From Genome to Organism - Biology Summary PDF

From genome to organism 1. Organization and reproduction of the human body =============================================== 1. Organic molecules ----------------- = the molecules of live 1. Carbohydrates = easily used energy source for the body - General structure: - Monosaccharide Single chain or single ring structure Most important in the body are pentose ( 5 carbon) and hexose (6 carbon) sugars - Disaccharide Formed when 2 monosaccharides are joined by dehydration synthesis - Polysaccharide Large, fairly insoluble molecules: perfect for storage - Starch: the storage carbohydrate formed by plants - Glycogen: the storage carbohydrate of animal tissues 2. Lipids = lipids insulate body organs, build cell membranes and provide stored energy - Triglycerides Neutral molecule with 1 glycerol and 3 fatty acids Energy storage Found mainly beneath the skin - Phospholipids Modified triglycerides: 2 fatty acids chains with a phosphorous containing group Chief material for building cell membrane - Steroids Flat molecules made of interlocking 4 hydrocarbon rings 3. Proteins = the body's basic structural material and have many functions - Structural level of proteins -Primary structure: linear sequence of amino acids composing the polypeptide chain -Secondary structure: alpha-helix and beta-sheet -Tertiary structure: when alpha-helices and beta-sheets fold upon one another to produce a compact, ball-like globular structure Hydrophobic R groups are on the inside, hydrophilic R groups on the outside -Quaternary structure: aggregation of 2 or more polypeptide chains - Types of proteins -Fibrous proteins: - Structural: extended and strand-like - Ideal for providing mechanical support and tensile strength to the tissues - Example: collagen -Globular proteins: - Functional: compact and spherical - Play crucial roles in all biological processes - Example: enzymes - Regulate and accelerate the rate of biochemical reactions - Substrate binds to enzyme's active site, temporarily forming an enzyme-substrate-complex - The complex undergoes internal rearrangements that form the products - The enzyme releases the product of the reaction and returns to its original shape - Enzyme inhibitors can block the enzyme's active site - Example: nucleotides - Cytosine - Thymine - Adenine - Guanine Cells ----- = basic structural and functional unit of living organisms\ = the microscopic package that contains all the parts necessary to survive in an ever-changing world Human cells have 3 main structures: - ![](media/image3.png)Plasma membrane: = the outer boundary of the cell which acts as a selective permeable barrier Phospholipid layer:\ -hydrophilic head\ -hydrophobic tail Membrane protein:\ -constitutive: forming part of something\ -inducible: capable of being moved - Cytoplasm: = the intracellular fluid packed with organelles, small structures that perform specific cell functions - Nucleus: = an organelle that controls cellular activities Encloses the genetic information = chromatin\ Nuclear pores: transport of molecules\ Nucleolus Cytoplasmic organelles - Mitochondria = a powerplant\ Enclosed by 2 membranes\ Contain their own DNA, RNA, and ribosomes, and they are able to reproduce themselves - Ribosomes 2 Subunits form a ribosomal complex together with mRNA -\> attach to the cytosolic side of the ER -\> synthesis of proteins\ Ribosomes who don't attach to any membrane, encode for proteins needed in the cytosol - Endoplasmatic reticulum Rough ER: Many ribosomes\ engaged in protein synthesis Smooth ER:\ no ribosomes\ communicates with rER\ role in lipid metabolism, synthesis of steroid hormones, detoxification of drugs... - Lysosomes Contain digestive enzymes, capable of digesting almost all kinds of biological molecules - Cytoskeleton - Centrosome and centrioles = cell centre; acts as a microtubule organizing centre Contains a granular-looking matrix that contains paired centrioles = small, barrel-shaped organelles oriented at right angles to each other Centrioles are involved in generating microtubules and in cell division Extracellular material:\ = substances that contribute to our body mass that are found outside the cells - Body fluids - Cellular secretions - Extracellular matrix: a jellylike substance that is composed of proteins and polysaccharides Cell junctions - Tight junction = impermeable junctions prevent molecules from passing through the intercellular space - Desmosome = anchoring junctions - This arrangement distribute tension and reduces risk of tearing - Gap junction = communication junction Diffusion - ![](media/image5.jpeg)Simple diffusion - Facilitated diffusion: - Carrier-mediated: transmembrane integral proteins - Channel-mediated: transmembrane proteins that transport substances through channels - Osmosis: diffusion of a solvent through a selectively permeable membrane Protein synthesis 4. Transport vesicles that bud off from rER, move to and fuse with membranes at the receiving of the Golgi apparatus 5. Inside the Golgi, the proteins are modified 6. Various proteins are tagged for delivery to a specific address, sorted and packaged in at least 3 types of vesicles i. Secretory vesicles or granules, containing proteins for export ii. Vesicles containing lipids and transmembrane proteins iii. Vesicles containing digestive enzymes are packaged into membranous lysosomes that remain in the cell Cell cycle 1. Interphase =period from cell formation to cell division G1 subphase: cell is metabolically active (growth, protein synthesis)\ S subphase: DNA is replicated\ G2 subphase: final preparations for cell division 2. Mitosis = division of the nucleus **Prophase** Chromatin coils and condenses, forming chromosomes\ Nucleoli disappear and centromeres separate from one another **Metaphase** 2 centromeres are at opposite poles of the cell\ the chromosomes cluster at the midline **Anaphase** **Telophase** Chromosome uncoild and resume their thread-like chromatin appearance\ A new nuclear envelope is formed, nucleoli reappear and spindle breaks down 3. Cytokinesis = division of the cytoplasm DNA: deoxyribonucleic acid -------------------------- **Nucleotide**: basic repeat unit of a DNA-strand Sugar: deoxyribose\ Base: a cyclic nitrogen-containing compound: [adenine], guanine, cytosine, [thymine]\ Phosphate group **Antiparallel double helix** Linear backbone of alternating sugar and phosphate groups DNA Replication 7. Uncoiling: enzymes unwind the DNA molecule, forming a replication bubble (helicase) 8. Separation 9. Assembly: the parental strand acts as a template and the enzyme DNA polymerase add complementary free nucleotides along the template strand iv. =semiconservative 10. Restoration: ligase enzyme splice short segments of DNA together, restoring the double helix Synthesis of the leading strand: 3' -\> 5' continuous\ Synthesis of the lagging strand: 5' -\> 3' discontinuous: okazaki fragments Transcription: RNA Differences with DNA:\ single-stranded\ uracil (U) instead of Thymine(T)\ ribose instead of deoxyribose During transcription, information from a DNA sequence is transferred to the complementary base sequence of an RNA molecule (=messengerRNA) Once the mRNA is formed, it leaves the nucleus via a nuclear pore and heads for the ribosome Translation During translation, the language of nucleic acids (the base sequence in DNA and RNA) is translated to the language of proteins (amino acid sequence) **Transfer RNA**\ -tRNA molecules mediate the decoding process\ -tRNA contains an anticodon sequence, which is complementary to and recognizes the codon sequence in mRNA during translation 1. Initiation A small rRNA subunit binds to a Metionine-carrying initiator tRNA, and then to the mRNA. It scans the mRNA until it finds the start codon (first AUG). The large rRNA subunit then unites with the small one, forming a functional ribosome 2. Elongation **Codon recognition**: the incoming tRNA binds to a complementary codon\ **Peptide bond formation**: an enzymatic component in the larger rRNA subunit catalyses peptide bond formation between the previous AA and the incoming peptide\ **Translocation**: the ribosomes moves by shifting its position one codon. The vacant tRNA is ready to be recharged by an AA in the cytoplasm 3. Termination When a stopcodon is reached, water is added, which hydrolyses (breaks) the bond between the polypeptide chain and the tRNA. The polypeptide is released from the ribosome, which separates in its small and large subunit. When the mRNA is no longer needed, it is degraded Tissues ------- = groups of cells that are similar in structure and perform a common or related function 11. Epithelial tissue Sheet of cells covering a body surface or lining a body cavity\ Forms boundaries between different environments, with many functions: protection, absorption, secretion, sensory... Classification: - Simple or stratified - Shape - Squamous - Cuboidal - Columnar 12. Connective tissue Common origin: all arise from the mesenchym\ Variable degrees of vascularity\ Consists of few cells, surrounded by an extracellular matrix **Structural components:** - Ground substance - Unstructured material that fills the space between the cells and contains fibers - Consists of interstitial fluid, cell adhesion proteins and proteoglycans - Connective tissue fibers - Provide support - Connective tissue cells - Cells that secrete the ground substance - Fibroblasts: connective tissue general - Osteoblasts: bone - Chondroblast: cartilage - Other cells - Fat cells - White blood cells - Mast cells - Macrophages **Types:** - Loose connective tissue - Under the skin - Adipose tissue - Fat droplets - Cell nucleus - Blood - Fibrous connective tissue - Forming a ligament - Cartilage - At the end of a bone - Bone 13. Muscle tissue Muscle cells\ Highly vascularized\ Responsible for active body movements **Types:** - Skeletal muscle - Attached to the bones - Striated - Under conscious control - Cardiac muscle - Only in walls of the heart - Contractions help to propel blood through blood vessels - Striated - Hollow organ muscle / smooth muscle - Found in walls of hollow organs other than heart - No visible striations 14. Nervous tissue Neurons: -highly specialised nerve cells\ -generate and conduct nerve impulses Supporting cells Human development ----------------- **Spermatogenesis** = the process that produce male sex cells or gametes which occurs in the testes **Oogenesis** = the process that produces female sex cells or gametes which occurs in the ovaria - Already during foetal life, oogonia (the diploid stem cells of the ovaria) multiply rapidly by mitosis - The primordial follicles occur as oogonia transform into primary oocytes and become surrounded by follicle cells **Meiosis** = the formation of gametes, it consists of 2 consecutive nuclear divisions that follow one round of DNA replication 15. Meiosis I Reduction division of meiosis (2n becomes n)\ Pairing of homologous chromosomes and crossing-over - Crossovers allow maternal and paternal chromosomes to exchange genetic material 16. Meiosis II Equational division of meiosis: mirrors mitosis, except that the chromosomes are not replicated before it begins **Fertilization** = the process that joins a sperm and an egg cell to produce a (diploid) zygote **Embryonic development** - Cleavage - A period of rapid mitotic divisions of the zygote without