Phys Exam 2
Net Filtration Pressure
(Pc + Piif) - (Pif + Pic) Pnet = DP - Dpi Filtration occurs at arterial end where capillary hydrostatic pressure is high Uptake occurs at venous end where capillary hydrostatic pressure is low
Muscle ATP
1. ATP from Creatine Phosphate ATP->ADP Creatine->Creatine Phosphate ADP->ATP Energy provided for 15 seconds 2. ATP from Anaerobic Glycolysis Muscle Glycogen Glucose 2 Pyruvic Acid 2 Lactic Acid Energy provided for 2 minutes 3. ATP from Aerobic Respiration Fatty Acids + Amino Acids + Pyruvic Acid + Oxygen = Krebs Cycle and ETC = Heat + 30/32 ATP + CO2 + H2O
Position of AV Valves and Aortic and Pulmonary Valves
AV open during ventricular filling Both closed during isovolumetric contraction AP open during ejection Both closed during relaxation
Events at the Neuromuscular Junction
AcCh binds allowing Na to enter causing depolarization and then action potential in muscle fiber Propagated action potential in muscle plasma membrane
Skeletal Muscle - Motor End Plate
Acetylcholine is the receptor
Cardiac Muscle Conduction System
Action Potential SA Node (Pacemaker rate 60/min) Depolarization wave propagates through Atria Atrioventricular Node Atrioventricular Bundle (Bundle of His) Right and Left Bundle Branches Purkinje Fibers Allows for things to be pushed from the bottom up in the heart
Skeletal muscle order of events
Action potential in skeletal muscle Rise in calcium Latent period: Time between action potential and beginning of force development Contraction occurs
Activation and Selection of T-Cells
Active helper T cells proliferate and differentiate into more active helper T cells and memory helper T cells Active cytotoxic T cells proliferate and differentiate into more active cytotoxic T cells and memory cytotoxic T cells
Immune Balance: T-Cells
Anti-inflammatory response: Tregs and Th2 Pro-inflammatory response: Th1 and Th17
Antigen Processing
Antigen is broken down and class II MHC proteins present antigen to CD4 Helper T Cell
Pressures
At peak of R Phase: Bicuspid valve closes S Phase: Aortic valve opens End of T Wave: Aortic valve closes Relaxation Period: Bicuspid valve opens
Muscle Contraction Cycle
Attached State ATP binds to myosin - No ATP - Rigor Mortis Released State ATP is hydrolyzed returning myosin to rest Cocked State When Ca levels increase a cross bridge forms and the myosin head binds to another position on actin Cross-Bridge State P is released Power-Stroke State ADP is released
Regulation from Multiple Sources
Autonomic System + Respiratory System + Hematopoietic Organs and Liver + Urinary and GI Systems + Endocrine System + Temperature Control System CO, MAP, TPR, BV, etc
Drugs Used to Treat Hypertension
BETA-BLOCKERS (Beta Antagonists) ACE INHIBITORS (ACEIs) DIURETICS
Drugs Used to Treat Heart Failure
BETA-BLOCKERS (Beta Antagonists) DIURETICS VASODILATORS CARDIAC INOTROPICS
Hypovolemic Shock
Baroreceptors in carotid sinus aorta detect blood pressure and volume decrease Decreased rate of nerve impulses affects medulla oblongata which increases sympathetic stimulation Increases HR and contractility in heart Constricts blood vessels
Ryanodine Receptor Channel - Beta Adrenergic Modulation
Beta Adrenergic Receptor is activated by nor/epinephrine Activates G protein Activates Adenylate cyclase Activates cAMP Activates PKA Phosphorylates Ryanodine: In unstimulated state is a little more leaky In stimulated state it is open for longer durations allowing greater flux of Ca Also phosphorylates SERCA, a calcium reuptake pump for the SR
Effect of Norepinephrine
Beta-adrenergic effect -> More Ca -> More force -> More contractility Isometric Contraction: Peak tension curve is higher Afterloaded Contraction: Peak tension curve is higher Beta-adrenergic effect on SV helps compensate for increased afterload effect (Lower SV)
Summary Contraction Cycle
Binding of Acetylcholine to muscarinic receptors Increased influx of Ca into the cell Activation of calmodulin-dependent myosin light chain kinase Phosphorylation of myosin Increased myosin ATPase activity and binding of myosin to actin Contraction Dephosphorylation of myosin by myosin light chain phosphotase Relaxation or sustained contraction due to the latch bridge and other mechanisms
Smooth
Blood vessels No sarcomeres Gap junctions Calmodulin and myosin light chain kinase Involuntary Acetylcholine and norepinephrine Considerable regeneration
Sympathetic Activity Effect on Arterioles
Neurons -> Norepinephrine -> Alpha 1 Blood -> Epinephrine -> Alpha 1 and Beta 2 Alpha 1 - Causes vasoconstriction Beta 2 Causes vasodilation
WBC Counts
Neutrophils: High - Bacterial infection and inflammation Lymphocytes: High - Viral infection and mononucleosis Monocytes: High - Chronic disease Eosinophils: High - Parasitic infections and autoimmune disease Basophils: High - Leukemias, cancers, and hypothyroidism
Major Factors Affecting Arteriolar Radius
Nitric Oxide is a vasodilator
Local Effectors of Vascular Tone
Nitric Oxide: Vasodilation Acetylcholine: Both; depending on receptor Endothelin: Vasoconstriction Histamine: Vasodilation
Skeletal Muscle Action Potential
No hyperpolarization due to a lower resting membrane potential (-90mV). Neurons hyperpolarize. Skeletal muscle does not
Fibromyalgia
Nonarticular rheumatic disorder - Inflammation of connective tissue in muscles
Centrifuged Blood and Hematocrit
Normal - 45% Low hematocrit - Anemia High hematocrit 65%+ - Polycythemia
Pressures
Normal: 120/-80 Prehypertension: 120+/80+ Hypertension Stage 1: 140+/90+ Hypertension Stage 2: 160+/100+
