Human Physiology: Muscle, Cardiovascular, and Respiratory Systems

Muscle Anatomy and Structure

1. Myofibrils: Rod-like structures inside muscle fibers. Contain:
   • Myosin filaments → A bands (thick)
   • Actin filaments → I bands (thin)
2. Sarcomere: Functional contractile unit of a muscle. Spans from Z-disc to Z-disc.
3. Muscle Fiber: Formed by fusion of multiple myoblasts. Multinucleated.
4. Fasciculus: Bundle of muscle fibers.
5. Connective Tissue Layers:
   • Endomysium: Surrounds individual muscle fibers.
   • Perimysium: Surrounds fasciculi.
   • Epimysium: Surrounds entire muscle.

Neuromuscular Junction (NMJ)

Synapse between an alpha (α)-motor neuron and a muscle fiber. The membrane is highly invaginated, which increases the surface area for Acetylcholine (ACh) receptors. Calcium channels in the neuron terminal open, leading to vesicles releasing acetylcholine (ACh). ACh binds to non-selective ion channels, allowing Na⁺, K⁺, Ca²⁺ in, but blocking Cl⁻, which causes an End Plate Potential (EPP). Acetylcholinesterase quickly breaks down ACh to end the signal.

Myofilament Structure

Actin (A)

Made of:

• F-actin strand
• Tropomyosin: Blocks active sites.
• Troponin: Binds Ca²⁺ → moves tropomyosin.
• Binding sites for myosin heads, staggered along actin.

Myosin (M)

Hundreds of molecules twisted together. Each has:

• Heavy-chain tail
• Light-chain head: Contains ATPase, binds to actin (cross-bridge).
• Can bend at the arm and head.

Titin

Connects Z-discs to myosin (acts like a spring).

Cross-Bridge Cycle (ATP-Driven)

1. Myosin head cocked: Actin + Myosin•ADP•Pi (ready to bind).
2. Binding: Myosin binds to Actin → Actin–Myosin•ADP•Pi.
3. Power stroke: Head tilts → releases ADP + Pi. If no ATP = rigor mortis.
4. Detachment: ATP binds to myosin → detaches from actin.
5. Reset: ATP hydrolyzed → head recocks (Actin + Myosin•ADP•Pi).

Cycle repeats if:

• Ca²⁺ is still present.
• ATP is available.
• Myosin hasn’t reached the Z-disc.
• Force doesn’t exceed contraction ability.

Muscle Fiber Metabolism

Muscle fiber metabolism involves three pathways:

• The phosphagen pathway uses phosphocreatine to produce creatine and phosphate without generating ATP per glucose; it supplies energy extremely fast but only for a very short duration.
• The glycolytic pathway produces 2 ATP per glucose by converting glycogen to lactic acid; it has a fast supply rate but low yield, depleting muscle glycogen quickly, and is the main system for Type IIB fast-twitch fibers.
• The oxidative pathway generates 36 ATP per glucose by metabolizing glucose, fatty acids, amino acids, and oxygen into CO₂, H₂O, and urea; it has a slow supply rate due to blood-derived substrates but provides energy for an unlimited duration, and is used by Type I slow-twitch and Type IIA fast-twitch fibers.

Muscle Contraction Types

• Isotonic contraction: Same force, muscle shortens (e.g., lifting a dumbbell).
• Isometric contraction: Same length, muscle doesn't move but still contracts (e.g., holding a weight still).

Contraction Velocity

Contraction velocity is highest when the muscle is unloaded. When the applied load equals the muscle’s maximum force, no shortening occurs despite activation. If the load exceeds the muscle's maximum force, it can disrupt the cross-bridge cycle and cause the muscle to lengthen.

Summation Principle: More Spikes, More Force

The faster the neuron fires, the more calcium stays in the muscle. This leads to stronger contraction. At very fast rates, the twitches add together into one strong contraction, known as tetanus.