intervening growth - To produce small cells with high surface-to-volume ratio, that can take up lots of nutrients and oxygen and dispose of waste. These cells are the building blocks for constructing the embryo - 36 hrs: blastomeres - 72 hrs: morula - Blastocyst formation - 4-5 days: embryo consists of about 100 cells - Blastocyst: fluid filled hollow sphere, composed of a single layer of trophoblast cells and a cluster of 20-30 cells (=inner cell mass) - Trophoblast takes part in placenta formation - Inner cell mass becomes the embryonic disc - Implantation - 6-7 days - Trophoblast cells bind to extracellular matrix components in the endometrium and the blastocyst implants in the uterus - The trophoblast cells proliferate and become 2 distinct layers - Gastrulation - The blastocyst is transformed in a gastrula, in which the 3 primary germ layers form - Endoderm: forms epithelial linings of the digestive , respiratory and urogenital systems and associated glands (=klieren) - Ectoderm: forms the structure of the nervous system and the skin epidermis - Mesoderm: forms virtually everything else - Sclerotome -\> vertebrae and ribs - Dermatome -\> skin - Myotome -\> skeletal muscle - The inner cell mass subdivides into 2 layers - Upper epiblast - Lower hypoblast Covering, support and movement of the body ========================================== The integumentary system ------------------------ = skin or integument 3 layers: 1. **Epidermis** Outermost protective shield of the body\ Epithelial cells\ Ectoderm\ Not vascularized **4 or 5 distinct layers:** - Stratum corneum - 20-30 layers of flattened anucleate cells, filled with keratin - Protective 'overcoat' for the body - Stratum lucidum - Only present in thick skin - 2-3 rows of clear, flat, dead keratinocytes - Stratum granulosum - 1-5 cell layers - Keratinization - Stratum spinosum - Several cell layers - Cells contain web-like system of intermediate filaments - Stratum basale - Deepest epidermal layer - Consists of a row of constantly renewing stem cells **4 distinct cell types:** - Keratinocytes - Keratin: fibrous protein that helps give the epidermis its protective properties - Keratin-producing cells - Melanocytes: - Melanin: forms a pigment shield that protects the nucleus from damaging effects of UV radiation in sunlight - Melanin-producing cells - Dendritic cells = Langerhans cells - Arise from bone marrow - Key activators of immune system - Tactile cells = Merkel cells - Closely associated with sensory nerve ending 2. **Dermis** Tough leathery layer of dense connective tissue\ Mesoderm\ Vascularized **2 layers:** - Papillary layer - Loose connective tissue with fine interlacing collagen and elastic fibers and many blood vessels - Dermal papillae: contain capillary loops, tactile corpuscles and free nerve endings - Reticular layer - Accounts for 80% of the dermis' thickness - Coarse, dense and irregular connective tissue 3. **Hypodermis** Storage of fat: shock absorber and insulator\ Anchors the skin to the underlying structures (muscles) **Skin colour** Determined by: - Melanin: - Reddish yellow to brownish black - Synthesis depends on the enzyme tyrosinase in the melanocytes - Carotene - Yellow to orange pigment found in plants such as carrots - Tends to accumulate in stratum corneum and in hypodermis - Can be converted to vitamin A, essential for normal vision and epidermal health - Oxygenated haemoglobin in red blood cells Albinism: defect in melanin production **Hair** - Produced by hair follicles - 3 concentric layers of dead keratinized cells - Medulla: central core - Cortex - Outermost cuticle - Arrector pili muscle - \> goose bumps **Sweat glands** - Eccrine sweat glands - Most abundant - Produce sweat - Protects body from overheating - Apocrine sweat glands - Confined to axillary and anogenital region - Odourless, but contact with bacteria gives it its unpleasant smell **Sebaceous glands** - 'oil' glands - Softens and lubricates hair and skin **Functions of skin or integument:** - Protection - Chemical barrier - Physical barrier - Biological barrier - Body temperature regulation - Cold -\> constriction of dermal blood vessels -\> warm blood bypasses the skin temporarily -\> conserving body heat - Cutaneous sensation - Tactile disc - Tactile corpuscles - Free nerve endings - Metabolic functions - Cholesterol is converted into vitamin D - Blood reservoir - 5% of total blood supply Bone and skeletal tissue ------------------------ **Hyaline, elastic and fibro-cartilage (=kraakbeen)** Human skeleton is initially made up of cartilages and fibrous membranes - \> most, but not all replaced by bone during embryogenesis **1) Hyaline cartilage** \- articular cartilage\ - joint cartilage\ - respiratory cartilage\ -nasal cartilage **2) Elastic cartilage** \- external ear\ - epiglottis **3) fibrocartilage: highly compressible, great tensile strength** \- menisci of the knee\ - disc of the vertebrae **Bone: classification** Axial skeleton: skull, vertebral column, rib cage -\> support/protection\ Appendicular skeleton: bones of upper/lower limbs and girdles -\> mobility 4. Long bones 5. Short bones 6. Flat bones 7. Irregular bones **Bone: structure** Bones contain different types of tissue -\> bones are organs Gross anatomy: - Compact bone: dense, smooth outer layer - Spongy bone: honeycomb, small pieces called trabeculae, open spaces filled with yellow or red bone marrow **Short, irregular and flat bones:** - Thin plates of spongy bone covered by compact bone - Compact bone is covered on the inside and outside by connective tissue membranes - Contains bone marrow **Long bones** - Diaphysis - Shaft - Collar of compact bone - Medullary cavity which contains fat (yellow marrow) - Epiphysis - Bone ends - Compact and spongy bone - Thin layer of articular cartilage covers the joint surface - Epiphyseal line: remnant of epiphyseal plate - Membranes - Periosteum - Endosteum **Functions** - Support - Protection - Anchorage: for the skeletal muscles - Mineral and growth factor storage: mostly calcium and phosphate - Blood cell formation: in red marrow cavities of certain bones - Fat (triglyceride) storage: in bone cavities - Hormone production: regulate insulin secretion, glucose homeostasis and energy expenditure **Hematopoietic tissue (=red marrow) in bones** Typically found in trabecular cavities of spongy bones of long bones and flat bones **Microscopic anatomy of bone** **Cells of bone tissue** - From bone cell lineage - Osteoprogenitor cell - Stem cell - Osteoblast - Matrix-synthesizing cell - Responsible for bone growth - Osteocyte - Mature bone cell - Monitors and maintains the mineralized bone matrix - From white blood cell lineage - Osteoclast - Bone-resorbing cell ![](media/image7.png)Osteon or haversian system: structural unit for compact bone: - Lamellae - Canaliculi - Haversian canals - Perforating canals - Lacunae: contain osteocytes **Chemical composition of bone** - **Organic components** - Cells - Osteoid: the organic part of the matrix - **Inorganic components** - Minera salts or hydroxyapatites **Bone development** Around 8 weeks bone tissue starts to develop - **Endochondral ossification** = a bone develops by replacing hyaline cartilage (zie pwp slide 29)\ -\> all bones below the base of the skull, except for clavicle (=sleutelbeen) - **Intramembranous ossification** = a bone develops from a fibrous membrane\ -\> cranial bones of the skull and clavicle **Bone remodelling** - Bone is a dynamic and active tissue - Spongy bones is replaced every 3 to 4 years, compact bone every 10 years - Control of bone remodelling - Hormonal controls to preserve blood calcium homeostasis - Response to mechanical stress - Wolff's law **Bone disorders** - Osteomalacia and rickets - Osteoporosis - Bones become very porous, light and fragile - Paget's disease Muscles and muscle tissues -------------------------- **Muscle tissues** - Types **Skeletal muscle tissue:\ **packaged into skeletal muscle, striated and voluntary **Cardiac muscle tissue:\ **heart wall, striated, involuntary **Smooth muscle tissue:\ **walls of hollow visceral organs, smooth (non-striated), involuntary - Characteristics **Excitability**: the ability of a cell to receive and respond to a stimulus by changing its membrane potential **Contractility**: the ability to shorten forcibly when adequately (=voldoende) stimulated **Extensibility**: the ability to extend or stretch **Elasticity**: the ability to recoil and resume its resting length after stretching **Muscle functions** - Produce movement - Skeletal muscle: locomotion - Heart muscle: blood flow - Smooth muscle: flow of contents in digestive/urinary/respiratory tract - Maintain posture and body position - Stabilize joints - Generate heat **Skeletal muscle fibres** **myofibrils:** - banding pattern: - A-band: dark - H-zone: lighter midzone - M-line: dark line - I-band: light - Z-disc: darker midline interruption - Contain sarcomeres: the contractile elements of skeletal muscle cells - Region between 2 Z-discs - Contain myofilaments: - Thick filaments: myosin - 2 heavy and 2 light polypeptide chains - Rod-like tail, flexible hinge region - 2 globular heads - Thin filaments: actin - Kidney-shaped polypeptide subunits (=G-actin) - Polymerized in filamentous (=F-actin) - Elastic filaments: titin **Sarcoplasmic reticulum:** - Elaborate smooth ER - Regulates intracellular levels of ionic calcium **Sliding filament model of contraction** - **Relaxed muscle fibre:** Thick and thin filaments overlap only at the ends of the A-band - **Sliding filament model of contraction:** During contractions, thin filaments slide past the thick one, actin and myosin overlap to greater degree Upon stimulation, myosin-heads on thick filaments bind to myosin-binding sites on actin, forming cross-bridges and the sliding begins These cross bridges form and break several types during contraction, generating tension and propelling the thin filaments to the centre of a sarcomere As this event occurs simultaneously in sarcomeres throughout the cell, the muscle cell shortens - **How is the contraction induced** The fibre must be 'activated': stimulated by a nerve ending so that a change in membrane potential occurs It must generate an electrical current (=action potential) along the sarcolemma (=plasma membrane) Intracellular calcium levels must rise briefly, providing the final trigger for contraction **Generation of action potential** 8. **Generation of an end plate potential** Binding of ACh to ACh receptors opens chemically gated ion channels that allow Na^+^ and K^+^ to pass Because driving force of Na^+^ is greater than that of K^+^ , more Na^+^ diffuses in, then K^+^ diffuses out - Interior of the sarcolemma becomes less negative 9. **Depolarization: generation and propagation of action potential** End plate potential ignites by spreading to adjacent membrane areas and opening voltage-gated sodium channels there Once a certain membrane voltage (threshold) is reached, an action potential is generated Action potential propagates in all directions away from the neuromuscular junction 10. **Repolarization: restoring sarcolemma to its original polarized state** Na^+^ channels close and voltage-gated K^+^ channels open, K^+^ rapidly diffuses out of muscle fibre, restoring negatively charged conditions inside **Excitation-contraction coupling** = sequence of events by