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PHYSIOLOGY
CIRCULATORY SYSTEM
The circulatory system - is an organ system that passes nutrients gases, hormones, waste products blood cells, etc. to and from cells to maintain homeostasis - composed of the cardiovascular system, which distributes blood, and the lymphatic system
The main components of the human cardiovascular system are: heart, blood, blood vessels: arteries, arterioles, capillaries, venules and veins heart is the pump, arteries are conduits, arterioles are resistance vessels, capillaries are exchange sites, veins are mainly blood reservoirs.
CIRCULATORY SYSTEM
CARDIOVASCULAR SYSTEM
THE HEART muscular pump whose main function is to propel blood throughout the body lies between the lungs and just to the left of the middle of the chest cavity has a mass of between 250 and 350 grams is about the size of a fist
THE HEART
has four chambers that are enclosed by thick, muscular walls: the right and left atria the right and left ventricles the interatrioventricular septum separates the left atrium and ventricle from the right atrium and ventricle, dividing the heart into two functionally separate and anatomically distinct units
THE HEART
Heart is enclosed in a double-walled protective sac, the pericardium The wall of the human heart is composed of three layers: - the epicardium, the outer layer - or visceral pericardium (it is also the inner wall of the (serous) pericardium). - the myocardium, the middle layer - composed of muscle which contracts. - the endocardium, the inner layer - is in contact with the blood that the heart pumps[. It merges with the inner lining (endothelium) of blood vessels and covers heart valves
THE HEART
the pericardium double membrane contains a small amount of the pericardial fluid which nourishes the heart and prevents from shocks. - protects the heart, - anchors its surrounding structures - prevents overfilling of the heart with blood. - Its inner layer provides a smooth lubricated sliding surface within which the heart can move in response to its own contractions and to movement of adjacent structures such as the diaphragm and lungs.
The endocardium - innermost layer of tissue that lines the chambers of the heart primarily made up of endothelial cells -
THE HEART
part of the myocardial function control systems controls the development of the heart in the embryo as well as in the adult, for example during hypertrophy. regulate contractility and electrophysiological environment of the cardiomyocyte act as a blood-heart barrier (analogous to the bloodbrain barrier), controlling the ionic composition of the extracellular fluid in which the cardiomyocytes bathe
the myocardium
THE HEART
-composed of highly organized cardiac muscle cells connected together to form a syncytium with tight electrical and mechanical connections - classified as a striated muscle with specificities in terms of organization, electrical and mechanical coupling and mechanisms to regulate the force of contraction. -cardiac muscle cells importance lie in heart continuous pumping activity Structure of a cardiac muscle cell. (MF)- myofibrils
(Mit)- mitochondria (ID)- intercalated disks (Nu)nucleus (BV)- blood vessel (ECF)- extracellular fluid (SL)- sarcolemma (TT)- T-tubules.
THE HEART
Muscle cells are composed of tubular myofibrils surounded by the sarcoplasmic reticulum (internal network of membranes whose terminal regions abut the T tubule-invaginations of sarcolemma positioned at the Z lines ) or lie just below the sarcolemma
Skeletal muscle cell ultrastructure: 1) myofibrils 2) sarcoplasmic reticulum 3). 4) T-tubules. 5) surface membrane .6) mitochondria
THE HEART
- each myofibril is surrounded by elements of the SR with their terminal cisterns. - T-tubules. are invaginations of the surface membrane that form a network of tubules extending into the center of the cell. - the lumen of the T-tubule is continuous with the extracellular space - numerous mitochondria lie between myofibrils
THE HEART
Myofibrils are composed of repeating sections of sarcomeres, the contractil units of the muscle cell limited by two Z membranes Sarcomeres are composed of long, fibrous proteins that slide past each other when the muscles contract and relax. Myofibrils are composed of arrays of thick and thin filaments. -Z lines are points of attachment of thin filaments - Thin filaments are composed of actin, tropomyosin and troponin and extend into the A band -A band is composed of thick filaments with some overlap of thin filaments -thick filaments are composed of myosin and extend from the centre of the sarcomere toward Z lines
THE HEART
Thin Filaments in Skeletal Muscle Are Composed of Major Proteins:
Actin is a globular protein (G-actin) with a molecular weight of 41,700 daltons made of G-actin monomers that aggregate to form strands resembling a string of pearls. The thin filament consists primarily of two helical strands of G-actin wound around each other Nebulin, 600-kDa protein molecule, runs along the thin filament and forms a template that limits the length of the actin filaments. Alfa-actinin, anchors actin filaments on Z line Tropomyosin and troponin, are regulatory proteins from the thin filament Tropomyosin , a long, rod-shaped protein dimer lies along both sides of the thin filament in grooves formed by the two strands of actin molecules. Each tropomyosin molecule binds to seven actin monomers in one of the strands. Troponin, which is bound to tropomyosin, is a complex of three proteins: troponin T (TnT), troponin C (TnC), and troponin I (TnI). Tropomyosin and troponin are involved in the calcium (Ca2+)-dependent regulation of skeletal muscle contraction Actin Tropomodulin, at the end of actin filaments control the length of thin filaments
THE HEART
Thick Filaments are composed mostly of myosin myosin - a large protein consisting of two heavy chains and two pairs of different light chains-a myosin essential light chain and a myosin regulatory light chain (RLC). - It has a long, rod-like tail with two globular heads - the rod-like portion of the molecule contains an "arm" adjacent to each globular head. - at each end of the arm is a flexible region that acts as a hinge, allowing rotation at that point.
