PHYSIOLOGY!!!!!!!

Cardiovascular Physiology Overview (PPT 5)

Cardiovascular System Function

Components of the Cardiovascular System

• Heart: The central organ that drives blood circulation through rhythmic contractions.

• Blood Vessels: A network of arteries, veins, and capillaries that transport blood throughout the body.

• Blood: A fluid connective tissue that delivers essential substances and removes waste materials from the body's cells.

General Functions

• Transportation: Blood serves as a transport medium for nutrients, gases (oxygen and carbon dioxide), hormones, and waste products.

• Regulation: The cardiovascular system helps maintain homeostasis by regulating the internal environment; it can be influenced by intrinsic factors (like local metabolic demands) or extrinsic systems (nervous and endocrine).

• Protection: Blood plays a crucial role in hemostasis (prevention of blood loss) and contains immune cells to defend against pathogens.

• Production/Synthesis: Blood cells, including red blood cells, white blood cells, and platelets, are produced in the bone marrow within the cardiovascular system.

Functional Anatomy of the Heart

Cardiac Muscle

• Characteristics: Composed of striated muscle fibers that are interconnected. The muscle cells are shorter and branch, allowing coordinated contractions.

• Structure: Primarily uninucleate (a single nucleus per cell) and contain specialized structures known as intercalated discs for effective communication between cells.

Heart Chambers

• Composition: The heart is divided into four chambers: two upper chambers known as atria (right and left) and two lower chambers known as ventricles (right and left).

• Function: Each chamber has specific roles in pulmonary circulation (right side) and systemic circulation (left side).

Heart Valves

• Atrioventricular Valves: Located between the atria and ventricles, these valves (tricuspid and mitral valves) prevent the backflow of blood into the atria during ventricular contraction, relying on chordae tendinae and papillary muscles for stability.

• Semilunar Valves: Located at the exit of the ventricles (pulmonary and aortic valves) that prevent backflow into the ventricles after contraction.

Intrinsic Conduction System

Overview

• The conduction system is a network of pacemaker cells that initiates and propagates electrical impulses, regulating the heartbeat.

Cardiac Pacemaker Cells

• Primary Pacemaker: The sinoatrial (SA) node, located in the right atrium, sets the natural rhythm of the heart (normal heart rate of 60-100 bpm).

• Secondary Pacemaker: The atrioventricular (AV) node serves as a backup pacemaker in case the SA node fails. It conducts impulses at a slower rate (40-60 bpm).

Electrical Pathway

• The sequence of activation of the conduction system is as follows: SA Node ➔ Internodal Pathways ➔ AV Node ➔ Bundle of His ➔ Purkinje Fibers. This pathway ensures a coordinated contraction of the myocardium.

Myocardial Physiology

Pacemaker Cells Functions

• Characteristics: Smaller than contractile cells and do not contribute to the force of contraction directly; they are specialized for spontaneous depolarization.

• Membrane Potential: Exhibit a unique property called "pacemaker potential," where the resting membrane potential gradually depolarizes to reach the threshold required to trigger an action potential.

Action Potentials in Myocardial Cells

• Phases: Stand out with a rapid influx of sodium ions (Na+) leading to depolarization, followed by a plateau phase where calcium ions (Ca2+) enter before the cell repolarizes as potassium ions (K+) exit.

Contractile Cells

• Characteristics: Make up about 99% of heart muscle cells and are responsible for generating the contraction.

• Action Potential Differences: The action potentials in contractile muscles are longer-lasting compared to skeletal muscles, permitting sustained contraction and preventing tetany.

Excitation-Contraction Coupling

• Calcium Induced Calcium Release (CICR): Action potentials lead to calcium entry into the cells that triggers additional calcium release from the sarcoplasmic reticulum (SR), crucial for muscle contraction.

• Force Generation: The force of contraction is modulated by intracellular calcium levels and the Frank-Starling mechanism, which relates muscle stretch to force generation.

Cardiac Cycle

Overview

• Definition: The cardiac cycle represents the series of mechanical and electrical events that occur during one heartbeat, involving the filling and ejection of blood.