which transmission of an action potential along sarcolemma causes the myofilaments to slide - **Types of ion channels** When nerve impulse reaches axon terminal: voltage-gated calcium channels in axonal membrane open, calcium entry releases ACh. Binding of ACh to ACh receptors open chemically-gated Na^+^ - K^+^ channels, generating local voltage change Local depolarization opens voltage-gated Na^+^ channels, further depolarizing the sarcolemma and generating and propagating AP Transmission of AP along T-tubules changes shape of voltage-sensitive proteins in the T-tubules, which in turn stimulate SR kalium-release channels, to release Ca^+^ in cytosol - As calcium rises inside the cells, it binds to tropomyosin -\> shape change of tropomyosin: it rolls into the groove of the actin helix, away from the myosin-binding sites -\> tropomyosin blockade is lifted - Once myosin-binding sites on actin are exposed -\> cross bridge cycle **ATP-production** ATP supplies energy to move and detach cross-bridges, operate the calcium pomp in the SR and return sodium and potassium after E-C coupling It is the only energy source used directly for muscle contraction -\> must be regenerated as fast as it is broken down 3 pathways to generate ATP: - Direct phosphorylation - Creatin phosphate: unique high-energy molecules stored in the muscle - Creatin phosphate is coupled with ADP, catalysed by creatin kinase, to rapidly generate ATP - Anaerobic pathway\ = Glycolysis and lactate acid formation - Breakdown of glucose, obtained from glycolysis or blood glucose - 2 ATP molecules per glucose - Glucose is broken down in 2 pyruvic acid molecules, generating ATP - When muscle contract vigorously, they compress the blood vessels, impairing oxygen delivery -\> pyruvic acid is converted into lactic acid - Lactic acid is released in blood and organs use it as an energy source - Aerobic respiration - Occurs in mitochondria and requires oxygen - Break down glucose entirely into water, carbon dioxide and ATP - As exercise begins, muscle glycogen provides most of the energy - Shortly thereafter blood glucose and pyruvic acid from glycolysis and free fatty acids are major energy sources - After 30 minutes: fatty acids become major energy source **Smooth muscle** **Peristalsis**: the propulsive action, coming from alternating constriction and relaxation **Smooth muscle fibres:** - Varicosities -\> release neurotransmitters - Multiple caveolae containing large amounts of Ca^2+^ channels - No T-tubules - Ca^2+^ comes from extracellular space - No striations, no sarcomeres - Contraction ends when cytoplasmic calcium is actively transported into the SR and out of the cell - organized in sheets: - Longitudinal layer -\> when they contract organ shortens - Circular layer -\> when they contract lumen constricts (=vernauwt) **Smooth muscle contraction** 1. Adjacent smooth muscle fibres exhibit slow, synchronized contractions, caused by electrical coupling of SMC by gap junctions -\> these allow SMC to transfer action potentials from fibre to fibre 2. Actin and myosin interact by sliding filament mechanism 3. Trigger for contraction is rise in intracellular calcium 4. ATP is the energy source **Regulation of SM contraction** - Neural regulation Different autonomic nerves, serving different SM of visceral organs, release different neurotransmitters - Hormonal regulation and local chemical factors Some SM have no nerve supply at all -\> they depolarize spontaneously or in response to chemical stimuli Certain hormones\ low oxygen, excess of carbon dioxide\ low Ph **Heart muscle** Short, fat, branched and interconnected cells Plasma membranes interlock at intercalated discs, which contain desmosomes and gap junctions Pacemaker cells: some cells are self-excitable\ depolarize spontaneously -\> the heart contracts as a unit **Pacemaker cells trigger action potentials throughout the heart** 1. Pacemaker potential Hyperpolarization at the end of AP closes K^+^ channels and opens slow Na^+^ channels\ -\> membrane interior becomes less negative 2. Depolarization At the threshold, Ca^+2^ channels open allowing explosive entry of Ca^2+^ from extracellular fluid 3. Repolarization Ca^2+^ channels inactivate, K^+^ channels open Regulation of heart rate - Autonomic nervous system - Sympathetic stimulation - Upon emotional or physical stimulation - Increasing heart rate - Parasympathetic stimulation - Reduces heart-rate when stressful moment has passed - Hormones - Epinephrine (adrenal glands) - Thyroxine (thyroid gland) - Ions 3. Regulation and integration of the body ====================================== 1. **The nervous system** ---------------------- 1. ### **Introduction** **Central nervous system**: brain and spinal cord\ = integrating and control centre **Peripheral nervous system**: nerves (bundles of axons) and ganglia (collections of neuron cell bodies) - Sensory (afferent) division: nerve fibres that convey impulses from sensory receptors throughout the body - Somatic sensory fibres: skin, muscle, joint and skeleton - Visceral sensory fibres: visceral organs - Motor (efferent) division: transmits impulses from CNS to effector organs (muscles and glands) - Somatic nervous system: voluntary nervous system, skeletal muscles - Autonomic nervous system: involuntary nervous system, smooth and cardiac muscle, glands - Sympathetic and parasympathetic 2. ### **Neuroglia** **Nervous tissue is made out of 2 cell types:** - Neurons: excitable nerve cells that transmit electrical signal - Neuroglia: small cells that surround and wrap the delicate neurons **Types of neuroglia in CNS:** - **Astrocytes**: support and brace neurons, anchor them to their nutrient supply line, guide migration of young neurons, recapture and recycle neurotransmitter - **Microglial cells**: defensive cells - **Ependymal cells**: line central cavities (=holte) of brain and central cord - **Oligodendrocytes**: insulating covering around ticker nerves in CNS **Types of neuroglia in PNS** - **Satellite cells**: surround neuron cell bodies - **Schwann cells**: surround nerve fibres and form myelin sheaths ### **3.1.3 Neurons** **Structural units of the nervous system:** - Neuron cell body - Neuron processes - Dendrites - Axons Typical large, highly specialized cells that conduct messages **Characteristics:** - Extreme longevity - Amitotic: they've lost their ability to divide, irreplaceable - Exceptionally high metabolic rate **3.1.4 Dendrites and axons** **Dendrites**: input or receptive region\ -\> convey incoming messages toward cell body **Axons**: conducting region\ -\> generates nerve impulses and transmits them **Myelin sheath**: protects and electrically insulates fibres and increases transmission speed ### **3.1.5 Classification of neurons** - **Sensory (afferent) neurons**: transmit impulses from sensory receptors in skin or internal organs toward or into CNS - Mostly unipolar - **Motor (efferent) neurons**: carry impulses away from the CNS to the effector organs - Mostly multipolar - **Interneurons**: lie between motor and sensory neurons, shuttle signals through CNS pathways - Mostly multipolar **3.1.6 Resting membrane potential\ **= the potential difference in a resting neuron between the cytoplasmic site of the plasma membrane and the outer side **Membrane is polarized**: cytoplasmic site (outside) of the membrane is negatively charged 2 factors are responsible: - **Differences in ionic composition** - Cell cytosol contains a lower concentration of Na^+^ and a higher concentration of K^+^ than the extracellular fluid - **Differences in plasma membrane permeability** - Impermeable to large negatively charged cytoplasmic proteins - Slightly permeable to Na^+^ - 25 time more permeable to K^+^ - Quite permeable to Cl^-^ **3.1.7 Changing the membrane potential\ **= neurons use change in their MP as signals to receive, integrate and send information **Produced by:** - Anything that alters ion concentrations at both sides of the plasma membrane - Anything that changes the membrane permeability to any ion **Changes in MP can produce:** - Graded potentials: incoming short-distance signals - Action potentials: long-distance signals of axons **Changes in MP relative to the resting MP:** - Depolarization: decrease in membrane potential (inside becomes less negative) - Hyperpolarization: increase in MP (insides becomes more negative) **3.1.8 Action potentials\ **= brief, long-distance signals within a neuron = nerve impulse - Only cells with excitable membranes (neurons and muscle cells) can generate AP **Generating AP:** 1. Resting state: All gated Na^+^ and K^+^ channels are closed 2. Depolarization Na^+^ channels open -\> cell interior becomes progressively less negative 3. Repolarization Na^+^ channels are inactivating and K^+^ channels open - \> restoring the internal negativity of the cell 4. Hyperpolarization Some K^+^ channels remain open and Na^+^ channels reset **Propagating AP** The AP moves away from its point of origin towards the axon's terminals The AP is self-propagating and continues along the axon at a constant velocity - The larger the axon diameter -\> the faster it conducts impulses - Degree of myelinisation: the presence of a myelin sheath increases the rate of AP propagation **3.1.9 Synapse\ **= a junction that mediates transfer of information from one neuron to the next or from a neuron to the effector cell - Presynaptic neuron: sends the information - Postsynaptic neuron: receives the information **Chemical synapses** - Most common types of synapses - Specialized to allow the release and reception of chemical messengers known as neurotransmitters **Postsynaptic potential\ **= either excite or inhibit the receiving neuron through chemically-gated channels - Excitatory synapses and EPSP - EPSP: local depolarization of the postsynaptic membrane - Inhibitory synapses and IPSP - IPSP: local hyperpolarization of the postsynaptic membrane ### **3.1.10 Integration and modification** - **Temporal summation**: one or more presynaptic neurons transmit impulses in rapid order and bursts of neurotransmitter ate released in quick succession - **Spatial summation**: the postsynaptic neuron is stimulated simultaneously by a large number of terminals from one or many presynaptic neurons **3.1.11 Neurotransmitters\ **= the language of the nervous system ( \> 50 neurotransmitters have been identified) - Acetylcholine - Biogenic amines - Amino acids - Peptides - Purines - Gases and lipids ### **3.1.12 Brain and spinal cord** **Basic pattern**: central cavity, surrounded by grey matter, surrounded by white matter - Grey matter: short, nonmyelinated neurons and neural cell bodies - ![](media/image9.jpeg)White matter: myelinated and non-myelinated axons **4 brain regions:** - Cerebral hemisphere - Superficial cerebral cortex of grey matter - Internal white matter - Basal nuclei, islands of grey matter deep within the white matter - Diencephalon - Brainstem - Cerebellum ### **3.1.13 Cerebral cortex** - **Motor areas** - Primary motor cortex: conscious control of precise or skilled voluntary movements - Premotor cortex: selects and sequences basic motor movements into more complex tasks - Broca's area: motor speech area - Frontal eye field: controls voluntary movement of the eye - **Sensory areas** - Primary somatosensory cortex: receives information from general sensory receptors in skin and proprioceptors