Human Physiology: Systems and Coordination

Breathing and Exchange of Gases

The continuous exchange of oxygen (O₂) from the atmosphere with carbon dioxide (CO₂) produced by cells is called breathing or respiration. Organisms utilize O₂ to break down simple molecules and derive energy, while CO₂ is a harmful byproduct that needs to be released.

Respiratory Organs

Mechanisms of breathing vary based on habitat and organization levels.

• Lower invertebrates (sponges, coelenterates, flatworms): Simple diffusion over entire body surface.
• Earthworms: Moist cuticle for gas exchange.
• Insects: Network of tracheal tubes.
• Aquatic arthropods and molluscs: Gills (branchial respiration).
• Terrestrial forms (vertebrates): Lungs (pulmonary respiration).
• Fishes: Gills.
• Amphibians (like frogs): Lungs and moist skin (cutaneous respiration).

Human Respiratory System

The human respiratory system consists of a pair of lungs and associated air passages.

• External nostrils: Open above the upper lips, leading to a nasal chamber.
• Nasal passage: Connects nasal chamber to pharynx.
• Pharynx: Common passage for food and air.
• Larynx: Cartilaginous box, helps in sound production (sound box).
  • Epiglottis: Thin elastic cartilaginous flap covering the glottis during swallowing to prevent food entry into the larynx.
• Trachea: Straight tube extending to the mid-thoracic cavity, divides at the 5th thoracic vertebra into right and left primary bronchi.
• Bronchi: Primary bronchi undergo repeated divisions to form secondary and tertiary bronchi, and then bronchioles, ending in very thin terminal bronchioles.
• Cartilaginous rings: Incomplete rings support the trachea, primary, secondary, tertiary bronchi, and initial bronchioles.
• Alveoli: Thin, irregular-walled, vascularised bag-like structures formed by terminal bronchioles.
• Lungs: Comprise the branching network of bronchi, bronchioles, and alveoli. Humans have two lungs.
• Pleura: Double-layered membrane covering the lungs, with pleural fluid between layers to reduce friction.
  • Outer pleural membrane: Contacts thoracic lining.
  • Inner pleural membrane: Contacts lung surface.
• Parts of the Respiratory System:
  • Conducting part: From external nostrils up to terminal bronchioles. Transports atmospheric air to alveoli, clears foreign particles, humidifies, and brings air to body temperature.
  • Respiratory or exchange part: Alveoli and their ducts. Site of actual diffusion of O₂ and CO₂ between blood and atmospheric air.
• Thoracic chamber: Air-tight chamber where lungs are situated. Formed dorsally by vertebral column, ventrally by sternum, laterally by ribs, and on the lower side by the dome-shaped diaphragm. Changes in thoracic volume are reflected in lung volume, essential for breathing.

Steps of Respiration

Respiration involves five main steps:

1. Breathing or pulmonary ventilation: Atmospheric air drawn in, CO₂-rich alveolar air released out.
2. Diffusion of gases: O₂ and CO₂ across the alveolar membrane.
3. Transport of gases: By the blood.
4. Diffusion of O₂ and CO₂: Between blood and tissues.
5. Utilisation of O₂: By cells for catabolic reactions and resultant CO₂ release (cellular respiration).

Mechanism of Breathing

Breathing involves two stages: inspiration (air drawn in) and expiration (alveolar air released out).

• Pressure gradient: Air movement is achieved by creating a pressure gradient between the lungs (intra-pulmonary pressure) and the atmosphere.
• Muscles involved: Diaphragm and external/internal intercostals between the ribs.
• Inspiration:
  • Initiated by contraction of the diaphragm, increasing thoracic volume in antero-posterior axis.
  • Contraction of external inter-costal muscles lifts ribs and sternum, increasing thoracic volume in dorso-ventral axis.
  • Overall increase in thoracic volume causes a similar increase in pulmonary volume.
  • This decreases intra-pulmonary pressure to less than atmospheric pressure, forcing air into the lungs.
• Expiration:
  • Relaxation of the diaphragm and inter-costal muscles returns them to normal positions, reducing thoracic and pulmonary volume.
  • This increases intra-pulmonary pressure slightly above atmospheric pressure, expelling air from the lungs.
• Forced breathing: Additional abdominal muscles can increase the strength of inspiration and expiration.
• Respiratory rate: A healthy human breathes 12-16 times/minute.
• Spirometer: Used to estimate the volume of air involved in breathing movements, helping in clinical assessment of pulmonary functions.

Respiratory Volumes and Capacities

These measurements are clinically significant.

• Tidal Volume (TV): Volume of air inspired or expired during a normal respiration. Approx. 500 mL (6000-8000 mL/minute for a healthy man).
• Inspiratory Reserve Volume (IRV): Additional volume of air a person can inspire by forcible inspiration. Averages 2500 mL to 3000 mL.
• Expiratory Reserve Volume (ERV): Additional volume of air a person can expire by forcible expiration. Averages 1000 mL to 1100 mL.
• Residual Volume (RV): Volume of air remaining in the lungs even after a forcible expiration. Averages 1100 mL to 1200 mL.
• Inspiratory Capacity (IC): Total volume of air a person can inspire after a normal expiration (TV + IRV).
• Expiratory Capacity (EC): Total volume of air a person can expire after a normal inspiration (TV + ERV).
• Functional Residual Capacity (FRC): Volume of air remaining in the lungs after a normal expiration (ERV + RV).
• Vital Capacity (VC): Maximum volume of air a person can breathe in after a forced expiration (ERV + TV + IRV) or breathe out after a forced inspiration.
• Total Lung Capacity (TLC): Total volume of air accommodated in the lungs at the end of a forced inspiration (RV + ERV + TV + IRV or Vital Capacity + Residual Volume).

Exchange of Gases

• Primary sites: Alveoli, and also between blood and tissues.
• Mechanism: Simple diffusion, mainly based on pressure/concentration gradient.
• Factors affecting diffusion rate: Solubility of gases and thickness of membranes.
• Partial Pressure: Pressure contributed by an individual gas in a mixture (e.g., pO₂ for oxygen, pCO₂ for carbon dioxide).

Partial Pressures (in mm Hg) of O₂ and CO₂

Table adapted from Table 14.1

• Concentration gradients:
  • O₂: From alveoli to blood, and blood to tissues.
  • CO₂: From tissues to blood, and blood to alveoli (opposite direction).
• Solubility: CO₂ is 20-25 times more soluble than O₂, meaning more CO₂ can diffuse per unit difference in partial pressure.
• Diffusion membrane: Made up of three layers:
  1. Thin squamous epithelium of alveoli.
  2. Endothelium of alveolar capillaries.
  3. Basement substance between them (thin basement membrane supporting epithelium and surrounding endothelial cells).
  • Total thickness is much less than a millimetre, facilitating efficient gas diffusion.

Transport of Gases

Blood is the primary medium for O₂ and CO₂ transport.

Transport of Oxygen

• 97%: Transported by RBCs (Red Blood Cells).
• 3%: Carried in a dissolved state through plasma.
• Haemoglobin: Red-coloured iron-containing pigment in RBCs.
  • Binds reversibly with O₂ to form oxyhaemoglobin. Each haemoglobin molecule can carry up to four O₂ molecules.
  • Factors affecting binding: Primarily partial pressure of O₂ (pO₂), also pCO₂, hydrogen ion concentration (H⁺), and temperature.
  • Oxygen dissociation curve: A sigmoid curve obtained when percentage saturation of haemoglobin with O₂ is plotted against pO₂. Useful for studying factors affecting O₂ binding.
  • In alveoli: High pO₂, low pCO₂, lesser H⁺ concentration, lower temperature favour oxyhaemoglobin formation.
  • In tissues: Low pO₂, high pCO₂, high H⁺ concentration, higher temperature favour dissociation of O₂ from oxyhaemoglobin.
  • Delivery: Every 100 ml of oxygenated blood delivers approximately 5 ml of O₂ to the tissues under normal physiological conditions.

Transport of Carbon dioxide

• 20-25%: Transported by haemoglobin as carbamino-haemoglobin.
  • Binding is related to pCO₂. High pCO₂ and low pO₂ (as in tissues) favour CO₂ binding. Low pCO₂ and high pO₂ (as in alveoli) favour CO₂ dissociation.
• 70%: Carried as bicarbonate (HCO₃⁻).
  • RBCs contain high concentration of carbonic anhydrase enzyme (minute quantities in plasma too). This enzyme facilitates the reversible reaction: CO₂ + H₂O ⇌ H₂CO₃ ⇌ HCO₃⁻ + H⁺
  • At tissues: High pCO₂ (due to catabolism) causes CO₂ to diffuse into blood (RBCs and plasma), forming HCO₃⁻ and H⁺.
  • At alveoli: Low pCO₂ causes the reaction to proceed in the opposite direction, releasing CO₂ and H₂O. CO₂ trapped as bicarbonate at the tissue level is released out as CO₂ at the alveoli.
• 7%: Carried in a dissolved state through plasma.
• Delivery: Every 100 ml of deoxygenated blood delivers approximately 4 ml of CO₂ to the alveoli.