Cycle Phases

1. Resting Phase: State of relaxation for both atria and ventricles.

2. Atrial Systole: Atrial contraction pushes blood into the ventricles.

3. Isovolumetric Ventricular Contraction: Ventricles contract with closed valves, resulting in pressure increase without change in volume.

4. Ventricular Ejection: Blood is expelled from the ventricles into the aorta and pulmonary arteries.

5. Isovolumetric Relaxation: Following ejection, ventricular pressure falls, causing semilunar valves to close.

Cardiac Output & Blood Pressure Controls

Cardiac Output (CO)

• Definition: The total volume of blood ejected by the left ventricle into the systemic circulation per minute (CO = Stroke Volume (SV) x Heart Rate (HR)).

• Components: Stroke Volume is influenced by the strength of contraction, heart rate, preload (degree of stretch), and afterload (pressure the heart must work against).

Summary: Influencing Factors

• Sympathetic Activity: Enhances heart rate and force of contraction via norepinephrine release.

• Parasympathetic Activity: Reduces heart rate through the vagus nerve, primarily increasing potassium permeability, which hyperpolarizes the cells and slows pacemaker activity.

Blood Pressure

• Systolic Pressure: Measures the force during ventricular contraction, typically around 120 mmHg.

• Diastolic Pressure: Measures the pressure in the arteries during relaxation between heartbeats, average around 80 mmHg.

Conclusion

Understanding cardiovascular physiology is essential for comprehending how the body maintains homeostasis, adapts to physical exertion, and addresses various cardiovascular pathologies. This knowledge is crucial for medical professionals and anyone studying the cardiovascular system.

Cardiac Muscle Properties (PPT 6)

Properties of Cardiac Muscle

1. Excitability

2. Conductivity

3. Contractility

4. Rhythmicity

I. Excitability (Irritability) - the ability of cardiac ms to respond to adequate stimuli by generating an action potential followed by a mechanical contraction.​

Excitability changes during action potential. passes through 3 different phases:

1. Absolute refractory period (ARP) - occupies whole period of systole. Period of depolarization (phase 0) and first 2 phases of repolarization.​

2. Relative refractory period (RRP) - occupies time of diastole. 3rd phase of repolarization ​

3. Dangerous period (supranormal period) - the excitability of cardiac ms is supranormal just ​at the end of the AP, i.e. weaker stimuli than normal ​can excite the ms.

II. Conductivity - the ability of cardiac ms fibers to conduct the cardiac impulses that are initiated in the SA-node (the pacemaker of the heart).​

Direction of Impulse:

1. Atrial Spread: SA node - conductive tissues - ventricles

2. Ventricular Spread: apex of the heart - base (via Purkinje fibers) - Endocardial surface of ventricles

Conduction of Impulse:

• SA node - 0.05 m/sec

• AV node - 0.01 m/sec (slowest)

  • Few number of intercalates discs

  • allow sufficient time for ventricles to be filled w blood before they contract

• Bundle of His - 1.00 m/sec

• Purkinje Fibers - 4.00 m/sec ( fastest)

  • Allow ventricles to contract at the same time simultaneously

• Atrial & Ventricular muscles - 0.3 to 0.4 m/sec

III. Contractility - ability of the cardiac muscle to convert ​

• chemical energy into mechanical work.

  • myocardial fibers have “Functional syncytium” not “anatomical syncytium” bc they are present in contact but not in continuity.

Excitation-Contraction Coupling in Heart Muscle - mechanism by which AP causes myofibrils of cardiac ms to contract

IV. Rhythmicity (Automaticity) - ability of cardiac muscle to contract in a regular constant manner without nerve supply

• Myogenic in origin not neurogenic

• Initiated by the pacemaker - SA node

The pacemaker of the heart SA Node

• contains p-cells which are probably the actual pacemaker cells

• Has the fastest rhythm (rate of discharge) of all parts of the heart

• Pacemaker potential - RMP -60mV

  • Pacemaker tissue characterzed by unstable membrane potential —> Prepotential

Ectopic Pacemaker: pacemaker other than the SA node

• If APs from SA node are prevented from reaching these areas, these cells will generate pacemaker potentials.