in muscle, joints and tendon - Somatosensory association cortex: integration of sensory inputs to produce an understanding of an object being felt - Visual/auditory/vestibular/olfactory/gustatory/visceral sensory areas - **Multimodal association areas** - Receive input from multiple senses and send outputs to multiple areas - Allows us to give meaning to the information that we receive, store it in the memory, tie it to previous experiences and knowledge and decide how to act on it - **Anterior association area = prefrontal cortex** - Intellect, complex learning abilities, personality - **Posterior association area** - Recognition of patterns and faces... - **Limbic association area** - Provides the emotional impact **3.1.14 Cerebral white matter** **Largely myelinated fibres** - Association fibres: connect different parts of same hemisphere - Commissural fibres: connect corresponding grey areas of the 2 hemispheres - Projection fibres: either enter the cortex from lower brain or descend from cortex to lower areas **Basal nuclei** - Nucleus caudatum - Putamen - Globus pallidus - Functionally associated with subthalamic nuclei and substantia nigra - Play a role in cognition and emotion; they seem to filter out incorrect or inappropriate responses ### **3.1.15 Diencephalon** **Thalamus: gateway to the cerebral cortex** - Relay station for information coming into the cerebral cortex - Relays impulses between cerebral motor cortex and lower subcortical motor centres, including cerebellum - Relays sensory impulses to cerebral cortex for interpretations - Plays a key role in mediating sensation, motor activities, cortical arousal, memory and learning **Hypothalamus: main visceral control centre** - Controls the autonomic nervous system - Initiate physical responses to emotions - Regulates body temperature - Regulates food intake - Regulates water balance and thirst - Regulates sleep-wake cycles - Controls endocrine system function: releasing and inhibiting hormones, oxytocin, ADH **Epithalamus** - Pineal gland: secrets melatonin (sleep inducing signal and anti-oxidant) which is involved in sleep-wake cycle ### **3.1.16 Brainstem** -\> brain stem centres produce the rigidly programmed , automatic behaviours, necessary for survival **Midbrain-cerebral aqueduct** - Substabtia nigra: high content of melanin, precursor of the neurotransmitter dopamine **Pons** - Chiefly composed of conduction tracts **Medulla oblongata**: crucial role as an autonomic reflex centre involved in maintaining homeostasis - Cardiovascular centre: adjust force and rate of heart contractions and changes blood vessel diameter to regulate blood pressure - Respiratory centres: ex. Vomiting, hiccupping, swallowing, coughing and sneezing ### **3.1.17 Cerebellum** Processes information from cerebral motor cortex, proprioceptors and visual and equilibrium pathways Provides precise timing and appropriate patterns of skeletal muscle contractions, necessary for smooth coordinated movement Responsible for balance and posture Possibly involved in thinking, language and emotion ### **3.1.18 Limbic system: functional brain system** Includes cerebral and diencephalon structure Mediates emotional response: our 'emotional' or 'affective' brain Involved in memory processing **RAS** = Reticular activating system sends a continuous stream of impulses to the cerebral cortex to keep it 'alert' and conscious and enhance its excitability **Brain protection** **Meninges**: 3 connective tissue membranes - Dura mater: 2-layered sheet of fibrous connective tissue - Arachnoid mater: loose brain covering - Subarachnoid space is filled with cerebral fluid - Pia mater: delicate connective tissue, enriched with tiny blood vessels **Cerebrospinal fluid**: forms a liquid cushion around brain and spinal cord that gives buoyancy to CNS structures **Blood brain barrier** - Protective mechanism that helps maintain the brain's stable environment - Major component: exceptionally impermeable tight junctions between capillary endothelial cells - Selective, not absolute - Ineffective against fat and fat-soluble substances, respiratory gasses - Nutrients move passively through facilitated diffusion - Bloodborne metabolic wastes, proteins, certain toxins and most drugs are denied access **Spinal cord** 2-way conduction pathway to and from the brain Major reflex centre: spinal reflexes are initiated and complete at the spinal cord levels Protected by bone, meninges and CFS Inferiorly, spinal cord terminates in a tapering, cone-shaped structure, called conus medullaris\ Filum medullare (fibrous extension of the conus) anchors spinal cord to the coccyx 31 pairs of spinal nerves (part of the peripheral nervous system) attach to the spinal cord by paired roots Each spinal cord segment is designated by the paired spinal nerves that arise from it Cauda equina: collection of nerve roots at the inferior end of the vertebral canal **Anatomy** - Grey matter - Dorsal horn: interneurons - Ventral horn: cell bodies of somatic motor neurons - Lateral horn: cell bodies of autonomic motor neurons - White columns - Dorsal funiculus - Lateral funiculus - Ventral funiculus - Ventral root: axons of the somatic motor neurons - Dorsal root: afferent fibres from peripheral sensory receptors - Dorsal root ganglia: contains the cell bodies of these sensory neurons ![](media/image11.png) **Neuronal pathways** Major spinal tracts are part of multineuron pathways that connect the brain to the body periphery - **Decussation**: most pathways cross from one side of CNS to the other at some point - **Relay**: most pathways consist of a chain of 2 or 3 neurons that contribute to successive tracts of the pathway - **Somatotopy**: most pathways exhibit a precise spatial relationship among the tract fibres that reflect the orderly mapping of the body - **Symmetry**: all pathways and tracts are paired symmetrically with a member of the pair present on each side of the spinal cord or brain - = conduct sensory impulses upward, typically through chains of successive neurons - **First-order neurons**: cell bodies reside in dorsal root ganglia;\ conduct impulses from cutaneous receptors of the skin and from proprioceptors to the spinal cord or brain stem, where they synapse with second-order neurons - **Second-order neurons**: cell bodies reside in dorsal horn of the spinal cord or medullary nuclei;\ transmit impulses to thalamus or cerebellum where they synapse - **Third-order neurons**: cell bodies in thalamus;\ relay impulses to somatosensory cortex of cerebrum **3 major pathways** - **Dorsal column-medial lemniscal pathways:\ **mediate precise, straight-through transmission of inputs from a single/few types of sensory receptors that can be localized precisely on the body surface such as touch, vibration - **Spinothalamic pathways**:\ receive input from many different types of sensory receptors and make multiple synapses in the brain stem;\ primarily transmission of pain and temperature - **Spinocerebral pathways:\ **convey information about muscle and tendon stretch to the cerebellum, which uses this information to coordinate skeletal muscle activity - Pyramidal or direct pathways - Originate mainly with pyramidal cells in the precentral gyri of the cerebrum - No synapse from pyramidal cells to spinal cord - They synapse with either interneurons or with ventral horn motor neurons - Stimulation of ventral horn neurons activates the skeletal muscle -\> regulates fast and fine movements such as writing Indirect pathways (the majority) - Brain stem motor nuclei and all motor pathways except for the pyramidal tract - Complex and multisynaptic - Involved in regulating: - Axial muscles that maintain balance and posture - Muscle controlling coarse limb movements - Head, neck and eye movements that follow objects in the visual field 2. ### Peripheral nervous system **Sensory receptors and sensation** Sensory receptors respond to changes in their environment, called stimuli Activation of a sensory receptor by an adequate stimulus results in graded potentials that in turn trigger nerve impulses along the afferent PNS fibres coursing to the CNS Sensation (awareness of the stimulus) and perception (interpretation of the stimulus) occur in the brain **Classification of sensory receptors by stimulus type** - Mechanoreceptors: mechanical force - Thermoreceptors: temperature change - Photoreceptors: light - Chemoreceptors: responds to chemicals in solution - Nociceptors: respond to potentially damaging stimuli that result in pain **Classification of sensory receptors by location** - Exteroceptors: respond to stimuli arising outside the body (touch, pain, smell, taste...) - Interoceptors: respond to stimuli arising inside the body - Proprioceptors: occur in skeletal muscle, tendons, joints and ligaments and in connective tissue covering bones and muscles;\ advising our brain on body movements by monitoring how much the organs containing these receptors are stretched **Classification of sensory receptors by receptor structure** - Simple receptors of the general senses: tactile sensation, temperature, pain and muscle sense (proprioception) - Nonencapsulated (free) nerve endings - Particularly abundant in epithelia and connective tissue - Mostly nonmyelinated small-diameter group C fibres - Chiefly respond to temperature and painful stimuli and itch - Others: tactile discs in epidermis and hair follicle receptors - Encapsulated nerve endings - Consist of one or more fibre terminals of sensory neurons enclosed in a connective tissue capsule - Receptors of the special senses - Vision - Hearing - Equilibrium - Smell - Taste **Somatosensory system: general organization** 3 main levels of neural integration operate in the somatosensory system - Receptor level: sensory receptors - Circuit level: processing in ascending pathways - Perceptual level: processing in cortical sensory areas **Nerves** - Spinal nerves - 31 pairs - All are mixed nerves - Supply all parts of the body except for head and some areas of neck - Each spinal nerve connects to the spinal cord via dorsal root and ventral root - Ventral root contain motor fibres - Dorsal root contain sensory fibres - Spinal nerve is only 1-2cm - Almost immediately after emerging from its foramen, it divides in ventral and dorsal ramus and a tiny meningeal branch - Cranial nerves - 12 pairs - Most are mixed nerves (except for olfactory and optic) - Sensory nerves: afferent - Motor nerves: efferent - Mixed nerves (majority) **Innervation of specific body regions** Nerve plexuses = complex interlacing neuronal networks - Cervical plexus: C1-C5 - Parts of head and neck - Brachial plexus: C5-T1 - arms - Lumbar plexus: L1-L4 - Legs - Sacral plexus: S1-S4 **Spinal reflexes** Spinal reflexes are somatic reflexes mediated by the spinal cord (no direct involvement of higher brain centres) Stretch and tendon reflexes help your nervous system smoothly coordinate the activity of skeletal muscle - Muscle spindles inform the nervous system on the length of the muscle - Tendon organs inform the nervous system on the amount of tension in the muscle - These provide essential feedback to cerebral cortex and cerebellum, so that the brain can compare what actually happened and what was supposed to happen **Muscle spindle and tendon organ anatomy** **Muscle spindle** - 3-10 modified muscle fibres: intrafusal muscle