Untitled Flashcards Set

Cardiac Physiology: This section focuses on the structure and function of the heart and the principles governing its activity.

General Organization and Function:

1. The heart, a "hollow muscle double pump," is located in the mediastinum and enclosed by the pericardium. 

2. It comprises four chambers: two atria (collecting chambers) and two ventricles (pumping chambers). 

3. The cardiovascular system is divided into three principal circulatory divisions:

   1. Systemic Circulation: "carries oxygenated blood from the left ventricle through the body, and returns venous blood to the right atrium."

   2. Pulmonary Circulation: "carries venous blood from the right ventricle through lungs (blood undergoes oxygenation) and delivers oxygenated blood through four (4) pulmonary veins into the left atrium."

   3. Coronary Circulation: "delivers oxygenated blood for the heart through the coronary arteries."

4. Both sides of the heart contract simultaneously, pumping equal volumes of blood in each cycle (systole and diastole). 

5. Blood flow through the heart follows a specific pathway: Systemic venous blood enters the right atrium via the vena cava, moves to the right ventricle, then to the pulmonary arteries for oxygenation in the lungs. Oxygenated blood returns to the left atrium via the pulmonary veins, moves to the left ventricle, and is then pumped into the aorta for systemic circulation.

Heart Wall and Cellular Structure:

1. The heart wall consists of three layers: the pericardium (fibrous and serous layers), the epicardium (outer layer), the myocardium (contractile muscle), and the endocardium (inner lining). 

2. Cardiac muscle cells (myocytes) differ from skeletal muscle cells by being shorter, typically having 1-2 nuclei, and being connected by "intercalated discs." 

   1. These discs contain "gap junctions" which "provide low electrical resistance," allowing the cardiac muscle to function as a "syncytium," meaning cells contract in a coordinated manner. 

   2. The functional unit of a cardiac cell is the "sarcomere," located between two Z-lines.

Electrical Properties and Action Potential:

1. Cardiac cells maintain a stable "resting membrane potential" (-85 to -95 mV). 

2. The action potential in cardiac muscle is prolonged and includes a "plateau" phase (Phase 2) due to "Ca2+ enters about 200 msec." 

   1. This prolonged action potential leads to a "very long (250ms) refractory period (impossible to cause summation of contractions)." 

3. The phases of the cardiac muscle action potential are:

   1. Phase 0: Depolarization (Na+ influx)

   2. Phase 1: Early Repolarization (Sodium channels inactivate)

   3. Phase 2: Plateau (Ca2+ influx)

   4. Phase 3: Repolarization (K+ channels open)

   5. Phase 4: Ion Distribution Restored (Na+/K+ pump)

Excitation-Contraction Coupling:

1. The process linking electrical excitation to mechanical contraction involves calcium ions. 

2. An action potential triggers calcium influx through T-tubules, leading to further calcium release from the sarcoplasmic reticulum. 

3. "Calcium combines with troponin," removing the inhibition of tropomyosin and allowing "Cross-bridges to be formed" between actin and myosin, resulting in contraction.

Cardiac Cycle and Heart Sounds:

1. The cardiac cycle comprises systole (contraction) and diastole (relaxation). 

2. Key events include atrial contraction, isovolumic ventricular contraction, ventricular ejection, isovolumic ventricular relaxation, and passive ventricular filling. 

3. Heart sounds are generated by valve closure:

   1. S1 ("LUB"): "A-V valves vibration at the beginning of systole."

   2. S2 ("DUP"): "Aortic valves vibration at the end of systole."

   3. Abnormal heart sounds are called murmurs and can indicate valve dysfunction.

Cardiac Output and Regulation:

1. "CARDIAC OUTPUT = HEART RATE x STROKE VOLUME." 

2. Heart rate is influenced by autonomic nervous system activity on the sinoatrial (SA) node. 

3. Stroke volume is controlled by intrinsic mechanisms (venous return, Frank-Starling Law: "HEART NORMALLY PUMPS ALL THE BLOOD DELIVERED TO IT") and extrinsic mechanisms (sympathetic stimulation). 

4. Sympathetic stimulation increases heart rate and contractility, while parasympathetic (vagal) stimulation decreases heart rate.

Electrocardiogram (ECG):

1. The ECG is a "complex recording" that represents the "ALGEBRAIC SUM OF ALL MYOCARDIAL ACTION POTENTIALS" measured from the body surface. Key waves and intervals include:

   1. P-wave: Atrial depolarization.

   2. QRS complex: Ventricular depolarization.

   3. T-wave: Ventricular repolarization.

   4. P-Q/P-R interval: Time between atrial and ventricular contraction.

   5. Q-T interval: Duration of ventricular contraction.

2. ECG provides insights into the timing and coordination of electrical events in the heart.

Coronary Circulation and Myocardial Ischemia:

1. The heart muscle receives oxygenated blood via the left and right coronary arteries. 

2. Most coronary blood flow occurs during diastole. 

3. The heart has a "very high level of oxygen consumption and oxygen extraction." 

4. Myocardial ischemia, a common cause of heart disease, results from a "sudden or gradual decrease of coronary blood flow," often due to atherosclerosis and thrombosis. 

