HUMAN STRUCTURE AND FUNCTION HUMB1000 Unit Coordinator: Flavia di Pietro Tutor: Giuseppe and Andrea Wednesday 10am-12pm 2 Table of Contents COMPENDIUM ONE: What is life? .................................... 3 Lecture Notes ..................................................... 3 Compendium 1 Lecture 1 of 3 – What is Life? P1: The human body ............................................................... 3 Compendium 2 Lecture 2 of 3 – What is life? P2: Anatomical terminology ............................................. 3 Compendium 3 Lecture 3 of 3 – What is life? P3 Serous membranes ..................................................... 4 Compendium 1 ................................................... 4 COMPENDIUM TWO: How do cells do what they do? ....... 4 Lecture Notes ..................................................... 4 Compendium 2 Lecture 1 of 4 – How do cells do what they do? P1 Cells and organelles ................................ 4 Compendium 2 Lecture 2 of 4 – how do cells do what they do? P2 Epithelial tissue....................................... 5 Compendium 2 Lecture 3 of 4 – how do cells do what they do? P3 Connective tissue ................................... 5 Compendium 2 Lecture 4 of 4 – how do cells do what they do? P4 Muscle and nervous tissue ..................... 6 Compendium 2 ................................................... 6 COMPENDIUM THREE: Are you what you eat? ................. 6 Lecture Notes ..................................................... 6 Compendium 3 Lecture 1 of 2 – Are you what you eat? P1 Anatomy of the digestive system .................. 6 Compendium 3 Lecture 2 of 2 – Are you what you eat? P2 Nutrition and macromolecules ...................... 8 COMPENDIUM FOUR: Why do we breathe? ....................10 Compendium Lecture 1 of 4 – Why do we breathe? P1 Anatomy of the respiratory system .......................... 10 Compendium 4 lecture 2 of 4 – Why do we breathe? P2 Gas exchange ....................................................... 12 Compendium 4 Lecture 3 of 4 – Why do we breathe? P3 Ventilation ........................................................... 12 Compendium 4 lecture 4 of 4 -Why do we breathe? P2 Respiratory volumes and capacitates .................. 13 Compendium 5 – Lecture 4 of 4 How do we fuel our body? P4 Kreb’s Cycle & Oxidative Phosphorylation 16 COMPENDIUM SIX: How do things get around the body? 17 Lecture ............................................................. 17 Compendium 6 – Lecture 1 of 2 How do things get around the body? P1 Cardiovascular system – the heart ......................................................................... 17 Compendium 6 – Lecture 2 of 2 How do things get around the body? P2 Cardiovascular system – blood, blood vessels and capillaries exchange .................... 18 COMPENDIUM SEVEN: How do we get rid of toxic waste? ....................................................................................... 19 Lecture ............................................................. 19 Compendium 7 – Lecture 1 of 2 How do we get rid of toxic wastes? P1: the anatomy of the renal system . 19 Compendium 7 – Lecture 2 of 2 How do we get rid of toxic wastes? P2: the physiology of the renal system .................................................................................. 20 COMPENDIUM EIGHT: How do we control ourselves ...... 21 Lecture Notes ................................................... 21 Compendium 8 – Lecture 1 of 4 How do we control ourselves? P1: Introduction to the nervous system . 21 Compendium 8 – Lecture 2 of 4 How do we control ourselves? P2: Cells of the nervous system .............. 22 Compendium 8 – Lecture 3 of 4 How do we control ourselves? P3: Electrical signals and action potentials .................................................................................. 23 Compendium 8 – Lecture 4 of 4 How do we control of ourselves? P4: Spinal reflex arcs ............................... 23 COMPENDIUM NINE: HOW DOES IT ALL WORK?............. 24 Lecture Notes ................................................... 24 Compendium 9 - Lecture 1 of 4 How does it all work? P1: The spinal cord and spinal nerves ...................... 24 Compendium 9 – Lecture 2 of 4 How does it all Work? P2: The brain and cranial nerves .............................. 24 Compendium 9 – Lecture 3 of 4 How does it all work? P3: The autonomic nervous system ......................... 25 Compendium 9 – Lecture 4 of 4 – The endocrine system....................................................................... 26 COMPENDIUM FIVE: How do we fuel our body? ..............14 COMPENDIUM TEN: HOW DO WE PROTECT OURSELVES?29 Lecture ............................................................. 14 LECTURE NOTES ................................................ 29 Compendium 5 – Lecture 1 of 4 How do we fuel our body? P1 Transport across the cell membrane ........ 14 Compendium 5 - Lecture 2 of 4 How do we fuel our body? P2 The movement of water (osmosis) ........... 15 Compendium 5 – Lecture 3 of 4 How do we fuel our body? P3 Glycolysis .................................................. 15 Compendium 10 – How do we protect ourselves? – Lecture 1 of 2 – P1: Immunity .................................. 29 Compendium 10 – How do we protect ourselves? – Lecture 2 of 2 – P2: Lymphatics ................................ 32 3 COMPENDIUM ONE: What is life? Lecture Notes Compendium 1 Lecture 1 of 3 – What is Life? P1: The human body Anatomy Anatomy: the branch of science that deals with structure of organisms and their parts Gross anatomy (microscopic): structures examined without the aid of a microscope o Systematic: the study by system o Regional: study by region Surface of anatomy (macroscopic): the study of the external form of the body Microscopic anatomy: study of structures under microscope o Cytology: cells o Histology: tissues Developmental anatomy: study of structural change that occurs in the body’s life span Physiology Physiology: the branch of science that deals with the normal function of living organisms (humans) and their parts Levels of physiology: o Molecular o Cellular o Systemic – neurophysiology, cardiovascular etc. Structural and functional organisation of the human body Chemical level: how atoms interact and bind to form molecules (e.g. DNA) Cellular level: molecules interact and bid to form organelles (e.g. nucleus) Tissue levels: numerous similar cells and tissue round them to form a tissue type Organ levels: 2 or more tissue types together form an organ (e.g. bladder) Organ system level: a group of organs performing a common function (e.g. urinary system – kidneys, bladder etc.) Organism level: anything living thing considered as a whole (e.g. child) Characteristics of life 1. Organisation – specific interactions between organism – perform functions 2. Metabolism – ability to use energy 3. Responsiveness – adjust changes in the environment 4. Growth – overall enlargement of the organism 5. Reproduction – formation of new cells and new organism Homeostasis Homeostasis: maintenance of relatively constant environment o Fluctuate around a set point o Slightly below / above the set point = normal range o Most occur by negative feedback mechanism Compendium 2 Lecture 2 of 3 – What is life? P2: Anatomical terminology What is anatomical position? The standard reference to describe body parts o Erect person with: Face directed forward Upper limbs hanging by side; palm forward Lower limbs straight Supine: laying down face up Prone: laying down face down Directional terms Superior: above/towards the head e.g. chin is superior to the navel Inferior: towards the feet (caudal) Anterior: towards the front e.g. breast is anterior to spine (ventral) Posterior: behind (dorsal) Distal: “far from” Medial: towards the midline Lateral: away from the midline Superficial: close to surface Deep: towards the interior of the body Body planes Sagittal: separates left and right part – median plane is mid-sagittal Frontal: (coronal) – separates anterior and posterior parts Transverse (horizontal): separates superior and inferior portion Oblique: doesn’t run parallel Body cavities Closed to the outside and provide protection Contain our internal organs, or viscera o Thoracic cavity – most superior (heart, trachea and esophagus) o Abdominal cavity – inferior to diaphragm (stomach, pancreas etc.) o Pelvic cavity – bladder, urethra etc) no define boundaries AKA ‘abdominopelvic cavity’ Subdivision of abdomen Quadrants (4) Right upper quadrant Left upper quadrant Right lower quadrant Left lower quadrant Regions (9) Right hypochondriac region (liver, Gallbladder, right kidney, small intestine) Right lumbar region (Gallbladder, liver, right colon) Right iliac region (appendix, cecum) Epigastric region (stomach, liver, pancreas, duodenum, spleen, adrenal glands) Umbilical region (Umbilicus – navel, parts of the small intestine, duodenum Hypogastric region (urinary bladder, sigmoid colon, female reproductive organs) Left hypochondriac region (Spleen, colon, left kidney, pancreas) Left lumbar region (Descending colon, left kidney) Left iliac region (Descending colon, sigmoid colon) 4 Compendium 3 Lecture 3 of 3 – What is life? P3 Serous membranes Serous membranes Aka serosa Double-layered membranes o Parietal serous membranes: lines the body cavity o Visceral serous membranes: lines the internal organs Membranes separated by thin film of serous fluid – produce by membranes which give friction reduction Pericardial cavity – parietal and visceral pericardium with pericardial fluid Pleural cavity – parietal and visceral pleura with pleural fluid Peritoneal cavity – parietal and visceral peritoneum with peritoneal fluid o Peri: around cardi: heart the heart cavity o Houses lungs and diaphragm o Peritoneum – abdominal cavity Compendium 1 o Cytoplasmic inclusion: aggregates of chemicals The Nucleus & the cytoplasmic organelles o Small, specialized structures o Most have membranes COMPENDIUM TWO: How do cells do what they do? Lecture Notes Compendium 2 Lecture 1 of 4 – How do cells do what they do? P1 Cells and organelles The cell Structural and functional unit of all living things, including humans Plasma membrane, cytoplasm containing organelles, nucleus Functional characteristics of a cell Cell metabolism and energy use Synthesis of molecules (e.g. RNA) Communication Reproductive and inheritance Plasma membrane Aka: cell membrane, sarcolemma, plasmalemma Function: o Encloses and supports cellular content o Controls what goes in and out o Regulates intra vs. extracellular material o Inter-cellular communication o Production of a charge different across the membrane Structure: o Lipid bilayer o Carbohydrates o Proteins o Fluid mosaic model o Glycocalyx (outer surface of cell membrane) o Glycoproteins (carbohydrates & proteins) o Glycolipids Cytoplasm Cellular fluid material outside nucleus but within plasma membranes Cytosol Fluid portion of cytoplasm (ions and proteins in water) o Cytoskeleton: supports cells and its organelles Nucleus o Control centre of the cell o DNA o Nuclear envelope: bilayer membrane o Nucleoplasm o Nucleolus – produces ribosomes Chromosome structure o Chromatid: DNA complexed with proteins (histones) Ribosomes o Sites of protein synthesis Nucleolus, nucleus and cytoplasm o Structure: 2 subunits (large and small) Endoplasmic Reticulum o Fattened, interconnecting sacs and tubules o Rough ER – with ribosomes (synthesis and modification of proteins) o Smooth ER – without ribosomes (lipid, steroid and carbs synthesis, detoxification of harmful substances & glycogen glucose) Golgi Apparatus o Structure: flattened membranal sacs with cisternae o Function: modifies, packages & distributes proteins and lipids that are made in the rough ER Lysosomes o Formed by the Golgi o Contains enzyme o “demolition crew” o Digestion of molecules no longer needed by the cell Mitochondria o Structure: outer membrane, intermembrane space and inner membrane matrix o Changes shape continually o Has own genetic material o Function: “power plants of the cell” – ATP o Increases in number when cell energy requirement increases Centrioles o Barrel shaped o Wall composed of microtubules o Cell division Cilia o Whip-like projection o Move substances across the surface of cells Flagella o Longer than cilia – found on humans (sperms cells only) Microvilli o 1/10 to 1/20 the size of the cilia: increases surface area Compendium 2 Lecture 2 of 4 – how do cells do what they do? P2 Epithelial tissue 4 primary tissue types Epithelium, connective, muscle and nervous Histology Study of tissue: thin slices of tissue (stain added) Preparation of tissue 1. Removal of tissue via biopsy or autopsy 2. Fixation of tissue 3. Embedding of tissue: e.g. surrounded by wax 4. Slicing & mounting tissue on slide 5. Staining and viewing using a microscope Haematoxylin and Eosin Abbreviated H&E Nuclei are stained purple (from H) others including cytoplasm are stained pink (eosin) Different histological images Frontal / coronal Transverse / horizontal Sagittal / median Primary tissues Epithelial tissues: covers Connective tissue: supports Muscle tissue: movement Nervous tissue: controls Epithelial tissue Covers and protects Types: o Covering and lining o Glandular Distinct cell surfaces o Free surface o Lateral surface o Basal surface Avascular but innervated – nerve supply (avascular means that it does not have a blood supply) Ability to regenerate Cell layers Simple – single layer Stratified – more than 1 layer Pseudostratified – looks like 1 + layer but really is 1 layer Cell shape Squamous: “paving stones” in surface view Cuboidal: cube with large round nucleus Columnar: tall cells with ovoid nuclei towards base Transitional: can change shape from columnar to cuboidal Examples of cell shapes & layers Simple squamous epithelium o Diffusion, filtration and some secretion o Alveoli of lungs, kidney glomeruli, serous membrane of pleura Simple cuboidal epithelium o Absorption, secretion and movement o Intestines, stomach, fallopian tubes and lungs Transitional epithelium o Accommodates changes in fluid volume of the organs 5 Urinary bladder, ureter and upper part of urethra Stratified squamous epithelium o Protection against abrasion and loss of water Keratinized (water proofing substance): sole of feet, palm of hands, skin Non-keratinized: mouth, oesophagus, anus and vagina Stratified cuboidal epithelium o Absorption, secretion and protection o Duct of sweat glands, salivary glands and developing ovum Stratified columnar epithelium o Secretion and protection o Ducts of mammary glands, larynx and urethra Pseudo-stratified columnar epithelium o Secretion and movement o Pharynx, trachea, male’s sperm carrying ducts Exceptions to the rule (combinations that do not exist): o Simple transitional o Stratified transitional o Pseudostratified squamous o Pseudostratified cuboidal o Pseudostratified transitional Compendium 2 Lecture 3 of 4 – how do cells do what they do? P3 Connective tissue Connective tissue Most abundant and widely distributed Very diverse Functions: o Connects and binds together, supports, strengthens, protects, insulates, compartmentalise, transports, provides energy Location o All organs and parts but amount vary Composition o Cells (produce extracellular matrix – ECM), ground substance (ECM), fibres (ECM) Cells of connective tissue Adipose cells – energy source and cushioning Fibroblast Mast cells White blood cells Macrophages Ground substance Fills the spaces between the cells of connective tissue Fibres – collagen, elastic and reticular fibres (supporting network) Classes of Connective tissue 1. CONNECTIVE TISSUE PROPER Dense: Regular, irregular, elastic Loose: Areolar, adipose and reticular Areolar o Loose packaging, support, and binding other tissues o Throughout body Adipose o Nutrient-storing ability, shock absorption, insulation o Fat under skin kidney, breast, abs