) Intrapulmonary pressure (PIP) = pressure in the lung Changes in pleural pressure causes changes in pulmonary pressure which helps ventilation Mechanics Made Easy Abnormal way of breathing Lungs could be inflated by increasing the pressure inside the alveoli (intrapulmonary pressure) Similar to mechanical ventilation This is not how we normally breathe Really How We Breathe The lungs could be inflated by decreasing the pressure surrounding the lungs to sub-atm pressures sub-atm pressures are sometimes called negative pressures Imagine a syringe -- Pulling on the syringe will inflate the lung by lowering the pressure around the lung Thus, to get to larger lung volumes, greater negative (sub-atm) (pleural?) pressures are required Outward forces In the respiratory system, the source of the -ve pleural pressure to keep the lungs inflated is the outward recoil of the chest wall Normally, the lung is always trying to collapse on itself and the thoracic cage is trying to expand Therefore, there is always tugging on the pleural space in both direction To get a larger lung volume, P pl can be made more negative through the action of inspiratory muscles Inward forces Elastic recoil of the lung tissue and the water molecules causing surface tension in the alveoli which try to collapse the lung Breathing Cycle Before Inspiration Atm pressure = PIP When no breathing is taking place and the muscles of breathing are relaxed (lung volume = functional residual capacity) Forces The lung elastic recoil makes lungs tend to empty (collapse inwards) The thoracic cage elastic recoil makes thoracic age tend to expand These elastic recoils match and result in a negative pleural pressure During Inspiration Forces The lung elastic recoil makes lungs tend to empty (collapse inwards) The thoracic cage elastic recoil makes thoracic age tend to expand Muscle forces make cage tend to expand The resulting outward motion of the thoracic cage pulls the lungs open Expansion of the lungs results in a greater lung recoil pressure, so P pl becomes more negative. As such, the lungs expand, the air inside becomes rarified (stretched) resulting in a negative (sub-atm) PIP Therefore, PIP overcomes the resistance of the airway and inspiration occurs End of Inspiration Forces The lung elastic recoil makes lungs tend to empty (collapse inwards) more than before cause the lung has been stretched The thoracic cage elastic recoil makes thoracic age tend to expand Muscle forces make cage tend to expand Expiratory recoil of lung is matched by inspiratory recoil of chest wall + action of muscles Ppl is negative (in fact it is the most negative it can be), exactly opposing the balances recoil and muscle forces B/c lung elastic recoil is matched by P pl, Pip =0 and there is no airflow
Anatomy Page 67

 B/c lung elastic recoil is matched by P pl, Pip =0 and there is no airflow During Expiration Forces The lung elastic recoil makes lungs tend to empty (collapse inwards) more than before cause the lung has been stretched The thoracic cage elastic recoil makes thoracic age tend to expand Muscles are resting no force exerted Inspiratory recoil of chest wall is less than expiratory recoil of lung so the lungs begin to empty as the lung volume decreases, Ppl become less negative due to the decrease in lung recoil pressure As the lungs begin to recoil, they compress the air within, producing an increase in P ip. This increase overcomes airway resistance and expiration occurs

Breathing Cycle

Volume of breath Bring in 1/2 L and then take it out Pip Is always negative More negative during inspiration (lung is trying to collapse and thoracic cage is trying to expand ) Alveolar Gas Exchange General The exchange of gases between alveolar air and blood Occurs due to differences in partial pressures of gases Partial pressure of gases Pressure of mixture of air in the room = Atmospheric pressure Measurement -- pan filled with mercury with a vacuum Note: The vaccum is not sucking the mercury there is no sucking in physics. Pressure in atm = how high the mercury is pushed up in the tube Partial Pressures of Gases Dalton Total pressures in the room = sum of all the individual gases in the room Each gas will contribute to the pressure, with direct proportion to its percentage in the mixed gas Diffusion When there is a difference in partial pressures across a membrane Membranes Alveolar Tissue Diffusion will go from highest to lowest pressure This is regardless of total pressure difference Henrys Law When a mixed gas is in contact with a liquid, each gas will exert the same pressure in the liquid as its partial pressure in the gas As the partial pressure of a gas increases in a liquid, more of that gas will go into solution Nomenclature of PP Room air (inspired air) = I Pressure of O2 in room = PIO2 I cause we are going to inspire it thats its purpose Alveoli = A Pressure of nitrogen in room = P AN2 Arterial = a Pressure of CO2 in room = PaCO2 Venous = v Pressure of O2 in room = PvO2 Gas exchange takes place between alveoli and blood due to differences in partial pressures
Anatomy Page 68

 Gas exchange takes place between alveoli and blood due to differences in partial pressures PAO2 > PvO2 PvCO2 > PACO2 PP Gradients in the Body As air moves from inspired to alveoli PO2 Due to increase in PH2O Air gets humidified Due to increase in PCO2 Adding in CO2 displacing the O2 PCO2 Due to addition from blood As air moves from alveoli to expired PO2 Due to mix with deadspace air P02 still less than inspired air PCO2 Due to mix with deadspace air Different places in the body See diagram At the Alveoli General Alveoli PAPO2 = 104 PAPCO2 = 40 Venous PvPO2 = 40 PvPCO2 = 45 Arterial PaPO2 = 104 PaPCO2 = 40 Note: Pressures of O2 and CO2 remain fairly constant at 104 and 40 -- explained in control of breathing Note that its called venous blood (cause its not oxygenated yet) even though its flowing through an artery and arterial blood even though its flowing through a vein Respiratory Disease Examples Pnemonia Pulmonary edema Fibrosis Barrier is created between alveoli and blood Alveoli PAPO2 = 104 PAPCO2 = 40 Venous PvPO2 = 40 PvPCO2 = 45 Arterial PaPO2 = 60 PaPCO2 = 40 CO2 is not very effected because it is highly soluble and can move through barriers if you had a CO 2 barrier, you'd die cause the O2 for sure would not move Ventilation/Perfusion Ratios Intro Sometimes, there are regions of the lung where there is an imbalance between how well it is ventilated and how well it is perfused with blood flow this imbalance is described as an abnormal Vdot/Qdot ratio Nomenclature Dot on top is rate of change V = volume of air Q = volume of liquid or blood Cases Normal Vdot/Qdot High Vdot/Qdot High ventilation, low perfusion Oxygen pressure will be high (not taking a lot of O2 out but bringing lots in) Examples Apex of the lung The top of the lung due to gravity will see this most perfusion is at the bottom Pulmonary embolism Not that big of a problem Arterioles relax Low Vdot/Qdot

Anatomy Page 69

 Low Vdot/Qdot Low ventilation, high to normal perfusion Something that obstructs airflow to some part of the lung Asthma Lung cancer This causes hypoxia Causes low alveolar pressure of oxygen send blood with not a lot of O2 Big problem Arterioles contact Compensations This is to correct abnormal Vdot/Qdot Arterioles Constrict if PCO2 is high or PO2 is low Relax if PCO2 is low or PO2 is high Problem Altitude Lets say you go up a mountain and your lung sees a low PP of oxygen the lung will therefore constrict the vessels This makes sense if you have a localized lung disease cause the parts of the lung will want to have blood flow go to another part here the thing is that the whole lung is affected so this doesnt help Whole lung is sick This mechanism will still kick in all the blood vessels constrict and therefore the body is trying to pump blood through constricted blood vessels Can cause pulmonary hypertension (heart has to work hard) Gas Transport in Blood Henry's Law Gas will enter into solution in a liquid in direct proportion to the PP of that gas The actual amount in solution will also depend on the solubility of that gas.

Note: Oxygen solubility = 0.003 ml/100 ml fluid / mm HG CO2 solubility = 0.06 Neither of these solubility's is sufficient for blood to carry the amounts of O2 and CO2 required by the body's metabolic demands However there are properties of blood that allow for greater amounts of gas to be carried at a given PP than would be possible based on the solubility of the gas CO2 Transport Diffusion From tissue to blood based on gradient between tissue PCO2 and PaCO2 From blood to alveoli due to pressure gradient between PvCO2 and PACO2 Forms in the blood Dissolved (7%) HCO3- (70%) Bound to hemoglobin (22%) Diagram + Explanation Out of tissue CO2 goes out of tissues into plasma (?) Some is dissolved CO2 Can also combine with water CO 2 + H2O HCO3- + H+ Slow cause there is no enzyme Soda bubbles and keeps bubbling for hours after you open the reason it bubbles for hours is cause its been in that can for so long that most of the CO2 has combined with water to make the two molecules and slowly after opening it goes in the opposite direction Some goes into red blood cell Same equation as before [CO 2 + H2O HCO3- + H+ ] This is way faster cause you have an enzyme called caarbonic anhydrase This however needs to exit the red blood cell so it exchanges with Cl Binds to hemoglobin Into alveoli CO2 thats dissolved goes out Bicarbonate in plasma (from the slow reaction) comes out Bicarbonate from RBC (fast reaction) comes out The hemoglobin bound one comes out as well Haldane Effect As blood passes the lung, not only does it release CO2 but also picks up O2 Oxygen saturated hemoglobin does not bind CO2 as well as unsaturated hemoglobin Thus, some CO2 is released from blood as O2 is bound, independent of changes in PCO2
Anatomy Page 70

 Thus, some CO2 is released from blood as O2 is bound, independent of changes in PCO2 In essence, O2 kicks CO2 off O2 Transport Oxygen is transported either in solution or bound to hemoglobin 1% dissolved 99% bound to hemoglobin Hemoglobin Central globin surround by 4 heme portions Heme: Portion including ferous iron ion Loose binding with oxygen (easiliy reversible) Bind oxygen in relation to partial pressure Higher affinity for carbon monoxide Globin: Central protein core Forms of Hemoglobin A = adult Characteristic dissociation for O2 F = fetal Higher affinity for O2 than adult Allows fetus to take O2 from mother S = sickle Crystalizes within cell -- fragile RBC Blood As you increase PO2, oxygen starts binding to the hemoglobin Four sites that can be filled 0 filled = blue blood 4 filled = red blood Note: After the first O2 binds, the other ones bind more easily Therefore the O2-hemoglobin dissociation curve is not a straight line Amount in Blood O2 Saturation = % of hemoglobin that has bound O 2 Normal = >97% Note: just cause it says >97%, this doesnt mean their ok. If their anemic, their respiratory system would be fine but just not enough hemoglobin O2 Concentration = volume of O2 per volume of blood (ml/100ml) Dissolved = 0.3 ml/100ml Bound to hemoglobin Therefore approximately 99% of O 2 in blood is bound to hemoglobin Dissociation Curves

Notes At the lungs the P02 is 100 and the hemoglobin is almost fully saturated As P02 decreases like in the tissue, about 1/4 of the hemoglobin molecules give up their O2 Therefore you are only releasing approx a 1/4 of the O2 molecules Exercise You take approx. 3/4 of the O2 off the hemoglobin Curve Flat top portion Therefore if you drop P02 from 100 to 60, the saturation decreases only from 100 to 90. This is good cause you can go up high mountains and stuff and still survive Also means that you can get a pretty big respiratory disease and still not really get owned Steep portion Allows tissues to pull off as much O2 as is needed
Anatomy Page 71

 Allows tissues to pull off as much O2 as is needed

Shifts to the right: PCO2 temperature pH Carbon Monoxide 100% saturation when PP is 0.5 (as compared to 100 for O 2)

Anatomy Page 72

Respiration 3
Tuesday, February 26, 2013 1:29 PM

Control of Breathing Purpose To ensure that alveolar ventilation is at an appox level for the amount of tissue respiration occurring at any given time Very simply Control mechanisms ensure that arterial gas pressures remain constant As long as arterial pressures are maintained, tissues will be able to obtain O2 and excrete CO2, at the required level Arterial gas pressures are very close to alveolar gas pressures (except with alveolar disease) Alveolar gas pressures are determined by VdotO2, VdotCO2 and alveolar ventilation Therefore, control of breathing involves ventilating at a level to maintain arterial gas pressures Brain Intro Medulla Dorsal and ventral respiratory group send bursts of neural activity to muscles of breathing Simplest ones sends burst of contractile signals but there are other signals as well Smoothness, intensity and frequency of these bursts are influenced by control from pneumotaxic and apneustic centers These centers receive input from many sites to ensure that level of ventilation matches bodies demands Input to apneustic and pneumotaxix sites Higher brain centers Allows conscious control E.g. breath holding Also sends corollary input when sending signals to skeletal muscles Stretch receptors in lungs Prevents overinflation This is to stop you from keep on taking deep breaths which could damage the lungs Irritant receptors Triggers cough reflex Also have something similar in the upper airways to start the sneeze reflex Receptors in muscles and joints Increases breathing when activity is increased Central chemoreceptors In the brain Blood CO2 levels Peripheral chemoreceptors Arch of the aorta and carotid artery Fine control of PaO2 and PaCO2 Other (through hypothalamus) Pain Stress Heightened emotional state Chemoreceptors Ensure that blood gas pressures remain constant Central chemoreceptors General Ventral surface of medulla High levels of CO2 for example would result in the CO 2 coming out of the circulation, crossing the blood brain barrier where it would combine with water to make H 2CO3 and H+ hydrogen ion acts on chemoreceptor this causes signal to breathe more This is an insuppressible signal thats why you cant hold your breath forever Are central chemoreceotors responsive to hydrogen ions or CO2 Receptor itself is responsive to hydrogen ion but not pH cause H + cant cross the blood brain barrier Ex. Response to increased metabolic rate Metabolic rate VdotCO2 PvCO2 PACO2 PaCO2 Chemoreceptor Ventillation PACO2 Therefore if you exercise and dont increase breathing this will happen This allows fine tuning of ventilation to keep P aCO2 ~ 40 mmHg Peripheral Chemoreceptors Where Carotid bodies Aortic bodies Responsivity O2 CO2 H+ pH Drop in pH will cause this to start firing as well

Anatomy Page 73

Case Study - Neonatal Lung

Tuesday, February 12, 2013 5:31 PM

Topic: RDS Developing RDS Premature babies are at risk for this Develops in first few hours in infants born <36 weeks gestational age (term=40 weeks) The premature infants lung is structurally immature which is exacerbated by problems with quantity and/or quality of pulmonary surfactant. From 26 weeks to term, the infant is developing more alveoli and specialized cells within the lung (type 1) are becoming thin ner to permit normal gas exchange. At 34-36 weeks adequate amount of surfactant produced. Surfactant 6 phospholipids and 4 apoproteins Maintains normal alveolar volume prevents collapse of each alveolar unit by allowing alveolus to expand and contract with respiratory cycle. At Birth Large pressures required to inflate lungs and to establish air-liquid interface necessary for gas exchange. Surfactant allows for less pressure required to distend Surfactant ensures retention of air in alveoli at end-expiration following first breath. Surfactant deficiency and RDS This is either a quantitative or qualitative deficiency More pressure is required to open small airways and alveoli. Develops macromolecular pulmonary edema formation of hyaline membranes atelectasis (collapsed ____) reduced compliance (stiff) increased work of breathing (symptom) Antenatal Corticosteroids Administration 29-34 weeks reduces incidence of RDS 24-28 weeks reduces severity of RDS Mechanism of Action Induces significant structural changes in lung accompanied by increased synthesis of all known components of lung surfactant Occur within 48 hours but improvement within 12 hours of initiation of therapy Increased lung compliance and volumes, etc. Clinical Manifestations May develop immediately at birth or within a few hours: Tachypnea Grunting Retractions Nasal flaring Apnea and cyanosis Treatment Prevention Is best I believe corticosteroids falls under this See above for a description of this Main goal: To provide support for respiratory and cardiovascular insufficiency by preventing alveolar atelectasis, hypoxia and hypercarb ia Treatment Oxygen Monitoring Ventilator therapy to provide effective gas exchange with least risk of lung damage Complications of ventilation: airway injury, endotracheal tube complications, chronic lung injury, air leaks, cardiovascular, etc. Surfactant replacement therapy Surfactant Replacement Therapy Why: Lower risk of RDS, lower mortality from respiratory causes, lower incidence of severe neurological complications. How: Improvements in gas exchange, pulmonary mechanics (increased alveolar recruitment with improved lung volumes and lung compliance). CPAP Continuous positive airway pressure Bronchopulmonary Dysplasia (BPD) General Form of chronic lung disease in preterm infants Attributed to injurious effects of high oxygen levels and airway pressures used during mechanical ventilation RDS and BPD Definition Requirement for supplemental oxygen at 36 weeks post-conceptual age Pathology reveals lungs with fewer, larger alveoli, impaired vascular development Structural development of lung arrested at immature stage normal septation and alveolarisation inhibited Inhibition of alveolarisation in the neonatal lung Inflammation Corticosteroids Hyperoxia Prenatal insults (can normalize in utero if not delivered until late in gestation) Surfactant dysfunction (abnormal composition and function in preterms?)