Recruitment Principle: More Fibers, More Force

To increase force, the body activates more motor units:

1. Small, slow fibers first (Type I)
2. Then medium fast (Type IIA)
3. Then big, fast ones (Type IIB)

This is efficient: start small, add power only when needed.

Types of Spinal Neurons

• Afferent neurons (sensory): Carry information from the body to the spinal cord.
  • Types: Aα: from muscle spindles
  • Aβ, Aδ, C: carry touch, pain, or temperature signals
  • Spinothalamic: relay pain and temperature to the brain.
• Interneurons: Live in the spinal cord and help with reflexes.
  • Examples: Ia and Ib inhibitory neurons, Renshaw cells.
• Efferent neurons (motor): Send signals from the spinal cord to muscles.
  • α (alpha) motor neurons: control muscle contraction (extrafusal fibers)
  • γ (gamma) motor neurons: control sensitivity of muscle spindles.

Muscle Spindles: Muscle Sensors

Muscle spindles are tiny stretch sensors inside muscles. They contain nuclear bag and nuclear chain fibers. They are contractile at the ends and sensory in the middle.

Two types of gamma motor neurons:

• γ static → affects nuclear chain fibers (senses steady stretch)
• γ dynamic → affects nuclear bag fibers (senses fast stretch)

Purpose: Tells the brain how much the muscle is stretched and adjusts contraction.

Motor Cortex

Areas of the brain involved:

• Primary motor cortex: Controls muscle groups (not individual muscles).
• Premotor cortex: Creates complex movement plans.
• Supplementary motor area: Controls whole-body motions (like turning, jumping).

Descending Motor Pathways

These are the nerves from the brain to the spinal cord that control movement.

• Corticospinal tract: Direct connection: brain → spinal cord → muscles. Controls fine movements, especially in hands and fingers.
• Other pathways (indirect): Rubrospinal, reticulospinal, tectospinal. Control posture, balance, and automatic movements.

Biomedical Engineering Applications

• Neuromuscular stimulation: Uses electricity to make muscles move.
• Deep brain stimulation (DBS): Used in Parkinson’s or tremors.
• Motor cortical prosthesis: Brain-machine interface (move devices with your brain).
• Myoelectric prosthesis: Artificial limbs controlled by EMG (muscle signals).

Key Features of Smooth Muscle

• Not striated (no stripes like skeletal or cardiac).
• Smaller cells than skeletal muscle.
• Can contract a lot more (up to 80% of length).
• Doesn’t use troponin — uses calmodulin for contraction.
• Has dense bodies instead of sarcomeres (for structure).
• Uses caveolae instead of T-tubules.
• Very energy efficient (uses ~1% of energy compared to skeletal).

Types of Smooth Muscle

• By activity:
  • Phasic: Contracts and relaxes (like bladder or intestines). Fires action potentials.
  • Tonic: Always slightly contracted (like blood vessels). Doesn’t need action potentials.
• By coordination:
  • Unitary smooth muscle: Cells are connected by gap junctions (contract together). Most common type. Found in bladder, GI tract, blood vessels.
  • Multi-unit smooth muscle: Each cell works independently. More precise control. Found in iris (eye), hair muscles, ciliary muscles.

Smooth Muscle Control

Controlled by the autonomic nervous system (you don’t consciously control it). Uses acetylcholine and norepinephrine as neurotransmitters. Can also respond to:

• Stretch
• Hormones
• Local chemical signals

Phasic Smooth Muscle Cross-Bridge Cycle

(Found in: intestines, bladder, uterus)

1. Calcium (Ca²⁺) enters the smooth muscle cell (from outside and SR).
2. Ca²⁺ binds to calmodulin (no troponin here).
3. This complex activates myosin light chain kinase (MLCK).
4. MLCK adds a phosphate to myosin (phosphorylation).
5. Phosphorylated myosin can bind to actin → contraction begins.
6. Myosin light chain phosphatase (MLCP) removes the phosphate → ends contraction.