Regulation of Respiration

The neural system maintains and moderates the respiratory rhythm.

• Respiratory rhythm centre: Specialised centre in the medulla region of the brain, primarily responsible for regulation.
• Pneumotaxic centre: Located in the pons region of the brain. Can moderate the respiratory rhythm centre functions, reducing inspiration duration and altering respiratory rate.
• Chemosensitive area: Adjacent to the rhythm centre, highly sensitive to CO₂ and hydrogen ions (H⁺). Increase in these substances activates this centre, signaling the rhythm centre for adjustments to eliminate them.
• Receptors: Associated with the aortic arch and carotid artery, recognise changes in CO₂ and H⁺ concentration and send signals to the rhythm centre.
• Role of oxygen: Relatively insignificant in the regulation of respiratory rhythm.

Disorders of the Respiratory System

• Asthma: Difficulty in breathing causing wheezing, due to inflammation of bronchi and bronchioles.
• Emphysema: Chronic disorder with damaged alveolar walls, decreasing respiratory surface. A major cause is cigarette smoking.
• Occupational Respiratory Disorders: Result from long exposure to dust (e.g., grinding, stone-breaking industries). Defense mechanisms cannot cope, leading to inflammation, fibrosis (proliferation of fibrous tissues), and serious lung damage. Protective masks are recommended.

Body Fluids and Circulation

Efficient mechanisms are essential for transporting nutrients and O₂ to cells and removing waste products. Blood and lymph are specialized body fluids for this purpose.

Blood

Blood is a special connective tissue with a fluid matrix (plasma) and formed elements.

Plasma

• Straw-coloured, viscous fluid, constituting nearly 55% of blood.
• 90-92% water.
• Proteins (6-8%):
  • Fibrinogen: Needed for blood clotting or coagulation.
  • Globulins: Primarily involved in defense mechanisms.
  • Albumins: Help in osmotic balance.
• Other constituents: Small amounts of minerals (Na⁺, Ca⁺⁺, Mg⁺⁺, HCO₃⁻, Cl⁻), glucose, amino acids, lipids (always in transit), and inactive clotting factors.
• Serum: Plasma without the clotting factors.

Formed Elements

Collectively constitute nearly 45% of blood.

1. Erythrocytes (Red Blood Cells - RBCs):

   • Most abundant blood cells: 5-5.5 million RBCs/mm³ in a healthy adult male.
   • Formed in red bone marrow in adults.
   • Devoid of nucleus in most mammals, biconcave in shape.
   • Contain haemoglobin (red-coloured, iron-containing complex protein), giving blood its color.
   • Healthy individual: 12-16 gms of haemoglobin in every 100 ml of blood.
   • Play a significant role in transport of respiratory gases.
   • Average lifespan of 120 days, destroyed in the spleen (graveyard of RBCs).

2. Leucocytes (White Blood Cells - WBCs):

   • Colourless (lack haemoglobin), nucleated, relatively lesser in number: 6000-8000 WBCs/mm³.
   • Generally short-lived.
   • Categories:
     • Granulocytes: Neutrophils, eosinophils, basophils.
       • Neutrophils: Most abundant (60-65% of total WBCs). Phagocytic cells that destroy foreign organisms.
       • Basophils: Least abundant (0.5-1%). Secrete histamine, serotonin, heparin, involved in inflammatory reactions.
       • Eosinophils: (2-3%). Resist infections, associated with allergic reactions.
     • Agranulocytes: Lymphocytes, monocytes.
       • Monocytes: (6-8%). Phagocytic cells that destroy foreign organisms.
       • Lymphocytes: (20-25%). Two major types (‘B’ and ‘T’ forms). Responsible for immune responses of the body.

3. Platelets (Thrombocytes):

   • Cell fragments produced from megakaryocytes (special cells in bone marrow).
   • Normal blood contains 1,500,00 - 3,500,00 platelets/mm³.
   • Release substances involved in coagulation or clotting of blood.
   • Reduction in number can lead to clotting disorders and excessive blood loss.

Blood Groups

Two widely used blood groupings are ABO and Rh.

ABO Grouping

• Based on presence or absence of two surface antigens (A and B) on RBCs.
• Plasma contains natural antibodies.

Table adapted from Table 15.1

• Universal donors: Group ‘O’ individuals can donate blood to any other blood group.
• Universal recipients: Group ‘AB’ individuals can accept blood from persons with any blood group.
• Careful matching of donor and recipient blood is crucial during transfusion to avoid clumping (destruction of RBCs).

Rh Grouping

• Based on presence or absence of the Rh antigen (similar to one found in Rhesus monkeys) on RBC surface.
  • Rh positive (Rh+ve): Individuals with the Rh antigen (nearly 80% of humans).
  • Rh negative (Rh-ve): Individuals without the Rh antigen.
• Rh incompatibility: An Rh-ve person exposed to Rh+ve blood will form specific antibodies against Rh antigens. Rh group must be matched before transfusions.
  • Special case: Rh-ve pregnant mother with Rh+ve foetus.
  • During first pregnancy delivery, maternal blood may be exposed to foetal Rh+ve blood, leading to antibody formation in mother.
  • In subsequent pregnancies, maternal Rh antibodies can leak into foetal blood and destroy foetal RBCs, leading to erythroblastosis foetalis (fatal, or severe anaemia and jaundice to baby).
  • Prevention: Administering anti-Rh antibodies to the mother immediately after delivery of the first child.

Coagulation of Blood (Clotting)

• A mechanism to prevent excessive blood loss in response to injury or trauma.
• Clot (coagulam): Dark reddish-brown scum formed at injury site, mainly a network of threads called fibrins trapping dead/damaged blood elements.
• Fibrins formation: Inactive fibrinogen (in plasma) is converted to fibrins by the enzyme thrombin.
• Thrombin formation: Inactive prothrombin (in plasma) is converted to thrombin by the enzyme complex thrombokinase.
• Thrombokinase complex: Formed by a series of linked enzymic reactions (cascade process) involving factors in inactive state in plasma.
• Initiation: Injury or trauma stimulates platelets to release factors that activate coagulation. Tissue factors at injury site can also initiate coagulation.
• Calcium ions (Ca²⁺): Play a very important role in clotting.

Lymph (Tissue Fluid)

• Interstitial fluid: Formed when water and small water-soluble substances move out from blood capillaries into spaces between tissue cells, leaving larger proteins and most formed elements in blood vessels.
• Composition: Has the same mineral distribution as plasma.
• Function: Exchange of nutrients, gases, etc., between blood and cells occurs through this fluid.
• Lymphatic system: Elaborate network of vessels that collects interstitial fluid and drains it back to major veins.
• Lymph: The fluid present in the lymphatic system.
  • Colourless fluid containing specialised lymphocytes.
  • Responsible for immune responses.
  • Important carrier for nutrients, hormones, etc..
  • Fats are absorbed through lymph in the lacteals present in the intestinal villi.

Circulatory Pathways

Circulatory patterns are of two types:

• Open Circulatory System: Present in arthropods and molluscs. Blood pumped by the heart passes through large vessels into open spaces or body cavities called sinuses.
• Closed Circulatory System: Present in annelids and chordates. Blood pumped by the heart is always circulated through a closed network of blood vessels. This pattern allows for more precise regulation of fluid flow.

Evolutionary Change in Vertebrate Hearts

All vertebrates possess a muscular chambered heart.

• Fishes: 2-chambered heart (one atrium, one ventricle). Pumps deoxygenated blood to gills for oxygenation, then supplied to body parts. Deoxygenated blood returns to heart (single circulation).
• Amphibians and most reptiles (except crocodiles): 3-chambered heart (two atria, one single ventricle). Left atrium receives oxygenated blood (from gills/lungs/skin), right atrium receives deoxygenated blood (from body). Blood gets mixed in the single ventricle, which pumps out mixed blood (incomplete double circulation).
• Crocodiles, birds, and mammals: 4-chambered heart (two atria, two ventricles). Oxygenated and deoxygenated blood received by left and right atria respectively, then pass to ventricles of the same side. Ventricles pump blood without mixing, creating two separate circulatory pathways (double circulation).