Anatomy Page 74

 Surfactant dysfunction (abnormal composition and function in preterms?) Preservation of normal lung development after preterm birth Variety of ventilatory strategies to reduce lung injury and avoid BPD CPAP role in preservation of normal lung development, promising studies

Anatomy Page 75

Case Study - Asthma

Sunday, March 10, 2013 2:04 PM

Bronchoconstriction Healthy airway wall Smooth muscle Not needed to keep the ventilation/perfusion ratios there is no controlling mechanism The reason is unknown Support structure Blood vessels Immune cells Airway epithelium (barrier stopping stuff from coming in) Can have cilia on it Diseased airway Smooth muscle contract More inflammatory cells Mainly eosinophils in asthma one of the defining features Mucous in the airways Where? Throughout the whole tracheal-bronchiole tree Probably more in the middle airways (Gen 4-10) At Gen 15 onwards there is less smooth muscle so it's less of a problem in the distal airways however, there would still be the inflammation there Pathophysiology Predisposing factors More likely to have it if parents had it Sensitization Often starts when your first exposed to a certain antigen (e.g. ragweed) Immune system presents the antigen to the t cell in a way to activate the t cell t cell responds in a similar way to which it would respond to a parasite Memory cells and (antigen-specific) IGE is produced Therefore the next time you see the same antigen, bad stuff happens Th2 response This is an immune response its a Th2 pattern of inflammation Airway remodeling Overtime, there are structural changes in the airways More mucous producing cells Fibrosis around the airway Proliferation of airway smooth muscle Hype-responsiveness The airway has more muscle which are activated by inflammatory mediators can contract more easily as compared to someone wi thout asthma Bronchoconstriction This results Bronchoconstriction Mechanisms Calcium G-coupled protein receptor being activated results in more calcium being released from the endoplasmic reticulum Mediators for contraction Histamine Ach Neurokinins Leukotrienes Prostaglandins Calcium Epinephrine binds to the beta receptor cAMP inhibits the release of calcium Results in bronchodialation Pathway Exposure to allergen (e.g. fur of cat) The cat-specific IgE picks up the allergen and activates the mast cell Mast cell Releases histamine and leukotrines These bind to the smooth muscle receptor and you get bronchoconstriction Also recruit inflammatory cells into the airway Pulmonary Function Volume vs. time First tell the person to breathe in fully (vital capacity) Measure the volume that you can get out of your lungs in one sec FEV Forced expired volume here we look at it for one second Have to compare the value to a predicted value of someone with the same age, height and sex Value FEV1/VC Immune Tolerance When an allergic person is consistently exposed on a regular basis to the antigen, it can suppress allergic inflammation Uses the t regulatory cell
Anatomy Page 76

 Uses the t regulatory cell Treatment Anti-inflammatories Beta-2 agonist to relax the smooth muscle

Anatomy Page 77

Review
Tuesday, February 26, 2013 1:46 PM

Functional Anatomy Upper Respiratory Tract Filtration Conditioning Controlling air flow Occluding air flow For coughing and speech Lower Respiratory Tract Structural support Cartilage rings Air conditioning Protection Immune system Gas exchange In alveoli Ventilation Minute ventilation Air breathing in and out per minute Determined by fb anf VT Alveolar ventilation Dead space Are of lung that doesnt take part in gas exchange need to subtract that This is not residual volume Determined by fb and (VT and VD) Mechanics Muscles of breathing Inspiratroy Diaphragm External intercostals SCM + scalenes Expiratory Internal intercostals Abdominal muslces Lung volumes Spirogram Impedances Elastance Stiffness of the lung Fibrosis Resistance How narrow the airways are Asthma and COPD Gas exchange Gas pressures Calculate partial pressures Gas exchange Gradients account for gas movement throughout the body Ventialtion/Perfusion Gas Transport CO2 Diffusion Bicarbonate Hemoglobin O2 Mainly hemoglobin Saturation vs. concentration
Anatomy Page 78

 Saturation vs. concentration Given the dissociation curve, how mch O2 is dropped off given partial pressures Control of Breathing Mechanics of Breathing Make the pressure around the lung negative (less than the atmosphere) Note that its not the negative pressure thats forcing open the lung its the atm pressure pushing it open Pleural pressure -5 at rest cause of the two opposite forces pulling?

Anatomy Page 79

Midterm Bellringer
Sunday, March 3, 2013 6:13 PM

Anatomy Page 80

Immuno/Blood Histology
Sunday, March 3, 2013 6:13 PM

White Blood Cells Neutrophils Granular Looks like they have more than two nuclei Eosinphils Granular Looks like they have two nuclei Basophils Granular Their nucleus and the granules look continuous Monocytes Agranular Have a kidney shaped nucleus Lymphocytes Agranular Have a nice circular nucleus that covers a lot of the cell

Anatomy Page 81

Gastrointestinal System
Friday, March 8, 2013 1:37 PM

Anatomy Page 82

GI-1
Friday, March 8, 2013 1:37 PM

Definitions Mastication: the process of chewing your food. Deglutition: the process of swallowing. Peristalsis: alternating waves of muscle contraction and relaxation used to move food through the GI tract. Partly regulated the enteric nervous system (another branch of the PNS) Mouth Lower and upper lips (labia) Help keep food in the oral cavity Superior and inferior labial frenula Appendages that attach the labia to the gums Limit the mobility that the lips have Lingulal frenulum Limits posterior movement of the tongue stops you from Submendibular gland At the base of the tongue (and the base of the lingulal frenulum?) Produces saliva Controlled by CN7 (which also provides the sensations from the anterior two thirds of the tongues) Uvula Part of the soft pallet Responsible for closing nasal cavity when you have food Palatoglossal arch Goes from the pallet to the tongue Palatopharyngeal arch Goes from the pallet to the ______ Tonsils Mucosal Associated lymphoid tissue Between the arches

Gustation Primary tastes Sweet Bitter Salty Sour Umami Most of the approximately 10,000 taste buds are found on the tongue. Taste buds are found on the papillae of the tongue: These are raised projections Vallate papillae: 12 each containing 100- 300 taste buds.
Anatomy Page 83

 12 each containing 100- 300 taste buds. Fungiform papillae: Scattered over tongue each containing 5 taste buds. Foliate papillae: In the lateral margins of tongue; degenerate in childhood. Account for the changes in your taste preference as you grow older Falliform papillae Helps create friction for your food Dont have taste buds associated with them Gustatory Receptor Cells Modified neuronal cells Constantly renew themselves These are your taste receptors Synapse with a sensory neuron to send the signal in the primary gustatory cortex in the temporal lobe Also passes through the thalamus Cranial Nerves Facial (VII) Anterior 2/3 of the tongue Glossopharyngeal (IX) Posterior 1/3 of the tongue Vagus (X) Throat (edges of the pharynx?) and epiglottis Nerves Nuclei arise from the brain stem Signal relayed through the thalamus Olfaction Taste is combined with smell Smell involves CN1 another example where the CNS escapes the bony confines of the skull cell bodies are sitting right in the mucous membrane Cells are specialized to recognize odorant molecules and to do this the stuff have to be dissolved in the liquid Therefore if you smoke and it dries the nose it will be hard to smell Mastication Mastication requires: Teeth, Tongue, Cheek Saliva Muscles of Mastication Note Partly voluntary and partly reflex (stretch receptors in the cheeks). Teeth Incisors Cutting Four above and four below Canine Tearing Two above and two below Premolars Crushing Four above and four below Molars Grinding Dentitions Note Full complement is 32 when you have all your molars (including wisdom teeth) Deciduous The one that you lose early on Permanent It comes behind the deciduous and push out the deciduous As the permanent teeth grow, they will grow up or down and push out the deciduous Closer Look Top to bottom Crown Neck Root Embedded in the bone of the maxilla Held in place by connective tissue (loosen up in scurvy) Dentin Has a lot of calcium cells (more than the bones you have) Enamel 95% calcium cells Hardest substance in the body AVN Neurovascular bundle supplies each tooth CN5 is involved Tongue Intrinsic muscles Help to change the shape of the tongue Can't help you stick your tongue out!
Anatomy Page 84

 Can't help you stick your tongue out! Longitudinal muscles Superior and inferior Contraction = tongue gets shorter Transverse muscles Superior and inferior Contraction together = make tongue skinnier Contraction of one group = curling the tongue Vertical muscles Contraction = flattening the tongue out Extrinsic muscles Connect to a bone as well as the tongue Hyoglossus Attaches to the base of the tongue and then the hyoid bone Brings the base of the tongue down letting you put it on the floor on the mouth Styloglossus Attaches to the base of the tongue and the styloid process (by the mastoid process) Helps you move the tongue up to the roof Genioglossus Attached to the anterior aspect of the mandible and then the base of the tongue Let's you stick the tongue out CN12 Hypoglossal nerve Hypo = below glossal = tongue Muscles of Mastication Introduction Help move the mandible up towards the maxilla Temporalis Right on top of the temporal bone Bulges on the side of the skull when you chew CN5 Masseter Runs from the maxilla down to the mandible Most beast of them all CN5 Buccinator Contributes to most of the muscle mass when you cheek Used for blowing CN7 (facial cause blowing changes the shape of your face) Obicularis Oris Allows you to close your lips Cn7 Muscle Summary Intrinsic tongue muscles (4) Hypoglossal Extrinsic tongue muscles (3) Hypoglossal Temporalis Masseter Buccinator Trigeminal Trigeminal Facial

Orbicularis oris

Facial

Cranial Nerves - Extra CN5 Also involved for sensations from the teeth CN7 Also allows you to convey sensations from the anterior two thirds of the tongue Controls secretions from the submandibular and sublingulal glands Innervation Parasympathetic functions is built into it CN9 Posterior 1/3 of the tongue sensations Controls parasympathetic saliva secretion from the parotid gland (by the ear) CN12 iClicker Muscles of mastication are controlled by the somatic nervous system Not: Symp Parasymp Enteric Vascular Supply Arteries Right or left facial artery Comes as a branch from the external carotid Drainage Facial vein Saliva

Anatomy Page 85

 Saliva 3 major extrinsic salivary glands: Parotid (CN9) Submandibular (CN7) Sublingual (CN7) Composition (1-1 litres/day): Water Pump cloride and sodium out so water follows into salivary gland Amylase Mucin Helps make saliva gummy Lysozyme IgA Defensins Electrolytes Control Parasympathetic (CN VII and IX) results in watery, enzyme-rich saliva. Sympathetic results in thick mucin-rich saliva. Different salivary gland = different composition
Parotid Only serous (with amylase) Submandibular Mostly serous Sublingual Mostly mucous (with lipase) This is the only one active with symp innervation? Note: lipase only works at lower pH secrete it right now so when it goes to the stomach it works Acronym (SA)(S)(ML) Talking with Mouth Full Trachea conducts air up past the epiglottis through the oropharynx through the oral and maybe nasal cavity Food must come down through the oral cavity to get to the esophagus Air coming out and food coming down together makes it likely to food get down to the lungs (more likely right lung) Swallowing Early Deglutination Introduction After mastication and added some enzymes Need to get food to the stomach Oral Phase All voluntary Using tongue to push food up against the soft pallet at the back of the mouth which set off stretch receptors to continue the rest of the swallowing manouver Phrayngeal phase Involves the oropharynx and laryngeopharynx Involuntary Contracting muscles in the pharynx to milk to the food to the esophagus (where the sphincter that closes it opens) As the sphincter relaxes, the larynx moves up to close the epiglottis to protect trachea also this sphincter is skeletal mu scle (?) Then the sphincter will close and the peristaltic waves will begin to dump food in the stomach

Between (a) and (b), the epiglottis closes off the opening to the trachea while the uvula closes off the opening to the nasal cavity Disordered Swallowing Difficulty initiating swallowing Some people have a hard time swallowing pills Nasophryngeal regurgitation Soft pallet doesnt separate nasal from oral cavity Milk coming through the nose Pulmonary aspiration Epiglottis doesnt function or larynx doesnt move up properly Residual If you havent produced enough saliva, can get dried bits of it being stuck at the margins of the tongue Esophagus Journey Passes structures that are ridges like the bifurcation of the broni + behind left atrium + skeletal muscle of diaphragm (?) These make a kink in the esophagus Blood Supply

Anatomy Page 86

 Blood Supply Branches from the descending thoracic aorta tiny blood vessels called esophageals Note from the aorta also comes the broncihals Drainage Esophageal veins which drain into hemizygous vein (on the left side of the thoracic cavity) Histology Doesnt aid in mechanical or chemical digestion is just a conduit Layers Mucosa Stratified squamous epithelium Lots of friction need a stratified layer Submucosa Muscularis Inner circular and outer longitudinal layer Work together to help push food from the oral cavity to the stomach Circular layer causes the lumen to get smaller Longitudinal layers helps shorten the path Adventitia Note: Most of the rest of the GI tract is simple cuboidal epithelium Some people say he meant columnar? Divisions First 1/3 Skeletal muscle Second 1/3 Mixture of smooth and skeletal Final 1/3 Completely smooth muscle Late Deglutition Food going from the lower portions of the esophagus to the stomach has to pass through the lower esophageal spincter Sits at the level of the diaphragm This is all involuntary Deglutition - Review Tongue pushes masticated food towards oropharynx Uvula closes of nasopharynx Larynx elevates and epiglottis closes off trachea Pharyngeal muscles push bolus passed UES Skeletal m. in first 1/3 of esophagus pushes bolus toward involuntary section (smooth m. controlled by ANS and E-(enteric)-NS) LES (lower esophageal spinchter) opens and bolus enters the stomach (AKA the grinder) Gastroesophageal Reflux Disease Reflux Something is travelling backwards in this case its the acidic contents of the stomach Lower esophageal sphincter Isn't that great has to rely on the diaphragm to help If the stomach goes through the hole (herniates) in the diaphragm (esophageal hiatus?), you dont have the diaphragm helping close the sphincter Muscosal lining of the esophagus erodes due to the acidic stuff that is coming backwards into it Notes Heartburn is often confused with cardiac disease. Causes Treatments

Anatomy Page 87

GI-2
Friday, March 8, 2013 4:00 PM

Basic Plan Mucosa (Mucus Membrane) (Innermost) Epithelium Simple cuboidal Lamin propria Tied epithelium down (connective tissue) Muscularis mucosa Muscle that helps puts the epithelium above into folds Submocosa General Find glands mucous glands In stomach it will be glands that produce HCl Well vascularized to help the glands Muscularis Externa Inner circular For peristalsis Outer longitudinal For peristalsis Serosa Mesothelium Secrete serosal fluid CT (thin) Enteric Nervous System General Control of peristalsis Can function independently of symp, para or technically even somatic input (even though you wouldnt find somatic in GI) Peristalsis: Alternating waves of muscle contraction and relaxation used to move food through the GI tract. ENS 100+ million neurons from esophagus to anus 2 components: Myenteric plexus (between circ. and long. Layers) Associated with the muscles Submucosal plexus (in submucosa) Controls the gastric secretions (and in fact entero secretions throughout the GI tract) Interstitial cells of Cajal Pacemakers of the gut Set up rhythm and intensity of peristaltic movement ANS + ENS

Food enters small intestine Sensed by stretch receptors in the wall of the intestine (mucosal epithelium?), which signals submucosal plexus to increase secretions and also tells muscle to set up a peristaltic wave Pain Referred pain with the ANS/CNS? Parasymp Secretions increase Peristalsis increases Can talk to the target organ Symp Secretions decreases Peristalsis decreases Sympathetic Innervation Thoracolumbar Turns down everything Does this by constricting blood vessels Parasympathetic Innervation Cranial + sacral
Anatomy Page 88

 Cranial + sacral Turns up everything CN10 Does most of the visceral organs inferior to the diaphragm Only last portion of the intestine is done by the splanchic nerve Abdominal Cavity

Peritoneal fold Flap that attaches the stomach to the inferior stomach of the liver Lesser Omentum In order to view the LI and SI, had to pull away this Large Colon Ascending, transverse (right to left) and then descending portions Then the sigmoid portion which is curving Straight part at the end = rectum Peritoneum

Mesentary Biggest peritoneal fold Suspends the entire section of the small intestine from the posterior abdominal wall As the organs were developing to get into the abdominal cavity Falciform Ligament Occurs down the midline of the liver Suspends the liver from the inferior surface of the diaphragm also has a small portion that attaches the liver to the anterior abdominal wall (note this is the only organ here that is attached to the anterior abdominal wall rest are suspended from the posterior abdominal wall) Meso colon Suspends the transverse colon from the posterior abdominal wall Greater Omentum Extends from greater curvature from the stomach, goes down, up and then attaches to the transverse colon Fat when you become old ends up here Lesser Omentum Helps to suspend the stomach from the inferior surface of the liver Order FL LO MC GO M Overall FLLOMC GOM Note: Retroperitoneum Behind the parietal peritoneum Structures Pancreas Duodenum (which wraps around the pancreas) Ascending & descending colon Kidney Diagram

Anatomy Page 89

Diagram

Digestion Introduction Digestion depends on: Mechanical (e.g. stretch) stimuli Chemical (e.g. pH) stimuli Digestion is controlled by: Extrinsic nervous input Input from the cortex ANS (parasymp + symp) Intrinsic nervous input Local reflexes (through enteric NS) Hormonal input Locally at the level of the GI tract Endocrine hormones that travel in the blood Stomach Make-up Standard four layers Serosa Muscularis externa Submucosa Mucous membrane Alterations Rugae Mucosa will be sent into these large folds called rugae Allow stomach to really expand if necessary (not here to increase SA) Oblique muscular layer Additional layer of muscle is innermost Stomach acts like a blender can get a lot of twisting motion going to mix food with juices Regions Cardia (top) Closest to heart Fundus Top most region Acts as a reservoir if there is more food Body Has the muscular layers Outer longitudinal Middle circular Innermost oblique One side is shorter than the other makes a lesser and greater curvature Lesser is attached to the liver through the lesser omentum Pyloric region Working region of the stomach Most mechanical digestion occurs here Pyloric anterom Things get prepared from grinding Pyloric canal Pyloris Really strong spincter Even when relaxes creates only a tiny hole Characteristics Extremely acidic environment (pH 1.5-3.5) Denatures/digests proteins Breaks down, mixes and puts chyme into duodenum Chyme = slurry = masticated food + gastric secretions Produces intrinsic factor Needed for vitamin B12 absorption Needed for hemoglobin This absorption occurs in the distal ileum Absorbs drugs like: Alcohol ASA (aspirin) Blood Supply Celiac trunk Supply for: Lesser curvature
Anatomy Page 90

