Muscle, Circulation, and Respiration Review

• Exam 2 Review Session
• PCS TAs: Gavin, Makenna, Vy
• Friday, Mar 21
• Exam content includes Muscle, Circulation, and Respiration

Muscle

• Voluntary movement occurs
• Muscle fibers are striated and multinucleated
• Muscles contract in response to motor neurons
• The neuromuscular junction is excitatory
• Ach binds to nAchRs on muscle
• A motor unit is composed of a motor neuron and the muscle fibers it controls
• Muscle fiber comprises myofibrils, which further comprise sarcomeres (the contractile unit)
• Sarcomeres consist of repeating units of thin actin and thick myosin filaments
• Z line anchors the thin filaments and marks the boundaries of the sarcomere
• The I band: a lighter portion of only thin filament surrounding the Z lines
• The H zone is a darker portion of only thick filament in the middle of the sarcomere
• Note: The I band, H zone, and the entire sarcomere itself can shorten during contraction
• The A band spans the length of the thick filament within the sarcomere
• The sarcoplasmic reticulum: specialized ER that surrounds myofibrils and functions as a pouch filled with calcium
• Cross bridges form when myosin heads bind to actin, causing the sliding of thin and thick filaments
• This sliding of filaments is the mechanism of muscle contraction
• Troponin: a regulatory protein that binds to calcium and interacts with tropomyosin
• Tropomyosin: a regulatory protein attached to actin that prevents myosin from binding
• AP in a motor neuron at the neuromuscular junction leads to an AP within muscle fibers
• The AP propagates along the muscle fiber membrane and into T-tubules
• Voltage increase in T-tubules leads to the conformational change of DHP receptors
• DHP receptors physically interact with and cause RyRs in the sarcoplasmic reticulum to open.
• Calcium flows out of the sarcoplasmic reticulum through the RyR and into the cytoplasm
• Cytosolic calcium binds to troponin, which causes tropomyosin to shift and reveal binding sites on actin
• Myosin cross bridges bind to actin and thick/thin filaments slide past each other, thus shortening the sarcomere (specifically shortening the H zone and I band) and contracting the muscle
• After contractions take place, Ca2+ ATPase (i.e. SERCA) pumps Ca2+ back into SR, thereby leading to low cytosolic Ca2+ that causes tropomyosin to block myosin from binding to actin once again
• Cytosolic Ca2+ levels rise and myosin cross-bridges bind to actin
• Cross-bridge moves
• When ATP binds to myosin, the cross-bridge detaches from actin
• Myosin acts as an enzyme that catalyzes ATP hydrolysis and re-energizes the cross-bridge
• AP frequency impacts the force generated by the muscle
• If the AP firing rate increases in the motor neuron, then the force of muscle contraction increases
• Motor units impact the force generated by the muscle
• If the number of recruited motor units increases, then the force of muscle contraction increases
• Types of Muscle Fibers include Fast glycolytic fibers, Fast oxidative glycolytic fibers, and Slow oxidative fibers
• Fast motor units rapidly generate a high amount of force over a short time span and will fatigue easily
• Slow motor units generate a lower amount of force over a longer time span and do not fatigue as easily
• Within a muscle, there is a mixture of different fiber types
• Slow fibers are recruited first and fast glycolytic fibers are recruited last
• Slow oxidative fibers have the smallest diameter, while fast glycolytic fibers have the largest diameter
• Slow oxidative fibers rely on oxidative phosphorylation for ATP giving them a high amount of mitochondria and capillaries
• Fast glycolytic fibers rely on glycolysis
• Skeletal muscle has voluntary movement, striated appearance, chemical synapses
• Smooth muscle has involuntary movement, unstriated, unstriated appearance
• Cardiac muscle has involuntary movement, striated, electrical synapses