ECGs: AV Conduction Block
Normally should have a P for every QRS Partial AV Block: Occasional P without a coupled QRS Complete AV Block: Ps not coupled to QRS (random)
Concentric and Eccentric Exercise
Concentric (isotonic) - Muscle shortens while contracting Isometric - Muscle contracts against physical resistance of equal force, muscle length unchanged. Most efficient way to induce hypertrophy Eccentric Exercise - Muscle attempts to contract while simultaneously being passively stretched. Used to control or cushion a movement. Only possible if some fibers contract and other relax at the same time, causing large differential forces that may result in structural disruption Delayed onset muscle soreness and muscular injury usually occur from extensive eccentric exercise
Dystrophin
Connects thin filaments to transmembrane proteins and bind to laminin Responsible for Duchenne and Becker muscular dystrophy
Lymphatic System
Consists of: Lymph Lymphatic vessels Lymphatic tissues Red bone marrow
Role of Phagocytosis in Innate Immune Response
Contact of phagocytes with microbes Phagocytosis: Intracellular killing of microbes Secretion of chemicals by phagocytes: Regulation of inflammatory process - Nitric Oxide Extracellular killing of microbes Activation of clotting pathway and anticlotting pathways Hormonal regulation of overall bodily responses to infection
Muscle Fatigue
Not due to depletion of ATP 1. Lactic Acid build up (pH) 2. Central command fatigue - Neurological 3. Failure of excitation contraction coupling 1. Depletion of Creatine Phosphate 2. Insufficient O2 3. Depletion of nutrients 4. Build up of Lactic Acid or ADP 5. Insufficient release of Ca from SR
Functional Differences Between Striated and Smooth Muscle
Contraction is much slower in smooth muscle Smooth muscle thin actin filaments lack troponin protein Smooth muscle Ca activates kinases that will eventually induce conformational changes of the myosin heads in order to form cross bridges Smooth muscle cell overall contraction squeezes the cell from every direction
Skeletal Muscle Electricity Contraction Coupling
Contraction: Discharge of motor neuron ACh release at motor end plate Activates ion channels Na and K causes potential Action potential propagation along T-tubules Release of Ca from SR to thick and thin filaments Binding of Ca to troponin C to uncover myosin binding sites on actin Formation of cross linkages and sliding of filaments to produce movement Relaxation: Ca pumped back into SR Release of Ca from troponin Actin and myosin dissociation
Activation of Smooth Muscle Contraction
Cytosolic Ca increases Ca binds calmodulin and is activated Activates myosin light-chain kinase Uses ATP to phosphorylate myosin Phosphorylation forces cross-bridges toward thin filament Cross-bridge cycling Myosin light-chain phosphatase causes relaxation and is activated by low Ca levels
Compensation for Hemorrhage
Decrease in arterial pressure Decrease in baroreceptor impulses Parasympathetic decrease + Sympathetic increase in heart Increase HR Sympathetic increases in veins and arterioles Increase in constriction All lead back to an increase of SV to normal CO increase to normal Pressure increase to normal
Compensation for Blood Loss
Decrease in arterial pressure + Constriction of arterioles Decrease in capillary hydrostatic pressure Increase in fluid absorption from interstitial compartment Plasma volume increases Restoration of pressure
Factors that Increase Blood Pressure
Decreased blood vessel radius Increased blood vessel length Increased blood viscosity Increase in Resistance MAP = CO x Total Peripheral Resistance
Heavy Load
Delay longer - Longer time to build tension Velocity slower - Increased crossbridge load Duration shorter - Can only do so much work with one AP
P Wave to R Wave Interval
Depolarization of atrial contractile fibers produce P wave Atria (systole) contract AV electrical conduction. Time needed for signal to go from atria to ventricular muscle cells
Cardiac Muscle
Desmosomes Gap Junctions
Heart Valves Operation - Mitral Valve
Differential hydrostatic pressures open and close valves
Factors in Blood Cell Differentiation
Differentiation into T cell occurs in the thymus
Anaerobic Pathways
Direct Phosphorylation Creatine Phosphate Oxygen Use: None Products: 1 ATP per CP and Creatine Duration of Energy Provided: 15 secs Anaerobic Pathway: Oxygen Use: None Products: 2 ATP per glucose and Lactate Duration of Energy Provided: 30 seconds
Beta Blockers
Dissociation of calstabin from RyR2 increases channel opening and causes Ca leak from the SR into the cytoplasm. Depletes Ca stores in cell An important contributor to impaired Ca handling in HF is PKA hyperphosphorylation of RyR2. Beta-adrenergic g coupled receptor is leads to cAMP and then PKA and RyR2 is phosphorylated making it move more Ca when activated but also leak a little
Functions of the Lymphatic System
Draining excess interstitial fluid Transporting dietary lipids from the GI to the blood Protecting against invasion through immune responses
Cardiac E-C Coupling
Dyad - Ca channel on T-tubule coupled with RyR on SR Peripheral Coupling - L type Ca channel not in T-tubule coupled with RyR Metabolism in cardiac fibers is exclusively through aerobic cellular respiration Cardiac cells also metabolize lactic acid into ATP Contain myoglobin and creatine kinase
Cytoskeletal proteins attachments to transmit force
Dystrophin complex connects to thin filament alpha actinin is also connected to thin filament Titin is a massive protein which connects to alpha actinin and thick filament PEVK region causes spring like movement