 Supply for: Lesser curvature Left and right gastric artery Supply for: Greater curvature Left and right gastroepiploic artery Anastomose with the gastric arteries Superior mesenteric Also supplies a lot of the SI Inferior mesenteric Drainage Eventually: Hepatic portal vein Liver filters toxins that comes through the blood that made the way through the GI tract Liver also responsible for storing sugars as well Left and right gastric Dump into HPV Short gastric + left gastroepiploic Im thinking that instead of a right gastroepiploic, there is a short gastroepiploic instead Go into the splenic vein That dumps into the HPV Gastric Wall Contains cup shaped structures called gastric glands In the center of the cup is where you find the gastric pit this is where the action occurs This has the parietal (produce HCl) and chief cells The pit is pretty much the empty space like the space between the two walls of the gastric wall Blood vessels supply the glands which come through the submucosa Gastric pits Mucous cells at the surface Mucous cells in the neck I think the neck is like the opening of the pit Parietal cells Secrete HCl + make intrinsic factor Chief cells Secrete pepsinogen, which when goes into the acidic environment becomes pepsin which digest proteins Secretes gastric lipase (this adds with that lingual lipase) G cells Secretes gastrin Turns everything on Turns up Parietal cells Chief cells LES (makes it tighter) Gastric motility Turns down Pyloric sphincter (tells it to relax) HCl Factory Make the proton and chloride separately and combine them in the lumen of the stomach Carbonic anhydrase is involved Bicarbonate and H+ is made from H2O and CO2 proton is pumped out into the gut of the stomach Bicarb cant sit around in the cell so its shuttled out into the blood stream and through an antiporter Cl- is brought it Chloride then goes through the apical part of the parietal cell into the gut If you vomit a lot, you lose a lot of the protons but keep the bicarb, so you have an condition called metabolic alkalosis Regulation Gastrin Ach Parasymp nerve fibers Histamine From mast cells Improves HCl secretion Digestion Phases Cephalic Phase Well before there is food This is thoughts of food or seeing it or smelling it or tasting Sends signals through paraymp tells stomach at levels of submucosal plexus to increase gastric juices. This also causes increase in gastrin release to increase peristalsis and secretion of juices Gastric phase When food enteres the stomach Food distends the stomach activates stretch receptors Food increasese pH activates chemoreceptors This sends signals to Submucosal plexus to increase the production of HCl (homeostasis) pH went up so u make more HCl to bring it down G cells to increase gastrin This leads to incresed gastric emptying Intestinal Phase Intestines control the activities of stomach Can tell it to slow down for example Recognition Stretch receptors recognize distention of the duodenum

Anatomy Page 91

 Stretch receptors recognize distention of the duodenum This can result in the enterogastric reflex Get signals to brain stem, which sends symp input to submucosal plexus to decrease activity This is an inhibitory neural signal Chemoreceptors detect fatty acids and glucose in the duodenum These are enteroendrocrine cells line the mucosa of the duodenum Release: CCK Acts on the smooth muscle of the stomach to decrease motility Secretin When there is food in the intestines, tells the cells of the gastric pits to reduce acid production to slow digestion in the stomach Also inhibits gastric motility Gastric Emptying Steps Propulsion Stuff is moved to the pylorus Grinding Most of the mechanical digestion takes place at the pylorus Retropulsion Only small bits of chyme go to the duodenum at a time so most is pushed back into the stomach Note: Only liquid goes to the duodenum Control Promotion Food in the stomach This causes increase in gastrin secretion Increases HCl and motility Also parasymp innervation Inhibition When chyme reaches duodenum, it tells the stomach to slow down Increases enterogastric reflex Secretion of cholesystokinin Decreases gastric motility Summary Neural PNS stimulates (Vagus) SNS inhibits (enterogastric reflex) Hormonal Gastrin stimulates CCK inhibits Duodenum controls gastric emptying based on content: Carbohydrates, water (chyme enters quickly) Carbs are easy to digest if you deliver that to the duodenum, it wont tell the stomach to slow it down High protein (moderate emptying) Fats (chyme enters slowly) Takes time to digest so stomach is told to slow down Hypersecretion of Acid Acid erodes the mucosa Reverse Peristalsis Why do we VOMIT? Causes Extreme stretch Irritants Bacterial toxins dont want to absorb them Excessive EtOH Certain foods & drugs Involves: Afferent stimulation of medulla irritant fibers send signals up Efferent signals Diaphragm (contraction) Abdominal muscles (contraction) This + diaphragm puts pressure on stomach Relaxation of LES Pressure is relieved by stuff going up through this and out of the mouth Closing of soft palate This is so food doesnt go through nasal cavity Syrup of Ippicac Activates the irritant receptors really well Pyloric Stenosis This is narrowing of the pyloric sphincter The only place for gastric contents to go is up the esophagus and passed the gums It is most common in first male babies If mild wait If severe treat by slitting the pyloric sphincter Overview of the Digestive Process Ingestion Food in oral cavity
Anatomy Page 92

 Food in oral cavity Mechanical digestion Mastication In the stomach through the churning action of the three layers of muscle Segmentation in the small intestine Chemical Digestion Mouth Saliva and the amylase in it Stomach Gastric juices which has HCl (denature proteins) and pepsin (break down proteins) Small intestine Receives enzymes from the accessory organs of GI tract (liver + pancreas) Absorption Small intestines Where we see absorption coming into play In the middle to distal segments, start to absorb nutrients Many nutrients go directly into the blood stream Lymphatic vessels Where we absorb some of the more complex fats Large intestine Absorption still occurs here as well Can pull electrolytes and along with it the water that is contained in the left over matter

Anatomy Page 93

GI-3
Thursday, March 7, 2013 12:32 PM

Small Intestine Introduction 4 generic layers (basic plan) Mucous membrane Submucosa Muscularis externa Serosa Alterations Mucosal layers have: Villi Help increase surface area Cell types Microvilli Each individual cells apical surface has a lot of folding in it and it looks like the ends of a brush and therefore call it microvilli or brush border Absorb nutrients Goblet cells Make mucous that has bicarb to protect the SI Also creates lubrication to make the food flow Enteroendrocine cells Secretin + cholecystokinin (CCK) is released Paneth cells Secrete lysozyme (innate immune system) Blood supply Goes to the tip of the vilus makes sense cause if you want absorbtion, the nutrients have to go into the blood stream Note: lympatic vessel also goes up the villus for fat absorbtion and here it is called a special name: lactyl Plicae circularis Alterations within the folding of the mucosa Help to increase the surface area of the small intestine Helps to mix chyme in the SI with the enzymes from the liver and pancreas Mesentary Suspends the small intestine from the posterior abdominal wall Highway of blood vessels and nerves and lymphatics which service the intestine Enteric Plexus - Parts Submucosal plexus Under the glands that are doing secretions Myenteric plexus Resides between the inner circular and outer longitudinal layers Help coordinate the muscular actions Blood Supply Superior mesenteric artery Main thing that supplies the small intestine Also sends out blood to half of the large intestine Celiac trunk Supplies the first part of the small intestine Inferior mesenteric Supplies the rest of the large intestine Venous Drainage Note Everything goes through the hepatic portal Pancreaticoduodenal Does the first segment Dumps into superior mesenteric vein which leads to hepatic portal Superior mesenteric vein Drains the jejunum and the ileum Hepatic Portal Everything goes through this Divisions Note: As you go down and down, the lumen becomes smaller and smaller Duodenum (25 cm) 4 parts Superior Descending Inferior Ascending Largest lumenal diameter Most dense plicae circularis Specialized mucosa in initial portion (superior segment) This part of the duodenum is accepting acidic content from stomach so it needs protection has Brunner's (duodenal) glands w hich secrete bicarb (rest of the intestine is protected by bicarb from liver and pancreas) Pancreatic duct and bile duct dump into descending portion via Hepatocpancreatic Ampula Jejunum (40%) (1m) Thick wall, wide lumen

Anatomy Page 94

Thick wall, wide lumen Denser mucosa Has plicae circularis Ileum (60%) (2m) Find mucosal associated lymphoid tissue (MALT) Here it is called Peyer's patches Contain T cells and B cells ready to initiate an adaptive immune response (dont need to get lymph nodes involved) Acidic Chyme Need to protect small intestine from acidic chyme Small amounts of chyme pass through pylorus in small 3 mL waves At the start of the SI Rapidly neutralized by bicarbonate-rich mucus (Brunners or duodenal glands). As you go deeper into the SI Chyme passes the pancreatic ampulla (ampulla of Vater). Bicarbonate-rich pancreatic juice completes neutralization of acidic chyme. Enteroendrocrine cells Secretin Causes the secretion of bicarb rich secretion from: Liver (bile) Pancreas (juices) CCK If you have chyme with food stuffs you release this This tells the liver to contract the gall bladder which releases bile salts These breaks down fats to small globules Tells pancreases to release its own enzymes which break down: Fats + proteins + sugars Motility General Changes when you have different states Fed Pattern During feeding Irregular contractions (alternating regions contract) mix contents with digestive juices Fasting Migrating motor complex (peristalsis) begins at duodenum and propels residual material into colon (prevents bacterial growth) Food left in the SI so you move it to the LI these are waves to get all the residual food out of the SI Good cause if you dont have this (stuff constantly go into the LI), can get bacteria from LI go back into SI Pancreatic Enymes Protein breakdown = Proteases Break down proteins Examples Trypsinogen trypsin Chymotripsinogen chymotrypsin Procarboxypeptidase carboxypeptidase Activation These aren't active yet Enteropeptidase causes trypsin That causes the activation of trypsin (yes it activates itselfs) + chymotrypsin + carboxypeptidase Digestive enzymes Carb breakdown = Amylase Amylase From saliva as well as pancreas Types Lactase Maltase Sucrase Brushborder Not only release them from the pancreas, they are released from the absorptive cells Protein breakdown = Types Pepsin Trypsin Chymotrypsin Carboxypeptidase Fat Digestion http://courses.washington.edu/conj/bess/fats/fats.html Enzymes Lipases (lingual, gastric and pancreatic) Hard to do Need to make it into tiny pieces Solution = Bile salts Emulsify the salts Have a section that is hydrophobic and another thats hydrophilic Break down the fats Digestions Enzymes from the pancreas like lipase break down the smaller globules This is pretty much breaking it down to its core components Micelle Bile salts and the monoglycerdies that came after the lipase activity create micelles which ferry the fats to the intestinal mucosa

Anatomy Page 95

 Bile salts and the monoglycerdies that came after the lipase activity create micelles which ferry the fats to the intestinal mucosa The mini globules or components of fats Chylomicron Fat globules have to be packaged so it can be transported Basically associate the fat with a protein, and this is called a chylomicron So first the fats leave the micelle, then they associate with other things and this creates a cholymicron These aggregations can get so big that the capillary beds in the wall of the gut dont have large enough gaps to accept them therefore have to get into the lymphatic vessels ( lactyl) Nucleic Acids Nucleases break them down Pancreatic ribo nuclease Deoxyribo nuclease Absorption Secondary Active Transport These are either symporters or antiporters Simple Sugars Simple sugars like glucose and galactose are absorbed through the intestinal epithelial cell in a process called secondary ac tive transport Uses the concentration gradient of high sodium outside the cell and low inside the cell to help pull the sugar in with the so dium Once inside the cell, there are transporters that help facilitate the movement of glucose into the blood stream Amino Acids Can come in using this as well uses the [] gradient of sodium Note: sodium comes from the mucous that is made Fats Small fats Get through by diffusion Large fats Need those bile salts that are made into micelles and then repackaged with a protein to make a chylomicron so it can get into the lactyl Note: Dont go through the liver go through the thoracic duct and therefore the subclavian vein circulates around the body first before the liver sees it Water and Electrolytes Small intestine is responsible for fluid balance (9L in and 8.5L reabsorbed) Produce a lot of liquid (like saliva for ex) need to reabsorb it Absorption Water absorption via osmotic gradient Na+ absorption coupled with glucose and amino acid absorption K+ follows osmotic gradient Ca2+ and Fe2+ are absorbed in the duodenum Vitamin Absorption Fat soluble vitamins (A,D,E,K) via micelles Remember the first time these enter the blood stream is the left thoracic duct Water soluble vitamins by diffusion Vitamin K and B Can be synthesized by bacteria in the colon (large intestine) Can absorb these as well in the small intestine Note: Vitamin B12 for absorption we need intrinsic factor (produced by parietal cells in the gastric mucosa in the stomach) (this allows for endocytosis in the distal lumen) Large Intestines Introduction Division 6 regions Make-up Layers 4 standard ones Alterations Smooth mucosa Not a lot of surface projections dont need high SA Tenia coli replaces muscle layers This is in the muscularis The circular layers of muscles taper off (dont disappear as you still have peristalsis) Longitudinal muscles become really prominent this is the tenia coli Contraction puts the LI into haustra or pouches Ileocaecal valve Separates colon from ileum Note: Caecum is blind-ended pouch of colon (i.e. only one opening) (appendix hangs from here) Not a sphincternot really a valve either Aids in establishing one-way flow of intestinal contents We are now talking about feces (not chyme) This is the changing point between chyme and feces (?) Anatomy (6 regions)

Anatomy Page 96

1) Ascending colon 2) Transverse colon 3) Descending colon 4) Sigmoid portion of the rectum 5) Rectum 6) Anus Flexures = 90 degree turns Right hepatic flexure Underneath liver Left splenic flexure Underneath spleen

Histology Mucosa If pretty flat Still have mucous producing cells helps for making stuff flow Absorptive cells Absorb water, vitamins and electrolytes Lymphatic Can absorb fat soluble vitamins Motility Very slow Haustral contractions occur every 30 minutes Mixes and aids water reabsorption makes it like a blender Peristalsis begins when food enters the stomach. Large intestine is preparing for the chyme that will come in within a few hours this is why you have to go to the bathroom soon after a meal 3-12 contractions/minute slower than small intestine. Numerous bacteria aid in the digestion of complex starches and sugars present in dietary fiber Rectum + Anus Rectum Straight component Anus (2 cm) Have strong sphincter there Inner involuntary one and an outer voluntary one Anal coluns Longitudinal folds (highly vascular) Defecation Reflex As fecal matter accumulates in the sigmoid rectum, it causes the rectal wall to distend Detected by stretch receptors in the sigmoid rectum Afferent signal sent Signal One signal will be conveyed up afferent pathways to the cortex so you feel the urge to go Another signal at the level of the spinal cord, get a local reflex, which sends motor output to the sigmoid rectum and the rectum itself to cause the muscle to contract (puts more pressure on the LI) Also sends inhibitory signals to the internal anal sphincter Note But we have an outer, voluntary anal sphincter so you can decide whether to go or not This is the ENS if the muscle of the sigmoid rectum is being stimulated to contract, its the Parasymp nervous system

Anatomy Page 97

GI-4
Tuesday, March 12, 2013 1:29 PM

Liver Anatomy Lobes Right lobe Left lobe Caudate lobe Towards the back Quadrate lobe Looks like a square Peritoneal fold Falciform ligament Separates the left and right lobes Connects it to the anterior abdominal wall Ligament Ligamentum teres (from the umbilical vein) Hepatic ducts A left one and a right one Form the common hepatic duct when they merge Bile Contain bile salts which are used to emulsify the fats that we are ingesting Produces this all day long but we dont always have food in the duodenum Not always being used, so bile a lot of times takes a u-turn and goes through the cystic tract to go into the gall bladder When you have food, muscle in gall bladder contracts so there is bile coming from gall bladder and liver These together go through the common bile duct Ducts Pathways

Pancreatic duct hooks up with the common bile duct at the ampulla of vater Opening is protected by a sphincter Hepatopancreatic sphincter Porta hepatis Door to the liver Coming in Hepatic portal vein Returns blood from the wall of the GI tract much of this blood has been spent (no O 2) but it is nutrient rich Hepatic artery Need this O2 rich blood Coming out Right and left hepatic duct Common hepatic duct Blood Supply Arteries Left and right hepatic artery from common hepatic artery from celiac trunk Dual blood supply Hepatic portal vein Oxygen poor but nutrient rich Hepatic artery Oxygen rich The venous and arterial blood mix Mixes in the sinusoids capillary bed has incomplete walls Drainage Hepatic veins Dump into IVC Cell Types Hepatocytes Comprise most of the liver Synthesis (proteins) Storage Detoxification (of toxins)

Anatomy Page 98

 Detoxification (of toxins) Metabolism Kupffer Cells Phagocytosis of microbes Modified macrophages tissue resident macrophages and they occupy the sinusoids (are filtering cells) If they encounter a pathogen they phagocytose it and make cytokines Cytokine production Recycle heme Protein that stabilizes central iron in hemoglobin Create waste product which is bilirubin Sinusoid Endothelial Cells Cells Has an incomplete basement membrane Has fenestrations Need the liver to dump the large proteins it makes into the blood stream Histology Lobule Blood comes from the outside, percolates through sinusoids to the central vein in the middle and then is taken away

Bile is excreted Have bile created in the cells Gets dumped into a separate duct a bile duct formed from bile canaliculi (?) Portal triad Found in the corner of each lobule: Hepatic portal vein Hepatic artery Bile duct
Roles Processing of Sugars The Liver stores glucose from dietary sources as glycogen Monosaccharide -> Polysaccharide If stored as glucose water would follow into the liver and the liver cells would burst Can provide 1-2 days' worth of glucose Brain needs glucose as energy so this is important The liver can convert glucose into: Fatty acids or triglycerides The liver can convert galactose & fructose into Glucose The liver can create new glucose Gluconeogenesis Making new glucose From: Lactic acid Pyruvate Amino acids Glycogenolysis Breaking down the glycogen stored in the liver Forms glucose Processing of Amino Acids Essential amino acids (only from diet) are used for protein synthesis Make e.g. albumin, fibrinogen, etc. Deamination Removes amino group from the end of the AA to allow for oxidation of amino acid in Krebs cycle Get ATP from AAs Can take the carbon skeleton thats left over to make ATP this is AA's as a fuel source Unfortunately results in the formation of toxic amonia Results in the formation of ammonia (toxic) This is then converted into urea Non-essential amino acids can be formed by transamination amino group transferred to an acid Processing of Fats Bile salt + fat Micelle Absorptive cell Repackaging w/ protein Chylomicron Lacteal L Thoracic duct Liver The liver packages fatty acids that come to it into forms that can be transported or stored (lipoproteins) I think this is the cholymicron that it is repackaged into things like VLDL etc VLDL to be delivered to adipocytes for storage in your body (makes you fat) LDL to transport cholesterol to tissues To make steroid hormones for ex. HDL returns excess cholesterol to liver Cholesterol is then catabolized & secreted in bile salts (which are released when you want to digest the fats) Transportation of Fats
Anatomy Page 99