Contraction happens quickly and is brief, in bursts (like bladder emptying).

Tonic Smooth Muscle Cross-Bridge Cycle

(Found in: blood vessels, sphincters)

1. Starts the same as phasic: Ca²⁺ binds calmodulin → activates MLCK → myosin gets phosphorylated → binds actin.
2. But then: Myosin stays bound to actin even after phosphate is removed = latch state.

This allows the muscle to stay contracted with very little ATP use. Tonic contraction is slow, sustained, and energy-efficient — perfect for maintaining vascular tone or closing sphincters.

Autonomic Control of Muscle

• Sympathetic: Adrenergic.
• Parasympathetic: Cholinergic.

Cardiac Action Potential (Electrical Signal)

Much longer than skeletal AP → gives heart time to fill with blood and relax.

Phases:

1. Na⁺ channels open → depolarization.
2. Small dip from K⁺ outflow.
3. Plateau: slow Ca²⁺ in and K⁺ out (keeps heart muscle contracting).
4. Repolarization: more K⁺ out.
5. Resting state (very long refractory period — can’t re-fire too fast).

This prevents the heart from twitching like skeletal muscle. It needs to beat, not spasm.

Cardiac Muscle Cross-Bridge Cycle

The cross-bridge cycle of cardiac muscle is much like skeletal muscle. Myoplasmic Ca²⁺ changes gate the troponin-tropomyosin complex. Ca²⁺ influx occurs through the sarcolemma as well as Ca²⁺ release from reticulum stores. The extracellular Ca²⁺ gradient (not internal) determines contractile force.

Cardiovascular System Design

Blood Streams

• Pulmonary circulation: Right heart → lungs → left heart.
• Systemic circulation: Left heart → rest of the body → right heart.

Blood Vessels

The O₂ content of blood does not define whether a vessel is an artery or vein.

• Arteries and arterioles: Heart to organs. Usually oxygenated blood. High pressure pipes (like a faucet).
• Veins and venules: Organs to heart. Usually deoxygenated blood. Low pressure pipes (like a drain).
• Capillaries: Small vessels (few µm in radius). Perfuse individual organs (sieve).

Blood Flow and Pressure Balance

If no leaks, then:

• Flow in = out (steady).
• Pressure doesn't have to match (veins hold more blood at lower pressure).

• Arteries: small volume, high pressure.
• Veins: large volume, low pressure → Veins are more elastic = they stretch to hold more blood.

Vascular Resistance and Organ Flow

Blood flow to organs is arranged in parallel:

• Allows each organ to get its own blood supply.
• Reduces total vascular resistance.

Modeling Blood Vessels (Like Circuits)

• Blood flow: Q = ΔP / R (Flow = pressure difference ÷ resistance).
• Vessel stretchiness: ΔP = ΔV / C (Pressure = volume change ÷ compliance).

Blood Properties and Components

Blood = non-Newtonian fluid (viscosity changes with flow rate). 6–8% of body weight.

Cellular Components of Blood

• Red Blood Cells (RBCs): Carry O₂.
• White Blood Cells (WBCs): Immunity.
  • Basophils: least common, release inflammation signals.
  • Eosinophils: kill parasites.
  • Neutrophils: most common, kill bacteria.
  • Monocytes: engulf invaders (big eaters).
  • Lymphocytes: B cells — make antibodies; T cells — kill infected or damaged cells.
• Platelets: Help blood clot.

Plasma

Fluid part of blood. Contains:

• Electrolytes (Na⁺, K⁺, etc.)
• Nutrients
• Hormones
• Proteins:
  • Albumin (controls osmotic pressure)
  • Globulins (immunity, transport)
  • Fibrinogen (for clotting)

Serum = plasma after clotting proteins are removed.

Osmotic Balance and Edema

Plasma proteins pull water into blood → oncotic pressure. If protein is low → fluid stays in tissues → edema (swelling).