Cardiac Cycle
ECG Pressures Hear Sounds Volumes 4 Phases
Factors that Determine Systemic Artery Pressure
End-diastolic volume + plasma epinephrine + para/sympathetic nerves to heart SV x HR CO x TPR MAP
Selected Human Colony Stimulating Factors (CSF)
Erythropoietin - RBC growth G-CSF - Granulocyte growth and differentiation M-CSF - Monocyte-macrophage growth and differentiation GM-CSF - Granulocyte and macrophage growth and differentiation IL-3 - Similar to GM-CSF
Factors in Blood Cell Differentiation
Erythropoietin GF leads to RBC Thrombopoietin GF leads to platelets In making RBC, there is a step in which mitochondria and ribosomes are lost and another in which there is exocytosis of the nucleus
Erythropoiesis
Erythropoietin comes from kidneys and is stimulated by a decrease in O2 to the kidneys Chronic Renal Failure - Anemia - Inability to produce erythropoietin Renal Artery Stenosis - Constant lack of O2 so constitutive erythropoietin
Skeletal Muscle - Impaired Metabolism Insulin Resistance
Excess energy supply leads to accumulation of intramyocellular lipids which leads to impaired metabolism
Control of Smooth Muscle Contraction
Extrinsic Control: Neuronal Control - Sympathetic fibers - usually hyperpolarize - Parasympathetic effect - usually depolarize - Humoral control Intrinsic Control: -Myogenic Autoregulation - Stretching of the smooth muscle cells which induce spontaneous depolarization and contraction -Local humoral control - autocrine and paracrine
Radius and Resistance Effects on Flow
F = Delta P / R F : Flow P: Pressure R: Resistance Poiseuille's Law: R = 8Ln / pi(r^4) L = Length n = Fluid Viscosity r = Inside Radius 8/pi = Constant R = 1/r^4
Type IIb (x in humans)
Fast Glycolytic: Small amount of myoglobin Few mitochondria Few capillaries White Fast to fatigue
Type IIa
Fast Oxidative-Glycolytic: Large amount of myoglobin Many mitochondria Many capillaries Red-pink Intermediate to fatigue
Abnormal ECGs
First Degree AV Block: Long P-Q Interval Atrial Fibrillation: No detectable P waves and irregular RR intervals Ventricular Tachycardia: Very fast ventricle contraction Ventricular Fibrillation: No blood being pumped
Innate Immunity
First Line of Defense: Skin and Mucous Membranes Second Line of Defense: Internal Defenses Interferons - Protect uninfected host cells from viral infection Complement System - Causes cytolysis of microbes, promotes phagocytosis, and contributes to inflammation Natural Killer Cells - Kill a wide variety of microbes and certain tumor cells Phagocytes - Ingest foreign particulate matter
Blood-Flow Distribution
Forgan = (MAP -Pvenous) / Rorgan Pvenous ~ 0 Forgan = MAP / Rorgan
Hematopoiesis
Formation of Blood Cells Pluripotent Stem Cell -> Lymphoid Stem Cell -> T cell -> B cell -> Plasma Cell -> NK cell Pluripotent Stem Cell -> Myeloid Stem Cell -> Monocyte -> Macrophage
Hematopoiesis
Formation of Blood Cells: Pluripotent Stem Cell Myeloid Stem Cell or Lymphoid Stem Cell Myeloid - Go to RBC Lymphoid - Go to lymphocytes
Q-T Interval
From beginning of ventricular depolarization through ventricular repolarization Time when ventricle (systole) is contracting
One sarcomere
From one z line to the next Z lines are made of alpha actinin
Muscle Mechanics
Fulcrum, Effort, Load EFL: First-class lever - Scissors and Jaw FLE: Second-class lever - Wheelbarrow and standing on toes FEL: Third-class lever - Tweezers and Bicep
Catecholamine Mediated Muscle Adaptation
Glycolysis in muscle Epinephrine stimulates breakdown of glycogen and more blood glucose/more energy
Cardiac
Heart Sarcomeres Gap junctions Troponin and tropomyosin Involuntary Acetylcholine and norepinephrine Limited regeneration
Portion of Blood Volume
Heart - 15% Pulmonary - 12% Systemic - 73% 18% Arteries 50% Veins 5% Capillaries
Basic Parts of Circulatory Systems
Heart - Organ of propulsion Arterial System - Distribution of blood + pressure reservoir Capillaries - Transfer of materials between blood and tissues/cells Venous System: Return of blood to heart + volume reservoir Blood
B-Cells (Humoral Immunity = Antibody Production)
Helper T cell activates B cell through IL-2 and cause proliferation for B cells which contain a specific antibody for original antigen and memory B cells
Killing of Virus Infected Cells
Helper T cell through IL-2 and other cytokines activate cytotoxic T cell and leads to proliferation so that they can go all over the body
Effects of Arteriolar Tone on Pcapillary
Higher Resistance = Greater Pressure Drop
Factors that Determine Systemic Artery Pressure
Hormonal control, neural control, local control Arteriolar radius + blood viscosity CO x TPR MAP
Functions of ATP in Skeletal Muscle
Hydrolysis of ATP by the NA/K-ATPase Hydrolysis of ATP by the Ca-ATPase Hydrolysis of ATP by myosin Binding of ATP to myosin dissociates cross-bridges
Cardiac Ion Channel Characteristics
I Ca - Ca Channel (Slow inward, L channels) - Enhanced by sympathetic stimulation and Beta-adrenergic agents I KACh - K Channel (Acetylcholine activated) - Responsible for effects of vagal stimulation I funny - Na (Pacemaker current) - Enhanced by sympathetic stimulation and Beta-adrenergic agents Is suppressed by vagal stimulation
Infection Induced Fever
IL-1 and IL-6 increase temperature setpoint in hypothalamus Leads to shivering, using blankets, and vasoconstriction Leads to increased heat production and less heat loss Heat production greater than that of loss Heat retention leads to increase in body temperature