Human Circulatory System

Also called the blood vascular system, consists of a muscular chambered heart, a network of closed branching blood vessels, and blood.

Heart

• Mesodermally derived organ, situated in the thoracic cavity between the two lungs, slightly tilted to the left. Size of a clenched fist.
• Protected by a double-walled membranous bag, pericardium, enclosing pericardial fluid.
• Four chambers: Two relatively small upper chambers (atria) and two larger lower chambers (ventricles).
• Septa:
  • Inter-atrial septum: Thin muscular wall separating right and left atria.
  • Inter-ventricular septum: Thick-walled, separating left and right ventricles.
  • Atrio-ventricular septum: Thick fibrous tissue separating atrium and ventricle on the same side, with an opening connecting them.
• Valves: Allow blood flow in only one direction (atria to ventricles, ventricles to pulmonary artery/aorta), preventing backward flow.
  • Tricuspid valve: Guards opening between right atrium and right ventricle (three muscular flaps).
  • Bicuspid or Mitral valve: Guards opening between left atrium and left ventricle (two cusps).
  • Semilunar valves: Guard openings of right and left ventricles into the pulmonary artery and aorta respectively.
• Cardiac muscles: Make up the entire heart. Ventricular walls are much thicker than atrial walls.
• Nodal tissue: Specialised cardiac musculature distributed in the heart, capable of generating action potentials without external stimuli (autoexcitable).
  • Sino-atrial node (SAN): Patch of tissue in the right upper corner of the right atrium. Generates maximum action potentials (70-75/min), initiating and maintaining rhythmic contractile activity. Hence, called the pacemaker.
  • Atrio-ventricular node (AVN): Mass of tissue in the lower left corner of the right atrium, close to the atrio-ventricular septum.
  • Atrio-ventricular bundle (AV bundle): Continues from AVN, passes through septa, divides into right and left bundles.
  • Purkinje fibres: Minute fibres branching from bundles throughout ventricular musculature.
• Heartbeat: Normally beats 70-75 times/minute (average 72 beats/min).

Cardiac Cycle

The sequential, cyclically repeated events in the heart (systole and diastole of both atria and ventricles) constitute the cardiac cycle.

1. Joint diastole: All four chambers relaxed. Tricuspid and bicuspid valves open, blood flows from pulmonary veins and vena cava into left and right ventricles via atria. Semilunar valves closed.
2. Atrial systole: SAN generates action potential, stimulating both atria to contract simultaneously. Increases blood flow into ventricles by ~30%.
3. Ventricular systole: Action potential conducted via AVN, AV bundle, Purkinje fibres to ventricular musculature, causing ventricular contraction. Atria relax (diastole).
   • Ventricular pressure increases, closing tricuspid and bicuspid valves (prevents backflow).
   • Further pressure increase forces semilunar valves open, blood flows into pulmonary artery and aorta.
4. Ventricular diastole: Ventricles relax, pressure falls, causing semilunar valves to close (prevents backflow).
   • As ventricular pressure declines further, tricuspid and bicuspid valves are pushed open by atrial pressure (from blood emptying into them from veins).
   • Blood once again moves freely to ventricles, returning to joint diastole.

• Duration: A cardiac cycle lasts 0.8 seconds (at 72 beats/min).
• Stroke volume: Volume of blood pumped out by each ventricle during a cardiac cycle. Approximately 70 mL.
• Cardiac output: Volume of blood pumped out by each ventricle per minute. Stroke volume × Heart rate. Averages 5000 mL or 5 litres in a healthy individual. The body can alter stroke volume and heart rate to change cardiac output.

Heart Sounds

Two prominent sounds are produced per cardiac cycle, audible with a stethoscope.

• First heart sound (lub): Associated with the closure of the tricuspid and bicuspid valves.
• Second heart sound (dub): Associated with the closure of the semilunar valves.
• These sounds have clinical diagnostic significance.

Electrocardiogram (ECG)

A graphical representation of the electrical activity of the heart during a cardiac cycle.

• Standard ECG involves leads connected to wrists and left ankle.
• Each peak corresponds to specific electrical activity:
  • P-wave: Represents electrical excitation (depolarisation) of the atria, leading to atrial contraction.
  • QRS complex: Represents depolarisation of the ventricles, initiating ventricular contraction. Marks the beginning of systole.
  • T-wave: Represents the return of the ventricles from excited to normal state (repolarisation). The end of the T-wave marks the end of systole.
• Counting QRS complexes determines heart beat rate.
• Deviations from normal ECG shape indicate possible abnormality or disease, making it of great clinical significance.

Blood Vessels

Arteries and veins typically consist of three layers:

• Tunica intima: Inner lining of squamous endothelium.
• Tunica media: Middle layer of smooth muscle and elastic fibres. Thinner in veins.
• Tunica externa: External layer of fibrous connective tissue with collagen fibres.

Double Circulation

Humans have a complete double circulation with two circulatory pathways:

1. Pulmonary Circulation:
   • Deoxygenated blood pumped by the right ventricle enters the pulmonary artery.
   • Carried to the lungs for oxygenation.
   • Oxygenated blood is then carried by pulmonary veins into the left atrium.
2. Systemic Circulation:
   • Oxygenated blood entering the aorta (from the left ventricle) is carried by a network of arteries, arterioles, and capillaries to the tissues.
   • Deoxygenated blood is collected by venules, veins, and vena cava and emptied into the right atrium.
   • Provides nutrients, O₂, and essential substances to tissues, while taking CO₂ and harmful substances away for elimination.

• Hepatic portal system: A unique vascular connection where the hepatic portal vein carries blood from the digestive tract to the liver before it is delivered to the systemic circulation.
• Coronary system: Special blood vessels exclusively for circulation of blood to and from the cardiac musculature.

Regulation of Cardiac Activity

• The heart is myogenic; its normal activities are intrinsically regulated by nodal tissue (auto-regulated).
• Neural control: A special neural centre in the medulla oblongata (part of the autonomic nervous system - ANS) moderates cardiac function.
  • Sympathetic nerves: Increase heart beat rate, strength of ventricular contraction, and cardiac output.
  • Parasympathetic neural signals: Decrease heart beat rate, speed of action potential conduction, and cardiac output.
• Hormonal control: Adrenal medullary hormones can also increase cardiac output.

Disorders of the Circulatory System

• High Blood Pressure (Hypertension): Blood pressure higher than normal (120/80 mmHg is normal). Repeated checks of 140/90 mmHg or higher indicate hypertension. Leads to heart diseases and affects vital organs like the brain and kidney.
• Coronary Artery Disease (CAD) / Atherosclerosis: Affects vessels supplying blood to the heart muscle. Caused by deposits of calcium, fat, cholesterol, and fibrous tissues, which narrow the lumen of arteries.
• Angina (Angina Pectoris): Symptom of acute chest pain occurring when insufficient oxygen reaches the heart muscle. More common among middle-aged and elderly, due to conditions affecting blood flow.
• Heart Failure: State where the heart is not pumping blood effectively enough to meet the body’s needs. Often called congestive heart failure due to lung congestion. Not the same as cardiac arrest (heart stops) or heart attack (heart muscle suddenly damaged by inadequate blood supply).

Excretory Products and their Elimination

Animals accumulate wastes like ammonia, urea, uric acid, CO₂, water, and ions (Na⁺, K⁺, Cl⁻, phosphate, sulphate) from metabolic activities or excess ingestion. These must be removed.

Major Nitrogenous Wastes

• Ammonia: Most toxic form, requires large amounts of water for elimination (Ammonotelism). Common in many bony fishes, aquatic amphibians, and aquatic insects. Excreted by diffusion across body surfaces or gill surfaces (in fish) as ammonium ions. Kidneys play insignificant role in its removal.
• Urea: Lesser toxic than ammonia, produced for water conservation in terrestrial adaptation. Mammals, many terrestrial amphibians, and marine fishes mainly excrete urea (Ureotelism). Ammonia is converted to urea in the liver, released into blood, filtered, and excreted by kidneys. Some urea retained in kidney matrix to maintain osmolarity.
• Uric Acid: Least toxic, removed with minimum water loss (Uricotelism). Excreted as pellet or paste by reptiles, birds, land snails, and insects.

Excretory Structures in Animals

• Protonephridia or flame cells: Excretory structures in Platyhelminthes (flatworms like Planaria), rotifers, some annelids, and cephalochordate (Amphioxus). Primarily concerned with ionic and fluid volume regulation (osmoregulation).
• Nephridia: Tubular excretory structures of earthworms and other annelids. Help remove nitrogenous wastes and maintain fluid/ionic balance.
• Malpighian tubules: Excretory structures of most insects (including cockroaches). Help in nitrogenous waste removal and osmoregulation.
• Antennal glands or green glands: Perform excretory function in crustaceans (like prawns).