 Transportation of Fats

Processing of Vitamins Fat-soluble vitamins = ADEK Vitamin A Stored in hepatic stellate cell (in the liver) Converted to retinyl esters (used for vision) Vitamin D Utilized in bone metabolism (helps for Ca2+ absorption (mainly in the duodenum)) Can be synthesized (but requires UV) Precursor goes to skin which gets the UV and then that goes to the liver which processes it and then the kidney which finally fully synthesizes it Vitamin E Antioxidant (free radical scavenger) Vitamin K Utilized by hepatocytes to form functional coagulation factors (e.g. prothrombin, VII, IX, X (dont memorize these)) Protein Synthesis The Liver synthesizes most of the plasma proteins Albumin (60%) Makes that colloid osmotic pressure If you dont have this, down have fluid reabsorption and the fluid will pool in the vessels This is why starving kids sometimes have pot bellies no albumin synthesized so have fluid build-up Binds and transports: Hormones, Cations, DRUGS Coagulations factors a & b globulins Alpha globulins Beta globulins (Angiotensinogen) Detoxification Most drugs pass through liver Excreted in bile, inactivated or converted into a form the kidney can excrete Liver tries to excrete them through the bile so they go with the feces Can also alter/excrete thyroid & steroid hormones Store Fe3+, Excrete Bilirubin Liver stores 10% of iron via Ferritin Free iron is toxic! Iron comes from either absorption in the gut or from broken down blood cells Iron bound to Transferrin for transport in circulation This is when liver sends iron to red bone marrow to make new RBC's (erythropoiesis) Heme from damaged RBCs returns to liver where Iron is scavenged & heme discarded as Bilirubin This is excreted through the bile to make it go into the feces Deals with Microbes 80% of bodys Macrophages (Kupffer Cells) in liver Phagocytose: bacteria/toxins, damaged RBCs & WBCs Produce buckets of cytokines (TNF-a) Also houses Natural Killer cells Not a T cell, nor a b cell. But it is still a lymphocyte Control of viral infections Control of atypical cells Note Monocyte Macrophage Kupffer cells Aids in Digestion Bile is essential for: Lipid digestion & absorption (emulsify fats + create micelle) Cholesterol metabolism HDL brings the cholesterol which is then dumped into the bile Excretion of lipid-soluble drugs Bile is composed of: Bile acids (salts) - emulsification Cholesterol Bilirubin Electrolytes Bile is concentrated & stored in the Gall Bladder until needed (1L produced daily!) Recycled by the ileum iClicker

Anatomy Page 100

 iClicker

Answer = D Gall Bladder Anatomy Neck (top that connects to duct?) Body (middle) Fundus (tip) General Thin green sack thats mostly muscle Bile is concentrated & stored until needed Note: Removal of gall bladder (if you have a problem with it) leads to expansion of extrahepatic bile duct (so it gets 'stored' in the ducts) Release in response to: Parasympathetic stimulation CCK Secretin Tells liver to switch its bile production to that of bile with lots of bicarbonate, such that you can deal with the acidic chyme better Pancreas Anatomy Head Body Tail Pancreatic duct Runs the length Note Its in the crux of the duodenum Blood Supply Pancreaticoduodenal artery (from celiac) Exocrine + Endrocrine General Exocrine secretions that go into the lumen of the gut Endocrine hormones that go into the blood stream Exocrine Regulation Panceatic amyalse Peptiadses (trypsin, chymotrypsin and carboxypeptidase) Pancreatic lipase Nucleases Note: All are inactive to protect the pancreas get activated by the peptidases on the enteroendocrine cells Note 2: CCK and secretin can affect the stomach, liver and now we see the pancreas CCK Tells the pancreas to release enzyme rich solutions Secretin Tells pancreas to release bi-carb rich bile Endocrine Regulation Has no ducts E.g. insulin (beta cells) + glucagon (alpha cells) Insulin Stimulates glycogen formation in the liver Glucagon Stimulates glycogen breakdown to make glucose

Anatomy Page 101

Summary
Thursday, April 4, 2013 7:10 PM

Blood Supply Esophagus Stomach Arteries Lesser curvature R/L gastric arteries from the celiac Greater curvature R/L gastroepiploic arteries from the celiac Note: Left is always closer to esophagus and righ is always closer to the duodenum Veins Lesser curvature R/L gastric veins hepatic portal Greater curvature Short gastric and left gastric splenic artery hepatic portal Small Intestine Arteries Superior mesenteric artery Main thing that supplies the small intestine Also sends out blood to half of the large intestine Celiac trunk Supplies the first part of the small intestine I think this is through the pancreaticoduodeal which supplies the duodenum Veins Large Intestine Superior mesenteric artery (first half of LI) Inferior mesenteric artery (rest of LI) Liver Arteries Left and right hepatic artery from common hepatic artery from celiac trunk Veins Hepatic veins to IVC Gall Bladder Pancreas Pancreaticoduodenal artery (from celiac) Kidney Enteroendocrine Cells CCK Acts on the smooth muscle of the stomach to decrease motility If you have chyme with food stuffs you release this This tells the liver to contract the gall bladder which releases bile salts These breaks down fats to small globules Tells pancreases to release its own enzymes which break down: Fats + proteins + sugars Organs Stimulates the gall bladder to release bile Tells the pancreas to release enzyme rich solutions Secretin When there is food in the intestines, tells the cells of the gastric pits to reduce acid production to slow digestion in the stomach Also inhibits gastric motility Organs Tells liver to switch its bile production to that of bile with lots of bicarbonate, such that you can deal with the acidic chyme better Tells pancreas to release bi-carb rich bile

Anatomy Page 102

This is key! Vitamins Vitamin A Stored in hepatic stellate cell (in the liver) Converted to retinyl esters (used for vision) Vitamin D Utilized in bone metabolism (helps for Ca2+ absorption (mainly in the duodenum)) Can be synthesized (but requires UV) Precursor goes to skin which gets the UV and then that goes to the liver which processes it and then the kidney which finally fully synthesizes it Vitamin E Antioxidant (free radical scavenger) Vitamin K Utilized by hepatocytes to form functional coagulation factors (e.g. prothrombin, VII, IX, X (dont memorize these)) Can be synthesized by bacteria in the colon (large intestine) Can absorb these as well in the small intestine Vitamin B Can be synthesized by bacteria in the colon (large intestine) Can absorb these as well in the small intestine Vitamin B12 for absorption we need intrinsic factor (produced by parietal cells in the gastric mucosa in the stomach) (this allows for endocytosis in the distal lumen)

Anatomy Page 103

Renal System
Friday, March 22, 2013 12:01 PM

Anatomy Page 104

Renal + Glomerulus
Thursday, March 14, 2013 12:28 PM

Kidneys (topic of today) Introduction Right side is lower cause the liver pushes it down Important Structures IVC Adrenal gland Renal artery + vein Arteries are really long Kidney Ureter Has to go over the psoas muscle to get to the bladder and therefore you get a kink in it Abdominal aorta Bladder Urethra Left gonadal vein Comes off the left renal vein Is way up in the abdomen cause the gonads started up there Gonadal arteries Come all the way down to go to the gonads Note All are plastered to the posterior body wall (retroperitoneum) Also, slides have a cadaver diagram good for bellringer practice Kidney Dissection (Renal Tubules) Renal cortex On top of the kidney there is a capsule on it Renal Corpuscle Gomerular capsule Glomerulus Afferent arteriole Efferent arteriole Proximal convoluted tubule Involved in making urine Distal convoluted tubule Distal cause its after the proximal convoluted tubule, despite the fact that its right beside the proximal one Juxtaglomerular apparatus At the level where the DCT meets the renal corpuscle Collecting duct Renal medulla Loop of Henle Collecting duct Collects the urine Comes off the DCT?

Facts About 20-25% of circulation goes directly to the kidney but the kidney is only about 0.5% of body weight. From this 20-25% of blood flow 180 L is made into filtrate however the filtrate has virtually no: Protein Formed elements of the blood Large molecules. Out of that 180 L of filtrate, only 1-2 L of urine are made in a day About 99% of the fluid is reabsorbed
Anatomy Page 105

 About 99% of the fluid is reabsorbed Even though the filtrate has lots of small molecules like glucose, amino acids and bicarbonate ions, the urine has basically no protein, glucose or bicarbonate. Big Picture Afferent arteriole Blood goes in Renal corpuscle This is the filtrate making machine Its what does the filtration Makes filtrate Renal tubule Makes filtrate into urine Reabsorption Where the peritubular capillaries reabsorb some of the stuff in the renal tubules This is pretty much the blood taking back the good stuff from the capillaries Secretion Of material from the blood in the peritubular capillaries to the tubule This is pretty much the blood getting rid of the stuff that wasnt initially filtered out by the corpuscle This is of things we dont want like poisons and drugs etx. Collecting duct Collects and concentrates the urine Is secretion here and not in the tubule??? Efferent arteriole Blood goes out Peritubular capillaries Absorb and secrete after filtration is already done interacts with the renal tubule

Renal Corpuscle Glomerular capsule This is on the outside Afferent + efferent arteriorles comes through this Glomerular capsule space This is between its visceral and parietal layer Notice that the glomerular capsule is a continuous layer of tissue with the glomerular capillaries jammed into the center. This is where the filtrate is pushed to after the blood is filtered Glomerulus Have capillaries of the glomerulus (covered by the visceral layer of the glomerular capsule) Proximal convoluted tubule Is connected to the glomerular capsular space filtrate is pushed through that Distal convoluted tubule Juxtaglomerular appartus Just tastes the filtrate and then controls the amount of blood coming in to make sure we are making the right amount of filtrate Sympathetic nerve This is on the afferent arteriole This constricts the arteriole when ur in symp mode so that u dont make urine then Microanatomy Glomerular capsule Glomerulas Fenestrated capillary wall Basal lamina Podocyte Make up the visceral layer of the glomerular capsule sit outside the capillary Pedicel Filtration slits Filtration Podoctye Has foot processes (pedicels) Steps

Anatomy Page 106

 From the glomerular capillary to the capsular space Blood has to go through first the capillary fenestrations and then the basal lamina After that, the blood has to get through the filtration slits Path Glomerulus Capillary fenestrations Basal lamina Fesenstration slits Capsular space

Key All small molecules can pass into the capsular space and form filtrate, but large molecules (> albumin size) cannot and stayin the blood

Net Filtration Pressure Have to have filtration pressure to make filtrate Out Blood hydrostatic pressure Have blood pressure pushing blood out of the glomerular capillaries This is positive pressure In Capsular hydrostatic pressure Hydrostatic pressure of the fluid already in the capsule Blood osmotic pressure Proteins want fluid to come back into the blood capillary Sum Net pressure of 10 mm HG pushing the fluid out of the capillaries This determines GFR (glomerular filtration rate) Renal Autoregulation + GFR (glomerular filtration rate) Introduction Maybe want to tweak the GFR based on the situation Decrease when dehydrated increased after drinking a lot The kidney itself can act to alter the GFR Call this autoregulation because the mechanisms are internal to the kidney The filtration rate is easily altered: By changing the blood pressure in the glomerulus If the GFR is too high Then it is because the blood pressure in the glomerulus is too high. Remedy for this is to have the afferent arteriole constrict so less blood flows to the glomerular capillaries under less pre ssure and the GFR goes down. Seems counter-intuitive cause you'd think it would relax if the pressure is too high im thinking its the afferent arteriole that contricts and therefore its the capillaries that face less pressure? The opposite occurs when GFR is too low. This changes in the afferent arteriole can be done by the kidney itself by either the myogenic mechanism or tubuloglomerular feedback The Myogenic Mechanism Smooth muscle of the afferent arteriole itself detects the increase in pressure and responds by constricting They dont like to stretch when they get stretched they contract So when there is too much blood its constricts and decreases GFR This is true of all smooth muscle Smooth muscle always responds to stretching by contracting against the stretch. Tubuloglomerular Feedback In this mechanism the macula densa of the juxtaglomerular apparatus detects high amounts of filtrate flow (i.e., lots of water, Na+ and Clflowing past) and this causes inhibition of nitric oxide release in the juxtaglomerular apparatus which inhibits afferent arteriole dilation Summary: if the juxta sees too much filtrate, it causes contraction of the afferent arteriole by inhibiting NO (stops dilatio n) Note: This is a bit confusing because the filtrate can be quite dilute when there is lots of filtrate production which makes it loo k like the low ionic concentration is driving the constriction. However the combination of the high flow with even modest levels of ions wil l lead to quite a high delivery of ions to the macula densa. By decreasing the GFR the flow rate of filtrate will decrease which allows more water and ions to be removed. The GFR can also be altered by other neural and hormonal mechanisms as shown on the next slides
Anatomy Page 107

 The GFR can also be altered by other neural and hormonal mechanisms as shown on the next slides Hormonal Regulation of GFR ANP Increases GFR Steps Distension of the heart leads to the release of ANP The ANP causes relaxation of the cells (mesangial cells) between the glomerular capillaries The glomerular capillaries become more spread out so more filtration occurs Basically increase the holes between the capillaries Result More filtrate More urine Less volume in the blood Once the blood volume goes down the pressure in the heart decreases and ANP is no longer secreted Angiotensin II Decreases GFR But it increases BP but it also constricts afferent arteriole So the high BP although normally would increase GFR but its also constricting the afferent arteriole so the high BP doesnt effect GFR in terms of increasing it Therefore increases your bodies overall BP but decreases amount of blood going to the glomerulus Angiotensin II and BP Juxtaglomerular apparatus Not only does the tubuloglomerular apparatus business but also makes renin when there is low BP or symp innervation If there is low BP kidney wants to reduce urine production cause it doesnt want you to go into hypovolemic shock isnt going to steal fluid for urine when you dont even have enough blood Eventually angiotensinogen II is made Neural Regulation of GFR Symp branch has inputs to the muscular wall of the afferent arteriole These are a1 receptors Stimulation = contraction Decreases blood going to the glomerulus This decrease blood hydrostatic pressure and therefore filtration Increases spare blood for muscles and makes it so there is no urine Also does this in case your fright and flight doesnt work and you get hurt need blood and not urine at that point

Anatomy Page 108

Renal Function + Tubular Phys

Tuesday, March 19, 2013 1:31 PM

Kidneys The nephron Afferent + efferent arteriole + renal corpuscle + renal tubule + collecting duct + peritubular capillaries Filtrate has lots of stuff what happens to it: Some completely reabsorbed e.g., glucose, amino acids, bicarbonate ion Some regulated and thus is partially reabsorbed e.g., water, sodium, potassium, chloride etc. Some excreted as waste e.g., urea, creatinine, drugs and drug metabolite Balance Water 180 L in filtrate but 1-2 liters of urine Glucose 162 g in the filtrate but none in the urine. Gets taken out completely Protein 2.0 g in the filtrate 0.1 g excreted Na 570 g in the filtrate but 4 g excreted Uric acid 8.5 g in filtrate and 0.8 g in urine Creatinine 1.6 g in filtrate and 1.6 g in the urine Completely excreted Can be used to see how well kidneys are working Beyond the renal corpuscle the nephron is completely consumed with these processes Renal Tubule Arcuate artery Running along providing blood pressure for the system Interlobular artery In between the lobules of the kidneys Comes of the arcuate From these come off the afferent arterioles Vasa Recta Straight vessel Run along the loop of Henle These are what connect to the efferent arterioles and take that blood out of the system Arcuate vein This is where the blood leaves Do the peritubular capillaries drain to this as well??? Reabsorption of Solutes and Water Reabsorption can occur by either by: Active transport Requires energy Passively Involves chemicals following their electrochemical gradients. Water Osmosis The movement of water is by osmosis (a passive mechanism by which water follows its concentration gradient through a semipermeable membrane) What drives osmosis is the movement of the solutes from the tubules to the interstitial fluid which often requires energy Water reabsorption About 90% of water reabsorption is obligatory which is to say that it is dragged along by the solutes being moved from tubules to interstitial fluid. Much of the obligatory reabsorption of water will occur in the proximal convoluted tubule and descending loop of Henle because these areas have tubules which are permeable to water. The last 10% of water reabsorption is facultative which is to say it can increase or decrease depending on the amount require d by the body The facultative water reabsorption is under control of the hormone called Antidiuretic Hormone (ADH) which makes the cells in the collecting duct permeable to water and thus water can leave the ducts and go back into the interstitial fluid and then enter the peritubular capillaries Osmosis and the Proximal Convoluted Tubule (PCT) Movement of water will all be by osmosis. This osmosis is linked to the passive reabsorption (diffusion) of a number of ions as well as the waste product urea. By far the most active area for reabsorption is the proximal convoluted tubule. By the end of the proximal convoluted tubule 100% of most of the organic solutes have been reabsorbed. About 65% of the water has also been reabsorbed. Summary Sodium leaves the tubule to the capillaries Water follows into the capillaries
Anatomy Page 109

 Water follows into the capillaries Now the remaining ions (like ions other than sodium) in the tubule have become more concentrated (cause water left), so now they move along their [] gradient into the capillary Passive Transport The movement of solutes often does not involve additional energy being added. Some solutes can slip between the tight junctions of the cells (i.e., the paracellular route) or into or out of the cells of the tubules (the transcellular route) strictly by following their electrochemical gradients. The diffusion may be facilitated by transport proteins as in the movement of glucose from inside of the tubular cells to the interstitial fluid Leakage channels also exist for some ions to facilitate their walk down the concentration gradient. Sodium Transport Passive Transport Fluid in the tubule lumen Tubule cell Has apical membrane (part of brush border) Has tight junctions Sodium goes from the tubule lumen through the tight junction (between the tubule cells) into the interstitial fluid and then into the peritubular capillaries Crosses the apical membrane and then the basolateral membrane in one go Note Magnesium and calcium move through a similar system Active Transport Two types Primary Active Transport Functions strictly with the use of ATP. Secondary Active Transport Uses the energy of the movement of ions down their concentration gradients to transport other solutes like ions and larger uncharged molecules like glucose or amino acids. Sodium is going down its [] gradient (high to low []), and therefore there is energy available and it drags along something else Symporter When the secondary active transport protein moves both the ion and the solute molecule in the same direction Antiporter When the secondary active transport protein moves the ion in one direction and the solute in the opposite direction Both active transport mechanisms require a carrier protein to assist the movement of the ions and other solutes. Because the transporters are proteins which can only bind and then move solutes at a fixed rate they have a maximum rate (Tm) at which they can function The saturation of the transport mechanism limits reabsorption of substances like glucose. Conditions like glucosuria (i.e., glucose in the urine) occur strictly because the Tm of the active transporter has been reached. The sign of glucosuria indicates that the pathology diabetes is present and the Tm has been reached for the Na+-glucose symporter. Note: this is in the proximal convoluted tubule The normal process in the kidney is to have all these active and passive mechanism running at once. The active process of the sodiumpotassium pump mechanisms consume about 6% of your total ATP when you are at rest Transcellular Sodium Reabsorption General Sneaks into the tubule cell (going through the apical membrane) This is a problem though cause water would come into the cell and the cell would explode Also I think this is passive cause its going down its [] gradient? Therefore, a Na/K pump pumps out the sodium This is on the basolateral membrane This brings in potassium in return, but potassium then then leaks out of the cell This I think is active cause you have to use energy to push sodium out (and K in)? Glucose Symporter In the PCT (coupled to the Na/K pump) There is facilitated diffusion of glucose Na-Glucose Symporter This is on the apical membrane Sodium wants to get into the tubule cell like we said above When it goes in, glucose gets pulled along with the symporter (against [] gradient) This is again a problem cause they drag water with them Does this use ATP I think no I think sodium goes down its [] gradient and this energy is used to drag glucose Note: this is what is saturated in diabetes Sodium Get rid of it by using the Na/K pump we described before Glucose Uses a transporter to go down its concentration gradient to go into the interstitial fluid and then into the blood stream This transporter is on basolateral membrane Na+/H+ Antiporter In the PCT Important to maintain proper pH in the blood stream If you have acid then you get CO 2 in the tubular cells Reminder: This is the cell that hasa a basolateral membrane on one side and a apical membrane on the other CO2 + H20 H2CO3 H+ + HCO3Anatomy Page 110