Characteristics of Human Immunoglobulins
IgG - 75-80% - Major Ab of secondary response Neutralizes toxin Activates complement Opsonization of phagocytosis Only class to cross placenta giving fetus and newborn protection
Tacrolimus
Immunosuppressant given to prevent organ transplantation rejection that binds to Calstabin1 (FKBP12)
Baroreceptor Reflex
Increase in MAP leads to decreased HR and vascular tone to reduce pressure
Cardiac Output
Increase in end-diastolic ventricular volume Increase in sympathetic nerves to the heart Increase in plasma epinephrine Decrease in activity of parasympathetic nerves to the heart Increase in stroke volume and increase in heart rate Increase in cardiac output Cardiac Output = SV x HR
Why is membrane potential lower
Increased K gradient Increased Cl gradient Greater resting Cl permeability
Factors Affecting Peripheral Venous Pressure
Increased activity of sympathetic nerves to veins Increased blood volume Increased skeletal muscle pump Increased inspiration movements All lead to increased venous pressure Increased venous return Increased atrial pressure Increased End-diastolic ventricular volume Increased stroke volume
Assessment of Contractility
Increased contractility - Increases SV Increased preload - Increases SV Increased afterload - Decreases SV Increased B-adrenergic - Increases SV
Factors Affecting Cardiac Output
Increased preload Increased contractility Decreased afterload Increased SV Nervous System Chemicals Other factors Increased HR Both lead to increased CO
Dexamethasone
Inhibits IL-1 and is a glucocorticoid that dampens immune system Causes salt water retention and causes puffiness
Non-Specific and Immunogen-Specific Mechanisms
Innate - Defense without having to recognize specific identities Nonspecific Adaptive - Defense recognizing specific identities Specific Cell-mediated Humoral
Leukocytes
Innate Immune Compartment: Dendritic Cells Macrophage - First line of defense NK Cells Adaptive Immune Compartment: Helper T Cells Regulatory T Cells Cytotoxic T Cells
Baroreceptors and Autonomic Innervation of Heart
Innervation to the Medullary Cardiovascular Center in the medulla oblongata
Lymph Node
Inputs: Afferent lymphatic vessels Route of lymph flow through lymph node: Afferent lymphatic vessels Subcapsular sinus Trabecular sinus Medullary sinus Efferent lymphatic vessel
Insulin Effects on Skeletal Muscle
Insulin binding to insulin receptor activates GLUT4 and transports glucose into the muscle cell Insulin can also bind to epinephrine receptor and activates cAMP Both lead to activation of Na/K-ATPase pump
Cascade Intrinsic and Extrinsic
Intrinsic - Minutes Extrinsic - Seconds Factor 8: A co-factor which when absent leads to hemophilia Procoagulant - Cleaves fibrinogen to fibrin, activates several factors, and leads to platelet activation
Isometric and Isotonic Contractions
Isometric - Constant Length Latent period is Ca buildup Relaxation is slower due to differences in speed of SERCA (Pump) compared to Ryanodine (Ion Channel) Isotonic - Constant Tension Latent period is Ca buildup and time for tension to equal the load Relaxation is faster due to weight of gravity on load
Types of Contraction
Isometric: No shortening Force increases Isotonic: Shortening Force is constant
Natural Killer Cells
Kill viral infected cells and some cancer cells Natural killers do not require activation to kill cells that are missing self markers of MHC class 1 Important because harmful cells that are missing MHC 1 markers cannot be detected by other immune cells
Summary of Adaptive Changes with Training
Krebs cycle enzymes increase Increase in conversion of phosphorylase b to a Increased capillary growth leading to more blood supply Increase maximal oxygen uptake ability Increase size of muscle fibers for more glycogen storage
Blood Vessels
Large Vein - Volume Reservoir Few layers of smooth muscle and connective tissue Less elastic Thin Large Artery - Pressure Reservoir Many layers of smooth muscle and connective tissue More elastic Thick
Cardiac Muscle Cells - Preload
Larger preload leads to more shortening Larger ventricular preload leads to more stroke volume
Cardiac Muscle Cells- Afterload
Larger total load leads to less shortening Larger ventricular afterload leads to lower stroke volume
Role of Liver in Blood Clotting
Liver synthesizes bile salts Bile salts in bile GI tract absorbs vitamin K Vitamin K in blood Liver synthesizes clotting factors Clotting factors in blood
Isotonic Contraction Heart
Load (preload): Filling Afterload: Aortic pressure
Filament Interaction
Low cytosolic Ca - Relaxed muscle High cytosolic Ca - Activated muscle: Calcium binds to troponin and cross-bridge binding sites are exposed for myosin and binding occurs generating force
Heart Sounds
Lub - AV valves closing Dub- Aortic valves closing
Cells Mediating Immune Response
Lymphocytes: Serve as recognition cells in specific immune responses and are essential for all aspects of these responses B Cells: Initiate antibody-mediated immune response by binding specific antigens to B cell immunoglobulins Upon activation, transformed into plasma cells which secrete antibodies Present antigen to helper T cells Cytotoxic T Cells: Bind to antigens on plasma membrane of target cells and directly destroy the cells Dendritic Cells: Phagocytosis, antigen presentation
PKC Phosphorylation of Myosin LC
MLCK phosphorylates myosin light chain Protein Kinase C also phosphorylates MYC at a different site Myosin-actin interactions are inhibited
Muscle Shortening and Load: Force-Velocity Relationship