Human Excretory System

Consists of a pair of kidneys, one pair of ureters, a urinary bladder, and a urethra.

Kidneys

• Reddish-brown, bean-shaped structures, situated between the last thoracic and third lumbar vertebra, close to the dorsal inner wall of the abdominal cavity.
• Adult human kidney size: 10-12 cm length, 5-7 cm width, 2-3 cm thickness, 120-170 g average weight.
• Hilum: A notch on the inner concave surface where ureter, blood vessels, and nerves enter.
• Renal pelvis: Broad funnel-shaped space inside the hilum, with projections called calyces.
• Outer layer: Tough capsule.
• Internal zones:
  • Outer cortex.
  • Inner medulla: Divided into conical masses called medullary pyramids that project into the calyces.
  • Columns of Bertini: Extensions of the cortex between the medullary pyramids.

Nephrons

• Functional units of the kidney, nearly one million per kidney.
• Each nephron has two parts:
  1. Glomerulus: A tuft of capillaries formed by the afferent arteriole (fine branch of renal artery). Blood is carried away by an efferent arteriole.
  2. Renal tubule: Begins with a double-walled cup-like structure called Bowman’s capsule, which encloses the glomerulus.
• Malpighian body or renal corpuscle: The glomerulus along with Bowman’s capsule.
• Parts of the renal tubule:
  • Proximal Convoluted Tubule (PCT): Highly coiled network continuous from Bowman’s capsule.
  • Henle’s loop: Hairpin-shaped, with a descending and an ascending limb.
  • Distal Convoluted Tubule (DCT): Another highly coiled region, continuous from the ascending limb of Henle’s loop.
  • Collecting duct: Straight tube into which DCTs of many nephrons open. Many collecting ducts converge and open into the renal pelvis through medullary pyramids.
• Location in kidney: Malpighian corpuscle, PCT, and DCT are in the cortical region. Henle’s loop dips into the medulla.
• Nephron types:
  • Cortical nephrons: Henle’s loop is short and extends little into the medulla.
  • Juxta medullary nephrons: Henle’s loop is very long and runs deep into the medulla.
• Peritubular capillaries: Fine capillary network around the renal tubule, formed by the efferent arteriole.
• Vasa recta: A minute U-shaped vessel of the peritubular network, running parallel to Henle’s loop. Absent or highly reduced in cortical nephrons.

Urine Formation

Involves three main processes in different parts of the nephron:

1. Glomerular Filtration:

   • First step, carried out by the glomerulus.
   • Ultrafiltration: Blood is filtered so finely that almost all plasma constituents except proteins pass into Bowman’s capsule lumen.
   • Filtration layers: Blood pressure forces filtration through three layers: endothelium of glomerular blood vessels, epithelium of Bowman’s capsule (podocytes arranged to leave filtration slits/slit pores), and a basement membrane between them.
   • Filtration rate: Average 1100-1200 ml of blood filtered by kidneys per minute (roughly 1/5th of cardiac output).
   • Glomerular Filtration Rate (GFR): Amount of filtrate formed per minute. In a healthy individual, approx. 125 ml/minute, or 180 litres per day.
   • GFR Regulation: Kidneys have built-in mechanisms. Juxta Glomerular Apparatus (JGA): A special sensitive region formed by cellular modifications in the DCT and afferent arteriole where they contact. A fall in GFR activates JG cells to release renin, stimulating glomerular blood flow and restoring GFR.

2. Reabsorption:

   • Nearly 99% of the filtrate is reabsorbed by renal tubules.
   • Tubular epithelial cells perform this by active (glucose, amino acids, Na⁺) or passive (nitrogenous wastes, water in initial segments) mechanisms.

3. Tubular Secretion:

   • Tubular cells secrete substances like H⁺, K⁺, and ammonia into the filtrate.
   • Important for maintaining ionic and acid-base balance of body fluids.

Function of the Tubules

• Proximal Convoluted Tubule (PCT):
  • Lined by simple cuboidal brush border epithelium (increases surface area for reabsorption).
  • Reabsorbs nearly all essential nutrients and 70-80% of electrolytes and water.
  • Helps maintain pH and ionic balance by selective secretion of H⁺ and ammonia into filtrate and absorption of HCO₃⁻.
• Henle’s Loop:
  • Minimum reabsorption in its ascending limb.
  • Plays a significant role in maintaining high osmolarity of medullary interstitial fluid.
  • Descending limb: Permeable to water, almost impermeable to electrolytes (concentrates filtrate as it moves down).
  • Ascending limb: Impermeable to water, allows active or passive transport of electrolytes (dilutes filtrate as it moves upward).
• Distal Convoluted Tubule (DCT):
  • Conditional reabsorption of Na⁺ and water.
  • Capable of HCO₃⁻ reabsorption and selective secretion of H⁺, K⁺, and NH₃ to maintain pH and sodium-potassium balance in blood.
• Collecting Duct:
  • Extends from kidney cortex to inner medulla.
  • Large amounts of water can be reabsorbed from this region to produce concentrated urine.
  • Allows passage of small amounts of urea into medullary interstitium to maintain osmolarity.
  • Plays a role in pH and ionic balance by selective secretion of H⁺ and K⁺ ions.

Mechanism of Concentration of the Filtrate (Counter Current Mechanism)

Mammals can produce concentrated urine (up to four times the initial filtrate).

• Henle’s loop and vasa recta: Play a significant role.
• Counter current flow: Flow of filtrate in the two limbs of Henle’s loop and flow of blood through the two limbs of vasa recta are in opposite directions, forming a counter current.
• Osmolarity gradient: The proximity and counter current help maintain an increasing osmolarity towards the inner medullary interstitium, from 300 mOsmolL⁻¹ in the cortex to about 1200 mOsmolL⁻¹ in the inner medulla.
• Mainly caused by NaCl and urea.
  • NaCl: Transported by ascending limb of Henle’s loop, exchanged with descending limb of vasa recta, and returned to interstitium by ascending vasa recta.
  • Urea: Small amounts enter thin segment of ascending limb of Henle’s loop and are transported back to interstitium by the collecting tubule.
• This mechanism facilitates easy passage of water from the collecting tubule, thereby concentrating the filtrate (urine).

Regulation of Kidney Function

Monitored and regulated by hormonal feedback mechanisms involving the hypothalamus, JGA, and heart.

• Antidiuretic Hormone (ADH) / Vasopressin:
  • Released from neurohypophysis (posterior pituitary) by hypothalamus stimulation due to activated osmoreceptors (from changes in blood/fluid volume, ionic concentration, excessive fluid loss).
  • Facilitates water reabsorption from later parts of the tubule, preventing diuresis (excessive urine production).
  • Increase in body fluid volume suppresses ADH release.
  • ADH also constricts blood vessels, increasing blood pressure, which in turn increases glomerular blood flow and GFR.
• Renin-Angiotensin Mechanism (JGA):
  • A fall in glomerular blood flow/pressure/GFR activates JG cells to release renin.
  • Renin converts angiotensinogen (in blood) to angiotensin I, then to angiotensin II.
  • Angiotensin II: Powerful vasoconstrictor, increases glomerular blood pressure and GFR. Also activates adrenal cortex to release Aldosterone.
  • Aldosterone: Causes reabsorption of Na⁺ and water from distal parts of the tubule, leading to increased blood pressure and GFR.
• Atrial Natriuretic Factor (ANF):
  • Released from the atria of the heart due to increased blood flow.
  • Causes vasodilation (dilation of blood vessels), thereby decreasing blood pressure.
  • Acts as a check on the renin-angiotensin mechanism.

Micturition (Urination)

• Urine formed by nephrons is carried to the urinary bladder and stored.
• Signal for release: Initiated by stretching of the urinary bladder as it fills. Stretch receptors on bladder walls send signals to the CNS (Central Nervous System).
• Micturition reflex: CNS sends motor messages to initiate contraction of bladder smooth muscles and simultaneous relaxation of the urethral sphincter, causing urine release.
• Average daily urine output: 1 to 1.5 litres.
• Urine characteristics: Light yellow, watery, slightly acidic (pH 6.0), characteristic odour.
• Urea excretion: On average, 25-30 gm of urea excreted per day.
• Clinical diagnosis: Urine analysis helps detect metabolic disorders or kidney malfunction. E.g., presence of glucose (Glycosuria) and ketone bodies (Ketonuria) indicates diabetes mellitus.