fibres - Extrafusal muscle fibres: effector fibres - 2 types of afferent nerve endings send input to CNS - Anulospiral endings: stimulated by rate and degree of stretch - Flower spray endings: stimulated only by degree of stretch - Intrafusal fibres have contractile region sonly at their ends, innervated by gamma efferent fibres (which differ from the alpha efferent fibres to the extrafusal fibres) **Stretch reflex** - Stretch reflex makes sure that muscle stay at their length - Important for maintaining muscle tone - Reflexive muscle contraction and reciprocal inhibition of antagonist muscle **Tendon reflex** - Opposite from stretch reflex: muscles relax and lengthen in response to tension - Help tendon and muscles from tearing when they are subjected to potential deleterious (schadelijk) stretching - When muscle contraction increases substantially during contraction or passive stretching, tendon organs are activated -\> reflexive muscle relaxation and reciprocal activation of antagonist muscle **Crossed-extensor reflex** Example: a stranger suddenly grasps the right arm, which is withdrawn reflexively while the left arm reflexively extends and pushes the stranger away **Autonomic nervous system** Innervates cardiac and smooth muscle and glands Efferent pathways and ganglia: - 2-neuron chain - Cell body of the first neuron, the preganglionic neuron, resides in the brain or spinal cord - Axons are thin, lightly myelinated - Postganglionic neuron, the second motor neuron, whose axon extends to effector organ - Axons are on-myelinated - Neurotransmitter effects - Norepinephrine: secreted by most sympathetic fibres - Acetylcholine: secreted by parasympathetic fibres **Parasympathetic division:** - Promotes maintenance functions and conserved body energy - The 'rest and digest' system - Fibres run in several cranial nerves - Sacral part of parasympathetic division (S1-S4) **Sympathetic division:** - Mobilizes the body during activity: 'fight or flight' response - Activities due to emotions - Also - Constricts visceral blood vessels, shunting blood to skeletal muscles and heart - Dilates bronchioles in the lungs, increasing air flow - Simulates liver to release more glucose in the blood - Cell bodies of the preganglionic neurons are located in the lateral horns of the spinal cord (T1-L2) - The preganglionic fibres pass through a white ramus communicans to enter an adjoining sympathetic trunk ganglion, forming part of the sympathetic trunk - The pre- and postganglionic neurons can - Synapse at the same level - Synapse at a higher or lower level - Synapse in a distant collateral ganglion - Sympathetic pathways with synapses in trunk ganglia - Pathways to the head - Pathways to the thorax: cardiac and pulmonary plexuses - Sympathetic pathways with synapses in collateral ganglia - Pathways to the abdomen - Pathways to the pelvis **Differences between parasympathetic and sympathetic:** - Sites or origin - Parasympathetic: craniosacral - Sympathetic: thoracolumbar - Length of fibres - Parasympathetic: long pre- and short postganglionic - Sympathetic: short pre- and long postganglionic - Location of ganglia - Parasympathetic: in/near visceral organs - Sympathetic: close to spinal cord **Visceral reflex arcs** Essentially the same as the somatic reflex arcs, but 2 differences: - 2 consecutive neurons in its motor component - Afferent fibres are visceral sensory neurons, which send information on stretch, chemical substances and irritation of the viscera Examples: visceral reflexes that empty rectum and bladder ANS control Hypothalamus - Main integration centre of ANS - Control directly or via relays through reticular formation which influences the preganglionic motor neurons in brain stem and spinal cord - Coordinates heart activity, blood pressure, body temperature, water balance and endocrine activity - Emotional responses of limbic system to danger and stress signal hypothalamus to activate sympathetic system to flight-or-fright status Brain stem and spinal cord control - Direct influence of autonomic functions Cortical control - Examples: - Remember a frightening event that makes your heart race (SS) - Thinking of your favourite food makes your mouth water (PS) **The endocrine system** ------------------------ One of the two major control systems in our body - Nervous system regulates activity of muscles and glands through electrochemical impulses delivered by neurons - Endocrine system influences metabolic activity through hormones\ = chemical messenger secreted by cells in the extracellular fluid that travels through the blood to our body cells Endocrine system is involved in - Reproduction - Growth and development - Maintenance of electrolyte, water and nutrient balance of the blood - Regulation of cellular metabolism and energy balance - Mobilization of body defences 2 types of glands: - Exocrine glands: produce nonhormonal substance such as sweat and saliva and have ducts - Endocrine glands or ductless glands: produce hormones 3. ### **Hormones** Act on cells that have specific receptors: target cells Effect through alteration of the target cell activity but the response depends on the target cell type **Hormone-influenced changes:** - Change in plasma membrane permeability or membrane potential by opening/ closing ion channels - Stimulation of enzyme/protein synthesis - Activation or deactivation of enzymes - Induction of secretory activity - Stimulation of mitosis **Water-soluble hormones** - All amino-acid base hormones except thyroid hormone - Act on receptors in the plasma membrane - These receptors are coupled via G-proteins (regulatory proteins) to one or more intracellular messengers which modulate the target cell's response **Lipid-soluble hormones** - Steroids and thyroid hormone - Act on receptors inside the cell, which directly activate genes 4. ### **Plasma membrane receptors** Cyclic AMP signalling mechanism - Ligand (1^st^ messenger) -\> receptor -\> G protein -\> enzyme -\> 2^nd^ messenger Target cell activation depends on: - Blood levels of the hormone - Relative number of receptors for that hormone - Affinity of the binding between the hormone and the receptor Receptors are dynamic structures: - Upregulation: formation of additional receptors - Downregulation: desensitization, uncoupling from signalling mechanism and degradation of receptors 5. ### **Intracellular receptors** 1. 2. 3. 4. 5. 6. ### **Three types of stimuli cause hormone release** Humoral stimuli - Changes in the blood levels of certain ions and nutrients - Example: changes in blood levels of Ca^2+^ influence parathyroid hormone levels;\ changes in blood levels of glucose influence insulin release Neural stimuli - In a few cases, nerve fibres stimulate hormone release - Examples: the sympathetic nervous system stimulates adrenal medulla to release norepinephrine and epinephrine Hormonal stimuli - Stimulation by hormones released by others endocrine organs - Examples: releasing and inhibitory hormones produced by hypothalamus regulate secretion of most anterior pituitary hormones 7. ### **Hypothalamic -- hypophyseal relationships** Hypothalamic-hypophyseal tract - Neural connection between hypothalamus and posterior lobe of pituitary gland - Nerve bundle that arises from neurons in the paraventricular and supraoptic nuclei of the hypothalamus - Neurons synthesize neurohormones and transport them along their axons to the posterior lobe of the pituitary gland Hypophyseal portal system - Vascular connection between hypothalamus and anterior lobe of the pituitary gland - Via hypophyseal portal system, releasing and inhibiting hormones secreted by neurons of hypothalamus circulate to anterior lobe where they regulate hormone secretion - This system prevents that the releasing and inhibiting hormones are diluted in systemic circulation 8. ### **Hypothalamus and pituitary gland** ### Pituitary gland ( =hypophysis): 2 major globes - **Posterior globe**: largely neural tissue that releases neurohormones - Oxytocin - Strong stimulus for uterine contraction during childbirth - Stimulates milk ejection - Also a neurotransmitter in the brain, involved in sexual and affectionate behaviour - Antidiuretic hormone (ADH) - Antidiuretic: prevents urine production - Osmoreceptors: hypothalamic neurons that continually monitor solute (=opgeloste stiffen) concentration of the blood - ADH is released as solutes threaten to become too concentrated - ADH targets kidney tubule cells, which respond by reabsorbing more water from the urine and returning it to the blood - ADH is also released by triggers such as pain, low blood pressure, drugs as nicotine, morphine and barbiturates 1. 2. 3. 4. - **Anterior globe or adenohypophysis**: glandular tissue that releases hormones - Growth hormone (GH, aka somatotropin) - Direct actions on metabolism - Mobilizes fat from fat depots - Decreases rate of glucose uptake and metabolism, conserving glucose - Encourages glycogen breakdown in liver and glucose release to the blood - Indirect actions on growth - Mediated via insulin-like growth factors (IGF), produced by liver, skeletal muscle, bone...upon GH stimulation - IGFs stimulate growth through - Nutrient uptake from the blood and incorporation into proteins and DNA, allowing growth by cell division - Formation of collagen and deposition of bone matrix - Regulation of secretion by hypothalamic hormones - Growth-hormone releasing hormone (GHRH) - Growth-hormone inhibiting hormone (GHIH) by feedback of GH and IGF - Thyroid stimulating hormone (TSH) (aka thyrotropin) - Stimulates normal development and secretor activity of the thyroid gland - Thyrotropin-releasing hormone (TRH) triggers release of TSH - Rising levels of thyroid hormones in the blood act on pituitary and hypothalamus to inhibit TSH secretion - GHIH also inhibits TSH secretion - Adrenocorticotropic hormone (ACTH) (aka corticotropin) - Stimulates the adrenal cortex to release corticosteroid hormones, most importantly glucocorticoids - Corticotropin-releasing hormone (CRH) triggers ACTH release - Daily rhythm, levels peaking in the morning just before awakening - Rising levels of glucocorticoids feedback and block CRH secretion - Gonadotropins (FSH and LH) - Follicle-stimulating hormone - Luteinizing hormone - Regulates the function of the gonads (=geslachtsklieren) - FSH stimulates production of the gametes - LH promotes production of gonadal hormones - During puberty, gonadotropic cells of anterior pituitary are activated - Gonadotropin-releasing hormone (GnRH) triggers gonadotropin release - Gonadal hormones feedback to suppress FSH and LH release - Prolactin (PRL) - Stimulates mild production - PRL release is primarily controlled by an inhibitory hormone: prolactin-inhibiting hormone (PIH) = dopamine 1. 2. 3. 9. ### **Thyroid gland** Follicles, walls of which are formed by follicle cells, that produce thyroglobulin Parafollicular cells produce **calcitonin** - Polypeptide hormone released by the parafollicular cells, in response to a rise in Ca^2+^ levels - Physiological effect in humans unknown -\> calcitonin does not need to be replaced in patients in whom thyroid gland is removed - Pharmacological effect: bone-sparing effect, given to patients with eg: Paget's disease or osteoporosis - Inhibits osteoclast activity - Stimulates Ca^2+^ uptake and incorporation in bone matrix **Thyroid hormone (TH)** - Thyroxine or T~4~ - Major hormone secreted by follicle cells - Triiodothyronine or T~3~ - Formed by conversion of T~4~ to T~3~ at target cells - Affects virtually every cell in the body - Increasing basal metabolic rate and body heat production, by turning on transcription of genes involved in glucose oxidation -\> calorigenic effect - Regulating tissue growth and development: TH is critical for skeletal and nervous tissue development and maturation of reproductive capabilities - Maintaining blood pressure by increasing number of adrenergic receptors in blood vessels - Synthesis: 1. 