THE HEART
- many myosin molecules align to form a thick filament - the tail regions of the molecules are bundled to form the body of the thick filament. - the globular heads and arm regions project out from the bundle. - the heads of the myosin molecules can bind to the thin filaments to form cross-bridges between the two filaments. T - the myosin heads in each half of the thick filament are oriented in opposite directions; the heads are not present in the central region Titin, large elastic protein, - tether myosin to the Z lines preventing overstretching of sarcomeres, - participate in cell signaling modulating protein synthesis, - might contribute to increase force upon strech
the heads of the myosin molecules can bind to the thin filaments to form cross-bridges between the two filaments. T
HEART CHAMBERS
Cardiac atria
- in the upper part of the heart - receive the blood entering the heart - the interatrial septum divides the atria - small chambers - thin muscular walls - operate more as passive reservoir. - they contract enhancing ventricular filling to additional 15 % of total ventricular filling - Internally, there is the rough musculae pectinati and crista terminalis which acts as a boundary inside the atrium and the smooth walled part derived from the sinus venosus Right atrium receives deoxygenated systemic venous returned from inferior and superior vena cava and coronary sinus Left atrium receives oxygenated blood from the lungs via left and right pulmonary veins
HEART CHAMBERS
Atrial function:
- prevent circulatory inertia and - allow uninterrupted venous flow to the heart becouse: (1) there are no atrial inlet valves to interrupt blood flow during atrial systole. (2) the atrial systole contractions are incomplete and thus do not contract to the extent that would block flow from the veins through the atria into the ventricles. During atrial systole, blood not only empties from the atria to the ventricles, but blood continues to flow uninterrupted from the veins right through the atria into the ventricles. (3) the atrial contractions must be gentle enough so that the force of contraction does not exert significant back pressure that would impede venous flow. (4) the "let go" of the atria must be timed so that they relax before the start of ventricular contraction, to be able to accept venous flow without interruption
HEART CHAMBERS
Cardiac ventricles
- pump blood out of the heart - the interventricular septum divides the ventricles - two large chambers collect blood from atria and expel it towards the peripheral beds within the body and lungs - have thicker walls than atria and generate higher blood pressures - the left ventricle has thicker walls (3-4X)than the right because it needs to pump blood to most of the body while the right ventricle fills only the lungs.
-the right ventricle receives blood through the right atrium and pumps it into the pulmonary circulation through the pulmonary artery, - the left ventricle receives blood through the left atrium and pumps it into the systemic circulation through the aorta (systemic circulation).
HEART VALVES
Heart valves are attached to the chordae tendinae (literally the heartstrings), which anchors the valves to the papilla muscles of the heart atrioventricular valves separate atria, from the ventricles through : - tricuspid valve between the right atrium and the right ventricle, -mitral valve between the left atrium and the left ventricle semilunar valves separate ventricles from the blood vessels through : -pulmonary valve between the right ventricle and the pulmonary artery -aortic valve between the left ventricle and aorta
Heart valves
Heart valves functions Allow blood flow in one direction only Open passively when upstream pressure exceeds downstream pressure Close passively when downstream pressure exceeds upstream pressure The movement of valve leaflets can be detected by echocardiography Their closure makes an important component of the heart sounds
Extracellular Fluid Na+ (mEq/L) K+ (mEq/L) Cl (mEq/L HCO3 (mEq/L) Ca++ (mmol/L)* Pi (mmol/L)* 135-147 3.5-5.0 95-105 22-28 2.1-2.8 (total) 1.1-1.4 (ionized) 1.0-1.4 (total) 0.5-0.7 (ionized)
Extracellular Fluid 10-15 120-150 20-30 12-16 107 (ionized) 0.5-0.7 (ionized)
Any stimulus that abruptly depolarizes Vm to a critical value (called the threshold) elicits an action potential. The rapid depolarization (phase 0) is related almost exclusively to the influx of Na+ into the myocyte as a result of a sudden increase in gNa. The action potential amplitude (the potential change during phase 0) is dependent on [Na+]o. When the resting membrane potential, Vm, is suddenly depolarized from 90 mV to the threshold level of about 65 mV, the cell membrane properties change dramatically. Na+ enters the myocyte through specific fast voltage-activated Na+ channels that exist in the membrane. The Na+ channels open very rapidly or activate (in about 0.1 msec), thereby resulting in an abrupt increase in gNa. However, once opened, the Na+ channels inactivate (time course 1 to 2 msec), and gNa rapidly decreases . The Na+ channels remain in the inactivated state until the membrane begins to repolarize. With repolarization, the channel transitions to the closed state, from which it can then be reopened by another depolarization of Vm to the threshold.
the steady inward leak of Na+ that enters the cell rapidly during phase 0 and more slowly throughout the cardiac cycle would gradually depolarize the resting membrane voltage were it not for Na+,K+ATPase, which is located in the cell membrane . Similarly, most of the excess Ca++ ions that had entered the cell mainly during phase 2 are eliminated principally by a 3Na+-1Ca++ antiporter, which exchanges 3 Na+ ions for 1 Ca++ ion. Some of the Ca++ ions are eliminated by an ATP-driven Ca++ pump.
Principal ionic currents and channels that generate the various phase in the AP in a cardiac cell:
Phase 0: the chemichal and electrostatic forces both in favour the entry of Na+ into the cell through fast Na channels. Phase 1: the chemichal and electrostatic forces both in favour the efflux of K+ through I to channels to generate early, partial repolarisation Phase 2: during the plateau, the net influx of Ca++ through Ca channels is balanced by the efflux of K+ through Ik, Ik1,Ito channels Phase 3: the chemichal forces that favour the efflux of K+ through Ik, Ik1,I o channels predominate over the electrostatic forces that favour the influx of K+ through these same channels Phase 4 the chemichal forces that favour the efflux of K+ through Ik, Ik1, Ito channels very slightly exceed the electrostatic forces that favour the influx of K+ through these same channels