Remember sabi sa PPT hmpk

• Intrinsic rhythmicity of denervated SA- node is  90 impulses/min, while that of AV- node is  60 ​impulses/min.​

• However, vagal tone controls SA- node to become 70 ​impulses/min, & AV- node to 40 impulses/min.​

• If SA- node activity is depressed by a disease, AV-node takes over & becomes the pacemaker instead, ​leading to bradycardia.

ECG Physiology (PPT 7)

Electrocardiogram (ECG) - record of the waves (impulses) of electrical excitation in the heart

• Helps in the diagnosis of muscle damage or electrical problems in the heart

• CARDIAC IMPULSE PASSES THROUGH THE HEART, ELECTRICAL CURRENT SPREADS FROM HEART INTO ADJACENT TISSUES SURROUNDING THE HEART. CURRENT SPREADS ALL THE WAY TO THE SURFACE OF THE BODY. IF ELECTRODES ARE PLACED ON THE CHEST, OPPOSITE SIDES OF THE HEART, ELECTRICAL POTENTIALS GENERATED BY THE CURRENT CAN BE RECORDED​

Normal Impulse Conduction

Sinoatrial (SA) node —> Atrioventricular (AV) node slowest—> Bundle of His —> Bundle Branches —> Purkinje Fibers fastest

Normal ECG. Composed of:

• P wave - Atrial Depolarization

  • Atria depolarize before atrial contraction begins

  • Completed in 0.1 second

  • Irregular or absent P wave may indicate arrythmia.

  • Since it is an atrial depolarization, shape of P waves may indicate atrial problems

  • PR interval - measured from P wave to the beginning of QRS complex through the AV node - 0.18 seconds (0.12 to 0.2 s)

• QRS complex - Ventricular Depolarization

  • Ventricles depolarize before contraction.

  • P wave and the component of QRS complex are depolarization waves.

  • 0.08 - 0.12 seconds (max time 0.1 second)

  • Very wide and deep Q waves indicate myocardial infarcatiomn

  • QT interval - ventricular depolarization & repolarization (equal 0.4 seconds)

  • ST segment - equal .32 seconds

• T wave - Ventricular Repolarization

  • Ventricles recover from the state of depolarization. This process normally occurs in ventricular muscle 0.25 to 0.35 second after depolarization.

  • T wave is known as repolarization wave.

ECG Leads - leads are electrodes which measure the difference in electrical potential between either:

1. Two different points on the body (bipolar leads)

2. One point on the body and a virtual reference point with zero electrical potential, located in the center of the heart (unipolar leads)

Standard ECG - has 12 leads. Axis of particular lead represents the viewpoint from which it looks at the heart.

• 3 Standard Limb Leads

• 3 Augmented Limb Leads

• 6 Precordial Leads

Summary of Leads

• Bipolar

  • Limb Leads - I, II, III (Standard limb leads)

  • Precordial Leads - n/a

• Unipolar

  • Limb Leads - aVR, aVL, aVF (augmented limb leads)

  • Precordial Leads - V1-V6

Determining the Heart Rate

1. Rule of 300

   • Take the number of “big boxes” between neighboring QRS complexes, and divide this into 300. The result will be approximately equal to the heart rate​.

   • Although fast, this method only works for regular rhythms.​

2. 10 second rule

   • As most ECGs record 10 seconds of rhythm per page, one can simply count the number of beats present on the ECG and multiply by 6 to get the number of beats per 60 seconds.​

   • This method works well for irregular rhythms.​

The QRS Axis - represents the net overall direction of the heart’s electrical activity

• Abnormalities of axis cant hint at:

  • Ventricular enlargement

  • Conduction blocks (i.e. hemiblocks)

  • Normal QRS axis: -30 degrees to +90 degrees.