Role of Other Organs in Excretion

• Lungs: Remove large amounts of CO₂ (approx. 200mL/min) and significant quantities of water daily.
• Liver: Largest gland. Secretes bile, containing substances like bilirubin, biliverdin, cholesterol, degraded steroid hormones, vitamins, and drugs. Most pass out with digestive wastes.
• Skin:
  • Sweat glands: Produce sweat (watery fluid with NaCl, small amounts of urea, lactic acid). Primary function is cooling, but also removes wastes.
  • Sebaceous glands: Eliminate sterols, hydrocarbons, and waxes through sebum, providing a protective oily skin covering.
• Small amounts of nitrogenous wastes can also be eliminated through saliva.

Disorders of the Excretory System

• Uremia: Accumulation of urea in blood due to kidney malfunction. Highly harmful, can lead to kidney failure.
  • Hemodialysis (Artificial Kidney): Process to remove urea. Blood drained from an artery, anticoagulant (heparin) added, pumped into a dialysing unit (coiled cellophane tube surrounded by dialysing fluid). Porous cellophane allows waste molecules to diffuse out (concentration gradient). Cleared blood (anti-heparin added) is pumped back into a vein. A boon for uremic patients.
• Kidney transplantation: Ultimate method for acute renal failures. Functioning kidney from a donor (preferably close relative to minimize rejection) is transplanted. Modern procedures have increased success rates.
• Renal calculi: Stone or insoluble mass of crystallised salts (e.g., oxalates) formed within the kidney.
• Glomerulonephritis: Inflammation of glomeruli of the kidney.

Locomotion and Movement

Movement is a significant feature of living beings, ranging from protoplasmic streaming to cilia, flagella, and limb movements. Locomotion refers to voluntary movements that result in a change of place or location (e.g., walking, running, swimming).

• All locomotions are movements, but not all movements are locomotions.
• Locomotion is generally for search of food, shelter, mate, breeding grounds, favorable climatic conditions, or to escape from enemies/predators.

Types of Movement in Human Cells

1. Amoeboid movement:
   • Exhibited by specialized cells like macrophages and leucocytes in blood.
   • Effected by pseudopodia formed by streaming of protoplasm (like in Amoeba).
   • Cytoskeletal elements like microfilaments are involved.
2. Ciliary movement:
   • Occurs in most internal tubular organs lined by ciliated epithelium.
   • Coordinated movements of cilia in the trachea help remove dust particles and foreign substances.
   • Facilitates passage of ova through the female reproductive tract.
3. Muscular movement:
   • Movement of limbs, jaws, tongue, etc., requires muscular movement.
   • The contractile property of muscles is effectively used for locomotion and other movements.
   • Locomotion requires a perfect coordinated activity of muscular, skeletal, and neural systems.

Muscle

Muscle is a specialized tissue of mesodermal origin, contributing about 40-50% of the body weight of a human adult.

• Special properties: Excitability, contractility, extensibility, and elasticity.
• Classification based on location, appearance, and nature of regulation:

1. Skeletal Muscles:

   • Closely associated with skeletal components.
   • Appear striped (striated) under the microscope.
   • Activities are under voluntary control of the nervous system (voluntary muscles).
   • Primarily involved in locomotory actions and changes of body postures.

2. Visceral Muscles (Smooth Muscles):

   • Located in the inner walls of hollow visceral organs (e.g., alimentary canal, reproductive tract).
   • Do not exhibit striations (smooth in appearance).
   • Activities are not under voluntary control (involuntary muscles).
   • Assist in transportation of food through digestive tract and gametes through genital tract.

3. Cardiac Muscles:

   • Muscles of the heart.
   • Cardiac muscle cells assemble in a branching pattern.
   • Appear striated.
   • Involuntary in nature as the nervous system does not control their activities directly.

Skeletal Muscle Structure (Myofibril)

• Each skeletal muscle is made of muscle bundles (fascicles) held together by collagenous connective tissue (fascia).
• Each muscle bundle contains many muscle fibres (cells).
  • Sarcolemma: Plasma membrane lining the muscle fibre.
  • Sarcoplasm: Cytoplasm within sarcolemma, contains many nuclei (syncitium).
  • Sarcoplasmic reticulum: Endoplasmic reticulum of muscle fibres, the storehouse of calcium ions (Ca²⁺).
• Myofilaments or Myofibrils: Large numbers of parallelly arranged filaments in the sarcoplasm.
  • Exhibit alternate dark and light bands due to the distribution of two proteins: Actin and Myosin.
  • I-band (Isotropic band): Light band, contains actin (thin filaments).
  • A-band (Anisotropic band): Dark band, contains myosin (thick filaments).
  • Both proteins are rod-like, parallel to each other and longitudinal axis of myofibrils.
  • Z-line: An elastic fibre in the centre of each I-band, bisecting it. Thin filaments are firmly attached to the Z-line.
  • M-line: A thin fibrous membrane in the middle of the A-band, holding thick filaments together.
  • Sarcomere: The portion of the myofibril between two successive Z-lines, considered the functional unit of contraction.
  • H-zone: In a resting state, the central part of the thick filament (A-band) not overlapped by thin filaments.

Structure of Contractile Proteins

1. Actin (Thin) Filament:

   • Made of two ‘F’ (filamentous) actins helically wound.
   • Each ‘F’ actin is a polymer of monomeric ‘G’ (Globular) actins.
   • Two filaments of tropomyosin run close to the ‘F’ actins.
   • Troponin: A complex protein distributed at regular intervals on tropomyosin. In the resting state, a subunit of troponin masks the active binding sites for myosin on the actin filaments.

2. Myosin (Thick) Filament:

   • Polymerised protein composed of many monomeric proteins called Meromyosins.
   • Each meromyosin has two parts:
     • Globular head with a short arm: Called the heavy meromyosin (HMM). Projects outwards as a cross arm.
     • Tail: Called the light meromyosin (LMM).
   • The globular head is an active ATPase enzyme and has binding sites for ATP and active sites for actin.

Mechanism of Muscle Contraction (Sliding Filament Theory)

Contraction occurs by the sliding of the thin (actin) filaments over the thick (myosin) filaments.

1. Neural Signal: A signal from the CNS (Central Nervous System) via a motor neuron arrives at the neuromuscular junction (motor-end plate).
2. Neurotransmitter Release: Acetylcholine (neurotransmitter) is released, generating an action potential in the sarcolemma.
3. Ca²⁺ Release: The action potential spreads through the muscle fibre, causing the release of calcium ions (Ca²⁺) into the sarcoplasm.
4. Active Site Exposure: Increased Ca²⁺ levels bind to a subunit of troponin on actin filaments, removing the masking of active sites for myosin.
5. Cross Bridge Formation: Utilising energy from ATP hydrolysis, the myosin head binds to the exposed active sites on actin to form a cross bridge.
6. Sliding and Shortening: This pulls the attached actin filaments towards the centre of the A-band. The Z-line attached to these actins are also pulled inwards, causing the sarcomere to shorten (contraction). During shortening, I-bands get reduced, while A-bands retain their length.
7. Cross Bridge Breaking: Myosin releases ADP and Pi, returning to its relaxed state. A new ATP binds, breaking the cross-bridge.
8. Cycle Repetition: ATP is again hydrolysed by the myosin head, and the cycle of cross bridge formation and breakage repeats, causing further sliding.
9. Relaxation: The process continues until Ca²⁺ ions are pumped back to the sarcoplasmic cisternae, resulting in the masking of actin filaments and the return of Z-lines to their original position.

• Fatigue: Repeated muscle activation can lead to lactic acid accumulation (due to anaerobic glycogen breakdown), causing fatigue.

Muscle Fibre Types

• Red fibres:
  • High content of myoglobin (red-coloured, oxygen-storing pigment).
  • Contain plenty of mitochondria, utilizing stored oxygen for ATP production (aerobic muscles).
• White fibres:
  • Very less myoglobin (pale or whitish appearance).
  • Few mitochondria, but high amount of sarcoplasmic reticulum.
  • Depend on anaerobic process for energy.

Skeletal System

Consists of a framework of 206 bones and a few cartilages.