2. 3. 4. 5. 6. 7. 10. ### **Parathyroid glands** Releases parathyroid hormone (PTH) (aka parathormone) - Most important hormone controlling calcium balance in blood - Calcium homeostasis is critical for many functions, such as nerve impulse transmission, muscle contraction and blood clotting 11. ### **Adrenal glands** ### All adrenal hormones cope with stressful situations Each adrenal gland is structurally and functionally 2 endocrine glands: - **Adrenal medulla**: part of the sympathetic nervous system - Contains modified postganglionic sympathetic neurons - These neurons produce the catecholamines epinephrine and norepinephrine - Involved in response to short-term stressors - **Adrenal cortex**: glandular tissue - Synthesizes corticosteroids - Mineralocorticoids: regulate electrolyte concentrations in extracellular fluids, particularly Na^+^ and K^+^ - Most potent mineralocorticoid = aldosterone (essential for life)\ -\> reduces excretion of Na^+^ from the body, the primary target being the kidney tubules - Glucocorticoids: influence energy metabolism of most body cells and help resist stressors - Effects when too much cortisol is present in the blood - Depress cartilage and bone formation - Inhibit inflammation by decreasing release of inflammatory chemicals - Depress immune system - Disrupt normal cardiovascular, neural and gastrointestinal function Mechanisms controlling aldosterone release - **Renin-angiotensin-aldosterone mechanism\ **-\> influences blood volume and blood pressure by regulating aldosterone release 1. When blood pressure or blood volume falls, specialized cells of the juxtaglomerular complex in the kidneys are excited 2. These cells respond by releasing renin into the blood 3. Renin cleaves off part of the plasma protein angiotensinogen, triggering an enzymatic cascade that forms angiotensin II, which stimulates production of aldosterone - **Plasma concentrations of potassium (K^+^)\ **-\> increase in K^+^ stimulates aldosterone release - **ACTH\ **-\> influences aldosterone secretion in severe stress situations - **ANP (atrial natriuretic peptide, released by the heart)\ **-\> blocks renin and aldosterone secretion ### ### **Pineal gland** Pinealocytes: secretory glands Produce melatonin, involved in the sleep-wake cycle Pineal gland indirectly receives input from the visual pathways ### **Pancreas** Mixed gland compose both of exocrine and endocrine gland cells Pancreatic islets (islets of Langerhals) - Alpha cells: synthesize glucagon - Beta cells: produce insulin Pancreatic acinar cells (exocrine cells): produce an enzyme-rich juice that is carried by ducts to the small intestine during digestion **Glucagon** - Hyperglycaemic hormone - 29-amino acid polypeptide - One molecule can cause release of 100 million glucose molecules into the blood - Major target: liver - Promotes: - Breakdown of glycogen to glucose - Synthesis of glucose from lactic acid and from noncarbohydrate molecules - Release of glucose to the blood by liver cells - Humoral stimuli stimulate alpha cells - Glucagon release is suppressed by rising glucose levels and rising insulin and somatostatin levels **Insulin** - Hypoglycaemic hormone - 51-amino acid polypeptide - Main effect is to lower glucose levels in the blood - Enhances membrane transport of glucose into most body cells, esp. muscle and fat - Inhibits the breakdown of glycogen to glucose - Inhibits the conversion of amino acids or fat to glucose - After glucose enters a target cell, insulin binding triggers enzymatic activities that - Catalyse oxidation of glucose for ATP production - Join glucose molecules to form glycogen - Convert glucose to fat - Beta cells secrete insulin when stimulated by - Elevated blood glucose levels - Rising blood levels of amino acids and fatty acids - Acetylcholine released by parasympathetic nerve fibres - Hyperglycaemic hormones 14. ### **Gonads and placenta** **Ovaries**: produce oestrogens and progesterone - Oestrogens: responsible for maturation of the reproductive organs and appearance of secondary sex characteristics of females during puberty - Oestrogens and progesterone promote breast development and cyclic changes in the uterine mucosae **Testes**: produce testosterone - Testosterone initiates maturation of the male reproductive organs and appearance of secondary sex characteristics and sex drive - Testosterone is also needed for normal sperm production and maintains the reproductive organs in their mature functional state in male adults 15. ### **Hormone secretion by other organs** **Adipose tissue** - Release leptin: tells the body how much stored energy there is: the more fat you have, the more leptin in the blood - Leptin binds to CNS neurons concerned with appetite control, producing sensation of satiety **Gastro-intestinal tract** - Enteroendocrine cells produces several peptides (hormones) that help regulate a wide variety of digestive functions - Gastrin: released in the stomach, stimulates glands in the stomach to release hydrochloric acid - Cholecystokinin (CKK): release in the duodenum, stimulates the pancreas to release enzyme-rich juice, relaxes the hepatopancreatic sphincter, allowing bile and pancreatic juice to enter duodenum **Kidney** - Erythropoietin (EPO): stimulates production of red blood cells by the red bone marrow **Heart** - Atrial natriuretic peptide (ANP) Maintenance of the body ======================= **4.1 The cardiovascular system** --------------------------------- ### **4.1.1 The heart** **Layers of the heart wall:** - Epicardium: inner pericardium layer - Myocardium: cardiac muscle layer - Endocardium: inner layer of heart **Heart: 2 pumps** - Right side: receive oxygen-poor blood from body and pumps this to the lungs - = pulmonary circuit - Left side: receives oxygen-rich blood from lungs and pumps this throughout the body - = systemic circuit - 2 receiving chambers: 'atria' - Right atrium receives blood from - Superior vena cava: returns blood from body regions superior to the diaphragm - Inferior vena cava: returns blood from body regions inferior to diaphragm - Coronary sinus: collects blood draining from the myocardium - Left atrium receives blood from - Pulmonary veins - 2 pumping chambers: 'ventricles' - Right ventricle pumps blood into: - Pulmonary trunk - Left ventricle pumps blood into - Aorta ### **4.1.2 Heart valves** **Atrioventricular valves** - Tricuspid valve: right AV valve ( 3 flexible cusps) - Mitral valve: left AV valve (2 cusps (=knobbels)) - Attached to each AV valve are tiny collagen cords 'chordae tendineae' which anchor the cusps to the papillary muscles in the ventricular wall - Function: 1. Blood returning to the heart fills atria , putting pressure against AV valves and they are forced open 2. As ventricles fill, AV valve flaps hang limply into ventricles 3. Atria contract, forcing additional blood into ventricles 4. Ventricles contract , forcing blood against AV valves cusps 5. AV valves close 6. Papillary muscles contract and chordae tendineae tighten, preventing valve flaps from everting into atria **Semilunar valves** - Aortic and pulmonary valves (3 cusps) - Function: 1. As ventricles contract and intraventricular pressures rises, blood is pushed against semilunar valves, forcing them open 2. As ventricles relax and intraventricular pressure falls, blood flows back from arteries -, filling the cusps of semilunar valves and forcing them to close ### **4.1.3 Coronary circulation** **Coronary arteries** Left and right coronary arteries branch from the base of the aorta Left: - Anterior interventricular artery - Circumflex artery Right: - Right marginal artery - Posterior interventricular artery **Coronary veins** Cardiac veins -\> coronary sinus ### **4.1.4 Blood vessels** **Arteries (slagaders)** - Carry blood away from the heart - Branch to smaller and smaller divisions - Elastic arteries - Thick-walled arteries near the heart - Contain more elastin than other arteries - Pressure reservoirs, expanding and recoiling as the heart ejects blood - Muscular arteries - Distal of the elastic arteries (verder van het centrum gelegen) - Deliver blood to the specific organs - Have thickest tunica media of all vessels, relatively more smooth muscle than elastic arteries - Arterioles - Smallest arteries (diameter \< 0.3mm) **Veins (aders)** - Carry blood to the heart - Merge-converge to larger vessels - Large veins - 3 distinct tunics - Thinner walls, larger lumens than arteries - Little smooth muscle cells and elastic fibres in tunica media - Can act as blood reservoirs - Venules - Smallest veins - Venous valves - Prevent blood from flowing back **Capillaries (haarvaten)** - Exchange vessels - Have intimate contact with tissue cells - Metarteriole, continuous with thoroughfare channel - Vascular shunt - True capillaries - True exchange vessels - Precapillary sphincter - Surrounds root of each true exchange vessel at the metarteriole and acts as a valve to regulate blood flow **Anatomy** - Tunica intima - Endothelium (simple squamous epithelium) - Subendothelial layer (basement membrane and loose connective tissue) - Tunica media - Circularly arranged smooth muscle cells (regulated by vasomotor nerve fibres of ANS) - Sheets of elastin - Tunica externa - Loosely woven collagen fibres - Has nerve fibres, lymphatic vessels - In larger vessels also elastic fibre network and 'vasa vasorum' (= vessels of the vessels) ### **4.1.5 Velocity of blood flow** As the arterial system branches, the velocity of the blood flow declines - Fast blood flow in the aorta - Slow blood flow in the capillaries Slow capillary flow is beneficial because it promotes exchange of respiratory gases and nutrients ### **4.1.6 Capillary transport mechanism** 1. 2. 3. 