and hips o Reticular o Framework to support free blood cells (white blood cells, mast cells etc) o Lymph nodes, spleen, bone marrow Regular o Attachment: T bundles highly organise) tendons and ligaments Irregular o Strength and stretch in 3D directions o Skin’s dermis, coverings surrounding bones, etc. Elastic o Recoil & strength o Aorta, arteries wall, spinal vertebrate 2. CARTILAGE Rigid matrix Avascular and not innervated Protection, flexibility, rigidity and withstand pressure Hyaline – rib cage, trachea, bones and nose surfaces Fibrocartilage – intervertebral discs and pubic symphysis Elastic – ear and epiglottis 3. BONE Support and protect body structures Cell and matrix Osteocytes (bone cells) 2 types: o Spongy – ends of long bone, sternum, vertebrae and pelvis o Compact – shaft of long bone, makes up outer portions of all cells 4. BLOOD Atypical connective tissue – doesn’t provide support or “connect” Mostly red blood cells and white blood cells and platelets Transports nutrients, wastes, respiratory gases around the body Compendium 2 Lecture 4 of 4 – how do cells do what they do? P4 Muscle and nervous tissue Muscle tissue Highly cellular, well vascularised and responsible for tension and body movement Types of muscle Skeletal muscle o Attached to skeleton o Heat regulation, metabolism, posture and breathing o Regenerate after injury o Hypertrophy in response to exercise or get smaller o Muscle cells: muscle fibres / myofibres o Striated muscle o Multinucleated o Peripheral nuclei o Mostly voluntary control but involuntary may occur (e.g. twitching) Cardiac muscle o Involuntary o Only found in walls of heart o Generates pressure which moves blood 6 Change the rate and force of heart contractions to meet metabolic needs o 3 layers Epicardium – (visceral pericardium): serous membrane underlying fatty connective tissue Myocardium – middle muscle layer. Majority cardiomyocytes Endocardium – inner layer. Endothelial lining o Striated muscle with intercalated disks o Cardiac muscle cells: cardiomyocytes o Cells are branched with central nuclei o Lots of mitochondria o Involuntary and cannot regenerate Smooth muscle o Mainly in walls of hollow organs and tubes (e.g. esophagus, blood vessels) o Regulates the size of organ/tube, moves contents along o Tunica media – smooth muscle cells arranged circularly around the blood vessel o Vasoconstriction o Vasodilation o No striations o Single nucleus per muscle cell o Involuntary control o Can regenerate Nervous tissue Nervous system: brain – spinal cord – nerves Main component of nervous system o Neuron (nerve cells) o Supporting cells (neuroglia) – nourish, protect and insulate neurons Neurons have the ability to produce and conduct action potential Neurons o Cell body (soma) contains nucleus o Dendrites receive information o Axon conducting or transmitting information Compendium 2 o COMPENDIUM THREE: Are you what you eat? Lecture Notes Compendium 3 Lecture 1 of 2 – Are you what you eat? P1 Anatomy of the digestive system Anatomy Digestive tract – also called alimentary tract – continuous tube. Accessory organs – primarily glands, secrete fluids into tract o Oral cavity (mouth) with salivary glands o Pharynx (throat) o Esophagus o Stomach o Small intestine (duodenum, ileum, jejunum) with liver, gallbladder and pancreas as accessory organs o Large intestines include Cecil, colon, rectum and anal canal o Anus Functions of the digestive system Ingestion: introduction of food into stomach (via mouth) Mastication: chewing. Chemical digestion requires large surface area so breaking down large particles mechanically facilitates chemical digestion Secretive: lubricate, liquefy, digest (e.g. Mucus: secreted along entire digestive tract, lubricates food, coats and protects lining) Digestion: Mechanical and chemical digestion of food into nutrients Absorption: Movement of nutrients out of digestive tract into cells Elimination: waste products removed from body; faeces. Defecation Histology of the digestive tract One large tube from mouth to anus plus the accessory organs 1. Mucosa: innermost layer, secretes mucus 2. Submucosa: connective tissue layer, contains blood vessels, nerves etc. 3. Muscularis: 2/3 muscle layers, movement & secretion 4. Serosa / adventitia: outermost layer, connective tissue, stability Peristalsis & segmentation Process by which food moves through the gut. Waves of smooth muscle relaxations and contractions Peritoneum The walls and organs of the abdominal cavity are line with serous membranes Visceral peritoneum: covers organs Parietal peritoneum: covers interior surface of body wall Mesenteries: peritoneum (epithelial tissue) which connects organs together and small intestine to back body wall Routes by which vessels and nerves pass from body wall to organs Greater omentum: connects stomach to transverse colon Lesser omentum: connects stomach to liver and diaphragm Oral cavity Digestion begins in the oral cavity Hard palate: hard bone, anterior Soft palate: soft muscle, posterior Tongue – taste buds Teeth – mechanical digestion of food Masticate (chew) food and turn it into a bolus Teeth Two sets of teeth: o primary, milk teeth (childhood) o Permanent or secondary adult (32) o Types: (8) Incisors - cutting, (4)canines – tearing food, (8)premolars- grinding and (12) molars – grinding Oral cavity – salivary glands Salivary glands – produce and secrete saliva into the oral cavity. (3 main – Parotid, Sublingual and submandibular glands) Saliva – protects oral cavity, moistens, lubricates and digests food 7 Amylase – enzyme found in saliva that breaks down carbohydrates into smaller sugars Lysozyme – antibacterial enzyme Pharynx & Esophagus Pharynx: throat – connects oral cavity to the esophagus. Uvula (soft palate) prevent food/drink from entering the nasopharynx o Nasopharynx (behind nose) o Oropharynx (behind oral cavity) o Laryngopharynx (behind the larynx) Esophagus: tube that connects pharynx to stomach. 25cm long, lies posteriorly to the trachea o Epiglottis prevents food/drink from entering trachea o ends as gastro-esophageal sphincter Swallowing Voluntary phase: tongue pushes bolus to the back of the oral cavity towards pharynx (oropharynx) Pharyngeal phase: soft palate (Uvula) closes off the nasopharynx. Bolus touches receptors on oropharynx and swallowing reflex moves bolus down pharynx and into esophagus. Epiglottis covers trachea Esophageal phase: bolus is moved down esophagus towards stomach by peristalsis Stomach Located in abdomen ‘holding point’ for food Food comes from the esophagus and the stomach mixes it (churns) into chyme (thick liquid) Produces mucus, hydrochloric acid, protein digesting enzymes (pepsin) Contains a thick mucus layer that lubricates and protects epithelial cells on stomach wall from acid pH 2-3 Openings / sphincters o Gastroesophageal (cardiac): to esophagus o Pyloric: to duodenum Parts o Cardiac o Fundus o Body o Pyloric: antrum and canal Layers o Visceral peritoneum or serosa o Muscularis: three layers Outer longitudinal Middle circular Inner oblique o Submucosa o Mucosa – simple columnar epithelium Rugae: folds in stomach wall that allows stomach to stretch after eating Movements of the stomach 3 muscular layers enable churning of food. Make chyme Combination of mixing waves (80%) and peristaltic waves (20%) Both esophageal and pyloric sphincters are closed Water takes about 1-2 hours to exit (via kidneys and urethra) after digestion) Stomach empties every 4hrs (6-8 after a fatty meal) Small intestine Very long – 6m small diameter Large surface area for efficient absorption of nutrients Connected to posterior body wall by mesenteries Divisions o Duodenum (first 25cm) beyond the pyloric sphincter Curves around the pancreases. Chyme mixes with various digestive enzymes. Mucous from Brunner’s glands neutralize acidic chyme. Located in epigastric and umbilical regions o Jejunum 2.5 m Large amount of nutrient absorption happens. Extensive villi. Located in left lumbar and umbilical region o Ileum 3.5 m Adaptations increase surface area of small intestine 600 fold o Plicae circulares: circular folds in the wall of the small intestine o Villi: finger like folds of epithelium. Contains capillaries and lacteals o Microvilli: small extensions on epithelial cell surface o Lipid – lacteals – lymph. Carbs and proteins – capillaries – blood Liver and gall bladder Liver – makes bile (100ml per day) o Filters blood nutrient rich coming from the intestines (portal system) o Stores glucose as glycogen and lipids for energy o Detoxification of drugs and toxins Gall bladder – muscular sac, stores and concentrates bile. Bile enters the duodenum via the common bile duct, emulsifies fats/lipids Pancreas Produces digestive enzymes. Produces insulin and glucagon for blood sugar homeostasis Lipase – breakdown lipids Pancreatic amylase – breakdown carbohydrates Trypsin – breakdown proteins Large intestine Absorption of water and NaCl Extends from ileocecal junction to anus Consists of cecum, colon (ascending, transverse, descending, sigmoid), rectum, anal canal Bacteria / microtubes synthesise vitamin B & K 18-24hr transit time; chyme faeces 1500mL chyme enter the cecum, 90% reabsorbed yielding 80-150 ml of faeces Defecation reflex – triggered by rectal distention Goblet cells – mucous The digestive process Digestion: mouth, stomach, small intestine. Breakdown of food molecules for absorption into circulation Mechanical: breaks large food particles to smaller ones. Chemical: breaking of covalent bonds by digestive enzymes Absorption: nutrients from the small intestine, water from the large intestine. Molecules are moved out of digestive tract and into circulation for distribution throughout body (via liver) 8 Compendium 3 Lecture 2 of 2 – Are you what you eat? P2 Nutrition and macromolecules Enzymes A protein catalyst that increases the rate at which a chemical reaction proceeds, without the enzyme being permanently changed Highly specific – active site on an enzyme can only bind to specific reactant Many different enzymes needed in the body for different chemical reactions Often named by adding ‘ASE’ as a suffix to their reactant Nutrients Chemical taken into body to o Produce energy o Provide building blocks to build other molecules 6 classes: carbohydrates, proteins, lipids, vitamins, minerals and water Carbohydrates, proteins and lipids are major organic nutrients (organic = contains carbon Need large amounts of vitamins and minerals o Taken into body without being digested Essential nutrients – are chemicals that must be taken into the body because we can’t make them ourselves o Includes some amino acids/fatty acids/carbs, water, most vitamins and minerals Six major classes of nutrients: o Carbohydrates – (sugars from plants and vegetables) o Lipids – animal products and oils o Proteins – meat, fish, poultry o Vitamins – organic molecules – plants and animals o Minerals – in organic (iron) o Water Recommended amounts o Carbohydrates (45-65%) o Lipids (20-35%) o Proteins (10-35%) o Consider personal needs o Consider source Carbohydrates Most come from plants (exception lactose from milk) Contains C, H and O =CHO Sugars e.g. glucose Don’t need to know the molecular structure Very large molecules – made up of many smaller building blocks Mono & disaccharides Monosaccharides o glucose (blood sugar) o fructose (fruit sugar) o galactose (milk sugar) Disaccharides o Sucrose (table sugar) glucose + fructose o Lactose (milk) glucose + galactose o Maltose – glucose + glucose Polysaccharides Long chain of monosaccharides 3000+ Glycogen o Animal polysaccharide o Glucose molecules stored in humans in liver and muscle Starch and cellulose o Plant polysaccharides o Humans break down starch Energy o Human can’t break down cellulose – dietary fibre Carbohydrate absorption Polysaccharide chain e.g. glycogen. Digested by saliva in oral cavity & pancreatic amylase in duodenum Disaccharide chain. E.g. sucrose digested by sucrase in the intestine Monosaccharide chain e.g. glucose absorbed into blood via villi / microvilli in intestine. Transported to liver via hepatic portal vein Carbohydrates uses in the body Glucose produce ATP energy Energy – warmth, movement, brain activity, muscle contraction etc. Excess glucose glycogen and stored in muscle and liver cells Excess beyond storage is converted to fat Sugars also become part of DNA, RNA and ATP glycoproteins, glycolipids (essential for cell membranes) Proteins Contain C, H, O, N and sometimes sulfur Amino acids are the basic building blocks Each amino acid has an amine group (NH2) and carboxyl group and a hydrogen and a side group Side group is what is different between amino acids Amino acids link together to form peptides and proteins Amino acids are not stored in the body Essential amino acids, can’t be produced by body so must be obtained from the diet Non-essential amino acids are still required by our body, but these we can synthesise from essential amino acids Functions of proteins: regulate body function e.g. o Globular proteins o Structural – muscle proteins o Cell membrane transport o Enzymes o Hormones o Antibodies Complete protein – food that contains enough of all 9 essentials amino acids e.g. meat, fish, poultry, milk, cheese, eggs Incomplete protein e.g. leafy green vegetables, grains, legumes Protein absorption Protein (long chain of amino acids) digested by pepsin in stomach Polypeptides digested by trypsin in duodenum Lipids Composed mostly of carbon, hydrogen, oxygen and sometimes nitrogen and phosphorus o Lower ratio of O to C than carbs o Lipids / fats ingested are broken down to release energy 9 Triglycerides make up 95% of fats in body Glycerol and fatty acids Fatty acids – can be different lengths Saturation: how many H atoms on each chain Saturated – animals fats e.g. beef, pork, milk Unsaturated – plant sources – contains one or more double bonds in the carbon chain so there is less H atoms. More relaxed structure (liquid at RT) Trans fats – unsaturated fats that are artificially altered Lipid absorption Lipid (triglycerides) digestion begins in the duodenum Bile from the gall bladder emulsifies lipids Lipase from the pancreas causes further breakdown Short chain fatty acids (monoglycerides) are absorbed Uses of lipids in the body Cholesterol: found in liver and egg yolks or manufactured by body. Component of plasma membranes ,modified to form bile salts Phospholipids: major components of plasma membranes, myelin sheath, part of bile Eicosanoids: derived from fatty acids. Involved in inflammation, blood clotting, tissue repair, smooth muscle contraction Water absorption Approximately 9L of water enters the digestive tract each day 99% of water entering the intestine is absorbed Water can move across the intestinal wall in either direction if required Ions: sodium, potassium, calcium, magnesium, phosphate are actively transported Vitamins Organic molecules in very small quantities in food Essential for normal metabolism and can’t be produced by the body No one food provides all necessary vitamins, some are produced by intestinal bacterial Vitamins can be fat soluble, or water soluble – consider route of admission Too much o Vt C- stomach inflammation; diarrhea o Vit A – toxic during pregnancy o Vit D – alter calcium metabolism Vitamin deficiencies o Vit D – rickets o Vit C – scurvy o Vit B beriberi Minerals Inorganic nutrients Major minerals: calcium, magnesium, sodium and potassium Trace minerals: selenium, zinc, copper Components of co-enzymes, some vitamins, haemoglobin, organic molecules Functions o Membrane potential and action potentials o o Add mechanical strength to bones and teeth Available from both plant and animals based foods Mineral deficiencies o Iron – anaemia o Potassium – muscle weakness, abnormal heart function o Iodine – goitre COMPENDIUM FOUR: Why do we breathe? Compendium Lecture 1 of 4 – Why do we breathe? P1 Anatomy of the respiratory system