• Bone: Very hard matrix due to calcium salts.
• Cartilage: Slightly pliable matrix due to chondroitin salts.
• Divisions:

1. Axial Skeleton (80 bones): Distributed along the main axis of the body.

   • Skull (22 bones):
     • Cranial bones (8): Form the hard protective outer covering (cranium) for the brain.
     • Facial bones (14 skeletal elements): Form the front part of the skull.
   • Hyoid bone: Single U-shaped bone at the base of the buccal cavity.
   • Ear Ossicles (3 tiny bones in each middle ear): Malleus, Incus, and Stapes.
   • Articulation: Skull articulates with the superior region of the vertebral column via two occipital condyles (dicondylic skull).
   • Vertebral Column (26 serially arranged vertebrae):
     • Dorsally placed, extends from skull base, main framework of the trunk.
     • Each vertebra has a central hollow portion (neural canal) for the spinal cord.
     • First vertebra is the atlas, articulates with occipital condyles.
     • Regions: Cervical (7), Thoracic (12), Lumbar (5), Sacral (1-fused), and Coccygeal (1-fused). Number of cervical vertebrae is seven in almost all mammals.
     • Functions: Protects spinal cord, supports head, serves as attachment for ribs and back musculature.
   • Sternum: Flat bone on the ventral midline of the thorax.
   • Ribs (12 pairs): Thin, flat bones, bicephalic (two articulation surfaces on dorsal end).
     • True ribs (first 7 pairs): Dorsally attached to thoracic vertebrae, ventrally to sternum with hyaline cartilage.
     • Vertebrochondral (false) ribs (8th, 9th, and 10th pairs): Do not articulate directly with sternum, but join the seventh rib via hyaline cartilage.
     • Floating ribs (last 2 pairs: 11th and 12th): Not connected ventrally.
     • Rib cage: Thoracic vertebrae, ribs, and sternum together form the rib cage.

2. Appendicular Skeleton: Bones of the limbs along with their girdles. Each limb has 30 bones.

   • Bones of the hand (fore limb): Humerus, radius, ulna, carpals (wrist bones - 8), metacarpals (palm bones - 5), phalanges (digits - 14).
   • Bones of the legs (hind limb): Femur (thigh bone - longest), tibia, fibula, tarsals (ankle bones - 7), metatarsals (5), phalanges (digits - 14).
   • Patella: Cup-shaped bone covering the knee ventrally (knee cap).
   • Pectoral Girdle (shoulder girdle): Articulates upper limbs with axial skeleton. Two halves, each with a clavicle and a scapula.
     • Scapula: Large triangular flat bone, dorsal part of thorax (between 2nd and 7th ribs). Has a spine (elevated ridge) projecting as a flat, expanded process called acromion (clavicle articulates here).
     • Glenoid cavity: Depression below acromion, articulates with humerus head to form the shoulder joint.
     • Clavicle: Long slender bone with two curvatures, commonly called the collar bone.
   • Pelvic Girdle (hip girdle): Articulates lower limbs with axial skeleton. Two coxal bones.
     • Each coxal bone formed by fusion of three bones: ilium, ischium, and pubis.
     • Acetabulum: Cavity at the fusion point, where the thigh bone articulates.
     • Pubic symphysis: The two halves of the pelvic girdle meet ventrally here, containing fibrous cartilage.

Joints

Points of contact between bones, or between bones and cartilages. Essential for all types of movements involving bony parts. Muscle-generated force is used to carry out movement through joints, where the joint acts as a fulcrum.

• Types of Joints:

1. Fibrous joints:
   • Do not allow any movement.
   • Flat skull bones fuse end-to-end with dense fibrous connective tissues in form of sutures to form the cranium.
2. Cartilaginous joints:
   • Bones joined by cartilages.
   • Permit limited movements (e.g., joint between adjacent vertebrae in the vertebral column).
3. Synovial joints:
   • Characterised by a fluid-filled synovial cavity between articulating surfaces of two bones.
   • Allow considerable movement, crucial for locomotion and other movements.
   • Examples:
     • Ball and socket joint: Between humerus and pectoral girdle.
     • Hinge joint: Knee joint.
     • Pivot joint: Between atlas and axis.
     • Gliding joint: Between the carpals.
     • Saddle joint: Between carpal and metacarpal of thumb.

Disorders of Muscular and Skeletal System

• Myasthenia gravis: Autoimmune disorder affecting neuromuscular junction, leading to fatigue, weakening, and paralysis of skeletal muscles.
• Muscular dystrophy: Progressive degeneration of skeletal muscle, mostly due to genetic disorder.
• Tetany: Rapid spasms (wild contractions) in muscle due to low Ca²⁺ in body fluid.
• Arthritis: Inflammation of joints.
• Osteoporosis: Age-related disorder characterized by decreased bone mass and increased chances of fractures. Decreased levels of estrogen are a common cause.
• Gout: Inflammation of joints due to accumulation of uric acid crystals.

Neural Control and Coordination

The neural system and the endocrine system jointly coordinate and integrate all activities of organs to maintain homeostasis and synchronize functions. The neural system provides an organized network of point-to-point connections for quick coordination.

Neural System

• Composed of highly specialized cells called neurons, which detect, receive, and transmit different kinds of stimuli.
• Neural organization complexity: Simple in lower invertebrates (e.g., Hydra - network of neurons), better organized in insects (brain, ganglia, neural tissues), most developed in vertebrates.

Human Neural System

Divided into two parts:

1. Central Neural System (CNS):

   • Includes the brain and the spinal cord.
   • Site of information processing and control.

2. Peripheral Neural System (PNS):

   • Comprises all the nerves of the body associated with the CNS.
   • Nerve fibres types:
     • Afferent fibres: Transmit impulses from tissues/organs to the CNS.
     • Efferent fibres: Transmit regulatory impulses from the CNS to concerned peripheral tissues/organs.
   • PNS Divisions:
     • Somatic Neural System: Relays impulses from CNS to skeletal muscles (voluntary actions).
     • Autonomic Neural System (ANS): Transmits impulses from CNS to involuntary organs and smooth muscles of the body.
       • Further classified into sympathetic neural system and parasympathetic neural system.
   • Visceral Nervous System: Part of the PNS comprising the complex of nerves, fibres, ganglia, and plexuses that carry impulses between the CNS and the viscera (internal organs).

Neuron (Structural and Functional Unit)

A microscopic structure composed of three major parts:

• Cell body: Contains cytoplasm, typical cell organelles, and granular bodies called Nissl’s granules.
• Dendrites: Short fibres branching repeatedly from the cell body, also containing Nissl’s granules. They transmit impulses towards the cell body.
• Axon: Long fibre, distally branched. Each branch terminates as a bulb-like structure called a synaptic knob, which possesses synaptic vesicles containing neurotransmitters. Axons transmit nerve impulses away from the cell body to a synapse or neuromuscular junction.
• Neuron Types (based on axon and dendrite number):
  • Multipolar: One axon and two or more dendrites (found in cerebral cortex).
  • Bipolar: One axon and one dendrite (found in the retina of eye).
  • Unipolar: Cell body with one axon only (usually in embryonic stage).
• Axon Types (based on myelin sheath):
  • Myelinated nerve fibres: Enveloped with Schwann cells forming a myelin sheath around the axon. Gaps between adjacent myelin sheaths are nodes of Ranvier. Found in spinal and cranial nerves.
  • Non-myelinated nerve fibres: Enclosed by a Schwann cell but without a myelin sheath. Commonly found in autonomous and somatic neural systems.

Generation and Conduction of Nerve Impulse

Neurons are excitable cells because their membranes are in a polarised state.

• Resting Potential:
  • When a neuron is not conducting an impulse (resting), the axonal membrane is comparatively more permeable to potassium ions (K⁺) and nearly impermeable to sodium ions (Na⁺). It’s also impermeable to negatively charged proteins inside the axoplasm.
  • Result: Axoplasm (inside) has high K⁺ and negatively charged proteins, low Na⁺. Fluid outside has low K⁺, high Na⁺, forming a concentration gradient.
  • These ionic gradients are maintained by the sodium-potassium pump, which actively transports 3 Na⁺ outwards for 2 K⁺ into the cell.
  • Consequently, the outer surface of the membrane is positively charged, and the inner surface is negatively charged; hence, it’s polarised. The electrical potential difference is the resting potential.
• Action Potential (Nerve Impulse):
  • When a stimulus is applied, the membrane at that site becomes freely permeable to Na⁺, leading to a rapid influx of Na⁺.
  • This reverses the polarity: outer surface becomes negatively charged, inner side positively charged (depolarised).
  • This electrical potential difference across the plasma membrane is called the action potential or nerve impulse.
  • Conduction: Current flows from the depolarised site (A) to the immediately adjacent polarised site (B) on the inner surface, and in the opposite direction on the outer surface, completing a circuit. This causes site B to depolarize, and the impulse is thus conducted along the axon.
• Repolarisation:
  • The rise in Na⁺ permeability is short-lived and quickly followed by a rise in K⁺ permeability.
  • K⁺ diffuses outside the membrane, restoring the resting potential at the excited site, making the fibre responsive again.