Hematocrit

% of blood that’s red cells (normal ~40–50%).

• Low = anemia.
• High = dehydration or disease.

Hemoglobin (Hb)

• Each Hb = 4 protein units + 4 heme groups.
• Each heme binds 1 O₂.
• Iron gives blood its color: Fe²⁺ (oxygen binds) = red; Fe³⁺ (oxidized) = dark red/blue.

Hemostasis: Stopping Blood Loss

1. Vasoconstriction: blood vessels tighten.
2. Platelet plug forms at the injury.
3. Fibrin clot seals the break.
4. Plasmin dissolves the clot after healing.

Inflammation

Tissue’s response to damage:

Causes

• Redness & warmth (more blood flow).
• Swelling (leaky capillaries).
• Pain (nerves get stretched).
• Loss of function.

Involves

• Cytokines & chemokines (signal molecules).
• White blood cells (neutrophils & monocytes).

Blood Flow Through the Heart

• Deoxygenated blood: Vena cava → Right atrium → Through tricuspid valve → Right ventricle → Through pulmonary valve → Pulmonary artery → Lungs.
• Oxygenated blood: From lungs → Pulmonary vein → Left atrium → Through mitral valve → Left ventricle → Through aortic valve → Aorta → Body.

Systole: Ventricles contract. Diastole: Ventricles relax.

Stages of the Cardiac Cycle

1. Ventricular Filling (0.45 s): Blood flows from atria → ventricles (passive). Atria contract at the end (adds extra blood).
2. Isovolumetric Contraction (0.05 s): Ventricles begin to contract. All valves closed → pressure builds up.
3. Ejection (0.30 s): Pressure opens pulmonary and aortic valves. Blood exits the ventricles.
4. Isovolumetric Relaxation (0.08 s): Ventricles relax. All valves closed → pressure drops until mitral/tricuspid reopen.

Types of Cardiac Action Potentials

1. SA Node (Pacemaker cells): No stable resting potential. Automatically depolarizes (slow Na⁺ in, low K⁺ out). Short, repeated APs → keeps the heart beating.
2. Atrial/Ventricular Muscle Cells: Stable resting potential. Long Ca²⁺ plateau → sustained contraction. Long refractory period → prevents re-firing too soon.

Heart Rate Modulation: Autonomic Control

• Sympathetic (fight or flight): Increases heart rate. Slows recovery (shorter refractory period).
• Parasympathetic (rest & digest): Decreases heart rate. Increases recovery time.

Both systems act on the SA node, which controls how fast the heart beats.

Arrhythmias: Abnormal Heart Rhythms

• Bradycardia: Too slow (<60 bpm).
• Tachycardia: Too fast (>100 bpm).

Cardiac Output: Factors Affecting Stroke Volume

• Preload: How much blood fills the ventricles before contraction. Related to central venous pressure. More preload → stronger contraction.
• Afterload: The pressure the heart has to work against to pump blood. Related to arterial pressure. More afterload → harder to eject blood.
• Contractility: How strongly the heart contracts. Can be increased by sympathetic stimulation or calcium.

Pressure-Volume (PV) Loop

Graph that shows how pressure and volume in the ventricle change during a beat.

• Lower preload → smaller stroke volume (less output).
• Higher preload → bigger stroke volume (more output).
• Lower afterload → higher stroke volume.

Frank-Starling Law of the Heart

The more the heart fills, the more it contracts.

Main Goals of the Cardiovascular System

• Deliver enough oxygen-rich blood to all organs (CO = HR × SV).
• Maintain blood pressure to:
  • Perfuse tissues.
  • Let kidneys filter blood (BP = CO × Total Peripheral Resistance (TPR)).

Vascular Compliance

Describes how stretchy a blood vessel is.

Pulse Pressure (PP)

PP = Systolic – Diastolic Pressure. PP increases with:

• Higher SV.
• Higher BP.
• Stiffer arteries (less compliance).