Circulation

• The heart is a mechanical pump that generates the force to move blood
• Blood vessels serve as tubing through which blood moves
• Arteries carry blood AWAY from the heart, but are not always carriers of high oxygen blood (pulmonary artery carries low oxygen blood)
• Veins bring blood TOWARD the heart, but are not always carriers of low oxygen blood (pulmonary vein carries high oxygen blood)
• Capillaries are the smallest vessels where nutrients, waste, exchange occurs between surrounding tissues
• Blood is a liquid carrier of cells, nutrients, proteins, and gases
• The circulatory system has two connected circuits: pulmonary and systemic
• Blood in the circulatory system is moved via bulk flow from regions of high pressure to regions of low pressure
• Valves are passive devices that open and close in response to pressures in the chambers they separate and only allow for one-way flow
• Heart anatomy includes 4 main chambers: left and right atria (top) and left and right ventricles (bottom)
• The septum separates the left and right side of the heart
• The pulmonary vein brings oxygenated blood from lungs to the left atrium
• The Vena Cava brings deoxygenated blood from the body to the right atrium
• AV valves separate the atria from the ventricles
• Blood exits the left ventricle through the aortic valve and enters the aorta
• Blood exits the right ventricle through the pulmonary valve and enters the pulmonary artery
• Blood Flow: Pulmonary capillaries pick up oxygen and oxygenated blood exits the lungs through the pulmonary vein (PV), and enters the heart at the left atrium (LA)
• Blood flows from the LA through the left atrioventricular valve (left AV valve, or mitral valve) into the left ventricle (LV)
• Blood exits the LV through the aortic valve, enters the aorta (biggest artery), and travels through networks of arteries, eventually branching into capillaries, delivering oxygen to targets in the body
• Once blood delivers oxygen to its target cell, it becomes deoxygenated
• Deoxygenated blood then travels through a network of veins, converging at the vena cava. The vena cava delivers deoxygenated blood into the right atrium (RA)
• The blood flows from the RA through the right atrioventricular valve (right AV valve or tricuspid valve) into the right ventricle
• The blood exits the right ventricle through the pulmonary valve, entering the pulmonary artery
• Deoxygenated blood becomes oxygenated at the lungs and then returns to the LA via the pulmonary vein
• Mechanical View of the Cardiac Cycle
• As blood enters the atria through the veins
• Once Patrial > Pventricular, the AV valves open. This allows blood to passively enter the ventricles until they are about 80% full. To push out the remaining 20% into the ventricles, the atrial muscle cells contract simultaneously
• The atrial cells are beginning to relax while simultaneously the ventricular cells contract Pressureventricular increases -The atrical atrial valves close, and isovolumetric contraction occurs in the ventricles. As the pressure continues to increase in the ventricles, the aortic and pulmonary valves open
• As the arteries fill with blood from the ventricles, Parterial increases. Meanwhile, Pressureventricular decreases as the cells of the ventricles relax, meaning that eventually the aortic and pulmonary valves close. Once they close, the ventricles undergo an isovolumetric relaxation
• The cycle repeats again as blood enters the atria from the veins
• Atrial Pressure>Ventricular Pressure: The AV valves are open
• When atrial pressure<Ventricular Pressure: The AV valves are closed
• When ventricular pressure>arterial pressure: The aortic/pulmonary valves are open
• When ventricular pressure<arterial pressure: The aortic/pulmonary valves are closed
• Isovolumetric relaxation/contraction: when the ventricles relax/contract while the AV valves and aortic/pulmonary valves are all closed
• Electrical point of view of the heart
• The SA node has the highest AP firing rate(pacemaker)/determines HR
• The AV node has an intermediate AP firing rate -The Bundle of His, bundle branches, and Purkinje fibers have the lowest AP firing rate
• Cells are connected via gap junctions, meaning that the SA node is the pacemaker of the heart causing all other cells to follow its firing rate
• The SA node generates an AP that quickly spreads throughout the atria, leading to a simultaneous contraction of the atrial muscle cells (contractile cells)
• The AP reaches the AV node via an internodal pathway. It then SLOWLY is transmitted from the AV node to the bundle of His and has a 150 msec delay between contractions in the form of 100 msecs due to the AV node
• The AP spreads from the bundle of His to bundle branches to the Purkinje fibers to then the ventricular muscle cells contracting simultaneously