 CO2 + H20 H2CO3 H+ + HCO3 This is the reaction that occurs in the tubular cell Result is H+, which is acidic and therefore bad, and HCO3-, which is good cause its a buffer Things to deal with H+ Use an antiporter, so when Na comes in past the apical membrane into the tubular cell, moves H + into the urine Gets kicked into the urine Na Is now in the tubular cell after going through the antiporter Use the Na/K pump to put it into the interstitial fluid and then the peritubular capillaries Bicarbonate Was formed therefore [] is high in the cell Use a diffusion transporter to make it diffuse into the interstitial fluid and then the peritubular capillaries Symporter System at the Thick Limb of the LOH Na+-K+-2Cl- symporter All go into the tubular cell past the apical membrane using the symporter Tubule cell Na Use the Na/K pump to get it out the tubular cell K Diffuses away Can control which way to goes to do this can put the diffusion transporter either on the apical membrane or the basal membrane Cl Can go either way (either into the tubular lumen or the interstitial fluid) using diffusion channels depending on whether you want more or less Cl To do this can put the diffusion transporter either on the apical membrane or the basal membrane Sodium Reabsorption in the Collecting Duct This is the last chance to do something with the filtrate Na leakage channels On the apical membrane Allows Na+ to enter the tubular cell Na/K pump Kick the Na out of the cell into the interstitial fluid Purpose To concentrate urine This is to pull the water out as well iClicker

Answer: E Importance If the kidneys fail then salts and waste products like urea build up and the pH of the blood goes down. Sodium is also needed for neurotransmission Massive edema results from the salt retention This is if the kidneys go into overdrive? cause if they fail wont you lose sodium and the water would follow? Or it might be that they dont get filtered in the first place Acidemia results from the inability to excrete acids When potassium levels get too high (hyperkalemia) then cardiac arrest occurs. Piting Edema Piting edema = when you stick your finder into their skin Cause = High potassium levels Lose the ability to have normal heart contractions Micturition Anatomy Detrusor Muscle Its the one that contracts to push urine out It its the thing that contracts the bladder External Urethral Spinchter Skeletal muscle Contracts to keep urine in Internal Urethral Sphincter Involuntary Note Females dont have an internal urethral sphincter They have an anatomic sphincter when the bladder gets full it kind of kinks off on its own Levator ani Pull up the anus Close the bladder as well
Anatomy Page 111

 Close the bladder as well Urethra Urine comes out through that Bladder trigone Opening between the two ureteral openings and the orfice of the urethra Micturition Reflex When the bladder fills with about 200-400 ml of urine The stretch receptors in the bladder wall are stimulated These send messages to the sacral portion of the spinal cord. Sensory input to this level triggers an autonomic reflex which sends parasympathetic motor signals to the detrusor muscle (a smooth muscle) to contract and the internal urethral sphincter to relax. This internal sphincter is made of smooth muscle and is thus controlled by the autonomic nervous system and is not under conscious control. There is, however, one more sphincter between the urine and the great outdoors so dont despair. The external urethral sphincter is striated muscle and thus can be consciously controlled. Other muscles like the levator ani and deep muscle of the perineum can help too The somatic nerves holding this sphincter closed are inhibited by the micturition reflex. The pressure build up is usually not enough to open the external sphincter. In adults there usually has to be a conscious effort to relax the external sphincter before urine can be passed, though this cannot last forever

Anatomy Page 112

Creating Urine + Renal Func.

Thursday, March 21, 2013 12:31 PM

Creating Dilute Urine General If there is too much water or too few ions in the body, dilute urine must be made to reestablish ionic balance This urine has to be more dilute in ions than the blood so it has to be less than 300 mOsm/L The next figure illustrates the formation of dilute urine using a short loop nephron.

The tubules emphasized with brown are always largely impermeable to water The collecting ducts (lined with blue) are largely permeable to water in the presence of antidiuretic hormone (ADH). Steps In the proximal convoluted tubule solutes are reabsorbed and water follows them out of the tubule The fluid travels through the descending LOH and equilibrates with the surrounding interstitial fluid in the renal medulla wh ich is high in solutes. The loss of water makes the fluid more concentrated and the osmolarity goes up. The fluid enters the thick ascending limb of the LOH and solutes continue to be pumped out by symporters. At this point the water cannot follow the solute (brown part of the diagram) so the filtrate loses solute and the osmolarity goes down. The fluid continues through the distal convoluted tubule and loses more solute. This area also does not allow water entry so osmolarity falls further The fluid enters the collecting ducts which, in the absence of ADH, are impermeable to water. A bit more solute is pumped out , but the water stays in the tubular fluid, so osmolarity falls further Characteristics of the Tubules Notice that the osmotic gradient which was set up on the previous slide was a result of the thick ascending limb of the loop of Henle which used symporters (chiefly the Na+-K+-2Cl- symporter) to increase the amount of ion in the interstitial fluid. This works because the ions came out but not the water. The descending loop of Henle runs through this region of high interstitial fluid osmolarity so water leaves the tubule and th e filtrate in the tubule becomes more concentrated. This descending limb of the LOH is not permeable to solutes so the solutes stay in the lumen of th e descending limb tubule and the osmolarity of the fluid increases all the way to the bottom of the loop Why is it that as you go down the descending LOH, the interstitial fluid is more salty? The answer is that when the fluid goes through the ascending impermeable limb, its kicking out solute into that interstitial fluid, which is coincidently beside the descending LOH. Creating Concentrated Urine General If there is too little water or too many ions in the body, urine must be made which will reestablish ionic balance This urine has to be more concentrated in ions than the blood to get rid of extra ions so it has to be more than 300 mOsm/L We can make urine that is about 1200 mOsm/L or about 4 times more concentrated than blood. The next figure illustrates the formation of concentrated urine using a long-loop nephron.

Steps In the proximal convoluted tubule solutes are reabsorbed and water follows them out of the tubule The fluid travels through a long-loop nephron. The interstitial fluid in this area is high in solutes. Water from the tubular fluid leaves to equilibrate with the surroundings. The loss of water makes the tubular fluid more concentrated and the osmolarity goes up.

Anatomy Page 113

with the surroundings. The loss of water makes the tubular fluid more concentrated and the osmolarity goes up. The fluid enters the thick ascending limb of the LOH and solutes continue to be pumped out by symporters. At this point the w ater cannot follow the solute so the fluid loses solute and the osmolarity goes down. The dilute filtrate continues through the distal convoluted tubule and begins lose water. The water is gained by the surround ing tissue which has higher osmolarity. The fluid enters the collecting ducts which, in the presence of ADH are permeable to water. Water begins to flow out of the duct to match the extremely high osmolarity of the surrounding interstitial fluid. Summary I think the difference from the dilute urine creation is that the blue part (collecting duct) is permeable to water so water leaves into the interstitial tissue Note I think that the DCT is different in short and long loop nephrons!!!!! Look at the picture! Characteristics The longer the loop the greater the time for the ascending limb of the loop of Henle has to pump out solutes with the symport s Because of the great loss of solute to the interstitial fluid, the interstitial fluid osmolarity becomes very high and the water is pulled more readily out of the descending limb of the loop of Henle and the collecting duct. Diuretics (water pills) such as furosemide (LASIX) work by inhibiting the Na+ -K+-2Cl- symporter so there is decreased water re-uptake and more urine. Now that we have some idea how to make concentrated and dilute urine and how do we fine tune the system? Hormonal Regulation of Tubular Reabsorption and Secretion Angiotensin II Recall As you may recall from an earlier lecture, angiotensin I and angiotensin II arose as a result of a fall in blood pressure or as a result of sympathetic nervous stimulation of the juxtaglomerular apparatus which releases renin.

Effector Function Constricts arteriole Increases sodium reabsorption through Na/H antiporter Water will follow which causes BP to increase Increases aldosterone release Increases sodium reabsorption in the collecting ducts Result Increases blood volume and blood pressure Aldosterone Increases sodium reabsorption in the collecting ducts Antidiuretic Hormone (ADH) Where From the posterior pituitary it goes all the way to the collecting duct Steps High osmolarity in the plasma and interstitial fluid is detected by the osmoreceptors in the hypothalamus which stimulate the neurosecretory cells in the hypothalamus to release ADH from the posterior pituitary. ADH leaves in the blood and leads to the synthesis of water pores (namely aquaporin 2) in the collecting ducts of the nephrons. This allows water to easily leave the tubular fluid. The water then dilutes the blood and brings the osmolarity down to normal. The hormone also increases the activity of the Na+-K+-2Cl- symporter. With maximal ADH release as little as 400-500 ml of urine is made in a day. Summary Makes holes in collecting duct Increases Na/K/Cl symporter iClicker

Answer = B Evaluating Kidney Function General To figure out how the kidney is functioning both the quantity and quality of the urine can be evaluated. Quantity measurements are easy to make but how do you look at the constituents of urine? The most obvious way is to do urinalysis which can summarize things like colour, turbidity, pH, odor and specific gravity. There are however a number of blood tests which provide information on the kidney function these include: Blood urea nitrogen (BUN) This is a measure of blood nitrogen which is mostly urea

Anatomy Page 114

 This is a measure of blood nitrogen which is mostly urea Because urea is a waste product and a substance which is not actively reabsorbed it will increase in the blood only when urine production is low such as with dehydration Plasma creatinine This waste product from creatine phospate in muscles and will only build up in blood when urine production is low. If it builds up in blood stream, that means your kidneys are failing If BUN or plasma creatinine are high than kidney dysfunction is usually suspected though many other tests often must be run. A more useful number is the renal plasma clearance How much plasma that is going through the kidneys is being cleared out Renal Plasma Clearance The effectiveness of the kidneys in removing a substance is calculated on the basis of the volume of plasma cleared of the su bstance per unit time (usually, milliliters per minute or ml/min) If a substance has a high clearance rate it is because is it not reabsorbed back in to the capillaries and it may also be act ively secreted into the tubules. Many substances have a clearance rate of 0 ml because they are completely reabsorbed. Glucose, amino acids and many essential substances are not normally cleared from the plasma so there clearance rate is 0. Why is this clearance rate calculated on volume of plasma cleared per minute and not a weight of substance per minute basis? The reason is that renal clearance follows first order kinetics which means more of the substance is cleared when more of the substance is present. The only fixed measure is the amount of blood cleared which has a decreasing amount of the substance over time. Amount you clear goes up and down based on how much you have in the blood stream -- therefore amount isnt that useful to look at. Whether you have lots in the blood or little, the amount you clear is different, but the volume is the same. Thats why we look at volume Importance It is a critical issue to figure out how much of a material is going out in the urine. You can use it to figure out how well the kidneys are working but also for drug calculations. If you want to know how much drug to give someone who is clearing the drug in the urine then you just balance renal clearance with dose. For example, if the renal drug clearance was 125 ml/min then all you have to do is give the amount of drug in thats in the 1 25 ml of plasma to keep the person at a steady state drug concentration. First Order Kinetics

Half-life is constant Therefore when you have more of the drug (like 10mg/L), in 3 min you clear half of that which is 5. But when you only have 5, in three minutes you clear half of that which is 2.5. Therefore, when you have more, you clear more Formula

= volume of blood plasma cleared of a substance by the kidneys Legend S = renal plasma clearance rate U = urine concentration V = urine flow (production) rate P = plasma concentration Interpretation If S is high there is lots in the urine Also if you have lots of urine flow there is high clearance If S is low there is lots in the plasma From slides What this formula tells you is that high urine levels (U) along with low plasma levels (P) indicates a substance is being cleared from a lot of plasma in a short period of time. The physiological explanation is this if a lot of the substance of interest is in the urine compared to the plasma then it must be that reabsorption is low and/or secretion is high. This formula also suggests that if the rate of urine production (V) is high, then the substance will be cleared at a particularly high rate. The renal clearance of drugs is often very important. For example many antibiotics (the penicillin-like drugs as well as cephalosporins) and digoxin are excreted by a renal mechanism and if urine production goes down (V = 0) then the drugs are kept in circulation a very long time and may build up to toxic levels.

Anatomy Page 115

if urine production goes down (V = 0) then the drugs are kept in circulation a very long time and may build up to toxic levels. The neat thing is that it can also make these antibiotics which are excreted unchanged useful for treating urinary tract infections (UTIs) because they get to the UT in their active form. Calculation Q: What is the renal clearance of uric acid when the urine concentration is 100 mg/ml while the plasma levels are 1 mg/ml giv en normal urine production. A:

Glomerular Filtration Rate It is often useful to estimate the GFR to assess kidney function since glomerular function is key. But how do you measure a value for the glomeruli when you cannot get fluid from the glomeruli? Some substances enter the filtrate but never return to the blood If the substance is both not reabsorbed and also not secreted (I think this is secretion as per the diagram below, not secret ion to the blood) or secreted to only a small degree then the amount in the urine should reflect glomerular filtration rate. Creatinine is such a substance (not reabsorbed, hardly secreted) so we can calculate glomerular filtration rate using the cr eatinine levels in urine. We can also use inulin since it is not reabsorbed at all and none is secreted but it is a substance you have to take. Normally we get a number like 120-140 ml/min (7.2-8.4 L/h) for the GFR. This number is very nearly the same as the renal plasma clearance for creatinine (if you think of it that has to be true sin ce all the creatinine that goes into the filtrate goes out into the urine).

Urea Filtered, and then goes back and forth Glucose Filtered and then fully reabsorbed Inulin/Creatinine Fully stays in the filtrate Substances that have renal plasma clearance rates in excess of 120 -140 ml/min must be secreted from blood to tubules since that flow exceeds the flow through the glomerulus Most substances have a renal plasma clearance rate that is a whole lot less than the GFR because of reabsorption. Calculation Using Inulin Inulin (like creatinine) is not secreted and not reabsorbed so whatever ends up in the urine must be equal to the amount that was in the filtrate. To calculate GFR you will need to know the amount of inulin that ends up in the urine and the amount of inulin in the plasma Let us assume that we have a case where the urine is collected over 10 hours and 150 mg of inulin is found in the urine. Duri ng this time, the blood plasma levels of inulin are 0.004mg/L The inulin excretion rate is 15 mg/h * 1h / 60 min = 0.25 mg/min . The amount of plasma with 0.25 mg of inulin is: 0.25 mg 0.004 mg/mL = 62.5 ml Since that amount of inulin that entered the filtrate in one hour from the plasma went out in the urine (we know that none was reabsorbed) then the glomerular filtration rate must be 62.5 ml/min or about 4.3 L/hr Isnt it supposed to be 3.75L/hr Note I think instead you can just use that original 150mg value, divide by 0.004 to get a GFR or 37500ml/10hr, and then you can convert that to ml/min if you want to This is a low number for an adult so there is likely to be some kidney disease.