Maximum velocity occurs at smallest load Maximum force develops at greatest load
RR Interval
Measures heart rate Hear rate = 1/cycle length
Systemic Response to Infection (Acute Phase Responses)
Monocytes and macrophages secrete IL-1, TNFalpha, and IL-6 * Glucocorticoids as an immunosuppressant due to inhibition of IL-1 and TLR signaling Increase in plasma Brain: Fever - Enhances protective responses Hypothalamus Anterior Pituitary: Negative feedback on immune system
Muscle and Glycolysis
Muscle is the largest glycogen storage organ 4x the liver A single bout of exercise improves whole-body insulin sensitivity for up to 48 hours Exercise is one of the most effective ways to prevent metabolic syndrome and type II diabetes mellitus
Delayed Onset Muscle Soreness (DOMS)
Muscle pain during exercise due to metabolite accumulation, soreness the next day is not First Phase: Microtrauma of the muscle Cell membrane damage Second Phase: Macrophages and neutrophils infiltration Soreness due to elevated extracellular K, PGE2, edematous pressure, and inflammatory bradykinin With or without treatment DOMS disappears after a few days
Muscle Fiber Type Switching
Muscle type can be modified to adapt to needs of functions performed
Thick and thin filaments that make up sarcomeres
Myofilaments: Thick: In center Thin: Go through z line M band in middle
Electrocardiogram
Only the contractile muscle depolarization is seen on the EKG. Ventricular contractile muscle repolarization can be seen but not atrial repolarization P: Atrial Depolarization QRS: Ventricular Depolarization T: Ventricular Repolarization Shortly after AP, Ca levels rise and then force is developed
Pericardium and Pericarditis
Outer layer of the heart Pericarditis - Inflammation in the fluid of the pericardium
Aerobic Pathway
Oxygen Use: Required Products: 32 ATP per glucose, CO2, and H2O Duration of Energy Provided: Hours
Platelet Aggregation
PGI2 and NO inhibit platelet aggregation TXA2 promotes platelet aggregation
Phosphorylation of Myosin LC
PKA phosphorylates Myosin light chain kinase When phosphorylated it is inactive and MLC can't be phosphorylated Actin-Myosin interactions do not occur
Summary
PKC: P of Caldesmon - Contraction P of Myosin LC - Relaxation PKA: P of MLCK - Relaxation Ca-Calmodulin: Bound to Caldesmon - Contraction Activates MLCK - Contraction
Ventricular and Pacemaker Action Potential
Pacemaker: Na enters Ca2 enters K exits Na conductance increases with pacemaker potential Ca T (Transient) increases with pacemaker potential K decreases with pacemaker potential Ca L (Long Lasting) increases with depolarization K returns to normal during repolarization Ventricular: Na enters K exits Ca enters and K exits K exits High K conductance at rest Very high Na conductance at depolarization spike and K drops Decreasing Ca plateau looking at plateau K conductance returns at repolarization
Mechanical Properties of Sarcomere Arrangement
Parallel: Force doubled No change in velocity No change in shortening capacity Series: No change in force Velocity doubled Shortening capacity doubled
Factors that Affect Heart Rate
Parasympathetic (slower): Acetylcholine - Decreases Ifunny, opens GIRK, reduces Ica Sympathetic (faster): Norepinephrine - Increases Ifunny and increases Ica
Autonomic Innervation of the Heart
Parasympathetic: Slows heart rate Vagus nerves Acetylcholine Muscarinic receptors Atria Sympathetic: Raises heart rate Thoracic spinal nerves/Bloodstream Norepinephrine/Epinephrine Beta-adrenergic receptors Atria + Ventricles
Functions of Complement Proteins
Part of both specific and nonspecific immunity Direct destruction of invading microbes by membrane attack complex Vasodilation and increased permeability of capillaries and venules to proteins Chemotaxis Enhancement of phagocytosis (opsonization)
Tension
Passive tension in relaxed fiber Active tension developed in stimulated fiber
Aortic Pressures
Peak at 120 mmHg Low at 70 mmHg
Pulmonary Artery Pressure
Peak at 24 mmHg Low at 8 mmHg
Ca Cycling
Phospholamban controls (lowers) the rate at which SERCA moves Ca Increased Beta Adrenergic stimulation reduces the association of these two proteins and increases Ca reuptake
Plasma and Serum Proteins
Plasma can form a clot but does not react because it lacks platelets Serum - Use plasma cross-link fibrinogen and spin out to get serum
Derivation of B and T Cells
Pluripotent stem cells in bone marrow produce lymphoid stem cells Mature in Bone Marrow - B Cell -> Plasma Cell -> Antibodies Mature in Thymus - T Cell -> Helper and Cytotoxic
Factors that Affect Stroke Volume
Preload - Frank-Starling Law Contractility - Strength of contraction at given preload Afterload - Pressure that the ventricle must produce to open a semilunar valve
Contraction Experiments
Preload: Passively stretches muscle to a certain point and stop it Afterload: Load added on top of the preload
Activation of Helper T Cells
Presentation of antigen Binding of matching nonantigenic proteins Secretion of cytokines act on Helper T-Cell Interleukin-1 (IL-1): Stimulates and activates T and B cells Steroids block release of IL-1 thus inhibiting T cell proliferation
Erythrocyte - RBC Life Cycle
Produced in blood marrow and circulate for 120 days RBC death and phagocytosis by macrophage Globin is broken down into amino acids Heme is broken down into biliverdin -> bilirubin -> bile -> urobilinogen -> urobilin + stercobilin -> urine + feces Iron Fe3+ from heme binds to transferrin and transfers it to circulation
Functions of muscular tissue