• Pacemaker cells are conducting cells and are non-contractile
• High expression of HCN4 gene, and have the F/funny channel
• Open when voltage is decreasing (V-gated, open when voltage is BELOW a certain threshold)
• High expression of HCN4/funny channel causing autorhythmicity in heart CCS cells (i.e. heart rate)
• Permeable to K+/Na+ (E funny ≈ 0 mV)
• When V > -40 mV, G1=0, channel is closed
• If V < -40 mV, Gf>0, channel is open
• When the cell is repolarizing AP, as K+ flows out of the cell, the voltage decreases. At this point, once voltage drops below -40 mV, the funny channel opens
• Once the V-gated potassium channels fully close, movement of K+ and Na+ through the funny channel cause a depolarization in the cell
• Once -40 mV is reached, the funny channel closes. At the same time, threshold is reached for V-gated calcium and V-gated potassium channels.
• At the ventricular muscle cell AP, when neighboring cells fire an AP, electrical synapses allow the cell to go from rest to threshold very quickly
• Voltage gated Na+ channels open quickly, and cause a cardiac muscle AP peak
• Voltage gated K+ channels open and begin to bring Vm down
• Voltage gated Ca2+ channels have a higher threshold and open slower than Na+ channels and voltage gated Ca2+ channels stay open for longer
• The ventricular ap is comprised of the following phases
• The P-wave indicates Atrial muscle depolarization
• From P-wave to QRS complex (lasts 150 ms) indicates Atrial muscle plateau
• The QRS complex(spike) indicates Atrial muscle repolarization & ventricular muscle depolarization
• From QRS complex to T-wave (lasts 300 ms) indicates Ventricular muscle plateau
• The T-wave indicates Ventricular muscle repolarization
• Large arteries are low resistance conducting vessels that withstand high levels of pressure with some elasticity (can stretch/expand) and transport a lot of blood under high pressure
• The Arteries contain several elastic layers, layers of smooth muscle and connective tissue, and an endothelial layer
• Arteriolesmain resistance vessels, control the distribution of blood flow to tissues and organs
• Smooth muscle regulates the diameter of arterioles, which regulates blood flow to different organs and is a key regulator of overall blood pressure
• They are smaller, surrounded by an endothelial layer and smooth muscle, with the following relationships: smoother muscle contraction leading to smaller arteriole diameter leading to less blood flow and smooth muscle relaxation leading to larger arteriole diameter and therefore more blood supply
• Capillaries are very small in diameter, one cell layer thick and are the site of exchange of gases, fluid, and nutrients
• They contain no smooth muscle or connective tissue, just endothelial cells
• Low blood flow, a high surface area and a very thin endothelial layer maximize substance exchange
• Key gas and nutrient exchange is largely driven by concentration gradients (diffusion): Glucose, oxygen, CO2
• Capillary lumen is the space inside the capillary where blood is
• Erythrocyte is the red blood cell and has to move in a single file since the diameter is so small
• The Endothelial layer is 1 cell thick and helps with the fast transfer of substances
• Intercellular clefts facilitate exchange by creating fluid-filled spaces in between capillary cells making the capillaries porous
• MAP=Cardiac Output (CO) x Total Peripheral Resistance (TPR
• MAP = average arterial pressure throughout one cardiac cycle
• TPR = resistance to flow in the circulatory system
  • Largely driven by constriction versus dilation of arterioles
• ----Relaxed smooth muscle→ dilated/lower TPR and MAP
• ----Contracted smooth muscle constricted/ higher TPR and MAP -CO = volume of blood pumped out per unit time (related to heart rate and how much blood is ejected each beat) -If MAP < set point, the brainstem responds by activating the sympathetic nervous system -If MAP > set point, the brainstem responds by activating the parasympathetic nervous system
• Mechanoreceptive neurons whose terminals are in the carotid artery have channels that respond to physical pressure
• At the set point, they fire at a non-zero baseline/steady-state firing rate as the firing rate of axons is directly related to blood pressure (higher firing rate with higher blood pressure)
• In cases wehre MAP is low, the firing rate is low, which leads to sympathetic nervous system activation causing sympathetic firing rate increases and parasympathetic firing rate decreases
• When neurons act on the heart resulting in Norepinephrine that increases cAMP, this then causes more current, less funny channels open, resulting in decrease slope, later APs.
• Arterial smooth muscle that is acted on by Neurons causes.