Anatomy Page 116

Hormones Summary
Saturday, April 6, 2013 6:32 PM

Angiotensinogen II Constricts afferent arteriole Increases activity of Na/H antiporter (PCT) Increases aldosterone release Aldosterone Increases Na/H reabsorption in collecting duct (water follows) ANP Makes holey capillaries Causes the mesangial cells by the glomerular capillaries to relax ADH Makes holes in the collecting duct (synthesis of water pores) Increases activity of Na/K/Cl symporter (in thick limb)

Anatomy Page 117

Case Study - Renal Failure

Tuesday, March 19, 2013 5:30 PM

NNN No new nephrons When your kidneys degrade over time, they will not regenerate Urine Path Minor calices + major? to renal pelvis to ureter to bladder to urethra Kidney Problems Renal Failure Groups Pre-renal Caused by a factor outside of the kidney initially, but eventually the kidney fails Renal The kidney itself Primary renal disease Post-renal Caused by a factor distal to the kidney in the urinary tract, but again the kidney is destroyed Urine backs up into the kidneys it becomes a fluid filled organ and loses its architecture Pre-Renal Prerenal conditions do not damage the kidney, but can cause diminished kidney function. They are the most common cause of acute renal failure, and include: Dehydration Hemorrhage Heart failure Burns Renal Intrarenal (Renal) conditions involve kidney disease or direct injury to the kidneys. These conditions include: Lack of blood supply to the kidneys (ischemia) Use of radiocontrast agents in patients with kidney problems Drug abuse or overdose (nephrotoxic medications) Acute inflammation of the glomeruli (glomerulonephritis) Kidney infections (pyelitis or pyelonephritis) Pyelo = renal pelvis this infection is involving the pelvis of the kidney and the nephron itself Post-Renal Postrenal conditions cause kidney failure by obstructing the urinary tract. These conditions include: Inflammation of the prostate gland in men (prostatitis) Enlargement of the prostate gland (benign prostatic hypertrophy) Bladder or pelvic tumors Kidney stones (calculi) Additional Causes Stone Stone can get stuck at: At the base of the renal pelvis (right were it connects to the ureter) Ureter when it is crossing over the psoas muscle there is a kink and it can get caught there The opening of the urethra Problem Even though there is a stone, the kidney still producing fluid which causes back-pressure to the kidney Bacteria Can come up backwards from the skin into the urethra up the bladder and into the ureters This can happen if you dont pee enough This can cause scarring in the urethra, making the lumen smaller making it harder to see Pelvic Tumour Stops you from expelling urine from the bladder Baby Uterus can squish ureters to the posterior abdominal wall can set you up for kidney stones getting stuck or a UTI Urinary Reflux Urine going backwards Normal anatomy Ureter pierces the bladder wall at an oblique angle When urine starts to fill the bladder and it starts to stretch, the bladder wall would kink the opening of the urethra, stopp ing urine from flowing backwards People who are anatomically more susceptible Short Intravesical Ureter Ureter comes into the bladder into an almost 90 o angle Urine runs right back up the ureter Can get kidney infection Horshoe Kidney Renal pelvises join low in the abdomen Some dilation of ureters but functional Note Can still have perfectly functional kidneys End Stage Renal Disease (ESRD) Causes Vascular arteriosclerosis, large vessel disease Prerenal Diabetes, small vessel disease
Anatomy Page 118

 Diabetes, small vessel disease Can affect the small vessels in the kidneys This is more a renal cause of failure Immune glomerulonephritis (streptococcus) Polycystic kidney disease (dominant, recessive) General Get cysts in the kidneys which ruins the architecture of the kidney Dominant form If you have one allele that is mutated, you get the disease Cycts occur all throughout the tubules of the kidney Kidney function declines over time Recessive form Need both alleles to be mutated to get the disease Cyst is at the ascending limb of the LOH Malignancy Infection What to do? The strategy is to preserve kidney function as long as possible with dietary change, diuretics and specific therapy Interventions are increased as the disease progresses Permanent dialysis or transplant is not usually considered until there is no chance of recovering kidney function Visualizing the Kidney Intravenous Pylogram or CT with Contrast Requires kidney function Position of the kidneys Right Lower due to liver Renal pelvis Ureter (thinning over psoas) Urinary bladder Note: Papillary tips (looks like a champagne glass) This is when you're looking closely at the calises When there is problems with the kidney, it doesnt look like a champagne glass anymore Angiography Segmental Arteries of the Kidney 5 of them come off the renal artery Normally they look like a tree If the branches spread too far, there is a problem Segments are like bronchopulmonary segments can take it out and you'll still have a 4/5th functioning kidney Treatment When Start sufficiently early to prevent complications of the existing disease When creatinine clearance equals or is less than 10 ml/min (about 1/12 of normal) Indicates approaching renal failure Dialysis vs. Transplant Initial do dialysis until transplant available: Hemodialysis Dialyzing your blood Extracorporeal kidney Blood goes through tubes which has a semi-tubular membrane allows solutes but not formed elements to go across it Inside the tubes is the blood and outside is the dialysis solution Waste products flow into the dialysis solution Peritoneal dialysis No need to mix the blood with the dialysis solution apply the dialysis solution right to the peritoneal cavity Visceral and parietal peritoneum are a huge SA for exchange of waste to occur Over time waste will flow into the solution and then can collect the solution and throw it away Ambulatory Can walk around with the solution in you and go about your normal life Dialysis Mechanisms of Dialysis

Can have glucose in the dialysis solution so it diffuses into the blood

Anatomy Page 119

 Can have glucose in the dialysis solution so it diffuses into the blood Renal Cysts Associated with Dialysis In ESRD, the disease process will continue Dialysis doesnt stop the progression of the disease In a small series of patients who go off dialysis and are not suitable for transplant, their renal function has not deteriora ted from the onset of dialysis Recall the endocrine effects of kidney: Too little Vitamin D and erythropoietin results Salt retention and volume expansion contribute to hypertension Transplant When not to Transplant Reversible situations or where conservative treatment will suffice Advance forms of major extra renal disease Infection Active glomerulonephritis (immune) Previous sensitization to donor tissue Possible Donors From best to worst Twin Sibling Family member Cadaver (patients who cannot recover cortical function) Unrelated Volunteer anonymous Logistics of Transplantation You dont attach the kidney to the renal artery You attach to the external iliac Can also use internal iliac if necessary (not as good) Note: Kidney will no longer be retroperitoneal Ureter Anastomoses Try to emulate the real anatomy of the kidney Send the ureter through the wall of the bladder in an oblique manner Also can insert a stent to maintain the angle Rejection Hyperacute: Minutes to hours Preexposure to antigen Immune system attacks someone elses MHC get damage to endothelium and also get blood clotting Damaged endothelium and thrombosis Prevention Make sure that the donor and recipient share MHC alleles. Acute 1-16 weeks Adaptive immune system it takes time Damage to both tubules and vessels Chronic Vascular Slow damage to the vasculature of the kidney Solution Make sure that the donor and recipient match in their MHC alleles

Anatomy Page 120

Acid-Base
Thursday, March 28, 2013 12:59 PM

pH Blood is basic Normal range 7.35-7.45 Fetus Tolerant of acidity Range of Acidity in Humans Humans can have urine that is a pH of 8 and stomach acid of a pH of 1.5 Almost all biological fluids have a very narrow range of pH except for urine The most important fluid to consider is human venous blood and it is normally between 7.35 and 7.45 Problems Above 7.45 is called physiological alkalosis Alkalosis is a much more rare problem and is almost never fatal. Below 7.35 is called physiological acidosis Acidosis is a serious problem and can be fatal, at a pH of about 7.0 the CNS becomes so depressed normal functioning ceases Equilibrium Reactions and Buffers An equilibrium reactions is a type of reversible chemical reaction wherein both products and reactants are present at the same time. The ratio in the products and reactants is maintained such that if one of the parts of the equilibrium is removed the reaction moves in such a way as to compensate for the loss. All of the buffers participate in equilibrium reactions so they always act to keep a balance between the reactants and products For buffers one of the reactants is H+ thus the buffer systems act to keep H+ in balance The buffer consumes H+ so if H+ increase the buffer will consume it If H+ decreases the buffer will produce H+. Ultimately a buffer system can be completely consumed by attempting to balance large changes in H+ There are both intracellular and extracellular buffers Intracellular Buffers Inside of cells protein and amino acids act as buffers. E.g. inside of red blood cells haemoglobin (which is constructed partially of the protein globin) is an effective buffer The carboxyl and amino groups can absorb or give off H+ The buffers give up an H+ in basic conditions and absorb an H+ in acidic conditions thus they buffer or dampen the changes in pH Diagram

Extracellular Buffers In the serum and other extracellular spaces we have the bicarbonate buffer system. This system consists of carbon dioxide, water, carbonic acid, bicarbonate ion and hydrogen ions. The elements of the system are normally always present because CO2 and water are normally present. In the urine we have both the phosphate buffer system and the bicarbonate buffer system playing a role. I am not going to write out the phosphate buffer system. The Dynamic Bicarbonate Buffer System Q1. What happens within the bicarbonate buffer system when you increase CO2 levels? A. The first thing that happens is that the CO2 combines with water and the carbonic acids levels go up. Next some of the carbonic acid decomposes to yield H+ and bicarbonate. In the end, the increased levels of H+ brings the pH down and the whole system is shifted to the right to maintain a balance in the reactants and products Q. What happens when you increase H+ levels? A. Some of the new H+ combines with the bicarbonate ions in solution to manufacture carbonic acid. Some of the carbonic acid then decomposes to form CO2 and water. The increase in water is insignificant but the CO2 increase is apparent as is the decrease in bicarbonate ion. There is a very modest increase in H+ so the pH will not change very much. Just as in the first slide, the whole system shifted to minimize the change and keep a balance between the products and reactants the difference is that the system shifted to the left to maintain the equilibrium. CO2 Generation and Transport

Anatomy Page 121

 CO2 Generation and Transport

CO2 made in the beige cells gets converted to H2CO3 and H+ Need carbonic anhydrase to make this fast Some CO2 goes and binds to hemoglobin CO2 Exodus Some CO2 in RBC's just gets out Some bicarb goes in the opposite reaction to make CO2 so it can get released Acidosis Respiratory Causes Dissolved CO2 yields H+ because of the carbonic acid-bicarbonate buffer reaction

Anything that interferes with respiration will increase dissolved CO2 because without being able to breath properly you cannot exhale the CO2 produced Causes of respiratory acidosis. Damage to the lungs (e.g., emphysema) or airways (e.g., obstruction) or breathing (damage to the muscles of respiration) Damage (trauma) or incapacitation (e.g., opiate poisoning) of respiratory centers in medulla oblongata Just holding your breath or running will do it too! Note: Acute respiratory acidosis increases epinephrine and norepinephrine release. This is so you become aggressive to try and breathe Nonrespiratory Causes Anything except for CO2 causing an increase in H+ is called nonrespiratory or metabolic acidosis Causes of Acidosis Anaerobic metabolism Lactic acid produced during glycolysis under anaerobic conditions Kidney dysfunction Normally the kidney secretes large amounts of acid and when it is not functioning properly pH will fall. Incomplete breakdown of fatty acids Uncontrolled diabetes and other forms of starvation lead to large increases in fatty acids When there are large amounts of unmetabolized fatty acids around this brings down the pH, ketones also arise so this state is called ketoacidosis. The breath smells fruity because of the ketones Consumption of ethanol in large quantities (it is converted from ethanol to acetaldehyde and then acetic acid) or small amounts of methanol or other toxic alcohols Normal metabolism produces lots of sulfuric and other acids every day These sorts of acids are called nonvolatile to distinguish them from carbon dioxide. Acidic fruits which have citric and other acid (this is a very minor contribution) Diarrhea The loss of bicarbonate rich intestinal fluid leads to acidosis Bowel normally dries feces and draws out water and bicarb which is a base Alkalosis Respiratory Causes Respiratory alkalosis is caused by low amounts of CO2 in the blood stream You can easily develop low carbon dioxide levels in the blood because of hyperventilation (i.e., excessive amounts of deep br eathing) Hyperventilation drives down the alveolar CO2 and since your blood stream CO2 is in equilibrium with the alveolar levels then your blood loses CO2 With low CO2 in the blood and the accompanying elevated pH one loses the drive to breath People commonly pass out when they hyperventilate and quit breathing for a few moments. This decrease in ventilation reesta blishes high enough CO2 levels to stimulate breathing. This is like a reboot this stops the breathing so there is a build up of CO2 Nonrespiratory Causes Vomiting Loss of H+ from the extremely acidic contents of the stomach will lead to an increase in pH Ingestion of bicarbonate Bicarbonate is a base so consumption of this basic material consumes some of the blood H+ and pH goes up Constipation Absorption of extra bicarbonate from the feces. Normally the feces are expelled with a small amount of water and bicarbonate. If the fecal material stays in the large bowel long enough it becomes very dehydrated and much of the bicarbonate, which is normally lost, is reabsorbed. What does one do about changes in pH? We compensate for the changes by one of two ways Respiratory Compensation If there is too much acid or lots of CO2 we breath more Greater ventilation of the alveoli decreases the amount of CO2 in the alveoli. The decrease in alveolar CO2 causes a greater concentration gradient between the CO2 in the blood and the alveolar space. With a large concentration gradient the CO2 rapidly leaves the blood. Wi th less CO2 the
Anatomy Page 122

between the CO2 in the blood and the alveolar space. With a large concentration gradient the CO2 rapidly leaves the blood. Wi th less CO2 the bicarbonate buffer system shifts to the left and consumes H+. If there is too little acidity or low CO2 we breath less Less ventilation causes an increase in alveolar CO2 which leads to a smaller concentration gradient between the CO2 in the bl ood and the alveolar space. With a smaller concentration gradient the CO2 builds up in the blood. More CO2 leads to a shift to the right in the bi carbonate buffer system which yields an increase in H+. Note: CO2 levels are more important than O 2 levels in terms of the breathing rate

Renal Compensation This is fundamentally a very, very simple system If there is too much acid (low pH), we pee out acids (H+) If there is too much base (high pH), we pee out base (HCO3-) Characteristics The process of renal compensation for acidosis is better than respiratory compensation because HCO3 - is preserved by the kidneys Respiratory compensation costs one HCO3 - for each H+ (i.e., one bicarbonate has to combine with a hydrogen ion which results in H2O and CO2. The CO2 is expired at the lungs thus one bicarbonate ion is lost) but renal compensation does not cost a bicarbonate. Therefore you are able to preserve HCO3- levels in the bod For long term compensation of acidosis the bicarbonate can be preserved by using the kidneys The kidneys are also the only way of dealing with nonvolatile acids i.e., acids which cannot leave in the respiratory gas. It takes hours for this system to kick in and days for it to become optimized Na+/H+ Antiporter in the Proximal C.T. High H+ levels will lead to increases in CO2 The CO2 can then move passively into the tubular cell. The CO2 combines with water to form H2CO3 which dissociates to HCO3- and H+ The H+ is put into the filtrate using the Na/H+ antiporter. The HCO3- is passively reabsorbed to the capillary blood The Na+ that came in on the antiporter is pumped out using a Na+ pump. The secret here is carbonic anhydrase (CA) which converts the CO2 to H2CO3 This rapid conversion of carbonic acid to the bicarbonate ion and H+ allows for the regulation of the ions. The CO2 could move in any direction but only the cell can deal can create the bicarbonate ions and shunt them back to the blood. Notice that the H+ is excreted and the HCO3- is reabsorbed which is not like the respiratory compensation for excess H+. An Introduction to Figuring out the Causes of Acidosis and Alkalosis If pH is >7.45 you have an alkalosis If pH is <7.35 you have an acidosis The next value to check is the amount of CO2 in the blood to discover if it is higher or lower than normal The final thing is to combine the two measures and think about what you are seeing! Steps First you have to decide whether the situation you are seeing is acidosis or alkalosis Next you have to figure our whether it is respiratory or nonrespiratory. Inference If the CO2 levels agree with the pH it will be called respiratory acidosis If the CO2 levels do not agree with (or explain) the pH then it will be called nonrespiratory acidosis THIS WILL BE ON THE EXAM FOR SURE Bicarbonate Levels You can also check bicarbonate levels when investigating the cause of an acid-base imbalance. Bicarbonate is a base so the pH should vary directly with the bicarbonate levels if the bicarbonate is causing the problems (i.e., low pH with low bicarbonate levels and high pH with high bicarbonate levels) Example 1. In severe diarrhea there is a loss of bicarbonate and the pH is low. The low bicarbonate is the problem (not CO2 I t is a case of metabolic acidosis because the low pH is not due to too much CO2 . A cure for this problem, besides stopping the diarrhea, is to provi de intravenous bicarbonate. Example 2. In the case of vomiting there is a loss of H+ and there is lot of excess bicarbonate left around in the plasma. T his is a metabolic alkalosis because the problem is not due to a low CO2. The cure for the problem is to stop the loss of the unbuffered H+. Problems Q: After spending several anxious hours waiting to begin the Anatomy and Physiology exam, a student collapses. In the emergency room the blood results show an elevated pH and a low CO2. What is the problem? A: 1. The pH is higher than normal, so this is a case of alkalosis. 2. In this case venous CO2 is low which leads to small amounts H+ and a high pH. The CO2 and the pH agree which is to say that the low CO2 is causing the problem. This must be a respiratory alkalosis. The person has likely hyperventilated since that is by far the commonest cause of this finding. You dont have to look at bicarbonate levels here because the cause is clear, however, bicarbonate would be low because there is little CO2 around to make bicarbonate. Q: Later that evening after the highly stressful but stimulating and rewarding A&P exam the same student is found semiconscious outside of residence clutching a
Anatomy Page 123

 Q: Later that evening after the highly stressful but stimulating and rewarding A&P exam the same student is found semiconscious outside of residence clutching a half-consumed bottle of peach schnapps mumbling the score to Mamma Mia. Back in the ER the blood results come back showing a depressed pH and a low CO2 and low bicarbonate. What is the problem? A: 1. There is low pH, so this is a case of acidosis. 2. Low CO2 alone leads to small amounts of H+ and a high pH but there is a low pH here. The pH reading and the CO2 measure do not agree therefore the CO2 cannot be causing the problem so it must be a nonrespiratory (metabolic) acidosis. The low CO2 is a result of compensation by the respiratory system. The low CO2likely means this person was or is breathing deeply. Notice as well that the low levels of bicarbonate are, in a sense, the cause of the problems. If there was more bicarbonate then the pH would be higher. The large amounts of alcohol consumed by the patient were converted to acetic acid which leads to increase amounts of fixed acids. If this person had vomited then the pH would have gone back up but she held on with great resolve. Summary The bicarbonate buffer system is an equilibrium reaction which is critical to understanding acid-base balance. The ventilation of the lungs is critical to maintenance of blood pH so any problems can cause alterations respiratory alkalosis or acidosis The kidneys can both generate new bicarbonate and excrete H+ as well as compensate for pH changes We can compensate for lots of problems with pH so you can have high CO2 and low CO2 and still have normal pH. But. when given a problem about pH on a test or in real life use a systematic approach or suffer the consequences!

Anatomy Page 124

Reproductive System
Tuesday, March 26, 2013 1:30 PM

Anatomy Page 125

Urogenital Anatomy
Tuesday, March 26, 2013 1:30 PM

Urogenital Anatomy

Renal fascia Connective tissue layer that holds the kindey in place Attaches to the liver which attaches to the diaphragm Perirenal fat Surrounds the kidney I think this is inside the fascia but outside the capsule Keeps a cushion on the kidney Renal Capsule Outside the kidney Keeps the pressure Close by Liver Respiratory Diaphragm

Renal hilum Stuff comes in and out Renal Cortex On top Renal Medulla Renal column Renal pyramid At the end of each pyramid is a renal papilla All of the collecting ducts of a nephron all funnel down papilla which is a collection of holes minor calyxes major calyxes renal pelvis ureter bladder

Places where stone gets stuck: Uretoropelvic junction Psoas muscle Ureter has to go over psoas and iliacs it's like a bridge Uretrovesicular junction Where ureter goes into the bladder Extrasegmental artery See below Kidney stone fragment Grind along the ureter which makes it hurt These fragments are from a calcium kidney stone (calculus) that was broken up by lithotripsy (high energy sounds waves) before removal.

Anatomy Page 126

Note: Extra segmental artery Can have more than one artery to the kidney this is another place the stone can get stuck as the artery kinks the ureter Sometimes the kidney will droop (ptosis) which will kink the ureter and cause an increase in fluid in the ureter which is called hydroureter. Anything that blocks the flow will back up fluid and can cause hydronephrosis. Hydronephrosis = water in the kidney

The muscle layers will produce waves of peristalsis to push urine to the bladder. The epithelial layer is a mucosa or mucous membrane (that is that it has mucus-producing cells) and it is transitional epithelium that can expand greatly with increased volume. The inner muscular layer is longitudinal while the outer layer is circular. This the opposite order of muscle from the GI tract which is confusing.