Transmission of Impulses (Synapses)

A nerve impulse is transmitted from one neuron to another through junctions called synapses. A synapse is formed by the membranes of a pre-synaptic neuron and a post-synaptic neuron, which may or may not be separated by a synaptic cleft.

1. Electrical Synapses:

   • Pre- and post-synaptic neuron membranes are in very close proximity.
   • Electrical current flows directly from one neuron to another.
   • Transmission is faster than chemical synapses.
   • Rare in the human system.

2. Chemical Synapses:

   • Pre- and post-synaptic neuron membranes are separated by a fluid-filled space called the synaptic cleft.
   • Neurotransmitters (chemicals) are involved in impulse transmission.
   • Process:
     • Axon terminals contain vesicles filled with neurotransmitters.
     • An impulse (action potential) arrives at the axon terminal, stimulating synaptic vesicles to fuse with the plasma membrane and release neurotransmitters into the synaptic cleft.
     • Released neurotransmitters bind to specific receptors on the post-synaptic membrane.
     • This binding opens ion channels, allowing ion entry, which generates a new potential in the post-synaptic neuron.
     • The new potential can be either excitatory or inhibitory.

Central Neural System (CNS)

Brain

The brain is the central information processing organ, acting as the ‘command and control system’ of the body.

• Functions: Controls voluntary movements, body balance, functioning of vital involuntary organs (lungs, heart, kidneys), thermoregulation, hunger and thirst, circadian rhythms, activities of endocrine glands, human behaviour. Also site for processing vision, hearing, speech, memory, intelligence, emotions, and thoughts.
• Protection: Well protected by the skull.
  • Inside the skull, covered by cranial meninges:
    • Dura mater: Outer layer.
    • Arachnoid: Very thin middle layer.
    • Pia mater: Inner layer, in contact with brain tissue.
• Major parts:

1. Forebrain: Consists of cerebrum, thalamus, and hypothalamus.

   • Cerebrum: Major part of human brain. Divided longitudinally into two cerebral hemispheres connected by the corpus callosum (tract of nerve fibres).
     • Cerebral cortex: Layer of cells covering the cerebral hemisphere, thrown into prominent folds. Referred to as grey matter due to concentrated neuron cell bodies.
     • Contains motor areas, sensory areas, and large association areas (responsible for complex functions like intersensory associations, memory, communication).
     • White matter: Inner part of cerebral hemisphere, made of myelinated fibres, giving opaque white appearance.
   • Thalamus: Cerebrum wraps around it. Major coordinating centre for sensory and motor signalling.
   • Hypothalamus: Lies at the base of the thalamus. Contains centres that control body temperature, urge for eating and drinking. Also contains neurosecretory cells secreting hypothalamic hormones.
   • Limbic Lobe / Limbic System: Inner parts of cerebral hemispheres and associated deep structures (e.g., amygdala, hippocampus). Involved in regulation of sexual behaviour, emotional reactions (excitement, pleasure, rage, fear), and motivation.

2. Midbrain:

   • Located between the thalamus/hypothalamus (forebrain) and pons (hindbrain).
   • Cerebral aqueduct: Canal passing through the midbrain.
   • Dorsal portion consists mainly of four round swellings called corpora quadrigemina.

3. Hindbrain: Comprises pons, cerebellum, and medulla (medulla oblongata).

   • Pons: Consists of fibre tracts that interconnect different regions of the brain.
   • Cerebellum: Has a very convoluted surface to provide additional space for many more neurons.
   • Medulla (oblongata): Connected to the spinal cord. Contains centres controlling respiration, cardiovascular reflexes, and gastric secretions.

• Brain Stem: Made up of the midbrain, pons, and medulla oblongata. Forms connections between the brain and spinal cord.

Chemical Coordination and Integration

The neural system provides rapid, point-to-point coordination, but it is fast and short-lived. Hormones, produced by the endocrine system, provide a special kind of chemical coordination and integration to continuously regulate cellular functions and reach all cells of the body. The neural and endocrine systems work jointly.

Endocrine Glands and Hormones

• Endocrine glands: Lack ducts (ductless glands); their secretions (hormones) are released directly into the blood.
• Hormones: Non-nutrient chemicals that act as intercellular messengers and are produced in trace amounts.
• Invertebrates have simple endocrine systems; vertebrates have a large number of hormones.

Human Endocrine System

Consists of organized endocrine glands and hormone-producing diffused tissues/cells.

• Major glands: Pituitary, pineal, thyroid, adrenal, pancreas, parathyroid, thymus, and gonads (testis in males, ovary in females).
• Other organs producing hormones: Gastrointestinal tract, liver, kidney, heart.

The Hypothalamus

• Basal part of diencephalon (forebrain).
• Regulates a wide spectrum of body functions.
• Contains neurosecretory cells (nuclei) that produce hormones regulating pituitary hormone synthesis and secretion.
• Two types of hypothalamic hormones:
  • Releasing hormones: Stimulate secretion of pituitary hormones (e.g., Gonadotrophin releasing hormone (GnRH) stimulates pituitary synthesis and release of gonadotrophins).
  • Inhibiting hormones: Inhibit secretions of pituitary hormones (e.g., Somatostatin inhibits growth hormone release from pituitary).
• These hormones are released from nerve endings and reach the anterior pituitary through a portal circulatory system.
• The posterior pituitary is under direct neural regulation of the hypothalamus.

The Pituitary Gland

Located in a bony cavity called sella tursica, attached to the hypothalamus by a stalk. Anatomically divided into adenohypophysis and neurohypophysis.

1. Adenohypophysis:

   • Pars distalis (Anterior Pituitary): Produces six trophic hormones:
     • Growth Hormone (GH): Regulates growth. Oversecretion leads to gigantism (abnormal growth) or acromegaly (severe disfigurement, especially of face, in adults). Low secretion results in pituitary dwarfism.
     • Prolactin (PRL): Regulates growth of mammary glands and milk formation.
     • Thyroid Stimulating Hormone (TSH): Stimulates synthesis and secretion of thyroid hormones from the thyroid gland.
     • Adrenocorticotrophic Hormone (ACTH): Stimulates synthesis and secretion of steroid hormones (glucocorticoids) from the adrenal cortex.
     • Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH): Called gonadotrophins, stimulate gonadal activity.
       • Males: LH stimulates androgen synthesis/secretion from testis. FSH and androgens regulate spermatogenesis.
       • Females: LH induces ovulation and maintains corpus luteum. FSH stimulates growth and development of ovarian follicles.
   • Pars intermedia: Secretes only one hormone in humans, Melanocyte Stimulating Hormone (MSH), which acts on melanocytes and regulates skin pigmentation. In humans, it’s almost merged with pars distalis.

2. Neurohypophysis (Pars nervosa / Posterior Pituitary): Stores and releases two hormones, which are actually synthesized by the hypothalamus and transported axonally.

   • Oxytocin: Acts on smooth muscles, stimulating vigorous contraction of the uterus during childbirth and milk ejection from mammary glands.
   • Vasopressin (Anti-diuretic Hormone - ADH): Acts mainly on the kidney, stimulating reabsorption of water and electrolytes by distal tubules, reducing water loss through urine (diuresis). Impairment affecting ADH synthesis/release causes Diabetes Insipidus (diminished kidney ability to conserve water, leading to water loss and dehydration).

The Pineal Gland

• Located on the dorsal side of the forebrain.
• Secretes Melatonin.
• Plays a very important role in regulating the 24-hour (diurnal) rhythm of the body (e.g., sleep-wake cycle, body temperature).
• Also influences metabolism, pigmentation, the menstrual cycle, and defense capability.

Thyroid Gland

• Composed of two lobes on either side of the trachea, interconnected by a thin flap of connective tissue called isthmus.
• Composed of follicles and stromal tissues; follicular cells synthesise two hormones:
  • Tetraiodothyronine or Thyroxine (T₄)
  • Triiodothyronine (T₃)
• Iodine is essential for normal thyroid hormone synthesis.
• Disorders:
  • Hypothyroidism: Deficiency of iodine leads to goitre (enlargement of thyroid gland).
    • During pregnancy: Causes defective development and maturation of the baby, leading to cretinism (stunted growth, mental retardation, low IQ, abnormal skin, deaf-mutism).
    • In adult women: May cause irregular menstrual cycle.
  • Hyperthyroidism: Increased synthesis and secretion of thyroid hormones (due to cancer or nodules). Adversely affects body physiology.
    • Exopthalmic goitre (Graves’ disease): Characterised by enlargement of thyroid gland, protrusion of eyeballs, increased basal metabolic rate, and weight loss.
• Thyroid hormone functions:
  • Regulation of basal metabolic rate.
  • Support red blood cell formation.
  • Control metabolism of carbohydrates, proteins, and fats.
  • Influence water and electrolyte balance.
• Also secretes a protein hormone called Thyrocalcitonin (TCT), which regulates (decreases) blood calcium levels.