Functions of the respiratory system Respiration o Ventilation – movement of air in and out of lungs o External respiration – gaseous exchange between lungs and blood o Respiratory gas transport – through blood to the whole body o Internal respiration (tissue level) – gaseous exchange between blood and tissues Blood pH regulation o How acidic or alkaline a medium is (0 is highly acidic, 7 neutral, 14 highly alkaline) o Blood maintains a specific pH between 7.35 and 7.45 o If there is an increase of CO2 in the blood it’s going to make the blood more acidic CO2 needs to be removed Sound production o As air passes through the vocal cords in the larynx of the tract, the sound can be modified in pitch – on the vocal folds Olfaction o Specialized cells in the nasal cavity which are sensitive to smell Protection o Protects us from bacteria and spores and other harmful substances in the air Organisation of the respiratory system Nares – nostrils Nasal cavity Pharynx Larynx Trachea Bronchi – primary, secondary, tertiary Bronchioles – terminal, respiratory Alveolar duct Alveoli Divisions of respiratory system Structural classification o Upper respiratory tract: nose, nasal cavity, pharynx o Lower respiratory tract: larynx, trachea, bronchi, bronchioles and alveoli of the lungs Functional classification o Conducting zone (no gaseous exchange occurring): from nose to terminal bronchioles o Respiratory zone (gaseous exchange takes place): respiratory bronchioles, alveolar duct and alveoli Nares and nasal cavity External nose Vestibules : area between nares 10 Nasal cavity o Nares to choana o Nares o Vestibule o Septum o Floor of nasal cavity Hard palate soft palate, uvula o Conchae and meatuses Superior, middle and inferior conchae (ridges) Superior, middle and inferior meatuses (depressions) Creates turbulence in air o Sinuses Paranasal sinuses and tear ducts Empty areas in the bones which makes your skull lighter and causes resonances as you speak Main function: to purify the air, the humidify the air, and to bring the air in the body at a normal temperature Functions of nasal cavity Passageway for air Hair – filters coarse particles from the inspired air Mucus – traps dust, bacteria and other debris from the inspired air, humidifies air Cilia – create gentle current by beating moving contaminated mucus towards throat to be swallowed Lysozyme – kills bacteria Rich capillary network – maintain temperature of inhaled and exhaled air Conchae and meatuses – increase mucosal surface, create turbulence facilitating above functions Olfaction – olfactory epithelium containing olfactory receptors Sinuses, nasal cavity – resonating chambers, lighten skull Pharynx Tube like structure from Common passage for food and air Divided into 3 regions o Nasopharynx Posterior to nasal cavity Choana to uvula Eustachian tube opening Pharyngeal tonsils o Oropharynx Posterior to oral cavity Uvula to epiglottis/hyoid bone Common passage for air and food Palatine and lingual tonsils o Laryngopharynx Posterior to epiglottis Epiglottis/hyoid bone to larynx/esophagus Larynx Voice box Passageway of air Superior: pharynx Inferior: trachea 9 cartilages o 3 unpaired Thyroid (Adam’s apple) Cricoid Epiglottis o 3 are paired (6) Arytenoid Corniculate Cuneiform o Ligaments extend from arytenoids to thyroid cartilage True vocal cords of vocal folds Vestibular folds or false vocal folds Opening between is glottis Function of larynx Maintains an open passageway for air movement (cartilages) Directs food into the oesophagus away from the respiratory tract Sound production via vocal folds Traps debris from entering lungs Trachea From larynx till carina (special cartilage) – really sensitive to any debris or dust Tough but flexible membranous tube, approximately 10-12 cm long and 2 cm in diameter Anterior oesophagus, passes through the mediastinum Cartilages dense regular CT and smooth muscle 15-20 C-shaped hyaline cartilage rings with smooth muscle in between Smooth muscle: it allows flexibility between esophagus and trachea for peristalsis Presence of trachealis muscle posteriorly Divides into two main bronchi at carina Mucosa of carina is very sensitive, cough reflex Function of trachea Cartilage keeps the airway open Trachealis muscle facilitates ease of peristaltic movements in esophagus Contraction of trachealis muscle causes expired air to rush out with greater force (puffing) Cleansing of air breathed in Sensitive nature of carina triggers coughing to expel foreign particles Tracheobronchial tree Primary (main) bronchi Secondary (lobar) bronchi – 2 in left and 3 in right lung Tertiary (segmental) bronchi – 10 on each side Bronchioles (<1 mm diameter) Terminal bronchioles (<0.5 mm in diameter Progressive changes in tracheobronchial tree Decrease in passageway diameter Decrease in cartilage – rings replaced by irregular cartilage plates and finally by elastic fibres in bronchioles Increase in smooth muscle – from in between cartilage rings to complete layer of circular smooth muscle (bronchioles) Changes in epithelium – from pseudostratified ciliated columnar to simple ciliated cuboidal epithelium Respiratory zone The difference between respiratory bronchiole and the terminal bronchiole is that you have occasional alveoli 11 on the respiratory bronchial – which leads to alveoli ducts which opens into alveoli sac Respiratory bronchioles o Very few alveoli Alveolar ducts o Have more alveoli, end in alveolar sacs Alveolar sac o Chambers connected to two or more alveoli Alveoli o Small bag like structures, richly supplied by blood capillaries, contains elastic fibres, 300-500 million alveoli, large surface area for gas exchange Lungs Located in the thoracic cavity, one on either side of the mediastinum Cone shaped, base on diaphragm, apex Costal, medial and diaphragmic surfaces Cardiac notch medially on left lung Right lung has three lobes (superior, middle and inferior) separated by two fissures (horizontal and oblique) Left lung has 2 lobes (superior and inferior), separated by one (oblique) fissure Hilum – indentation on medal surface, entry/exit point for blood vessels, nerves, lymphatic vessels and bronchi Lungs in segments Bronchopulmonary segments – 10 in right and 8/9 in left lung Lobules Lobules are separated by partially by connective tissues 25 orders / levels of branching from trachea to alveoli duct Primary bronchi o (main) bronchi, supply each lung Secondary bronchi o (lobar), bronchi, supply the lobes Tertiary bronchi o (segmental), bronchi, supply bronchopulmonary segments Pleura/Pleural membrane Double-layered serous membrane Parietal pleura – superficial, lines inner wall of thoracic cavity (attached to rib cage) Visceral pleura – deep, covers the lungs (attached to lung) In between the 2 pleura is the pleural cavity In the pleural cavity there is pleural fluid, which is lubricating fluid secreted by pleura, fills pleural cavity Reduces friction cases two membranes to adhere, protects and reduces impact of force Respiratory system epithelium Epithelium changes along respiratory track to accommodate the specific function of the structure o Vestibule – keratinised stratified squamous epithelium o Nasal cavity – pseudostratified ciliated columnar epithelium o Nasopharynx – pseudo stratified ciliated columnar epithelium o Oropharynx – stratified squamous epithelium o o Laryngopharynx – stratified squamous epithelium Trachea – pseudostratified ciliated columnar epithelium (with goblet cells) Between trachea and alveoli, epithelium gradually changes from PSCC (bronchi) to ciliated simple columnar (larger bronchioles) to ciliated simple cuboidal (terminal bronchioles) to simple cuboidal (respiratory bronchioles) to simple squamous (alveoli) o Alveoli – simple squamous epithelium Compendium 4 lecture 2 of 4 – Why do we breathe? P2 Gas exchange Alveolus (alveoli, pl) Alveoli – cup shaped pouches, 300 - 500 million Alveolar sac – contains 2 or more alveoli sharing a common opening Lined by simple squamous epithelium and supported by thin elastic basement membrane Two types of epithelial cells: o Type 1 pneumocytes – simple squamous epithelial cells, site of gas exchange o Type 2 pneumocytes – simple cuboidal cells, secrete alveolar fluid and surfactant Dust cells – alveoli macrophages, remove fine dust and debris from alveolar spaces Respiratory membrane Very thin, 0.5 micrometres Alveoli increase surface area for gas exchange (70m^2) Gas exchange through simple diffusion Consists of 3 layers o Alveolar epithelium (type 1 and type 2 pneumocytes) o Fused alveolar and capillary basement membrane o Capillary endothelium Red blood cells, macrophages Alveolar fluid lining the inside of the alveolus – mixed the surfactant which doesn’t allow the alveolus to collapse Characteristics of a respiratory membrane Thickness of the respiratory membrane o Thinner membrane increases the rate of movement of gas Surface area o Higher surface area the more gas exchange Diffusion coefficient o Diffusion coefficient – how easily a gas can diffuse in and out of a liquid or tissue o Relative number (02 is 4, whereas Co2 has 20) Partial pressure o Pressure exerted by a particular gas would be its partial pressure o The gas moves from the side with the higher Pp to the side with the lower Pp (partial pressure) Moist membranes o Gases dissolve in the fluid helping them to diffuse o Alveolar fluid, plasma Gas transport and exchange Gases does not move as gas bubbles O2 o Travels in blood Red blood cells (haemoglobin) – 98.5% 12 Dissolved in blood plasma (1.5%) o Exchange in body From alveoli to blood- external respiration From blood to tissues – internal respiration CO2 o Travels in blood HCO3 dissolved in plasma (70%) CO2 dissolved in plasma (7%) Bound to haemoglobin (23%) o Exchange in body From blood to alveoli – external respiration From tissue to blood – internal respiration 4 stages of respiration 1. Pulmonary ventilation 2. External respiration 3. Internal respiration 4. ??? Pulmonary ventilation Breathing in and out/inhalation and exhalation Prevents build-up of CO2 in blood, supply O2 to tissues Involves partial pressure changes, muscle movement, respiratory rates and volumes As you breathe in air it gets humified – it drops the partial pressure from 160-104 Residual volume of air in your lungs – increases Co2 levels External respiration Gas exchange between alveoli and the capillaries The blood is coming through the pulmonary artery, which contains a de oxygenated blood from the different parts of the body There is a partial pressure gradient Exchanges keeps happening until the partial pressure equalises Gas exchange between alveolar air spaces and alveolar capillaries across respiratory membrane Partial pressure gradient for O2 and CO2 dictates the direction of movement Gases move from higher partial pressure to lower partial pressure Internal respiration Partial pressure of oxygen in tissue is 20 Gas exchange between tissue capillaries and tissues across capillary walls Partial pressure gradient for O2 and CO2 dictates the direction of movement Gases move from higher partial pressure to lower partial pressure Compendium 4 Lecture 3 of 4 – Why do we breathe? P3 Ventilation Pulmonary ventilation Process of moving air into and out of the lungs Structures involved in ventilation o Sternum o Rubs o Lungs o Muscles – intercostal muscles, sternocleidomastoid, scalene, pectoralis minor Muscles involved in breathing Quiet breathing o Inhalation Diaphragm External intercostal muscles o Exhalation Relaxation if inspiratory muscles Elastic recoil of lungs, surface tension (no muscles really involved) Active Breathing o Inhalation Diaphragm External intercostal muscles Sternocleidomastoid Pectoralis minor Scalene muscle o Exhalation Relaxation of inspiratory muscles Elastic recoil of lungs, surface tension Internal intercostal muscles Abdominal muscles Basic facts Boyle’s law o Volume is inversely proportional to pressure Partial pressure gradient o Air moves from areas of high pressure to areas of low pressure Barometric air pressure (PB) o Atmospheric air pressure outside the body Intra-alveolar pressure (Palv) o Pressure inside the alveoli Barometric pressure is normally 760 mm Hg so will be equal to 0mm Hg o If Palv is 759mm Hg, it will be equal to -1mm Hg o If Palv is 761 mm Hg, it will be equal to 1mm Hg Process of ventilation End of respiration o PB = Palv o No flow of air Inspiration o PB > Palv o Diaphragm contracts ,moves inferiorly and flattens o External intercostal muscles contract, elevating rib cage and sternum o Result: Lung volume increase Intra alveolar pressure decreases Air rushes in in equalise pressure End of inspiration o PB = Palv o No flow of air Forceful inhalation breathing muscles o More muscles o Chest muscles o They elevate the ribcage much further high up increasing the volume more Forceful exhalation breathing muscles o Intercostal muscles – layer of muscles between ribs – Press the ribcage further down, and pushes diaphragm further up Changing alveolar volume Intrapleural pressure = pressure in the pleural cavity Forces which promote alveoli recoil: o Alveoli are covered in fine elastic fibres 13 Fluid which coats alveoli on the inside Surfactant (breaks up surface tension and doesn’t allow the alveoli to completely collapse) Forces which promote lungs expansion: o Intra-pleural pressure < intra-alveolar pressure Visceral pleura adhering to parietal pleura Compendium 4 lecture 4 of 4 -Why do we breathe? P2 Respiratory volumes and capacitates Pulmonary volumes Once we have taken a tidal breath in, we can forcefully inhale more air = Tidal volume of 500 mL (the amount of air inspired or expired with each breath Inspiratory reserve volume: the amount of air that can be inspired forcefully after inspiration of the tidal volume Expiratory reserve volume: the amount of air that can be forcefully expired after expiration of the tidal volume Residual volume: the volume of air remaining in the respiratory passages and lungs after the most forceful expiration Pulmonary capacities The sum of two or more pulmonary volumes Inspirational capacity: the amount of air a person can inspire maximally after normal expiation (tidal volume + inspiratory reserve volume) Functional residual capacity: the amount of air remaining in the lungs at the end of a normal expiration (expiratory reserve volume + residual volume) Vital capacity: the maximum volume that can be expelled from the respiratory tract after a maximum inspiration Total lung capacity: inspiratory reserve volume + expiratory reserve volume + tidal volume Definitions Respiratory rate: number of breaths taken per minute Minute ventilation: the total amount of air moved into and out of the respiratory system each minute (tidal volume X respiratory rate) o E.g. 500ml X 12 breaths per minute = 6000ml per minute) Anatomic dead space: space formed by nasal cavity, pharynx, larynx, trachea, bronchi, bronchioles and terminal bronchioles Alveolar ventilation: volume of air available for gas exchange per minute Forced vital capacity (FVC): maximal volume of air that can be forcefully expired as fast as possible after a deep breath in Forced expiratory volume in 1 second (FEV1sec): the volume of air expired in the first second of the test Forced expiratory volume 1% (FEV1%): FEV1sec expressed as a percentage of the FVC Lung function Diagnose and monitor diseases of lungs e.g. asthma, chronic obstructive pulmonary diseases Dynamic testing o Lung volume measured in relation to time o o Dependant on rate of flow of air o Usually determined during repetitive breathing o Essential for diagnosis of obstructive lung disease Static testing o Independent of rate of air flow o Usually determined during one maximal inspiration and or expiration o The following 5 static lung volumes can be measured: VT (tidal volume) IRV (inspiratory reserve volume) ERV (expiratory reserve volume) IC (inspiratory capacity) VC (vital