Structures Ureter + ureteral opening Peritoneum Lines everything in the abdomen Detrusor muscle Trigone Smooth area in the bladder between the ureteral opening and the urethral opening External urethral sphincter No internal sphincter in females Deep muscles of perineum Holds contents of that part of the pelvis in Note: pelvic diaphragm doesnt hold the whole abdomen in pelvis is tilted forwards and the pubic symphsis is pointing downwards and therefore all the weight is concentrated on that (as well as the abdominal muscles) Inferior + Superior pubic ramus of hip bone What are these What connects the two is the levator ani Urethra Is short in females

Anatomy Page 127

Prostate In between the bladder and erectile tissue of the penis Has prostatic urethra Urethra Sections Prostatic urethra Membreanous urethra Penline (spongy) urethra

Bulbourethral gland Produces mucous and alkaline substance Lines penile urethra with mucous so when there is sprem in there it doesnt get activated in the urethra

Seminal vesicles Produce most of the fluid that ends up on the semen Vas deferens Goes to testicle (catching sperm) Goes over top ureter and mixes together Ejaculatory duct Vas and seminal vesicles join together Does it secrete into urethra or prostate? Based on the wiki screenshot above its the urethra (prostatic urethra to be specific) Internal urethral sphincter This is so that the urine and semen doesnt mix

Male

Anatomy Page 128

Male Pubic symphysis Urinary bladder Colon Rectum Prostate Root of penis Corpus spongiosum Completely surrounds urethra all the way Corpus cavernosum Two tubes of this Erectile tissue Glas penis Head of the penis

The erectile tissue is not as apparent in the female as the male. Its not as if there is nothing in the female pelvis and th us it is a bit hard to imagine a babys head coming through. Notice that this uterus is anteverted (i.e., leaning forward) and retroflexed (i.e., bent backward). Normally the uterus would be both anteverted (leaning forward) and anteflexed (flexed forward). Because of the version of the uterus, it is almost horizontal in the nonpregnant state. Female Clitoris Homologous to the corpus cavernosum in males Mons pubic Layer of fat in front of the pubis symphsis Urinary bladder Dont confuse with uterus Uterus On top of the urinary bladder Is leaning forward (anti-verted) and its bent so its anti-flexed Could also be retroverted and retro-flexed but you want anti, anti External Os of the Cervix Part of the uterus From this is the vagina? Uterine tube Fibriae Catches the egg (when there is ovulation) Note that the the fimbriae of the infundibulum of the uterine tube are tight to the ovary at ovulation (lets the egg go into the fallopian tube (the infundibulum) from the ovary) Ovary Labium Minus Mucosal layer Mucous connective tissue Labium majus Stratified squamous epithelium Also has hair on it Completely different from labium minus Vesicouterine pouch Peritoneum goes to here this is I think between the bladder and the uterus Pouch of Douglas Also called retrouterine cul-de-sac

Anatomy Page 129

 Also called retrouterine cul-de-sac This is the lowest place in the abdominal cavity so mucous from infection can gather here Vaginal lumen Should have rugae in it

Bony pelvis Holds everything in Ilium, ischium and pubis are three separate bones that grow together

Joints Sacroiliac Sacrococcygeal Pubic symphsis Note In the last 3 months of gestation all of these joints relax remarkably. Birth Movement of the SI joint, when the women is in the dorsal lithotomy position (bottom right of the picture), may increase pelvic diameter 1.5-2.0 cm. That being said, you dont want to give birth like this cause baby would block the mom's IVC

Light and thin Shallow false pelvis Large, slightly oval pelvic brim Pubic arch greater than 90 degrees Base of the red triangle is long
Coccyx angled towards the anterior

Heavy and thick Deep, cup shaped false pelvis Small, heart-shaped pelvic brim Pubic arch less than 90 degrees Base of the red triangle is shorter
Coccyx angled strongly towards the anterior Cups the pelvic contents

Widest point of the pelvic hole thing (when Widest point is closer to the posterior you try to make a horizontal line) is right in the middle

Anatomy Page 130

Anterioposterior diameter >10 cm This is the size of a baby's head Distance between the sacral promontory and the pubic symphsisis Transverse diameter Also has to be >10 cm

Monkeys Babies have small heads and females have large pelvic outlets easy to give birth Ausrilopicathus Decided to walk upright smaller pelvic hole Also became smarter so had bigger heads Full explanation It is generally assumed that there are two great drivers of change in the female human pelvis- the first is the adoption of an upright posture to accommodate a bipedal gait. That narrow the pelvic outlet and inlet because there was more pressure on the pelvic diaphragm. while the second is the development of a fetus with a large cranium (smarter_. As can be seen here, the chimpanzee which is neither bipedal nor has a fetus with a large cranium offers few problems for the pelvis. The australopithecines had a wide ilium but narrow pelvis adapted for a bipedal gait which forced the fetal head into a lateral position. The large head of the human fetus adds a further complication and the human fetus normally ends up filling the pelvis in a occiput-anterior position. And that is how we ended up with such a peculiar pelvis

There are additional ligaments which are not obvious until the broad ligament and peritoneum is removed. These include the uterosacral ligament and the suspensory ligament of the ovary. Uterine fundus Is the top of the uterus Suspensory ligament of the ovary Is not a ligament It is a neurovascular bundle doesnt hold the ovary up Utero-ovarian ligament Connects the uterus and the ovary Round ligament Joining the uterine fundus forwards keeps it from moving around Utero-sacral ligament Holds the uterus back to the sacrum Broad ligament Goes all over the sides of the uterus and fallopian topes and ovaries holds it to the sides Note
Anatomy Page 131

 Note Without estrogen these get loose

Notice that everything is covered with peritoneum everything! No exceptions. The peritoneum provides some support particular ly since it folds over the sides of the uterus and tubes to make a double thick layer of parietal peritoneum which is called the broad ligament.

Prolapsed uterus Use a pessery to stop it from coming out (bottom left picture) Can also use colposususpension Prolapse vs. inversion Homologs

Embryological All of the primary sexual characteristics (the internal and external organs of reproduction) develop from same starting point in males and females. All of these organs have homologs in both sexes. Development In the case study we will talk about how all these homologous structures develop from the indifferent stage of embryology Ovary is like the testes Crus of the clitorus is like the corpus cavernosum Glans of penis is like glans of clitoris Round ligament is homologus to the gubernaculum Labia majora fuse in males to become to become the scrotum

Anatomy Page 132

Reproductive Physiology
Tuesday, April 2, 2013 1:30 PM

25:12 Part #1: Gamete to Fertilization Introduction Old fashioned fertilization Sperm to egg In vitro fertilization Put the nucleus of the sperm right inside the egg Oogenesis Makin eggs The process of oogenesis begins in the fetal ovaries where stem cells (called oogonia) produce primary oocytes At birth there are about 2 million of these primary oocytes hanging about in the ovary These primary oocytes are diploid (i.e., they have a full set of 46 chromosomes) They cannot be fertilized unless you wanted a triploid fetus (i.e., 69 chromosomes) 23+23+23 At the onset of puberty (about 11 or so) there are about 300,000 primary oocytes and by the time of the menopause there will essentially no primary oocytes left in the ovary If a woman runs out of eggs early then menopause starts early Only about 500 eggs could ever be released if you never became pregnant and always ovulated with every menstrual cycle Steps? The primary oocytes are held in prophase of meiosis I They are unchanged from the way they were produced in the fetus With every menstrual cycle, a few of the primary oocytes wake up A number of primary oocytes restart meiosis 1 early in the menstrual cycle and a few become secondary oocytes. This cohort of eggs develop at the same time however only one of these secondary oocytes will be released from the ovary at o vulation Fertility drugs such as clomiphene can lead to superovulation which means a number of eggs will go to the secondary oocyte stage and then be ovulated The completion of meiosis II begins exactly at the time when the sperm contacts the egg (fertilization) The development of eggs in every cycle is called the ovarian cycle and there are two phases to the cycle Follicular phase Is where the egg and surrounding cells (the follicle) develop up to the point of ovulation Luteal phase Is where the leftover bits of the follicle hang around and secrete hormones (particularly progesterone) to prepare the lining of the uterus (the endometrium) for a fertilized egg

Follicular Phase Secondary follicle develops Really only one wins Luteal Make the corpus luteum which is to rescue the system Follicular Phase Primordial to Primary Follicle

Anatomy Page 133

Primary Oocyte Wakes up then the follicular cells wake up and then you have the primary follicle as the granulosa develops Primordial follicles have squamous granulosa cell layer while primary have cuboidal granulosa cell layer Zona Pellucida Shell Protects the oocyte Transition to Secondary Follicle Granulosa cells secrete follicular fluid and form and antrum, this is now a secondary follicle. Secondary to Mature Follicle Once of them begins to mature Granulosa cells continued to secrete follicular fluid which forms a continuous antrum, this is now a mature follicle Granulosa cells around the oocyte are referred to as the corona radiata The primary oocyte completes meiosis 1 just prior to ovulation and becomes a secondary oocyte Ovulated Secondary Oocyte Nucleus stuck in meiosis 2 Barriers Zona pellucida Corona radiata Meiosis

Note that the original diploid cell has 46 chromosomes, and each of the four haploid cells after meiosis 2 have 23 chromosomes Homeostasis in Ovary Steps 1. Stimulus: low estrogen (variable) in blood Due to just finishing menstruating 2. The hypothalamus (receptor and control center) detects low estrogen levels 3. GnRH released from hypothalamus 4. LH and FSH released from the pituitary which leads to follicle growth This follicular growth is to make the granulosa to build up, which will then make estrogen and progesterone 5. LH stimulates production of estrogen which inhibits GnRH, LH and FSH release Negative feedback But the thing is that the follicle still continues to grow (doesnt need LH and FSH anymore) and it produces more and more estrogen This increase in estrogen levels triggers a positive feedback mechanism 6. Continued estrogen production stimulates GnRH, LH and FSH release. This is positive feedback in the midst of negative feedback 7. LH surges causing the follicle to rupture and the egg to be released Then you can get ovulation Legend GnRH = gonadotropin releasing hormone Gonadotropins are: LH (luteinizing hormone) FSH (follicle stimulating hormone, so called cuz it makes ovarian follicles grow)

Anatomy Page 134

Even though estrogen levels increase LH and FSH levels increase Menstrual Cycle Introduction This cycle is sometimes called the uterine cycle since most of the changes occur in the uterus, particularly the endometrium,the lining of the uterus. The purpose of this cycle is to prepare the lining of the uterus for the fertilized egg to implant. It takes from 21 to about 40 days to complete the endometrium preparation (usually it is about 28 days). The development of the endometrium is highly variable in length but it all begins with the growth of the stratum functionalis which is lost in the previous menstrual cycle above the stratum basalis which remains. The development of the functionalis is chiefly due to the a) Proliferation of the endometrial stroma and the elongation b) Growth of endometrial glands. The glands will produce material that will provide nutrition for the fertilized egg.

Endometrium Stratum functionalis Stratum basalis Myometrium Muscular layer Steps

Menstral phase This is the bleeding End up with the basal layer Proliferative Phase Functional layer (?) becomes bigger and bigger Around 14 days This is when ovulation occurs
Anatomy Page 135

 This is when ovulation occurs When the egg leaves, it leaves those granulosa cells that make the corpus luteum Then it is going to be the secretory phase Corpus lueteum produces progesterone and causes the thick functional layer to become secretory (according to textbook it secretes glycogen)

Menstrual Phase Have lots of primodial follicles and primary follicles Get secondary follicles which make estrogen Proliferative phase Estrogen makes functional layer to get bigger causes endometrium to grow Ovulation Mature follicle ovulates This is due to that positive feedback the surge of LH and FSH causes the egg to be released from the follicle Follicle has blood vessels and then you get a bloody spot (corpus hemorhhagicum) then it makes estrogen and progesterone as the corpus luteum Now the endometrium becomes secretory Corpus Luteum After 14 days it gives up and quits working and becomes the corpus albicans Cause estrogen and progesterone levels decrease you get the menstrual bleed Uterine Cervix Dont want things to go up the vagina into the cervix cause there are bacteria this would go into the uterus and then into the pelvis (peritoneum) Fallopian tubes are open cause when the eggs are ovulated, they are pushed into the peritoneal fluid and they have to find the fallopian tube But we do want the cervix to be open when there is sperm around so right around the end of the proliferative phase when there is lots of estrogen, the cervical mucus becomes thin and the sperm can move up .. Then you get lots of progesterone and the mucus becomes thick again (blocking stuff from coming in) SUMMARY!!!!! So during the proliferative phase the secondary and mature follicles release estrogen which causes the functional layer to grow. This also causes the positive feedback which results in a surge of LH and thereafter ovlulation. Now, there is a corpus luteum which secretes estrogen and progesterone this causes the endometrium to get secretory. If the egg is not implanted, the corpus luteum gives up, there is a drop in estrogen and progesterone and then the functional layer sloughs off This is my understanding Rescuing the Endometrium Pregnancy stops the degeneration of the corpus luteum because the implanting egg and then the placenta release human chorionic gonadotropin (hCG). Human chorionic gonadotropin acts like luteinizing hormone and stimulates the corpus luteum to produce lots of progesterone and a little estrogen. The progesterone inhibits the uterine contractions and disintegration of the stratum functionalis that precedes the menstrualflow.

Anatomy Page 136

The egg is fertilized, then it still atkes time to make hCG Most eggs get fertilized its just that they dont hit the uterus at a time that is optimal and therefore the hCG wasnt made in time

Answer: D Sperm Sperm Construction Acrosome Of the sperm head contains vesicles of digestive enzymes for penetrating the zona pellucida Nucleus Has the haploid number of chromosomes Midpiece Supplies the energy for the flagellum Has mitochondria Flagellum Provides the motive power for the sperm to swim in search of true love and an egg

Spermatogenesis The process of making spermatozoa (sperm) Stem cells (spermatogonia) constantly divide and then undergo meiosis to give mature sperm The whole process takes 64-72 days These exist in the testes The process begins at about 14 years of age and continues throughout life or until castration Each ml of semen has about 50-130 million sperm If counts fall below about 20 million sperm/ml of semen then infertility is a concern Pathway Spermatogonia in migrate through the seminiferous tubes and mature as they move towards the lumen and once they get to th e lumen they make their way up to the vas defrens for ejaculation Semen Introduction Semen volume is about 2.5-5

Anatomy Page 137

 Semen volume is about 2.5-5 Only a miniscule fraction is actually sperm The majority of the volume is made up of other fluids secreted by the Prostate Seminal vesicles Bulbourethral glands Seminal vesicles Produce the majority of the semen (60%) In their secretions are : Fructose Clotting proteins These secretions are also somewhat alkaline. The alkaline fluid neutralizes the vaginal pH to some degree. Prostaglandins These are also found in the seminal vesicular fluid which stimulate the sperm to swim and the uterus to contract. Prostate Secretes: Thin acidic or neutral fluid which provides a medium for sperm to swim Citric acid (energy) Protein digesting enzymes (proteases) Breaks down the clot so you can get the sperm out Out of what and what clot About 25-30% of semen volume. During arousal the bulbourethral glands release alkaline fluid into the urethra to neutralize acidic urine and some mucus to decrease sperm damage later during ejaculation. This gland does not make up much of the seminal fluid. Gamete Manufacture Similarities Both rely on the pituitary gonadotropins, LH (luteinizing hormone) and FSH (follicle stimulating hormone) FSH Stimulates the growth of the gametes (oocytes and sperm) LH Stimulate the production of hormones from the gonad LH Stimulates the ovarian follicle to make estrogen and progesterone Stimulates the (interstitial cells of) Leydig cells in the testes to make testosterone The hormones produced by the ovary or testes feedback on the pituitary to decrease the production of the gonadotropins

Fertilization The path to the egg to the sperm is a difficult one. On the male side >20 million well-formed sperm ml of semen are required for reliable fertilization The sperm have to get passed the cervix, up the uterus and into the uterine tube (Fallopian tube) On the female side The egg has to be in the uterine tube The endometrium has to be ready (i.e., in the secretory phase) for a fertilized egg but before the cervical mucus has becomethick Part #2 Fertilization 1. Sperm become capacitated (they begin to swim more vigorously and the acrosome becomes ready to degranulate) and ready to fertilize 2o oocyte 2. The sperm penetrate the corona radiata. 3. Many sperm contact the the glycoprotein of the ZP and the acrosome reaction occurs which causes the ZP to be digested I think it is the acrosome of the sperm which are being used to eat away at the blots 4. One sperm contacts the plasma membrane of the oocyte 5. The cell membrane of the oocyte depolarizes and cannot bind further sperm (the fast block to polyspermy) and the cortical reaction occurs 6. The ZP hardens (the second block to polyspermy). 7. Given that the sperm has attached to the plasma membrane, this stimulates the nucleus of the oocyte to finish meiosis 2. The 2nd polar body is formed & meiosis II is finally complete The haploid male & female pronuclei are formed. 8. The female and male pronuclei fuse resulting in the zygote. Note: Fertilization occurs in the ampulla of the uterus

Anatomy Page 138

Answer: C Egg to Blastocyte Note: At this stage the endometrium will have to be in the secretory phase or just getting into the phase The fimbriae of the infundibulum of the uterine tube are tight to the ovary at ovulation (lets the egg go into the fallopian tube (the infundibulum) from the ovary)Steps Sperm meets egg Two cell embryo at day 1 (going from infundibulum to ampulla to isthmus (opening to uterus) of tube) Then four cell embryo Then its a morula (still in the ZP at day 4 after fertilization) Its a collection of different cells in the one (?) zona pelucida Then blastocyst hatches from ZP and is ready to implant (in endometrium) If you look closely you can see two parts to the blastocyte Inner cell mass This is whats going to becomes the baby Trophoblast That becomes the placenta Note: These are separated by the blastocyst cavity