Parathyroid Gland

• Four parathyroid glands are present on the back side of the thyroid gland, one pair in each lobe.
• Secrete a peptide hormone called Parathyroid Hormone (PTH).
• Secretion of PTH is regulated by circulating levels of calcium ions (Ca²⁺).
• PTH functions:
  • **Increases Ca²⁺ levels in the blood (**hypercalcemic hormone**).
  • Acts on bones and stimulates bone resorption (dissolution/demineralisation).
  • Stimulates reabsorption of Ca²⁺ by renal tubules and increases Ca²⁺ absorption from digested food.
  • Plays a significant role in calcium balance in the body, along with TCT.

Thymus

• Lobular structure located between the lungs, behind the sternum, on the ventral side of the aorta.
• Plays a major role in the development of the immune system.
• Secretes peptide hormones called Thymosins.
• Thymosin functions:
  • Major role in differentiation of T-lymphocytes, which provide cell-mediated immunity.
  • Promote production of antibodies to provide humoral immunity.
• Thymus degenerates in old individuals, decreasing thymosin production, leading to weaker immune responses.

Adrenal Gland

• One pair of adrenal glands, located above each kidney.
• Composed of two types of tissues:

1. Adrenal Medulla (centrally located tissue):

   • Secretes two hormones called adrenaline (epinephrine) and noradrenaline (norepinephrine), collectively called catecholamines.
   • Rapidly secreted in response to stress and emergency situations, hence called emergency hormones or hormones of Fight or Flight.
   • Functions: Increase alertness, pupillary dilation, piloerection (raising of hairs), sweating, heart beat, strength of heart contraction, and rate of respiration. Also stimulate breakdown of glycogen (increased blood glucose), lipids, and proteins.

2. Adrenal Cortex (outer tissue):

   • Divided into three layers: zona reticularis (inner), zona fasciculata (middle), and zona glomerulosa (outer).
   • Secretes many hormones called corticoids.
   • Glucocorticoids (e.g., Cortisol): Involved in carbohydrate metabolism.
     • Stimulate gluconeogenesis (glucose formation from non-carbs), lipolysis (fat breakdown), and proteolysis (protein breakdown).
     • Inhibit cellular uptake and utilization of amino acids.
     • Maintain cardiovascular system and kidney functions.
     • Produce anti-inflammatory reactions and suppress the immune response.
     • Stimulate RBC production.
     • Underproduction leads to Addison’s disease (altered carbohydrate metabolism, acute weakness, fatigue).
   • Mineralocorticoids (e.g., Aldosterone): Regulate water and electrolytes.
     • Act mainly at renal tubules to stimulate reabsorption of Na⁺ and water, and excretion of K⁺ and phosphate ions.
     • Help maintain electrolytes, body fluid volume, osmotic pressure, and blood pressure.
   • Androgenic steroids: Small amounts secreted, play a role in growth of axial, pubic, and facial hair during puberty.

Pancreas

• A composite gland, acting as both exocrine and endocrine gland.
• Endocrine pancreas consists of Islets of Langerhans (1-2 million islets, 1-2% of pancreatic tissue).
• Two main types of cells in islets:
  • α-cells: Secrete Glucagon (peptide hormone).
    • Maintains normal blood glucose levels (hyperglycemic hormone).
    • Acts mainly on liver cells (hepatocytes) to stimulate glycogenolysis (glycogen breakdown) and gluconeogenesis (glucose formation).
    • Reduces cellular glucose uptake and utilization.
  • β-cells: Secrete Insulin (peptide hormone).
    • Plays a major role in regulating glucose homeostasis.
    • Acts mainly on hepatocytes and adipocytes (fat cells) to enhance cellular glucose uptake and utilization, decreasing blood glucose levels (hypoglycemia).
    • Stimulates conversion of glucose to glycogen (glycogenesis) in target cells.
• Glucose homeostasis in blood is maintained jointly by insulin and glucagon.
• Diabetes Mellitus: Prolonged hyperglycemia due to insulin deficiency and/or insulin resistance. Associated with loss of glucose through urine and formation of harmful ketone bodies. Treated with insulin therapy.

Testis (Male Gonad)

• A pair of testes present in the scrotal sac (outside abdomen) in males.
• Performs dual functions: primary sex organ and endocrine gland.
• Composed of seminiferous tubules and stromal (interstitial) tissue.
• Leydig cells (interstitial cells): Present in intertubular spaces, produce a group of hormones called androgens (mainly testosterone).
• Androgen functions:
  • Regulate development, maturation, and functions of male accessory sex organs (epididymis, vas deferens, seminal vesicles, prostate gland, urethra).
  • Stimulate muscular growth, growth of facial and axillary hair, aggressiveness, low pitch of voice.
  • Play a major stimulatory role in spermatogenesis (formation of spermatozoa).
  • Act on CNS and influence male sexual behaviour (libido).
  • Produce anabolic (synthetic) effects on protein and carbohydrate metabolism.

Ovary (Female Gonad)

• A pair of ovaries located in the abdomen in females.
• Primary female sex organ, produces one ovum during each menstrual cycle.
• Produces two groups of steroid hormones: estrogen and progesterone.
• Composed of ovarian follicles and stromal tissues.
  • Estrogen: Synthesised and secreted mainly by the growing ovarian follicles.
    • Stimulates growth and activities of female secondary sex organs, development of ovarian follicles, appearance of female secondary sex characters (e.g., high pitch of voice), and mammary gland development.
    • Regulates female sexual behaviour.
  • Progesterone: Secreted mainly by the corpus luteum (formed from ruptured follicle after ovulation).
    • Supports pregnancy.
    • Acts on mammary glands to stimulate formation of alveoli (milk-storing structures) and milk secretion.

Hormones of Heart, Kidney, and Gastrointestinal Tract

Some tissues not considered endocrine glands also secrete hormones.

• Heart:

  • Atrial wall secretes Atrial Natriuretic Factor (ANF), a peptide hormone.
  • ANF decreases blood pressure by causing vasodilation when blood pressure is increased.

• Kidney:

  • Juxtaglomerular cells produce Erythropoietin, a peptide hormone.
  • Erythropoietin stimulates erythropoiesis (formation of RBC).

• Gastro-intestinal (G.I.) Tract:

  • Endocrine cells in different parts secrete four major peptide hormones:
    • Gastrin: Acts on gastric glands, stimulates secretion of hydrochloric acid and pepsinogen.
    • Secretin: Acts on exocrine pancreas, stimulates secretion of water and bicarbonate ions.
    • Cholecystokinin (CCK): Acts on both pancreas and gall bladder, stimulates secretion of pancreatic enzymes and bile juice, respectively.
    • Gastric Inhibitory Peptide (GIP): Inhibits gastric secretion and motility.

• Growth Factors: Several other non-endocrine tissues secrete growth factors, essential for normal tissue growth, repairing, and regeneration.

Mechanism of Hormone Action

Hormones produce effects by binding to specific proteins called hormone receptors located in target tissues. Each receptor is specific to one hormone.

• Receptor types:
  • Membrane-bound receptors: Present on the cell membrane of target cells.
  • Intracellular receptors: Present inside the target cell, mostly nuclear receptors (in the nucleus).
• Hormone-receptor complex: Binding of a hormone to its receptor leads to its formation, causing biochemical changes in the target tissue. This regulates target tissue metabolism and physiological functions.
• Hormone classification by chemical nature:
  • Peptide, polypeptide, protein hormones: Insulin, glucagon, pituitary hormones, hypothalamic hormones.
  • Steroids: Cortisol, testosterone, estradiol, progesterone.
  • Iodothyronines: Thyroid hormones.
  • Amino-acid derivatives: Epinephrine.
• Mechanisms of action based on chemical nature:
  • Hormones interacting with membrane-bound receptors (e.g., protein hormones):
    • Normally do not enter the target cell.
    • Generate second messengers (e.g., cyclic AMP, IP₃, Ca²⁺) inside the cell, which then regulate cellular metabolism.
  • Hormones interacting with intracellular receptors (e.g., steroid hormones, iodothyronines):
    • Typically enter the target cell.
    • The hormone-receptor complex interacts with the genome.
    • Regulate gene expression or chromosome function, leading to cumulative biochemical actions that result in physiological and developmental effects.