5. Ischemia leads to metabolic changes (decreased O2, ATP, increased H+, lactate, intracellular Ca2+) and functional impairments (reduced contractility, stroke volume, and cardiac output). 

6. Coronary blood flow is regulated by local metabolic factors (e.g., adenosine, nitric oxide), humoral factors (vasoconstrictors and vasodilators like epinephrine, angiotensin, bradykinin), and nervous regulation (sympathetic and parasympathetic effects).

Blood Plasma and Blood Cells: This section outlines the composition and functions of blood.

Blood Functions and Characteristics:

1. Blood, constituting approximately 6-8% of body weight, performs crucial functions including "Transportation," "Communication," "Regulation," and "Protection." 

2. Key characteristics include a viscosity of 3-5, a pH of 7.36-7.4, and an osmotic pressure of about 300 mOsm. 

3. Blood volume comprises "Cells (45% of blood volume)" and "Plasma (55% of blood volume)." 

4. The hematocrit represents the "Ratio of RBC volume to the whole volume of blood."

Plasma Composition:

1. Plasma is primarily "WATER - 92%" and contains "PLASMA PROTEINS - 7%" and "ELECTROLYTES, NUTRIENTS, GASES, VITAMINS, PIGMENTS, HORMONES, CHEMICAL MESSENGERS - 1%." 

2. Major plasma proteins include:

   1. Albumins (60%): Primarily responsible for "Osmotic Pressure" and "Transport Function."

   2. Globulins (35%): Involved in "Transport Function" and "Immune Function" (antibodies).

   3. Fibrinogen (4%): Crucial for the "Clotting System."

Formed Elements (Blood Cells): The formed elements include:

1. Red Blood Cells (Erythrocytes): Highly specialized cells lacking a nucleus and organelles, primarily responsible for oxygen and carbon dioxide transport via "HEMOGLOBIN." Erythropoiesis, RBC production in the bone marrow, is regulated by "Hormone erythropoietin" in response to hypoxia. Anemia, indicated by low hemoglobin levels, can have various causes including iron deficiency, vitamin B12 deficiency, bone marrow defects, and hemolytic conditions like sickle cell anemia ("Erythrocytes contain abnormal hemoglobin - HbS").

2. White Blood Cells (Leukocytes): Involved in immune defense. Granulocytes (neutrophils, eosinophils, basophils) and agranulocytes (lymphocytes, monocytes) each have distinct roles in the immune response. Leukopenia (low WBC count) increases infection risk, while leukocytosis (high WBC count) often indicates an immune response.

3. Platelets (Thrombocytes): Small, anucleated cell fragments stored in the spleen, essential for "Blood clotting." Their production, thrombopoiesis, is regulated by thrombopoietin from the liver. Thrombocytopenia (low platelet count) increases the risk of bleeding.

Hematopoiesis:

1. Blood cells originate from "PLURIPOTENT STEM CELL" in the bone marrow, differentiating into myeloid stem cells (giving rise to RBCs, platelets, granulocytes, monocytes) and lymphoid stem cells (producing lymphocytes).

Hemostasis: This section details the physiological processes that prevent blood loss.

Major Steps in Hemostasis: "Hemostasis - the physiological processes that prevent blood loss." It involves four major steps:

1. Vascular Spasm: "DECREASES THE AMOUNT OF BLOOD LOST" through vasoconstriction, mediated by prostaglandins like thromboxane A2 (TXA2 - vasoconstriction) and prostacyclin (PGI2 - vasodilation), and nitric oxide (NO - vasodilation). The balance between PGI2 and TXA2 regulates arteriole diameter.

2. Platelets Activation: "PLATELETS AGGREGATION FORMS THE BLOOD CLOT." Platelets are activated by factors like TXA2, ADP, serotonin, and fibrin, and inhibited by PGI2 and cAMP. Activated platelets release mediators like ADP and serotonin and synthesize TXA2, further promoting aggregation. Platelet adhesion to damaged vessel walls involves receptors like GPIb (binding to von Willebrand factor - vWf) and GPIa (binding to collagen), while aggregation occurs through GPIIb/IIIa receptors cross-linking via fibrinogen.

3. Coagulation: "Blood coagulation involves the conversion of soluble fibrinogen (Factor I) into insoluble strand of fibrin (Fg ---->Fb)." This occurs via a complex cascade involving intrinsic and extrinsic pathways that converge on a common pathway leading to thrombin formation. Thrombin then converts fibrinogen to fibrin, forming the structural meshwork of the blood clot. Clotting factors (e.g., Factors VIII, IX, X) are essential for this process.

4. Fibrinolysis: "Fibrinolytic cascade is a physiological process initiated together with the coagulation cascade." It involves the breakdown of fibrin by the enzyme plasmin, which is formed from plasminogen by plasminogen activators like tissue-plasminogen activator (tPA). Fibrinolysis resolves the clot after tissue repair.