capacity) Vitalogram Spirometer Obstructive vs Restrictive Obstructive o FVC: = normal o FEV1 sec <<< normal o FEV1%: <<< normal o FEV1sec is an indicator of an obstructed airway o Lung volume normal, airways are narrower o E.g. asthma, bronchitis, chronic obstructive pulmonary disorder (COPD) Restrictive o FVC: <<< normal o FEV1sec: <normal o FEV1%: = normal o FVC is an indicator of a restricted airway o Overall lung volume decreases o E.g. pulmonary fibrosis, pneumonia and pulmonary edema, emphysema Exercise and ventilation Ventilation increases abruptly o Onset of exercise o Movement of limbs has a strong influence Ventilation increases gradually Exercise adaptations o Slight increase in vital capacity o Slight decrease in residual volume o At maximal exercise, tidal volume and minute ventilation increases COMPENDIUM FIVE: How do we fuel our body? Lecture Compendium 5 – Lecture 1 of 4 How do we fuel our body? P1 Transport across the cell membrane Plasma membrane Forms a complete boundary around the cell Composed of phospholipids, proteins and cholesterol The bi-molecular layer of the phospholipid molecules forms the basic structure Cholesterol molecules are inserted between the phospholipid molecules are regular intervals Also incorporates both integral and peripheral proteins The plasma membrane: composition Lipid bilayer serves as a highly impermeable barrier to most “charged (polar)” and “non-lipid soluble substances” 14 Integral proteins acting as “pores, channels” or “carriers” to allow these substances to cross the membrane Selectively permeable o Solubility in lipids o Driving forces (up or down a gradient) o Molecular size Transport can either be active or passive Water – soluble substances require specialized transmembrane proteins to function as channels or carriers Transport across the membrane 3 types of passive transport o Diffusion through the lipid bilayer o Diffusion through ion channels o Facilitated diffusion using a carrier Active transport requires cellular energy (ATP) Diffusion THROUGH the lipid bilayer Lipid-soluble substances, e.g. respiratory gases, lipids, small alcohols and urea can diffuse across the lipid bilayer A concentration gradient is using the driving force Diffusion ACROSS the lipid bilayer Water-soluble substances e.g. ions, small sugars, amino acids and water need integral membrane proteins to move across the cell membrane o Small ions (channels) o Water (channels) o Sugars and amino acids (facilitated diffusion) Gradient is driving force Facilitated diffusion A solute binds to a specific transporter on one side of the membrane and is released on the other side Solutes that move in this way include glucose (out of the cell) and fructose (into the cell) Rate of movement depends on o How steep of conc. Gradient o Number of transporter proteins in the membrane “gated” Protein channels Some membrane proteins are ion channels An electrochemical gradient is often the driving force ion channels are selective and specific some channels formed by train property and are continually open, but others are only open transiently – said to be gated Transport much faster a than facilitated diffusion Active transport Active transport is an energy requiring process that moves solutes against a concentration gradient In primary active transport energy is derived directly from ATP In secondary active transport energy is derived indirectly from ATP Primary Active transport The most common primary active transport mechanism is the sodium and potassium iron pump o Requires 40% of cellular ATP o All cells have thousands of them o maintained low concentration of sodium and a higher concentration of potassium in the cytosol o operates continually Secondary Active transport The energy is stored in sodium or hydrogen concentration gradient which is used to drive other substance against their own concentration gradients plasma membranes contained several antiporters and symporters powered by the sodium ion gradient Membrane transport of complex molecules Exocytosis: o movement of large molecules out of the cell o occurs in secretory cells o secretion in vesicles which are membrane packets o neurotransmitter secretion at the synapse endocytosis: o movement of large molecules in particles into the cell Pinocytosis: engulfing small particle and fluids Phagocytosis: engulfing large particles Receptor-mediated endocytosis: the movement of specific substances into the cell involving the caveolae regions of the cell membrane Compendium 5 - Lecture 2 of 4 How do we fuel our body? P2 The movement of water (osmosis) The plasma membrane: composition Water molecules penetrate the membrane by diffusion through the lipid bilayer or through aquaporins (transmembrane proteins) that function as water channels The movement of water is called “osmosis” which is defined as the “movement of water from a low solute concentration to a high solute concentration across a semi-permeable membrane” Osmosis: the driving forces When explaining the driving forces behind water movement we never talk about water concentration, instead we refer to the concentration of solutes dissolved in it This is because water is the solvent for all solutes and is present at a very high concentration: 56 molar This means that when solutes are dissolved in water, its concentration changes very little When a solute dissolves in water, the solution displays an “osmotic pressure” or “drawing power” to encourage water to move towards it Therefore where possible, water always moves to the solution with the highest osmotic pressure (highest solute concentration) Hence the definition of osmosis Osmosis Osmosis is the net movement of water through a selectively permeable membrane Osmosis occurs only when the membrane is permeable to water but not to certain solutes The osmotic pressure that a solute exerts is proportional to the number of “osmotically-active particles” in solution The osmotic pressure of a solution is proportional to the concentration of the solute particles that cannot cross the membrane Tonicity 15 Tonicity is a measure of a solution’s ability to change the volume of cells by altering their water content In an isotonic solution – no net movement of water so cells maintain their normal shape In a hypotonic solution – cells gain water and are in danger of swelling/bursting In a hypertonic solution – cells lose water and are in danger of shrinking and becoming dehydrated There are important medical uses of isotonic, hypotonic and hypertonic solutions Tonicity can be best demonstrated with red blood cells when they are placed in different saline solutions o Isotonic solution – red blood cells maintain their normal shape o Hypotonic solution – red blood cells undergo haemolysis o Hypertonic solution – red blood cells undergo crenation Compendium 5 – Lecture 3 of 4 How do we fuel our body? P3 Glycolysis Introduction 3 major destinations for the nutrients we eat: o Energy o Structural or functional molecules o Storage compounds Most energy is derived from the oxidation of CHO, fat & protein. o About 60-70% of the energy released is lost as heat o Remainder is stored as chemical energy (ATP) Metabolic Reactions Metabolism: all chemical reactions in the body Catabolism: chemical reactions that break down complex organic molecules Anabolism: chemical reactions that build-up simple molecules into complex molecules All molecules have energy stored in the bonds between their atoms Chemical reactions depend on transfer of small amounts of energy from one molecule to another This transfer is usually performed by ATP ATP A molecule for the temporary storage of energy 3 phosphate groups attached to an adenine base and a 5C sugar (ribose) ATP is used for muscle contraction, active transport, movement of structures within cells etc. Large amounts of energy are released when ther terminal phosphate bond is hydrolysed (broken) Stage in energy generation First stage o Large molecules smaller units: Proteins peptides and amino acids Fats glycerol and fatty acids Polysaccs simple sugars Second stage o Smaller units are degraded to a few simple key compounds that play a central role in metabolism Third stage o Citric acid (Krebs) cycle and o Oxidative phosphorylation Carbohydrate metabolism During digestion, polysaccharides and disaccharides are converted to monosaccharides o CHO metabolism is primarily concerned with glucose metabolism Glucose is catabolised in three pathways o Glycolysis o Krebs cycle o The electron transport chain & oxidative phosphorylation Cellular Respiration Metabolic pathways synthesise ATP o Anaerobic: ATP production in absence of O2: glycolysis o Aerobic: ATP production using O2: Oxidative Phosphorylation 4 steps Anaerobic o Glycolysis o Formation of acetyl CoA as a transitional stem Aerobic o Krebs cycle o Electron transport chain Glycolysis Initial step activate glucose Later in glycolysis 4ATP liberated as energy Phase 1: Sugar activation o Two ATP molecules are used to activate glucose (fructose-1, 6-bisphophate) Phase 2: Sugar cleavage o 6C sugar is split into two 3C sugars o Each 3C has a phosphate group o Inorganic phosphate groups are attached to each oxidised sugar fragment Phase 3: Oxidation & ATP formation o The phosphates are split from the sugar and captured by ADP to form 4 ATP molecules o The remaining 3C sugars are pyruvic acid o The final products 2 pyruvic acid molecules 2 NADH and H molecules A net gain of 2 ATP molecules o If O2 is available, pyruvic acid prepares to enter the Krebs’s Cycle o If o2 is not available, PA accepts H2 from NADH2 to form lactic acid Glycolysis: Fate of Pyruvic acid The fate of pyruvic acid depends on the availability of O2 When O2 is not available o The pyruvic acid is reduced to lactic acid o Lactic acid rapidly diffuses out of cell into the blood o Liver cells remove lactic acid from blood & convert it back to pyruvic acid When O2 is available o Pyruvic acid proceeds to the Krebs cycle in the mitochondrion Compendium 5 – Lecture 4 of 4 How do we fuel our body? P4 Kreb’s Cycle & Oxidative Phosphorylation Formation of Acetyl Coenzyme A Pyruvic acid enters the mitochondria & undergoes decarboxylation (removes Co2) 16 Pyruvate dehydrogenase converts 3C pyruvic acid to 2C acetyl group plus Co2 2C acetyl group is attached to coenzyme A to form acetyl coenzyme A which enter Krebs cycle o Coenzyme A is derived from Vitamin B o It behaves as a “carrier or taxi” for the 2C acetyl group Krebs cycle The Krebs cycle is also called the citric acid cycle, or the tricarboxylic acid (TCA) cycle It is a series of biochemical reactions that occur in the matrix of mitochondria The 2C component of acetyl CoA is pulled apart bit-bybit to release Co2 and H The H are sent to the Electron Transport Chain (ETC) as NADH and FADH to be converted into energy The Krebs (Citric acid, TCA) cycle Krebs cycle is a series of reaction which occur in the matrix of mitochondria o Acetyl CoA (2C) enters the cycle & combines with a 4C compound to form citric acid Potential energy in the chemical bonds is released step-by-step to reduce the coenzymes which temporarily store this energy NAD+ and FAD+ are H2 carriers (2C) acetyl CoA + (4C) oxalo-acetic acid (6C) citric acid A series of reactions involving the elimination of 2C & 4O as 2CO2, and the removal of hydrogen occurs 6C citric acid becomes 4C oxalo-acetic acid to complete the cyclic pathway The Krebs cycle summary Each acetyl CoA molecule that enters the Krebs cycle produces: o 2 molecules of Co2 o 3 molecules of NADH2 o 1 molecule of ATP o 1 molecule of FADH2 Each glucose produced 2 acetyl CoA molecules Total yield = (above produces) x 2 Electron transport chain The ETS is located in the mitochondria Integral membrane proteins (cytochromes) form a chain which is located in the inner mitochondrial membrane Each cytochrome picks up electrons and passes them on to the next in the chain Small amounts of energy are released as this occurs This energy is used to form ATP Oxidative phosphorylation produces the vast majority of ATP in cell The Electron transport chain The ETC is a series of cytochromes located in the inner mitochondrial membranes Hydrogens delivered to the chain are split into protons and electrons As electrons are passed through the chain, there is a stepwise release of energy from the electrons for the generation of ATP Steps in the Electron transport chain Proteins of the ETC are clustered into 3 complexes that each act as proton pumps (move H+ into the inner membrane space) The electrons are shuttled from one cytochrome complex to the next Final complex passes its electrons(2H+) to a half of O2 molecule to form water H20 The build-up of H+ outside the inner membrane creates a positive charge o Electrochemical gradient of potential energy ATP synthase enzyme within H+ channel uses this potential energy to form ATP from ADP and iP Electron transport chain H+ ions are transported from matrix into the space between the inner and outer membranes This ensures a high concentration of H+ is established between the inner and outer membranes ATP is formed as H+ diffuse through special ATP synthase channels back to the matrix Summary of Aerobic Cellular Respiration Glucose (+O2) is broken down into CO2 + H2O + energy used to form ATP: o 2 ATPs are formed during glycolysis o 2 NADH2 are formed during glycolysis o 2 NADH2 are formed when converting pyruvate to acetyl CoA o 2ATPs are formed directly during Krebs cycle o 6 NADH2 are formed during Krebs Cycle o 2 FADH2 are formed during Krebs cycle For each NADH2 the proton gradient generates 3 ATP: o 10 NADH2, generates 10x3 ATP = 30 ATP For each FADH2 the proton gradient generates 2 ATP: o 2 FADH2 generates 2x2 ATP = 4 ATP From each glucose molecule 4 ATPS are generated o Oxidative phosphorylation generates 36-38 ATPs from one glucose molecule 2x NADH2 formed during glycolysis produce less ATP via OP The complete oxidation of glucose can be represented as follows: o C6H12O6 36 or 38 ATP + 6CO2 +6H2O Benefit: H2 obtained from a wide variety organic molecules funnelled common energy carrier, ATP Involves a complex series of reactions in the mitochondrion Oxidative phosphorylation produces the vast majority of ATP in cell COMPENDIUM SIX: How do things get around the body? Lecture Compendium 6 – Lecture 1 of 2 How do things get around the body? P1 Cardiovascular system – the heart The cardiovascular system Heart, blood vessels, capillary beds and blood Transports fluids, nutrients, waste products, gases and hormones throughout the body Exchange materials between blood, cells and extracellular fluid Plays a role in the immune response, blood pressure and the regulation of body temperature 17 The heart has to Generate blood pressure – moves blood through vessels Route blood: separates pulmonary (lung) and systematic (body) circulations Ensure a one-way blood flow Regulate blood supply – nervous or endocrine system 60-100 beats per minute Pumps around 5.2L of blood per minute (7200L per day) The heart – location Located in the thoracic cavity in mediastinum Size of a closed fist Shape - inverted pyramid o Base: flat part at opposite end of cone (superior) o Apex: blunt rounded point of cone (inferior) The heart – pericardium Fibrous pericardium: tough fibrous outer layer, prevents over distention; acts as anchor Serous pericardium: thin, transparent, inner layer, simple squamous epithelium o Parietal pericardium: lines the fibrous outer layer o Visceral pericardium: covers heart surface The two are continuous and have a pericardial cavity between them filled with pericardial fluid The heart is inside its own fluid sac Heart wall Three layers of tissue o Epicardium: serous membrane; smooth outer surface of heart (visceral pericardium) – there are loose connective tissues called epicardium fat o Myocardium: middle layer composed of cardiac muscle cells – contractibility (majority of the heart) o Endocardium: smooth inner surface of heart chambers Pectinate muscles: muscular ridges in auricles and right atrial wall – run parallel to each other Trabeculae carnae: muscular ridges and columns on inside walls of ventricles (meaty columns) The heart – 2 pumps in 1 It is feeding two different circulations – lung and body Right side of heart is pumping blood to lungs and left side of lungs is pumping from lungs to body The heart – chambers Right atrium: three major openings to receive blood returning from the body Left atrium: four openings that receive blood from pulmonary veins Atrioventricular canals: opening between atria and respective ventricles Right ventricle: opens to pulmonary trunk Left ventricle: opens to aorta – very muscular wall Interventricular septum: between the two ventricles The heart – valves Atrioventricular valves (right and left AV valves) o Each valve has a leaf-like cusps attached to coneshaped papillary muscles by tendons (chordae tendineae) Right has three cusps (tricuspid) Left has two cusps (bicuspid, mistrial) o When valve is open blood flows from A V o When closed blood exits ventricles Semilunar valves (right -pulmonary) (left- aortic) o Each cusp is shaped like a cup o When cusps are filled valve is closed to stop backflow o When cusps are empty valve is open blood exits heart The heart – great vessels Blood into the heart: o Intro right atrium – superior and inferior vena cava from systematic circuit o Into left atrium – left and right pulmonary veins from pulmonary circuit Blood out of the heart: o Out of right ventricle – pulmonary trunk to pulmonary circuit o Out of left ventricle – aorta to systemic circuit The heart – cycle and control Contraction of heart produces the pressure o Blood moves through circulatory system from areas of higher to lower pressure Cardiac cycle o Repetitive contractions (systole) and relaxation (diastole) of heart chambers – moves blood o Blood flow is proportional to metabolic needs of tissues o Brain, kidneys, liver, exercising skeletal muscle – very high o Can change - cardiac output = heart rate x stroke volume Nervous system: o Maintains blood pressure and thus blood flow Hormonal control: o Epinephrine (adrenaline) from adrenal gland – increase HR and SV The heart – conducting system Action potential – a rapid change in membrane potential. Acts as an electrical signal / impulse The heart can generate its own action potentials Auto-rhythmicity – repetitive contractions Sinoatrial node (SA) – pacemaker Atrioventricular node (AV) Action potentials spread through the conducting system of the heart to all cardiac muscles cells – as a result the cardiac muscle cells contract. Blood is pumped Compendium 6 – Lecture 2 of 2 How do things get around the body? P2 Cardiovascular system – blood, blood vessels and capillaries exchange Why do we need a CVS? Transport o Humans are multicellular o Sales around the body only need a constant supply of oxygen and nutrients and constant removal of waste products o we need a circulating fluid for transportation o exchange materials between blood, cells and extracellular fluid o blood and blood vessels o capillaries - exchange Pump: 18 generating blood pressure - move blood through vessels o routing blood - separates pulmonary and systematic circulations Blood -function transport – gases, nutrients, waste products, processed molecules, hormones and enzymes regulation of pH and osmosis (normal 7.4) maintenance of body temperature shunting protection against foreign substances Clot formation Blood – composition 55% plasma (water, proteins and other solutes) and 45% formed elements (red blood cells, white blood cells, platelets) Blood -red blood cells Aka erythrocytes No nucleus and bi concave shape to increase SA and thus oxygen carrying capacity Main component is a pigmented protein called haemoglobin Oxygen from lungs to body cells: 1.5% dissolved in plasma 98.5% attached to haemoglobin Blood vessels – overview Arteries o Elastic, muscular, arterioles o Take blood away from the heart o Contain blood under pressure Capillaries o Site of exchange with tissues (interstitial fluid) Veins o Venules, small, medium, large o Take blood to the heart o Thinner walls than arteries, contain less elastic tissue less smooth muscle o Valves to prevent backflow Blood vessels – arteries and veins Tunica intima: simple squamous endothelium Tunica media: smooth muscle cells and elastin arranged circularly Smooth muscle changes diameter of the lumen Tunica externa (adventitia): connective tissue Blood vessels – capillaries Capillary beds – extensive networks for exchange Wall consists of endothelial cells (simple squamous epithelium), basement membrane and a delicate layer of C.T. Substances move through capillaries by diffusion Types o Continuous No gaps between the endothelial cells Less permeable to larger molecules Found in muscle and nervous tissue o Fenestrated Holes or fenestrae in the endothelial cells (70100nm diam.) Highly permeable Found in gut and kidney o Sinusoidal Irregular incomplete wall of endothelial cells o Larger in size – allows large molecules to pass Found in endocrine glands and liver Capillary exchange Capillary exchange: the movement of substances into and out of capillaries. How cells receive what they need to survive and eliminate waste products Most important means of exchange: diffusion, Oxygen, hormones, nutrients diffuse from a high concentration in the capillary to low concentration in the interstitial fluid o Lipid soluble substances – diffuse trough plasma membrane of epithelial cells o Water soluble – diffuse through intercellular spaces or through fenestrations of capillaries o Large spaces between endothelial cells – proteins and whole cells can pass Very small spaces between cells – very few molecules can pass Capillary permeability, blood pressure, and osmotic pressure affect movement of fluid from capillaries Cells are bathed in interstitial fluid (extracellular fluid) Transport (diffusion) in and out of cells – requires a pressure gradient Interstitial fluid needs constant turnover Comes via capillaries and CVS The lymphatic system Fluid moves out of capillaries into interstitial space and most returns to capillaries The fluid which remains in tissues is picked up by the lymphatic system then eventually returned to venous circulation Edema in lymphatic system Edema: swelling caused by excess fluid accumulated in body tissues Causes: o Problems with capillaries, hear failure kidney disease etc. If capillaries become ‘leaky’ to blood proteins can leak into interstitial fluid. This increases osmotic pressure outside the capillary and draws more fluid from the capillaries into the interstitial fluid COMPENDIUM SEVEN: How do we get rid of toxic waste? Lecture Compendium 7 – Lecture 1 of 2 How do we get rid of toxic wastes? P1: the anatomy of the renal system Gross anatomy of the renal system 2 kidneys – formation of urine formation 2 ureters – passage of urine Urinary bladder – storage of urine Urethra – passage of urine Location of kidneys Posterior to the parietal peritoneum, on the posterior abdominal wall, lateral to the spine Note the R kidney is slightly inferior to the L – due to the position of the liver Partially protected by lumbar vertebrae and ribs Approx. 11cm long, 5 cm wide, 130g Location and gross anatomy 19 Renal capsule – connective tissue surrounding each kidney Adipose tissue – surrounds the outside of the capsule for protection Renal fascia – thin layer of connective tissue surrounds the adipose tissue, anchor kidneys to abdominal wall Kidney internal anatomy Hilum: om the concave (medial side: renal artery and nerves enter. Renal vein, ureter, lymphatics exit The hilum opens into the renal sinus which is filled with fat and loose CT Kidneys are organised into two major regions o Outer cortex o Inner medulla Renal pyramids – bases project into cortex Renal columns are extensions of cortisol tissue into the medulla Renal pyramids – bases project into cortex. Coneshaped. The base is the boundary between cortex and medulla Apex of pyramid is renal papilla Papillae extend into minor calyces, which are funnelshaped chambers Minor calyces funnel into larger chamber called major calyces Renal pelvis, a single large funnel-shaped chamber Renal pelvis is embedded in the renal sinus. At the hilum, it narrows, forming the ureter The nephron The functional unit of the kidney 4 separate regions of the nephron: renal corpuscle, proximal convoluted tubule, loop of Henle, distal convoluted tubule Blood enters the nephron for filtration Filtrate/urine is produced Urine flow: nephron papillary ducts minor calyces -> major calyces renal pelvis ureter Types of nephrons Approximately 1.3 million nephrons in each kidney Approximately 50-55 mm in length Juxtamedullary nephrons: o The renal corpuscle is deep in the cortex near the medulla o Long loop of Henle extending deep into the medulla o 15% of nephrons Cortical nephrons o Renal corpuscle located near the periphery/cortex o Shorter loop of Henle o 85% of nephrons Renal Corpuscle The filtration portion of the nephron Consists of the glomerulus and the Bowman capsule Glomerulus: o Network/ball of capillaries Bowman capsule: o Enlarged end of the nephron, double walled chamber. Filters blood/fluid, which then enters the proximal convoluted tubule Blood enters glomerulus through afferent arteriole, filtered blood exists through efferent arteriole Note size difference- pressure difference Bowman Capsule Parietal layer o Outer layer: simple squamous epithelium o Becomes cuboidal in the PCT Visceral layer o Inner layer. Constructed of specialized cells called podocytes, which wraps around the glomerular capillaries The filtration membrane Fenestrae: the glomerular capillaries are highly permeable. Fenestrae are little windows Basement membrane: sandwiched between the endothelial cells of the glomerular capillaries and the podocytes Filtration slits: gaps between the cell processes of the podocytes Thus, the filtration membrane is specialized for filtration The renal tubules Proximal convoluted tubules: filtrate drains into here from the Bowman capsule Loop of Henle has a descending and ascending limb Distal convoluted tubule: shorter than PCT Collecting duct: several DCTs connect to a single collecting duct. Large diameter. Extends through medulla towards renal papilla ureter Nephron histology Proximal convoluted tubule: simple cuboidal epithelium with many microvilli. Mitochondria. Active reabsorption of Na+, K+ & Cl Loop of Henle: thick pats – simple cuboidal epithelium. Thin parts – simple squamous epithelium – for osmosis/diffusion Distal convoluted tubule: simple cuboidal epithelium, and very few microvilli. Numerous mitochondria. Active reabsorption Collecting duct: simple cuboidal epithelium Major Renal veins and arteries Abdominal aorta R. renal artery L. renal artery R. renal vein L. renal vein Inferior vena cava Urine movement Pressure forces urine through nephron 20 Smooth muscles forces urine through ureters. Peristalsis moves urine from the renal pelvis in the kidneys ureters urinary bladder Ureters enter bladder obliquely through trigone. Pressure in bladder compresses ureter and prevents backflow Ureters Passageway for urine From renal pelvis urinary bladder Lined with transitional epithelium Urinary bladder Hollow muscular container. Located in pelvic cavity posterior to symphysis pubis o Trigone: histologically unique region. Triangular area on posterior wall between the entry of the two ureters and the exit of the urethra Urethra Transports urine from the urinary bladder to the outside of the body Transitional epithelium at the top of the urethra; the remainder is stratified columnar At the junction of the urinary bladder and the urethra is the internal urinary sphincter o Elastic CT and smooth muscle, prevents urine leakage External urinary sphincter: skeletal muscle surrounds urethra as it extends through pelvic floor. o We can voluntary start/stop flow of urine Male urethra: extends from the inferior part of the urinary bladder through to the tip of the penis Female urethra: shorter; opens into vestibule anterior to vaginal opening Compendium 7 – Lecture 2 of 2 How do we get rid of toxic wastes? P2: the physiology of the renal system Function of the renal system Excretion: rid the body of waste products. Urine production occurs in the kidney via filtration of the blood and reabsorption of nutrients. Metabolic wastes and toxic molecules are excreted in urine Regulation of blood volume and blood pressure – we control our extracellular fluid volume by producing large amounts of dilute urine of small amounts of concentrated urine Also – solute concentration in the blood, extracellular pH, regulation of red blood cell synthesis, regulation of vitamin D synthesis The production of urine Kidneys regulate body fluid composition. Sorts chemicals in the blood for removal or for return into the blood Nephrons: the structural component of the kidneys that ‘sorts’ the blood Urine production: recall 3 stages – filtration, tubular reabsorption, tubular secretion Process 1: Filtration Movement of fluid, derived from blood flowing through the glomerulus, across filtration membrane Filtrate: water, small molecules & ions that can pass through membrane o Doesn’t include red blood cells, proteins or large molecules Renal fraction: the proportion of total cardiac output that passes through the kidneys o Varies from 12-30% in a healthy resting adult Glomerular filtration rate (GFR): amount of filtrate produced each minute – 125 ml/minute; 180 L/day Average urine production/day: 1-2L Most of filtrate (99%) must be reabsorbed Removes toxins quickly from blood The filtration membrane – remember the anatomy o Fenestrae: the glomerular capillaries are highly permeable. Fenestrae are little windows o Basement membrane – sandwiched between the endothelial cells of the glomerular capillaries and the podocytes o Filtration slits: gaps between the cell processes of the podocytes o Thus the filtration membrane is specialized for filtration Filtration membrane – a filtration barrier o Learn and remember the components of the filtration membrane o Filtrate consists of: water, glucose, fructose, amino acids, urea, urate ions, creatinine, Na, Ca, Cl Very little protein normally found in filtrate and urine o Filtration is driven by pressure Blood pressure o Filtration pressure: the force that causes filtration Pressure gradient responsible for forcing fluid out of the glomerular capillary across the membrane into the lumen of the Bowman capsule The juxtaglomerular apparatus o An important regulatory structure, located next to the glomerulus o Where the afferent arteriole enters the renal corpuscle, a cuff of smooth mm cells surrounds it – the juxtaglomerular cells o A group of specialized cells at a section of the DCT – called the macula densa o These secrete renin, important in regulation of filtrate formation and BP regulation Process 2: Tubular reabsorption This is the return of water, small molecules and ions back into the blood As the filtrate flows through the lumen of the renal tubules First, substances are reabsorbed across the renal tubule into the interstitial fluid, then from here into the peritubular capillaries back into the circulation Substances – water, amino acids, glucose, fructose, Na, K, Ca, Cl, HCO3 Proximal convoluted tubule – majority of reabsorption here: filtrate remaining is about 35% Active and passive mechanisms of cell membrane transport Note the apical surface of the PCT simple cuboidal lining the nephron o Borders with nephron lumen Note the basal surface borders with the interstitial fluid 21 Loop of Henle: some reabsorption of water and ions. Remember thick and thin segments o Thin segments – simple squamous epithelium, highly permeable to water. And some solutes can move by diffusion too o Filtrate further reduced by another 15% Distal convoluted tubule and collecting duct: some reabsorption o Most of this is under control of Antidiuretic hormone ADH makes the tubule wall more permeable to water. Tubular reabsorption in the PCT o Active transport of Na across the basal surfaces – associated with the reabsorption of most solutes o With Na being pumped out of the cell, the concentration of Na is low inside the cell. Therefore Na moves into the nephron cell through apical surface. Other substances can move in by symport Glucose Process 3: Tubular secretion The movement of non-filtered substances, toxic byproducts of metabolism, drugs or molecules not normally produced by the body, into the nephron for excretion. Occurs mainly in the distal convoluted tubule As with reabsorption it can be active or passive Ammonia is a toxic by-product of protein metabolism. Diffuses into lumen of nephron H, K and penicillin: actively secreted into nephron Urine movement Pressure forces urine through the nephron Peristalsis moves the urine through ureters to urinary bladder. Every few seconds to every few minutes o Parasympathetic stimulation: increase frequency o Sympathetic stimulation: decreases frequency Prevention of backflow of urine – trigone pressure What is urine? 