Eggs like to grow on the top of the uterus so the baby can come out from the bottom 7 days Trophoblast Digests the maternal endometrium for food as it gets closer to the blood supply (maternal blood vessels) Amniotic Cavity The sac grows around the embyo thats how the baby ends up in it 9 day Trophoblast finds the maternal blood supply and interacts with it can cause an i mplantation bleed If you ovulated at 14 days this would happen at 28 days so people mistake this for a menstrual bleed Yolk sac Not that important Starts to develop 14 days Implantation is complete Yolk sac Not that important in humans 16 Day Embryo

Anatomy Page 139

16 Day Embryo

Yolk sac Still there Mesoderm Out of the edges of the embryo comes mesoderm (mesoderm gives muscles) The embyo starts shooting out this mesoderm to give the placenta tissue its extraembryonic mesoderm Connecting Stalk Becomes the umbilical cord Has that extraembyonic mesoderm Ectoderm Neural plate folds up to make the neural tube Endoderm Will make your gut Allantois This will also become part of your gut Not too important Amniotic Cavity Starts to develop it starts to fill up with fluid and therefore starts to surround the fetus (?) 28 Days - The Folded Embryo

Amiotic cavity Starts to really go around the embryo Yolk sac Squish this out with the future umbilical cord Foregut Part of the gut that is supplied with the celiac artery E.g. stomach and duodenum From endoderm Hindgut Supplied by the inferior mesenteric artery Mostly the colon Midgut Supplied by the superior mesenteric artery Heart Is dividing into four chambers 10 weeks

Anatomy Page 140

Overall: Embryonic and Fetal Development There are three main phases of development Pre-embryonic phase <14 days after fertilization The conceptus is about 1.5 mm in length by the end of this phase and the very poorly differentiated By the end of this period there is a tiny trophoblast (the beginning of the fetal part of the placenta) For much of the earlier parts of this phase the zona pellucida is still present and the embryo is isolated from the maternal environment. This is before it is connected to the maternal blood supply Embryo 2-8 weeks after fertilization All major organs are assembled in this time so it is called the period of organogenesis The embryo grows to about 28 mm (2.8 cm or just a shade over one inch) The placenta is far larger than the embryo at this point and there is complete access to materials in maternal circulation Note: Q: This phase from 14 days to about 8 weeks is where embryo/fetus is particularly sensitive to exposure to toxins. Why? A: Have lots of development going on Fetus >8 weeks to term The organs grow during this period so it is called the histogenesis phase Problems in Development Embryonic Major dysgenesis in organ systems. Examples Thalidomide (drug) caused phocomelia Flippers instead of limbs develop Valproic acid (drug) causes spina bifida When Mainly occurs in the embyonic phase of development Fetal Incomplete or abnormal development in organ systems. Examples Microtia Cataracts Due to rubella Key This is most of histogenesis rather than embryogenesis not as bad

Myometrium Muscular layer of the uterus Placenta Decidua Mothers contribution to the placenta Comes from the functional layer of the endometrium

Anatomy Page 141

 Comes from the functional layer of the endometrium Arises from the decidua basalis of the endometrium Chorion Baby's contribution to the placenta This is the extraembyonic mesoderm and trophoblast

Choronic Villi These are the structures hanging in the maternal blood so that the fetal blood can get oxygen and give up CO 2 to the maternal blood Placental Circulation

Maternal Endometrial arteriole Is a spiralling down of the maternal artery such that the choronic villi can interact with it Specifically, it spews its blood into the intervillous space Endometrial venule Picks up the deoxygenated blood and carries it out through the maternal vein Fetal Umbilical arteries Bring deoxy blood Umbilical vein Takes oxygenated blood to the fetal heart Maternal Adaptation to Pregnancy During this time, maternal physiology has to adapt. Cellular immunity decreases The fetus is an allograft (i.e., not the mom but not the dad either) but the mother has to remain tolerant of paternal antigens and yet maintain normal immune competence for defense against microorganisms The placental villi do not exhibit very many antigens and the activity of many types of helper-T cells decreases The placenta requires a lot of blood Blood volume increases 30-50% Cardiac output increases 20-30% Tidal volume increases 30-40% and airway resistance decreases to increase CO2 loss. Lower maternal CO2 levels create a stronger concentration gradient between mom and fetus. Really need this [] gradient to get rid of baby's CO2 thats the key reason why the mother breathes so much Its less the fact that you need more oxygen (cause the fetus is so small) and more to keep maternal CO2 levels low to keep that [] gradient Myometrial mass (of the uterus?) increases from 60-80g to 900-1200g (about a 15X increase) to accommodate the fetus.

Anatomy Page 142

hCG Has a huge increase after ovulation This comes from the placenta and keeps the corpus luteum alive until the placenta begins to make steroids So levels drop after the placenta takes over the job of the corpus luteum Estrogen + Progesterone Increase till birth at first it was made by the CL and then by the placenta Note that the ratio of estrogen to progesterone increases until birth Parturition

Anatomy Page 143

Textbook
Friday, April 5, 2013 8:11 AM

Steps Menstrual Phase Ovaries This is a part of the follicular phase Primodial follicles mature primary follicles secondary follicles Uterus Part of menstrual phase Decreasing levels of estrogen and progesterone causes the stratum functionalis to slough off Preovulatory Phase General Time between the end of menstruation and ovulation Ovaries This is part of the follicular phase One of the secondary follicles becomes the dominant follicle, which then becomes the mature (graafian) follicle Uterus This is part of the proliferative phase The stratum functionalis grows Ovulatory Phase This is part of the proliferative phase High levels of estrogen cause positive feedback Increase LH levels cause the rupture of the mature (graafian) follicle and the release of the secondary oocyte into the pelvic cavity Can have mittelschmerz Postovulatory Phase General Between ovulation and the start of the next menses Ovary This is the luteal phase Mature follicle breaks down, clot forms and the follicle becomes the corpus hemorrhagicum Then you somehow get the corpus luteum If oocyte is not fertilized Corpus luteum stays for 2 weeks If oocyte is fertilized Corpus luteum stays for more than 2 weeks it is resuced by hCG Uterus This is the secretory phase Progesterone and estrogens produced by the corpus luteum promote growth and coiling of the endometrial glands, vascularization of the superficial endometrium, and thickening of the endometrium Endometrial glands begin to secrete glycogen, which is why it is called the secretory phase

Anatomy Page 144

Case Study - Intersex

Tuesday, March 26, 2013 5:28 PM

Types of Sex Genetic sex XX = female and XY = male Phenotypic sex Appearance Gonadal sex Testes = male and ovaries = female Behavioral/psychological How the person self-identifies. Embryo At the 5th Week Mesonephric kidney Dont have this in adults Mesonephric (Wolffian) duct Drains the kidney Paramesonephric (Mllerian) duct Looks like its doing nothing at this time Indifferent gonad Potential ovary on outer surface, potential testis in stroma If it becomes an ovary outside will develop If it becomes a testis the inside will develop Cloaca Will divide and become rectum in the back and bladder up front Urogenital sinus Later on If there is a functioning Y chromosome SRY (sex-determining region of Y) gene product is TDF (testis determining factor) stimulates the Sertoli cells make MIS (Mllerian inhibiting substance) Mllerian (paramesonephric) ducts to disappear Human chorionic gonadotropin (hCG) Leydig cells androgens development of the male secondary sexual characteristics (through the Wolfian system). Stroma also becomes a testicle Mesonephric duct becomes the vas defrens Females: If there is no Y chromosome then there is no SRY gene and female sex characteristics develop. The male duct work is not actively inhibited but neither is it stimulated so the mesonephric (Wolffian) ducts slowly become unrecognizable. Muellerian system is what gets developed Kidney Comes out of nowhere its a metanephric kidney It doesnt come from the mesonephric kidney I think Persistent Mllerian Duct Syndrome But if the paramesonephric ducts (Muellerian system) do not degenerate (usually because of a shortage of MIS) then the testicles can be held up in the abdomen or pelvis. Those ducts would still be attached to the testicle and it doesnt let them descend Testes Inguinal Descent of the Testes The descent of the testes into the scrotum must occur through the inguinal canal The inguinal canal has a deep ring (opens to the abdomen) and a superficial ring which opens to the scrotum The testes will move downwards with gubernaculum (the little governor) They get pulled out by this long thin connective tissue piece that can contract this is the gubernaculum This gubernaculum is homologous to the round ligament in females

Canal goes over top the inguinal ligament Orchidopexy Premebabies have a higher rate of undescended testical Palpate the inguinal canal to see if the testicles are there if they are theyll prob descend eventually Usually you wait to see if the testicles will come down on their own Orchidopexy Surgery Cut the testicle off from the gubernaculum and then pull the artery and nerve and vein that feeds the testicle and loosen it up (cause its too short) then they push it all the way through the end of the canal then they pull the testicle to the scrotum and tie it down then you wait
Anatomy Page 145

short) then they push it all the way through the end of the canal then they pull the testicle to the scrotum and tie it down then you wait for the AVN to stretch out Why outside the body? Because sperm like it that way. Essentially spermatozoa will only develop at temperatures a 2-3 C below body temperature To maintain this temperature the testes will move up and down in an attempt to keep at the proper temperature The movement upwards is accomplished with the cremaster muscle Contraction makes the testicle warm brings them closer to the body The dartos muscle compresses the scrotum. This makes the testicles come closer together This is smooth muscle These are both activated to keep the scrotum close to the body and warm the testes. Thermostat Pampinoform lexus such that the venous blood can warm down the blood coming in (which is hot cause its coming from the inside of the body) Price This is a highly inconvenient place to put the reproductive glands Males have almost all of the inguinal hernias (going through the inguinal canal This is a direct inguinal hernia because the hernia went directly through the abdominal wall into the inguinal canal. This is a hernia normally acquired later in life. For example the bowel can come into the inguinal canal External Generalia Development Male Indifferent stage (5 weeks) Genital tubercle Labioscrotal swelling Urogenital (urethral) folds Urogenital sinus 10 weeks At ten weeks and under the influence of the androgens the urethral folds begin to meet and seal up. The labioscrotal swellings swell towards each other and the tip of the genital tubercle becomes the glans penis. Near birth Near birth the scrotum has fused at the midline and only the midline raphe is visible. The urethra has sealed and now opens at the tip of the penis in the glans. Female In the female near birth the labioscrotal swellings do not fuse at the midline rather they stay intact as the labia majora. The urogenital folds do not meet in the female and persist as the vestibule and labia minora. The genital tubercle becomes the clitoris. Intersex General Definition (adj); having both male and female sexual characteristics and organs; at birth an unambiguous assignment of male or female cannot be made Traditional synonyms for the intersex adjective include hermaphroditic or gynandromorphic As a general rule very few are true gonadal intersex (true hermaphrodites) which would mean both male and female gonads. The greatest number of intersex individuals simply have ambiguous genitalia (i.e., not clearly one sex or the other) XX Intersex Chromosomally female with external genitalia which appear male This typically results because of virilization of the female fetus by male hormones. The male hormones (particularly testosterone) arises because of an overactive adrenal gland in fetal development. The disease of the adrenal is called congenital adrenal hyperplasia (CAH). XY Intersex Chromosomally male with external genitalia which appear to be female or at least incompletely formed XY intersex has many causes but generally they are the results of inadequate supply or insensitivity to male hormones The most common cause is androgen insensitivity syndrome (AIS) The receptors for the androgens are not working A shortage of androgen can also cause a similar result. There are typically no female internal organs except for a short, blind ended vagina.

Anatomy Page 146

Case Study - Contraception

Tuesday, April 2, 2013 5:30 PM

Definitions Contraceptives Are supposed to block conception of a fetus. They work to keep sperm and egg from being united E.g., combination oral contraceptive pills, mini-pills, progesterone injections, contraceptive patches and mechanical methods like condoms Contragestational agents They work to keep the fertilized egg from implanting (in the uterus) E.g., morning after pills Intrauterine devices (IUDs) Abortifacients They cause the termination of an established pregnancy Ex. mifepristone (RU 486) Loci of Intervention Male Steps Production of viable sperm Transport of viable sperm Vasectomy Deposit of sperm in vagina Condoms or coitus interruptus Survival of sperm in vagina Spermicides Movement of sperm to uterine tubes Cervical cap, diaphragm Female Steps Production of viable oocytes Oral contraceptives Ovulation Oral contraceptives Movement of oocytes to uterine tubes Tubal ligation Together Fertilization of oocytes with sperm Morning after pill Implantation of oocytes MAP, OCs, IUDs Growth of the fetus Abortions Surgical (dilatation and curretage) Medical (RU 486) Fertility Awareness Fertility awareness method of birth control relies on noticing the signs of ovulation Temperature The slight drop in body temperature that occurs just before ovulation and the slight increase in temperature that occurs after ovulation Production of thin, clear, watery and elastic cervical mucus (i.e., maximum spinnbarkeit) that shows maximal ferning Spinnbarkeit is the word that describes this This allows the sperm to get though Mittelschmerz One-sided, cyclical abdominal pain associated with ovulation Position of the cervix Lower harder cervix= less fertile Elevated, softer and wetter cervix= more fertile Intercourse has to be planned around the times when ovulation is not going to occur. Epidemiology The rhythm method of birth control works by practicing abstinence from sexual intercourse (usually 3 days before and 3 days after) the likely date of ovulation Failure rates is 9% if used perfectly but more like 25% in typical use. Testing Mucus

When fertile it looks like there are ferns

Note:
Anatomy Page 147

 Note: Fertility awareness methods do not alter the endometrium in any way, they just monitor the process. Contraceptive pills, patches and injections look to manipulate hormone levels and the uterine and ovarian cycles. Oral Contraceptives Types Combination Pills Combine an estrogen and a progestin The estrogen and progestin inhibit the release of GnRH (i.e., they suppress the hypothalamo -pituitary axis) Low FSH (so little follicle development) No LH surge (no ovulation) Creates A thick cervical mucus Thick and scanty which inhibits sperm migration this is as opposed to the thin watery mucus that would allow the sperm to go through Progesterone causes this Hostile endometrium The endometrium is not in the secretory phase (it is atrophic) thus it does not allow the zygote to implant one of the most effective reversible forms of birth control Additional Information These are very effective forms of birth control Failure rate of 0.7 per 100 women years One or two missed pills are enough to cause the endometrium to proliferate and allow ovulation Compliance has to be very high for this to be effective Most combination preparations involve taking 21 days of hormones followed by 7 days without hormones to allow for menstruation This causes women to have very large number of menstrual cycles compared to early history In reality they aren't really menstrual bleed just bleeds this is cause all the steps of menstruation aren't really being followed Some of the pills have extended the time between withdrawal bleeds (e.g., Seasonale, Lybrel) Make it longer than 21 days This is hard though cause it becomes harder and harder to keep your pituitary asleep Other Combined Steroid Contraceptives Contraceptive patches (Evra) work the same as pills except the delivery of the steroids is transdermal This should allow for low levels of steroids since the drug enters the system very slowly The patch is put on once a week The contraceptive ring (Nuvaring) is another form of combined steroid contraceptives It is put into the vagina for three weeks and removed for one. It does not provide any sort of a barrier to the movement of sperm, it is just a way of delivering steroids.

Answer: D Progestin-Only Contraception Formulated to avoid the side effects of estrogen (mainly nausea and vomitting but also breast tenderness) Do not reliably suppress ovulation It doesnt decrease LH and FSH levels that much Cause thick and scanty cervical mucus Prevent the movement of sperm across the cervix The endometrium is also kept in a pregnant or atrophic state which will not usually allow a zygote to implant This is like the hostile endometrium The Mini Pill Taken PO every day except for 7 days in a 28 day cycle Missing a dose of the pill by hours can lead to ovulation and possible pregnancy Its cause it doesnt turn the pituitary off Risk of contraceptive failure greater than the combination pills Depo-Provera Made of Provera (medroxyprogesterone acetate) Given IM to the buttock or deltoid or as implants Its like the mini pill given in injection form 150 mg of the depot form of PROVERA (medroxyprogesterone acetate, MPA) q 3 months by deep IM injection given only during the first 5 days after the onset of a normal menstrual period, within 5 days postpartum if not breastfeeding, or 6 weeks postpartum if breastfeeding.
Anatomy Page 148

weeks postpartum if breastfeeding. Risks of Progesterone Only Contraception An iatrogenic cause of dysfunctional uterine bleedings (DUB) is the main problem with progestin -only compounds for birth control. Get random bleeding Physiology of this centers on: Progesterone inhibits estrogen and its estrogen that normally keeps endometrium fluffy To stop bleeding: Give estrogen which normally keeps endometrium fluffy 50% of women are amenorrheic after 1 year = No cycles after 1 year Mean time to pregnancy of 10 months after cessation Other side effects on slide Post-Coital Contraception Morning After Pills (MAPs) or Emergency Contraceptive Pills (ECPs) High dose progestin (Plan B) Administered within 72 h of coitus and two pills are taken- one right away and the other within 12 hours. It is about 90% effective (i.e., instead of a 8% chance of becoming pregnant you have a 1% chance of becoming pregnant) Appears to inhibit ovulation but even if ovulation is not inhibited there is likely to be a luteal phase defect caused by the large amounts of progestin in the pills which inhibits natural progesterone/estrogen production. The greater the delay in taking this, the higher the chance of getting pregnant Other Chemical Methods of Birth Control Antiprogestin Mifepristone (RU 486) antagonizes the effects of progesterone Progesterone causes the uterus to be quiescent then antagonism causes the myometrium to become active Progesterone is also necessary for maintaining the endometrium The combination of the two effects usually causes the endometrium to slough off after 12-72 hours Often a prostaglandin is often given to increase uterine contractions This combination of drugs can used for abortions up to about 8 weeks. Crazy Contraception! Immunocontraception Vaccination with a synthetic zona pellucida peptide produces long-term contraception in female mice Make woman allergic to sperm New spermicide/microbicide BufferGel Acidifies semen and maintains the protective acidity of the vagina ACIDFORM An acid-buffering and bio-adhesive gel with activity against bacterial vaginosis and Trichomonas vaginalis in vitro These both have some spermicidal activity and provide a moderate barrier but should not be considered as birth control Vasectomy Cut the vas deferens Essure A device inserted into the isthmus of the uterine tube to cause (essentially a non-surgical transcervical or hysteroscopic procedure) Causes and essentially irreversible obstruction in the uterine tube when scares form over the inserts Can be surgically reversed but fertility may not be restored and there is a chance of tubal and uterine penetration. Male Birth Control Pills Surprisingly doesnt work

Anatomy Page 149