4. ### **4.1.7 Bulk flow** Bulk flow is extremely important in determining relative fluid volumes in the bloodstream and in the interstitial space Hydrostatic pressure: the force exerted by a fluid pressing against the wall - In capillaries: hydrostatic pressure = capillary blood pressure - Capillary hydrostatic pressure tends to force fluids through capillary walls (filtration), leaving behind proteins and blood cells Colloid osmotic pressure: the force opposing hydrostatic pressure, created by large non-diffusible molecules (which draw water, through osmosis) - In capillaries, the abundant plasma proteins develop a capillary colloid osmotic pressure ( oncotic pressure) - In interstitial fluid, oncotic pressure is considerably lower **4.2 Blood** ------------- ### **4.2.1 Functions** - Transport - Delivering oxygen and nutrients - Transporting metabolic waste, including carbon dioxide - Transporting hormones from the endocrine system to target organs - Regulation - Body temperature - Maintaining normal pH in body tissues - Maintaining adequate fluid volume in the circulatory system - Protection - Preventing blood loss: blood clot formation - Preventing infections ### **4.2.2 Plasma and formed elements** **Plasma** - Water (90% of plasma volume) - Electrolytes - Plasma proteins - Other: nutrients, hormones, respiratory gasses **Formed elements** - Erythrocytes: red blood cells\ = 'bags' of haemoglobin - The small size and shape provides a huge surface area to volume, ideal for optimal gas exchange - The disc shape is ideally suited for gas exchange because no point within cytoplasm is far from surface - Over 97% of erythrocyte is haemoglobin - Because they have no mitochondria, they do not consume any of the oxygen they carry - Leucocytes: white blood cells - Platelets - Not cells in the strict sense - Cytoplasmic fragments of extraordinary large cells, called megakaryocytes - Contain granules, with chemicals that act in the clotting process, such as serotonin, Ca^2+^ platelet-derived growth factor (PDGF) and enzymes - Essential for the clotting process - Formation of platelets regulated by thrombopoietin - Normally about 150000-400000 platelets/µL blood **Haemoglobin structure** - Heme: red pigment - Globin: consists of 4 polypeptide chains binding a ring-like hemegroups - Each heme group has a central iron atom - Each iron atom can combine reversibly with one molecule of oxygen - When oxygen binds to iron, haemoglobin, now called oxyhaemoglobin, becomes ruby red - When oxygen detaches from iron (deoxyhaemoglobin) blood becomes dark red **Haematopoiesis**: blood cell formation in red bone marrow **Erythropoiesis**: red blood cell formation - Regulation: erythropoietin (EPO): a glycoprotein hormone, released by the kidneys, that stimulates the formation of RBC - Disorders - Anaemia - A condition in which the blood's oxygen-carrying capacity is too low to support normal metabolism - Causes: - Blood loss: 'haemorrhagic anaemia' - Not enough RBC produced - Too many RBC destroyed: 'haemolytic anaemia' - Sickle cell anaemia - Polycythaemia - Excess of erythrocytes, that increases blood viscosity ### **4.2.3 leucocytes** Crucial for our defence against diseases Able to slip out of the capillary blood vessels through diapedesis Normal count: 4800-10800 WBC/µL of blood\ \> 11000 µL: leucocytosis 2 major classes: - **Granulocytes** - Lobed nuclei - Membrane-bound cytoplasmic granules 1. - - - - 2. - - - - 3. - - - **Agranulocytes** - Nuclei are spherical or kidney-shaped - Lack visible cytoplasmic granules 1. - - - 2. - - - **Leucopoiesis regulated by** - Interleukins - Colony-stimulating factors **Phagocytosis** = the process by which solid materials (such as pathogens) are ingested by a cell **Disorders** - Leukemia - A group of cancerous disease involving overproduction of abnormal WBC - Named according to the cell type primarily involved - Acute if they derive from stem cells - Chronic if it involves proliferation of later cell stages - Infectious mononucleosis - 'kissing disease' - Highly contagious viral disease, caused by Epstain-Barr virus - Hallmarked by excess number of leucocytes - Leucopenia - Abnormally low WBC count, commonly induced by drugs, such as glucocorticoids and anticancer agents ### **4.2.4 Haemostasis** Series of reactions that is started when the wall of blood vessels breaks, in order to stop the bleeding Fast, localized and carefully controlled Involves many clotting factors, normally present in plasma, as well as several substances that are released by platelets and injured tissue cells 1. **Vascular spasm** Triggered by direct injury to vascular smooth muscle cells Chemicals released by endothelial cells and platelets Reflexes initiated by local pain receptors A strongly contracted artery can significantly reduce blood loss for 20-30 min 2. **Platelet plug formation (vorming van bloedplaatjespluggen)** Platelets aggregate (stick together), forming a temporary plug Intact endothelial cells release nitric oxide and a prostaglandin called prostacyclin that prevents platelets aggregation in undamaged tissue When the endothelium is damaged, platelets strongly adhere to underlying collagen fibres Von Willebrand Factor (large plasma protein) stabilizes bound platelets by forming a bridge between platelets and collagen Platelets become activated: they swell, form spiked processes and become stickier They release chemicals: - ADP (adenosine diphosphate): a potent aggregating agent - Serotonin and thromboxane A~2~: messengers that enhance vascular spasm and platelet aggregation 3. **Coagulation** Reinforces the platelet plug with fibrin threads that acts as molecular glue for the aggregated platelets Necessary to seal larger breaks in a blood vessel Multistep process that involves a series of substances, called clothing factors or procoagulants Most clotting factors are plasma proteins synthesized by the liver Numbered from I to XII Vitamin K necessary for the synthesis of 4 clotting factors Activation turns clotting factors into enzymes, which activates the next step in the sequence 1. - - - - - - - - - - 2. - 3. - - - - ### **4.2.5 Clot retraction** A platelet-induced process that further stabilizes the clot within 30-60 min Platelets contain actin and myosin and they can contract just like smooth muscle cells As they contract, they compact the clot and draw the ruptured edges of the damaged blood vessels together Platelets release platelet-derive-growth-factor (PDGF): stimulates sSMC and fibroblasts to divide and rebuild the blood vessel wall As fibroblasts form a connective tissue patch in the injured area, endothelial cells (stimulated by vascular endothelial growth factor (VEGF), multiply and restore the endothelial lining ### **4.2.6 Fibrinolysis** Removes unneeded clots when healing was occurred Fibrinolysis mainly done by plasmin, which is produced when the plasma protein plasminogen is activated Large amounts of plasminogen are incorporated into forming a clot, where they remain inactive The presence of a clot induces endothelial cells to secrete tissue plasminogen activator (tPA) Factor XII and thrombin (released during clotting) also activates plasminogen Therefore, most plasmin activity is confined to the clot Fibrinolysis starts within 2 days and continues slowly over several days, until the clot finally dissolves ### **4.2.7 disorders of haemostasis** **Thrombo-embolic disorders** - Conditions that cause undesirable clot formation - Thrombus - A clot that develops and persists in an unbroken blood vessel - May block circulation and lead to death of the cells and tissues beyond the occlusion - Embolus - If the thrombus breaks away from the blood vessel and floats freely in the blood stream, it becomes an embolus - This becomes a problem when the embolus encounters a blood vessel that is too narrow -\> embolism - Conditions that roughen the vessel endothelium, such as atherosclerosis or inflammation, cause thromboembolic disease, by allowing platelets to gain a foothold - Patients that are bedridden also have higher risk of thromboembolic disease, due to slowly flowing blood **Anti-coagulant drugs** - Drugs that are used to prevent undesirable clotting - Examples: - Aspirin - Warfarin **Bleeding disorders** - Thrombocytopenia - Platelet deficiency - Causes spontaneous bleeding from small blood vessels all over the body - Petechiae: small purple spots - Can arise from any condition that supresses or destroys red bone marrow - Impaired liver function - Cells fail to produce clotting factors - Cells fail to produce bile, that is required to absorb fat and vitamin K - Haemophilia - Hereditary bleeding disorders that have similar signs and symptoms - Haemophilia A: deficiency of factor VIII - Haemophilia B: deficiency of factor IX - Haemophilia C: deficiency of factor XI ### **4.2.8 Human blood groups** RBC plasma membranes bear highly specific molecular markers at their external surfaces, called antigens One person's RBC antigens may be recognized as foreign if transfused into someone with a different RBC type and the transfused cells may be agglutinated (clumped together) and destroyed At least 30 groups of naturally occurring RBC antigens (blood groups) are found in humans Antigens determining the ABO and Rh blood groups cause vigorous transfusion reactions, in which the foreign RBC are destroyed -\> blood typing is necessary before transfusion **ABO blood groups** - Based on the presence of 2 agglutinogens, type A and type B - O blood group has no agglutinogen: is most common - AB blood group least common - Unique to ABO blood groups is the presence of preformed antibodies in the plasma called agglutinins - Agglutinins act against RBCs carrying ABO antigens that are not present on a person's own RBC - Example: a person with group A will have anti-B antibodies Rhesus blood groups - 52 named Rhesus agglutinogens each of which is called a Rh factor - Only 5 of these C, D, E, c and e are fairly common - About 85% of Caucasian population is Rh^+^ , meaning that their RBC carry the D antigen - As a rule a person's ABO and rhesus blood groups are reported together - Anti-rhesus antibodies do not form spontaneously in the blood of Rh^-^ individuals - However, if a Rh^-^ person receives Rh^+^ blood, the immune system becomes sensitized and begins producing Rh antibodies against the foreign antibody soon after transfusion - The second time and every time after, a typical 'transfusion reaction' occurs in which the recipients antibodies attack and destroy the donor RBCs - Pregnant women who are Rh^-^ who carry a Rh^+^ child are a particular problem - When bleeding occurs as the placenta detaches from the uterus, the mother may become sensitized by her baby's Rh^+^ antigens that pass into her bloodstream - RhoGAM: a serum containing anti-Rh antibodies, which can agglutinate the Rh factor and as such block the mother's immune response and prevent sensitization (should be given shortly before or after delivery) - If the mother is not treated and becomes pregnant again with a Rh^+^ baby, her antibodies will cross through the placenta and destroy the baby's RBC, producing a condition called 'haemolytic disease of the new-born' **4.3 respiratory system** -------------------------- ### **4.3.1 Major functions** To supply the body with oxygen and to dispose of carbon dioxide - - **Pulmonary ventilation**: breathing - **External respiration**: oxygen diffuses from lungs to blood and carbon dioxide from blood to lungs - **Transport of respiratory gasses**: through the blood in the cardiovascular system - **Internal respiration**: oxygen diffuses from blood to lungs and carbon dioxide from lungs to blood Also involved with the sense of smell and speech ### **4.3.2 Upper respiratory system** **Nose** - Only external part of the respiratory system - Functions: - Provides an airway of respiration - Moistens and warms the air - Filters and cleans inspired air - Serves as a resonating chamber of speech - Houses the olfactory (smell) receptors **Nasal cavity** - Divided by nasal septum, the anterior part of which is cartilage, the posterior part is formed by bone - Continuous with nasal part of pharynx through the posterior nasal apertures - Roof is formed by skull bone - Floor is formed by the palate: - Hard palate: anterior part - Soft palate: posterior part (muscular) - Nasal vestibule: part of the nasal cavity just superior to nostrils - Lined with skin with