1% of filtrate 1-2L per day produced Proportion of water Depending on body’s needs o Dilute or concentrated Urea, uric acid, ammonia, creatine, H, K Bile pigments Drugs and toxins e.g. penicillin The micturition reflex While the flow of urine from ureter to bladder is continuous, the flow from the bladder to urethra is not Bladder capacity 1L Micturition – elimination of urine from the bladder Full bladder – stretch receptors CNS message Voluntary control (CNS) of the EUS. Relax urination COMPENDIUM EIGHT: How do we control ourselves Lecture Notes Compendium 8 – Lecture 1 of 4 How do we control ourselves? P1: Introduction to the nervous system Functions of the nervous system Maintaining homeostasis Receives sensory input o Internal – e.g. stomach acids o External – e.g. touch a hot stove Integrating information Motor output Establish and maintain mental activity Structural divisions of the nervous system Central nervous system (CNS) o Brain and spinal cord Peripheral nervous system (PNS) o Spinal nerves and cranial nerves Functional divisions of the nervous system Peripheral nervous system o Autonomic nervous system (Automatic) Motor (efferent) Sensory (afferent) o Somatic nervous system (Voluntary) Motor (efferent) Sensory (afferent) o Enteric nervous system Motor (efferent) Sensory (afferent) Central nervous system Motor (efferent) can be divided into two parts o Parasympathetic o Sympathetic Terminology Neuron: basic structural unit of the nervous system Axon: nerve fibre Nerve: bundle of axons (nerve fibres) and their sheaths (outer covering) Sensory receptors: separate specialized cells which detect temperature, pain, touch, pressure, light, sound, odour and stimuli Action potential: electrical signal Effector organ / effector cell: organ, tissue or cell in which the effect/action that takes place Ganglion: collection of cell bodies located outside the CNS Plexus: extensive network of axons or cell bodies Synapse: junction of a neuron with another neuron Autonomic subdivision Involuntary and under subconscious control Action potentials in the motor neurons travel from the CNS to smooth or cardiac muscles or glands Two-neuron system Cell bodies of the neuron are located in the CNS and autonomic ganglion Somatic subdivision Voluntary and under conscious control Action potentials in the motor neurons travel from the CNS to skeletal muscles Single neuron system Cell bodes are located in the CNS Compendium 8 – Lecture 2 of 4 How do we control ourselves? P2: Cells of the nervous system Neuron Structural unit of the nervous system Dendrites 22 o Dendritic spines Cell body (soma) Axon o Axon hillock o Initial segment o Trigger zone o Axon collaterals o Axon terminal or presynaptic terminals o Terminal boutons or synaptic knobs o Types of neurons Functional classification o Sensory neuron – information to the CNS o Motor neuron – information away from the CNS o Inter-neuron – information from one neuron to another neuron Structural classification o Multipolar – Many dendrites and a single axon (e.g. motor neuron) o Bipolar – axon, and dendrites (on either end) (rare – found in eyes) o Unipolar – axon only from the cell body (sensory receptors) Astrocytes cells From the CNS Abundant neuroglia cells in the nervous system Forming a supporting framework for blood vessels and neurons Assist in the formation of tight junctions between endothelial cells of the capillaries Respond to tissue damage in the CNS Ependymal cells Line the central cavities of the brain and spinal cord Form lining of the cavities of the cerebrospinal fluid Microglial cells Monitor the health of surrounding neurons Phagocytose microorganisms, infections, trauma or inflammation Oligodendrocytes Cover axons which form an insulating sheath around them – myelin sheath Cells of the PNS Schwann cells o Also called neurolemmocytes o Form a myelin sheath around axons insulating Satellite cells o Provide support and nutrition to cell bodies in ganglia o Protect cell bodies from harmful substances Myelinated and unmyelinated axons Myelinated axons o Nodes of Ranvier Unmyelinated axons Grey and white matter Grey matter (cell body and dendrite) – CNS – brain: outer cortex of brain and nuclei. SPINAL CORD – inner part “grey” part Grey matter (cell body and dendrites) – PNS – ganglion White matter (axon) – CNS – brain: deeper nerve tracts SPINAL CORD: outer part White matter (axon) – PNS – nerves Compendium 8 – Lecture 3 of 4 How do we control ourselves? P3: Electrical signals and action potentials Electrical signals Action potential Membrane potential – the difference in charge across the cell membrane Characteristics of the cell membrane which allows a membrane potential to be generated o Differences in ionic concentration (particularly for Na+ and K+) across the cell membrane o Permeability of the cell membrane to ions Membrane ion channels Non-gated ion channels o Also known as ‘leak’ ion channels o Ion specific o Cell membrane has more K+ leak ion channels to Na+ leak ion channels Gated ion channels – require signals to open them o Ligand-gated ion channel o Voltage-gated ion channel o Other-gated ion channel Establishing resting membrane potential Resting membrane potential – the difference in charge across the cell membrane in a resting cell o Intracellular side is more negative o RMP of neurons = -70mV where the negative sign indicates the charge on the intracellular side of the cell RMP caused by leak ion channels and the Na+/K+ pump Changing the resting membrane potential Depolarisation – when the membrane potential becomes more positive i.e. the inside of the cell becomes more positive. E.g. -70mV -30mV Hyperpolarisation – when the membrane potential becomes more negative. i.e. the inside of the cell becomes more negative E.g. -70mV 75 -75mV Repolarisation – membrane potential returns to normal Graded potential Graded potentials can lead to action potentials Graded potential – short lived, localised changes in membrane potential Often occur in dendrites or the cell body of a neuron Ability to summate Decremental not able to transfer information over long distances Action potential Afterpotential – short period of hyperpolarisation of an action potential Action potential takes a few milliseconds Action potential s not decremental Operation of gates: action potential Resting membrane potential o All gated Na+ and K+ channels are closed o K+ leaked channels are open which allows movement of K+ to the outside of the cell. This creates a negative intracellular charge =RMP o Na+/K+ pump also creates the RMP Depolarisation 23 Na+ gated channels open and Na+ moves into the cell and inside of the cell becomes more positive o K+ gated channels are closed o Membrane potential becomes more positive Repolarisation o Na+ gated channels close o K+ gated channels open and K+ moves out of the cell and the intracellular side becomes more negative o Membrane potential becomes more negative End of repolarisation, and the afterpotential: o Na+ gated channels close o K+ gated channels close as well but they close slowly so K+ continues to leave the cell and this produces the afterpotential o Membrane potential becomes very negative Resting membrane potential o Na+ gated channels are closed o K+ gated channels are closed o Resting membrane potential is re-established by Na+/K+ pump which redistributes ions as all Na+ and K+ gated channels are closed Some relevant concepts to add All or none principle Refractory period o Absolute refractory period o Relative refractory period Propagation of axon potentials o Takes place in unmyelinated axons only Following depolarisation, each segment of the axon membrane becomes repolarised The propagation of the action potential occurs in one direction Saltatory conduction – myelinated axons Compendium 8 – Lecture 4 of 4 How do we control of ourselves? P4: Spinal reflex arcs Introduction to spinal cord Meninges: connective tissue membrane surrounding the brain and spinal cord Reflexes Automatic response to a stimulus Are somatic or autonomic Homeostatic Components o Sensory receptor o Sensory neuron o Interneuron o Motor neuron o Effector organ The simplest reflex arcs do not involve interneurons o Monosynaptic vs. polysynaptic COMPENDIUM NINE: HOW DOES IT ALL WORK? Lecture Notes Compendium 9 - Lecture 1 of 4 How does it all work? P1: The spinal cord and spinal nerves Spinal cord Starts at the foramen magnum and extends inferiorly to the first or second lumbar vertebrae Can be divided into cervical, thoracic, lumber, sacral and coccygeal regions 31 pairs of spinal nerves Dura mater – covering around spinal cord (protective) Cervical nerves (1-8 first nerves) Thoracic nerves (12 second set of nerves) Lumbar nerves (5) Sacral nerves (5) Coccygeal (1) Diameter of spinal cord changes from top to bottom Conus medullaris – finishes at the second lumbar vertebrae Cauda equina Meninges Meninges: the connective tissue coverage the spinal cord and the brain Function o Protects the CNS and blood vessels o Contains the cerebrospinal fluid o Forms partitions in the skull 3 layers o Dura mater – surrounds the brain and outer layer of spinal cord Subdural space (space between dura matter and arachnoid mater) Contains serous fluid o Arachnoid mater – next layer of meninges Subarachnoid space Cerebrospinal fluid and blood vessels o Pia mater Has many small blood vessels Grey matter contains cell bodies and dendrites o Cortex of brain and muscles (CNS) o Ganglion (PNS) o Outer cortex (Brain) o Inner (Spinal Cord) White matter contains myelinated and unmyelinated axons o Nerves tracts (CNS) o Nerves (PNS) o Deeper (Brain) o Outer (Spinal Cord) Organisation of neurons in the spinal cord and spinal nerves Sensory neurons travel through the dorsal roots Motor (somatic and autonomic) neurons travel through the ventral roots 24 Spinal nerves contain sensory neurons and motor (somatic and autonomic) neurons Cell bodies of motor neurons are horns of grey matter o Somatic motor neuron cell bodies in an anterior (ventral) horn (motor horn) o Autonomic motor neuron cell bodies in lateral horn Nerve structure Endoneurium o Surrounds each axon and its associated Schwann cells Perineurium o Surrounds a group of axons or a nerve fascicle Epineurium o Surrounds a group of fascicles Organisation of spinal nerves Compendium 9 – Lecture 2 of 4 How does it all Work? P2: The brain and cranial nerves The brain Forebrain o Cerebrum o Diencephalon Midbrain Hindbrain o Pons o Medulla oblongata o Cerebellum Midbrain, Hindbrain (Pons & Medulla) = brain stem Medulla oblongata Autonomic reflex centre maintaining body homeostasis Cardiovascular centre o Regulates heart rate, force of heart contraction and blood vessel diameter Respiratory centre o Regulates rate and depth of breathing Other reflexes o Swallowing, vomiting, hiccupping, coughing and sneezing Pons Pons = bridge Contains conduction tracts: o Longitudinal tracts from the spinal cord to higher brain centres o Transverse tracts form the cerebrum (motor cortex) and cerebellum Sleep centre o Rapid eye movement Respiratory centre Midbrain Receives visual, auditory and tactile sensory input generating reflex movements of the head, eyes and body Controlling movement of the eye Cerebellum Cerebellum = little brain Controls locomotion, in association with the cerebrum Controls fine motor control Controls posture and balance Diencephalon Thalamus Subthalamus Epithalamus Hypothalamus Diencephalon: thalamus Sensory relay centre or “gateway” o Anything you hear, see, feel by touch, but NOT smell Regulates mood, memory and strong emotions o E.g. fear and rage Diencephalon: hypothalamus Maintains homeostasis via the endocrine system Regulates heart rate Regulates digestive activities Controls muscles in swallowing Controls body temperature Regulates sex drive and sexual pleasure Regulates mood, motivation and emotions Regulates the sleep-wake cycle Cerebrum Longitudinal fissure – separates left and right hemisphere Lateral fissure – separates the temporal lobe from the rest of the cerebrum Central sulcus – separates frontal lobe from parietal lobe Lobes: o Frontal o Parietal o Occipital o Temporal o Insula Gyri – elevated tissue or folds Sulci – grooves Fissures – deep grooves Precentral gyrus – primary somatic motor cortex Postcentral gyrus – primary somatic sensory cortex Frontal lobe – voluntary motor function, motivation, planning, aggression, sense of smell, regulation of emotion behaviour and mood Parietal lobe – area which receives most the sensory input, except from smell, hearing, taste and vision Occipital lobe – receives and processes visual input Temporal lobe – receives and processes smell and hearing, and has a role in memory Insula – receives and processes taste information Grey matter in the cerebral cortex o Cell bodies, dendrites, unmyelinated axons, axon terminals and neuroglial cells White matter in the cerebral medulla 25 o Myelinated axons Corpus callosum – connects two cerebral hemispheres together Limbic system Role in memory Emotional brain Meninges Dura matter o Periosteal dura o Dural venous sinus Venous blood Dural folds o Meningeal dura o Subdural space Serous fluid Arachnoid mater o Subarachnoid space Cerebrospinal fluid and blood vessels Pia mater o Has many small blood vessels Ventricles 4 ventricles that are continuous with each other Lined with ependymal cells Lateral ventricle: first and second ventricle Third ventricle Cerebrospinal fluid produced in ventricles Cerebrospinal fluid Most cerebrospinal fluid is produced by the choroid plexus Fluid found around the brain and spinal cord Protects the brain and spinal cord from trauma and provides buoyancy to the brain CSF composition: similar to blood plasma but less proteins and different ionic concentration Cranial nerves 12 pairs Sensory, motor and/or parasympathetic functions Compendium 9 – Lecture 3 of 4 How does it all work? P3: The autonomic nervous system Functional divisions of the nervous system Autonomic nervous system – motor neuron and sensory o Sympathetic and parasympathetic Somatic nervous system o Motor & sensory Anatomy of the autonomic nervous system Sympathetic division o Thoracolumbar division T1-L2 Parasympathetic division o Craniosacral division S2-S4 Cranial nerve Nuclei Functional generalisations of the sympathetic and parasympathetic nervous systems Dual innervation of the autonomic nervous system (ANS) Opposing effects Responses generated by both ANS divisions can regulate: o Heart rate o Blood pressure o Airway in lungs o Digestive tract o Glands (salivary, gastric, lacrimal) o Pupil of the eye Sympathetic division: o Fight or flight o ‘E division’ Exercise, emergency, excitement and embarrassment