    • -30 to -90 - referred to as left axis deviation (LAD)

    • +90 to +180 - right axis deviation (RAD)

Clinical Significance of Diff Waves and Segments of ECG

• ST Elevation - Acute MI or Angina​
  ST depression >1 mm - Ischemia/Angina (flat), digoxin (sloping)​

• Q waves in 2 or more leads - Previous MI (Transmural)​
  Diffuse ST elevation with PR depression – Pericarditis​
  T wave inversions and non-specific ST changes - Can be seen both in normal cases and in many diseases, therefore not useful for diagnosis.​

• Tall P waves - Right atrial hypertrophy​
  Broad (and often bifid) P waves - Left atrial hypertrophy​
  Peaked T waves or loss of P wave – Hyperkalemia​
  U waves - Hypokalemia ('Hump' at the end of T wave)​
  Prolonged QT interval – Hypocalcemia​
  Shortened QT interval - Hypercalcemia​

Blood Physiology (PPT 8)

General Characteristics of Blood

1. Color

   • Bright red —> Oxygenated (Systemic)

   • Dark red/purple —> Deoxygenated (Venous)

2. pH - 7.35 - 7.45

3. Osmolality - 285 - 295 mOsm

4. Viscosity - 3-4x more viscous than water

5. Almost all blood cells are found in the red bone marrow.

Functions of the Blood​

1. Transport function​

   • infection WBC, antibodies​

   • blood loss platelets, clotting factors​

   • waste products urea, lactic acid , creatinine​

   • gases O2 , CO2​

   • electrolytes Na+ K+ Cl- Ca++​

2. Regulation

   • ph buffers​

   • temperature​

   • hormonal carries hormones and distributes

3. Protection

   • infection WBC , antibodies​

   • blood loss platelets, clotting factors

Composition of Blood

1. Liquid (Plasma) - 55%

2. “Buffy Coat” (white blood cells and platelets)

3. Red blood cells - 45% (hematocrit)

   • Hematocrit - percentage by volume of red cells in your blood

     • It is an indicator of anemia, polycythemia, and other conditions.

Blood Volume and Composition

• Volume varies with size. ​

• Blood is about 8% of the total body weight.​

• Average adult has 5 liters of blood​

• Blood is 40-45% cells ​

  • This is also known as the percent packed cell volume​

  • Red blood cells - 95.1%

  • Blood platelets (4.8%)

  • White blood cells (0.1%)

    • ​​Neutrophils (54-62%)

    • Eosinophils (1-3%)

    • Basophils (<1%)

    • Monocytes (3-9%)

    • Lymphocytes (25-33%)

• Blood is 55 -60% plasma​

  • Electrolytes

  • Water (92%)

  • Organic Molecules

    • Amino Acids

    • Proteins (7%)

      • Albumins

      • Globulins

      • Fibrinogen

    • Glucose

    • Lipids

    • Nitrogenous Wastes

  • Electrolytes - release ions when dissolved in water. Maintains osmotic pressure and the pH of the plasma. Includes:

    • Sodium

    • Potassium

    • Calcium

    • Magnesium

    • Chloride. Bicarbonate, Phosphate, and Sulfate Ions

  • Nutrients, Vitamins, Hormones

  • Gases

    • N2, O2, CO2

Plasma Characteristics

1. Straw Colored

2. Mainly water (92%), plasma CHONs, nutrients, gases, non-CHON nitrogen subs, and electrolytes

• FUNCTIONS​

1. transport of nutrients, gases, metabolites, hormones, antibodies and vitamins​

2. regulate fluid and electrolyte balance​

3. maintain pH​

Plasma Proteins - most abundant dissolved substances in plasma

• Three main plasma proteins (all produced from the liver except for gamma globulins):

  1. Albumin - 60% to 80% of plasma CHONs, made in the liver and they help to maintain oncotic pressure, and transport certain molecules such as bilirubin and fatty acids. Smallest in size.​

  2. Globulins – 36% of plasma CHONs​

     • Alpha and beta – produced in the liver, transport lipids and fat soluble vitamins​