Producing motions Stabilizing body positions Storing and moving substances within the body Generating heat (thermogenesis) In order to have movement all elements need to be connected
Clotting Pathway
Prothrombin to Thrombin Fibrinogen to Loose Fibrin Loose Fibrin to Stabilized Fibrin
Circulation in the Body
Pulmonary side has low resistance and low pressure Systemic side has high resistance and high pressure Parallel and Series arrangement of capillary beds Kidney - Series GI System - Series connected through portal
Formed Elements in Blood
RBCs - Hemoglobin within RBS transport most oxygen and part of CO2 in blood WBCs - Combat pathogens and other foreign substances that enter the body Neutrophils: Phagocytosis Eosinophils: Combats histamine allergic reactions Basophils: Inflammatory response
T Wave
Repolarization of ventricular contractile fibers Ventricular (diastole) relax
Malignant Hyperthermia
Results in muscle rigidity, acidosis, and very high body temperatures Dantrolene, a muscle relaxant, is used as treatment for this condition. Prevents release of Ca2+
Autoimmunity
Rheumatoid Arthritis - Autoreactive T cells against antigens of joint synovium Leads to joint inflammation and destruction causing arthritis
Lymphatic System Drainage
Right lymphatic duct Thoracic (left) duct Thoracic duct - Main duct for return of lymph to venous blood at junction of left internal jugular and left subclavian veins
What receptor gene is defective in most cases of malignant hypothermia
Ryanodine Receptor Gene RyR1
Mechanisms of Cytosolic Ca Removal
SERCA - Sarcoendoplasmic Reticulum Calcium Pump - Calcium ATPase for Calcium reuptake - Pumps out H+ and brings in Ca with ATP PMCA - Plasma Membrane Calcium Pump - Brings H+ in and Ca out with ATP NCX - Sodium Calcium Exchanger - Brings in Na and pumps out Ca
Volumes
SV = EDV - ESV SV: Stroke Volume EDV: End Diastolic Volume ESV: End Systolic Volume
Skeletal Muscle Triad
Sarcoplasmic reticulum Cisterna Transverse tubule Cisterna Sarcoplasmic reticulum
B and T Cells
Secondary Lymphatic Organs and Tissues Cell-Mediated Immunity: Directed against intracellular pathogens, some cancer cells, and tissue transplants Antibody-Mediated Immunity: Directed against extracellular pathogens
Activity of Cytotoxic T-Cell
Secrete granulysin and perforin to poke holes in membrane of infected cells and cause cytolysis
Short and Long Term Blood Pressure Regulation
Short Term: Baroreceptor Reflex Long Term: Fluid Balance Kidneys regulate long term BP by regulating volume
Sliding Filament Mechanism
Shows change in overlap of bands as thin filaments move towards M band
Myogram - Change in Frequency of Stimulation
Single twitch - One action potential Wave summation - Provide another action potential before tension fully drops Unfused tetanus - Repetitive action potentials causing stair stepped tension Fused tetanus - Fast repetitive action potentials causing linear tension increase
Muscle Type Comparison
Skeletal: Troponin, Sarcoplasmic Reticulum, Motor neuron Cardiac: Troponin, SR and Sarcolemma, SNS or PNS Smooth: Calmodulin, SL and SR, SNS or PNS
Type I
Slow oxidative: Large amount of myoglobin Many mitochondria Many capillaries Red Slow to fatigue
Smooth vs Skeletal Muscle Cell Contraction Pathway
Smooth muscle cells do not have troponin Smooth muscle myosin needs to be phosphorylated to bind actin Smooth Muscle: Cytosolic Ca up Ca binds to calmodulin in cytosol Ca-calmodulin complex binds to myosin light-chain kinase Myosin light-chain kinase uses ATP to phosphorylate myosin cross-bridges MLCK Phosphorylated cross-bridges bind to actin filaments Cross-bridge cycle produces tension and shortening Skeletal Muscle: Ca up Ca binds to troponin on thin filaments Conformational change in troponin moves tropomyosin out of blocking position Myosin cross-bridges bind to actin Cross-bridge cycle produces tension and shortening
Starlings Length Tension Diagram for an Entire Heart
Steep curve on systolic side Less drastic on diastole
Neural Regulation of the Heart
Sympathetic Stimulation: Increases HR Decreases AV Node Effective Refractory Period Decreases PR Interval Increases Contractility Parasympathetic Stimulation: Decreases HR Increases AV Node Effective Refractory Period Increases PR Interval
Distribution of Total Blood Volume
Systemic Veins and Venules 64% Pulmonary Vessels 9% Heart 7% Systemic Arteries and Arterioles 13% Systemic Capillaries 7%
Toll-Like Receptors
TLR4 - Lipopolysaccharide (LPS) TLRs bridge gaps between innate and adaptive immunity
Skeletal
Tendons and bones Sarcomeres Troponin and tropomyosin Voluntary Acetylcholine Limited regeneration
Factors Determining Muscle Tension
Tension Developed by Each Fiber: Action potential frequency Fiber length Fiber diameter Fatigue Number of Active Fibers: Number of fibers per motor unit Number of active motor units
Helper T-Cell Types
Th1 (pro-inflammatory) - Mainly involved in activating macrophages Th2 (anti-inflammatory) - Mainly involved in stimulating B cells to produce antibody Treg (anti-inflammatory) - Maintain tolerance to self-antigens and prevent autoimmune disease Th17 (pro-inflammatory) - Maintains mucosal barriers and contributes to pathogen clearance at mucosal surfaces
Abnormal Conduction - Re-entrant Excitation
The system behaves as an independent pacemaker with a rate much higher than that of the originating impulse
Anticlotting Systems
Thrombin: Thrombomodulin (receptor) Thrombin + Protein C Activated Protein C Inactivates Factor VIIIa + Factor Va Fibrinolytic System: Plasminogen activators Plasminogen -> Plasmin Fibrin -> Soluble fibrin fragments Anticoagulants: Activates protein C which inactivates clotting factors