Parasympathetic system o Rest and digest o D Division Digestion, defecation and diuresis Regulation of the autonomic nervous system Autonomic regulation occurs mostly via autonomic reflexes o Reflexes are an automatic response to a stimulus and are homeostatic Autonomic reflex activity is also influenced by the CNS, in particular the hypothalamus Compendium 9 – Lecture 4 of 4 – The endocrine system Basics of chemical communication Autocrine o Released by cells and have a local effect on same cell type from which chemical signals are released Paracrine o Released by cells and affect other cell types locally without being transported in blood Neurotransmitter o Produced by neurons and secreted into extracellular spaces by presynaptic nerve terminals; travels short distances; influences postsynaptic cells Endocrine o Produced by cells of an endocrine glands, enter circulatory system, and affect distant cells Characteristics of the endocrine system Body control system where regulation requires duration rather than speed Glands that secrete chemical messengers (hormones) into circulatory system (blood) Hormone characteristics o Produced in small quantities o Transported some distance in circulatory system o Acts on target tissues elsewhere in body Hormone secretion can be: o Acute – sudden release due to stimulus e.g. adrenaline 26 Chronic – small variations over long periods e.g. thyroid hormones o Episodic – e.g. estrogen and progesterone during menstrual cycle Target cells respond to a hormone because they have the correct receptor Functions of the endocrine system Metabolism Control of food intake and digestion Tissue maturation Ion regulation Water balance Heart rate and blood pressure regulation Control of blood glucose and other nutrients Control of reproductive functions Uterine contractions and milk release Immune system regulation Endocrine glands of the body Pineal gland Hypothalamus Pituitary gland Thyroid gland Parathyroid glands Thymus gland Adrenal gland Pancreas Ovary Testes Nervous vs Endocrine systems Similarities o Both systems associated with the brain Endocrine – hypothalamus o Many use same chemical messenger as neurotransmitter and hormone E.g. epinephrine o Two systems are cooperative E.g. some parts of endocrine system innervated directly by nervous system (adrenal medulla) Differences o Mode of transport Axon Blood o Speed of response Nervous – instantaneous Endocrine – delayed o Duration of response Nervous – seconds/ milliseconds Endocrine – minutes / days Structure of the pituitary gland Posterior pituitary: extension of the nervous system via the infundibulum o Secretes neuropeptides Anterior pituitary: develops from embryonic oral cavity; secretes traditional hormones Pituitary gland and hypothalamus Where nervous and endocrine systems interact Hypothalamus regulates secretions of anterior pituitary Posterior pituitary is an extension of the hypothalamus The pituitary gland produces nine major hormones that o o Regulate body functions o Regulate the secretions of other endocrine glands Hypothalamic control of posterior pituitary: o Hormones produced in neurons in hypothalamus, stored in posterior pituitary Axons from hypothalamohypophysial tract o Action potentials in these neurons cause hormone release Hypothalamic control of anterior pituitary o Blood vessels make up hypothalamohypophysial portal system, connect the areas o Hypothalamic releasing and inhibiting hormones stimulate or inhibit anterior pituitary hormone release Hypothalamus, anterior pituitary, target tissues Stimuli within nervous system regulate secretion of releasing hormones from neurons in hypothalamus Releasing hormones pass to anterior pituitary Releasing hormones stimulates the release of hormones from anterior pituitary Anterior pituitary hormones travel in blood stream to target tissue, which may be another endocrine gland Hypothalamic hormones Growth hormone-releasing hormone o Causes increased secretion of GH Growth hormone-inhibiting hormone o Causes decreased secretion of GH Thyrotropin-releasing hormone o Causes TSH secretion Melanocyte releasing hormone o Causes MSH secretion Corticotrophin-releasing hormone o Causes ACTH secretion Gonadotropin-releasing hormone o Causes secretion of gonadotropins LH and FSH Prolactin-releasing hormone o Causes increased prolactin secretion Dopamine (prolactin-inhibiting hormone, PIH) o Causes decreased prolactin secretion Anterior pituitary hormones Growth hormone o Acts on most cells of body overall metabolism and growth Thyroid stimulating hormone o Stimulates thyroid to secrete T3 and T4 Adrenocorticotropic hormone o Stimulates adrenal cortex to secrete cortisol and aldosterone Melanocyte-stimulating hormone o Causes melanocytes to produce more melanin Luteinizing hormone Follicle stimulating hormone o Both hormones regulate production of gametes and reproductive hormones Testes – to make testosterone and spermatogenesis (sperm) Ovaries – to make estrogen and progesterone, and oogenesis (oocytes) Prolactin o Role in milk production (lactation) Tropic vs Non tropic 27 Tropic hormones: stimulate the secretion of other hormones from target tissues Non-tropic: initiate an effect Hypothalamus, posterior pituitary, target tissues Stimuli within nervous system cause neurons in hypothalamus to increase or decrease action potential frequency AP’s conducted along neurons from hypothalamus to posterior pituitary. Axon terminals of these neurons store neuro-hormones AP’s cause release of neurohormones into circulatory system Posterior pituitary hormones travel in blood stream to target tissue Posterior Pituitary hormones Antidiuretic hormone (ADH) o Stimulates increased reabsorption of sodium and water from nephrons, so less urine is produced. If BP decreases, then ADH secretion is stimulated o Also called vasopressin (vasoconstrictor, increase BP) Oxytocin o Uterine contractions during birth o Ejection of milk from lactating breast (let down reflex) Control of hormone secretion – negative feed back Anterior pituitary secretes a tropic hormone which travels in blood to target endocrine cell Hormone from target endocrine cell travels to it target Hormone from target endocrine cells has negative feedback (opposite) effect on hypothalamus and anterior pituitary to decrease secretion of tropic hormone Control of hormone secretion – positive feedback Anterior pituitary secretes a tropic hormone which travels in blood to target endocrine cell Hormone from target endocrine cell travels to its target Hormone from target endocrine cells has positive feedback effect on hypothalamus and anterior pituitary to increase secretion of tropic hormone Growth hormone Stimulates uptake of amino acids, protein synthesis Stimulates breakdown of fats to be sued as an energy source Promotes bone and cartilage growth Regulates blood levels of nutrients after a meal GH stimulates liver and skeletal muscles to make IGF-1 o Peak GH levels during deep sleep Thyroid stimulating hormone T3 and T4 Stress and hypothermia cause TRH to be released from neurons within the hypothalamus. It passes through the hypothalamohypophysial portal system to the anterior pituitary TRH causes cells of the anterior pituitary to secrete TSH, which passes through the general circulation to the thyroid gland TSH causes increased synthesis and release of T3 and T4 into the general circulation T3 and T4 act on target tissues to produce a response 28 T3 and T4 also have an inhibitory effect on the secretion of TRH from the hypothalamus and TSH from the anterior pituitary Thyroid Gland One of largest endocrine glands Highly vascular Only gland that stores hormone Composed of follicles: follicular cells surrounding thyroid hormones Iodine and tyrosine necessary for production of T3 and T4 Increase rate of glucose, fat, protein metabolism in many tissues thus increasing body temperature Normal growth of many tissues ACTH Near superior poles of kidneys (Adrenocorticotropic) Inner medulla; outer cortex CRH from hypothalamus causes release of ACTH from anterior pituitary which causes cortisol secretion from the adrenal cortex Causes aldosterone secretion from the adrenal cortex Causes androgen ACTH – Cortisol Adrenal Medulla Stress, physical activity, and low blood glucose levels act as stimuli to the hypothalamus, resulting in increased sympathetic nervous system activity. An increased frequency of action potentials conducted through the sympathetic division of the autonomic nervous system stimulates the adrenal medulla to secrete epinephrine and norepinephrine into CVS. Secretion of hormones prepares body for physical activity. Short lived responses. Epinephrine and norepinephrine increase heart rate and force of contraction; cause blood vessels to constrict in skin, kidneys, gastrointestinal tract, and other viscera. Melanocyte stimulating hormone – MSH Acts on receptors in skin cells and stimulates melanin in the skin MSH also has a role regulating appetite and sexual behaviour Poorly understood LH and FSH GnRH from hypothalamus stimulates LH and FSH secretion Gonadotropins: glycoprotein hormones that promote growth and function of the gonads LH and FSH o Both hormones regulate production of gametes and reproductive hormones o Frome testes – testosterone: spermatogenesis, secondary sex characteristics o From ovaries – estrogen and progesterone: sex organ development and characteristics, menstrual cycle, pregnancy Prolactin Non tropic hormone Breast milk production Supply and demand Oxytocin Posterior pituitary Non-tropic hormone Positive feedback Breast milk release (let down) Supply and demand ADH Reduced urine formation. Keeps water in the body Increases blood volume and thus blood pressure. Hot day / dehydrated = lots of ADH. Diuretic – tea, coffee, alcohol Pancreas – regulation of insulin secretion Located along near intestine and stomach; retroperitoneal Exocrine gland: Produces pancreatic digestive juices Endocrine gland: Consists of pancreatic islets. Alpha cells - secrete glucagon Beta cells - secrete insulin Endocrine pancreas – regulation COMPENDIUM TEN: HOW DO WE PROTECT OURSELVES? LECTURE NOTES Compendium 10 – How do we protect ourselves? – Lecture 1 of 2 – P1: Immunity Pathogens & antigens Pathogen – foreign agents o Protozoa o Viruses o Worms o Toxins o Fungi o Prions Bacteria – infection, food poisoning o Pathogens introduce foreign (non-self) proteins in the body called antigens o Antigenic receptors on T cells and B cells recognize these foreign proteins as not being “self” and aims to remove them from the body Immunity Ability to resist damage from foreign substances and internal threats Can be distinguished between “self” and “non-self” o External – micro-organisms e.g. bacteria, virus, fungi, toxins o Internal – cancer cells Categories o Innate or nonspecific immunity o Adaptive or specific immunity Innate and adaptive immunity are fully integrated in the body Immune system vs. lymphatic system Lymphatic system o Transport system for cells of the immune system and antigens (foreign substances/cells) to move around the body 29 Tissues where cells of the immune system “hang out” Immune system o Collection of proteins, cells, tissues and organs widely distributed throughout the body Immune system Immunity: ability to resist damage from foreign substances e.g. microbes chemicals and internal threats (e.g. cancer) Innate (non-specific) o Physical barriers - skin & mucous membranes o Inflammation o Chemical mediators o White blood cells (leukocytes) e.g. macrophages Adaptive (specific) o Cell mediated immunity – T cells o Antibody mediated immunity – B cells Innate immune system Non-specific defence, present at birth Each time body is exposed to a substance, response is the same (no memory) Provides immediate protection from pathogens & antigen First line of defence are external features o Physical barriers Second line of defence o Chemical mediators o White blood cells o Inflammation o fever Innate immunity: 1. physical Physical barriers – prevent entry or remove microbes o Skin o Mucous o Saliva o Tears o Acid in stomach, urinary tract, vagina o Urine flushes urinary passageways o Cilia in respiratory tract, coughing and sneezing 2. Chemical mediators Chemical mediators – promote phagocytosis and inflammation o Promote inflammation E.g. histamine Cause vasodilation, increased vascular permeability, attract white blood cells, stimulate phagocytosis o Cytokines Secreted by one cell, and stimulates a neighbouring cell to respond Regulate intensity and length of immune response o Complement – stimulate lysis of invading pathogen cells o Interferons – anti-viral activity 3. white blood cells White blood cells produced in bone marrow & lymphatic tissue Released into blood and transported around the body o When a tissue is damaged it releases chemicals that attract white blood cells White blood cells ingest foreign particles – phagocytosis Produce chemicals to attract other immune cells to local area Neutrophils and macrophages are most important phagocytic cells o Neutrophils First cell to arrive at a site of insult o Macrophages Most effective phagocyte, important in later stages of inflammation and repair Help activate cells of the specific immune system Basophils, eosinophils, Natural killer cells 4. Inflammation Local tissue response to damage o Pathogens o Cuts and abrasions Aims to o Rid of body debris/invader o Prevent further pathogen entry Four features o Redness – increased blood flow to region o Heat – increased blood flow to region o Swelling – capillaries become leaky (increased permeability) fluid leaves capillaries – surrounding tissue o Pain – increased fluid stimulates pain receptors, chemical released by cells can also stimulate pain receptors Inflammatory response Heat, redness, swelling & pain 5. Fever 30 Generalized response of the body to tissue damage & infection Common in inflammation and infection Can cause macrophages to release chemicals Body temperature abnormally high High temperatures o Increase some antimicrobial substances o Decrease microbial growth o Increase body reactions that help tissue repair Adaptive immunity Specificity – ability to recognise a particular substance Memory – ability to remember previous encounters with a particular substance and respond rapidly Acquired during lifetime, depending on exposure Fights invaders once innate system is over-run Mediated by lymphocytes (special type of white blood cells ) B & T cells Activation of lymphocytes o Lymphocytes must recognise antigen o After recognition, lymphocytes must increase in number to destroy antigen Helper T cells Effector (cytotoxic/killer) T cells B Cells Cell-mediated immunity T lymphocytes o Helper T cells o Cytotoxic T cells Activated by special antigen Specific “clones” bind to antigen Co-stimulation required (Helper T cells) Activated cytotoxic T cells divide Eliminate antigen (pathogen) – makes holes in cell wall and causes cells to explode Form memory cells – if the same antigen re-appears, the response will be faster (memory) Most effective against intracellular pathogens Antibody-mediated immunity B cells Phagocytosis of an extracellular pathogen that matches the specific B cell receptor on that B cell Required co-stimulation by a helper T cell that also recognises the same pathogen (antigen) B cells divide to form o Plasma cells – make antibodies o Memory B cells – if the same pathogen (antigen) is encountered again, the response is much faster 31 Antibody production Primary response o when a B cell is first activated by an antigen. o B cell proliferates to produce plasma cells (antibody production) and memory cells. Secondary response o occurs during later exposure to same antigen. o Memory cells divide rapidly to form plasma cells and additional memory cells. Faster and greater response. Ways to acquire adaptive immunity Immune interactions Immune system dysfunction – HIV HIV = human