Blood Anti Clotting Systems: Natural anticoagulants prevent excessive clot formation, including:

1. Tissue Factor Pathway Inhibitor (TFPI): "INHIBITS FACTOR X."

2. Protein C / Protein S: "INHIBITS FACTORS VIII and V."

3. Antithrombin III: "INHIBITS THROMBIN (II) + FACTORS IX, X, XI, & XII."

Major Antithrombotic Drugs: Pharmacological agents are used to prevent and treat thrombosis:

1. Aspirin: "Irreversibly inhibits thromboxane synthesis by blocking the enzyme cyclooxygenase," thus inhibiting platelet aggregation.

2. Heparin: "Increases activity of antithrombin III - inhibits thrombin + Factors IX, X, XI, and XII."

3. Warfarin: "Synthesis of clotting Factors II, VII, IX, and X in liver depends upon vitamin K Warfarin inhibits vitamin K1," thus reducing the production of these clotting factors.

Bleeding Disorders:

1. Bleeding disorders can arise from thrombocytopenia ("drop of count below 50,000/microL"), liver disease (clotting factor deficiency), vitamin K deficiency, and genetic disorders such as "VON WILLEBRAND'S DISEASE" and "HEMOPHILIAS" (e.g., Hemophilia A - lack of Factor VIII).

Virchow's Triad: "It is a Physiological axiom that predisposition for platelet aggregation, and thrombi formation is determined by the Virchov’s Triad:"

1. "Decrease of the Blood Flow"

2. “Changes in the Blood" (hypercoagulability)

3. "Damage to the Endothelial Cells"

Nanoparticles in Blood Clots:

1. Analysis of blood clots has revealed the presence of various "nanoparticles" including "Silver, gold, cobalt, titanium, antimony, tungsten, nickel, mercury, zinc, barium, iron, chromium, nickel, silicon, glass and stainless steel," the clinical significance of which requires further investigation.

Conclusion

1. The provided sources offer a detailed overview of the intricate mechanisms governing cardiac physiology, blood composition, and hemostasis. 

2. These systems are tightly interconnected, ensuring efficient oxygen and nutrient delivery, waste removal, and protection against blood loss. 

3. Understanding these fundamental principles is crucial for comprehending both normal physiological function and the pathophysiology of various cardiovascular and hematological disorders.

Key Terms:

• Action Potential: A rapid, transient change in the electrical potential across a cell membrane, propagated along excitable tissues like nerve and muscle.

• Atrium (plural: Atria): A collecting chamber of the heart that receives blood from the circulation

• Cardiac Cycle: The complete sequence of events in one heartbeat, including contraction (systole) and relaxation (diastole) of the atria and ventricles.

• Cardiac Output: The volume of blood pumped by the heart (specifically by the left ventricle) per minute, usually expressed in liters per minute (L/min).

• Diastole: The phase of the cardiac cycle when the heart muscle relaxes, and the ventricles fill with blood.

• Electrocardiogram (ECG): A recording of the electrical activity of the heart over time, measured by electrodes placed on the body surface.

• Endocardium: The thin, smooth membrane lining the inside of the heart chambers and covering the heart valves.

• Epicardium: The visceral layer of the serous pericardium, forming the outermost layer of the heart wall.

• Erythropoiesis: The process of red blood cell formation in the bone marrow.

• Fibrinolysis: The enzymatic breakdown of fibrin in blood clots.

• Frank-Starling Law of the Heart: The principle that the stroke volume of the heart increases in response to an increase in the volume of blood filling the heart (the end diastolic volume) when all other factors remain constant.

• Gap Junctions: Specialized channels in the intercalated discs of cardiac muscle cells that allow for direct electrical communication and coordinated contraction.

• Hematocrit: The radio of the volume of red blood cells to the total volume of blood.

• Hemostasis: The physiological processes that prevent blood loss following injury to a blood vessel.

• Intercalated Discs: specialized cell junctions that connect cardiac muscle cells, containing desmosomes for structural integrity and gap junctions for electrical coupling.

• Myocardium: The middle the thickest layer of the heart wall, composed of cardiac muscle tissue responsible for the heart’s contractions.

• Pericardium: The double-layered sac that encloses the heart, consisting of a fibrous outer layer and a serous inner layer.

• Plasma: The liquid component of blood, in which blood cells are suspended, containing water, proteins, electrolytes, nutrients, and waste products.

• Platelets (Thrombocytes): Small, anucleated cell fragments in the blood that play a crucial role in hemostasis.

• Pulmonary Circulation: The circulation of blood from the right ventricle to the lungs for oxygenation and back to the left atrium.

• Resting Membrane Potential: The electrical potential difference across the plasma membrane of a cell when it is in a non-excited state.

• Sarcomere: The basic contractile unit of striated muscle (both skeletal and cardiac), defined as the region between two Z-lines.

• Stroke Volume: The volume of blood ejected by the left ventricle during each heartbeat.

• Systemic Circulation: The circulation of oxygenated blood from the left ventricle to all parts of the body and the return of deoxygenated blood to the right atrium.

• Systole: The phase of the cardiac cycle when the heart muscle contracts and pumps blood.

• Ventricle: A pumping chamber of the heart that ejects blood into the arteries.