numerous sebaceous and sweat glands and hair follicles - Hairs (vibrissae) filter coarse particles from the inspired air - Rest of nasal cavity - Lined with 2 types of mucous membrane - Small patch of olfactory mucosae: contains smell receptors in its olfactory epithelium - Respiratory mucosae: pseudostratified ciliated columnar epithelium, containing goblet cells, that rests on a lamina propria richly supplied with seromucous nasal glands **Lysozyme**: antibacterial enzyme secreted by mucus cells and serous cells of the seromucous nasal glands **Mucus**: sticky, traps dust, bacteria and other debris **Defensins**: natural antibiotics, secreted by epithelial cells High water content of mucus warms and moistens the inspired air Ciliated cells of respiratory mucosae create a gentle wave that moves the air posteriorly Nasal mucosae is richly innervated with sensory nerve endings -\> contact with irritating particles triggers a sneeze Rich capillary plexuses underly nasal epithelium -\> warm the incoming air **Rhinitis:** - Inflammation of nasal mucosa - Nasal mucosa is continuous with mucosa of respiratory tract, so infections spread from nose to throat to chest - Can also spread to tear ducts and paranasal sinuses, causing blockage of sinus passageways - Can lead to absorption of air, producing a vacuum, resulting in sinus headache **Paranasal sinuses** - Located in the frontal, sphenoidal, ethmoid and maxillary bone - Lighten the skull - Help warm and moistens the air **Pharynx (keelholte)** - Connects nasal cavity and mouth to larynx and oesophagus (throat) **Adenoids (neusamandelen)** - Infected and swollen adenoids can block air passage in nasopharynx, making it necessary to breathe through the mouth - As a result, air is not properly moistened, warmed or filtered before reaching lungs - When adenoids are chronically enlarged, both speech and sleep may be disturbed ### **4.3.3 lower respiratory system** **Functionally:** - Conducting zone - Respiratory passageways - They cleanse, humidify\ and warm incoming air - Respiratory zone - Actual site of gas exchange - Respiratory bronchioles - Alveolar ducts - Alveolar sacs/saccules **Larynx: (strottenhoofd)** - 3 functions - Provide a patent (open) airway - Acts as a switching mechanism to route air and food into the proper channels - Voice production (vocal chords) - Framework is an intricate arrangement of 9 cartilages, connected to membranes and ligaments - Laryngitis (=keelontsteking) - = inflammation of the vocal folds that causes the vocal folds to swell, interfering with vibrations - Results in changes to vocal tone, causing hoarseness, in severe cases speaking is limited to a whisper - ![](media/image13.png)Laryngitis is most often caused by viral infections but may also be due to overuse of the voice, very dry air, bacterial infections, tumours on the vocal folds or inhalation of irritating chemicals **Trachea: (luchtpijp)** **Bronchi and subdivisions:** **Conducting zone structures: tissue composition changes** - Support structure change: irregular plates of cartilage replaces cartilage rings - Epithelium type changes: mucosal epithelium thins; goes from pseudostratified columnar -\> columnar -\> cuboidal - Amount of smooth muscle increases Respiratory membrane: 'blood air barrier' - Walls of the alveoli - Single layer of squamous epithelial cells (type I alveolar cells) - Surrounded by a flimsy basement membrane - External surfaces are extensively covered with a cobweb of pulmonary capillaries - Type II alveolar cells: produce surfactant, which coats the gas-exposed alveolar surface ### **4.3.4 Gas exchange** Gas exchange occurs between lungs and blood and between blood and tissue Gas exchange occurs by simple diffusion of respiratory gases through the respiratory membrane **External respiration**: diffusion of gases between lungs and blood **Internal respiration**: diffusion of gases between blood and tissues Procedures depend on: - Basic properties of gases - Composition of alveolar gases **Dalton's law of partial pressure** - The total pressure exerted by a mixture of gases is the sum of the pressures exerted independently by each gas in the mixture - The pressure exerted by each gas (the partial pressure) is directly proportional to the percentage of that gas in the mixture **Henry's law** - When a gas is in contact with a liquid the gas will dissolve in this liquid in proportion to its partial pressure **Oxygen transport** - Mainly bound to haemoglobin - Small amount is dissolved in plasma **Carbon dioxide transport** - Dissolved in plasma - Chemically bound to haemoglobin - As bicarbonate ions in plasma **4.4 metabolism and energy balance** ------------------------------------- ### **4.4.1 Nutrients\ **=substances in the food the body uses to promote normal growth, maintenance and repair **Macronutrients** - Carbohydrates - Lipids - Proteins **Micronutrients** - Vitamins - Minerals **Water**: about 60% of the body volume Energy value of food is measured in kilocalories:\ 1kcal is the amount of heat energy needed to raise the temperature of 1kg of water 1°C ### **4.4.2 Metabolism** = the sum of all biochemical reactions in the body **Anabolism**: all reactions that build larger molecules or structures from smaller ones **Catabolism**: all processes that break down complex structures to simpler ones **Cellular respiration**: the breaking down of food fuels, such as glucose, to capture the released energy to produce ATP - **ATP** is the cell's energy currency that links energy-releasing catabolic reactions to cellular work 3 major stages in processing energy-containing nutrients in the body - Digestion in the **GI tract** - Anabolism (lipids, proteins, glycogen) or catabolism (pyruvic acid and acetyl CoA) in **tissue cells** - Oxidative breakdown of stage 2 products in **mitochondria** ### **4.4.3 Oxidation-reduction reactions** Oxidation: the gain of oxygen or the loss of hydrogen - Oxidized substances always loses electrons as they move to a substance that more strongly attracts them - Oxidation of food cells: step-by-step removal of pairs of hydrogen atoms from the substrate molecules, eventually leaving only CO~2~. Molecular oxygen is the final electron acceptor it combines with the removed hydrogen atoms at the end of the process to form water - Oxidation is always coupled with reduction: when one substance loses electrons, another gains them -\> redox-reactions ### **4.4.4 ATP synthesis** 1. **Substrate-level phosphorylation** Direct transfer of high-energy phosphate groups from phosphorylated substrates to ADP Enzyme are located in cytosol and in the mitochondria 2. **Oxidative phosphorylation** More complex Carried out by electron transport proteins embedded in inner mitochondrial membranes Chemi-osmotic process: the coupling of movement of substances across membranes to chemical reactions Some of the energy released during the oxidation of food fuels is used to pump protons across inner mitochondrial membrane into intermembrane space. When the protons flow back across the membrane through ATP synthase membrane channels, the gradient energy is captured and used to attach phosphate groups to ADP **4.4.5 Carbohydrate metabolism\ **= central player in ATP production All food carbohydrates are eventually transformed to glucose Glucose enters tissue cells by facilitated diffusion After entering the cell, glucose is phosphorylated to glucose-6-phosphate Glucose + ATP \ glucose-6-PO~4~ + ADP As most cells lack enzymes needed to reverse this reaction, it traps glucose inside the cell Intestinal epithelial cells, liver cells and kidney cells have these enzymes, reflecting their central roles in glucose uptake and release ### **4.4.6 Oxidation of glucose** Glucose is the pivotal fuel molecule in oxidative, ATP-producing, pathways Glucose is oxidized via the following reaction: C~6~H~12~O~6~ + 6O~2~ \ 6H~2~O + 6CO~2~ +32ATP + heat Involves 3 pathways - Glycolysis - Citric acid cycle - Electron transport chain and oxidative phosphorylation ### **4.4.7 Glycolysis = glycolytic pathway** Occurs in the cytosol of cells Converts glucose to 2 pyruvic acid molecules in a series of 10 chemical steps Anaerobic process: reaction does not use oxygen and occurs whether or not oxygen is present 3 major phases: - Sugar activation: formation of fructose-1,6-biphosphonate - Sugar cleavage: formation of two 3-carbon fragments - Sugar oxidation and ATP formation - The 3-carbon elements are oxidized by removal of hydrogen with NAD^+^ picks up - Inorganic phosphate groups are attached to each oxidized fragment by high-energy bonds. Later, when the phosphates are split off, enough energy is captured to form 4 ATP molecules Final products are 2 pyruvic acid molecules and 2 reduced NAD^+^ molecules Net gain of 2 ATP molecules per glucose molecule When oxygen is available: NADH + H^+^ delivers hydrogen atoms to the enzymes of the electron chain in the mitochondria, which delivers them to O~2~ to form water When no oxygen is available, lactic acid is oxidized back to pyruvic acid and enters the aerobic pathways The liver may also convert lactic acid back to glucose-6-phosphate Prolonged anaerobic metabolism ultimately results in acid-base problems -\> only a temporary route for rapid ATP production ### **4.4.8 Citric acid cycle (= Krebs cycle)** Occurs in the mitochondrial matrix Fuelled largely by pyruvic acid, produced during glycolysis, and by fatty acids, resulting from fat breakdown Pyruvic acid enters the mitochondria via a transport protein 1. **Transitional phase: converts pyruvic acid to acetyl CoA** 1. 2. 3. Co-enzyme A shuttles the 2-carbon acetic acid to an enzyme that joins it to 4-carbon oxaloacetic acid to produce 6-carbon citric acid 2. **Citric acid cycle** 8 successive steps, through which atoms of citric acid are rearranged to form intermediate molecules, called keto-acids Citric acid is broken down carbon by carbon (decarboxylated) and oxidized, generating NADH+H^+^ and FADH~2~ At the end citric acid has been disposed of and oxaloacetic acid is regenerated For each turn of the cycle we get - 2 CO~2~ molecules from 2 decarboxylations - 4 molecules of reduced coenzymes (3 NADH+H^+^ and 1 FADH~2~) - 1 molecule of ATP (via substrate-level phosphorylation) Taking into account the transitional phase and the citric acid cycle, each pyruvic acid molecule yields - 3 CO~2~ molecules - 5 molecules of reduced coenzymes (4 NADH+H^+^ and 1 FADH~2~) - 1 molecules of ATP (via substrate-level phosphorylation) - Each glucose molecule yields 2 pyruvic acid molecules ### **4.4.9 Electron transport chain** Occurs in the inner mitochondrial membrane Final catabolic reactions Because the reduced coenzymes produced in the citric acid cycle are the substrates for the electron transport chain, the 2 pathways are coupled and both are aerobic In the electron transport chain, the hydrogens removed during oxidation of food fuels are combined with O~2~ to form water and the energy released during those reactions is used to attach phosphate groups to ADP, to form ATP Most components of the electron transport chain are proteins that bind metal atoms, called cofactors Most of these cofactors are brightly coloured iron-containing pigments called cytochromes Neighbouring carriers are clustered together to form respiratory enzyme complexes th

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