immunodeficiency virus Virus binds to CD4 protein and infects Helper T cells Cells infected with HIV are ultimately destroyed by the virus or by immune response Gradual destruction of Helper T cells impairs cell mediated and antibody mediated immunity Normal amounts of Helper T’s = 1200 cells/mm3 When Helper T’s get below 200 cells/mm3 Acquired immune deficiency syndrome (AIDS) Antibody levels decline and cell mediated immunity reduced Believed to have spread from The Congo to Haiti to US in late 1960’s/70s First described by the CDC in the US in 1981 o Long incubation period, and initially low incidence rate Initially reported mainly the gay community, IV drug users, people who received blood transfusions HIV-AIDS Body is vulnerable to microbial invaders Ordinarily harmless microorganisms can cause lethal infections o Pneumocystis pneumonia o TB, syphilis o candidiasis Increased risk of cancer – Kaposi’s sarcoma Infection due to intimate contact with body fluids of infected people Treatment o When first described no treatment available HIV pretty much considered a “death sentence” (see Grim Reaper ad, Australia, 1987) 1. control HIV replication o Highly active anti-retroviral therapy (HAART) o Can live for many years o Chronic disease rather than death sentence 32 Lymphatic organs contain lymphatic tissue o Lymphocytes, macrophages, dendritic cells Lymphocytes: B & T cells – white blood cells derived from bone marrow Fine network of reticular fibres. Produced by reticular cells. Act as filter to trap microorganisms and other particles May be encapsulated (in a CT capsule) o Encapsulated – lymph nodes, spleen, thymus o Nonencapsulated – mucosa-associated lymphoid tissue (MALT). Found beneath epithelium as first line of attack against invaders Diffuse lymphatic tissue & lymphatic nodules Diffuse lymphatic tissue: o Dispersed lymphocytes, macrophages; blends with other tissues Lymphatic nodules: o Denser aggregations. Numerous in loose connective tissue of digestive, respiratory, urinary, reproductive systems Lymph nodes Only structures to filter lymph Substances removed by phagocytosis or stimulate lymphocytes to proliferate o Cancer cells often migrate to lymph nodes, are trapped there, and proliferate. Can move from lymphatic system to circulatory system spreading cancer throughout the body Afferent and efferent vessels Organized into cortex and medulla with dense connective tissue capsule surrounding 2. manage secondary infections/malignancies Compendium 10 – How do we protect ourselves? – Lecture 2 of 2 – P2: Lymphatics Functions of the lymphatic system Fluid balance o Excess interstitial fluid enters lymphatic capillaries and become lymph (30L from capillaries into interstitial fluid, 27L return leaving 3L called lymph) Fat absorption o Absorption of fat and other substances from digestive tract via lacteals Defence o Lymphatic system – fights infection. Microorganisms and other foreign substances are filtered from lymph and by lymph nodes and from blood by spleen Anatomy of the lymphatic system Lymph Lymphatic vessels Lymphatic tissue Lymphatic nodules Lymph nodes Tonsils Spleen Thymus Lymph Water plus solutes from two sources o Plasma: ions, nutrients, gases, some proteins o Cells: hormones, enzymes, waste products Returns to circulatory system via veins, essential for fluid balance Lymphatic vessels Carry lymph away from tissues Lymphatic capillaries o More permeable than blood capillaries o Epithelium functions as series of one-way valves o Found in all parts of the body except nervous system, bone and avascular tissues Lymphatic capillaries: join to form lymphatic vessels Lymphatic vessels: have valves that ensure one-way flow Lymph nodes: distributed along vessels and filter lymph Lymphatic trunks: jugular, subclavian, broncho mediastinal, intestinal, lumbar Lymphatic ducts: drain tissues of body and move lymph onto major veins o Right lymphatic duct: drains right side of head, right-upper limb, right thorax o Thoracic duct: drains remainder of the body Lymphatic tissue and organs Tonsils Large groups of lymphoid tissue in nasopharynx and oral cavity Provide protection against bacteria and other harmful material o Palatine (tonsils) o Pharyngeal (adenoids) o Lingual Spleen Red pulp associated with veins (75%) – fibrous network of macrophages and RBCs White pulp associated with arteries (25%) – lymphatic tissue Functions o Monitors blood, detects and responds to foreign antigens o Destroys defective red blood cells o Regulates blood volume o Limited reserve of RBC Can be ruptured in traumatic abdominal injuries Splenectomy Thymus Located in superior mediastinum Cortex (numerous lymphocytes) and medulla (fewer) Sites of maturation of T cells: many T cells produced here, but most degenerate Those that remain can react to foreign substances Endocrine functions Disorders Tonsilitis – inflammation of the tonsils – bacterial infection Lymphoma – cancer (benign or malignant) of the lymphoid tissue or cells, often begins in the lymph nodes, immune system suppressed Hodgkin’s disease – malignancy in lymphoid tissue (malignant B cells). Chemotherapy/radiation Non-Hodgkin’s lymphoma – any cancer of lymphoid tissue – except Hodgkin’s. Can affect cells, nodes or organs. Young vs Old Bubonic plague (the black death) – severe bacterial infection (fleas/rats), enlarged lymph nodes, septicaemia COMPENDIUM ELEVEN: HOW DO CELLS SPECIALISE AND DIE? Compendium 11 – How do cells specialise and die? Lecture 1 of 4 – P1: Introduction to DNA Introduction to DNA DNA; deoxyribonucleic acid Genetic information contained in nucleus Contains genetic information for protein formation Approximately 23 000 genes in human genome Genes code for proteins Only 1.5% of DNA is due to genes 98.5% of DNA is non-coding – e.g. regulatory sequences, introns and noncoding DNA – e.g. repeat elements Structure of DNA Double-stranded (double helix twisted ladder) Sugar phosphate backbone Complementary nitrogenous bases o Adenine – thymine 33 o Guanine – cytosine Organisation of DNA Double strand of DNA – twisted ladder DNA wrapped around proteins called histones Histones & DNA bundled together – chromatin Chromatin twists around to make chromosomes How much DNA is in a cell? Each somatic human cell has two copies of each chromosome – one you inherit from each parent The maternal and paternal chromosomes of a pair are called homologous chromosomes Humans have 22 pairs of autosomal chromosomes and 1 pair of sex chromosomes o Women have 2 X chromosomes and men have an X and Y Somatic cells with 46 chromosomes (23 pairs) are said to be diploid (have the full amount of DNA) Gametes (sperm and egg) only have 1 chromosome of each homologous pair (have 23 chromosomes) and are called haploid When cells are dividing, the chromosomes become easier to see and we can arrange them next to their pair – this kind of map is a karyotype Definitions Genetics – study of heredity Gene – piece of DNA that codes for a protein Allele – alternative form of a gene Genotype – the actual gene (allele) Phenotype – person’s appearance Dominant and recessive alleles Sex-linked traits: traits affected by genes on sex chromosomes Compendium 11 – How do cells specialise and die? Lecture 2 of 4 – P2: Protein synthesis The “proteome” Cells are protein factories that constantly synthesise many different proteins These proteins are used for cell functions or can be exported The cell’s DNA contains all the instructions the cell needs for making proteins Not all cells make proteins – some proteins are needed only by specific cells o The “proteome” of a cell is all the proteins that a cell makes, and “proteomics” is the study of the proteins in a cell o The proteome of one cell can be compared to another to see how they are different A muscle cell vs a skin cell Protein synthesis Transcription o DNA > RNA Translation o RNA > protein Flow of information from DNA to RNA to protein: The Central Dogma Transcription DNA has two strands, but only one strand of the DNA is used as a template to make RNA Genetic information (a gene) is copied from strand of DNA to make a strand of ribonucleic acid (RNA) called mRNA (messenger RNA) RNA is like DNA except – o Sugar ribose instead of deoxyribose o It is single-stranded o Contains uracil instead of thymine RNA acts as an intermediary between DNA and protein Initiated by transcription factors that recruit RNA polymerase enzyme The mRNA produced is called an RNA transcript There are special sequences/signals in DNA that indicate when a gene starts and stops Within a gene there are exons (coding) and introns (non-coding) The initial mRNA transcript (pre-mRNA) contains both the exons and introns The RNA introns are the cut out and the exons are all joined together. This transcript is called processed RNA Three kinds of RNA are transcribed from DNA o Messenger RNA (mRNA) – is translated in the cytoplasm to make proteins o Ribosomal RNA (rRNA): together with ribosomal proteins rRNA makes up the ribosomes o Transfer RNA (tRNA): each tRNA can bind specifically to one of the 20 different amino acids used to build proteins, important in translating mRNA into amino acid peptide The strands of DNA are separated RNA polymerase binds at a promoter region RNA polymerase catalyses the formation of a mRNA chain using the DNA as a template and following the rules of complimentary base pairing o A with U o C with G Transcription ends at a terminator sequence Translation Turns mRNA into a protein Occurs in the cytoplasm – by ribosomes o On rough ER o Free within cytoplasm mRNA carries genetic information from the nucleus to the ribosomes The sequence is “read” by translational machinery in the ribosome, in lots of three nucleotides (nucleotide triplets = codon) Translation starts at the start codon (AUG) of each gene in the mRNA Each codon codes for a specific amino acid As each codon is read, a tRNA with a complimentary sequence (anticodon) binds to each triplet The tRNA also carries the amino acid specified by the codon Amino acids are joined together by peptide bonds, in the sequence specified by the mRNA, to make a peptide/protein Codons & amino acids There are 64 possible codons in mRNA and only 20 naturally occurring amino acids Some amino acids are specified by only one codon 34 Others are specified by up to six different codons Thus the DNA code is “degenerate” Three codons do not code for an amino acid but signal termination of the peptide chain Post-translational modification The chemical modification of a protein following translation It is one of the last steps in protein synthesis After translation, proteins can be modified by attaching other functional groups which can change or extend its functions Amino acids may be cleaved off the end of protein or the polypeptide can be cut in half Other modifications, such as phosphorylation are a common way of controlling the behaviour of a protein, for instance activating or inactivating an enzyme Compendium 11 – How do cells specialise and die? Lecture 3 of 4: P3: Protein structure Protein structure A protein molecule is a long chain of amino acids, each linked to its neighbour by a peptide bond There are many thousands of proteins, each has a unique sequence of amino acids Each amino acid has specific properties due to its side chains Some of the side chains are non-polar and hydrophobic (water fearing), others are hydrophilic or positively or negatively charged In a long chain of amino acids, interactions between these side groups, as well as the peptide bonds, affect the way a protein can fold and what shape it is Peptide – 2 or more amino acids Polypeptide – 10 or more Protein – 50 or more Primary o Sequence of amino acids linked by peptide bonds Secondary o Proteins fold to form secondary structures because the amino acids have different side chains o Two regular folding patterns are seen: alpha helices and beta pleated sheets Tertiary o The 3D shape is determined by the folding of the secondary structure. The a-helices and b-sheets fold to form unique structures which are held together my bonds between amino acids that may be far apart in the actual polypeptide chain Quaternary o Combined three-dimensional structure of two or more polypeptide chains o E.g. haemoglobin Fibrous and globular proteins The 3D structure of a protein is related to its function Proteins can be classified according to overall shape and appearances as whether fibrous or globular Globular proteins o Polypeptide chain folds up into a compact shape, like a ball with a rough surface o Usually water soluble o Mobile o Chemically active o Plays crucial roles in nearly all biological processes Fibrous proteins o Simple, elongated 3D structures o Are insoluble in water and stable o Provide mechanical support and tensile strength o Are abundant outside the cell where they make up a lot of the matrix in between cells Compendium 11 – how do cells specialise and die? Lecture 4 of 4: P4: Mitosis and Meiosis Cell life cycle Cells spend the majority of their life in interphase Interphase: phase between cell division. Ongoing normal cell activities Mitosis: series of events that leads to the production of 2 somatic cells by division or one mother cell into two daughter cells. Cells are genetically identical o Prophase o Metaphase o Anaphase o Telophase Cytokinesis: division of cell cytoplasm Chromosomes & chromatin Chromatin: DNA complexed with proteins (histones) During cell division, chromatin condenses into pairs of chromatids called chromosomes. Each pair of chromatids is joined by a centromere Chromosomes Humans: 23 pairs of chromosomes. 46 diploid number, 22 autonomic pairs 1 sex determining pair Homologous: pairs of chromosomes -where one is from father and mother is from mother Locus: the location of a gene on a chromosome Allele: different forms of the same gene DNA replication Interphase – DNA replication occurs. Each chromosome becomes doubled, consisting of 2 identical strands of DNA Structure of a mitotic chromosome The DNA of a chromosome is dispersed as chromatin The DNA molecule unwinds, and each strand of the molecule is replicated During mitosis, the chromatin from each replicated DNA strand condenses to form a chromatid. The chromatids are joined at the centromere to form a single chromosome The chromatids separate to form two new, identical chromosomes. The chromosomes will unwind to form chromatin in the nuclei of the two daughter cells Mitosis Produces 2 identical daughter cells Prophase – chromatin condenses to form chromosomes, centrioles migrate to end of each cell, spindle fibres attach to centromeres, nuclear envelope disintegrates Metaphase – chromosomes are aligned at the nuclear equator Anaphase – spindle fibres separate the chromatids, 2 identical sets of chromosomes are moved to separate ends of the cell, cytokinesis begins 35 Telophase – nuclear envelope reforms around each set of chromosomes, chromosomes decondense into chromatin, cytokinesis continues Centrioles & spindle fibres 2 centrioles, located in centrosome Centre of microtubule (spindle fibre) formation Before cell division, centrioles divide, move to ends of cell and organise spindle fibres Mitosis I.P.M.A.T Meiosis Germ cells divide and produce gametes Specialized for sexual reproduction DNA replication followed by two cell divisions Produces 4 genetically different daughter cells o Gametes (haploid) o Only 1 homolog from each homologous pair Resulting gametes unite to form a zygote – a new “genetically unique” human being Spermatogenesis Where is meiosis happening? In the gonads. The testes make gametes (sperm) via meiosis. 4 functional sperm cells per division. Non identical. 23 chromosomes. Lifelong process in testes. Oogenesis The ovaries make gametes (oocytes) via meiosis. At birth, the ovaries contain all the oocytes they will ever have – stalled in prophase 1. 1 functional oocyte per division. 3 polar bodies. Non identical. 23 chromosomes