Veins are ~20× more compliant than arteries → main blood reservoir.

Bernoulli Principle in Circulation

As blood moves into narrower vessels:

• Resistance increases.
• Pressure drops.
• Velocity increases.

This helps exchange materials in capillaries.

Poiseuille's Law of Fluid Flow

Q = (π × a⁴ × ΔP) / (8 × η × L)

Where:

• a = radius
• ΔP = pressure difference
• η = viscosity
• L = length

Flow depends a lot on radius (a⁴!) → small radius change = big flow change.

Assumptions of Poiseuille's Law

Valid in large vessels (>0.5 mm radius):

• Laminar flow (Reynolds number < 2000).
• Fluid is Newtonian (like water).
• Cylindrical, rigid, smooth tubes.

Doesn’t fully apply to capillaries, which are tiny and irregular.

Blood Pressure Regulation

• Short-term: Controlled by:
  • Baroreflex (seconds).
  • Central nervous system (sympathetic/parasympathetic).

  Affects heart rate, contractility, and vessel tone.

• Long-term: Controlled by blood volume. Managed by kidneys and hormones.

  Affects preload and thus stroke volume.

Four Functions of Respiratory Physiology

1. Pulmonary Ventilation – moving air in and out.
2. Gas Exchange – O₂ into blood, CO₂ out.
3. Gas Transport – moving gases via blood.
4. Ventilation Control – adjusting breathing rate.

Respiratory Anatomy

• Nasal passages: warm, filter, humidify air.
• Larynx (epiglottis): keeps food out of trachea.
• Trachea → bronchi → bronchioles → alveoli (gas exchange area).

Dead Space and Alveolar Ventilation

• Some air never reaches alveoli = dead space (VD).
• Tidal Volume (VT) = total air per breath.
• Alveolar Volume (VA) = VT – VD.
• Alveolar ventilation = RR × (VT – VD).

RQ = CO₂ produced / O₂ consumed.

Alveolar Partial Pressures

• Inspired air is dry → nasal passages humidify.
• Water vapor reduces gas partial pressures.
• At 37°C, vapor pressure = 47 mmHg.
• PO₂ = fO₂ × (PB – 47).

Fick’s Law: flow &propto; surface area × pressure difference / membrane thickness.

Dissociation Curves

• Bohr Effect: ↑CO₂ → Hgb gives up more O₂.
• Haldane Effect: ↑O₂ → more CO₂ released.

Acid-Base and pH Control

Normal blood pH: 7.35–7.44.

Regulation

• Buffers (fast but incomplete).
• Respiration (adjusts PCO₂).
• Kidneys (adjusts HCO₃⁻, slower but complete).

• Hypoventilation → acidosis.
• Hyperventilation → alkalosis.

Respiratory Disorders

• Obstructive: ↓ FEV1/FVC, ↑ RV & TLC. E.g., asthma, emphysema.

  Airflow limited by:

  • Elasticity loss.
  • Lumen narrowing.
  • Wall thickening.
• Restrictive: ↓ TLC, normal/increased FEV1/FVC. E.g., fibrosis, muscle weakness.

  Limited volume or chest expansion.

Respiratory Control

• DRG: normal inspiration.
• VRG: active inspiration/expiration.

Controlled by medulla, modulated by:

• Vagus and glossopharyngeal nerves (pH, stretch).

Biomedical Engineering Applications in Respiration

• Iron lung ventilator.
• CPAP machines.
• Artificial lungs.

Lung Compliance and Resistance

• Compliance = how stretchy lungs are.
• Expiration is mostly passive (muscle-assisted if forced).
• Resistance depends on flow type:
  • Laminar → Poiseuille’s Law.
  • Turbulent → more pressure needed.

Surface Tension and Surfactant

• Water at alveoli surface creates surface tension.
• Small alveoli would collapse without help.
• Surfactant:
  • Reduces surface tension.
  • Stabilizes alveoli.
  • Lowers work of breathing.