     • Gamma globulins – made by lymph tissue, a type of antibody

  3. fibrinogen - 4% of plasma CHONs, made in the liver, help in blood coagulation

     CHON - Carbon, Hydrogen, Oxygen, ​Nitrogen

Blood Cells - originate in red marrow from hemocytoblasts or hematopoietic stems cells. Stem cells can then:

• Give rise to more stem cells

• Specialize or differentiate

REMEMBER:

• Hematopoiesis - making of blood cells

• Erythropoiesis - making of RBC

• Leukopoiesis - making of WBC

• Anemia - low hematocrit (below normal oxygen-carrying capacity of the blood)

• Polycythemia - abnormally high hematocrit (too many RBCs in circulation)

Production of RBC

• Early embryonic life : nucleated RBC —> yolk sac​

• Middle trimester: liver —> main organ for production,​ some are produced in the spleen and lymph nodes​

• Last month of gestation and after birth: exclusively produced in the bone marrow​

• Bone marrow of essentially all bones —> produces RBCs until 5 years old​

• Bone marrow of the long bones, except proximal portions of the humeri and tibiae —> no RBCs after​ 20 yrs old​

• >20 yo —> membranous bones , like vertebrae, sternum, ribs, ilia —> less productive as age increases.​

Function of RBC

• To transport Hemoglobin, which carries oxygen from the lungs to the tissues​

• As an enzyme that catalyzes the reversible reaction between carbon dioxide (CO2) and water to form carbonic acid (H2CO3) carbonic anhydrase​

• As an excellent acid-base buffer​

Characteristics of RBC

Red blood cells are:​

• Erythrocytes​

• Biconcave discs ​

  • Able to readily squeeze through capillaries​

• Lack nuclei and mitochondria​

• average volume: 90 -95 cubic micrometers​

• Normal men: 5,200,00 cubic mm​

• Normal women: 4,700,00 cubic mm

Regulation of RBC

• Regulated within narrow limits:​

  1. Adequate number is always available to provide sufficient transport of O2​

  2. cells do not become so numerous that they impede blood flow​

• Tissue oxygenation is the most essential regulator of RBC ​

​

RBC Cell Production and Control

• Low blood oxygen causes the kidneys and the liver to release erythropoietin (EPO) which stimulates RBC production​

  • This is a negative feedback mechanism —​within a few days many new blood cells appear in the circulating blood​

Formation of Hemoglobin

• Synthesis of hemoglobin begin in the proerythroblast and continues into Reticulocyte

  • Process of producing RBC ano??? erythropoiesis​!

• Hemoglobin molecule compose of 4 hemoglobin chains​

• There are four different chains of hemoglobin (alpha, beta, gamma and delta chain)​

• Hemoglobin A is a combination of two alpha and two beta chain

IMPORTANT!!!!

Catabolism of Hemoglobin (Diagram from slide 39)

1. Breakdown of Hemoglobin (Blood Cells)

   • Hemoglobin from aged red blood cells is broken down into:

     • Globin (protein part, reused for protein synthesis)

     • Heme (iron-containing component)

   —> Heme oxygenase enzyme converts heme into biliverdin IX, releasing carbon monoxide (CO) as a byproduct.

2. Conversion to Bilirubin

   • Biliverdin reductase enzyme, using NADPH, converts biliverdin into bilirubin (which is water-insoluble).

3. Transport to the Liver

   • Bilirubin is transported in the blood to the liver, where it undergoes further processing.

4. Liver Processing

   • The liver converts bilirubin into bilirubin diglucuronide (which is water-soluble) by adding 2 UDP-glucuronic acid.

   • This water-soluble form is secreted into bile and transported to the intestines.

5. Intestinal Processing and Excretion

   • In the intestines, bacteria convert bilirubin into urobilinogen.

   • Urobilinogen has two fates:

     1. Some is reabsorbed into the blood, transported to the kidney, and excreted in urine as urobilin.

     2. The rest is converted into stercobilin and excreted in feces, giving stool its brown color.

Key Points:

• The liver plays a crucial role in making bilirubin water-soluble for excretion.

• Bilirubin metabolism affects urine and stool color.

• Any disruption in this process can lead to jaundice (yellowing of the skin due to excess bilirubin).