Respiration Topics

• Ventilation handles the movemnt of air

• Perfusion handles the exchange of Oxygen and Carbon Dioxide

• Regulation handles the short and long term feedback loops

• Pleural cavity contains the lungs, which are divided by a septum

• Gas exchange occurs between the alveoli and capillaries

• The conducting zone has thick walls and wide pathways to facilitate gas movement

• The respiratory zone has thin walls and narrow pathways to facilitate gas exchange

• Inspiration: moving air in

• This is an active movement

• There is a contracture of the diaphragm and intercostal muscles

• This expands the space resulting in less pressure so air moves into the lungs

• Expiration: letting air out

  • This is a passive movement
  • Diaphragm and intercostal muscles relax, decreasing the space causing the space so air moves out All muscle contractions are generated by skeletal muscle

• Ach binds to nAChR for ventilation

• There are no muscles in the lungs

• Pneumothoraxes occur when the pressure in the pleural cavity(the space between the ribs and the lung) becomes greater than the pressure in lung space

• Maximal Inspiration is when neurons release a small amount of air from our lungs in their natural situation, we breathe out all of the air in our lungs

• There is no barrier between Air to Alveoli, however, there is ab arrier between the Alveoli and the capillaries

• Oxygen is almost all bound to Hb

• CO2 is comprised of 10%in the blood & in RBC cytoplasm, 30% bound to Hb, and 60% as bicarbonate

• Hb S curve works with cooperativity when O2 binds, induces conformational change making easier for next to bind

• Hb acidity also have effect -when O2 Binds at the tissues where PO2 decreases, the Hb affinity for O2 decreases so more O2 can bind tissues

  • PO2 decreases, so more O2 can bind when the blood returns to the heart

• When oxygen binds to Hb, it is not longer considered a gas, which allows more oxygen to enter the RBC

• Carbonic Anhydrase (CA) catalyzes the following reaction: CO2+H2O H2CO3 HCO3 + H+ and AE1 is responsible for the movement of Cl- & bicarbonate

• bicarbonate always moves with its concentration gradient

• Short Term Peripheral feedback regulation loops control+ H+ via the following loop

• Neurons in the brainstem/medulla oblongata release motor neuron activity that affect muscles that control ventilation

• Chemoreceptor cells in the aortic control and carotid arteries will increase frequency with high content

• The Short Term Central H feedback regulation loops includes

• Neurons in the brainstem/medulla oblongata, release motor neuron activity that affect muscles that control ventilation

• Chemoreceptor neurons in brainstem/medulla oblongata

• The Short Term Peripheral O2 feedback loop is used primarily in those with COPD which include

• Neurons in the brainstem/medulla oblongata release activity within the muscles that control ventilation in response O2 levels in cartoid arteries

• The Longterm term regulation loop is

• Increased EPO in peritubular intstitial cells in kidney leads to a increase in RBC precursor cells in bone marrow generating more RBC

To tying all the topics together

1. Muscle activation think about the motor neurons being activated.
2. [CO2] increases, more CO2 binds to Hb
3. Hb affinity for O² decreases so more O² is offloaded at the tissues think about the bicarbonate exchange with AE1 and conversion with CA
4. PO² decreases, so more O² can bind when the blood returns to the heart
5. O² is brought back to the area, blood flow increases due to increased metabolic activity.