Modulation of Tone in Smooth Muscle
Thromboxane + TXA receptor activates Rho kinase pathway and inactivates MLC phosphatase
Thymus Function
Thymus serves a role in the training and development of T-lymphocytes T cells are critical to the adaptive immune system Thymic stromal cells allow for the selection of a functional and self-tolerant T cell repertoire
Troponin
TnT: Binds to tropomyosin TnC: Binds to Ca TnI: Binds to actin (Inhibits contraction)
Sequence of Cardiac Excitation
Total amount of current going into depolarization equals that for hyperpolarization. Don't see atrial repolarization because it is small and broad so it is covered up by ventricular depolarization
Functions of Blood
Transportation Regulation Protection
ATP Production
Under most normal circumstance the intracellular ATP concentration is relatively stable Creatine Phosphate: Rapid Glycolysis: ~70% maximal rate of ATP breakdown Oxidative Phosphorylation: Moderate levels of activity
Energy Systems
Under most normal circumstances the intracellular ATP concentration is relatively stable
Complement Activation
Used in both innate and adaptive immunity Activation: 1. Adaptive Classic Pathway - Antibody binding to microbes 2. Innate Alternative Pathway - Lipid-carbohydrate binding to microbe surface 3. Innate C-Reactive Protein - Macrophage digest microbes -> Liver releases CRP -> CRP binds microbes -> C3 activation C3 -> C3b (promotes phagocytosis/opsonization) and C3a (goes with C5a) C3b activates C5 -> C5b and C5a (promote histamine production in mast cells for inflammation) C5b activates C6. C7,8,9 join and form MAC Cause cytolysis
Lymphatic Fluid Flow
Valve ensures one way flow of lymph Sequence of flow: Blood caps Interstitial spaces Lymphatic caps Lymph vessels Lymph ducts Junction of internal jugular and subclavian veins
Adrenergic and Muscarinic Receptors
Vascular Smooth Muscle - Sphincters - Contraction Cardiac Muscle - cAMP up - Force and rate of contraction increased Cardiac Muscle - cAMP down - Rate decreases
Local Control of Organ Blood-Flow
Vasodilation - Bigger, lower resistance = more flow Vasoconstriction - Smaller, higher resistance = less flow In the pulmonary capillaries: Drop in O2 leads to constriction
Length Tension Relations
Ventricular Function Curve: Frank-Starling Law of the Heart: As end-diastolic volume increases, stroke volume increases Cardiac active and passive tension curve start steep increase at same point Changes in passive tension can have large effect on force development
Left Ventricular Pressure Loop and Muscle Tension
Ventricular Preload: End-diastolic ventricular pressure Ventricular Afterload: Systemic arterial pressure
QRS Waves
Ventricular contractile fibers depolarize Ventricles contract Ventricular electrical conduction. Time needed for signal to spread through ventricles from apex to top Blood pressures: Big Number = High Pressure - Systole Low Number = Low Pressure - Diastole
Formation of Platelet Plug
Vessel damage Collagen exposed Activation of platelets - Also release PDGF for proliferation of endothelial cells, VSM, and fibroblasts Discharge of mediators and synthesis of thromboxane Contraction of vascular smooth muscle Vasoconstriction and platelet plug
Role of Type 1 Interferon
Virus infected cell secretes type 1 interferon Autocrine and paracrine effect -> INF Type 1 binding to other cells Antiviral protein synthesis induced Inhibition of viral replication
Skeletal and Cardiac Muscle Ryanodine Receptors
Voltage Sensitive RYR (Skeletal Muscle) - RyR1 - Physical coupling of Dihydropyridine and Ryanodine receptors. When DHP is activated cork is pulled on R and Ca leaves SR Ca2+ Sensitive RYR (Cardiac and Neurons) - RyR2 and RyR3 - Voltage gated Ca channel is activated which then send Ca to R to release more Ca (Ca induced Ca release)
Muscular Fatigue and Pain
pH sensors act as receptors in afferent neurons H+: ASIC (Acid Sensing Ion Current) receptors Lactate: Transient Receptor Potential Channel (TRPV1) ATP: Purinergic (P2X) Receptors Sensation of muscle fatigue is actually a function of the brain. Blocking of afferent signals would allow muscle to go on, a process likely ending in serious damage
Three types of muscle
skeletal, cardiac, smooth
Smooth Muscle Length-Tension Relationship
Wider range of lengths at which active tension can be generated than skeletal muscle Resting length is below optimal length (more stretchability) Actin myosin overlap persists in stretched state (no loss of cross bridge potential)
Hematopoiesis Throughout Life
You Love a Smart Bunny Yolk Sac Liver Spleen Bone Marrow
Sarcomere Cross Section
Close to Z line: Only see thin filaments Close to M line: Only see thick filaments In between: See both
Vessel Compliance
Compliance = Delta V / Delta P Venus system is more compliant - Volume Reservoir Atrial system is less compliant - Pressure Reservoir
Smooth Muscle Ca Entry
1. Ca enters the cytoplasm through channels located in caveoli 2. Ca release from the sarcoplasmic reticulum can occur either via Ca induced Ca release or more importantly via IP3 activation of SR Ca channels 3. When the SR Ca stores deplete, the SR signals a store-operated Ca channel to open allowing more Ca to enter
Smooth Muscle Cell Response
1. Can be a graded response 2. Neurotransmitter may depolarize or hyperpolarize 3. Effect of Vm determined by the receptor not the neurotransmitter 4. Can be contraction without a change in Vm
Ventricular Action Potential
1. Rapid depolarization due to Na inflow when voltage-gated fast Na channels open 2. Plateau (maintained depolarization) due to Ca inflow when voltage gated slow Ca channels open and K outflow when some K channels open 3. Repolarization due to closure of Ca channels and K outflow when additional voltage-gated K channels open Resting Membrane Potential: Phase 4 Steep Depolarization: Phase 0 Peak: Phase 1 Plateau: Phase 2 Repolarization: Phase 3 Absolute refractory period: Phase 0 - Start of 3 Relative refractory period: Phase 3 Supranormal period: After Phase 3
Blood Flow in the Heart
1. Right atrium (Deoxygenated Blood) 2. Tricuspid valve 3. Right ventricle (thin one) 4. Pulmonary valve 5. Pulmonary artery to the lungs 6. Pulmonary veins from the lungs (Oxygenated Blood) 7. Left atrium 8. Bicuspid valve (mitral valve) 9. Left ventricle (thick one) 10. Aortic valve 11. Body 12. Superior/Inferior Vena Cava
Input Influencing Smooth Muscle Contraction
1. Spontaneous electrical activity in cell membrane 2. Neurotransmitter released by autonomic neurons 3. Hormones 4. Locally induced changes in chemical composition (pH, O2, osmolarity, ions) 5. Stretch
Steps in Hemostasis
1. Vascular Spasm - Rapid Vasoconstriction 2. Platelet Plug Formation 3. Blood Coagulation
4 Phases
1. Ventricular Filling EDV 2. Isovolumetric Contraction 3. Ventricular Ejection ESV 4. Isovolumetric Relaxation
Heat Production During Muscle Activity
40% of energy released in muscle activity as useful work 60% given off as heat
ClC-1
A chloride channel contained in T-tubule membranes that contributes to the resting Vm along with the K leak channel
Motor Unit
A motor unit consists of a somatic motor neuron plus all of the muscle fibers it stimulates
Length-Tension Relationship
A muscle fiber develops its greatest tension when there is an optimal zone of overlap between thick and thin filaments 2.2 micrometer length of sarcomere
The Heart (The Pump)
A) Heart Muscle - Myocardium B) Three Types of Myocardial Fibers 1. Sinus Node and Atrioventricular Node - Pacemaker cells Small Weakly contractile Autorhythmic Slow conduction 2. Inner Surface of Ventricular Wall - Spreading excitation Large Weakly contractile Fast conduction 3. Bulk of Heart Muscle Fibers - Doing the work Medium Strongly contractile
Dihydropyridine Receptor - Ryanodine Receptor Coupling RyR1
ACh in motor neuron is released activating ion channels on motor end plate Action potential is generated and propagated DHP receptor is activated and conformationally changed Due to coupling R receptor is conformationally changed and plug is pulled to release Ca Ca binds to sarcomeres
Heme Synthesis
ALA-dehydratase can be inhibited by lead Lead poisoning leads to anemia Addition of Fe also is sensitive to lead Ferrochelatase is inhibited by lead
Pathological stress
Ca leak leads to higher cytosolic Ca and can activate calcium activated proteases (Calpain) and degrades myosin and actin Myofibrillar disarray
Removal of Ca from Smooth Muscle
Ca-ATPase pump in the plasma membrane (PMCA) 3 Na / 1 Ca exchanger in plasma membrane Ca-ATPase pump in the SR (SERCA)
Ca2+ and Muscle ATP
Ca2+ activates phosphorylase kinase and leads to generation of ATP Glucose transport brings Ca2+ into cell
Caldesmon Regulation of Actin
Caldesmon binds to actin and causes relaxed state Ca binds to Calmodulin and then binds to Caldesmon to pull it off of actin Actin now goes towards contraction Phosphorylated Caldesmon does not bind to Actin
Mean Arterial Pressure (MAP)
Cardiac Output x Total Peripheral Resistance DP + 1/3 (SP-DP)
Skeletal Muscle Cramps
Caused by excessively excited nerves that stimulate the muscles Can occur after injury to nerve or muscle, dehydration, low blood levels of Ca, Mg, or K, and certain medications
MAP = CO x TPR
Change in TPR changes BP CO = HR x SV So MAP = HR x SV x TPR Change in HR or SV changes BP
Flow = DP/R
Change in local resistance leads to change in local pressure
Neural Control of Heart
Chemoreceptors: Monitor blood chemistry Baroreceptors: Monitor blood pressure Medulla Oblongata: Cardiovascular Center Cardiac Accelerator Nerves - Sympathetic Vagus X Nerves - Parasympathetic
Viral Antigen to a T Cell
Class I MHC protein presents antigen to CD8 cytotoxic T cell
Dantrolene
Clinically used antagonist of ryanodine receptor Skeletal muscle relaxant
Cardiac Parameters
Stoke Volume = EDV - ESV Ejection Fraction = SV / EDV Cardiac Output = HR x SV Can change CO by either a change in HR or SV
Stress on Ca Cycling
Stress causes elevates levels of nor/epinephrine Leads to more beta adrenergic activation In turn, PKA phosphorylates Ryanodine and causes leakage of Ca when unexcited Leak of Ca leads to decreased Ca in SR and have less Ca for contraction and can't develop force In heart leads to less blood pumping
Cardiac Muscle
Striated Less SR Involuntary Troponin SR and SL for Ca 100ms time for contraction Oxidative Less rapid ATPase reactions
Innervation by Postganglionic Autonomic Neurons
Sympathetic Neurons - Hyperpolarize - Epinephrine Parasympathetic Neurons - Depolarize - Acetylcholine
SA Node Pacemaker Activity
Sympathetic Stimulation - Norepinephrine - Increases rate - via multiple conductance effects Parasympathetic Stimulation - Acetylcholine - Slows rate - via increase in K channel activity
Calcium Sensitivity of Myosin Light Chain Phosphatase
alpha q leads to increase in intracellular Ca alpha 12/13 leads to Ca sensitization and can inhibit MLCP alpha s leads to Ca desensitization and activates MLCP
